Moderate smoking during pregnancy is associated with a reduced risk of preeclampsia.

BACKGROUND: To investigate the effects of maternal smoking during pregnancy on the development of preeclampsia (PE). METHODS: The study comprised two populations with singleton pregnancies, one collected from 1990 to 1994 at the Malm? University Hospital (Malm? series, n=14,510) and the other from the National Birth Registry of Sweden 1993 (National series, n=113,211). Women with PE (n=281 and n=2,865, respectively) were compared to those without PE, delivered in 1993 (n=2,811 and n=110,346, respectively). The subgroups of women who had PE associated with preterm birth (n=58 and n=693, respectively) were compared with the same control groups in both series. RESULTS: Multiple logistic regression analysis showed that, in comparison with non-smokers, moderate smokers (1-9 cigarettes per day) were characterized by a lower incidence of PE (odds ratio (OR) 0.4; 95% confidence interval (CI) 0.22-0.60), and PE associated with preterm birth (OR 0.1; 95% CI 0.01-0.67). The corresponding figures in the validating National series were also significantly lower for moderate smokers (OR 0.6; 95% CI 0.5-0.7 and OR 0.6; 95% CI 0.5-0.8, respectively). CONCLUSION: Moderate smoking during pregnancy seems to protect against the development of PE and PE associated with preterm birth. Nicotine might be the agent responsible for this protective effect.     

Combined vitamin C and E supplementation during pregnancy for preeclampsia prevention: a systematic review

The effect of combined vitamin C and E supplementation during pregnancy on the prevention of preeclampsia and major adverse infant outcomes has been reviewed. We searched MEDLINE and the Central Library of Controlled Trials of the Cochrane Library through August 2006 for relevant clinical trials. Interstudy heterogeneity was evaluated using the chi(2) statistic (Q statistic) test. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with a fixed or random-effects model as appropriate. Four trials that collectively randomized 4680 pregnant women to either the combination of vitamin C and vitamin E or placebo were included in the analysis. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia, 11% versus 11.4%, RR 0.97 (95% CI 0.82-1.13), fetal or neonatal loss, 2.6% versus 2.3%, RR 1.10 (95% CI 0.78-1.57), or small for gestational age (SGA) infant, 20.6% versus 20%, RR 0.94 (95% CI 0.74-1.19). Although there was a higher risk for preterm birth in the vitamin group, 19.5% versus 18%, RR 1.07 (95% CI 0.96-1.20), this finding was not significant. Combined vitamin C and E supplementation during pregnancy does not reduce the risk of preeclampsia, fetal or neonatal loss, small for gestational age infant, or preterm birth. Such supplementation should be discouraged unless solid supporting data from randomized trials become available. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that many methods have been used to prevent preeclampsia, state that increased oxidative stress has been postulated and many trials have used antioxidants to prevent the disease, and explain that MEDLINE analysis of the literature questions the use of vitamin C and E supplements.     

Immunogenetic determinants of preeclampsia and related pregnancy disorders: a systematic review

OBJECTIVE: We sought to systematically review the impact of immunogenetic factors, specifically human leukocyte antigen (HLA) allele frequencies, maternal homozygosity, couple sharing, and maternal-fetal sharing, on the risk of preeclampsia and intrauterine growth restriction. DATA SOURCES: A computerized search of PubMed databases from 1975 to 2003 was performed with the terms "preeclampsia," "eclampsia," "intrauterine growth restriction," and "human leukocyte antigens" and limited to studies of human subjects in English. No restrictions were placed on study design. All bibliographies were cross-referenced to identify additional pertinent studies. METHODS OF STUDY SELECTION: Titles and abstracts were reviewed carefully. Observational and basic science research studies were selected if their main objective was to assess the relationship of any aspect of HLA genotypes with preeclampsia and related disorders of pregnancy. TABULATION, INTEGRATION, AND RESULTS: Data were abstracted and tabulated from 22 original research studies. Meta-analytic techniques were not performed owing to variations in disease and exposure definitions as well as research methodologies. Studies that examined maternal, paternal, and fetal HLA allele frequencies, maternal homozygosity, and couple sharing yielded inconsistent results. Although the cumulative evidence points to the HLA-DR locus (particularly DR4) as a correlate of preeclampsia, it remains unclear whether any specific HLA allele, haplotype, or susceptibility gene in linkage disequilibrium with the HLA region is responsible. Although genetic evidence is suggestive of gene-gene interaction between mother and fetus, few studies have evaluated the influence of maternal-fetal HLA sharing. CONCLUSION: In the early 1990s, HLA genotypes were dismissed as possible etiologic factors for preeclampsia, based on studies that are heterogeneous with respect to study design, outcome, and exposure assessment. Many of these studies did not take into account the interactions between maternal, paternal, and infant genotypes. Thus, adequately powered studies designed specifically to assess the effect of maternal-fetal HLA sharing on risk of preeclampsia are needed.     

