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.

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.

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.

Decreased vascular reactivity associated with increased IL-8 in 6-month-old infants of mothers with pre-eclampsia.

BACKGROUND: Offspring born to mothers with pre-eclampsia (Pre-E) suffer higher risks of adult cardiovascular diseases, suggesting that exposure to an antiangiogenic environment in-utero has a lasting impact on the development of endothelial function. The goal of this study is to test the hypothesis that in-utero exposure to Pre-E results in alterations of angiogenic factors/cytokines that negatively impact vascular development during infancy. METHODS: Infants born from mothers with and without Pre-E were recruited and followed up at 6 months. Plasma cytokines, blood pressure, microvessel density, and vascular reactivity were assessed. RESULTS: 6-month-old infants born to mothers with Pre-E had unchanged blood pressure (p = 0.86) and microvessel density (p = 0.57). Vascular reactivity was decreased in infants born to mothers with Pre-E compared to infants born to healthy mothers (p = 0.0345). Interleukin 8 (IL-8) (p = 0.03) and Angiopoeitin-2 (Ang-2) (p = 0.04) were increased in infants born to mothers with Pre-E. We observed that higher IL-8 was associated with lower vascular reactivity (rho = -0.14, p < 0.0001). CONCLUSION: At 6 months of age, infants born to mothers with Pre-E had impaired vascular reactivity and higher IL-8 and Ang-2, but similar blood pressure and microvessel density compared to infants born to non-Pre-E mothers. IMPACT STATEMENT: Changes in cord blood antiangiogenic factors are documented in infants of mothers with pre-eclampsia and may contribute to offspring risks of adult cardiovascular disease. How these factors evolve during early infancy and their correlation with offspring vascular development have not been studied. This study found that 6-month-old infants born to mothers with pre-eclampsia had decreased vascular reactivity, which was correlated with higher IL-8. These findings underscore the lasting impact of maternal pre-eclampsia on offspring vascular development and highlight the need for long-term follow-up in children born to mothers with pre-eclampsia.

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.

NuMoM2b Study Insights: Primary Exposures, Outcomes, and Directions for Future Research.

OBJECTIVE: To summarize the publications to date from a large obstetric cohort of nulliparous individuals. STUDY DESIGN: We summarized all of the publications from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b). We descriptively summarized the most common outcomes and exposures reported in current publications. RESULTS: Fifty-six publications to date are discussed. The most common primary exposures reported are participant baseline characteristics such as body mass index (24%), sociodemographic characteristics (22%), and sleep factors (16%). These exposures were most commonly measured in the first trimester (77%). The most commonly reported primary outcomes were related to adverse pregnancy outcomes (APOs, 51.6%), with 25% using a composite of multiple APOs as the primary outcome. At least 8,000 participants were used in the analyses of over half of the publications. CONCLUSION: The nuMoM2b study has generated a diverse array of publications and conclusions on factors associated with APOs. The publicly available data set from the nuMoM2b study continues to hold potential for considerable advances, new insights, and future research opportunities to optimize pregnancy and pregnancy-related health. KEY POINTS: · The nuMoM2b pregnancy cohort has generated 56 publications thus far.. · The main findings of these publications are summarized and categorized in this work.. · The data and specimens from this cohort are available and can answer many clinical questions..

The Association between Sleep and Depression during Late Pregnancy and the Early Postpartum Period.

Objective To assess and correlate sleep quality and depressed mood symptoms in the late pregnancy and early postpartum periods. Study Design In a prospective pilot observational study, participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Edinburgh Postnatal Depression Scale (EPDS) questionnaires at delivery, 1, and 2 months postpartum. Pearson's correlation coefficients and PROC MIXED function estimated overall correlation for repeated measures. Results Twenty-six women were enrolled with a mean gestational age at delivery of 38.4 (± 2.4) weeks. Sleep quality and mood data were available at the three time points for 24, 16, and 11 participants, respectively. Poor sleep scores were noted by 75.0, 87.5, and 72.7% of women at the three time points. An elevated EPDS score of 10 or higher was claimed by 20.8, 12.5, and 18.2% of women, respectively. Higher PSQI scores were positively associated with higher EPDS scores overall ( r = 0.71, p < 0.001) and at each of the individual time points ( r = 0.79, p < 0.0001; r = 0.52, p = 0.04; and r = 0.70, p = 0.016, respectively). None of the women reporting good sleep quality had elevated EPDS scores. Conclusion Poor sleep is commonly reported around delivery, and at 1 and 2 months postpartum, and there is an association between poor sleep and depression symptoms.

