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.     

Parental age as a risk factor for isolated congenital malformations in a Polish population

Currently available data on the relationship between the prevalence of isolated congenital malformations and parental age are inconsistent and frequently divergent. We utilised the data from the Polish Registry of Congenital Malformations (PRCM) to accurately assess the interplay between maternal and paternal age in the risk of isolated non-syndromic congenital malformations.
Out of 902 452 livebirths we studied 8683 children aged 0–2 years registered in the PRCM. Logistic regression was used to simultaneously adjust the risk estimates for maternal and paternal age. Our data indicated that paternal and maternal age were independently associated with several congenital malformations. Based on our data, young maternal and paternal ages were independently associated with gastroschisis. In addition, young maternal age, but not young paternal age, carried a higher risk of neural tube defects. Advanced maternal and paternal ages were both independently associated with congenital heart defects. Moreover, there was a positive association between advanced paternal age and hypospadias, cleft palate, and cleft lip (with or without cleft palate).
No significant relationships between parental age and the following congenital malformations were detected: microcephaly, hydrocephaly, oesophageal atresia, atresia or stenosis of small and/or large intestine, ano-rectal atresia or stenosis, renal agenesis or hypoplasia, cystic kidney disease, congenital hydronephrosis, diaphragmatic hernia and omphalocele.     

Spatial and temporal clustering of isolated cleft lip with or without cleft palate in Poland

Background: Geographic variation in the prevalence of isolated cleft lip with or without cleft palate may be due to exogenous environmental factors or genetic variation. In this study, we aim to evaluate the prevalence of isolated cleft lip with or without cleft palate in Polish urban and rural environments in order to identify geographic areas with high prevalence (defect clusters). Methods: We use all cases of congenital malformations reported to the Polish Registry of Congenital Malformations in the years 1998–2008 from the total population of 2,362,502 births. Results: We detect a strong signal of increased prevalence of isolated cleft lip with or without cleft palate in a single region of Poland, the Dolno?l?skie voivodeship. Furthermore, we demonstrate a statistically significant prevalence differences between the urban and rural areas within this region. Through our comprehensive spatiotemporal analysis, we precisely define the cluster of the highest risk that comprises the eastern part of this voivodeship.     

Congenital defects and electric bed heating in New York State: a register-based case-control study.

Exposure to 60-cycle electromagnetic fields has been hypothesized to be a cause of childhood cancer and congenital defects. Because electric bed heaters are a major source of variation in electromagnetic field exposure in the population, the authors conducted a case-control study in 1988-1989 to examine the relations between congenital defects and the use of electric blankets and heated waterbeds. Cases were identified by the New York State Congenital Malformations Registry as babies with cleft palate (n = 121), cleft lip with or without cleft palate (n = 197), born in 1983-1984, and anencephalus and spina bifida (n = 224), born in 1983-1986, all to upstate New York residents. Controls were selected at random from birth registrations individually matched to cases by maternal race, age, home county, month of last menses, and child's sex. Information on periconceptional electric blanket and heated waterbed use as well as known and suspected risk factors for defects was obtained from questionnaires mailed to the mothers. Matched odds ratio estimates and 95% confidence intervals (CIs) for electric blanket use relative to nonuse were 0.8 (95% CI 0.3-2.1) for cleft palate, 0.7 (95% CI 0.3-1.3) for cleft lip, and 0.9 (95% CI 0.5-1.6) for neural tube defects. The respective odds ratios for heated waterbed use were nearly identical to these. Adjustment for potential confounding factors (maternal education, vitamin use, smoking) and stratification by season of conception and bed heat control setting had no meaningful effect on odds ratios. These results suggest that 60-cycle fields do not cause neural tube and oral cleft defects.     

