Maternal Hypertensive Disorders Of Pregnancy Research Articles

COVID-19 and Hypertensive Disorders of Pregnancy (HDP): A Portuguese Multicentric Retrospective Cohort Study of HDP in SARS-CoV-2 Infected Patients.

An increased incidence of hypertensive disorders of pregnancy (HDP) has been reported among pregnant women infected by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen behind coronavirus disease-19 (COVID-19). Although it is primarily a respiratory infection, the extra-pulmonary manifestations of COVID-19 mimic those found in preeclampsia (PE). Moreover, the two conditions share common risk factors and pathological mechanisms, hindering the ability to understand the interaction between them. Current literature on this topic is controversial and as there is an overlap of clinical and laboratory findings, HDP can be an overreported outcome in pregnant women with COVID-19.The aim of our study is to assess whether there is an association between maternal SARS-CoV-2 infection and HDP. We designed a multicenter retrospective cohort study with data collected from fivematernity hospitals in Almada, Porto,Lisboa, Penafiel and Coimbra, Portugal, between March 2020 and March 2021. We obtained a sample of 789 pregnant women who were followed up or delivered their babies in one of the participating centers. Each pregnant woman who tested positive for SARS-CoV-2 on a real-time polymerase chain reaction test -- exposure group (n= 263), was paired with two negative pregnant women (1:2), who received the same antenatal care and had similar gestational age and parity -- control group (n=526). Data were collected on maternal characteristics, medical history, obstetric outcomes, and delivery. Outcomes:The primary outcome of our study is to assess the incidence of HDPin pregnant women infected and not infected by SARS-CoV-2.The secondary outcomes of our study are to assess the incidence of HDP across all COVID-19 severity subgroupsand to assess whether SARS-CoV-2 infection in pregnancy modified the odds of a set of risk factors developingHDP. Results: There was a slightly increased, but not statistically significant, incidence of PE (relative risk, RR, 1.33; 95% confidence interval, CI 0.68-2.57) in the SARS-CoV-2 positive group.There was no statistically significant association between having COVID-19 in pregnancy and developing PE/eclampsia/ hemolysis, elevated liver enzymes, and low platelets, HELLP syndrome [X2(1) = 0.732; p = 0.392] as well as developing gestational hypertension (GH) [X2(1) = 0.039; p = 1]. There was no statistically significant association [X2(2) = 0.402; p = 0.875), [X2(2) = 1.529; p = 0.435] between COVID-19 severity and incidence of HDP. The SARS-CoV-2 infection did not modify the odds of each maternal risk factor causing HDP. Conclusion: Our study did not demonstrate an association between maternal COVID-19 and HDP. We did not observe a significantly increased incidence of HDP in pregnant women infected by SARS-CoV-2. As current literature is controversial on this topic, clinicians should be aware that HDP is a possible complication of maternal SARS-CoV-2 infection and further research studies urge to better assess the association between COVID-19 in pregnancy and HDP.

Relation of Disaster Exposure With Maternal Characteristics and Obstetric Outcomes: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

The present study analyzed the relation of disaster exposure prior to pregnancy with maternal characteristics and obstetric outcomes. The participants were 13,148 pregnant women recruited from 2013 to 2017. The women were classified into three groups by the severity of housing damage caused by the Great East Japan Earthquake of 2011: group A, house was not destroyed/did not live in the disaster area; group B, half/part of the house was destroyed; and group C, house was totally/mostly destroyed. Maternal characteristics, hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), and gestational weeks were obtained using questionnaires and medical records. Multiple logistic regression analyses were performed to investigate the relation between disaster exposure and maternal characteristics, HDP, and GDM. A structural equation model was applied to investigate the relation of disaster exposure with HDP and gestational weeks. The homes of about 11% of the women were totally/mostly destroyed. For groups B and C compared with those in group A, the adjusted ORs for HDP were 1.04 and 1.26 (P for trend = 0.01), and for GDM were 0.89 and 1.14 (P for trend = 0.9), respectively. Pre-pregnancy body mass index (BMI) mediated 23.2% of the relation between disaster exposure and HDP. Disaster exposure was associated with gestational weeks. Disaster exposure at least 2.5 years before pregnancy was found to be associated with maternal characteristics and the prevalence of HDP. Pre-pregnancy BMI mediated the relation between disaster exposure and the prevalence of HDP, and gestational weeks were reduced through HDP.

