Periconceptional glycaemic load and intake of sugars and their association with neural tube defects in offspring

In a California population, we previously observed increased neural tube defect (NTD) risks associated with maternal intakes of periconceptional diets predicting higher glycaemic responses and higher sucrose. Our objective here was to replicate these results in a larger study of multiple regions within the United States. This population‐based case–control study included deliveries from 1997 to 2003 from the National Birth Defects Prevention Study. NTD cases were infants or fetuses born with spina bifida or anencephaly. Infants without malformations were eligible as controls. Interview participation was 71% among case mothers and 68% among control mothers. There were 720 NTD case and 4699 control mothers with completed interviews included in analyses. Diet was assessed using a 58‐item food frequency questionnaire focusing on the year before conception, whereas cereals, beverages and supplement use was assessed periconceptionally. We found no increased risks of NTD‐affected pregnancies with increased intakes (adjusted for kcal/day) of sucrose, glucose, fructose or with maternal diets with a higher glycaemic load. The reasons for current findings to be inconsistent with previous findings are unknown.     

Physical Activity and Risk of Neural Tube Defects

Objective: Owing to its association with known risk factors for neural tube defects (NTDs) and its impact on physiologic processes relevant to fetal development, physical activity was identified as a potential risk factor for NTD-affected pregnancy. Methods: Using data from a population-based case-control study of deliveries occurring in California from 1989 to 1991, we estimated the potential risk of having an NTD-affected pregnancy associated with variation in maternal physical activity. In-person interviews were conducted with 538 (88% of eligible) mothers of NTD cases and with mothers of 539 (88%) nonmalformed controls on average 5 months from the term delivery date. An index reflecting reported frequency and exertion level for six activity groups (e.g., jogging and running) was used to summarize each woman's physical activity level in the periconceptional period. Results: Unadjusted analyses indicated that compared to women considered inactive by this index, physically active women had 30–50% lower risk for NTD-affected pregnancies. After adjustment for several potential confounders and an evaluation of potential effect modification, results suggested that the association was restricted to women who did not take multivitamin/mineral supplements during the periconceptional period. Excluding mothers with reported medical problems did not substantially alter findings. Conclusions: This study suggests that the benefits of physical activity may extend to reduction of NTD risk among certain subgroups of women.     

Periconceptional nutrient intake and risk for neural tube defect-affected pregnancies.

We investigated whether intakes of nutrients, including folate, by women in the periconceptional period were associated with risks of neural tube defect (NTD)-affected pregnancies. Data were part of a case-control study of fetuses and infants with NTDs among 1989-1991 California births. We conducted interviews with mothers of 409 NTD cases and 420 nonmal-formed controls. Nutrient intake for the 3 months before conception was derived from food frequency questionnaires and from questions to mothers about vitamin/mineral supplement use. We computed NTD risk for each nutrient controlling for the influence of all other studied nutrients and for maternal education, race/ethnicity, height, and prepregnancy weight. Most single nutrients reduced NTD risks when intakes were considered in quartiles and unadjusted for other nutrients. Some of the same nutrients, however, did not provide similar interpretations when we adjusted for other nutrients. Adjusted analyses revealed decreased NTD risks with increased intakes of methionine, lutein, magnesium, zinc, and thiamin for women who did not use vitamin supplements periconceptionally. We observed decreased NTD risks associated with increased intakes of linoleic acid, cysteine, calcium, and zinc for women who used supplements. We also observed increased NTD risks with increased intakes of oleic acid. For users as well as nonusers of vitamin supplements, we observed reduced risks with increased intakes of grains and dairy products. Chance was a likely alternative explanation for many of the observed risk patterns.     

Exposure to fumonisins and the occurrence of neural tube defects along the Texas-Mexico border

