Neural Tube Defects from Antenatal Diagnosis to Discharge - a Tertiary Academic Centre Experience.

Background: Bleeding Worldwide, approximately 300,000 infants are born annually with neural tube defects (NTDs), which carry a high risk of morbidity and mortality. Objective: The aim of the study was to describe the experience with NTD patients born at a tertiary academic center. Methods: A retrospective record review of all neonates with NTD admitted to the neonatal intensive care unit over six years. Results: Out of the 39 patients identified, 32 (82.1%) were diagnosed antenatally. Most NTD cases were of the myelomeningocele 26 (66.7%) type. The most common site of the myelomeningocele was lumbar, and the thoracolumbar site had the worst prognosis. Conclusion: Early detection of the disease allows better planning of delivery and treatment decisions. Nevertheless, understanding the magnitude of the problem necessitates adopting public health prevention strategies for better outcomes.

Post-traumatic stress disorder and congenital anomalies in prenatal care / Transtorno de estresse pós-traumático e anomalias congênitas no pré-natal

Abstract Objective: to assess post-traumatic stress disorder (PTSD) symptoms in pregnant women diagnosed with congenital anomaly. Methods: his is a quantitative and cross-correlational study. The sample consisted of 111 pregnant women diagnosed with congenital anomaly between 2013 and 2014. We used a semi-structured questionnaire and the Impact of Events Scale - Revised (IES-R). For statistical analysis, the chi-square test, Student's t test or Mann-Whitney test, Cronbach Alpha coefficients, Pearson's correlation and simple linear regression models. Results: viable congenital anomalies corresponded to 66.6%, and non-viable, to 33.3%. The average of all areas of IES-R, as well as the sum of matters concerning IES-R, were high in all pregnant women diagnosed with congenital anomaly. Using a cut of 5.6 units in the IES-Rtotal score, we found that 46.8% of pregnant women diagnosed with a congenital anomaly showed PTSD symptoms; however, symptoms were more frequent among pregnant women diagnosed with non-viable congenital anomaly (64.9%). The IES-R intrusion and hyperstimulation dimensions were more correlated. We observed a decreasing connection with PTSD symptoms in relation to the time of the notification of congenital anomaly diagnosis. Conclusions: PTSD symptoms were more frequent in pregnant women diagnosed with non-viable congenital anomaly.

Resumo Objetivos: avaliar os sintomas do Transtorno de Estresse Pós-Traumático (TEPT) em gestantes com diagnóstico fetal de anomalia congênita. Métodos: estudo quantitativo e transversal-correlacional. A amostra foi composta por 111 gestantes com diagnóstico de anomalia, entre 2013 a 2014. Foi utilizado um questionário semiestruturado e a Escala do Impacto do Evento - Revisada (IES-R). Para a análise estatística o teste Qui quadrado, t de Student ou Mann-Whitney, coefficientes alfa de Cronbach, correlação de Pearson e modelos de regressão linear simples. Resultados: as anomalias congênitas viáveis corresponderam a 66,6% e as inviáveis, a 33,3%. A média de todos os domínios da IES-R como a soma das questões dos domínios da IES-R foram altas nas gestantes com diagnóstico de anomalia congênita. Ao se utilizar um corte de 5,6 unidades no escore total da IES-R, 46,8% de todas as gestantes com diagnóstico de anomalia congênita apresentaram sintomas de TEPT, sendo mais frequente entre as gestantes com diagnóstico de anomalia congênita inviável (64,9%). As questões de intrusão e hiperestimulação da escala IES-R estiveram mais correlacionadas entre si. Pareceu existir uma relação decrescente dos sintomas de TEPT, em relação ao tempo da notícia do diagnóstico de anomalia congênita. Conclusão: os sintomas do TEPT estiveram mais presentes em gestantes com diagnóstico de anomalia congênita inviável.

Cardiometabolic outcomes of women exposed to hyperglycaemia first detected in pregnancy at 3-6 years post-partum in an urban South African setting.

