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We explored the relationship between neighborhood socioeconomic disadvantage (NSED) and gestational weight gain and loss and if the association differed by race. A census tract level NSED index (categorized as low, mid-low, mid-high, and high) was generated from 12 measures from the 2000 US Census data. Gestational weight gain and other individual-level characteristics were derived from vital birth records for Allegheny County, PA for 2003-2010 (n = 55,608). Crude and adjusted relative risks were estimated using modified multilevel Poisson regression models to estimate the association between NSED and excessive and inadequate gestational weight gain (GWG) and weight loss (versus adequate GWG). Black women lived in neighborhoods that were more likely to be socioeconomically disadvantaged compared to white women. Almost 55% of women gained an excessive amount of weight during pregnancy, and 2% lost weight during pregnancy. Black women were more likely than white women to have inadequate weight gain or weight loss. Mid-high (aRR = 1.3, 95% CI 1.2, 1.3) and high (aRR = 1.5, 95% CI 1.5, 1.6) NSED compared to low NSED was associated with inadequate weight gain while NSED was not associated with excessive weight gain. Among black women, high versus low NSED was associated with weight loss during pregnancy (RR = 1.6, 95% CI 1.1, 2.5). Among white women, each level of NSED compared to low NSED was associated with weight loss during pregnancy. This study demonstrates how neighborhood socioeconomic characteristics can contribute to our understanding of inadequate weight gain and weight loss during pregnancy, having implications for future research and interventions designed to advance pregnancy outcomes.

Background: Studies using vital records-based maternal weight data have become more common, but the validity of these data is uncertain., Methods: We evaluated the accuracy of prepregnancy body mass index (BMI) and gestational weight gain (GWG) reported on birth certificates using medical record data in 1204 births at a teaching hospital in Pennsylvania from 2003 to 2010. Deliveries at this hospital were representative of births statewide with respect to BMI, GWG, race/ethnicity, and preterm birth. Forty-eight strata were created by simultaneous stratification on prepregnancy BMI (underweight, normal weight/overweight, obese class 1, obese classes 2 and 3), GWG (<20th, 20-80th, >80th percentile), race/ethnicity (non-Hispanic white, non-Hispanic black), and gestational age (term, preterm)., Results: The agreement of birth certificate-derived prepregnancy BMI category with medical record BMI category was highest in the normal weight/overweight and obese class 2 and 3 groups. Agreement varied from 52% to 100% across racial/ethnic and gestational age strata. GWG category from the birth registry agreed with medical records for 41-83% of deliveries, and agreement tended to be the poorest for very low and very high GWG. The misclassification of GWG was driven by errors in reported prepregnancy weight rather than maternal weight at delivery, and its magnitude depended on prepregnancy BMI category and gestational age at delivery., Conclusions: Maternal weight data, particularly at the extremes, are poorly reported on birth certificates. Investigators should devote resources to well-designed validation studies, the results of which can be used to adjust for measurement errors by bias analysis., (© 2014 John Wiley & Sons Ltd.)

To investigate the relationship among parity, length of the inter-pregnancy intervals and excessive pregnancy weight gain in the first pregnancy and the risk of obesity. Using a prospective cohort study of 3,422 non-obese, non-pregnant US women aged 14-22 years at baseline, adjusted Cox models were used to estimate the association among parity, inter-pregnancy intervals, and excessive pregnancy weight gain in the first pregnancy and the relative hazard rate (HR) of obesity. Compared to nulliparous women, primiparous women with excessive pregnancy weight gain in the first pregnancy had a HR of obesity of 1.79 (95% CI 1.40, 2.29); no significant difference was seen between primiparous without excessive pregnancy weight gain in the first pregnancy and nulliparous women. Among women with the same pregnancy weight gain in the first pregnancy and the same number of inter-pregnancy intervals (12 and 18 months or ≥18 months), the HR of obesity increased 2.43-fold (95% CI 1.21, 4.89; p = 0.01) for every additional inter-pregnancy interval of <12 months; no significant association was seen for longer inter-pregnancy intervals. Among women with the same parity and inter-pregnancy interval pattern, women with excessive pregnancy weight gain in the first pregnancy had an HR of obesity 2.41 times higher (95% CI 1.81, 3.21; p < 0.001) than women without. Primiparous and nulliparous women had similar obesity risk unless the primiparous women had excessive pregnancy weight gain in the first pregnancy, then their risk of obesity was greater. Multiparous women with the same excessive pregnancy weight gain in the first pregnancy and at least one additional short inter-pregnancy interval had a significant risk of obesity after childbirth. Perinatal interventions that prevent excessive pregnancy weight gain in the first pregnancy or lengthen the inter-pregnancy interval are necessary for reducing maternal obesity.

