Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Large-Scale Proteomics in Early Pregnancy and Hypertensive Disorders of Pregnancy.

Importance: There is no consensus regarding the best method for prediction of hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia. Objective: To determine predictive ability in early pregnancy of large-scale proteomics for prediction of HDP. Design, Setting, and Participants: This was a nested case-control study, conducted in 2022 to 2023, using clinical data and plasma samples collected between 2010 and 2013 during the first trimester, with follow-up until pregnancy outcome. This multicenter observational study took place at 8 academic medical centers in the US. Nulliparous individuals during first-trimester clinical visits were included. Participants with HDP were selected as cases; controls were selected from those who delivered at or after 37 weeks without any HDP, preterm birth, or small-for-gestational-age infant. Age, self-reported race and ethnicity, body mass index, diabetes, health insurance, and fetal sex were available covariates. Exposures: Proteomics using an aptamer-based assay that included 6481 unique human proteins was performed on stored plasma. Covariates were used in predictive models. Main Outcomes and Measures: Prediction models were developed using the elastic net, and analyses were performed on a randomly partitioned training dataset comprising 80% of study participants, with the remaining 20% used as an independent testing dataset. Primary measure of predictive performance was area under the receiver operating characteristic curve (AUC). Results: This study included 753 HDP cases and 1097 controls with a mean (SD) age of 26.9 (5.5) years. Maternal race and ethnicity were 51 Asian (2.8%), 275 non-Hispanic Black (14.9%), 275 Hispanic (14.9%), 1161 non-Hispanic White (62.8% ), and 88 recorded as other (4.8%), which included those who did not identify according to these designations. The elastic net model, allowing for forced inclusion of prespecified covariates, was used to adjust protein-based models for clinical and demographic variables. Under this approach, no proteins were selected to augment the clinical and demographic covariates. The predictive performance of the resulting model was modest, with a training set AUC of 0.64 (95% CI, 0.61-0.67) and a test set AUC of 0.62 (95% CI, 0.56-0.68). Further adjustment for study site yielded only minimal changes in AUCs. Conclusions and Relevance: In this case-control study with detailed clinical data and stored plasma samples available in the first trimester, an aptamer-based proteomics panel did not meaningfully add to predictive utility over and above clinical and demographic factors that are routinely available.

Diet quality, community food access, and glycemic control among nulliparous individuals with diabetes.

Better diet quality regardless of community food access was associated with a higher likelihood of glycemic control in early pregnancy among nulliparous individuals with pregestational diabetes. These findings highlight the need for interventions that address nutrition insecurity for pregnant individuals living with diabetes.

Induction of labor vs expectant management among low-risk patients with 1 prior cesarean delivery.

