Late amniocentesis: better late than never? A single referral centre experience.

INTRODUCTION: Several congenital abnormalities present late in pregnancy necessitating invasive testing to rule out genetic/infectious causes at late gestation. Not many studies have described the indications/safety of a late gestation amniocentesis. METHODS: All records of amniocentesis performed beyond 24 weeks were reviewed and evaluated for indications, positive yield and complications. RESULTS: About 187 women had an amniocentesis after 24 weeks for various indications with CNS abnormalities being the commonest. The total yield of positive findings was 14.60% (22/150; excluding 2 VOUS). CNS, multiple system involvement and skeletal system anormalities yielded maximum results. About 32.05% abnormalities could have potentially been detected at the time of a routine anomaly scan. Amongst all the deliveries, 2.1%  delivered spontaneously within a week of the procedure and about 5.4% delivered spontaneously within a month of the procedure. CONCLUSION: The study emphasises the need for additional accreditation (FMF, ISUOG) of sonographers to ensure the detection of anomalies at the routine 18-20 weeks scan. Inspite of a normal mid-trimester scan, central nervous system and gastrointestinal abnormalities presented more commonly after 24 weeks. The high positive yield in our study highlights the importance of testing even in late pregnancy beyond the legal age of termination. The test could clearly stratify the pregnancies with a poor outcome whilst reassuring the others. The procedure itself did not lead to a neonatal death due to prematurity.

Performance of Ductus Venosus Doppler (at 11-13 + 6 Weeks) in Predicting Adverse Fetal Outcomes in Indian Population: Going Beyond Aneuploidies: Going Beyond Aneuploidies.

OBJECTIVES: The objective of this study is to examine the performance of Ductus venosus (DV) Doppler done at the routine first trimester screening (11-13 + 6 weeks) in predicting the adverse fetal outcomes in Indian population. METHODS: This observational study was conducted between 2013 and 2019, on 4340 singleton pregnancies. Ductus Doppler were considered abnormal if DV pulsatility index values were >95th centile for that gestation or with a reversed "a" wave. Anatomical survey was done to rule out other abnormalities. Women were followed up till delivery and outcomes were divided into 4 groups: 1) aneuploidies; 2) cardiac defects; 3) non-cardiac structural abnormalities; and 4) miscarriages before 24 weeks or fetal deaths after 24 weeks. RESULTS: Prevalence of abnormal DV Doppler is 5.12% (205/4004). There were significantly higher number of fetal losses (4.4 versus 0.3%), aneuploidies (10.2 versus 1.7%), fetal cardiac defects (5.9 versus 1.4%), and non-cardiac structural defects (5.4 versus 1.4%) among the pregnancies with abnormal DV Doppler in comparison to those with normal flow (P < .001). Logistic regression analysis has shown that significant contribution to fetal chromosomal abnormalities and cardiac defects was associated with abnormal DV. Other factors which were found to have a significant association with adverse fetal outcome were increased nuchal translucency and increased body mass index (BMI). CONCLUSION: DV Doppler in first trimester can be used as a screening tool for cardiac defects and fetal deaths. Women with abnormal DV Dopplers should be offered fetal echocardiography at 18-22 weeks and third trimester growth scans with Dopplers.

Performance of Fetal Medicine Foundation algorithm for first trimester preeclampsia screening in an indigenous south Asian population.

BACKGROUND: To evaluate the performance of the Fetal Medicine Foundation (FMF) preterm preeclampsia (PE) screening algorithm in an indigenous South Asian population. METHODS: This was a prospective observational cohort study conducted in a tertiary maternal fetal unit in Delhi, India over 2 years. The study population comprised of 1863 women carrying a singleton pregnancy and of South Asian ethnicity who were screened for preterm pre-eclampsia (PE) between 11 and 14 weeks of gestation using Mean Arterial Pressure (MAP), transvaginal Mean Uterine Artery Pulsatility Index (UtAPI) and biochemical markers - Pregnancy Associated Plasma Protein-A (PAPP-A) and Placental Growth Factor.. Absolutemeasurements of noted biomarkers were converted to multiples of the expected gestational median (MoMS) which were then used to estimate risk for preterm PE < 37 weeks using Astraia software. Women with preterm PE risk of ≥1:100 was classified as as high risk. Detection rates (DR) at 10% false positive rate were calculated after adjusting for prophylactic aspirin use (either 75 or 150 mg). RESULTS: The incidence of PE and preterm PE were 3.17% (59/1863) and 1.34% (25/1863) respectively. PAPP-A and PlGF MoM distribution medians were 0.86 and 0.87 MoM and significantly deviated from 1 MoM. 431 (23.1%) women had a risk of ≥1:100, 75 (17.8%) of who received aspirin. Unadjusted DR using ≥1:100 threshold was 76%.Estimated DRs for a fixed 10% FPR ranged from 52.5 to 80% depending on biomarker combination after recentering MoMs and adjusting for aspirin use. CONCLUSION: The FMF algorithm whilst performing satisfactorily could still be further improved to ensure that biophysical and biochemical markers are correctly adjusted for indigenous South Asian women.

