Folic acid and multivitamin supplement use and risk of placental abruption: a population-based registry study

The authors investigated a possible association of supplemental folic acid and multivitamin use with placental abruption by using data on 280,127 singleton deliveries recorded in 1999-2004 in the population-based Medical Birth Registry of Norway. Odds ratios, adjusted for maternal age, marital status, parity, smoking, pregestational diabetes, and chronic hypertension, were estimated with generalized estimating equations for logistic regression models. Use of folic acid and/or multivitamin supplements before or any time during pregnancy was reported for 36.4% of the abruptions (0.38% of deliveries) and 44.4% of the nonabruptions. Compared with no use, any supplement use was associated with a 26% risk reduction of placental abruption (adjusted odds ratio = 0.74, 95% confidence interval: 0.65, 0.84). Women who had taken folic acid alone had an adjusted odds ratio of 0.81 (95% confidence interval: 0.68, 0.98) for abruption, whereas multivitamin users had an adjusted odds ratio of 0.72 (95% confidence interval: 0.57, 0.91), relative to supplement nonusers. The strongest risk reduction was found for those who had taken both folic acid and multivitamin supplements (adjusted odds ratio = 0.68, 95% confidence interval: 0.56, 0.83). These data suggest that folic acid and other vitamin supplementation during pregnancy may be associated with reduced risk of placental abruption.     

Environmental and urinary markers of prenatal exposure to drinking water disinfection by-products, fetal growth, and duration of gestation in the PELAGIE birth cohort (Brittany, France, 2002-2006)

Although prenatal exposure to water disinfection by-products does not appear to affect the duration of gestation, its impact on fetal growth remains an open question. The authors studied the associations between prenatal exposure to disinfection by-products and fetal growth restriction (FGR) and preterm birth in the PELAGIE cohort, a French birth cohort comprising 3,421 pregnant women recruited between 2002 and 2006. Exposure was assessed by estimating levels of trihalomethanes (THMs) in tap water during pregnancy and maternal water use and by measuring maternal urinary levels of trichloroacetic acid (TCAA) during early pregnancy in a nested case-control design that compared 174 FGR cases, 114 preterm births, and 399 controls. Higher uptake of THMs (especially brominated THMs) was associated with a higher risk of FGR. Women with TCAA detected in their urine (>0.01 mg/L) had a higher risk of FGR than those with TCAA levels below the detection limit (adjusted odds ratio = 1.8, 95% confidence interval: 0.9, 3.7) and had an odds ratio for preterm birth below 1 (adjusted odds ratio = 0.8, 95% confidence interval: 0.3, 2.6). Results from this prospective study, the first to use a biomarker of disinfection by-product exposure, suggest that prenatal exposure affects fetal growth, but the causal agent or agents remain to be identified.     

Periconceptional multivitamin use reduces the risk of preeclampsia

The objective was to assess the independent effect of regular periconceptional multivitamin use on the risk of preeclampsia. Pregnant women (n=1,835) enrolled in the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997-2001) at less than 16 weeks' gestation were asked whether they regularly used multivitamins or prenatal vitamins in the past 6 months. Women were classified as users or nonusers. The unadjusted prevalence of preeclampsia was 4.4% in nonusers and 3.8% in users. After adjustment for race/ethnicity, marital status, parity, prepregnancy physical activity, and income in a multiple logistic regression model, regular use of multivitamins was associated with a 45% reduction in preeclampsia risk compared with nonuse (odds ratio (OR)=0.55, 95% confidence interval (CI): 0.32, 0.95). Prepregnancy overweight modified this effect. After confounder adjustment, lean multivitamin users had a 71% reduction in preeclampsia risk compared with lean nonusers (OR=0.29, 95% CI: 0.12, 0.65). In contrast, there was no relation between multivitamin use and preeclampsia among overweight women (OR=1.08, 95% CI: 0.52, 2.25). A sensitivity analysis for unmeasured confounding by fruit and vegetable intake supported these conclusions. If confirmed by others, these results suggest that regular use of a multivitamin supplement in the periconceptional period may help to prevent preeclampsia, particularly among lean women.     

