Hypertension Persisting after Pre-Eclampsia: A Prospective Cohort Study at Mulago Hospital,Uganda

Background

Pre-eclampsia/eclampsia usually resolves after delivery but sometimes hypertension persists and cardiovascular disease develops later. Our objective was to determine the incidence and maternal socio-demographic and obstetric risk factors for persistence of hypertension in women with pre-eclampsia/eclampsia.

Methods

This was a prospective cohort study conducted from July 2009 to June 2011 at Mulago Hospital labour ward and postnatal clinics. We followed up 188 women admitted with pre-eclampsia/eclampsia until 3 months after delivery. Data was collected using interviewer-administered questionnaires, examination of participants and review of medical records. Stata (version12) software was used for data analysis. Univariable analysis was used to compute the relative risk of persistent hypertension at the 95% confidence level. This was followed by multivariable logistic regression analysis to determine factors independently associated with persistence of hypertension.

Results

64 (34%) out of the 188 women analysed had persistent hypertension three months after delivery. Maternal age, gestational age at delivery and parity were predictors of persistent hypertension.

Conclusion

The proportion of women with pre-eclampsia/eclampsia at risk of persistent hypertension at three months after delivery was high, with nearly one of three mothers remaining hypertensive. Follow up of mothers who develop pre-eclampsia is important so that early diagnosis and management of chronic hypertension can be made to avoid long term morbidity and mortality.     

Relationships of risk factors for pre-eclampsia with patterns of occurrence of isolated gestational proteinuria during normal term pregnancy

Background

Isolated gestational proteinuria may be part of the pre-eclampsia disease spectrum. Confirmation of its association with established pre-eclampsia risk factors and higher blood pressure in uncomplicated pregnancies would support this concept.

Methods

Data from 11,651 women from the Avon Longitudinal Study of Parents and Children who had a term live birth but did not have pre-existing hypertension or diabetes or develop gestational diabetes or preeclampsia were used. Proteinuria was assessed repeatedly (median 12 measurements per woman) by dipstick and latent class analysis was used to identify subgroups of the population with different patterns of proteinuria in pregnancy.

Results

Higher maternal pre-pregnancy body mass index (BMI), younger age, nulliparity and twin pregnancy were independently associated with increased odds of any proteinuria in pregnancy. Women who experienced proteinuria showed five patterns: proteinuria in early pregnancy only (≤20 weeks gestation), and onset at 21–28 weeks, 29–32 weeks, 33–36 weeks and ≥37 weeks gestation. There were higher odds of proteinuria onset after 33 weeks in obese women and after 37 weeks in nulliparous women compared with normal weight and multiparous women respectively. Smoking in pregnancy was weakly negatively associated with odds of proteinuria onset after 37 weeks. Twin pregnancies had higher odds of proteinuria onset from 29 weeks. In women with proteinuria onset after 33 weeks blood pressure was higher in early pregnancy and at the end of pregnancy.

Conclusions

Established pre-eclampsia risk factors were related to proteinuria occurrence in late gestation in healthy term pregnancies, supporting the hypothesis that isolated gestational proteinuria may represent an early manifestation of pre-eclampsia.     

Pregnancy complications among women born preterm

Background:

Adults who were born with low birth weights are at increased risk of cardiovascular and metabolic conditions, including pregnancy complications. Low birth weight can result from intrauterine growth restriction, preterm birth or both. We examined the relation between preterm birth and pregnancy complications later in life.

Methods:

We conducted a population-based cohort study in the province of Quebec involving 7405 women born preterm (554 < 32 weeks, 6851 at 32–36 weeks) and a matched cohort of 16 714 born at term between 1976 and 1995 who had a live birth or stillbirth between 1987 and 2008. The primary outcome measures were pregnancy complications (gestational diabetes, gestational hypertension, and preeclampsia or eclampsia).

Results:

Overall, 19.9% of women born at less than 32 weeks, 13.2% born at 32–36 weeks and 11.7% born at term had at least 1 pregnancy complication at least once during the study period (p < 0.001). Women born small for gestational age (both term and preterm) had increased odds of having at least 1 pregnancy complication compared with women born at term and at appropriate weight for gestational age. After adjustment for various factors, including birth weight for gestational age, the odds of pregnancy complications associated with preterm birth was elevated by 1.95-fold (95% confidence interval [CI] 1.54–2.47) among women born before 32 weeks’ gestation and 1.14-fold (95% CI 1.03–1.25) among those born at 32–36 weeks’ gestation relative to women born at term.

