Hypertensive Disorders Of Pregnancy Group Research Articles

Early-pregnancy N-terminal pro-brain natriuretic peptide level is inversely associated with hypertensive disorders of pregnancy diagnosed after 35 weeks of gestation

Hypertensive disorders of pregnancy (HDP) are among the major causes of high maternal and fetal/neonatal morbidity and mortality rates. Patients with HDP have significantly elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at diagnosis; however, the NT-proBNP levels during early pregnancy are largely unknown. This study aimed to validate the association between HDP and NT-proBNP levels. This retrospective study evaluated 103 pregnant women who developed HDP diagnosed after 35 weeks of gestation and 667 who did not. The HDP group had significantly lower early-pregnancy NT-proBNP levels than the without HDP group. However, the two groups did not significantly differ in terms of the late-pregnancy NT-proBNP levels. After adjusting for confounding factors such as age, body mass index, parity, and blood pressure levels, high early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Early-pregnancy NT-proBNP levels ≥ 60.5 pg/mL had a negative predictive value of 97.0% for ruling out HDP, with a sensitivity of 87.4% and specificity of 62.5%. In conclusion, elevated early-pregnancy NT-proBNP levels were associated with a lower HDP risk. Moreover, a cutoff point of ≥ 60.5 pg/mL for early-pregnancy NT-proBNP levels had a high negative predictive value and sensitivity for ruling out HDP. These findings can provide new clinical implications.

Inflammatory, Metabolic and Endothelial Biomarkers Before and After Pregnancy Complications.

Women with gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB) have excess cardiovascular disease compared to those with uncomplicated births, perhaps related to pre-pregnancy inflammation, dysmetabolism or endothelial dysfunction. We included 1238 women in the Coronary Artery Risk Development in Young Adults Study (1985-2011) with 2215 births classified according to outcomes (term, uncomplicated births were the referent). Repeated measures ANOVA estimated pre-pregnancy, post-pregnancy and biomarker change according to pregnancy outcomes, adjusted for confounders. GDM and HDP groups had higher pre-pregnancy hsCRP (+0.37 [0.08, 0.65]; +0.29 [0.04, 0.55] log mg/L), leptin (+0.29 [0.09, 0.50]; +0.37 [0.17, 0.56] log ng/ml), and lower adiponectin (-0.25 [-0.36, -0.13); -0.11 [-0.22, -0.01] log ng/ml) than those with uncomplicated births and these profiles persisted in magnitude post-pregnancy. Controlling for BMI attenuated most profiles, except lower pre-pregnancy adiponectin remained associated with GDM. PTB without HDP or GDM was related to lower pre-pregnancy hsCRP and sICAM-1 (-0.31 [-0.56, -0.06] log mg/L; -0.05 [-0.09, - 0.01] log ng/ml) and a larger leptin increase from pre- to post-pregnancy, (+0.20 [0.02, 0.37] log ng/ml). Pre-pregnancy inflammation and metabolic dysfunction contributed to GDM and HDP, perhaps due to higher BMI. PTB may be related to adverse metabolic changes post-pregnancy, though the unexpected endothelial biomarker profile warrants further study.

A comparison among oscillometric waveforms in healthy nonpregnant women, pregnancy and hypertensive disorders of pregnancy.

Understanding of how oscillometric waveforms (OMW) vary between pregnant and nonpregnant individuals remains low. An exploratory analysis was completed to assess for quantitative and qualitative changes in OMW and oscillometric envelope features in pregnancy. Eighteen pregnant individuals (over 20 weeks gestational age) and healthy, nonpregnant (HNP) women were recruited. Six HNP were matched to six healthy pregnant (HP) women, and six pregnant women with a hypertensive disorder of pregnancy (HDP) by age, arm circumference, and cuff size. Blood pressure measurements were completed per the International Organization for Standardization (ISO) protocol using a custom-built oscillometric device as the test device and two-observer mercury auscultation as the reference measurement. Auscultatory blood pressure and blood pressure derived from slope-based and fixed ratio algorithms were determined. OMW and envelope features were compared among groups. In HNP, HP, and HDP groups respectively: mean auscultatory blood pressure (systolic mean ± SD/diastolic mean ± SD) was 103.4 ± 12.2/67.1 ± 7.9; 109.5 ± 3.1/58.1 ± 6.4; 135.6 ± 18.9/85.1 ± 14.2 mmHg. HDP had significantly higher auscultatory systolic and diastolic blood pressure than the HP group (P = 0.001). The pregnant groups had a lower average pulse width (mean ± SD: HNP = 0.8 ± 0 s, HP = 0.6 ± 0.1 s, HDP = 0.6 ± 0.1 s; HP vs. HNP mean difference [adjusted P value]: 0.2 [P = 0.004], HDP vs. HNP 0.1 [P = 0.018]) compared with the HNP group. The HDP group had a larger area under the OMW envelope than the HNP group (mean ± SD: HNP = 22.6 ± 3.4; HDP = 28.5 ± 4.2; HDP vs. HNP mean difference [adjusted P value]: 5.9 P = 0.05). In this exploratory work, differences in the OMW morphology and parameters were found in pregnancy and in hypertensive disorders of pregnancy compared with healthy controls. Even small differences may have important implications in algorithm development; further work comparing OMW envelopes in pregnancy is needed to optimize the algorithms used to determine blood pressure in pregnancy.