Association of periconceptional multivitamin use and risk of preterm or small-for-gestational-age births

The authors' objective was to determine the relation between periconceptional multivitamin use and the risk of small-for-gestational-age (SGA: <5th percentile; 5th-<10th percentiles) or preterm (<34 weeks; 34-<37 weeks) births. Women in the Pregnancy Exposures and Preeclampsia Prevention Study (1997-2001) reported at enrollment their regular multivitamin use in the past 6 months (n=1,823). Women were classified as users or nonusers in multinomial logistic models. After adjustment for race, age, education, enrollment gestational age, and household density, periconceptional multivitamin use was associated with a reduced risk of preterm births (<34 weeks) (odds ratio (OR)=0.29, 95% confidence interval (CI): 0.13, 0.64) and spontaneous preterm births (<34 weeks) (OR=0.40, 95% CI: 0.16, 0.99). Risk of SGA (<5th percentile) was marginally lower (OR=0.64, 95% CI: 0.40, 1.03) after adjustment for smoking, education, parity, enrollment gestational age, and body mass index. Prepregnancy body mass index modified this relation. Nonobese users had a reduction (OR=0.54, 95% CI: 0.32, 0.91) in risk of SGA (<5th percentile); there was no effect among obese women. There was no effect of multivitamin use on risk of preterm births (34-<37 weeks) or SGA (5th-<10th percentiles). Sensitivity analysis for unmeasured confounding by folate intake supported these findings. Study results indicate lower rates of severe preterm births and extreme SGA in women who report periconceptional vitamin use, although these should be considered cautiously until replicated.     

Smoking and pregnancy outcome among African-American and white women in central North Carolina.

Despite extensive research on tobacco smoking during pregnancy, few studies address risks among African-American and white women, groups that differ in brand preference and smoking habits. The Pregnancy, Infection, and Nutrition Study is a prospective cohort study that included 2,418 women with detailed information on smoking during pregnancy, including brand, number of cigarettes per day, and changes during pregnancy. We analyzed risk of preterm birth (<37 and <34 weeks' gestation) and small-for-gestational-age deliveries in relation to tobacco use. Pregnant African-American smokers differed markedly from whites in brand preference (95% vs 26% smoked menthol cigarettes) and number of cigarettes per day (1% of African-Americans and 12% of whites smoked 20+ cigarettes per day). Smoking was not related to risk of preterm birth overall, but cotinine measured at the time of delivery was (adjusted odds ratio = 2.2, 95% confidence interval = 1.1-4.5). A clear association and dose-response gradient was present for risk of fetal growth restriction (risk ratio for 20+ cigarettes/day = 2.4, 95% confidence interval = 1.4-4.0). Associations of tobacco use with preterm premature rupture of amniotic membrane resulting in preterm birth were notably stronger than the associations with other types of preterm birth.     

Vigorous leisure activity and pregnancy outcome

BACKGROUND: Preterm birth is the leading cause of perinatal mortality in North America and Europe and a major predictor of neonatal and infant morbidity. Postterm birth is associated with increased infant mortality and morbidity, as well as increased frequency of surgical or induced labor. Because vigorous leisure activity may affect timing of delivery, this study examined association between vigorous leisure activity and birth outcomes. METHODS: Women (N = 1,699) with a singleton pregnancy were recruited at 24-29 weeks' gestation from prenatal clinics in central North Carolina between 1995 and 1998. The type and duration of any regular vigorous leisure activity was assessed in a telephone interview covering the 3-month period before pregnancy and during the first and second trimesters of pregnancy. RESULTS: The prevalence of vigorous leisure activity was 22% before pregnancy, 14% during the first trimester, and 8% during the second trimester. Vigorous leisure activity before pregnancy was unrelated to preterm (<37 weeks) as compared with term delivery (37 to <42 weeks). The risk of preterm birth was somewhat reduced with vigorous leisure activity during the first trimester (odds ratio = 0.80; 95% confidence interval = 0.48-1.35) and more so during the second trimester (odds ratio = 0.52; 95% confidence interval = 0.24-1.11). Vigorous leisure activity before pregnancy or during the first or second trimester was not associated with postterm delivery (>/=42 weeks). CONCLUSIONS: Vigorous leisure activity during the first trimester, and even more so in the second trimester, was associated with a reduced risk of preterm birth. There was no association with postterm birth. To address the etiologic role of activity on pregnancy outcome and to overcome self-selection, a randomized clinical trial would be needed.     

