A Comparison of Vaginal and Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth

Objective To examine whether vaginal progesterone is noninferior to 17-α hydroxyprogesterone caproate (17OHP-C) in the prevention of recurrent preterm birth (PTB). Study Design This retrospective cohort study included singleton pregnancies among women with a history of spontaneous PTB who received prenatal care at a single tertiary center from 2011 to 2016. Pregnancies were excluded if progesterone was not initiated prior to 24 weeks or the fetus had a major congenital anomaly. The primary outcome was PTB <37 weeks. A priori, noninferiority was to be established if the upper bound of the adjusted two-sided 90% confidence interval (CI) for the difference in PTB fell below 9%. Inverse probability of treatment weighting (IPTW) was used to carefully control for confounding associated with choice of treatment and PTB. Adjusted differences in PTB proportions were estimated via IPTW regression, with standard errors adjustment for multiple pregnancies per woman. Secondary outcomes included PTB <34 and <28 weeks, spontaneous PTB, neonatal intensive care unit admission, and gestational age at delivery. Results Among 858 pregnancies, 41% (n = 353) received vaginal progesterone and 59% (n = 505) were given 17OHP-C. Vaginal progesterone use was more common later in the study period, and among women who established prenatal care later, had prior PTBs at later gestational ages, and whose race/ethnicity was neither non-Hispanic white nor non-Hispanic black. Vaginal progesterone did not meet noninferiority criteria compared with 17-OHPC in examining PTB <37 weeks, with an IPTW adjusted difference of 3.4% (90% CI: −3.5, 10.3). For secondary outcomes, IPTW adjusted differences between treatment groups were generally small and CIs were wide. Conclusion We could not conclude noninferiority of vaginal progesterone to 17OHP-C; however, women and providers may be willing to accept a larger difference (>9%) when considering the cost and availability of vaginal progesterone versus 17OHP-C. A well-designed randomized trial is needed. Key Points

Monogenic Syndromes with Congenital Heart Diseases in Newborns (Diagnostic Clues for Neonatologists): A Critical Analysis with Systematic Literature Review

Congenital heart disease (CHD), the most common major congenital anomaly, is associated with a genetic syndrome (chromosomal anomalies, genomic disorders, or monogenic disease) in 30% of patients. The aim of this systematic review is to evaluate if, in the neonatal setting, clinical clues that orient the diagnostic path can be identified. For this purpose, we revised the most frequent dysmorphic features described in newborns with CHD, comparing those associated with monogenic syndromes (MSG) with the ones reported in newborns with genomic disorders. For this systematic review according to PRISMA statement, we used PubMed, Medline, Google Scholar, Scopus database, and search terms related to CHD and syndrome. We found a wide range of dysmorphisms (ocular region, ears, mouth, and/or palate and phalangeal anomalies) detected in more than half of MSGs were found to be associated with CHDs, but those anomalies are also described in genomic rearrangements syndromes with equal prevalence. These findings confirm that etiological diagnosis in newborns is challenging, and only the prompt and expert recognition of features suggestive of genetic conditions can improve the selection of appropriate, cost-effective diagnostic tests. However, in general practice, it is crucial to recognize clues that can suggest the presence of a genetic syndrome, and neonatologists often have the unique opportunity to be the first to identify abnormalities in the neonate.

Mid-Trimester Scan is better for Detecting Congenital Anomalies: An Experience from Dhulikhel Hospital

Introduction: Ultrasound is a valuable diagnostic tool for detecting the congenital anomalies in the fetus. Congenital anomalies are detected in 14% of new born. Major anomalies are detected in 2 to 5% of new born. This accounts for 20 % to 30% of total perinatal deaths. Prenatal diagnosis provides variety of management options for the pregnant women ranging from termination of pregnancy, elective delivery or intrauterine manipulation of the anomalies. Aims: To determine the prevalence of the fetal congenital anomalies at 20- 24 weeks ultrasonography. Methods: This is prospective study conducted at Dhulikhel Hospital. Pregnant ladies with singleton pregnancy at 20 to 24 weeks were enrolled for transabdominal ultrasound for detecting congenital anomalies. Results: Of 1027 pregnant ladies screened, anomalies were detected in 31 ladies during mid trimester ultrasound. The overall prevalence of congenital anomalies detected in our study is 3.02% (31 cases), which has sensitivity of 87.8%, specificity of 99.7% and positive predictive values of 93.5%. In our study, mean gestational age during scan was 21+5 weeks of gestation. And 13 pregnant ladies pregnancies were terminated between 20-24 weeks for having major congenital anomaly in fetus. Conclusion: Mid trimester ultrasonography is a valuable method for pregnant ladies to detect the congenital anomalies in fetus. When major anomalies are detected, timely termination of pregnancy have saved the cost and tragedy of losing viable fetus.