Impact of hypertensive disorders of pregnancy on offspring cardiovascular function. Study from fetal life to early childhood.

Epidemiological studies suggest that children following in utero exposure to hypertensive disorders of pregnancy (HDP) may be at increased long term cardiovascular risk. However, data in early childhood are lacking. We aimed to investigate the independent influence of HDP on childhood heart after accounting for differences in childhood risk factor profile. We performed detailed cardiovascular assessment in fetuses at mid-gestation and at a median of 2.3 years (IQR: 2.1, 2.4 years) postnatally in 71 cases where the mothers had HDP and 304 who did not have HDP. There were no differences in demographic characteristics between groups but in the HDP group delivery was earlier and birthweight was lower. In fetal life, there were no significant differences in cardiac function or structure between the HDP and non-HDP groups. In early childhood, in the HDP compared to the non-HDP group, there was greater relative wall thickness (0.7 SD 0.3 vs. 0.6 SD 0.3 mm, p=0.047) and increased left ventricular mass (80.9 SD 20.4 vs. 75.7 SD 16.5, p=0.024); however, these differences were abolished following multivariable analysis. Longitudinal analysis revealed that in HDP, compared to the non-HDP group, there was no difference in the change of cardiac functional indices from fetal life to early childhood. Epidemiological studies suggest that HDP have an adverse impact on offspring cardiovascular health, but such an effect is not apparent in fetal life or in early childhood. This article is protected by copyright. All rights reserved.

Long-term cardiovascular assessment of women who had a pregnancy complicated by a hypertensive disorder.

Women with hypertensive disorders of pregnancy (HDP) are at increased risk of developing hypertension and cardiovascular disease later in life. However, from studies so far, it is difficult to define whether this association reflects preexisting maternal cardiovascular risk or merely reflect a potentially causal relationship between HDP and later cardiovascular risk. We performed detailed cardiovascular assessment in women at mid-gestation, prior to development of a HDP and at 2 years post-partum aiming to identify cardiovascular changes prior to development of HDP and to assess persistent cardiovascular alterations long after the HDP event. This was a prospective observational study in which we performed detailed cardiovascular assessment at mid-gestation and at median of 2.3 years (interquartile range 2.1 to 2.4 years) post-partum. We examined 112 women who developed a HDP and 451 women whose pregnancy was not complicated by hypertension. We used conventional and more advanced echocardiographic techniques, i.e. speckle tracking, to accurately determine left ventricular systolic and diastolic function. We used M-mode measurements to determine left ventricular remodeling and estimate left ventricular mass. Maternal vascular status was assessed using ophthalmic artery Doppler and by calculating peak systolic velocity (PSV) ratio, as a marker of peripheral vascular resistance. At mid-gestation, women who subsequently developed HDP had increased ophthalmic artery PSV ratio. These women also had mild cardiac functional and morphological alterations which were mostly accounted for by maternal cardiovascular risk factors. At 2 years post-partum, women who experienced HDP, compared to those who did not, had cardiovascular abnormalities with reduction in left ventricular systolic and diastolic function which remained after multivariable analysis. Longitudinal analysis demonstrated that the evolution of cardiovascular changes in the HDP and non-HDP groups was similar. Mild cardiac functional and morphological alterations precede the development of HDP and such changes persist for at least 2 years postpartum. The cardiac changes are likely to be the consequence of preexisting maternal cardiovascular risk factors rather than an adverse consequence of HDP. This article is protected by copyright. All rights reserved.