BACKGROUND: Hyperglycaemia first detected during pregnancy(HFDP) has far-reaching maternal consequences beyond the pregnancy. Our study evaluated the cardiometabolic outcomes in women with prior HFDP versus women without HFDP 3-6 years post-partum in urban South Africa. DESIGN AND METHODS: A prospective cohort study was performed of 103 black African women with prior HFDP and 101 without HFDP, 3-6 years post-partum at Chris Hani Baragwanath Academic Hospital, Soweto. Index pregnancy data was obtained from medical records. Post-partum, participants were re-evaluated for anthropometric measurements, body composition utilizing dual energy X-ray absorptiometry(DXA) and biochemical analysis (two-hour 75gm OGTT fasting insulin, lipids, creatinine levels and glucose levels). Cardiovascular risk was assessed by Framingham risk score(FRS). Carotid intima media thickness(cIMT) was used as a surrogate marker for subclinical atherosclerosis. Factors associated with progression to cardiometabolic outcomes were assessed using multivariable logistic and linear regression models. RESULTS: Forty-six(45.1%) HFDP women progressed to diabetes compared to 5(4.9%) in non HFDP group(p<0.001); only 20(43.4%) were aware of their diabetic status in the whole group. The odds(OR, 95% confidence interval(CI)) of progressing to type 2 diabetes(T2DM) and metabolic syndrome(MetS) after correcting for confounders in the HFDP group was 10.5(95% CI 3.7-29.5) and 6.3(95%CI 2.2-18.1), respectively. All visceral fat indices were found to be significantly higher in the HFDP group after adjusting for baseline body mass index. Ten-year estimated cardiovascular risk(FRS) and mean cIMT was statistically higher in the HFDP group(8.46 IQR 4.9-14.4; 0.48 mm IQR 0.44-0.53 respectively) compared to the non-HFDP group(3.48 IQR 2.1-5.7; 0.46mm IQR 0.42-0.50) respectively and this remained significant for FRS but was attenuated for cIMT after correcting for confounders. HIV did not play a role in progression to any of these outcomes. CONCLUSION: Women with a history of HFDP have a higher risk of cardiometabolic conditions within 6 years post-partum in an urban sub-Saharan African setting.

Frequency and clinical significance of chromosomal inversions prenatally diagnosed by second trimester amniocentesis.

To compare the frequency and clinical significance of familial and de novo chromosomal inversions during prenatal diagnosis. This was a retrospective study of inversions diagnosed prenatally in an Asian population by applying conventional GTG-banding to amniocyte cultures. Data from 2005 to 2019 were extracted from a single-center laboratory database. The types, frequencies, and inheritance patterns of multiple inversions were analyzed. Pericentric variant inversions of chromosome 9 or Y were excluded. In total, 56 (0.27%) fetuses with inversions were identified in the 15-year database of 21,120 confirmative diagnostic procedures. Pericentric and paracentric inversions accounted for 62.5% (35/56) and 37.5% of the inversions, respectively. Familial inversions accounted for nearly 90% of cases, and de novo mutation was identified in two pericentric and two paracentric cases. Inversions were most frequently identified on chromosomes 1 and 2 (16.1% of all inversions), followed by chromosomes 6, 7, and 10 (8.9% of all cases). The indications for invasive testing were as follows: advanced maternal age (67.3%), abnormal ultrasound findings (2.1%), abnormal serum aneuploidy screening (20.4%), and other indications (10.2%). The mode of inheritance was available for 67.9% of cases (38/56), with 89.5% of inversions being inherited (34/38). A slight preponderance of inheritance in female fetuses was observed. Three patients with inherited inversions opted for termination (two had severe central nervous system lesions and one had thalassemia major). Gestation continued for 53 fetuses, who exhibited no structural defects at birth or significant developmental problems a year after birth. Our study indicates that approximately 90% of prenatally diagnosed inversions involve familial inheritance, are spreading, and behave like founder effect mutations in this isolated population on an island. This finding can help to alleviate anxiety during prenatal counseling, which further underscores the importance of parental chromosomal analysis, further genetic studies, and appropriate counseling in cases where a nonfamilial inversion is diagnosed.

Pregnancy outcomes of fetuses with congenital heart disease after a prenatal diagnosis with chromosome microarray.

OBJECTIVE: To evaluate the pregnancy outcomes of fetuses with congenital heart disease (CHD) after chromosome microarray (CMA)-based prenatal diagnosis. METHOD: Amniocentesis was performed in 1035 pregnant women carrying fetuses with CHD between September 2014 and December 2019. Chromosomal aberrations in fetuses with CHD were evaluated using CMA. The pregnancy outcomes were followed up from 6 months to 5 years. RESULTS: The overall CHD detection rate by CMA was 10.1% (105/1035; 50 fetuses: aneuploidy, 55 fetuses: pathogenic or likely pathogenic copy number variations). Among 1003 fetuses who were followed up, 4, 236, 763, and 18 cases were of miscarriages, pregnancy termination, live births, and postnatal deaths, respectively. Self-healed CHD was observed in 401 (52.6%) fetuses. The pregnancy termination rate of fetuses with chromosomal anomalies was significantly higher than that of fetuses without chromosomal anomalies (93.1% vs. 15.5%, p < 0.001). However, other pregnancy outcomes, including mortality, preterm labor, and low-weight birth rate, were similar between the two groups. CONCLUSION: The outcome of CMA is an important factor influencing parents' choice of whether to continue the pregnancy. Self-healing rate of prenatal diagnosed CHD is high. The mortality and morbidity of fetuses with CHD following prenatal CMA testing are relatively low.

