Hypertensive Disease Of Pregnancy Research Articles

Newborn screen metabolic panels reflect the impact of common disorders of pregnancy.

Hypertensive disorders of pregnancy and maternal diabetes profoundly affect fetal and newborn growth, yet disturbances in intermediate metabolism and relevant mediators of fetal growth alterations remain poorly defined. We sought to determine whether there are distinct newborn screen metabolic patterns among newborns affected by maternal hypertensive disorders or diabetes in utero. A retrospective observational study investigating distinct newborn screen metabolites in conjunction with data linked to birth and hospitalization records in the state of California between 2005 and 2010. A total of 41,333 maternal-infant dyads were included. Infants of diabetic mothers demonstrated associations with short-chain acylcarnitines and free carnitine. Infants born to mothers with preeclampsia with severe features and chronic hypertension with superimposed preeclampsia had alterations in acetylcarnitine, free carnitine, and ornithine levels. These results were further accentuated by size for gestational age designations. Infants of diabetic mothers demonstrate metabolic signs of incomplete beta oxidation and altered lipid metabolism. Infants of mothers with hypertensive disorders of pregnancy carry analyte signals that may reflect oxidative stress via altered nitric oxide signaling. The newborn screen analyte composition is influenced by the presence of these maternal conditions and is further associated with the newborn size designation at birth. Substantial differences in newborn screen analyte profiles were present based on the presence or absence of maternal diabetes or hypertensive disorder of pregnancy and this finding was further influenced by the newborn size designation at birth. The metabolic health of the newborn can be examined using the newborn screen and is heavily impacted by the condition of the mother during pregnancy. Utilizing the newborn screen to identify newborns affected by common conditions of pregnancy may help relate an infant's underlying biological disposition with their clinical phenotype allowing for greater risk stratification and intervention.

Associations of maternal hypertensive disorders during pregnancy with offspring risks of ischemic heart disease and stroke: a Nordic cohort study

Abstract Background A substantial body of evidence suggests that children exposed to maternal hypertensive disorders during pregnancy (HDP) have increased risks of preterm birth, fetal growth restriction and several cardiovascular risk factors (e.g., hypertension, obesity, diabetes) later in life. However, the direct evidence on the link between maternal HDP and the risk of severe cardiovascular diseases such as ischemic heart disease (IHD) and stroke in the offspring is very limited. Objective To investigate the associations between maternal HDP and the risk of IHD and stroke in the offspring. Methods We conducted a population-based cohort study by linking several national registers in Sweden and Finland. Live singleton births from the Swedish Medical Birth Register (1973–2014) and the Finnish Medical Birth Register (1987- 2014) were followed for IHD and stroke until 2014 by the national patient and cause of death registers. We performed Cox regression models to examine the association between maternal HDP and its subtypes, i.e., pre-existing chronic hypertension, gestational hypertension, and preeclampsia, and the risk of IHD, and stroke in the offspring while adjusting for relevant maternal and pregnancy-related confounders. We conducted sibling analyses to control for unmeasured shared familial (genetic and/or environmental) risk factors. Results Among the 5,807,122 singletons included in the study, 218,322 (3.76%) children were born to mothers with HDP. During the up to 41 years of follow-up, 2,340 (0.04%) offspring were diagnosed with IHD and 5,360 (0.09%) were diagnosed with stroke. Offspring exposed to maternal HDP had an increased risk of IHD (adjusted hazard ratio (aHR), 1.29; 95% confidence interval (CI), 1.01–1.63), and stroke (aHR,1.33; 95% CI, 1.14–1.56). Significantly increased rates of stroke were also observed in children exposed to the subtypes of maternal HDP: pre-existing chronic hypertension (aHR, 1.64; 95% CI, 1.03–2.60), gestational hypertension (HR, 1.38; 95% CI, 1.08–1.77), and preeclampsia (HR, 1.26; 95% CI, 1.02–1.55). The associations between maternal HDP and offspring's IHD and stroke were independent of preterm birth and small for gestational age at birth. Maternal HDP remained associated with stroke in the offspring (aHR, 1.94; 95% CI, 1.16–3.22), but not with IHD (aHR, 0.89; 95% CI, 0.47–1.67) in the sibling analyses. Conclusion Children to mothers with HDP have increased rates of IHD and stroke from childhood to young adulthood. While the link between maternal HDP and IHD in the offspring seemed to be attributed to confounding by familial factors, the relation between maternal HDP and stroke persisted even when considering such confounding. Persons born to mothers with HDP may benefit from early screening and prevention efforts to reduce the risk of IHD and stroke later in life. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Heart and Lung Foundation

First- and Third-Trimester Urinary Phthalate Metabolites in the Development of Hypertensive Diseases of Pregnancy.

