The association between perinatal depressive symptoms and child neurodevelopment.

BACKGROUND: Perinatal depression has been suggested to adversely impact child neurodevelopment. However, the complexity of the early childhood environment challenges conclusive findings. OBJECTIVE: To evaluate whether there is an association between perinatal depressive symptoms and child intelligence quotient (IQ) at 5 years of age. STUDY DESIGN: Secondary analysis of an ancillary study to a multicenter randomized trial of thyroxine therapy for pregnant individuals with subclinical hypothyroidism. Dyads of infants and birthing parent, with completed Center for Epidemiological Studies-Depression (CES-D) screens during pregnancy and postpartum and child neurodevelopment testing completed at five years of age (n=209) were included. CES-D screening was performed at 11-20 weeks, 34-38 weeks, and one-year postpartum. Depressive symptoms were categorized as antenatal (i.e., a positive screen at any point during pregnancy) or postpartum. The primary outcome was child IQ score < 85 at 5 years of age using the Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III) Full Scale test. Secondary outcomes included other assessments of childhood neurodevelopment. Bivariable analyses and multivariable logistic regressions were utilized. RESULTS: Of the 209 birthing people included, 72 (34%) screened positive for depression during pregnancy and 32 (15%) screened positive one year postpartum. Children born to individuals with a positive antenatal depression screen had a higher odds of IQ <85 at 5 years of age compared with children born to individuals with a CES-D <16 (35% vs. 18 %, OR 2.4, 95% CI 1.2-4.7). Similar findings were seen for children born to individuals with a positive postpartum depression screen (47% vs. 21%, OR 3.3, 95% CI 1.5-7.3). These associations did not persist in multivariable analyses that controlled for social determinants of health and clinical characteristics (adjusted odd ratio (aOR) 1.4, 95% CI 0.7-3.1; aOR 2.1, 95% CI 0.9-5.1, for antenatal and postpartum depressive symptoms, respectively). Similar findings were observed for other adverse neurodevelopmental outcomes. CONCLUSIONS: Having a positive perinatal depression screen was not associated with child cognitive outcomes after controlling for covariates including social determinants of health.

Blood Pressure Control in Pregnant Patients with Chronic Hypertension and Diabetes: Should <130/80 be the Target?

BACKGROUND: The Chronic Hypertension and Pregnancy Study (CHAP) demonstrated that a target blood pressure of <140/90 mm Hg during pregnancy is associated with improved perinatal outcomes. Outside of pregnancy, pharmacologic therapy for patients with diabetes and hypertension is adjusted to a target blood pressure of <130/80 mm Hg. During pregnancy, patients with both diabetes and chronic hypertension may also benefit from tighter control with a target blood pressure (BP) <130/80 mm Hg. OBJECTIVE: We compared perinatal outcomes in patients with hypertension and diabetes who achieved BP <130/80 versus 130-139/80-89 mm Hg. STUDY DESIGN: This was a secondary analysis of a multi-center randomized controlled trial. Participants were included in this secondary analysis if they had diabetes diagnosed prior to pregnancy or at <20 weeks' gestation and at least two recorded BP measurements prior to delivery. Average systolic and diastolic BP were calculated using ambulatory antenatal BPs. The primary composite outcome was preeclampsia with severe features, indicated preterm birth <35 weeks, or placental abruption. Secondary outcomes were components of the primary outcome, cesarean delivery, fetal or neonatal death, neonatal intensive care unit (NICU) admission, and small for gestational age (SGA). Comparisons were made between those with an average systolic BP <130 mm Hg and average diastolic BP <80 mm Hg and those with an average systolic blood pressure 130-139 mm Hg or diastolic blood pressure 80-89 mm Hg using Student's t-test and chi-squared tests. Multivariable log-binomial regression models were used to evaluate risk ratios between blood pressure groups for dichotomous outcomes while accounting for baseline covariates. RESULTS: Of 434 participants included, 150 (34.6%) had an average blood pressure less than 130/80 mm Hg. Participants with an average blood pressure less than 130/80 were more likely to be on antihypertensive medications at the start of pregnancy and more likely to have newly diagnosed DM prior to 20 weeks. Participants with an average blood pressure less than 130/80 mm Hg were less likely to have the primary adverse perinatal outcome (19.3% vs 46.5%, adjusted relative risk (aRR) 0.43, 95% CI 0.30-0.61, p<0.01), with decreased risks specifically of preeclampsia with severe features (aRR 0.35, 95% CI 0.23-0.54) and indicated preterm birth prior to 35 weeks (aRR 0.44, 95% CI 0.24-0.79). The risk of NICU admission was lower in the lower blood pressure group (aRR 0.74, 95% CI 0.59-0.94). No differences were noted in cesarean delivery (aRR 1.04, 95% CI 0.90-1.20), fetal or neonatal death (aRR 0.59, 95% CI 0.12-2.92). SGA less than the 10th percentile was lower in the lower blood pressure group (aRR 0.37, 95% CI 0.14-0.96). CONCLUSION: In those with chronic hypertension and diabetes prior to 20 weeks, achieving an average goal blood pressure of <130/80 mm Hg may be associated with improved perinatal outcomes.