The objective of this study was to determine the association between maternal 25-hydroxyvitamin D (25(OH)D) and the risk of spontaneous preterm birth (sPTB) before 35 weeks' gestation. A random subcohort from the US Collaborative Perinatal Project (1959-1965) was sampled (n = 2,629) and augmented with all remaining cases of sPTB before 35 weeks' gestation for a total of 767 cases. Banked serum samples collected at 26 weeks' gestation or earlier were assayed for 25(OH)D. Constructs for vascular histology and inflammatory histology were developed from placental pathology examinations. There was no relationship between 25(OH)D and sPTB among white women. Among nonwhite mothers, serum 25(OH)D levels of 30-<50, 50-<75, and ≥75 nmol/L were associated with reductions of 1.0-1.6 cases of sPTB per 100 live births and 20%-30% reductions in risk of sPTB compared with 25(OH)D levels less than 30 nmol/L after adjustment for prepregnancy body mass index (weight (kg)/height (m)(2)), season, and other confounders. This association was driven by inflammation-mediated cases of sPTB and sPTB cases without placental lesions. A sensitivity analysis for unmeasured confounding by exercise, fish intake, and skin color suggested some bias away from the null in the conventional results, but conclusions were generally supported. The vitamin D-sPTB relationship should be examined in modern cohorts with detailed data on skin pigmentation and other covariates.

Context: Inconsistent associations between maternal vitamin D status and fetal size have been published in small studies., Objective: Our objective was to examine the association between maternal 25-hydroxyvitamin D [25(OH)D] levels and measures of newborn and placental weight., Design and Setting: We measured maternal 25(OH)D in mothers from the Collaborative Perinatal Project, an observational cohort conducted in 12 U.S. medical centers from 1959 to 1965., Participants: Women delivering singleton, term, live births with 25(OH)D measured at a gestation of 26 wk or less (n = 2146)., Main Outcome Measures: Birth weight, ponderal index, placental weight, the placental to fetal weight ratio, and small for gestational age were measured. Hypotheses were formulated after data collection., Results: After confounder adjustment, mothers with 25(OH)D of 37.5 nmol/liter or greater gave birth to newborns with 46 g [95% confidence interval (CI), 9-82 g] higher birth weights and 0.13 cm (0.01-0.25 cm) larger head circumferences compared with mothers with less than 37.5 nmol/liter. Birth weight and head circumference rose with increasing 25(OH)D up to 37.5 nmol/liter and then leveled off (P < 0.05). No association was observed between 25(OH)D and ponderal index, placental weight, or the placental to fetal weight ratio. Maternal 25(OH)D of 37.5 nmol/liter or greater vs. less than 37.5 nmol/liter in the first trimester was associated with half the risk of small for gestational age (adjusted odds ratio 0.5; 95% CI 0.3-0.9), but no second-trimester association was observed., Conclusions: Maternal vitamin D status is independently associated with markers of physiological and pathological growth in term infants. Adequately powered randomized controlled trials are needed to test whether maternal vitamin D supplementation may improve fetal growth.

Conventional measures of gestational weight gain (GWG), such as average rate of weight gain, are likely to be correlated with gestational duration. Such a correlation could introduce bias to epidemiological studies of GWG and adverse perinatal outcomes because many perinatal outcomes are also correlated with gestational duration. This study aimed to quantify the extent to which currently used GWG measures may bias the apparent relationship between maternal weight gain and risk of preterm birth. For each woman in a provincial perinatal database registry (British Columbia, Canada, 2000-2009), a total GWG was simulated such that it was uncorrelated with risk of preterm birth. The simulation was based on serial antenatal GWG measurements from a sample of term pregnancies. Simulated GWGs were classified using three approaches: total weight gain (kg), average rate of weight gain (kg/week) or adequacy of GWG in relation to Institute of Medicine recommendations. Their association with preterm birth ≤32 weeks was explored using logistic regression. All measures of GWG induced an apparent association between GWG and preterm birth ≤32 weeks even when, by design, none existed. Odds ratios in the lowest fifths of each GWG measure compared with the middle fifths ranged from 4.4 [95% confidence interval (CI) 3.6, 5.4] (total weight gain) to 1.6 [95% CI 1.3, 2.0] (Institute of Medicine adequacy ratio). Conventional measures of GWG introduce serious bias to the study of maternal weight gain and preterm birth. A new measure of GWG that is uncorrelated with gestational duration is needed., (© 2012 Blackwell Publishing Ltd.)

Vitamin D deficiency is highly prevalent worldwide, and is linked to several major chronic, inflammatory and autoimmune diseases. Vitamin D deficiency has not been evaluated in dark skinned individuals living in areas of high sun exposure utilizing more reliable mass spectrometry assay techniques. We determined the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency in Afro-Caribbean men on the tropical island of Tobago, where there is a high level of sunshine year round. Serum 25(OH)D2 and 25(OH)D3 metabolites were measured following extraction and purification using liquid chromatography and tandem mass spectrometry in 424 Afro-Caribbean men aged > 65 years from a larger population-based cohort study. The mean (+/- SD) serum total 25(OH)D concentration was 35.1 +/- 8.9 ng/mL. Deficiency (< 20 ng/mL) was present in only 2.8% and insufficiency (< 30 ng/mL) in 24% of the men. Multiple linear regression analysis identified age, BMI and daily vitamin D supplementation as the independent correlates of 25(OH)D. None of the men who consumed fish more than once per week had vitamin D deficiency, compared to 4% of the men who consumed fish once per week or less (P = .01, adjusted for age, BMI, and daily vitamin D supplementation). In conclusion, vitamin D deficiency is very uncommon in this Afro-Caribbean population. Longitudinal studies are needed to delineate the possible effects of high vitamin D levels in this population on major diseases hypothesized to be associated with vitamin D deficiency.

