The association between attention deficit hyperactivity disorder and pregnancy, delivery and neonatal outcomes-an evaluation of a population database.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the more common neuropsychiatric disorders in women of reproductive age. Our objective was to compare perinatal outcomes between women with an ADHD diagnosis and those without. METHODS: A retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS) United States database. The study included all women who either delivered or experienced maternal death from 2004 to 2014. Perinatal outcomes were compared between women with an ICD-9 diagnosis of ADHD and those without. RESULTS: Overall, 9,096,788 women met the inclusion criteria. Amongst them, 10,031 women had a diagnosis of ADHD. Women with ADHD, compared to those without, were more likely to be younger than 25 years of age; white; to smoke tobacco during pregnancy; to use illicit drugs; and to suffer from chronic hypertension, thyroid disorders, and obesity (p < 0.001 for all). Women in the ADHD group, compared to those without, had a higher rate of hypertensive disorders of pregnancy (HDP) (aOR 1.36, 95% CI 1.28-1.45, p < 0.001), cesarean delivery (aOR 1.19, 95% CI 1.13-1.25, p < 0.001), chorioamnionitis (aOR 1.34, 95% CI 1.17-1.52, p < 0.001), and maternal infection (aOR 1.33, 95% CI 1.19-1.5, p < 0.001). Regarding neonatal outcomes, patients with ADHD, compared to those without, had a higher rate of small-for-gestational-age neonate (SGA) (aOR 1.3, 95% CI 1.17-1.43, p < 0.001), and congenital anomalies (aOR 2.77, 95% CI 2.36-3.26, p < 0.001). CONCLUSION: Women with a diagnosis of ADHD had a higher incidence of a myriad of maternal and neonatal complications, including cesarean delivery, HDP, and SGA neonates.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with hypertensive disorders of pregnancy in the Atlanta African American Maternal-Child cohort.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are slow to break down in the environment and widely detected in humans. Epidemiological evidence suggests that prenatal exposure to perfluorooctanoic acid (PFOA), a legacy PFAS, is linked to gestational hypertension and preeclampsia. However, the relationship between other PFAS, which are structurally similar, and these outcomes remains largely understudied, despite biologic plausibility. Here, we examined associations between serum PFAS mixtures in relation to hypertensive disorders of pregnancy within a birth cohort of African Americans. METHODS: Participants in the present study were enrolled in the Atlanta African American Maternal-Child cohort between 2014 and 2020 (n = 513). Serum samples collected between 8 and 14 weeks gestation were analyzed for four PFAS. Logistic regression was used to assess associations between individual natural log transformed PFAS and specific hypertensive disorders of pregnancy (preeclampsia, gestational hypertension), while quantile g-computation was used to estimate mixture effects. Preeclampsia and gestational hypertension were treated as separate outcomes in individual models. All models were adjusted for maternal education, maternal age, early pregnancy body mass index, parity, and any alcohol, tobacco, or marijuana use. RESULTS: The geometric mean of PFOS and PFHxS was slightly lower among those with preeclampsia relative to those without a hypertensive disorder (e.g., geometric mean for PFOS was 1.89 and 1.94, respectively). Serum concentrations of PFAS were not strongly associated with gestational hypertension or preeclampsia in single pollutant or mixture models. For example, using quantile g-computation, a simultaneous one quartile increase in all PFAS was not associated with odds of gestational hypertension (odds ratio = 0.86, 95% CI = 0.60, 1.23), relative to those without a hypertensive disorder of pregnancy. CONCLUSIONS: In this birth cohort of African Americans, there was no association between serum PFAS measured in early pregnancy and hypertensive disorders of pregnancy, which may be reflective of the fairly low PFAS levels in our study population.

Effect of Bakri balloon tamponade combined with different suture methods on preventing postpartum hemorrhage in women with pregnancy-induced hypertension undergoing cesarean delivery.

OBJECTIVE: To investigate the effect of Bakri balloon tamponade (BBT) combined with different suture methods on preventing postpartum hemorrhage in women with pregnancy-induced hypertension (PIH) undergoing cesarean delivery (CD). METHODS: This randomized, double-blind, controlled trial was conducted at The First Affiliated Hospital of Xingtai Medical College from October 2020 to June 2023. Patients with PIH who had persistent bleeding after CD and were unresponsive to uterine contractions, sutures, or uterine disconnection procedures were eligible participants. Eligible participants were randomly assigned to control and study groups, with 50 patients in each group. The control group used BBT combined with B-lynch uterine compression sutures, while the study group used BBT combined with modified Hayman suture. Intraoperative and postoperative bleeding and changes in vital signs were compared between the 2 groups. Moreover, changes in inflammation levels, coagulation function, and sex hormone levels were compared between the 2 groups before and after surgery. RESULTS: A total of 122 patients with persistent bleeding after CD were recruited, of whom 22 were excluded (16 cases of uterine contractions and/or local uterine myometrial sutures for hemostasis, 4 cases of preoperative uterine artery embolization, and 2 cases of uterine malformations). The intraoperative blood loss, postoperative blood loss at 2 hours, postoperative blood loss at 24 hours, and decrease in red blood cell and hemoglobin in the study group were significantly lower than those in the control group (P < .05). After surgery, the levels of inflammation, coagulation function, and sex hormone in both groups improved compared to before surgery, and the study group was significantly better than the control group (P < .05). In addition, the incidence of postoperative adverse events in the study group was significantly lower than that in the control group (P < .05). CONCLUSIONS: The hemostatic effect of BBT combined with B-lynch uterine compression sutures is comparable to that of BBT combined with modified Hayman suture for postpartum hemorrhage in pregnant women with PIH undergoing CD, but the latter has less blood loss, attenuated inflammatory response, reduced impact on coagulation function and ovarian function, and a lower incidence of adverse events.

