Search

BackgroundIntrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth.MethodsWe did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134.FindingsWe assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73-2·89]; I2=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74-0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35-0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02-0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 μmol/L versus four (0·28%; 0·08-0·72) of 1412 cases with total bile acids of 40-99 μmol/L (hazard ratio [HR] 2·35 [95% CI 0·52-10·50]; p=0·26), and versus 18 (3·44%; 2·05-5·37) of 524 cases for bile acids of 100 μmol/L or more (HR 30·50 [8·83-105·30]; p

Objective This study aimed to compare adverse neonatal outcomes associated with the trial of labor after cesarean (TOLAC) at term in pregnancies according to maternal prepregnancy body mass index (BMI; kg/m 2) and the presence of previous vaginal delivery (VD). Study Design This was a repeated cross-sectional analysis of individuals with singleton, cephalic, and term deliveries with a history of one or two cesarean deliveries in the Linked Birth/Infant Death data from 2011 to 2020. Outcomes were examined according to the BMI category including BMI <30, 30 to 39.9, and 40 to 69.9 kg/m 2. The primary outcome was a composite neonatal outcome, defined as any presence of neonatal death, neonatal intensive care unit admission, assisted ventilation, surfactant therapy, or seizures. Outcomes were compared between TOLAC and elective repeat cesarean delivery (eRCD) after stratifying by BMI category and previous VD. Log-binomial regression was performed to obtain adjusted relative risk (aRR) with 99% confidence intervals, controlling for covariates. Results Of 4,055,440 individuals, 2,627,131 had BMI <30 kg/m 2 , 1,108,278 had BMI 30 to 39.9 kg/m 2 , and 320,031 had BMI 40 to 69.9 kg/m 2. In individuals with no previous VD, VD rates after TOLAC were 66.7, 57.2, and 48.1%, respectively. In individuals with previous VD, VD rates after TOLAC were 81.4, 74.7, and 67.3%, respectively. In individuals without previous VD, compared with those who had an eRCD, those who had TOLAC were more likely to experience composite neonatal outcomes in individuals with BMI < 30 kg/m 2 (5.0 vs. 6.5%; aRR = 1.33 [1.30–1.36]), BMI 30 to 39.9 kg/m 2 (6.1 vs. 7.8%; aRR = 1.29 [1.24–1.34]), and BMI 40 to 69.9 kg/m 2 (8.2 vs. 9.0%; aRR = 1.15 [1.07–1.23]). In individuals with previous VD, there was no difference in the composite neonatal outcomes in BMI < 30 kg/m 2 (6.2 vs. 5.8%; aRR = 0.98 [0.96–1.00]), BMI 30 to 39.9 kg/m 2 (7.4 vs. 7.1%; aRR = 0.99 [0.95–1.02]), and BMI 40 to 69.9 kg/m 2 (9.4 vs. 8.7%; aRR = 0.96 [0.91–1.02]). Conclusion TOLAC among obese individuals could be offered in selected cases. Key Points TOLAC among obese individuals could be offered selectively, despite their reduced likelihood of attempting or succeeding at it. Higher BMI individuals show decreased rates of both attempting and achieving successful TOLAC. Despite these trends, attempting TOLAC after a previous vaginal delivery does not heighten neonatal complications. [ABSTRACT FROM AUTHOR]

Objective Combining pharmacologic agents with mechanical ripening achieves the shortest labor duration, yet there is no clear evidence on route of drug administration in obese individuals. The use of buccal misoprostol has shown greater patient acceptance but remains understudied. Our objective was to evaluate the difference in time to delivery of buccal compared with vaginal misoprostol in combination with a Foley catheter (FC) for induction of labor (IOL) in the obese population. Study Design This was a secondary analysis of a randomized controlled trial comparing identical dosages (25 μg) of buccal and vaginal misoprostol in combination with a FC. The parent trial was an institutional review board-approved, randomized clinical trial conducted from June 2019 through January 2020. Labor management was standardized among participants. Women undergoing IOL at ≥37 weeks with a singleton gestation and cervical dilation ≤2 cm were included. Body mass index (BMI, kg/m 2) was stratified. The primary outcome was time to delivery. Results A total of 215 participants were included. Demographic characteristics were similar between the three groups. Vaginal drug administration achieved a faster median time to delivery than the buccal route among patients with a body mass index greater than or equal to 30 kg/m 2 (vaginal misoprostol–FC: 21.3 hours vs. buccal misoprostol–FC: 25.2 hours, p = 0.006). There was no difference in the cesarean delivery rate between the two groups. Furthermore, patients with a BMI greater than or equal to 30 kg/m 2 receiving vaginal misoprostol delivered 1.2 times faster than women who received buccal misoprostol after censoring for cesarean delivery and adjusting for parity (hazard ratio: 1.2, 95% confidence interval: 1.1–1.7). There were no significant differences in maternal and neonatal outcomes. Conclusion We found that vaginal misoprostol was superior to buccal misoprostol when combined with a FC among individuals with a BMI greater than or equal to 30 kg/m 2. Vaginal misoprostol should be the preferred route of drug administration for term IOL in this population. Key Points Vaginal misoprostol was superior to buccal route among patients with obesity. There was no difference in the cesarean delivery rate between the two groups. Vaginal misoprostol should be the preferred route of administration among patients with obesity. [ABSTRACT FROM AUTHOR]

