Interaction between maternal smoking and malnutrition in infant risk of gastroschisis

BACKGROUND: Gastroschisis is a severe birth defect characterized by a tear in the infant's abdominal wall. Young mothers have the highest risk of having an infant with gastroschisis. In an animal model, the defect resulted from exposure of pregnant mice to carbon monoxide (CO) in combination with a low protein and low zinc diet. METHODS: We evaluated this model in a study of 55 infants with gastroschisis and 94 age-matched controls that included maternal interview with a food frequency questionnaire. Smoking cigarettes (> or = 1 pack/day) or marijuana (more than once) 3 months prior to pregnancy indicated CO exposure. Low protein or zinc intake and a low body mass index (BMI) indicated maternal malnutrition. RESULTS: When assessed separately, high CO, low protein, low zinc, and low BMI were each significantly associated with an increased risk of gastroschisis. Although we observed significant CO-BMI and CO-zinc interactions after adjusting for income, only a combination of high CO exposure and low BMI yielded a synergistic adverse effect. Compared to the low risk of having an infant with gastroschisis for mothers who did not have low BMI and did not smoke, the risk of having an infant with gastroschisis was 16.3 times (95% CI, 2.49-113.4) higher for mothers who did not have low BMI but smoked, and 19.7 times (95% CI, 4.33-89.6) higher for mothers who did not smoke but had low BMI. However, the risk was 26.5 times (95% CI, 7.85-89.4) higher for mothers who had low BMI and smoked. CONCLUSIONS: Our results suggest that young mothers are at increased risk of having an infant with gastroschisis if they smoke and are also malnourished.     

Craniosynostosis and maternal smoking

BACKGROUND: Several previous studies suggested increased risk of craniosynostosis among infants born to women who smoked. METHODS: This study used data from the National Birth Defects Prevention Study, a multi‐state, population‐based case‐control study of infants delivered from 1997–2003. Nonmalformed, liveborn controls were selected randomly from birth certificates or birth hospitals. Data from maternal telephone interviews were available for 531 cases and 5008 controls. RESULTS: Smoking during the first month of pregnancy was not associated with craniosynostosis. Smoking later in pregnancy was associated with increased risk, but only among mothers who smoked at least one pack/day. For example, during the second trimester, the odds ratio for smoking <5 cigarettes/day was 1.0 (95% confidence interval [CI] 0.6, 1.8), but the odds ratio (OR) for smoking 15 or more cigarettes/day was 1.6 (95% CI 0.9, 2.8), after adjustment for maternal age, education, race‐ethnicity, sub‐fertility, parity, folic acid supplement intake, body mass index, and study center. Among women who did not smoke, adjusted odds ratios suggested that secondhand smoke exposure at home, but not at work/school, was associated with modestly increased risk; the OR for home exposure was 1.3 (95% CI 0.9, 1.9). Results followed a similar pattern for some, but not all, specific suture types, but numbers for some groupings were small. CONCLUSIONS: The results suggest moderately increased risk of craniosynostosis among mothers who were the heaviest smokers and who continued to smoke after the first trimester. Results are somewhat equivocal, given that most confidence intervals included one. Birth Defects Research (Part A), 2008. © 2007 Wiley‐Liss, Inc.     

Risk factors for gastroschisis

The prevalence at birth of gastroschisis, a rare abnormality of the abdominal wall, appears to have increased over the past decade. To characterize risk factors that might explain this increase, birth certificates for Washington State residents were compared for 62 infants born with gastroschisis during the years 1984 to 1987 and 617 randomly selected unaffected infants matched for birth year. After simultaneously adjusting for 14 potential risk factors, 4 factors stood out. Infants born during January, February, or March were at greater risk than infants born in any other months (odds ratio 2.2, 95% confidence interval 1.1, 4.1). Mothers less than 25 years old were at greater risk than mothers 25 years and older, with the highest risk to mothers less than 20 years old (odds ratio 4.1, 95% confidence interval 1.4, 12.0). Women who smoked during pregnancy were at greater risk than women who did not smoke (odds ratio 2.0, 95% confidence interval 1.03, 3.8). Finally, mothers receiving inadequate prenatal care were at greater risk than mothers receiving adequate prenatal care (odds ratio 2.1, 95% confidence interval 0.99, 4.6). Unidentified behavioral and environmental exposures may explain the associations with month of birth, maternal age, and prenatal care. However, smoking during pregnancy is a plausible risk factor that should be examined further as an explanation of the apparently increasing prevalence at birth of gastroschisis in developed nations.     