Effects of Antihypertensive Therapy During Pregnancy on Postpartum Blood Pressure Control.

OBJECTIVE: To compare differences in postpartum blood pressure (BP) control (BP below 140/90 mm Hg) for participants with hypertension randomized to receive antihypertensive treatment compared with no treatment during pregnancy. METHODS: This study was a planned secondary analysis of a multicenter, open-label, randomized controlled trial (The CHAP [Chronic Hypertension and Pregnancy] trial). Pregnant participants with mild chronic hypertension (BP below 160/105 mm Hg) were randomized into two groups: active (antihypertensive treatment) or control (no treatment unless severe hypertension, BP 160/105 mm Hg or higher). Study outcomes were BP control below 140/90 mm Hg (primary) and medication nonadherence based on a composite score threshold (secondary) at the 6-week postpartum follow-up visit. Participants without follow-up BP measurements were excluded from analysis of the BP control outcome. Participants without health care professional-prescribed antihypertensives at delivery were excluded from the analysis of the adherence outcome. Multivariable logistic regression was used to adjust for potential confounders. RESULTS: Of 2,408 participants, 1,684 (864 active, 820 control) were included in the analysis. A greater percentage of participants in the active group achieved BP control (56.7% vs 51.5%; adjusted odds ratio [aOR] 1.22, 95% CI, 1.00-1.48) than in the control group. Postpartum antihypertensive prescription was higher in the active group (81.7% vs 58.4%, P<.001), and nonadherence did not differ significantly between groups (aOR 0.81, 95% CI, 0.64-1.03). CONCLUSION: Antihypertensive treatment of mild chronic hypertension during pregnancy was associated with better BP control below 140/90 mm Hg in the immediate postpartum period.

Comparative effectiveness trial of metformin versus insulin for the treatment of gestational diabetes in the USA: clinical trial protocol for the multicentre DECIDE study.

INTRODUCTION: Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycaemic control decreases the risk of adverse pregnancy outcomes for the affected pregnant individual and the infant exposed in utero. One in four individuals with GDM will require pharmacotherapy to achieve glycaemic control. Injectable insulin has been the mainstay of pharmacotherapy. Oral metformin is an alternative option increasingly used in clinical practice. Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterised, adequately powered study of a diverse US population remain lacking. Because metformin crosses the placenta, long-term safety data, in particular, the risk of childhood obesity, from exposed children are also needed. In addition, the patient-reported experiences of individuals with GDM requiring pharmacotherapy remain to be characterised, including barriers to and facilitators of metformin versus insulin use. METHODS AND ANALYSIS: In a two-arm open-label, pragmatic comparative effectiveness randomised controlled trial, we will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. We plan to recruit 1572 pregnant individuals with GDM who need pharmacotherapy at 20 US sites using consistent diagnostic and treatment criteria for oral metformin versus injectable insulin and follow them and their children through delivery to 2 years post partum. More information is available at www.decidestudy.org. ETHICS AND DISSEMINATION: The Institutional Review Board at The Ohio State University approved this study (IRB: 2024H0193; date: 7 December 2024). We plan to submit manuscripts describing the results of each study aim, including the pregnancy outcomes, the 2-year follow-up outcomes, and mixed-methods assessment of patient experiences for publication in peer-reviewed journals and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER: NCT06445946.