Isolated Fetal Ascites: Etiology and Prognosis - A 10-Year Experience from a Tertiary Referral Care Center in India.

INTRODUCTION: Isolated fetal ascites is an uncommon finding, and it may be difficult to elucidate the underlying pathology. This is more so when there are limited resources to investigate the patient adequately. This study was undertaken to see the etiology of isolated fetal ascites and analyze the outcomes. MATERIALS AND METHODS: Twenty-three cases of isolated fetal ascites were retrospectively analyzed from December 2007 to June 2018. All cases were investigated with detailed ultrasound with other investigations as required. Postnatal data included gestational age at birth, mode of delivery, weight, and postnatal outcome. RESULTS: The mean age at diagnosis was 26 gestational weeks. Structural abnormalities without any underlying chromosomal or genetic cause were identified in 10/23 (43.4%) cases with the most common structural abnormality related to the gastrointestinal tract where ultrasound proved to the most useful tool. The overall good prognosis was seen in 13/23 (56.5%) cases. CONCLUSION: Appropriate perinatal care, timely referral and delivery at tertiary care setup, and timely surgical intervention are measures which can improve the outcome and survival in fetuses diagnosed with isolated fetal ascites.

Elective Fetal Reduction in Dichorionic Diamniotic Twin Pregnancies on Parental Request: A Single-Centre Experience.

OBJECTIVES: Our study aimed to examine a subset of electively reduced twins and compare their outcomes with those of expectantly managed twins, along with a cohort of singleton pregnancies. The secondary aim was to ascertain the procedure-related miscarriage risks. METHODS: A retrospective cohort analysis was performed at Apollo Centre for Fetal Medicine, New Delhi, comparing pregnancy outcomes in dichorionic diamniotic twin pregnancies which were reduced to singletons (group 1) with that of women with dichorionic twins managed expectantly (group 0) and women with a singleton pregnancy (group 2). Comparison of continuous and categorical variables was conducted using standard statistical tests. RESULTS: We analysed 35 twins which were reduced to singletons, 421 expectantly managed dichorionic twins and 1915 women with a singleton pregnancy. In the reduction group, the rate of procedure related pregnancy loss<24 weeks was lower, compared to the expectantly managed twins, although the difference was not statistically significant (5.71% [2/35] vs. 7.13% [30/421]; p = 1.000). The median gestational age at delivery was significantly higher in reduced twins compared to expectantly managed twin pregnancies (38.0 vs. 35.4 weeks respectively, p < 0.001) with a higher mean birth weight at delivery, both of which were comparable to that among the singleton pregnancies (38.3 weeks). The rates of preterm birth <32 weeks and <34 weeks in the expectantly managed twins were significantly higher at 19.8% (66/334) and 25.7% (86/334) compared to the reduced twins, all of whom delivered beyond 34 weeks. The rates of preterm births <32 weeks, <34 weeks, and the late preterm births in the reduced twins were comparable to those in the singleton cohort. CONCLUSIONS: The obstetric and perinatal outcomes after reduction of a dichorionic twin are better than an expectantly managed twin without an associated increase in pregnancy loss rates. Fetal reduction of dichorionic twin to a singleton appears to be a safe procedure in expert hands.

Performance of second-trimester maternal biochemistry screening (quadruple test vs. triple test) for trisomy 21: An Indian experience.