The purpose of this study was to determine whether maternal urinary phthalate metabolite concentrations are associated with the development of higher blood pressure or pregnancy-induced hypertension (PIH). Participants were women without chronic hypertension who enrolled in The Infant Development and the Environment Study, a prospective pregnancy cohort conducted at four U.S. academic medical centers from 2010–2012. Prenatal records were reviewed to obtain blood pressure measurements and diagnoses of PIH (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome, defined as hemolysis, elevated liver enzymes, and low platelet count). Complete-case analyses used multivariable linear and logistic regression for analysis of blood pressure measurements and PIH diagnoses, respectively. In the final dataset (N = 668), higher concentrations of first-trimester monoethyl phthalate (MEP) and mono-3-carboxypropyl phthalate (MCPP) and third-trimester mono-isobutyl phthalate (MiBP) were significantly associated with a medical chart diagnosis of PIH. First-trimester mono-n-butyl phthalate (MBP) and MEP along with the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) were each associated with increased systolic blood pressure across pregnancy. In conclusion, several phthalate metabolite concentrations were significantly associated with PIH and greater increases in systolic blood pressure across pregnancy.

Complement Genetic Variants and Hypertensive Diseases of Pregnancy

Complement Genetic Variants and Hypertensive Diseases of Pregnancy

Maternal Hypertension and Hypertensive Disorders of Pregnancy Are Associated with Increased Risk of Hypertension in Offspring

Maternal Hypertension and Hypertensive Disorders of Pregnancy Are Associated with Increased Risk of Hypertension in Offspring

Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study.

The prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades. Exposure to adverse intrauterine environment in fetal life may contribute to the elevated risk of early-onset CVD. Many studies have shown that maternal hypertensive disorders of pregnancy (HDP) are associated with increased risks of congenital heart disease, high blood pressure, increased BMI, and systemic vascular dysfunction in offspring. However, empirical evidence on the association between prenatal exposure to maternal HDP and early-onset CVD in childhood and adolescence remains limited. We conducted a population-based cohort study using Danish national health registers, including 2,491,340 individuals born in Denmark from 1977 to 2018. Follow-up started at birth and ended at the first diagnosis of CVD, emigration, death, or 31 December 2018, whichever came first. Exposure of maternal HDP was categorized as preeclampsia or eclampsia (n = 68,387), gestational hypertension (n = 18,603), and pregestational hypertension (n = 15,062). Outcome was the diagnosis of early-onset CVD from birth to young adulthood (up to 40 years old). We performed Cox proportional hazards regression to evaluate the associations and whether the association differed by maternal history of CVD or diabetes before childbirth. We further assessed the association by timing of onset and severity of preeclampsia. The median follow-up time was 18.37 years, and 51.3% of the participants were males. A total of 4,532 offspring in the exposed group (2.47 per 1,000 person-years) and 94,457 in the unexposed group (2.03 per 1,000 person-years) were diagnosed with CVD. We found that exposure to maternal HDP was associated with an increased risk of early-onset CVD (hazard ratio [HR]: 1.23; 95% CI = 1.19 to 1.26; P < 0.001). The HRs for preeclampsia or eclampsia, gestational hypertension, and pregestational hypertension were 1.22 (95% CI, 1.18 to 1.26; P < 0.001), 1.25 (95% CI, 1.17 to 1.34; P < 0.001), and 1.28 (95% CI, 1.15 to 1.42; P < 0.001), respectively. We also observed increased risks for type-specific CVDs, in particular for hypertensive disease (HR, 2.11; 95% CI, 1.96 to 2.27; P < 0.001) and myocardial infarction (HR, 1.49; 95% CI, 1.12 to 1.98; P = 0.007). Strong associations were found among offspring of mothers with CVD history (HR, 1.67; 95% CI, 1.41 to 1.98; P < 0.001) or comorbid diabetes (HR, 1.56; 95% CI, 1.34 to 1.83; P < 0.001). When considering timing of onset and severity of preeclampsia on offspring CVD, the strongest association was observed for early-onset and severe preeclampsia (HR, 1.48, 95% CI, 1.30 to 1.67; P < 0.001). Study limitations include the lack of information on certain potential confounders (including smoking, physical activity, and alcohol consumption) and limited generalizability in other countries with varying disparities in healthcare. Offspring born to mothers with HDP, especially mothers with CVD or diabetes history, were at increased risks of overall and certain type-specific early-onset CVDs in their first decades of life. Further research is warranted to better understand the mechanisms underlying the relationship between maternal HDP and early-onset CVD in offspring.

