prenatal care essay

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What is prenatal care and why is it important?

Having a healthy pregnancy is one of the best ways to promote a healthy birth. Getting early and regular prenatal care improves the chances of a healthy pregnancy. This care can begin even before pregnancy with a pre-pregnancy care visit to a health care provider.

Pre-Pregnancy Care

A pre-pregnancy care visit can help women take steps toward a healthy pregnancy before they even get pregnant. Women can help to promote a healthy pregnancy and birth of a healthy baby by taking the following steps before they become pregnant: 1

• Develop a plan for their reproductive life.
• Increase their daily intake of folic acid (one of the B vitamins) to at least 400 micrograms. 2
• Make sure their immunizations are up to date.
• Control diabetes and other medical conditions.
• Avoid smoking, drinking alcohol, and using drugs.
• Attain a healthy weight.
• Learn about their family health history and that of their partner.
• Seek help for depression, anxiety, or other mental health issues.

Prenatal Care

Women who suspect they may be pregnant should schedule a visit to their health care provider to begin prenatal care. Prenatal visits to a health care provider usually include a physical exam, weight checks, and providing a urine sample. Depending on the stage of the pregnancy, health care providers may also do blood tests and imaging tests, such as ultrasound exams. These visits also include discussions about the mother's health, the fetus's health, and any questions about the pregnancy. 3

Pre-Pregnancy and prenatal care can help prevent complications and inform women about important steps they can take to protect their infant and ensure a healthy pregnancy. With regular prenatal care women can:

• Reduce the risk of pregnancy complications. Following a healthy, safe diet; getting regular exercise as advised by a health care provider; and avoiding exposure to potentially harmful substances such as lead and radiation can help reduce the risk for problems during pregnancy and promote fetal health and development. 4 Controlling existing conditions, such as high blood pressure and diabetes, is important to prevent serious complications and their effects. 5
• Reduce the fetus's and infant's risk for complications. Tobacco smoke and alcohol use during pregnancy have been shown to increase the risk for  Sudden Infant Death Syndrome . 6 Alcohol use also increases the risk for fetal alcohol spectrum disorders, which can cause a variety of problems such as abnormal facial features, having a small head, poor coordination, poor memory, intellectual disability, and problems with the heart, kidneys, or bones. 7 According to one recent study supported by the NIH, these and other long-term problems can occur even with low levels of prenatal alcohol exposure. 8 In addition, taking 400 micrograms of folic acid daily reduces the risk for neural tube defects by 70%. 2 , 9  Most prenatal vitamins contain the recommended 400 micrograms of folic acid as well as other vitamins that pregnant women and their developing fetus need. 1 , 10  Folic acid has been added to foods like cereals, breads, pasta, and other grain-based foods. Although a related form (called folate) is present in orange juice and leafy, green vegetables (such as kale and spinach), folate is not absorbed as well as folic acid.
• Help ensure the medications women take are safe. Women should not take certain medications , including some acne treatments 11  and dietary and herbal supplements, 12  during pregnancy because they can harm the fetus.

Learn more about  prenatal and pre-pregnancy care .

• Centers for Disease Control and Prevention. (2015). Preconception health and health care. Retrieved May 20, 2016, from http://www.cdc.gov/preconception/planning.html
• Centers for Disease Control and Prevention. (2011).  Fetal alcohol spectrum disorders. Retrieved August 1, 2012, from  http://www.cdc.gov/Features/FASD
• Eckstrand, K. L., Ding, Z., Dodge, N. C., Cowan, R. L., Jacobson, J. L., Jacobson, S. W., et al. (2012). Persistent dose-dependent changes in brain structure in young adults with low-to-moderate alcohol exposure in utero.  Alcoholism: Clinical and Experimental Research, 36 (11), 1892–1902.  PMID: 22594302
• Centers for Disease Control and Prevention. (2016). Folic acid. Data and statistics. Retrieved December 12, 2016, from https://www.cdc.gov/ncbddd/folicacid/data.html
• NIH Office of Dietary Supplements. (2016).  Folate. Dietary supplement fact sheet. Retrieved May 20, 2016, from  http://ods.od.nih.gov/factsheets/Folate-HealthProfessional  
• Office on Women's Health. (2012).  Prenatal care fact sheet.  Retrieved May 20, 2016, from  http://www.womenshealth.gov/publications/our-publications/fact-sheet/prenatal-care.html

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Prenatal and Postpartum Care

The care domain is a defined area of social welfare provision and plays a crucial role in the overall quality of care. Fields of care are necessary because they provide a framework for organizing and delivering care. Ease of access, quality of care received, satisfaction with treatment, health plan description, effectiveness of care, and outcome metrics are all part of the care domains. The fields of care have various performance measures, and prenatal and postpartum care is among the performance measures (Gratziou & Rovina et al., 2018). Prenatal care is the health care you receive during pregnancy. Prenatal care includes regular check-ups, tests, and screenings to help keep the mother and baby healthy. On the other hand, postpartum care is the care the mother receives after giving birth, including caring for the baby, recovering from childbirth, and adjusting to life with a new baby.

Prenatal and postpartum care are essential to the well-being of both child and mother. Unfortunately, due to various factors, including lack of access to care, financial constraints, and societal norms, many women do not receive the care they need during these crucial times. As a result, both mothers and children can suffer from health problems, both short- and long-term (Gratziou & Rovina et al., 2018). It is crucial, then, that women have access to improved prenatal and postpartum care. Various performance measures have been developed to ensure that women receive the care they need. Prenatal and postpartum care have various primary patient interventions that have improved patient outcomes and saved patient costs.

Patient Interventions

Prenatal and postpartum care is critical to ensuring a healthy pregnancy and birth. The National Committee for Quality Assurance (NCQA) recognizes three patient prenatal and postpartum care interventions as performance measures: comprehensive prenatal care, adequate weight gain during pregnancy, and smoking cessation.

Comprehensive Prenatal Care

Comprehensive prenatal care includes a broad range of services designed to care for the whole person, not just the pregnancy. These services should be tailored to the patient’s needs and may include nutrition counseling, mental health support, and social services (Groenhof & Veerbeek et al., 2018). To implement this intervention, providers should assess the needs of each patient and connect them with the appropriate resources—Archived through referrals to community organizations or on-site services. To measure the outcomes of this intervention, providers can track the patients who receive comprehensive prenatal care and the number of patients who experience adverse consequences, such as preterm birth or low birth weight.

Appropriate Weight Gain throughout Pregnancy

Furthermore, both the mother and the baby benefit significantly from the woman accumulating a healthy weight throughout pregnancy. Women who are overweight have a higher chance of developing several health problems during and after pregnancy. To help ensure adequate weight gain, providers should assess a woman’s weight at each prenatal visit and guide diet and exercise (Ells & Scott et al., 2018). To measure the outcomes of this intervention, providers can track the number of patients who gain the recommended amount of weight during pregnancy and patients who experience complications.

Smoking Cessation During Pregnancy

Last but not least, smoking causes several pregnancy problems, including delivery difficulties, low birth weight, and placental abruption. Providers should do tobacco use screenings at each prenatal appointment and provide counseling and services to assist pregnant women quit smoking (Gratziou & Rovina et al., 2018). To measure the outcomes of this intervention, providers can track the number of patients who quit smoking during pregnancy.

Improved Patient Outcomes

Patient experience outcomes include patient-reported experience measures. According to the Agency for Clinical Innovation (ACI), Patient-reported experience measures patient satisfaction with healthcare. This data may provide a more accurate picture of patient satisfaction and help improve local services and address concerns faster. Patients may be asked to rate their treatment on a 1-to-5 scale. A care delivery mechanism may reduce the Length of stay, which is good, but if patients feel rushed out, their satisfaction scores will drop (NCQA, 2021). The interventions can result in improved patient outcomes for the practice of prenatal and postpartum care.

Comprehensive prenatal care reduces preterm birth, low birth weight, and neonatal death. It can also lead to improved maternal health outcomes, including reduced risk of hypertension and postpartum hemorrhage. In addition, comprehensive prenatal care can reduce healthcare costs by preventing complications that require more expensive interventions, such as hospitalization or surgery. Adequate weight gain during pregnancy is essential for optimizing maternal and fetal outcomes (Guo & Chen et al., 2019). Women who do not acquire enough weight during pregnancy are more likely to have premature infants, low birth weights, or infant deaths.

Increased dangers for the mother include hypertensive problems throughout pregnancy and postpartum bleeding if the baby doesn’t grow enough weight. Smoking cessation during pregnancy is vital for improving maternal and fetal health outcomes. Babies born to mothers who smoke during pregnancy have a higher chance of being born prematurely, having a low birth weight, and dying shortly after delivery. Furthermore, smoking increases the probability of developing hypertensive disorders during pregnancy and postpartum hemorrhage, both dangerous to the mother.

Cost Savings

Comprehensive prenatal care, appropriate weight gain, and smoking cessation may lower prenatal and postpartum costs. A thorough literature analysis indicated that treatments to enhance pregnancy outcomes are cost-effective (Naughton & Fulton et al., 2018). The interventions found to be cost-effective were comprehensive prenatal care, smoking cessation, and adequate weight gain during pregnancy. Comprehensive prenatal care is associated with a reduction in the number of preterm births, low birth weight babies, and neonatal deaths. These reductions in adverse outcomes are associated with reduced healthcare costs. Therefore, Comprehensive prenatal care measures save money.

Pregnancy weight gain minimizes low-birth-weight babies. Low birth weight promotes neonatal mortality and childhood health concerns. According to a comprehensive study, moderate weight gain therapies are cost-effective during pregnancy (Naughton & Fulton et al., 2018). Preterm births, low birth weight newborns, and neonatal fatalities may be prevented if mothers quit smoking throughout their pregnancies. The healthcare savings attributable to these decreases in bad outcomes are substantial. Research on the cost-effectiveness of smoking cessation during pregnancy has shown that such programs save money.

Patient Ratings

Patient ratings are one way to measure how well a provider is doing. Comprehensive prenatal care, adequate weight gain during pregnancy, and smoking cessation during pregnancy can improve patient ratings for various reasons. Comprehensive prenatal care aims to decrease mother and newborn mortality and enhance pregnancy outcomes. For the best results, it’s best to start this sort of treatment as soon during pregnancy as possible so that all women may get it. The likelihood of having a premature delivery, a baby with a low birth weight, or a baby who dies shortly after birth may all be decreased with the help of comprehensive prenatal care. The health of the mother and child depends on the woman gaining enough weight during pregnancy.

Too little or too much weight gain during pregnancy can cause the baby to be born early, the baby to be born with a low birth weight, or both the mother and the baby to die. So, women need to gain the right amount of weight while pregnant. Lastly, it is essential for both the mother’s and the baby’s health for the mother to stop smoking while she is pregnant. The risks of having a premature baby, a baby with a low birth weight, and a baby dying shortly after delivery are amplified when the mother smokes. Women who smoke during pregnancy are also more likely to experience placental abruption and placenta previa. To reduce these risks, women must quit smoking before or during pregnancy.

Prenatal care is essential for a healthy pregnancy. It is vital for pregnant women to see a healthcare provider early in their pregnancy and to continue to receive care throughout their pregnancy. Prenatal care can help identify potential health problems, manage complications, and promote a healthy pregnancy. Postpartum care is also crucial for the health of the mother and baby (NCQA, 2021). Women should have regular check-ups and screenings in the postpartum period. Nutrition and weight loss are essential in the postpartum period, and women should aim to lose the weight they gain during pregnancy. Smoking is also harmful to the mother and baby and should be avoided postpartum. Several interventions can help pregnant women have a healthy pregnancy, including comprehensive, adequate weight gain, prenatal care, and smoking cessation during pregnancy. These interventions can help to improve outcomes for both the baby and the mother.