Impact of an Impaired Maternal-Fetal Environment on Death in Children With Congenital Heart Defects Undergoing Surgery in Denmark From 1994 to 2018.

BACKGROUND: Studies show that an impaired maternal-fetal environment (iMFE) increases the mortality risk in children with single-ventricle congenital heart defects (CHDs). We investigated the impact of an iMFE on death in children with various surgically corrected CHDs. METHODS AND RESULTS: In this nationwide register-based study, we examined the association between an iMFE (including preeclampsia, gestational hypertension, gestational diabetes, maternal smoking during pregnancy) and death in a large cohort of children with surgically corrected CHDs in Denmark (1994-2018). Survival analysis was done using Cox regression, adjusted for confounding and mediating covariates. The cohort included 3304 children: 1662 (50.3%) with minor CHD and 1642 (49.7%) with major CHD. Among them, 792 (24%) children were exposed to an iMFE. During the study, there were 290 deaths: 71 (9.3%) in children exposed to an iMFE and 219 (8.7%) in those unexposed. There were no differences in mortality risk between children with CHD exposed to an iMFE and those unexposed (hazard ratio [HR], 1.12 [95% CI, 0.86-1.47]; P=0.4). This was consistent across subgroups, including minor CHD (HR, 0.76 [95% CI, 0.39-1.47]; P=0.4), major CHD (HR, 1.23 [95% CI, 0.92-1.64]; P=0.2), and hypoplastic left heart syndrome/univentricular heart (HR, 1.08 [95% CI, 0.64-1.85]; P=0.8). CONCLUSIONS: Impairment of the maternal-fetal environment did not impact the mortality rate in children with CHD undergoing operation in Denmark from 1994 to 2018. We believe the cause of these discrepant findings to previous studies may be due to differences in the composition of CHD and prenatal maternal health care and health status of the population.

Risk factors for premature rupture of membranes in pregnant women: a systematic review and meta-analysis.

OBJECTIVE: To identify risk factors for premature rupture of membranes (PROM) in pregnant women. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database (VIP) and China Biology Medicine Disc were searched from inception to October 2022. ELIGIBILITY CRITERIA: Cross-sectional, case-control and cohort studies published in English or Chinese that reported the risk factors for PROM were eligible for inclusion. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted the data and evaluated the risk of bias using the Newcastle-Ottawa Scale and American Agency for Healthcare Research and Quality tools. Analyses were performed using RevMan 5.4 software, and heterogeneity was assessed using χ2 tests and I2 statistics. The sensitivity analyses included a methodological transition between fixed-effect and random-effect models and the systematic stepwise exclusion of studies. RESULTS: A total of 21 studies involving 18 174 participants with 18 risk factors were included. The significant risk factors were low Body Mass Index (BMI) (OR 2.18, 95% CI 1.32 to 3.61), interpregnancy interval (IPI) <2 years (OR 2.99, 95% CI 1.98 to 4.50), previous abortion (OR 2.35, 95% CI 1.76 to 3.14), previous preterm birth (OR 5.72, 95% CI 3.44 to 9.50), prior PROM (OR 3.95, 95% CI 2.48 to 6.28), history of caesarean section (OR 3.06, 95% CI 1.72 to 5.43), gestational hypertension (OR 3.84, 95% CI 2.36 to 6.24), gestational diabetes mellitus (GDM) (OR 2.16, 95% CI 1.44 to 3.23), abnormal vaginal discharge (OR 2.17, 95% CI 1.45 to 3.27), reproductive tract infection (OR 2.16, 95% CI 1.70 to 2.75), malpresentation (OR 2.26, 95% CI 1.78 to 2.85) and increased abdominal pressure (OR 1.45, 95% CI 1.07 to 1.97). The sensitivity analysis showed that the pooled estimates were stable. CONCLUSIONS: This meta-analysis indicated that low BMI, IPI <2 years, previous abortion, previous preterm birth, prior PROM, history of caesarean section, gestational hypertension, GDM, abnormal vaginal discharge, reproductive tract infection, malpresentation and increased abdominal pressure might be associated with a greater risk of PROM. Associations between smoking status, short cervical length, fine particulate matter (PM2.5) and PROM require further investigation. PROSPERO REGISTRATION NUMBER: CRD42022381485.

Expression and influence of KATP in umbilical artery smooth muscle cells of patients with hypertensive disorders of pregnancy.

The objective of this study is to investigate the expression and influence of adenosine triphosphate-sensitive potassium channel (KATP) in human umbilical arterial smooth muscle cells (HUASMCs) of patients with hypertensive disorders of pregnancy (HDP). Western blotting was used to detect the protein expression levels of KATP inwardly rectifying potassium channel (Kir)6.1 and sulphonylurea receptor (SUR)2B subunits in HUASMCs from patients with normal parturients (NP), gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE) and chronic hypertension with superimposed preeclampsia (CHSP), respectively. There was no significant difference in the protein expression of Kir6.1 subunit in NP group, GH group, CH group, PE group and CHSP group (P > 0.05). The protein expression of SUR2B subunit was gradually decreased in NP group, GH group, CH group, PE group and CHSP group, with statistically significant difference among the groups (P < 0.05). The altered expression level of KATP SUR2B subunit may be involved in the pathogenesis of HDP. The severity of HDP may be related to the degree of decrease of SUR2B subunit.

