Preeclampsia Onset, Days to Delivery, and Autism Spectrum Disorders in Offspring: Clinical Birth Cohort Study.

BACKGROUND: Maternal preeclampsia is associated with a risk of autism spectrum disorders (ASD) in offspring. However, it is unknown whether the increased ASD risk associated with preeclampsia is due to preeclampsia onset or clinical management of preeclampsia after onset, as clinical expectant management of preeclampsia allows pregnant women with this complication to remain pregnant for potentially weeks depending on the onset and severity. Identifying the risk associated with preeclampsia onset and exposure provides evidence to support the care of high-risk pregnancies and reduce adverse effects on offspring. OBJECTIVE: This study aimed to fill the knowledge gap by assessing the ASD risk in children associated with the gestational age of preeclampsia onset and the number of days from preeclampsia onset to delivery. METHODS: This retrospective population-based clinical cohort study included 364,588 mother-child pairs of singleton births between 2001 and 2014 in a large integrated health care system in Southern California. Maternal social demographic and pregnancy health data, as well as ASD diagnosis in children by the age of 5 years, were extracted from electronic medical records. Cox regression models were used to assess hazard ratios (HRs) of ASD risk in children associated with gestational age of the first occurrence of preeclampsia and the number of days from first occurrence to delivery. RESULTS: Preeclampsia occurred in 16,205 (4.4%) out of 364,588 pregnancies; among the 16,205 pregnancies, 2727 (16.8%) first occurred at <34 weeks gestation, 4466 (27.6%) first occurred between 34 and 37 weeks, and 9012 (55.6%) first occurred at ≥37 weeks. Median days from preeclampsia onset to delivery were 4 (IQR 2,16) days, 1 (IQR 1,3) day, and 1 (IQR 0,1) day for those first occurring at <34, 34-37, and ≥37 weeks, respectively. Early preeclampsia onset was associated with greater ASD risk (P=.003); HRs were 1.62 (95% CI 1.33-1.98), 1.43 (95% CI 1.20-1.69), and 1.23 (95% CI 1.08-1.41), respectively, for onset at <34, 34-37, and ≥37 weeks, relative to the unexposed group. Within the preeclampsia group, the number of days from preeclampsia onset to delivery was not associated with ASD risk in children; the HR was 0.995 (95% CI 0.986-1.004) after adjusting for gestational age of preeclampsia onset. CONCLUSIONS: Preeclampsia during pregnancy was associated with ASD risk in children, and the risk was greater with earlier onset. However, the number of days from first preeclampsia onset to delivery was not associated with ASD risk in children. Our study suggests that ASD risk in children associated with preeclampsia is not increased by expectant management of preeclampsia in standard clinical practice. Our results emphasize the need to identify effective approaches to preventing the onset of preeclampsia, especially during early pregnancy. Further research is needed to confirm if this finding applies across different populations and clinical settings.

Effect of early vitamin D supplementation on the incidence of preeclampsia in primigravid women: a randomised clinical trial in Eastern Democratic Republic of the Congo.

BACKGROUND: Previous studies have reported the association between maternal vitamin D deficiency and preeclampsia. However, the efficacy of vitamin D supplementation in reducing the occurrence of preeclampsia remains unclear. The objective of this study was to evaluate the effect of cholecalciferol supplementation on the incidence of preeclampsia in primigravid women and its related maternal and foetal outcomes. METHODS: A single-blinded clinical trial was conducted in fourteen antenatal care health facilities in the North (Goma, Mwesso, Nyiragongo) and South Kivu (Bukavu-Panzi) provinces of the Democratic Republic of Congo from March 1, 2020, to June 30, 2021. A total of 1300 primigravid women not exceeding 16 weeks of gestation were randomised with a 1:1 ratio to either the supplemented (A) or control (B) group. Each pregnant woman (A) presenting for antenatal care received a single monthly dose of cholecalciferol (60,000 IU) orally for 6 months. The control group received no vitamin D supplementation or placebo. Serum 25(OH)D was measured at recruitment and at 34 weeks of gestation. Outcomes were assessed monthly until delivery. RESULTS: The median maternal age was 21 years (14-40), while the median gestational age was 15 weeks (5.4-29.0). A significant reduction in the risk of preeclampsia [RR = 0.36 (0.19-0.69); p = 0.001] and preterm delivery [RR = 0.5 (0.32-0.78); p = 0.002] was observed in the intervention group. An RR of 0.43 [(0.27-0.67); p < 0.001] was found for low birth weight. The RR for caesarean section was 0.63 [(0.52-0.75); p < 0.001]. The APGAR score at the 5th minute (p = 0.021) and the size of the newborn were significantly higher in the supplemented group (p = 0.005). CONCLUSION: A single monthly dose (60,000 IU) of vitamin D supplementation, started in earlypregnancy, significantly reduced the incidence of preeclampsia and its maternal and foetal complications. TRIAL REGISTRATION: ISRCTN Register with ISRCTN46539495 on 17 November 2020.

Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

BACKGROUND: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers. METHODS: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively. RESULTS: A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin. CONCLUSIONS: In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5).

Prediction Model of Adverse Pregnancy Outcome in Pre-Eclampsia Based on Logistic Regression and Random Forest Algorithm.

Aim: To construct a prediction model for adverse pregnancy outcomes of preeclampsia (PE). Thus assisting clinicians to identify high-risk patients. Provide guidance for treatment intervention. Methods: A retrospective study was conducted on 319 PE patients admitted to the Huzhou Maternal and Child Health Hospital from April 2021 to December 2022, The patients were divided into an adverse group (93 cases) and a non-adverse group (226 cases) based on whether they had adverse pregnancy outcomes after admission. Collect clinical data from patients, using a single factor analysis to screen statistically significant indicators as input variables, the outcome of the analysis is dependent on the incidence of PE adverse pregnancy outcomes. Divide patients into training and testing sets in a 7:3 ratio, Logistic regression model and random forest model were constructed respectively. Evaluate the predictive performance of two statistical models. Results: Among the 319 PE patients included 93 had adverse pregnancy outcomes after admission. Among them, Age (OR: 1.702, 95%CI: 1.069~2.710), small gestational age (OR: 0.757,95%CI: 0.607~0.945), more clinical symptoms (OR: 3.618, 95%CI: 1.682~7.783), high 24 h proteinuria (OR: 2.532, 95%CI: 1.290~4.968), low PLT index (OR: 0.616, 95%CI: 0.419~0.906), high AST index (OR: 1.554, 95%CI: 1.012~2.387), high D-Dimer index (OR:1.966, 95%CI: 1.183~3.267) were the influencing factors of adverse pregnancy outcomes in PE patients. The test set found that the random forest model was superior to the Logistic regression model in predicting the risk of adverse pregnancy outcomes in PE patients. Conclusions: The random forest model has good stability in predicting the risk of adverse pregnancy outcomes in PE, and its prediction efficiency is better than the Logistic regression model.

Association between calcium supplementation and gestational hypertension, and preeclampsia: A Meta-analysis of 26 randomized controlled trials.

BACKGROUND: Pre-eclampsia and eclampsia are common causes of morbidity and mortality, especially in low-income countries. Reducing adverse outcomes associated with hypertensive disorders of pregnancy has been the ultimate priority in recent years. We aim to evaluate the association between calcium supplementation and preeclampsia and gestational hypertension risk among pregnant women. METHODS: A systematic literature search was performed in electronic databases from inception to 15th July 2023, including only randomized controlled trials. Odds ratio (OR) were, and their corresponding 95% confidence interval (95% CI). RESULTS: A total of 26 studies with 20,038 patients (10,003 patients with calcium supplements and 10,035 patients with placebo group) were included in the analysis. The Pooled analysis of primary outcome shows that calcium supplements reduce the risk of preeclampsia by 49% (OR, 0.51(95%CI: 0.40-0.66), P<0.001), and reduce the risk of gestational hypertension by 30% (OR, 0.70 (95%CI: 0.58-0.85)), P<0.001) compared to placebo. There was a trend of lower incidence of preterm delivery (OR, 0.88 (95%CI: 0.71-1.09), P=0.23), labor induction (OR, 0.90 (95%CI: 0.78-1.03), P=0.13), small for gestational age (OR, 0.70 (95% CI:0.37-1.32), P = 0.27), low birth weight (OR, 0.96 (95%CI: 0.86-1.08), P=0.53), perinatal mortality (OR, 0.88 (95%CI: 0.72-1.09), P=0.24), and maternal mortality (OR, 0.48 (95%CI: 0.12-1.84), P=0.28) among calcium supplementation group compared with the placebo group, however, statistical signifance was not achieved. CONCLUSION: This study shows that calcium supplements are associated with a significant reduction in the risk of preeclampsia and gestational hypertension and a trend toward better maternal and fetal-related outcomes.

Association of age at menarche with gestational hypertension and preeclampsia: A large prospective cohort in China.

