Non-proteinuric Hypertension Research Articles

The impact of pre-eclampsia definitions on the identification of adverse outcome risk in hypertensive pregnancy - analyses from the CHIPS trial (Control of Hypertension in Pregnancy Study).

To examine the association between pre-eclampsia definition and pregnancy outcome. Secondary analysis of Control of Hypertension in Pregnancy Study (CHIPS) trial data. International multicentre randomised controlled trial (RCT). In all, 987 women with non-severe non-proteinuric pregnancy hypertension. We evaluated the association between pre-eclampsia definitions and adverse pregnancy outcomes, stratified by hypertension type and blood pressure control. Main CHIPS trial outcomes: primary (perinatal loss or high-level neonatal care for >48hours), secondary (serious maternal complications), birthweight <10th centile, severe maternal hypertension, delivery at <34 or <37weeks, and maternal hospitalisation before birth. Of 979/987 women with informative data, 280 (28.6%) progressed to pre-eclampsia defined restrictively by new proteinuria, and 471 (48.1%) to pre-eclampsia defined broadly as proteinuria or one/more maternal symptoms, signs or abnormal laboratory tests. The broad (versus restrictive) definition had significantly higher sensitivities (range 62-79% versus 36-50%), lower specificities (range 53-65% versus 72-82%), and similar or higher diagnostic odds ratios and 'true-positive' to 'false-positive' ratios. Stratified analyses showed similar results. Addition of available fetoplacental manifestations (stillbirth or birthweight <10th centile) to the broad pre-eclampsia definition improved sensitivity (74-87%). A broad (versus restrictive) pre-eclampsia definition better identifies women who develop adverse pregnancy outcomes. These findings should be replicated in a prospective study within routine healthcare to ensure that the anticipated increase in surveillance and intervention in a larger number of women with pre-eclampsia is associated with improved outcomes, reasonable costs and congruence with women's values. A broad (versus restrictive) pre-eclampsia definition better identifies the risk of adverse pregnancy outcomes.

393. InterPregGen: The discovery and validation of genetic variants associated with pre-eclampsia in mothers and babies

30 years of molecular genetic studies of common disorders have demonstrated the need for large, well-powered studies to detect genetic variants with individually small effects on disease susceptibility; pre-eclampsia is no exception. InterPregGen is a collaboration between research groups from Europe and Central Asia seeking to identify DNA sequence variants predisposing to pre-eclampsia. The primary approach is meta-analysis of genome-wide association screening (GWAS) data from over 9000 affected mothers, 6500 offspring, and 370,000 control subjects. Variants with evidence of association with pre-eclampsia are followed-up by targeted genotyping in independent sample collections. In offspring affected by pre-eclampsia there is a highly significant association with a common variant located close to the FLT1 gene, which encodes Fms-like tyrosine kinase 1 and its soluble isoform sFlt-1 (P = 5.38 × 10 - 11 ) . The strongest association was in pregnancies with onset of pre-eclampsia after 34 weeks gestation. Investigation of the maternal genome in pre-eclampsia has highlighted associations with multiple DNA variants which also have confirmed associations with essential hypertension in non-pregnant individuals. In a further 2800 women with non-proteinuric gestational hypertension there is a similar profile of susceptibility variants shared with essential hypertension and pre-eclampsia. Typical of many common complex disorders, there is no single ‘pre-eclampsia gene’. Current parental or fetal genotype data do not enable prediction of preeclampsia in individual pregnancies. However, the results highlight specific biological pathways responsible for pre-eclampsia’s aetiology. Larger studies are essential to identify additional variants and other pathways affecting pre-eclampsia. The genetic findings justify targeted investigation of FLT1 regulation in the placenta, and indicate that raised sFlt-1 has a causal role in pre-eclampsia, and is not just a consequence of the disease. Maternal genotyping results confirm a pathophysiological overlap between essential hypertension, gestational hypertension and pre-eclampsia, and emphasise the imperative for long-term cardiovascular monitoring of women with a history of hypertension in pregnancy.