Diamanti, A., Papadakis, S., Schoretsaniti, S., Rovina, N., Vivilaki, V., Gratziou, C., & Katsaounou, P. A. (2019). Smoking cessation in pregnancy: An update for maternity care practitioners.  Tobacco-induced diseases ,  17 . https://doi.org/10.18332%2Ftid%2F109906

Farpour-Lambert, N. J., Ells, L. J., Martinez de Tejada, B., & Scott, C. (2018). Obesity and weight gain in pregnancy and postpartum: an evidence review of lifestyle interventions to inform maternal and child health policies.  Frontiers in endocrinology ,  9 , 546. https://doi.org/10.3389/fendo.2018.00546

Griffiths, S. E., Parsons, J., Naughton, F., Fulton, E. A., Tombor, I., & Brown, K. E. (2018). Are digital interventions for smoking cessation in pregnancy effective? A systematic review and meta-analysis.  Health Psychology Review ,  12 (4), 333–356. https://doi.org/10.1080/17437199.2018.1488602

Guo, H., Zhang, Y., Li, P., Zhou, P., Chen, L. M., & Li, S. Y. (2019). Evaluating the effects of a mobile health intervention on weight management, glycemic control, and pregnancy outcomes in patients with gestational diabetes mellitus.  Journal of endocrinological investigation ,  42 (6), 709–714. https://doi.org/10.1007/s40618-018-0975-0

NCQA. (2021).  Adult BMI Assessment – NCQA . NCQA. Retrieved November 13, 2022, from https://www.ncqa.org/hedis/measures/adult-bmi-assessment/

Parekh, N., Jarlenski, M., & Kelley, D. (2018). Prenatal and postpartum care disparities in a large Medicaid program.  Maternal and child health journal ,  22 (3), 429-437. https://doi.org/10.1007/s10995-017-2410-0

Van Den Heuvel, J. F., Groenhof, T. K., Veerbeek, J. H., Van Solinge, W. W., Lely, A. T., Franx, A., & Bekker, M. N. (2018). eHealth as the next-generation perinatal care: an overview of the literature.  Journal of medical Internet research ,  20 (6), e9262. https://doi.org/10.2196/jmir.9262

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Prenatal Care, Essay Example

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Prenatal refers to the period between conception and giving birth. This is the pregnancy period in which a lot of attendance and care is taken for the woman awaiting birth to ensure the wellbeing of the child to be born and the mother. Basically, staying healthy is the main part of prenatal.

There are various operations and tests carried out by doctors during the appointments within the prenatal period and patients behave differently towards these tests when being attended. One of the screening tests carried out is the alphafetoprotein (AFP) test. It is mainly done for screening complications or problems like spinal Bifida and to help in finding out babies who suffer from neural tube diseases i.e. NTD commonly referred to as Down syndrome and it’s done between the 14 th and the 17 th week of pregnancy.

Another critical test taken during the prenatal is that of the ultrasounds. It helps in screening for genetic defects as well as predicting the weight of the fetal. Prenatal testing can be exciting and at same time very scaring and disturbing to the patient. Some women are so positive about knowing the status of their babies to be. It however gets complicated as the patient does not know what to expect from the tests. Sometimes it’s very difficult for the doctors to give the test results especially where they are negative. Some patients even go to the extent of breaking down in tears and worse of even faint after testing positive for downs test. It becomes completely difficult for the patient to interpret the results, details and the decisions outlined by the doctor and very hard to accept and deal with them.

Some of frequently asked questions by the doctors and the patient are based on the body changes and transformation and feeding habits of the expectant mother. For instance, a doctor may ask whether the patient experiences upper-abdominal pains or less frequent urination than in normal conditions. Some of these questions are meant to identify any ailments of the patient that she might not have discovered. For instance, those conditions signify that the patient might be suffering from preeclampsia, a condition of extreme blood pressure which can be fatal to the baby or even to the mother. Despite the mixed reactions and tension involved in the prenatal tests, the importance of taking these tests cannot be overemphasized all for the good of the baby to be born and the mother.

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• Open access
• Published: 09 August 2022

Whole genome non-invasive prenatal testing in prenatal screening algorithm: clinical experience from 12,700 pregnancies

• Elena E. Baranova 1 , 2 ,
• Olesya V. Sagaydak 1 ,
• Alexandra M. Galaktionova 1 ,
• Ekaterina S. Kuznetsova 1 ,
• Madina T. Kaplanova 1 ,
• Maria V. Makarova 1 ,
• Maxim S. Belenikin 1 ,
• Anton S. Olenev 3 &
• Ekaterina N. Songolova 4  

BMC Pregnancy and Childbirth volume  22 , Article number:  633 ( 2022 ) Cite this article

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A fast adoption of a non–invasive prenatal testing (NIPT) in clinical practice is a global tendency last years. Firstly, in Russia according a new regulation it was possible to perform a widescale testing of pregnant women in chromosomal abnormality risk. The aim of the study—to assess efficiency of using NIPT as a second-line first trimester screening test in Moscow.

Based on the first trimester combined prenatal screening results 12,700 pregnant women were classified as a high-risk (cut-off ≥ 1:100) and an intermediate-risk (cut-off 1:101 – 1:2500) groups followed by whole genome NIPT. Women from high-risk group and those who had positive NIPT results from intermediate-risk group were considered for invasive prenatal diagnostic.

258 (2.0%) samples with positive NIPT results were detected including 126 cases of trisomy 21 (T21), 40 cases of T18, 12 cases of T13, 41 cases of sex chromosome aneuploidies (SCAs) and 39 cases of rare autosomal aneuploidies (RAAs) and significant copy number variations (CNVs). Statistically significant associations ( p  < 0.05) were revealed for fetal fraction (FF) and both for some patient’s (body mass index and weight) and fetus’s (sex and high risk of aneuploidies) characteristics. NIPT showed as a high sensitivity as specificity for common trisomies and SCAs with an overall false positive rate 0.3%.

Conclusions

NIPT demonstrated high sensitivity and specificity. As a second-line screening test it has shown a high efficiency in detecting fetus chromosomal anomalies as well as it could potentially lower the number of invasive procedures in pregnant women.

Peer Review reports

Infant mortality is a major medical and social problem, reflecting the quality of the public health system and the future of the country. The main unfavorable factors promoting to high infant mortality are low socioeconomic status of the country, low quality and availability of medical care, severe maternal, fetal or placental conditions, advanced maternity age [ 1 ]. The evolution of reproductive technologies over the last few decades has contributed to an advanced maternal age, which is associated with an increased fetal chromosomal anomaly rates and congenital diseases [ 2 ]. Among other reasons congenital diseases lead to as much as 20% of all infant deaths [ 3 ].

To evaluate and prevent fetus congenital disease, including chromosomal abnormalities, traditional first trimester screening is performed. It includes blood screening combined with an ultrasound examination in the first trimester of pregnancy. Fetus congenital disease can be well diagnosed by ultrasound examinations only from the 11th gestational week. Biochemical blood pregnancy marker risk assessment of chromosomal fetus anomalies is based on the human chorionic gonadotrophin (hCG), the free-β subunit of hCG, and the pregnancy-associated plasma protein (PAPP-A) blood tests. Though widely used biochemical assessment combined with ultrasound is still an indirect evaluation of chromosomal anomalies and results in a false positive rate of up to 5%, leading to increases number of invasive prenatal diagnostic (IPD) procedures [ 4 , 5 ].

To address these limitations, a new screening method, known as a non-invasive prenatal testing (NIPT), was introduced [ 6 ]. The method is based on the massive parallel sequencing of cell-free DNA (cfDNA) fragments derived from a maternal plasma [ 7 ]. The sensitivity of NIPT for most common trisomies including trisomies 21 (T21), 18 (T18), and 13 (T13) is high and reaches up to 99, 96 and 91%, respectively [ 8 ] with a false-positive results rate as low as 0.08% compared to traditional prenatal screening [ 9 ].

There are several types of NIPT – tests targeted on chromosomes of interest (usually 21, 18 and 13) and a whole genome NIPT, that allows to assess all chromosomes and its anomalies. Whole genome NIPT can be used to detect sex chromosome abnormalities and other anomalies, including rare autosomal aneuploidies (RAAs) and significant copy number variations (CNVs), though accuracy of the test for these anomalies is a bit lower due to the fact that RAAs are usually present as a placental mosaicism or a true fetal mosaicism. That could be associated with adverse pregnancy outcomes such as early miscarriage, intrauterine growth restriction, and in-utero fetal demise [ 10 ]. In nonmosaic form these chromosomal anomalies usually lead to a fetus death [ 11 ].

The American College of Obstetricians and Gynecologists (ACOG) originally suggested the use of NIPT for women previously determined to be in a high-risk group by traditional screening [ 12 ]. But it has been shown that the sensitivity and specificity of the test among all pregnant women are similar to those in the high-risk population [ 13 ]. Therefore, current international guidelines recommend the use of NIPT for prenatal screening during pregnancy for all women, regardless of the predetermined risk of fetal anomalies [ 5 , 13 ].

Until recently, in Russia NIPT was primarily a commercially available test used to supplement other screening approaches. On March 13, 2020, NIPT was included as a standard method for prenatal screening as part of a pilot project in Moscow [ 14 ]. The large-scale project was run by the Moscow City Healthcare Department with the participation of 23 prenatal care hospitals and one genetic laboratory. Since the beginning, work on national standards and clinical guidelines for NIPT has been ongoing. The aim of the study was to assess the efficiency of NIPT as a second-line first trimester screening test in Moscow. Preliminary results were published before [ 15 ]. The project is finished now, and its first results are presented.

Recruitment criteria

Pregnant women at high-risk of fetus chromosomal anomalies (cut-off ≥ 1:100) after the traditional prenatal screening were referred for genetic counseling, a IPD and a blood sampling for NIPT according the local regulation [ 14 ]. Blood test for NIPT was performed in the same day of the IPD (Fig.  1 ).

Recruitment criteria for samples that were able to undergo NIPT. *Low-risk group samples were not included into the study. **IPD is obligatory for a high-risk group of pregnant women and is optional for an intermediate-risk group. Abbreviations: NIPT, non–invasive prenatal testing; IPD, invasive prenatal diagnostic

Pregnant women at group of risk 1:101–1:2500 were as well offered to perform NIPT. When receiving a positive (high-risk) NIPT result, pregnant women were considered to undergo a genetic consulting and IPD.

Sample’s collection and blood preparation for sequencing

To perform NIPT 10.0 ml pregnant women peripheral blood samples were collected in STRECK (Cell-Free DNA BCT CE) tubes before IPD. Plasma was separated within 8 h following a double-centrifugation protocol. Tubes were stored temporarily (up to one week) at -20 °C before further processing or stored at – 80 °C for a long-term storage.

The cfDNA isolation, sample library preparation and DNA sequencing were performed according to manufacturer’s protocols. Each sample was sequenced using a BGISEQ-500 (China) platform. Sequencing reads were trimmed and aligned to a universal unique read set incised from the human reference genome (hg19, NCBI build 37). Combined GC-correction and z-score testing methods were used to identify fetal autosomal aneuploidies. The quality control parameters were as follows: the library concentration was higher than 4 ng/μL; the unique mapped reads number was higher than 6 × 106; the GC content was 38%–42%; and the fetal DNA fraction was higher than 3.5%. The original BGI proprietary software (HALOS NIFTY-2.3.2.1011) was used for a bioinformatic data processing.

Fetal fraction calculation

The fetus fetal fraction (FF) was calculated using the FF-QuantSC method, that employs neural network model and utilizes differential genomic patterns between fetal and maternal genomes [ 16 ].

NIPT results

The final report included a risk assessment for T21, T18, T13 and SCAs. Whole genome results for RAAs and clinically significant CNVs were included in the report optionally for women who consented to receive that information.

Invasive prenatal diagnostics

Pregnant women from the high-risk group as well as women with a fetal chromosomal abnormalities risk revealed by NIPT («positive» NIPT results) from the intermediate-risk group were advised to undergo IPD by amniocentesis or chorionic villus sampling (CVS) with a subsequent karyotyping and/or array-based comparative genomic hybridization (aCGH). IPD was also recommended for pregnant women with abnormalities during their second trimester ultrasound examination. CVS or amniocentesis were performed under sterile conditions and an ultrasound guidance in specialized medical hospitals in Moscow.

Karyotype analysis

For karyotype analysis, 10–20 ml of amniotic fluid was obtained by amniocentesis. The amniotic fluid cells with 4.5 ml medium (RPMI-1640, Paneco, Russia) were cultured in a 37 °C incubator with 5% carbon dioxide. The cells were harvested at 10–12 days. After colchicine treatment for 2 h, the cells were digested using 1:250 trypsin, and incubated with 0.075 M KCl for 30 min. The prefixation, fixation, dropping, baking, and G-band staining were performed next. A total of 100 dividing phases were counted using an all-chromosome image analysis system based on the “An International System for Human Cytogenetic Nomenclature, ISCN2016”.

Agilent SurePrint G3 human aCGH array 8*60 K chips were used for aCGH. DNA from amniotic fluid or chorionic villus after IPD was extracted (New iGENatal Kit, igen biotech, Spain). Agilent CytoGenomics (version 5.0) was used for data analyses. CNVs were classified through Online Mendelian Inheritance in Man (OMIM), Database of Genome Variants (DGV) and Decipher databases. Pathogenic, likely pathogenic, variant of uncertain significance (VUS), likely benign, and benign categories were used for CNVs’ allocation. For VUS aCGH was further performed for parents to verify whether the CNVs were inherited from the parents with a normal phenotype. Inherited CNVs from the parents with a normal phenotype were considered as benign.

Statistical analysis was performed as described earlier [ 15 ]. The statistical software package Wizard 2 Version 2.0.4 (250) was used for data analyses.