Maternal gestational hypertension, smoking and pre-eclampsia are associated with metabolic dysfunction-associated fatty liver disease in overweight offspring.

INTRODUCTION: Due to a steep increase in obesity, metabolic dysfunction-associated fatty liver disease (MAFLD) has also become the most common chronic hepatic condition among children and adolescents. Various maternal and pregnancy-related factors have also been implicated in the development of MAFLD, but human studies remain scarce. MATERIAL AND METHODS: Comprehensive data of 460 overweight or obese children aged 2-16 years were collected and combined with data on selected maternal and pregnancy-related factors for a case-control study. MALFD was defined as alanine aminotransferase >2× upper limit of normal. Children with and without MAFLD were compared regarding to the study variables and multivariable regression analysis was utilized. RESULTS: Median age of the study children was 11.8 (quartiles 9.1-14.2) years; 44% were girls and 17.8% had MAFLD. Children with MAFLD were older (12.7 vs. 11.6 years, p = 0.002), while the groups did not differ age-standardized body mass index (BMI-SDS) or gender. Factors associated with MAFLD in a multivariable model considering also the offspring's present BMI-SDS, sex, and maternal prepregnancy overweight, were child's older age (odds ratio [OR] 1.16, 95% confidence interval [CI]: 1.06-1.28), maternal gestational smoking (OR 2.01, 95% CI: 1.16-3.47), gestational hypertension (OR 3.44, 95% CI: 1.08-11.0) and pre-eclampsia (OR 2.93, 95% CI: 1.15-7.45). There was no significant association between MAFLD and maternal BMI, birth anthropometrics or perinatal complications. CONCLUSIONS: Maternal smoking, gestational hypertension and pre-eclampsia were associated with MAFLD among overweight or obese children. Further prospective studies are needed to verify causal relationships.

Obstetrical and neonatal outcomes in patients with surgically repaired heart disease.

BACKGROUND: Congenital and acquired heart disease complicate 1% to 4% of pregnancies in the United States. Beyond the risks of the underlying maternal congenital heart disease, cardiac surgery and its sequelae, such as surgical scarring resulting in higher rates of arrhythmias and implanted valves altering anticoagulation status, have potential implications that could affect gestation and delivery. OBJECTIVE: This study aimed to investigate whether history of maternal cardiac surgery is associated with adverse obstetrical or neonatal outcomes compared with patients without a history of cardiac disease or surgery, considered "healthy controls." STUDY DESIGN: This is a secondary analysis of retrospective cohort studies performed at a tertiary care facility in the United States comparing obstetrical outcomes in patients with a history of open cardiac surgery who delivered from January 2007 to December 2018 with healthy controls, who delivered from April 2020 to July 2020. There were 74 pregnancies in 61 patients with a history of open cardiac surgery that were compared with pregnancies in healthy controls. Of the 74 pregnancies, 65 were successfully matched based on gestational age to controls at a 1:3 (case-to-control) ratio. The remainder of cases were matched at a 1:2 or 1:1 ratio; therefore, a total of 219 control pregnancies were included in the analysis. Our primary outcome was the incidence of hypertensive disorders of pregnancy, as well as cesarean delivery, in patients with a history of open cardiac surgery compared with healthy controls. Our secondary outcome was the incidence of low-birthweight neonates in patients with a history of open cardiac surgery compared with healthy controls. RESULTS: Patients with a history of cardiac surgery were not more likely to have any hypertensive disorder diagnosed than healthy controls. Patients with a history of cardiac surgery were more likely to have an operative delivery (P<.0001) but equally likely to have a cesarean delivery (P=.528) compared with healthy controls. Birthweight was not statistically different of 2655±808 g in neonates born to patients with a history of cardiac surgery vs 2844±830 g born to healthy controls (P=.092). CONCLUSION: Patients with a history of cardiac surgery may not be at higher risk of hypertensive disorder diagnosis during pregnancy. Similarly, most patients with a history of cardiac surgery are also likely not at higher risk of cesarean delivery or low-birthweight neonates.

Pathologic maternal and neonatal outcomes associated with programmed embryo transfer.

