HELLP Syndrome at 20 Gestational Weeks Managed Using the Mississippi Protocol: A Case Report.

Hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome is one of the most severe complications of hypertensive disorders of pregnancy. HELLP syndrome occurring before 22 gestational weeks (GWs) is extremely rare, and patients prevalently exhibit underlying maternal diseases or fetal abnormalities. Here, we report the case of a pregnant woman who had HELLP syndrome at 20 GWs without any obvious underlying maternal diseases or fetal abnormalities. A 38-year-old pregnant woman was referred to Kobe University Hospital from another hospital at 19 + 5/7 GWs for hypertension, proteinuria, generalized edema, and fetal growth restriction. She was diagnosed with partial HELLP syndrome according to the Mississippi classification at 20 + 2/7 GWs. The patient was managed following the Mississippi protocol, including intravenous dexamethasone, magnesium sulfate, and antihypertensive drugs. She received intensive blood pressure and laboratory data monitoring using an arterial line and additional treatments, including platelet transfusion, intravenous haptoglobin infusion, and human atrial natriuretic peptide. The pregnancy ended in an induced delivery at 20 + 3/7 GWs, and she was discharged without complications 10 days postnatal. We performed laboratory tests for diagnosing underlying diseases but identified no obvious underlying diseases. This report indicates that early and intensive treatment of patients with HELLP syndrome occurring before 22 GWs according to the Mississippi protocol may enable clinicians to complete pregnancy termination without maternal complications and provide useful information to clinical practitioners in perinatal medicine.

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

Background: 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. Methods: 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. Results: 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. Conclusion: Even though HDP were associated with significantly diminished BAFMD, it was not a good marker for HDP.

Exposure to DEP Modifies the Human Umbilical Artery Vascular Resistance Contributing to Hypertension in Pregnancy.

Hypertensive disorders in pregnancy (HDP) are the most prevalent diseases during pregnancy. In addition to the already identified risk factors, exposure to environmental contaminants has been also considered a new one. Phthalates, which are classified as priority environmental pollutants due to their ubiquitousness and endocrine disrupting properties, have been implicated in HDP in some epidemiological studies. Nevertheless, phthalates' vascular impacts still need to be clarified. Thus, we aimed to understand the connection between phthalates exposure and the occurrence of gestational hypertension, as well as the pathway involved in the pathological vascular effects. We investigated diethyl phthalate's (DEP) effect on the vascular reactivity of the human umbilical arteries (HUAs) from normotensive and hypertensive pregnant women. Both DEP's nongenomic (within minutes effect) and genomic (24 h exposure to DEP) actions were evaluated, as well as the contribution of cyclic guanosine monophosphate and Ca2+ channel pathways. The results show that short-term exposure to DEP interferes with serotonin and histamine receptors, while after prolonged exposure, DEP seems to share the same vasorelaxant mechanism as estrogens, through the NO/sGC/cGMP/PKG signaling pathway, and to interfere with the L-type Ca2+ channels. Thus, the vascular effect induced by DEP is similar to that observed in HUA from hypertensive pregnancies, demonstrating that the development of HDP may be a consequence of DEP exposure.

Early Postpartum Blood Pressure Screening is Associated with Increased Detection of Cardiovascular Risk Factors in Women with Hypertensive Disorders of Pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP), including gestational hypertension, preeclampsia, and eclampsia, are risk factors for cardiovascular (CV) disease. Guidelines recommend that women with HDP be screened for the development of hypertension (HTN) within 6-12 months postpartum. However, the extent to which this early blood pressure (BP) screening is being performed and the impact on detection of CV risk factors is unknown. METHODS: Women with HDP and without pre-existing hypertension (HTN) who had at least 6 months of clinical follow-up were categorized by postpartum BP screening status: early BP screen (6-12 months after delivery) or late BP screen (≥12 months after delivery). Multivariable logistic regression identified factors associated with early screening. Multivariable Cox proportional hazards modeling examined the association between early screening and detection of incident CV risk factors: HTN, prediabetes, diabetes mellitus type 2, or hyperlipidemia. RESULTS: Among 4194 women with HDP, 1172 (28%) received early BP screening. Older age, pre-existing hyperlipidemia, diabetes, sickle cell disease, hypothyroidism, gestational diabetes, and delivery during or after 2014 were independently associated with early BP screening, whereas Hispanic ethnicity was associated with late BP screening. Early BP screening was most commonly performed at a primary care visit. After a median follow-up of 3.7 years, 1012 (24%) women had at least one new risk factor detected. Even after adjustment for baseline risk, women receiving early BP screening had a significantly higher rate of incident CV risk factor detection than women receiving late BP screening (56% vs 28%; adj. HR 2.70, 95% CI: 2.33-3.23, p<0.001). CONCLUSIONS: Early postpartum BP screening was performed in a minority of women with HDP, but was associated with greater detection of CV risk factors. More intensive postpartum CV screening and targeted interventions are needed to optimize CV health in this high-risk population of women with HDP.

