Sarah D. McDonald

Cardiovascular sequelae of preeclampsia/eclampsia: A systematic review and meta-analyses

BACKGROUND Preeclampsia affects 3% to 5% of gestations and eclampsia 0.05% to 0.93%, but their subsequent cardiovascular sequelae are unclear. The aim of this study was to determine if women with a history of preeclampsia/eclampsia are at increased risk of long-term cardiovascular sequelae. METHODS From Medline and Embase searches, we included case-control and cohort studies that examined cardiac, cerebrovascular or peripheral arterial disease, or cardiovascular mortality>6 weeks postpartum, in women with and without a history of preeclampsia/eclampsia and that controlled for or matched for confounders. Two independent reviewers determined study eligibility and extracted data. RESULTS Five case-control and 10 cohort studies met eligibility criteria, with a total of 116,175 women with and 2,259,576 women without preeclampsia/eclampsia. Most studies focused on women<56 years of age. Relative to women with uncomplicated pregnancies, women with a history of preeclampsia/eclampsia had an increased risk of subsequent cardiac disease in both the case-control studies (odds ratio 2.47, 95% CI 1.22-5.01) and the cohort studies (relative risk [RR] 2.33, 1.95-2.78), as well as an increased risk of cerebrovascular disease (RR 2.03, 1.54-2.67), peripheral arterial disease (RR 1.87, 0.94-3.73), and cardiovascular mortality (RR 2.29, 1.73-3.04). Meta-regression revealed a graded relationship between the severity of preeclampsia/eclampsia and the risk of cardiac disease (mild: RR 2.00, 1.83-2.19, moderate: RR 2.99, 2.51-3.58, severe: RR 5.36, 3.96-7.27, P<.0001). CONCLUSIONS Women with a history of preeclampsia/eclampsia have approximately double the risk of early cardiac, cerebrovascular, and peripheral arterial disease, and cardiovascular mortality. Further research is needed to determine the mechanisms underlying these associations and to identify effective prevention strategies.

Overweight and obesity in mothers and risk of preterm birth and low birth weight infants: systematic review and meta-analyses

Objective To determine the relation between overweight and obesity in mothers and preterm birth and low birth weight in singleton pregnancies in developed and developing countries. Design Systematic review and meta-analyses. Data sources Medline and Embase from their inceptions, and reference lists of identified articles. Study selection Studies including a reference group of women with normal body mass index that assessed the effect of overweight and obesity on two primary outcomes: preterm birth (before 37 weeks) and low birth weight (<2500 g). Data extraction Two assessors independently reviewed titles, abstracts, and full articles, extracted data using a piloted data collection form, and assessed quality. Data synthesis 84 studies (64 cohort and 20 case-control) were included, totalling 1 095 834 women. Although the overall risk of preterm birth was similar in overweight and obese women and women of normal weight, the risk of induced preterm birth was increased in overweight and obese women (relative risk 1.30, 95% confidence interval 1.23 to 1.37). Although overall the risk of having an infant of low birth weight was decreased in overweight and obese women (0.84, 0.75 to 0.95), the decrease was greater in developing countries than in developed countries (0.58, 0.47 to 0.71 v 0.90, 0.79 to 1.01). After accounting for publication bias, the apparent protective effect of overweight and obesity on low birth weight disappeared with the addition of imputed “missing” studies (0.95, 0.85 to 1.07), whereas the risk of preterm birth appeared significantly higher in overweight and obese women (1.24, 1.13 to 1.37). Conclusions Overweight and obese women have increased risks of preterm birth and induced preterm birth and, after accounting for publication bias, appeared to have increased risks of preterm birth overall. The beneficial effects of maternal overweight and obesity on low birth weight were greater in developing countries and disappeared after accounting for publication bias.