Associations between post translational histone modifications,myelomeningocele risk,environmental arsenic exposure,and folate deficiency among participants in a case control study in Bangladesh

Arsenic exposure may contribute to disease risk in humans through alterations in the epigenome. Previous studies reported that arsenic exposure is associated with changes in plasma histone concentrations. Posttranslational histone modifications have been found to differ between the brain tissue of human embryos with neural tube defects and that of controls. Our objectives were to investigate the relationships between plasma histone 3 levels, history of having an infant with myelomeningocele, biomarkers of arsenic exposure, and maternal folate deficiency. These studies took place in Bangladesh, a country with high environmental arsenic exposure through contaminated drinking water. We performed ELISA assays to investigate plasma concentration of total histone 3 (H3) and the histone modification H3K27me3. The plasma samples were collected from 85 adult women as part of a case-control study of arsenic and myelomeningocele risk in Bangladesh. We found significant associations between plasma %H3K27me3 levels and risk of myelomeningocele (P<0.05). Mothers with higher %H3K27me3 in their plasma had lower risk of having an infant with myelomeningocele (odds ratio: 0.91, 95% confidence interval: 0.84, 0.98). We also found that arsenic exposure, as estimated by arsenic concentration in toenails, was associated with lower total H3 concentrations in plasma, but only among women with folate deficiency (β = ?9.99, standard error = 3.91, P=0.02). Our results suggest that %H3K27me3 in maternal plasma differs between mothers of infants with myelomeningocele and mothers of infants without myelomeningocele, and may be a marker for myelomeningocele risk. Women with folate deficiency may be more susceptible to the epigenetic effects of environmental arsenic exposure.     

Associations between periconceptional alcohol consumption and craniosynostosis, omphalocele, and gastroschisis

BACKGROUND: Alcohol consumption during pregnancy is known to be associated with certain birth defects, but the risk of other birth defects is less certain. The authors examined associations between maternal alcohol consumption during pregnancy and craniosynostosis, omphalocele, and gastroschisis among participants in the National Birth Defects Prevention Study, a large, multicenter case–control study. METHODS: A total of 6622 control infants and 1768 infants with birth defects delivered from 1997–2005 were included in the present analysis. Maternal alcohol consumption was assessed as any periconceptional consumption (1 month prepregnancy through the third pregnancy month), and by quantity‐frequency, duration, and beverage type. Alcohol consumption throughout pregnancy was explored for craniosynostosis since the period of development may extend beyond the first trimester. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression analysis. OR were adjusted for age, race/ethnicity, and state of residence at time of infant's birth. Gastroschisis OR were also adjusted for periconceptional smoking. RESULTS: Periconceptional alcohol consumption and craniosynostosis showed little evidence of an association (OR = 0.92; CI: 0.78–1.08), but alcohol consumption in the second (OR = 0.65; CI: 0.47–0.92) and third trimesters (OR = 0.68; CI: 0.49–0.95) was inversely associated with craniosynostosis. Periconceptional alcohol consumption was associated with omphalocele (OR = 1.50; CI: 1.15–1.96) and gastroschisis (OR = 1.40; CI: 1.17–1.67). CONCLUSIONS: Results suggest that maternal periconceptional alcohol consumption is associated with omphalocele and gastroschisis, and second and third trimester alcohol consumption are inversely associated with craniosynostosis. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc.     

First trimester maternal medication use in relation to gastroschisis.