External validation and comparison of four prediction scores for severe maternal morbidity.

BACKGROUND: Severe maternal morbidity (SMM) is increasing in the United States. Several tools and scores exist to stratify an individual's risk of SMM. OBJECTIVE: We sought to examine and compare the validity of four scoring systems for predicting SMM. STUDY DESIGN: This was a retrospective cohort study of all individuals in the Consortium on Safe Labor dataset, which was conducted from 2002 to 2008. Individuals were excluded if they had missing information on risk factors. SMM was defined based on the Centers for Disease Control and Prevention excluding blood transfusion. Blood transfusion was excluded due to concerns regarding the specificity of International Classification of Diseases codes for this indicator and its variable clinical significance. Risk scores were calculated for each participant using the Assessment of Perinatal Excellence (APEX), California Maternal Quality Care Collaborative (CMQCC), Obstetric Comorbidity Index (OB-CMI), and modified OB-CMI. We calculated the probability of SMM according to the risk scores. The discriminative performance of the prediction score was examined by the areas under receiver operating characteristic curves and their 95% confidence intervals (95% CI). The area under the curve for each score was compared using the bootstrap resampling. Calibration plots were developed for each score to examine the goodness-of-fit. The concordance probability method was used to define an optimal cutoff point for the best-performing score. RESULTS: Of 153, 463 individuals, 1115 (0.7%) had SMM. The CMQCC scoring system had a significantly higher area under the curve (95% CI) (0.78 [0.77-0.80]) compared to the APEX scoring system, OB-CMI, and modified OB-CMI scoring systems (0.75 [0.73-0.76], 0.67 [0.65-0.68], 0.66 [0.70-0.73]; P<.001). Calibration plots showed excellent concordance between the predicted and actual SMM for the APEX scoring system and OB-CMI (both Hosmer-Lemeshow test P values=1.00, suggesting goodness-of-fit). CONCLUSION: This study validated four risk-scoring systems to predict SMM. Both CMQCC and APEX scoring systems had good discrimination to predict SMM. The APEX score and the OB-CMI had goodness-of-fit. At ideal calculated cut-off points, the APEX score had the highest sensitivity of the four scores at 71%, indicating that better scoring systems are still needed for predicting SMM.

Impact of the ARRIVE Trial on Stillbirth Rates in Nulliparous Individuals.

OBJECTIVE: We aim to examine the population-level rates of induction, stillbirth, perinatal mortality, and neonatal death before and after the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial. STUDY DESIGN: This study was a cross-sectional analysis of publicly available U.S. Live Birth data linked with Infant Death and Fetal Death certificate data from National Vital Statistics Online. We limited analyses to nulliparous individuals with singleton pregnancy and cephalic presentation who delivered at 39 weeks or greater. The pre- and post-ARRIVE periods spanned from August 2016 to July 2018, and from January 2019 to December 2020, respectively. Our primary outcome was a stillbirth. Secondary outcomes included induction of labor, perinatal mortality, and neonatal death. Outcomes were compared between the pre- and post-ARRIVE periods. Modified Poisson regression was used to calculate adjusted relative risks (aRRs). RESULTS: Of 2,817,071 births, there were 1,454,346 births in the pre-ARRIVE period and 1,362,725 in the post-ARRIVE period; there were 1,196 and 1,062 stillbirths in the pre- and post-ARRIVE periods, respectively. Compared to the pre-ARRIVE period, the post-ARRIVE period was not associated with a significant decrease in the risk of stillbirth at 39 weeks or greater (aRR 0.92 [95% confidence interval {95% CI} 0.85-1.00]) and stillbirth at 40 weeks or greater (aRR 0.92 [95% CI 0.82-1.04]). Compared to the pre-ARRIVE trial period, the post-ARRIVE trial was associated with increased rates of induction of labor at 39 weeks (aRR 1.37 [95% CI 1.37-1.38]) and 40 weeks (aRR 1.24 [95% CI 1.24-1.25]. Similar to stillbirth, there was no significant decrease in the risk of perinatal mortality at 39 weeks or greater or 40 weeks or greater. There was also no statistically significant change in neonatal death rates at 39 weeks or greater or at 40 weeks or greater. CONCLUSION: The increase in induction of labor at 39 weeks was not large enough to impact the stillbirth rate at 39 weeks or greater. KEY POINTS: · Post-ARRIVE trial, rate of induction of labor increased at 39 and 40 weeks.. · Post-ARRIVE trial, stillbirth and perinatal mortality rates remained unchanged.. · Induction rate rise post-ARRIVE trial did not impact neonatal death rates..