Chlorination disinfection by-products and risk of congenital anomalies in England and Wales

BACKGROUND: Increased risk of various congenital anomalies has been reported to be associated with trihalomethane (THM) exposure in the water supply. OBJECTIVES: We conducted a registry-based study to determine the relationship between THM concentrations and the risk of congenital anomalies in England and Wales. METHODS: We obtained congenital anomaly data from the National Congenital Anomalies System, regional registries, and the national terminations registry; THM data were obtained from water companies. Total THM (< 30, 30 to < 60, > or =60 microg/L), total brominated exposure (< 10, 10 to < 20, > or =20 microg/L), and bromoform exposure (< 2, 2 to < 4, > or =4 microg/L) were modeled at the place of residence for the first trimester of pregnancy. We included 2,605,226 live births, stillbirths, and terminations with 22,828 cases of congenital anomalies. Analyses using fixed- and random-effects models were performed for broadly defined groups of anomalies (cleft palate/lip, abdominal wall, major cardiac, neural tube, urinary and respiratory defects), a more restricted set of anomalies with better ascertainment, and for isolated and multiple anomalies. Data were adjusted for sex, maternal age, and socioeconomic status. RESULTS: We found no statistically significant trends across exposure categories for either the broadly defined or more restricted sets of anomalies. For the restricted set of anomalies with isolated defects, there were significant (p < 0.05) excess risks in the high-exposure categories of total THMs for ventricular septal defects [odds ratio (OR) = 1.43; 95% confidence interval (CI), 1.00-2.04] and of bromoform for major cardiovascular defects and gastroschisis (OR = 1.18; 95% CI, 1.00-1.39; and OR = 1.38; 95% CI, 1.00-1.92, respectively). CONCLUSION: In this large national study we found little evidence for a relationship between THM concentrations in drinking water and risk of congenital anomalies.     

The contribution of maternal epilepsy and its treatment to the etiology of oral clefts: A population based case-control study

The associations between maternal epilepsy and anticonvulsant drug therapy with the risk of oral clefts in the offspring were investigated using data from a population-based case-control study. Cases included 238 infants with cleft lip ± cleft palate (CLP) and 107 infants with cleft palate (CP) ascertained through the Metropolitan Atlanta Congenital Defects Program (MACDP) between 1968 and 1980. Controls included 3029 population-based normal infants. Histories of maternal epilepsy and drug therapy during pregnancy were compared between cases and controls using maternal interviews and reviews of hospital medical records. Maternal epilepsy was associated with increased risk of nonsyndromic CLP (OR = 3.78, 95% C.I. 1.65–7.88), and less with CP (OR = 1.75, 95% C.I. 0.20–6.99). Therapy during pregnancy was associated with the greatest excess risk (CLP OR = 7.77, C.I. 2.02–26.0; CP OR = 3.61, C.I. 0.08–26.5). The use of polytherapy was associated with the highest risk (CLP OR = 10.5, C.I. 1.52–59.9). Adjustment for potential confounding variables in the study did not change these findings. In this well-defined population, maternal epilepsy and its treatment account for a small proportion of nonsyndromic oral clefts (attributable fraction CLP = 3.3%, CP = 0.9%). © 1994 Wiley-Liss, Inc.     

Endothelial nitric oxide synthase (NOS3) genetic variants, maternal smoking, vitamin use, and risk of human orofacial clefts

Orofacial clefts have been associated with maternal cigarette smoking and lack of folic acid supplementation (which results in higher plasma homocysteine concentrations). Because endothelial nitric oxide synthase (NOS3) activity influences homocysteine concentration and because smoking compromises NOS3 activity, genetic variation in NOS3 might interact with smoking and folic acid use in clefting risk. The authors genotyped 244 infants with isolated cleft lip with or without cleft palate (CL/P), 99 with isolated cleft palate, and 588 controls from a California population-based case-control study (1987-1989 birth cohort) for two NOS3 polymorphisms: A(-922)G and G894T. Analyses of gene-only effects for each polymorphism revealed a 60% increased risk of CL/P among NOS3 A(-922)G homozygotes (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.6). There was some evidence for higher risk of CL/P with maternal periconceptional smoking in infants with an NOS3 -922G allele (for homozygotes, OR = 2.5, 95% CI: 1.2, 5.6) but not in those with an 894T allele. For CL/P risk, odds ratios were over 4 among mothers who smoked, who did not use vitamins, and whose infants had at least one variant allele for each NOS3 polymorphism (for A(-922)G, OR = 4.6, 95% CI: 2.1, 10.2; for 894T, OR = 4.4, 95% CI: 1.8, 10.7). No similar patterns were observed for risk of cleft palate.     

