Association between particulate air pollution and hypertensive disorders in pregnancy: A retrospective cohort study.

BACKGROUND: Epidemiological findings regarding the association of particulate matter ≤2.5 µm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy. METHODS AND FINDINGS: A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 µg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochran's Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP. CONCLUSIONS: Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.

Associations between hypertension with reproductive and menopausal factors: An integrated women's health programme (IWHP) study.

BACKGROUND: Women are less likely to have classic cardiovascular risk factors than men, and events during their reproductive and menopausal years may increase hypertension risk. The aim of this study is to examine woman-specific factors, including menstrual, reproductive and pregnancy complications, in relation to the prevalence of hypertension in mid-life Asian women. METHODS: This is a cross-sectional study of 1146 healthy women aged 45-69 years, from a multi-ethnic Asian cohort. The women completed an extensive questionnaire that included their sociodemographic details, medical history, lifestyle and physical activity, and reproductive and menopausal history. They also underwent objectively measured physical performance tests and a dual X-ray absorptiometry scan. Hypertension was defined as a systolic BP ≥140 and/or diastolic BP ≥90mm Hg, past diagnosis by a physician, or use of antihypertensive medications. Multivariable logistic regression was used to assess the independent risk factors for hypertension. RESULTS: The average age of the 1146 women analysed was 56.3 (SD 6.2) years, and 55.2 percent of them were hypertensive. The prevalence of gestational diabetes and gestational hypertension was 12.6% and 9.4%, respectively. Besides age, abnormal menstrual cycle length at 25 years of age (OR:2.35, CI:1.34-4.13), preeclampsia (OR:2.46, CI:1.06-5.74), increased visceral adiposity (OR:4.21, CI:2.28-7.79) and reduced physical performance (OR:2.83, CI:1.46-5.47) were independently associated with hypertension in Asian women. CONCLUSIONS: Our findings highlight the necessity of including features of menstrual and reproductive history as possible indicators of hypertension risk in cardiovascular disease risk assessment and prevention among Asian women. Reducing visceral adiposity and exercise to improve physical performance may help women avoid developing hypertension.

Racial and Economic Segregation Over the Life Course and Incident Hypertensive Disorders of Pregnancy Among Black Women in California.

Black women in the United States have the highest incidence of hypertensive disorders of pregnancy (HDP) and are disproportionately burdened by its adverse sequalae, compared with women of all racial and ethnic groups. Segregation, a key driver of structural racism for Black families, can provide information critical to understanding these disparities. We examined the association between racial and economic segregation at 2 points and incident HDP using intergenerationally linked birth records of 45,204 Black California-born primiparous mothers (born 1982-1997) and their infants (born 1997-2011), with HDP ascertained from hospital discharge records. Women's early childhood and adulthood neighborhoods were categorized as deprived, mixed, or privileged based on the Index of Concentration at the Extremes (a measure of concentrated racial and economic segregation), yielding 9 life-course trajectories. Women living in deprived neighborhoods at both time points experienced the highest odds of HDP (from mixed effect logistic regression, unadjusted odds ratio = 1.26, 95% confidence interval: 1.13, 1.40) compared with women living in privileged neighborhoods at both time points. All trajectories involving residence in a deprived neighborhood in early childhood or adulthood were associated with increased odds of HDP, whereas mixed-privileged and privileged-mixed trajectories were not. Future studies should assess the causal nature of these associations.

Effects of Sedentary Behavior on the Complications Experienced by Pregnant Women: A Systematic Review.

Pregnant women are encouraged to reduce sitting time and replace it with physical activity. Complications arising during pregnancy include gestational hypertension, preeclampsia, gestational diabetes mellitus (GDM), and prenatal and postpartum depression. In this systematic review, we examined effects of sedentary behavior on the health of pregnant women. We conducted a systematic review with PubMed from year 2000 to identify the relationship between a sedentary lifestyle and psychological effects, occurrence of GDM, gestational hypertension, and preeclampsia. Data extracted included sedentary time of pregnant women, psychological effects, occurrence of GDM, gestational hypertension, and preeclampsia as outcomes. Among the 200 studies retrieved, 11 were finally included after screening. The mean age of eligible pregnant women ranged from 28.5 to 32.9 years. Five studies were extracted with outcomes of psychological effects on the mother, five with GDM, and one with gestational hypertension/preeclampsia. Longer sedentary time was associated with increased risks of prepartum/postpartum depression in three of five studies and GDM in three of five studies. No association was found between sedentary behavior and the risk for gestational hypertension/preeclampsia. Higher sedentary behavior in the second trimester of pregnancy was likely to be associated with postpartum depression. Longer sitting time may increase the risk of prenatal or postnatal depression and GDM, but no relationship was proven for gestational hypertension and preeclampsia in one study. High sedentary behavior in the second trimester may have psychological impacts. The number of studies was small and further research is needed to statistically evaluate impacts of sedentary behavior during pregnancy.