Hypertensive Diseases in Pregnancy and Kidney Function Later in Life: The Genetic Epidemiology Network of Arteriopathy (GENOA) Study

ObjectiveTo evaluate the relationship between hypertensive diseases in pregnancy and kidney function later in life. MethodsWe evaluated measured glomerular filtration rate (mGFR) using iothalamate urinary clearance in 725 women of the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Women were classified by self-report as nulliparous (n=62), a history of normotensive pregnancies (n=544), a history of hypertensive pregnancies (n=102), or a history of pre-eclampsia (n=17). We compared adjusted associations among these four groups with mGFR using generalized estimating equations to account for familial clustering. Chronic kidney disease (CKD) was defined as mGFR of less than 60 mL/min per 1.73 m2 or urinary albumin-creatinine ratio (UACR) greater than or equal to 30 mg/g. ResultsAmong women with kidney function measurements (mean age, 59±9 years, 52.9% African American), those with a history of hypertensive pregnancy had lower mGFR (–4.66 ml/min per 1.73 m2; 95% CI, -9.12 to -0.20) compared with women with a history of normotensive pregnancies. Compared with women with a history of normotensive pregnancies, women with a history of hypertensive pregnancy also had higher odds of mGFR less than 60 ml/min per 1.73 m2 (odds ratio, 2.09; 95% CI, 1.21 to 3.60). Additionally, women with a history of hypertensive pregnancy had greater odds for chronic kidney disease (odds ratio, 4.89; 95% CI, 1.55 to 15.44), after adjusting for age, race, education, smoking history, hypertension, body mass index, and diabetes. ConclusionA history of hypertension in pregnancy is an important prognostic risk factor for kidney disease. To our knowledge, this is the first and largest investigation showing the association between hypertensive diseases in pregnancy and subsequent kidney disease using mGFR in a large biracial cohort.

Incidence and disability-adjusted life years of maternal disorders at the global, regional, and national levels from 2007 to 2017: A systematic analysis for the Global Burden of Disease Study 2017.

To report the global burden of maternal disorders and their main subcategories in 195 countries and territories between 2007 and 2017. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimated maternal disease burden at global, regional, and country levels. Maternal disorders were disaggregated into 10 categories, and estimated incidence and disability-adjusted life years (DALYs) of maternal disorders were reported separately. Indicators were estimated in different geographic settings and different sociodemographic index (SDI) regions. Based on GBD 2017 estimates, we systematically examined the incidence and DALYs of maternal disorders and their main subcategories at the global, regional, and national levels during the period from 2007 to 2017 by age and SDI. Globally, a total of 7.98million maternal disorders occurred in 2017, with a 4.33% (95% uncertainty interval [UI] 3.24%-5.60%) decrease in age-standardized incidence rate and a more significant decrease (30.26%) in the age-standardized rate of DALYs. Most incidences and DALYs were found in low-income and middle-income countries, especially in the sub-Saharan region. The greatest incidence of maternal disorders was found to be in maternal abortion and miscarriage (2.00million), and the highest disease burden was in maternal hemorrhage (2.23million). A slight increase in the incidence of maternal disorders and substantial reductions in DALYs of overall maternal disorders and their main subcategories were found from 2007 to 2017, especially in low-income countries and the sub-Saharan region. Maternal hemorrhage, hypertensive disorders, and indirect maternal death were the top three causes of maternal disorders disease burden.

