Maternal periconceptional alcohol consumption and risk of orofacial clefts

Using data from the National Birth Defects Prevention Study, the authors investigated the association between maternal reports of periconceptional alcohol consumption and clefting. Cases with a cleft lip, cleft palate, or both and unaffected controls delivered from 1997 through 2002 were ascertained. Interview reports of alcohol consumption were obtained from 1,749 (75.1%) case and 4,094 (68.2%) control mothers. Adjusted odds ratios and 95% confidence intervals were calculated to assess associations. Compared with odds ratios for mothers with no reported consumption, those for mothers who consumed alcohol tended to be near to (cleft lip, cleft lip with cleft palate) or to exceed (cleft palate) unity. The odds ratios associated with binge drinking were elevated but did not demonstrate significantly increased risk for any phenotype; however, the odds ratios differed by the type of alcohol consumed, particularly for cleft palate (distilled spirits > wine > beer). These odds ratios were further increased among mothers with no reported folic acid intake. Although these findings suggest that the association between alcohol consumption and clefting might be most influenced by the type of beverage consumed and folic acid intake, they are preliminary and might reflect chance associations. Such findings need exploration in additional, large studies.     

Maternal smoking and environmental tobacco smoke exposure and the risk of orofacial clefts

BACKGROUND: Smoking during pregnancy has been associated with orofacial clefts in numerous studies. However, most previous studies have not been able to assess the relation between maternal smoking and specific phenotypes (eg, bilateral clefts). METHODS: We examined the association between periconceptional maternal smoking, environmental tobacco smoke (ETS) exposure, and cleft lip with or without cleft palate (CLP) (n = 933) and cleft palate only (CPO) (n = 528) compared with infants with no major birth defects (n = 3390). Infants were born between 1 October 1997 and 31 December 2001, and exposures were ascertained from maternal telephone interviews for the National Birth Defects Prevention Study. We excluded infants who had a first-degree relative with an orofacial cleft. Effect estimates were adjusted for folic acid use, study site, prepregnancy obesity, alcohol use, gravidity, and maternal age, education, and race/ethnicity. RESULTS: Periconceptional smoking was associated with CLP (odds ratio = 1.3; 95% confidence interval = 1.0-1.6), and more strongly associated with bilateral CLP (1.7; 1.2-2.6), with a weaker association observed for CPO. Heavy maternal smoking (25+ cigarettes/day) was associated with CLP (1.8; 1.0-3.2), bilateral CLP (4.2; 1.7-10.3), and CPO with Pierre Robin sequence (2.5; 0.9-7.0). ETS exposure was not associated with CLP or CPO. CONCLUSIONS: This study confirmed the modest association between smoking and orofacial clefts that has been consistently reported, and identified specific phenotypes most strongly affected.     

Maternal smoking, genetic variation of glutathione s-transferases, and risk for orofacial clefts

BACKGROUND: Maternal smoking is a known risk factor for orofacial clefts. We investigated whether risk is greater among offspring who lack the genetic capacity to produce glutathione S-transferase enzymes relevant to detoxification of chemicals in cigarette smoke. METHODS: Using a population-based case-control design, we genotyped 423 California infants with an isolated cleft and 294 nonmalformed controls for null variants of the glutathione S-transferases GSTT1 and GSTM1. RESULTS: If a mother smoked during pregnancy and her fetus was homozygous null for GSTT1, the risk of isolated cleft lip with or without cleft palate was tripled (odds ratio = 2.9; 95% confidence interval = 1.2-7.2). For fetuses who were homozygous null for GSTM1 and whose mothers smoked >/=20 cigarettes per day, we found nearly a 7-fold increased risk (6.8; 0.82-57). Combined absence of GSTM1 and GSTT1 enzymes among the offspring of smoking mothers was associated with a nearly 6-fold increased risk for cleft lip (6.3; 1.3-42). A similar increased risk for cleft palate was associated with absence of GSTM1, but not for absence of GSTT1. CONCLUSIONS: Maternal smoking during pregnancy increases risks for clefts among fetuses lacking enzymes involved in the detoxification of tobacco-derived chemicals.     