BACKGROUND: Studies that have compared induction of labor in individuals with 1 prior cesarean delivery to expectant management have shown conflicting results. OBJECTIVE: To determine the association between clinical outcomes and induction of labor at 39 weeks in a national sample of otherwise low-risk patients with 1 prior cesarean delivery. STUDY DESIGN: This cross-sectional study analyzed 2016 to 2021 US Vital Statistics birth certificate data. Individuals with vertex, singleton pregnancies, and 1 prior cesarean delivery were included. Patients with prior vaginal deliveries, delivery before 39 weeks 0 days or after 42 weeks 6 days of gestation, and medical comorbidities were excluded. The primary exposure of interest was induction of labor at 39 weeks 0 days to 39 weeks 6 days compared to expectant management with delivery from 40 weeks 0 days to 42 weeks 6 days. The primary outcome was vaginal delivery. The main secondary outcomes were separate maternal and neonatal morbidity composites. The maternal morbidity composite included uterine rupture, operative vaginal delivery, peripartum hysterectomy, intensive care unit admission, and transfusion. The neonatal morbidity composite included neonatal intensive care unit admission, Apgar score less than 5 at 5 minutes, immediate ventilation, prolonged ventilation, and seizure or serious neurological dysfunction. Unadjusted and adjusted log binomial regression models accounting for demographic variables and the exposure of interest (induction vs expectant management) were performed. Results are presented as unadjusted and adjusted risk ratios with 95% confidence intervals. RESULTS: From 2016 to 2021, a total of 198,797 individuals with vertex, singleton pregnancies, and 1 prior cesarean were included in the primary analysis. Of these individuals, 25,915 (13.0%) underwent induction of labor from 39 weeks 0 days to 39 weeks 6 days and 172,882 (87.0%) were expectantly managed with deliveries between 40 weeks 0 days and 42 weeks 6 days. In adjusted analyses, patients induced at 39 weeks were more likely to have a vaginal delivery when compared to those expectantly managed (38.0% vs 31.8%; adjusted risk ratio 1.32, 95% confidence interval 1.28, 1.36). Among those who had vaginal deliveries, induction of labor was associated with increased likelihood of operative vaginal delivery (11.1% vs 10.0; adjusted risk ratio 1.15, 95% confidence interval 1.07, 1.24). The maternal morbidity composite occurred in 0.9% of individuals in both the induction and expectant management groups (adjusted risk ratio 0.92, 95% confidence interval 0.79, 1.06). The rates of uterine rupture (0.3%), peripartum hysterectomy (0.04% vs 0.05%), and intensive care unit admission (0.1% vs 0.2%) were all relatively low and did not differ significantly between groups. There was also no significant difference in the neonatal morbidity composite between the induction and expectant management groups (7.3% vs 6.7%; adjusted risk ratio 1.04, 95% confidence interval 0.98, 1.09). CONCLUSION: When compared to expectant management, elective induction of labor at 39 weeks in low-risk patients with 1 prior cesarean delivery was associated with a significantly higher likelihood of vaginal delivery with no difference in composite maternal and neonatal morbidity outcomes. Prospective studies are needed to better elucidate the risks and benefits of induction of labor in this patient population.

Optimizing Opioid Prescription Quantity After Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To test whether an individualized opioid-prescription protocol (IOPP) with a shared decision-making component can be used without compromising postcesarean pain management. METHODS: In this multicenter randomized controlled noninferiority trial, we compared IOPP with shared decision making with a fixed quantity of opioid tablets at hospital discharge. We recruited at 31 centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Study participants had uncomplicated cesarean births. Follow-up occurred through 12 weeks postdischarge. Individuals with complicated cesarean births or history of opioid use in the pregnancy were excluded. Participants were randomized 1:1 to IOPP with shared decision making or fixed quantity (20 tablets of 5 mg oxycodone). In the IOPP group, we calculated recommended tablet quantity based on opioid use in the 24 hours before discharge. After an educational module and shared decision making, participants selected a quantity of discharge tablets (up to 20). The primary outcome was moderate to severe pain (score 4 or higher [possible range 0-10]) on the BPI (Brief Pain Inventory) at 1 week after discharge. A total sample size of 5,500 participants was planned to assess whether IOPP with shared decision making was not inferior to the fixed quantity of 20 tablets. RESULTS: From September 2020 to March 2022, 18,990 individuals were screened and 5,521 were enrolled (n=2,748 IOPP group, n=2,773 fixed-quantity group). For the primary outcome, IOPP with shared decision making was not inferior to fixed quantity (59.5% vs 60.1%, risk difference 0.67%; 95% CI, -2.03% to 3.37%, noninferiority margin -5.0) and resulted in significantly fewer tablets received (median 14 [interquartile range 4-20] vs 20, P<.001) through 90 days postpartum. CONCLUSION: Compared with fixed quantity, IOPP with shared decision making was noninferior for outpatient postcesarean analgesia at 1 week postdischarge and resulted in fewer prescribed opioid tablets at discharge. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04296396.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

A multisite study to develop and validate first trimester, circulating microparticle biomarkers for tiered risk stratification of spontaneous preterm birth in nulliparas.