Preterm birth increases cerebral palsy hazards in children of mothers with chronic hypertension in pregnancy

BackgroundChildren of mothers with chronic-hypertension in pregnancy have high rates of preterm-birth (<37 weeks of gestation) and small-for-gestational-age (SGA), both of which are risk factors of cerebral palsy (CP). This study investigated the cumulative risks of CP in children exposed to maternal chronic-hypertension vs. other types of hypertensive-disorders-of-pregnancy (HDP), and whether preterm-birth and SGA potentiate the antenatal impact of chronic-hypertension to increase CP hazards. MethodsThis population-based cohort study enrolled 1,417,373 mother-child pairs with singleton live births between 2004 and 2011 from the Taiwan Maternal and Child Health Database. A total of 19,457 pairs with HDP were identified and propensity-score-matched with 97,285 normotensive controls. Children were followed up for CP outcome until age 6–13 years. HDP were classified into chronic-hypertension, gestational-hypertension, preeclampsia, and preeclampsia-with-chronic-hypertension. Using the normotensive group as the reference, the associations between chronic-hypertension and CP hazard were assessed with adjusted hazard ratios (HR) and 95% confidence intervals (CI) in Cox proportional hazards regression models, and the effects of preterm-birth and SGA on the associations were examined. ResultsThe HDP group had higher rates of CP (0.8%) than the normotensive group (0.5%), particularly the subgroup of preeclampsia-with-chronic-hypertension (1.0%), followed by preeclampsia (0.9%), chronic-hypertension (0.7%) and gestational-hypertension (0.6%). Preterm-birth, but not SGA, exerted moderating effects to increase CP risks in children exposed to maternal chronic-hypertension. Before adjustments, chronic-hypertension alone had no substantial contribution to CP hazard (HR 1.35, 95% CI 1.00–1.83), while preeclampsia alone (1.64, 1.28–2.11) or with superimposed-chronic-hypertension (1.83, 1.16–2.89) had significant effects. After including preterm-birth in the multivariable model, the CP hazard for chronic-hypertension alone rather than other types of HDP was raised and became significant (1.56, 1.15–2.12), and the significance remained after stepwise adjustments in the final model (1.74, 1.16–2.60). ConclusionsPreterm-birth might potentiate CP hazards in children of mothers with chronic-hypertension in pregnancy.

Effects of hypertensive disorders of pregnancy on the complications in very low birth weight neonates

ABSTRACT Objective This study was designed to investigate the effects of hypertensive disorders of pregnancy (HDP) on the complications in very low birth weight (VLBW) neonates. Methods We retrospectively included VLBW neonates (<37 weeks) who were delivered by HDP pregnant women with a body weight of < 1,500 g (HDP group) hospitalized in our hospital between January 2016 and July 2021. Gestational age matched VLBW neonates delivered by pregnant women with a normal blood pressure, with a proportion of 1:1 to the HDP group in number, served as normal control. Results Then we compared the peripartum data and major complications between HDP group and control. The body weight, prelabor rupture of membrane (PROM), maternal age, cesarean section rate, fetal distress, small for gestational age (SGA), mechanical ventilation, RDS, necrotizing enterocolitis (NEC) (≥2 stage), Apgar score at 1 min, and mortality in HDP group showed statistical differences compared with those of the control (all p < 0.05). To compare the major complications among HDP subgroups, we classified the VLBW neonates of the HDP group into three subgroups including gestational hypertension group (n = 72), pre-eclampsia (PE) group (n = 222), and eclampsia group (n = 14), which showed significant differences in the fetal distress, Apgar score at 1 min, SGA, ventilation, RDS and NEC (≥2 stage) among these subgroups (all p < 0.05). Multivariate regression analysis showed that eclampsia and PE were the independent risk factors for SGA and NEC, respectively. Conclusion HDP was associated with increased incidence of neonatal asphyxia, fatal distress, SGA, mechanical ventilation, RDS, NEC and mortality. Besides, eclampsia and PE were independent risk factors for SGA and NEC.

Retinal oximetry and microvascular assessment after hypertensive pregnancy complications