Background & objectives: Down syndrome (DS) is one of the most common causes of developmental delay. In India, there is no protocol for prenatal screening of DS. Second-trimester biochemical screening is still being done by triple test. Quadruple test is with better sensitivity and specificity but is not advised routinely. So, the objective of this study was to evaluate the sensitivity and accuracy of the second-trimester screening (quadruple test with genetic sonogram) for trisomy 21 as compared to biochemical testing. Methods: This retrospective observational study was carried out in a Fetal Medicine Centre to analyze the odds of being affected with DS, given a positive risk (OAPR) upon screening in the quadruple test; triple test and quadruple test plus a genetic sonogram for high-risk singleton pregnancies (in view of advanced maternal age; an anomaly scan showing some abnormality, etc). Results: 3175 high-risk singleton pregnancies were screened for trisomy 21. 394 women underwent amniocentesis on the basis of triple test, quadruple test or quadruple plus genetic sonogram positive. 17 foetuses were diagnosed to have DS. The quadruple test was found to have a higher OAPR as compared to the triple test (1:30.1 as compared to 1: 40.2). Quadruple test plus the genetic sonogram was found to have the highest OAPR of 1:6. Interpretation & conclusions: Best screening for trisomy 21 is provided with quadruple test with genetic sonogram which can lower the rates of unnecessary amniocentesis in high-risk population.

First-Trimester Crown-Rump Length (CRL) and Nuchal Translucency (NT) Discordance in Monochorionic Twins: An Ominous Sign or a Benign Feature?

BACKGROUND: This study aimed to evaluate the usefulness of the first-trimester crown-rump length (CRL) and nuchal translucency (NT) discordance in monochorionic diamniotic twins (MCDA) for the prediction of complications-twin-twin transfusion syndrome (TTTS), selective fetal growth restriction (sFGR) or intrauterine fetal demise (IUFD). METHODS: Intertwin discordance in the CRL and NT was calculated as a percentage of the larger CRL and NT, respectively. The performance of inter twin discordance (CRL ≥ 10% and NT≥ 20%) for predicting complications was analysed using standard statistical screening test methods. RESULTS: Fifty-eight MCDA twin pregnancies were studied. Out of them, 19 (32%) pregnancies resulted in one of the complications studied (4 TTTS, 10 sFGR, 5 IUFD). CRL and NT discordance showed an increased probability of developing complications positive likelihood ratio (LR+) {95% confidence interval}: 2.05 {0.46-9.23} and 1.88 {1.03-3.45}, respectively. NT discordance showed a sensitivity of 57%. CONCLUSIONS: Although discordant first-trimester CRL and NT in monochorionic twins are poor screening tools for early prediction, if positive, they increase the risk of developing complications.

Performance of Common Down Syndrome Screening Methods Used in India with Construction of an Indian Normogram for Nuchal Translucency/Crown-Rump Length Measurements in 14,337 Subjects.

BACKGROUND/PURPOSE OF STUDY: Sonologists often lack access to the Fetal Medicine Foundation Down syndrome risk calculation software or cannot offer the combined test for aneuploidy screening because of resource constraints. Instead, sonologists use nuchal translucency (NT) measurements that rely on fixed NT cut-offs for labelling foetuses with high risks for Down syndrome. In the present study, we aimed to plot normative data for NT and the crown-rump length (CRL) in Indian foetuses and to assess the value of using the 95th/99th centiles of NT for CRL cut-offs instead of fixed NT cut-offs to calculate the risk for aneuploidies during the first trimester. METHODS: We conducted a retrospective observational study measuring the NT/CRL in 14,337 Indian foetuses between 11 and 13 + 6 weeks of gestation. We used regression analysis and calculated the 95th/99th centiles of NT distribution. We compared performances of NT > 95th/99th centiles and fixed NT cut-offs of 2.5- and 3.5-mm  as screening. RESULTS: The NT measurements increased with increasing CRL values. NT > 95th centile for a particular CRL for detecting all aneuploidies had the maximum sensitivity of 73.9% for a false positive rate (FPR) of 4.3%. Similar values for fixed cut-off > 2.5 mm were 63.0% FPR 3.7% (T21 68.2 FPR 3.8%) and for NT > 3.5 mm 36.9% FPR 0.43% (T21 36.5% FPR 0.5%). CONCLUSION: A fixed NT cut-off point is not appropriate for the first trimester screening. The best sensitivity for assessing aneuploidies is achieved using the 95th centile, but the 99th centile achieves higher specificity for gestational age.

Prenatal Presentation of Medulloepithelioma: Case and Literature Review.