How COVID-19 pandemic is changing the practice of prenatal screening and diagnosis?

OBJECTIVES: To evaluate the impact of the COVID-19 pandemic on prenatal screening and diagnostic tests. METHODS: We conducted a retrospective study with pregnant women attending to the perinatology department of a tertiary referral center. The pre-COVID-19 period between 11 March 2019 and 10 March 2020 and COVID-19 period between 11 March 2020 and 10 March 2021 were evaluated. Both periods were compared in terms of outpatient visits, ultrasound examinations, prenatal screening and diagnostic tests. The correlation of deaths related to COVID-19 pandemic on these parameters was also assessed. RESULTS: A total of 38,918 patients were examined and 28,452 ultrasound examinations, 26,672 prenatal screening tests and 1,471 prenatal diagnostic tests were performed over two years. During COVID-19 pandemic, number of outpatient visits decreased by 25.2%, ultrasound examinations decreased by 44.2%, prenatal screening tests decreased by 36.2% and prenatal diagnostic tests decreased by 30.7%. Statistically significant correlation was not observed between deaths related to COVID-19 and outpatient visits (p=0.210), ultrasound examinations (p=0.265), prenatal screening (p=0.781) and diagnostic tests (p=0.158). Among indications of prenatal diagnostic tests, maternal anxiety was significantly higher in COVID-19 period (p=0.023). There was significant decrease in the detection of fetuses with trisomy 21 (p=0.047) and a significant increase in the detection of fetuses with Turner syndrome (p=0.017) during COVID-19 period. CONCLUSIONS: The COVID-19 pandemic has severely impacted antenatal care. Prenatal fetal screening and diagnosis was adversely affected by the pandemic in terms of detecting genetic and structural anomalies.

Knowledge, attitudes, and practices of healthcare professionals working in prenatal diagnosis toward expanded non-invasive prenatal testing in China.

OBJECTIVES: To investigate the knowledge, attitudes, and practices of healthcare professionals (HCPs) working in prenatal diagnosis toward expanded non-invasive prenatal testing (NIPT) in China. METHODS: We conducted a national online survey among HCPs working in prenatal diagnosis, including specialists in prenatal diagnosis and foetal medicine, obstetricians and gynaecologists, nurses in obstetrics and gynaecology, obstetric ultrasound doctors, and technicians in prenatal diagnosis laboratories. A total of 1882 questionnaires were collected, among which 1822 questionnaires met the research criteria and were included in the analysis. RESULTS: More than 99% of all participants opted for NIPT for trisomies 21, 18, and 13. The rates of support for expanded NIPT for sex chromosome aneuploidies, rare autosomal trisomies, microdeletions and microduplications, and single-gene disorders were 93.9%, 88.6%, 89.4%, and 86.8%, respectively. Specialists in prenatal diagnosis and foetal medicine had greater knowledge but were less likely to support expanded NIPT compared to other participants. Knowledge increased with educational level, whereas support for expanded NIPT decreased with educational level. CONCLUSIONS: More than 80% of HCPs working in prenatal diagnosis in China expressed support for expanding NIPT to conditions other than common trisomies. The degree of knowledge was negatively associated with the rate of support.

Association of prenatal renal ultrasound abnormalities with pathogenic copy number variants in a large Chinese cohort.