BACKGROUND: Despite much research, advances in early prediction of spontaneous preterm birth (sPTB) has been slow. The evolving field of circulating microparticle (CMP) biology may identify novel blood-based, and clinically useful, biomarkers. OBJECTIVE: To test the ability of a previously identified, 7-marker set of CMP-derived proteins from the first trimester of pregnancy, in the form of an in vitro diagnostic multivariate index assay (IVDMIA), to stratify pregnant patients according to their risk for sPTB. STUDY DESIGN: We employed a previously validated set of CMP protein biomarkers, utilizing mass spectrometry assays and a nested case-control design in a subset of participants from the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be (nuMoM2b). We evaluated these biomarkers in the form of an IVDMIA to predict risk for sPTB at different gestational ages. Plasma samples collected at 9- to 13-weeks' gestation were analyzed. The IVDMIA assigned subjects to 1 of 3 sPTB risk categories: low risk (LR), moderate risk (MR), or high risk (HR). Independent validation on a set-aside set confirmed the IVDMIA's performance in risk stratification. RESULTS: Samples from 400 participants from the nuMoM2b cohort were used for the study; of these, 160 delivered<37 weeks and 240 delivered at term. Through Monte Carlo simulation in which the validation results were adjusted based on actual weekly sPTB incidence rates in the nuMoM2b cohort, the IVDMIA stratifications demonstrated statistically significant differences among the risk groups in time-to-event (birth) analysis (P<.0001). The incidence-rate adjusted cumulative risks of sPTB at ≤32 weeks' gestation were 0.4%, 1.6%, and 7.5%, respectively for the LR, MR, and HR groups, respectively. Compared to the LR group, the corresponding risk ratios of the IVDMIA assigned MR and HR group were 4.25 (95% confidence interval [CI] 2.2-7.9) and 19.92 (95% CI 10.4-37.4), respectively. CONCLUSION: A first trimester CMP protein biomarker panel can be used to stratify risk for sPTB at different gestational ages. Such a multitiered stratification tool could be used to assess risk early in pregnancy to enable timely clinical management and interventions, and, ultimately, to enable the development of tailored care pathways for sPTB prevention.

Socioeconomic Disadvantage in Pregnancy and Postpartum Risk of Cardiovascular Disease.

BACKGROUND: Pregnancy is an educable and actionable life stage to address social determinants of health (SDOH) and lifelong cardiovascular disease (CVD) prevention. But the link between a risk score that combines multiple neighborhood-level social determinants in pregnancy and the risk of long-term CVD remains to be evaluated. OBJECTIVE: To examine whether neighborhood-level socioeconomic disadvantage measured by the Area Deprivation Index (ADI) in early pregnancy is associated with a higher 30-year predicted risk of CVD postpartum, as measured by the Framingham Risk Score. METHODS: An analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study longitudinal cohort. Participant home addresses during early pregnancy were geocoded at the Census-block level. The exposure was neighborhood-level socioeconomic disadvantage using the 2015 ADI by tertile (least deprived [T1], reference; most deprived [T3]) measured in the first trimester. Outcomes were the predicted 30-year risks of atherosclerotic CVD (ASCVD, composite of fatal and non-fatal coronary heart disease and stroke) and total CVD (composite of ASCVD plus coronary insufficiency, angina pectoris, transient ischemic attack, intermittent claudication, and heart failure) using the Framingham Risk Score measured 2-to-7 years after delivery. These outcomes were assessed as continuous measures of absolute estimated risk in increments of 1%, and, secondarily, as categorical measures with high-risk defined as an estimated probability of CVD >10%. Multivariable linear regression and modified Poisson regression models adjusted for baseline age and individual-level social determinants, including health insurance, educational attainment, and household poverty. RESULTS: Among 4,309 nulliparous individuals at baseline, the median age was 27 years (IQR: 23-31) and the median ADI was 43 (IQR: 22-74). At 2-to-7 years postpartum (median: 3.1 years, IQR: 2.5, 3.7), the median 30-year risk of ASCVD was 2.3% (IQR: 1.5, 3.5) and of total CVD was 5.5% (IQR: 3.7, 7.9); 2.2% and 14.3% of individuals had predicted 30-year risk >10%, respectively. Individuals living in the highest ADI tertile had a higher predicted risk of 30-year ASCVD % (adj. ß: 0.41; 95% CI: 0.19, 0.63) compared with those in the lowest tertile; and those living in the top two ADI tertiles had higher absolute risks of 30-year total CVD % (T2: adj. ß: 0.37; 95% CI: 0.03, 0.72; T3: adj. ß: 0.74; 95% CI: 0.36, 1.13). Similarly, individuals living in neighborhoods in the highest ADI tertile were more likely to have a high 30-year predicted risk of ASCVD (aRR: 2.21; 95% CI: 1.21, 4.02) and total CVD ≥10% (aRR: 1.35; 95% CI: 1.08, 1.69). CONCLUSIONS: Neighborhood-level socioeconomic disadvantage in early pregnancy was associated with a higher estimated long-term risk of CVD postpartum. Incorporating aggregated SDOH into existing clinical workflows and future research in pregnancy could reduce disparities in maternal cardiovascular health across the lifespan, and requires further study.