AbstractPurposeWomen with hypertensive disorders of pregnancy (HDP) are at increased risk of developing premature cardiovascular disease (CVD). The mechanisms behind this are not fully understood, but microvascular alterations have been documented in retinal arterioles and venules. The aim of this study was to use non‐invasive retinal imaging to investigate the structural and functional properties of arterioles, venules and capillaries in this patient group.MethodsWe examined 27 women with previous HDP and 23 controls at 3 years postpartum. The retinal microvasculature was assessed by vessel calibre measurements, retinal oximetry and optical coherence tomography angiography. Differences were analysed using non‐parametric tests and multiple regression analyses, adjusted for age and body mass index.ResultsMedian arteriolar oxygen saturation (SaO2; 94.2% vs. 93.0%), venular oxygen saturation (SvO2; 60.1% vs. 62.4%) and arteriovenous saturation difference (AV‐difference; 32.8% vs. 32.3%) were similar across groups. Capillary vessel density (VD; 46.2% vs. 46.3%), skeletonised VD (VSD; 21.3 vs. 21.1 mm/mm2) and vessel diameter index (21.65 vs. 21.86) were also comparable. In the HDP group, mean arterial pressure (MAP) was positively correlated with AV‐difference (R2 = 0.209) and negatively correlated with arteriolar diameter (CRAE; r2 = 0.382).ConclusionsStructural microvascular alterations appear not to be key biomarkers for CVD risk after HDP as early as 3 years postpartum in otherwise healthy women. Further studies are needed to evaluate whether such changes occur later in life. MAP was associated with AV‐difference only in the HDP group, suggesting specific mechanisms affecting functional microvascular properties in these women.

Angiogenic markers and maternal echocardiographic indices in women with hypertensive disorders of pregnancy.

The maternal cardiovascular system of women with hypertensive disorders of pregnancy (HDP) can be impaired, with higher rates of left ventricular (LV) remodeling and diastolic dysfunction compared to those with normotensive pregnancy. The primary objective of this prospective study was to correlate cardiac indices obtained by transthoracic echocardiography (TTE) and circulating angiogenic markers, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). In this study, 95 women with a pregnancy complicated by HDP and a group of 25 with an uncomplicated pregnancy at term underwent TTE and blood tests to measure sFlt-1 and PlGF during the peripartum period (before delivery or within a week of giving birth). Spearman's rank correlation was used to derive correlation coefficients between biomarkers and cardiac indices in the HDP and control populations. The HDP group included 61 (64.2%) pre-eclamptic patients and, among them, 42 (68.9%) delivered before 37 weeks' gestation. Twelve women with HDP (12.6%) underwent blood sampling and TTE after delivery, and, as they showed significantly lower levels of angiogenic markers, they were excluded from the analysis. There was a correlation between sFlt-1 and LV mass index (LVMI) (r = 0.246; P = 0.026) and early diastolic mitral inflow velocity (E) and early diastolic mitral annular velocity (e') ratio (r = 0.272; P = 0.014) in the HDP group (n = 83), while in the controls, sFlt-1 showed a correlation with relative wall thickness (r = 0.409; P = 0.043), lateral e' (r = -0.562; P = 0.004) and E/e' ratio (r = 0.417; P = 0.042). PlGF correlated with LVMI (r = -0.238; P = 0.031) in HDP patients and with lateral e' (r = 0.466; P = 0.022) in controls. sFlt-1/PlGF ratio correlated with lateral e' (r = -0.568; P = 0.004) and E/e' ratio (r = 0.428; P = 0.037) in controls and with LVMI (r = 0.252; P = 0.022) and E/e' ratio (r = 0.269; P = 0.014) in HDP. Although the current data are not able to infer causality, they confirm the intimate relationship between the maternal cardiovascular system and angiogenic markers that are used both to diagnose and indicate the severity of HDP. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Risk factors and prediction model for new-onset hypertensive disorders of pregnancy: a retrospective cohort study.

Hypertensive disorders of pregnancy (HDP) is a significant cause of maternal and neonatal mortality. This study aims to identify risk factors for new-onset HDP and to develop a prediction model for assessing the risk of new-onset hypertension during pregnancy. We included 446 pregnant women without baseline hypertension from Liyang People's Hospital at the first inspection, and they were followed up until delivery. We collected maternal clinical parameters and biomarkers between 16th and 20th weeks of gestation. Logistic regression was used to determine the effect of the risk factors on HDP. For model development, a backward selection algorithm was applied to choose pertinent biomarkers, and predictive models were created based on multiple machine learning methods (generalised linear model, multivariate adaptive regression splines, random forest, and k-nearest neighbours). Model performance was evaluated using the area under the curve. Out of the 446 participants, 153 developed new-onset HDP. The HDP group exhibited significantly higher baseline body mass index (BMI), weight change, baseline systolic/diastolic blood pressure, and platelet counts than the control group. The increase in baseline BMI, weight change, and baseline systolic and diastolic blood pressure significantly elevated the risk of HDP, with odds ratios and 95% confidence intervals of 1.10 (1.03-1.17), 1.10 (1.05-1.16), 1.04 (1.01-1.08), and 1.10 (1.05-1.14) respectively. Restricted cubic spline showed a linear dose-dependent association of baseline BMI and weight change with the risk of HDP. The random forest-based prediction model showed robust performance with the area under the curve of 0.85 in the training set. This study establishes a prediction model to evaluate the risk of new-onset HDP, which might facilitate the early diagnosis and management of HDP.