Induction of labor versus expectant management in patients with idiopathic polyhydramnios.

OBJECTIVE: To evaluate whether induction of labor is associated with lower risk of cesarean section compared to expectant management in patients with isolated polyhydramnios. STUDY DESIGN: This is a single-center, retrospective cohort study of patients with pregnancies complicated by idiopathic polyhydramnios, documented between 34 and 38 weeks gestation, who were delivered between July 2012 and February 2020. The primary outcome was cesarean delivery. Secondary outcomes included chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, and composite neonatal morbidity. RESULTS: There were 194 patients included with idiopathic polyhydramnios - 115 underwent induction and 79 patients were expectantly managed. Planned induction was associated with a lower rate of CD compared with expectant management but did not meet statistical significance (19.1 % vs 30.4 %, aOR 0.51, 95 % CI 0.24, 1.05). A similar effect was seen when stratifying for parity: both nulliparous (9.1 % vs 16.3 %, aOR 0.59, 95 % CI 0.17, 1.98) and multiparous (32.7 % vs 47.2 %, aOR 0.45, 95 % CI 0.18, 1.15) patients had a lower CD rate when there was a planned induction, though neither group met statistical significance. No differences in maternal or fetal secondary outcomes were identified (chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, composite neonatal morbidity). CONCLUSION: Lower rates of cesarean section were associated with labor induction for patients with isolated polyhydramnios, but confidence intervals did not reach statistical significance.

Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis.

CONTEXT: Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. OBJECTIVE: To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes. METHODS: We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders. RESULTS: The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA. CONCLUSION: This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

Gestational intermittent hypoxia induces endothelial dysfunction and hypertension in pregnant rats: role of endothelin type B receptor†.

Obstructive sleep apnea is a recognized risk factor for gestational hypertension, yet the exact mechanism behind this association remains unclear. Here, we tested the hypothesis that intermittent hypoxia, a hallmark of obstructive sleep apnea, induces gestational hypertension through perturbed endothelin-1 signaling. Pregnant Sprague-Dawley rats were subjected to normoxia (control), mild intermittent hypoxia (10.5% O2), or severe intermittent hypoxia (6.5% O2) from gestational days 10-21. Blood pressure was monitored. Plasma was collected and mesenteric arteries were isolated for myograph and protein analyses. The mild and severe intermittent hypoxia groups demonstrated elevated blood pressure, reduced plasma nitrate/nitrite, and unchanged endothelin-1 levels compared to the control group. Western blot analysis revealed decreased expression of endothelin type B receptor and phosphorylated endothelial nitric oxide synthase, while the levels of endothelin type A receptor and total endothelial nitric oxide synthase remained unchanged following intermittent hypoxia exposure. The contractile responses to potassium chloride, phenylephrine, and endothelin-1 were unaffected in endothelium-denuded arteries from mild and severe intermittent hypoxia rats. However, mild and severe intermittent hypoxia rats exhibited impaired endothelium-dependent vasorelaxation responses to endothelin type B receptor agonist IRL-1620 and acetylcholine compared to controls. Endothelium denudation abolished IRL-1620-induced vasorelaxation, supporting the involvement of endothelium in endothelin type B receptor-mediated relaxation. Treatment with IRL-1620 during intermittent hypoxia exposure significantly attenuated intermittent hypoxia-induced hypertension in pregnant rats. This was associated with elevated circulating nitrate/nitrite levels, enhanced endothelin type B receptor expression, increased endothelial nitric oxide synthase activation, and improved vasodilation responses. Our data suggested that intermittent hypoxia exposure during gestation increases blood pressure in pregnant rats by suppressing endothelin type B receptor-mediated signaling, providing a molecular mechanism linking intermittent hypoxia and gestational hypertension.

Chronic hypertension diagnosed by the American Heart Association and American College of Cardiology criteria is associated with increased risk of developing hypertensive disorders of pregnancy.