Genetic polymorphisms associated with adverse pregnancy outcomes in nulliparas.

Adverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.

Adverse Pregnancy Outcomes and Predicted 30-Year Risk of Maternal Cardiovascular Disease 2-7 Years After Delivery.

OBJECTIVE: To determine whether adverse pregnancy outcomes are associated with a higher predicted 30-year risk of atherosclerotic cardiovascular disease (CVD; ie, coronary artery disease or stroke). METHODS: This was a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be Heart Health Study longitudinal cohort. The exposures were adverse pregnancy outcomes during the first pregnancy (ie, gestational diabetes mellitus [GDM], hypertensive disorder of pregnancy, preterm birth, and small- and large-for-gestational-age [SGA, LGA] birth weight) modeled individually and secondarily as the cumulative number of adverse pregnancy outcomes (ie, none, one, two or more). The outcome was the 30-year risk of atherosclerotic CVD predicted with the Framingham Risk Score assessed at 2-7 years after delivery. Risk was measured both continuously in increments of 1% and categorically, with high predicted risk defined as a predicted risk of atherosclerotic CVD of 10% or more. Linear regression and modified Poisson models were adjusted for baseline covariates. RESULTS: Among 4,273 individuals who were assessed at a median of 3.1 years after delivery (interquartile range 2.5-3.7), the median predicted 30-year atherosclerotic CVD risk was 2.2% (interquartile range 1.4-3.4), and 1.8% had high predicted risk. Individuals with GDM (least mean square 5.93 vs 4.19, adjusted ß=1.45, 95% CI, 1.14-1.75), hypertensive disorder of pregnancy (4.95 vs 4.22, adjusted ß=0.49, 95% CI, 0.31-0.68), and preterm birth (4.81 vs 4.27, adjusted ß=0.47, 95% CI, 0.24-0.70) were more likely to have a higher absolute risk of atherosclerotic CVD. Similarly, individuals with GDM (8.7% vs 1.4%, adjusted risk ratio [RR] 2.02, 95% CI, 1.14-3.59), hypertensive disorder of pregnancy (4.4% vs 1.4%, adjusted RR 1.91, 95% CI, 1.17-3.13), and preterm birth (5.0% vs 1.5%, adjusted RR 2.26, 95% CI, 1.30-3.93) were more likely to have a high predicted risk of atherosclerotic CVD. A greater number of adverse pregnancy outcomes within the first birth was associated with progressively greater risks, including per 1% atherosclerotic CVD risk (one adverse pregnancy outcome: 4.86 vs 4.09, adjusted ß=0.59, 95% CI, 0.43-0.75; two or more adverse pregnancy outcomes: 5.51 vs 4.09, adjusted ß=1.16, 95% CI, 0.82-1.50), and a high predicted risk of atherosclerotic CVD (one adverse pregnancy outcome: 3.8% vs 1.0%, adjusted RR 2.33, 95% CI, 1.40-3.88; two or more adverse pregnancy outcomes: 8.7 vs 1.0%, RR 3.43, 95% CI, 1.74-6.74). Small and large for gestational age were not consistently associated with a higher atherosclerotic CVD risk. CONCLUSION: Individuals who experienced adverse pregnancy outcomes in their first birth were more likely to have a higher predicted 30-year risk of CVD measured at 2-7 years after delivery. The magnitude of risk was higher with a greater number of adverse pregnancy outcomes experienced.

