Prenatal screening has evolved dramatically over the past few decades, aiming to identify pregnancies at risk for chromosomal abnormalities and adverse perinatal outcomes as early as measurement and maternal serum double marker testing (β-hCG and PAPP-A), plays a pivotal role in detecting fetal aneuploidy and evaluating the risk of conditions such as Down syndrome (Trisomy 21), Edward syndrome (Trisomy 18), and Patau syndrome (Trisomy 13). Chromosomal anomalies are among the leading causes of perinatal morbidity and mortality worldwide. These abnormalities may result in pregnancy complications such as spontaneous abortion, fetal growth restriction, intrauterine fetal demise, and neonatal complications requiring intensive care support. Early identification of high-risk pregnancies enables healthcare providers and parents to make informed decisions about further diagnostic testing and pregnancy management.

The practice of prenatal screening began in the 1960s, initially targeting women of advanced maternal age due to the increased risk of chromosomal abnormalities in this group [1]. However, age-based screening was found to be insufficiently sensitive and specific. The introduction of NT measurement in the late 1990s by the Fetal Medicine Foundation, London, marked a significant advancement in prenatal screening [2]. NT refers to the subcutaneous fluid-filled space at the back of the fetal neck, and its increased thickness is associated with chromosomal abnormalities, congenital heart defects, and genetic syndromes. The double marker test combines the measurement of two maternal serum biochemical markers—pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (β-hCG)—to enhance the predictive value of NT measurement. Abnormal levels of these markers have been linked to various adverse outcomes including fetal aneuploidy, preeclampsia, and fetal growth restriction [3,4].

Despite the utility of these screening methods in identifying chromosomal abnormalities, their predictive capacity for broader adverse perinatal outcomes remains uncertain. Some studies have reported associations between abnormal first-trimester screening results and adverse events such as intrauterine growth restriction, stillbirth, and preterm birth [5,6]. However, the sensitivity and specificity of these tests for non-chromosomal adverse outcomes are still not well-established [7,8]. In India, where a significant proportion of pregnancies remain unscreened due to socioeconomic and healthcare access limitations, improving the predictive value of existing screening tools is particularly important. Identifying women at higher risk early in pregnancy can facilitate timely referrals, closer monitoring, and interventions that may improve maternal and fetal outcomes. This study aims to evaluate the association between first-trimester prenatal screening tests—specifically NT measurement and the double marker test—and adverse perinatal outcomes among pregnant women. Understanding these associations may improve the clinical utility of these screening tools beyond chromosomal abnormality detection, potentially contributing to better risk stratification and maternal-fetal care planning.

This was a diagnostic cross-sectional study conducted over a period of two years, from June 2021, to May 2023, in the Department of Obstetrics and Gynecology at NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital, Nagpur. The study aimed to evaluate the association between first-trimester prenatal screening tests—namely, nuchal translucency (NT) on ultrasound and the double marker test (PAPP-A and β-hCG)—with adverse perinatal outcomes. Ethical clearance was obtained from the Institutional Ethics Committee before commencement. A total of 63 pregnant women were enrolled based on a sample size calculation using 90% specificity, 10% allowable error, and 50% prevalence. The sampling method used was convenient sampling.

Eligible participants included primigravidae or multigravidae with singleton pregnancies between 11 and 13 weeks of gestation, as confirmed by last menstrual period or ultrasound scan. Women who opted for NT measurement and double marker testing, and who were willing to deliver at the study center, were included. Exclusion criteria included maternal BMI <20 or >30, multiple pregnancies, vaginal bleeding, steroid therapy, thyroid disorders, chronic hypertension, gestational diabetes, chronic liver disease, and medically indicated abortion due to maternal illness.

After obtaining informed consent, demographic and obstetric history was collected using a structured case record form. NT measurement and double marker testing were performed during 11–13 weeks of gestation. Women who tested positive on screening were advised to undergo amniocentesis at 16 weeks. Participants were followed through delivery, and neonatal outcomes were assessed by a neonatologist. Outcome measures included abortion, fetal distress, intrauterine growth restriction (IUGR), stillbirth, small for gestational age, chromosomal anomalies (Trisomy 21, 18, 13), and NICU admissions. Data were entered in Microsoft Excel and analyzed using Epi Info Version 7, with descriptive and inferential statistics including t-test and Chi-square test used to determine associations.

The present study evaluated the association between first trimester prenatal screening tests—including nuchal translucency (NT) and double marker test—and adverse perinatal outcomes. Data were analyzed for 64 antenatal women, and their demographic, clinical, and biochemical parameters were compared in relation to perinatal outcomes. The findings are presented below.