Interpretation:

Being born preterm, in addition to, and independent of, being small for gestational age, was associated with a significantly increased risk of later having pregnancy complications.Numerous studies examining cohorts born mostly in the first half of the 20th century have emphasized the inverse relation between low birth weight and incidence later in life of cardiovascular and metabolic conditions, such as hypertension and type 2 diabetes.¹ Epidemiologic studies seldom consider the effects of preterm birth and intrauterine growth restriction separately when studying the relation of these factors to low birth weight. Studies have suggested that adolescents and young adults born preterm have higher incidence of risk factors for metabolic (insulin resistance) and cardiovascular (higher blood pressure) dysfunctions.^2–4 With the increased survival of preterm newborns over the past 30 years, a substantially greater proportion of young adults are born before 37 or even 32 weeks’ gestation and thus may represent a growing population at risk for conditions related to metabolic syndrome as they get older.Pregnancy can be considered a stress test for future cardiovascular and metabolic health. Women with a history of gestational diabetes, gestational hypertension or preeclampsia are at increased risk of metabolic syndrome later in life.^5–7 Furthermore, studies have shown that women born with low birth weights are at increased risk of gestational hypertension, preeclampsia and gestational diabetes.^8–10 However, many of these studies either have not taken into account gestational age or have a number of shortcomings, such as small sample, young population (mostly teenagers), degree of prematurity not specified or study population consisting mostly of late preterm births.^6,11,12In the province of Quebec, weight and gestational age have been recorded in a registry for all births since 1976, and data on all hospital-based diagnoses have been collected since 1987. The aim of our study was to examine the relation between preterm birth and later pregnancy complications, independently of intrauterine growth restriction, among women born preterm in Quebec between 1976 and 1995 who delivered at least 1 newborn between 1987 and 2008. We also examined whether this association represents a dose–response relation, namely, whether the more prematurely born a woman is, the greater her risk of gestational diabetes, gestational hypertension, preeclampsia or eclampsia.     

Retinal Vein Occlusion and Pregnancy,Pre-Eclampsia,and Eclampsia: The Results from a Nationwide,Population-Based Study Using the National Claim Database

Objective

To investigate the incidence of retinal vein occlusion (RVO) in pregnant women and in the subpopulation of pregnant women with pre-eclampsia/eclampsia compared to that in the age-matched general female population to determine if there is increased risk of RVO in pregnancy.

Design

Nationwide population-based retrospective study using data entered into the Korean national health claims database from 2007 to 2011.

Setting and Participants

Of the incident RVO cases in the database, RVO cases that occurred during the pregnancy-associated period, which spanned a 52-week period from 40-weeks-before to 12-weeks-after childbirth, were identified. Of these cases, the presence of pre-eclampsia/eclampsia was determined.

Main Outcome and Measure

The standardized incidence ratios (SIRs) of RVO in the general pregnant population and in the pregnant population with pre-eclampsia/eclampsia were determined with respect to the age-matched general female population.

Results

Pregnancy-related RVO was identified in 33 cases from the 1.8 million women who experience childbirth during the study period, while the expected number of cases calculated by the direct standardization to the age-matched general population was 113. Of the 33 patients, 12 patients (36.4%) had pre-eclampsia or eclampsia. The SIR for the general pregnant population in reference to the age-matched general female population was 0.29 (95% CI, 0.20–0.41). In contrast, the SIR for the pregnant population with pre-eclampsia/eclampsia in reference to the age-matched general female population and the age-matched general pregnant population was 67.50 (95% CI, 34.88–117.92) and 246.50 (95% CI, 127.37–430.59), respectively.

Conclusions and Relevance

The results suggest that pre-eclampsia/eclampsia is a risk factor for RVO, while pregnancy itself may not be a risk factor for RVO.     

Association between hypertensive disorders during pregnancy and end-stage renal disease: a population-based study

Background:

Studies into the association between hypertensive disorders during pregnancy and end-stage renal disease are limited. We investigated the risk of end-stage renal disease after delivery among women with hypertensive disorders during pregnancy.

Methods:

We used insurance claims data from 1998 to 2009 to identify 26 651 women aged 19–40 years old who experienced hypertensive disorders during pregnancy; these women had no history of hypertension, diabetes, kidney disease or lupus. We also randomly selected 213 397 women without hypertensive disorders during pregnancy as a comparison cohort; the frequency was matched by age and index year of pregnancy. We compared the incidence of end-stage renal disease in the 2 cohorts. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) after controlling for demographic and clinical factors.

Results:

Women with hypertensive disorders during pregnancy had a greater risk of chronic kidney disease and end-stage renal disease, with adjusted HRs of 9.38 (95% CI 7.09–12.4) and 12.4 (95% CI 8.54–18.0), respectively, after controlling for urban status, coronary artery disease, congestive heart failure, hyperlipidemia and abruption. The HR for end-stage renal disease was 2.72 (95% CI 1.76–4.22) after we also controlled for hypertension and diabetes. Women with preeclampsia or eclampsia had a higher risk of end-stage renal disease (adjusted HR 14.0, 95% CI 9.43–20.7) than women who had gestational hypertension only (adjusted HR 9.03, 95% CI 5.20–15.7).