The authors tested whether the relation between gestational weight gain (GWG) and 5 adverse pregnancy outcomes (small-for-gestational-age (SGA) birth, large-for-gestational-age (LGA) birth, spontaneous preterm birth, indicated preterm birth, and unplanned cesarean delivery) differed according to maternal race/ethnicity, smoking, parity, age, and/or height. They also evaluated whether GWG guidelines should be modified for special populations by studying GWG and risk of at least 1 adverse outcome within different subgroups. Data came from a cohort of 23,362 normal-weight mothers who delivered singletons at Magee-Womens Hospital in Pittsburgh, Pennsylvania (2003-2008). Adequacy of GWG was defined as observed GWG divided by recommended GWG. The synergy analysis found that the combination of smoking, black race/ethnicity, primiparity, or short height with poor GWG was associated with an excess risk of SGA birth, while high GWG combined with each of these characteristics diminished risk of LGA birth in comparison with the same GWG among the women's counterparts. Nevertheless, there were no significant or meaningful differences in the risk of at least 1 adverse outcome between the GWG recommended by the Institute of Medicine in 2009 and the GWG that minimized risk of the composite outcome. These findings do not support the tailoring of GWG guidelines on the basis of a mother's smoking status, race/ethnicity, parity, age, or height among normal-weight women.

Objective: We previously reported that elevated antiinflammatory cervical cytokines in early pregnancy were associated with spontaneous preterm birth. Our objective was to explore the relation between serum folate vitamers and the lower genital tract inflammatory milieu., Study Design: Pregnant women (n = 417) at <16 weeks' gestation had serum samples that were analyzed for folate species 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and cervical fluid that was assayed for cytokine concentrations. Patterns in proinflammatory cytokines (interleukin [IL]-1β, -6, -8, and -10; monocyte chemotactic protein-1) and antiinflammatory cytokines (IL-4, IL-10, IL-13) were identified with factor analysis., Results: After confounder adjustment, maternal serum 5-methyltetrahydrofolate concentrations had a strong negative association with elevated antiinflammatory scores; serum 5-formyltetrahydrofolate concentrations were associated positively with elevated antiinflammatory scores (both P < .05). Maternal folate was not associated with proinflammatory scores., Conclusion: Maternal serum folate vitamers are associated with cervical cytokine concentrations, which suggests a possible mechanistic link between folate and preterm birth risk., (Copyright © 2011 Mosby, Inc. All rights reserved.)

The inflammatory milieu of the cervix may play a role in preventing intrauterine infection and subsequent preterm birth. The objectives of this study were to use exploratory factor analysis to discover the underlying structure of cytokines in the lower genital tract immunological milieu, and evaluate the association between the cytokine factors and risk of preterm birth. Women (n=613) enrolled in a prospective pregnancy cohort study in Pittsburgh, Pennsylvania had cervical cytokine concentrations assayed at <16 weeks and were followed for data on pregnancy outcomes. Principal factor analysis identified two primary cytokine patterns at <16 weeks gestation: Factor 1 (pro-inflammatory/immunomodulatory factor), which loaded highly on interleukin (IL)-1β, IL-6, IL-8, monocyte chemotactic protein-1, and IL-10, and Factor 2 (anti-inflammatory factor), which loaded heavily on IL-4, IL-10, and IL-13. Women in the highest tertile of anti-inflammatory cytokine factor scores at <16 weeks had an increased risk of spontaneous preterm birth (confounder-adjusted odds ratio [95% confidence interval]: 2.4 [1.1, 5.7]). There was no association between pro-inflammatory cytokine factor scores and preterm birth risk. These data support the hypothesis that increased concentrations of anti-inflammatory cytokines may represent a cervical immune milieu that permits subsequent microbial invasion of the uterus during pregnancy, leading to subsequent spontaneous preterm birth., (© 2011 Blackwell Publishing Ltd.)

Background: Poor maternal folate status has been associated with an increased risk of preterm birth. However, major gaps remain in our understanding of how individual folate species relate to preterm birth., Objective: Our objective was to assess the association between maternal folate status as measured by 5-methyltetrahydrofolate (5MeTHF), 5-formyltetrahydrofolate (5FoTHF), and folic acid concentrations, which are the 3 primary folate species in serum, and the risk of preterm birth and spontaneous preterm birth (sPTB)., Design: A cohort of 313 pregnant women who received care at resident antepartum clinics at Magee-Womens Hospital (Pittsburgh, PA) (2003-2007) was enrolled at <16 wk gestation. We analyzed nonfasting blood samples that were drawn from subjects at enrollment for the 3 folate species by using HPLC-tandem mass spectrometry., Results: Serum 5MeTHF and 5FoTHF concentrations comprised 65% and 33% of total folate concentrations, respectively. In confounder-adjusted, multivariable, log-binomial regression models, 1-SD increases in serum total folate and serum 5MeTHF concentrations were associated with significant reductions in the risk of sPTB (P < 0.05). There was a significant interaction between serum 5MeTHF and 5FoTHF concentrations and risk of preterm birth (P = 0.01). When serum 5MeTHF concentrations were low, there was a positive linear relation between 5FoTHF and risk of preterm birth. When 5MeTHF concentrations were high, there was a strong negative relation between 5FoTHF and preterm birth., Conclusions: Our results imply that the relative concentrations of folate species may be more critical than total folate in preventing preterm birth. An improved understanding of folate metabolism during pregnancy may lead to targeted intervention strategies that decrease the rate of preterm birth.