Pregnancy Outcomes in Women Who Developed Elevated Blood Pressure and Stage I Hypertension after 20 Weeks Gestation.

OBJECTIVE: The American College of Obstetrics threshold for hypertension (≥140/90 mm Hg) differs from those of the American College of Cardiology (ACC) and the American Heart Association (AHA). It is unknown if ACC/AHA hypertension levels are associated with adverse pregnancy outcomes (APOs) after 20 weeks gestation. The purpose of this study is to analyze APOs in women with blood pressure (BP) in the elevated or stage 1 range after 20 weeks gestation. STUDY DESIGN: This was a secondary analysis of the nuMoM2b prospective cohort study of 10,038 nulliparous, singleton pregnancies between 2010 and 2014. BP was measured at three visits during the pregnancy using a standard protocol. Women without medical comorbidities, with normal BP by ACC/AHA guidelines (systolic BP [SBP] < 120 and diastolic BP [DBP] < 80 mm Hg) up to 22 weeks, were included. Exposure was BP between 22 and 29 weeks gestation: normal (SBP < 120 and DBP < 80 mm Hg), elevated (SBP: 120-129 and DBP < 80 mm Hg), and stage 1 (SBP: 130-139 or DBP: 80-89 mm Hg). The primary outcome was hypertensive disorder of pregnancy (HDP) at delivery. Secondary outcomes included fetal growth restriction (FGR), placental abruption, preterm delivery, and cesarean delivery. Multivariable-adjusted odds ratio (aORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: Of 4,460 patients that met inclusion criteria, 3,832 (85.9%) had BP in the normal range, 408 (9.1%) in elevated, and 220 (4.9%) in stage 1 range between 22 and 29 weeks. The likelihood of HDP was significantly higher in women with elevated BP (aOR 1.71, 95%CI: 1.18,2.48), and stage 1 BP (aOR: 2.79, 95%CI: 1.84,4.23) compared to normal BP (p < 0.001). Stage 1 BP had twice odds of FGR (aOR: 2.33, 95%CI: 1.22,4.47) and elevated BP had three times odds of placental abruption (aOR: 3.03; 95%CI: 1.24,7.39). CONCLUSION: Elevated or stage 1 BP >20 weeks of pregnancy are associated with HDP, FGR, and placental abruption. KEY POINTS: · Elevated and stage 1 BP increases risk for HDP.. · Elevated BP increases risk for placental abruption.. · Stage 1 BP increases risk for FGR..

Prediction of metabolic syndrome following a first pregnancy.