Abstract 16723: Comparison of Myocardial Strain During Active Labor in Parturients With Hypertensive Disorders of Pregnancy via Speckle-Tracking Echocardiography

Introduction: Hypertensive disorders of pregnancy (HDP) are increasing in prevalence in the USA and affect maternal morbidity and mortality. Hypothesis: Echocardiographic strain abnormalities may be more prevalent in patients with HDP in active labor, which may unmask subclinical left ventricular dysfunction. Methods: A total of 59 healthy term parturients (≥37 wks gestational age) in active labor (≥6cm cervical dilation) underwent echocardiography to assess cardiac function during peak physiologic stress. Speckle tracking strain analysis was performed using apical 4-, 3- and 2-chamber views during uterine contraction and relaxation with a S5-1 Philips Sparq probe and analyzed with Qlab 9 strain analysis software (Philips, Andover, MA, USA). Abnormal strain cutoff was &gt;-20%. Mean ± SD summarized continuous variables; absolute and relative frequencies for categorical. Welch T-test and Chi-square were used for group comparisons. Results: HDP was present in 21 subjects and absent in 39. Mean age, parity, and prevalence of diabetes did not differ significantly between the two groups. The HDP group had a higher mean BMI (Table 1). The non-HDP group had strain abnormalities in two segments during uterine relaxation, absent during contraction. The HDP group had abnormalities in 5 segments during uterine relaxation, 4 of which were persistently abnormal during uterine contraction (Fig 1). Conclusions: Abnormal strain values were detected at a higher rate in HDP group than in non-HDP group in active labor. Future research is needed to determine if subclinical strain abnormalities in those with HDP during active labor are predictive of developing future cardiovascular disease.

Flow-mediated Dilation of the Brachial Artery in Women with Hypertensive Disorders of Pregnancy.

Hypertensive disorder of pregnancy (HDP) comprise chronic hypertension, gestational hypertension, preeclampsia/eclampsia, and preeclampsia superimposed on chronic hypertension. HDP complicate up to 10% of pregnancies worldwide and carry significant risks of maternal and perinatal morbidity and mortality. The aim of this study was to evaluate the derangement and characteristics of brachial artery flow-mediated dilation (BAFMD) in women with HDP. The BAFMD of the right brachial artery of 80 women with HDP (pregnant HDP), 80 normotensive pregnant women (pregnant non-HDP), and 80 healthy nonpregnant women (nonpregnant controls) was evaluated with B-mode ultrasound. The age, blood pressure, body mass index (BMI), brachial artery diameter, and BAFMD of the participants were compared. P ≤ 0.05 was statistically significant. The pregnant HDP group had significantly lower mean BAFMD compared to pregnant non-HDP and nonpregnant controls (6.9% ± 2.53% vs. 8.32% ± 3.4% vs. 9.4% ± 2.68%; P < 0.001). There was no significant difference between the mean BAFMD of the pregnant HDP subgroups: preeclampsia (5.81% ± 1.7%) versus gestational hypertension (6.43% ± 3.02%); P = 0.57. BAFMD diminished with advancing gestational age in both the pregnant HDP and pregnant non-HDP groups. On regression analysis, BAFMD was a poor marker for HDP, while BMI was an independent predictor for HDP. Even though HDP were associated with significantly diminished BAFMD, it was not a good marker for HDP.

Dynamic changes in blood lipid levels and their associations with hypertensive disorders of pregnancy in twin pregnancy: A retrospective study

Little knowledge onthe association of blood lipid levels with hypertensive disorders of pregnancy(HDP) in twin pregnancy. To investigate the associationof blood lipid levels with HDP in twin pregnancy. This is a retrospective study in the Beijing Birth Cohort on patients followed betweenJanuary 2014 andNovember 2021.A total of2628 women pregnant with twins were includedand dividedinto HDP (n=565) and normal blood pressure (NBP,n=2063) groups. HDP subtypes includedgestational hypertension (GH, n=190) and preeclampsia(PE,n=375). Dynamic changes in blood lipidprofiles and theirassociations with HDP were assessed. Compared to NBP group, higher triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c) in the first (T1)and secondtrimesters (T2)existed in women with PE.In addition, TG increased significantly from T1 to T2,and HDL-c decreased significantly since T2 in women with PE, especially in women with early-onset PE and severe PE. Elevated TG and LDL-c were associated with HDP, mainlyPE.Ina subgroup analysis,higher TG or LDL-c increased the risk of HDP for underweight, overweight and primipara women. In twin pregnancy, women with PE had higher TG and LDL-c, and elevatedTG andLDL-cwere associated with PE. A significant increase inTG or decrease inHDL-cwere more prone to PE, especially early-onset PE and severe PE. It is helpful to monitorblood lipid levels in womenpregnant with twins, especially in underweight, overweight, and primipara women.