All in all, 12,700 pregnant women blood samples were analyzed during the Apr.1, 2020 till Apr. 5, 2021 period (Fig.  2 ). The average pregnant women age was 34.4 ± 4.3 years. 53.2% (6756/12700) of pregnant women were in the advanced maternal age (35 and older). The average gestation period was 14 weeks and 1 day ± 1 week and 3 days. 36.7% (4655/12700) of pregnant women had a body mass index (BMI) above 25 kg/m 2 . The majority of pregnancies were spontaneous (96.1%, 12,198/12700) and singleton (98.5%, 12,512/12700) (Table 1 ).

Flowchart of non-invasive prenatal test (NIPT) results and invasive prenatal diagnostics outcomes of pregnant women undergoing screening for aneuploidies between 1 April 2020 and 5 April 2021. Abbreviations: T, trisomy; SCA, sex chromosomal aneuploidy; RAA, rare autosomal aneuploidy; CNV, copy number variation; aCGH, array comparative genomic hybridization

Blood samples of 502 (3.9%) women in the high-risk group and of 12,198 (96.1%) women in the intermediate-risk group were evaluated. Out of 12,700 samples in 346 (2.7%) cases blood retesting was recommended due to a low FF (below 3.5%).

NIPT results in high-risk pregnant women

Out of 502 women in the high-risk group (≥ 1:100) 148 (29.5%) were considered positive (high risk) by NIPT, and 347 women were considered negative (low risk) (Fig.  2 ). IPD results data is available only for 144 cases: 140 case was confirmed by IPD, 4 cases were not confirmed.

The following anomalies were confirmed by IPD in 140 cases: T21 (Down syndrome) in 93 cases, T18 (Edward syndrome) in 35 cases, T13 (Patau syndrome) in 4 cases, X-monosomy (Turner syndrome) in 3 cases, X-chromosome disomy with Y-chromosome monosomy (Klinefelter syndrome) in 1 case and Y-chromosome disomy (XYY syndrome) in 1 case, RAAs in 2 cases (T7 and T22), CNVs in 1 case (del7p14.1p11.2). In 2 cases different chromosomal anomaly was shown by IPD: in 1 case balanced translocation between chromosomes 14 and 22 was shown by IPD, when NIPT showed high risk for T22; in 1 case X triploidy by IPD was shown, when NIPT was positive for T18 and monosomy X.

NIPT results were not confirmed in 1 case for T18, in 1 case for T13 and 2 cases for trisomy of chromosome 16 (Fig.  2 ).

NIPT results in intermediate-risk pregnant women

Of the 12,198 cases in the intermediate-risk group (1:101 – 1:2500), 110 (0,9%) cases were considered NIPT positive. IPD results data is available for the group: 58 cases were confirmed by IPD, 52 cases were not confirmed.

The following anomalies were confirmed by IPD in 58 cases: T21 in 31 cases, T18 – in 3 case, T13 in 3 cases, X-chromosome monosomy (Turner syndrome) in 5 cases, X-chromosome disomy with Y-chromosome monosomy (Klinefelter syndrome) in 6 cases, X-chromosome monosomy with Y-chromosome disomy (XYY syndrome) in 2 cases, trisomy of X-chromosome in 1 case, RAA in 1 case (T8), CNVs in 6 cases.

NIPT results were not confirmed in 2 cases of T21, 4 cases of T13, 21 cases of SCAs and 19 cases of RAAs and 6 CNVs.

In the risk group, IPD was performed in 24 patients with negative NIPT due to their abnormal 2nd trimester ultrasound results: congenital malformations or ultrasound markers of fetus chromosomal pathology. According to the IPD results: 23 received a normal karyotype in the fetus, in 1 case a pathology was detected—46,XX,del (18)(p11.2)—a deletion of the short arm of chromosome 18 (false-negative result) (Fig.  2 ).

Secondary findings

Thirty-nine cases were considered positive for RAAs or CNVs by NIPT (7 cases in the high-risk group and 32 cases in the intermediate-risk group). The most common were T7 ( n  = 6), T16 ( n  = 4), T8 ( n  = 3) and T22 ( n  = 3). Thirty-seven women (5 cases in the high-risk group and 32 cases in the intermediate-risk group) proceeded with IPD, and chromosomal pathology was confirmed only in 10 cases (Fig.  2 ). These chromosomal anomalies are rare and are not detectable by widely used NIPT techniques.

NIPT performance

All in all, the following chromosomal abnormalities have been identified and confirmed: T21 in 124 cases; T18 in 38 cases; T13 in 7 cases; SCAs in 19 cases; RAAs or CNVs – in 10 cases. Comparison of NIPT and IPD results in detection of chromosomal abnormalities is presented in Table 2 . Totally, the rate of false-positive results was 0.3%.

IPD results and/or pregnancy outcomes are available for 9941 women, of whom 9737 had no fetal chromosomal abnormalities and 199 had prenatal and/or postnatal chromosomal abnormalities confirmation. On the basis of the NIPT results and the outcome data available, we calculated the performance of the test in detection of chromosomal anomalies. For T21, T18 and 13, SCAs, RAAs and CNVs the sensitivity was 100%, 100%, 100%, and 92.86%; specificity was 99.50%, 99.15%, 97.47% and 96.88%; positive predictive value (PPV) was 98.26%, 91.67%, 57.14% and 44.83%; negative predictive value (NPV) was 100%, 100%, 100% and 99.80%, respectively (Table 3 ).

To calculate NIPT performance parameters the “true positive” results were defined as positive NIPT results that were confirmed by IPD. The “false positive” results were defined as positive NIPT results for chromosomal anomaly that were shown to be negative by follow‐up IPD. The “true negative” results were defined as negative NIPT results confirmed by karyotyping or aCGH results. The “false negative” results were defined as negative NIPT results with an aneuploidy karyotype confirmed by IPD.

Association of results with fetal fraction

It was shown that FF differs between gestational weeks, p  < 0.001 (Fig.  3 ).

A density distribution of fetal fraction and its relationship with gestational weeks of pregnant women. The average fetal fraction in each week is shown by a black line

Also, it was revealed that samples with low FF (< 3.5%) were observed in women with significantly higher weight and BMI in comparison with women with normal FF: 77.5 kg [62.3;91.1] for low FF and 64.0 kg [58.2;74.4] for normal, ( p  < 0.001), BMI – 28.2 kg/m 2 [23.1;33.6] for low FF and 23.4 kg/m 2 [21.0;26.8] for normal, p  < 0.001 (Fig.  4 a).

The average level of fetal fraction for patients depending on the BMI ( a ), fetus sex ( b ) and NIPT results: risk of T21 ( c ) and T18 ( d ). Abbreviations: NIPT, non-invasive prenatal testing; T, trisomy; BMI, body mass index.

It was also shown, that the FF is significantly higher in women with male fetus, than female: 9.9% [7.4;13.2] and 6.8% [4.9;8.9], p  < 0.001 (Fig.  4 b).

It was also shown, that T21 positive NIPT results were associated with a higher FF, than samples with negative results: 10.4% [7.1;14.4] and 8.3% [6.0;11.2], p  < 0.001 (Fig.  4 c). The cut point for significant difference was 9.0% FF, p  < 0.001. For T18 it was shown vice versa – T18 positive NIPT results were associated with a lower FF, than samples with negative results: 7.1% [4.4;10.9] and 8.3% [6.0;11.3], p  = 0.048 (Fig.  4 d). The same tendency was not revealed for T13 probably due to a small number of samples.

NIPT results according to age and mode of conception

We found a significant difference between the age of women with positive and negative NIPT results for T21: 37 yr [33;40] for high T21 risk and 35 yr [31;38] for low risk, p  = 0.017. Summarizing all the positive NIPT results for all anomalies showed, that these were significantly higher in older women. Mean age of women with a high risk was 37 yr [32;40], and for women with a low risk – 35 yr [31;38], p  < 0.001.

There was no significant difference in frequency of positive NIPT results in spontaneous and in vitro fertilization pregnancies, p  = 0.212.

NIPT was first released in Hong Kong in August 2011 and soon after was introduced commercially in the US in October 2011 [ 17 , 18 , 19 ]. Afterward, in many countries, multiple companies and their distribution partners offered several NIPT tests to pregnant women, either in a commercial or in a state-regulated setting [ 20 ].

The current standard of care for prenatal screening in many high-income countries involves a ultrasound examination combined with biomarker serum screens in the first and/or second trimesters of pregnancy. Despite the fact that in some countries NIPT is performed as a commercial test, or with partial government funding, there is a certain international strategy for introducing NIPT into the structure of prenatal diagnostics. NIPT could be implemented into prenatal testing pipeline in different ways. The most commonly used are as a replacement for serum screening – a first-line test, and as an intermediate step between screening and invasive procedures – a second-line test. The most commonly used implementation model is a combined prenatal screening with the formation of high, intermediate and low risk groups, followed by NIPT in the high and/or intermediate risk group [ 21 ]. NIPT as a first-line test is performed to all pregnant women before an expert ultrasound in the first trimester of pregnancy and successfully used in Belgium and the Netherlands [ 22 , 23 , 24 , 25 ]. NIPT as a second-line test for pregnant women in high or intermediate risk groups determined by the results of combined prenatal screening implemented in some European countries (Germany, Great Britain, France, Italy etc.) [ 26 ]. The main advantage of introducing NIPT precisely as a second-line test is economic feasibility.

In Russia the effectiveness of NIPT integration in traditional prenatal screening as a second-line test was shown in the current study. NIPT showed clear accuracy and revealed 37 additional positive (high risk) cases in the intermediate group of pregnant women at risk, compared to traditional prenatal screening. These results included clinically significant CNVs, that were detected only because NIPT was based whole genome sequencing. CNVs are of particular importance because 20 to 30% of congenital diseases are associated with microdeletions and microduplications, which are not detected by traditional prenatal screening and standard cytogenetic studies [ 27 ].

The main NIPT advantages are its high sensitivity and specificity for common aneuploidies – T21, T18, T13. Multiple validation studies have reported NIPT high sensitivity (98.6%-100%) and specificity (99.7%-100%) for T21 in different populations [ 28 , 29 ]. Our results revealed high sensitivity and specificity both for the common trisomies, SCAs and RAAs/CNVs, which is comparable to other studies as well [ 30 , 31 ].

NIPT shows a very low rate of false-positive and false-negative results compared to traditional prenatal screening results. Several conditions have been known to contribute to false-positive and negative NIPT results: low FF, maternal CNVs and fetal/placental mosaicism are among them [ 32 ]. False-negative results are rare for NIPT, with a frequency of only 0.08% [ 22 ]. In our study we didn’t have false-negative results for common trisomies, SCAs and RAAs. CNVs false-negative rates was 0.008%.

The false-positive rate for common trisomies in our study reached 0.05%, that is much lower than that reported in other studies [ 33 ]. False-positive rate for RAAs and CNVs in our study was 0,09% and 0,04%, respectively. It is assumed that low positive predictive values as well as false-positive rate for CNVs detection are connected with their low frequencies in population.

More over to proven effects there is also one potential effect – decreasing the number of IPD performed in pregnant women. Among 366 women considered to be high risk by traditional prenatal screening, only 105 were confirmed to be high risk by NIPT. That means that 366 women were advised to undergo IPD, although only one third needed these invasive procedures. Currently, the decrease in the number of IPDs is only theoretical, since the regulation of prenatal screening in Russia does not take into account the results of NIPT, and all women at high risk after traditional prenatal screening are considered to undergo IPD.

NIPT has clinical, social and economic benefits. We found social NIPT benefits in its methodology and sample collection. NIPT is safe in blood sampling. Any surgical interventions for are not required. All these can diminish the patient’s anxiety level, which is quite important for pregnant women who may experience hormone-related emotional changes. Moreover, the low false-positive and false-negative rates results reported here and in previous studies [ 34 ], suggests that pregnant women can have high confidence in their NIPT results. In our study, we assessed women’s approaches towards NIPT. The results are processing.

Although NIPT is expensive to perform, its economic benefit manifests over an extended period. NIPT can decrease the direct and indirect costs by decreasing budget payments for the maintenance of people with disabilities.

However, despite the obvious advantages of NIPT adoption, there is a downside. The adoption of NIPT in many countries has led to a decrease in IPD procedures, which has had negative consequences, as some authors have proposed [ 35 ]. One report has suggested that a decline in IPD procedures causes a downturn in opportunities for physicians to practice the skills needed for IPD procedures, leading to significantly higher miscarriage rates associated with these procedures.