Vascular emergencies in pregnant patients : Peripartum hemorrhage, thromboembolic events and hypertensive diseases in pregnancy

In developed countries, peripartum hemorrhage, thromboembolic events and hypertensive pregnancy disorders are the most frequent complications in pregnancy. They pose asignificant challenge for the interdisciplinary team of gynecology and anesthesiology. Untreated, these pregnancy-related complications result in a fulminant course. Close consultation between the specialist departments and knowledge of the area of responsibility are essential. In the case of acute bleeding the anesthesiologist is responsible for maintaining adequate circulatory conditions and management of hemostasis. Thromboembolic events require immediate anticoagulation and focused diagnostics. Thereby, both the fetal and the maternal risks must be weighed up. The hypertensive diseases in pregnancy have avery high risk of complications. In addition to symptomatic treatment in the intensive care unit, the optimal time of delivery must be determined by an interdisciplinary consensus. This is the only causal treatment option possible.

Perinatal Outcomes Among Patients With Sepsis During Pregnancy

Rates of maternal sepsis are increasing, and prior studies of maternal sepsis have focused on immediate maternal morbidity and mortality associated with sepsis during delivery admission. There are no data on pregnancy outcomes among individuals who recover from their infections prior to delivery. To describe perinatal outcomes among patients with antepartum sepsis who did not deliver during their infection hospitalization. This retrospective cohort study was conducted using data from August 1, 2012, to August 1, 2018, at an academic referral center in San Francisco, California. Included patients were all individuals with nonanomalous, singleton pregnancies who delivered after 20 weeks' gestation during the study period. Data were analyzed from March 2020 through March 2021. Antepartum admission for infection with clinical concern for sepsis and hospital discharge prior to delivery. The primary outcome was a composite of perinatal outcomes associated with placental dysfunction and consisted of 1 or more of the following: fetal growth restriction, oligohydramnios, hypertensive disease of pregnancy, cesarean delivery for fetal indication, child who is small for gestational age, or stillbirth. Among 14 565 patients with nonanomalous singleton pregnancies (mean [SD] age at delivery, 33.1 [5.2] years), 59 individuals (0.4%) were in the sepsis group and 14 506 individuals (99.6%) were in the nonsepsis group; 8533 individuals (59.0%) were nulliparous. Patients with sepsis, compared with patients in the reference group, were younger (mean [SD] age at delivery, 30.6 [5.7] years vs 33.1 [5.2] years; P < .001), were more likely to have pregestational diabetes (5 individuals [8.5%] vs 233 individuals [1.6%]; P = .003), and had higher mean (SD) pregestational body mass index scores (26.1 [6.1] vs 24.4 [5.9]; P = .03). In the sepsis group, the most common infections were urinary tract infections (24 patients [40.7%]) and pulmonary infections (22 patients [37.3%]). Among patients with sepsis, 5 individuals (8.5%) were admitted to the intensive care unit, the mean (SD) gestational age at infection was 24.6 (9.0) weeks, and the median (interquartile range) time from infection to delivery was 82 (42-147) days. Antepartum sepsis was associated with higher odds of placental dysfunction (21 patients [35.6%] vs 3450 patients [23.8%]; odds ratio, 1.77; 95% CI, 1.04-3.02; P = .04). On multivariable logistic regression analysis, antepartum sepsis was an independent factor associated with placental dysfunction (adjusted odds ratio, 1.88; 95% CI, 1.10-3.23; P = .02) after adjusting for possible confounders. This study found that pregnancies complicated by antepartum sepsis were associated with higher odds of placental dysfunction. These findings suggest that increased antenatal surveillance should be considered for these patients.

Intrauterine Growth Restriction Causes Abnormal Embryonic Dentate Gyrus Neurogenesis in Mouse Offspring That Leads to Adult Learning and Memory Deficits.

Human infants who suffer from intrauterine growth restriction (IUGR), which is a failure to attain their genetically predetermined weight, are at increased risk for postnatal learning and memory deficits. Hippocampal dentate gyrus (DG) granule neurons play an important role in memory formation; however, it is unknown whether IUGR affects embryonic DG neurogenesis, which could provide a potential mechanism underlying abnormal postnatal learning and memory function. Using a mouse model of the most common cause of IUGR, induced by hypertensive disease of pregnancy, we first assessed adult learning and memory function. We quantified the percentages of embryonic hippocampal DG neural stem cells (NSCs) and progenitor cells and developing glutamatergic granule neurons, as well as hippocampal volumes and neuron cell count and morphology 18 and 40 d after delivery. We characterized the differential embryonic hippocampal transcriptomic pathways between appropriately grown and IUGR mouse offspring. We found that IUGR offspring of both sexes had short-term adult learning and memory deficits. Prenatally, we found that IUGR caused accelerated embryonic DG neurogenesis and Sox2+ neural stem cell depletion. IUGR mice were marked by decreased hippocampal volumes and decreased doublecortin+ neuronal progenitors with increased mean dendritic lengths at postnatal day 18. Consistent with its known molecular role in embryonic DG neurogenesis, we also found evidence for decreased Wnt pathway activity during IUGR. In conclusion, we have discovered that postnatal memory deficits are associated with accelerated NSC differentiation and maturation into glutamatergic granule neurons following IUGR, a phenotype that could be explained by decreased embryonic Wnt signaling.

