Prenatal Exposure to Nitrosatable Drugs, Dietary Intake of Nitrites, and Preterm Birth.

Prenatal exposure to nitrosatable drugs, including secondary or tertiary amines, has been associated with preterm birth. Associations may be accentuated by higher intakes of dietary nitrites because of the increased formation of N-nitroso compounds. Using data from mothers of babies without major birth defects (controls) from the National Birth Defects Prevention Study, we examined the relationship between nitrosatable drug exposure in conjunction with dietary nitrite intake and preterm birth among 496 mothers of preterm infants and 5,398 mothers with full-term deliveries in 1997-2005. A protective association was observed with a high intake of plant nitrites (adjusted hazard ratio (AHR) = 0.72, 95% confidence interval (CI): 0.53, 0.97). Secondary amines in conjunction with high nitrite intake were associated with preterm birth during the first (AHR = 1.84, 95% CI: 1.14, 2.98), second (AHR = 1.89, 95% CI: 1.17, 3.07), and third (AHR = 2.00, 95% CI: 1.22, 3.29) trimesters. The adjusted hazard ratios for tertiary amine use in the third trimester by increasing tertiles of nitrite intake were 0.67 (95% CI: 0.35, 1.31), 1.25 (95% CI: 0.71, 2.19), and 2.02 (95% CI: 1.17, 3.49). Prenatal exposure to nitrosatable drugs, particularly secondary and tertiary amines, in conjunction with higher levels of dietary nitrite intake may increase the risk of preterm birth.

Nitrosatable Drug Exposure during Pregnancy and Preterm and Small-for-Gestational-Age Births.

BACKGROUND: Nitrosatable drugs react with nitrite in the stomach to form N-nitroso compounds, observed in animal models to result in adverse pregnancy outcomes, such as birth defects and reduced fetal weight. Previous studies examining prenatal exposure to medications classified as nitrosatable have reported an increased risk of preterm births (PTBs) and small-for-gestational-age (SGA) infants. METHODS: Using data from mothers (controls) of babies without major birth defects from the National Birth Defects Prevention Study, prenatal nitrosatable drug usage by trimester and month of gestation was examined in relation to PTBs and SGA infants. RESULTS: Positive associations were observed with nitrosatable drug use and PTBs, with the strongest relationship with second trimester exposure (adjusted hazard ratio [aHR] 1.37, [95% confidence interval (CI) 1.10, 1.70]). Of the nitrosatable functional groups, secondary amines were the most notable, with a higher association among women with second (aHR 1.37, [95% CI 1.05, 1.79]) and third (aHR 1.34, [95% CI 1.02, 1.76]) trimester exposure compared with women with no prenatal nitrosatable drug use. Among SGA infants, a borderline association was noted with amide exposure during the third trimester (adjusted odds ratio 1.43 [95% confidence interval [CI] 1.00, 2.05]). CONCLUSIONS: Prenatal exposure to nitrosatable drugs during the second and third trimester of pregnancy, particularly secondary amines, might increase the risk of PTBs. However, prenatal exposure to nitrosatable drugs was not associated with SGA infants, with the exception of amide drugs.

Dietary intake of choline and neural tube defects in Mexican Americans.

BACKGROUND: Low maternal intake of dietary choline and betaine (a choline derivative) has recently been investigated as a possible risk factor for neural tube defects (NTDs). METHODS: This case-control study examined the NTD risk associated with choline and betaine in 409 Mexican-American women who gave birth during 1995 to 2000 in the 14-county border region of Texas. RESULTS: Using data from the food frequency questionnaire and the lowest quartiles of intake as the reference categories, a protective association was suggested between higher intakes of choline and betaine and NTD risk although the 95% confidence intervals for all risk estimates included 1.0. For choline intake in the second, third, and fourth quartiles, adjusted odds ratios were 1.2, 0.80, and 0.89, respectively. Betaine appeared more protective with odds ratios of 0.62, 0.73, and 0.61, respectively, for the second, third, and fourth quartiles of intake. CONCLUSION: Study findings suggest that dietary betaine may help to prevent NTDs.

Maternal residential proximity to chlorinated solvent emissions and birth defects in offspring: a case-control study.