Abstract 17: Using Mobile Phone Location Data to Estimate the Association of Daytime Racial and Economic Segregation With Hypertensive Disorders of Pregnancy in Metro Atlanta

Background: Hypertensive disorders of pregnancy (HDPs) are a group of conditions that contribute to maternal morbidity and mortality, disproportionately affecting minority and low-income individuals. Complications from these HDPs may result in poor outcomes for mother and child during pregnancy or post-pregnancy. Disparities in HDPs may be associated with concentrated racial and income inequality in an individual’s activity space, such that the social exposure of places is not only formed by residence but also by daily mobility of the population at large. A novel aspect of women’s residential neighborhood environment can be explored by measuring daytime population mixing. Mobile phone data can be used to estimate social mixing during the daytime for income and racial/ethnic groups by describing the undercurrents of population mobility in neighborhoods. Objective: To estimate the association of daytime racial and income segregation with HDPs among women who gave birth from 2018 to 2019 in metro Atlanta. Methods: Data for women who gave birth in Metro Atlanta in 2018 and 2019 were abstracted from vital statistics records to determine HDP diagnosis and maternal residence by census tract. HDPs were grouped into pre-pregnancy hypertension, gestational hypertension, and eclampsia. Mobile phone location data from CUEBIQ were used to estimate median household income density in each census tract and racial/ethnic density, as a function of where devices moved between the hours of 7am and 10pm. Racial and economic composition of the device was assigned by the user’s estimated home census tract. The Index of Concentration at Extremes (ICE) was calculated as the mixing of mobile devices in each census tract, by race and income. Tracts were categorized as concentrated disadvantage for an ICE score less than -0.3 and concentrated privileged for an ICE score greater than 0.3. Logistic regression models were used to estimate odds of HDPs in census tracts with micro-segregation and income inequality during the daytime, compared to not at extremes. Results: There were 122,482 births included in the maternal cohort, and 8.1% of births occurred among women with a diagnosed HDP. Black women had a higher rate of HDPs compared to White women (9.7% versus 6.9%). Census tracts with higher daytime micro-segregation were associated with higher odds of HDPs compared to tracts not in the extremes (OR = 1.42; 95% CI= 1.35, 1.49). Census tracts with higher daytime income inequality were also associated with higher odds of HDPs (1.26;1.20, 1.33). Conclusions: The odds of maternal HDPs were higher among women in census tracts with greater racial daytime segregation and more income disparity, compared to tracts that were not identified as extremes. Describing and distinguishing social epidemiologic patterns for HDPs by population mobility may provide a better understanding of the social context of who is most at risk.

Impact of hypertensive disorders of pregnancy on neonatal outcomes among infants born at 24+0-31+6 weeks' gestation in China: A multicenter cohort study.

To describe the rate of hypertensive disorder of pregnancy (HDP) among mothers of very preterm infants (VPIs) admitted to Chinese neonatal intensive care units (NICUs), and to investigate the relationship between HDP and the outcomes of VPIs. Cohort study of all VPIs born at a gestational age of 24+0-31+6 weeks and admitted to 57 tertiary NICUs of the Chinese Neonatal Network (CHNN) in 2019. Infants with severe congenital anomalies or missing maternal HDP information were excluded. Two multivariate logistic regression models were generated to assess the relationship between HDP and neonatal outcomes. Among 9,262 infants enrolled, 1,744 (18.8%) infants were born to mothers with HDP, with an increasing incidence with increasing gestational age. VPIs born to mothers with HDP had higher gestational age but lower birth weight and were more likely to be small for gestational age. Mothers with HDP were more likely to receive antenatal steroids, MgSO4 and cesarean section. Infants in the HDP group showed higher observed rates of mortality or any morbidity than infants in the non-HDP group (50.2% vs. 47.2%, crude odds ratio (OR) 1.13, 95% CI 1.02-1.26). However, the associations between HDP and adverse outcomes were not significant after adjustment. In the HDP group, mothers of 1,324/1,688 (78.4%) infants were diagnosed with preeclampsia/eclampsia. Infants born to mothers with preeclampsia/eclampsia had significantly lower odds of early death and severe retinopathy of prematurity. Nearly one-fifth of VPIs were born to mothers with HDP in Chinese NICUs. No significant association was identified between HDP and adverse neonatal short-term outcomes of VPIs, while long-term follow-up of these infants is needed.