Pregnancy Outcomes in Patients With Hepatitis C Virus Infection.

OBJECTIVE: To evaluate the risks of adverse maternal and neonatal outcomes associated with pregnancies complicated by hepatitis C virus (HCV) infection. METHODS: This is a secondary analysis of a multicenter prospective cohort study of HCV infection in pregnancy. Participants were screened for HCV infection with serum antibody tests, and each participant with a positive HCV result (case group) was matched with up to two individuals with negative HCV results (control group) prospectively by gestational age (±2 weeks) at enrollment. Maternal outcomes included gestational diabetes, abruption, preeclampsia or gestational hypertension, cholestasis, and preterm delivery. Neonatal outcomes included hyperbilirubinemia, admission to neonatal intensive care (NICU); small-for-gestational-age (SGA) birth weight; and neonatal infection, defined as sepsis or pneumonia. Models were adjusted for maternal age, body mass index, injection drug use, and maternal medical comorbidities. RESULTS: The 249 individuals in the case group were prospectively matched to 486 individuals in the control group who met eligibility criteria. There were significant differences in demographic characteristics between the groups, including race, socioeconomic markers, education, insurance status, and drug and tobacco use. The frequencies of maternal outcomes of gestational diabetes, preeclampsia, and abruption were similar between the case and control groups. Preterm birth was similar between groups, but neonates born to individuals in the case group were more likely to be admitted to the NICU (45.1% vs 19.0%, adjusted odds ratio [aOR] 2.6, 95% CI, 1.8-3.8) and to have SGA birth weights below the 5th percentile (10.6% vs 3.1%, aOR 2.9, 95% CI, 1.4-6.0). There were no increased odds of hyperbilirubinemia or neonatal infection. CONCLUSION: Despite no increased odds of preterm birth or other adverse maternal outcomes in adjusted analyses, maternal HCV infection was associated with twofold increased odds of NICU admission and nearly threefold increased odds of SGA birth weight below the 5th percentile.

Maternal implications of fetal anomalies: a population-based cross-sectional study.