Influence of smoking and snuff cessation on risk of preterm birth

The mechanisms by which antenatal smoking exposure increases the risk of preterm birth remain unknown. Swedish oral moist snuff contains quantities of nicotine comparable to those typically absorbed from cigarette smoking, but does not result in exposure to the products of combustion, for example carbon monoxide. In a nation-wide study of 776,836 live singleton births in Sweden from 1999 to 2009, the authors used multiple logistic regression models to examine associations between cessation of smoking and Swedish snuff use early in pregnancy and risk of preterm birth (before 37 weeks). Compared with non-tobacco users both before and in early pregnancy, the adjusted odds ratios (OR), 95% confidence interval (CI) were OR=0.92, 95% CI 0.84-1.01, for women who stopped using snuff, and OR=0.90, 95% CI 0.87-0.94, for women who stopped smoking. In contrast, continued snuff use and smoking were associated with increased risks of preterm birth (adjusted OR=1.29, 95% CI 1.17-1.43, adjusted OR=1.30, 95% CI 1.25-1.36, respectively). The snuff and smoking-related risks were, if anything, higher for very (before 32 weeks) than moderately (32-36 weeks) preterm birth, and also higher for spontaneous than induced preterm birth. These findings suggest that antenatal exposure to nicotine is involved in the mechanism by which tobacco use increase the risk of preterm birth.     

Sources of prenatal care data and their association with birth outcomes of HIV-infected women

OBJECTIVES: Different sources of prenatal care data were used to examine the association between birth outcomes of HIV-infected women and the Adequacy of Prenatal Care Utilization (APNCU) index. METHODS: Adjusted odds ratios of birth outcomes for 1858 HIV-positive mothers were calculated for APNCU indexes on the basis of birth certificate data or 3 types of physician visits on Medicaid claims. RESULTS: Claims- and birth certificate-based APNCU indexes agreed poorly (kappa < 0.3). Only the broadest claims-based APNCU index had lower adjusted odds ratios for low birthweight (0.64; 95% confidence interval [CI] = 0.49, 0.84) and preterm birth (0.70; 95% CI = 0.54, 0.91). The birth certificate-based index had a reduced adjusted odds ratio (0.73; 95% CI = 0.56, 0.95) only for preterm birth. CONCLUSIONS: The association of birth outcomes and adequacy of prenatal care in this HIV-infected cohort differed significantly depending on the source of prenatal care data.     

Prenatal active or passive tobacco smoke exposure and the risk of preterm delivery or low birth weight

We examined the association of exposure to environmental tobacco smoke with birth weight and gestational age in a large, prospective study. We also compared these endpoints between infants of active maternal smokers and those of non-smoking, non-ETS exposed women. Pregnant women were interviewed by telephone during the first trimester, and pregnancy outcome was determined for 99%. Among the 4,454 singleton live births that could be linked to their birth certificate, we confirmed increased risks of low birth weight and small for gestational age with heavier maternal smoking (> 10 cigarettes/day), as well as noting an increased risk for "very preterm" birth (< 35 weeks). These associations were generally stronger among infants of older (> or = 30 years) than those of younger mothers, as well as among non-whites. High environmental tobacco smoke exposure (> or = 7 hours/day in non-smokers) was moderately associated with low birth weight (adjusted odds ratio (AOR) 1.8, 95% confidence limits (95% CL) = 0.82, 4.1), preterm birth (AOR 1.6, 95% CL = 0.87, 2.9), and most strongly with very preterm birth (AOR 2.4, 95% CL = 1.0, 5.3). These associations were generally greater among non-whites than whites. The data support earlier studies suggesting that prenatal environmental tobacco smoke exposure, in addition to maternal smoking, affects infant health.     