446. Large randomized trials to reduce the burden of preeclampsia

In this presentation, we will review the conduct, results and impact of two types of pregnancy hypertension-oriented clinical trials. First we will describe the CHIPS trial that randomised 987 women with non-proteinuric pregnancy hypertension in 95 sites in 16 countries. In the series of CHIPS trial publications there has been a consistent message that tight blood pressure control (target dBP = 85 mmHg) offers maternal safety without perinatal harm, and that methyldopa is a reasonable first choice of antihypertensive. Second, we will describe the CLIP trials that recruited 69,445 women in 44 clusters (unit of randomisation) in Mozambique (12 clusters), Pakistan (20 clusters) and India (12 clusters). The results will be summarised and implications of both types of trials and their results for widespread implementation discussed.

Iodine Status during Pregnancy in a Region of Mild-to-Moderate Iodine Deficiency is not Associated with Adverse Obstetric Outcomes; Results from the Avon Longitudinal Study of Parents and Children (ALSPAC).

Severe iodine deficiency during pregnancy has been associated with pregnancy/neonatal loss, and adverse pregnancy outcomes; however, the impact of mild–to–moderate iodine insufficiency, though prevalent in pregnancy, is not well-documented. We assessed whether mild iodine deficiency during pregnancy was associated with pregnancy/infant loss, or with other adverse pregnancy outcomes. We used samples and data from the Avon Longitudinal Study of Parents and Children (ALSPAC), from 3140 singleton pregnancies and from a further 42 women with pregnancy/infant loss. The group was classified as mildly-to-moderately iodine deficient with a median urinary iodine concentration of 95.3 µg/L (IQR 57.0–153.0; median urinary iodine-to-creatinine ratio (UI/Creat) 124 µg/g, IQR 82–198). The likelihood of pregnancy/infant loss was not different across four UI/Creat groups (<50, 50–149, 150–250, >250 µg/g). The incidence of pre-eclampsia, non-proteinuric gestational hypertension, gestational diabetes, glycosuria, anaemia, post-partum haemorrhage, preterm delivery, mode of delivery, being small for gestational age, and large for gestational age did not differ significantly among UI/Creat groups, nor were there any significant differences in the median UI/Creat. We conclude that maternal iodine status was not associated with adverse pregnancy outcomes in a mildly-to-moderately iodine-deficient pregnant population. However, in view of the low number of women with pregnancy/infant loss in our study, further research is required.

OP 41 Postpartum levels of maternal anti-angiogenic proteins in hypertensive disorders of pregnancy

Background Levels of anti-angiogenic proteins (soluble fms-like tyrosine kinase [sFlt1] and soluble endoglin [sEng]) are elevated during pregnancy in women with hypertensive disorders of pregnancy (HDP). The objective was to assess whether women with HDP have an angiogenic factor imbalance in the postpartum period that may predispose them to a future cardiovascular disease. Methods This is a secondary analysis of a prospective study of singleton pregnancies in which anti-angiogenic proteins and cardiovascular function was assessed throughout pregnancy and up to one year postpartum. sFlt1 (pg/ml) and sEng (ng/ml) were measured by ELISA. Women with preeclampsia, were labeled as proteinuric hypertension and gestational/chronic hypertension were labeled as non-proteinuric hypertension. Comparison of baseline characteristics and anti-angiogenic factors was assessed with a parametric or non-parametric t -test, as appropriate. Results Of 86 patients with both antepartum and postpartum levels of angiogenic factors, 25 were normal, 26 had non-proteinuric hypertension and 35 had proteinuric hypertension. Antepartum levels of anti-angiogenic proteins were significantly elevated in proteinuric hypertension (median sFlt1 15955.9, IQR: 8207.1–20076.4; sEng 32.0, IQR: 15.4–56.9) in comparison to non-proteinuric hypertension (sFlt1 5567.7, IQR: 3340.4–7077.9; sEng 13.5, IQR: 8.1–20.2) and normal patients (sFlt1 1915.76, IQR: 1263.65–4357.84; sEng 8.21, IQR: 5.44–11.46; all p p = 0.87) or sEng (means 4.69, 4.41, and 4.05 for normal, non-proteinuric and proteinuric hypertension, respectively; p = 0.20). There was no significant difference in postpartum levels at 3, 6 or 12 months. Conclusion Postpartum circulating plasma levels of anti-angiogenic factors were not different among women who were hypertensive during pregnancy compared to normal women. Interactions of angiogenic proteins with other factors or local abnormality in angiogenesis in specific organs such as the heart may be contributing to increased long-term cardiovascular morbidity among these women.