COHESION: a core outcome set for the treatment of neonatal encephalopathy.

BACKGROUND: Heterogeneity in outcomes reported in trials of interventions for the treatment of neonatal encephalopathy (NE) makes evaluating the effectiveness of treatments difficult. Developing a core outcome set for NE treatment would enable researchers to measure and report the same outcomes in future trials. This would minimise waste, ensure relevant outcomes are measured and enable evidence synthesis. Therefore, we aimed to develop a core outcome set for treating NE. METHODS: Outcomes identified from a systematic review of the literature and interviews with parents were prioritised by stakeholders (n = 99 parents/caregivers, n = 101 healthcare providers, and n = 22 researchers/ academics) in online Delphi surveys. Agreement on the outcomes was achieved at online consensus meetings attended by n = 10 parents, n = 18 healthcare providers, and n = 13 researchers/ academics. RESULTS: Seven outcomes were included in the final core outcome set: survival; brain injury on imaging; neurological status at discharge; cerebral palsy; general cognitive ability; quality of life of the child, and adverse events related to treatment. CONCLUSION: We developed a core outcome set for the treatment of NE. This will allow future trials to measure and report the same outcomes and ensure results can be compared. Future work should identify how best to measure the COS. IMPACT: We have identified seven outcomes that should be measured and reported in all studies for the treatment of neonatal encephalopathy. Previously, a core outcome set for neonatal encephalopathy treatments did not exist. This will help to reduce heterogeneity in outcomes reported in clinical trials and other studies, and help researchers identify the best treatments for neonatal encephalopathy.

Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function.

Importance: Cannabis use is increasing among reproductive-age individuals and the risks associated with cannabis exposure during pregnancy remain uncertain. Objective: To evaluate the association between maternal cannabis use and adverse pregnancy outcomes known to be related to placental function. Design, Setting, and Participants: Ancillary analysis of nulliparous individuals treated at 8 US medical centers with stored urine samples and abstracted pregnancy outcome data available. Participants in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort were recruited from 2010 through 2013; the drug assays and analyses for this ancillary project were completed from June 2020 through April 2023. Exposure: Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol using frozen stored urine samples from study visits during the pregnancy gestational age windows of 6 weeks and 0 days to 13 weeks and 6 days (visit 1); 16 weeks and 0 days to 21 weeks and 6 days (visit 2); and 22 weeks and 0 days to 29 weeks and 6 days (visit 3). Positive results were confirmed with liquid chromatography tandem mass spectrometry. The timing of cannabis exposure was defined as only during the first trimester or ongoing exposure beyond the first trimester. Main Outcome and Measure: The dichotomous primary composite outcome included small-for-gestational-age birth, medically indicated preterm birth, stillbirth, or hypertensive disorders of pregnancy ascertained by medical record abstraction by trained perinatal research staff with adjudication of outcomes by site investigators. Results: Of 10 038 participants, 9257 were eligible for this analysis. Of the 610 participants (6.6%) with cannabis use, 32.4% (n = 197) had cannabis exposure only during the first trimester and 67.6% (n = 413) had ongoing exposure beyond the first trimester. Cannabis exposure was associated with the primary composite outcome (25.9% in the cannabis exposure group vs 17.4% in the no exposure group; adjusted relative risk, 1.27 [95% CI, 1.07-1.49]) in the propensity score-weighted analyses after adjustment for sociodemographic characteristics, body mass index, medical comorbidities, and active nicotine use ascertained via urine cotinine assays. In a 3-category cannabis exposure model (no exposure, exposure only during the first trimester, or ongoing exposure), cannabis use during the first trimester only was not associated with the primary composite outcome; however, ongoing cannabis use was associated with the primary composite outcome (adjusted relative risk, 1.32 [95% CI, 1.09-1.60]). Conclusions and Relevance: In this multicenter cohort, maternal cannabis use ascertained by biological sampling was associated with adverse pregnancy outcomes related to placental dysfunction.

