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Background Intrahepatic cholestasis of pregnancy (ICP) is characterised by otherwise unexplained maternal pruritus, increased serum bile acid concentration over 10 μmol/L and spontaneous relief of symptoms and liver abnormalities after delivery. It occurs most frequently during the third trimester and is usually not induced by medication. Besides, azathioprine is recommended as first-line immunosuppressant in patients with steroid-dependent inflammatory bowel disease and is allowed during pregnancy, in order to stabilize maternal disease. Methods We reviewed all cases of ICP between 2010 and 2018 in two French perinatal centers. Results We encountered eight pregnancies complicated by atypical ICP among patients treated with azathioprine. ICP associated with azathioprine appears to be biologically more severe and to occur earlier than "standard" ICP. Furthermore, clinical and biochemical abnormalities related to ICP disappear when azathioprine is discontinued. Azathioprine safety should be reconsidered and practitioners advised to discuss discontinuing this drug as soon as ICP diagnosis is established.

Preterm premature rupture of membranes (PPROM) is associated with an increased risk of serious maternal, fetal, and neonatal morbidities. We compared neonatal outcomes of women with PPROM before 34+0 weeks of gestation according to inpatient or outpatient management policy. 587 women with PPROM >48 hours, 246 (41.9%) in the group with an inpatient care policy (ICP) and 341 (58.1%) in the group with an outpatient care policy (OCP), were identified in France, from 2009 to 2012. Neonatal outcomes were compared between the two groups using logistic regression. A second analysis was performed to compare inpatient care and effective outpatient care (discharge from hospital) through propensity score matching. The outcome was a neonatal composite variable including one or more of the neonatal morbidity complications. The perinatal composite outcome was 14.6% with the ICP and 15.5% with the OCP (p = 0.76). After using the 1:1 ratio propensity score matching, effective outpatient care was not associated with a significantly higher risk of the perinatal composite outcome (OR 0.88, CI 0.35 to 2.25; p = 0.80) compared with inpatient care. Outpatient care is not associated with an increased rate of obstetric or neonatal complications and can be an alternative to hospital care for women with uncomplicated PPROM.

Objective To study changes in the reasons for third-trimester termination of pregnancy (TOP) for fetal anomalies over a 20-year period in France. Study design We compared a consecutive series of third-trimester TOPs from a single centre in 2005–2014 to those performed by Dommergues et al. in a similar centre in 1986–1994, using the same criteria. Main outcome measures The process leading to late TOP, using the same categories in both studies. Results In the present series, 205 of 1409 TOPs were performed in the third trimester, vs. 305/956 in the historical series. There were 33 (16.1 %) diagnoses missed at the screening before the third trimester, 55 (26.8 %) cases in which the anomaly was impossible to diagnose until the third trimester, 86 (42 %) cases in which fetal prognosis could not be established until the third trimester despite earlier diagnosis, 31 (15.1 %) TOPs postponed to allow more time for the women/couples to contemplate, versus respectively 113 (37 %), 55 (18 %), 122 (40 %), and 15 (5%) in the historical series. Conclusion There was a significant drop in the rate of anomalies missed earlier. The increase in late TOP due to couples requiring additional time for contemplation might result from changes in counselling processes.

Objective Pyruvate dehydrogenase deficiency (PDHD) and pyruvate carboxylase deficiency (PCD) are diseases with severe neonatal forms, and their low prevalence makes them difficult to diagnose during pregnancy. Our objective was to describe prenatal ultrasound features that may be suggestive of these diagnoses. Methods We analyzed 3 cases from our institution and reviewed 12 published cases of PDHD and 6 cases of PCD, recording all of the ultrasound signs, as well as magnetic resonance findings when available. Because of the small number of cases of PCD, we also included postnatal signs that could have been observed during imaging during pregnancy, for a total of 11 cases of PCD. Results We conclude that PDHD can be suggested in the presence of ventriculomegaly or paraventricular cysts, associated with an abnormality of the cerebral parenchyma such as abnormal gyration or involvement of the corpus callosum. Pyruvate carboxylase deficiency can be suggested in the presence of ventriculomegaly, frontal horn impairment associated with subependymal, and paraventricular cysts. Conclusion When confronted to the ultrasound abnormalities we described, and after eliminating the most frequent etiologies, a metabolic deficiency should be considered. Furthermore, the hereditary character of these diseases makes that it is important to send the family with genetic advice in particular in case of history of a fetal death in utero or a death neonatal unexplained.