Interpretation:

Women with hypertensive disorders during pregnancy were at a high risk of end-stage renal disease. The risk was much greater for women who had preeclampsia or eclampsia than those who had gestational hypertension only.Hypertensive disorders during pregnancy are major causes of maternal and fetal morbidity and mortality, affecting 5%–10% of pregnancies.^1,2 Hypertensive disorders during pregnancy include gestational hypertension and preeclampsia.³ Gestational hypertension is referred to as new-onset hypertension (blood pressure > 140/90 mm Hg) without proteinuria after 20-weeks’ gestation.³ Preeclampsia is characterized by new-onset hypertension (blood pressure > 140/90 mm Hg) with proteinuria of at least 300 mg in a 24-hour urine sample after 20-weeks’ gestation.³ Gestational hypertension progresses to preeclampsia in 10%–20% of pregnant women.⁴ The risk factors associated with preeclampsia include family history of preeclampsia, first pregnancy, multiple gestation, advanced maternal age, obesity, pre-existing hypertension, renal disease and diabetes mellitus.⁵ Women with a history of hypertensive disorders during pregnancy are at higher risk of hypertension, diabetes mellitus and cardiovascular disease in later life. Hypertensive disorders during pregnancy and cardiovascular disease share several common risk factors, such as obesity, pre-existing hypertension, renal disease and insulin resistance.^6–14 Hypertensive disorders during pregnancy also increase the risk of cardiovascular disease because of long-term metabolic and vascular changes.¹⁵Hypertensive disorders during pregnancy affect the function and morphology of the kidney.¹⁶ Previous studies have reported an increased prevalence of microalbuminuria after pregnancy in women who had a hypertensive disorder during pregnancy.^17,18 In a case–control study, there was an association between biopsy-proven renal disease and a history of preeclampsia.¹⁹ However, studies about whether hypertensive disorders during pregnancy are associated with end-stage renal disease in later life are limited.²⁰ Only 1 study, performed using birth and renal registries from Norway, has reported that women with preeclampsia during their first pregnancy had a 3.2-fold higher risk of end-stage renal disease.²⁰ In the present study, we investigated the risk of end-stage renal disease among Taiwanese women who had a hypertensive disorder during pregnancy.     

Salinity in Drinking Water and the Risk of (Pre)Eclampsia and Gestational Hypertension in Coastal Bangladesh: A Case-Control Study

Background

Hypertensive disorders in pregnancy are among the leading causes of maternal and perinatal death in low-income countries, but the aetiology remains unclear. We investigated the relationship between salinity in drinking water and the risk of (pre)eclampsia and gestational hypertension in a coastal community.

Methods

A population-based case-control study was conducted in Dacope, Bangladesh among 202 pregnant women with (pre)eclampsia or gestational hypertension, enrolled from the community served by the Upazilla Health Complex, Dacope and 1,006 matched controls from the same area. Epidemiological and clinical data were obtained from all participants. Urinary sodium and sodium levels in drinking water were measured. Logistic regression was used to calculate odds ratios, and 95% confidence intervals.

Findings

Drinking water sources had exceptionally high sodium levels (mean 516.6 mg/L, S.D 524.2). Women consuming tube-well (groundwater) were at a higher disease risk than rainwater users (p<0.001). Adjusted risks for (pre)eclampsia and gestational hypertension considered together increased in a dose-response manner for increasing sodium concentrations (300.01–600 mg/L, 600.1–900 mg/L, >900.01 mg/L, compared to <300 mg/L) in drinking water (ORs 3.30 [95% CI 2.00–5.51], 4.40 [2.70–7.25] and 5.48 [3.30–9.11] (p-trend<0.001). Significant associations were seen for both (pre)eclampsia and gestational hypertension separately.

Interpretation

Salinity in drinking water is associated with increased risk of (pre)eclampsia and gestational hypertension in this population. Given that coastal populations in countries such as Bangladesh are confronted with high salinity exposure, which is predicted to further increase as a result of sea level rise and other environmental influences, it is imperative to develop and evaluate affordable approaches to providing water with low salt content.     

Maternal weight change from prepregnancy to 18 months postpartum and subsequent risk of hypertension and cardiovascular disease in Danish women: A cohort study