BACKGROUND: ACOG uses a systolic blood pressure (SBP) ≥140 or diastolic blood pressure (DBP) ≥90 documented at <20 weeks of gestation to define chronic hypertension. In the nonpregnant state, the American Heart Association (AHA) and the American College of Cardiology (ACC) define chronic hypertension using lower diagnostic thresholds of SBP ≥130 or DBP ≥80. It remains unclear whether using more conservative guidelines in pregnancy improves identification of those at risk for gestational hypertension (GHTN) or preeclampsia (PRE). OBJECTIVE: We sought to investigate whether subjects with chronic hypertension based on the American Heart Association and American College of Cardiology criteria had an increased risk for gestational hypertension and preeclampsia than those without chronic hypertension. STUDY DESIGN: We conducted a retrospective cohort study utilizing a clinical database at a diverse, large urban, safety-net hospital. Subjects aged 18 to 40 years with singleton gestations and first trimester prenatal care were included. We defined subjects that met the criteria for stage 1 chronic hypertension based on first trimester systolic blood pressure and diastolic blood pressure cutoffs satisfying the American Heart Association and American College of Cardiology criteria (systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg). Those who did not meet these criteria had a systolic blood pressure <130 mm Hg and a diastolic blood pressure <90 mm Hg. We did not include those with chronic hypertension based on the American College of Obstetricians and Gynecologists criteria in this cohort (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg at <20 weeks); therefore, those who met the American Heart Association and American College of Cardiology criteria solely consisted of subjects with systolic blood pressure of 130 to 139 mm Hg and diastolic blood pressure of 80 of 89 mm Hg. By doing this, we were able to specifically investigate the increased risk for this specific population, which remains unclear. Diagnoses of gestational hypertension and preeclampsia were based on the established American College of Obstetricians and Gynecologists criteria. Preeclampsia included those with and without severe features. Tests for normality were performed. Student t-tests or rank sum tests were performed as appropriate for continuous variables; chi-square or Fisher's exact tests were performed for categorical variables. Generalized linear models were performed to calculate risk ratios while controlling for appropriate confounders. RESULTS: Of N=3354 subjects, 18% (n=629) were diagnosed with stage 1 chronic hypertension based on American Heart Association and American College of Cardiology criteria. Those with American Heart Association and American College of Cardiology stage 1 chronic hypertension had increased rates of gestational hypertension (35.4% vs 20%; P<.001) and preeclampsia (22.3% vs 10%; P<.001) than those without Stage 1 chronic hypertension based on these criteria. When controlling for maternal age, race, first trimester body mass index, pregestational diabetes, and substance use, those with the American Heart Association and American College of Cardiology stage 1 chronic hypertension had an almost 1.5-fold higher adjusted risk ratio of experiencing gestational hypertension (adjusted risk ratio, 1.49±0.10; P<.001) and almost 2-fold increased adjusted risk ratio of experiencing preeclampsia (adjusted risk ratio, 1.98±0.19; P<.001). CONCLUSION: Our data suggest an increased risk for developing gestational hypertension and preeclampsia for subjects satisfying the American Heart Association and American College of Cardiology cutoff for stage 1 chronic hypertension. Future studies need to consider whether diagnosis of chronic hypertension in pregnancy should conform with American Heart Association and American College of Cardiology criteria, and if those with stage 1 chronic hypertension based on American Heart Association and American College of Cardiology criteria require the same preventative measures and interventions utilized by those diagnosed by American College of Obstetricians and Gynecologists criteria.

Arterial hypertension and smoking in pregnant women in the Valencian Community: maternal and neonatal outcomes.

OBJECTIVE: Hypertension and smoking during pregnancy have been linked to various adverse maternal and fetal outcomes. The objective of this work is to study how the smoking influences the development of hypertension, its effects on the pregnant woman, and on the newborn. MATERIALS AND METHODS: An observational study in two phases was carried out: the descriptive first phase allows characterization of the sample and the analytical second phase is a case-control nested in a retrospective cohort corresponding to pregnancy. RESULTS: A total of 712 women were included in the study. Of the 672 (94.4%) non-hypertensive women, 533 (79.3%) were non-smoking and 139 (20.7%) smoking. For the 40 (5.6%) hypertensive women, 30 (75.0%) were non-smoking and 10 (25.0%) smoking. The prevalence of hypertension was of 5.6%. Women who quit smoking before pregnancy saw a reduced risk of hypertension. For women who smoke during pregnancy, those of younger ages, with a normal body mass index, who are primiparous, employed and with a low-medium level of education have higher risk of hypertension. The risk of hypertension according to the level of physical activity during leisure time follows a "U" shape, with those who perform light physical activity at the lowest risk of hypertension. Hypertensive women have a higher risk of small for gestational age newborns. Smoking does not pose an additional risk for adverse outcomes once hypertension is diagnosed. CONCLUSIONS: Future studies should aim to determine the role of smoking habit in the appearance of hypertension in pregnancy in order to establish adequate intervention guidelines that may aid in reducing the prevalence of hypertension.