Maternal venous Doppler characteristics are abnormal in pre-eclampsia but not in gestational hypertension.

To compare functional characteristics of maternal thoraco-abdominal arteries and veins in proteinuric and non-proteinuric hypertension in pregnancy. This retrospective study included women with singleton pregnancies during the third trimester, which were either uncomplicated or complicated with different clinical types of hypertension: non-proteinuric gestational hypertension (GH), early-onset pre-eclampsia (PE) diagnosed < 34 weeks or late-onset PE diagnosed ≥ 34 weeks. Demographic maternal and neonatal data were recorded, together with maternal serum and urine analytes. All women underwent standardized automated blood-pressure measurement, together with non-invasive impedance cardiography (ICG), for measurement of cardiac output (CO), aortic flow velocity index (VI) and aortic flow acceleration index (ACI). A standardized combined Doppler-electrocardiography assessment of maternal venous hemodynamics was performed to measure renal interlobar vein impedance index (RIVI), hepatic vein impedance index (HVI) and venous pulse transit time (VPTT) in liver and kidneys. Finally, resistance index (RI), pulsatility index (PI) and arterial pulse transit time (APTT) were measured in the uterine arcuate arteries. Mann-Whitney U-tests and Fisher's exact tests were used for intergroup comparisons, and linear dependence between variables was assessed using Pearson's correlation coefficient (r). A total of 150 pregnancies were evaluated: 22 with uncomplicated pregnancy, 41 GH, 31 early PE and 56 late PE. Aortic VI and ACI were lower in GH, early PE and late PE than in uncomplicated pregnancy. Both early PE and late PE differed from GH by having shorter APTT in the uterine arcuate arteries and higher RIVI. Hemodynamic abnormalities were most pronounced in early PE, during which uterine arcuate artery RI was higher and VPTT in kidneys was shorter than in late PE. There was a significant correlation between degree of proteinuria and RIVI for the left (r = 0.381) and right (r = 0.347) kidney in late PE, but this was not true for early PE. There is a gradient of worsening arterial and venous hemodynamic abnormalities from GH to late PE and then to early PE. Venous hemodynamic abnormalities are present only in PE, with a linear correlation between proteinuria and RIVI in late PE. The role of the maternal venous compartment in the pathophysiology and etiology of PE-related symptoms may be much more important than considered at present.

Characterization of Atypical Preeclampsia

Objective: To characterize patients with atypical preeclampsia (PE), in relation to socio-demographic characteristics, clinical presentation, maternal complications and perinatal outcome. Materials and Methods: Between July 1, 2011 and November 30, 2013, a cohort was created of women attended at a Obstetric High-dependency Unit who met criteria for atypical PE: gestational hypertension with severe hypertension or symptoms or laboratory signs suggestive of microangiopathy/hemolysis; normotensive proteinuria with the presence of symptoms or laboratory signs suggestive of microangiopathy/hemolysis; presence of PE or eclampsia or HELLP syndrome appearing after 48 h postpartum, and, PE or eclampsia appearing before 20 weeks of pregnancy. Results: A total of 200 women fulfilling criteria for atypical PE, were included: 61.5% corresponded to non-proteinuric gestational hypertension, 35.5% to normotensive proteinuria and 3% to PE/eclampsia in late postpartum. Criteria for severe maternal morbidity were present in 12% of the cases and there were no maternal deaths. There were 6 perinatal deaths. Conclusion: Atypical preeclampsia is a type of preeclampsia not fully recognized that is associated with maternal and neonatal morbidity, mainly related to smallness-for-gestational-age and low birth weight. Vasospasm symptoms are a key element to detect this condition.