PURPOSE: In this first of two companion papers, we critically review the evidence recently published in the primary literature, which addresses adverse maternal and neonatal pregnancy outcomes associated with programmed embryo transfer cycles. We next consider whether these pathological pregnancy outcomes might be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation. Finally, in the second companion article, we explore potential etiologies and suggest strategies for prevention. METHODS: Comprehensive review of primary literature. RESULTS: The preponderance of retrospective and prospective observational studies suggests that increased risk for hypertensive disorders of pregnancy (HDP) and preeclampsia in assisted reproduction involving autologous embryo transfer is associated with programmed cycles. For autologous frozen embryo transfer (FET) and singleton live births, the risk of developing HDP and preeclampsia, respectively, was less for true or modified natural and stimulated cycles relative to programmed cycles: OR 0.63 [95% CI (0.57-0.070)] and 0.44 [95% CI (0.40-0.50)]. Though data are limited, the classification of preeclampsia associated with programmed autologous FET was predominantly late-onset or term disease. Other adverse pregnancy outcomes associated with autologous FET, especially programmed cycles, included increased prevalence of large for gestational age infants and macrosomia, as well as higher birth weights. In one large registry study, FET was associated with fetal overgrowth of a symmetrical nature. Postterm birth and placenta accreta not associated with prior cesarean section, uterine surgery, or concurrent placenta previa were also associated with autologous FET, particularly programmed cycles. The heightened risk of these pathologic pregnancy outcomes in programmed autologous FET does not appear to be attributable to traditional risk factors, unknown parental factors, embryo culture, culture duration, or cryopreservation, although the latter may contribute a modest degree of increased risk for fetal overgrowth and perhaps HDP and preeclampsia in FET irrespective of the endometrial preparation. CONCLUSIONS: Programmed autologous FET is associated with an increased risk of several, seemingly diverse, pathologic pregnancy outcomes including HDP, preeclampsia, fetal overgrowth, postterm birth, and placenta accreta. Though the greater risk for preeclampsia specifically associated with programmed autologous FET appears to be well established, further research is needed to substantiate the limited data currently available suggesting that the classification of preeclampsia involved is predominately late-onset or term. If substantiated, then this knowledge could provide insight into placental pathogenesis, which has been proposed to differ between early- and late-onset or term preeclampsia (see companion paper for a discussion of potential mechanisms). If a higher prevalence of preeclampsia with severe features as suggested by some studies is corroborated in future investigations, then the danger to maternal and fetal/neonatal health is considerably greater with severe disease, thus increasing the urgency to find preventative measures. Presupposing significant overlap of these diverse pathologic pregnancy outcomes within subjects who conceive by programmed embryo transfer, there may be common etiologies.

The Risk of Hypertension and Diabetes Mellitus According to Offspring's Birthweight in Women With Normal Body Mass Index: A Nationwide Population-Based Study.

BACKGROUND: Maladaptation to vascular, metabolic, and physiological changes during pregnancy can lead to fetal growth disorders. Moreover, adverse outcomes during pregnancy can further increase the risk of cardiovascular and metabolic diseases in mothers. Delivering a large-for-gestational-age (LGA) baby may indicate a pre-existing metabolic dysfunction, whereas delivering a small-for-gestational-age (SGA) baby may indicate a pre-existing vascular dysfunction. This study aims to assess the risk of hypertension (HTN) and diabetes mellitus (DM) in women with normal body mass index (BMI) scores who did not experience gestational DM or hypertensive disorders during pregnancy based on the offspring's birthweight. METHODS: This retrospective nationwide study included women with normal BMI scores who delivered a singleton baby after 37 weeks. Women with a history of DM or HTN before pregnancy and those with gestational DM or hypertensive disorders, were excluded from the study. We compared the risk of future maternal outcomes (HTN and DM) according to the offspring's birthweight. Multivariate analyses were performed to estimate the hazard ratio (HR) for the future risk of HTN or DM. RESULTS: A total of 64,037 women were included in the analysis. Of these, women who delivered very LGA babies (birthweight > 97th percentile) were at a higher risk of developing DM than those who delivered appropriate-for-gestational-age (AGA) babies (adjusted HR = 1.358 [1.068-1.727]), and women who delivered very SGA babies (birthweight < 3rd percentile) were at a higher risk of developing HTN than those who delivered AGA babies (adjusted HR = 1.431 [1.181-1.734]), even after adjusting for age, parity, gestational age at delivery, fetal sex, maternal BMI score, and a history of smoking. CONCLUSION: These findings provide a novel support for the use of the offspring's birthweight as a predictor of future maternal diseases such as HTN and DM.

Impact of adenomyosis on pregnancy outcomes: a retrospective consecutive cohort study.

OBJECTIVE: This retrospective study explored the potential connection between adenomyosis and pregnancy outcomes. PATIENTS AND METHODS: A study included data from a total of 1,208 pregnancies. The adenomyosis group included 334 pregnant women with adenomyosis, and women in the control group (n=874) had uncomplicated pregnancies. Data on pregnancy complications and maternal and neonatal outcomes were compared. RESULTS: The incidence of gestational hypertension, gestational diabetes, and placenta previa was higher in the adenomyosis group compared to the control group (p<0.05). Adenomyosis was linked to a higher risk of postpartum hemorrhage (1,000-1,500 ml) but a lower risk of premature rupture of membranes (PROM) (p<0.05). Diagnosis of adenomyosis correlated with increased incidence of low fetal weight (20.3% vs. 21.3%, p<0.05) and a low APGAR score at 1 min (p<0.05). CONCLUSIONS: Adenomyosis correlated with a higher incidence of gestational hypertension, placenta previa, and gestational diabetes. At the same time, adenomyosis correlated with a significantly lower incidence of PROM compared to uncomplicated pregnancy. There was a significant increase in the incidence of postpartum hemorrhage and a higher risk of low fetal weight and lower APGAR score at 1 min in pregnancies with adenomyosis.

Hematological profiles of newborns of mothers with hypertensive disorders of pregnancy delivered at the University of Gondar comprehensive specialized hospital: a comparative cross-sectional study.

