Time points and risk factors for RhD immunizations after the implementation of targeted routine antenatal anti-D prophylaxis:a retrospective nationwide cohort study

Abstract Background: Targeted routine antenatal anti-D prophylaxis was introduced to the national prophylaxis program in Finland in late 2013. The aim of this study was to assess the incidence, time-points, and risk factors for Rhesus D immunization after the implementation of routine antenatal anti-D prophylaxis, in all women in Finland with antenatal anti-D antibodies detected in 2014–2017. Material and methods: In a nationwide population-based retrospective cohort study, the incidence, time-points, and risk factors of anti-D immunizations were analyzed. Information on antenatal screening was obtained from the Finnish Red Cross Blood Service database, and obstetric data from hospital records and the Finnish Medical Birth Register. Results: The study included a total of 228 women (197 with complete data for all pregnancies). After the implementation of routine antenatal anti-D prophylaxis, the prevalence of pregnancies with anti-D antibodies decreased from 1.52% in 2014 to 0.88% in 2017, and the corresponding incidence of new immunizations decreased from 0.33% to 0.10%. Time-points for detection of new anti-D antibodies before and after 2014 were the first screening sample at 8–12 weeks of gestation in 52% vs 19%, the second sample at 24–26 weeks in 20% vs 50%, and the third screening at 36 weeks in 28% vs 32%. Conclusions: The incidence of new anti-D immunizations decreased as expected after the implementation of routine antenatal anti-D prophylaxis. True failures are rare and they mainly occur when the prophylaxis is not given appropriately, suggesting a need for constant education of healthcare professionals on the subject

The efficacy of misoprostol vaginal insert compared with oral misoprostol in the induction of labor of nulliparous women:a randomized national multicenter trial

Abstract Introduction: Our objective was to compare the efficacy of a 200‐μg misoprostol vaginal insert vs oral misoprostol regarding the cesarean section rate and the time interval to vaginal delivery in nulliparous women with unfavorable cervix. Material and methods: In this prospective multicenter trial, 283 nulliparous women at term with Bishop score <6 were randomized to induction of labor with either a misoprostol vaginal insert (n = 140) or oral misoprostol (n = 143). In the oral misoprostol group, a 50‐μg dose of oral misoprostol was administered every 4 hours up to three times during the first day; during the second day, the dose was increased to 100‐μg every 4 hours up to three times during the first day, if necessary. Primary outcome was the cesarean section rate. Secondary outcomes were the time from induction of labor to vaginal delivery, the rate of other induction methods needed, labor augmentation with oxytocin and/or amniotomy, use of tocolytics and adverse neonatal and maternal events. Results: In the misoprostol vaginal insert group, median time to vaginal delivery was shorter (24.5 hours vs 44.2 hours, P < 0.001), whereas no difference was found in the cesarean section rate (33.8% vs 29.6%, odds ratio [OR] 1.21, 95% confidence interval [CI] 0.66–1.91, P = 0.67). Other induction methods and labor augmentation with oxytocin and/or amniotomy were less frequent in the misoprostol vaginal insert group (OR 0.32, 95% CI 0.18–0.59 and OR 0.56, 95% CI 0.32–0.99, respectively). Need for tocolysis and meconium‐stained amniotic fluid were more common in the misoprostol vaginal insert group (OR 3.63, 95% CI 1.12–11.79 and OR 2.38, 95% CI 1.32–4.29, respectively). Maternal and neonatal adverse events did not differ between groups. Conclusions: Misoprostol vaginal insert proved to shorten the time to vaginal delivery and to reduce the use of other methods of labor induction and augmentation, but it did not reduce the cesarean section rate compared with oral misoprostol. The benefit of more rapid delivery associated with misoprostol vaginal insert should be weighed against the greater risks for uterine hyperstimulation and meconium‐stained amniotic fluid

Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy

In pregnancy, trophoblast invasion and uterine spiral artery remodeling are important for lowering maternal vascular resistance and increasing uteroplacental blood flow. Impaired spiral artery remodeling has long been implicated in preeclampsia, a major complication of pregnancy, but the underlying mechanisms remain unclear(1, 2). Corin is a cardiac protease that activates atrial natriuretic peptide (ANP), a cardiac hormone important in regulating blood pressure(3). Unexpectedly, corin expression was detected in the pregnant uterus(4). Here we identify a novel function of corin and ANP in promoting trophoblast invasion and spiral artery remodeling. We show that pregnant corin- or ANP-deficient mice developed high blood pressure and proteinuria, characteristics of preeclampsia. In these mice, trophoblast invasion and uterine spiral artery remodeling were markedly impaired. Consistently, we find that ANP potently stimulated human trophoblasts in invading Matrigels. In patients with preeclampsia, uterine corin mRNA and protein levels were significantly lower than that in normal pregnancies. Moreover, we have identified corin gene mutations in preeclamptic patients, which decreased corin activity in processing pro-ANP. These results indicate that corin and ANP are essential for physiological changes at the maternal-fetal interface, suggesting that defects in corin and ANP function may contribute to preeclampsia