Association between intrahepatic cholestasis of pregnancy and risk of gestational diabetes and preeclampsia: a systematic review and meta-analysis

ABSTRACT

Objective

To investigate the association between intrahepatic cholestasis of pregnancy (ICP) and the risk of gestational diabetes mellitus (GDM) and preeclampsia via meta-analysis.     

Helicobacter pylori infection and risk of preeclampsia: a systematic review and meta-analysis

Objective: Helicobacter pylori is associated with many pregnancy adverse effects such as preeclampsia (PE). We performed this systematic review and meta-analysis study to assess the possible association between H. pylori infection and PE and this is the first meta-analysis to clarify this issue.

Methods: PubMed, ISI (Web of Science), SCOPUS, and Google Scholar databases were searched (up to April 2017) to identify the relevant studies. The Meta-analysis of Observational Studies in Epidemiology and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines were used to do this study. Pooled odds ratio (OR) and 95% confidence intervals (CI) were estimated using a random-effects meta-analysis model. Heterogeneity was assessed with the χ²-based Q-test and I² statistic.

Results: A total of eight studies including 889 participants (460 preeclamptic women and 429 controls) met the eligibility criteria. A positive association was found between H. pylori infection and PE (OR: 3.35; 95% CI: 2.21–5.10). Heterogeneity was acceptable (χ²?=?13.39; I²?=?47.7, 95% CI: 0–77). In subgroup analysis, cytotoxin-associated antigen A seropositivity was a substantial risk factor for PE when immunoblotting methods (OR: 11.12; 95% CI: 5.34–23.16; χ²?=?6.42; I²?=?53.3, 95% CI: 0–85) were used, whereas it was not potential risk factor for PE when ELISA was used as a detecting method (OR: 1.11; 95% CI: 0.6–2.06; χ²?=?1.83; I²?=?0, 95% CI: 0–90).

Conclusions: This study indicated that women with H. pylori infection, especially those infected with Cag A positive strains are more likely to have PE compared with the uninfected women.     

Cigarette smoking during pregnancy in relation to placenta previa.

To evaluate the relationship between cigarette smoking and the occurrence of placenta previa, we used interview and medical record data to conduct a case-control analysis of 69 placenta previa cases and 12,351 controls. The unadjusted relative risk estimate of placenta previa for women reported to have "ever smoked" during pregnancy relative to nonsmoking mothers was 1.9 (95% confidence interval, 1.2 to 3.0). The risk rose after adjusting for potential confounders (odds ratio, 2.6; 95% confidence interval, 1.3 to 5.5). In contrast to a previous report, the duration of smoking was not an independent risk factor for placenta previa. These results suggest that cigarette smoking during pregnancy is a determinant of placenta previa. Carbon monoxide hypoxemia, which is one possible mechanism for this association, may result in compensatory placental hypertrophy. Placentas with increased surface areas are more likely to cover the cervical os, causing placenta previa.     

Cigarette smoking and pregnancy II: vascular effects.

The act of smoking introduces a complex set of chemicals that have a broad range of effects, both complementary and antagonistic, at various levels within the vascular tree. A general review of these systemic effects is followed by a summary of documented effects of smoking on the uterine vasculature and of relationships of smoking to pregnancy outcomes known to be associated with vascular pathology. Last, we offer a potential resolution for the apparent paradox of the seemingly 'protective' effect of smoking to reduce the incidence of pre-eclampsia, one of the most serious vascular complications of pregnancy.     

Maternal infection and risk of preeclampsia: systematic review and metaanalysis

There are lingering questions regarding the association between maternal infection and preeclampsia. Systematic review and metaanalysis was conducted of observational studies that examined the relationship between maternal infection and preeclampsia. Forty-nine studies met the inclusion criteria. The risk of preeclampsia was increased in pregnant women with urinary tract infection (pooled odds ratio, 1.57; 95% CI, 1.45-1.70) and periodontal disease (pooled odds ratio, 1.76; 95% CI, 1.43-2.18). There were no associations between preeclampsia and presence of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus, treated and nontreated HIV infection, and malaria. Individual studies did not find a relationship between herpes simplex virus type 2, bacterial vaginosis, and Mycoplasma hominis and preeclampsia. Urinary tract infection and periodontal disease during pregnancy are associated with an increased risk of preeclampsia. More studies are required to verify this as well as to explore whether or not such relationships are causal and, if so, the mechanisms involved.     