Bronchopulmonary Dysplasia in Extremely Premature Infants: A Scoping Review for Identifying Risk Factors

Over the years, bronchopulmonary dysplasia (BPD) affects the pulmonary function of infants, resulting in chronic health burdens for infants and their families. The aim of this scoping review was to screen available evidence regarding perinatal risk factors associated with the development and severity of BPD. The eligibility criteria of the studies were year of publication between 2016 and 2021; setting of a developed country; English or Japanese as the study language; and randomized controlled, cohort, or case-control design. The titles and abstracts of the studies were screened by independent reviewers. Of 8189 eligible studies, 3 were included for severe BPD and 26 were included for moderate BPD. The risk factors for severe BPD were male sex, iatrogenic preterm birth, maternal hypertensive disorders of pregnancy (HDP), low gestational age, small-for-gestational-age (SGA) birth weight, mechanical ventilation on day 1, and need for patent ductus arteriosus (PDA) management. The risk factors for moderate or severe BPD included male sex, premature rupture of membranes, clinical chorioamnionitis, maternal HDP, SGA birth weight, bubbly/cystic appearance on X-ray, and PDA management. We identified several risk factors for BPD. We plan to confirm the validity of the new classification using the existing dataset.

Association of maternal hypertensive disorders in pregnancy with infant neurodevelopment.

Inconsistent findings have been reported regarding the associations between hypertensive disorders in pregnancy (HDP) and infant neurodevelopment. Leveraging data from the Jiangsu Birth Cohort, in the present study, we re-visited such associations in one-year-old infants from 2576 singleton pregnancies and 261 twin pregnancies. We first assessed infant neurodevelopment by the Bayley Scales of Infant and Toddler Development Screening Test (the Third Edition), and then estimated its association with maternal HDP using general linear regression models and Poisson regression models. In singleton pregnancies, compared with mothers unexposed to HDP, infants born to mothers with chronic hypertension exhibited a lower score ( β, -0.67; 95% confidence interval [CI], -1.19--0.15) and a higher risk of "non-optimal" gross motor development (risk ratio [RR], 2.21; 95% CI, 1.02-4.79); in twin pregnancies, infants born to mothers with HDP exhibited lower scores in cognition ( β, -0.49; 95% CI, -0.96--0.01), receptive communication ( β, -0.55; 95% CI, -1.03--0.06), and gross motor ( β, -0.44; 95% CI, -0.86--0.03), and at a higher risk of "non-optimal" gross motor development (RR, 2.12; 95% CI, 1.16-3.88). These findings indicate that infants born to mothers with HDP may have inferior neurodevelopment outcomes at the age of one year.

Fetal growth restriction and a single umbilical artery are independent predictors of hypospadias during pregnancy

IntroductionLittle is known about the association between hypospadias and small fetuses, as well as the pathological implications of fetal growth restriction (FGR). Thus, we aimed to investigate the association between hypospadias and small fetuses using a database of fetal ultrasound and obstetric events. MethodsA cohort of male singleton infants delivered after 22 weeks of gestation at Keio University Hospital between 2013 and 2019 was retrospectively reviewed. FGR was defined according to the Delphi criteria. Logistic regression analysis was performed to identify the significant predictors of hypospadias. Placental pathology was reviewed in cases with hypospadias. ResultsOf the 2,040 male infants included in the present study, 23 had hypospadias. The prevalences of a single umbilical artery (SUA), small for gestational age, maternal hypertensive disorders of pregnancy, and a small placenta, were significantly higher in infants with hypospadias. Multiple logistic regression analysis revealed that FGR (odds ratio [OR] = 9.39; 95% confidence interval [CI], 2.50–35.3) and the presence of a SUA (OR = 33.4; 95% CI, 8.00–139.5) were independently and significantly associated with hypospadias. When FGR was stratified by the time of onset, its association with hypospadias was significant regardless of the time of onset. Moreover, placental histological findings suggested that fetal vascular malperfusion might play a role in hypospadias. DiscussionFGR and SUAs are independent prenatal predictors of the development of hypospadias, and fetal vascular malperfusion of the placenta may be involved in the etiology of hypospadias.

Maternal hypertensive disorder of pregnancy and mortality in offspring from birth to young adulthood: national population based cohort study

ObjectiveTo examine the association of maternal hypertensive disorder of pregnancy (HDP) with overall and cause specific mortality in offspring from birth to young adulthood.DesignNationwide population based cohort study.SettingDanish national health...