Along the Texas-Mexico border, the prevalence of neural tube defects (NTDs) among Mexican-American women doubled during 1990-1991. The human outbreak began during the same crop year as epizootics attributed to exposure to fumonisin, a mycotoxin that often contaminates corn. Because Mexican Americans in Texas consume large quantities of corn, primarily in the form of tortillas, they may be exposed to high levels of fumonisins. We examined whether or not maternal exposure to fumonisins increases the risk of NTDs in offspring using a population-based case-control study. We estimated fumonisin exposure from a postpartum sphinganine:sphingosine (sa:so) ratio, a biomarker for fumonisin exposure measured in maternal serum, and from maternal recall of periconceptional corn tortilla intake. After adjusting for confounders, moderate (301-400) compared with low (< or = 100) consumption of tortillas during the first trimester was associated with increased odds ratios (ORs) of having an NTD-affected pregnancy (OR = 2.4; 95% confidence interval, 1.1-5.3). No increased risks were observed at intakes higher than 400 tortillas (OR = 0.8 for 401-800, OR = 1.0 for > 800). Based on the postpartum sa:so ratio, increasing levels of fumonisin exposure were associated with increasing ORs for NTD occurrences, except for the highest exposure category (sa:so > 0.35). Our findings suggest that fumonisin exposure increases the risk of NTD, proportionate to dose, up to a threshold level, at which point fetal death may be more likely to occur. These results also call for population studies that can more directly measure individual fumonisin intakes and assess effects on the developing embryo.     

Dietary methionine is involved in the etiology of neural tube defect-affected pregnancies in humans

Research has provided evidence of the role of multivitamin supplementation in the prevention of neural tube defects (NTD). Failure of the neural tube to close is one of the most frequent and severe human developmental defects. The etiology of NTD is complex, encompassing genetic, dietary and environmental factors. The purpose of this study was to explore the relationship between maternal dietary intake of methionine and the risk of having a NTD-affected pregnancy. We hypothesized that women with high maternal dietary methionine intake were at a decreased risk for a NTD. Combinations of methionine, folate and vitamin B-12 intakes and NTD risk were also examined. Data from a 5-y, population-based, case-control study of 170 NTD-affected pregnancies and 269 controls were provided by the South Carolina NTD Surveillance, Prevention, and Research Project. There was a 30-55% lower NTD risk among women whose average daily dietary intake of methionine was greater than the lowest quartile of intake (>1580 mg/d). The odds ratios associated with the three quartiles of methionine intake > 1580 mg/d after adjusting for energy, race and body mass index were 0.72 (P < 0.07), 0.68 (P < 0.07) and 0.45 (P < 0.06), respectively. These findings indicate that a reduction in the risk of having a NTD-affected pregnancy is associated with maternal dietary intake of methionine (3 mo pre- to 3 mo postconception). This finding is consistent with the hypothesis that methionine plays a role in the etiology of NTD and suggests the need for further research in the area of maternal diet and pregnancy.     

Periconceptional dietary intake of choline and betaine and neural tube defects in offspring

Periconceptional intake of folic acid prevents some neural tube defects (NTDs). Other nutrients may also contribute to NTD etiologies; a likely candidate is choline. Similar to folic acid, choline is involved in one-carbon metabolism for methylation of homocysteine to methionine. The authors investigated whether maternal periconceptional dietary intakes of choline and its metabolite betaine influence NTD risk. Data were derived from a case-control study of fetuses and infants with NTDs among 1989-1991 California births. In-person interviews were conducted with mothers of 424 NTD cases and with mothers of 440 nonmalformed controls. A standard 100-item food frequency questionnaire was used to assess nutrient intake. Dietary intakes of choline were associated with reduced NTD risks. Controlling for intake of supplemental folic acid, dietary folate, dietary methionine, and other covariates did not substantially influence risk estimates for choline. NTD risk estimates were lowest for women whose diets were rich in choline, betaine, and methionine. That is, for women whose intake was above the 75th percentile compared with below the 25th percentile for all three nutrients, the odds ratio was 0.17 (95% confidence interval: 0.04, 0.76). Study findings for dietary components other than folic acid offer additional clues about the complex etiologies of NTDs.     

Maternal height and prepregnancy body mass index as risk factors for selected congenital anomalies