Abstract 30: Role For Adverse Childhood Experiences And Depression In Preeclampsia

Hypertensive diseases are associated with adverse experiences in childhood as well as depression. In order to determine if these associations were present in women with preeclampsia (PreE), a particularly devastating hypertensive disease in pregnancy, the scores from three questionnaires: Adverse Childhood Experiences (ACE), Edinburgh Postnatal Depression Scale (EPDS), and the Patient Health Questionnaire-9 (PHQ-9) were compared between women with PreE (n=32) and women without PreE (n=46) between 9 and 48 months postpartum (IRB# 201808705). ACE scores are calculated by summing an individual’s affirmative responses to specific adverse experiences during childhood. In our study, the average ACE score of individuals with PreE was higher than that of women without PreE (1.69 vs. 1.02, P=.04). We also divided women into groups based on whether their ACE score was ≤3 or ≥4 due to evidence that individuals who have experienced ≥4 ACEs are at greatest risk for physical and mental health conditions. Among our participants, 80% of women with an ACE score ≥4 (n=10) had PreE while only 35.3% of women with a score ≤3 (n=68) developed the condition (P=0.01). As well, the odds of having PreE were higher in those with ACE scores ≥4, compared with those with scores ≤3 (OR= 7.34; 95% CI = 1.44, 37.33). In a subset of participants, scores were available from EPDS, survey that identifies women who have postpartum depression 6 weeks after birth, and from the PHQ-9, another assessment for depression. Among our participants, the average EPDS score was higher in women with PreE than women without PreE (6.38, n=21 vs. 3.71, n=42 P=0.01), indicating more severe symptoms of postpartum depression in women who also had PreE. In addition, the average PHQ-9 score among women with PreE was higher than that of women without PreE (3.71, n=15 vs 1.86, n=37 P=.02) with a higher score indicating more severe depression. The average PHQ-9 score was also higher in women who had ACE scores ≥4 than women with scores ≤3 (4.00, n=4 vs. 2.27, n=48 P=.01) indicating that women with more adverse childhood events were more likely to experience depression. Together, these findings indicate that PreE may be associated with adverse events during childhood as well as depression in late pregnancy and/or postpartum.

Association between low fetal fraction in cell-free DNA testing and adverse pregnancy outcome: A systematic review.

ObjectiveLow fetal fraction (LFF) in prenatal cell‐free DNA (cfDNA) testing is an important cause of test failure and no‐call results. LFF might reflect early abnormal placentation and therefore be associated with adverse pregnancy outcome. Here, we review the available literature on the relationship between LFF in cfDNA testing and adverse pregnancy outcome.MethodA systematic literature search was conducted in MEDLINE and EMBASE up to November 1, 2020.ResultsFive studies met the criteria for inclusion; all were retrospective observational cohort studies. The cohort sizes ranged from 370 to 6375 pregnancies, with all tests performed in the first trimester or early second trimester. A 4% cutoff for LFF was used in two studies, two studies used the 5th and 25th percentiles, respectively, and one study used a variety of cutoff values for LFF. LFF in prenatal cfDNA testing was observed to be associated with hypertensive disease of pregnancy, small for gestational age neonates, and preterm birth. Conflicting results were found regarding the association between LFF and gestational diabetes mellitus.ConclusionsLFF in cfDNA testing is associated with adverse pregnancy outcome,specifically pregnancy‐related hypertensive disorders, preterm birth, and impaired fetal growth related to placental dysfunction. Since the available evidence is limited, a large prospective cohort study on the relationship between fetal fraction and pregnancy outcomes is needed.

