Cluster analysis to estimate the risk of preeclampsia in the high-risk Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study

Objectives Preeclampsia is divided into early-onset (delivery before 34 weeks of gestation) and late-onset (delivery at or after 34 weeks) subtypes, which may rise from different etiopathogenic backgrounds. Early-onset disease is associated with placental dysfunction. Late-onset disease develops predominantly due to metabolic disturbances, obesity, diabetes, lipid dysfunction, and inflammation, which affect endothelial function. Our aim was to use cluster analysis to investigate clinical factors predicting the onset and severity of preeclampsia in a cohort of women with known clinical risk factors. Methods We recruited 903 pregnant women with risk factors for preeclampsia at gestational weeks 12(+0)-13(+6). Each individual outcome diagnosis was independently verified from medical records. We applied a Bayesian clustering algorithm to classify the study participants to clusters based on their particular risk factor combination. For each cluster, we computed the risk ratio of each disease outcome, relative to the risk in the general population. Results The risk of preeclampsia increased exponentially with respect to the number of risk factors. Our analysis revealed 25 number of clusters. Preeclampsia in a previous pregnancy (n = 138) increased the risk of preeclampsia 8.1 fold (95% confidence interval (CI) 5.711.2) compared to a general population of pregnant women. Having a small for gestational age infant (n = 57) in a previous pregnancy increased the risk of early-onset preeclampsia 17.5 fold (95%CI 2.160.5). Cluster of those two risk factors together (n = 21) increased the risk of severe preeclampsia to 23.8-fold (95%CI 5.160.6), intermediate onset (delivery between 34(+0)-36(+6) weeks of gestation) to 25.1-fold (95%CI 3.179.9) and preterm preeclampsia (delivery before 37(+0) weeks of gestation) to 16.4-fold (95%CI 2.052.4). Body mass index over 30 kg/m(2) (n = 228) as a sole risk factor increased the risk of preeclampsia to 2.1-fold (95%CI 1.13.6). Together with preeclampsia in an earlier pregnancy the risk increased to 11.4 (95%CI 4.520.9). Chronic hypertension (n = 60) increased the risk of preeclampsia 5.3-fold (95%CI 2.49.8), of severe preeclampsia 22.2-fold (95%CI 9.941.0), and risk of early-onset preeclampsia 16.7-fold (95%CI 2.057.6). If a woman had chronic hypertension combined with obesity, gestational diabetes and earlier preeclampsia, the risk of term preeclampsia increased 4.8-fold (95%CI 0.121.7). Women with type 1 diabetes mellitus had a high risk of all subgroups of preeclampsia. Conclusion The risk of preeclampsia increases exponentially with respect to the number of risk factors. Early-onset preeclampsia and severe preeclampsia have different risk profile from term preeclampsia.Peer reviewe

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

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