Previous studies have observed an increased risk of approximately twofold or more for neural tube defects (NTD) associated with maternal obesity before pregnancy based on a body mass index (BMI) of > 29 kg/m2. No additional maternal factor appeared substantially to influence this association. Here, we explore further the association between BMI and NTD risk by considering the separate contributions of maternal prepregnant BMI and height. We also explore whether selected congenital anomalies, in addition to NTDs, were associated with maternal height or prepregnant BMI. Data were derived from two California population-based case-control studies. One study comprised 538 NTD cases and 539 non-malformed control infants. The other study included an additional 265 NTD cases, as well as 207 conotruncal cases, 165 limb anomaly cases, 662 orofacial cleft cases and 734 non-malformed controls. Maternal interviews in both studies elicited information on maternal height and prepregnant weight. Anomaly risk was described using additive linear logistic regression models. Results revealed increasing NTD risk with increasing maternal prepregnant BMI, controlling for maternal height. These patterns were observed overall as well as for most race/ethnic groups. Increasing NTD risk for decreasing height controlling for maternal BMI was also observed in one NTD study, but was not as evident in the other. Elevated risks for increasing maternal BMI and decreasing maternal height were not observed consistently for the other studied anomalies. The mechanisms underlying the association between maternal weight, or possibly maternal height, and NTD-affected pregnancy risk are unknown. Exploration of other data sets will be needed to determine whether similar patterns of NTD risk or lack of risk for other anomalies are associated with the two maternal anthropometric variables, height and prepregnant weight.     

Dietary glycemic load, added sugars, and carbohydrates as risk factors for pancreatic cancer: the Multiethnic Cohort Study

BACKGROUND: Because elevated blood glucose concentrations have been shown to be associated with greater risk of pancreatic cancer, a high dietary glycemic load, which is based on an empirical measure of blood glucose response after food consumption, has been hypothesized as a pancreatic cancer risk factor. However, results so far are scarce and inconsistent. OBJECTIVE: We analyzed data for 162 150 participants in the Hawaii-Los Angeles Multiethnic Cohort Study to investigate associations between glycemic load, dietary carbohydrates, sucrose, fructose, total sugars, and added sugars and the risk of pancreatic cancer. DESIGN: Dietary intake was assessed at baseline by using a quantitative food-frequency questionnaire. During 8 y of follow-up, 434 incident pancreatic cancer cases occurred. RESULTS: Glycemic load and added sugars were not significantly associated with pancreatic cancer risk. The risk increased with higher intakes of total sugars, fructose, and sucrose, and the association with fructose was significant when the highest and lowest quartiles were compared (relative risk: 1.35; 95% CI: 1.02, 1.80; P for trend = 0.046). A significant association was found with fruit and juices intake (1.37; 1.02, 1.84; P for trend = 0.04) but not with soda intake. Statistical evidence of a significant interaction with body mass index was present only for sucrose intake (P = 0.04). A comparison of the highest and lowest quartiles of sucrose intake in overweight or obese participants gave a relative risk of 1.46 (0.95-2.25; P for trend = 0.04), but the comparison was not significant in normal-weight participants. CONCLUSIONS: High fructose and sucrose intakes may play a role in pancreatic cancer etiology. Conditions such as overweight or obesity in which a degree of insulin resistance may be present may also be important.     

Lowered weight gain during pregnancy and risk of neural tube defects among offspring

BACKGROUND: Maternal nutritional factors have been implicated in the complex aetiology of neural tube defects (NTD). We investigated whether the amount of weight a woman gained during pregnancy was associated with her risk of delivering an infant with an NTD. METHODS: We conducted a population-based case-control study within the cohort of 708 129 live births and fetal deaths occurring in selected California counties in 1989-1991. Face-to-face interviews were conducted with mothers of 538 (88% of eligible) NTD cases (including those electively terminated, stillborn, or liveborn) and with mothers of 539 (88%) non-malformed liveborn controls within an average of 5 months from the term delivery date. Respondent-reported weight gain during pregnancy (kg) was analysed. Risks of infants having NTD were estimated among women who gained <10 kg compared to those who gained > or =10 kg during > or =38 week gestations. RESULTS: Compared to women who gained > or =10 kg, an increased risk for NTD offspring was observed among women who gained <10 kg (odds ratio [OR] = 3.2, 95% CI : 2.3-4.6). The OR was 5.0 (95% CI : 2.6-9.7) among those women who gained <5 kg during pregnancy. The increased risk was not attributable to maternal non-use of a multivitamin containing folic acid, diabetes, NTD-pregnancy history, age, race/ethnicity, education, gravidity, alcohol use, cigarette use, prepregnant obesity, low socioeconomic status, dieting, nausea, nor to lower dietary intakes of folate, zinc, energy, protein, fat, carbohydrates, and methionine. An increased risk was observed even after simultaneous adjustment for most of these factors (OR = 2.2, 95% CI : 1.2-3.8). The risk associated with gaining <10 kg was greater for anencephaly, but still elevated for spina bifida. CONCLUSIONS: We did not have information on weight gain during early pregnancy. Because weight gain during the relevant embryological period for NTD (first month post-conception) is relatively small and often variable, it seems less likely that elevated NTD risks indicate a causal association between lowered weight gain throughout pregnancy and abnormal development of the neural tube. It seems more likely that lowered weight gain is a consequence of carrying an NTD-affected fetus. However, what this consequence is and why risk was substantially larger for anencephaly is unknown.     