Delivery risks and outcomes associated with grand multiparity

Background There is limited recent US national data on risk for adverse outcomes associated with grand multiparity. Objective To examine the association between grand multiparity and severe maternal morbidity (SMM) and other adverse outcomes during delivery hospitalizations in the United States. Methods This repeat cross-sectional study evaluated delivery hospitalizations from 2000 through the third quarter of 2015 to women aged 15–54 in the National (Nationwide) Inpatient Sample database. Temporal trends in deliveries to women with grand multiparity were analyzed using the Cochran–Armitage trend test. The primary outcome studied was SMM, a composite of adverse outcomes defined by the Centers for Disease Control and Prevention. The exposure of interest was grand multiparity diagnosis during delivery hospitalization. Other adverse outcomes analyzed included placental abruption, preterm delivery, postpartum hemorrhage, disseminated intravascular coagulation, shock, hysterectomy, pulmonary edema and acute heart failure, transfusion of blood or blood products, hypertensive diseases of pregnancy, cesarean delivery, eclampsia, and acute renal failure. Log linear regression models were performed to determine the relationship between grand multiparity and adverse outcomes with measures of association demonstrated as unadjusted (RR) and adjusted risk ratios (aRR) with 95%CIs. Results From 2000 to 2015, there were an estimated 62,672,862 hospital deliveries with 386,019 deliveries in the setting of grand multiparity. The number of deliveries with a grand multiparity diagnosis increased over the study period from 4.2 per 1000 deliveries in 2000 to 8.6 per 1000 in 2015 (p < .01). Women with grand multiparity were more likely to be older, have comorbidities, be Hispanic or non-Hispanic Black, be from a lower ZIP code income quartile, have Medicaid insurance, and present to an urban teaching hospital for delivery (p < .01 for all). On univariable analysis, grand multiparity was associated with SMM (RR 1.27, 95%CI 1.23–1.32). However, in adjusted analyses accounting for hospital, clinical, and demographic factors, women with grand multiparity were at lower risk of SMM (aRR 0.93, 95%CI 0.89, 0.96). On analysis of individual adverse outcomes, grand multiparity was associated with a higher risk of placental abruption (RR 1.28, 95%CI 1.24–1.31), preterm delivery (RR 1.17, 95%CI 1.16–1.18), postpartum hemorrhage (RR 1.30, 95%CI 1.28–1.32), disseminated intravascular coagulation (RR 1.23, 95%CI 1.16–1.31), shock (RR 2.50, 95%CI 2.20–2.85), hysterectomy (RR 3.20, 95%CI 3.30, 3.41), pulmonary edema and acute heart failure (RR 1.33, 95%CI 1.24–1.42), and transfusion of blood or blood products (RR 1.74, 95%CI 1.70–1.79). Conversely, grand multiparity was associated with a lower risk of hypertensive diseases of pregnancy (RR 0.85, 95%CI 0.84–0.86), cesarean delivery (RR 0.96, 95%CI 0.95–0.96), and eclampsia (RR 0.69, 95%CI 0.60–0.79). There was no significant association between grand multiparity and acute renal failure. Conclusions Delivery hospitalizations with a grand multiparity diagnosis were not associated with increased risk for SMM in adjusted analysis. Grand multiparity was associated with increased risk for hysterectomy and shock although absolute increased risk for these complications was small.

Association between maternal hypertensive disorders, fetal growth and childhood learning outcomes.

Both small for gestational age (SGA) birthweight and pregnancies complicated by maternal hypertension (HTN) are independently associated with poorer childhood learning outcomes, however the relative contribution of each remains unknown. A retrospective cohort was created in which 2014-2017 third grade Rhode Island Department of Education data were linked to Rhode Island Department of Health birth certificate data. The study population was composed of non-anomalous, singleton births between 22- and 42-weeks' gestation. Reading and math proficiency were compared among four groups: 1) appropriate for gestational age (AGA) and no maternal HTN (referent), 2) AGA with HTN, 3) SGA without HTN and 4) SGA with HTN. Bivariable and multivariable log-binomial regression were used to examine the association between subject proficiency and pregnancy complication, adjusting for potential confounders. Of the 23,097 who met inclusion criteria, 1004 (4%) were AGA with HTN, 1575 (7%) were SGA without HTN and 176 (1%) were SGA with HTN. Overall, when adjusted for maternal age, gestational age, sex and socioeconomic factors, only children born SGA without HTN had reduced reading proficiency (relative risk (RR) 0.86 95% confidence interval (CI) 0.78, 0.92) and math proficiency (RR 0.88 95% CI 0.82, 0.94) compared to children born AGA without HTN. In a diverse, statewide cohort, only SGA without HTN was associated with lower reading and math proficiency compared to uncomplicated pregnancies. This suggests that only decreased fetal growth from causes other than HTN is associated with risk of poorer school-age outcomes, and has implications for early resource allocation.