Frequency of eating during pregnancy and its effect on preterm delivery

Frequency of eating or meal patterns during pregnancy may be a component of maternal nutrition relevant to pregnancy outcome. To identify meal patterns of pregnant women and investigate the relation between these meal patterns and preterm delivery, the authors performed an analysis using data from the Pregnancy, Infection, and Nutrition Study (n = 2,065). Women recruited from August 1995 to December 1998 were categorized by meal patterns on the basis of their reported number of meals (breakfast, lunch, and dinner) and snacks consumed per day during the second trimester. An optimal pattern was defined according to the Institute of Medicine recommendation of three meals and two or more snacks per day. In this population, 72 percent of the women met this recommendation, and 235 delivered preterm. Women who consumed meals/snacks less frequently were slightly heavier prior to pregnancy, were older, and had a lower total energy intake. In addition, these women had a higher risk of delivering preterm (adjusted odds ratio = 1.30, 95 percent confidence interval: 0.96, 1.76). There was no meaningful difference in the risk by early versus late preterm delivery, but those who delivered after premature rupture of the membranes (adjusted odds ratio = 1.87, 95 percent confidence interval: 1.02, 3.43) had a higher risk than those who delivered after preterm labor (adjusted odds ratio = 1.11, 95 percent confidence interval: 0.64, 1.89). This study supports previous animal model work of an association between decreased frequency of eating and preterm delivery.     

Occurrence of congenital heart defects in relation to maternal mulitivitamin use

The purpose of this study was to assess the relation between maternal multivitamin use and risk for cardiac defects in the offspring, using a population-based approach. The Atlanta Birth Defects Case-Control study is a population-based case-control study of infants born between 1968 and 1980 to mothers residing in metropolitan Atlanta, Georgia. The 958 case infants with nonsyndromic cardiac defects were actively ascertained from multiple sources. The 3,029 infants without birth defects (control infants) were selected from birth certificates by stratified random sampling. Periconceptional multivitamin use, defined as reported regular use of multivitamins from 3 months before pregnancy through the first 3 months of pregnancy, was contrasted with no use during the same time period. Periconceptional multivitamin use was associated with a reduced risk for nonsyndromic cardiac defects in the offspring (odds ratio (OR) = 0.76; 95% confidence interval (Cl): 0.60, 0.97). The risk reduction was strongest for outflow tract defects (OR = 0.46; 95% Cl 0.24, 0.86) and ventricular septal defects (OR = 0.61; 95% Cl: 0.38, 0.99). No risk reduction was evident when multivitamin use was begun after the first month of pregnancy. If these associations are causal, the results suggest that approximately one in four major cardiac defects could be prevented by periconceptional multivitamin use.     

Obesity subtypes and risk of spontaneous versus medically indicated preterm births in singletons and twins

Using data from the Missouri maternally linked files (1989-1997), the authors examined the association among maternal obesity, obesity subtypes, and spontaneous and medically indicated preterm (<37 weeks) and very preterm (<33 weeks) births in singletons and twins. Adjusted odds ratios were obtained with correction for intracluster correlation. The prevalence of obesity increased by 77% over the study period (p(trend) < 0.001). Obese mothers had a lower risk for spontaneous preterm birth, and this was more pronounced among twins (odds ratio = 0.68, 95% confidence interval: 0.62, 0.75) than singletons (odds ratio = 0.84, 95% confidence interval: 0.82, 0.87). However, this association was present only among obese women who gained less than 0.69 kg/week for singletons and between 0.23 and 0.69 kg/week for twins. By contrast, obese mothers with singleton gestation had about 50% greater odds of medically indicated preterm (odds ratio = 1.46, 95% confidence interval: 1.39, 1.54) and very preterm (odds ratio = 1.49, 95% confidence interval: 1.34, 1.65) births, and the risk increases with ascending severity of obesity (p(trend) < 0.01). For extreme obesity, the risk of medically indicated preterm and very preterm births was almost double that for nonobese women. Similar findings were observed in twins. These data suggest that obesity increases the risk for medically indicated but not spontaneous preterm birth in both singletons and twins.     