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Objectives Normalizing blood pressure in pregnancy may reduce maternal complications but increase adverse perinatal effects. CHIPS aimed to determine whether a higher (vs. lower) blood pressure target improves perinatal outcome, without compromising maternal safety in non-severe pregnancy hypertension. Methods In an open pragmatic international multicenter trial, women at 14 + 0 − 33 + 6 weeks gestation with non-proteinuric pre-existing or gestational hypertension, office diastolic BP (dBP) 90–105 mmHg (or 85–105 mmHg if on antihypertensives) and a live fetus were randomized to ‘less tight’ (target dBP 100 mmHg) or ‘tight’ control (target dBP 85 mmHg). The composite primary outcome was pregnancy loss or high level neonatal care for >48 h in the first 28 d of life, and the secondary, serious maternal complications before 6 weeks postpartum. Outcomes were compared between groups using logistic regression adjusted for key prognostic factors. Results Of 1030 women randomized, 987 (94 sites) were included in the analysis. 74.6% had pre-existing hypertension. Women in ‘less tight’ ( n = 497) compared with ‘tight’ ( n = 490) control had similar rates of adverse perinatal (31.4% vs. 30.7%; aOR 1.02 [0.77, 1.35]) and maternal outcomes (3.7% vs. 2.0%; aOR 1.74 [0.79, 3.84]), despite higher mean dBP by 4.6 mmHg (95% confidence interval 3.7, 5.4). Severe hypertension (⩾160/110 mmHg) developed more frequently in ‘less tight’ (vs. ‘tight’) control (40.6% vs. 27.5%; aOR 1.80 [1.36, 2.38]). Conclusions ‘Less tight’ (vs. ‘tight’) control did not improve perinatal outcome, but did result in more severe hypertension. Our results do not support ‘less tight’ control of non-severe pregnancy hypertension. Disclosures L.A. Magee: Research Support Recipient; Commercial Interest(s): BMGF. P. von Dadelszen: Consultant; Commercial Interest: Alere International; Research Support Recipient; Commercial Interest: BMGF. E. Rey: None. S. Ross: None. E. Asztalos: None. K.E. Murphy: None. J. Menzies: None. J. Sanchez: None. J. Singer: None. A. Gafni: None. A. Gruslin: None. M. Helewa: None. E. Hutton: None. S.K. Lee: None. A.G. Logan: None. W. Ganzevoort: None. R. Welch: None. J.G. Thornton: None. J. Moutquin: None. T. Study Group: None.

Oxidative stress markers in hypertensive states of pregnancy: preterm and term disease.

Discussion continues as to whether de novo hypertension in pregnancy with significant proteinuria (pre-eclampsia; PE) and non-proteinuric new hypertension (gestational hypertension; GH) are parts of the same disease spectrum or represent different conditions. Non-pregnant hypertension, pregnancy and PE are all associated with oxidative stress. We have established a 6 weeks postpartum clinic for women who experienced a hypertensive pregnancy. We hypothesized that PE and GH could be distinguished by markers of oxidative stress; thiobarbituric acid reactive substances (TBARS) and antioxidants (ferric ion reducing ability of plasma; FRAP). Since the severity of PE and GH is greater pre-term, we also compared pre-term and term disease. Fifty-eight women had term PE, 23 pre-term PE, 60 had term GH and 6 pre-term GH, 11 pre-existing (essential) hypertension (EH) without PE. Limited data were available from normotensive pregnancies (n = 7) and non-pregnant controls (n = 14). There were no differences in postpartum TBARS or FRAP between hypertensive states; TBARS (P = 0.001) and FRAP (P = 0.009) were lower in plasma of non-pregnant controls compared to recently-pregnant women. Interestingly FRAP was higher in preterm than term GH (P = 0.013). In PE and GH, TBARS correlated with low density lipoprotein (LDL)-cholesterol (P = 0.036); this association strengthened with inclusion of EH (P = 0.011). The 10 year Framingham index for cardiovascular risk was positively associated with TBARS (P = 0.003). Oxidative stress profiles do not differ between hypertensive states but appear to distinguish between recently-pregnant and non-pregnant states. This suggests that pregnancy may alter vascular integrity with changes remaining 6 weeks postpartum. LDL-cholesterol is a known determinant of oxidative stress in cardiovascular disease and we have shown this association to be present in hypertensive pregnancy further emphasizing that such a pregnancy may be revealing a pre-existing cardiovascular risk.

