Periodontal disease and pregnancy outcomes: state-of-the-science

To examine the existing evidence on the relationship between periodontal disease and adverse pregnancy outcomes, we conducted a systematic review of studies published up to December 2006. Studies published in full text were identified by searching computerized databases (e.g., MEDLINE, EMBASE). A meta-analysis was performed to pool the effect size of the clinical trials. Forty-four studies were identified (26 case-control studies, 13 cohort studies, and 5 controlled trials). The studies focused on preterm low birth weight, low birth weight, preterm birth, birth weight by gestational age, miscarriage or pregnancy loss, preeclampsia, and gestational diabetes mellitus. Of the chosen studies, 29 suggested an association between periodontal disease and increased risk of adverse pregnancy outcome (odds ratios [ORs] ranging from 1.10 to 20.0) and 15 found no evidence of an association (ORs ranging from 0.78 to 2.54). A meta-analysis of the clinical trials suggested that oral prophylaxis and periodontal treatment may reduce the rate of preterm low birth weight (pooled risk ratio (RR): 0.53, 95% confidence interval [CI]: 0.30-0.95, P < 0.05), but did not significantly reduce the rates of preterm birth (pooled RR: 0.79, 95% CI: 0.55-1.11, P > 0.05) or low birth weight (pooled RR: 0.86, 95% CI: 0.58%1.29, P > 0.05). The authors conclude that periodontal disease may be associated with increased risk of adverse pregnancy outcomes. More methodologically rigorous studies are needed in this field. Currently, there is insufficient evidence to support the provision of periodontal treatment during pregnancy for the purpose of reducing adverse pregnancy outcomes. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to state that the published literature is not vigorous to clinically link periodontal disease and/or its treatment to specific adverse pregnancy outcomes, and explain that more rigorous studies with world-wide agreed-upon definitions are particularly needed before periodontal disease treatment can be recommended.     

Genetic thrombophilias and preeclampsia: a meta-analysis

OBJECTIVE: To assess the relationship between the factor V Leiden (1691 G-A) single nucleotide polymorphism (SNP), the methylene tetrahydrofolate reductase (MTHFR) 677 C-T SNP, and the prothrombin 20210 G-A SNP and the risk of preeclampsia, by conducting a meta-analysis of all case-control studies with data on these polymorphisms and the risk of preeclampsia. DATA SOURCES: MEDLINE (1966 to November 2002), EMBASE (1980 to November 2002). Search terms included "preeclampsia," "thrombophilia," "factor V Leiden," "protein C," "MTHFR," "methylenetetrahydrofolate reductase," "homocysteine," and "prothrombin gene 20210."METHODS OF STUDY SELECTION: Case-control studies of genetic thrombophilias and preeclampsia were included. TABULATION, INTEGRATION, AND RESULTS: We identified 349 titles and reviewed 47 articles for inclusion and exclusion criteria. Thirty-one studies with 7,522 patients were included in the meta-analysis. Data from patients characterized as having severe preeclampsia were extracted and analyzed separately. The pooled odds ratio (OR) for the association of factor V Leiden and all cases of preeclampsia was 1.81 (95% confidence interval [CI] 1.14-2.87) and 2.24 (95% CI 1.28-3.94) for cases of severe preeclampsia. The pooled OR for the MTHFR 677 TT genotype and all preeclampsia was 1.01 (95% CI 0.79-1.29) and 1.38 (95% CI 0.93-2.06) for severe preeclampsia. The OR for the prothrombin 20210 polymorphism and all preeclampsia was 1.37 (95% CI 0.72-2.57) and 1.98 (.94-4.17) for severe preeclampsia. CONCLUSION: This meta-analysis suggests that the factor V Leiden SNP is associated with an increased risk of preeclampsia. Further studies are warranted to determine whether subgroups of high-risk women should be screened for this mutation.     