BACKGROUND: Hypertensive disorders in pregnancy can cause prenatal placental perfusion with insufficient blood supply to the fetus, resulting in fetal exposure to hypoxia and leading to disturbance of neonatal hematopoietic stem cells. This study aimed to compare the hematological profiles of newborns from mothers with hypertensive disorders and normotensive delivered at the University of Gondar comprehensive specialized hospital. METHODS: A comparative cross-sectional study was conducted from March to May 2022 among 308 newborns from hypertensive and normotensive mothers in equal proportions. A systematic random sampling technique was used to select study participants. Three milliliters of cord blood were collected to perform a complete blood count by Beckman coulter. The results were presented using tables and graphs. Independent t-test and Mann-Whitney U test were done to compare the hematological profiles of the two groups. P-value < 0.05were considered statistically significant. RESULTS: The majority of hypertensive and normotensive mothers' ages were between 20 and 34 years (83.77% and 90.91%, respectively). The hematocrit levels were significantly higher in neonates of hypertensive mothers than the neonates of normotensive mothers (49.10 ± 5.19% and 46.09 ± 7.63% respectively) (P < 0.001) while neutrophil counts were significantly lower in neonates of hypertensive mothers than the neonates of normotensive mothers (6.62 ± 3.30 and 7.55 ± 3.31 × 103 /ul respectively) (P = 0.007). Also, platelets counts were significantly lower in neonates of hypertensive mothers than neonates of normotensive mothers (221.25 ± 83.56 and 260.24 ± 83.01 × 103/ul respectively) (P < 0.001). The platelet and nucleated red blood cell count showed a statistically significant difference among newborns from mothers with superimposed preeclampsia and gestational hypertension. CONCLUSION: Newborns delivered from hypertensive disorders of pregnancy had low white blood cell parameters, low platelet count and high red blood cell parameters compared to controls. As result, newborns may develop leukopenia, thrombocytopenia and polycythemia, respectively. Therefore, newborns should be monitored for early detection and follow-up of hematological abnormalities before complications occurred.

The association between dyslipidaemia in the first trimester and adverse pregnancy outcomes in pregnant women with subclinical hypothyroidism: a cohort study.

BACKGROUND: Subclinical hypothyroidism (SCH) is linked to dyslipidaemia and adverse pregnancy outcomes. However, the impact of dyslipidaemia on the outcome of pregnancy in SCH is unclear. METHODS: We enrolled 36,256 pregnant women and evaluated their pregnancy outcomes. The following data was gathered during the first trimester (≤ 13+ 6 weeks of gestation): total cholesterol (TC), low-density lipoprotein (LDL-C), triglyceride (TG), high-density lipoprotein (HDL-C), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations. The reference ranges for lipids were estimated to range from the 5th to the 95th percentile. Logistic regression assessed the relationships between dyslipidaemia and adverse pregnancy outcomes, including abortion, preeclampsia/eclampsia, low birth weight, foetal growth restriction, premature rupture of foetal membranes, gestational hypertension, preterm birth, macrosomia and gestational diabetes mellitus (GDM). Additionally, the best thresholds for predicting adverse pregnancy outcomes based on TSH, FT4, and lipid levels were determined using receiver operating characteristic curves. RESULTS: In the first trimester, LDL-C > 3.24 mmol/L, TG > 1.92 mmol/L, HDL-C < 1.06 mmol/L, and TC > 5.39 mmol/L were used to define dyslipidaemia. In this cohort, 952 (3.56%) patients were diagnosed with SCH, and those who had dyslipidaemia in the first trimester had higher incidences of gestational hypertension (6.59% vs. 3.25%), preeclampsia/eclampsia (7.14% vs. 3.12%), GDM (22.53% vs. 13.77%), and low birth weight (4.95% vs. 2.08%) than did those without dyslipidaemia. However, after adjusting for prepregnancy body mass index (pre-BMI), dyslipidaemia was no longer related to these risks. Furthermore, elevated TG dyslipidaemia in SCH patients was connected to an enhanced potential of gestational hypertension (odds ratio [OR]: 2.687, 95% confidence interval [CI]: 1.074 ~ 6.722), and elevated LDL-C dyslipidaemia correlated with increased preeclampsia/eclampsia risk (OR: 3.172, 95% CI: 1.204 ~ 8.355) after accounting for age, smoking status, alcohol use, pre-BMI, and levothyroxine use. Additionally, the combination of TC, TG, LDL-C, pre-BMI, and TSH exhibited enhanced predictive capabilities for gestational hypertension, preeclampsia/eclampsia, and GDM. Values of 0.767, 0.704, and 0.706 were obtained from the area under the curve. CONCLUSIONS: Among pregnant women with SCH, dyslipidaemia in early pregnancy was related to elevated risks of adverse pregnancy consequences. The combined consideration of age, pre-BMI, TSH, and lipid levels in the first trimester could be beneficial for monitoring patients and implementing interventions to reduce adverse pregnancy outcomes.

Plasma trimethylamine N-oxide metabolites in the second trimester predict the risk of hypertensive disorders of pregnancy: a nested case-control study.

The relationship between gut microbiota products trimethylamine oxide (TMAO) and related metabolites including betaine, choline and L-carnitine and hypertensive disorders of pregnancy (HDP) is unclear. In order to examine whether plasma TMAO and related metabolites predict the risk of HDP, a nested case-control study was conducted in Chinese women based on a prospective cohort including 9447 participants. 387 pairs of pregnant women (n = 774) were matched and their plasma TMAO, betaine, choline, and L-carnitine at 16-20 gestational weeks were measured by liquid chromatography-mass spectrometry. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated using the conditional logistic regression, to examine the association between TMAO metabolites and HDP. The findings showed that higher plasma betaine (≥24.94 µmol/L) was associated with a decreased risk of HDP and its subtype gestational hypertension (GH), with adjusted ORs of 0.404 (95% CI: 0.226-0.721) and 0.293 (95% CI: 0.134-0.642), respectively. Higher betaine/choline ratio (>2.64) was associated with a lower risk of HDP and its subtype preeclampsia or chronic hypertension with superimposed preeclampsia (PE/CH-PE), with adjusted ORs of 0.554 (95% CI: 0.354-0.866) and 0.226 (95% CI: 0.080-0.634). Moreover, compared with traditional factors (TFs) model, the TMAO metabolites+ TFs model had a higher predictive ability for PE/CH-PE (all indexes P values < 0.0001). Therefore, it suggests that the detection of plasma betaine and choline in the early second trimester of pregnancy can better assess the risk of HDP.