The BRAzil MAGnesium (BRAMAG) trial: a randomized clinical trial of oral magnesium supplementation in pregnancy for the prevention of preterm birth and perinatal and maternal morbidity.

BackgroundPreterm birth is the leading cause of infant mortality globally, including Brazil. We will evaluate whether oral magnesium citrate reduces the risk of placental dysfunction and its negative consequences for both the fetus and mother, which, in turn, should reduce the need for indicated preterm delivery.Methods/DesignWe will complete a multicenter, randomized double-blind clinical trial comparing oral magnesium citrate 150 mg twice daily (n = 2000 women) to matched placebo (n = 1000 women), starting at 121/7 to 206/7 weeks gestation and continued until delivery. We will include women at higher risk for placental dysfunction, based on clinical factors from a prior pregnancy (e.g., prior preterm delivery, stillbirth or preeclampsia) or the current pregnancy (e.g., chronic hypertension, pre-pregnancy diabetes mellitus, maternal age > 35 years or pre-pregnancy maternal body mass index > 30 kg/m2). The primary perinatal outcome is a composite of preterm birth < 37 weeks gestation, stillbirth > 20 weeks gestation, neonatal death < 28 days, or SGA birthweight < 3rd percentile. The primary composite maternal outcome is preeclampsia arising < 37 weeks gestation, severe non-proteinuric hypertension arising < 37 weeks gestation, placental abruption, maternal stroke during pregnancy or ≤ 7 days after delivery, or maternal death during pregnancy or ≤ 7 days after delivery.DiscussionThe results of this randomized clinical trial may be especially relevant in low and middle income countries that have high rates of prematurity and limited resources for acute newborn and maternal care.Trial registrationClinicalTrials.gov Identifier NCT02032186, registered December 19, 2013.

Maternal venous hemodynamics in gestational hypertension and preeclampsia.

BackgroundTo evaluate characteristics of venous hemodynamics, together with cardiac and arterial function, in uncomplicated pregnancies (UP), non-proteinuric gestational hypertension (GH) and preeclampsia (PE).MethodsIn this observational cross-sectional study, venous hemodynamics was assessed using a standardised protocol for combined electrocardiogram (ECG)-Doppler ultrasonography, together with a non-invasive standardised cardiovascular assessment using impedance cardiography (ICG) in 13 women with UP, 21 with GH, 34 with late onset PE ≥ 34 w (LPE) and 22 with early onset PE < 34 w (EPE). ECG-Doppler parameters were impedance index at the level of hepatic veins (HVI) and renal interlobar veins (RIVI) together with venous pulse transit times (VPTT), as well as resistive and pulsatility index, and arterial pulse transit time (APTT) at the level of uterine arcuate arteries. ICG parameters were aortic flow velocity index (VI), acceleration index (ACI) and thoracic fluid content. Mann Whitney U-test, Kruskall-Wallis test and linear regression analysis with heteroskedastic variance was used for statistical analysis.ResultsRIVI in both kidneys was >15% higher (P ≤ .010) in LPE and EPE, as compared to GH and UP. Next to this, >30% lower values for VI and ACI (P ≤ .029), and > 15% lower values for APTT (P ≤ .012) were found in GH, LPE and EPE, as compared to GH.ConclusionIn comparison to UP, similar abnormalities of central arterial function and APTT were found in GH, EPE and LPE. Proteinuria of LPE and EPE was associated with increased RIVI, this was not observed in GH.