BackgroundOne-fourth of women experience substantially higher weight years after childbirth. We examined weight change from prepregnancy to 18 months postpartum according to subsequent maternal risk of hypertension and cardiovascular disease (CVD).Methods and findingsWe conducted a cohort study of 47,966 women with a live-born singleton within the Danish National Birth Cohort (DNBC; 1997–2002). Interviews during pregnancy and 6 and 18 months postpartum provided information on height, gestational weight gain (GWG), postpartum weights, and maternal characteristics. Information on pregnancy complications, incident hypertension, and CVD was obtained from the National Patient Register. Using Cox regression, we estimated adjusted hazard ratios (HRs; 95% confidence interval [CI]) for hypertension and CVD through 16 years of follow-up. During this period, 2,011 women were diagnosed at the hospital with hypertension and 1,321 with CVD. The women were on average 32.3 years old (range 18.0–49.2) at start of follow-up, 73% had a prepregnancy BMI <25, and 27% a prepregnancy BMI ≥25. Compared with a stable weight (±1 BMI unit), weight gains from prepregnancy to 18 months postpartum of >1–2 and >2 BMI units were associated with 25% (10%–42%), P = 0.001 and 31% (14%–52%), P < 0.001 higher risks of hypertension, respectively. These risks were similar whether weight gain presented postpartum weight retention or a new gain from 6 months to 18 months postpartum and whether GWG was below, within, or above the recommendations. For CVD, findings differed according to prepregnancy BMI. In women with normal-/underweight, weight gain >2 BMI units and weight loss >1 BMI unit were associated with 48% (17%–87%), P = 0.001 and 28% (6%–55%), P = 0.01 higher risks of CVD, respectively. Further, weight loss >1 BMI unit combined with a GWG below recommended was associated with a 70% (24%–135%), P = 0.001 higher risk of CVD. No such increased risks were observed among women with overweight/obesity (interaction by prepregnancy BMI, P = 0.01, 0.03, and 0.03, respectively). The limitations of this observational study include potential confounding by prepregnancy metabolic health and self-reported maternal weights, which may lead to some misclassification.ConclusionsPostpartum weight retention/new gain in all mothers and postpartum weight loss in mothers with normal-/underweight may be associated with later adverse cardiovascular health.

Helene Kirkegaard and co-workers study maternal weight changes and cardiovascular risk over 16 years of follow-up.     

Genome-Wide Identification of Epigenetic Hotspots Potentially Related to Cardiovascular Risk in Adult Women after a Complicated Pregnancy

Background

The physiological demands of pregnancy on the maternal cardiovascular system can catapult women into a metabolic syndrome that predisposes to atherosclerosis in later life. We sought to identify the nature of the epigenomic changes associated with the increased cardiovascular disease (CVD) risk in adult women following pre-eclampsia.

Findings

We assessed the genome wide epigenetic profile by methyl-C sequencing of monozygotic parous twin sister pairs discordant for a severe variant of pre-eclampsia. In the adult twin sisters at risk for CVD as a consequence of a complicated pregnancy, a set of 12 differentially methylated regions with at least 50% difference in methylation percentage and the same directional change was found to be shared between the affected twin sisters and significantly different compared to their unaffected monozygous sisters.

Conclusion

The current epigenetic marker set will permit targeted analysis of differentially methylated regions potentially related to CVD risk in large cohorts of adult women following complicated pregnancies.     

Risk Factors and Adverse Perinatal Outcomes among Term and Preterm Infants Born Small-for-Gestational-Age: Secondary Analyses of the WHO Multi-Country Survey on Maternal and Newborn Health

Background

Small for gestational age (SGA) is not only a major indicator of perinatal mortality and morbidity, but also the morbidity risks in later in life. We aim to estimate the association between the birth of SGA infants and the risk factors and adverse perinatal outcomes among twenty-nine countries in Africa, Latin America, the Middle East and Asia in 359 health facilities in 2010–11.

Methods

We analysed facility-based, cross-sectional data from the WHO Multi-country Survey on Maternal and Newborn Health. We constructed multilevel logistic regression models with random effects for facilities and countries to estimate the risk factors for SGA infants using country-specific birthweight reference standards in preterm and term delivery, and SGA’s association with adverse perinatal outcomes. We compared the risks and adverse perinatal outcomes with appropriate for gestational age (AGA) infants categorized by preterm and term delivery.

Results

A total of 295,829 singleton infants delivered were analysed. The overall prevalence of SGA was highest in Cambodia (18.8%), Nepal (17.9%), the Occupied Palestinian Territory (16.1%), and Japan (16.0%), while the lowest was observed in Afghanistan (4.8%), Uganda (6.6%) and Thailand (9.7%). The risk of preterm SGA infants was significantly higher among nulliparous mothers and mothers with chronic hypertension and preeclampsia/eclampsia (aOR: 2.89; 95% CI: 2.55–3.28) compared with AGA infants. Higher risks of term SGA were observed among sociodemographic factors and women with preeclampsia/eclampsia, anaemia and other medical conditions. Multiparity (> = 3) (AOR: 0.88; 95% CI: 0.83–0.92) was a protective factor for term SGA. The risk of perinatal mortality was significantly higher in preterm SGA deliveries in low to high HDI countries.

Conclusion

Preterm SGA is associated with medical conditions related to preeclampsia, but not with sociodemographic status. Term SGA is associated with sociodemographic status and various medical conditions.     