In a case-control surveillance program, first trimester medication use was studied in relation to gastroschisis. There were 76 cases of gastroschisis which were compared with 2,142 controls with other major malformations. For pseudoephedrine use, we found a significantly elevated relative risk of 3.2 (95% confidence interval, 1.3-7.7), with adjustment for confounding. Multivariate relative risks for analgesic/antipyretics and another decongestant were as follows: salicylates, 1.6 (0.9-2.7); acetaminophen, 1.7 (1.0-2.9); ibuprofen, 1.3 (0.4-3.7); and phenylpropanolamine, 1.5 (0.4-5.4). No increases in risk were identified for use of antihistamines, antibiotics, oral contraceptives, or spermicides. Because salicylates, pseudoephedrine, and phenylpropanolamine are vasoactive, the elevated risks for these drugs support the hypothesis of vascular disruption in the etiology of gastroschisis. We therefore examined maternal use of vasoactive medications in relation to a second case group of 416 infants with hetereogeneous defects suspected to have a vascular etiology. Relative risks for salicylates, ibuprofen, pseudoephedrine, phenylpropanolamine, and other decongestants approximated unity. These positive associations must be considered tentative. They have not been reported previously and should be confirmed independently. Also, acetaminophen, which may be taken for the same indications as salicylates and decongestants, but is not thought to be vasoactive, was associated with gastroschisis, suggesting that identified associations may be due to an underlying maternal illness.     

Fat intake and the risk of gastroschisis

BACKGROUND: Young age has been associated with an increased risk of gastroschisis. It has been suggested that the pathogenesis of gastroschisis may be related to vascular disruption. Nutrients that may be associated with vasoconstriction include dietary fat and its subtypes. The objective of this study was to examine the association between dietary fats and gastroschisis and whether maternal age modified this association. METHODS: Data came from the National Birth Defects Prevention Study (NBDPS), which included 304 isolated gastroschisis cases and 3313 controls. Dietary intake in the year prior to conception was ascertained using a food frequency questionnaire, and included total, saturated, monosaturated, and polyunsaturated fat and cholesterol. Unconditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for confounders. Age and smoking were tested as effect modifiers. RESULTS: Higher mean intakes of total energy, total fat, and cholesterol as well as the subtypes of fats were found for gastroschisis cases compared to controls. Cases were more likely to be in the middle (adjusted OR [AOR], 1.3; 95% CI, 0.9-1.9) and highest (AOR, 1.2; 95% CI, 0.8-1.7) tertile of total fat intake compared to controls. This pattern was also true for saturated fat intake. No association was found for mono or polyunsaturated fat. Cases were less likely to be in the middle (AOR, 0.6; 95% CI, 0.4-0.9) and highest (AOR, 0.8; 95% CI, 0.6-1.2) tertiles for cholesterol. There was no evidence of effect modification. CONCLUSIONS: A possible weak effect of increased risk of gastroschisis associated with higher intakes of total fat or saturated fat was found in the NBDPS; however, this did not help to explain why younger aged women are at greater risk of having an infant with this type of birth defect.     

Proximity of residence to trichloroethylene-emitting sites and increased risk of offspring congenital heart defects among older women

BACKGROUND: Previous studies suggest that trichloroethylene (TCE) is a selective cardiac teratogen. We tested the hypothesis that the odds of maternal residence close to TCE-emitting sites would be greater among infants with congenital heart defects (CHDs) than among infants without CHDs. METHODS: We conducted a case-control study of 4025 infants, identified from hospital and birth records, born from 1997 to 1999 to Milwaukee, Wisconsin mothers. A geographic information system was used to calculate distances between maternal residences and TCE sites. We used classification tree analysis to determine appropriate values by which to dichotomously categorize mothers by TCE exposure (exposed: residence within 1.32 miles of at least one TCE site) and age (older: >/=38 years), and logistic regression to test for CHD risk factors. RESULTS: The proportion of mothers who were both older and had presumed TCE exposure was more than six-fold greater among case infants than among control infants (3.3% [8/245] versus 0.5% [19/3780]). When adjusted for other variables, CHD risk was over three-fold greater among infants of older, exposed mothers compared to infants of older, nonexposed mothers (adjusted OR, 3.2; 95% CI, 1.2-8.7). Older maternal age, alcohol use, chronic hypertension, and preexisting diabetes were each associated with CHDs (adjusted ORs, 1.9, 2.1, 2.8, 4.1; 95% CIs, 1.1-3.5, 1.1-4.2, 1.2-6.7, 1.5-11.2, respectively), but residence close to TCE sites alone was not. CONCLUSIONS: Our findings suggest that maternal age and TCE exposure interact to increase CHD risk, although the mechanism by which this occurs is unknown. A prospective study is underway to confirm this finding.     