BACKGROUND: Some studies have noted an association between maternal occupational exposures to chlorinated solvents and birth defects in offspring, but data are lacking on the potential impact of industrial air emissions of these solvents on birth defects. METHODS: With data from the Texas Birth Defects Registry for births occurring in 1996-2008, we examined the relation between maternal residential proximity to industrial air releases of chlorinated solvents and birth defects in offspring of 60,613 case-mothers and 244,927 control-mothers. Maternal residential exposures to solvent emissions were estimated with metrics that took into account residential distances to industrial sources and annual amounts of chemicals released. Logistic regression was used to generate odds ratios and 95% confidence intervals for the associations between residential proximity to emissions of 14 chlorinated solvents and selected birth defects, including neural tube, oral cleft, limb deficiency, and congenital heart defects. All risk estimates were adjusted for year of delivery and maternal age, education, race/ethnicity, and public health region of residence. RESULTS: Relative to exposure risk values of 0, neural tube defects were associated with maternal residential exposures (exposure risk values >0) to several types of chlorinated solvents, most notably carbon tetrachloride (adjusted odds ratio [aOR] 1.42, 95% confidence interval [CI] 1.09, 1.86); chloroform (aOR 1.40, 95% CI 1.04, 1.87); ethyl chloride (aOR 1.39, 95% CI 1.08, 1.79); 1,1,2-trichloroethane (aOR 1.56, 95% CI 1.11, 2.18); and 1,2,3-trichloropropane (aOR 1.49, 95% CI 1.08, 2.06). Significant associations were also noted between a few chlorinated solvents and oral cleft, limb deficiency, and congenital heart defects. We observed stronger associations between some emissions and neural tube, oral cleft, and heart defects in offspring of mothers 35 years or older, such as spina bifida with carbon tetrachloride (aOR 2.49, 95% CI 1.09, 5.72), cleft palate with 1,2-dichloroethane (aOR 1.93, 95% 1.05, 3.54), cleft lip with or without cleft palate with ethyl chloride (aOR 1.81, 95% CI 1.06, 3.07), and obstructive heart defects with trichloroethylene (aOR 1.43, 95% CI 1.08, 1.88). CONCLUSIONS: These findings suggest that maternal residential proximity to industrial emissions of chlorinated solvents might be associated with selected birth defects in offspring, especially among older mothers.

Assessing bottled water nitrate concentrations to evaluate total drinking water nitrate exposure and risk of birth defects.

Previous epidemiologic studies of maternal exposure to drinking water nitrate did not account for bottled water consumption. The objective of this National Birth Defects Prevention Study (NBDPS) (USA) analysis was to assess the impact of bottled water use on the relation between maternal exposure to drinking water nitrate and selected birth defects in infants born during 1997-2005. Prenatal residences of 1,410 mothers reporting exclusive bottled water use were geocoded and mapped; 326 bottled water samples were collected and analyzed using Environmental Protection Agency Method 300.0. Median bottled water nitrate concentrations were assigned by community; mothers' overall intake of nitrate in mg/day from drinking water was calculated. Odds ratios for neural tube defects, limb deficiencies, oral cleft defects, and heart defects were estimated using mixed-effects models for logistic regression. Odds ratios (95% CIs) for the highest exposure group in offspring of mothers reporting exclusive use of bottled water were: neural tube defects [1.42 (0.51, 3.99)], limb deficiencies [1.86 (0.51, 6.80)], oral clefts [1.43 (0.61, 3.31)], and heart defects [2.13, (0.87, 5.17)]. Bottled water nitrate had no appreciable impact on risk for birth defects in the NBDPS.

Prenatal exposure to nitrosatable drugs, vitamin C, and risk of selected birth defects.

UNLABELLED: Nitrosatable drugs, such as secondary or tertiary amines and amides react with nitrite in an acidic environment to form N-nitroso compounds, teratogens in animal models. Vitamin C is a known nitrosation inhibitor. METHODS: Using data from the National Birth Defects Prevention Study, we assessed nitrosatable drug exposure and vitamin C intake during the first trimester among 11,606 case-mothers of infants with oral clefts, limb deficiencies (LDs), or congenital heart defects and 6807 control-mothers of infants without major birth defects during 1997-2005. Daily intake of vitamin C was estimated from maternal interviews that elicited information about supplement use and dietary intake. RESULTS: With no reported use of nitrosatable drugs as the referent group, a lower odds ratio (OR) was observed for transverse LDs among births to mothers exposed to secondary amine drugs and daily vitamin C supplementation (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 0.83-1.8) compared with women taking these drugs and no supplementation (aOR 2.7, 95% CI 1.5-4.6). The OR for longitudinal LDs associated with secondary amine exposure was lower with daily dietary vitamin C intake ≥85 mg (aOR 1.2, 95% CI 0.68-2.0) compared with <85 mg (aOR 1.9, 95% CI 1.2-3.1). Daily vitamin C supplementation in combination with higher dietary vitamin C intake reduced associations between nitrosatable drug exposures and limb deficiencies and atrial septal defects not otherwise specified. CONCLUSION: Prenatal dietary and vitamin C supplement intake may diminish the association between nitrosatable drug exposure during pregnancy and selected birth defects.

