Causes of stillbirths at Kgapane hospital, Limpopo province.

BACKGROUND:  Stillbirths are a global public health challenge, predominantly affecting low- and middle-income countries. The causes of most stillbirths are preventable. OBJECTIVES:  this study reviewed perinatal clinical audit data from Kgapane Hospital over a 4-year period with a special focus on the factors associated with stillbirths. METHODS:  File audits were done for all stillbirths occurring at Kgapane Hospital and its catchment area from 2018 to 2021. The data from these audits were analysed to identify factors associated with stillbirths. RESULTS:  A total of 392 stillbirths occurred during the study period at Kgapane Hospital and its surrounding clinics, resulting in a stillborn rate of 19.06/1000 births. Of the 392 stillbirths recorded, audits were conducted on 354 of the maternal case records. The five most common causes of stillbirths identified were: hypertensive disorders in pregnancy (HDP) (29.7%), intrauterine growth restriction without HDP (11.6%), birth asphyxia (7.1%), premature labour ( 1000 g) (6.5%) and maternal infections (5.9%) including HIV with unsuppressed VL, intrauterine infection, coronavirus disease (COVID) and syphilis. Modifiable factors that can form the basis of improvement strategies should include training, timeous referral, plus improved resources and staffing. CONCLUSION:  Understanding the causes of stillbirths can guide improvement strategies to reduce this heart-breaking complication of pregnancy.Contribution: Family physicians working in rural hospitals are also responsible for perinatal care. Understanding the factors associated with stillbirths will guide them to develop improvement strategies to reduce these preventable deaths.

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.

[Clinical characteristics of pregnancy complicated with inflammatory bowel disease].

OBJECTIVE: To analyze the clinical characteristics of patients with inflammatory bowel diseases (IBD) in pre-pregnancy, pregancy and loctation. METHODS: The clinical data of pregnancy complicated with IBD in Department of Obstetrics and Gynecology of Peking University Third Hospital and deli-very from September 2011 to June 2022 were collected. The clinical characteristics of the patients were analyzed retrospectively. According to the state of diseases during pre-pregnancy, pregnancy and lactation, the patients were divided into active and remission group, and the two groups were compared interms of pre-pregnancy counseling, nutritional status, pregnancy and delivery complications, gestational week, mode of delivery, and neonatal outcome. RESULTS: A total of 33 pregnant women with IBD were included in this study, of which 7 delivered a second child, for a total of 40 deliveries, with 36 natural pregnancies (90.0%) and 4 assisted reproductions (10.0%). Among the 40 cases, 21 cases (52.5%) were sustained in remission in pre-pregnancy, pregnancy and lactation, and 19 cases (47.5%) in disease activity, of which 8 cases (42.1%) were due to self-withdrawal of drugs or failure to take medicine regularly. Compared with the activity group, the disease remission group had a higher rate of pre-pregnancy counseling (57.1% vs. 15.8%, P=0.010), and higher levels of hemoglobin [(112.67±8.53) g/L vs. (102.84±5.23) g/L, P < 0.001], serum total protein [(66.58±6.34) g/L vs. (60.83±6.25) g/L, P=0.006], serum albumin [36.4 (35.1, 38.3) g/L vs. 34.3 (31.1, 35.6) g/L, P=0.006], serum calcium [(2.25±0.10) µmol/L vs. (2.13±0.15) µmol/L, P=0.004], but a lower incidence of gestational hypertensive disorders (0 vs. 31.6%, P=0.007). In 40 deliveries, there were 27 cases of vaginal delivery (67.5%), 13 cases of cesarean section (32.5%). The analysis of neonatal outcomes showed 38 full-term deliveries and 2 preterm deliveries; 1 case of macrosomia, 1 case of small-for-gestational-age, 1 case of low birth weight and 3 cases of birth defects. There were 10 newborns admitted to neonatal intensive care unit, including 4 cases of neonatal infections and 2 cases of neonatal jaundice. CONCLUSION: Pre-pregnancy counseling and evaluation of IBD patients are very important, and good pregnancy outcomes can be obtained through careful management during pregnancy in the most of the patients.

Early Mortality, Cardiovascular, and Renal Diseases in Women's Lives Following Hypertensive Disorders of Pregnancy: The Prospective Nationwide Study CONCEPTION.