OBJECTIVES: To assess the clinical utility of prenatal chromosomal microarray analysis (CMA) in fetuses with abnormal renal sonographic findings, and to evaluate the association of pathogenic or likely pathogenic copy number variants (P/LP CNVs) with different types of renal abnormality. METHODS: This was a retrospective study of fetuses at 14-36 weeks screened routinely for renal and other structural abnormalities at the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. We retrieved and analyzed data from fetuses with abnormal renal sonographic findings, examined between January 2013 and November 2019, which underwent CMA analysis using tissue obtained from chorionic villus sampling (CVS), amniocentesis or cordocentesis. We evaluated the CMA findings according to type of renal ultrasound anomaly and according to whether renal anomalies were isolated or non-isolated. RESULTS: Ten types of renal anomaly were reported on prenatal ultrasound screening, at a mean ± SD gestational age of 24.9 ± 4.8 weeks. The anomalies were diagnosed relatively late in this series, as 64% of cases with an isolated renal anomaly underwent cordocentesis rather than CVS. Fetal pyelectasis was the most common renal ultrasound finding, affecting around one-third (34.32%, 301/877) of fetuses with a renal anomaly, but only 3.65% (n = 11) of these harbored a P/LP CNV (comprising: isolated cases, 2.37% (4/169); non-isolated cases, 5.30% (7/132)). Hyperechogenic kidney was found in 5.47% (n = 48) of fetuses with a renal anomaly, of which 39.58% (n = 19) had a P/LP CNV finding (comprising: isolated cases, 44.44% (16/36); non-isolated cases, 25.00% (3/12)), the highest diagnostic yield among the different types of renal anomaly. Renal agenesis, which accounted for 9.92% (n = 87) of all abnormal renal cases, had a CMA diagnostic yield of 12.64% (n = 11) (comprising: isolated cases, 11.54% (9/78); non-isolated cases, 22.22% (2/9); unilateral cases, 11.39% (9/79); bilateral cases, 25.00% (2/8)), while multicystic dysplastic kidney (n = 110), renal cyst (n = 34), renal dysplasia (n = 27), crossed fused renal ectopia (n = 31), hydronephrosis (n = 98), renal duplication (n = 42) and ectopic kidney (n = 99) had overall diagnostic rates of 11.82%, 11.76%, 7.41%, 6.45%, 6.12%, 4.76% and 3.03%, respectively. Compared with the combined group of CMA-negative fetuses with any other type of renal anomaly, the rate of infant being alive and well at birth was significantly higher in CMA-negative fetuses with isolated fetal pyelectasis or ectopic kidney, whereas the rate was significantly lower in fetuses with isolated renal agenesis, multicystic dysplastic kidney or severe hydronephrosis. The most common pathogenic CNV was 17q12 deletion, which accounted for 30.14% (22/73) of all positive CMA findings, with a rate of 2.51% (22/877) among fetuses with an abnormal renal finding. Fetuses with 17q12 deletion exhibited a wide range of renal phenotypes. Other P/LP CNVs in the recurrent region that were associated with prenatal renal ultrasound abnormalities included 22q11.2, Xp21.1, Xp22.3, 2q13, 16p11.2 and 1q21, which, collectively, accounted for 2.17% (19/877) of the fetuses with prenatal renal anomalies. CONCLUSIONS: In this retrospective review of CMA findings in a large cohort of fetuses with different types of renal ultrasound abnormality, the P/LP CNV detection rate varied significantly (3.03-39.58%) among the different types of kidney anomaly. Our data may help in the decision regarding whether to perform prenatal genetic testing in fetuses with renal ultrasound findings. Specifically, prenatal CMA testing should be performed in cases of hyperechogenic kidney, regardless of whether or not the anomaly is isolated, while it should be performed postnatally rather than prenatally in cases of fetal pyelectasis. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Diagnostic yield of next-generation sequencing in fetuses with isolated increased nuchal translucency: systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic yield of exome or genome sequencing (ES/GS) over chromosomal microarray analysis (CMA) in fetuses with increased nuchal translucency (NT) and no concomitant anomalies. METHODS: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. PubMed, Scopus and Web of Science were searched for studies describing ES/GS in fetuses with isolated increased NT. Inclusion criteria were: (1) study written in English; (2) more than two fetuses with increased NT > 99th percentile and no concomitant anomalies; and (3) a negative CMA result considered as the reference standard. Only positive variants identified on ES/GS that were classified as likely pathogenic or pathogenic and determined to be causative of the fetal phenotype were considered. Risk was assessed as the pooled effect size by single-proportion analysis using random-effects modeling (weighted by inverse of variance). RESULTS: Eleven studies reporting on the diagnostic yield of ES/GS in fetuses with isolated increased NT > 99th percentile were identified and included 309 cases. All studies were high quality according to Standards for Reporting of Diagnostic Accuracy. Overall, a pathogenic or likely pathogenic variant was identified on ES/GS in 15 fetuses, resulting in a pooled incremental yield of 4% (95% CI, 2-6%). Six (40%) of these fetuses had NT of 5 mm or more. The observed inheritance pattern was autosomal dominant in 12 cases, including four fetuses with Noonan syndrome, autosomal recessive in two cases and X-linked in one case. CONCLUSIONS: There is a 4% incremental diagnostic yield of ES/GS over CMA in fetuses with increased NT > 99th percentile without a concomitant anomaly. It is unclear whether a NT cut-off higher than 3.5 mm may be more useful in case selection for ES/GS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Effect of routine first-trimester combined screening for pre-eclampsia on small-for-gestational-age birth: secondary interrupted time series analysis.