The Effects of Preeclamptic Milieu on Cord Blood Derived Endothelial Colony-Forming Cells.

Preeclampsia is one of the leading causes of infant and maternal mortality worldwide. Many infants born from preeclamptic pregnancies are born prematurely with higher risk of developing cardiovascular later in their life. A key mechanism by which these complications occur is through stress-induced dysfunction of endothelial progenitor cells (EPCs), including endothelial colony-forming cells (ECFCs). To gain insight into this, cord blood derived ECFCs isolated from preeclamptic pregnancies (PRECs) were analyzed and compared to their healthy counterparts. While PRECs preserve key endothelial markers, they upregulate several markers associated with oxidative stress and inflammatory response. Compared to ECFCs, PRECs also exhibit lower migratory behaviors and impaired angiogenic potential. Interestingly, treatment of neuropilin-1 can improve tube formation in vitro. Collectively, this study reports that preeclamptic milieu influence phenotypes and functionality of PRECs, which can be rejuvenated using exogenous molecules. Promising results from this study warrant future investigations on the prospect of the rejuvenated PRECs to improve lung function of infants born from preeclamptic pregnancies.

Perinatal health effects of herbicides exposures in the United States: the Heartland Study, a Midwestern birth cohort study.

BACKGROUND: The objective of the Heartland Study is to address major knowledge gaps concerning the health effects of herbicides on maternal and infant health. To achieve this goal, a two-phased, prospective longitudinal cohort study is being conducted. Phase 1 is designed to evaluate associations between biomarkers of herbicide concentration and pregnancy/childbirth outcomes. Phase 2 is designed to evaluate potential associations between herbicide biomarkers and early childhood neurological development. METHODS: People (target enrollment of 2,000) who are seeking prenatal care, are ages 18 or older, and are ≤ 20 + 6 weeks gestation will be eligible for recruitment. The Heartland Study will utilize a combination of questionnaire data and biospecimen collections to meet the study objectives. One prenatal urine and buccal sample will be collected per trimester to assess the impact of herbicide concentration levels on pregnancy outcomes. Infant buccal specimens will be collected post-delivery. All questionnaires will be collected by trained study staff and clinic staff will remain blinded to all individual level research data. All data will be stored in a secure REDCap database. Hospitals in the agriculturally intensive states in the Midwestern region will be recruited as study sites. Currently participating clinical sites include Indiana University School of Medicine- affiliated Hospitals in Indianapolis, Indiana; Franciscan Health Center in Indianapolis, Indiana; Gundersen Lutheran Medical Center in La Crosse, Wisconsin, and University of Iowa in Iowa City, Iowa. An anticipated 30% of the total enrollment will be recruited from rural areas to evaluate herbicide concentrations among those pregnant people residing in the rural Midwest. Perinatal outcomes (e.g. birth outcomes, preterm birth, preeclampsia, etc.) will be extracted by trained study teams and analyzed for their relationship to herbicide concentration levels using appropriate multivariable models. DISCUSSION: Though decades of study have shown that environmental chemicals may have important impacts on the health of parents and infants, there is a paucity of prospective longitudinal data on reproductive impacts of herbicides. The recent, rapid increases in herbicide use across agricultural regions of the United States necessitate further research into the human health effects of these chemicals, particularly in pregnant people. The Heartland Study provides an invaluable opportunity to evaluate health impacts of herbicides during pregnancy and beyond. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov, NCT05492708 with initial registration and release 05 August, 2022.

The Childhood Opportunity Index's Association with Adverse Pregnancy and Newborn Outcomes in Nulliparous Persons.