Genetic Associations of Circulating Cardiovascular Proteins With Gestational Hypertension and Preeclampsia.

Importance: Hypertensive disorders of pregnancy (HDPs), including gestational hypertension and preeclampsia, are important contributors to maternal morbidity and mortality worldwide. In addition, women with HDPs face an elevated long-term risk of cardiovascular disease. Objective: To identify proteins in the circulation associated with HDPs. Design, Setting, and Participants: Two-sample mendelian randomization (MR) tested the associations of genetic instruments for cardiovascular disease-related proteins with gestational hypertension and preeclampsia. In downstream analyses, a systematic review of observational data was conducted to evaluate the identified proteins' dynamics across gestation in hypertensive vs normotensive pregnancies, and phenome-wide MR analyses were performed to identify potential non-HDP-related effects associated with the prioritized proteins. Genetic association data for cardiovascular disease-related proteins were obtained from the Systematic and Combined Analysis of Olink Proteins (SCALLOP) consortium. Genetic association data for the HDPs were obtained from recent European-ancestry genome-wide association study meta-analyses for gestational hypertension and preeclampsia. Study data were analyzed October 2022 to October 2023. Exposures: Genetic instruments for 90 candidate proteins implicated in cardiovascular diseases, constructed using cis-protein quantitative trait loci (cis-pQTLs). Main Outcomes and Measures: Gestational hypertension and preeclampsia. Results: Genetic association data for cardiovascular disease-related proteins were obtained from 21 758 participants from the SCALLOP consortium. Genetic association data for the HDPs were obtained from 393 238 female individuals (8636 cases and 384 602 controls) for gestational hypertension and 606 903 female individuals (16 032 cases and 590 871 controls) for preeclampsia. Seventy-five of 90 proteins (83.3%) had at least 1 valid cis-pQTL. Of those, 10 proteins (13.3%) were significantly associated with HDPs. Four were robust to sensitivity analyses for gestational hypertension (cluster of differentiation 40, eosinophil cationic protein [ECP], galectin 3, N-terminal pro-brain natriuretic peptide [NT-proBNP]), and 2 were robust for preeclampsia (cystatin B, heat shock protein 27 [HSP27]). Consistent with the MR findings, observational data revealed that lower NT-proBNP (0.76- to 0.88-fold difference vs no HDPs) and higher HSP27 (2.40-fold difference vs no HDPs) levels during the first trimester of pregnancy were associated with increased risk of HDPs, as were higher levels of ECP (1.60-fold difference vs no HDPs). Phenome-wide MR analyses identified 37 unique non-HDP-related protein-disease associations, suggesting potential on-target effects associated with interventions lowering HDP risk through the identified proteins. Conclusions and Relevance: Study findings suggest genetic associations of 4 cardiovascular disease-related proteins with gestational hypertension and 2 associated with preeclampsia. Future studies are required to test the efficacy of targeting the corresponding pathways to reduce HDP risk.

Luteal phase support of intramuscular progesterone associated with lower hypertensive disorders of pregnancy as compared to vaginal progesterone: A cohort study.

OBJECTIVE: To compare the hypertensive disorders of pregnancy (HDP) risk between vaginal and intramuscular (IM) progesterone in programmed frozen-thawed embryo transfer (FET) cycles. METHODS: This was a retrospective cohort study at a tertiary hospital, and only women who achieved ongoing pregnancy after programmed FET between January 2018 and June 2022 were included. Women with chronic hypertension before pregnancy or with history of gestational hypertension or pre-eclampsia in previous pregnancies were excluded. All women were divided into IM progesterone or vaginal progesterone groups according to the route of progesterone supplementation. Follow-up information on obstetric complications and neonatal outcomes were obtained by telephonic interviews. The primary outcome was HDP. Association between routes of progesterone supplementation and HDP was assessed by subgroup analysis and multivariable logistic regression. RESULTS: A total of 5891 programmed FET cycles (3196 IM progesterone cycles and 2695 vaginal progesterone cycles) were included in the analysis. The prevalence of HDP in the IM progesterone group was significantly lower than that of the vaginal progesterone group (6.54% vs 9.17%, P < 0.001). Therein, the prevalence of gestational hypertension (3.57% vs 4.94%, P = 0.009) and pre-eclampsia (2.97% vs 4.23%, P = 0.009) in the IM progesterone group were all significantly lower as compared to the vaginal progesterone group. According to subgroup analysis, IM progesterone was associated with lower HDP risk in all subgroups. The logistic regression analysis showed that the IM progesterone cycles were associated with lower risk of HDP compared to vaginal progesterone cycles (adjusted odds ratio 0.66, 95% CI: 0.54-0.80, P < 0.001). CONCLUSION: Among women undergoing programmed FET cycles, progesterone supplementation with IM progesterone was associated with reduced HDP risk compared to vaginal progesterone.

Positive Airway Pressure Treatment of Obstructive Sleep Apnea-Hypopnea in Hypertensive Disorders of Pregnancy: A Pilot Randomized Proof-of-Concept Clinical Trial.