This study explored the potential association between age at menarche and the risks of gestational hypertension and preeclampsia in Chinese women. Data were sourced from the China-US Collaborative Project for Neural Tube Defects Prevention, a large population-based cohort study. Our study consisted of 209 411 women pre-registered for pregnancy in two provinces in South China. Trained healthcare workers measured blood pressure at registration and recorded other pertinent health information. Using logistic regression, we assessed the correlations between age at menarche and the likelihood of developing gestational hypertension and preeclampsia, considering confounders such as maternal age, body mass index, ethnicity, parity, folic acid supplementation, education level, and occupation. The observed incidences for gestational hypertension and preeclampsia were 9.65% and 2.54%, respectively. The adjusted odds ratios (ORs) for gestational hypertension, based on age at menarche, were as follows: ≤13 years, 1.18 (95% confidence interval: 1.11-1.26); 14 years, 1.09 (1.04-1.15); 15 years, 1.11 (1.06-1.16); 16 years, 1.06 (1.01-1.12); and ≥17 years, 1.00 (reference; P for trend < .001). The correlation between age at menarche and preeclampsia varied across age groups, with the following respective ORs: 1.35 (1.20-1.52), 1.21 (1.09-1.34), 1.27 (1.15-1.39), 1.14 (1.03-1.26), and 1.00 (reference; P for trend < .001). This association appeared to be more pronounced in women with no folic acid supplementation and those with a lower education level. In conclusion, an earlier age at menarche seems to be linked to increased risks of gestational hypertension and preeclampsia.

The association between dietary mineral intake and the risk of preeclampsia in Chinese pregnant women: a matched case-control study.

Previous studies on the relationship between dietary minerals and preeclampsia (PE) have given inconsistent results. The aim of this study was to further clarify the relationship between dietary minerals intake and PE in Chinese pregnant women. In this study, 440 pairs of hospital-based preeclamptic and healthy women were matched 1:1. Dietary intake was obtained through a 78-item semi-quantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were plotted to evaluate the dose-response relationship between dietary minerals intake and PE. This study found significant inverse associations for dietary intake of calcium, magnesium, phosphorus, iron, copper, manganese and zinc and the risk of PE in both univariate and multivariate models (all P- trend < 0.05). After adjusting for possible confounders, compared with the lowest quartile, the odds ratio of the highest quartile was 0.74 (95% CI 0.56-0.98) for calcium, 0.63 (95% CI 0.42-0.93) for magnesium, 0.45 (95% CI 0.31-0.65) for phosphorus, 0.44 (95% CI 0.30-0.65) for iron, 0.72 (95% CI 0.53-0.97) for copper, 0.66 (95% CI 0.48-0.91) for manganese and 0.38 (95% CI 0.25-0.57) for zinc. In addition, a reverse J-shaped relationship between dietary minerals intake and PE risk was observed (P-overall association < 0.05). In Chinese pregnant women, a higher intake of dietary minerals, including calcium, magnesium, phosphorus, copper, iron, manganese, and zinc was associated with a lower odds of PE.

Prenatal Health Care Outcomes Before and During the COVID-19 Pandemic Among Pregnant Individuals and Their Newborns in an Integrated US Health System.

Importance: The COVID-19 pandemic accelerated the use of telemedicine. However, data on the integration of telemedicine in prenatal health care and health outcomes are sparse. Objective: To evaluate a multimodal model of in-office and telemedicine prenatal health care implemented during the COVID-19 pandemic and its association with maternal and newborn health outcomes. Design, Setting, and Participants: This cohort study of pregnant individuals using longitudinal electronic health record data was conducted at Kaiser Permanente Northern California, an integrated health care system serving a population of 4.5 million people. Individuals who delivered a live birth or stillbirth between July 1, 2018, and October 21, 2021, were included in the study. Data were analyzed from January 2022 to May 2023. Exposure: Exposure levels to the multimodal prenatal health care model were separated into 3 intervals: unexposed (T1, birth delivery between July 1, 2018, and February 29, 2020), partially exposed (T2, birth delivery between March 1, 2020, and December 5, 2020), and fully exposed (T3, birth delivery between December 6, 2020, and October 31, 2021). Main Outcomes and Measures: Primary outcomes included rates of preeclampsia and eclampsia, severe maternal morbidity, cesarean delivery, preterm birth, and neonatal intensive care unit (NICU) admission. The distributions of demographic and clinical characteristics, care processes, and health outcomes for birth deliveries within each of the 3 intervals of interest were assessed with standardized mean differences calculated for between-interval contrasts. Interrupted time series analyses were used to examine changes in rates of perinatal outcomes and its association with the multimodal prenatal health care model. Secondary outcomes included gestational hypertension, gestational diabetes, depression, venous thromboembolism, newborn Apgar score, transient tachypnea, and birth weight. Results: The cohort included 151 464 individuals (mean [SD] age, 31.3 [5.3] years) who delivered a live birth or stillbirth. The mean (SD) number of total prenatal visits was similar in T1 (9.41 [4.75] visits), T2 (9.17 [4.50] visits), and T3 (9.15 [4.66] visits), whereas the proportion of telemedicine visits increased from 11.1% (79 214 visits) in T1 to 20.9% (66 726 visits) in T2 and 21.3% (79 518 visits) in T3. NICU admission rates were 9.2% (7014 admissions) in T1, 8.3% (2905 admissions) in T2, and 8.6% (3615 admissions) in T3. Interrupted time series analysis showed no change in NICU admission risk during T1 (change per 4-week interval, -0.22%; 95% CI, -0.53% to 0.09%), a decrease in risk during T2 (change per 4-week interval, -0.91%; 95% CI, -1.77% to -0.03%), and an increase in risk during T3 (change per 4-week interval, 1.75%; 95% CI, 0.49% to 3.02%). There were no clinically relevant changes between T1, T2, and T3 in the rates of risk of preeclampsia and eclampsia (change per 4-week interval, 0.76% [95% CI, 0.39% to 1.14%] for T1; -0.19% [95% CI, -1.19% to 0.81%] for T2; and -0.80% [95% CI, -2.13% to 0.55%] for T3), severe maternal morbidity (change per 4-week interval , 0.12% [95% CI, 0.40% to 0.63%] for T1; -0.39% [95% CI, -1.00% to 1.80%] for T2; and 0.99% [95% CI, -0.88% to 2.90%] for T3), cesarean delivery (change per 4-week interval, 0.06% [95% CI, -0.11% to 0.23%] for T1; -0.03% [95% CI, -0.49% to 0.44%] for T2; and -0.05% [95% CI, -0.68% to 0.59%] for T3), preterm birth (change per 4-week interval, 0.23% [95% CI, -0.11% to 0.57%] for T1; -0.37% [95% CI, -1.29% to 0.55%] for T2; and -0.15% [95% CI, -1.41% to 1.13%] for T3), or secondary outcomes. Conclusions and Relevance: These findings suggest that a multimodal prenatal health care model combining in-office and telemedicine visits performed adequately compared with in-office only prenatal health care, supporting its continued use after the pandemic.