Incidence and predictors of severe obstetric morbidity: case-control study

ObjectiveTo estimate the incidence and predictors of severe obstetric morbidity.DesignDevelopment of definitions of severe obstetric morbidity by literature review. Case-control study from a defined delivery population with four randomly selected pregnant women as controls for every case.SettingAll 19 maternity units within the South East Thames region and six neighbouring hospitals caring for pregnant women from the region between 1 March 1997 and 28 February 1998.Participants48 865 women who delivered during the time frame.ResultsThere were 588 cases of severe obstetric morbidity giving an incidence of 12.0/1000 deliveries (95% confidence interval 11.2 to 13.2). During the study there were five maternal deaths attributed to conditions studied. Disease specific morbidities per 1000 deliveries were 6.7 (6.0 to 7.5) for severe haemorrhage, 3.9 (3.3 to 4.5) for severe pre-eclampsia, 0.2 (0.1 to 0.4) for eclampsia, 0.5 (0.3 to 0.8) for HELLP (Haemolysis, Elevated Liver enzymes, and Low Platelets) syndrome, 0.4 (0.2 to 0.6) for severe sepsis, and 0.2 (0.1 to 0.4) for uterine rupture. Age over 34 years, non-white ethnic group, past or current hypertension, previous postpartum haemorrhage, delivery by emergency caesarean section, antenatal admission to hospital, multiple pregnancy, social exclusion, and taking iron or anti-depressants at antenatal booking were all independently associated with morbidity after adjustment.ConclusionSevere obstetric morbidity and its relation to mortality may be more sensitive measures of pregnancy outcome than mortality alone. Most events are related to obstetric haemorrhage and severe pre-eclampsia. Caesarean section quadruples the risk of morbidity. Development and evaluation of ways of predicting and reducing risk are required with particular emphasis paid on the management of haemorrhage and pre-eclampsia.

What is already known on this topic

Maternal mortality is used internationally as a measure of the quality of obstetric intervention, although it is now rare in the developed worldHospital based series estimating the incidence of severe obstetric morbidity have used different definitionsEstimated incidence of severe obstetric morbidity ranges from 0.05 to 1.09

What this study adds

With clear definitions and population based estimates of some severe obstetric morbidities this study estimated the overall incidence of severe obstetric morbidity as 1.2 % of deliveriesTwo thirds of the cases are related to severe haemorrhage, one third to hypertensive disordersRisk factors for severe maternal morbidity include maternal age >34, social exclusion, non-white, hypertension, previous postpartum haemorrhage, induction of labour, and caesarean section     

Hypertensive Disorders of Pregnancy: A Systematic Review of International Clinical Practice Guidelines

Background

Clinical practice guidelines (CPGs) are developed to assist health care providers in decision-making. We systematically reviewed existing CPGs on the HDPs (hypertensive disorders of pregnancy) to inform clinical practice.

Methodology & Principal Findings

MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, Health Technology Assessments, and Database of Abstracts of Reviews of Effects (Ovid interface), Grey Matters, Google Scholar, and personal records were searched for CPGs on the HDPs (Jan/03 to Nov/13) in English, French, Dutch, or German. Of 13 CPGs identified, three were multinational and three developed for community/midwifery use. Length varied from 3–1188 pages and three guidelines did not formulate recommendations. Eight different grading systems were identified for assessing evidence quality and recommendation strength. No guideline scored ≧80% on every domain of the AGREE II, a tool for assessing guideline methodological quality; two CPGs did so for 5/6 domains. Consistency was seen for (i) definitions of hypertension, proteinuria, chronic and gestational hypertension; (ii) pre-eclampsia prevention for women at increased risk: calcium when intake is low and low-dose aspirin, but not vitamins C and E or diuretics; (iii) antihypertensive treatment of severe hypertension; (iv) MgSO4 for eclampsia and severe pre-eclampsia; (v) antenatal corticosteroids at <34 wks when delivery is probable within 7 days; (vi) delivery for women with severe pre-eclampsia pre-viability or pre-eclampsia at term; and (vii) active management of the third stage of labour with oxytocin. Notable inconsistencies were in: (i) definitions of pre-eclampsia and severe pre-eclampsia; (ii) target BP for non-severe hypertension; (iii) timing of delivery for women with pre-eclampsia and severe pre-eclampsia; (iv) MgSO4 for non-severe pre-eclampsia, and (v) postpartum maternal monitoring.

Conclusions

Existing international HDP CPGs have areas of consistency with which clinicians and researchers can work to develop auditable standards, and areas of inconsistency that should be addressed by future research.     

The Association between Prenatal Psychosocial Stress and Blood Pressure in the Child at Age 5-7 Years

Objective

Prenatal maternal stress could have permanent effects on the offspring’s tissue structure and function, which may predispose to cardiovascular diseases. We investigated whether maternal psychosocial stress is a prenatal factor affecting the blood pressure (BP) of offspring.

Study Design

In the Amsterdam Born Children and their Development (ABCD) study, around gestational week 16, depressive symptoms, state-anxiety, pregnancy-related anxiety, parenting daily hassles and job strain were recorded by questionnaire. A cumulative stress score was also calculated (based on 80^th percentiles). Systolic and diastolic BP and mean arterial pressure (MAP) were measured in the offspring at age 5–7 years. Inclusion criteria were: no use of antihypertensive medication during pregnancy; singleton birth; no reported cardiovascular problems in the child (N = 2968 included).