The accuracy of NIPT is affected by numerous factors both biological and technical and include the number of sequencing tags, FF, GC base content, and others. FF is a crucial quality control parameter for NIPT interpretation [ 36 ]. Low FF can result in a test failure or a “no call” result. In our study in 2.7% (346/12700) of cases FF was less than 3.5% and a blood sample redraw was required. Any biological factors that increase the maternal contribution and/or reduce the placental contribution may lower the FF [ 37 ]: feto-placental – gestational age, crown rump length, mosaicism, fetal aneuploidy, triploidy, multiple pregnancy, and maternal – maternal age, maternal weight, maternal autoimmune disease, low molecular weight heparin, ethnicity, mode of conception [ 38 , 39 ]. Maternal characteristics such as BMI and gestational age are the main factors that influence FF [ 40 ]. Previous data showed that FF below 4% increased with maternal weight from < 1% at 60 kg to > 50% at 160 kg [ 41 ]. Therefore, the clinical application of NIPT is limited by low FF of cfDNA in obese women. The rate of increase in FF is not constant across gestational age. From 10–12.5 weeks, 12.5–20 weeks, and > 20 weeks, the FF increases at rates of 0.44%, 0.083%, and 0.821% per week, respectively [ 42 ]. Waiting for a later gestational age and repeating blood sampling is not a reliable approach to overcome the low FF in subjects with higher BMIs and earlier gestational ages [ 43 ].

In our study, we analyzed the influence of some available parameters on FF and observed no significant differences between FF and maternal age, gestational age, mode of conception and type of pregnancy. However, we noticed a statistically significant decrease in FF with increased BMI and maternal weight.

In our study it was also shown, that higher FF was more common for male fetuses and for fetuses with high risk for T21, lower FF – for fetuses with high risk for T18. The same was also published in some other studies, showing that euploid male fetus pregnancies with high risk of T21 had higher FF [ 44 ]. For T18, T13 and monosomy X, vice versa other studies has shown lower FF. Higher FF in fetuses with T21 may be one of the reasons the test performance is better for T21 than for T18 and T13. In our study the cut-off for high T21 risk was 9.0% FF. We didn’t find any significant difference in FF for T13 and monosomy X, that is probably due to low incidence yet.

Pregnant women aged over 35 years are usually categorized as advanced maternal age [ 42 ]. It is reported that advanced maternal age is associated with various pregnancy complications, including infant chromosomal anomalies. It is known that such chromosomal abnormalities as T21, T18, T13, triple X syndrome, and XYY syndrome have a close association with maternal age [ 7 ]. However, pathogenic chromosomal deletions and duplications also occur de novo, and the risk of microdeletions and microduplications is the same for all pregnancies regardless of maternal age [ 45 ]. In our study, we detected a significantly higher risk of the genetic abnormalities in women aged 39 and older.

Some studies have also reported that even when the NIPT result was negative, many other chromosomal anomalies could be detected by other technical methods [ 46 ]. The major types of missed fetal abnormalities include structural (balanced or unbalanced) rearrangements, mosaic and triploidies [ 47 ]. Chena et al. declare that 12.4% of fetal chromosomal abnormalities will be missed if NIPT completely replaces IPD in advanced aged pregnant women [ 46 ]. In 2020 ACOG proposed prenatal screening for aneuploidy for all pregnant women, regardless of age or baseline risk factors [ 48 ], but NIPT cannot completely replace IPD in advanced maternal aged women.

NIPT as a second-line test in Moscow, Russia have shown its effectiveness. The major advantage of NIPT was safety, detection of additional chromosomal anomalies and reduction in false-positive rates. Moreover, our findings suggest that NIPT merits serious consideration as a primary screening method for fetal autosomal aneuploidy. NIPT should be recommended for all pregnant women in risk groups, but using it as a first-tier screening and diagnostic tool requires further study.

Limitations of the present study

Main limitations are lack of data due to women refused to undergo IPD and lack of information about pregnancies outcomes.

Availability of data and materials

The datasets generated during and analyzed during the current study are not publicly available due to prohibition of sending raw sequencing data to foreign repositories but are available from the corresponding author on reasonable request.

Abbreviations

Array-based comparative genomic hybridization

American College of Obstetricians and Gynecologists

Body mass index

Cell-free DNA

Copy umber variants

Chorionic villus sampling

Deoxyribonucleic acid

Fetal fraction

False negative

False positive

Glyceraldehyde-3-phosphate dehydrogenase

Human chorionic gonadotrophin

Invasive prenatal diagnosis

Non–invasive prenatal testing

Negative predictive value

Pregnancy-associated plasma protein A

Positive predictive value

Rare autosomal aneuploidies

True positive

True negative

Sex chromosomal aneuploidy

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Acknowledgements

The authors thank the members of Evogen genome sequencing team for help with sequencing.

This study is funded by grant № 01–04-410 from 06.02.2020.

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Elena E. Baranova, Olesya V. Sagaydak, Alexandra M. Galaktionova, Ekaterina S. Kuznetsova, Madina T. Kaplanova, Maria V. Makarova & Maxim S. Belenikin

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Elena E. Baranova

Moscow City Health Department, City clinical hospital №24, Moscow, Russian Federation

Anton S. Olenev

Moscow City Health Department, City clinical hospital №67 named after L.A. Vorokhobova, Moscow, Russian Federation

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EEB, OVS, ASO, ESK were involved in conception and design of the study. MSB, MTK and AMG performed the observations and the data collection. ESK and OVS performed a statistical data processing. ESK drafted the manuscript, MVM, OVS and EEB assisted with the manuscript and ASO and ENS revised the manuscript. All authors edited the manuscript and read and approved the final draft.

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Baranova, E.E., Sagaydak, O.V., Galaktionova, A.M. et al. Whole genome non-invasive prenatal testing in prenatal screening algorithm: clinical experience from 12,700 pregnancies. BMC Pregnancy Childbirth 22 , 633 (2022). https://doi.org/10.1186/s12884-022-04966-8

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Received : 10 March 2022

Accepted : 03 August 2022

Published : 09 August 2022

DOI : https://doi.org/10.1186/s12884-022-04966-8

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• Non-invasive prenatal testing
• Prenatal screening
• Fetal aneuploidy
• Amniocentesis
• Rare autosomal trisomies

BMC Pregnancy and Childbirth

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Non-Invasive Prenatal Testing (NIPT): Reliability, Challenges, and Future Directions

Siva shantini jayashankar.

1 Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia; ym.ude.mku.awsis@226311p (S.S.J.); ym.ude.mku@niddurasanlm (M.L.N.); ym.ude.mku@liamsisan (N.A.S.I.)

Muhammad Luqman Nasaruddin

Muhammad faiz hassan.

2 Department of Surgery, Hospital Batu Pahat, Batu Pahat 83000, Malaysia; moc.oohay@iap_naf

Rima Anggrena Dasrilsyah

3 Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia; ym.ude.mpu@lirsadamir

Mohamad Nasir Shafiee

4 Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia; ym.ude.mku@eeifahsrisan

Noor Akmal Shareela Ismail

Ekram alias, associated data.

No data were generated from this study; all input was from the literature.

Non-invasive prenatal testing was first discovered in 1988; it was primarily thought to be able to detect common aneuploidies, such as Patau syndrome (T13), Edward Syndrome (T18), and Down syndrome (T21). It comprises a simple technique involving the analysis of cell-free foetal DNA (cffDNA) obtained through maternal serum, using advances in next-generation sequencing. NIPT has shown promise as a simple and low-risk screening test, leading various governments and private organizations worldwide to dedicate significant resources towards its integration into national healthcare initiatives as well as the formation of consortia and research studies aimed at standardizing its implementation. This article aims to review the reliability of NIPT while discussing the current challenges prevalent among different communities worldwide.

1. Introduction

1.1. the role of aneuploidy and trisomy in congenital disorders.

Classically, humans possess two sets of haploid cells, one from the father and another from the mother, forming euploid cells [ 1 ]. Aneuploidy occurs when a person inherits an inaccurate number of haploid cells, either having more or fewer chromosomes than a typical set of 46 chromosomes, and is thus considered a type of chromosomal abnormality [ 1 ]. The common cause for aneuploidy is non-disjunction during meiosis I or II, or mitosis, resulting in trisomic or monosomic zygotes, like those associated with Patau syndrome (T13), Edward syndrome (T18), and Down syndrome (T21) [ 1 ]. According to the American College of Obstetricians and Gynecologists, chromosomal abnormalities affect 1 in 150 pregnancies [ 2 ] and are also a factor in 50% of early pregnancy losses [ 3 ]. The risk worsens with increasing maternal age, regardless of singleton or twin pregnancies [ 2 ]. Aneuploidies may provoke severe obstetric complications, such as stillbirth, miscarriage, foetal anomalies, and typical facial dysmorphics, along with physical and intellectual disabilities [ 4 ]. As foetal aneuploidies are associated with congenital malformation, health organizations and medical committees strongly recommend prenatal screening for foetal anomalies to be performed during the first trimester of pregnancy to mitigate pregnancy complications [ 4 , 5 ].

1.2. Cell-Free Foetal DNA: A Discovery with Promising Application

Lo and colleagues proposed the presence of cell-free foetal DNA in maternal blood circulation in 1997 [ 6 ]. Cell-free foetal DNA (cffDNA) originates from the placenta and then moves as a result of maternal blood circulation [ 7 ]. Initially, placental cytotrophoblasts fuse with syncytiotrophoblasts in order to mature, before being incorporated into maternal circulation through syncytial knots [ 7 ]. The breakdown of these knots in maternal circulation sheds foetal DNA, which typically has less than 313 DNA base pairs, as compared to maternal cellular DNA, which displays an average length of 400–500 base pairs [ 8 , 9 ]. This allows easier identification of cffDNA in maternal serum with simple methods like phlebotomy. cffDNA is detected as early as 4 weeks of gestation [ 10 ], and the foetal fraction increases to 10–15% of overall maternal plasma from 10 to 20 weeks of gestation [ 11 , 12 ]. However, it is rapidly cleared once the placenta is delivered at the final phase of childbirth. This fact makes cffDNA highly favoured as a biomarker to detect chromosomal aneuploidy, even as early as in the first trimester of pregnancy [ 13 ].

1.3. Non-Invasive Prenatal Testing (NIPT): A Promising Technique

In addition to its purpose as a biomarker in forecasting obstetrics cases such as pre-eclampsia [ 14 ], monogenic disorders [ 15 ], and placenta accreta [ 16 , 17 ], cffDNA is invaluable for the analysis and detection of foetal chromosomal abnormalities during the early phase of pregnancy [ 18 , 19 ]. NIPT is a non-invasive prenatal screening technique performed using next-generation sequencing (NGS) to sequence short cffDNA fragments in order to identify the genetic variants that represent chromosomal abnormalities. This screening method was first commercialized in Hong Kong [ 20 ], where the research team demonstrated its high sensitivity and specificity when screening for pregnancies at high risk of T21. By using NIPT as the initial screening procedure for high-risk pregnancies with regard to T21, only those who are screened positive in NIPT will proceed with invasive procedures such as chorionic villus sampling or amniocentesis to diagnose T21. This minimizes the unnecessary risk of exposing all pregnant women to invasive diagnostic procedures and the associated complications.

1.4. Next-Generation Sequencing (NGS): Surpassing Traditional Molecular Testing

The ability to sequence base pairs of cffDNA would be a laborious task if not for the existence of NGS. Traditional approaches to DNA separation and replication, such as polymerase chain reaction (PCR) and gel electrophoresis, have been part of the Sanger and Maxam–Gilbert methods. Sanger sequencing uses the chain termination method, which produces DNA fragments at different lengths when any dideoxynucleotide (ddNTP) attaches to a DNA sequence to stop the replication [ 21 , 22 ]. The various DNA fragments then undergo gel electrophoresis before sequence analysis.

On the other hand, Maxam–Gilbert sequencing involves the cleavage of different nucleotides in DNA using several different combinations of chemicals [ 23 ]. The radioactively labelled fragments are then run on gel electrophoresis, with lanes specified with the cleaved nucleotides before analysis. This technique, also known as the chemical cleavage method, is not favoured over the Sanger method, as the chemicals and radioactive reagents used in the process are hazardous. Moreover, Sanger sequencing can be automated, which makes it suitable for the development of NGS, although larger DNA samples and long hours of work can result in increased costs.

NGS evolves alongside the expansion of advanced sequencing tools with various techniques, such as pyrosequencing and bridge amplification [ 24 ]. It reduces the time and costs needed to analyse nucleic acids as compared to conventional methods, hence strengthening research and offering diagnostic potential for NIPT using cffDNA [ 25 ].

2. Global Introduction of NIPT Via Studies and Consortiums

The global implementation of non-invasive prenatal testing (NIPT) has been facilitated through collaborative research studies and consortiums, with governments and private authorities making significant efforts to integrate such testing into national healthcare programs. Recognizing the immense potential of NIPT in improving prenatal care, these entities have invested considerable resources in promoting its integration into national healthcare programs. By establishing partnerships and fostering research initiatives, they aim to streamline the adoption of NIPT as a routine screening tool, ensuring its accessibility and effectiveness for expectant parents worldwide. This concerted effort underscores the commitment to harness the benefits of advanced genetic testing technologies, ultimately contributing to enhanced prenatal care and improved maternal and foetal outcomes on a global scale. In many countries, NIPT is seen as an promising tool and is in the process of being integrated as a screening technique. In this article, we review some of the prominent NIPT consortiums and programs across continents.