OBJECTIVE: The objective of the study was to determine if using a novel measure of social determinants of health, the Childhood Opportunity Index (COI), at the time of delivery was associated with development of adverse pregnancy outcomes (APO) in nulliparous pregnant persons. STUDY DESIGN: Data were extracted from the 779 participants from a single nuMoM2b (Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be) study site, a prospective cohort study designed to identify contributors to APOs. Residential address information at delivery was linked to the location's COI. The overall composite and component scores in education, health and environmental, and socioeconomic indices were recorded. APOs of interest included preterm birth, hypertensive disorders of pregnancy, small for gestational age at birth, stillbirth, and gestational diabetes. Participant characteristics were compared by COI category and the association of COI with APOs was analyzed by logistic regression, controlling for age and self-reported race/ethnicity. RESULTS: The overall COI distribution was very low (45%), low (17%), moderate (10%), high (15%), and very high (13%). A total of 329 (43.5%) participants experienced at least one APO. Overall COI was associated with developing an APO (p = 0.02). Each component score was also associated with developing APOs and with race/ethnicity (p < 0.05). Compared with higher COI categories, an overall low or very low categorized location was independently associated with developing an APO (odds ratio: 1.636, 95% confidence interval: 1.16-2.31). Adjusting for gestational age at birth, those in lower COI areas had newborns with lower birth weight, birth length, and head circumference (estimate [95% confidence interval] birth weight: -0.0005 g [-0.0008 to -0.0001]; length: -0.065 cm [-0.124 to -0.0091]; head circumference: -0.123 cm [-0.208 to -0.045]). COI was not associated with other newborn outcomes. CONCLUSION: COI, a marker for social determinants of health, is independently associated with APOs. The COI may be a tool for risk stratification for pregnant people to help with APO-reducing strategies. KEY POINTS: · The COI is a neighborhood-level marker for social determinants of health.. · The COI at time of delivery is associated with APO and newborn birth weight, length, and head circumference.. · The COI may be usable in pregnancy clinics to help identify resource needs to optimize outcomes for pregnant individuals and newborns..

Perinatal Outcomes Associated With Management of Stage 1 Hypertension.

OBJECTIVE: To evaluate the association between maternal blood pressure (BP) below 130/80 mm Hg compared with 130-139/80-89 mm Hg and pregnancy outcomes. METHODS: We conducted a planned secondary analysis of CHAP (Chronic Hypertension and Pregnancy), an open label, multicenter, randomized controlled trial. Participants with mean BP below 140/90 mm Hg were grouped as below 130/80 mm Hg compared with 130-139/80-89 mm Hg by averaging postrandomization clinic BP throughout pregnancy. The primary composite outcome was preeclampsia with severe features, indicated preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The secondary outcome was small for gestational age (SGA). RESULTS: Of 2,408 patients in CHAP, 2,096 met study criteria; 1,328 had mean BP 130-139/80-89 mm Hg and 768 had mean BP below 130/80 mm Hg. Participants with mean BP below 130/80 mm Hg were more likely to be older, on antihypertensive medication, in the active treatment arm, and to have lower BP at enrollment. Mean clinic BP below 130/80 mm Hg was associated with lower frequency of the primary outcome (16.0% vs 35.8%, adjusted relative risk 0.45; 95% CI 0.38-0.54) as well as lower risk of severe preeclampsia and indicated birth before 35 weeks of gestation. There was no association with SGA. CONCLUSION: In pregnant patients with mild chronic hypertension, mean BP below 130/80 mm Hg was associated with improved pregnancy outcomes without increased risk of SGA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

The INGENIOUS trial: Impact of pharmacogenetic testing on adverse events in a pragmatic clinical trial.