Congenital brain tumors (CBTs) are extremely rare and account for only 0.5%-1.9% of all pediatric brain tumors. Medulloepithelioma is one of the rare tumors with an incidence of about 1% among all CBTs with a very dismal prognosis and typically diagnosed at the median age of 24 months. The objective is reporting medulloepithelioma presenting in the intrauterine period with very few prior cases being reported in the prenatal period, and to add to the limited existing literature on medulloepithelioma. We present a rare case of medulloepithelioma referred to us in the antenatal period at 27 weeks and subsequently causing intrauterine fetal demise. Prenatal MRI of the fetal brain and postnatal histopathological findings on autopsy were suggestive of intracranial medulloepithelioma.

Prenatal diagnosis of congenital harlequin ichthyosis with fetal MRI.

Most of the fetal deformities are caused due to genetic abnormalities. Although magnetic resonance imaging (MRI) may be used to accurately diagnose these deformities, it has been reported that gene analysis is a more accurate diagnostic method. Harlequin ichthyosis (HI) or Ichthyosis fetalis (IF) is a rare and extremely severe hereditary skin disorder with autosomal recessive inheritance. The ultrasound features have been described well and the diagnosis can be made with a fair degree of confidence. However, the final diagnosis needs to be established by prenatal invasive tests. In the present study, we describe the diagnosis of HI in the third trimester on fetal MRI referred to our department with suspicion of anterior encephalocele which was later confirmed through postnatal genetic evaluation.

Single Nucleotide Polymorphism-Based Noninvasive Prenatal Testing: Experience in India.

INTRODUCTION: Noninvasive prenatal testing (NIPT) has revolutionized prenatal screening for chromosomal aneuploidies in some countries. Its implementation has been sporadic in developing countries. Given the genetic variation of the people in different countries, we evaluated the performance of the SNP-based NIPT in India . MATERIALS AND METHODS: The Panorama™ NIPT was performed in 516 pregnancies, which had tested intermediate-to-high risk on conventional first and second trimester screening. Results were confirmed either by invasive diagnostic testing or by clinical evaluation after birth. RESULTS: Of 511 samples analyzed, results were obtained in 499 (97.7%). Of these, 480 (98.2%) were low risk and 19 were high risk. A sensitivity of 100% was obtained for detection of trisomies 21, 18, 13 and sex chromosomal abnormalities. The specificity ranged from 99.3 to 100% for abnormalities tested. Taken together, the positive predictive value for trisomies 21, 18, 13 and monosomy X was 85.7%. The average fetal fraction was 8.2%, which is lower than the average observed elsewhere. CONCLUSION: This is the first report of detailed experience with NIPT in India and demonstrates comparable performance in all aspects of testing to the results elsewhere.

Role of Ultrasound-Based Prenatal Prediction of Pulmonary Function in Congenital Diaphragmatic Hernia: Does It Have Prognostic Significance Postnatally?

BACKGROUND AND OBJECTIVES: The incidence of congenital diaphragmatic hernia (CDH) in India is 1 in 1000. About 60 % of these are isolated, and the survival prognosis in them depends upon the quantum of contralateral functional lung. Out of the various pulmonary and extrapulmonary sonological predictors, observed to expected lung-head ratio (O/E LHR) is an efficient gestation-independent predictor of pulmonary function. This study was carried out to see the correlation of this prenatal predictor with the postnatal outcome depending on the pulmonary function. METHODOLOGY: This study was carried out at Apollo Center of Fetal Medicine, New Delhi, from January 2009 to December 2015. A total of 14 fetuses with isolated left-sided CDH were included. The contralateral lung area was measured in 2D transverse view of the thorax at the level of four-chamber view of the heart by tracing method. The obtained value (square mm) was then divided by the expected mean lung area at that gestation and multiplied with 100 to express O/E LHR as percentage. These were then classified as severe (O/E LHR <25 %), moderate (25-45 %) or mild (>45 %) varieties of CDH. The parents to be were counselled for termination or continuation of pregnancy based on severity of CDH and total lung area. The patients were followed up for obstetrical and neonatal outcome till the time of first postoperative visit (diaphragmatic repair). RESULTS: The survival correlation in mild cases was 100 % (n = 5 out of 5) and 50 % in moderate cases (n = 2 out of 4), and both severe cases were terminated. There was a significant difference (p < 0.01) in the survival rate in the mild versus severe cases. CONCLUSIONS: The prenatal predictor for postnatal pulmonary function correlates well with the neonatal outcome and hence is an important tool in prenatal counseling and triaging those who require termination of pregnancy versus expectant management. An obstetrician who is a first point of contact to the pregnant women can understand this and use it for counseling and differentiating the patients who need termination with regard to CDH.