The mediating role of pregnancy-induced hypertension on pre-pregnancy body mass index and adverse neonatal outcomes in women with assisted reproductive technology.

OBJECTIVE: To explore whether pregnancy-induced hypertension (PIH) mediates the association between pre-pregnancy body mass index (BMI) and adverse neonatal outcomes in women undergoing assisted reproductive technology (ART) for singleton pregnancies. METHODS: This cohort study collected 79437 maternal data from the National Vital Statistics System (NVSS) between 2020 and 2021. Univariable and multivariable logistic regression models were applied to estimate the association between pre-pregnancy BMI and PIH in women receiving ART as well as the associations between pre-pregnancy BMI and PIH and adverse neonatal outcomes. The mediation effect of PIH on the association between pre-pregnancy BMI and adverse neonatal outcomes was estimated according to the total effect, natural direct effect, natural indirect effect, and percentage of mediation. RESULTS: There were 25769 participants had adverse neonatal outcomes at the end of the follow-up. After adjusting for confounding factors, an increased risk of PIH in women receiving ART was identified in those with pre-pregnancy BMI ≥25 kg/m2 [odds ratio (OR)=1.92, 95% confidence interval (CI):1.84-2.01]. Pre-pregnancy BMI ≥25 kg/m2 was associated with an increased risk of adverse neonatal outcomes (OR = 1.26, 95%CI:1.22-1.30). Women with PIH had an increased risk of adverse neonatal outcomes (OR = 1.79, 95%CI:1.71-1.87). The percentage mediated by PIH in the association between pre-pregnancy BMI and adverse neonatal outcomes was 21.30%. CONCLUSION: PIH partially mediated the association between pre-pregnancy BMI and adverse neonatal outcomes in women receiving ART, which recommends that women control weight before receiving ART.

Associations between extreme temperature exposure and hypertensive disorders in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Hypertensive disorders in pregnancy (HDP) are a major cause of maternal mortality and morbidity. Recent studies indicated that pregnant women are the most vulnerable populations to ambient temperature influences, but it affected HDP with inconsistent conclusions. Our objective is to systematically review whether extreme temperature exposure is associated with a changed risk for HDP. METHOD: We searched PubMed, EMBASE, Web of Science and Cochrane Library databases. We included cohort or case control studies examining the association between extreme temperature exposure before or during pregnancy and HDP. Heat sources such as saunas and hot baths were excluded. We pooled the odds ratio (OR) to assess the association between extreme temperature exposure and preeclampsia or eclampsia. RESULTS: Fifteen studies involving 4,481,888 patients were included. Five studies were included in the meta-analysis. The overall result demonstrated that in the first half of pregnancy, heat exposure increases the risk of developing preeclampsia or eclampsia and gestational hypertension, and cold exposure decreases the risk. The meta-analysis revealed that during the first half of pregnancy, heat exposure increased the risk of preeclampsia or eclampsia (OR 1.54, 95% confidence interval (CI): 1.10, 2.15), whereas cold exposure decreased the risk (OR 0.90, 95% CI: 0.84, 0.97). CONCLUSION: The ambient temperature is an important determinant for the development of HDP, especially for preeclampsia or eclampsia. The effects of extreme temperatures may be bidirectional during the different trimesters of pregnancy, which should be evaluated by future studies. This review provided hints of temperature regulation in HDP administration.

The adverse effect of gestational diabetes mellitus and hypertensive disorders of pregnancy on maternal-perinatal outcomes among singleton and twin pregnancies: a retrospective cohort study (2011-2019).