OBJECTIVE: To evaluate the impact of a first-trimester combined screening program for pre-eclampsia, based on the Fetal Medicine Foundation (FMF) algorithm, on the rate of small-for-gestational age (SGA) at birth and adverse pregnancy outcome. METHODS: This was a retrospective cohort study of data obtained from a London tertiary hospital between January 2017 and March 2019. The data were derived from a secondary analysis of the cohort evaluated in a clinical-effectiveness study on the implementation of a first-trimester screening program for pre-eclampsia. The cohort included 7720 women screened according to the UK National Institute for Health and Care Excellence (NICE) risk-based approach and 4841 women screened by the FMF multimodal approach, which combines maternal risk factors, blood pressure, pregnancy-associated plasma protein-A and uterine artery Doppler indices. The care package for the FMF-screened group included 150-mg aspirin prophylaxis, ultrasound scans at 28 and 36 weeks' gestation and scheduled delivery at 40 weeks. Outcome measures included the rates of SGA neonates at birth, admission to the neonatal unit, intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy assessed by interrupted time series analysis (ITSA). RESULTS: There was no significant difference in the rates of intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy between the FMF-screened and NICE-screened cohorts. ITSA showed a significant reduction in the rate of term SGA birth < 10th percentile at 21 months following implementation of the FMF screening program, with a relative effect reduction of 45.1% (P = 0.004). However, there was no significant relative effect reduction in term SGA birth < 5th or < 3rd percentile. CONCLUSIONS: First-trimester combined screening for pre-eclampsia based on the FMF algorithm accompanied by a care package including serial ultrasound scans for growth evaluation and elective birth from 40 weeks' gestation resulted in a significant 45% relative effect reduction in term SGA birth < 10th percentile but did not affect term SGA birth < 5th or < 3rd percentile. Further screening strategies to detect and improve the outcome of cases with SGA birth < 5th percentile need to be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of pre-pregnancy body mass index and gestational weight gain on the risk of maternal and infant pregnancy complications in Korean women.

BACKGROUND/OBJECTIVE: Healthy weight maintenance before and during pregnancy has a significant effect on pregnancy outcomes; however, there are no specific guidelines for gestational weight gain in pregnant Korean women. Therefore, we investigated the impact of pre-pregnancy body mass index (BMI) and gestational weight gain on the risk of maternal and infant pregnancy complications in pregnant Korean women. METHODS: Study participants comprised 3454 singleton pregnant women from the Korean Pregnancy Outcome Study who had baseline examination and pregnancy outcome data. Maternal pre-pregnancy BMI and gestational weight gain were categorized according to the Asia-pacific regional guidelines and the Institute of Medicine recommendations, respectively. The primary outcome was any adverse outcomes, defined as the presence of one or more of the following: hypertensive disorders of pregnancy, gestational diabetes mellitus, peripartum depressive symptom, cesarean delivery, delivery complications, preterm birth, small or large weight infant, neonatal intensive care unit admission, or a congenital anomaly. Multiple logistic regression models were applied to examine the independent and combined impact of pre-pregnancy BMI and gestational weight gain on the risk of maternal and infant outcomes. RESULTS: Obesity before pregnancy significantly increased the risk of perinatal adverse outcomes by more than 2.5 times [odds ratio (OR): 2.512, 95% confidence interval (CI): 1.817-3.473]. Compared to that in women with appropriate gestational weight gain, women with excessive weight gain had a 36.4% incremental increase in the risk of any adverse outcomes [OR: 1.364, 95% CI: 1.115-1.670]. Moreover, women who were overweight or obese before pregnancy and had excessive gestational weight gain had a three-fold increase in the risk of adverse outcomes [OR: 3.460, 95% CI: 2.210-5.417]. CONCLUSION: This study highlights the need for appropriate weight recommendations before and during pregnancy to prevent perinatal complications in Korean women of childbearing age.

Maternal and fetal characteristics for predicting risk of Cesarean section following induction of labor: pooled analysis of PROBAAT trials.