BACKGROUND: We aimed to evaluate the impact of hypertensive disorders of pregnancy occurrence, recurrence, onset time, and severity on mortality and on a wide range of cardiovascular outcomes in France. METHODS AND RESULTS: CONCEPTION (Cohort of Cardiovascular Diseases in Pregnancy) is a French nationwide prospective cohort using data from the National Health Data System. We included all women in CONCEPTION with no history of a cardiovascular event who delivered in France for the first time between 2010 and 2018 (N=2 819 655). Hypertensive disorders of pregnancy and cardiovascular outcomes during the study follow-up were identified using algorithms combining International Classification of Diseases, Tenth Revision (ICD-10) coded diagnoses during hospitalization and purchases of medication between 2010 and 2021. We fitted Cox models with time-varying exposure to assess the associations of hypertensive disorders of pregnancy with mortality and cardiovascular events. Women with gestational hypertension had a 1.25- to 2-fold higher risk of stroke, acute coronary syndrome, peripheral arterial disease, pulmonary embolism, and chronic kidney disease, and a 2- to 4-fold higher risk of rhythm and conduction disorder and heart failure. Women with preeclampsia had a 1.35- to 2-fold higher risk of rhythm or conduction disorder and pulmonary embolism during follow-up; a 2- to 4-fold higher risk of stroke, acute coronary syndrome, and peripheral arterial disease; and a 7- to 9-fold higher risk of heart failure and chronic kidney disease. They were 1.8 times more likely to die and 4.4 times more likely to die of cardiovascular causes. CONCLUSIONS: Hypertensive disorders of pregnancy drastically increase the risk of mortality, cardiovascular, and renal events early after pregnancy. Recurrent, severe, and early-onset preeclampsia further increases this risk.

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.

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.

Association of maternal leukocyte, monocyte, and neutrophil counts with hypertensive disorders of pregnancy: the Japan Environment and Children's Study (JECS).

Hypertensive disorders of pregnancy (HDP) increase the risk of preterm births and cesarean delivery. This study aimed to investigate whether maternal blood leukocyte, monocyte, or neutrophil counts in the first trimester are related to the development of HDP. Data were collected from the Japan Environment and Children's Study, a large birth cohort study (n = 38,194) that recruited pregnant women in 15 Regional Centers across Japan (from January 2011 to March 2014). The odds ratios (ORs) for mild/severe HDP according to the cut-off value of leukocyte/neutrophil/monocyte counts by the receiver operating characteristic curve showed high ORs. Furthermore, pregnant women with the highest quartiles of leukocyte and monocyte counts had higher adjusted ORs (aORs) for mild (leukocyte: aOR = 1.27, 95% confidence interval [CI]: 1.02-1.58; monocyte: aOR = 1.30, 95% CI 1.04-1.63) and severe HDP (leukocyte: aOR = 1.51, 95% CI 1.08-2.13; monocyte: aOR = 1.44, 95% CI 1.03-2.01) compared with those with the lowest quartiles of those counts. In addition, pregnant women with the highest neutrophil counts had higher aOR for mild HDP (aOR = 1.26, 95% CI 1.02-1.56) compared with those with the lowest count. In conclusion, high leukocyte and monocyte counts in the first trimester are associated with the development of HDP. Thus, they may be used to predict subsequent HDP.

The epidemiology of gestational diabetes, gestation hypertension, and anemia in North Palestine from 2018 to 2020: A retrospective study.