Maternal employment status and isolated orofacial clefts in Hungary

AIMS: To study the role of maternal employment status as indicator of socioeconomic status in the origin of isolated orofacial clefts (OFC) and in the use of periconceptional folic acid/multivitamin supplementation. METHODS: 1,975 cases with OFC (1,374 cases with cleft lip +/- palate and 601 cases with posterior cleft palate), 38,151 population controls without any defects and 20,868 patient controls with other isolated defects were compared in the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996. RESULTS: The proportion of professionals and managerials was lower, while the proportion of unskilled workers, housewives and others was higher in the mothers of cases with OFC compared with the population control group. However, the comparison of OFC and patient control groups did not show any difference in the employment status of mothers. A lower level of folic acid supplementation occurred in the professional and skilled worker mothers of cases with OFC compared with the population control group. This difference was confirmed by the comparison of folic acid used by mothers of cases with OFC compared with patient controls. An infrequent multivitamin use was displayed in the studied groups. CONCLUSIONS: The prevalence of OFC at birth shows a slightly lower maternal employment status as indicator of socioeconomic status than in the population control group. The higher level of maternal education does not imply a higher rate of folic acid supplementation in the group of OFC.     

Maternal smoking and the risk of orofacial clefts: Susceptibility with NAT1 and NAT2 polymorphisms

BACKGROUND: Orofacial clefts are etiologically heterogeneous malformations. One probable cause is maternal smoking during pregnancy. The effect of maternal smoking may be modified by genes involved in biotransformation of toxic compounds derived from tobacco. We investigated whether polymorphic variants of fetal acetyl-N-transferases 1 (NAT1) and 2 (NAT2) interact with maternal cigarette smoking during early pregnancy to increase the risk of delivering an infant with an orofacial cleft. METHODS: In a California population-based case-control study, we genotyped 421 infants born with an isolated cleft and 299 nonmal-formed controls for 2 NAT1 and 3 NAT2 single nucleotide polymorphisms RESULTS: Although smoking was independently associated with increased risks for both isolated cleft lip +/- cleft palate and isolated cleft palate, no independent associations were found for NAT1 1088 or 1095 genotypes or for NAT2 acetylator status. However, the infant NAT1 1088 and 1095 polymorphisms were strongly associated with the risk of clefts among smoking mothers; infants with NAT1 1088 genotype AA versus TT (odds ratio [OR] = 3.9; 95% confidence interval = 1.1-17.2) and with NAT1 1095 genotype AA versus CC (OR = 4.2; 1.2-18.0). Infant NAT2 acetylator status did not appreciably affect susceptibility of the fetus to the teratogenic effects of maternal smoking. CONCLUSIONS: Our results suggest that maternal smoking during pregnancy may increase risk for orofacial clefts particularly among smokers whose fetuses have polymorphic variants of NAT1, an enzyme involved in phase II detoxification of tobacco smoke constituents.     

Maternal dietary intake of vitamin A and risk of orofacial clefts: a population-based case-control study in Norway

A population-based case-control study was carried out in Norway between 1996 and 2001. The aim was to evaluate the association between maternal intake of vitamin A from diet and supplements and risk of having a baby with an orofacial cleft. Data on maternal dietary intake were available from 535 cases (188 with cleft palate only and 347 with cleft lip with or without cleft palate) and 693 controls. The adjusted odds ratio for isolated cleft palate only was 0.47 (95% confidence interval: 0.24, 0.94) when comparing the fourth and first quartiles of maternal intake of total vitamin A. In contrast, there was no appreciable association of total vitamin A with isolated cleft lip with or without cleft palate. An intake of vitamin A above the 95th percentile was associated with a lower estimated risk of all isolated clefts compared with the 40th-60th percentile (adjusted odds ratio = 0.48, 95% confidence interval: 0.20, 1.14). Maternal intake of vitamin A is associated with reduced risk of cleft palate only, and there is no evidence of increased risk of clefts among women in our study with the highest 5% of vitamin A intake.     

Periconceptional folates and the prevention of orofacial clefts: role of dietary intakes in France

BACKGROUND: Orofacial clefts are among the most frequent congenital malformations at birth with a prevalence of 1 in 700 births in Europe. The implication of environmental factors in their etiology has been demonstrated. The role of folic acid, or folates, in the prevention of orofacial clefts is still debated although its efficacy has been demonstrated for the prevention of neural tube defects. METHODS: A case-control study was conducted in 7 hospitals in 4 centers in France. Cases (N=240) were children with non-syndromic orofacial cleft referred to one of the study hospitals for initial surgical repair in 1998 and 1999. Controls (N=236) matched for gender, geographic origin, and age were chosen in paediatric departments of the same hospitals. Usual dietary intake of folates was estimated using a food frequency questionnaire submitted to the mother at hospital. During the same interview, data on sociodemographic characteristics, medical and obstetrical history, tobacco and alcohol consumption, and vitamin supplements, were obtained. Odds ratios associated with quintiles of dietary intake of folates were estimated using logistic regression adjusting for known confounders. RESULTS: A significant dose-response relationship between the risk of orofacial clefts and a decrease in the intake of folates from diet was found, stronger for cleft palate without cleft lip. Only few women (<1%) declared having taken vitamin supplements containing folic acid when planning their pregnancy. CONCLUSION: Our study further suggests that folates are useful for the prevention of orofacial clefts during the periconceptual period. In our study, the estimated average daily intake of folates (270 microg/day) was below French national recommendations for the prevention of neural tube defects (400 microg/day). Since those insufficient folate intakes during the periconceptual period are not presently met by vitamin supplementation, the solution may come from the food fortification program proposed and implemented by the National Agency for Food Safety (AFSSA).     