Congenital Diaphragmatic Hernia: A Major Challenge for Neonatologists

Congenital diaphragmatic hernia (CDH) is a major congenital anomaly of the neonates, characterized by the herniation of abdominal contents into the thoracic cavity during fetal life. This results in significant pulmonary hypertension and hypoxemia after birth, which responds poorly to therapeutic interventions. CDH is associated with high morbidity and mortality. The exact pathogenesis is not well understood, and genetic factors have been proposed. The management starts in utero, with antenatal diagnosis and identification of prenatal predictors for the outcomes, which help in the selection of cases suitable for fetal therapy. The postnatal management is complicated by the need for variable cardio-respiratory support and even extra corporeal membrane oxygenation (ECMO), before corrective surgery is undertaken. Improvement in the understanding of the pathophysiology of the underdeveloped lungs and pulmonary vessels has contributed to substantial progress in the management of CDH, which has translated into improved outcomes and survival. Still, many questions regarding CDH remain unanswered and the management is largely based on weak evidence.

Pregnancy outcomes after exposure to interferon beta: a register-based cohort study among women with MS in Finland and Sweden

Background Our aim was to estimate and compare the prevalence of adverse pregnancy outcomes among pregnant women with multiple sclerosis (MS) exposed to interferon beta (IFNB) and among women with MS unexposed to any MS disease-modifying drug (MSDMD). Methods This cohort study used Finnish (1996–2014) and Swedish (2005–2014) national register data. Women with MS having IFNB dispensed 6 months before or during pregnancy as the only medication were considered as IFNB exposed (only IFNB-exposed), whereas women with MS unexposed to any MSDMD were considered unexposed (MSDMD-unexposed). Prevalence was described and compared using log-binomial or logistic regression and adjusted for potential confounders including maternal age and comorbidity. Results Among 2831 pregnancies, 2.2% of the only IFNB-exposed and 4.0% of the MSDMD-unexposed women had serious adverse pregnancy outcomes [elective termination of pregnancy due to foetal anomaly (TOPFA), major congenital anomaly (MCA) in live, or stillbirth]. After adjustments, the prevalence of serious adverse pregnancy outcomes was lower among the only IFNB-exposed compared with the MSDMD-unexposed [relative risk 0.55, 95% confidence interval (CI) 0.31–0.96]. The prevalence of individual outcomes, including MCA, spontaneous abortions, and stillbirths was not increased with IFNB exposure. Women with MS exposed to IFNB appeared more likely to terminate their pregnancy for reasons other than foetal anomaly, compared with MSDMD-unexposed pregnant MS patients (odds ratio 1.71, 95% CI 1.06–2.78). Conclusion In this large cohort study, no increase in the prevalence of adverse pregnancy outcomes was observed in women with MS exposed to IFNB compared with MS patients unexposed to any MSDMDs. This study together with other evidence led to a change in the labels of the IFNB products in September 2019 in the European Union, and IFNB use today may be considered during pregnancy, if clinically needed.

Insulin analogues use in pregnancy among women with pregestational diabetes mellitus and risk of congenital anomaly: a retrospective population-based cohort study

ObjectivesTo evaluate the risk of major congenital anomaly associated with first-trimester exposure to insulin analogues compared with human insulin in offspring of women with pregestational diabetes.Design and settingA population-based cohort of women with pregestational diabetes (n=1661) who delivered between 1996 and 2012 was established retrospectively from seven European regions covered bythe European Surveillance of Congenital Anomalies (EUROCAT) congenital anomaly registries.Primary outcome measuresThe risk of non-chromosomal major congenital anomaly in live births, fetal deaths and terminations for a fetal anomaly exposed to insulin analogues in the first trimester of pregnancy was compared with the risk in those exposed to human insulin only.ResultsDuring the first trimester, 870 fetuses (52.4%) were exposed to human insulin only, 397 fetuses (23.9%) to insulin analogues only and 394 fetuses (23.7%) to both human insulin and insulin analogues. The risk of major congenital anomaly in fetuses exposed to insulin analogues only was lower than those exposed to human insulin only; the relative risk adjusted for glycaemic control and region was 0.56 (95% CI 0.29 to 1.06). The significantly lower risk related to exposure of insulin analogues only was observed in congenital heart defects: adjusted relative risk 0.14 (95% CI 0.03 to 0.62).ConclusionsIn this retrospective population-based cohort study across Europe, first-trimester exposure to insulin analogues did not increase the risk of major congenital anomaly compared with exposure to human insulin. A possible lower risk of congenital heart defects among fetuses exposed to insulin analogues only deserves further investigation.

Dystocia due to Schistosoma Reflexus and its Management through Fetotomy: A Case Report

Schistosomus reflexus (SR) is seen most commonly in cattle, but is rare in sheep, goat and swine (Roberts et al., 1971). The highest prevalence of SR is believed to occur in cattle ranging from a low of 0.01% (Sloss and Johnston, 1967) to a high of 1.3% (Knight, 1996) of bovine dystocia. Such occurrences are costly to the cattle industry because of the reduction in the number of viable offspring, loss of milk production, infertility or prolonged inter-calving interval and expenses on management of dystocia. Schistosomus reflexus is a major congenital anomaly which occurs during embryonic development. The aetiology is unknown but it may be due to genetic factors, mutation, chromosomal anomalies, infectious agents and environmental factors or combination of all the factors (Ozsoy et al., 2009). The main defect is acute angulations of the vertebral column such that the tail lies close to the head. This fatal congenital syndrome is characterized by the presence of exposed abdominal and sometimes thoracic viscera (Noakes et al., 2002). The present case report describes dystocia due to schistosomus reflexus in a Hariana cow and its successful management through fetotomy.