Methionine in the multifactorial etiology of neural tube defect affected pregnancies

PURPOSE: Research in the last 40 years has provided evidence of the role of dietary nutrients in the development of NTDs. Failure of the neural tube to close is one of the most frequent and severe fetal developmental defects. The etiology of NTDs is complex encompassing genetic, dietary, and environmental factors. With regard to diet, it appears that in humans, a combination of low levels of methionine, folate, and Vitamin B(12) may lead to the occurrence of NTDs. The purpose of this study was to explore the relationship between maternal dietary intake of methionine and the risk of having a NTD affected pregnancy.METHODS: It was hypothesized that women with high maternal dietary methionine intake were at a decreased risk for NTDs. Combinations of methionine and folate without supplements, methionine and folate with supplements, and methionine and Vitamin B(12) and NTD risk were also examined. Data from a case-control study of 170 NTD-affected pregnancies and 269 controls were provided by a CDC sponsored NTD Surveillance, Prevention, and Research Project.RESULTS: There was an approximately 30-55% reduction in NTD risk among women whose average daily dietary intake of methionine was greater than the lowest quartile of intake (>1580 mg/day). The odds ratios (95% CI) associated with the 3 quartiles of methionine intake greater than 1580 mg/day after adjusting for Kcal, race, and BMI were 0.72 (0.4030-1.288), 0.68 (0.3390-1.347), and 0.45 (0.1830-1.088).CONCLUSIONS: These findings indicate a reduction in the risk of having a NTD affected pregnancy is associated with maternal periconceptional dietary intake of methionine.     

The dietary glycemic index during pregnancy: influence on infant birth weight, fetal growth, and biomarkers of carbohydrate metabolism

During pregnancy, lower levels of maternal glucose before and during a glucose load have been associated with reduced infant birth weight and an increased risk of small-for-gestational-age births. A lower incremental area under the glucose response curve defines a low glycemic diet. Thus, during pregnancy the maternal diet, as measured by the glycemic index, may influence fetal growth and infant birth weight. A total of 1,082 gravidas who enrolled in the Camden Study between August 1996 and October 2002 were followed prospectively during pregnancy. The dietary glycemic index was computed from three 24-hour recalls in the course of pregnancy. Samples for plasma glucose and for glycosylated hemoglobin were obtained at 24-28 weeks' gestation. The glycemic index was positively and significantly related to maternal glycosylated hemoglobin and plasma glucose. There were as well significant linear trends for dietary fat intake to decrease and for intakes of carbohydrate, sucrose, fiber, and folate to increase as the glycemic index declined. Gravidas with a low dietary glycemic index had reduced infant birth weight and approximately a twofold increased risk of a small-for-gestational-age birth. Consistent with data on maternal plasma glucose, data in this study show that the type of carbohydrate in the diet of urban, low-income women influences fetal growth and infant birth weight.     

Periconceptional vitamin use, dietary folate and occurrent neural tube defected pregnancies in a high risk population