2.1.1. China

NIPT has existed in China since 2010 [ 26 ], but it has recently gained wide attention for its potential in prenatal care. Since the Chinese government’s abolishment of the one-child policy in 2016, older women have expressed concern regarding the risk of carrying a second child in middle age. A study conducted based on a Discrete Choice Experiment in 2020 among Chinese women reported that the participants had a dominant preference for NIPT and suggested it become a part of health insurance coverage in China [ 27 ]. The authors also reported participants’ willingness to spend more to ensure the health of the foetus and to take early measures to avoid carrying a child with foetal aneuploidy [ 27 ]. Liu and colleagues’ pilot study on implementing NIPT as a first-tier alternative screening test demonstrated its potential use in detecting T13, T18, T21, and sex chromosome aneuploidies, thus suggesting NIPT as a possible replacement for tests used in second-trimester screening, including the traditional serum biochemistry tests used in routine practice [ 28 ]. In 2016, the National Health Commission of China published clinical guidelines for the use of NIPT at 12–22 weeks of gestation. Nevertheless, complete government sponsorship of NIPT has not yet been established in China. Some areas, such as Shenzhen, have partial coverage of NIPT with public health insurance. In contrast, in areas such as Zhengzhou, the costs of NIPT are covered by private health insurance or are paid out of pocket [ 29 ]. Hong Kong’s public health system has free-of-charge routine prenatal screening for trisomy 21 for women of all ages [ 30 ]. As of 2019, NIPT has been incorporated into the publicly funded system as a second-tier screening option for women shown to be at high risk of T13, T18, or T21 through conventional biochemistry analysis [ 30 ]. People can opt for NIPT followed by invasive methods like chorionic villus sampling or amniocentesis to have a confirmatory diagnosis or can continue with standard follow-ups without genetic testing. This principle is believed to improve the detection rate for trisomies throughout pregnancy while improving cost-effectiveness.

2.1.2. Japan

NIPT was introduced in Japan in 2013. There was increase in the total prevalence for prenatal testing from 3% in 2008 to 5.3% in 2013 [ 31 , 32 ]. A total of 44,644 pregnant women underwent NIPT by the end of March 2017 [ 32 ] There is no comprehensive policy on prenatal testing and NIPT in Japan. In addition, NIPT is primarily paid out of pocket by individuals who need it, despite the cost of NIPT in Japan being among the highest in the world [ 32 ]. Thus, NIPT in Japan is only recommended for pregnant women with known high risks of foetal abnormalities [ 2 ]. This includes pregnant women with a maternal age of 35 and above, those with detected foetal chromosomal abnormalities via foetal ultrasonography or maternal serum marker tests, or those having a history of a child with a chromosomal aberration. A one-year nationwide clinical study was conducted as a demonstration project to evaluate the screening outcome of NIPT in detecting foetal aneuploidies [ 33 ]. The project served to discuss methods to implement NIPT in Japan by testing 7740 women with high-risk pregnancies with regard to aneuploidies, from which 142 positive cases were found. A total of 126 cases went on to confirm the aneuploidies with karyotyping; there were three cases of T21, eight cases of T18, and two cases of T13. The study showed that 98% of cases avoided invasive diagnostic procedures while having a very low false-negative rate of 0.06%.

2.1.3. India

Pregnant women in India prefer NIPT as a prenatal screening option, despite most prenatal care expenditures being paid out of pocket and most procedures being performed at private health institutions [ 34 ]. NIPT was first introduced in 2012 in limited regions of India, due to a lack of expertise and the relative unaffordability of the procedure [ 35 ]. The Preconception and Prenatal Diagnostic Techniques (PCPNDT) Act of 1994 is responsible for regulating prenatal screening and diagnosis, including NIPT, primarily to prevent parents or physicians misusing prenatal screening techniques for foetal-sex determination and sex-selective abortion [ 36 , 37 ]. NIPT is permitted to be used for the screening of T13, T18, T21, and microdeletions, but foetal sex disclosure to parents is only permitted if genetic abnormalities are detected through prenatal testing [ 36 ]. The preference for NIPT to be introduced as second-tier screening is greatly emphasized in some studies [ 35 , 38 ], while others consider it more rational to be used in first-tier screening, as the Medical Termination of Pregnancy Act 1974 allows abortion until 20 weeks of gestation, and NIPT provides opportunities for the early detection of aneuploidies that would assist in decision making regarding termination of pregnancy by the second trimester [ 37 ]. Overall, NIPT is slowly being adopted thanks to the PCPNDT Act of 1994.

2.1.4. The Middle East

In Lebanon, there are no official guidelines for the implementation of NIPT; it is recommended as either a first-tier screening or second-tier screening for detecting trisomies or sex chromosome anomalies, depending on the physician and the healthcare centre. In Lebanon, procedures like amniocentesis and maternal serum tests are offered primarily by the private sector, although the public system does cover some of these. A qualitative study indicated that most Lebanese pregnant women or couples having children are more concerned with knowing the genetic condition of their child than with the costs required for NIPT, although, at the same time, they are enthusiastic about NIPT being publicly funded [ 39 ]. Similarly, NIPT is available in the private health sector in many other Middle Eastern countries [ 40 , 41 , 42 ]. The first study on NIPT in Saudi Arabia was published in 2021; NIPT was implemented as a potential choice for first-tier screening to facilitate the detection of high-risk pregnancies with chromosomal aneuploidies in prenatal care [ 42 ]. NIPT is also known to be offered in healthcare facilities in Iran [ 43 ].

The Israeli National Health Screening framework for prenatal genetic care focuses primarily on combined first-trimester screening (cFTS) and is fully funded by Israel’s Ministry of Health (MOH) or health maintenance organizations (HMOs) [ 44 ]. cFTS has an uptake of 60–70% among pregnant women, with appropriate follow-up recommendations given based on the risk assessments performed during the tests [ 44 ]. NIPT is currently not a part of the National Health Screening guidelines for detecting chromosomal aneuploidies [ 44 ]. In the clinical setting, NIPT is advised as an option for screening for aneuploidies where high risk is determined during the conventional screening of T21 but not as a replacement for invasive diagnostic procedures. Although not funded by the government, some HMOs support the uptake of NIPT by providing up to 75% reimbursement for such services, depending on insurance policies [ 44 ].

2.1.5. Southeast Asia

In the Southeast Asia region, governmental bodies have yet to establish guidelines and funding for NIPT, and its application in prenatal screening is predominantly provided by the private sector. In Thailand, Next Generation Genomic Co., Ltd. (Bangkok, Thailand) collaborated with Illumina to launch a new, certified CE-IVD-based NIPT technique to increase the reliability of NIPT for detecting trisomies [ 45 , 46 ]. Another molecular diagnostics and research organization, Sengenics, worked with Lifecodexx AG of Europe to increase the accessibility of their successful PrenaTest ® NIPT among pregnant women from Malaysia, Singapore, Brunei, and Vietnam [ 47 ]. These efforts served to enlighten women and their families on NIPT as a non-invasive screening method, emphasizing the high level of sensitivity and specificity in detecting pregnancies with chromosomal abnormalities.

2.2. Africa

In Africa, NIPT is still considered a novel screening method, as many African countries are in the process of adopting it as part of prenatal screening. According to the South African Society of Obstetrics and Gynecology (SASOG), pregnant women are recommended to undergo NIPT for assessing foetal aneuploidies if they have the financial means, as NIPT is not publicly funded in South Africa [ 48 ]. In a similar vein, government initiatives for funding non-invasive prenatal testing (NIPT) are lacking in other African countries. However, private health centres have taken the lead in establishing widespread NIPT services, aiming to educate individuals about this alternative screening option for assessing foetal genetic conditions.

2.3. Europe

2.3.1. the united kingdom.

The UK National Screening Committee proposed the use of NIPT for the screening of T13, T18, and T21 in November 2015; the official implementation took place in April 2018 in Wales, September 2020 in Scotland, and May 2021 in England [ 49 , 50 ]. The committee suggested that women with high-risk pregnancies as identified through first-trimester combined screening or second-trimester quadruple screening be eligible for free NIPT [ 51 ]. The Nuffield Council of Bioethics concluded that the ethical delivery of NIPT within the Fetal Anomaly Screening Programme is possible provided that accurate information is provided to the public, sufficient education and training is provided for developing medical expertise, and appropriate time is allowed for discussing concerns. In support of this, the Reliable Accurate Prenatal Non-Invasive Diagnosis (RAPID) study suggested the reliability of NIPT as a contingency screening by the National Health Services to minimize the exposure of pregnant women to invasive techniques, while reporting that high levels of informed choice could be achieved if the criteria described by the Nuffield Council were in place [ 52 ].

2.3.2. The Netherlands

The Netherlands implemented NIPT as part of a publicly funded foetal aneuploidy screening program in April 2014 via the Trial by Dutch Laboratories for Non-invasive Prenatal Testing-1 (TRIDENT-1) [ 53 ], to screen pregnant women at risk of T13, T18, and T21. The government further initiated the TRIDENT-2 study to fund the testing of all pregnant women, regardless of risk exposure, for the screening of foetal aneuploidies [ 54 ]. Since the introduction of first-tier NIPT in 2017, the uptake rates were steady at 46% in 2018, while a steep decline for first-trimester combined tests has been observed [ 55 ].

2.3.3. Germany

In Germany, the coverage for NIPT for pregnancies with the likelihood of T13, T18, and T21 is suggested to be provided by a publicly funded health insurance system [ 56 ]. Since its introduction over a decade ago in Germany, the number of NIPT procedures performed in gynaecological clinics increased from 70 in 2013 to 3000 in 2018 [ 57 ]. The current policy on NIPT focuses on individualized decision making with the support of public reimbursement [ 58 ].

2.3.4. France

NIPT was initially implemented in France for the screening of T21 only, and occasionally for T13 and T18, with the support of public health insurance. In 2020, the test was further expanded by the private laboratory Cerba to cover the screening of rare aneuploidies like trisomies 2, 8, and 9 as well as large deletions and duplications [ 59 ]. At present, the French public system adopts NIPT as an additional screening option that is free of charge for pregnancies involving a high risk of foetal chromosomal abnormalities as determined by the combined first-trimester screening (ultrasound and biochemical markers) [ 60 ].

2.3.5. Denmark

In Denmark, NIPT became available as a screening option for chromosomal aneuploidies through the Danish public and tax-financed healthcare system in 2013 [ 61 ]. However, in 2017, the Danish Health Authority revised its guidelines on prenatal screening and diagnosis to include NIPT as a standard screening test. The guidelines suggest that all pregnant women should undergo combined first-trimester screening; only high-risk pregnancies as detected by the screening are given the option to proceed with NIPT [ 61 ]. Research was conducted using Danish clinical data between 2013 and 2017 to evaluate the use of NIPT before being integrated as a part of the national guidelines [ 61 ]. The study reported that in contrast to a high rate of termination observed from a positive invasive test, most pregnant women with a true-positive NIPT result ultimately had live births. Moreover, a minority of women considered NIPT as a risk-free alternative to invasive tests for gaining knowledge regarding genetic conditions to inform their pregnancy decision making.

2.3.6. Belgium

Belgium is the first country to introduce public reimbursement for NIPT as a first-tier screening test and offer it to all pregnant women, while eliminating the necessity for combined first-trimester screening [ 62 ]. Currently, serum biochemical analysis is not given priority, but ultrasound tests are still offered as complementary procedures to detect foetal anomalies [ 62 ]. Furthermore, the Belgian Advisory Committee on Bioethics specifies that any non-common aneuploidies detected during NIPT must be reported to the patients, accompanied by in-depth genetic counselling [ 63 ]. This is to ensure that proper preventive and therapeutic steps are taken to manage these conditions. A two-year consortium involving all Belgian genetic testing centres reported successful implementation of NIPT in first-tier screening; they observed a 52% decrease in the number of invasive procedures conducted and a lower number of T21 live births [ 64 ].

2.3.7. Italy

In 2016, the first pilot study validating the use of NIPT in assessing risks for foetal aneuploidies was reported by the Italian Public Health System [ 65 ]. The testing accuracies from the study led NIPT to be incorporated into clinical use for detecting T13, T18, and T21. Currently, guidelines for NIPT are specified by the Sistema Sanitario Nazionale (SSN) [ 66 ], which is the national public health system, for the screening of foetal aneuploidies among high-risk pregnancies; however, the test is only reimbursed in certain regions, like Toscana and Bolzano [ 67 ]. Nevertheless, NIPT is also extensively used in the private sector, leading to an overall uptake of 25% to 50% in the country [ 68 ].

2.3.8. Switzerland

Since the formal introduction of NIPT in 2012, there has been a substantial increase in the use of the testing by pregnant women and an overall decrease of 67.4% in invasive prenatal tests, as noted in an early clinical study [ 69 ]. According to the Swiss Federal Office of Public Health (FOPH), NIPT has been publicly funded since 2019 by basic health insurance for limited medical reasons, such as to screen for T13, T18, and T21 [ 70 ].