Pregnancy outcomes in women with gestational hypertension and preeclampsia at Paropakar Maternity and Women's Hospital, Nepal: A retrospective study.

INTRODUCTION: Gestational hypertension and preeclampsia are the most common types of hypertensive disorder in pregnancy and these conditions are associated with adverse maternal and fetal outcomes. This study aims to determine the differences in pregnancy outcomes in women with gestational hypertension and preeclampsia. METHODS: A retrospective study was done at The Paropakar Maternity and Women's Hospital, a tertiary level hospital, in the Kathmandu, Nepal. Pregnant women who had given birth at the hospital between September 17 and December 18 of 2017 were included. Data were obtained from the non-digitalized hospital records. The adjusted odds ratio (AOR) and 95% confidence interval were computed using logistic regression analysis. Multivariable analysis of pregnancy outcomes (cesarean sections, low birth weight, and preterm birth) was adjusted for maternal age, parity, twin birth, gestational age, calcium supplementation, and maternal co-morbidity. RESULTS: Preeclampsia was strongly associated with cesarean section compared to normal pregnancies (OR = 8.11, p<0.001). Whereas the odds of cesarean section among women with gestational hypertension was almost 2 times (OR = 1.89, p<0.001). Preterm birth was not significantly associated with gestational hypertension but was associated with preeclampsia (OR = 3.39, p<0.001). Gestational hypertension and preeclampsia were not associated with low birth weight. CONCLUSION: In Nepal, women who develop preeclampsia seem at higher risk of having adverse pregnancy outcomes than women with gestational hypertension. These findings should be considered by national health authorities and other health organizations when setting new priorities to improve pregnancy outcomes.

Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy.

BACKGROUND: Whether treatment of gestational diabetes before 20 weeks' gestation improves maternal and infant health is unclear. METHODS: We randomly assigned, in a 1:1 ratio, women between 4 weeks' and 19 weeks 6 days' gestation who had a risk factor for hyperglycemia and a diagnosis of gestational diabetes (World Health Organization 2013 criteria) to receive immediate treatment for gestational diabetes or deferred or no treatment, depending on the results of a repeat oral glucose-tolerance test [OGTT] at 24 to 28 weeks' gestation (control). The trial included three primary outcomes: a composite of adverse neonatal outcomes (birth at <37 weeks' gestation, birth trauma, birth weight of ≥4500 g, respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia), pregnancy-related hypertension (preeclampsia, eclampsia, or gestational hypertension), and neonatal lean body mass. RESULTS: A total of 802 women underwent randomization; 406 were assigned to the immediate-treatment group and 396 to the control group; follow-up data were available for 793 women (98.9%). An initial OGTT was performed at a mean (±SD) gestation of 15.6±2.5 weeks. An adverse neonatal outcome event occurred in 94 of 378 women (24.9%) in the immediate-treatment group and in 113 of 370 women (30.5%) in the control group (adjusted risk difference, -5.6 percentage points; 95% confidence interval [CI], -10.1 to -1.2). Pregnancy-related hypertension occurred in 40 of 378 women (10.6%) in the immediate-treatment group and in 37 of 372 women (9.9%) in the control group (adjusted risk difference, 0.7 percentage points; 95% CI, -1.6 to 2.9). The mean neonatal lean body mass was 2.86 kg in the immediate-treatment group and 2.91 kg in the control group (adjusted mean difference, -0.04 kg; 95% CI, -0.09 to 0.02). No between-group differences were observed with respect to serious adverse events associated with screening and treatment. CONCLUSIONS: Immediate treatment of gestational diabetes before 20 weeks' gestation led to a modestly lower incidence of a composite of adverse neonatal outcomes than no immediate treatment; no material differences were observed for pregnancy-related hypertension or neonatal lean body mass. (Funded by the National Health and Medical Research Council and others; TOBOGM Australian New Zealand Clinical Trials Registry number, ACTRN12616000924459.).