Rationale: Maternal obstructive sleep apnea-hypopnea (OSAH) is associated with hypertensive disorders of pregnancy (HDP). OSAH treatment with positive airway pressure (PAP) in the general population lowers blood pressure (BP). However, there are limited data on the effects of PAP therapy in maternal OSAH. Objectives: Our primary objective was to assess the feasibility of recruitment to a pilot randomized trial and adherence to PAP therapy for OSAH in women with HDP. Secondary objectives included assessment of PAP effects on 24-h BP, arterial stiffness, and maternal and fetal outcomes. Methods: Women with singleton pregnancies at ⩾12 weeks' gestation and hypertension underwent home level 2 polysomnography; those with mild to moderate OSAH (apnea-hypopnea index ⩾ 5 events/h; women with severe OSAH with apnea-hypopnea index > 30 events/h and oxygen desaturation index > 30 were excluded) were randomized to either PAP or nasal dilator strip (NDS; control) therapy. After PAP education, adherence was monitored online with episodic phone or in-person support by research personnel. Twenty-four-hour BP and arterial stiffness were assessed at baseline and before delivery. Maternal and fetal outcomes were also recorded. Results: Of 105 potentially eligible participants, 67 agreed to undergo screening for OSAH over 38 months; 48 women meeting OSAH inclusion criteria were randomized to PAP (n = 27) or NDS (n = 21) therapy. Of these, 14 PAP (52%) and 13 NDS (62%) participants completed all predelivery measurements, with lack of completion due to urgent delivery (19% in the PAP group, 14% in the NDS group), PAP intolerance at initiation (19%), or other factors. Mean PAP use was 3.1 ± 2.5 h/night, with use ⩾4 h/night on 38.4 ± 33.7% of nights during 9.6 ± 4.0 weeks of treatment. BP was controlled within the target range in most participants. There were no differences in mean change in 24-hour BP or arterial stiffness measurements or in adverse maternal and fetal outcomes between the PAP and NDS groups in either intention-to-treat or per-protocol analyses. Conclusions: PAP adherence was suboptimal in this HDP cohort despite education and troubleshooting. Further work is required to identify optimal OSAH treatment strategies during pregnancy. Clinical trial registered with www.clinicaltrials.gov (NCT03309826).

Prepregnancy plant-based diets and risk of hypertensive disorders of pregnancy.

BACKGROUND: Plant-based diets have been associated with a lower risk of cardiovascular disease in nonpregnant adults, but specific evidence for their effects on risk of hypertensive disorders of pregnancy is scarce. OBJECTIVE: This study aimed to evaluate the prospective association between adherence to plant-based diets before pregnancy and the risk for hypertensive disorders of pregnancy. We hypothesized that women with higher adherence to plant-based diets would have a lower risk for hypertensive disorders of pregnancy. STUDY DESIGN: We followed 11,459 parous women (16,780 singleton pregnancies) without chronic diseases, a history of preeclampsia, and cancers who participated in the Nurses' Health Study II (1991-2009), which was a prospective cohort study. Diet was assessed every 4 years using a validated food frequency questionnaire from which we calculated the plant-based diet index (higher score indicates higher adherence) to evaluate the health associations of plant-based diets among participants while accounting for the quality of plant-based foods. Participants self-reported hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension. We estimated the relative risk of hypertensive disorders of pregnancy in relation to plant-based diet index adherence in quintiles using generalized estimating equations log-binomial regression while adjusting for potential confounders and accounting for repeated pregnancies for the same woman. RESULTS: The mean (standard deviation) age at first in-study pregnancy was 35 (4) years. A total of 1033 cases of hypertensive disorders of pregnancy, including 482 cases of preeclampsia (2.9%) and 551 cases of gestational hypertension (3.3%) were reported. Women in the highest quintile of plant-based diet index were significantly associated with a lower risk for hypertensive disorders of pregnancy than women in the lowest quintile (relative risk, 0.76; 95% confidence interval, 0.62-0.93). There was an inverse dose-response relationship between plant-based diet index and risk for hypertensive disorders of pregnancy. The multivariable-adjusted relative risk (95% confidence interval) of hypertensive disorders of pregnancy for women in increasing quintiles of plant-based diet index were 1 (ref), 0.93 (0.78-1.12), 0.86 (0.72-1.03), 0.84 (0.69-1.03), and 0.76 (0.62-0.93) with a significant linear trend across quintiles (P trend=.005). This association was slightly stronger for gestational hypertension (relative risk, 0.77; 95% confidence interval, 0.60-0.99) than for preeclampsia (relative risk, 0.80; 95% confidence interval, 0.61-1.04). Mediation analysis suggested that body mass index evaluation for dietary assessment and pregnancy explained 39% (95% confidence interval, 15%-70%]) of the relation between plant-based diet index and hypertensive disorders of pregnancy and 48% (95% confidence interval, 12%-86%]) of the relation between plant-based diet index and gestational hypertension. CONCLUSION: Higher adherence to plant-based diets was associated with a lower risk of developing hypertensive disorders of pregnancy. Much of the benefit seems to be related to improved weight control.

[Effect of gestational weight gain in a cohort of pregnancy women with obesity operated and not operated for bariatric surgery]. / Efecto de la ganancia ponderal gestacional en una cohorte de gestantes con obesidad operadas y no operadas de cirugía bariátrica.