Electroencephalography during normotensive and hypertensive pregnancy: a systematic review

The objective of this review was to evaluate the available medical literature concerning the electroencephalogram (EEG) during hypertensive disorders of pregnancy. All articles found during a MEDLINE and Embase database search on the subject of EEG differences associated with hypertensive disorders in pregnancy were screened for eligibility. In all, 22 articles which describe the EEG during preeclampsia (PE)/eclampsia were retrieved. Abnormal EEG findings were observed in the majority of the preeclamptic/eclamptic patients, consisting of slow waves most frequently localized in the occipital lobe, as well as spike discharges. The EEG abnormalities in PE/eclampsia were reversible in the majority of the cases. We conclude that these described abnormalities may be interpreted as a warning sign of deterioration of brain function in PE/eclampsia. However, some caution regarding this conclusion is advised because most of the retrieved articles were published in the 1950s and 1960s, and were not consistent with current clinical guidelines or medical terminology. Further research is needed to establish the clinical value of implementing EEGs in the assessment of the preeclamptic/eclamptic patient. TARGET AUDIENCE: Obstetricians & Gynecologists, Neurologists, Family Physicians. LEARNING OBJECTIVES: After completion of this educational activity, the obstetrician, gynecologist and neurologist should be better able to evaluate whether the EEG is normal for pregnancy; distinguish EEG abnormalities in hypertensive disorders in pregnancy, and assess the value of EEG abnormalities in preeclampsia (PE)/eclampsia for the detection of early signs of ischemia.     

Effect of folic acid supplementation during pregnancy on gestational hypertension/preeclampsia: A systematic review and meta-analysis

Objective: To evaluate the effect of folic acid supplementation during pregnancy on the risk of gestational hypertension/preeclampsia. Methods: A systematic review and meta-analysis were conducted. Medline, Embase, Scopus, and the Web of Science were searched from inception to December 2014. Results: Out of 1224 potentially relevant studies, 13 studies met our inclusion criteria (2 randomized controlled trials (RCTs), 10 cohort studies, and 1 case–control study). The pooled relative risk (RR) and 95% confidence interval (CI) of the two RCTs were 0.62 (0.45–0.87) in the trial arm as compared with the placebo arm. The pooled RR was 0.92 (95% CI: 0.79–1.08) for nine cohort studies with available data on folic acid supplementation in pregnancy and gestational hypertension/preeclampsia. Pooled RR was 0.88 (95% CI: 0.76–1.02) for eight cohort studies with available data on folic acid supplementation and preeclampsia. Conclusion: Whether folic acid supplementation in pregnancy can prevent the occurrence of gestational hypertension/preeclampsia remains uncertain.     

Prevalence of depression during pregnancy: systematic review

OBJECTIVE: Current estimates of the prevalence of depression during pregnancy vary widely. A more precise estimate is required to identify the level of disease burden and develop strategies for managing depressive disorders. The objective of this study was to estimate the prevalence of depression during pregnancy by trimester, as detected by validated screening instruments (ie, Beck Depression Inventory, Edinburgh Postnatal Depression Score) and structured interviews, and to compare the rates among instruments. DATA SOURCES: Observational studies and surveys were searched in MEDLINE from 1966, CINAHL from 1982, EMBASE from 1980, and HealthSTAR from 1975. METHODS OF STUDY SELECTION: A validated study selection/data extraction form detailed acceptance criteria. Numbers and percentages of depressed patients, by weeks of gestation or trimester, were reported. TABULATION, INTEGRATION, AND RESULTS: Two reviewers independently extracted data; a third party resolved disagreement. Two raters assessed quality by using a 12-point checklist. A random effects meta-analytic model produced point estimates and 95% confidence intervals (CIs). Heterogeneity was examined with the chi(2) test (no systematic bias detected). Funnel plots and Begg-Mazumdar test were used to assess publication bias (none found). Of 714 articles identified, 21 (19,284 patients) met the study criteria. Quality scores averaged 62%. Prevalence rates (95% CIs) were 7.4% (2.2, 12.6), 12.8% (10.7, 14.8), and 12.0% (7.4, 16.7) for the first, second, and third trimesters, respectively. Structured interviews found lower rates than the Beck Depression Inventory but not the Edinburgh Postnatal Depression Scale. CONCLUSION: Rates of depression, especially during the second and third trimesters of pregnancy, are substantial. Clinical and economic studies to estimate maternal and fetal consequences are needed.     