2.3.9. Russia

NIPT was initially considered as an additional commercial test to screen for foetal aneuploidies in intermediate- and high-risk pregnancies, as evaluated from conventional screening methods like ultrasonography and serum biochemical markers at weeks 11–14 of gestation. On 13 March 2020, a pilot project consisting of NIPT in the prenatal screening system was conducted by Moscow City Health Department with the collaboration of 23 prenatal care hospitals and one genetic testing laboratory [ 71 ]. The project was started in the hope of providing successful adoption of NIPT and establishing official clinical guidelines for NIPT screening at the national level [ 71 ]. A preliminary clinical study carried out in the same year to investigate the adoption of NIPT showed it to be effective at screening foetal chromosomal aneuploidies [ 72 ]. When the project was completed, the clinical study was repeated to analyse the efficiency of NIPT as a second-line screening test in the first trimester for 12,700 pregnancies [ 73 ]. The results showed NIPT as a safe and highly sensitive screening test recommended for all pregnant women in risk groups to detect foetal aneuploidies.

2.3.10. Slovenia

In Slovenia, NIPT is offered only when invasive procedures are contraindicated due to maternal factors such as a pregnancy with a high risk of miscarriage, mothers with transmissible infection to the foetus, and contraction of the uterus [ 67 ]. These cases allow NIPT to be offered through public funding despite the test being conducted at full cost to the patient in most private healthcare centres.

2.3.11. Romania

NIPT is offered as a self-financed commercial prenatal screening option in Romania [ 67 ]. The first study to report the clinical experience of NIPT among pregnant women in Romania was conducted from the retrospective analysis of 380 NIPT cases from a genetic centre in Western Romania [ 74 ]. NIPT was able to demonstrate a high detection rate for autosomal aneuploidies, which led to the suggestion that NIPT be offered as a screening method to all pregnant women [ 74 ].

2.4. North America and South America

2.4.1. united states.

The United States is one of the first countries to routinize NIPT for T21 screening, i.e., since 2011 [ 75 ]. While the American College of Obstetrics and Gynaecology recommends NIPT be offered to all pregnant women regardless of their gestational history or risks [ 67 ], statistics have shown that an estimated 25% to 50% of pregnant women use NIPT [ 76 ], mainly as second-tier screening.

2.4.2. Canada

Canada has adopted NIPT as a publicly funded second-tier prenatal test in three provinces (Quebec, British Columbia, and Ontario) and one territory (Yukon). The Personalized Genomics for Prenatal Abnormalities Screening Using Maternal Blood (PEGASUS) is a national study that was conducted from 2013 to 2017 to provide an evidence-based approach to validating NIPT for its cost-effectiveness in second-tier prenatal screening [ 77 ]. The study was a success, as NIPT presented a better decision-making tool for informed choices with regard to prenatal screening, instigated the development of provincial genomic testing technologies, and most importantly, showed that the use of serum screening with conditional NIPT as second-tier screening resulted in the lowest cost for detecting T21, with a rate of $63,139 per case detected [ 78 ]. Moreover, this strategy resulted in more than a 90% reduction in invasive procedures such as amniocentesis for the detection of T21. PEGASUS-2 began as a follow-up study in 2018 and ran until 2022, to assess the effectiveness of introducing NIPT as a first-tier prenatal test to screen foetal aneuploidies and other conditions [ 77 ].

2.4.3. Mexico

Like most countries, NIPT became widely available in the private sector in Mexico when it was first introduced in 2013 by Natera, a leading US-based organization in prenatal genetic testing, in collaboration with the well-known Mexican fertility institute Médica Fértil, for prenatal genetic screening of chromosomal abnormalities [ 79 ]. In 2015, the Genetics Clinic of the Hospital Angeles Lamas employed NIPT for the screening of chromosomal abnormalities and foetal-sex determination among Mexican pregnant women. As predicted, they were able to minimize the number of pregnant women exposed to invasive tests as a result of NIPT. Moreover, the study indicated that NIPT could be a reliable prenatal screening option due to its very high detection rate, specificity, and sensitivity [ 80 ]. However, there remain no standard guidelines for NIPT, and most tests are not publicly funded.

2.4.4. Brazil

NIPT received attention among Brazilians when two NIPT test producers from the United States—Ariosa and Natera—partnered with Brazilian biotechnology laboratories to offer the tests to pregnant women in Brazil [ 81 ]. This approach was firmly integrated into prenatal genetic screening in the private healthcare sector. Although an expensive procedure, it was welcomed by Brazilian women and achieved significant uptake for numerous reasons, including reducing the expense of frequent ultrasound tests to detect foetal anomalies, ensuring better coverage in detecting all chromosomal abnormalities, not only T13, T18, and T21, and helping the family prepare for the delivery of child with special needs [ 81 ].

2.5. Oceania

2.5.1. australia.

In Australia, NIPT has been offered to the public since 2012 [ 82 ], as a first-tier test for all pregnant women and as a second-tier test for high-risk pregnancies [ 67 ]. The prevalence of NIPT has seen a substantial increase, while the frequency of invasive tests has decreased [ 83 ]. The test is currently funded out of pocket, with patients seeking reimbursement through a local universal health insurance scheme known as Medicare [ 84 ]. Several professional bodies and legal committees have made calls to increase awareness of NIPT among all pregnant women as an available choice for prenatal screening of T21, T13, and T18, though a first-trimester ultrasound test should precede it [ 85 , 86 ]. A total of 25% to 30% of pregnant women are estimated to undergo NIPT in Australia, relating their choice to NIPT’s positive testing experience [ 84 ]. Currently, it remains the primary source of diagnosis of T21 during antenatal care [ 87 ].

2.5.2. New Zealand

NIPT has been widely accessible in Aotearoa New Zealand since 2013; however, similar to Australia, it is not covered by the public health system [ 88 ]. The Royal Australian and New Zealand College of Obstetricians and Gynecologists acknowledge the use of NIPT for screening trisomies and other foetal genetic conditions during pregnancy; however, screening guidelines or specific regulations have yet to be put in place [ 47 ]. A report published by Filoche and colleagues outlined the precautions, criteria, and fundamental aspects that should be handled by the National Screening Unit (NSU) and the Ministry of Health when exploring plans to routinize NIPT via the public funding system [ 88 ].

3. NIPT Is Reliable at Detecting T13, T18, and T21

Numerous studies have evaluated the application of NIPT for detecting T13, T18, and T21 to gain insights into testing accuracy and positive detection. Achieving a better detection rate as compared to the conventional screening methods has been the primary goal of implementing NIPT as part of prenatal screening. A meta-analysis of 37 studies compared cffDNA testing outcomes with foetal karyotype analysis from invasive methods to screen for T13, T18, T21, and other aneuploidies in singleton and twin pregnancies [ 89 ]. It was found that the detection rate for T21 was 99.2% for singleton pregnancies and 93.7% for twin pregnancies. Meanwhile, the detection rates for T18 and T13 were 96.3% and 91%, respectively. The study summarized that NIPT provides better detection rates compared to traditional techniques [ 89 ]. In a study from Belgium, comparisons among pregnant women who underwent primary NIPT, combined first-trimester screening, or second-trimester triple testing showed that the detection rates for T13, T18, and T21 were the highest in the NIPT screening group. NIPT was also indicated to effectively reduce the invasive tests needed to detect these trisomies by 92.8% [ 90 ]. In addition, the study showed a high specificity rate of 99.90% for NIPT in detecting T21 in singleton pregnancies and 99.98% for T18 and T13 [ 90 ].

In a retrospective study in South Korea [ 91 ], in which all 1055 stored maternal serum samples suspected of foetal aneuploidies underwent NIPT to determine positive testing for trisomies and were further confirmed by karyotype analysis, 108 cases of foetal aneuploidy were identified by NIPT, with a remarkably high sensitivity rate of 100% and specificity of 99.99% for both T21 and T13 [ 91 ]. Meanwhile, NIPT had a sensitivity of 92.9% and a specificity of 100% for T18. The overall positive predictive value was 98.1%, showing a range of 90% to 100% in T13, T18, and T21 [ 91 ].

In China, a retrospective study conducted in 2020 reported similar results for NIPT outcomes in detecting T13, T18, and T21 among singleton pregnancies [ 92 ]. A total of 36,913 pregnancies were involved in NIPT testing, showing 100% sensitivity in determining positive cases for T13, T18, and T21 [ 92 ]. The specificity for T13, T18, and T21 was 99.94%, 99.95%, and 99.95%, respectively. Meanwhile, the positive predictive value was the highest for T21, at 84.67%, followed by 58.70% for T18 and 41.94% for T13. Both studies are believed to be significant in establishing NIPT as a highly accurate test for detecting T21, T18, and T13.

Several other studies also reported convincing and high percentages of the sensitivity and specificity of NIPT in detecting T13, T18, and T21 [ 43 , 93 ]. A large international blinded study of 18 955 women detected T21 with 100% sensitivity using NIPT compared to 78.9% using the standard screening method; T18 was detected with 90% sensitivity and T13 with 100% sensitivity by NIPT. Moreover, the specificity for T21, T18, and T13 from NIPT was near perfect, producing rates of 100%, 100%, and 99.9%, respectively. A small study comprising 100 pregnancies found 100% sensitivity of NIPT in detecting T21 [ 43 ]. All these studies have shown consistent results, with NIPT having a sensitivity of more than 90% and a specificity of over 99% in identifying T13, T18, and T21; these values are the closest to those produced by invasive testing, suggesting that NIPT could be considered a preferable error-free testing method for the prenatal screening of trisomies.

Another important aspect to be looked at in evaluating NIPT’s ability to detect trisomies is the positive predictive value, which is an indicator of the rate of true positives. A higher positive predictive value represents good reliability for determining positive cases. The positive predictive value from a study in China comprising 17,428 singleton pregnancies using NIPT showed a value of 75% for T13, T18, and T21. An 84.38% positive predictive value was noted for T21, followed by T18 with 61.54% and T13 with 33.33% [ 94 ]. A high positive predictive value based on NIPT seems to be most prevalent for T21; for example, a study in Iran found a value of 100% [ 43 ].

Another element to note in deducing the effectiveness of NIPT is its ability to reduce the rate of false positives. The findings from Akbari et al.’s study (2018) indicated that NIPT produced a false positive rate of 0.10% for screening T21, which is substantially lower than the 5% rates seen for nuchal translucency ultrasonography and maternal serum marker screening [ 43 ]. Meanwhile, in the study by Norton et al. (2015), in which a much larger cohort was involved, the false positive rate was lower, with only 0.05% noted compared to the standard screening method group, which had a rate of 5.4% [ 93 ]. An extremely low incidence of false positives for T13, T18, and T21 was also reported in other publications [ 89 , 94 , 95 ], ranging from 0% to 0.23%.

Twin pregnancies are commonly more complex than singleton pregnancies, particularly due to the presence of the genetic differences in dizygotic twins that can generate only one foetus with a trisomy. However, a multitude of research involving twin pregnancies and NIPT screening has shown perfect or near-perfect results for sensitivity, specificity, and positive predictive value, suggesting that NIPT is also good for the prenatal screening of twins [ 24 , 96 ]. In studies on twin pregnancies, 100% sensitivity of NIPT for detecting T21 was consistently seen [ 95 , 97 , 98 , 99 ]. In a study of 25 twin pregnancies that produced seven cases with T21 and one case with T13, no false positives were observed, along with 100% sensitivity and specificity [ 97 ]. In addition, 100% specificity for T21 detection with NIPT was reported in a study involving 12 twin pregnancies [ 98 ]. Similar findings were seen in the detection of T13, T18, and T21 in 6471 twin pregnancies, i.e., the specificity for T13, T18, and T21 was over 99%; meanwhile, the sensitivity for these aneuploidies was 100% [ 99 ]. Similarly, Gill MM’s meta-analysis indicates that NIPT in twin pregnancies can be as reliable and accurate in detecting trisomies as it is for singleton pregnancies [ 89 ] (see Table 1 ).

Summary of clinical studies of NIPT test outcomes.

4. Limitations and Challenges

4.1. false positives and false negatives.

Unlike invasive tests such as chorionic villus sampling and amniocentesis, NIPT is still not considered a first-line diagnostic screening method for confirmation of trisomies in pregnancies. The presence of false positives and false negatives reported in studies using NIPT is a stigma for promoting it as a definitive test for diagnosing trisomies. However, the false positives and false negatives generated in studies have been relatively low, including in analyses of large samples [ 94 , 101 , 102 , 103 ].