Maternal periodontal disease is associated with an increased risk for preeclampsia

OBJECTIVE: To determine if maternal periodontal disease is associated with the development of preeclampsia. METHODS: A cohort of 1,115 healthy pregnant women were enrolled at less than 26 weeks' gestation and followed until delivery. Maternal demographic and medical data were collected. Periodontal examinations were performed at enrollment and within 48 hours of delivery to determine the presence of severe periodontal disease or periodontal disease progression. Preeclampsia was defined as blood pressure greater than 140/90 on two separate occasions, and at least 1+ proteinuria on catheterized urine specimen. The potential effects of maternal age, race, smoking, gestational age at delivery, and insurance status were analyzed, and adjusted odds ratios for preeclampsia were calculated using multivariable logistic regression. RESULTS: During the study period, 763 women delivered live infants and had data available for analysis. Thirty-nine women had preeclampsia. Women were at higher risk for preeclampsia if they had severe periodontal disease at delivery (adjusted odds ratio 2.4, 95% confidence interval 1.1, 5.3), or if they had periodontal disease progression during pregnancy (adjusted odds ratio 2.1, 95% confidence interval 1.0, 4.4). CONCLUSION: After adjusting for other risk factors, active maternal periodontal disease during pregnancy is associated with an increased risk for the development of preeclampsia.     

Weight at birth and subsequent risk of preeclampsia as an adult

OBJECTIVE: We examined the influence of maternal birth weight on the risk of the development of preeclampsia, a likely precursor to adult chronic disease. STUDY DESIGN: This hospital-based case-control study included 181 preeclampsia cases and 349 control subjects. Participants provided information about their birth weight and other covariates that included medical and reproductive history, prepregnancy weight, and adult height. Odds ratios and 95% CIs were estimated by logistic regression. RESULTS: The risk of preeclampsia decreased as maternal birth weight increased (P=.01). After an adjustment was made for confounders, data showed that women with a low birth weight (<2500 g) had a 2.3-fold increased risk of experiencing preeclampsia (95% CI, 1.0-5.3) as compared with women who weighed 2500 to 2999 g at birth. Conversely, women with a birth weight of >/=4000 g appeared to have a nonstatistically significant, but >50%, reduction in the risk of experiencing preeclampsia (95% CI, 0.2-1.2). This relationship differed for lean and overweight women (body mass index, <25 kg/m(2) vs >/=25 kg/m(2)). Among lean women, those who were low birth weight had a near doubling in risk of the development of preeclampsia (odds ratio, 1.9; 95% CI, 0.8-4.6), although this association did not reach statistical significance. However, among overweight women, those women who weighed <2500 g at birth had an almost 4-fold increased risk of experiencing preeclampsia (odds ratio, 3.8; 95% CI, 1.1-13.8). CONCLUSION: These results confirm two earlier reports and expand the literature by showing that women who are small at birth and who become overweight as adults are at particularly high risk of the development of preeclampsia.     

Maternal smoking and preeclampsia

OBJECTIVE: To study the relationship between maternal smoking and preeclampsia and whether this association differs between primiparous and multiparous women. STUDY DESIGN: We conducted a population-based, retrospective, cohort study of 58,216 singleton pregnancies from northern and central Alberta, Canada, between 1995 and 1997. Multivariate logistic regression was used to control for maternal alcohol consumption, drug dependence, maternal age, maternal weight, prior intrauterine growth restriction and other confounders. RESULTS: Maternal smoking was associated with a significantly reduced overall risk of preeclampsia (adjusted odds ratio [aOR]: .61; 95% confidence interval [CI]: .50-.75; P < .01). Stratified analyses showed that in primiparous pregnancies, maternal smoking was associated with a significantly decreased risk (aOR: .63; 95% CI: .50-.80; P < .01); in multiparous women, maternal smoking was not associated with a statistically significant decreased risk of preeclampsia (aOR: 0.72; 95% CI: .51-1.02; P > .05). CONCLUSION: Maternal smoking is protective against preeclampsia. Understanding the underlying biologic mechanisms of this protective effect may advance our knowledge of the pathogenesis of preeclampsia.     

Risk factors for urinary tract infection in the postpartum period.