Low molecular weight heparin use during pregnancy and risk of postpartum hemorrhage: a systematic review and meta-analysis

Introduction: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide with a prevalence rate of approximately 6%. Although most cases of PPH have no identifiable risk factors, the incidence of PPH has been associated to the thromboprophylaxis in pregnancy with low molecular weight heparin (LMWH). Thus, the aim of the study is to evaluate the risk of PPH in cases of pregnant women exposed to LMWH.

Materials and methods: Electronic research was performed in OVID, Scopus, ClinicalTrials.gov, MEDLINE, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE, and the Cochrane Central Register of Controlled Trials through April 2016. We included randomized controlled trials, cohort and case-control studies of women who underwent thromboprophylaxis with LMWH during pregnancy compared to a control group (either placebo or no treatment). The primary outcome was the incidence of PPH. The summary measures were reported as relative risk (RR) or as mean differences (MD) with 95% confidence interval (CI).

Results: Eight studies including 22,162 women were analyzed. Of the 22,162 women, 1320 (6%) were administered LMWH, 20,842 (94%) women formed the nonexposed group (control group). Women treated with LMWH had a higher risk of PPH (RR 1.45, 95%CI 1.02–2.05) compared to controls; there was no difference in mean of blood loss at delivery (MD ?32.90, 95%CI 68.72–2.93) and in risk of blood transfusion at delivery (RR 1.24, 95%CI 0.62–2.51), respectively.

Conclusions: Women who receive LMWH during pregnancy have a significantly higher risk of developing PPH. Women who receive LMWH during pregnancy have neither significantly higher mean blood loss at delivery nor higher risk of blood transfusion.     

Aspirin for prevention of preeclampsia in women with historical risk factors: a systematic review

OBJECTIVE: To examine the effectiveness of aspirin in preventing perinatal death and preeclampsia in women with predisposing historical risk factors, such as previous history of preeclampsia, chronic hypertension, diabetes, and renal disease. DATA SOURCES: Searches were conductes in Medline, Embase, Cochrane Library, National Research Register, SCISEARCH, AND ISI Conference Proceedings without any language restrictions, using the following medical subject headings and text words: "aspirin," "antiplatelet*," "salicyl*," "acetylsalicyl*," "platelet aggregation inhibitors," "pre-eclamp*," "preeclamp*," and "hypertens*. METHODS OF STUDY SELECTION: We included all randomized trials that evaluated the effectiveness of aspirin compared with placebo or no treatment in women with predisposing historical risk factors and reported clinically relevant perinatal or maternal outcomes. Study selection, quality appraisal, and data extractions were performed independently and in duplicate.We identified 14 relevant trials, including a total of 12,416 women. Meta-analysis showed a significant benefit of aspirin therapy in reducing perinatal death (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.64, 0.96) and preeclampsia (OR 0.86, 95% CI 0.76, 0.96). Aspirin was also associated with a reduction in rates of spontaneous preterm birth (OR 0.86, 95% CI 0.79, 0.94), and an increase of 215 g in mean birth weight (weighted mean difference 215, 95% CI 90, 341). There was no increase in the risk of placental abruption with aspirin (OR 0.98, 95% CI 0.79, 1.21). Funnel plot analysis indicated that publication and related biases were unlikely (Egger test, P =.84). CONCLUSION: Aspirin reduces the risk of perinatal death and preeclampsia in women with historical risk factors. Given the importance of these outcomes and the safety and low cost of aspirin, aspirin therapy should be considered in women with historical risk factors.     

Cigarette smoking and pregnancy I: ovarian, uterine and placental effects.

This review examines the major observations and principal controversies relating to the effects of smoking and the constituents of tobacco on ovarian, uterine and placental tissues. Maternal exposure is assessed relative to specific tobacco-related chemicals and the feto-placental impact of mutagenic products, in addition to nicotine replacement as a pharmacological intervention for smoking cessation. Important new information is being learned from clinical in vitro fertilization and assisted reproduction technologies regarding the effects of smoking on fertility. Present evidence supports an adverse effect of smoking on ovarian function which is prolonged and dose-dependent, whereas there appear to be more reversible effects on implantation and ongoing pregnancy. The anti-oestrogenic effect of smoking is reviewed in terms of direct effects of nicotine, cadmium and polyaromatic hydrocarbons on oestrogen synthesis and metabolism, oocytes and granulosa-luteal function. Innovative new models provide evidence that smoking may alter fertility through effects on uterine-fallopian tube functions which mediate gamete and conceptus transport. It is of interest that smoking is associated with a decreased incidence of uterine fibroids, endometriosis and uterine cancer, which may reflect inhibitory effects of smoke constituents on uterine cell proliferation and extracellular matrix interactions. The increased miscarriage rate among mothers who smoke may be related to direct adverse effects of nicotine, cadmium and polyaromatic hydrocarbons on trophoblast invasion and proliferation. In this respect, alterations in trophoblast differentiation along invasive or proliferative pathways may explain the changes in endocrine function and vascular morphology that are observed in smokers. In summary, significant advances are being made in the understanding of cellular and molecular mechanisms which underlie the differential effects of cigarette smoking on reproductive tissues.     