Impact of maternal hypertensive disorders of pregnancy on brain volumes at term-equivalent age in preterm infants: A voxel-based morphometry study.

Infants born to mothers with hypertensive disorders of pregnancy (HDP) reportedly have negative behavioral and neurodevelopmental outcomes. However, the effects of maternal HDP on infant brain growth have not been fully evaluated. We aimed to evaluate brain volumes and brain injury in preterm infants born to mothers with HDP using magnetic resonance (MR) imaging at term-equivalent age. In this cohort study, MR imaging was performed for 94 preterm infants born before 34weeks of gestation at Nagoya University Hospital between 2010 and 2018. Twenty infants were born to mothers with HDP and 74 to mothers without HDP. Total brain volumes and regional volumetric alterations were assessed by voxel-based morphometry, and brain injury was evaluated using the Kidokoro global brain abnormality score. Developmental quotient was assessed at a corrected age of 1.5years in 59 infants (HDP, n=11; non-HDP, n=48). No significant differences were observed in the gray and white matter volumes of the two groups (HDP: 175±24mL, 137±13mL, respectively; non-HDP: 172±24mL, 142±13mL, respectively). Additionally, no regional volumetric alterations were observed between the two groups after covariate adjustment (gestational age and infant sex). The total Kidokoro score and developmental quotient were similar in both groups. No significant differences in the global and regional brain volumes were observed. Further research is needed to confirm our findings at different time points of MR imaging and in different populations.

Clinical Practice Patterns of Hypertensive Disease in Pregnancy among Korean Obstetricians

Purpose: The purpose of this study was to investigate the clinical practice patterns of Korean obstetricians and gynecologists the diagnosis and management of hypertensive disease in pregnant women. Methods: From April 2015 to October 2015, questionnaire was distributed via email to obstetricians who were members of the Society for Maternal and Fetal Medicine. The survey consisted of 37 questions in 6 categories. Responses to the questions on the management of hypertensive disorders of pregnancy, from diagnosis to treatment, were evaluated. Results: A total of 93 obstetricians and gynecologists responded to the survey. High blood pressure was allocated the highest priority as an index mainly used when deciding to hospitalize patients with hypertensive disease during pregnancy, followed by pregnancy symptoms, proteinuria, and blood test results. Calcium channel blocker (CCB) for oral administration and hydralazine for injection were preferred as antihypertensive drugs mainly used to control severe hypertension. Regarding the delivery method for hypertensive disease during pregnancy, in cases of preeclampsia, 63% of the respondents chose the delivery method according to the cervical status, and in cases of hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and eclampsia, which increased in severity, 52% and 31% responded that the delivery method was determined according to the cervical status, respectively. In cases of mild preeclampsia, the 70% of respondents preferred 37–38 weeks of gestation for the delivery time. Regarding the use of aspirin in patient with hypertension during pregnancy, 52% of the respondents occasionally administered aspirin, and in patients with a history of hypertensive disease during pregnancy, only 43% were administered prophylactic aspirin. Conclusion: Domestic obstetricians regarded blood pressure as the most meaningful factor when treating women with hypertension during pregnancy and considered blood pressure control as important. The preferred antihypertensive agents were oral CCB and hydralazine injections, and the choice of delivery method was determined according to the condition of the cervix and severity of the disease. Even in women with high risk factors for preeclampsia, prophylactic aspirin was administered in as low as 50%, of patients, possibly may due to the absence of domestic guidelines for aspirin use during pregnancy. Korean guidelines for prophylactic aspirin administration during pregnancy is needed based on additional research on the efficacy of aspirin for domestic women in the future.