Maternal dietary intake of nitrates, nitrites and nitrosamines and selected birth defects in offspring: a case-control study.

BACKGROUND: Dietary intake of nitrates, nitrites, and nitrosamines can increase the endogenous formation of N-nitroso compounds in the stomach. Results from animal studies suggest that these compounds might be teratogenic. We examined the relationship between maternal dietary intake of nitrates, nitrites (including plant and animal sources as separate groups), and nitrosamines and several types of birth defects in offspring. METHODS: For this population-based case-control study, data from a 58-question food frequency questionnaire, adapted from the short Willett Food Frequency Questionnaire and administered as part of the National Birth Defects Prevention Study (NBDPS), were used to estimate daily intake of dietary nitrates, nitrites, and nitrosamines in a sample of 6544 mothers of infants with neural tube defects (NTD)s, oral clefts (OC)s, or limb deficiencies (LD)s and 6807 mothers of unaffected control infants. Total daily intake of these compounds was divided into quartiles based on the control mother distributions. Odds ratios (OR)s and 95% confidence intervals (CI)s were estimated using logistic regression; estimates were adjusted for maternal daily caloric intake, maternal race-ethnicity, education, dietary folate intake, high fat diet (>30% of calories from fat), and state of residence. RESULTS: While some unadjusted ORs for NTDS had 95% (CI)s that excluded the null value, none remained significant after adjustment for covariates, and the effect sizes were small (adjusted odds ratios [aOR]<1.12). Similar results were found for OCs and LDs with the exception of animal nitrites and cleft lip with/without cleft palate (aORs and CIs for quartile 4 compared to quartile 1 =1.24; CI=1.05-1.48), animal nitrites and cleft lip (4th quartile aOR=1.32; CI=1.01-1.72), and total nitrite and intercalary LD (4th quartile aOR=4.70; CI=1.23-17.93). CONCLUSIONS: Overall, odds of NTDs, OCs or LDs did not appear to be significantly associated with estimated dietary intake of nitrate, nitrite, and nitrosamines.

Neural tube defects on the Texas-Mexico border: what we've learned in the 20 years since the Brownsville cluster.

We reviewed the published findings from the Texas Neural Tube Defect Project, a 6-year case-control study (1995-2000) of neural tube defects (NTDs) on the Texas-Mexico border. In this review, we highlight what was learned about environmental, genetic, and nutritional factors (i.e., those related to the folate and other metabolic pathways) and the novel putative risk factors that emerged from this study of Mexican American women living on the Texas-Mexico border. Our investigations of the micronutrients and metabolic pathways involved confirmed the findings of other researchers that increased folate intake has a protective effect and that low serum B(12) , high serum homocysteine levels, and obesity independently contribute to risk. Studies of this population also have implicated hyperinsulinemia and low ferritin, metabolic risk factors, which require additional study to elucidate their physiologic mechanism. Environmental contaminants such as heavy metals, pesticides, and polychlorinated biphenyls (PCBs), which were of community concern, did little to explain NTD risk. Studies in this folic acid deficit-population also revealed several novel risk factors, namely, diarrhea, stress, fumonisins, and the combination of nitrosatable drug exposure with high nitrate/nitrite intake. In conclusion, the 23 studies among the Mexican American women living along the Texas-Mexico border have demonstrated the multifactorial nature of NTDs and that a population deficient in folic acid will be vulnerable to a variety of insults whether brought on by individual behaviors (e.g., obesity) or through the surrounding environment (e.g., fumonisins). Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.

Nitrosatable drug exposure during the first trimester of pregnancy and selected congenital malformations.