Preterm birth and low birth weight among in vitro fertilization singletons: A systematic review and meta-analyses

Our objective was to determine the risks of preterm birth (PTB) and low birth weight (LBW) in singletons conceived through in vitro fertilization (IVF)+/-intracytoplasmic sperm injection (ICSI) compared to spontaneously conceived singletons after matching or controlling for at least maternal age. The MOOSE guidelines for meta-analysis of observational studies were followed. Medline and Embase were searched using comprehensive search strategies. Bibliographies of identified articles were reviewed. English language studies examining LBW or PTB in singletons conceived by IVF or IVF/intracytoplasmic sperm injection, compared with spontaneously conceived singletons, that matched or controlled for at least maternal age. Two reviewers independently assessed titles, abstracts, full articles and study quality and extracted data. Dichotomous data were meta-analyzed using relative risks (RR) as measures of effect size with a random effects model and for continuous data weighted mean difference was calculated. Seventeen studies were included with 31,032 singletons conceived through IVF (+/-ICSI) and 81,119 spontaneously conceived singletons. After matching or controlling for maternal age and often other factors, compared to spontaneously conceived singletons, IVF singletons had increased risks of our two primary outcomes, PTB (RR 1.84, 95% CI 1.54, 2.21) and LBW (<2500 g, RR 1.60, 95% CI 1.29, 1.98). Singletons conceived through IVF or IVF/ICSI were at increased risk for late PTB (32-36 weeks, RR 1.52, 95% CI 1.01, 2.30), moderate PTB <32-33 weeks (RR 2.27, 95% CI 1.73, 2.97), very LBW (<1500 g, RR 2.65, 95% CI 1.83, 3.84), and intrauterine growth restriction (RR 1.45, 95% CI 1.04, 2.00), lower birth weights (-97 g, 95% CI -161 g, -33 g) and shorter mean gestations (-0.6 weeks, 95% CI -0.9 weeks, -0.4 weeks). In conclusion, IVF singletons have significantly increased risks of PTB, LBW and other adverse perinatal outcomes compared to spontaneously conceived singletons after matching or controlling for maternal age at least.

Vitamin D deficiency and depression in adults: systematic review and meta-analysis

BACKGROUND There is conflicting evidence about the relationship between vitamin D deficiency and depression, and a systematic assessment of the literature has not been available. AIMS To determine the relationship, if any, between vitamin D deficiency and depression. METHOD A systematic review and meta-analysis of observational studies and randomised controlled trials was conducted. RESULTS One case-control study, ten cross-sectional studies and three cohort studies with a total of 31 424 participants were analysed. Lower vitamin D levels were found in people with depression compared with controls (SMD = 0.60, 95% CI 0.23-0.97) and there was an increased odds ratio of depression for the lowest v. highest vitamin D categories in the cross-sectional studies (OR = 1.31, 95% CI 1.0-1.71). The cohort studies showed a significantly increased hazard ratio of depression for the lowest v. highest vitamin D categories (HR = 2.21, 95% CI 1.40-3.49). CONCLUSIONS Our analyses are consistent with the hypothesis that low vitamin D concentration is associated with depression, and highlight the need for randomised controlled trials of vitamin D for the prevention and treatment of depression to determine whether this association is causal.

Environmental tobacco smoke exposure and perinatal outcomes: a systematic review and meta-analyses

Background. While active maternal tobacco smoking has well established adverse perinatal outcomes, the effects of passive maternal smoking, also called environmental tobacco exposure (ETS), are less well studied and less consistent. Objective: To determine to the effect of ETS on perinatal outcomes. Search strategy. Medline, EMBASE and reference lists were searched. Selection criteria. Studies comparing ETS‐exposed pregnant women with those unexposed which adequately addressed active maternal smoking. Data collection and analysis. Two reviewers independently assessed titles, abstracts, full studies, extracted data and assessed quality. Dichotomous data were pooled using odds ratios (OR) and continuous data with weighted mean differences (WMD) using a random effects model. Main results. Seventy‐six articles were included with a total of 48,439 ETS‐exposed women and 90,918 unexposed women. ETS‐exposed infants weighed less [WMD –60 g, 95% confidence interval (CI) –80 to –39 g], with a trend towards increased low birthweight (LBW, < 2,500 g; RR 1.16; 95% CI 0.99–1.36), although the duration of gestation and preterm delivery were similar (WMD 0.02 weeks, 95% CI –0.09 to 0.12 weeks and RR 1.07; 95% CI 0.93–1.22). ETS‐exposed infants had longer infant lengths (1.75 cm; 95% CI 1.37–2.12 cm), increased risks of congenital anomalies (OR 1.17; 95% CI 1.03–1.34) and a trend towards smaller head circumferences (–0.11 cm; 95% CI –0.22 to 0.01 cm). Conclusions. ETS‐exposed women have increased risks of infants with lower birthweight, congenital anomalies, longer lengths, and trends towards smaller head circumferences and LBW.