Tobacco and alcohol use during pregnancy and risk of oral clefts. Occupational Exposure and Congenital Malformation Working Group

OBJECTIVES: This study examined the relationship between maternal tobacco and alcohol consumption during the first trimester of pregnancy and oral clefts. METHODS: Data were derived from a European multicenter case-control study including 161 infants with oral clefts and 1134 control infants. RESULTS: Multivariate analyses showed an increased risk of cleft lip with or without cleft palate associated with smoking (odds ratio [OR] = 1.79, 95% confidence interval [CI] = 1.07, 3.04) and an increased risk of cleft palate associated with alcohol consumption (OR = 2.28, 95% CI = 1.02, 5.09). The former risk increased with the number of cigarettes smoked. CONCLUSIONS: This study provides further evidence of the possible role of prevalent environmental exposures such as tobacco and alcohol in the etiology of oral clefts.     

Congenital malformations and maternal occupation: a registry based case-control study.

OBJECTIVES: To investigate the relations between congenital malformations and maternal occupation during pregnancy with a registry based case-control study. METHODS: Analysis was performed on data derived from the Florence Eurocat registry surveillance programme. The study included cases with isolated conditions, including chromosomal anomalies (n = 1351), cases with multiple anomalies registered during the 1980-91 period (n = 440), and babies with no congenital malformations recognised at birth who were born from 1982 to 1989 and selected as controls (n = 3223). 11 categories were defined, 10 including cases with isolated malformations and one for cases with multiple congenital anomalies. Four categories of maternal occupation were selected for the study. Odds ratio (OR) values were adjusted for maternal origin, maternal and paternal education, number of previous live births, illness during pregnancy, and maternal age when the group of chromosomal anomalies was analysed. RESULTS: A notable and significant association between oral clefts and mothers involved in leather and shoe manufacturing was found (adjusted OR 3.9; 99% confidence interval (99% CI) 1.5 to 9.8) and the risk consistently increased when considering cases with isolated cleft palate separately (OR 5.4; 95% CI 1.8 to 13.4). Moreover, a significant risk was identified for the association between multiple anomalies and textile dye workers (adjusted OR 1.9; 99% CI 1.0 to 3.8). CONCLUSIONS: This study indicates a notable, significant relation between maternal occupation as a pelt or leather worker and orofacial clefts in offspring. This finding is in agreement with the suggested inheritance models. The dilution effect due to studying large and heterogeneous groups of workers and occupations limits the value of the study; but it provides a good example of the use of a large database to search for teratogenic risk with the aid of malformation registries.     

Periconceptional folate intake by supplement and food reduces the risk of nonsyndromic cleft lip with or without cleft palate

BACKGROUND: Inadequate maternal vitamin intake during pregnancy has been suggested as a risk factor for cleft lip with or without cleft palate (CLP). The independent role of folate has not been clarified. METHODS: To investigate the association between maternal folate intake by supplement and food and the risk of CLP offspring, a case-control study was conducted in the Netherlands (1998-2000) among 174 mothers of a child with nonsyndromic CLP and 203 mothers of a child without congenital malformations. RESULTS: Daily use of a folic acid supplement by mothers starting from 4 weeks before until 8 weeks after conception gave a 47% CLP risk reduction compared to mothers who did not use these supplements [odds ratio (OR): 0.53, 95% confidence interval (CI): 0.33, 0.85]. Ninety-three percent of the users took a supplement containing folic acid only. Dietary folate intake reduced CLP risk independently in a dose-response manner. The largest risk reductions were found on those mothers who had a diet of more than 200 microg folate per day in combination with a folic acid supplement (OR: 0.26, 95% CI: 0.09, 0.72). CONCLUSIONS: We demonstrated that periconceptional maternal folic acid supplement use was beneficial to reduce the risk for CLP. An additional effect of food folate was shown.     