Maternal vitamin D deficiency has been associated with numerous adverse health outcomes, but its association with fetal growth restriction remains uncertain. We sought to elucidate the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations in early pregnancy and the risk of small-for-gestational age birth (SGA) and explore the association between maternal single nucleotide polymorphisms (SNP) in the vitamin D receptor (VDR) gene and the risk of SGA. We conducted a nested case-control study of nulliparous pregnant women with singleton pregnancies who delivered SGA infants (n = 77 white and n = 34 black) or non-SGA infants (n = 196 white and n = 105 black). Women were followed from <16 wk gestation to delivery. Women's banked sera at <22 wk were newly measured for 25(OH)D and DNA extracted for VDR genotyping. SGA was defined as live-born infants that were <10th percentile of birth weight according to nomograms based on gender and gestational age. After confounder adjustment, there was a U-shaped relation between serum 25(OH)D and risk of SGA among white mothers, with the lowest risk from 60 to 80 nmol/L. Compared with serum 25(OH)D 37.5-75 nmol/L, SGA odds ratios (95% CI) for levels <37.5 and >75 nmol/L were 7.5 (1.8, 31.9) and 2.1 (1.2, 3.8), respectively. There was no relation between 25(OH)D and SGA risk among black mothers. One SNP in the VDR gene among white women and 3 SNP in black women were significantly associated with SGA. Our results suggest that vitamin D has a complex relation with fetal growth that may vary by race.

Bacterial vaginosis (BV) is a highly prevalent vaginal infection that is associated with adverse pregnancy outcomes. Vitamin D exerts an influence on the immune system and may play a role in BV. The objective of this study was to examine the association between maternal vitamin D status and the prevalence of BV in early pregnancy. Women (n = 469) enrolled in a pregnancy cohort study at <16 wk underwent a pelvic examination and provided a blood sample for determination of serum 25-hydroxyvitamin D [25(OH)D]. BV was diagnosed using Gram-stained vaginal smears interpreted using the method of Nugent. Approximately 41% of women had BV (Nugent score 7-10) and 52% had a serum 25(OH)D concentration <37.5 nmol/L. The mean unadjusted serum 25(OH)D concentration was lower among BV cases (29.5 nmol/L; 95% CI: 27.1, 32.0) compared with women with normal vaginal flora (40.1 nmol/L; 95% CI: 37.0, 43.5; P < 0.001). BV prevalence decreased as vitamin D status improved (P < 0.001). Approximately 57% of the women with a serum 25(OH)D concentration <20 nmol/L had BV compared with 23% of women with a serum 25(OH)D concentration >80 nmol/L. There was a dose-response association between 25(OH)D and the prevalence of BV. The prevalence declined as 25(OH)D increased to 80 nmol/L, then reached a plateau. Compared with a serum 25(OH)D concentration of 75 nmol/L, there were 1.65-fold (95% CI: 1.01, 2.69) and 1.26-fold (1.01, 1.57) increases in the prevalence of BV associated with a serum 25(OH)D concentration of 20 and 50 nmol/L, respectively, after adjustment for race and sexually transmitted diseases. Vitamin D deficiency is associated with BV and may contribute to the strong racial disparity in the prevalence of BV.

Preterm birth is a major obstetric problem. An exploration of the season of conception in relation to preterm birth may provide direction in the search for risk factors. We conducted a retrospective cohort study of 82 213 singleton livebirths (20-45 weeks' gestation) to 61,630 women at Magee-Womens Hospital, Pittsburgh, PA, from 1995 to 2005. Conception was estimated based on gestational age determined by best obstetric estimate. Fourier series analysis was used to model seasonal trends. Spontaneous preterm birth at <37 weeks was associated with conception season (P < 0.05). The peak prevalence occurred among conceptions in winter and spring (peaking February 23 at 6.9%), with an average trough among late summer/early autumn conceptions (August 25 at 6.2%). The pattern for spontaneous preterm birth <32 weeks was similar (P < 0.05), with the peak on March 13 (1.7%), and nadir on September 12 (1.4%). Results were similar when indicated preterm births were included. These seasonal changes may increase our insight into the role of exposures with seasonal periodicity in the pathophysiology of preterm birth.