One study detected a false negative rate of 0.09% with NIPT in determining T21 [ 101 ]. A prospective study by Xue and colleagues (2020) reported a false negative rate of 0.01% among 81601 pregnancies [ 102 ]; nine cases of false negatives were detected, but with size-selection NIPT retesting on these cases, two of the false negatives turned out to be confined placental mosaicism (CPM), and one was a twin pregnancy [ 102 ]. The occurrence of false negatives is believed to be due to a low amount of cffDNA in the maternal plasma, influenced by advanced maternal age, high BMI, and early gestation [ 104 , 105 ]. Having shorter cffDNA fragments during DNA extraction and library sequencing would be a good strategy for increasing the cffDNA fraction [ 106 ]. Thus, repeating size NIPT (using shorter cffDNA fragments) on false negative cases can identify cases overlooked due to low cffDNA fractions, e.g., CPM or twin pregnancy.

The false positives present in NIPT are always a concern when suggesting NIPT as a first-line choice for prenatal screening. Although the rates are typically less than 1% and are not alarming in most studies, the causes for false positives are not avoidable with technical improvements and can represent future birth complications such as foetal growth retardation, spontaneous foetal reduction, and preterm rupture of membranes [ 107 , 108 ]. CPM is the most common cause [ 98 , 109 , 110 ]; others, like ‘vanishing twins’ [ 111 , 112 ], maternal copy variants [ 13 , 104 ], and maternal tumours [ 113 , 114 ], are also possible causes. ‘Vanishing twins’ happens when cffDNA floods into the maternal plasma due to necrotic cytotrophoblasts, which in turn causes an influx of foetal DNA in a short time. This phenomenon can last for at least 7-8 weeks but does not last beyond 12-14 weeks of gestation [ 111 ]. Tumour-derived cell-free DNA from maternal serum can mask the cffDNA and its chromosomal profile, eventually leading to aberrant NIPT results. Thus, NIPT is a contraindication for pregnant women with malignancies who undergo screening for foetal anomalies [ 115 ].

Due to these limitations, NIPT is suggested to be accompanied by other prenatal tests, like ultrasonography, for safer analysis and to avoid mistakes in diagnosis. The capability of early detection and differentiation of false-positive cases from trisomies could also reduce pregnancy complications. Technical and bioinformatic improvements could be made in the future for wider analysis and detection coverage using NIPT [ 116 ].

4.2. Lack of Expertise

Regarded as patients’ first point of access to information about maternal health and clinical genetics services, obstetricians, gynaecologists, clinical geneticists, and genetic counsellors are essential experts in assisting patients with informed choices and decision making regarding NIPT. However, due to a lack of well-trained clinical experts on prenatal care, patients might not be able to access knowledgeable genetic service providers to provide information on NIPT. In a survey conducted among obstetricians in Texas, it was discovered that all participants were familiar with both NIPT and expanded NIPT [ 117 ]. However, 91% of respondents expressed that their understanding was not comprehensive, highlighting the need for ongoing education for healthcare professionals. This emphasis on continuing education aims to enhance the effectiveness of prenatal screening counselling and enable patients to make informed decisions. Furthermore, in-depth interviews conducted with 20 obstetrics experts revealed that inadequate clinical guidance on NIPT contributed to physicians having insufficient skills in introducing the test to their patients [ 118 ]. Instances of insufficient NIPT counselling knowledge have been documented, wherein obstetricians and gynaecologists referred pregnant women with abnormal trisomy detected through NIPT for amniocentesis. However, these healthcare providers often struggled to provide adequate interpretations of mosaic trisomy and small supernumerary marker chromosome (sSNMC) as confirmed by amniocentesis [ 119 ].

In underprivileged cities or villages where people rely on primary care physicians (PCPs) for medical care, it is a reasonable expectation that PCPs possess appropriate genetics and genomics knowledge and skills to cater to their patients, including providing information on NIPT screening. Unfortunately, there are significant barriers for PCPs, with them citing fewer genetics resources as crucial challenges, including a lack of clinical guidelines, training, and genetics experts [ 120 , 121 , 122 ]. Such situations must be improved, as patients value opinions and clarifications from clinicians with expertise in NIPT for screening trisomies, considering their inputs as supportive of informed decision making [ 119 , 123 ].

4.3. Inadequate Pre-Test and Post-Test NIPT Counselling

During pre-test and post-test counselling on NIPT, pregnant women should also be informed about the test characteristics, screening efficiencies, associated risks, and importance of follow-ups. This allows women to make informed choices on whether they want to opt for the test or choose alternative care. Care providers must show full proficiency in NIPT counselling while assessing for T13, T18, and T21 so that their patients have more assurance and confidence throughout the decision-making process, including before taking the test and after receiving the results [ 124 , 125 ].

Medical or genetics experts that offer pre-test counselling often assume patients have basic knowledge of trisomies like T21 and thus do not thoroughly address the genetic condition. Moreover, some physicians need to inform patients of the other foetal chromosomal abnormalities (including microdeletions) that can also be detected by NIPT [ 53 ]. Another misconception provided during pre-test counselling is that NIPT gives high accuracy and thus is proposed as a diagnostic procedure. This mistake was evident from the NIPT screening program in the Netherlands [ 125 ]. Furthermore, there is also dissatisfaction with the short counselling time, as many queries regarding the test go unaddressed due to time constraints [ 123 ]. On the other hand, too much information provided to patients at one counselling session made patients feel overwhelmed and made it difficult to prioritize information for decision making [ 126 , 127 ].

In a survey among Japanese women regarding NIPT test outcomes, most of the respondents claimed that a lack of information and support after being given the results of the tests promoted negative feelings throughout their pregnancies [ 128 ]. They wished for physicians to provide post-test counselling that covered follow-up procedures in the case of receiving a positive result, such as guidance on termination, if needed, or how to prepare for raising a child with anomalies. Thus, professionals should consider these critiques and opinions when establishing a more informative and satisfying counselling session for NIPT.

In the UK, the government assessed health professional counselling skills on NIPT after training sessions; as expected, training helped care providers to be more confident in providing patients with NIPT counselling [ 129 ]. Equally, the provider should ensure appropriate counselling techniques. Before introducing NIPT, sufficient data on the patient’s gestation history and reproductive history are essential inputs for the physicians or genetic counsellors [ 125 , 130 ]. It is recommended that practitioners gain consent from patients regarding the intention to be educated and suggesting NIPT as a screening choice for identifying trisomies [ 128 , 130 ]. Overall, a high level of informed choice can avoid biased discussions about NIPT. In addition, post-test follow-ups are mandatory to assist patients with their pregnancy planning, especially in light of positive results [ 125 , 131 , 132 ].

4.4. Culture and Religion

Ethical issues around NIPT have become a concerning topic. Participants in surveys have expressed their concern about the growing reluctance in accepting a child with disabilities and parental rejection of any child that carries genetic abnormalities via termination of pregnancies; they feel that NIPT contributes to this factor, apart from detecting foetal anomalies [ 128 , 131 ]. Cultural differences that exist in societies contribute to a diverse range of views on applying genomic technologies to facilitate decision making. A study in New Zealand described that the Māori believe in the flow of life force (whakapapa) that is interconnected through genealogy and maintained through events like an arranged marriage; the utmost importance of avoiding disruption of this force is emphasized [ 88 ]. NIPT is viewed as a contradictory approach towards their belief of whakapapa, especially with regard to abortions following genetic testing [ 88 , 133 ].

Societal acceptance of NIPT could also be greatly influenced by religious views. For example, in a survey conducted among obstetricians in a Muslim country, Pakistan, 94% of respondents felt that NIPT results would significantly affect pregnant women’s decision to continue or terminate pregnancy [ 134 ]. The majority of the respondents also agreed that NIPT might increase social pressure on pregnant women to terminate affected pregnancies. This finding suggests that religion could have a great impact on the acceptance of NIPT, because in Muslim countries like Lebanon, for instance, abortion is not allowed unless the mother’s life is at risk [ 39 ]. Nonetheless, since NIPT could allow the detection of aneuploidies at a very early stage of pregnancy, NIPT should not be viewed as against Islamic principles, because in Islam, termination of pregnancy is also permissible in early gestational weeks, before the “ensoulment” [ 135 ].

It has been reported that some Christian political groups are not in favour of NIPT because of concerns that it would normalize abortions for suspected pregnancies with Down syndrome [ 136 , 137 ]. However, it is interesting to note that findings from a study indicated that health professionals of the Christian faith were more likely to agree that NIPT should be routinely offered to all women, as compared to non-Christians [ 138 ]. Nonetheless, it should also be noted that Christian health workers see abortion, in the case of foetal anomalies, as unethical [ 139 ].

NIPT appears to be acceptable in the Jewish community; however, it is interesting to note that there is a negative correlation between women who underwent NIPT and their level of religiosity; more religious women are less willing to undergo NIPT [ 140 ]. Nevertheless, recent data on the Israeli population, with 74.2% Jewish origin (2013–2019), indicated that a steadily high prevalence of 60–70% of the pregnant population underwent NIPT [ 44 ].

Altogether, even though NIPT is still allowed, cultural and religious points of view undeniably have a significant influence on society’s acceptance of NIPT, mainly due to concerns that NIPT would encourage the termination of pregnancies.

4.5. Inequality of Accessibility

Healthcare and governmental bodies around the globe have become aware of the significance of NIPT compared to conventional screening methods. Although some countries have approved publicly funded NIPT programs in the primary screening of all pregnant women and introduced NIPT as part of antenatal care [ 54 , 56 , 141 ], other countries are still hesitant to implement it due to cost restraints. A survey of 28 countries predicted the cost of NIPT to range from USD 350 to 2900, which is considered expensive and limits the widespread use of NIPT [ 141 ].

In 2016, the National Health and Family Planning Commission of China published the clinical guideline for NIPT practice, recommending that NIPT be offered throughout the second trimester of gestation [ 99 ]. Instead of applying second-trimester screening alone in detecting trisomies, the idea of combining NIPT and the evaluation of maternal age is more productive than China’s current screening strategy in terms of cost-effectiveness and safety [ 99 ]. However, the price of NIPT in China could range from USD 202.49 to USD 332.46 in the private sector and is only partially covered by health insurance in most provinces [ 142 ]. This situation can become a financial burden for low- to middle-income families when bearing fees under the out-of-pocket scheme. Another study of Chinese women suggested positive support for incorporating NIPT into health insurance coverage in China and emphasized the population’s wish to undergo NIPT [ 27 ].

Similarly, restricted insurance coverage is also observed in first-world countries. Many private insurance companies in the US do not cover the initial cost of NIPT for low-risk pregnancies; thus, there is a lack of accessibility with regard to NIPT, which leads some to choose conventional screening methods. Further assessments discovered that women who are covered by public insurance for NIPT to screen for aneuploidies are 3.43 times more likely to opt for the test than those covered by private insurance [ 143 ]. The testing is more widely utilized by women from higher-income households, hampering efforts to reduce general exposure to invasive procedures. Interviews with professionals from a combined study in the Netherlands found that pregnant women refrain from NIPT due to financial constraints, especially those from a lower socioeconomic background, who perceive the out-of-pocket contribution to NIPT as a financial burden [ 125 ]. This clearly explains why there is a disproportionate relationship between socioeconomic status and access to NIPT.

5. Future Directions and Conclusions

NIPT is a rising novel screening technique in medicine, globally acknowledged for its efficiency and embraced by many countries around the world. Despite the aforementioned limitations, NIPT has shown huge potential to be a reliable screening technique, as demonstrated by its high sensitivity and specificity for detecting chromosomal aneuploidies. Although not wholly infallible, NIPT still exceeds conventional screening methods in terms of providing more accurate results in detecting chromosomal aneuploidies.

Governments, including in Southeast Asian countries, should consider routinizing NIPT for detecting T13, T18, and T21 through public funding programs to mitigate disparities among women of diverse socioeconomic backgrounds; meanwhile, health insurance companies can provide testing coverage to assist with reducing the burden of out-of-pocket costs. We can see that the success of public funding for NIPT has benefited women across developed nations like Denmark, the Netherlands, France, and Switzerland in promoting equal access to NIPT for patients [ 144 ]. To enhance the informativeness of prenatal screening, it is recommended that physicians or genetic experts who are responsible for NIPT counselling possess sufficient knowledge and skills, enabling them to effectively facilitate the counselling process for pregnant women. Through wider availability of trustworthy information and ease of access to NIPT, future programs and strategies can increase the uptake of NIPT to screen for T13, T18, and T21.

Acknowledgments

We would like to thank Mok Sook Chen from ScienceVision Sdn. Bhd. for her technical input in the writing of this manuscript. The authors also wish to thank all the reviewers for their comments and suggestions for improving the manuscript.

Funding Statement

The APC was funded by the Faculty of Medicine, Universiti Kebangsaan Malaysia.

Author Contributions

Conceptualization, E.A., N.A.S.I., M.N.S. and R.A.D.; methodology, S.S.J. and E.A.; resources, M.L.N.; writing—original draft preparation, S.S.J.; writing—review and editing, E.A., N.A.S.I., M.L.N., M.N.S., R.A.D. and M.F.H.; supervision, E.A. and M.L.N.; project administration, E.A.; funding acquisition, E.A. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Data availability statement, conflicts of interest.