Gestational weight gain and adverse maternal and perinatal outcomes among women with gestational diabetes mellitus according to International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria: A cross sectional study.

To evaluate the association of gestational weight gain and adverse maternal and perinatal outcomes among Brazilian women with gestational diabetes mellitus (GDM). Cross-sectional study conducted in women with GDM, and their newborns, who attended a public maternity hospital. The Institute of Medicine criteria were adopted to assess adequacy of gestational weight gain (GWG). Cesarean delivery, maternal hypertensive disorders of pregnancy (HDP), premature birth, macrosomia, and birth weight adequacy for gestational age were analyzed as outcomes. Simple and multiple logistic regression models were tested to assess the effect of adequacy of GWG on maternal and newborn outcomes. Among the 545 women studied, 64.2% (n=344) had inadequate weight gain: 27.2% (n=146) insufficient and 37% (n=198) excessive. Women with insufficient GWG were more likely to have a preterm birth (OR 2.57; 95% CI: 1.06-6.19), while those with excessive GWG had a greater chance of HDP (OR 2.62; 95% CI: 1.54-4.45) and large for gestational age newborn (OR 1.88; 95% CI: 1.08-3.29), compared with those with adequate weight gain. Inadequate gestational weight gain was frequent in women with GDM, especially in pregnant women with overweight and obesity, and is associated with unfavorable outcomes.

Maternal Hypertensive Disorders of Pregnancy and Cardiac Structure and Function in the Newborn

BackgroundMaternal hypertensive disorders of pregnancy (HDPs) are strongly associated with offspring congenital heart defects. ObjectivesThis study assessed whether infants exposed to maternal HDPs were also more likely to have subtle cardiac structural and functional abnormalities than unexposed infants. MethodsWe used regression analyses to compare: 1) left ventricular parameters from conventional echocardiography performed in infants from the Copenhagen Baby Heart Study born to mothers with preeclampsia, gestational hypertension (GH), or no HDP; and 2) advanced echocardiographic parameters for 545 term infants born to mothers with preeclampsia and 545 matched infants not exposed to HDPs. ResultsCompared with infants unexposed to HDPs (n = 17,384), infants exposed to preeclampsia (n = 754) had a thicker interventricular septum in end-diastole (adjusted mean difference [± SD] 0.05 [±0.02] mm; P = 0.004), thicker left ventricular posterior wall (0.04 [±0.02] mm; P = 0.009), larger left ventricular internal diameter (0.12 [±0.06] mm; P = 0.04), and larger left ventricular volume (0.21 [±0.10] mL; P = 0.03). Systolic function changes included increased fractional shortening (0.36% [±0.14%]; P = 0.01) and stroke volume (0.18 [±0.07] mL; P = 0.006), whereas diastolic function changes included lower transmitral early peak inflow velocity (−1.76 [±0.49] mL; P = 0.0003), lower mitral annulus lateral wall a' (−0.21 [±0.09] cm/s; P = 0.02), and smaller lateral E/e’ (−1.06 [±0.38] cm/s; P = 0.005). Conversely, there was little evidence of any association between maternal GH (n = 469) and offspring left ventricular parameters. ConclusionsMaternal preeclampsia, but not GH, was associated with subtle newborn cardiac morphological and functional alterations, including thickening of the left ventricular myocardium and altered systolic and diastolic function.

Impact of hypertensive disorders of pregnancy on respiratory outcomes in extremely and very preterm infants: A population-based study in Japan.

We aimed to evaluate the impact of hypertensive disorders of pregnancy (HDP) on short- and medium-term respiratory outcomes in extremely and very preterm infants using the Neonatal Research Network of Japan database. This was a population-based retrospective study of preterm infants weighing≤1500g born between 22 and 31weeks of gestation between 2003 and 2017. After 1:1 stratification matching by four factors (maternal age, gestational age, parity, and year of delivery), a total of 5137 infants in each group (HDP and non-HDP groups) were selected. The association between HDP and various respiratory outcomes was evaluated using univariate and multivariate logistic regression analyses. In the multivariate analyses, HDP was associated with higher odds for respiratory distress syndrome (RDS) (odds ratio 1.83, 95% confidence interval [1.65-2.03]), but reduced odds of persistent pulmonary hypertension of the newborn (PPHN) (0.34 [0.26-0.46]) and inhaled nitric oxide use (0.43 [0.33-0.55]). Although HDP was associated with an increased risk of chronic lung disease (CLD) in the univariate analysis, this association was not significant after adjustment for covariates (0.94 [0.83-1.07]). No significant association was found between HDP and home oxygen therapy (HOT) and medium-term oxygen use. The impact of maternal HDP largely differed depending on respiratory disorders and respiratory support. HDP was associated with higher odds of RDS but reduced odds of PPHN. The risks for CLD, HOT, and medium-term respiratory outcomes in the HDP group were comparable to those in the non-HDP group.