In the past decade, research on the relation between vitamin D exposure and disease in population-based studies has increased exponentially. These studies have involved measurement of vitamin D exposure by means of several methods: blood assays, self-reported dietary and supplemental intakes, and sunlight exposure questionnaires or diaries. As with all exposure measurements, researchers must consider the validity of their assessment tools for capturing vitamin D exposure. The purpose of this article is to summarize our current understanding of the various approaches to measuring vitamin D status within populations as reviewed at the 2007 Experimental Biology symposium, "Assessment of Vitamin D in Population-Based Studies." In summary, serum 25-hydroxyvitamin D is the accepted biomarker for short-term vitamin D status, but estimates of long-term dietary and supplemental intakes of vitamin D and long-term sunlight exposure may be the most logistically feasible indicators of lifetime vitamin D exposure in population-based studies. Also discussed are issues investigators should consider when analyzing relations between vitamin D exposure and disease outcomes in population-based studies as well as research avenues that need further exploration. The best method for assessing vitamin D status in population-based studies will depend primarily on the research question asked and the critical window of vitamin D exposure hypothesized to be most important.

Women who deliver preterm are at increased risk for cardiovascular disease, but mechanisms are not understood. The authors considered that inflammation in women with spontaneous preterm birth (sPTB) might be related to their metabolic profile, such as lipids, and tested this in a nested case-control study from the Pregnancy Exposures and Preeclampsia Prevention Study (1997-2001). Cases were women with sPTB at 34-<37 weeks (n = 76) or < 34 weeks (n = 33). Controls were randomly selected women with term births (n = 228). Early pregnancy inflammation (C-reactive protein: > or = 8 microg/ml) and dyslipidemia (cholesterol: > 230 mg/dl or triglycerides: > 140 mg/dl) were evaluated in serum collected at < 21 weeks. Late pregnancy elevated C-reactive protein (> or = 12 microg/ml) was measured in a subset (n = 295). Polycotomous logistic regression was used to estimate the joint effects of C-reactive protein elevations and dyslipidemia on the risk of sPTB subtypes. After adjustment for race, body mass index, periconceptional vitamin use, and gestational age at sampling, early pregnancy inflammation (odds ratio = 2.9, 95% confidence interval (CI): 1.1, 7.2) and dyslipidemia (odds ratio = 2.0, 95% CI: 1.0, 4.2) were independently associated with sPTB at 34-<37 weeks. The presence of both conditions increased risk of sPTB at < 34 weeks 6.4-fold (95% CI: 1.7, 24.1). Half of the women with early pregnancy inflammation had elevated C-reactive protein late in gestation, and each was independently related to the risk of sPTB at < 34 weeks. The results indicate that some metabolic factors together with inflammation may be related to the risk of sPTB.

Obesity is a risk factor for vitamin D deficiency, but this relation has not been studied among pregnant women, who must sustain their own vitamin D stores as well as those of their fetuses. Our objective was to assess the effect of prepregnancy BMI on maternal and newborn 25-hydroxyvitamin D [25(OH)D] concentrations. Serum 25(OH)D was measured at 4-21 wk gestation and predelivery in 200 white and 200 black pregnant women and in their neonates' cord blood. We used multivariable logistic regression models to assess the independent association between BMI and the odds of vitamin D deficiency [25(OH)D <50 nmol/L] after adjustment for race/ethnicity, season, gestational age, multivitamin use, physical activity, and maternal age. Compared with lean women (BMI <25), pregravid obese women (BMI >or=30) had lower adjusted mean serum 25(OH)D concentrations at 4-22 wk (56.5 vs. 62.7 nmol/L; P < 0.05) and a higher prevalence vitamin D deficiency (61 vs. 36%; P < 0.01). Vitamin D status of neonates born to obese mothers was poorer than neonates of lean mothers (adjusted mean, 50.1 vs. 56.3 nmol/L; P < 0.05). There was a dose-response trend between prepregnancy BMI and vitamin D deficiency. An increase in BMI from 22 to 34 was associated with 2-fold (95% CI: 1.2, 3.6) and 2.1-fold (1.2, 3.8) increases in the odds of mid-pregnancy and neonatal vitamin D deficiency, respectively. The rise in maternal obesity highlights that maternal and newborn vitamin D deficiency will continue to be a serious public health problem until steps are taken to identify and treat low 25(OH)D.

Objective: To investigate the association between pregravid weight status and diet quality., Design: Institute of Medicine body mass index (BMI) cut-off points of 26.0-29.0 kg m- 2 for overweight and >29 kg m- 2 for obese were used to categorise women's weight status. Dietary information was obtained by self-report at 26-28 weeks' gestation using a modified Block food-frequency questionnaire. The Diet Quality Index for Pregnancy (DQI-P) included: servings of grains, vegetables and fruits, folate, iron and calcium intake, percentage calories from fat, and meal pattern score. Multinomial logistic regression models were used to estimate the association between weight status and tertiles of DQI-P controlling for potential individual confounders., Setting: A clinical-based population recruited through four prenatal clinics in central North Carolina., Subjects: A total of 2394 women from the Pregnancy, Infection and Nutrition study were included in this analysis., Results: Evidence of a dose-response relationship was found between BMI and inadequate servings of grains and vegetables, and iron and folate intake. Pregravid obesity was associated with 76% increased odds of falling into the lowest diet quality tertile compared with underweight women after controlling for potential confounders., Conclusion: A modest association was found between pregravid weight status and diet quality. If corroborated, these findings suggest that overweight pregnant women should be targeted for nutrition counselling interventions aimed to improve diet quality.