BACKGROUND: In Palestine, women face a challenging environment and a demanding lifestyle, which puts them at a higher risk of experiencing complications during pregnancy. This study aimed to examine the risk factors linked with abnormal hemoglobin (Hb) levels, gestational diabetes (GD), and gestational hypertension (GH) among pregnant women. The results was compared between women residing in cities or villages areas and those in refugee camps. METHODS: Medical records (N = 7889) for pregnant women at primary healthcare centers in the North West Bank were reviewed for sociodemographic and medical data along with the reported fasting blood sugar, hemoglobin, and blood pressure in the first and second trimesters from July 2018 to July 2020. However, only 6640 were included in the analysis as 1249 were excluded for having multiple pregnancy or lost to follow up. Complications and risk factors were defined according to the available global guidelines. Then, descriptive analysis was used to show the percentages of different risk factors and complications among them. The correlation between the several characteristics and variables with these complications was assessed by calculating the odds ratios (OR) using logistic regression. P-values of <0.05 were considered significant. RESULTS: The prevalence of adolescent pregnancy was the highest among women living in rural areas (9.8%) and grand multigravidity among refugee women (22%). The overall prevalence of anemia was higher in the second-trimester (16.2%) than in the first-trimester (11.2%), with anemic women in the first-trimester being more likely to be anemic in the second-trimester (OR = 8.223, P-value<0.001). Although anemia was less common in the first-trimester among refugees than among women living in urban areas (OR = 0.768, P-value = 0.006), it was more prevalent in the second-trimester (OR = 1.352, P-value<0.001). Moreover, refugee women were at lower risk than women living in urban areas of having GD (OR = 0.687, P-value<0.001) and diabetes mellitus (OR = 0.472, P-value<0.001) in the second-trimester. GH was associated with GD (OR = 1.401, P-value = 0.003) and DM (OR = 1.966, P-value<0.001). CONCLUSION: The findings of this study provide evidence-based data on the considerable prevalence of pregnancy complications, anemia, GD, and GH among Palestinian pregnant women living in the north of the West Bank. Multi gravida, gestational age, Hb levels, and the type of settings were strong predictors of pregnancy complications. Therefore, a national plan is needed to ensure adequate maternal care for all, especially disadvantaged women, those in rural areas and refugee camps.

Caring for Patients with Gestational Hypertensive Disorders: Essential Takeaways.

Hypertensive disorders in pregnancy (HDP) are a group of conditions-including chronic hypertension, gestational hypertension, preeclampsia with and without end-organ damage, and acute complications, which include HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and eclampsia-that could lead to severely adverse outcomes for both mother and fetus. The incidence of HDP has increased, affecting one out of seven delivery hospitalizations. Physicians should be aware of HDP for early identification and proper treatment to improve patient outcomes.

Hypertensive Disorders of Pregnancy.

According to the American College of Obstetricians and Gynecologists (ACOG), women who have a systolic blood pressure ≥ 140 mm Hg and/or a diastolic pressure ≥ 90 mm Hg before pregnancy or before 20 weeks of gestation have chronic hypertension. Up to 1.5% of women in their childbearing years have a diagnosis of chronic hypertension, and 16% of pregnant women develop hypertension during their pregnancy. Physiological cardiovascular changes from pregnancy may mask or exacerbate hypertensive diseases during gestation, which is why prepregnancy counseling is emphasized for all patients to optimize comorbidities and establish a patient's baseline blood pressure. This review provides an overview of the diagnoses and treatments of hypertensive diseases that can occur in pregnancy, including definitions of key terms and types of hypertension as well as ACOG recommendations.

Co-exposure to phthalates and polycyclic aromatic hydrocarbons and the risk of gestational hypertension in Chinese women.

Phthalates (PAEs) and polycyclic aromatic hydrocarbons (PAHs) are frequently detected in females of reproductive age. Many studies have found that environmental PAE and PAH levels are independent risk factors for gestational hypertension. However, exposure to both components is a more realistic scenario. To better assess the health effects of PAEs and PAHs in pregnant women, we explored the associations of exposure to both individual and combined PAEs and PAHs with gestational hypertension. This nested case-control study was a component of a prospective cohort study conducted in Beijing, China. We included 206 women with gestational hypertension and 214 pregnant controls. We used gas chromatography/tandem mass spectrometry (GC-MS/MS) to detect 8 PAEs and 13 PAHs in > 80 % of all collected hair samples. Multiple linear regression models were employed to test the individual associations between each component and gestational hypertension. A quantile-based g-computation (qgcomp) model and a weighted quantile sum (WQS) regression model were used to estimate whether exposure to both PAEs and PAHs increased the risk of gestational hypertension. The individual exposure analyses revealed that diethyl phthalate (DEP), diisobutyl phthalate (DIBP) (both PAEs), benzo(k)fluoranthene (BKF), anthracene, (ANT), and benzo(a)pyrene (BAP) (all PAHs) were positively associated with increased risk of gestational hypertension. In mixed-effect analyses, the qgcomp model indicated that co-exposure to PAEs and PAHs increased the risk of gestational hypertension (odds ratio = 2.01; 95 % confidence interval: 1.02, 3.94); this finding was verified by the WQS regression model. Our findings support earlier evidence that both PAEs and PAHs increase the risk of gestational hypertension, both individually and in combination. This suggests that reductions in exposure to endocrine system-disrupting chemicals such as PAEs and PAHs might reduce the risk of gestational hypertension.

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.