PURPOSE: This 5 year (1992-1997) population-based case control study was conducted to determine if supplemental or dietary folate taken during the periconceptional period reduces the risk of occurrent neural tube defect (NTD) affected pregnancies in a high risk population.METHODS: Cases were all NTD pregnancies including elective terminations, fetal deaths and live births in South Carolina. Only isolated, occurrent NTD affected pregnancies were included (N = 179). Controls (N = 288) were randomly selected from each hospital in proportion to the hospital's contribution to the total live births in the state for the previous year. All mothers were interviewed in person using a modified Centers for Disease Control and Prevention Birth Defect Risk Factor Surveillance Mother's Questionnaire and the Harvard Food Frequency Questionnaire.RESULTS: Women who used a vitamin with 0.4 mg or more of folate at least 3 times per week during the 3 months before and 3 months after conception had a lower risk of having an NTD affected pregnancy than women who took no folate supplementation at any time during pregnancy [adjusted odds ratio (AOR) = 0.42; 95% confidence interval (CI) = 0.19-0.94]; women who used a vitamin with 0.4 mg or more of folic acid for less than 3 times per week or in partial months during the 6 month periconceptional period also had a slightly lower risk of having an NTD affected pregnancy relative to women who used no folate supplementation at any time during pregnancy [AOR =.72; 95% CI = 0.41-1.30]. The risk of NTD affected pregnancy was also lower for women who daily consumed foods containing higher levels of folate: AORs were 0.36 (95% CI = 0.18-0.73), 0.72 (95% CI = 0.42-1.22), and 0.61 (95% CI 0.36-1.04) from the highest to lowest quartile of dietary folate which were 0.457-3.12 mg, 0.322-0.457 mg, and 0.236-0.322 mg respectively.CONCLUSIONS: A reduction in occurrent NTD risk associated with folate supplementation and dietary intake was observed.     

Trihalomethane exposures from municipal water supplies and selected congenital malformations

BACKGROUND: Concerns about potential health effects of trihalomethanes (THMs) have prompted investigations on whether infants whose mothers were periconceptionally exposed to drinking water containing THMs are at greater risk of congenital malformations. METHODS: We used two large case-control maternal interview studies that were conducted among California deliveries from 1987 through 1991. One study comprised 538 infants/fetuses with neural tube defects (NTDs) and 539 nonmalformed control infants. The second study included an additional 265 infants with NTDs, 207 infants with conotruncal heart defects, 409 infants with orofacial clefts, and 481 control infants. Expert personnel from municipal water companies estimated THM levels for a particular residence and specific periconceptional time period using quarterly monitoring measurements. Estimates were also made for four individual THM levels and for the total THM level. RESULTS: NTD risk in the first study was inversely associated with total THM exposure. Although the second study did not show the same inverse relationship for NTDs, there were no positive associations of NTDs or the other malformations with total THM as estimated from continuous models. Elevated risks were observed for the lowest category of exposure (1-24 ppb), but risks were either not substantially elevated or were imprecise for higher exposure levels. Thus no evidence was observed for an exposure-response relation. CONCLUSIONS: Our results do not provide a clear pattern of association between THM exposure and risks of specific congenital malformations. Imprecise exposure measures coupled with a lack of information about other possible sources of THM exposure may have caused associations to be underestimated.     

Maternal stress, social support, and risk of neural tube defects among Mexican Americans

BACKGROUND: Studies suggest that maternal psychologic stress can increase the risk of congenital malformations, including neural tube defects (NTDs). We examined whether maternal stress and lack of social support contribute to NTD risk in a population living along the Texas-Mexico border. METHODS: Case mothers (N = 184) were Mexican-American women with NTD-affected pregnancies who delivered during 1995 to 2000 in one of the 14 Texas counties bordering on Mexico. Control mothers (N = 225) were randomly selected from Mexican-American women residing in the same area and delivering normal live births. We measured maternal stress by tallying the number of job changes, residential moves, and major injuries occurring during the year before conception. Social support was measured using social integration and perceived emotional support scales. RESULTS: Mothers who experienced one or more stressful life events during the year before conception had increased risks for NTDs (odds ratio [OR] = 2.9; 95% confidence interval [CI] = 1.8-4.7) compared with mothers experiencing no events. Mothers who scored low on emotional support had an elevated risk compared with those who scored high (OR = 4.6; CI = 2.2-9.7). Social support measures, such as network size and satisfaction, group interactions, and church attendance, were unrelated to NTD risk. The estimated effects were not modified or confounded by age, education, country of birth, income, obesity, vitamin supplements, dietary folate, cigarette smoking, or alcohol consumption. CONCLUSION: In this Mexican-American population, the occurrence of stressful life events was associated with NTD risk. These findings suggest that stress may exacerbate risk in populations with poor nutritional status and meager economic resources.     