Context: Vitamin D has direct influence on molecular pathways proposed to be important in the pathogenesis of preeclampsia, yet the vitamin D-preeclampsia relation has not been studied., Objectives: We aimed to assess the effect of maternal 25-hydroxyvitamin D [25(OH)D] concentration on the risk of preeclampsia and to assess the vitamin D status of newborns of preeclamptic mothers., Design and Setting: We conducted a nested case-control study of pregnant women followed from less than 16 wk gestation to delivery (1997-2001) at prenatal clinics and private practices., Patients: Patients included nulliparous pregnant women with singleton pregnancies who developed preeclampsia (n = 55) or did not develop preeclampsia (n = 219). Women's banked sera were newly measured for 25(OH)D., Main Outcome Measure: The main outcome measure was preeclampsia (new-onset gestational hypertension and proteinuria for the first time after 20 wk gestation). Our hypotheses were formulated before data collection., Results: Adjusted serum 25(OH)D concentrations in early pregnancy were lower in women who subsequently developed preeclampsia compared with controls [geometric mean, 45.4 nmol/liter, and 95% confidence interval (CI), 38.6-53.4 nmol/liter, vs. 53.1 and 47.1-59.9 nmol/liter; P < 0.01]. There was a monotonic dose-response relation between serum 25(OH)D concentrations at less than 22 wk and risk of preeclampsia. After confounder adjustment, a 50-nmol/liter decline in 25(OH)D concentration doubled the risk of preeclampsia (adjusted odds ratio, 2.4; 95% CI, 1.1-5.4). Newborns of preeclamptic mothers were twice as likely as control newborns to have 25(OH)D less than 37.5 nmol/liter (adjusted odds ratio, 2.2; 95% CI, 1.2-4.1)., Conclusions: Maternal vitamin D deficiency may be an independent risk factor for preeclampsia. Vitamin D supplementation in early pregnancy should be explored for preventing preeclampsia and promoting neonatal well-being.

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.

In utero or early-life vitamin D deficiency is associated with skeletal problems, type 1 diabetes, and schizophrenia, but the prevalence of vitamin D deficiency in U.S. pregnant women is unexplored. We sought to assess vitamin D status of pregnant women and their neonates residing in Pittsburgh by race and season. Serum 25-hydroxyvitamin D (25(OH)D) was measured at 4-21 wk gestation and predelivery in 200 white and 200 black pregnant women and in cord blood of their neonates. Over 90% of women used prenatal vitamins. Women and neonates were classified as vitamin D deficient [25(OH)D<37.5 nmol/L], insufficient [25(OH)D 37.5-80 nmol/L], or sufficient [25(OH)D>80 nmol/L]. At delivery, vitamin D deficiency and insufficiency occurred in 29.2% and 54.1% of black women and 45.6% and 46.8% black neonates, respectively. Five percent and 42.1% of white women and 9.7% and 56.4% of white neonates were vitamin D deficient and insufficient, respectively. Results were similar at <22 wk gestation. After adjustment for prepregnancy BMI and periconceptional multivitamin use, black women had a smaller mean increase in maternal 25(OH)D compared with white women from winter to summer (16.0+/-3.3 nmol/L vs. 23.2+/-3.7 nmol/L) and from spring to summer (13.2+/-3.0 nmol/L vs. 27.6+/-4.7 nmol/L) (P<0.01). These results suggest that black and white pregnant women and neonates residing in the northern US are at high risk of vitamin D insufficiency, even when mothers are compliant with prenatal vitamins. Higher-dose supplementation is needed to improve maternal and neonatal vitamin D nutriture.

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.

The authors sought to quantify the overall and race/ethnic-specific relations between prepregnancy body mass index and both preterm birth and vaginal inflammation. Data from a cohort of 11,392 women who enrolled in the multicenter Vaginal Infections and Prematurity Study (1984-1989) at 23-26 weeks' gestation were used. Compared with a prepregnancy body mass index of 22, a body mass index of 16 increased the risk of preterm birth by 90% (odds ratio = 1.9, 95% confidence interval (CI): 1.5, 2.6), and a body mass index of 18 increased the risk by 40% (odds ratio = 1.4, 95% CI: 1.2, 1.7). Ethnicity substantially modified the magnitude of the body mass index effect and the shape of the preterm birth risk curve, with underweight having a greater impact on preterm birth among Blacks and Hispanics than among Whites. Low body mass index increased the risk of a high level of neutrophils (> 5 per oil immersion field) and a high vaginal pH measurement (> or = 5.0) among Black women; for a body mass index of 16 versus 22, the odds ratio = 1.7 (95% CI: 1.1, 2.6). Compared with Black women with a body mass index of 22, Blacks with a body mass index of 16 had a 1.7-fold increased risk for a high level of neutrophils and a high vaginal pH measurement, while those with a body mass index of 18 had a 1.3-fold increased risk.