Introduction: Objective: to determine the effect of gestational weight gain and perinatal outcomes in obese women who underwent and did not undergo bariatric surgery. Material and methods: a retrospective observational cohort study was conducted. The gestational weight gain was classified as insufficient, adequate or excessive according to the guidelines of the United States Institute of Medicine: 4.99-9.07 kg for body mass index (BMI) > 30 kg/m2. Weight gain was calculated as the difference between the weight at the first visit of the 1st trimester and the weight at the visit of the 3rd trimester. Outcomes examined included antepartum variables (gestational diabetes, gestational hypertension, preeclampsia, premature rupture of membranes, placenta previa, placental abruption, intrauterine growth retardation, chorioammionitis, spontaneous abortion), intrapartum variables (induced delivery, vaginal delivery, vacuum, forceps delivery, cesarean section, shoulder dystocia), postpartum variables (postpartum hemorrhage, need for postpartum transfusion, postpartum anemia, need for emergency care, maternal death, postpartum tear, postpartum thrombosis) and neonatal variables (preterm delivery, weight percentile > 90, weight percentile < 10, Apgar score < 7, malformations). Using the statistical package SPSS 22.0, a statistical analysis of the data was performed. Results: two hundred and fifty-six women were recruited; 38 (14.58 %) were pregnant after bariatric surgery and 218 (85.15 %) were pregnant women with obesity who had not been operated on. Of the pregnant women with obesity who had not been operated on, 119 (46.68 %) had grade 1 obesity (BMI 30-34.9), and 99 (38.67 %) had grade 2 and 3 obesity (BMI > 35). A global and subgroup analysis was performed. In the overall analysis, 78 (30.46 %) had insufficient gain, 117 (45.70 %) had adequate gain, and 61 (23.82 %) excessive gain. Overall, insufficient weight gain was associated with a lower probability of gestational hypertension (p < 0.015) and forceps delivery (p < 0.000) and large for gestational age newborn (p < 0.000). On the other hand, insufficient weight gain was associated with a higher probability of intrauterine growth retardation (p 0.044), peripartum infection (0.022), preterm delivery (0.006), and delivery < 35 weeks (p 0.016). Excessive weight gain was associated with a higher probability of gestational hypertension (p 0.025), induced labor (p 0.009), forceps delivery (p 0.011) and large for gestational age newborn (p 0.006). Pregnancies after bariatric surgery had fewer overall complications compared to the other groups. Conclusions: insufficient and excessive weight gain worsens perinatal outcomes. Adequate weight gain does not increase complications and produces some benefits.

Introducción: Objetivo: determinar el efecto de la ganancia de peso gestacional y los resultados perinatales en mujeres con obesidad operadas y no operadas de cirugía bariátrica. Material y métodos: se realizó un estudio retrospectivo observacional de cohortes. La ganancia ponderal gestacional fue clasificada como insuficiente, adecuada o excesiva según las guías del Instituto de Medicina de Estados Unidos: 4,99-9,07 kg para índice de masa corporal (IMC) > 30 kg/m2. La ganancia ponderal se calculó con la diferencia entre el peso de la primera visita del primer trimestre y el peso en la visita del tercer trimestre. Los resultados examinados incluyeron variables anteparto (diabetes gestacional, hipertensión gestacional, preeclampsia, ruptura prematura de membranas, placenta previa, desprendimiento prematuro de placenta, retraso de crecimiento intrauterino, corioamnionitis, aborto espontáneo), intraparto (parto inducido, parto vaginal, ventosa, fórceps, cesárea, distocia de hombros), posparto (hemorragia posparto, necesidad de trasfusión posparto, anemia posparto, necesidad de asistencia a Urgencias, muerte materna, desgarro posparto, trombosis posparto) y neonatales (parto pretérmino, percentil peso > 90, percentil peso < 10, puntuación Apgar < 7, malformaciones). Mediante el paquete estadístico SPSS 22.0 se realizó un análisis estadístico de los datos. Resultados: se reclutaron 256 mujeres; 38 (14,58 %) eran gestantes poscirugía bariátrica y las 218 (85,15 %) restantes eran gestantes con obesidad no operadas. De las gestantes con obesidad no operadas, 119 (46,68 %) tenían obesidad grado 1 (IMC 30-34,9) y 99 (38,67 %) tenían obesidad grados 2 y 3 (IMC > 35). Se realizó un análisis global y por subgrupos. En el análisis global tuvieron ganancia insuficiente 78 (30,46 %), ganancia adecuada 117 (45,70 %) y excesiva 61 (23,82 %). En conjunto, la ganancia ponderal insuficiente se asoció con menor probabilidad de hipertensión arterial (HTA) gestacional (p 0,015) y parto con fórceps (p 0,000) y grande para edad gestacional (p 0,000). Por otro lado, la ganancia ponderal insuficiente se asoció a mayor probabilidad de retraso de crecimiento intrauterino (p 0,044), infección periparto (0,022), parto pretérmino (0,006) y parto < 35 semanas (p 0,016). La ganancia ponderal excesiva se asoció a mayor probabilidad de HTA gestacional (p 0,025), parto inducido (p 0,009), parto por fórceps (p 0,011) y grande para edad gestacional (p 0,006). Las gestaciones poscirugía bariátrica tuvieron menos complicaciones globales respecto al resto de grupos. Conclusiones: la ganancia ponderal insuficiente y excesiva empeora los resultados perinatales. La ganancia ponderal adecuada no aumenta las complicaciones y produce algunos beneficios.

Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis.

BACKGROUND: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored. OBJECTIVES: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP. SEARCH STRATEGY: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023. SELECTION CRITERIA: We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications. DATA COLLECTION AND ANALYSIS: We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology. MAIN RESULTS: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I2 = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I2 = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I2 = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I2 = 0%; low-certainty evidence). CONCLUSIONS: Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.