BACKGROUND: Nitrosatable drugs can react with nitrite in the stomach to form N-nitroso compounds, and results from animal studies suggest that N-nitroso compounds are teratogens. With data from the National Birth Defects Prevention Study, the relation between prenatal exposure to nitrosatable drugs and limb deficiencies, oral cleft, and heart malformations in offspring was examined. METHODS: Maternal reports of drugs taken during the first trimester of pregnancy were classified with respect to nitrosatability for mothers of 741 babies with limb deficiencies, 2774 with oral cleft malformations, 8091 with congenital heart malformations, and 6807 without major congenital malformations. Nitrite intake was estimated from maternal responses to a food frequency questionnaire. RESULTS: Isolated transverse limb deficiencies and atrioventricular septal defects were associated with secondary amine drug exposures (adjusted odds ratios [aORs], 1.51; 95% confidence limit [CI], 1.11-2.06 and aOR, 1.97; 95% CI, 1.19-3.26, respectively). Tertiary amines were associated with hypoplastic left heart syndrome (aOR, 1.50; 95% CI, 1.10-2.04) and single ventricle (aOR, 1.61; 95% CI, 1.06-2.45). These two malformations were also significantly associated with amide drugs. For several malformations, the strongest associations with nitrosatable drug use occurred among mothers with the highest estimated dietary nitrite intake, especially for secondary amines and atrioventricular septal defects (highest tertile of nitrite, aOR, 3.30; 95% CI, 1.44-7.58). CONCLUSION: Prenatal exposure to nitrosatable drugs may be associated with several congenital malformations, especially with higher nitrite intake. The possible interaction between nitrosatable drugs and dietary nitrite on risk of congenital malformations warrants further attention.

Dieting to lose weight and occurrence of neural tube defects in offspring of Mexican-American women.

Lowered maternal weight gain and reduction in early pregnancy have been associated with risk of neural tube defects (NTDs) in offspring. We examined the association of self-reported maternal dieting behaviors on the occurrence of NTDs. We conducted a population based case-control study among Mexican-American women who were residents of the 14 Texas counties bordering Mexico. Case women had an NTD-affected pregnancy identified at birth or prenatally and had deliveries during the years 1995-2000. Control women were those who delivered live born infants without an apparent congenital malformation, randomly selected and frequency-matched to cases by year and facility. One hundred eighty-four case women and 225 control women were asked in person about the use of nutritional supplements, dieting to lose weight, and type of weight reduction supplements used during the 3 months before conception. Women who reported being on a diet to lose weight during the 3 months before conception had an NTD odds ratio (OR) of 1.9 (95% confidence interval (CI) = 1.1, 3.3) compared with those not reporting being on a diet. Neither consuming vitamin drinks (OR = 1.2) nor using diet pills (OR = 1.6) during the 3 months before conception had ORs that were different from the null, when compared to women not reporting those behaviors. The risk effect for dieting did not differ markedly among normal or underweight (OR = 2.0, 95% CI = 0.7, 5.6), overweight (OR = 1.9, 95% CI = 0.7, 5.0), or obese women (OR = 1.5, 95% CI = 0.6, 4.0). No effect was seen among dieting women who were consuming at least 1.0 mg/day of folate (OR = 1.1, CI = 0.3, 4.5). Maternal dieting prior to conception may increase the risk of NTDs in offspring.

Nitrosatable drug exposure during early pregnancy and neural tube defects in offspring: National Birth Defects Prevention Study.

Nitrosatable drugs, such as secondary or tertiary amines and amides, form N-nitroso compounds in the presence of nitrite. Various N-nitroso compounds have been associated with neural tube defects in animal models. Using data from the National Birth Defects Prevention Study, the authors examined nitrosatable drug exposure 1 month before and 1 month after conception in 1,223 case mothers with neural tube defect-affected pregnancies and 6,807 control mothers who delivered babies without major congenital anomalies from 1997 to 2005. Nitrite intakes were estimated from mothers' responses to a food frequency questionnaire. After adjustment for maternal race/ethnicity, educational level, and folic acid supplementation, case women were more likely than were control women to have taken tertiary amines (odds ratio = 1.60, 95% confidence interval (CI): 1.31, 1.95). This association was strongest with anencephalic births (odds ratio = 1.96, 95% CI: 1.40, 2.73); odds ratios associated with tertiary amines from the lowest tertile of nitrite intake to the highest tertile were 1.16 (95% CI: 0.59, 2.29), 2.19 (95% CI: 1.25, 3.86), and 2.51 (95% CI: 1.45, 4.37), respectively. Odds ratios for anencephaly with nitrosatable drug exposure were reduced among women who also took daily vitamin supplements that contained vitamin C. Prenatal exposure to nitrosatable drugs may increase the risk of neural tube defects, especially in conjunction with a mother's higher dietary intake of nitrites, but vitamin C might modulate this association.