Socio-economic status and risk of conotruncal heart defects and orofacial clefts

Studies of socio-economic status (SES) have figured prominently in research related to a variety of health outcomes, although the question remains as to whether SES contributes to the aetiologies of congenital anomalies. This study examines the association of SES with risks of conotruncal heart defects and orofacial clefts, using interview data from 696 case mothers (86% of eligible) and 734 (78%) control mothers from a population-based case-control study. Socio-economic measures from maternal interview included mother's education and employment. Reported addresses were linked with the US census to characterise six measures of neighbourhood SES (education, poverty, unemployment, occupation, crowding and rental occupancy). Results were adjusted for race-ethnicity, multivitamin/mineral supplement intake, cigarette smoking and binge drinking. Results for individual and neighbourhood measures suggested that low SES was associated with increased risk of d-transposition of the great arteries (dTGA), reduced risk of tetralogy of Fallot (TOF), but was not associated with risk of orofacial clefts. For example, when examining odds ratios (OR) that compared risks among women whose neighbourhoods were in the lowest vs. highest quartile of the census-based SES measures, ORs for five of the six measures were> 1.4 for dTGA, and ORs for all six measures were < 0.7 for TOF. ORs for clefts tended to be closer to 1. This study suggests that SES risks are birth defect specific.     

Maternal alcohol binge-drinking in the first trimester and the risk of orofacial clefts in offspring: a large population-based pooling study

Using individual participant data from six population-based case–control studies, we conducted pooled analyses to examine maternal alcohol consumption and the risk of clefts among >4600 infants with cleft lip only, cleft lip with cleft palate, or cleft palate only and >10,000 unaffected controls. We examined two first-trimester alcohol measures: average number of drinks/sitting and maximum number of drinks/sitting, with five studies contributing to each analysis. Study-specific odds ratios (ORs) were estimated using logistic regression and pooled to generate adjusted summary ORs. Across studies, 0.9–3.2 % of control mothers reported drinking an average of 5+ drinks/sitting, while 1.4–23.5 % reported drinking a maximum of 5+ drinks/sitting. Compared with non-drinkers, mothers who drank an average of 5+ drinks/sitting were more likely to deliver an infant with cleft lip only (pooled OR 1.48; 95 % confidence intervals 1.01, 2.18). The estimate was higher among women who drank at this level 3+ times (pooled OR 1.95; 1.23, 3.11). Ever drinking a maximum of 5+ drinks/sitting and non-binge drinking were not associated with cleft risk. Repeated heavy maternal alcohol consumption was associated with an increased risk of cleft lip only in offspring. There was little evidence of increased risk for other cleft types or alcohol measures.     

Food and nutrient intakes and asthma risk in young adults

BACKGROUND: Some aspects of diet are relatively newly recognized potential risk factors for asthma, but the evidence to date is conflicting. OBJECTIVE: The goal was to determine whether the food and nutrient intakes of adults with asthma differ from those of adults without asthma. DESIGN: This was a community-based, cross-sectional study of 1601 young adults ( +/- SD age: 34.6 +/- 7.1 y) who were initially recruited by random selection from the federal electoral rolls in Melbourne in 1999. Subjects completed a detailed respiratory questionnaire, a validated semiquantitative food-frequency questionnaire, skin-prick testing, and lung function tests, including a methacholine challenge test for bronchial hyperreactivity (BHR). A total of 25 nutrients and 47 food groups were analyzed by using multiple logistic regression with alternate definitions of asthma and atopy as the outcomes. RESULTS: Whole milk appeared to protect against current asthma (odds ratio: 0.66; 95% CI: 0.46, 0.97), doctor-diagnosed asthma (0.73; 0.54, 0.99), BHR (0.68; 0.48, 0.92), and atopy (0.71; 0.54, 0.94). Conversely, soy beverage was associated with an increased risk of current asthma (2.05; 1.19, 3.53), doctor-diagnosed asthma (1.69; 1.04, 2.77), and BHR (1.65; 1.00, 2.71). Apples and pears appeared to protect against current asthma (0.83; 0.71, 0.98), asthma (0.88; 0.78, 1.00), and BHR (0.88; 0.77, 1.00). CONCLUSIONS: The consumption of dairy products, soy beverages, and apples and pears, but not of nutrients per se, was associated with a range of asthma definitions. Dietary modification after diagnosis is one possible explanation for this finding. Intervention studies using whole foods are required to ascertain whether such modifications of food intake could be beneficial in the prevention or amelioration of asthma.     