Mode of delivery and maternal vitamin D deficiency: an optimized intelligent Bayesian network algorithm analysis of a stratified randomized controlled field trial.

This study aimed to elucidate the algorithm of various influential factors relating to the association between 25-hydroxyvitamin D (25(OH)D) concentration at delivery and mode of delivery. The investigation constituted a secondary analysis using data collected as part of the Khuzestan Vitamin D Deficiency Screening Program in Pregnancy, which is a stratified randomized vitamin D supplementation-controlled trial comprising 1649 eligible pregnant women. The Bayesian Network (BN) method was utilized to determine the association algorithm between diverse influential factors associated with maternal vitamin D and mode of delivery. The optimized intelligent BN algorithm revealed that women presenting with moderate (35.67%; 95% CI: 33.36-37.96) and severe vitamin D deficiency (47.22%; 95% CI: 44.81-49.63) at delivery were more likely to undergo cesarean section than those presenting with normal concentrations of this nutritional hormone (18.62%; 95% CI: 16.74-20.5). The occurrence probabilities of preeclampsia in mothers with normal, moderate, and severe vitamin D deficiency at delivery were (1.5%; 95% CI: 0.92-2.09), (14.01%; 95% CI: 12.33-15.68), and (26.81%; 95% CI: 24.67-28.95), respectively. Additionally, mothers with moderate (11.81%; 95% CI: 10.25-13.36) and severe (27.86%; 95% CI: 25.69-30.02) vitamin D deficiency exhibited a higher probability of preterm delivery in comparison to those presenting with normal concentrations (1.12%; 95% CI: 0.62-1.63). This study demonstrated that the vitamin D status of pregnant women at delivery could directly affect the mode of delivery and indirectly through maternal complications, such as preeclampsia and preterm delivery, leading to a higher occurrence probability of cesarean section.

Persisting risk factors for preeclampsia among high-risk pregnancies already using prophylactic aspirin: a multi-country retrospective investigation.

BACKGROUND: Low-dose aspirin is recommended for pregnant individuals at high-risk of developing preeclampsia, but less is known about those that develop preeclampsia even while using prophylactic aspirin for preeclampsia prevention as the best course of treatment. OBJECTIVES: The objective of this study is to investigate the risk factors with the highest risk of developing preeclampsia among pregnant individuals already using aspirin from high-risk obstetrical centers across five countries. DESIGN: This is a secondary analysis of pregnant individuals from the Folic Acid Clinical Trial (FACT) who were using prophylactic aspirin before 16 weeks gestation. The FACT randomized control trial took place in 70 high risk obstetrical centers in Canada, United Kingdom, Australia, Jamaica, and Argentina between 2011-2015. Participants were included if they had any of the risk factors for preeclampsia: diabetes, chronic hypertension, twin pregnancy, history of preeclampsia, and/or obesity (Body Mass Index ≥35). The outcomes of interest were preeclampsia and preterm preeclampsia (<37 weeks). Log binomial regressions assessed factors significantly associated with any preeclampsia or preterm-preeclampsia (<37 weeks) using adjusted risk ratios (ARR) and 95% confidence intervals (CI). RESULTS: There were 2296 pregnant individuals with complete information on aspirin included in this study. At baseline, all patients were at high risk of preeclampsia and were eligible for aspirin prophylaxis, however, only 660 (28.7%) were taking aspirin. Among the 660 pregnant individuals taking aspirin, 132 (20%) developed preeclampsia and 60 (9.09%) preterm preeclampsia. Among pregnant individuals using aspirin, the risks of preeclampsia were highest for twins (ARR:2.62, 95% CI: 1.68-4.11), history of preeclampsia (ARR: 2.42, 95% CI: 1.74-3.38), and hypertension (ARR:1.92, 95% CI: 1.37-2.69). Similar trends were found for preterm-preeclampsia for twins (ARR:4.10, 95% CI:2.15-7.82), history of preeclampsia (ARR:2.75, 95% CI:1.62-4.67), and hypertension (ARR:2.18, 95% CI:1.28-3.72). No significant differences were found for obesity or diabetes. CONCLUSION: These findings suggest that individuals with twin pregnancies, a history of preeclampsia, or hypertension may not benefit from aspirin to the same extent as those with other complications such as obesity or diabetes. Careful clinical monitoring for these risks factors is recommended and future research into the effectiveness in these populations would increase our understanding of the current best practice of prophylactic aspirin use to prevent preeclampsia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.