Maternal hypertensive pregnancy disorders increase childhood intellectual disability hazards independently from preterm birth and small for gestational age

BackgroundChildren of mothers with hypertensive-disorders-of-pregnancy (HDP) have high rates of preterm-birth (<37 weeks' gestation) and small-for-gestational-age (SGA), both of which are risk factors of intellectual disability (ID). AimsTo test the multiple-hit hypothesis that preterm-birth and SGA in the neonatal period might potentiate the antenatal impact of HDP to increase childhood ID hazards, and HDP might not have independent effects. MethodsThis population-based cohort study enrolled 1,417,373 mother-child pairs between 2004 and 2011. A total of 19,457 pairs with HDP were identified and propensity-score-matched with 97,285 normotensive controls. Children were followed up for ID outcome until 6–13 years of age. HDP were classified into chronic-hypertension, gestational-hypertension, preeclampsia, and preeclampsia-with-chronic-hypertension. Using the normotensive group as the reference, the associations between HDP subgroups and ID hazards were assessed with adjusted hazard ratios (aHR) and 95 % confidence intervals (CI), and the effects of preterm-birth and SGA on the associations were examined. ResultsThe HDP group had higher cumulative rates of ID (1.6 %) than the normotensive group (0.9 %), particularly the subgroup of preeclampsia-with-chronic-hypertension (2.4 %), followed by preeclampsia (1.7 %), chronic-hypertension (1.5 %) and gestational hypertension (1.0 %). Preterm-birth and SGA exerted aggravating effects on ID hazards in children exposed to any HDP. After adjustments, maternal chronic-hypertension (aHR 1.59, 95 % CI 1.28–1.97), preeclampsia (1.52, 1.26–1.83), and preeclampsia-with-chronic-hypertension (1.86, 1.38–2.51) independently contributed to ID outcome. ConclusionsMaternal HDP other than gestational hypertension increased offspring's ID hazards independently from the potentiating hits of preterm-birth and SGA, implicating long-lasting influence of in-utero HDP exposure on children's cognitive development.

Preterm birth and small for gestational age potentiate the association between maternal hypertensive pregnancy and childhood autism spectrum disorder

Children of mothers with hypertensive disorders of pregnancy (HDP) have high rates of preterm-birth (gestational age < 37 weeks) and small-for-gestational-age (SGA), both of which are risk factors of autism spectrum disorder (ASD). This study tested the multiple-hit hypothesis that preterm-birth and SGA in the neonatal period might potentiate the antenatal impact of HDP to increase childhood ASD hazards, and HDP might not be a major contributor. The propensity-score-matched cohort enrolled 18,131 mother–child pairs with HDP and 90,655 normotensive controls between 2004 and 2011. Children with siblings born to the same mothers were excluded for analysis to reduce the potential familial-genetic influence. HDP were classified into chronic-hypertension, gestational-hypertension, preeclampsia, and preeclampsia-with-chronic-hypertension. Using the normotensive group as the reference, the associations between HDP subgroups and the cumulative ASD risks were assessed with hazard ratios, and the effects of preterm-birth and SGA on the associations were examined. The HDP group had a higher cumulative rate of ASD (1.5%) than the normotensive group (1.2%). Preterm-birth and SGA exerted moderating effects to aggravate ASD hazards in children exposed to chronic-hypertension or gestational-hypertension. None of HDP types significantly contributed to ASD after adjustments. In conclusion, antenatal HDP exposure might predispose to ASD outcome through susceptibility to the impact of preterm-birth and SGA.