Maternal Height and Preterm Birth: A Study on 192,432 Swedish Women

BackgroundThere is increasing evidence that lower maternal stature is associated with shorter gestational length in the offspring. We examined the association between maternal height and the likelihood of delivering preterm babies in a large and homogeneous cohort of Swedish women.MethodsThis study covers antenatal data from the Swedish Medical Birth Register on 192,432 women (aged 26.0 years on average) born at term, from singleton pregnancies, and of Nordic ethnicity. Continuous associations between women''s heights and the likelihood of preterm birth in the offspring were evaluated. Stratified analyses were also carried out, separating women into different height categories.ResultsEvery cm decrease in maternal stature was associated with 0.2 days shortening of gestational age in the offspring (p<0.0001) and increasing odds of having a child born preterm (OR 1.03), very preterm (OR 1.03), or extremely preterm (OR 1.04). Besides, odds of all categories of preterm birth were highest among the shortest women but lowest among the tallest mothers. Specifically, women of short stature (≤155 cm or ≤-2.0 SDS below the population mean) had greater odds of having preterm (OR 1.65) or very preterm (OR 1.47) infants than women of average stature (-0.5 to 0.5 SDS). When compared to women of tall stature (≥179 cm), mothers of short stature had even greater odds of giving birth to preterm (OR 2.07) or very preterm (OR 2.16) infants.ConclusionsAmong Swedish women, decreasing height was associated with a progressive increase in the odds of having an infant born preterm. Maternal short stature is a likely contributing factor to idiopathic preterm births worldwide, possibly due to maternal anatomical constraints.     

Orofacial clefts, parental cigarette smoking, and transforming growth factor-alpha gene variants.

Results of studies to determine whether women who smoke during early pregnancy are at increased risk of delivering infants with orofacial clefts have been mixed, and recently a gene-environment interaction between maternal smoking, transforming growth factor-alpha (TGFa), and clefting has been reported. Using a large population-based case-control study, we investigated whether parental periconceptional cigarette smoking was associated with an increased risk for having offspring with orofacial clefts. We also investigated the influence of genetic variation of the TGFa locus on the relation between smoking and clefting. Parental smoking information was obtained from telephone interviews with mothers of 731 (84.7% of eligible) orofacial cleft case infants and with mothers of 734 (78.2%) nonmalformed control infants. DNA was obtained from newborn screening blood spots and genotyped for the allelic variants of TGFa. We found that risks associated with maternal smoking were most elevated for isolated cleft lip with or without cleft palate, (odds ratio 2.1 [95% confidence interval 1.3-3.6]) and for isolated cleft palate (odds ratio 2.2 [1.1-4.5]) when mothers smoked > or =20 cigarettes/d. Analyses controlling for the potential influence of other variables did not reveal substantially different results. Clefting risks were even greater for infants with the TGFa allele previously associated with clefting whose mothers smoked > or =20 cigarettes/d. These risks for white infants ranged from 3-fold to 11-fold across phenotypic groups. Paternal smoking was not associated with clefting among the offspring of nonsmoking mothers, and passive smoke exposures were associated with at most slightly increased risks. This study offers evidence that the risk for orofacial clefting in infants may be influenced by maternal smoke exposures alone as well as in combination (gene-environment interaction) with the presence of the uncommon TGFa allele.     