Does heterogeneity underlie differences in treatment effects estimated from SuperLearner versus logistic regression? An application in nutritional epidemiology.

PURPOSE: A strength of SuperLearner is that it may accommodate key interactions between model variables without a priori specification. In prior research, protective associations between fruit intake and preeclampsia were stronger when estimated using SuperLearner with targeted maximum likelihood estimation (TMLE) compared with multivariable logistic regression without any interaction terms. We explored whether heterogeneity (i.e., differences in the effect estimate due to interactions between fruit intake and covariates) may partly explain differences in estimates from these two models. METHODS: Using a U.S. prospective pregnancy cohort (2010-2013, n = 7781), we estimated preeclampsia risk differences (RDs) for higher versus lower fruit density using multivariable logistic regression and included two-way statistical interactions between fruit density and each of the 25 model covariates. We compared the RDs with those from SuperLearner with TMLE (gold standard) and logistic regression with no interaction. RESULTS: From the logistic regression models with two-way statistical interactions, 48% of the preeclampsia RDs were ≤-0.02 (closer to SuperLearner with TMLE estimate); 40% equaled -0.01 (same as logistic regression with no interaction estimate); the minority of RDs were at or crossed the null. CONCLUSIONS: Our exploratory analysis provided preliminary evidence that heterogeneity may partly explain differences in estimates from logistic regression versus SuperLearner with TMLE.

The interaction between no folic acid supplementation during early pregnancy and preeclampsia increased the risk of preterm birth.

OBJECTIVES: To explore if there is a positive additive interaction between no folic acid (FA) supplementation in early period of pregnancy and preeclampsia which increases the risk of preterm birth (PTB). METHODS: We matched 1471 women who had live-birth singleton preterm infants with 1471 women who had live-birth singleton term infants at 15 Chinese hospitals in 2018. We excluded women who took folic acid less than 0.4 mg/d or less than 12 weeks in early stage, women with gestational hypertension, chronic hypertension, or preeclampsia during previous pregnancy. We calculate odds ratios for PTB by performing conditional logistic regression comparing preterm group with term group.We quantified the interaction between 2 exposures by synergy (S) and relative excess risk due to interaction (RERI). RESULTS: Approximately 40% of preterm cases did not take FA in early pregnancy. After adjusting confounding factors by logistic regression, when the 2 exposures (no early FA supplementation and preeclampsia) co-existed, the risk of all PTB increased significantly (aOR11=12.138; 95% CI 5.726-25.73), the interaction between 2 exposures was positive (S=1.27) and increased 2.385-fold risk of all PTB (RERI=2.385); and there were similar results on iatrogenic PTB (aOR11=23.412; 95% CI 8.882-60.71, S=1.18, RERI=3.347). CONCLUSION: Our multicenter study showed, for the first time, that there was a positive additive interaction between no FA supplementation in early pregnancy and preeclampsia which increased the risk of all PTB, especially iatrogenic PTB.

Perinatal Outcomes After Bariatric Surgery Compared With a Matched Control Group.