PM.04 Cardiovascular Indices in the Early Identification of Pre-Eclampsia in Women at High-Risk For Hypertensive Disorders of Pregnancy

ObjectiveBiochemical markers such as PlGF have been proposed as point-of-care tests for the early identification of women at risk of hypertensive disorders. The aim of this study was to ascertain...

Offspring’s blood pressure and metabolic phenotype after exposure to gestational hypertension in utero

The aim of the study was to investigate the impact of de novo hypertension in pregnancy, i.e. gestational (non-proteinuric) hypertension (GH) and preeclampsia (PE), on the long-term metabolic outcome of the offspring. Data was obtained from the Northern Finland Birth Cohort 1986 (NFBC 1986), including 9,362 pregnancies and subsequent births between 1985 and 1986. Pregnancies were categorised into three groups: (1) GH with blood pressure (BP) ≥ 140/90 mmHg, (2) PE with BP ≥ 140/90 mmHg and proteinuria, and (3) reference group with normal BP. The final study population included 331 offspring of mothers with GH, 197 with PE and 5,045 offspring of normotensive mothers. The main outcome measures were systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), body mass index (BMI), and serum lipid, glucose and insulin levels of the 16 year-old offspring. The children of mothers with GH had higher BP compared to the reference group (SBP percentage difference 2.7 (95% CI 1.6, 3.8); DBP 3.4 (2.1, 4.6); MAP 3.1 (2.0, 4.1), P < 0.001 for all) and a tendency towards higher cholesterol and apolipoprotein B values. The offspring of mothers with PE had higher DBP and MAP, however after the adjustments this difference disappeared. Maternal de novo hypertension during pregnancy is associated with offspring's elevated blood pressure level already in adolescence. GH may also be associated with unfavourable lipid profile of the offspring.

Subclinical Left Ventricular Dysfunction in Preeclamptic Women With Preserved Left Ventricular Ejection Fraction

Background— Patients with preeclampsia are at risk for cardiovascular disease. Changes in cardiac function are subtle in preeclampsia and are difficult to quantify with conventional imaging. Strain measurements using speckle-tracking echocardiography have been used to sensitively quantify abnormalities in other disease settings. Methods and Results— We evaluated the feasibility and sensitivity of strain imaging using speckle-tracking echocardiography in women with preeclampsia. Forty-seven women were enrolled in this pilot study and 39 were analyzed: 11 with preeclampsia, 17 without a hypertensive disorder, and 11 with nonproteinuric hypertension. Echocardiographic ejection fraction and global peak longitudinal, radial, and circumferential strain were measured. Longitudinal strain was significantly worsened in women with preeclampsia compared with women without a hypertensive disorder ( P =0.0001). Similar results were observed for radial strain ( P =0.006) and circumferential strain ( P =0.03). Women with preeclampsia also had significantly worsened longitudinal ( P =0.04), radial ( P =0.01), and circumferential ( P =0.002) strain compared with women with nonproteinuric hypertension. Women with preeclampsia did not have a significantly different ejection fraction compared with women without a hypertensive disorder ( P =0.16) and women with nonproteinuric hypertension ( P =0.44). Conclusions— Myocardial strain imaging using speckle tracking is more sensitive than left ventricular ejection fraction to detect differences in left ventricular systolic function in women with and without preeclampsia.