Oral Misoprostol alone versus oral misoprostol followed by oxytocin for labour induction in women with hypertension in pregnancy (MOLI): protocol for a randomised controlled trial

BackgroundEvery year approximately 30,000 women die from hypertensive disease in pregnancy. Magnesium sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. Low dose oral misoprostol, a prostaglandin E1 analogue, is a highly effective method for labour induction. Usually, once active labour has commenced, the misoprostol is replaced with an intravenous oxytocin infusion if ongoing stimulation is required. However, some studies have shown that oral misoprostol can be continued into active labour, a simpler and potentially more acceptable protocol for women. To date, these two protocols have never been directly compared.MethodsThis pragmatic, open-label, randomised trial will compare a misoprostol alone labour induction protocol with the standard misoprostol plus oxytocin protocol in three Indian hospitals. The study will recruit 520 pregnant women being induced for hypertensive disease in pregnancy and requiring augmentation after membrane rupture. Participants will be randomised to receive either further oral misoprostol 25mcg every 2 h, or titrated intravenous oxytocin. The primary outcome will be caesarean birth. Secondary outcomes will assess the efficacy of the induction process, maternal and fetal/neonatal complications and patient acceptability. This protocol (version 1.04) adheres to the SPIRIT checklist. A cost-effectiveness analysis, situational analysis and formal qualitative assessment of women’s experience are also planned.DiscussionAvoiding oxytocin and continuing low dose misoprostol into active labour may have a number of benefits for both women and the health care system. Misoprostol is heat stable, oral medication and thus easy to store, transport and administer; qualities particularly desirable in low resource settings. An oral medication protocol requires less equipment (e.g. electronic infusion pumps) and may free up health care providers to assist with other aspects of the woman’s care. The simplicity of the protocol may also help to reduce human errors associated with the delivery of intravenous infusions. Finally, women may prefer to be mobile during labour and not restricted by an intravenous infusion. There is a need, therefore, to assess whether augmentation using oral misoprostol is superior clinically and economically to the standard protocol of intravenous oxytocin.Trial registrationClinical Trials.gov, NCT03749902, registered on 21st Nov 2018.

Out-of-Hours Delivery and Pregnancy Outcomes Among Low-Risk Parturients in a Hospital Without Advanced Fetal Surveillance Technology

Purpose: The effect of out-of-hours delivery on obstetric and perinatal outcomes in centres without advanced fetal surveillance has not been fully explored. Methods: Pregnancy, labour, and neonatal outcomes were compared for women who delivered ‘out-of-hours’ (00:00 – 07:59 hours) or at other times/‘within-hours’ (08:00 – 23:59 hours). Results: Twenty-nine percent of the women studied had out-of-hours’ deliveries. Women who had reduced perception of fetal movements had more babies out-of-hours. Hypertensive disease in pregnancy and occurrence of at least one adverse obstetric outcome were associated with lower odds of out-of-hours’ birth. The mean duration of labour augmentation (minutes) was significantly longer in women who had out-of-hours’ delivery (p = 0.032). Vaginal birth (p < 0.001), fifth-minute APGAR scores at least 7 (p = 0.038), and augmentation of labour (p = 0.041) occurred commonly out-of-hours. Conclusion: There was no evidence of poorer outcomes with out-of-hours’ births despite the absence of advanced fetal surveillance technology.

Trial of Labor After Cesarean of Small for Gestational Age Neonates Among Women with No Prior Vaginal Delivery - a Retrospective Study.

To evaluate the characteristics and outcomes of women who had never delivered vaginally and underwent a trial of labor after cesarean (TOLAC) of small for gestational age (SGA) neonates, and to identify risk factors for unplanned repeat cesarean delivery. A retrospective cohort study from two tertiary medical centers. All women undergoing a TOLAC with no prior vaginal delivery, delivering a singleton SGA neonate at term between 2005 and 2020 were included. Factors associated with successful vaginal delivery were examined by a multivariable analysis. Of the 255 women who met the inclusion criteria and underwent TOLAC, 72.2% delivered vaginally. In a multivariable analysis, maternal height [adjusted odds ratio (aOR) (95% CI): 1.10 (1.02-1.19), p = 0.012] and epidural administration [aOR (95% CI): 2.78 (1.0-7.73), p = 0.050] were positively independently associated with TOLAC success, and hypertensive disorders were negatively independently associated with TOLAC success [aOR (95% CI): 0.52 (0.004-0.74), p = 0.029]. The success rate of TOLAC among women with no prior vaginal delivery, delivering a SGA neonate is relatively high. Maternal height, hypertensive disorders, and epidural administration are independent factors associated with TOLAC success. Epidural administration is a modifiable factor and should be taken in consideration during TOLAC management.