Effect of hypertensive disorders of pregnancy on pubertal development in daughters and sons: a systematic review and meta-analysis.

Hypertensive disorders of pregnancy (HDP) are a major cause of maternal and offspring morbidity and mortality worldwide. Several studies in recent years have focused on the link between HDP and pubertal development in offspring. The goal of this study was to synthesize the published literature on the effect of HDP on pubertal development in offspring by a systematic review and meta-analysis (PROSPERO 2021: CRD42020148736). A systematic literature search of several databases was conducted through December 2021, focusing on studies reporting pubertal development in offspring of women with and without HDP exposure. Primary outcomes of interest included offspring body mass index (BMI), height, waist and hip circumference, fat mass, pubarche, thelarche, and age at menarche. A total of 21 studies were finally included. Significantly higher values of BMI (SMD: 0.16 [0.11, 0.22]; p < 0.01) and waist circumference (SMD: 0.21 [0.14, 0.29]; p < 0.01) were found in offspring exposed to maternal HDP. In addition, a tendency of the early development of secondary sexual characteristics only in daughters was presented in offspring whose mothers were diagnosed with HDP. The findings imply a possible effect of HDP on pubertal development in offspring, especially for their BMI and waist circumference, which highlights the importance of focusing on adolescent developmental abnormalities in offspring exposed to HDP.

Perinatal risk factors for congenital hypothyroidism in very preterm infants: a multicenter prospective study

Objective: To investigate the incidence and perinatal risk factors of congenital hypothyroidism (CH) in very preterm infants. Methods: This prospective, multicenter observational cohort study was conducted at 33 neonatal intensive care units based on the data from Sina-northern Neonatal Network (SNN). Perinatal information and thyroid function of 3 179 very preterm infants with gestational age <32 weeks who were born from January 2019 to June 2021 was collected. According to the occurrence of CH during hospitalization, all the infants were assigned into CH group and non-CH group. Chi square test, Fisher exact probability method, rank sum test and multivariate Logistic regression model were tested to detect the perinatal risk factors for CH. Results: A total of 3 179 very preterm infants were enrolled with 56.4% (1 793/3 179) male. The incidence of CH was 6.9% (220/3 179), in which the incidence for extremely low birth weight infant (ELBWI) and extremely preterm infants (EPI) of gestational age <28 weeks were 13.5% (64/475) and 13.9% (66/475), respectively. On Logistic regression analysis, maternal hypertensive disorders of pregnancy (OR=1.59, 95%CI 1.14-2.23, P=0.007) and multiple birth (OR=1.60, 95%CI 1.18-2.17, P=0.003) were both significant perinatal risk factors of CH. In addition, gestational age (OR=0.81, 95%CI 0.71-0.93, P=0.002), birth weight (OR=0.99, 95%CI: 0.98-0.99, P<0.001) and 1 min Apgar score (OR=0.92, 95%CI 0.86-0.98, P=0.008) were protective factors. Conclusions: The incidence of CH is high in very preterm infants which increased with the decreased birth weight and gestational age. For very premature infants with perinatal high risk factors such as hypertensive disorders of pregnancy, attention should be paid to assess thyroid function status dynamically.

Risk Factors and Outcomes Associated With Hypertensive Disorders of Pregnancy in Maternal Congenital Heart Disease

