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.     

Maternal intake of vitamin E and birth defects,national birth defects prevention study, 1997 to 2005

BACKGROUND In a recent study, high maternal periconceptional intake of vitamin E was found to be associated with risk of congenital heart defects (CHDs). To explore this association further, we investigated the association between total daily vitamin E intake and selected birth defects. METHODS: We analyzed data from 4525 controls and 8665 cases from the 1997 to 2005 National Birth Defects Prevention Study. We categorized estimated periconceptional energy‐adjusted total daily vitamin E intake from diet and supplements into quartiles (referent, lowest quartile). Associations between quartiles of energy‐adjusted vitamin E intake and selected birth defects were adjusted for demographic, lifestyle, and nutritional factors. RESULTS: We observed a statistically significant association with the third quartile of vitamin E intake (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01–1.35) and all CHDs combined. Among CHD sub‐types, we observed associations with left ventricular outflow tract obstruction defects, and its sub‐type, coarctation of the aorta and the third quartile of vitamin E intake. Among defects other than CHDs, we observed associations between anorectal atresia and the third quartile of vitamin E intake (OR, 1.66; 95% CI, 1.01–2.72) and hypospadias and the fourth quartile of vitamin E intake (OR, 1.42; 95% CI, 1.09–1.87). CONCLUSION: Selected quartiles of energy‐adjusted estimated total daily vitamin E intake were associated with selected birth defects. However, because these few associations did not exhibit exposure‐response patterns consistent with increasing risk associated with increasing intake of vitamin E, further studies are warranted to corroborate our findings. Birth Defects Research (Part A), 100:647–657, 2014. © 2014 Wiley Periodicals, Inc.     

Maternal occupational exposure to polycyclic aromatic hydrocarbons and congenital heart defects among offspring in the national birth defects prevention study

BACKGROUND: There is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) results in congenital heart defects (CHDs); however, to our knowledge, this relationship has not been examined in humans. Therefore, we conducted a case‐control study assessing the association between estimated maternal occupational exposure to PAHs and CHDs in offspring. METHODS: Data on CHD cases and control infants were obtained from the National Birth Defects Prevention Study for the period of 1997 to 2002. Exposure to PAHs was assigned by industrial hygienist consensus, based on self‐reported maternal occupational histories from 1 month before conception through the third month of pregnancy. Logistic regression was used to evaluate the association between maternal occupational PAH exposure and specific CHD phenotypic subtypes among offspring. RESULTS: The prevalence of occupational PAH exposure was 4.0% in CHD case mothers (76/1907) and 3.6% in control mothers (104/2853). After adjusting for maternal age, race or ethnicity, education, smoking, folic acid supplementation, and study center, exposure was not associated with conotruncal defects (adjusted odds ratio [AOR], 0.98; 95% confidence interval [CI], 0.58–1.67), septal defects (AOR, 1.28; 95% CI, 0.86–1.90), or with any isolated CHD subtype. CONCLUSIONS: Our findings do not support an association between potential maternal occupational exposure to PAHs and various CHDs in a large, population‐based study. For CHD phenotypic subtypes in which modest nonsignificant associations were observed, future investigations could be improved by studying populations with a higher prevalence of PAH exposure and by incorporating information on maternal and fetal genotypes related to PAH metabolism. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.     

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.     

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.     

Role of p53 family in birth defects: lessons from zebrafish

p53 Protein family is an important teratologic suppressor, but in certain conditions it can cause congenital abnormalities. p53 Family performs this dual role in development by integrating information from cell's interior with that from the environment to determine the choice between life and death. Understanding of p53 family developmental functions may lead to new therapeutic approaches for treatment and prevention of birth defects. Zebrafish is becoming the vertebrate system of choice for studying p53 family role in development.     

Preconceptional folic acid‐containing supplement use in the national birth defects prevention study

Background: Despite public health campaigns encouraging women to take a daily folic acid supplement, the proportion of reproductive age women, in the United States, who comply with this recommendation is less than optimal. The objective of this analysis was to identify predictors of preconceptional folic acid‐containing supplement use to define subgroups of women who may benefit from targeted folic acid campaigns. Methods: This study included 6570 mothers of live born infants from the control population of National Birth Defects Prevention Study (1997–2005). Logistic regression analyses were used to identify predictors of preconceptional folic acid supplementation. A classification and regression tree (CART) analysis was used to define subgroups of women with different patterns of preconceptional folic acid supplementation. Results: Race/ethnicity, education, age at delivery, nativity, employment, income, number of dependents, smoking, and birth control use were significantly associated with preconceptional folic acid‐containing supplement use. Based on a CART analysis, education, race/ethnicity, and age were the most distinguishing factors between women with different preconceptional supplementation patterns. Non‐white women with <4 years of a college education were the least likely to use folic acid‐containing supplements (11%). However, even in the most compliant subgroup (women with ≥4 years of college), only 60% of women supplemented with folic acid. Conclusion: These results demonstrate the need for continued efforts to increase folic acid supplementation among all reproductive aged women. However, the success of such efforts may be improved if maternal characteristics such as education, race/ethnicity, and age, are considered in the development of future interventions. Birth Defects Research (Part A) 100:472–482, 2014. © 2014 Wiley Periodicals, Inc.     