Parental occupational pesticide exposure and nonsyndromic orofacial clefts

Nonsyndromic orofacial clefts are common birth defects. Reported risks for orofacial clefts associated with parental occupational pesticide exposure are mixed. To examine the role of parental pesticide exposure in orofacial cleft development in offspring, this study compared population-based case-control data for parental occupational exposures to insecticides, herbicides, and fungicides, alone or in combinations, during maternal (1 month before through 3 months after conception) and paternal (3 months before through 3 months after conception) critical exposure periods between orofacial cleft cases and unaffected controls. Multivariable logistic regression was used to estimate odds ratios, adjusted for relevant covariables, and 95% confidence intervals for any (yes, no) and cumulative (none, low [相似文献   

Diet and nutrient intakes and risk of non-Hodgkin's lymphoma in Connecticut women

A population-based case-control study (601 cases and 717 controls) was conducted in 1995-2001 among Connecticut women to evaluate the relation between diet and nutrient intakes and the risk of non-Hodgkin's lymphoma (NHL). When the highest quartile of intake was compared with the lowest, the authors found an increased risk of NHL associated with animal protein (odds ratio = 1.7, 95% confidence interval: 1.2, 2.4) and saturated fat (odds ratio = 1.9, 95% confidence interval: 1.1, 2.3) but a reduced risk for polyunsaturated fat (odds ratio = 0.6, 95% confidence interval: 0.4, 0.9) and no relation for vegetable protein and monounsaturated fat. An increased risk was also observed for higher intakes of retinol, eggs, and dairy products. On the other hand, a reduced risk was found for higher intakes of dietary fiber and for several fruit and vegetable items. Risk of NHL associated with diet and nutrient intakes appeared to vary based on NHL subtype. An association between dietary intake and NHL risk is biologically plausible because diets high in protein and fat may lead to altered immunocompetence, resulting in an increased risk of NHL. The antioxidant or inhibiting nitrosation reaction properties of vegetables and fruits may result in a reduced risk. Further investigation of the role of dietary intakes on the risk of NHL is warranted.     

Incidence of orofacial clefts in the Slovak Republic

Orofacial clefts (OC) are quite common congenital defects. Retrospective active survey collecting clinical data of children with OC examined and operated on in the three main specialized departments of plastic surgery in the Slovak Republic over 16 years (1985-2000) revealed total incidence of 1.61/10(3) live births (LB). 1,849 children suffering from OC were recognised out of 1,147,236 live births. Total incidence (TI) of OC per 1,000 live births was determined by types, gender, regions, districts and seasonal variation. The highest rate, 40.5% of clefts, affected the primary and secondary palate (CLP), more than 32% were of cleft palate type (CP), about 26% cleft lip (CL) and about 1% of associated malformations (AM). Clefts in males (1.71/10(3) LB) were significantly more common than in females (1.50/10(3) LB), sex ratio 1.14:1. Morbidity rates (TI) varies from 1.29/10(3) LB in the east Slovakia to the highest incidence of 1.93/10(3) LB in the middle Slovakia with wide range by district. Comparing data from the study and from the national register, 17% of children with OC were missed. Presented survey assessed risk of OC in Slovakia at the rate 1 newborn with OC per 620 LB compared with notified frequency of 1 OC per 745 LB.     