Preeclampsia With Posterior Reversible Encephalopathy Syndrome at 19 Weeks Gestation Resulting in Intrauterine Fetal Demise.

Posterior reversible encephalopathy syndrome (PRES) can be defined as a clinical syndrome of headache, seizures, visual disturbance, altered mental status, and characteristic magnetic resonance imaging (MRI) findings of vasogenic edema in the posterior subcortical parietal-occipital white matter. There are numerous potential inciting factors, including immunosuppression, renal disease, malignancy, cytotoxic medications, hypertension, preeclampsia, and eclampsia. In this paper, we present the case of a 21-year-old female at 19 weeks gestation presenting with symptoms consistent with preeclampsia with severe features and PRES. She was transferred to our facility after initial stabilization. She had an atypical course of preeclampsia prior to 20 weeks gestation, PRES lacking seizure activity, and ultimately her case resulted in intrauterine fetal demise (IUFD) at 20 weeks and six days gestation. As indicated by its name, PRES is considered a fully reversible syndrome, and the patient recovered after stabilization of her hypertensive disorder and delivery of the fetus. This case illustrates the importance of prompt recognition and treatment of hypertensive disorders in pregnant patients and the possibility of complications that can result in significant morbidity and mortality for both the mother and fetus.

Magnesium sulfate and risk of hypoxic ischemic encephalopathy in a high-risk cohort.

BACKGROUND: Hypoxic ischemic encephalopathy contributes to morbidity and mortality among neonates ≥ 360 weeks' gestation. Evidence of preventative antenatal treatment is limited. Magnesium sulfate has neuroprotective properties among preterm fetuses. Hypertensive disorders of pregnancy are a risk factor for hypoxic ischemic encephalopathy and magnesium sulfate is recommended for maternal seizure prophylaxis among patients with pre-eclampsia with severe features. OBJECTIVES: 1) Determine trends in incidence of hypertensive disorders of pregnancy, antenatal magnesium sulfate and hypoxic ischemic encephalopathy, 2) evaluate the association between hypertensive disorders of pregnancy and hypoxic ischemic encephalopathy and 3) evaluate if, among patients with hypertensive disorders of pregnancy, the odds of hypoxic ischemic encephalopathy is mitigated by receipt of antenatal magnesium sulfate. STUDY DESIGN: We conducted an analysis of a prospective cohort of live births ≥360 weeks' gestation between 2012-2018 within the California Perinatal Quality Care Collaborative registry, linked with the California Department of Health Care Access and Information files. We used Cochran-Armitage tests to assess trends in hypertensive disorders, encephalopathy diagnoses, and magnesium sulfate utilization, and compared demographic factors between patients with or without hypertensive disorders of pregnancy or treatment with magnesium sulfate. Hierarchical logistic regression models were built to explore if hypertensive disorders of pregnancy were associated with any severity and moderate/severe hypoxic ischemic encephalopathy. Separate hierarchical logistic regression models were built among those with hypertensive disorders of pregnancy to evaluate the association of magnesium sulfate with hypoxic ischemic encephalopathy. RESULTS: Among 44,314 unique infants, the diagnosis of hypoxic ischemic encephalopathy, maternal hypertensive disorders of pregnancy and the use of magnesium sulfate increased over time. Compared to patients with hypertensive disorders of pregnancy alone, patients with hypertensive disorders treated with magnesium sulfate represented a higher risk population. They were more likely to be publicly insured, born 36-38 weeks' gestation, be small for gestational age, have lower Apgar scores, require a higher level of resuscitation at delivery, have prolonged rupture of membranes, preterm labor, fetal distress, and undergo operative delivery (all p-values <0.002). Hypertensive disorders of pregnancy were associated with hypoxic ischemic encephalopathy (aOR 1.26, 95% CI 1.13-1.40, p-value <.001) and specifically moderate/severe hypoxic ischemic encephalopathy (aOR 1.26, 95% CI 1.11-1.42, p-value <.001). Among patients with hypertensive disorders of pregnancy, treatment with magnesium sulfate was associated with 29% reduction in the odds of neonatal hypoxic ischemic encephalopathy (aOR 0.71, 95% CI 0.52-0.97, p-value= 0.03) and a 37% reduction in the odds of moderate/severe neonatal hypoxic ischemic encephalopathy (aOR 0.63, 95% CI 0.42-0.94, p-value=0.03). CONCLUSION: Hypertensive disorders of pregnancy are associated with hypoxic ischemic encephalopathy and specifically, moderate/severe disease. Among people with hypertensive disorders, receipt of antenatal magnesium sulfate is associated with significant reduction in the odds of hypoxic ischemic encephalopathy and moderate/severe disease in a neonatal cohort admitted to the NICU ≥360 weeks' gestation. The findings of this observational study cannot prove causality and are intended to be hypothesis generating for future clinical trials on MgSO4 in term infants.