Maternal prenatal exposure to environmental factors and risk of childhood acute lymphocytic leukemia: A hospital-based case-control study in China

Objective: To investigate an association between maternal prenatal exposure to several environmental factors and risk of childhood acute lymphocytic leukemia (ALL), and the possible interactions in the Chinese population.Methods: 345 cases with ALL and their 1:1 age, gender, residence region matched controls aged 0–15 years were recruited from four hospitals in Henan Province from 2014 to 2016. Information was collected by interviews using a questionnaire. Unconditional logistic regression adjusted for age, gender, residence region and relevant confounders was carried out to generate the odds ratios (ORs) and 95% confidence intervals (CIs).Results: Our data indicate that maternal prenatal exposure to interior housing renovation (adjusted OR: 2.98, 95% CI: 1.51–5.86) or pesticides (adjusted OR: 1.48, 95% CI: 1.67–2.28) increased the risk of childhood ALL. Various subgroup analyses stratified by child's gender, age at diagnosis and other factors also supported these results. However, no interaction was detected between exposure to internal housing renovation and pesticides using an additive model. No significant links between maternal exposures to, environmental tobacco smoking (ETS), antipyretic analgesia intake, or viral infectious diseases with risk of ALL were detected.Conclusion: Findings in our study are in line with the existing literatures, which support the hypothesis that maternal prenatal exposure to interior housing renovation and pesticides are risk factors for childhood ALL. Notably, we found no interaction between these two risk factors, these findings may inform prevention and early detection strategies.     

Gastroschisis, low maternal age, and fetal morbidity outcomes

OBJECTIVE: To determine if the risk for fetal growth inhibition among gastroschisis-afflicted fetuses is heightened among younger gravidas (teen mothers). METHOD: This was a retrospective cohort study on live-born infants with isolated gastroschisis delivered in New York State from 1983 through 1999. We compared infants of mature (>20 years) mothers with those of younger (<20 years) mothers with respect to the following indices of fetal morbidity outcomes: low birth weight and very low birth weight, preterm and very pre-term, and small for gestational age. We used adjusted odds ratios to approximate relative risks. RESULTS: A total of 368 infants with isolated gastroschisis were analyzed. The two groups differed in terms of mean gestational age at delivery [Mean + standard deviation(SD) for infants with gastroschisis born to mature mothers = 37.2 weeks +/- 2.8 versus 36.3 weeks + 3.6 for those of teenage mothers(p = 0.01)], as well as mean birth weight [mean birth weight +/- SD for infants with gastroschisis born to mature mothers = 2562.4 grams +548.8 versus 2367.9 grams +/- 645.2 for those of younger mothers (p = 0.004)]. Infants of teen mothers were about twice as likely to be of low birth weight (OR = 1.70; 95% CI = 1.05-2.77) and about three times as likely to be born very preterm when compared to those of mature mothers (OR = 2.80; 95% Cl = 1.02-8.00). No significant differences were observed with respect to very low birth weight, pre-term and small for gestational age. CONCLUSION: Low maternal age appears to be a risk factor for low birth weight and very preterm birth among gastroschisis-affected fetuses. This information is potentially useful for planning by care providers and in counseling affected parents.     

Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: a report from the National Down Syndrome Project

BACKGROUND: Maternal folic acid supplementation has been associated with a reduced risk for neural tube defects and may be associated with a reduced risk for congenital heart defects and other birth defects. Individuals with Down syndrome are at high risk for congenital heart defects and have been shown to have abnormal folate metabolism. METHODS: As part of the population‐based case‐control National Down Syndrome Project, 1011 mothers of infants with Down syndrome reported their use of supplements containing folic acid. These data were used to determine whether a lack of periconceptional maternal folic acid supplementation is associated with congenital heart defects in Down syndrome. We used logistic regression to test the relationship between maternal folic acid supplementation and the frequency of specific heart defects correcting for maternal race or ethnicity, proband sex, maternal use of alcohol and cigarettes, and maternal age at conception. RESULTS: Lack of maternal folic acid supplementation was more frequent among infants with Down syndrome and atrioventricular septal defects (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.08–2.63; p = 0.011) or atrial septal defects (OR, 1.69; 95% CI, 1.11–2.58; p = 0.007) than among infants with Down syndrome and no heart defect. Preliminary evidence suggests that the patterns of association differ by race or ethnicity and sex of the proband. There was no statistically significant association with ventricular septal defects (OR, 1.26; 95% CI, 0.85–1.87; p = 0.124). CONCLUSIONS: Our results suggest that lack of maternal folic acid supplementation is associated with septal defects in infants with Down syndrome. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.     