Background: Gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) are the predominant pregnancy complications among singleton and twin pregnancies worldwide. Our primary objective was to explore the adverse effect of GDM and HDP on maternal-perinatal outcomes compared with non-GDM and non-HDP in singleton and twin pregnancies. The secondary objective was to find the risk of adverse maternal-perinatal outcomes in twin pregnancies compared with singleton pregnancies complicated with GDM and HDP in Hubei, China. Methods: A tertiary hospital-based retrospective study was conducted at Wuhan University Renmin Hospital, Hubei Province, China, from 2011 to 2019. A chi-square test was used to determine the difference in adverse maternal-perinatal outcomes between singleton and twin pregnancies. A multiple binary logistic regression model and a joinpoint regression model were used to determine the association of GDM and HDP with adverse maternal-perinatal outcomes and GDM and HDP temporal trend among singleton and twin pregnancies. Results: The trend of HDP [average annual percentage change (AAPC) 15.1% (95% confidence interval (95%CI): 5.3, 25.7)] among singleton pregnancies and GDM [AAPC 50.4% (95%CI: 19.9, 88.7)] among twin pregnancies significantly increased from 2011 to 2019. After adjusting for confounding factors, GDM is associated with an increased risk of C-section (adjusted odds ratio (aOR), 1.5; 95%CI: 1.3, 1.6) and macrosomia (aOR, 1.3; 95%CI: 1.1, 1.6) in singleton and preterm birth (PTB) (aOR, 2.1; 95%CI: 1.2, 3.3) in twin pregnancies compared with non-GDM. HDP was associated with a higher risk of C-section, PTB, perinatal mortality, and low birth weight (LBW) in both singleton and twin pregnancies compared with the non-HDP. Compared with singleton pregnancies complicated with GDM and HDP, twin pregnancies showed higher odds of C-section [(aOR, 1.7; 95%CI: 1.1, 2.7), (aOR, 4.6; 95%CI: 2.5, 8.7), respectively], PTB [(aOR, 22.9; 95%CI: 14.1, 37.3), (aOR, 8.1; 95%CI: 5.3, 12.3), respectively], LBW [(aOR, 12.1; 95%CI: 8.2, 18.1), (aOR, 5.1; 95%CI: 3.6, 7.4), respectively], and low Apgar score [(aOR, 8.2; 95%CI: 4.4, 15.1), (aOR, 3.8; 95%CI: 2.4, 5.8), respectively] complicated with GDM and HDP. Conclusion: In conclusion, GDM showed an increased risk of a few adverse maternal-perinatal outcomes and HDP is associated with a higher risk of several adverse maternal-perinatal outcomes in singleton and twin pregnancies compared to non-GDM and non-HDP. Moreover, twin pregnancies complicated with GDM and HDP showed higher odds of adverse maternal-neonatal outcomes compared with singleton pregnancies complicated with GDM and HDP.

Considering gestational diabetes and gestational hypertension history across two pregnancies in relationship to cardiovascular disease development: A retrospective cohort study.

AIMS: Gestational diabetes (GDM) and hypertension (GHTN) occurrences signal elevated cardiovascular disease (CVD) risk. There is little study of occurrence and recurrence of these conditions in relationship to CVD. Among women with two singleton pregnancies, we aimed to quantify CVD risk in relationship to the number of GDM/GHTN occurrences. METHODS: In this Quebec-based retrospective cohort study (n = 431,980), we ascertained the number of GDM/GHTN occurrences over two pregnancies and assessed for CVD over a median of 16.4 years (cohort inception 1990-2012, outcomes 1990-2019). We defined CVD as a composite of myocardial infarction, stroke, and angina, requiring hospitalization and/or causing death. We adjusted Cox proportional hazards models for offspring size, preterm/term birth status, maternal age group, time between deliveries, ethnicity, deprivation level, and co-morbid conditions. RESULTS: Compared to absence of GDM/GHTN in either pregnancy, one GDM/GHTN occurrence increased CVD hazards by 47% (hazard ratio [HR] = 1.47, 95% confidence interval [CI] 1.35-1.61), two occurrences nearly doubled hazards (HR = 1.91, 95% CI 1.68-2.17), and three or more approximately tripled CVD hazards (HR = 2.93, 95% CI 2.20-3.90). Individual components of the composite demonstrated similar findings. CONCLUSIONS: Health care providers and mothers should consider a complete history of GDM/GHTN occurrences to ascertain the importance and urgency of preventive action.

Pre-gravid body mass index is associated with a higher risk of gestational hypertension in singleton pregnancy following frozen-thawed embryo transfer.

