A homozygous variant in growth and differentiation factor 2 (GDF2) may cause lymphatic dysplasia with hydrothorax and nonimmune hydrops fetalis.

The etiology of nonimmune hydrops fetalis is extensive and includes genetic disorders. We describe a term-born female neonate with late onset extensive nonimmune hydrops, that is, polyhydramnios, edema, and congenital bilateral chylothorax. This newborn was successfully treated with repetitive thoracocentesis, total parenteral feeding, octreotide intravenously and finally surgical pleurodesis and corticosteroids. A genetic cause seemed plausible as the maternal history revealed a fatal nonimmune hydrops fetalis. A homozygous truncating variant in GDF2 (c.451C>T, p.(Arg151*)) was detected with exome sequencing. Genetic analysis of tissue obtained from the deceased fetal sibling revealed the same homozygous variant. The parents and two healthy siblings were heterozygous for the GDF2 variant. Skin and lung biopsies in the index patient, as well as the revised lung biopsy of the deceased fetal sibling, showed lymphatic dysplasia and lymphangiectasia. To the best of our knowledge, this is the first report of an association between a homozygous variant in GDF2 with lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis.

Risks versus benefits of medication use during pregnancy: what do women perceive?

BACKGROUND: Understanding perception of risks and benefits is essential for informed patient choices regarding medical care. The primary aim of this study was to evaluate the perception of risks and benefits of 9 drug classes during pregnancy and associations with women's characteristics. METHODS: Questionnaires were distributed to pregnant women who attended a Dutch Obstetric Care facility (first- and second-line care). Mean perceived risk and benefit scores were computed for 9 different drug classes (paracetamol, antacids, antibiotics, antifungal medication, drugs against nausea and vomiting, histamine-2 receptor antagonists/proton pump inhibitors, antidepressants, nonsteroidal anti-inflammatory drugs, and sedatives/anxiolytics). For each participant, we computed weighted risk and benefit sum scores with principal component analysis. In addition, major concerns regarding medication use were evaluated. RESULTS: The questionnaire was completed by 136 women (response rate 77%). Pregnant women were most concerned about having a child with a birth defect (35%), a miscarriage (35%), or their child developing an allergic disease (23%), respectively, as a result of drug use. The majority of studied drug classes were perceived relatively low in risk and high in benefit. Higher risk scores were reported if women were in their first trimesters of pregnancy (p=0.007). Lower benefit scores were reported if women were single (p=0.014), smoking (p=0.028), nulliparous (p=0.006), or did not have a family history of birth defects (p=0.005). CONCLUSION: Pregnant women's concerns regarding potential drug adverse effects were not only focused on congenital birth defects but also included a wider range of adverse outcomes. This study showed that most of the studied drug classes were perceived relatively low in risk and high in benefit.

Prediction of cesarean section risk in women with gestational hypertension or mild preeclampsia at term.

OBJECTIVE: In a recent randomized controlled trial we found that induction of labor in women with gestational hypertension (GH) or mild (preeclampsia) PE at term prevented high risk situations without increasing the cesarean section (CS) rate. We aimed to assess the predictability of the risk of CS. STUDY DESIGN: We used multivariable logistic regression analysis to identify predictive factors. Two models were created, one including antepartum and one including antepartum and intrapartum variables. The predictive capacity was assessed with ROC analysis and calibration. RESULTS: 126 (17%) of the 756 women delivered by CS. In multivariable analysis parity (OR 5.4), ethnicity (OR 2.4), previous miscarriage (OR 1.7), creatinine (OR 1.02), proteinuria (OR 2.4), cervical length (OR 1.02), engagement (OR 0.5) and dilatation (OR 0.7) were independent antepartum predictors. Intrapartum variables were parity (OR 3.6), ethnicity (OR 1.9), previous miscarriage (OR 1.5), gestational age at delivery (OR 1.2), antibiotic use (OR 8.0), disease progression (OR 2.4), uric acid (OR 1.4), proteinuria (OR 3.50) and dilatation (OR 0.76). Both models showed good discrimination (AUC 0.74 and 0.80) but calibration was moderate (Hosmer-Lemeshow P-value 0.42 and 0.70). CONCLUSION: In women with GH or mild PE at term, the risk of CS can be predicted.

The effect of maternal ketanserin use on the circulation of the neonate: a prospective, observational study.

OBJECTIVE: High ketanserin levels are found in the umbilical cord after maternal treatment. However, the effect on the circulation of the neonate has never been investigated. STUDY DESIGN: A prospective, observational study was performed at the neonate ward at the Medical Centre Leeuwarden, The Netherlands. All neonates exposed in utero to ketanserin administered to the mother, from May 2007 to December 2009 (n=58), were included. We studied the effect of ketanserin exposure on the circulation of the neonate, by monitoring heart rate and blood pressure during the first 24h of life. Non-parametric as well as parametric tests were used to analyze the effect of gestational age, birth weight, gender, various ketanserin factors (cumulative dosage, duration of therapy and last dosage rate), other maternal drug use and maternal diagnosis on the blood pressure of the neonate. RESULTS: Eight neonates became hypotensive during the first 8h of life (13.8%). The last dosage rate as well as the mean dosage rate (cumulative dosage divided by duration of therapy in hours) were significantly higher in the group with hypotension (P=.005 and P=.002, respectively). All hypotensive neonates were exposed to a last dosage rate of at least 8 mg/h. Maternal HELLP syndrome was diagnosed more often in hypotensive compared to normotensive neonates (P=.048). CONCLUSION: In utero exposure to ketanserin lowers the blood pressure of the neonate. The risk of hypotension is associated with the last dosage rate of maternal ketanserin treatment and the co-existence of maternal HELLP syndrome.

Thrombophilia is not associated with an increase in placental abnormalities in women with intra-uterine fetal death.

BACKGROUND: The aim of this study was to investigate whether women with thrombophilia and intrauterine fetal death have a higher incidence of placental lesions as compared with those without thrombophilia. METHOD: In a case-control study comprising 50 women with an obstetrical history of intrauterine fetal death, placental histology comparison was made between those with thrombophilia and those without thrombophilia. RESULTS: Of the women who had an intrauterine fetal death, eight (16%) had a thrombophilia factor. There were no differences in birth weight, gestational age and parity or in placental volume and weight between the eight women with and the 42 women without thrombophilia. There was no statistically significant difference between placentas of the women with and those without thrombophilia. CONCLUSION: In a group of women who had an obstetrical history of intrauterine fetal death, those with thrombophilia do not have a difference in placental histological lesions compared with the women without a thrombophilia factor. Future thrombophilia research should be focused on placental bed specimens.