Maternal nutritional status and the risk for orofacial cleft offspring in humans

Periconceptional folate and folic acid intake prevents orofacial clefts (OFC) in the offspring. It has been suggested that other nutrients also play a role. We investigated the preconceptional intake of macronutrients (protein, fat, carbohydrate, fiber, and cholesterol), vitamins (vitamin A, retinol, beta-carotene, ascorbic acid, and alpha-tocopherol), minerals (calcium, phosphorus, iron, magnesium, and zinc) and food groups in mothers of OFC children and controls. At approximately 14 mo after the index pregnancy, 206 mothers of a child with a nonsyndromic OFC and 203 control mothers completed a FFQ on current food intake and a general questionnaire. After exclusion of pregnant and lactating mothers, mothers who reported a change in diet compared with the preconceptional period, and those for whom periconceptional folic acid supplement use was unclear, 182 OFC mothers and 173 control mothers were evaluated. Macronutrient, vitamin, mineral, and food group intakes were compared. After adjustment for energy, quintiles of dietary nutrient intake and odds ratios with 95% CI were calculated. The preconceptional intake of all macronutrients, vitamins, minerals, and food groups with the exception of milk (products), potatoes, pies/cookies were lower in OFC mothers than in controls. The energy-adjusted intakes of vegetable protein, fiber, beta-carotene, ascorbic acid, alpha-tocopherol, iron, and magnesium were significantly lower in cases compared with controls. Increasing intakes of vegetable protein, fiber, ascorbic acid, iron, and magnesium decreased OFC risk. In conclusion, a higher preconceptional intake of nutrients predominantly present in fruits and vegetables reduces the risk of offspring affected by OFC.     

Maternal cigarette smoking during pregnancy and risk of oral clefts in newborns.

The results of previous epidemiologic research on the possible association between maternal smoking during pregnancy and risk of oral clefts in offspring have been inconsistent. This may be due in part to methodological limitations, including imprecise measurement of tobacco use, failure to consider etiologic heterogeneity among types of oral clefts, and confounding. This analysis, based on a large case-control study, further evaluated the effect of first trimester maternal smoking on oral facial cleft risk by examining the dose-response relationship according to specific cleft type and according to whether or not additional malformations were present. A number of factors, including dietary and supplemental folate intake and family history of clefts, were evaluated as potential confounders and effect modifiers. Data on 3,774 mothers interviewed between 1976 and 1992 by the Slone Epidemiology Unit Birth Defects Study were used. Study subjects were actively ascertained from sites in areas around Boston, Massachusetts and Philadelphia, Pennsylvania; the state of Iowa; and southeastern Ontario, Canada. Cases were infants with isolated defects--cleft lip alone (n = 334), cleft lip and palate (n = 494), or cleft palate alone (n = 244)--and infants with clefts plus (+) additional malformations: cleft lip+ (n = 58), cleft lip and palate+ (n = 140), or cleft palate+ (n = 209). Controls were infants with defects other than clefts, excluding defects possibly associated with maternal cigarette use. There were no associations with maternal smoking for any oral cleft group, except for a positive dose response among infants with cleft lip and palate+ (for light smokers, odds ratio (OR) = 1.09 (95% confidence interval (CI): 0.6, 1.9); for moderate smokers, OR = 1.84 (95% CI: 1.2, 2.9); and for heavy smokers, OR = 1.85 (95% CI: 1.0, 3.5), relative to nonsmokers). This finding may be related to the additional malformations rather than to the cleft itself.     

山西省4县唇腭裂环境危险因素调查

目的 筛选山西省出生缺陷高发区唇腭裂发生的各种环境危险因素,为深入的病因研究提供线索. 方法 以人群为基础的出生缺陷病例对照研究.病例组为2003年1月～2006年12月在山西省4县监测到的96例唇腭裂患儿,对照为同期调查的680名无体表可见出生缺陷的正常婴儿.在妇女分娩后1周内,通过面对面调查方式,收集妇女一般情况,怀孕前后生活方式、饮食情况、居住环境等信息.先采用单因素分析方法,筛选可能的危险因素;将有统计学意义的因素纳入多因素非条件Logistic模型.采用比值比（OR）估计危险度,并计算95%可信区间（95%CI）.结果多因素logisitic回归分析结果显示,怀孕前后感冒高热（OR=4.6,95%CI：2.6～8.3）、服用解热镇痛类药物（OR=7.5,95%CI：1.8～31.5）、每周被动吸烟≥1次（OR=1.8,95%CI：1.0～3.0）、每周饮白酒≥1次（OR=6.3,95%CI：1.1～35.3）、有毒物质接触（OR=11.8,95%CI：1.2～117.3）、较长时间的噪声接触（OR=3.0,95%CI：1.2～7.4）、食用肉类〈1次/周（OR=1.8,95%CI：1.1～3.1）与唇腭裂发生的危险性有关. 结论 怀孕前后感冒或高热、服用解热镇痛类药物、被动吸烟、饮白酒、接触有毒化学物质、较长时间的噪声接触以及肉类食用频率低可能是山西省唇腭裂发生的危险因素.这些因素通过健康教育和孕前保健应能避免.