Introduction: Although it is well-known that obesity increases the risk of gestational hypertension (GH) in both spontaneous and assisted reproductive technology (ART) pregnancies. Recent data show that, in ART pregnancies, frozen-thawed embryo transfer (FET) is associated with an even higher risk of GH compared with fresh transfer. However, the relationship between pre-gravid body mass index (BMI) and GH in FET pregnancies has seldom been reported. Objective: The aim of this study is to examine the effect of pre-gravid BMI on GH in singleton pregnancy following FET. Methods: A retrospective cohort study at a tertiary hospital, including a total of 7,502 women who achieved singleton pregnancy after FET, was included. All patients were enrolled only once. On the basis of the BMI definitions of the Working Group on Obesity in China (WGOC) and the World Health Organization, the women were divided into normal BMI, overweight, and obese groups. The main outcome was GH, and the effect of pre-pregnancy BMI on GH was assessed by generalized linear model. Results: The risk of GH in our study population was 6.15%. According to the BMI definitions of the WGOC, the risk of GH in the obese group (15.55%) was significantly higher than that of the overweight group (8.26%, P < 0.001) and the normal BMI group (4.68%, P < 0.001). Pre-gravid overweight and obesity were associated with higher GH risk (OR, 1.77; 95% CI, 1.41-2.20; P < 0.001; OR, 3.69; 95% CI, 2.77-4.91; P < 0.001). A non-linear relationship between pre-gravid BMI and GH was observed. The risk of GH decreased with pre-gravid BMI level up to the turning point of BMI = 28.6 kg/m2 (OR, 1.16; 95% CI, 1.12-1.21; P < 0.001). Conclusion: Pre-gravid overweight and obesity are associated with higher GH risk among singleton pregnancy following FET. Before the turning point of BMI = 26.8 kg/m2, the risk of GH may increase 16.4% with each one-unit increment of maternal BMI. Women preparing for FET should maintain a normal BMI to lower the chances of GH.

Intake of Energy Drinks Before and During Pregnancy and Adverse Pregnancy Outcomes.

Importance: Consumption of energy drinks has increased drastically in recent years, particularly among young people. It is unknown whether intake of energy drinks is associated with health during pregnancy. Objective: To examine associations of energy drink intake before and during pregnancy with risk of adverse pregnancy outcomes (APOs). Design, Setting, and Participants: This prospective cohort study included data from women enrolled in the Nurses' Health Study 3 (NHS3) between June 1, 2010, and September 27, 2021, and the Growing Up Today Study (GUTS) who reported 1 or more singleton pregnancy from January 1, 2011, to June 1, 2019. Data were analyzed from October 1, 2021, to September 28, 2023. Exposure: Intake of energy drinks, assessed by food frequency questionnaire. Main Outcomes and Measures: The main outcomes were self-reported APOs, including pregnancy loss, gestational diabetes, gestational hypertension, preeclampsia, or preterm birth, and a composite APO, defined as development of any of the APOs. Risk of APOs was compared between consumers and nonconsumers of energy drinks. Results: This study included 7304 pregnancies in 4736 participants with information on prepregnancy energy drink intake and 4559 pregnancies in 4559 participants with information on energy drink intake during pregnancy. There were 1691 GUTS participants (mean [SD] age, 25.7 [2.9] years) and 3045 NHS3 participants (mean [SD] age, 30.2 [4.1] years). At baseline, 230 GUTS participants (14%) and 283 NHS3 participants (9%) reported any intake of energy drinks. While no associations were found for pregnancy loss (odds ratio [OR], 0.89; 95% CI, 0.71-1.11), preterm birth (OR, 1.07; 95% CI, 0.71-1.61), gestational diabetes (OR, 0.89; 95% CI, 0.58-1.35), preeclampsia (OR, 0.73; 95% CI, 0.41-1.30), or the composite APO (OR, 1.05; 95% CI, 0.87-1.26), prepregnancy energy drink use was associated with a higher risk of gestational hypertension (OR, 1.60; 95% CI, 1.12-2.29). A significant interaction was found between age and energy drink intake in relation to hypertensive disorders (P = .02 for interaction for gestational hypertension; P = .04 for interaction for any hypertensive disorders), with stronger associations for participants above the median age. No associations of energy drink intake during pregnancy with any of the APOs were found in NHS3 (eg, any APO: OR, 0.86; 95% CI, 0.41-1.79). Conclusions and Relevance: In this study, energy drink intake before pregnancy was associated with an elevated risk of gestational hypertension. Given the low prevalence of energy drink intake and low consumption levels among users, the results should be interpreted cautiously.

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.

No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture.

STUDY QUESTION: Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception? SUMMARY ANSWER: There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study. WHAT IS KNOWN ALREADY: Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions. STUDY DESIGN, SIZE, DURATION: This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia). PARTICIPANTS/MATERIALS, SETTING, METHODS: From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders. MAIN RESULTS AND THE ROLE OF CHANCE: In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer. LIMITATIONS, REASONS FOR CAUTION: This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables. WIDER IMPLICATIONS OF THE FINDINGS: Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation. STUDY FUNDING/COMPETING INTEREST(S): The study was financed by a research grant from Gedeon Richter. There are no conflicts of interest for all authors to declare. TRIAL REGISTRATION NUMBER: N/A.