Vascular health years after a hypertensive disorder of pregnancy: The EPOCH study.

BACKGROUND: Preeclampsia is associated with a two-fold increase in a woman's lifetime risk of developing atherosclerotic cardiovascular disease (ASCVD), but the reasons for this association are uncertain. The objective of this study was to examine the associations between vascular health and a hypertensive disorder of pregnancy among women ≥ 2 years postpartum. METHODS: Pre-menopausal women with a history of either a hypertensive disorder of pregnancy (cases: preeclampsia or gestational hypertension) or a normotensive pregnancy (controls) were enrolled. Participants were assessed for standard ASCVD risk factors and underwent vascular testing, including measurements of blood pressure, endothelial function, and carotid artery ultrasound. The primary outcomes were blood pressure, ASCVD risk, reactive hyperemia index measured by EndoPAT and carotid intima-medial thickness. The secondary outcomes were augmentation index normalized to 75 beats per minute and pulse wave amplitude measured by EndoPAT, and carotid elastic modulus and carotid beta-stiffness measured by carotid ultrasound. RESULTS: Participants had a mean age of 40.7 years and were 5.7 years since their last pregnancy. In bivariate analyses, cases (N = 68) were more likely than controls (N = 71) to have hypertension (18% vs 4%, P = .034), higher calculated ASCVD risk (0.6 vs 0.4, P = .02), higher blood pressures (systolic: 118.5 vs 111.6 mm Hg, P = .0004; diastolic: 75.2 vs 69.8 mm Hg, P = .0004), and higher augmentation index values (7.7 vs 2.3, P = .03). They did not, however, differ significantly in carotid intima-media thickness (0.5 vs 0.5, P = .29) or reactive hyperemia index (2.1 vs 2.1, P = .93), nor in pulse wave amplitude (416 vs 326, P = .11), carotid elastic modulus (445 vs 426, P = .36), or carotid beta stiffness (2.8 vs 2.8, P = .86). CONCLUSION: Women with a prior hypertensive disorder of pregnancy had higher ASCVD risk and blood pressures several years postpartum, but did not have more endothelial dysfunction or subclinical atherosclerosis.

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.

Incident Cardiovascular Disease in Women With Type 1 or Type 2 Diabetes Following a Hypertensive Disorder of Pregnancy.

BACKGROUND: The extent to which a history of hypertensive disorders of pregnancy is associated with incident cardiovascular disease also among women with diabetes is unknown. METHODS: In this nationwide register-based cohort study, parous women aged 18 to 69 years with a first delivery in the Swedish Medical Birth Register, regardless of diabetic status at that time, and a subsequent clinical visit in the Swedish National Diabetes Register were included. Time to first cardiovascular disease event (myocardial infarction, stroke, or heart failure) before age 70 years by hypertensive disorders of pregnancy history was separately analyzed by diabetes type using Cox regression models that included conventional risk factors. RESULTS: In total, 1748 (18.9%) of 9230 women with type 1 and 5904 (10.6%) of 55 773 women with type 2 diabetes had their first delivery complicated by a hypertensive disorder of pregnancy. Median time (25-75th percentile) between first delivery and start of follow-up was 3.3 (1.4-13.0) years for women with type 1 and 29.8 (22.4-35.6) years for women with type 2 diabetes. In modeling, the risk for any cardiovascular disease event among women with a history of hypertensive disorders of pregnancy was generally 10% to 20% higher, with main models estimating hazard ratios to 1.20 (95% CI, 0.99-1.47) for women with type 1 and 1.15 (95% CI, 1.02-1.29) for women with type 2 diabetes. CONCLUSIONS: In women with diabetes, a history of hypertensive disorders of pregnancy was associated with an increased risk of incident cardiovascular disease and should be considered as a risk enhancer.

Heterogeneity in the risk of cardiovascular disease mortality after the hypertensive disorders of pregnancy across mothers' lifetime reproductive history.