Maternal cigarette smoking during pregnancy in relation to oral clefts

Studies on maternal smoking in relation to oral cleft defects have yielded inconsistent findings, with results ranging from no association to sixfold increases in risk. The authors examined this relation in a case-control study conducted in Boston, Massachusetts, Philadelphia, Pennsylvania, Toronto, Ontario, Canada, and the state of Iowa during the years 1983-1987, in which mothers of malformed infants were interviewed within 6 months after delivery about prenatal events and exposures. Maternal cigarette smoking during pregnancy for 400 infants with cleft lip with or without cleft palate and for 215 infants with cleft palate alone was compared with that for 2,710 infants with other malformations (controls). Relative risks (and 95% confidence intervals) were estimated for smokers of 1-14, 15-24, and greater than or equal to 25 cigarettes per day relative to never smokers; the respective estimates for cleft lip with or without cleft palate were 1.2 (95% confidence interval (CI) 0.9-1.6), 1.4 (95% CI 1.0-2.1), and 0.7 (95% CI 0.3-1.6), and for cleft palate alone, estimates were 1.0 (95% CI 0.7-1.5), 0.9 (95% CI 0.5-1.5), and 0.8 (95% CI 0.3-2.2). Relative risks were also close to unity for case subgroups divided according to the presence or absence of an associated malformation. Multivariate control of several potential confounders did not alter these estimates. Based on this large series of cases, maternal smoking during pregnancy does not appear to increase the risk of oral clefts.     

孕早期感冒或发热与常见体表出生缺陷关系的病例对照研究

一些研究表明孕早期感冒或发热与某些出生缺陷的发生有关[1~6]。中国北方地区是体表重大出生缺陷高发的地区,同时由于气候寒冷,也是感冒或发热高发的地区。因此,研究感冒或发热与出生缺陷危险性的关系,对于有效预防和控制出生缺陷具有重要意义。山西省属于我国乃至世界上体表出     

Genetic epidemiology of cleft lip with or without cleft palate in the population of Hawaii

Orientals consisting of Japanese, Chinese, Koreans, and Filipinos are clearly at higher risk for cleft lip with or without cleft palate [CL(P)] than whites, Puerto Ricans, and Hawaiians/part-Hawaiians in Hawaii. Using the model of diallele cross, CL(P) incidences in incrosses and outcrosses involving 564,002 live births distributed among 669 mating types were analyzed to study the extent of major gene involvement in the difference in the two groups and to investigate maternal effect in the etiology of CL(P). CL(P) cases excluding syndrome cases were classified into two types: all CL(P) cases and CL(P) cases without additional malformations. For either type there was no evidence to suggest that simple major gene plays a dominant role in accounting for racial differences as measured by deviations from additivity in the hybrids. For CL(P) cases without additional defects, a negative "maternal effect" was detected in Filipinos such that higher risk for this racial group depends on when the father is Filipino. Implications of the findings are discussed.     

A case-control study of maternal smoking and congenital malformations

We conducted a population-based case-control study to assess the association between maternal smoking during pregnancy and the risk of giving birth to a child with a congenital malformation. Cases were all singleton livebirths with a congenital malformation recorded on the 1984-1986 Washington State Birth Records (n = 3284). The smoking histories of these mothers were compared to a randomly selected group of mothers with a singleton livebirth of a child without a malformation during these same years (n = 4500). When all malformations were taken as a group, there was no association with maternal smoking (relative risk (RR) = 1.0, 95% CI 0.9-1.1). However, increased risks were observed for a number of specific malformations, including microcephalus (RR = 2.0, 95% CI 1.0-4.0), cleft defects (RR = 1.4, 95% CI 1.0-2.0), and club foot (RR = 1.4, 95% CI 1.0-2.0). We did not find any association with Down's syndrome (RR = 0.8 95% CI 0.5-1.3) or any other malformation. We conclude that maternal smoking during pregnancy may be associated with an increased risk for some malformations.     