Dietary nitrites and nitrates, nitrosatable drugs, and neural tube defects

BACKGROUND: Amine-containing (nitrosatable) drugs can react with nitrite to form N-nitroso compounds, some of which are teratogenic. Data are lacking on whether dietary intake of nitrates and nitrites modifies the association between maternal nitrosatable drug exposure and neural tube defects (NTDs) in offspring. METHODS: We examined nitrosatable drug exposure and NTD-affected pregnancies in relation to dietary nitrite and total nitrite intake in a case-control study of Mexican American women. We interviewed 184 women with NTD-affected pregnancies and 225 women with normal live births, including questions on periconceptional drug exposures and dietary intake. For 110 study participants, nitrate was also measured in the usual source of drinking water. RESULTS: Women who reported taking drugs classified as nitrosatable were 2.7 times more likely to have an NTD-affected pregnancy than women without this exposure (95% confidence interval [CI] = 1.4-5.3). The effect of nitrosatable drugs was observed only in women with higher intakes of dietary nitrite and total nitrite (dietary nitrite + 5% dietary nitrate). Women within the highest tertile (greater than 10.5 mg/day) of total nitrite were 7.5 times more likely to have an NTD-affected pregnancy if they took nitrosatable drugs (95% CI = 1.8-45.4). The association between nitrosatable drug exposure and NTDs was also stronger in women whose water nitrate levels were higher. CONCLUSIONS: Findings suggest that effects of nitrosatable drug exposure on risk for neural tube defects in offspring could depend on the amounts of dietary nitrite and total nitrite intake.     

Neural tube defects among Mexican Americans living on the US-Mexico border: effects of folic acid and dietary folate

Populations of Mexican descent have high occurrences of neural tube defects (NTDs). A recent study suggested that folic acid supplements may not protect these populations from NTDs. In a case-control study, the authors investigated the role of folic acid and dietary folate intake in NTD risk among Mexican Americans living along the Texas-Mexico border. From January 1995 to February 1999, 148 Mexican-American women with NTD-affected pregnancies and 158 women with normal live births were interviewed in person about use of vitamin supplements and dietary intakes during a 6-month periconceptional period (from 3 months before conception to 3 months after conception). Daily preconceptional consumption of vitamin supplements containing folic acid was 2.5% in control women and 2.0% in case women (odds ratio = 0.77; 95% confidence interval (CI): 0.19, 3.22). With adjustment for maternal age, education, obesity, and previous stillbirth or miscarriage, the risk estimate was essentially null (odds ratio = 1.12; 95% CI: 0.22, 5.78). Combined folic acid intake from diet and supplements showed only a modest risk reduction for intakes of > or = 1.0 mg per day (adjusted odds ratio = 0.73; 95% CI: 0.31, 1.72). The fact that the primary folic acid exposure was in the form of dietary polyglutamates rather than the more easily absorbed supplemental monoglutamates may explain an apparent decreased effect in this population.     

Glycemic response and health--a systematic review and meta-analysis: relations between dietary glycemic properties and health outcomes

BACKGROUND: Reduction of dietary glycemic response has been proposed as a means of reducing the risk of diabetes and coronary heart disease. The impact of glycemic response on markers of health remains to be elucidated. OBJECTIVE: We assessed the evidence relating the glycemic impact of foods to measures relevant for health maintenance and management of disease. DESIGN: This was a systematic review and synthesis of interventional evidence from literature reported on glycemic index and markers of health through the use of meta-analyses and meta-regression models. RESULTS: Data from 45 relevant publications were found to January 2005. Lower glycemic index (GI) diets reduced both fasting blood glucose and glycated proteins independently of variance in available and unavailable carbohydrate intakes. Elevated unavailable carbohydrate added to improvements in both blood glucose and glycated protein control. These effects were greater in persons with poor fasting blood glucose control. No effects were seen on fasting insulin<100 pmol/L; above this, study numbers were few but consistent with prevention of hyperinsulinemia in some but not all overweight persons. Insulin sensitivity according to a variety of measurement methods was improved by lower GI, higher unavailable carbohydrate interventions in persons with type 2 diabetes, in overweight and obese persons, and in all studies combined. Fasting triacylglycerol in addition to body weight reduction related more to glycemic load than to GI. Glycemic load reduction by >17 g glucose equivalents/d was associated with reduced body weight. CONCLUSIONS: Consumption of reduced glycemic response diets are followed by favorable changes in the health markers examined. The case for the use of such diets looks compelling. Unavailable carbohydrate intake is equally important.     