Observational study comparing the performance of first-trimester screening protocols for detecting trisomy 21 in a North Indian population.

OBJECTIVE: To evaluate first-trimester screening protocols for detecting trisomy 21 in an Indian population. METHODS: The present prospective study collected data from women with singleton pregnancies and a crown-to-rump length of 45-84 mm who presented at the fetal medicine unit of a tertiary care center in North India between June 1, 2006, and December 31, 2015, for combined first-trimester screening. Maternal age, nuchal translucency, nasal bone, and maternal serum levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A were assessed for calculating the risk of trisomy 21. Tricuspid regurgitation and qualitative analysis of ductus venosus data were available from June 2010, and were included where available. Trisomy-21 detection rates were calculated for various screening protocols and were compared. RESULTS: There were 4523 women screened and 24 records of trisomy 21. Combined screening with maternal age, nuchal translucency, nasal bone, tricuspid regurgitation, and ductus venosus demonstrated optimal detection and false-positive rates of 93.8% and 1.9%, respectively. Screening using only maternal age yielded a detection rate of 37.5%; using fixed nuchal translucency cut-off values of 2.5 and 3 mm resulted in detection rates of 66.7% and 37.5%, respectively. CONCLUSION: Combined first-trimester screening performed well in an Indian population; combining maternal age, nuchal translucency, nasal bone, ductus venosus, and tricuspid regurgitation yielded the most accurate screening.

Anti-G antibody in alloimmunized pregnant women: Report of two cases.

Anti-G has been reported as a possible cause of hemolytic disease of the fetus and newborn (HDFN), either independently or in association with anti-D, anti-C or both. The antibody mimics the pattern of anti-C and anti-D reactivity in the identification panel and is often present along with either or both of these antibodies. The differentiation of anti-D, -C and-G in routine pretransfusion workup is particularly essential in antenatal cases. We report two antenatal cases where anti-G was identified on advanced immunohematological workup, in addition to other alloantibodies.

An analysis of pregnancy outcome in dichorionic and monochorionic twins given special antenatal and intranatal care: a four-year survey.

OBJECTIVE: The present study aims to analyze perinatal outcomes in twins given special care during pregnancy and labor and to compare fetal and neonatal outcomes in dichorionic twins with monochorionic twins. STUDY DESIGN: Eighty eight (88) twin pregnancies booked for care at a tertiary care Fetal Medicine centre were included in this study. The maternal demographic variables, course of pregnancy, fetal problems, and specialized fetal therapeutic and diagnostic interventions were noted. The above parameters were compared in the sub-groups of dichorionic and monochorionic twin pregnancies and related to the perinatal outcome. Statistical analysis was done using the student's t test and the two-tailed chi sqaure tests with Yate's continuity correction. A p value <0.05 was considered as significant. RESULTS: Mean maternal age was 30.34 + 4.81 years (range 19-48). 81 % of the twins were DCDA, and 19 % were MCDA. The mean gestational age at delivery was 34.4 ± 3.5 weeks, and this was not significantly different in MCDA and DCDA groups. Serious fetal problems warranting intervention at the time of initial referral were significantly higher in MCDA twins although overall perinatal outcome in both groups were not different. CONCLUSION: Specialized care during pregnancy and labor including active fetal surveillance and therapeutic intervention when indicated improves the perinatal outcome in twin pregnancies and ensured at least one healthy live birth in over 90 % cases, although with an increase in late prematurity.

Diagnosis of sirenomelia in the first trimester.

Sirenomelia or "mermaid syndrome" is a rare congenital abnormality with an incidence of 1 in 60,000. We report a case diagnosed in the first trimester using two-dimensional, three-dimensional, and color Doppler ultrasound. With increasing emphasis on early diagnosis of fetal abnormalities, this case highlights the importance of looking for anomalies in the first trimester itself. In fact, the diagnosis of sirenomelia should be easier in the first trimester as severe oligohydramnios in later gestation hampers vision.