Maternal and fetal effects of chocolate consumption during pregnancy: a systematic review

Objectives: The purpose of this review is to explore the effects of chocolate consumption during pregnancy on fetus and mother herself.

Methods: Randomized controlled trials/quasi-experimental/observational/controlled before and after studies involving chocolate/cocoa/cacao consumption (irrespective of type or dose, composition, exposure period, and method of administration) among pregnant women/animals; and measuring any outcome (beneficial or harmful) related to fetus or mother after chocolate exposure were included. Databases searched were PubMed, Web of Science and Scopus; between April and May 2017. Risk of bias within each human randomized controlled trial (RCT) and animals’ experimental studies was evaluated by “The Cochrane Collaboration’s tool” and SYRCLE’s tool respectively.

Results: Fourteen human studies including a total of 6639 participants and nine animal studies were selected. Outcome variables investigated in human studies were maternal blood pressure, fetal heart rate, and striae gravidarum. Animal studies explored chocolate-induced teratogenicity and fetal metabolic derangements. Ten out of these 23 studies reported chocolate to be “beneficial”; five studies reported adverse effects, whereas eight studies declared chocolate as “neutral”.

Conclusions: Maternal chocolate intake has acute stimulatory effects on fetal reactivity and chronic blood pressure reducing effect in mothers. Chocolate is nonteratogenic and does not affect reproductive indices. Metabolic derangements in offsprings born to chocolate fed dams have been reported. Pregnant females must be careful about consumption of cocoa and chocolate. Future studies should be planned, keeping in view heterogeneities identified across the selected studies in this review.     

Prediction of preeclampsia in type 1 diabetes in early pregnancy by clinical predictors: a systematic review

Purpose: The purpose of this study is to evaluate the prevalence and possible clinical predictors of preeclampsia present in early pregnancy among women with type 1 diabetes.

Methods: A systematic search of PubMed was conducted in April 2017. Inclusion criteria were largely unselected cohort, including at least 100 women with type 1 diabetes, dealing with either the prevalence of preeclampsia or possible clinical predictors of preeclampsia identified in early pregnancy.

Results: Based on 11,518 pregnancies in 11 articles, the prevalence of preeclampsia in women with type 1 diabetes was 17%, five to six times more than in the background population. In early pregnancy, the following clinical predictors were associated with increased prevalence of preeclampsia: diabetic nephropathy (OR 3.7–23.5), microalbuminuria (OR 3.8–11.7), diabetic retinopathy (OR 1.9–2.9) and pre-existing hypertension (OR 3.8–17.1) as well as high blood pressure within the normotensive range. HbA1C, body mass index and nulliparity were positively associated with preeclampsia, but not consistently.

Conclusion: The prevalence of preeclampsia in women with type 1 diabetes was 17%. In early pregnancy pre-existing hypertension and high blood pressure within the normotensive range as well as presence of microangiopathy were predictors of preeclampsia. Poor glycaemic control, obesity and nulliparity probably also contribute to the increased risk.     

Herb remedies during pregnancy: a systematic review of controlled clinical trials

Objective: The use of herbal remedies has been documented both among various patient groups and in the general population to promote health. The aim of this systematic review is to analyze the benefits of herb use during pregnancy. Methods: A systematic literature search covering the period from January 1990 to September 2010 was performed using various electronic databases. Randomized controlled clinical trials (RCTs) were included. Paper quality was evaluated using the Jadad scale. Results: Of the 511 articles identified, 14 RCTs were eligible. Ginger was the most investigated remedy and was consistently reported to ameliorate nausea and vomiting during pregnancy better than placebo; its efficacy in doing so was noted to be equal to that of vitamin B6 and dimenhydrinate. A single trial also supported the use of Hypericum perforatum for wound healing. Cranberry, however, was not efficacious in the treatment of urinary tract infections; finally, raspberry leaf did not shorten the first stage of labor, and garlic did not prevent pre-eclampsia. Conclusions: Despite the widespread, popular use of herbal remedies during pregnancy, too few studies have been devoted to specific clinical investigations. With the exception of ginger, there is no data to support the use of any other herbal supplement during pregnancy.