Birth characteristics and subsequent risk for breast cancer in very young women

There is growing evidence that prenatal exposures may influence later breast cancer risk. This matched case-control study used linked New York State birth and tumor registry data to examine the association between birth characteristics and breast cancer risk among women aged 14-37 years. Cases were women diagnosed with breast cancer between 1978 and 1995 who were also born in New York after 1957 (n = 484). For each case, selected controls were the next six liveborn females with the same maternal county of residence. The authors found a J-shaped association between birth weight and breast cancer risk, and very high birth weight (> or =4,500 g) was associated with the greatest elevation in risk (adjusted odds ratio (OR) = 3.10, 95% confidence interval (CI): 1.18, 7.97). The association of maternal age with breast cancer risk was also J-shaped, with maternal age of more than 24 years showing a positive, linear association (adjusted OR = 1.94, 95% CI: 1.18, 3.18 for maternal age > or =35 vs. 20-24 years; p for trend = 0.02). In contrast, women born very preterm had a lower risk (adjusted OR = 0.11, 95% CI: 0.02, 0.79 for gestational age <33 vs. > or =37 weeks). These findings support a role for early life factors in the development of breast cancer in very young women.     

Does inadequate prenatal care contribute to growth retardation among second-born African-American babies?

The authors evaluated the relation between adequacy of prenatal care and risk of delivery of full term small-for-gestational-age (SGA) infants. Data were derived from maternally linked birth certificates for 6,325 African-American women whose first two pregnancies ended in singleton, full term live births in Georgia from 1989 through 1992. The authors used stratified analysis to assess the effect of prenatal care on the risk of having an SGA baby in the second pregnancy among women with and without an SGA baby in their first pregnancy. The group of women with a history of SGA birth may be more likely to include persons for whom SGA delivery is related to factors, such as genetics, that are not amenable to intervention by prenatal care. Inadequate prenatal care was not associated with the risk of SGA delivery among women who had previously delivered an SGA baby. In unadjusted analyses, inadequate prenatal care was associated with an increased risk of delivering a full term SGA baby in the second pregnancy among women whose first baby was not SGA (risk ratio = 1.28; 95% confidence interval: 1.05, 1.55). The association did not persist when data were adjusted for confounding variables (odds ratio = 1.11; 95% confidence interval: 0.89, 1.38). Regardless of outcome in the first pregnancy, adequate prenatal care did not reduce the risk of full term SGA birth among second pregnancies in this population.     

Abortion,changed paternity,and risk of preeclampsia in nulliparous women

A prior birth confers a strong protective effect against preeclampsia, whereas a prior abortion confers a weaker protective effect. Parous women who change partners in a subsequent pregnancy appear to lose the protective effect of a prior birth. This study (Calcium for Preeclampsia Prevention Trial, 1992-1995) examines whether nulliparous women with a prior abortion who change partners also lose the protective effect of the prior pregnancy. A cohort analysis was conducted among participants in this large clinical trial of calcium supplementation to prevent preeclampsia. Subjects were nulliparous, had one prior pregnancy or less, delivered after 20 weeks' gestation, and were interviewed at 5-21 weeks about prior pregnancies and paternity. Women without a history of abortion served as the reference group in logistic regression analyses. Women with a history of abortion who conceived again with the same partner had nearly half the risk of preeclampsia (adjusted odds ratio = 0.54, 95 percent confidence interval: 0.31, 0.97). In contrast, women with an abortion history who conceived with a new partner had the same risk of preeclampsia as women without a history of abortion (adjusted odds ratio = 1.03, 95 percent confidence interval: 0.72, 1.47). Thus, the protective effect of a prior abortion operated only among women who conceived again with the same partner. An immune-based etiologic mechanism is proposed, whereby prolonged exposure to fetal antigens from a previous pregnancy protects against preeclampsia in a subsequent pregnancy with the same father.     

Alteration in vaginal microflora,douching prior to pregnancy,and preterm birth

We aimed to determine the relationship of douching prior to pregnancy and bacterial vaginosis (BV) during pregnancy on preterm birth, addressing individual and joint effects. We used a prospective cohort study and assessed vaginal microflora using gram stains and Nugent's criteria. Douching behaviour was based on self‐report about the 12 months prior to pregnancy. Preterm births were categorised as spontaneous or medically indicated. A total of 2561 women provided vaginal specimens and 1492 provided self‐reports on douching behaviour. Bacterial vaginosis assessed at 24–28 weeks' gestation in the absence of douching prior to pregnancy was associated with spontaneous preterm birth (odds ratio = 2.74 [95% confidence interval 1.13, 6.66]) as was douching in the absence of BV (OR = 2.20 [1.29, 3.75]). The combination of BV and douching was unrelated to spontaneous or medically indicated preterm birth. We concluded that acute alterations in vaginal microflora at mid‐pregnancy or douching prior to pregnancy were associated with an increased risk of preterm birth, but the combination did not appear to increase the risk further than would be expected.     