Implication of viruses in the etiology of preeclampsia.

Preeclampsia is one of the most common disorders that poses threat to both mothers and neonates and a major contributor to perinatal morbidity and mortality worldwide. Viral infection during pregnancy is not typically considered to cause preeclampsia; however, syndromic nature of preeclampsia etiology and the immunomodulatory effects of viral infections suggest that microbes could trigger a subset of preeclampsia. Notably, SARS-CoV-2 infection is associated with an increased risk of preeclampsia. Herein, we review the potential role of viral infections in this great obstetrical syndrome. According to in vitro and in vivo experimental studies, viral infections can cause preeclampsia by introducing poor placentation, syncytiotrophoblast stress, and/or maternal systemic inflammation, which are all known to play a critical role in the development of preeclampsia. Moreover, clinical and experimental investigations have suggested a link between several viruses and the onset of preeclampsia via multiple pathways. However, the results of experimental and clinical research are not always consistent. Therefore, future studies should investigate the causal link between viral infections and preeclampsia to elucidate the mechanism behind this relationship and the etiology of preeclampsia itself.

Posterior Reversible Encephalopathy Syndrome in a Late Postpartum Patient With a Rare Complication of Subarachnoid Hemorrhage.

Posterior reversible encephalopathy syndrome (PRES) is considered a neuroclinical syndrome of headache, confusion, visual changes, and seizures associated with neuroimaging findings of posterior cerebral white matter edema. Although the incidence of the syndrome is largely unknown, this condition is becoming increasingly recognized. The prognosis is generally good with most symptoms resolving within one week and lesions on imaging resolving in two weeks. Death and significant neurological disability have been reported but are relatively rare. In this report, we present a 10-day postpartum patient with an atypical history of headache and seizure-like activity. Neuroimaging revealed findings consistent with PRES as well as a rare complication of subarachnoid hemorrhage. This case highlights the importance of clinicians considering preeclampsia/eclampsia-induced PRES when encountering a postpartum patient with headache and hypertension to further reduce morbidity and mortality in this patient population.

Risk factors for relaparotomy after a cesarean delivery: a case-control study.