OBJECTIVE: We sought to examine risk factors for urinary tract infection in postpartum women.Study Design: Subjects (n = 931) with maternal urinary tract infections and control subjects (n = 1862) were identified by using a linked Washington State birth certificate and Birth Events Records Database for the years 1987-1993; stratified analysis was performed by using Mantel-Haenszel procedures. RESULTS: Increased risk for postpartum urinary tract infection was associated with black, Native American, or Hispanic race-ethnicity (odds ratio, 1.30; 95% confidence interval, 1.03-1.64) and unmarried status (odds ratio, 1.33; 95% confidence interval, 1.11-1.58). Cesarean delivery (odds ratio, 2.70; 95% confidence interval, 2.27-3.20) and tocolysis (odds ratio, 3.30; 95% confidence interval, 2.15-5.06) also contributed to maternal risk of acquiring a urinary tract infection. Maternal risk factors included renal disease (adjusted odds ratio, 3.89; 95% confidence interval, 1.80-8.41) and preeclampsia-eclampsia (adjusted odds ratio, 3.21; 95% confidence interval, 2.36-4.38). Among women undergoing vaginal delivery, renal disease (odds ratio, 5.47; 95% confidence interval, 2.04-14.64) and abruptio placentae (odds ratio, 5.02; 95% confidence interval, 1.84-13.64) were risk factors. Length of hospital stay was significantly associated with urinary tract infection. CONCLUSION: Maternal medical conditions and procedures that predispose to urinary tract infections are those that also are associated with urethral catheterization. In addition, maternal urinary tract infections may contribute significantly to duration of postpartum hospital stay.     

Maternal complications and perinatal outcomes associated with gestational hypertension and severe preeclampsia in Taiwanese women.

BACKGROUND/PURPOSE: The role of proteinuria in disease severity of preeclampsia and gestational hypertension has not been determined. The objective of this study was to compare the effects of disease severity on maternal complications and pregnancy outcome between women with severe preeclampsia and women with gestational hypertension. METHODS: A retrospective case-control study using daily records from the birth registry for the years 1994 to 2003 was conducted. Cases (n = 364) were defined as women with severe preeclampsia. Controls (n = 249) were selected from women with gestational hypertension. The outcome measures were maternal complications and perinatal-related factors. RESULTS: Women with severe preeclampsia had an increased risk of intrauterine growth restriction (adjusted odds ratio [aOR], 2.16; 95% confidence interval [CI], 1.10-4.24; p = 0.026). Risk factors associated with severe preeclampsia patients were lack of prenatal care (aOR, 2.95; 95% CI, 1.45-5.99), systolic blood pressure >or= 180 mmHg (aOR, 14.3; 95% CI, 1.69-121.0), and diastolic blood pressure >or= 105mmHg (aOR, 21.2; 95% CI, 6.99-64.3) compared with women with gestational hypertension in Model I. When we added proteinuria as a variable, two significant risk factors, diastolic blood pressure >or= 105mmHg (aOR, 18.2; 95% CI, 4.85-68.3) and significant proteinuria (aOR, 1.01; 95% CI, 1.006-1.014), were associated with severe preeclampsia patients in Model II. A subgroup of women with gestational hypertension and proteinuria had an increased risk of placental abruption (unadjusted OR, 4.36; 95% CI, 1.05-18.1) and disseminated intravascular coagulation (unadjusted OR, 6.46; 95% CI, 1.05-39.8). Finally, maternal complications (aOR, 2.59; 95% CI, 1.34-5.04) became the single significant factor associated with gestational hypertension and proteinuria. CONCLUSION: Proteinuria may play a role in the progression of gestational hypertension to severe forms of preeclampsia associated with subsequent maternal complications and extremely-low-birth-weight babies.     

A study of female urinary tract infection caused by urodynamic investigation

OBJECTIVE: The purpose of this study was to assess the prevalence of female urinary tract infection before and after urodynamic investigation and to identify the risk factors for urinary tract infection after urodynamic investigation. STUDY DESIGN: Eight hundred twenty-two consecutive incontinent women were recruited. All women were "double-screened" and treated for urinary tract infection before urodynamic investigation: first by mid stream urine culture 4 to 6 weeks before investigation and then by reagent strips for urine leukocytes and nitrites at the time of investigation. The investigation was postponed until the urinary tract infection had been treated. All women then received a standard urodynamic investigation. RESULTS: The prevalence of urinary tract infection before urodynamic investigation was 5.1% (95% CI, 3.6-6.6), and the prevalence after the investigation was 8.4% (95% CI, 6.5-10.3). Three independent risk factors were identified: age >or=70 years (odds ratio, 1.99; 95% CI, 1.14-3.48), previous continence surgery (odds ratio, 1.90; 95% CI, 1.05-3.43), and urinary tract infection before urodynamic investigation (odds ratio, 3.13; 95% CI, 1.43-6.83). The 3 most common uropathogens in the urinary tract infections after the urodynamic investigation were Escherichia coli (46.3%), Enterococcus spp (16.4%), and Enterococcus faecalis (11.9%). CONCLUSION: Despite a stringent screen-and-treat protocol before urodynamic investigation, patients still experienced urinary tract infection.     