The authors declare no conflict of interest.

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

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Rise in pregnant women turned away from US emergency rooms, papers show

Cases listed in federal documents raise alarms around emergency pregnancy care, especially in states with strict abortion laws

One woman miscarried in the restroom lobby of a Texas emergency room as front desk staff refused to admit her to the hospital.

Another woman learned that her fetus had no heartbeat at a Florida hospital, the day after a security guard turned her away from the facility. And in North Carolina, a woman gave birth in a car after an emergency room couldn’t offer an ultrasound, and the baby later died.

Complaints that pregnant women were turned away from US emergency rooms spiked in 2022 after the US supreme court overturned Roe v Wade , federal documents obtained by the Associated Press reveal.

The cases raise alarms about the state of emergency pregnancy care, especially in states that enacted strict abortion laws and sparked confusion around the treatment doctors can legally provide.

“It is shocking, it’s absolutely shocking,” said Amelia Huntsberger, an obstetrician/gynecologist in Oregon. “It is appalling that someone would show up to an emergency room and not receive care – this is inconceivable.”

And it has happened despite federal mandates that the women be treated. Federal law requires emergency rooms to treat or stabilize patients who are in active labor and provide a medical transfer to another hospital if they don’t have the staff or resources to treat them. Medical facilities must comply with the law if they accept funding from the federal government Medicare program.

The supreme court will hear arguments next Wednesday that could weaken those protections. The Biden administration has sued Idaho over its abortion ban, even in medical emergencies, arguing it conflicts with the federal law.

“No woman should be denied the care she needs,” Jennifer Klein, director of the White House gender policy council, said in a statement. “All patients, including women who are experiencing pregnancy-related emergencies, should have access to emergency medical care required under the Emergency Medical Treatment and Labor Act [Emtala].”

Pregnant patients have “become ‘radioactive’ to emergency departments” in states with extreme abortion restrictions, said Sara Rosenbaum, a George Washington University health law and policy professor, adding: “They are so scared of a pregnant patient, that the emergency medicine staff won’t even look. They just want these people gone.”

A woman who was nine months pregnant and having contractions arrived at the Falls Community hospital in Marlin, Texas, in July 2022, a week after the supreme court’s ruling on abortion. The doctor on duty refused to see her.

“The physician came to the triage desk and told the patient that we did not have obstetric services or capabilities,” hospital staff told federal investigators during interviews, according to documents. “The nursing staff informed the physician that we could test her for the presence of amniotic fluid. However, the physician adamantly recommended the patient drive to a Waco hospital.”

Investigators with the Centers for Medicare and Medicaid Services federal agency concluded that Falls Community hospital broke the law. Reached by phone, an administrator at the hospital declined to comment on the incident.

The investigation was one of dozens the AP obtained from a Freedom of Information Act request filed in February 2023 that sought all pregnancy-related Emtala complaints the previous year and, one year later, received limited results from just 19 states.

Federal investigators looked into just over a dozen pregnancy-related complaints in those states in the run-up to the Roe ruling, but more than two dozen complaints in the months following. It is not known how many complaints were filed last year as the records request only asked for 2022 complaints and the information is not publicly available otherwise.

The documents did not detail what happened to the patient turned away from the Falls Community hospital. Other pregnancies ended in catastrophe, the documents show.

At Sacred Heart emergency center in Houston, front desk staff refused to check in one woman after her husband asked for help delivering her baby that September. She miscarried in a restroom toilet in the emergency room lobby while her husband called 911 for help.

“She is bleeding a lot and had a miscarriage,” the husband told first responders in his call, which was transcribed from Spanish in federal documents. “I’m here at the hospital but they told us they can’t help us because we are not their client.”

Emergency crews, who arrived 20 minutes later and transferred the woman to a hospital, appeared confused over the staff’s refusal to help the woman, according to 911 call transcripts.

One first responder told federal investigators that when a Sacred Heart emergency center staffer was asked about the gestational age of the fetus, the staffer replied: “No, we can’t tell you, she is not our patient. That’s why you are here.”

A manager for Sacred Heart emergency center declined to comment. The facility is licensed in Texas as a freestanding emergency room, which means it is not physically connected to a hospital. State law requires those facilities to treat or stabilize patients, a spokeswoman for the Texas health and human services agency said in an email to AP.

Sacred Heart emergency’s website says that it no longer accepts Medicare, a change that was made some time after the woman miscarried, according to publicly available archives of the center’s website.

Meanwhile, the staff at Person Memorial hospital in Roxboro, North Carolina, told a pregnant woman, who was complaining of stomach pain, that they would not be able to provide her with an ultrasound. The staff failed to tell her how risky it could be for her to depart without being stabilized, according to federal investigators. While en route to another hospital 45 minutes away, the woman gave birth in a car to a baby who did not survive.

Person Memorial hospital self-reported the incident. A spokeswoman said the hospital continued to “provide ongoing education for our staff and providers to ensure compliance”.

In Melbourne, Florida, a security guard at Holmes Regional medical center refused to let a pregnant woman into the triage area because she had brought a child with her. When the patient came back the next day, medical staff were unable to locate a fetal heartbeat. The center declined to comment on the case.

Emergency rooms are subject to hefty fines when they turn away patients, fail to stabilize them or transfer them to another hospital for treatment. Violations can also put hospitals’ Medicare funding at risk.

But it is unclear what fines might be imposed on more than a dozen hospitals that the Biden administration says failed to properly treat pregnant patients in 2022. It can take years for fines to be levied in these cases.

For Huntsberger, Emtala law was one of the few ways she felt protected to treat pregnant patients in Idaho, despite the state’s abortion ban. She left Idaho last year because of the ban, to practice in Oregon instead.

Joe Biden and Xavier Becerra, the health secretary, have both publicly vowed vigilance in enforcing the law.

Even as states have enacted strict abortion laws, the White House has argued that if hospitals receive Medicare funds they must provide stabilizing care, including abortions.

In a statement to AP, Becerra called it the “nation’s bedrock law protecting Americans’ right to life- and health-saving emergency medical care … And doctors, not politicians, should determine what constitutes emergency care.”

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Key facts about the abortion debate in America

The U.S. Supreme Court’s June 2022 ruling to overturn Roe v. Wade – the decision that had guaranteed a constitutional right to an abortion for nearly 50 years – has shifted the legal battle over abortion to the states, with some prohibiting the procedure and others moving to safeguard it.

As the nation’s post-Roe chapter begins, here are key facts about Americans’ views on abortion, based on two Pew Research Center polls: one conducted from June 25-July 4 , just after this year’s high court ruling, and one conducted in March , before an earlier leaked draft of the opinion became public.

This analysis primarily draws from two Pew Research Center surveys, one surveying 10,441 U.S. adults conducted March 7-13, 2022, and another surveying 6,174 U.S. adults conducted June 27-July 4, 2022. Here are the questions used for the March survey , along with responses, and the questions used for the survey from June and July , along with responses.

Everyone who took part in these surveys is a member of the Center’s American Trends Panel (ATP), an online survey panel that is recruited through national, random sampling of residential addresses. This way nearly all U.S. adults have a chance of selection. The survey is weighted to be representative of the U.S. adult population by gender, race, ethnicity, partisan affiliation, education and other categories.  Read more about the ATP’s methodology .

A majority of the U.S. public disapproves of the Supreme Court’s decision to overturn Roe. About six-in-ten adults (57%) disapprove of the court’s decision that the U.S. Constitution does not guarantee a right to abortion and that abortion laws can be set by states, including 43% who strongly disapprove, according to the summer survey. About four-in-ten (41%) approve, including 25% who strongly approve.

About eight-in-ten Democrats and Democratic-leaning independents (82%) disapprove of the court’s decision, including nearly two-thirds (66%) who strongly disapprove. Most Republicans and GOP leaners (70%) approve , including 48% who strongly approve.

Most women (62%) disapprove of the decision to end the federal right to an abortion. More than twice as many women strongly disapprove of the court’s decision (47%) as strongly approve of it (21%). Opinion among men is more divided: 52% disapprove (37% strongly), while 47% approve (28% strongly).

About six-in-ten Americans (62%) say abortion should be legal in all or most cases, according to the summer survey – little changed since the March survey conducted just before the ruling. That includes 29% of Americans who say it should be legal in all cases and 33% who say it should be legal in most cases. About a third of U.S. adults (36%) say abortion should be illegal in all (8%) or most (28%) cases.

Generally, Americans’ views of whether abortion should be legal remained relatively unchanged in the past few years , though support fluctuated somewhat in previous decades.

Relatively few Americans take an absolutist view on the legality of abortion – either supporting or opposing it at all times, regardless of circumstances. The March survey found that support or opposition to abortion varies substantially depending on such circumstances as when an abortion takes place during a pregnancy, whether the pregnancy is life-threatening or whether a baby would have severe health problems.

While Republicans’ and Democrats’ views on the legality of abortion have long differed, the 46 percentage point partisan gap today is considerably larger than it was in the recent past, according to the survey conducted after the court’s ruling. The wider gap has been largely driven by Democrats: Today, 84% of Democrats say abortion should be legal in all or most cases, up from 72% in 2016 and 63% in 2007. Republicans’ views have shown far less change over time: Currently, 38% of Republicans say abortion should be legal in all or most cases, nearly identical to the 39% who said this in 2007.

However, the partisan divisions over whether abortion should generally be legal tell only part of the story. According to the March survey, sizable shares of Democrats favor restrictions on abortion under certain circumstances, while majorities of Republicans favor abortion being legal in some situations , such as in cases of rape or when the pregnancy is life-threatening.

There are wide religious divides in views of whether abortion should be legal , the summer survey found. An overwhelming share of religiously unaffiliated adults (83%) say abortion should be legal in all or most cases, as do six-in-ten Catholics. Protestants are divided in their views: 48% say it should be legal in all or most cases, while 50% say it should be illegal in all or most cases. Majorities of Black Protestants (71%) and White non-evangelical Protestants (61%) take the position that abortion should be legal in all or most cases, while about three-quarters of White evangelicals (73%) say it should be illegal in all (20%) or most cases (53%).

In the March survey, 72% of White evangelicals said that the statement “human life begins at conception, so a fetus is a person with rights” reflected their views extremely or very well . That’s much greater than the share of White non-evangelical Protestants (32%), Black Protestants (38%) and Catholics (44%) who said the same. Overall, 38% of Americans said that statement matched their views extremely or very well.

Catholics, meanwhile, are divided along religious and political lines in their attitudes about abortion, according to the same survey. Catholics who attend Mass regularly are among the country’s strongest opponents of abortion being legal, and they are also more likely than those who attend less frequently to believe that life begins at conception and that a fetus has rights. Catholic Republicans, meanwhile, are far more conservative on a range of abortion questions than are Catholic Democrats.

Women (66%) are more likely than men (57%) to say abortion should be legal in most or all cases, according to the survey conducted after the court’s ruling.

More than half of U.S. adults – including 60% of women and 51% of men – said in March that women should have a greater say than men in setting abortion policy . Just 3% of U.S. adults said men should have more influence over abortion policy than women, with the remainder (39%) saying women and men should have equal say.

The March survey also found that by some measures, women report being closer to the abortion issue than men . For example, women were more likely than men to say they had given “a lot” of thought to issues around abortion prior to taking the survey (40% vs. 30%). They were also considerably more likely than men to say they personally knew someone (such as a close friend, family member or themselves) who had had an abortion (66% vs. 51%) – a gender gap that was evident across age groups, political parties and religious groups.

Relatively few Americans view the morality of abortion in stark terms , the March survey found. Overall, just 7% of all U.S. adults say having an abortion is morally acceptable in all cases, and 13% say it is morally wrong in all cases. A third say that having an abortion is morally wrong in most cases, while about a quarter (24%) say it is morally acceptable in most cases. An additional 21% do not consider having an abortion a moral issue.

Among Republicans, most (68%) say that having an abortion is morally wrong either in most (48%) or all cases (20%). Only about three-in-ten Democrats (29%) hold a similar view. Instead, about four-in-ten Democrats say having an abortion is morally  acceptable  in most (32%) or all (11%) cases, while an additional 28% say it is not a moral issue. 

White evangelical Protestants overwhelmingly say having an abortion is morally wrong in most (51%) or all cases (30%). A slim majority of Catholics (53%) also view having an abortion as morally wrong, but many also say it is morally acceptable in most (24%) or all cases (4%), or that it is not a moral issue (17%). Among religiously unaffiliated Americans, about three-quarters see having an abortion as morally acceptable (45%) or not a moral issue (32%).

• Religion & Abortion

What the data says about abortion in the U.S.

Support for legal abortion is widespread in many countries, especially in europe, nearly a year after roe’s demise, americans’ views of abortion access increasingly vary by where they live, by more than two-to-one, americans say medication abortion should be legal in their state, most latinos say democrats care about them and work hard for their vote, far fewer say so of gop, most popular.

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