Improved birth outcomes among HIV-infected women with enhanced Medicaid prenatal care

OBJECTIVES: This study evaluated the impact of enhanced prenatal care on the birth outcomes of HIV-infected women. METHODS: Medicaid claims files linked to vital statistics were analyzed for 1723 HIV-infected women delivering a live-born singleton from January 1993 to October 1995. Prenatal care program visits were indicated by rate codes. Logistic models controlling for demographic, substance use, and health care variables were used to assess the program's effect on preterm birth (less than 37 weeks) and low birthweight (less than 2500 g). RESULTS: Of the women included in the study, 75.3% participated in the prenatal care program. Adjusted program care odds were 0.58 (95% confidence interval [CI] = 0.42, 0.81) for preterm birth and 0.37 (95% CI = 0.24, 0.58) for low-birthweight deliveries in women without a usual source of prenatal care. Women with a usual source had lower odds of low-birthweight deliveries if they had more than 9 program visits. The effect of program participation persisted in sensitivity analyses that adjusted for an unmeasured confounder. CONCLUSIONS: A statewide prenatal care Medicaid program demonstrates significant reductions in the risk of adverse birth outcomes for HIV-infected women.     

Effects of short interpregnancy intervals on small-for-gestational age and preterm births

We examined the effects of short interpregnancy intervals on small-for-gestational age and preterm births in a biracial population using North Carolina birth certificate data from 1988 to 1994. We defined small-for-gestational age birth as being below the 10th percentile on a race-, sex-, and parity-specific growth curve after a gestation of 37-42 weeks. We defined preterm birth as a gestation of less than 37 weeks. We analyzed birth records from all eligible singleton births to black or white women ages 15-45 years after an interpregnancy interval of 0-3 months (N = 11,451) and a random sample of singleton births after an interval of 4-24 months (N = 23,118). We defined interpregnancy interval exposure categories as 0-3, 4-12, and 13-24 months. The multivariate adjusted odds ratio for small-for-gestational age births after interpregnancy intervals of 0-3 months compared with 13-24-month intervals was 1.6 (95% confidence interval = 1.4-1.8). The odds ratio for preterm birth after interpregnancy intervals of 0-3 months was 1.2 (95% confidence interval = 1.1-1.3). Odds ratios did not vary substantially by race for either outcome.     

Changing paternity and the risk of preterm delivery in the subsequent pregnancy

I studied whether changing a partner, and thus changing the likelihood of human leukocyte antigen (HLA) sharing between mating partners, affects the risk of preterm delivery in the subsequent pregnancy. I identified a total of 128,239 women who had two consecutive births during 1989-1991 through data linkage of the California birth certificates. Paternal date of birth and names on the records of the two consecutive births were compared to determine whether the same father was reported on both records. Three cohorts of women were formed on the basis of the gestational age of their first delivery: <34, 34-36, and >36 weeks. If parental HLA sharing is associated with preterm delivery, the likelihood of HLA sharing was expected to be in a decreasing order from most likely among a <34-week cohort to least likely among a >36-week cohort. Among women in the <34-week cohort, changing partners resulted in a 33% reduction in the risk of early preterm delivery in the subsequent pregnancy compared with those who did not change partners [95% confidence interval (CI), 0.52-0.88]. In contrast, among women in the >36-week cohort, changing partners led to a 16% increase in the risk of early preterm delivery in the subsequent pregnancy (95% CI = 1.04-1.30). Among women in the 34-36-week cohort, changing partners did not affect the risk of preterm delivery (95% CI = 0.78-1.25). These estimates were adjusted for maternal race/ethnicity, age, educational level, prenatal smoking, prenatal care, parity, and interval from birth to conception of the subsequent pregnancy. The findings from this study suggest that the effect of changing paternity depends on the pregnancy outcome with the previous partner and support the hypothesis that parental HLA sharing may be related to preterm delivery.