BACKGROUND: Relaparotomy following a cesarean delivery (CD) is an infrequent complication, with inconsistency regarding risk factors and indications for its occurrence. We therefore aimed to determine risk factors and indications for a relaparotomy following a CD at a single large tertiary center. METHODS: A retrospective case-control single-center study (2013-2023). We identified all women who had a relaparotomy up to six weeks following a CD (study group). Maternal characteristics, obstetrical and surgical data were compared to a control group in a 1:2 ratio. Controls were women with a CD before and immediately after each case in the study group, who did not undergo a relaparotomy. Included were CDs occurring after 24 gestational weeks. CD performed at different centers and indications for repeat surgery unrelated to the primary surgery (e.g., appendicitis) were excluded. Logistic regression was used to adjust for potential confounders. RESULTS: During the study period, 131,268 women delivered at our institution. Of them, 28,280 (21.5%) had a CD, and 130 patients (0.46%) underwent a relaparotomy. Relaparotomies following a CD occurred during the first 24 h, the first week, and beyond the first week, in 59.2%, 33.1%, and 7.7% of cases, respectively. In the multivariable logistic regression analysis, relaparotomy was significantly associated with Mullerian anomalies (aOR 3.33, 95%CI 1.08-10.24, p = 0.036); uterine fibroids (aOR 3.17, 95%CI 1.11-9.05,p = 0.031); multiple pregnancy (aOR 4.1, 95%CI 1.43-11.79,p = 0.009); hypertensive disorders of pregnancy (aOR 3.46, 95%CI 1.29-9.3,p = 0.014); CD during the second stage of labor (aOR 2.54, 95%CI 1.15-5.88, p = 0.029); complications during CD (aOR 1.62, 95%CI 1.09-3.21,p = 0.045); and excessive bleeding during CD or implementation of bleeding control measures (use of tranexamic acid, a hemostatic agent, or a surgical drain) (aOR 2.23, 95%CI 1.29-4.12,p = 0.012). Indications for relaparotomy differed depending on the time elapsed from the CD, with suspected intra-abdominal bleeding (36.1%) emerging as the primary indication within the initial 24 h. CONCLUSION: We detected several pregnancy, intrapartum, and intra-operative risk factors for the need for relaparotomy following a CD. Practitioners may utilize these findings to proactively identify women at risk, thereby potentially reducing their associated morbidity.

First trimester plasma PER- AND Polyfluoroalkyl Substances (PFAS) and blood pressure trajectories across the second and third trimesters of pregnanacy.

BACKGROUND: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes. OBJECTIVES: To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity. METHODS: In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity. RESULTS: We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories. CONCLUSION: Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother.

Hypertensive disorders of pregnancy among women with cardiovascular disease in Norway: A historical cohort study.

INTRODUCTION: Women with cardiovascular disease may be at increased risk of hypertensive disorders of pregnancy (HDP). We aimed to: (1) Investigate the occurrence of HDP in a cohort of pregnant women with cardiovascular disease and compare it with the occurrence in the general population. (2) Assess the association between maternal cardiovascular risk and risk of HDP. MATERIAL AND METHODS: We reviewed clinical data on a cohort of 901 pregnancies among 708 women with cardiovascular disease who were followed at the National Unit for Pregnancy and Heart Disease and gave birth at Oslo University Hospital between 2003 and 2018. The exposure under study was maternal cardiovascular risk, classified as low, moderate, or high based on a modified classification by the World Health Organization. The main outcome of interest was HDP, which included pre-eclampsia and gestational hypertension. The proportion of HDP cases in the general population in the same period was extracted from the Medical Birth Registry of Norway. We used logistic regression to estimate crude and adjusted odds ratios (OR) of HDP, with associated 95% confidence intervals (CIs), for women with moderate- and high cardiovascular risk compared to women with low risk. RESULTS: The occurrence of HDP in the study cohort was 12.1% (95% CI: 10.0%-14.4%) and varied between 8.7% (95% CI: 6.5%-11.3%) in the low-risk group, 15.7% (95% CI: 11.1%-21.4%) in the moderate-risk group, and 22.2% (95% CI: 15.1%-30.8%) in the high-risk group. By contrast, the nationwide occurrence of HDP was 5.1% (95% CI: 5.1%-5.2%). In the study cohort, the proportions of pregnancies with gestational hypertension and pre-eclampsia were similar (6.3% and 5.8%, respectively). Compared to pregnancies with low cardiovascular risk, the adjusted OR of HDP was 2.04 (95% CI: 1.21-3.44) in the moderate-risk group and 2.99 (95% CI: 1.73-5.18) in the high-risk group. CONCLUSIONS: The occurrence of hypertensive disease of pregnancy in the study cohort was more than doubled compared to the general population in Norway. The risk of HDP increased with maternal cardiovascular risk group. We recommend taking into account maternal cardiovascular risk group when assessing risk and prophylaxis of HDP.