Effect of maternal herpes simplex virus (HSV) serostatus and HSV type on risk of neonatal herpes

BACKGROUND: Neonatal herpes simplex virus (HSV) is a rare but devastating disease. We have conducted pooled analyses of data from 3 cohorts to evaluate the effects of maternal HSV serostatus and HSV type on risk of neonatal HSV acquisition and severity. METHODS: Data from cohorts in Seattle, WA, and Stanford, CA, USA, and Stockholm, Sweden were pooled using Mantel-Haenszel methods. RESULTS: Seventy-eight infants with documented neonatal HSV and known maternal HSV serostatus were included. The risk of neonatal HSV-2 infection was similar in infants born to HSV seronegative women compared with HSV-1 seropositive women (pooled OR: 1.6; 95% CI: 0.6-4.0). The odds of neonatal HSV infection was increased in the presence of exposure to maternal HSV-1 versus HSV-2 (adjusted pooled OR: 19.2; 95% CI: 5.8-63.6). An elevated odds of disseminated HSV in infants born to women with newly acquired genital herpes was observed in Stockholm (OR=13.5; 95% CI: 1.4-630), but not in Seattle or Stanford. CONCLUSION: Our results suggest that maternal HSV-1 antibody offers little, if any, protection against neonatal HSV-2 infection. During reactivation, HSV-1 appears more readily transmissible to the neonate than HSV-2, a concerning finding given the rising frequency of genital HSV-1 infection.     

Association between allelic variants in cytokine genes and preeclampsia

OBJECTIVE: The purpose of this study was to examine the relationship between cytokine genotypes and preeclampsia. STUDY DESIGN: We conducted a case-control study that examined cytokine genotypes among 150 primiparous preeclamptic women and 661 primiparous, normotensive women. Analyses were adjusted for age, prepregnancy cigarette smoking, and education. RESULTS: Preeclamptic white women were more likely than normotensive white women to carry the up-regulating tumor necrosis factor-alpha-308 A/A (odds ratio, 4.1; 95% CI, 1.1-15.3) genotype. Both black and white women with preeclampsia were more likely than normotensive control subjects to carry the interleukin-1alpha-producing-4845 G/G genotype (black odds ratio, 11.6; 95% CI, 1.5-89.3; white odds ratio, 1.7; 95% CI, 0.7-3.9), -889 C/C genotype (black odds ratio, 5.1; 95% CI, 0.6-41.6; white odds ratio, 1.9; 95% CI, 0.8-4.7), and the interleukin-1alpha-4845/interleukin-1alpha-889/interleukin-1beta-3957 GCC/GCC haplotype (black odds ratio, 3.4; 95% CI, 1.3-8.7; white odds ratio, 2.1; 95% CI, 1.4-3.2). CONCLUSION: Cytokine genotypes were associated with preeclampsia and may identify women who are at high risk for preeclampsia.     

Maternal plasma transforming growth factor-beta1 concentrations in preeclamptic and normotensive pregnant Zimbabwean women.