Results

After adjustment for confounders, the single stress scales were not associated with systolic and diastolic BP, MAP and hypertension (p>0.05). The presence of 3–4 psychosocial stressors prenatally (4%) was associated with 1.5 mmHg higher systolic and diastolic BP (p = 0.046; p = 0.04) and 1.5 mmHg higher MAP in the offspring (p = 0.02) compared to no stressors (46%). The presence of 3–4 stressors did not significantly increase the risk for hypertension (OR 1.8; 95% CI 0.93.4). Associations did not differ between sexes. Bonferroni correction for multiple testing rendered all associations non-significant.

Conclusions

The presence of multiple psychosocial stressors during pregnancy was associated with higher systolic and diastolic BP and MAP in the child at age 5–7. Further investigation of maternal prenatal stress may be valuable for later life cardiovascular health.     

Optimal Timing of Delivery among Low-Risk Women with Prior Caesarean Section: A Secondary Analysis of the WHO Multicountry Survey on Maternal and Newborn Health

Objective

To investigate optimal timing of elective repeat caesarean section among low-risk pregnant women with prior caesarean section in a multicountry sample from largely low- and middle-income countries.

Design

Secondary analysis of a cross-sectional study.

Setting

Twenty-nine countries from the World Health Organization Multicountry Survey on Maternal and Newborn Health.

Population

29,647 women with prior caesarean section and no pregnancy complications in their current pregnancy who delivered a term singleton (live birth and stillbirth) at gestational age 37–41 weeks by pre-labour caesarean section, intra-partum caesarean section, or vaginal birth following spontaneous onset of labour.

Methods

We compared the rate of short-term adverse maternal and newborn outcomes following pre-labour caesarean section at a given gestational age, to those following ongoing pregnancies beyond that gestational age.

Main Outcome Measures

Severe maternal outcomes, neonatal morbidity, and intra-hospital early neonatal mortality.

Results

Odds of neonatal morbidity and intra-hospital early neonatal mortality were 0.48 (95% confidence interval [CI] 0.39–0.60) and 0.31 (95% CI 0.16–0.58) times lower for ongoing pregnancies compared to pre-labour caesarean section at 37 weeks. We did not find any significant change in the risk of severe maternal outcomes between pre-labour caesarean section at a given gestational age and ongoing pregnancies beyond that gestational age.

Conclusions

Elective repeat caesarean section at 37 weeks had higher risk of neonatal morbidity and mortality compared to ongoing pregnancy, however risks at later gestational ages did not differ between groups.     

Pulse Wave Analysis in Normal Pregnancy: A Prospective Longitudinal Study

Background

Outside pregnancy, arterial pulse wave analysis provides valuable information in hypertension and vascular disease. Studies in pregnancy using this technique show that vascular stiffness is raised in women with established pre-eclampsia. We aimed to establish normal ranges for parameters of pulse wave analysis in normal pregnancy and to compare different ethnic groups.

Methodology/Principal Findings

This prospective study was conducted at The Homerton University Hospital, London between January 2006 and March 2007. Using applanation tonometry, the radial artery pulse waveform was recorded and the aortic waveform derived. Augmentation pressure (AP) and Augmentation Index at heart rate 75/min (AIx-75), measures of arterial stiffness, were calculated.We recruited 665 women with singleton pregnancies. Women who developed pre-eclampsia (n = 24, 3.6%) or gestational hypertension (n = 36, 5.4%) were excluded. We also excluded 47 women with other pregnancy complications or incomplete follow-up, leaving 541 healthy normotensive pregnant women for subsequent analysis. In the overall group of 541 women, there were no significant changes in AP or AIx-75 as pregnancy progressed. In 45 women followed longitudinally, AP and AIx-75 fell significantly from the first to the second trimester, then rose again in the third (P<0.001). The two main ethnic groups represented were Caucasian (n = 229) and Afrocaribbean (n = 216). There were no significant differences in AP or AIx-75 in any trimester between these two ethnic groups.

Conclusions

This study is the largest to date of pulse wave analysis in normal pregnancy, the first to report on a subset of women studied longitudinally, and the first to investigate the effect of ethnicity. These data provide the foundation for further investigation into the potential role of this technique in vascular disorders in pregnancy.     

Plasma S1P and Sphingosine are not Different Prior to Pre-Eclampsia in Women at High Risk of Developing the Disease