OS082. CHIPS-Child: Testing the developmental origins hypothesis

CHIPS-Child is a natural test of the Developmental Origins of Health and Disease hypothesis (DOHaD) [1,2]. Reduced fetal growth rate is associated with adult cardiovascular risk markers (e.g., obesity) and disease [3,4]. Evidence worldwide indicates that this relationship is independent of birth weight. The leading theory describes 'developmental programming'in utero leading to permanent alteration of the fetal genome. While those changes are adaptive in utero, they may be maladaptive postnatally. To directly test, for the first time in humans, whether differential blood pressure (BP) control in pregnancy has developmental programming effects, independent of birth weight. We predict that, like famine or protein malnutrition, 'tight' (vs. 'less tight') control of maternal BP will be associated with fetal under-nutrition and effects will be consistent with developmental programming. CHIPS-Child is a parallel, ancillary study to the CHIPS randomized controlled trial (RCT). CHIPS is designed to determine whether 'less tight' control [target diastolic BP (dBP) 100mmHg] or 'tight' control [target dBP 85mmHg] of non-proteinuric hypertension in pregnancy is better for the baby without increasing maternal risk. CHIPS-Child will examine offspring of CHIPS participants non-invasively at 12m corrected post-gestational age (±2m) for anthropometry, hair cortisol, buccal swabs for epigenetic testing and a maternal questionnaire about infant feeding practices and background. Annual contact will be maintained in years 2-5 and will include annual parental measurement of the child's height, weight and waist circumference. CHIPS will recruit 1028 women. We estimate that 80% of CHIPS centres will participate in CHIPS-Child, approximately 97% of babies will survive, and 90% of children will be followed to 12m resulting in a sample size of 626. Power will be >80% to detect a between-group difference of ⩾0.25 in 'change in z-score for weight' between birth and 12m (2-sided alpha=0.05, SD 1). Recruitment has begun. The primary outcome will be the between-group difference in early postnatal weight gain ('change in z score for weight') between birth and 12m (p<0.05). Secondary:outcomes are (i) hypothalamic pituitary adrenal axis function (hair cortisol for overall cortisol production); and (ii) between-groups differences in DNA methylation, using targeted (genes associated with growth, obesity, cardiovascular disease, and/or a developmental programming effect) and global (genome-wide microarray) methods. CHIPS-Child offers a unique opportunity to both clarify whether differential dBP control in pregnancy has developmental programming effects and contribute to our understanding of human biology and diversity in a way that a cross-sectional or other observational studies cannot.

Recurrence and long-term maternal health risks of hypertensive disorders of pregnancy: a population-based study

The purpose of this study was to investigate the recurrence risk of hypertensive disorders in subsequent pregnancies and to explore the associations among hypertensive disorders of pregnancy and maternal cardiovascular risk factor profile and the development of cardiovascular diseases later in life. We used population-based, cross-sectional data from the fourth survey of the Tromsø Study. Preeclampsia in the first pregnancy increased the risk of recurrence in later pregnancies (relative risk, 6.6; 95% confidence interval, 5.5-7.9) compared with a normotensive first pregnancy. Women with a history of preeclampsia or nonproteinuric hypertension had an unfavorable cardiovascular risk profile. Hypertension was prevalent in 25% and 28% of the women, respectively. The carotid artery intima-media thickness and total carotid plaque area were significantly larger in women with previous preeclampsia. A strong association between hypertensive disorders of pregnancy and an increased risk of atherosclerosis and cardiovascular diseases was demonstrated by the assessment of risk factors that can be potentially modified.

Tight control of mild-moderate pre-existing or non-proteinuric gestational hypertension

The question of the target blood pressure in pregnant women with mild-moderate hypertension continues to be an area of debate. To compare tight versus very tight control of mild-moderate pre-existing or non-proteinuric gestational hypertension for improving outcomes We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2011), CENTRAL (The Cochrane Library 2011, Issue 3), MEDLINE (January 1966 to March 2011), and the metaRegister of Controlled Trials (31 March 2011). We handsearched citation lists of relevant publications, review articles, and included studies. Randomized controlled trials of tight versus very tight control in pregnant women with mild or moderate pre-existing or non-proteinuric gestational hypertension. Two authors independently assessed trial quality and extracted data. We expressed results as risk ratio (RR) or mean differences, together with their 95% confidence intervals (CI). We included two studies (256 participants) with mild-moderate pre-existing or non-proteinuric gestational hypertension. There was no evidence of a difference between tight and very tight control groups regarding severe pre-eclampsia (risk ratio (RR) 1.28, 95% CI 0.97 to 1.70; two trials, 256 participants). More women in the tight group were hospitalized during their pregnancy (RR 2.53, 95% CI 1.14 to 5.63; one trial, 125 participants). There was no evidence of a difference in other outcome measures including fetal distress, IUGR, neonatal admission to a NICU, perinatal deaths, induction of labor and cesarean delivery between the tight and the very tight control groups. Gestational age at delivery had a non-significant mean difference (MD) of -0.15 weeks between the tight and very tight control groups (MD -0.15, 95% CI -1.52 to 1.21, random-effects, T² = 0.75, I² = 77%; two trials, 256 participants). The MD in birthweight between the tight and the very tight control group was not significant (MD -100.00 grams, 95% CI -363.69 to 163.69; one trial, 125 participants). For pregnant women with non-severe pre-existing or non-proteinuric gestational hypertension, there is insufficient evidence to determine how tight control of hypertension should be achieved to improve maternal and fetal-neonatal outcomes.