OBJECTIVE To determine the transplacental pharmacokinetics of the HIV integrase strand transfer inhibitor elvitegravir and of cobicistat, a cytochrome P450 inhibitor used as a pharmacoenhancer in antiretroviral therapy. DESIGN AND METHODS Maternal-to-fetal transfer across the term human placenta was investigated with the ex-vivo dually perfused cotyledon model, in seven open-circuit experiments and 10 closed-circuit (recirculating) experiments. Elvitegravir and cobicistat were added to a maternal perfusate containing 2 g/l of human serum albumin and antipyrine, as a marker to validate the cotyledon's viability. Elvitegravir and cobicistat concentrations were measured using ultraperformance liquid chromatography coupled with tandem mass spectrometry. RESULTS For elvitegravir, in open-circuit experiments the mean (±SD) fetal transfer rate (FTR) (fetal/maternal concentration at steady state from 30 to 90 min) was 19 ± 13% and the mean clearance index was 0.46 ± 0.21; in the closed-circuit model, after 3 h of perfusion the FTR was 20 ± 10% and the mean accumulation index was 12.28 ± 5.57. For cobicistat, in the open perfusions the FTR was 23 ± 13% and the mean clearance index was 0.63 ± 0.34; in the closed perfusions after 3 h the fetal-to-maternal ratio of cobicistat was 21 ± 11%. The mean accumulation index was 3.46 ± 2.19 CONCLUSION:: The two models concurred to show moderate placental transfer of elvitegravir and cobicistat across the placenta as well as elvitegravir accumulation in the placenta tissue. Whether this may lead to toxicities and modifications in fetal or placental metabolism requires clinical studies.

Preterm prelabor rupture of membranes is a frequent obstetric condition associated with increased risks of maternal and neonatal morbidity and mortality. Conventional management is in hospital. Outpatient management is an alternative in selected cases; however, the safety of home management has not been established.To study the obstetric and neonatal outcomes of women with preterm premature rupture of membranes between 24 and 34 weeks who were managed as outpatient (outpatient care group), compared with those managed in hospital (hospital care group).A retrospective cohort study between 1 January 2009 and 31 December 2013 in three French tertiary care centers.Ninety women were included in the outpatient care group and 324 in the hospital care group. In the outpatient care group, the gestational age at membrane rupture was lower, compared to the hospital care group (28.8 (26.6-30.5) vs. 30.3 (27.6-32.1) weeks; p .01) and the cervical length at admission was higher (31.7 ± 10.4 vs. 24.3 ± 11.8 mm; p .01). In the outpatient care group, no delivery or major obstetric complication occurred at home.We observed no major complication related to home care after a period of observation. A randomized study would be necessary to confirm its safety.

Background Delayed interval delivery is a rare practice aiming at prolonging gestation for the second twin in case of pre-viable birth of twin one. Our objective was to identify factors related to successful delayed delivery of the second twin, among cases in which the interval after delivery of the first twin was above 24 h. Method A descriptive, retrospective and multicenter study of all delayed interval deliveries in dichorionic twins in 4 perinatal centers in Paris over a 14-year period. Results In 13 cases of delayed interval delivery, delivery of twin 1 was at a median of 18 weeks’ gestation (range 14 W G+2days to 24 W G), and none survived. Delivery of the second twin occurred at a median of 25 weeks’ gestation +3 days, 51 days after twin 1 (range 13–138 days). Seven of the 13 s twins (54 %) survived. There were 5 cases of chorioamnionitis and 1 case of maternal disseminated intravascular coagulation. Poor outcome was not significantly associated with the gestational age, presentation for PPROM or inflammatory markers (C-reactive protein and white blood cell count) at the time of delivery of twin 1. Conclusion Delayed-interval delivery of the second twin may prolong pregnancy and lead the second twin child to a viable term of birth; but carries a risk of maternal complications.