Pregnancy outcomes in women with chronic kidney disease: a systematic review.

BACKGROUND AND OBJECTIVES Pregnant women with chronic kidney disease (CKD) are at risk of adverse maternal and fetal outcomes. We conducted a systematic review of observational studies that described this risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched several databases from their date of inception through June 2010 for eligible articles published in any language. We included any study that reported maternal or fetal outcomes in at least five pregnant women in each group with or without CKD. We excluded pregnant women with a history of transplantation or maintenance dialysis. RESULTS We identified 13 studies. Adverse maternal events including gestational hypertension, pre-eclampsia, eclampsia, and maternal mortality were reported in 12 studies. There were 312 adverse maternal events among 2682 pregnancies in women with CKD (weighted average of 11.5%) compared with 500 events in 26,149 pregnancies in normal healthy women (weighted average of 2%). One or more adverse fetal outcomes such as premature births, intrauterine growth restriction, small for gestational age, neonatal mortality, stillbirths, and low birth weight were reported in nine of the included studies. Overall, the risk of developing an adverse fetal outcome was at least two times higher among women with CKD compared with those without. CONCLUSIONS This review summarizes current available evidence to guide physicians in their decision-making, advice, and care for pregnant women with CKD. Additional studies are needed to better characterize the risks.

Kidney Disease After Preeclampsia: A Systematic Review and Meta-analysis

BACKGROUND Preeclampsia (the development of proteinuria and hypertension after 20 weeks of gestation) is common; however, there is uncertainty about the natural history of subsequent kidney disease. Our objective is to undertake a systematic review and meta-analysis to determine whether women with a history of preeclampsia are at increased risk of subsequent kidney disease. STUDY DESIGN Systematic review and meta-analyses of observational studies. SETTING & POPULATION Studies examining kidney outcomes in women with a history of preeclampsia compared with women with unaffected pregnancies. SELECTION CRITERIA From MEDLINE and EMBASE searches, we included case-control and cohort studies of kidney outcomes at least 6 weeks postpartum in women with and without a history of preeclampsia. 2 independent reviewers determined study eligibility, extracted data, and assessed quality. STUDY FACTOR: Preeclampsia. OUTCOMES Microalbuminuria, proteinuria, serum creatinine level, and estimated glomerular filtration rate. RESULTS 7 cohort studies were included, involving 273 patients with preeclampsia and 333 patients with uncomplicated pregnancies. At a weighted mean of 7.1 years postpartum, 31% of women with a history of preeclampsia had microalbuminuria compared with 7% of women with uncomplicated pregnancies, a 4-fold increased risk, whereas women with severe preeclampsia had an 8-fold increase. Serum creatinine level and estimated glomerular filtration rate were not significantly different at follow-up in women with and without preeclampsia, making it unlikely that they would have been different at baseline. LIMITATIONS Limitations of this systematic review include potential confounders that were not explored in most or any of the original studies, the small size of many studies, and possible publication bias (lack of negative studies). CONCLUSION Women with a history of preeclampsia have an increased risk of microalbuminuria with a prevalence similar to the published prevalence in patients with type 1 diabetes mellitus. Further research is needed to determine whether the increased risk of microalbuminuria persists after adjustment for a thorough set of confounding factors in larger populations and the mechanisms underlying this association.