Hypertensive Disorders of Pregnancy and the Risk of Developing Hypertension Outside of Pregnancy Based on Updated Hypertension Guidelines [ID: 1377015

INTRODUCTION: The purpose of this study is to determine whether hypertensive disorders of pregnancy (HDP) affect the development of chronic hypertension (HTN) within 5 years postdelivery based on updated guidelines by the American Heart Association (AHA). METHODS: This IRB-approved study evaluated women who delivered at one hospital from 2014 to 2016. Participants were determined to be normotensive or with HDP. Inclusion criteria for the HDP group was diagnosis of gestational HTN or preeclampsia at 20 weeks of gestation or greater. Exclusion criteria were previous diagnosis of HTN and age over 40. Women were followed up to 5 years postdelivery to assess development of chronic HTN, defined by the 2017 AHA guidelines as systolic greater than 130 mm Hg or diastolic greater than 80 mm Hg. RESULTS: Sixty-four participants (30.9%) developed chronic HTN within 5 years of delivery. Of these participants, 6.25% were from the normotensive pregnancy group, while 84.4% were from the preeclampsia with severe features group, with adjusted odds ratio of 11.38 (CI 4.67–22.46). Compared to the 5-year normotensive group, the 5-year chronic HTN group was associated with higher maternal body mass index (BMI) (P=.0146), preterm delivery (P=.0231), and neonatal intensive care unit (NICU) admission (P=.04). CONCLUSION: The rate of chronic HTN development 5 years postdelivery was significantly higher in participants with HDP, notably preeclampsia with severe features. Participants with development of chronic HTN had increased BMI during pregnancy, preterm delivery, and NICU admission rates as compared to participants with 5-year normotensive pressures. Awareness of the prevalence and risk factors for development of chronic hypertension provides areas of focus for future investigations.

Association between Pregestational Vaginal Dysbiosis and Incident Hypertensive Disorders of Pregnancy Risk: a Nested Case-Control Study.

A balanced vaginal microbiome dominated by Lactobacillus can help promote women's reproductive health, with Lactobacillus crispatus showing the most beneficial effect. However, the potential role of vaginal microbiomes in hypertensive disorders of pregnancy (HDP) development is not thoroughly explored. In this nested case-control study based on an assisted reproductive technology follow-up cohort, we prospectively assessed the association between pregestational vaginal microbiomes with HDP by collecting vaginal swabs from 75 HDP cases (HDP group) and 150 controls (NP group) and using 16S amplicon sequencing for bacterial identification. The vaginal microbial composition of the HDP group significantly differed from that of the NP group. The abundance of L. crispatus was significantly lower, and the abundances of Gardnerella vaginalis was significantly higher, in the HDP group than in the NP group. Of note, L. crispatus-dominated vaginal community state type was associated with a decreased risk for HDP (odds ratio = 0.436; 95% confidence interval, 0.229 to 0.831) compared with others. Additionally, network analysis revealed different bacterial interactions with 61 and 57 exclusive edges in the NP and HDP groups, respectively. Compared with the HDP group, the NP group showed a higher weighted degree and closeness centrality. Several taxa, including G. vaginalis, L. iners, and bacterial vaginosis-associated bacteria (Prevotella, Megasphaera, Finegoldia, and Porphyromonas), were identified as "drivers" for network rewiring. Notable alterations of predicted pathways involved in amino acid, cofactor, and vitamin metabolism; membrane transport; and bacterial toxins were observed in the HDP group. IMPORTANCE The etiology of HDP remains unclear to date. Effective methods for the individualized prediction and prevention are lacking. Pregestational vaginal dysbiosis precedes the diagnosis of HDP, providing a novel perspective on the etiology of HDP. Early pregnancy is the critical period of placental development, and abnormal placentation initiates HDP development. Thus, disease prevention should be considered before pregnancy. Vaginal microbiome characterization and probiotic interventions before pregnancy are preferred because of their safety and potential for early prevention. This study is the first to prospectively assess associations between pregestational vaginal microbiome and HDP. L. crispatus-dominated vaginal community state type is linked to a reduced risk for HDP. These findings suggest that vaginal microbiome characterization may help identify individuals at high risk for HDP and offer potential targets for the development of novel pregestational intervention methods.

Association between endotypes of prematurity and pharmacological closure of patent ductus arteriosus: A systematic review and meta-analysis.

