Lasix for the prevention of de novo postpartum hypertension: A randomized placebo-controlled trial (LAPP Trial).

BACKGROUND: Birthing people with de novo postpartum hypertensive disorders remain among the highest risk for severe maternal morbidity. Randomized controlled trials demonstrate a benefit to oral loop-diuretics in decreasing postpartum hypertensive morbidity in patients with an antenatal diagnosis of preeclampsia. It is not known whether this same therapy benefits patients at risk for new-onset postpartum hypertension OBJECTIVE: To evaluate whether oral furosemide can reduce risk for de novo postpartum hypertension (dnPPHTN) among high-risk birthing people by reducing post-delivery blood pressure. STUDY DESIGN: From October 2021 to April 2022, we conducted a randomized triple-masked placebo-controlled clinical trial of individuals at high risk for dnPPHTN at a single university-based tertiary care medical center. A total of 82 postpartum patients with no antenatal diagnosis of chronic hypertension or a hypertensive disorder of pregnancy who were at high-risk for the development of dnPPHTN based on a pre-specified risk factor algorithm were enrolled after childbirth. The participants were randomly assigned in a 1:1 ratio to a five-day course of oral furosemide 20 mg daily or identical-appearing placebo starting within eight hours of delivery. Participants were followed for 6 weeks postpartum using Bluetooth-enabled remote blood pressure monitoring and electronic surveys. The primary outcome was the difference in mean arterial pressure (MAP) averaged over the 24 hours prior to discharge or the 24 hours prior to antihypertensive therapy initiation. The study was powered to detect a 5 mmHg difference in mean MAP (standard deviation 6.4 mmHg) with 90% power at an alpha of 0.05, requiring a sample size of 41 per group. Secondary outcomes included the rate of dnPPHTN, readmission data, other measures of hypertensive and maternal morbidity, breastfeeding data, and drug-related neonatal outcomes. RESULTS: The primary outcome was assessed in 80 of the 82 participants. Baseline characteristics were similar between groups. There was no significant difference in mean MAP 24 hours prior to discharge (or antihypertensive initiation) in the furosemide group (88.9 ± 7.4 mmHg) compared to the placebo group (86.8 ± 7.1 mmHg; absolute difference 2.1 mmHg, 95% CI -1.2 to 5.3). Of the 79 participants for whom secondary outcomes were assessed, 10% (n=8) developed dnPPHTN and 9% (n=7) were initiated on antihypertensive therapy. Rates were not significantly different between groups. CONCLUSIONS: De novo postpartum hypertension is a common phenomenon among at-risk patients, warranting close monitoring for severe hypertension and other maternal morbidity. There is insufficient evidence to suggest that furosemide reduces mean MAP in the 24 hours prior to discharge from the delivery hospitalization (or antihypertensive medication initiation) compared to placebo.

Cervical Ripening Efficacy of Synthetic Osmotic Cervical Dilator Compared With Oral Misoprostol at Term: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether a synthetic osmotic cervical dilator is noninferior to oral misoprostol for cervical ripening. METHODS: In an open-label, noninferiority randomized trial, pregnant women undergoing induction of labor at 37 weeks of gestation or more with Bishop scores less than 6 were randomized to either mechanical cervical dilation or oral misoprostol. Participants in the mechanical dilation group underwent insertion of synthetic osmotic cervical dilator rods, and those in the misoprostol group received up to six doses of 25 micrograms orally every 2 hours. After 12 hours of ripening, oxytocin was initiated, with artificial rupture of membranes. Management of labor was at the physician's discretion. The primary outcome was the proportion of women achieving vaginal delivery within 36 hours of initiation of study intervention. Secondary outcomes included increase in Bishop score, mode of delivery, induction-to-delivery interval, total length of hospital stay, and patient satisfaction. On the basis of a noninferiority margin of 10%, an expected primary outcome frequency of 65% for misoprostol and 71% for mechanical methods, and 85% power, a sample size of 306 participants was needed. RESULTS: From November 2018 through January 2021, 307 women were randomized, with 151 evaluable participants in the synthetic osmotic cervical dilator group and 152 in the misoprostol group (there were four early withdrawals). The proportion of women achieving vaginal delivery within 36 hours was higher with mechanical cervical dilation compared with misoprostol (61.6% vs 59.2%), with an absolute difference of 2.4% (95% CI -9% to 13%), indicating noninferiority for the prespecified margin. No differences were noted in the mode of delivery. Tachysystole was more frequent in the misoprostol group (70 [46.4%] vs 35 [23.3%]; P=.01). Participants in the synthetic osmotic cervical dilator group reported better sleep, less unpleasant abdominal sensations, and lower pain scores (P<.05). CONCLUSION: Synthetic osmotic cervical dilator is noninferior to oral misoprostol for cervical ripening. Advantages of synthetic osmotic cervical dilator include a better safety profile and patient satisfaction, less tachysystole, lower pain scores, and U.S. Food and Drug Administration approval. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03670836. FUNDING SOURCE: Medicem Technology s.r.o., Czech Republic.

Histological chorioamnionitis is predicted by early infant C-reactive protein in preterm infants and correlates with neonatal outcomes.

AIM: Histological chorioamnionitis (HCA) is associated with preterm birth and adverse neonatal outcomes. We evaluated the rise in C-reactive protein (CRP) in preterm infants as a predictor of HCA severity and outcomes. METHODS: Consecutive preterm infants, born January 2009 to January 2014 in the National Maternity Hospital, Dublin, under 32 weeks' gestation or <1.5 kg birthweight, were included. Histological chorioamnionitis was staged as maternal inflammatory response, foetal inflammatory response and non-HCA. RESULTS: Preterm infants (n = 518) were included with a mean gestational age 28.5 ± 2.8 weeks, birthweight 1.1 ± 0.3 kg, and 53.5% were male. Histological chorioamnionitis was found in 25.4%. Histological chorioamnionitis was present in 93.7% when CRP > 5 mg/L, 65.2% when CRP 1-5 mg/L and in 19.4% when CRP < 1 mg/L. When both the immature to total neutrophil (IT) ratio was >0.2 and the CRP > 1 mg/L the positive predictive value and negative predictive value for HCA were 92.5% and 84.9%, respectively. Histological chorioamnionitis was associated with more resuscitation and respiratory distress syndrome (both P < .001). A CRP > 10 mg/L was associated with a foetal inflammatory response and increased early-onset sepsis. CONCLUSION: Higher early CRP was a surrogate predictor of HCA and correlated with the severity of HCA. Higher CRP and HCA were associated with adverse early outcomes.