OBJECTIVE: Induction of labor (IOL) is one of the most widely used obstetric interventions. However, one-fifth of IOLs result in Cesarean section (CS). We aimed to assess maternal and fetal characteristics that influence the likelihood of CS following IOL, according to the indication for CS. METHODS: This was a secondary analysis of pooled data from four randomized controlled trials, including women undergoing IOL at term who had a singleton pregnancy and an unfavorable cervix, intact membranes and the fetus in cephalic presentation. The main outcomes of this analysis were CS for failure to progress (FTP) and CS for suspected fetal compromise (SFC). Restricted cubic splines were used to determine whether continuous maternal and fetal characteristics had a non-linear relationship with outcome. Optimal cut-offs for those characteristics with a non-linear pattern were determined based on the maximum area under the receiver-operating-characteristics curve. Adjusted odds ratios (aOR) were computed, using multivariable logistic regression analysis, for the associations between optimally categorized characteristics and outcome. RESULTS: Of a total of 2990 women undergoing IOL, 313 (10.5%) had CS for FTP and 227 (7.6%) had CS for SFC. The risk of CS for FTP was increased in women aged 31-35 years compared with younger women (aOR, 1.51 (95% CI, 1.15-1.99)), in nulliparous compared with parous women (aOR, 8.07 (95% CI, 5.34-12.18)) and in Sub-Saharan African compared with Caucasian women (aOR, 2.09 (95% CI, 1.33-3.28)). Higher body mass index (BMI) increased incrementally the risk of CS for FTP (aOR, 1.06 (95% CI, 1.04-1.08)). High birth-weight percentile was also associated with an increased risk of CS due to FTP (aOR, 2.66 (95% CI, 1.74-4.07) for birth weight between the 80.0th and 89.9th percentiles and aOR, 4.08 (95% CI, 2.75-6.05) for birth weight ≥ 90th percentile, as compared with birth weight between the 20.0th and 49.9th percentiles). For CS due to SFC, higher maternal age (aOR, 1.09 (95% CI, 1.05-1.12)) and BMI (aOR, 1.05 (95% CI, 1.03-1.08)) were associated with an incremental increase in risk. The risk of CS for SFC was increased in nulliparous compared with parous women (aOR, 5.91 (95% CI, 3.76-9.28)) and in South Asian compared with Caucasian women (aOR, 2.50 (95% CI, 1.23-5.10)). Birth weight < 10.0th percentile increased significantly the risk of CS due to SFC (aOR, 1.93 (95% CI, 1.22-3.05)), as compared with birth weight between the 20.0th and 49.9th percentiles. Bishop score did not demonstrate a significant association with the risk of CS for FTP or for SFC. CONCLUSIONS: In women undergoing IOL, maternal age, BMI, parity, ethnicity and birth-weight percentile are predictors of CS due to FTP and of CS due to SFC, but the direction and magnitude of the associations differ according to the indication for CS. These characteristics should be considered in combination with the Bishop score to stratify the risk of CS for different indications in women undergoing IOL. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Development and validation of model for prediction of placental dysfunction-related stillbirth from maternal factors, fetal weight and uterine artery Doppler at mid-gestation.

OBJECTIVE: To examine the performance of a model combining maternal risk factors, uterine artery pulsatility index (UtA-PI) and estimated fetal weight (EFW) at 19-24 weeks' gestation, for predicting all antepartum stillbirths and those due to impaired placentation, in a training dataset used for development of the model and in a validation dataset. METHODS: The data for this study were derived from prospective screening for adverse obstetric outcome in women with singleton pregnancy attending for routine pregnancy care at 19 + 0 to 24 + 6 weeks' gestation. The study population was divided into a training dataset used to develop prediction models for placental dysfunction-related antepartum stillbirth and a validation dataset to which the models were then applied. Multivariable logistic regression analysis was used to develop a model based on a combination of maternal risk factors, EFW Z-score and UtA-PI multiples of the normal median. We examined the predictive performance of the model by, first, the ability of the model to discriminate between the stillbirth and live-birth groups, using the area under the receiver-operating-characteristics curve (AUC) and the detection rate (DR) at a fixed false-positive rate (FPR) of 10%, and, second, calibration by measurements of calibration slope and intercept. RESULTS: The study population of 131 514 pregnancies included 131 037 live births and 477 (0.36%) stillbirths. There are four main findings of this study. First, 92.5% (441/477) of stillbirths were antepartum and 7.5% (36/477) were intrapartum, and 59.2% (261/441) of antepartum stillbirths were observed in association with placental dysfunction and 40.8% (180/441) were unexplained or due to other causes. Second, placental dysfunction accounted for 80.1% (161/201) of antepartum stillbirths at < 32 weeks' gestation, 54.2% (52/96) at 32 + 0 to 36 + 6 weeks and 33.3% (48/144) at ≥ 37 weeks. Third, the risk of placental dysfunction-related antepartum stillbirth increased with increasing maternal weight and decreasing maternal height, was 3-fold higher in black than in white women, was 5.5-fold higher in parous women with previous stillbirth than in those with previous live birth, and was increased in smokers, in women with chronic hypertension and in parous women with a previous pregnancy complicated by pre-eclampsia and/or birth of a small-for-gestational-age baby. Fourth, in screening for placental dysfunction-related antepartum stillbirth by a combination of maternal risk factors, EFW and UtA-PI in the validation dataset, the DR at a 10% FPR was 62.3% (95% CI, 57.2-67.4%) and the AUC was 0.838 (95% CI, 0.799-0.878); these results were consistent with those in the dataset used for developing the algorithm and demonstrate high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 1.029 and the intercept was -0.009, demonstrating good agreement between the predicted risk and observed incidence of placental dysfunction-related antepartum stillbirth. The performance of screening was better for placental dysfunction-related antepartum stillbirth at < 37 weeks' gestation compared to at term (DR at a 10% FPR, 69.8% vs 29.2%). CONCLUSIONS: Screening at mid-gestation by a combination of maternal risk factors, EFW and UtA-PI can predict a high proportion of placental dysfunction-related stillbirths and, in particular, those that occur preterm. Such screening provides poor prediction of unexplained stillbirth or stillbirth due to other causes. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal metal exposure, cord blood DNA methylation and persistence in childhood: an epigenome-wide association study of 12 metals.