BackgroundAmong women with congenital heart disease (CHD), risk factors for hypertensive disorders of pregnancy (HDP) and the association of HDP with adverse outcomes are unknown. ObjectivesThe purpose of this study was to identify risk factors for HDP among women with and without CHD and to assess the association of HDP with adverse events. MethodsThis retrospective cohort study included the first live birth for each woman who was pregnant in Alberta, Canada, between January 1, 2005, and December 31, 2018. The prevalence of HDP among women with and without CHD was compared. Multivariable models were used to determine the independent associations between maternal characteristics and HDP and to assess the strength of associations between HDP and CHD with adverse events. ResultsOf the total birth events, 0.6% (N = 2,575) occurred in women with CHD. HDP were more common among women with CHD (11.2% vs 8.1%, P < 0.0001). Chronic hypertension and diabetes mellitus were strongly associated with HDP among women with CHD (adjusted odds ratio [aOR]: 4.56; 95% confidence interval [CI]: 2.95-7.03; and aOR: 3.33; 95% CI: 1.48-7.49, respectively). Coarctation of the aorta was the only CHD lesion independently associated with increased risk for HDP (aOR: 1.76; 95% CI: 1.02-3.02). HDP, as opposed to CHD, was more strongly associated with having a complicated delivery admission, preterm delivery, and small for gestational age infant. ConclusionsHDP were more common among women with CHD. The strongest risk factors for HDP among women with CHD were acquired. The presence of HDP, rather than CHD, was more strongly associated with certain adverse outcomes.

Hypertensive Disorders in Pregnancy Are Associated With Congenital Heart Defects in Offspring: A Systematic Review and Meta-Analysis.

BackgroundAlthough research indicates an association between hypertensive disorders of pregnancy (HDP) and congenital heart defects (CHDs) in offspring, consistency is still lacking. Therefore, we aimed to synthesize the updated published epidemiologic evidence to estimate the association of maternal HDP with the risk of total CHDs and its phenotypes in offspring.MethodsA systematic search of Web of Science Database, PubMed, and Embase were searched from inception through April 30, 2021 based on a preprepared protocol, and the reference lists were also manually searched. The combined risk estimates were calculated using either the fixed-effect models or random-effect models. Possible heterogeneity moderators were detected by subgroup, sensitivity analyses, and Galbraith plot.ResultsTwenty-four studies involving 477,839 CHDs cases among 40,394,699 participants were included in our meta-analysis. Mothers who had HDP exposure were significantly associated with an increased risk of total CHDs compared with non-exposure. When maternal HDP exposure was further subdivided into pre-eclampsia (OR = 1.79, 95% CI: 1.50–2.13), gestational hypertension (OR = 1.16, 95% CI: 1.02–1.31), and chronic hypertension (OR = 1.68, 95% CI: 1.49–1.89), a significantly increased risk of total CHDs were still presented. Furthermore, a statistically significant increased association was found between maternal HDP exposure and most CHD phenotypes. Besides, relevant heterogeneity moderators have been identified by subgroup and sensitivity analyses.ConclusionOur study suggested that maternal HDP exposure may be associated with an increase in the risk of CHDs in offspring. These findings highlight the need for greater surveillance of pregnant women with HDP exposure to allow early prevention that may be good for reducing the risk of CHDs in offspring.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [CRD42021268093].

Maternal hypertensive disorders of pregnancy and the risk of childhood asthma

The prenatal environment, including maternal hypertensive disorders of pregnancy (HDP), may influence the development of asthma; however, this relationship remains unclear. We investigated the relation of maternal HDP and childhood asthma.

Association between Hypertensive Disorders of Pregnancy and Long-Term Neurodevelopmental Outcomes in the Offspring.

The long-term impact of hypertensive disorders of pregnancy (HDP) exposure on offspring health is an emerging research area. The objective of this study was to evaluate the association between a maternal diagnosis of HDP (gestational hypertension and preeclampsia) and adverse neurodevelopmental outcomes in the offspring. This was a secondary analysis of two parallel multicenter clinical trials of thyroxine therapy for subclinical hypothyroid disorders in pregnancy. Women with singleton nonanomalous gestations diagnosed with subclinical hypothyroidism or hypothyroxinemia were randomized to thyroxine therapy or placebo. The primary outcome was child intelligence quotient (IQ) at 5 years of age. Secondary outcomes included several neurodevelopmental measures, including the Bayley-III cognitive, motor, and language scores at 12 and 24 months, Differential Ability Scales-II (DAS-II) scores at 36 months, the Conners' rating scales-revised at 48 months, and scores from the Child Behavior Checklist at 36 and 60 months. Thyroxine therapy did not influence neurodevelopment in either of the primary studies. Associations between neurodevelopment outcomes and maternal HDP were examined using univariable and multivariable analyses. A total of 112 woman-child dyads with HDP were compared with 1,067 woman-child dyads without HDP. In univariable analysis, mean maternal age (26.7 ± 5.9 vs. 27.8 ± 5.7 years, p = 0.032) and the frequency of nulliparity (45.5 vs. 31.0%, p = 0.002) differed significantly between the two groups. Maternal socioeconomic characteristics did not differ between the groups. After adjusting for potential confounders, there were no significant differences in any primary or secondary neurodevelopment outcome between offspring exposed to HDP and those unexposed. However, when dichotomized as low or high scores, we found higher rates of language delay (language scores <85: -1 standard deviation) at 2 years of age among offspring exposed to HDP compared with those unexposed (46.5 vs. 30.5%, adjusted odds ratio = 2.22, 95% confidence interval [CI]: 1.44-3.42). In this cohort of pregnant women, HDP diagnosis was associated with language delay at 2 years of age. However, other long-term neurodevelopmental outcomes in offspring were not associated with HDP. · No differences were found in neurodevelopment between offspring exposed to HDP and controls.. · Higher rates of language delay at 2 years of age were found in offspring exposed to HDP.. · The results did not differ when analysis was stratified by preterm birth..