Risk factors for early onset severe pre-eclampsia and eclampsia among north Indian women

SummaryA case–control study was conducted in India between April 2007 and January 2008, to identify the clinical and historical risk factors associated with early onset pre-eclampsia/eclampsia (PE-E) in women attending a tertiary care hospital in North India. The study group comprised 100 women with early onset severe pre-eclampsia/eclampsia (≤34 weeks) and a control group of 100 women with mild non-proteinuric hypertension (>34 weeks). A detailed history including past, personal and family history, pregnancy outcome including delivery details and perinatal outcome and available investigations were recorded in a pre-designed proforma. Multiple logistic regression analysis was used to determine the risk factors for pre-eclampsia. The risk factors that were associated with increased risk of early onset severe PE-E were: history of PE-E in a previous pregnancy (adjusted odds ratio, aOR 71.40); exposure to passive smoking (aOR 16.40); inadequate antenatal supervision (aOR 15.21); family history of hypertension in one or more 1st-degree relative (aOR 8.92); living in a joint family (aOR 6.93); overweight (>120% to 150% of pre-pregnancy ideal body weight, aOR 4.65) and lower socioeconomic class (Kuppuswamy’s class III–V) (aOR 3.00). Based on the above risk factors, a risk model can be constituted as practised in other places and implemented in the primary preventive measure of early-onset severe pre-eclampsia among the North Indian women attending this tertiary care hospital.

Fat necrosis of abdominal pannus following caesarean section in a woman with morbid obesity

The authors present the first case report of a patient with morbid obesity who developed fat necrosis of the abdominal pannus following caesarean section. The patient was a 40-year-old primigravida...

Genotype of the CYBA promoter −930A/G, polymorphism C677T of the MTHFR and APOE genotype in patients with hypertensive disorders of pregnancy: An observational study

Background and objective Hypertensive disorders of pregnancy could be favoured by polymorphisms in genes affecting vascular physiology. The aim of our work was to study several variants in the genes regulating oxidative stress, plasma lipids metabolism and endothelial function (observational study). Material and methods We studied the −930A/G polymorphism of the CYBA gene promoter, the apolipoprotein E (APOE) genotype and the methylene-tetrahydrofolate reductase (MTHFR) gene C677T polymorphism in 134 healthy pregnant women, 266 pregnant with non-proteinuric hypertension (NPH) and 184 patients with preeclampsia (PE). Results The GG genotype of the CYBA gene promoter was present in 32.1% of the control population, 38.7% of patients with NPH ( P=0.19) and 21.2% of the women with PE ( P=0.03). A higher frequency of ∈3/∈4 and ∈4/∈4 genotypes of APOE was observed in patients with PE or NPH compared with controls ( P<0.01). There were no significant differences detected in genotype or allele distribution of the MTHFR, C677T polymorphism. APOE ∈3/∈4 and ∈4/∈4 genotypes had a worse lipoprotein profile characterized by higher plasma values of total cholesterol ( P<0.05) and triglycerides ( P<0.005). Despite no differences in MTHFR C677T polymorphism distribution, higher levels of plasma homocysteine were observed in patients with PE than in patients with NPH or controls. Conclusions CYBA and APOE polymorphism showed a different distribution in the groups studied, while no differences were observed in MTHFR C677T polymorphism. APOE genotype was associated with changes in lipid and lipoprotein profiles in pregnant women.