Low gestational weight gain and the risk of preterm birth and low birthweight: a systematic review and meta‐analyses

Background. Low gestational weight gain is common, with potential adverse perinatal outcomes. Objective. To determine the relation between low gestational weight gain and preterm birth and low birthweight in singletons in developing and developed countries. Data sources. Medline, EMBASE and reference lists were searched, identifying 6 283 titles and abstracts. Methods of study selection. Following the MOOSE consensus statement, two assessors independently reviewed titles, abstracts, full articles, extracted data and assessed quality. Results. Fifty‐five studies, 37 cohort and 18 case‐control, were included, involving 3 467 638 women. In the cohort studies (crude data, generally supported where available by adjusted data and case‐control studies), women with low total gestational weight gain had increases in preterm birth <37 weeks [RR 1.64 (95%CI 1.62–1.65)], 32–36 weeks [RR 1.39 (95%CI 1.38–1.40)] and ≤32 weeks [RR 3.80 (95%CI 3.72–3.88)]. Low total gestational weight gain was associated with increased risks of low birthweight <2 500 g [RR 1.85 (95%CI 1.72–2.00)], in developing and developed countries [RR 1.84 (95%CI 1.71–1.99) and RR 3.02 (95%CI 1.37–6.63), respectively], 1 500–2 500 g [RR 2.02 (95%CI 1.88–2.17)] and <1 500 g (RR 2.00 (95%CI 1.67–2.40)]. Women with low weekly gestational weight gain were at increased risk of preterm birth [RR 1.56 (95%CI 1.26–1.94)], 32–36 weeks [RR 2.43 (95%CI 2.37–2.50)] and ≤32 weeks [RR 2.31 (95%CI 2.20–2.42)] but not low birthweight [RR 1.64 (95%CI 0.89–3.02)]. Conclusions. In this systematic review, we determined that singletons born to women with low total gestational weight gain have higher risks of preterm birth and low birthweight, with the lower the gain, the higher the risks.

Despite 2009 guidelines, few women report being counseled correctly about weight gain during pregnancy

OBJECTIVE The purpose of this study was to determine the information that pregnant women report receiving when being counseled about weight gain and the risks of inappropriate gain. STUDY DESIGN With the use of a self-administered questionnaire at prenatal clinics in Hamilton, Ontario, Canada, a cross-sectional survey was conducted of women who had had at least 1 prenatal visit, who could read English, and who had a live singleton gestation. RESULTS Three hundred ten women completed the survey, which was a 93.6% response rate. Although 28.5% (95% confidence interval, 23.5-33.6%) reported that their health care provider had made a recommendation about how much weight they should gain, only 12.0% (95% confidence interval, 8-16.1%) of the women reported having achieved the recommended weight gain in accordance with the 2009 guidelines. One quarter of the women reported being told that there were risks with inappropriate gain. CONCLUSION Despite the recent 2009 publication of the gestational weight gain guidelines, only 12% of women reported being counseled correctly, which suggests an urgent need for improved patient education.

Metabolic Syndrome and the Risk of Placental Dysfunction

BACKGROUND Placental dysfunction (PD), which may manifest partly as the hypertensive disorders of pregnancy and abruption or infarction of the placenta, occurs more commonly in women with obesity, chronic hypertension, diabetes mellitus, and dyslipidemia-each a major feature of the metabolic syndrome. However, the relationship between the metabolic syndrome and the future risk of PD or fetal demise is unknown. METHODS We completed a retrospective cohort study of 1.03 million women who had a first documented delivery in the province of Ontario between 1990 and 2002. Using linked administrative databases, we categorized women as having zero, one, two, or three to four features of the metabolic syndrome up to 24 months before their index delivery hospitalization. Women were considered to have placental dysfunction if they had a diagnosis of preeclampsia, gestational hypertension, placental abruption, or placental infarction during their first hospitalization for delivery in the period of study. RESULTS At the time of delivery, 75 380 women (7.3%) were diagnosed as having PD. There was a progressive increase in the risk of PD in women with one (adjusted odds ratio [OR] 3.1; 95% confidence interval [CI] 3.0-3.1), two (OR 5.5; 95% CI 5.2-5.8), or three to four (OR 7.7; 95% CI 6.7-8.9) features of the metabolic syndrome, compared with none. A similar gradient effect was seen for the combined outcome of PD with poor fetal growth, or of PD with concomitant fetal death. CONCLUSIONS Women who exhibit features of the metabolic syndrome before pregnancy have a higher graded risk of PD and fetal demise. Studies are needed to determine whether modifying a womans metabolic profile before pregnancy, through modest caloric restriction and increased physical activity, can lower her future risk of PD.