Maternal and perinatal outcomes in primiparous singleton pregnancies conceived with assisted reproductive technology in British Columbia.

OBJECTIVE: To evaluate the odds of developing adverse maternal and perinatal outcomes in primiparous singleton pregnancies conceived with assisted reproductive technology (ART) compared with pregnancies conceived without ART. STUDY DESIGN: A retrospective population-based cohort study using data from the British Columbia Perinatal Data Registry. The population included primiparous women with singleton live or stillbirths delivering at or after 20 weeks' gestation between April 1st 2008-March 31st, 2021. Women who conceived with ART were compared with those who conceived without ART. The main outcome measures were gestational diabetes, hypertensive disorders of pregnancy, preterm birth, low birth weight, neonatal intensive care unit admission, stillbirth, and 5-minute Apgar score. Adjusted odds ratios were calculated. RESULTS: The study population included 191,059 primiparous women: 183,819 conceived without ART, 7,240 conceived using ART. After controlling for age, body mass index, pre-gestational diabetes, and smoking status, singleton pregnancies conceived by ART had significantly higher odds of gestational diabetes (OR 1.18, 95 % confidence interval [CI] 1.10-1.26) and hypertensive disorders of pregnancy (OR 1.39, 95 % CI 1.29-1.51). There were also significantly increased odds of preterm birth (OR 1.35, 95 % CI 1.25-1.46), low birth weight (OR 1.35, 95 % CI 1.23-1.49), and neonatal intensive care unit admission (OR 1.21, 95 % CI 1.11-1.32). There was not a statistically significant difference in the odds of stillbirth (OR 1.06, 95 % CI 0.72-1.57) or 5-minute Apgar score < 7 (OR 1.10, 95 % CI 0.97-1.26). CONCLUSION: There is an increased odds of developing several adverse maternal or neonatal outcomes in primiparous singleton pregnancies conceived by ART including gestational diabetes, hypertensive disorders of pregnancy, preterm birth, low birth weight, and increased incidence of neonatal intensive care unit admissions.

The influence of embryo stage on obstetric complications and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis.