OBJECTIVE: We examined the relationship between maternal plasma transforming growth factor-beta1 (TGF-beta1) concentrations and risk of preeclampsia among women delivering at Harare Maternity Hospital in Zimbabwe. We evaluated the relationship in the context of maternal systemic inflammation using plasma tumor necrosis factor-a soluble receptor p55 (sTNFp55) as a marker. METHODS: 132 women with preeclampsia and 180 controls were included in this case-control study analysis. Maternal post-diagnosis plasma TGF-beta1 and sTNFp55 concentrations were determined using immunoassays. Logistic regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounders. RESULTS: A linear increase in preeclampsia risk was observed with increasing quartiles of TGF-beta1 concentrations (p<0.01). Women whose TGF-beta1 concentrations were >or=25.1 ng/ml (quartile 4) had a 2.5-fold (95% CI 1.2-5.6) increased risk of preeclampsia as compared with those women whose concentrations were <11.2 ng/ml (quartile 1). Relative to women with no evidence of systemic inflammation and no elevated TGF-beta1 concentrations, those women who were jointly positive for elevated TGF-beta1 and sTNFp55 concentrations experienced a 5.3-fold (95% CI 2.3-12.0) increased risk of preeclampsia. CONCLUSION: Overall, we noted that elevated TGF-beta1 is associated with an increased risk of preeclampsia. We also noted that the preeclampsia risk is exaggerated in the presence of maternal systemic inflammation.     

Periodontal disease and adverse pregnancy outcomes: a systematic review

BACKGROUND: Recent studies suggest that periodontal disease, as a source of subclinical and persistent infection, may induce systemic inflammatory responses that increase the risk of adverse pregnancy outcomes. OBJECTIVES: To examine the existing evidence on the relationship between periodontal disease and adverse pregnancy outcomes. SEARCH STRATEGY: Published studies identified via searches of the MEDLINE, EMBASE, CINAHL, and Current Contents full-text databases. SELECTION CRITERIA: We identified and selected observational studies (i.e. case-control, cross-sectional, and cohort) and nonrandomised controlled studies or randomised controlled trials that examined periodontal disease as a risk factor for adverse pregnancy outcomes. DATA COLLECTION AND ANALYSIS: Odds ratios (OR) or risk ratios (RR) were extracted or calculated from the studies' data. We calculated pooled effect size for two clinical controlled trials but not for the observational studies due to the heterogeneity in definitions for periodontal disease and adverse pregnancy outcomes across studies. MAIN RESULTS: Twenty-five studies (13 case-control, 9 cohort, and 3 controlled trials) were identified. The studies focused on preterm low birthweight, low birthweight, preterm birth, birthweight by gestational age, miscarriage or pregnancy loss, and pre-eclampsia. Of the chosen studies, 18 suggested an association between periodontal disease and increased risk of adverse pregnancy outcome (ORs ranging from 1.10 to 20.0) and 7 found no evidence of an association (ORs ranging from 0.78 to 2.54). Three clinical trial studies suggest that oral prophylaxis and periodontal treatment can lead to a 57% reduction in preterm low birthweight (pooled RR 0.43; 95% CI 0.24-0.78) and a 50% reduction in preterm births (RR 0.5; 95% CI 0.20-1.30). AUTHOR'S CONCLUSIONS: Periodontal disease may be associated with an increased risk of adverse pregnancy outcome. However, more methodologically rigorous studies are needed for confirmation.     

Pregnancy outcomes in systemic sclerosis, primary pulmonary hypertension, and sickle cell disease

OBJECTIVE: Systemic sclerosis, primary pulmonary hypertension, and sickle cell disease are uncommon vasculopathic diseases affecting women. We estimated the nationwide occurrence of pregnancies in women with these conditions and compared pregnancy outcomes to the general obstetric population. METHODS: We studied the 2002-2004 Nationwide Inpatient Sample, of the Healthcare Cost and Utilization Project to estimate the number of obstetric hospitalizations and deliveries among women with systemic sclerosis, primary pulmonary hypertension, sickle cell disease, and women in the general population. Pregnancy outcomes included length of hospital stay, hypertensive disorders including preeclampsia, intrauterine growth restriction (IUGR), and cesarean delivery. Multivariable regression analyses were performed using maternal age, race or ethnicity, antiphospholipid antibody syndrome, diabetes mellitus, and renal failure as covariates. RESULTS: Of an estimated 11.2 million deliveries, 504 occurred in women with systemic sclerosis, 182 with primary pulmonary hypertension, and 4,352 with sickle cell disease. Systemic sclerosis, was associated with an increased risk of hypertensive disorders including preeclampsia (odds ratio [OR] 3.71, 95% confidence interval [CI] 2.25-6.15), IUGR (OR 3.74, 95% CI 1.51-9.28), and increased length of hospital stay. Primary pulmonary hypertension was associated with an increase in the odds of antenatal hospitalization (OR 4.67, 95% CI 2.88-7.57), hypertensive disorders including preeclampsia (OR 5.62, 95% CI 2.60-12.15) and a substantial increase in length of hospital stay. Sickle cell disease was associated with an increased odds of antenatal hospitalization (OR 5.56 95% CI 5.08-6.09), hypertensive disorders including preeclampsia (OR 1.78, 95% CI 1.48-2.14), and IUGR (OR 2.91, 95% CI 2.16-3.93), with a modest increase in length of hospital stay. CONCLUSION: Women with systemic sclerosis, primary pulmonary hypertension, and sickle cell disease have significantly increased rates of adverse pregnancy outcomes, requiring extensive preconceptional counseling about the risks of pregnancy.     