BACKGROUND: Prior studies on maternal cardiovascular disease (CVD) mortality and hypertensive disorders of pregnancy (HDP) have focused only on a woman's first birth and have not accounted for successive affected pregnancies. OBJECTIVES: The objective of this study is to identify mothers' risk of CVD mortality considering lifetime reproductive history. METHODS: We used data from the Medical Birth Registry of Norway, the Norwegian Cause of Death Registry, and the Norwegian National Population Register to identify all mothers who gave birth from 1967 to 2020. Our outcome was mothers' CVD death before age 70. The primary exposure was the lifetime history of HDP. The secondary exposure was the order of HDP and gestational age at delivery of pregnancies with HDP. We used Cox regression models to estimate hazard ratio (HR) and 95% confidence interval (CI), adjusting for education, mother's age, and year of last birth. These models were stratified by the lifetime number of births. RESULTS: Among 987,378 mothers, 86,294 had HDP in at least one birth. The highest CVD mortality, relative to mothers without HDP, was among those with a pre-term HDP in their first two births, although this represented 1.0% of mothers with HDP (HR 5.12, 95% CI 2.66, 9.86). Multiparous mothers with term HDP in their first birth only had no increased risk of CVD relative to mothers without HDP (36.9% of all mothers with HDP; HR 1.12, 95% CI 0.95, 1.32). All other mothers with HDP had a 1.5- to 4-fold increased risk of CVD mortality. CONCLUSIONS: This study identified heterogeneity in the risk of CVD mortality among mothers with a history of HDP. A third of these mothers are not at higher risk compared to women without HDP, while some less common patterns of HDP history are associated with severe risk of CVD mortality.

Hypertension in Pregnancy Among Immigrant and Swedish Women: A Cohort Study of All Pregnant Women in Sweden.

BACKGROUND: Little is known about risks of hypertensive disorders of pregnancy in both first- and second-generation immigrant women in Europe and other Western countries; such knowledge may help elucidate the influence of genetic versus social factors on such risks. We aimed to study both first- and second-generation immigrant women for the presence of all types of hypertension (preexisting hypertension, gestational hypertension, preeclampsia, and eclampsia) during pregnancy. METHODS AND RESULTS: A cohort study was conducted using data derived from the Swedish National Birth Register, the National Patient Register, and the Total Population Register. We used Cox regression analysis to compute hazard ratios (HRs) and 99% CIs while adjusting for sociodemographic factors and comorbidities. The first-generation study included a total of 1 084 212 deliveries and 68 311 hypertension cases, and the second-generation study included 989 986 deliveries and 67 505 hypertension cases. The fully adjusted HR (with 99% CI) for hypertension in pregnancy among first-generation immigrant women was 0.69 (0.66-0.72), and among second-generation immigrant women, it was 0.88 (0.86-0.91), compared with Swedish-born women with 2 Swedish-born parents. Women born in Finland or with parent(s) from Finland had higher risks, with fully adjusted HRs (99% CIs) of 1.30 (1.18-1.43) and 1.12 (1.07-1.17), respectively. CONCLUSIONS: Both first- and second-generation immigrant women had overall lower risks of hypertension in pregnancy compared with other Swedish women. However, the risk reduction was less pronounced in second-generation compared with first-generation immigrant women, suggesting that environmental factors in Sweden may have an important influence on risk of hypertension during pregnancy.

Maternal Dietary Patterns During Pregnancy Are Linked to Hypertensive Disorders of Pregnancy Among a Predominantly Low-Income US Hispanic/Latina Pregnancy Cohort.

BACKGROUND: Diet during pregnancy may be a potential intervention for preventing hypertensive disorders of pregnancy that disproportionally burdens Hispanic/Latina women. METHODS AND RESULTS: The MADRES (Maternal And Developmental Risks from Environmental and Social stressors) study (n=451) is a prospective pregnancy cohort of predominantly low-income Hispanic/Latina women in Los Angeles, California, who completed up to 2 staff-administered 24-hour dietary recalls in the third trimester of pregnancy. Hypertensive disorders of pregnancy were abstracted from medical records and based on a physician's diagnosis or systolic or diastolic blood pressure (≥140 or ≥90 mm Hg, respectively) at ≥2 consecutive prenatal visits. Using multivariable logistic regression, we evaluated associations of 2 previously derived dietary patterns in this population (solid fats, refined grains, and cheese and vegetables, oils, and fruit) and the Healthy Eating Index 2015 with (1) gestational hypertension, (2) preeclampsia, and (3) any hypertensive disorder of pregnancy (either gestational hypertension or preeclampsia). In separate models, we additionally tested interactions with prepregnancy body mass index. Comparing highest-to-lowest quartiles, the solid fats, refined grains, and cheese dietary pattern was associated with an increased odds of any hypertensive disorder of pregnancy (odds ratio [OR], 3.99 [95% CI, 1.44-11.0]; Ptrend=0.014) and preeclampsia (OR, 4.10 [95% CI, 1.25-13.5]; Ptrend=0.036), whereas the vegetables, oils, and fruit pattern was associated with reduced odds of preeclampsia (OR, 0.32 [95% CI, 0.10-0.99]; Ptrend=0.041). Among the overweight prepregnancy body mass index category, inverse associations of vegetables, oils, and fruit and Healthy Eating Index 2015 with preeclampsia were more pronounced (both Pinteractions=0.017). Healthy Eating Index 2015 findings were generally nonsignificant. CONCLUSIONS: While the solid fats, refined grains, and cheese diet was strongly associated with preeclampsia during pregnancy, findings suggest the vegetables, oils, and fruit diet may be more relevant than Healthy Eating Index 2015 for preventing preeclampsia among low-income Hispanic/Latina women.