BACKGROUND: Although it is well-known that the presence of fetal anomalies is associated with maternal morbidity, granular information on these risks by type of anomaly is not available. OBJECTIVE: To examine adverse maternal outcomes according to the type of fetal anomaly. STUDY DESIGN: This was a repeated cross-sectional analysis of US vital statistics Live Birth/Infant Death linked data from 2011 to 2020. All pregnancies at 20 weeks or greater were included. Our primary outcome was severe maternal morbidity (SMM), defined as any maternal intensive care unit admission, transfusion, uterine rupture, or hysterectomy. Outcomes were compared between pregnancies with a specific type of fetal anomaly and pregnancies without any fetal anomaly. Fetal anomalies that were available in the dataset included anencephaly, meningomyelocele/spina bifida, cyanotic congenital heart disease, congenital diaphragmatic hernia, omphalocele, gastroschisis, cleft lip and/or palate, hypospadias, limb anomaly, and chromosomal disorders. If a fetus had more than one anomaly, it was classified as multiple anomalies. Adjusted relative risks (aRR) with 99% confidence intervals (99% CI) were calculated using modified Poisson regression. Adjusted risk differences (aRDs) were calculated using the marginal standardization form of predictive margins. RESULTS: Of 35,760,626 pregnancies included in the analysis, 35,655,624 pregnancies had no fetal anomaly and 105,002 had isolated or multiple fetal anomalies. Compared to pregnancies without fetal anomaly, all fetal anomalies were associated with an increased risk of SMM except for gastroschisis and limb anomaly in order of aRRs (99% CI): 1.58 (1.29-1.92) with cleft lip and/or palate; 1.75 (1.35-2.27) with multiple anomalies; 1.76 (1.18-2.63) with a chromosomal disorder; 2.19 (1.82-2.63) with hypospadias; 2.20 (1.51-3.21) with spina bifida; 2.39 (1.62-3.53) with congenital diaphragmatic hernia; 2.66 (2.27-3.13) with congenital heart disease; 3.15 (2.08-4.76) with omphalocele; and 3.27 (2.22-4.80) with anencephaly. Compared to pregnancies without fetal anomaly, all fetal anomalies were associated with an increased absolute risk of SMM except for gastroschisis and limb anomaly in order of aRDs (99% CI): 0.26 (0.12-0.40) with cleft lip and/or palate, 0.34 (0.13-0.55) with multiple anomalies, 0.34 (0.02-0.66) with a chromosomal disorder, 0.54 (0.36-0.72) with hypospadias, 0.54 (0.17-0.92) with spina bifida, 0.63 (0.21-1.05) with congenital diaphragmatic hernia, 0.75 (0.56-0.95) with congenital heart disease, 0.97 (0.38-1.56) with omphalocele, and 1.03 (0.46-1.59) with anencephaly. CONCLUSION: The presence of fetal anomalies is associated with adverse maternal health outcomes. The risk of SMM varies according to the type of fetal anomaly. Counseling mothers about the maternal implications of fetal anomalies is paramount to help them make informed decisions regarding their pregnancy outcome.

Activity restriction and risk of adverse pregnancy outcomes.

BACKGROUND: Activity restriction is a common recommendation given to patients during pregnancy for various indications, despite lack of definitive data showing improvements in pregnancy outcomes. OBJECTIVE: To determine if activity restriction (AR) in pregnancy is associated with decreased odds of adverse pregnancy outcomes (APOs). STUDY DESIGN: Secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) prospective cohort. Nulliparous singletons were followed at 8 sites from October 2010 - September 2013. Demographic and clinical data were collected at 4 timepoints, and participants were surveyed about AR recommendations at 22w0d-29w6d and delivery. We excluded participants missing data on AR and age. Participants were grouped according to history of AR, and APOs included: gestational hypertension (gHTN), preeclampsia/eclampsia, preterm birth (PTB), and small for gestational age (SGA) neonate. Associations between AR and APOs were examined using uni- and multivariable logistic regression models adjusting for a priori identified APO risk factors. RESULTS: Of 10,038 nuMoM2b participants, 9,312 met inclusion criteria and 1,386 (14.9%) were recommended AR; participants identifying as Black [aOR 0.81 (95% CI 0.68-0.98)] or Hispanic [aOR 0.73 (95% CI 0.61-0.87)] were less likely to be placed on AR when compared to those identifying as White. Overall, 3,197 (34.3%) experienced at least one APO [717 (51.7%) of participants with AR compared to 2,480 (31.3%) participants without AR]. After adjustment for baseline differences, the AR group had increased odds of gHTN [aOR 1.61 (95% CI 1.35-1.92)], preeclampsia/eclampsia [aOR 2.52 (95% CI 2.06-3.09)] and iatrogenic and spontaneous PTB [aOR 2.98 (95% CI 2.41-3.69)], but not delivery of an SGA neonate. CONCLUSION: AR in pregnancy was independently associated with increased odds of hypertensive disorders of pregnancy and PTB, but future prospective work is needed to determine potential causality. Further, participants identifying as Black or Hispanic were significantly less likely to be recommended AR compared to those identifying as White. While AR is not an evidence-based practice, these findings suggest bias may impact which patients receive advice to limit activity in pregnancy.