Objective: We investigated changes in serum uric acid across pregnancy in women with gestational hyperuricemia at delivery, with and without preeclampsia, compared with normal pregnant and women with preeclampsia without gestational hyperuricemia., Study Design: This was a nested case-control study of 116 controls, 27 women with preeclampsia with predelivery hyperuricemia, 37 women with preeclampsia without predelivery hyperuricemia, and 35 women with gestational hypertension with hyperuricemia at delivery but without proteinuria. Serum uric acid and creatinine was measured across pregnancy., Results: Women with predelivery hyperuricemia, with and without preeclampsia, had increased uric acid concentrations across pregnancy compared with controls, after 25 weeks' gestation compared with women with preeclampsia without predelivery hyperuricemia. Adjusting for differences in glomerular filtration by serum creatinine accounted for part but not all of the increase in serum uric acid among women with preeclampsia and predelivery hyperuricemia., Conclusions: Among women with hyperuricemia at delivery, elevations in uric acid occur early. Multiple mechanisms may contribute to increased uric acid including changes in renal function.

The objective of this study was to quantify the mediating role of inflammation and triglycerides in the association between prepregnancy body mass index (weight (kg)/height (m)2) and preeclampsia. The authors conducted a nested case-control study of 55 preeclamptic women and 165 pregnant controls from the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997-2001). Serum samples collected at < or = 20 weeks' gestation were analyzed for levels of C-reactive protein and triglycerides. The adjusted odds ratio (AOR) from a multivariable conditional logistic regression model assessing the total effect of body mass index on preeclampsia risk was compared with the AOR from the same model after results were controlled for C-reactive protein, triglycerides, and confounding factors (direct-effects model). The percentage of the total effect that was mediated through inflammation and triglycerides was calculated as 100 - [ln(direct-effects AOR)/ln(total-effects AOR)]. In the total-effects model, 4- and 8-unit increases in body mass index were associated with 1.7-fold (95% confidence interval (CI): 1.3, 2.3) and 2.9-fold (95% CI: 1.6, 5.2) increases in preeclampsia risk, whereas in the direct-effects model, these AORs were 1.4 (95% CI: 1.0, 1.9) and 2.0 (95% CI: 1.0, 3.8), respectively. Inflammation was a more important mediator than triglycerides. These findings suggest that approximately one third of the total effect of body mass index on preeclampsia risk is mediated through inflammation and triglyceride levels.

Purpose: To explore the dose-dependent relation between prepregnancy body mass index (BMI) and the risk of preeclampsia after adjusting for measured confounders., Methods: We studied 1179 primiparous women who enrolled at < 16 weeks' gestation into a prospective cohort study of the pathogenesis of preeclampsia. Multivariable logistic regression was used to quantify the independent effect of prepregnancy BMI on the risk of preeclampsia after adjusting for race and smoking status. BMI was specified as a restricted quadratic spline., Results: Preeclampsia risk rose strikingly from a BMI of 15 to 30 kg/m(2). Compared with women with a BMI of 21, the adjusted risk of preeclampsia doubled at a BMI of 26 (odds ratio 2.1 [95% confidence interval, 1.4, 3.4]), and nearly tripled at a BMI of 30 (2.9 [1.6, 5.3]). Women with a BMI of 17 had a 57% reduction in preeclampsia risk compared with women with a BMI of 21 (0.43 [0.25, 0.76]), and a BMI of 19 was associated with a 33% reduction in risk (0.66 [0.50, 0.87])., Conclusions: These results indicate that preeclampsia risk rises through most of the BMI distribution. The dramatic elevation in overweight prevalence in the United States may increase preeclampsia incidence in the future.

Context: An excess of the soluble receptor, fms-like tyrosine kinase 1 (sFlt-1) may contribute to maternal vascular dysfunction in women with preeclampsia by binding and thereby reducing concentrations of free vascular endothelial growth factor and placental growth factor (PlGF) in the circulation. The putative stimulus for increased sFlt-1 during preeclampsia, placental hypoxia due to poor perfusion, is common to both preeclampsia and idiopathic intrauterine growth restriction. However, the latter condition occurs without maternal vascular disease., Objective: We asked whether, as with preeclampsia, sFlt-1 is increased and free PlGF is decreased in villous placenta and maternal serum of normotensive women with small-for-gestational-age (SGA) neonates., Study Design: This was a case-control study using banked samples. Groups of women with SGA neonates (birth weight centile < 10th) and women with preeclampsia were matched to separate sets of normal pregnancy controls based on gestational age at blood sampling (serum) or gestational age at delivery (placenta)., Results: sFlt-1 levels were higher in preeclamptics than controls (serum, P < 0.0001; placental protein, P = 0.03; placental mRNA, P = 0.007) but not increased in SGA pregnancies. PlGF was lower in both preeclampsia (serum, P < 0.0001; placental protein, P = 0.05) and SGA (serum, P = 0.0008; placental protein, P = 0.03) compared with their controls. PlGF in preeclampsia and SGA groups did not differ., Conclusions: These data are consistent with a role for sFlt-1 in the maternal manifestations of preeclampsia. In contrast to preeclampsia, sFlt-1 does not appear to contribute substantially to decreased circulating free PlGF in SGA pregnancies in the absence of a maternal syndrome.