Sphingolipids like sphingosine-1-phosphate (S1P) have been implicated in the pathophysiology of pre-eclampsia. We hypothesized that plasma S1P would be increased in women at high risk of developing pre-eclampsia who subsequently develop the disease. Low circulating placental growth factor (PlGF) is known to be associated with development of pre-eclampsia; so further, we hypothesized that increased S1P would be associated with concurrently low PlGF. This was a case-control study using stored maternal blood samples from 14 to 24 weeks of pregnancy, collected from 95 women at increased risk of pre-eclampsia. Pregnancy outcome was classified as uncomplicated, preterm pre-eclampsia (<37 weeks), or term pre-eclampsia. Plasma lipids were extracted and analyzed by ultraperformance liquid chromatography coupled to electrospray ionization MS/MS to determine concentrations of S1P and sphingosine. Median plasma S1P was 0.339 nmol/ml, and median sphingosine was 6.77 nmol/l. There were no differences in the plasma concentrations of S1P or sphingosine in women who subsequently developed pre-eclampsia, no effect of gestational age, fetal sex, ethnicity, or the presence of pre-existing hypertension. There was a correlation between S1P and sphingosine plasma concentration (P < 0.0001). There was no relationship between S1P or sphingosine with PlGF. Previous studies have suggested that plasma S1P may be a biomarker of pre-eclampsia. In our larger study, we failed to demonstrate there are women at high risk of developing the disease. We did not show a relationship with known biomarkers of the disease, suggesting that S1P is unlikely to be a useful predictor of the development of pre-eclampsia later in pregnancy.     

Asthma during Pregnancy in a Population-Based Study - Pregnancy Complications and Adverse Perinatal Outcomes

Background

Asthma is one of the most common chronic diseases, and prevalence, severity and medication may have an effect on pregnancy. We examined maternal asthma, asthma severity and control in relation to pregnancy complications, labour characteristics and perinatal outcomes.

Methods

We retrieved data on all singleton births from July 1, 2006 to December 31, 2009, and prescribed drugs and physician-diagnosed asthma on the same women from multiple Swedish registers. The associations were estimated with logistic regression.

Results

In total, 266 045 women gave birth to 284 214 singletons during the study period. Maternal asthma was noted in 26 586 (9.4%) pregnancies. There was an association between maternal asthma and increased risks of pregnancy complications including preeclampsia or eclampsia (adjusted OR 1.15; 95% CI 1.06–1.24) and premature contractions (adj OR 1.52; 95% CI 1.29–1.80). There was also a significant association between maternal asthma and emergency caesarean section (adj OR 1.29; 95% CI 1.23–1.34), low birth weight, and small for gestational age (adj OR 1.23; 95% CI 1.13–1.33). The risk of adverse outcomes such as low birth weight increased with increasing asthma severity. For women with uncontrolled compared to those with controlled asthma the results for adverse outcomes were inconsistent displaying both increased and decreased OR for some outcomes.

Conclusion

Maternal asthma is associated with a number of serious pregnancy complications and adverse perinatal outcomes. Some complications are even more likely with increased asthma severity. With greater awareness and proper management, outcomes would most likely improve.     

血清VEGF、sFlt-1、IL-4水平与妊娠期高血压疾病患者预后的关系研究

摘要 目的：探讨血清血管内皮生长因子（VEGF）、可溶性Fms样酪氨酸激酶-1（sFlt-1）、白细胞介素-4（IL-4）水平与妊娠期高血压疾病（HDP）患者分类及妊娠结局的关系。方法：选取2019年7月～2021年1月我院收治的204例HDP患者（HDP组）,根据指南分类原则分为妊娠期高血压组（n=88）、子痫前期组（n=66）、子痫组（n=50）,根据妊娠结局分为结局不良组和结局良好组,另选取同期100名于我院产检健康孕产妇为对照组。采用单因素及多因素Logistic回归和受试者工作特征（ROC）曲线分析HDP患者妊娠结局不良的影响因素及血清VEGF、sFlt-1、IL-4水平对妊娠结局不良的预测价值。结果： 与对照组比较,HDP组血清VEGF、IL-4水平降低,sFlt-1水平升高（P＜0.05）。妊娠期高血压组、子痫前期组、子痫组血清VEGF、IL-4水平依次降低,sFlt-1水平依次升高（P＜0.05）。204例HDP患者妊娠结局不良发生率为29.90%（61/204）。单因素分析显示,妊娠结局不良与年龄、不同疾病分类、SBP、DBP、尿蛋白、VEGF、sFlt-1、IL-4有关（P＜0.05）。多因素Logistic回归分析显示,HDP患者妊娠结局不良的独立危险因素与独立保护因素分别为子痫、sFlt-1升高与VEGF、IL-4升高（P＜0.05）。血清VEGF、sFlt-1、IL-4水平单独与联合预测HDP患者妊娠结局不良的曲线下面积（AUC）分别为0.766、0.774、0.770、0.905,VEGF、sFlt-1、IL-4联合预测HDP患者妊娠结局不良的AUC最大。结论：HDP患者血清VEGF、IL-4水平降低,sFlt-1水平升高,与HDP分类和妊娠结局不良有关,VEGF、sFlt-1、IL-4联合对HDP患者妊娠结局不良的预测价值较高。     

Pre-Conception Dyslipidemia Is Associated with Development of Preeclampsia and Gestational Diabetes Mellitus