BACKGROUND: The prevalence of metabolic syndrome is rapidly increasing in the United States. We hypothesized that prediction models using data obtained during pregnancy can accurately predict the future development of metabolic syndrome. OBJECTIVE: This study aimed to develop machine learning models to predict the development of metabolic syndrome using factors ascertained in nulliparous pregnant individuals. STUDY DESIGN: This was a secondary analysis of a prospective cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study [nuMoM2b-HHS]). Data were collected from October 2010 to October 2020, and analyzed from July 2023 to October 2023. Participants had in-person visits 2 to 7 years after their first delivery. The primary outcome was metabolic syndrome, defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, which was measured within 2 to 7 years after delivery. A total of 127 variables that were obtained during pregnancy were evaluated. The data set was randomly split into a training set (70%) and a test set (30%). We developed a random forest model and a lasso regression model using variables obtained during pregnancy. We compared the area under the receiver operating characteristic curve for both models. Using the model with the better area under the receiver operating characteristic curve, we developed models that included fewer variables based on SHAP (SHapley Additive exPlanations) values and compared them with the original model. The final model chosen would have fewer variables and noninferior areas under the receiver operating characteristic curve. RESULTS: A total of 4225 individuals met the inclusion criteria; the mean (standard deviation) age was 27.0 (5.6) years. Of these, 754 (17.8%) developed metabolic syndrome. The area under the receiver operating characteristic curve of the random forest model was 0.878 (95% confidence interval, 0.846-0.909), which was higher than the 0.850 of the lasso model (95% confidence interval, 0.811-0.888; P<.001). Therefore, random forest models using fewer variables were developed. The random forest model with the top 3 variables (high-density lipoprotein, insulin, and high-sensitivity C-reactive protein) was chosen as the final model because it had the area under the receiver operating characteristic curve of 0.867 (95% confidence interval, 0.839-0.895), which was not inferior to the original model (P=.08). The area under the receiver operating characteristic curve of the final model in the test set was 0.847 (95% confidence interval, 0.821-0.873). An online application of the final model was developed (https://kawakita.shinyapps.io/metabolic/). CONCLUSION: We developed a model that can accurately predict the development of metabolic syndrome in 2 to 7 years after delivery.

Infection and Sepsis Trends during United States' Delivery Hospitalizations from 2000 to 2020.

OBJECTIVE: This study aimed to evaluate trends, risk factors, and outcomes associated with infections and sepsis during delivery hospitalizations in the United States. STUDY DESIGN: The 2000-2020 National Inpatient Sample was used for this repeated cross-sectional analysis. Delivery hospitalizations of patients aged 15 to 54 with and without infection and sepsis were identified. Common infection diagnoses during delivery hospitalizations analyzed included (i) pyelonephritis, (ii) pneumonia/influenza, (iii) endometritis, (iv) cholecystitis, (v) chorioamnionitis, and (vi) wound infection. Temporal trends in sepsis and infection during delivery hospitalizations were analyzed. The associations between sepsis and infection and common chronic health conditions including asthma, chronic hypertension, pregestational diabetes, and obesity were analyzed. The associations between clinical, demographic, and hospital characteristics, and infection and sepsis were determined with unadjusted and adjusted logistic regression models with unadjusted odds ratio (OR) and adjusted odds ratios with 95% confidence intervals as measures of association. RESULTS: An estimated 80,158,622 delivery hospitalizations were identified and included in the analysis, of which 2,766,947 (3.5%) had an infection diagnosis and 32,614 had a sepsis diagnosis (4.1 per 10,000). The most common infection diagnosis was chorioamnionitis (2.7% of deliveries) followed by endometritis (0.4%), and wound infections (0.3%). Infection and sepsis were more common in the setting of chronic health conditions. Evaluating trends in individual infection diagnoses, endometritis and wound infection decreased over the study period both for patients with and without chronic conditions, while risk for pyelonephritis and pneumonia/influenza increased. Sepsis increased over the study period for deliveries with and without chronic condition diagnoses. Risks for adverse outcomes including mortality, severe maternal morbidity, the critical care composite, and acute renal failure were all significantly increased in the presence of sepsis and infection. CONCLUSION: Endometritis and wound infections decreased over the study period while risk for sepsis increased. Infection and sepsis were associated with chronic health conditions and accounted for a significant proportion of adverse obstetric outcomes including severe maternal morbidity. KEY POINTS: · Sepsis increased over the study period for deliveries with and without chronic condition diagnoses.. · Endometritis and wound infection decreased over the study period.. · Infection and sepsis accounted for a significant proportion of adverse obstetric outcomes..