OBJECTIVE: To evaluate perinatal outcomes associated with pregnancy after bariatric surgery within a large integrated health care system using propensity score matching. METHODS: We conducted a retrospective cohort study that evaluated perinatal outcomes in pregnant patients after bariatric surgery from January 2012 through December 2018. History of bariatric surgery was identified by using International Classification of Diseases codes and a clinical database. Primary outcomes were preterm birth (PTB), gestational hypertension, preeclampsia, impaired glucose tolerance or gestational diabetes, a large-for-gestational-age (LGA) or small-for-gestational-age (SGA) neonates, and cesarean birth. Propensity scores were estimated by using logistic regression that accounted for age at delivery, prepregnancy body mass index, year of delivery, parity, neighborhood deprivation index, race and ethnicity, insurance status, initiation of prenatal visit in the first trimester, smoking during pregnancy, chronic hypertension, and preexisting diabetes. Five patients in the control group were matched to each patient in the case group on linear propensity score, and modified Poisson regression was used to adjust for covariates. Sensitivity analyses by timing and type of surgery were performed. RESULTS: We identified a case cohort of 1,591 pregnancies in patients after bariatric surgery and a matched cohort of 7,955 pregnancies in patients who had not undergone bariatric surgery. Demographic characteristics were similar in both groups. In multivariate models, pregnancy after bariatric surgery was associated with a decreased risk of preeclampsia (7.5% vs 10.2%, adjusted relative risk [aRR] 0.72, 95% CI 0.60-0.86), gestational diabetes or impaired fasting glucose (23.5% vs 35.0%, aRR 0.73, 95% CI 0.66-0.80), and LGA (10.6% vs 19.9%, aRR 0.56, 95% CI 0.48-0.65) and an increased risk of SGA (10.9% vs 6.6%, aRR 1.51, 95% CI 1.28-1.78). No significant differences were observed in PTB, gestational hypertension and cesarean delivery. CONCLUSION: Pregnancy after bariatric surgery in a racially and ethnically diverse cohort of patients is associated with decreased risk of preeclampsia, gestational diabetes or impaired fasting glucose, and LGA neonates; it is also associated with an increased risk of SGA neonates compared with pregnant patients in a matched control group.

The association between selenium levels and hypertensive disorders of pregnancy: a systematic review of the literature.

Selenium (Se) is essential for selenoprotein synthesis, being thus important for immune and thyroid function, and for antioxidant defence. Some studies have shown that low levels of Se may associate with hypertensive disorders of pregnancy (HDP). Nevertheless, evidence supporting Se supplementation in pregnant or childbearing-age women is still lacking. In this context, this work aimed to systematically review the most recent scientific evidence to understand the relationship between Se levels and HDP. We performed a systematic review (protocol number: CRD42022310424) with literature of the last decade. PubMed, Scopus, Web of Science, registers and grey literature were searched to identify studies reporting measurement of Se levels in normotensive and hypertensive pregnant women (supplemented or not with Se). Study quality was assessed using the National Heart, Lung, and Blood Institute Study Quality Assessment Tools. Among the thirty included studies, a majority, 61 % (n 19) of the 'good' or 'fair' studies, reported a negative association between Se and HDP, and some studies, 39 % (n 11) of the 'good' or 'fair' studies, reported a lack of association. This review provides an important amount of quality evidence suggesting that low Se levels associate with the occurrence of HDP. Nevertheless, the gathered information is not enough to underlie a recommendation for Se supplementation in pregnancy to protect against HDP. Thus, this review emphasises the need for further well-designed randomised controlled trials that may provide blunt evidence regarding the benefits of Se supplementation during pregnancy.

Counseling pregnant women on calcium: effects on calcium intake.

OBJECTIVES: To evaluate the effect of incorporating calcium advice into early pregnancy counseling on calcium intake during pregnancy in the Netherlands. METHODS: A multicenter prospective before-after cohort study was conducted introducing risk-based care including calculating individual pre-eclampsia risk. Part of the intervention was to incorporate calcium advice into routine counseling. We calculated individual daily calcium intake and adequacy of calcium intake (≥1,000 mg/day) at 16, 24 and 34 weeks of pregnancy. We performed a multiple logistic regression adjusting for covariates to identify any differences in the risk of inadequate calcium intake between RC and CAC. RESULTS: In regular care (RC, 2013-2015, n=2,477) 60% had inadequate calcium intake, compared to 49% during calcium advice care (CAC, 2017-2018, n=774) (aOR 0.75, 95% CI 0.64-0.88). Specific calcium supplements were used by 2% and 29% in RC and CAC, respectively (OR 25.1, 95% CI 17.8-36.0). Determinants of an inadequate calcium intake were lower age (aOR per additional year 0.96, 95% CI: 0.94-0.98), nulliparity (aOR 1.22, 95% CI: 1.03-1.45) and non-Caucasian origin (aOR 1.83, 95% CI 1.09-3.09). In CAC, risk of inadequate intake decreased with increasing predicted pre-eclampsia risk, which was a trend reversal compared to RC. CONCLUSIONS: Incorporating calcium advice into early pregnancy counseling was shown to lead to a decrease in the risk of inadequate calcium intake during pregnancy, but still inadequate intake in half of the women suggesting the need for further study on improving implementation. Awareness of individual increased PE risk had positive effect on calcium intake.

Maternal obesity, diabetes, preeclampsia, and asthma during pregnancy and likelihood of autism spectrum disorder with gastrointestinal disturbances in offspring.