Maternal hypertensive disorders in pregnancy and early childhood cardiometabolic risk factors: The Generation R Study.

The objective of this study was to determine the associations between hypertensive disorders of pregnancy and early childhood cardiometabolic risk factors in the offspring. Therefore, 7794 women from the Generation Rotterdam Study were included, an ongoing population-based prospective birth cohort. Women with a hypertensive disorder of pregnancy were classified as such when they were affected by pregnancy induced hypertension, pre-eclampsia or the haemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome during pregnancy. Early childhood cardiometabolic risk factors were defined as the body mass index at the age of 2, 6, 12, 36 months and 6 years. Additionally, it included systolic blood pressure, diastolic blood pressure, total fat mass, cholesterol, triglycerides, insulin and clustering of cardiometabolic risk factors at 6 years of age. Sex-specific differences in the associations between hypertensive disorders and early childhood cardiometabolic risk factors were investigated. Maternal hypertensive disorders of pregnancy were inversely associated with childhood body mass index at 12 months (confounder model: -0.15 SD, 95% CI -0.27; -0.03) and childhood triglyceride at 6 years of age (confounder model: -0.28 SD, 95% CI -0.45; -0.10). For the association with triglycerides, this was only present in girls. Maternal hypertensive disorders of pregnancy were not associated with childhood body mass index at 2, 6 and 36 months. No associations were observed between maternal hypertensive disorders of pregnancy and systolic blood pressure, diastolic blood pressure, body mass index, fat mass index and cholesterol levels at 6 years of age. Our findings do not support an independent and consistent association between maternal hypertensive disorders of pregnancy and early childhood cardiometabolic risk factors in their offspring. However, this does not rule out possible longer term effects of maternal hypertensive disorders of pregnancy on offspring cardiometabolic health.

Risk Factors for Adverse Maternal and Fetal Outcomes in Pregnant Patients with Sickle Cell Disease