BACKGROUND: Prenatal exposure to essential and non-essential metals impacts birth and child health, including fetal growth and neurodevelopment. DNA methylation (DNAm) may be involved in pathways linking prenatal metal exposure and health. In the Project Viva cohort, we analyzed the extent to which metals (As, Ba, Cd, Cr, Cs, Cu, Hg, Mg, Mn, Pb, Se, and Zn) measured in maternal erythrocytes were associated with differentially methylated positions (DMPs) and regions (DMRs) in cord blood and tested if associations persisted in blood collected in mid-childhood. We measured metal concentrations in first-trimester maternal erythrocytes, and DNAm in cord blood (N = 361) and mid-childhood blood (N = 333, 6-10 years) with the Illumina HumanMethylation450 BeadChip. For each metal individually, we tested for DMPs using linear models (considered significant at FDR < 0.05), and for DMRs using comb-p (Sidak p < 0.05). Covariates included biologically relevant variables and estimated cell-type composition. We also performed sex-stratified analyses. RESULTS: Pb was associated with decreased methylation of cg20608990 (CASP8) (FDR = 0.04), and Mn was associated with increased methylation of cg02042823 (A2BP1) in cord blood (FDR = 9.73 × 10-6). Both associations remained significant but attenuated in blood DNAm collected at mid-childhood (p < 0.01). Two and nine Mn-associated DMPs were identified in male and female infants, respectively (FDR < 0.05), with two and six persisting in mid-childhood (p < 0.05). All metals except Ba and Pb were associated with ≥ 1 DMR among all infants (Sidak p < 0.05). Overlapping DMRs annotated to genes in the human leukocyte antigen (HLA) region were identified for Cr, Cs, Cu, Hg, Mg, and Mn. CONCLUSIONS: Prenatal metal exposure is associated with DNAm, including DMRs annotated to genes involved in neurodevelopment. Future research is needed to determine if DNAm partially explains the relationship between prenatal metal exposures and health outcomes.

Syphilis testing adherence among women with livebirth deliveries: Indianapolis 2014-2016.

BACKGROUND: The number of congenital syphilis (CS) cases in the United States are increasing. Effective prevention of CS requires routine serologic testing and treatment of infected pregnant women. The Centers for Disease Control and Prevention (CDC) recommends testing all pregnant women at their first prenatal visit and subsequent testing at 28 weeks gestation and delivery for women at increased risk. METHODS: We conducted a cross-sectional cohort study of syphilis testing among pregnant women with a livebirth delivery from January 2014 to December 2016 in Marion County, Indiana. We extracted and linked maternal and infant data from the vital records in a local health department to electronic health records available in a regional health information exchange. We examined syphilis testing rates and factors associated with non-testing among women with livebirth delivery. We further examined these rates and factors among women who reside in syphilis prevalent areas. RESULTS: Among 21260 pregnancies that resulted in livebirths, syphilis testing in any trimester, including delivery, increased from 71.7% in 2014 to 86.6% in 2016. The number of maternal syphilis tests administered only at delivery decreased from 16.6% in 2014 to 4.04% in 2016. Among women living in areas with high syphilis rates, syphilis screening rates increased from 79.6% in 2014 to 94.2% in 2016. CONCLUSION: Improvement in prenatal syphilis screening is apparent and encouraging, yet roughly 1-in-10 women do not receive syphilis screening during pregnancy. Adherence to recommendations set out by CDC improved over time. Given increasing congenital syphilis cases, the need for timely diagnoses and prevention of transmission from mother to fetus remains a priority for public health.

Prenatal diagnosis of thalassemia in 695 pedigrees from southeastern China: a 10-year follow-up study.