Blood Pressure and Heart Rate Variability and the Impact on Pregnancy Outcomes: A Systematic Review.

BACKGROUND: Long-term (visit-to-visit) blood pressure variability (BPV) and heart rate variability (HRV) outside pregnancy are associated with adverse cardiovascular outcomes. Given the limitations of relying solely on blood pressure level to identify pregnancies at risk, long-term (visit-to-visit) BPV or HRV may provide additional diagnostic/prognostic counsel. To address this, we conducted a systematic review to examine the association between long-term BPV and HRV in pregnancy and adverse maternal and perinatal outcomes. METHODS AND RESULTS: Databases were searched from inception to May 2023 for studies including pregnant women, with sufficient blood pressure or heart rate measurements to calculate any chosen measure of BPV or HRV. Studies were excluded that reported short-term, not long-term, variability. Adjusted odds ratios were extracted. Eight studies (138 949 pregnancies) reporting BPV met our inclusion criteria; no study reported HRV and its association with pregnancy outcomes. BPV appeared to be higher in women with hypertension and preeclampsia specifically, compared with unselected pregnancy cohorts. Greater BPV was associated with significantly more adverse pregnancy outcomes, particularly maternal (gestational hypertension [odds ratio range, 1.40-2.15], severe hypertension [1.40-2.20]), and fetal growth (small-for-gestational-age infants [1.12-1.32] or low birth weight [1.18-1.39]). These associations were independent of mean blood pressure level. In women with hypertension, there were stronger associations with maternal outcomes but no consistent pattern for perinatal outcomes. CONCLUSIONS: Future work should aim to confirm whether BPV could be useful for risk stratification prospectively in pregnancy, and should determine the optimal management path for those women identified at increased risk of adverse outcomes.

The Association of Racism and Discrimination in Disparities of Hypertensive Disorders of Pregnancy in the United States: An Analysis of PRAMS Data.

BACKGROUND: Hypertensive disorders of pregnancy are a leading cause of maternal mortality. Racial disparities in maternal outcomes such as maternal mortality in the United States (US) are well-documented, but the relationship of racism and/or discrimination with one's risk of developing a hypertension during pregnancy (HDP) is not well-studied. METHODS: Data from 17 sites that asked questions regarding experiences with racism and/or discrimination during pregnancy via the Pregnancy Risk Assessment Monitoring System (PRAMS) Phase 8 (2016-2020) was used. Logistic regression models were used compare the potential of stress induced HDP from perceived experiences of racism and/or discrimination versus the effect of systemic racism and/or discrimination (in healthcare settings and generally) on racial disparities in HDP diagnosis. RESULTS: Among 9,907 live births, 18% of participants reported they were diagnosed with hypertension during pregnancy, with non-Hispanic Black individuals having the highest rate (21.8%). Regarding experiences of racism and/or discrimination, 76.4% of participants responded "yes", with all races/ethnicities studied here except non-Hispanic White individuals responding "yes" at rates higher than 89%. Perceived experiences of racism and/or discrimination did not statistically significantly affect one's odds of being diagnosed with HDP (OR = 0.94, CI: 0.74, 1.20). The disparity in odds of having hypertension during pregnancy between Non-Hispanic Black individuals and non-Hispanic White individuals was not statistically significant when perceived experiences of racism and/or discrimination were included in the model. CONCLUSIONS: Experiences of racism and/or discrimination drive racial disparities in hypertensive disorders in pregnancy. PUBLIC HEALTH IMPLICATIONS: It is vital to eliminate racist and discriminatory practices and behaviors to reduce maternal morbidity and mortality.