Maternal nutrient intakes and risk of orofacial clefts

BACKGROUND: Information about nutritional factors as potential risks of orofacial clefts is limited. METHODS: In this population-based case-control study, we investigated whether periconceptional intakes of supplemental folic acid, dietary folate, and several other nutrients were associated with orofacial clefts. We included data on deliveries from 1997 through 2000 in the National Birth Defects Prevention Study. Orofacial cleft cases were infants or fetuses born with cleft palate (CP) or with cleft lip with or without cleft palate (CLP). Infants without malformations were eligible as controls. Interview participation was 71% among case mothers and 68% among control mothers. Interviews were completed for 704 CLP cases, 404 CP cases, and 2594 controls. RESULTS: The odds ratio (OR) for CLP associated with use of vitamin supplements containing folic acid was 0.88 (95% confidence interval = 0.73-1.07) and for CP was 1.09 (0.84-1.40). Adjusting for maternal race/ethnicity, age, and education produced an OR of 1.01 (0.82-1.24) for CLP and 1.02 (0.77-1.34) for CP. We found some evidence for decreased CLP risks (>or=30% reduction in risk) with increasing intakes of total protein, choline, and methionine. Decreased CP risk was associated with increased intake of cysteine. Intakes of only 2 micronutrients, iron and riboflavin, were found to reduce CLP risk when adjusted for other nutrients. CONCLUSION: Our observations contribute to the limited body of evidence suggesting a woman's periconceptional diet may influence clefting risks in her offspring. Our finding of no reduction in clefting risk with periconceptional use of supplements containing folic acid is inconsistent with many previous observations but not all.     

母亲饮食因素与神经管畸形危险性的病例对照研究

目的探讨母亲饮食因素在神经管畸形（NTD）发病中的作用。方法选择山西省出生缺陷高发的平定、昔阳、太谷和泽州4个县，进行以人群为基础的出生缺陷病例对照研究。病例为2003年1月至2005年6月在4个县监测到的363例NTD病例，对照为同期在同地区出生的523名无体表畸形的健康婴儿。结果单因素分析结果表明，与NTD发生有关的饮食因素有食用肉类、蛋奶、豆类、腌菜、发芽土豆、食物烹调习惯、饮用水水源类型、饮啤酒、红酒或米酒和饮茶。在调整妇女文化程度和畸形生育史的基础上，多因素logistic回归分析表明，肉类和豆类为NTD的保护因素，NTD的危险性随着肉类、豆类食用频率的增加逐渐下降，其在人群中的归因危险度（PAR）分别为69．4％和22．0％。食用腌菜为危险因素，NTD危险性随着腌菜食用频率增加而显著增加，具有明显的剂量反应关系，其PAR值为18．5％。此外，饮用河水或池塘水的妇女较饮用井水或自来水者的危险性增高（OR=3．42，95％CI：1．44～8．09），每天饮茶者较不饮或偶尔饮茶妇女的危险性增高（OR=4．65，95％CI：1．41～15．36），但二者PAR值较低，分别为4．7％和2．6％。结论富含叶酸的肉类和豆类对NTD发生具有显著的保护作用。怀孕前后食用腌菜、饮用河水或池塘水以及每天饮茶是NTD的危险因素。     

还原叶酸载体基因多态性与先天性心脏病和唇腭裂关联的研究

目的 检验还原叶酸载体基因(RFC1)A80G多态性与先天性心脏病(CHD)和唇腭裂之间的关联,为寻找CHD和唇腭裂危险因素的遗传易感标志物提供流行病学依据。方法 采用RFLP-PCR方法,对67个CHD患儿家庭、82个唇腭裂患儿家庭和100个正常儿童家庭成员的外周血DNA进行RFC1第80位SNP检测,利用核心家庭标本进行以家庭为基础的关联检验(FBAT),并分析了子代RFC1基因型与母亲孕期前后增补叶酸的相互作用。结果 不增补叶酸的母亲生育CHD儿的危险高于增补叶酸的母亲(OR=2 68,95％CI:1 14-6 41),即母亲孕期未增补叶酸与CHD发生危险的关联有统计学意义(x2=6.213,P=0 013);在FBAT检验中,RFC1 G等位基因与CHD发病危险有统计学关联(Z=2 140,P<0 05),表明RFC1 G等位基因可能是CHD发病的遗传易感基因,未发现唇腭裂与RFC1之间的统计学关联。结论 RFC1 G等位基因可能是CHD发生的遗传易感基因之一,子代RFC1基因GG或GA基因型、母亲孕期叶酸缺乏可能增加CHD的发病危险。