The association between hyaline membrane disease and preeclampsia

OBJECTIVE: The purpose of this study was to determine whether hyaline membrane disease is increased in newborn infants who are born to women with preeclampsia compared with control subjects. STUDY DESIGN: This was a historic cohort study of deliveries between 24 and 37 weeks of gestation at the Medical University of South Carolina from 1996 through 2002. Singleton infants who were born to women with preeclampsia were compared with nonpreeclamptic control subjects. The incidence of hyaline membrane disease was compared by chi 2 analysis and Fisher exact test, with significance at a probability value of <.05. Logistic regression analysis was performed to address potential confounders. RESULTS: There were 814 women with preeclampsia and 3021 control subjects. When we controlled for confounding factors, there was a significant increase in the incidence of hyaline membrane disease in the preeclamptic group overall (odds ratio, 1.35; 95% CI, 1.03-1.78). The risk was more pronounced in neonates who were born at 32 weeks of gestation (odds ratio, 1.93; 95% CI, 1.28-2.91). CONCLUSION: The risk of hyaline membrane disease in neonates at < 32 weeks of gestation is increased in patients with preeclampsia. This supports the contention that fetal lung maturity is not accelerated in preeclampsia.     

Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis

OBJECTIVE: We performed a meta-analysis to evaluate bacterial vaginosis as a risk factor for preterm delivery. STUDY DESIGN: Selection criteria were (1). the data appeared in original, published English-language reports of prospective studies or control groups of clinical trials that included women at <37 weeks of gestation with intact amniotic membranes, (2). all the women had to have been screened for bacterial vaginosis that was diagnosed by either clinical criteria or criteria that were based on Gram stain findings, and (3). the outcomes were preterm delivery, spontaneous abortion, maternal or neonatal infection, and perinatal death. RESULTS: Eighteen studies with results for 20,232 patients were included. Bacterial vaginosis increased the risk of preterm delivery >2-fold (odds ratio, 2.19; 95% CI, 1.54-3.12). Higher risks were calculated for subgroups of studies that screened for bacterial vaginosis at <16 weeks of gestation (odds ratio, 7.55; 95% CI, 1.80-31.65) or at <20 weeks of gestation (odds ratio, 4.20; 95% CI, 2.11-8.39). Bacterial vaginosis also significantly increased the risk of spontaneous abortion (odds ratio, 9.91; 95% CI, 1.99-49.34) and maternal infection (odds ratio, 2.53; 95% CI, 1.26-5.08). No significant results were calculated for the outcome of neonatal infection or perinatal death. CONCLUSION: Bacterial vaginosis, early in pregnancy, is a strong risk factor for preterm delivery and spontaneous abortion.     

Maternal dyslipidemia during pregnancy may increase the risk of preterm birth: A meta-analysis