IntroductionThe association between glucose intolerance, elevated blood pressure and abnormal lipid levels is well established and comprises the basis of metabolic syndrome pathophysiology. We hypothesize that abnormal preconception lipid levels are associated with the increased risk of severe pregnancy complications such as preeclampsia and gestational diabetes mellitus.MethodsWe included all singleton deliveries (n = 27,721) of women without known cardiovascular morbidity and preeclampsia and gestational diabetes mellitus during previous pregnancies. Association between preconception low high density lipoprotein cholesterol (HDLc level≤50 mg/dL), high triglycerides (level≥150 mg/dL) and the primary outcome (composite of gestational diabetes mellitus/or preeclampsia) was assessed using Generalized Estimation Equations.ResultsPrimary outcome of preeclampsia and/or gestational diabetes was observed in a total of 3,243 subjects (11.7%). Elevated triglycerides and low HDLc were independently associated with the primary outcome: with odds ratio (OR) of 1.61 (95% CI 1.29–2.01) and OR = 1.33 (95% CI 1.09–1.63), respectively, after adjusting for maternal age, weight, blood pressure, repeated abortions, fertility treatments and fasting glucose. There was an interaction between the effects of HDLc≤50 mg/dL and triglycerides≥150 mg/dL with an OR of 2.69 (95% CI 1.73–4.19).ConclusionsOur analysis showed an increased rate of preeclampsia and/or gestational diabetes in women with low HDLc and high triglycerides values prior to conception. In view of the severity of these pregnancy complications, we believe this finding warrants a routine screening for the abnormal lipid profile among women of a child-bearing age.     

Maternal cardiovascular disease after twin pregnancies complicated by hypertensive disorders of pregnancy: a population-based cohort study

Background:People whose singleton pregnancy is affected by hypertensive disorders of pregnancy (HDP) are at risk of future cardiovascular disease. It is unclear, however, whether this association can be extrapolated to twin pregnancies. We aimed to compare the association between HDP and future cardiovascular disease after twin and singleton pregnancies.Methods:We conducted a population-based retrospective cohort study that included nulliparous people in Ontario, Canada, 1992–2017. We compared the future risk of cardiovascular disease among pregnant people from the following 4 groups: those who delivered a singleton without HDP (referent) and with HDP, and those who delivered twins either with or without HDP.Results:The populations of the 4 groups were as follows: 1 431 651 pregnant people in the singleton birth without HDP group; 98 631 singleton birth with HDP; 21 046 twin birth without HDP; and 4283 twin birth with HDP. The median duration of follow-up was 13 (interquartile range 7–20) years. The incidence rate of cardiovascular disease was lowest among those with a singleton or twin birth without HDP (0.72 and 0.74 per 1000 person-years, respectively). Compared with people with a singleton birth without HDP, the risk of cardiovascular disease was highest among those with a singleton birth and HDP (1.47 per 1000 person-years; adjusted hazard ratio [HR] 1.81 [95% confidence interval (CI) 1.72–1.90]), followed by people with a twin pregnancy and HDP (1.07 per 1000 person-years; adjusted HR 1.36 [95% CI 1.04–1.77]). The risk of the primary outcome after a twin pregnancy with HDP was lower than that after a singleton pregnancy with HDP (adjusted HR 0.74 [95% CI 0.57–0.97]), when compared directly.Interpretation:In a twin pregnancy, HDP are weaker risk factors for postpartum cardiovascular disease than in a singleton pregnancy.

Cardiovascular disease has been shown to be the leading cause of death among women.^1–3 Classic risk factors for cardiovascular disease include obesity, diabetes mellitus, hypertension and family history of cardiovascular disease. ³ More recently, an association has been established between a history of hypertensive disorders of pregnancy (HDP) — gestational hypertension and pre-eclampsia — and future risk of cardiovascular disease.^1,4–11 Consequently, some recommend using a history of HDP for cardiovascular disease risk stratification in women.^3,12The leading hypothesis for the pathogenesis of HDP is that it results from abnormal placentation due to impaired trophoblast invasion,^13–16 resulting in reduced placental perfusion.^17–19 This, in turn, leads to abnormal secretion of the angiogenic factors soluble FMS-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng),²⁰ which induce endothelial dysfunction and the clinical manifestations of HDP.^19,21–24 The mechanisms underlying the association between HDP and future cardiovascular disease are under debate.²⁵ One hypothesis is that HDP are merely a marker of underlying subclinical or clinical vascular risk factors that predispose a person to both HDP and future cardiovascular disease.A person who is pregnant with twins is at about 3–4 times higher risk of HDP than a person with a singleton pregnancy,^26–33 with rates of 14% and 5%, respectively.³⁴ The higher risk of HDP in twin pregnancies may be due to higher circulating sFlt1 and sEng owing to greater placental mass in twin pregnancies, ^35–37 and less related to the classic vascular risk factors for HDP in a singleton pregnancy. Therefore, a logical question is whether the established higher risk of future cardiovascular disease after singleton pregnancies with HDP also occurs in twin pregnancies with HDP. Limited data are available to answer this question.³⁸ In the current study, we aimed to test the hypothesis that the association between HDP and future cardiovascular disease is less pronounced in twin versus singleton pregnancies.