A case-control study of maternal smoking and congenital malformations

Summary. We conducted a population-based case-control study to assess the association between maternal smoking during pregnancy and the risk of giving birth to a child with a congenital malformation. Cases were all singleton livebirths with a congenital malformation recorded on the 1984–1986 Washington State Birth Records (n = 3284). The smoking histories of these mothers were compared to a randomly selected group of mothers with a singleton livebirth of a child without a malformation during these same years (n = 4500). When all malformations were taken as a group, there was no association with maternal smoking (relative risk (RR) = l.0, 95% CI 0.9–1.1). However, increased risks were observed for a number of specific malformations, including microcephalus (RR = 2.0, 95% CI 1.0–4.0), cleft defects (RR=1.4, 95% CI 1.0–2.0), and club foot (RR= 1.4, 95% CI 1.0–2.0). We did not find any association with Down's syndrome (RR=0.8, 95% CI 0.5–1.3) or any other malformation. We conclude that maternal smoking during pregnancy may be associated with an increased risk for some malformations.     

Ethnic differences in congenital malformations in the Netherlands: analyses of a 5-year birth cohort

Congenital malformations are among the major causes of perinatal mortality and morbidity at present. Research into the ethnic diversity of congenital malformations can form a basis both for aetiological studies and for health care advice and planning. This study compared the overall prevalence of congenital malformations, the prevalence in different organ systems and of several specific malformations between different maternal ethnic groups in the Netherlands using a 5-year national birth cohort (1996-2000) containing 881 800 births. Maternal ethnic groups considered were Dutch; Mediterranean (Moroccan/Turkish); other European; Black; Hindu and Asian. Mediterranean women had a 20% higher risk of having a child with a congenital malformation than Dutch women (age-adjusted OR = 1.21 [95% CI 1.16, 1.27]). They showed an increased risk of malformations in several organ systems such as the central nervous system and sensory organs, the urogenital system and skin and abdominal wall. Further, they had an increased risk of the group of chromosomal malformations/multiple malformations/syndromes. For the specific group of multiple malformations the maternal age adjusted OR was 1.80 [95% CI 1.47, 2.20]. The Black group showed a significantly increased risk of skeletal and muscular malformations (age adjusted OR = 1.76 [95% CI 1.53, 2.02]) with a sixfold increased risk of polydactyly compared with the Dutch group. For Mediterranean women, the largest and fastest growing group of immigrants in the Netherlands, this study demonstrated an increased risk of congenital malformations.     

Maternal occupational risk factors for oral clefts. Occupational Exposure and Congenital Malformation Working Group

OBJECTIVES: This study investigated the role of maternal exposures at work during pregnancy in the occurrence of oral clefts. METHODS: The occupational exposures of 851 women (100 mothers of babies with oral clefts and 751 mothers of healthy referents) who worked during the first trimester of pregnancy were studied. All the women were part of a multicenter European case-referent study conducted using 6 congenital malformation registers between 1989 and 1992. In each center, the mother's occupational history, obtained from an interview, was reviewed by industrial hygienists who were blinded to the subject's status and who assessed the presence of chemicals and the probability of exposure. Odds ratios (OR) were estimated by a multivariate analysis including maternal occupation or occupational exposures during the first trimester of pregnancy and possible confounding factors such as center of recruitment, maternal age, urbanization, socioeconomic status, and country of origin. RESULTS: After adjustment for confounding factors, cleft palate only was significantly associated with maternal occupation in services such as hairdressing [OR 5.1, 95% confidence interval (95% CI) 1.0-26.0] and housekeeping (OR 2.8, 95% CI 1.1-7.2). The analysis suggests that the following occupational exposures are associated with orofacial clefts: aliphatic aldehydes (OR 2.1, 95% CI 0.8-5.9) and glycol ethers (OR 1.7, 95% CI 0.9-3.3) for cleft lip with or without cleft palate and lead compounds (OR 4.0, 95% CI 1.3-12.2), biocides (OR 2.5, 95% CI 1.0-6.0), antineoplastic drugs (OR 5.0, 95% CI 0.8-34.0), trichloroethylene (OR 6.7, 95% CI 0.9-49.7), and aliphatic acids (OR 6.0, 95% CI 1.5-22.8) for cleft palate only. CONCLUSIONS: Due to the limited number of subjects, these results must be interpreted with caution. However, they point out some chemicals already known or suspected as reproductive toxins.     

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   

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.     

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。