Epidemiological studies have reported an inconsistent relationship between maternal lipid levels and preterm birth (PTB). We performed this meta-analysis to evaluate the association between maternal dyslipidemia and PTB. Overall, three nested case-control studies and eight cohort studies were eligible. Effect estimates [odds ratio(OR)/relative risk] were pooled using a fixed-effects or a random-effects model. Subgroup and metaregression analyses were conducted to evaluate the sources of heterogeneity. Eleven studies involving 13,025 pregnant women were included. Compared with pregnant women with normal lipid levels, the women with elevated levels of lipids had an increased risk of PTB, and the pooled OR was 1.68 [95% confidence interval (CI): 1.25–2.26)]; meanwhile, women with lower levels of lipids also had a trend of an increased risk of PTB (OR = 1.52, 95% CI = 0.60–3.82). The pooled ORs for elevated levels of total cholesterol, triglycerides, low density lipoprotein-cholesterol, and lower levels of high density lipoprotein-cholesterol were 1.71 (95% CI: 1.05–2.79), 1.55 (95% CI: 1.13–2.12), 1.19 (95% CI: 0.95–1.48), and 1.33 (95% CI: 1.14–1.56), respectively. The present meta-analysis found that maternal dyslipidemia during pregnancy, either the elevated total cholesterol or triglycerides, was associated with an increased risk of PTB. These findings indicate that a normal level of maternal lipid during pregnancy may reduce the risk of PTB.     

Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: A systematic review.

Placental infarction or abruption, recurrent pregnancy loss and pre-eclampsia are thought to arise due to defects within the placental vascular bed. Deficiencies of vitamin B12 and folate, or other abnormalities within the methionine-homocyst(e)ine pathway have been implicated in the development of such placental diseases. We conducted a systematic literature review to quantify the risk of placental disease in the presence of these metabolic defects.Studies were identified through OVID Medline between 1966 and February 1999. Terms relating to the measurement of vitamin B12, folic acid, methylenetetrahydrofolate reductase or homocyst(e)ine were combined with those of pre-eclampsia, placental abruption/infarction or spontaneous and habitual abortion. Human studies comprising both cases and controls and published in the English language were accepted. Their references were explored for other publications.Data were abstracted on the matching of cases with controls, the mean levels of folate, B12 or homocyst(e)ine in each group or the frequency of the homozygous state for the thermolabile variant of methylenetetrahydrofolate reductase. The definition of 'abnormal' for each exposure was noted and the presence or absence of the exposure of interest for each outcome was calculated as an absolute rate with a 95 per cent confidence interval. The crude odds ratios were calculated for each study and then pooled using a random effects model.Eighteen studies were finally included. Eight studies examined the risk of placental abruption/infarction in the presence of vitamin B12 or folate deficiency, or hyperhomocyst(e)inaemia. Folate deficiency was a prominent risk factor for placental abruption/infarction among four studies, though not statistically significant (pooled odds ratio 25.9, 95 per cent CI 0.9-736.3). Hyperhomocyst(e)inaemia was also associated with placental abruption/infarction both without (pooled odds ratio 5.3, 95 per cent CI 1.8-15.9) and with methionine loading (pooled odds ratio 4.2, 95 per cent CI 1.2-15.0), as was the homozygous state for methylenetetrahydrofolate reductase (pooled odds ratio 2.3, 95 per cent CI 1.1-4.9). Vitamin B12 deficiency was not a demonstrable risk factor.Eight studies examined blood levels among women with spontaneous abortion or recurrent pregnancy loss. The pooled odds ratios were 3.4 (95 per cent CI 1.2-9.9) for folate deficiency, 3.7 (95 per cent CI 0.96-16.5) for hyperhomocyst(e)inaemia following methionine challenge, and 3.3 (95 per cent CI 1.2-9.2) for the methylenetetrahydrofolate reductase mutation.Five case-control studies examined the relationship between pre-eclampsia and abnormal levels of vitamin B12, folate, homocyst(e)ine or methylenetetrahydrofolate reductase. Folate deficiency was not an associated risk factor (odds ratio 1.2, 95 per cent CI 0.5-2.7), but hyper-homocyst(e)inaemia was (pooled odds ratio 20.9, 95 per cent CI 3.6-121.6). Similarly, homozygosity for the methylenetetrahydrofolate reductase thermolabile variant was associated with a moderate risk of preeclampsia (odds ratio 2.6, 95 per cent CI 1.4-5.1). Some pooled data were associated with significant statistical heterogeneity, however.There is a general agreement among several observational studies that folate deficiency, hyperhomocyst(e)inaemia and homozygosity for the methylenetetrahydrofolate reductase thermolabile variant are probable risk factors for placenta-mediated diseases, such as pre-eclampsia, spontaneous abortion and placental abruption. Vitamin B12 deficiency is less well defined as an important risk factor. Due to the limited quality of these data, including insufficient matching of cases with controls, and possible laboratory measurement bias relating to pregnancy, prospective studies are needed to confirm these findings and guide future preventative and therapeutic research.     