Neonatal and Maternal Outcomes in Nulliparous Individuals according to Prepregnancy Body Mass Index.

OBJECTIVE: This study aimed to examine the effect of incremental changes in body mass index (BMI, kg/m2) on the association with adverse pregnancy outcomes. STUDY DESIGN: This was a retrospective cohort study of U.S. vital statistics Live Birth and Infant Death linked data from 2011 to 2020. We limited analyses to nulliparas with singleton pregnancies who delivered at 20 weeks or greater. Outcomes were compared according to the prepregnancy BMI category using 5 kg/m2 increments, with each of the other BMI categories sequentially as the referent. The composite neonatal outcome was defined as any neonatal death, neonatal intensive care unit (ICU), surfactant use, ventilation use, or seizure. Severe maternal morbidity was defined as any maternal ICU, transfusion, uterine rupture, and hysterectomy. Adjusted relative risks were calculated for each BMI category as a referent group, using modified Poisson regression and adjusting for confounders. RESULTS: A total of 11,174,890 nulliparous individuals were included. From 2011 to 2020, the proportions of individuals with BMI 40 or greater, BMI 50 or greater, and BMI 60 or greater increased significantly (from 3.1 to 4.9%, from 0.4 to 0.6%, from 0.03 to 0.06%, respectively; all trend p-values < 0.001). As BMI deviated from normal BMI, risks of neonatal and maternal adverse outcomes increased progressively. For example, as BMI deviated from normal BMI (18.5-24.9), the risk of composite neonatal outcome increased by 2% in individuals with BMI < 18.5 and up to 2.11-fold in individuals with BMI 65-69.9. When compared with BMI 40 to 44.9, BMI 35 to 39.9 was associated with an 8% decreased risk of composite neonatal outcome, whereas BMI 45 to 49.9 was associated with an 8% increased risk of composite neonatal outcome. CONCLUSION: Incremental increases in prepregnancy BMI are linked to higher risks of adverse pregnancy outcomes, highlighting the need for effective weight management before conception. KEY POINTS: · Incremental BMI increases raise pregnancy risks.. · Higher BMI linked to adverse neonatal outcomes.. · Elevated BMI heightens severe maternal morbidity..

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.

Longitudinal associations between urinary biomarkers of phthalates and replacements with novel in vivo measures of placental health.

STUDY QUESTION: What is the longitudinal association between gestational phthalate exposure and in vivo placental outcomes? SUMMARY ANSWER: Phthalates were adversely associated with placental microvasculature, stiffness, and presence of calcification, with different metabolites associated with different outcomes. WHAT IS KNOWN ALREADY: Phthalate exposure is ubiquitous and implicated as a contributor to adverse pregnancy outcomes, possibly through impacts on the placenta. STUDY DESIGN, SIZE, DURATION: A total of 303 women were recruited in early pregnancy and prospectively followed for up to eight visits across gestation in the Human Placenta and Phthalates study. PARTICIPANTS/MATERIALS, SETTING, METHODS: At each visit, women provided urine samples and underwent placental ultrasounds. Urine was analyzed for 18 metabolites of phthalates and replacements. We took the geometric mean of repeated measurements to reflect pregnancy-averaged phthalate or replacement exposure for each participant (n = 303). Placental microvasculature, stiffness, and microcalcification presence were quantified from ultrasounds at each visit. Higher scores reflected worse placental function for all measures. Generalized linear mixed models were created to estimate the association between pregnancy-averaged exposure biomarker concentrations and repeated outcome measurements for microvasculature and stiffness. Gestational age at the time of calcification detection was modeled using Cox proportional hazards models. MAIN RESULTS AND THE ROLE OF CHANCE: Monocarboxyisononyl phthalate and summed di(2-ethylhexyl) phthalate metabolites were associated with impaired microvasculature development, such that an interquartile range increase in concentration was associated with 0.11 standard deviation increase in the microvasculature ratio, indicating poorer vascularization (95% CI: 0.00, 0.22); 0.11 [95% CI: -0.01, 0.22], respectively. Monoethyl phthalate was associated with increased placental stiffness (0.09 [95% CI: -0.01, 0.19]) while summed di-iso-butyl phthalate metabolites and monobenzyl phthalate were associated with increased hazard of calcification detection (hazard ratios: 1.18 [95% CI: 0.98, 1.42]; 1.13 [95% CI: 0.96, 1.34]). LIMITATIONS, REASONS FOR CAUTION: Outcomes used in this study are novel and further investigation is needed to provide clinical context and relevance. WIDER IMPLICATIONS OF THE FINDINGS: We found evidence of associations between select phthalate biomarkers and various aspects of in vivo placental health, although we did not observe consistency across placental outcomes. These findings could illustrate heterogeneous effects of phthalate exposure on placental function. STUDY FUNDING/COMPETING INTEREST(S): This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZIA ES103344), and NIEHS T32ES007018. The authors declare that they have no competing interests to disclose. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services. TRIAL REGISTRATION NUMBER: N/A.