Endotypes leading to very and extremely preterm birth are clustered into two groups: infection/inflammation and dysfunctional placentation. We conducted a systematic review of observational studies exploring the association between these two endotypes and the pharmacological closure of patent ductus arteriosus (PDA) induced by cyclooxygenase (COX) inhibitors. Chorioamnionitis represented the infectious-inflammatory endotype, while dysfunctional placentation proxies were hypertensive disorders of pregnancy (HDP) and small for gestational age (SGA) or intrauterine growth restriction. PubMed/Medline and Embase databases were searched. The random-effects odds ratio (OR) and 95% confidence interval (CI) were calculated for each association. We included 30 studies (12,639 infants). Meta-analysis showed a significant association between exposure to HDP and increased rate of pharmacological closure of PDA (17 studies, OR 1.41, 95% CI 1.10-1.81, p = 0.006). In contrast, neither chorioamnionitis (13 studies, OR 0.75, 95% CI 0.47-1.18, p = 0.211) nor SGA (17 studies, OR 1.20, 95% CI 0.96-1.50, p= 0.115) were significantly associated with the response to therapy. Subgroup analyses showed that the higher response to COX inhibitors in the HDP group was significant for indomethacin (OR 1.568, 95% CI 1.147-2.141, p = 0.005) but not for ibuprofen (OR 1.107, 95% CI 0.248-4.392, p = 0.894) or for the studies using both drugs (OR 1.280, 95% CI 0.935-1.751, p = 0.124). However, meta-regression showed that this difference between the drugs was not statistically significant (p = 0.404). Our data suggest that the pathologic condition that triggers prematurity may alter the response to pharmacological treatment of PDA. The DA of infants exposed to HDP appears to be more responsive to COX inhibitors.

Impact of hypertensive disorders of pregnancy on neonatal outcomes among infants born at 24+0-31+6 weeks' gestation in China: A multicenter cohort study.

To describe the rate of hypertensive disorder of pregnancy (HDP) among mothers of very preterm infants (VPIs) admitted to Chinese neonatal intensive care units (NICUs), and to investigate the relationship between HDP and the outcomes of VPIs. Cohort study of all VPIs born at a gestational age of 24+0-31+6 weeks and admitted to 57 tertiary NICUs of the Chinese Neonatal Network (CHNN) in 2019. Infants with severe congenital anomalies or missing maternal HDP information were excluded. Two multivariate logistic regression models were generated to assess the relationship between HDP and neonatal outcomes. Among 9,262 infants enrolled, 1,744 (18.8%) infants were born to mothers with HDP, with an increasing incidence with increasing gestational age. VPIs born to mothers with HDP had higher gestational age but lower birth weight and were more likely to be small for gestational age. Mothers with HDP were more likely to receive antenatal steroids, MgSO4 and cesarean section. Infants in the HDP group showed higher observed rates of mortality or any morbidity than infants in the non-HDP group (50.2% vs. 47.2%, crude odds ratio (OR) 1.13, 95% CI 1.02-1.26). However, the associations between HDP and adverse outcomes were not significant after adjustment. In the HDP group, mothers of 1,324/1,688 (78.4%) infants were diagnosed with preeclampsia/eclampsia. Infants born to mothers with preeclampsia/eclampsia had significantly lower odds of early death and severe retinopathy of prematurity. Nearly one-fifth of VPIs were born to mothers with HDP in Chinese NICUs. No significant association was identified between HDP and adverse neonatal short-term outcomes of VPIs, while long-term follow-up of these infants is needed.

The effectiveness of the Congo Red Dot paper test in hypertensive disorders of pregnancy: Asystematic review and meta-analysis.

Congo Red Dot Paper Test (CRDPT) appears to be a simple, cost-effective, non-invasive diagnostic tool for hypertensive disorders of pregnancy (HDP). The main objective of the study is to assess the effectiveness of CRDPT in detecting HDP. This is a systemic review and meta-analysis of published studies on the effectiveness of CRDPT in the detection of HDP. The study was conducted in line with the PRISMA-DTA guidelines. The PICOS framework was used to search for relevant articles using Medline, PubMed, Google Scholar, Web of Science, and the Cochrane Library databases. The articles were screened against a set of inclusion and exclusion criteria and analysed using the Review Manager 5.4 software. A title, abstract and full article screening was conducted on 18,153 potential articles based on the inclusion and exclusion criteria. The screening yielded five articles for meta-analysis. The total number of normotensive pregnant women (n = 3,380) in the included studies was five times higher than the total number of women with pre-eclampsia (n = 535). A difference between the HDP and normotensive group was noted. This is indicated by a significantly decreased in the effectiveness of CRDPT in detecting HDP as compared to normotensive group [Risk Ratio (RR) = 6.32 (2.17, 18.43) p < 0.00001]. The included studies had a high nature of heterogeneity (I 2 = 98%, p < 0.00001) partially due to different study designs included in the analysis and different regions where studies were conducted given that none of these studies were conducted in African countries where HDP is prominent. According to results generated from 5 studies in this meta-analysis, it was found that CRDPT might not be effective in the detection of hypertensive disorder of pregnancy. Moreover, more research, especially in African women where hypertensive disorders of pregnancy are prevalent, are re-quired to ascertain these findings. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021283679, identifier: CRD42021283679.