Residential proximity to environmental hazards and adverse health outcomes.

How living near environmental hazards contributes to poorer health and disproportionate health outcomes is an ongoing concern. We conducted a substantive review and critique of the literature regarding residential proximity to environmental hazards and adverse pregnancy outcomes, childhood cancer, cardiovascular and respiratory illnesses, end-stage renal disease, and diabetes. Several studies have found that living near hazardous wastes sites, industrial sites, cropland with pesticide applications, highly trafficked roads, nuclear power plants, and gas stations or repair shops is related to an increased risk of adverse health outcomes. Government agencies should consider these findings in establishing rules and permitting and enforcement procedures to reduce pollution from environmentally burdensome facilities and land uses.

Disproportionate proximity to environmental health hazards: methods, models, and measurement.

We sought to provide a historical overview of methods, models, and data used in the environmental justice (EJ) research literature to measure proximity to environmental hazards and potential exposure to their adverse health effects. We explored how the assessment of disproportionate proximity and exposure has evolved from comparing the prevalence of minority or low-income residents in geographic entities hosting pollution sources and discrete buffer zones to more refined techniques that use continuous distances, pollutant fate-and-transport models, and estimates of health risk from toxic exposure. We also reviewed analytical techniques used to determine the characteristics of people residing in areas potentially exposed to environmental hazards and emerging geostatistical techniques that are more appropriate for EJ analysis than conventional statistical methods. We concluded by providing several recommendations regarding future research and data needs for EJ assessment that would lead to more reliable results and policy solutions.

Maternal smoking, passive tobacco smoke, and neural tube defects.

BACKGROUND: Although cigarette smoke is a well-established toxin and harmful to the developing embryo, the evidence for an independent effect on the occurrence of neural tube defects (NTDs) is mixed. In this study, we examined the relation between NTDs and maternal exposures to cigarette smoke, including passive smoke exposure. METHODS: We used cases and controls from the large, multistate, population-based National Birth Defects Prevention Study. A total of 1041 NTD cases and 5862 live birth controls, delivered during 1997 to 2004, were available for analyses. Mothers were interviewed by telephone between 6 weeks and 24 months after delivery. Participation rates were 71% for NTD case mothers and 69% for control mothers. RESULTS: Compared with nonsmokers (and also not exposed to passive cigarette smoke), mothers exposed only to passive smoke had an increased NTD odds ratio (OR, 1.7; 95% confidence interval [CI], 1.4-2.0), adjusted for race-ethnicity, and study center. There was no increased OR for mothers who actively smoked 24 or fewer cigarettes per day. Mothers who smoked 25 or more cigarettes per day had an elevated OR (OR, 1.6; 95% CI, 0.9-3.0), but the OR adjusted for race-ethnicity, and center was compatible with the null. CONCLUSION: Results suggest that maternal exposure to passive smoke is associated with NTDs. Women who plan on becoming pregnant should minimize their exposure to passive smoke and refrain from smoking.

Prevalence and patterns of nitrosatable drug use among U.S. women during early pregnancy.

BACKGROUND: Experimental evidence indicates that certain drugs, that are secondary or tertiary amines or amides, form N-nitroso compounds in the presence of nitrite in an acidic environment. Nitrosatable drugs have been associated with birth defects in a few epidemiologic studies. This study describes the prevalence and patterns of nitrosatable drug use among U.S. women during early pregnancy and examines maternal factors associated with such use. METHODS: Data were analyzed from the National Birth Defects Prevention Study and included 6807 mothers who gave birth to babies without major congenital malformations during 1997 to 2005. Information was collected by telephone interview about medication use, demographic factors, and maternal health. Drugs taken during the first trimester were classified according to nitrosatability, amine and amide functional groups, and primary indication of use. RESULTS: Approximately 24% of the women took one or more nitrosatable drugs during the first trimester, including 12.4%, 12.2%, and 7.6% who respectively took secondary amines, tertiary amines, or amides. Five of the ten most commonly taken drugs were available over the counter. Women who were non-Hispanic white (29.5%), with 1 year or more college education (27.3%) or 40 years or older (28.8%) had the highest prevalence of use. Supplemental vitamin C, an inhibitor of nitrosation, was not taken by 41.6% and 19.3% of nitrosatable drug users during the first and second months of pregnancy, respectively. CONCLUSIONS: In this U.S. population, ingestion of drugs classified as nitrosatable was common during the first trimester of pregnancy, especially among non-Hispanic white, more educated, and older mothers.