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.

Optimal Timing of Delivery for Pregnant Individuals With Mild Chronic Hypertension.

OBJECTIVE: To investigate the optimal gestational age to deliver pregnant people with chronic hypertension to improve perinatal outcomes. METHODS: We conducted a planned secondary analysis of a randomized controlled trial of chronic hypertension treatment to different blood pressure goals. Participants with term, singleton gestations were included. Those with fetal anomalies and those with a diagnosis of preeclampsia before 37 weeks of gestation were excluded. The primary maternal composite outcome included death, serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit admission, intubation, renal failure), preeclampsia with severe features, hemorrhage requiring blood transfusion, or abruption. The primary neonatal outcome included fetal or neonatal death, respiratory support beyond oxygen mask, Apgar score less than 3 at 5 minutes, neonatal seizures, or suspected sepsis. Secondary outcomes included intrapartum cesarean birth, length of stay, neonatal intensive care unit admission, respiratory distress syndrome (RDS), transient tachypnea of the newborn, and hypoglycemia. Those with a planned delivery were compared with those expectantly managed at each gestational week. Adjusted odds ratios (aORs) with 95% CIs are reported. RESULTS: We included 1,417 participants with mild chronic hypertension; 305 (21.5%) with a new diagnosis in pregnancy and 1,112 (78.5%) with known preexisting hypertension. Groups differed by body mass index (BMI) and preexisting diabetes. In adjusted models, there was no association between planned delivery and the primary maternal or neonatal composite outcome in any gestational age week compared with expectant management. Planned delivery at 37 weeks of gestation was associated with RDS (7.9% vs 3.0%, aOR 2.70, 95% CI, 1.40-5.22), and planned delivery at 37 and 38 weeks was associated with neonatal hypoglycemia (19.4% vs 10.7%, aOR 1.97, 95% CI, 1.27-3.08 in week 37; 14.4% vs 7.7%, aOR 1.82, 95% CI, 1.06-3.10 in week 38). CONCLUSION: Planned delivery in the early-term period compared with expectant management was not associated with a reduction in adverse maternal outcomes. However, it was associated with increased odds of some neonatal complications. Delivery timing for individuals with mild chronic hypertension should weigh maternal and neonatal outcomes in each gestational week but may be optimized by delivery at 39 weeks.

Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) After Infection During Pregnancy.