Postpartum readmission risk: a comparison between stillbirths and live births.

BACKGROUND: Stillbirth occurs more commonly among pregnant people with comorbid conditions and obstetrical complications. Stillbirth also independently increases maternal morbidity and imparts a psychosocial hazard when compared with live birth. These distinct needs and burden may increase the risk for postpartum readmission after stillbirth. OBJECTIVE: This study aimed to examine the risk for maternal postpartum readmission after stillbirth in comparison with live birth and to identify indications for readmission and the associated risk factors. STUDY DESIGN: This was a retrospective cohort of patients with singleton stillbirths or live births, delivered at ≥20 weeks' gestation, who were identified from the 2019 Nationwide Readmissions Database. The primary outcome was all-cause readmission within 6 weeks of discharge from the childbirth hospitalization. The association between stillbirth (vs live birth) and risk for readmission was assessed using multivariable regression models with adjustment for maternal age, sociodemographic characteristics, maternal and obstetrical conditions, and delivery characteristics. Within the stillbirth group, risk factors for readmission were further examined using multivariable regression. The secondary outcomes included principal indication for readmission (categorized based on principal diagnosis code of the readmission hospitalization) and timing of readmission (number of weeks after childbirth hospitalization). Differences in these secondary outcomes were compared between the stillbirth and live birth groups using chi-square tests. All analyses accounted for the complex sample design to generate nationally representative estimates. RESULTS: Postpartum readmission occurred in 2.7% of 16,636 patients with stillbirths, whereas it occurred in 1.6% of 2,870,677 patients with live births (unadjusted risk ratio, 1.65; 95% confidence interval, 1.47-1.86). The higher risk for readmission after stillbirth (vs live birth) persisted after adjusting for maternal, obstetrical, and delivery characteristics (adjusted risk ratio, 1.27; 95% confidence interval, 1.11-1.46). The distribution of principal indication for readmission differed after stillbirth and after live birth and included hypertension (30.2% vs 39.5%; unadjusted risk ratio, 0.76; 95% confidence interval, 0.63-0.93), mental health or substance use disorders (6.8% vs 3.6%; unadjusted risk ratio, 1.90; 95% confidence interval, 1.15-3.16), and venous thromboembolism (5.8% vs 2.0%; unadjusted risk ratio, 2.87; 95% confidence interval, 1.60-5.17). Among patients with stillbirths, 56.0% of readmissions occurred within 1 week, 71.8% within 2 weeks, and 88.1% within 4 weeks; the timing of readmission did not differ significantly between the stillbirth and live birth cohorts. Pregestational diabetes (adjusted risk ratio, 1.87; 95% confidence interval, 1.20-2.93), gestational diabetes (adjusted risk ratio, 1.67; 95% confidence interval, 1.03-2.71), hypertensive disorders of pregnancy (adjusted risk ratio, 1.80; 95% confidence interval, 1.31-2.47), obesity (adjusted risk ratio, 1.46; 95% confidence interval, 1.01-2.12), and primary cesarean delivery (adjusted risk ratio, 1.74; 95% confidence interval, 1.17-2.58) were associated with a higher risk for readmission after stillbirth, whereas higher household income was associated with a lower risk for readmission (eg, adjusted risk ratio for income ≥$82,000 vs $1-$47,999, 0.48; 95% confidence interval, 0.30-0.77). CONCLUSION: When compared with live births, the risk for postpartum readmission was higher after stillbirths, even after adjustment for differences in the patient demographic and clinical characteristics. Readmission for mental health or substance use disorders and venous thromboembolism is more common after stillbirths than after live births.

Association of Mild Iodine Insufficiency during Pregnancy with Child Neurodevelopment in Patients with Subclinical Hypothyroidism or Hypothyroxinemia.