Predicting Time to Delivery in Hypertensive Disorders: Assessing PlGF and sFlt-1 with the Novel Parameter 'Mtp-Multiples of a Normal Term Placenta'.

Background: Imbalanced angiogenesis is characteristic of normal placental maturation but it also signals placental dysfunction, underlying hypertensive disorders during pregnancy. This study aimed to investigate the relationship between angiogenic placental aging, measured by markers placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) using the new index "Multiples of a normal term placenta" (Mtp) and the duration of pregnancy. Methods: A retrospective observational study was conducted, including singleton pregnancies diagnosed or suspected of hypertensive disorders after the 20th gestational week. Mtp measures how far a single dosage of angiogenic marker deviates from the expected value in an uncomplicated full-term pregnancy (Mpt = sFlt-1/sFlt-1 reference value or PIGF/PIGF reference value). We considered the 90th, 95th, and 97.5th centiles for sFlt-1 and the 2.5th, 5th, and 10th centiles for PlGF as references. Results: The categories with longer time to delivery, regardless of gestational age, were: Mtp PlGF 10th c ≥ 2, ≥3 and Mtp sFlt-1 90th c ≤ 0.5 (median days of 9, 11, 15 days, respectively). These two categories Mtp sFlt-1 90th c ≥ 3 and Mtp sFlt-1 97.5th c ≥ 2 allow the identification of women at risk for imminent delivery within 1 day. Women who were deemed at low/medium risk based on the sFlt-1/PIGF ratio appeared to be at high risk when considering the individual values of sFlt-1 and/or PIGF. Conclusions: This new Mtp index for sFlt-1 and PlGF could be employed to assess the degree of placental aging in women with hypertensive disorders. It represents a valid tool for evaluating the risk of imminent birth, irrespective of gestational age, surpassing the current stratification based on the sFlt-1/PIGF ratio.

N-terminal prohormone of brain natriuretic peptide in gestational hypertension and preeclampsia - State of the art.

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a non-active prohormone secreted by ventricular cardiomyocytes into the circulation in response to ventricle overload, mainly due to increased blood volume. The changes in NT-proBNP levels during pregnancy have been investigated in multiple studies. In the case of hypertensive disorders of pregnancy, increased vasoconstriction leads to increased blood pressure and afterload. Together with the volume overload of pregnancy, it leads to higher NT-proBNP secretion. As hypertensive disorders of pregnancy are among the leading causes of prematurity and perinatal mortality, early prediction and diagnosis of gestational hypertension, and preeclampsia are essential for improving maternal and infant prognosis. NT-proBNP has been regarded as a potential biomarker of hypertensive disorders of pregnancy. In this review, we have thoroughly summarized the current data on the prognostic and diagnostic utility of NT-proBNP in patients with gestational hypertension and preeclampsia. NT-proBNP values may help distinguish between non-preeclamptic and preeclamptic patients, even if there are no significant differences in blood pressure. Moreover, in pregnancies complicated by preeclampsia, the value of increased NT-proBNP level is related to the stage and the severity of the disease. Further improvement of our knowledge about NT-proBNP as a diagnostic biomarker and a putative predictor of adverse cardiac events in women with hypertensive disorders of pregnancy should lead to better management of these 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.

Biomarkers of Pre-eclampsia in Pregnant Women With Gestational Diabetes and Pre-existing Type 2 Diabetes: A Systematic Review.