OBJECTIVE: To estimate the prevalence of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) after infection with SARS-CoV-2 during pregnancy and to characterize associated risk factors. METHODS: In a multicenter cohort study (NIH RECOVER [Researching COVID to Enhance Recovery]-Pregnancy Cohort), individuals who were pregnant during their first SARS-CoV-2 infection were enrolled across the United States from December 2021 to September 2023, either within 30 days of their infection or at differential time points thereafter. The primary outcome was PASC , defined as score of 12 or higher based on symptoms and severity as previously published by the NIH RECOVER-Adult Cohort, at the first study visit at least 6 months after the participant's first SARS-CoV-2 infection. Risk factors for PASC were evaluated, including sociodemographic characteristics, clinical characteristics before SARS-CoV-2 infection (baseline comorbidities, trimester of infection, vaccination status), and acute infection severity (classified by need for oxygen therapy). Multivariable logistic regression models were fitted to estimate associations between these characteristics and presence of PASC. RESULTS: Of the 1,502 participants, 61.1% had their first SARS-CoV-2 infection on or after December 1, 2021 (ie, during Omicron variant dominance); 51.4% were fully vaccinated before infection; and 182 (12.1%) were enrolled within 30 days of their acute infection. The prevalence of PASC was 9.3% (95% CI, 7.9-10.9%) measured at a median of 10.3 months (interquartile range 6.1-21.5) after first infection. The most common symptoms among individuals with PASC were postexertional malaise (77.7%), fatigue (76.3%), and gastrointestinal symptoms (61.2%). In a multivariable model, the proportion PASC positive with vs without history of obesity (14.9% vs 7.5%, adjusted odds ratio [aOR] 1.65, 95% CI, 1.12-2.43), depression or anxiety disorder (14.4% vs 6.1%, aOR 2.64, 95% CI, 1.79-3.88) before first infection, economic hardship (self-reported difficulty covering expenses) (12.5% vs 6.9%, aOR 1.57, 95% CI, 1.05-2.34), and treatment with oxygen during acute SARS-CoV-2 infection (18.1% vs 8.7%, aOR 1.86, 95% CI, 1.00-3.44) were associated with increased prevalence of PASC. CONCLUSION: The prevalence of PASC at a median time of 10.3 months after SARS-CoV-2 infection during pregnancy was 9.3% in the NIH RECOVER-Pregnancy Cohort. The predominant symptoms were postexertional malaise, fatigue, and gastrointestinal symptoms. Several socioeconomic and clinical characteristics were associated with PASC after infection during pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT05172024.

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.

The role of point-of-care ultrasound to monitor response of fluid replacement therapy in pregnancy.

Fluid management in obstetrical care is crucial because of the complex physiological conditions of pregnancy, which complicate clinical manifestations and fluid balance management. This expert review examined the use of point-of-care ultrasound to evaluate and monitor the response to fluid therapy in pregnant patients. Pregnancy induces substantial physiological changes, including increased cardiac output and glomerular filtration rate, decreased systemic vascular resistance, and decreased plasma oncotic pressure. Conditions, such as preeclampsia, further complicate fluid management because of decreased intravascular volume and increased capillary permeability. Traditional methods for assessing fluid volume status, such as physical examination and invasive monitoring, are often unreliable or inappropriate. Point-of-care ultrasound provides a noninvasive, rapid, and reliable means to assess fluid responsiveness, which is essential for managing fluid therapy in pregnant patients. This review details the various point-of-care ultrasound modalities used to measure dynamic changes in fluid status, focusing on the evaluation of the inferior vena cava, lung ultrasound, and left ventricular outflow tract. Inferior vena cava ultrasound in spontaneously breathing patients determines diameter variability, predicts fluid responsiveness, and is feasible even late in pregnancy. Lung ultrasound is crucial for detecting early signs of pulmonary edema before clinical symptoms arise and is more accurate than traditional radiography. The left ventricular outflow tract velocity time integral assesses stroke volume response to fluid challenges, providing a quantifiable measure of cardiac function, which is particularly beneficial in critical care settings where rapid and accurate fluid management is essential. This expert review synthesizes current evidence and practice guidelines, suggesting the integration of point-of-care ultrasound as a fundamental aspect of fluid management in obstetrics. It calls for ongoing research to enhance techniques and validate their use in broader clinical settings, aiming to improve outcomes for pregnant patients and their babies by preventing complications associated with both under- and overresuscitation.