OBJECTIVE: Our objective was to evaluate whether iodine status in pregnant patients with either subclinical hypothyroidism or hypothyroxinemia in the first half of pregnancy is associated with measures of behavior and neurodevelopment in children through the age of 5 years. STUDY DESIGN: This is a secondary analysis of a multicenter study consisting of two randomized, double-masked, placebo-controlled treatment trials conducted in parallel. Patients with a singleton gestation before 20 weeks' gestation underwent thyroid screening using serum thyrotropin and free thyroxine. Participants with subclinical hypothyroidism or hypothyroxinemia were randomized to levothyroxine replacement or an identical placebo. At randomization, maternal urine was collected and stored for subsequent urinary iodine excretion analysis. Urinary iodine concentrations greater than 150 µg/L were considered iodine sufficient, and concentrations of 150 µg/L or less were considered iodine insufficient. The primary outcome was a full-scale intelligence quotient (IQ) score at the age of 5 years, the general conceptual ability score from the Differential Ability Scales-II at the age of 3 if IQ was not available, or death before 3 years. RESULTS: A total of 677 pregnant participants with subclinical hypothyroidism and 526 with hypothyroxinemia were randomized. The primary outcome was available in 1,133 (94%) of children. Overall, 684 (60%) of mothers were found to have urinary iodine concentrations >150 µg/L. Children of iodine-sufficient participants with subclinical hypothyroidism had similar primary outcome scores when compared to children of iodine-insufficient participants (95 [84-105] vs. 96 [87-109], P adj = 0.73). After adjustment, there was also no difference in IQ scores among children of participants with hypothyroxinemia at 5 to 7 years of age (94 [85 - 102] and 91 [81 - 100], Padj 1/4 0.11). Treatment with levothyroxine was not associated with neurodevelopmental or behavioral outcomes regardless of maternal iodine status (p > 0.05). CONCLUSION: Maternal urinary iodine concentrations ≤150 µg/L were not associated with abnormal cognitive or behavioral outcomes in offspring of participants with either subclinical hypothyroidism or hypothyroxinemia. KEY POINTS: · Most pregnant patients with subclinical thyroid disease are iodine sufficient.. · Mild maternal iodine insufficiency is not associated with lower offspring IQ at 5 years.. · Iodine supplementation in subclinical thyroid disease is unlikely to improve IQ..

Breastfeeding Initiation, Duration, and Associated Factors Among People With Hepatitis C Virus Infection.

OBJECTIVE: To characterize breastfeeding behaviors and identify factors associated with breastfeeding initiation among people with hepatitis C virus (HCV) infection. METHODS: We conducted a secondary analysis of a multicenter observational cohort of pregnant people with singleton gestations and HCV seropositivity. This analysis includes individuals with data on breastfeeding initiation and excludes those with human immunodeficiency virus (HIV) co-infection. The primary outcome was self-reported initiation of breastfeeding or provision of expressed breast milk. Secondary outcomes included duration of breastfeeding. Demographic and obstetric characteristics were compared between those who initiated breastfeeding and those who did not to identify associated factors. Univariable and multivariable analyses were performed. RESULTS: Overall, 579 individuals (75.0% of participants in the parent study) were included. Of those, 362 (62.5%) initiated breastfeeding or provided breast milk to their infants, with a median duration of breastfeeding of 1.4 months (interquartile range 0.5-6.0). People with HCV viremia , defined as a detectable viral load at any point during pregnancy, were less likely to initiate breastfeeding than those who had an undetectable viral load (59.4 vs 71.9%, adjusted odds ratio [aOR] 0.61, 95% CI, 0.41-0.92). People with private insurance were more likely to initiate breastfeeding compared with those with public insurance or no insurance (80.0 vs 60.1%; aOR 2.43, 95% CI, 1.31-4.50). CONCLUSION: Although HCV seropositivity is not a contraindication to breastfeeding regardless of viral load, rates of breastfeeding initiation were lower among people with HCV viremia than among those with an undetectable viral load. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01959321 .