Adverse drug events (ADEs) account for a significant mortality, morbidity, and cost burden. Pharmacogenetic testing has the potential to reduce ADEs and inefficacy. The objective of this INGENIOUS trial (NCT02297126) analysis was to determine whether conducting and reporting pharmacogenetic panel testing impacts ADE frequency. The trial was a pragmatic, randomized controlled clinical trial, adapted as a propensity matched analysis in individuals (N = 2612) receiving a new prescription for one or more of 26 pharmacogenetic-actionable drugs across a community safety-net and academic health system. The intervention was a pharmacogenetic testing panel for 26 drugs with dosage and selection recommendations returned to the health record. The primary outcome was occurrence of ADEs within 1 year, according to modified Common Terminology Criteria for Adverse Events (CTCAE). In the propensity-matched analysis, 16.1% of individuals experienced any ADE within 1-year. Serious ADEs (CTCAE level ≥ 3) occurred in 3.2% of individuals. When combining all 26 drugs, no significant difference was observed between the pharmacogenetic testing and control arms for any ADE (Odds ratio 0.96, 95% CI: 0.78-1.18), serious ADEs (OR: 0.91, 95% CI: 0.58-1.40), or mortality (OR: 0.60, 95% CI: 0.28-1.21). However, sub-group analyses revealed a reduction in serious ADEs and death in individuals who underwent pharmacogenotyping for aripiprazole and serotonin or serotonin-norepinephrine reuptake inhibitors (OR 0.34, 95% CI: 0.12-0.85). In conclusion, no change in overall ADEs was observed after pharmacogenetic testing. However, limitations incurred during INGENIOUS likely affected the results. Future studies may consider preemptive, rather than reactive, pharmacogenetic panel testing.

Risk factors and perinatal outcomes for persistent placenta previa in nulliparas.

BACKGROUND: Placenta previa diagnosed on midtrimester ultrasound often resolves by the third trimester. Multiparity and previous cesarean delivery have been associated with persistence of placenta previa at delivery. Risk factors for persistent placenta previa in nulliparas are not well characterized. OBJECTIVE: This study aimed to identify risk factors for persistent placenta previa in the nulliparous population, and evaluate differences in outcomes between persistent and resolved placenta previa. STUDY DESIGN: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b), a prospective cohort study that observed 10,037 nulliparous individuals throughout pregnancy. Nulliparas diagnosed with placenta previa on midtrimester ultrasound were included in this analysis. Baseline characteristics and delivery outcomes of nulliparas with persistent placenta previa were compared with those of nulliparas with resolved placenta previa. Multivariate logistic regression with stepwise model selection was used for adjusted analyses. RESULTS: A total of 171 nulliparas (1.7%) in the nuMoM2b study were diagnosed with placenta previa on midtrimester ultrasound, of whom 17% (n=29) had persistent placenta previa at delivery. When compared with those with resolved placenta previa, nulliparas with persistent placenta previa were more likely to be older (median, 32 years [interquartile range, 30-37] vs 29 years [interquartile range, 25-31]; P<.01), have a previous pregnancy of <20 weeks (48.3% vs 22.5%; P=.01), have a previous dilation and curettage/evacuation procedure (27.6% vs 10.6%; P=.03), or have a pregnancy that resulted from assisted reproductive technology (31% vs 4.9%; P=.01). After adjusting for potential confounders, maternal age (adjusted odds ratio, 1.11; 95% confidence interval, 1.02-1.21), in vitro fertilization (adjusted odds ratio, 9.00; 95% confidence interval, 1.97-41.14), and previous pregnancy of <20 weeks (adjusted odds ratio, 2.77; 95% confidence interval, 1.10-6.95) remained statistically significant risk factors for persistent placenta previa. Persistent placenta previa was also associated with higher likelihood of antepartum admission (10.3% vs 0%; P<.01), preterm delivery (34.5% vs 12%; P<.01), lower neonatal birthweight (median, 2847 g [interquartile range, 2655-3310] vs 3263 g [interquartile range, 2855-3560]), and cesarean delivery (100% vs 20.4%; P<.001), but there were no differences in overall pregnancy or neonatal outcomes. CONCLUSION: In nulliparous individuals diagnosed with placenta previa on midtrimester ultrasound, older maternal age, previous pregnancy of <20 weeks, and in vitro fertilization are associated with persistent placenta previa at delivery.