The postpartum period is conventionally thought to be the time of lowest iron deficiency risk because iron status is expected to improve dramatically after delivery. Nonetheless, recent studies have reported a high prevalence of postpartum iron deficiency and anemia among ethnically diverse low-income populations in the United States. In light of the recent emergence of this problem in the medical literature, we discuss updated findings on postpartum iron deficiency, including its prevalence, functional consequences, risk factors, and recommended primary and secondary prevention strategies. The productivity and cognitive gains made possible by improving iron nutriture support intervention. We therefore conclude that postpartum iron deficiency warrants greater attention and higher quality care.

Marginal structural models (MSMs) are causal models designed to adjust for time-dependent confounding in observational studies of time-varying treatments. MSMs are powerful tools for assessing causality with complicated, longitudinal data sets but have not been widely used by practitioners. The objective of this paper is to illustrate the fitting of an MSM for the causal effect of iron supplement use during pregnancy (time-varying treatment) on odds of anemia at delivery in the presence of time-dependent confounding. Data from pregnant women enrolled in the Iron Supplementation Study (Raleigh, North Carolina, 1997-1999) were used. The authors highlight complexities of MSMs and key issues epidemiologists should recognize before and while undertaking an analysis with these methods and show how such methods can be readily interpreted in existing software packages, including SAS and Stata. The authors emphasize that if a data set with rich information on confounders is available, MSMs can be used straightforwardly to make robust inferences about causal effects of time-dependent treatments/exposures in epidemiologic research.

The authors evaluated the utility of selective screening criteria for postpartum anemia developed by the Centers for Disease Control and Prevention (CDC) versus criteria developed among low-income women using prevalence-based screening principles. Pregnant women in Raleigh, North Carolina, were followed up to the postpartum visit in 1997-1999 (n = 345). Prevalence of postpartum anemia was 19.1%. Independent risk markers, arrived at through multivariate logistic regression, were multiparity (odds ratio (OR) = 1.5, 95% confidence interval (CI): 0.8, 2.9), obesity (OR = 3.0, 95% CI: 1.6, 5.5), anemia at 24-29 weeks' gestation (OR = 2.3, 95% CI: 1.2, 4.4), anemia before delivery (OR = 3.4, 95% CI: 1.8, 6.7), and not exclusively breastfeeding (OR = 2.8, 95% CI: 1.0, 7.7). Risk scores were calculated by counting risk markers present. Likelihood ratios were determined for all possible risk scores of our algorithm and CDC's algorithm. Anemia screening decisions differed depending on clinic anemia prevalence. For example, if low test thresholds are assumed, when clinic prevalence is 10%, women with risk scores >3 on the authors' algorithm and >0 on CDC's algorithm should be screened. The authors' algorithm, in combination with prevalence information, can save clinics more money than CDC's current algorithm because a broader range of likelihood ratios was obtained, indicating a better ability to distinguish high- from low-risk women. However, if resources are available, universal screening should be considered in high-prevalence settings.

We estimated the prevalence of postpartum iron deficiency, anemia and iron deficiency anemia in the United States and compared risk of iron deficiency between women 0-24 mo postpartum (n = 680) and never-pregnant women, 20-40 y old (n = 587). We used data from National Health and Nutrition Examination Survey, 1988-1994. Iron deficiency was defined as abnormal values for > or = 2 of 3 iron status measures (serum ferritin, free erythrocyte protoporphyrin, transferrin saturation). Iron deficiency prevalences for women 0-6, 7-12 and 13-24 mo postpartum were 12.7, 12.4 and 7.8%, respectively, and 6.5% among never-pregnant women. After adjustment for confounding, the risk of iron deficiency among women with a poverty index ratio < or = 130% who were 0-6, 7-12 and 13-24 mo postpartum was 4.1 (95% confidence interval 2.0, 7.2), 3.1 (1.3, 6.5) and 2.0 (0.8, 4.1) times as great, respectively, as never-pregnant women with a poverty index ratio > 130%, but risk was not elevated for never-pregnant women with a poverty index ratio < or = 130%. Compared with the same referent, the risk of iron deficiency was not meaningfully different for women with a poverty index ratio > 130% who were 0-6, 7-12 or 13-24 mo postpartum. Given that low income postpartum women bear a substantially greater iron deficiency risk than never-pregnant women, more attention should be given to preventing iron deficiency among low income women during and after pregnancy.

Objective: The purpose of this study was to identify foods that contributed most to nutrient and fiber intake in a sample of pregnant women in North Carolina., Study Design: This was a prospective study of women in the Pregnancy, Infection, and Nutrition Study (n = 2247 women). Dietary information during the second trimester was collected with the use of a food frequency questionnaire. The contribution of each food item to the population's intake was calculated., Results: Overall, low nutrient-dense foods were major contributors to energy, fat, and carbohydrates, whereas fortified foods were important sources of iron, folate, and vitamin C. The median energy intake for this population was 2478 kcal. The median dietary intakes of iron were below the recommended levels. Although black women consumed more calories on average, white women, after energy adjustment, consumed greater amounts of protein, iron, folate, and fiber., Conclusion: These data emphasize the importance of evaluating both the nutrient density in the diet and the frequency of consumption in the assessment of the diets of pregnant women.