Pre-eclampsia (PE) is one of the leading causes of maternal and perinatal health morbidity, producing more than 4.6% of complications in pregnancy worldwide. This systematic review was conducted to determine the significance of specific biomarkers in predicting PE in gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM). The review measured and explained the significant abnormalities in lipids, blood glucose, cytokines, inflammatory markers, placental proteins, urinary proteins, and other serum biomarkers that contribute to the development of PE in GDM and type 2 DM populations. We searched CINAHL, EMBASE, Medline, Maternity and Infant care, Scopus, and Web of Science. Studies were included if they had a measurable component in the blood serum or urine of women who developed PE and suffered from GDM or pre-existing type 2 DM. A narrative synthesis was conducted instead of a meta-analysis due to the high heterogeneity of data from the studies. A total of 2,593 studies were screened, producing eight relevant studies. Twenty-seven different biomarkers were investigated from the study group of 40 to 1,344 participants. No single biomarker was identified; however, there is a need for further research on specific biomarkers of PE, especially in CRP, FABP4, and microalbuminuria in the GDM-PE group and calprotectin in the type 2 DM population. Many biomarkers were identified as practical in predicting PE when combined with other biomarkers and more data are required to verify the predictability of the diagnostic markers in pregnant women.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Hypertensive disorders of pregnancy, neonatal outcomes and offspring developmental delay in Japan: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

INTRODUCTION: Developmental delay at an early age indicates the probability of continued problems after school age. Hypertensive disorders of pregnancy (HDP) are associated with developmental delays in offspring, with inconsistent outcomes. Neonatal outcomes vary according to HDP exposure and are relevant to development in later years. Here we aimed to clarify the relationship between HDP and developmental delay in offspring and whether neonatal outcomes mediate this association. MATERIAL AND METHODS: We used data from 5934 mother-child pairs from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a prospective cohort study conducted in Japan between July 2013 and March 2017. The Ages and Stages Questionnaires, third edition, at 24 and 42 months of age, measured developmental delay in five areas. We performed multivariate quasi-Poisson regression and causal mediation analysis by neonatal outcomes. RESULTS: At 24 months of age, compared to offspring born from normotensive mothers, offspring born from HDP-affected mothers were more likely to experience developmental delay (risk ratio [RR] 1.29, 95% confidence interval [CI]: 1.09-1.52) in the areas of communication (RR 1.21, 95% CI: 1.00-1.45) and personal-social (RR 1.15, 95% CI: 1.03-1.28). This association was mediated by neonatal outcomes: preterm birth, neonatal asphyxia, NICU admission, and neonatal small head circumference. No association was observed between HDP and developmental delay at 42 months of age. CONCLUSIONS: Exposure to HDP during fetal life is associated with offspring developmental delay. This association is partly mediated by neonatal outcomes.

Postpartum and interpregnancy care of women with a history of hypertensive disorders of pregnancy.

Hypertensive disorders of pregnancy (HDP) are common complications associated with maternal and neonatal morbidity and mortality worldwide. Insights gained from long-term cohort studies have revealed that women with a history of HDP are predisposed to recurrent HDP in subsequent pregnancies and face heightened risks for cardiovascular and metabolic diseases later in life. Pregnancy is a unique condition that overloads maternal cardiac and metabolic functions, and is recognized as a "maternal stress test" for future cardiovascular and metabolic diseases. Pregnancy and postpartum period provide a valuable opportunity for identifying women with underlying and unrecognized cardiovascular and metabolic risk factors. Establishing an effective postpartum healthcare program for women who have experienced HDP is crucial in reducing the future risk of health complications. Postpartum care consists of supportive care for both mothers and children, including not only the assessment of physical and psychological well-being but also long-term postpartum preventive health management. Interpregnancy care is a continuum from postpartum care and includes supportive care to prepare for future pregnancies. Various initiatives across nations have been initiated to establish follow-up programs for women with a history of HDP; however, sufficient evidence of the impact of such programs is not available. Substantial challenges persist in establishing an efficient postpartum follow-up program, including educational strategies, selection of effective lifestyle interventions, and collaboration among various healthcare providers. This review outlines the postpartum and interpregnancy care of women who have experienced HDP as well as the current status and challenges of related healthcare initiatives in Japan.