Objective This study aimed to examine the temporal trends of severe maternal morbidity (SMM) in the U.S. population in relation to trends in maternal comorbidity. Study Design We performed a repeated cross-sectional analysis of data from individuals at 20 weeks' gestation or greater using U.S. birth certificate data from 2011 to 2021. Our primary outcome was SMM defined as the occurrence of intensive care unit admission, eclampsia, hysterectomy, uterine rupture, and blood product transfusion. We also examined the proportions of maternal comorbidity. Outcomes of the adjusted incidence rate ratio (IRR) with 99% confidence intervals (99% CIs) for 2021 m12 compared with 2011 m1 were calculated using negative binomial regression, controlling for predefined confounders. Results There were 42,504,125 births included in the analysis. From 2011 m1 to 2021 m12, there was a significant increase in the prevalence of advanced maternal age (35–39 [45%], 40–44 [29%], and ≥45 [43%] years), morbid obesity (body mass index 40–49.9 [66%], 50–59.9 [91%], and 60–69.9 [98%]), previous cesarean delivery (14%), chronic hypertension (104%), pregestational diabetes (64%), pregnancy-associated hypertension (240%), gestational diabetes (74%), and preterm delivery at 34 to 36 weeks (12%). There was a significant decrease in the incidence of multiple gestation (9%), preterm delivery at 22 to 27 weeks (9%), and preterm delivery at 20 to 21 weeks (22%). From 2011 m1 to 2021 m12, the incidence of SMM increased from 0.7 to 1.0% (crude IRR 1.60 [99% CI 1.54–1.66]). However, the trend was no longer statistically significant after controlling for confounders (adjusted IRR 1.01 [95% CI 0.81–1.27]). The main comorbidity that was associated with the increase in SMM was pregnancy-associated hypertension. Conclusion The rise in the prevalence of comorbidity in pregnancy seems to fuel the rise in SMM. Interventions to prevent SMM should include the management and prevention of pregnancy-associated hypertension. Key Points The rise in maternal mortality is related to morbidity. Pregnancy-associated hypertension increases morbidity. There were increasing trends in age, body mass index, and medical conditions. [ABSTRACT FROM AUTHOR]

Objective Our objective was to describe infant mortality within 1 year of life according to gestational age and birth weight percentile in infants delivered between 22 and 28 weeks of gestation. Study Design This study was a retrospective cohort study based on publicly available U.S. birth certificate data linked to infant death data between 2014 and 2020. Maternal–neonate pairs of singleton live births between 22 0/7 and 28 6/7 weeks' gestation (vaginal or cesarean) were evaluated. We excluded infants with major fetal anomalies, chromosomal disorders, and birth weight outliers. Our primary outcome was infant mortality within 1 year of life. Individuals were categorized into eight sex-specific birth weight percentiles categories: less than the 3rd, 3rd-less than the 10th, 10th-less than the 25th, 25th-to less than the 50th, 50th-less than the 75th, 75th-to less than the 90th, 90th-less than the 97th, and 97th or higher. Results Of 27,014,444 individuals with live births from January 2014 to December 2020, 151,677 individuals who gave birth at 22 to 28 weeks of gestation were included in the study population. The mortality rate ranged from 4.2% for the 50th-less than the 75th percentiles at 28 weeks to 80.3% for the 3rd-less than the 10th percentile at 22 weeks. Using the 50th-less than the 75th birth weight percentile at each gestational age as a reference group, birth weight less than the 50th percentile was associated with increased mortality at all gestational ages in a dose-dependent manner. From 22 to 25 weeks of gestation, higher birth weight percentiles were associated with lower mortality, while the 97th or higher birth weight percentile was associated with increased mortality compared with the 50th-less than the 75th birth weight percentile at 26 to 28 weeks of gestation. Conclusion The lower birth weight percentiles were associated with higher mortality across all gestational ages, but the association between higher birth weight percentiles and infant mortality exhibited an opposite pattern at 22 to 25 weeks as compared to later gestational age. Key Points Birth weight ≥97th percentile was associated with increased infant mortality at 26 to 28 weeks. Higher birth weight percentiles were associated with a lower risk of mortality at 22 to 25 weeks. Lower birth weight percentiles were associated with a higher risk of mortality at 22 to 28 weeks. [ABSTRACT FROM AUTHOR]