LAY ABSTRACT: Autism spectrum disorder is heterogeneous and often accompanied by co-occurring conditions. Previous studies have shown that maternal health conditions during pregnancy including obesity, diabetes, preeclampsia, and asthma were associated with increased likelihood of autism. However, little has been done examining the likelihood associated with autism with co-occurring conditions. This study assessed these maternal health conditions in relationship to autism and gastrointestinal disturbances, a common co-occurring condition in children diagnosed with autism. Data included 308,536 mother-child pairs from one integrated health care system with comprehensive electronic medical records. Among the study cohort, 5,131 (1.7%) children had a diagnosis of autism by age 5. Gastrointestinal disturbances were present in 35.4% of children diagnosed with autism and 25.1% of children without autism diagnoses. Our results showed that each of the four maternal health conditions during pregnancy was associated with increased likelihood of gastrointestinal disturbances, autism without gastrointestinal disturbances, and autism with gastrointestinal disturbances. For all four maternal health conditions, the association was greatest for likelihood of autism with gastrointestinal disturbances. Given that children diagnosed with autism are more likely to have gastrointestinal disturbances and over 80% of gastrointestinal disturbances in this cohort were diagnosed prior to autism diagnosis, this study suggests that there may be common biological pathways between autism and gastrointestinal disturbances impacted by these maternal exposures. Future studies are warranted to assess associations between different exposures and autism with other co-occurring conditions to increase our understanding of autism heterogeneity.

The association between maternal tea consumption and the risk of pregnancy induced hypertension: A retrospective cohort study in Lanzhou, China.

BACKGROUND: Existing evidence on the relationship between maternal tea consumption and pregnancy induced hypertension (PIH) is inconclusive. This study aimed to evaluate the association between maternal tea consumption and the risk of PIH. METHODS: This study analysed the data of women without chronic hypertension who participated in a retrospective birth cohort study conducted from 2010 to 2012 at the Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China. Multivariable logistic regression models were used to estimate the association between tea consumption and the risk of PIH and its clinical subtypes by different tea exposure time windows. RESULTS: Among the 10,452 women included in this study, tea consumption during pregnancy was significantly associated with an increased risk of PIH (odds ratio [OR] = 1.44, 95 % confidence interval [CI]: 1.01, 2.05), gestational hypertension (OR = 1.86, 95 % CI: 1.07, 3.21), and early-onset preeclampsia (OR = 2.93, 95 % CI: 1.21, 7.09). This was especially the case with black tea (OR = 3.57, 95 % CI: 1.67, 7.62). CONCLUSIONS: Tea consumption during pregnancy might be associated with an increased risk of PIH, gestational hypertension, and early-onset preeclampsia. These findings have important implications for public health in reducing the PIH.

Vitamin D supplementation higher than 2000 IU/day compared to lower dose on maternal-fetal outcome: Systematic review and meta-analysis.

INTRODUCTION: Although vitamin D is widely known as an essential micronutrient during pregnancy, the exact supplementation dose to prevent maternal-fetal outcomes remains a question. This study aims to provide a systematic review and a meta-analysis of data from randomized controlled trial on > 2000 IU/day vitamin D supplementation compared to ⩽ 2000 IU/day; and ⩽ 2000 IU/day compared to placebo, on their effects on the incidence of preeclampsia, gestational diabetes mellitus, preterm birth, and differences on birth weight. METHODS: A systematic literature search on PubMed, EBSCO-MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases was carried out to evaluate randomized controlled trial studies on the effects of oral vitamin D > 2000 IU/day versus ⩽ 2000 IU/day; and ⩽ 2000 IU/day versus placebo, on preeclampsia, gestational diabetes mellitus, preterm birth and birth weight. Risk ratio, mean difference, and 95% confidence interval were calculated. RESULTS: There were a total of 27 randomized controlled trials selected. Maternal vitamin D supplementation > 2000 IU/day had a positive effect only on gestational diabetes mellitus (seven randomized controlled trials; risk ratio = 0.70, 95% confidence interval: 0.51-0.95, I2 = 0). Vitamin D supplementation ⩽ 2000 IU/day has reduced the risk of preeclampsia (three randomized controlled trials; risk ratio = 0.29, 95% confidence interval: 0.09-0.95, I2 = 0), with no significant difference when compared to > 2000 IU/day (eight randomized controlled trials; risk ratio = 0.80, 95% confidence interval: 0.51-1.24, I2 = 31). No difference in preterm birth risk and birth weight after vitamin D supplementation. The quality of evidence varies from moderate to very low certainty. The risk of preeclampsia and gestational diabetes mellitus after high-dose versus low-dose vitamin D supplementation was the ones with moderate certainty. CONCLUSION: Vitamin D supplementation > 2000 IU/day might be important to reduce the risk of gestational diabetes mellitus. Lower dose vitamin D supplementation (⩽ 2000 IU/day) seemed adequate to reduce the risk of preeclampsia, with no significant difference compared to the higher dose.