The baseline characteristics of the study population (n = 64) indicate that the majority of participants (56.3%) were aged between 26–30 years, with a mean age of 27.91 ± 4.07 years, ranging from 20 to 42 years. Half of the women were primigravida (50%), while 23.4% were gravida 2 and 15.6% were gravida 3. Parity distribution showed that 57.8% had not delivered previously (para 0), while 40.6% had one prior delivery. All women were normotensive prior to pregnancy, but by the time of delivery, 17.2% developed hypertension, and 1.6% experienced hypotension, with 79.7% remaining normotensive. The mean pre-pregnancy weight was 55.61 kg (SD = 8.92), which increased to 64.34 kg (SD = 9.28) by the time of delivery. The average height of the participants was 155.51 cm (SD = 5.03), with a range from 143 cm to 167 cm. These baseline metrics provide a clear demographic and physiological profile of the study cohort.

In this study, a comparison of maternal and clinical parameters between those with and without adverse perinatal outcomes revealed no statistically significant differences in age, gravidity, parity, blood pressure (pre-pregnancy and pre-delivery), weight (before and after pregnancy), or height. However, nuchal translucency (NT) and dual marker values showed a highly significant association with adverse outcomes. The mean NT was notably higher in the adverse outcome group (1.89 mm) compared to the non-adverse group (1.22 mm), and similarly, the dual marker MoM was elevated (1.90 vs. 1.22), both with p-values less than 0.001. These findings suggest that increased NT and abnormal dual marker results in the first trimester are strong predictors of adverse perinatal outcomes, underscoring their importance in early risk stratification.

The association between double marker status and various perinatal outcomes did not reveal any statistically significant differences, though certain trends were observed. Maternal complications were slightly more frequent in the marker-positive group (52.6%) compared to the negative group (40%), but this was not significant (p = 0.352). Similarly, full-term normal deliveries (FTND) were more common among marker-negative women (60%) compared to marker-positive women (31.6%), while emergency LSCS was more frequent in the marker-positive group (36.8%), though this association also lacked statistical significance (p = 0.115). Low birth weight (<2.5 kg), fetal complications, NICU admissions, and perinatal deaths were numerically higher in the marker-positive group but did not reach statistical significance (p > 0.05 in all cases). These findings suggest that while positive double marker status may be associated with increased risk for adverse outcomes, this study did not demonstrate a statistically significant association across the measured variables.

The present study aimed to evaluate the association between first-trimester prenatal screening tests—specifically nuchal translucency (NT) and double marker test—and adverse perinatal outcomes. Our findings demonstrated a statistically significant association between increased NT measurements and elevated double marker values (MoM) with adverse outcomes such as intrauterine growth restriction (IUGR), fetal distress, and NICU admissions. These results underscore the potential utility of first-trimester screening not only in detecting chromosomal anomalies but also in predicting a broader spectrum of perinatal complications. This aligns with findings from the study by Shiefa et al., 2013, that have reported abnormal NT and serum markers being linked with adverse outcomes beyond aneuploidy, including preeclampsia and growth restriction [4].

Alldred et al. (2015) emphasized that first trimester serum tests are valuable for aneuploidy screening, especially for trisomies 21, 18, and 13, but their extended role in predicting adverse perinatal events has gained increasing attention in recent literature [3]. Schmidt et al. (2008) demonstrated that increased NT measurements are not only predictive of chromosomal anomalies but also associated with structural anomalies, including congenital heart defects, which may contribute to poor perinatal outcomes [2]. In our study, the mean NT and dual marker MoM values were significantly higher among women who experienced adverse perinatal outcomes, which supports these associations. This also aligns with a study by Seyedoshohadaei et al. (2024) which found significant associations between abnormal first-trimester screening markers and adverse outcomes such as preterm birth and fetal growth restriction, echoing the trends observed in our cohort [6].

However, not all findings were statistically significant. While trends such as higher maternal complications, increased NICU admissions, and higher perinatal death rates were observed among women with positive double marker tests, the differences did not reach statistical significance. This could be attributed to the relatively small sample size of our study, which may have limited the power to detect significant differences. Similar limitations were discussed in studies by Kulkarni et al. (2017) and Kjaergaard et al. (2008), where smaller cohorts led to less robust correlations between serum markers and outcomes [5,7].

In the context of developing countries like India, where access to advanced diagnostic tools is limited and a large proportion of pregnancies remain unscreened, enhancing the clinical utility of existing, cost-effective first-trimester screening methods is particularly valuable. By identifying high-risk pregnancies early, clinicians can adopt a more individualized approach to antenatal care. The findings of this study support previous literature by Avătăjitei et al., 2012 and Ekelund et al., 2008, which suggest that first-trimester screening should be viewed as a tool for broader maternal-fetal risk stratification, rather than being restricted to aneuploidy screening alone [1,8]

In summary, while most baseline maternal characteristics showed no significant association with adverse perinatal outcomes, elevated nuchal translucency and abnormal double marker values in the first trimester were significantly associated with increased risk. Although trends toward higher rates of complications were observed in marker-positive cases, these did not reach statistical significance. These results underscore the potential role of first trimester screening markers in early risk identification and the need for closer monitoring in high-risk pregnancies."

Conflict of Interest: The authors declare that there is no conflict of interest related to this study.

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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