Reduced folate carrier gene is a risk factor for neural tube defects in a Chinese population

BACKGROUND: There is a considerable body of data demonstrating that periconceptional supplementation of folic acid can prevent a significant proportion of neural tube defects (NTDs). At present, the mechanism by which folic acid exerts its beneficial effect remains unknown. Folate transporter genes, including the reduced folate carrier gene (RFC1), have been proposed as NTD risk factors. METHODS: The study population included 104 nuclear families with NTDs and 100 nonmalformed control families. We investigated the possible association between a common RFC1 polymorphism (A80G) and NTD risk among offspring, as well as potential gene-environment interactions between the infant RFC1 genotype and maternal periconceptional use of folic acid through a population-based case-control study. RESULTS: We observed that the infants of the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared to the AA genotype (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.04-6.36) in our study population. Among mothers who did not utilize folic acid supplements, the risk for having a child with an NTD was 3.30 (95% CI, 1.15-9.65) for offspring with the GG genotype, compared to the reference (AA) genotype. Children who had the GG genotype and whose mothers did not take folic acid had an elevated risk for NTDs (OR, 8.80; 95% CI, 2.83-28.69), compared to offspring with the AA and GA genotypes whose mothers utilized folic acid supplements. CONCLUSIONS: Our findings suggest that the RFC1 G allele is likely to be an important genetic factor in determining folate transport and subsequently may be a risk factor for NTDs in this Chinese population.     

Absence of limbs and gross body wall defects: an epidemiological study of related rare malformation conditions.

The study is based on almost 10 million births and reports on 215 infants with two unusual malformations: amelia and gross body wall defect. Amelia without body wall defect was present in 116 cases, 67 had body wall defects without amelia, and 32 had both. The total rate was 2.2 per 100,000 births. The infants were divided into five mutually exclusive groups. There were 40 infants (0.4 per 100,000) with agenesis of the body stalk, 18 with amelia and other types of gross body wall defects (0.2 per 100,000), 56 with amelia and malformations other than gross body wall defects (0.6 per 100,000), 41 with amelia (with or without other limb reduction defects) but no nonlimb malformations (0.4 per 100,000), and 60 infants with gross body wall defects of a type other than agenesis of body stalk and without amelia (0.6 per 100,000). A weak trend of decreasing prevalence of these malformations was found during the observation period. Infants with agenesis of the body stalk and infants with amelia combined with other types of gross body wall defects occurred at an increased rate in infants of young women. This maternal age effect is also found with gastroschisis, but not with omphalocele, and may indicate etiological or pathogenetic similarities between gastroschisis and the two former groups of defect. In infants with amelia, additional limb reduction defects could be of any type: transverse, longitudinal, or intercalary. Therefore, amelia may be the end result of different types of disturbances of limb morphogenesis. There was an increased rate of twinning. The relationship with amniotic band syndrome is discussed.     

The Effects of Periconceptional Risk Factor Exposure and Micronutrient Supplementation on Birth Defects in Shaanxi Province in Western China

Objectives

1) To understand the current prevalence and main types of birth defects, 2) assess the periconceptional exposure of factors associated with birth defects in Shaanxi Province, and 3) provide scientific evidence for local governments to formulate services for the primary prevention of birth defects.

Methods

We sampled 16,541 households from 128 townships in 16 counties/districts in Shaanxi province using a multi-stage random sampling method. Among them, 10,544 women who had live born or stillborn infants with gestational age ≥28 weeks between 2008 and 2009 were interviewed using a structured questionnaire designed to collect information about periconceptional risk factor exposure, health care service utilization, and micronutrient supplements. Logistic regression was performed to assess the risk factors associated with birth defects and adjustments were made for imbalanced social-demographic characteristics between case and control groups.