Dietary methionine intake and neural tube defects in Mexican-American women.

BACKGROUND: Nutrients other than maternal folic acid are also thought to play a role in preventing neural tube defects (NTDs). Evidence suggests that methionine interacts with folic acid and vitamin B(12) in the methylation of contractile proteins involved in closing the neural folds. The role of dietary intake of methionine in NTD risk has not been specifically studied among Mexican Americans, a population with one of the highest prevalences of NTDs in the United States. METHODS: We conducted a case-control study of 184 Mexican American women with NTD-affected pregnancies (case women) and 225 women with normal offspring (control women) who resided along the Texas-Mexico border. The average daily intakes of methionine were calculated from periconceptional food frequency questionnaire data. Women were categorized according to quartiles of daily methionine intake, based on the control mothers' distribution, and the risk for an NTD-affected pregnancy was calculated using the lowest quartile of intake as the referent. RESULTS: With adjustment for income, body mass index, hyperinsulinemia, and diarrhea, the odds ratios for increasing quartile of methionine intake were: 0.95 (95% confidence interval [CI], 0.48,1.90), 0.92 (95% CI, 0.46,1.84), and 0.66 (95% CI, 0.30,1.45). Some evidence of interaction between dietary methionine and serum vitamin B(12) was noted particularly at higher levels of both components. CONCLUSIONS: This study was limited by a small sample size but examined this association in an exclusively Hispanic population. Results were suggestive of a potential protective effect for NTDs with increasing maternal dietary methionine intake.

Maternal characteristics associated with the dietary intake of nitrates, nitrites, and nitrosamines in women of child-bearing age: a cross-sectional study.

BACKGROUND: Multiple N-nitroso compounds have been observed in animal studies to be both mutagenic and teratogenic. Human exposure to N-nitroso compounds and their precursors, nitrates and nitrites, can occur through exogenous sources, such as diet, drinking water, occupation, or environmental exposures, and through endogenous exposures resulting from the formation of N-nitroso compounds in the body. Very little information is available on intake of nitrates, nitrites, and nitrosamines and factors related to increased consumption of these compounds. METHODS: Using survey and dietary intake information from control women (with deliveries of live births without major congenital malformations during 1997-2004) who participated in the National Birth Defects Prevention Study (NBDPS), we examined the relation between various maternal characteristics and intake of nitrates, nitrites, and nitrosamines from dietary sources. Estimated intake of these compounds was obtained from the Willet Food Frequency Questionnaire as adapted for the NBDPS. Multinomial logistic regression models were used to estimate odds ratios and 95% confidence intervals for the consumption of these compounds by self-reported race/ethnicity and other maternal characteristics. RESULTS: Median intake per day for nitrates, nitrites, total nitrites (nitrites + 5% nitrates), and nitrosamines was estimated at 40.48 mg, 1.53 mg, 3.69 mg, and 0.472 microg respectively. With the lowest quartile of intake as the referent category and controlling for daily caloric intake, factors predicting intake of these compounds included maternal race/ethnicity, education, body mass index, household income, area of residence, folate intake, and percent of daily calories from dietary fat. Non-Hispanic White participants were less likely to consume nitrates, nitrites, and total nitrites per day, but more likely to consume dietary nitrosamines than other participants that participated in the NBDPS. Primary food sources of these compounds also varied by maternal race/ethnicity. CONCLUSIONS: Results of this study indicate that intake of nitrates, nitrites, and nitrosamines vary considerably by race/ethnicity, education, body mass index, and other characteristics. Further research is needed regarding how consumption of foods high in nitrosamines and N-nitroso precursors might relate to risk of adverse pregnancy outcomes and chronic diseases.

Maternal serum homocysteine and risk for neural tube defects in a Texas-Mexico border population.