BackgroundApproximately 100,000 Americans are affected by sickle cell disease (SCD), an inherited hematologic disorder. In women with sickle cell disease, pregnancy is associated with increased maternal and fetal adverse outcomes (Elenga et al). However, there is a paucity of data on risk factors for adverse events in this population. This retrospective study seeks to add to the deficient repertoire of information regarding maternal and fetal outcomes in patients with sickle cell disease and their children.MethodsWe retrospectively evaluated pregnancy outcomes of women with SCD who had previously undergone echocardiography from the year 2000-2021. The associations between clinical variables and adverse hematologic (AHE), cardiac (ACE), obstetric (AOE) and fetal/neonatal (ANE) events were evaluated by the Generalized Linear Model (GLM). The adverse hematologic events were vaso-occlusive crisis (VOC) antepartum and postpartum, acute chest syndrome, venous thromboembolism antepartum and postpartum, and transfusion antepartum.ResultsWe identified 43 women/59 pregnancies with a median maternal age 27 years old (interquartile range [IQR] 20), pre-pregnancy BMI 25 kg/m2 (IQR 16). Maternal sickle cell genotype was SS in 31 (72%) women/37 (63%) pregnancies, SC in 8 (18%) women/18 (31%) pregnancies, and other genotype in 4 (9%) women/4 (7%) pregnancies. Prior venous thromboembolism was present in 12 (27%) women/15 (25%) pregnancies and prior acute chest syndrome (ACS) in 33 (80%) women/41 (75%) pregnancies. In the year before pregnancy, 24 (56%) women were admitted at least once for VOC. There were no maternal deaths during pregnancy or up to 1 year postpartum. AHE (n = 171) occurred in 43 (73%) pregnancies (Figure A), with a median of 2 (range 0-13) AHE per pregnancy. AHE were more common with genotype SS, history of ACS, history of ³ 10 lifetime transfusions, admission for VOC in the year before pregnancy, tricuspid regurgitation velocity (TRV) >2.5 m/s on echocardiogram, and increased maternal age, and less common with increased hemoglobin (Figure B). ACE were rare (n = 3) (Figure A) and weakly associated with increased maternal age (Figure C). AOE (n = 37) occurred in 27 (45%) pregnancies (Figure A) and were associated with lower pre-pregnancy maternal BMI (Figure D). ANE (n = 54) occurred in 27 (46%) of pregnancies, and were associated with maternal hypertensive disorders of pregnancy (Figure E).ConclusionsWe found that AHE during pregnancy in women with SCD were associated with genotype SS, history of ACS, ³ 10 lifetime transfusions, admission for VOC in the year before pregnancy, higher maternal age, and inversely related to hemoglobin. In addition, AHE during pregnancy were associated with TRV >2.5 m/s on echocardiogram, which has not been previously shown in women with SCD. These data may be useful to identify women at increased risk during pregnancy. Data show that patients with sickle cell disease who have more disease-related complications including history of acute chest syndrome, frequent pain crisis, elevated TRV on echocardiogram, and lower hemoglobin are at greater risk for AHE. This suggests that disease severity is directly related to outcomes. The association between increased maternal age and ACE has been demonstrated in the past in women without SCD (DeViti et al). The same can be noted for the association of AOE with lower maternal BMI (Verma et al), and ANE being associated with maternal hypertensive disorders of pregnancy (Lugobe et al). In the future, prevention of these complications will be key. Future directions include determining the effect of disease-modifying therapy on these outcomes, though safety during pregnancy has not yet been demonstrated for more novel agents such as voxelotor and crizanlizumab. With more information on these risk factors, we hope that modification and treatment can result in better outcomes. [Display omitted] DisclosuresDesai: Pfizer: Other: Publication Fee, Research Funding; Foundation for Sickle Cell Research: Honoraria; Forma: Consultancy; Novartis: Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Research Funding.

Maternal urinary OPE metabolite concentrations and blood pressure during pregnancy: The HOME study

BackgroundFew studies have examined the association between maternal exposure to organophosphate esters (OPEs) and systolic/diastolic blood pressure (SBP/DBP) during pregnancy. MethodsWe analyzed data from 346 women with a singleton live birth in the HOME Study, a prospective birth cohort in Cincinnati, Ohio, USA. We quantified four OPE metabolites in maternal spot urine samples collected at 16 and 26 weeks pregnancy, standardized by specific gravity. We calculated intraclass correlation coefficients (ICCs). We extracted the first two recorded BP measurements (<20 weeks), the two highest recorded BP measurements (≥20 weeks), and diagnoses of hypertensive disorders of pregnancy (HDP) via chart review. Women with two BP measurements ≥140/90 mmHg or HDP noted in the chart at ≥20 weeks pregnancy were defined as HDP cases. We used linear mixed models and modified Poisson regression with covariate adjustment to estimate associations between OPE concentrations as continuous variables or in tertiles with maternal BP and HDP. ResultsICCs of OPEs were 0.17–0.45. Diphenyl phosphate (DPHP) had the highest geometric mean concentration among OPE metabolites. Increasing the average bis(2-chloroethyl) phosphate (BCEP) concentrations were positively associated with two highest recorded DBP ≥20 weeks pregnancy. Compared with women in the 1st DPHP tertile, women in the 3rd tertile at 16 weeks pregnancy had 1.72 mmHg (95% CI: -0.01, 3.46) higher DBP <20 weeks pregnancy, and women in the 3rd tertile of the average DPHP concentrations had 2.25 mmHg (95% CI: 0.25, 4.25) higher DBP ≥20 weeks pregnancy. 33 women (9.5%) were identified with HDP. Di-n-butyl phosphate (DNBP) concentrations at 16 weeks were positively associated with HDP, with borderline significance (RR = 2.98, 95% CI 0.97–9.15). Other OPE metabolites were not significantly associated with HDP. ConclusionMaternal urinary BCEP and DPHP concentrations were associated with increased BP during pregnancy. Maternal urinary DNBP concentrations were associated with HDP, with borderline significance.