The frequency and severity of placental findings in women with preeclampsia are gestational age dependent

OBJECTIVE: The purpose of this study was to evaluate placental lesions found in women with preeclampsia compared with normotensive control subjects and to determine whether the presence of these lesions are related to gestational age at delivery. STUDY DESIGN: Placental disease of women with preeclampsia at 24 to 42 weeks of gestation was compared with the placental disease of normotensive gestational age-matched control subjects. The placental lesions that were studied specifically included decidual arteriolopathy, thrombi in the fetal circulation, central infarction, intervillous thrombi, and hypermaturity of villi. Data analysis involved the chi(2) test, the Student t test, and logistic regression; odds ratios and CIs were estimated. RESULTS: Placentas from women with preeclampsia (n=158) and normotensive control subjects (n=156) were evaluated. Among women with preeclampsia, 67% had severe disease. Placental lesions were studied according to gestational age at delivery: <28, 28 to 32, 33 to 36, and >or=37 weeks of gestation. Of the placental lesions that were studied, decidual arteriolopathy (odds ratio, 23.8, 95% CI 10.0-57.0), hypermaturity of villi (odds ratio, 12.4; 95% CI 5.3-29.2), intervillous thrombi (odds ratio, 1.95;95% CI 1.0-3.7), central infarction (odds ratio, 5.9; 95% CI 3.1-11.1), and thrombi in the fetal circulation (odds ratio, 2.8; 95% CI 1.2-6.6) were found to have significantly higher rates in the preeclamptic group. In contrast, the rate of chorioamnionitis was significantly lower in the preeclamptic group (odds ratio, 0.2; 95% CI 0.1-0.4). The rates of abruptio placentae and meconium staining were not different between the two groups. Within the preeclamptic group, the rates of decidual arteriolopathy (P<.0001), central infarction (P=.0001), and hypermaturity of villi (P<.0001) were higher the earlier the gestational age at delivery. CONCLUSION: Placentas in women with preeclampsia have increased amounts of disease. The rate is increased with lower gestational ages at the time of delivery for women with preeclampsia.     

Interaction between risk factors for fetal growth retardation associated with abnormal umbilical artery Doppler studies

BACKGROUND: The role of antenatal risk factors associated with the occurrence of fetal growth restriction complicated by abnormal umbilical artery Doppler studies has not yet been studied extensively. We evaluated the role and the interactions of antenatal antecedents of fetal growth restriction complicated by abnormal umbilical artery end-diastolic velocities. METHODS: We compared antenatal variables in 183 pregnancies complicated by fetal growth retardation and abnormal umbilical artery Doppler studies and 549 appropriately grown fetuses with normal end-diastolic velocity waveform in the umbilical artery. Logistic regression was used to evaluate the association between antenatal variables and fetal growth retardation and to test for interaction. RESULTS: In logistic models, increasing maternal age [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.01-1.11], nulliparity (OR 2.2, 95% CI 1.37-3.5), smoking during pregnancy (OR 2.56, 95% CI 1.56-4.22), preeclampsia (OR 27.5, 95% CI 15.1-49.9), first-trimester hemorrhage (OR 2.25, 95% CI 1.32-3.82) and low (< 0.2 kg/week) weight gain in pregnancy (OR 3.48, 95% CI 1.71-3.05) were significantly associated with an increased risk of fetal growth restriction complicated by abnormal Doppler studies. These risk factors were also significantly correlated with the occurrence of absent/reversed end-diastolic blood flow in the umbilical artery. Maternal smoking during pregnancy interacted negatively with preeclampsia but positively with a low weight gain in pregnancy. CONCLUSIONS: The results of this study have shown that antenatal risk factors for intrauterine growth retardation (IUGR) complicated by abnormal Doppler studies are similar to those associated with the birth of a small-for-gestational-age infant. Preeclampsia, maternal smoking and low weight gain in pregnancy play a significant causal role in the origin of fetal growth restriction associated with abnormal uteroplacental blood flow.