Objective Fetal growth restriction (FGR) is defined as an estimated fetal weight (EFW) or abdominal circumference (AC) <10th percentile (%ile) for gestational age (GA). An EFW <3rd %ile for GA is considered severe FGR (sFGR). It remains unknown if fetuses with isolated AC <3rd %ile should be considered sFGR. Our primary objective was to assess composite neonatal outcomes in fetuses with an AC <3 rd %ile and overall EFW 3rd to 9th %ile compared with those with an EFW <3rd %ile. Study Design This retrospective cohort study was undertaken at a tertiary academic center from January 2016 to December 2021. Inclusion criteria were singleton fetuses with an EFW <3rd %ile (Group 1) or AC <3rd %ile with EFW 3rd to 9th %ile (Group 2) at 28 weeks' gestation or greater. Exclusion criteria were multiple gestations, presence of a major fetal anomaly, resolution of FGR, genetic syndrome, or infection. Composite neonatal outcome was defined by any of the following: neonatal intensive care unit admission >48 hours, necrotizing enterocolitis, sepsis, respiratory distress syndrome, mechanical ventilation, retinopathy of prematurity, seizures, intraventricular hemorrhage, stillbirth, or death before discharge. Small for gestational age (SGA) was defined as birth weight <10th %ile for GA. Results A total of 743 patients fulfilled our study criteria, with 489 in Group 1 and 254 in Group 2. The composite neonatal outcome occurred in 281 (57.5%) neonates in Group 1 and 53 (20.9%) in Group 2 (p < 0.01). The rates of SGA at birth were 94.9 and 75.6% for Group 1 and Group 2, respectively (OR 5.99, 95% confidence interval 3.65–9.82). Conclusion Although AC <3rd %ile with EFW 3rd to 9th %ile is associated with a lower frequency of SGA and neonatal morbidity than EFW <3 %ile, fetuses with AC <3 %ile still exhibited moderate rates of these adverse perinatal outcomes. Consideration should be given to inclusion of an AC <3rd %ile with EFW 3rd to 9th %ile as a criterion for sFGR. However, prospective studies comparing delivery at 37 versus 38 to 39 weeks' gestation are needed to ensure improved outcomes before widespread adaptation in clinical practice. Key Points The composite neonatal outcome occurred in 57.5% of fetuses with an overall EFW <3rd %ile and 20.9% of fetuses with an AC <3rd %ile but EFW 3rd to 9th %ile. Both groups demonstrated a high positive predictive value for SGA birth weight. Consideration should be given to inclusion of an AC <3rd %ile as a criterion for sFGR. [ABSTRACT FROM AUTHOR]

Objective Pregnancy outcomes of individuals receiving cervical cerclage when the cervix is dilated are not well known. We sought to examine preterm birth rates after ultrasound or physical examination-indicated cerclage placement according to the degree of cervical dilation. Study Design This was a retrospective cohort study of individuals with singleton pregnancies undergoing ultrasound or physical examination-indicated cerclage before 24 0/7 weeks of gestation from 2004 to 2018. Individuals were categorized based on the degree of cervical dilation at the time of cerclage. Our primary outcome was preterm delivery at less than 37 weeks of gestation. Multivariable logistic regression was performed to calculate adjusted odds ratios (aOR) with 95th confidence intervals (95% CI), controlling for predefined covariates. Results Of 147 individuals undergoing ultrasound or physical examination-indicated cerclage, 90/147 (61%) had a closed or 0.5 cm dilated cervix at the time of cerclage placement, 45/147 (31%) had a cervical dilation of 1 to 2.5 cm, and 12/147 (8%) had a cervical dilation of 3 to 4 cm at the time of placement. Individuals with a cervical dilation of 1 to 2.5 cm compared with those who had a closed cervix did not have increased odds of preterm delivery (58 vs. 42%; aOR: 1.95; 95% CI: 0.93–4.07). However, individuals with a cervical dilation of 3 to 4 cm compared with individuals who had a closed cervix had significantly increased odds of preterm delivery (75 vs. 42%; aOR: 4.33; 95% CI: 1.05–17.77). Conclusion The rate of preterm birth increases with increasing cervical dilation at the time of cerclage placement. However, individuals who have a cerclage placed when the cervix is 1 to 2.5 cm can achieve an outcome that is not significantly different from those who had a cerclage placed when the cervix is closed. Key Points Time from cerclage placement to delivery decreases as cervical dilation increases. Individuals 1 to 2.5 cm dilated at the time of cerclage can achieve a favorable outcome. A cervical dilation of ≥3 cm at cerclage placement was associated with extreme prematurity. [ABSTRACT FROM AUTHOR]