Results

The prevalence of congenital birth defect in Shaanxi province was 14.3/1000 births. The environment risk factors associated with birth defects include unhealthy lifestyle (Alcohol, odds ratio (OR): 3.60, 95% confidence interval (CI) 1.64−7.91; Smoking, OR: 1.32, 95% CI: 0.99−1.75; Drink strong tea, OR: 1.81, 95% CI: 1.27−2.59), exposure to heavy pollution (OR: 1.53, 95% CI: 1.01−2.30), maternal diseases (OR: 1.77, 95% CI: 1.35−2.33), drug use (OR: 2.11, 95% CI: 1.51−2.95), maternal chemical pesticide exposure (OR: 2.30, 95% CI: 1.16−4.57), and adverse pregnancy history (OR: 10.10, 95% CI: 7.55−13.53). Periconceptional folic acid or multiple micronutrients including folic acid supplementation, was associated with a reduced rate of birth defects (OR: 0.54, 95% CI: 0.29−0.998).

Conclusions

Health care service utilization, unhealthy lifestyle factors, and environment risk factors seem to be associated with birth defects in Shaanxi province. Governmental agencies should focus on effective primary preventative methods, such as the delivery of periconceptional health education for minimizing potential risk factor exposures, periconceptional folic acid or micronutrient supplementation, environment monitoring, and assessment of factories with high levels of pollution.     

Case-control study of self reported genitourinary infections and risk of gastroschisis: findings from the national birth defects prevention study, 1997-2003

Objective To assess the association between genitourinary infections in the month before conception to the end of the first trimesterand gastroschisis.Design Case-control study with self reported infections from a computer assisted telephone interview.Setting National birth defects prevention study, a multisite, population based study including 10 surveillance systems for birth defects in the United States.Participants Mothers of 505 offspring with gastroschisis and 4924 healthy liveborn infants as controls.Main outcome measure Adjusted odds ratios for gastroschisis with 95% confidence intervals.Results About 16% (n=81) of case mothers and 9% (n=425) of control mothers reported a genitourinary infection in the relevant time period; 4% (n=21) and 2% (n=98) reported a sexually transmitted infection and 13% (n=67) and 7% (n=338) reported a urinary tract infection, respectively. Case mothers aged <25 years reported higher rates of urinary tract infection alone and in combination with a sexually transmitted infection compared with control mothers. In women who reported both types of infection, there was a greater risk of gastroschisis in offspring (adjusted odds ratio 4.0, 95% confidence interval 1.4 to 11.6).Conclusion There is a significant association between self reported urinary tract infection plus sexually transmitted infection just before conception and in early pregnancy and gastroschisis.     

Microsatellites proximal to leptin and leptin receptor as risk factors for spina bifida

Several recent studies have observed an association between neural tube defect risk and prepregnant obesity. This association was generally stronger for spina bifida and was observed irrespective of additional maternal factors, including periconceptional intake of vitamin supplements. Other studies have identified mutations within the genes that code for leptin (LEP) and its receptor (LEPR), which have been linked to obesity in mice and humans. We investigated the potential association between nucleotide variation at the LEP and LEPR loci, and increased risk of spina bifida. We searched specifically for allelic association at a pair of highly polymorphic microsatellites closely linked to either the LEP or LEPR gene. Data were derived from a population-based case-control study that had previously identified an association between a woman's prepregnant obesity and her risk of delivering an infant with spina bifida. A total of 56 spina bifida case infants and 126 nonmalformed control infants were genotyped for 10 microsatellite alleles closely linked to the LEP gene, and 49 cases and 125 controls were genotyped for 10 microsatellite alleles closely linked to the LEPR gene. In general, alleles were not observed to be exclusively associated with substantially greater spina bifida risk in the body mass index (BMI) category (obese) of >29 kg/m(2) compared with the BMI category (nonobese) of 29 kg/m; (2) having either allele and BMI 29 kg/m(2). The odds ratios (95% confidence interval) for these comparisons were: for allele 257, 4.5 (1.1-19.4), 1.9 (0.5-6.3), and 2.9 (1.3-6.4), respectively, and for allele 271, 6.7 (1.6-30.4), 2.7 (0.7-10.9), and 2.7 (1.2-5.9), respectively. Owing to the exploratory nature of this investigation, the significance of these latter results is unclear.