BACKGROUND: To better understand the neural tube defect (NTD) causal pathway, the authors measured homocysteine, an indicator of tissue micronutrient deficiencies. The authors examined independent and joint associations of serum homocysteine, B12, and folate and red blood cell (RBC) folate with NTD-affected pregnancies. METHODS: Case women in this population-based study had NTD-affected pregnancies and resided and delivered in one of the 14 Texas-Mexico border counties from 1995 through 2000. Control women were study area residents delivering normal live births during the same period. The authors measured homocysteine levels using tandem mass spectroscopy; competitive binding was used for other biomarkers. RESULTS: Homocysteine testing was done on 103 cases and 139 controls. Odds ratios (ORs) were increased in all upper homocysteine quintiles compared to the lowest quintile (1.7, 1.3, 2.8, 2.4). Women with high homocysteine values had increased ORs regardless of high versus low levels for B12 (OR = 3.5, 4.8, respectively) or RBC folate (OR = 2.9, 3.5, respectively). CONCLUSIONS: High serum homocysteine levels are associated with NTD-affected pregnancies. Moreover, high homocysteine levels have a detrimental effect on NTD-risk even when serum B12 or RBC folate levels are high. Excess homocysteine might play an independent role in the development of NTDs.

The prevalence and predictors of anencephaly and spina bifida in Texas.

Texas shares a 1255-mile border with Mexico and encompasses a variety of ecosystems, industries and other potential environmental exposures. The Texas Birth Defects Registry is an active surveillance system which covers all pregnancy outcomes (livebirths, fetal deaths and elective pregnancy terminations). This study describes the occurrence and the predictors of neural tube defects (anencephaly and spina bifida) in Texas between 1999 and 2003. Birth prevalence, crude and adjusted prevalence ratios and 95% confidence intervals were calculated using Poisson regression, for each defect, by fetal/infant sex, delivery year and maternal sociodemographic characteristics. Among approximately 1.8 million livebirths, a total of 1157 neural tube defects cases were ascertained by the Registry, resulting in an overall prevalence of 6.33 cases per 10 000 livebirths. The prevalences of anencephaly and spina bifida were 2.81 and 3.52 per 10 000 livebirths respectively. Prevalences of both defects were highest in Hispanics, among mothers living along the border with Mexico, among women of higher parity and among mothers who were 40+ years of age. In addition, the prevalence of each defect was higher among women with no record of prenatal care and among women with less than 7 years of education. Hispanic ethnicity was an important predictor for anencephaly, along with sex, maternal age, parity and border residence. However, only border residence and delivery year were significant predictors for spina bifida.

Maternal residential proximity to waste sites and industrial facilities and conotruncal heart defects in offspring.

Most studies of the relationship between maternal residential proximity to sources of environmental pollution and congenital cardiovascular malformations have combined heart defects into one group or broad subgroups. The current case-control study examined whether risk of conotruncal heart defects, including subsets of specific defects, was associated with maternal residential proximity to hazardous waste sites and industrial facilities with recorded air emissions. Texas Birth Defects Registry cases were linked to their birth or fetal death certificate. Controls without birth defects were randomly selected from birth certificates. Distances from maternal addresses at delivery to National Priority List (NPL) waste sites, state superfund waste sites, and Toxic Release Inventory (TRI) facilities were determined for 1244 cases (89.5% of those eligible) and 4368 controls (88.0%). Living within 1 mile of a hazardous waste site was not associated with risk of conotruncal heart defects [adjusted odds ratio (aOR) = 0.83, 95% confidence interval (CI) = 0.54, 1.27]. This was true whether looking at most types of defects or waste sites. Only truncus arteriosus showed statistically elevated ORs with any waste site (crude OR: 2.80, 95% CI 1.19, 6.54) and with NPL sites (crude OR: 4.63, 95% CI 1.18, 13.15; aOR 4.99, 95% CI 1.26, 14.51), but the latter was based on only four exposed cases. There was minimal association between conotruncal heart defects and proximity to TRI facilities (aOR = 1.10, 95% CI = 0.91, 1.33). Stratification by maternal age or race/ethnic group made little difference in effect estimates for waste sites or industrial facilities. In this study population, maternal residential proximity to waste sites or industries with reported air emissions was not associated with conotruncal heart defects or its subtypes in offspring, with the exception of truncus arteriosus.