Thalassaemia is highly prevalent in southeastern China. This 10-year follow-up study aimed to characterize the genotype and karyotype of thalassaemia in fetal samples derived from thalassemia carriers in Fujian province, southeastern China. A total of 476 prenatal samples from 472 couples carrying α-thalassaemia traits and 224 samples from 223 couples carrying ß-thalassaemia traits were collected for STR analysis, detection of thalassemia genotypes and karyotyping. The common deletional α-thalassemias and rare thalassemia genotypes were detected using Gap-PCR assay, and the common ß-globin gene mutations were detected using PCR-RDB assay. We detected 43.49% prevalence of α-thalassaemia minor, 26.05% prevalence of α-thalassaemia intermediate and major and 1.89% prevalence of rare form among the 476 prenatal samples from couples with α-thalassaemia, and 85 fetuses with ß-thalassemia heterozygote, 16 with homozygote and 21 with double heterozygote, and a rare ßIVS-2-654(C→T) /Chinese Gγ (A γδß)0  genotype among the 224 prenatal samples from couples with ß-thalassemia. Karyotyping showed 7 fetuses with abnormal karyotypes. Totally 153 pregnancies were terminated, and genetic diagnosis of thalassemia using fetal umbilical cord blood following induction of labor showed consistent results with prenatal diagnosis. No thalassemia phenotypes were identified in normal infants half a year after birth, and the infants with α-thalassemia and ß-thalassemia minor had no or mild anemia symptoms, but normal development, while 15 babies with hemoglobin H disease presented moderate anemia symptoms. Our data suggest the pregestational screening of thalassemia, notably compound and rare forms of thalassemia, for couples carrying thalassemia traits.

Cell-free DNA screening for fetal aneuploidy using the rolling circle method: A step towards non invasive prenatal testing simplification.

OBJECTIVE: To assess the efficacy of cell-free (cf)DNA screening for aneuploidy using the automated system based on rolling circle replication. METHODS: A prospective study among women referred for invasive prenatal diagnosis between July 2018 and December 2019. The plasma fraction was extracted within 5 days from blood collection, stored at -20°C and cfDNA measured between January and December 2019. RESULTS: A total of 805 women were recruited; 778 with singleton pregnancies and 27 twins. There were 48 Down syndrome, 25 Edwards syndrome and 3 Patau syndrome cases. Overall, the no-call rate was 2.6% (95% confidence interval 1.6%-3.9%) which reduced from 4.7% to 1.1% after relocation of the system (p < 0.002) to ensure a constant ambient temperature below 25°C. In singletons the Down syndrome detection rate (DR) was 100% (93%-100%) and false-positive rate (FPR) 0.14% (0.00%-0.79%). The Edwards syndrome DR was 96% (80%-100%) and FPR 0.78% (0.29%-1.7%). One false-positive had a confined placental trisomy 18 and the remaining five a z-score requiring sample repetition; all the false-positives occurred before system relocation (p < 0.005). Patau syndrome DR and FPR were 67% (9.4%-99%) and 0.26% (0.03%-0.95%). CONCLUSION: The cfDNA rolling circle method yields similar results to other methods provided that room temperature is adequately controlled.

Mothers' perception of prenatal counseling following diagnosis of congenital anomalies of the urinary tract.

Congenital abnormalities of the genitourinary tract are the most common sonographically identified malformations. Although prenatal diagnosis seldom modifies perinatal management, it can cause significant anxiety in parents. We aimed to assess how parents perceived the prenatal counseling they had received in our institution. Using a questionnaire, we evaluated by phone the mothers of 78 children diagnosed prenatally with urological tract anomalies between January 2018 and May 2019. Overall, mothers were satisfied and reassured by the prenatal counseling they received, although 19% of the mothers found the time from diagnosis to specialist consultation to be too long. Forty percent of the responders stated that the most important information they needed to hear during the specialist consultation was management and not diagnosis. Specialist counseling should focus on explaining postnatal management, should be offered as soon as possible, and should include practical aspects, especially concerning outpatient care.

Gestational body weight gain and risk of low birth weight or macrosomia in women of Japan: a nationwide cohort study.

OBJECTIVE: Both maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) influence maternal and pediatric outcomes. We sought to clarify the impact of prepregnancy BMI-specific GWG and its patterns on the risk of low birth weight (LBW) or macrosomia using data from a large nationwide study in Japan. METHODS: This cohort study (n = 98,052) used data from the Japan Environment and Children's Study (JECS). The outcome variables in this study were LBW and macrosomia. We stratified the subjects into groups according to prepregnancy BMI. RESULTS: GWG from pre-pregnancy to the first trimester had a small effect on the risk of LBW and macrosomia. From the first to second trimesters, insufficient GWG was associated with the risk of LBW, and from the second trimester to delivery, a GWG of less than 2 kg was associated with the risk of LBW. These associations were commonly observed in all prepregnancy BMI categories. Irrespective of the GWG from pre-pregnancy to the first trimester, GWG from the first to second trimesters affects LBW and/or macrosomia. Irrespective of the GWG from the first to second trimesters, GWG from the second trimester to delivery affects LBW and/or macrosomia. LBW or macrosomia was associated with the prevalence of a sustained low or high BMI percentile until three years of age, respectively. CONCLUSIONS: The present large national cohort study indicates that the risk of LBW or macrosomia is associated with GWG in women in Japan; the significance of this risk depends on the GWG patterns.