Maternal self-reported genital tract infections during pregnancy and the risk of selected birth defects

BACKGROUND: Genital tract infections are common during pregnancy and can result in adverse outcomes including preterm birth and neonatal infection. This hypothesis‐generating study examined whether these infections are associated with selected birth defects. METHODS: We conducted a case‐control study of 5913 children identified as controls and 12,158 cases with birth defects from the National Birth Defects Prevention Study (1997–2004). Maternal interviews provided data on genital tract infections that occurred from one month before pregnancy through the end of the first trimester. Infections were either grouped together as a single overall exposure or were considered as a subgroup that included chlamydia/gonorrhea/pelvic inflammatory disease. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression with adjustment for potential confounders. RESULTS: Genital tract infections were associated with bilateral renal agenesis/hypoplasia (OR, 2.89; 95% CI, 1.11–7.50), cleft lip with or without cleft palate (OR, 1.46; 95% CI, 1.03–2.06), and transverse limb deficiency (OR, 1.84; 95% CI, 1.04–3.26). Chlamydia/gonorrhea/pelvic inflammatory disease was associated with cleft lip only (OR, 2.81; 95% CI, 1.39–5.69). These findings were not statistically significant after adjustment for multiple comparisons. CONCLUSIONS: Caution is needed in interpreting these findings due to the possible misclassification of infection, the limited sample size that constrained consideration of the effects of treatment, and the possibility of chance associations. Although these data do not provide strong evidence for an association between genital tract infections and birth defects, additional research on the possible effects of these relatively common infections is needed. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.     

Maternal thyroid disease,thyroid medication use,and selected birth defects in the National Birth Defects Prevention Study

BACKGROUND: Although thyroid disorders are present in approximately 3% of pregnant women, little is known about the association between maternal thyroid disease and birth defects. METHODS: We assessed the association between maternal thyroid disease, thyroid medication use, and 38 types of birth defects among 14,067 cases and 5875 controls in the National Birth Defects Prevention Study, a multisite, population‐based, case‐control study. Infants in this study were born between October 1997 and December 2004. Information on exposures including maternal diseases and use of medications was collected by telephone interview. RESULTS: We found statistically significant associations between maternal thyroid disease and left ventricular outflow tract obstruction heart defects (1.5; 95% CI, 1.0–2.3), hydrocephaly (2.9; 95% CI, 1.6–5.2), hypospadias (1.6; 95% CI, 1.0–2.5), and isolated anorectal atresia (2.4; 95% CI, 1.2–4.6). Estimates for the association between periconceptional use of thyroxine and specific types of birth defects were similar to estimates for any thyroid disease. Given that antithyroid medication use was rare, we could not adequately assess risks for their use for most case groups. CONCLUSIONS: Our results are consistent with the positive associations between maternal thyroid disease or thyroid medication use and both hydrocephaly and hypospadias observed in some previous studies. New associations with left ventricular outflow tract obstruction heart defects and anorectal atresia may be chance findings. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Association between reported venlafaxine use in early pregnancy and birth defects,national birth defects prevention study, 1997–2007

BACKGROUND

Few epidemiologic studies have investigated the use of venlafaxine (Effexor XR capsules, Product Monograph, Wyeth, Montreal, Canada), an antidepressant used to treat major depression and anxiety disorders in adults, during pregnancy. Our objective was to determine whether use of venlafaxine during pregnancy is associated with specific birth defects.

METHODS

We used data from the National Birth Defects Prevention Study (NBDPS), a population‐based, case‐control study in the United States. Our analysis included mothers with pregnancies affected by one of 30 selected birth defects (cases) and babies without birth defects (controls) with estimated dates of delivery between 1997 and 2007. Exposure was any reported use of venlafaxine from 1 month preconception through the third month of pregnancy. We calculated adjusted odds ratios (aORs) and 95% Fisher Exact confidence intervals (CIs) for 24 birth defect groups for which at least 400 case mothers were interviewed. Our adjusted analyses controlled for maternal age and race/ethnicity.

RESULTS

Among the 27,045 NBDPS participants who met inclusion criteria, 0.17% (14/8002) of control mothers and 0.40% (77/19,043) of case mothers reported any use of venlafaxine from 1 month preconception through the third month of pregnancy. Statistically significant associations were found for anencephaly, atrial septal defect (ASD) secundum, or ASD not otherwise specified, coarctation of the aorta, cleft palate, and gastroschisis.

CONCLUSIONS

Our data suggest associations between periconceptional use of venlafaxine and some birth defects. However, sample sizes were small, CIs were wide, and additional studies are needed to confirm these results. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.