Objective: To investigate the effect of embryo stage at the time of transfer on obstetric and perinatal outcomes in programmed frozen-thawed embryo transfer (FET) versus natural FET cycles. Design: Systematic review and meta-analysis. Setting: Not applicable. Patients: Women with programmed frozen-thawed embryo transfer (FET) and natural FET. Interventions: The PubMed, MEDLINE, and EMBASE databases and the Cochrane Central Register of Controlled Trials (CCRT) were searched from 1983 to October 2022. Twenty-three observational studies were included. Primary outcome measure: The primary outcomes were hypertensive disorders of pregnancy (HDPs), gestational hypertension and preeclampsia (PE). The secondary outcomes were gestational diabetes mellitus (GDM), placenta previa, postpartum haemorrhage (PPH), placental abruption, preterm premature rupture of membranes (PPROM), large for gestational age (LGA), small for gestational age (SGA), macrosomia, and preterm delivery (PTD). Results: The risk of HDP (14 studies, odds ratio (OR) 2.17; 95% confidence interval (CI) 1.95-2.41; P<0.00001; I2 = 43%), gestational hypertension (11 studies, OR 1.38; 95% CI 1.15-1.66; P=0.0006; I2 = 19%), PE (12 studies, OR 2.09; 95% CI 1.88-2.32; P<0.00001; I2 = 0%), GDM (20 studies, OR 1.09; 95% CI 1.02-1.17; P=0.02; I2 = 8%), LGA (18 studies, OR 1.11; 95% CI 1.07-1.15; P<0.00001; I2 = 46%), macrosomia (12 studies, OR 1.15; 95% CI 1.07-1.24; P=0.0002; I2 = 31%), PTD (22 studies, OR 1.21; 95% CI 1.15-1.27; P<0.00001; I2 = 49%), placenta previa (17 studies, OR 1.2; 95% CI 1.02-1.41; P=0.03; I2 = 11%), PPROM (9 studies, OR 1.19; 95% CI 1.02-1.39; P=0.02; I2 = 40%), and PPH (12 studies, OR 2.27; 95% CI 2.02-2.55; P <0.00001; I2 = 55%) were increased in programmed FET cycles versus natural FET cycles with overall embryo transfer. Blastocyst transfer had a higher risk of HDP (6 studies, OR 2.48; 95% CI 2.12-2.91; P<0.00001; I2 = 39%), gestational hypertension (5 studies, OR 1.87; 95% CI 1.27-2.75; P=0.002; I2 = 25%), PE (6 studies, OR 2.23; 95% CI 1.93-2.56; P<0.00001; I2 = 0%), GDM (10 studies, OR 1.13; 95% CI 1.04-1.23; P=0.005; I2 = 39%), LGA (6 studies, OR 1.14; 95% CI 1.07-1.21; P<0.0001; I2 = 9%), macrosomia (4 studies, OR 1.15; 95% CI 1.05-1.26; P<0.002; I2 = 68%), PTD (9 studies, OR 1.43; 95% CI 1.31-1.57; P<0.00001; I2 = 22%), PPH (6 studies, OR 1.92; 95% CI 1.46-2.51; P<0.00001; I2 = 55%), and PPROM (4 studies, OR 1.45; 95% CI 1.14-1.83; P=0.002; I2 = 46%) in programmed FET cycles than in natural FET cycles. Cleavage-stage embryo transfers revealed no difference in HDPs (1 study, OR 0.81; 95% CI 0.32-2.02; P=0.65; I2 not applicable), gestational hypertension (2 studies, OR 0.85; 95% CI 0.48-1.51; P=0.59; I2 = 0%), PE (1 study, OR 1.19; 95% CI 0.58-2.42; P=0.64; I2not applicable), GDM (3 study, OR 0.79; 95% CI 0.52-1.20; P=0.27; I2 = 21%), LGA (1 study, OR 1.15; 95% CI 0.62-2.11; P=0.66; I2not applicable), macrosomia (1 study, OR 1.22; 95% CI 0.54-2.77; P=0.64; I2 not applicable), PTD (2 studies, OR 1.05; 95% CI 0.74-1.49; P=0.79; I2 = 0%), PPH (1 study, OR 1.49; 95% CI 0.85-2.62; P=0.17; I2not applicable), or PPROM (2 studies, OR 0.74; 95% CI 0.46-1.21; P=0.23; I2 = 0%) between programmed FET cycles and natural FET cycles. Conclusions: The risks of HDPs, gestational hypertension, PE, GDM, LGA, macrosomia, SGA, PTD, placenta previa, PPROM, and PPH were increased in programmed FET cycles versus natural FET cycles with overall embryo transfer and blastocyst transfer, but the risks were not clear for cleavage-stage embryo transfer.

Young women were associated with higher risk of hypertensive disorders of pregnancy and cesarean section from hormone replaced cycles in frozen-thawed embryo transfer: a retrospective study of 5316 singleton deliveries.

Background: The utilization of frozen-thawed embryo transfer (FET) cycles has been linked to heightened risks of adverse perinatal outcomes. However, the potential association between adverse perinatal outcomes and distinct endometrial preparation regimens remains unclear. Therefore, we aim to investigate the maternal and neonatal outcomes after hormone replacement treatment (HRT) cycles, natural cycles (NC) and HRT cycles with pretreatment using GnRHa (HRT + GnRHa) for ovulatory women undergoing FET cycles. Methods: A large sample retrospective cohort study was carried out from 2016 to 2020. The data included a total of 5316 women who had singleton deliveries undergoing FET cycles and which were divided into three groups based on different endometrial preparation protocols: 4399 patients in HRT groups, 621 in GnRHa+HRT groups, 296 in NC groups. The outcomes consisted of maternal outcomes (cesarean section, hypertensive disorders of pregnancy (HDP), placenta previa, gestational diabetes mellitus (GDM));and neonatal outcomes (preterm birth, newborn birthweight, low birthweight, small for gestational age (SGA), macrosomia, large for gestational age (LGA), fetal malformation). Results: After adjusting for a series of confounding variables, we found an increased risk of HDP (aOR=3.362; 95%CI, 1.059-10.675) and cesarean section (aOR=1.838; 95%CI, 1.333-2.535) in HRT cycles compared with NC, especially for ovulatory women under 35 years old. However, in all three groups, newborn birth weight was not significantly different. Meanwhile, perinatal outcomes did not differ significantly in terms of perinatal outcomes in HRT +GnRHa cycles compared with HRT cycles solely. Conclusion: During FET cycles, singletons from HRT were related to higher risks of HDP and cesarean section, particularly for young women. GnRHa pretreatment didn't bring any benefit to perinatal outcomes compared with HRT cycles alone. Therefore, the natural cycle may be a more appropriate and safer option for young ovulatory women.