母亲、子代血管紧张素原基因单核苷酸多态性与先兆子痫/子痫的关联研究

目的 探讨母亲、子代血管紧张素原（AGT）基因单核苷酸多态性（SNP）与先兆子痫/子痫的关联。方法 2008年1月至2015年10月，采用病例-父母/对照-母亲混合研究设计，调查347组病例和700组对照的基本人口学特征，并检测AGT相关SNP的基因型，运用对数线性模型及非条件logistic回归的方法分析母亲、子代AGT各SNP与先兆子痫/子痫的关联。结果 当子代rs3789679基因型为GA和AA时，其母亲发生先兆子痫/子痫的风险降低（OR=0.73，95% CI：0.55~0.96；OR=0.62，95% CI：0.39~0.98）；当子代rs2493132为TT基因型时，其母亲发生先兆子痫/子痫的风险增加（OR=1.60，95% CI：1.08~2.37），此结果经多重检验校正后无统计学意义。遗传模型分析显示，子代rs3789679在显性模型下（GA+AA/GG）降低了其母亲发生先兆子痫/子痫的风险（OR=0.73，95% CI：0.55~0.96）；子代rs2493132在隐性模型（TT/CT+CC）下增加了其母亲发生先兆子痫/子痫的风险（OR=1.66，95% CI：1.13~2.44）；母亲rs5051在显性模型下（TC+CC/TT）增加了自身发生先兆子痫/子痫的风险（OR=1.33，95% CI：1.01~1.76）。结论 在显性遗传模型下，子代rs3789679 GA和AA基因型降低了其母亲发生先兆子痫/子痫的风险，母亲rs5051 TC和CC基因型增加了自身发生先兆子痫/子痫的风险。在隐性遗传模型下，子代rs2493132 TT基因型增加了其母亲发生疾病的风险。     

母亲MTHFR 677C/T多态性和孕期状况与子代发生先天性心脏病的相关性研究

目的 探讨母亲孕期MTHFR 677C/T多态性、孕期状况在子代先天性心脏病(CHD)发生中的相互关系。方法 采用病例对照研究,调查100对CHD胎儿和无CHD胎儿生物学母亲有关人口学、孕期环境相关情况、优生认知,并检测MTHFR 677C/T基因多态性以及血清同型半胱氨酸(HCY)、叶酸、VitB12水平,进行单因素和多因素非条件logistic回归分析。结果 病例组和对照组MTHFR 677C/T基因型和等位基因频率差异无统计学意义(χ²=1.08,P=0.582;χ²=0.53,P=0.468),血清HCY水平两组差异有统计学意义(t=-8.14,P=0.000)。单因素分析,14个因素有统计学意义(P<0.05);多因素logistic逐步回归分析,母亲教育程度(OR=3.386,95%CI:1.279~8.961)、家庭年收入(OR=8.699,95%CI:2.177~34.765)、患慢性病(OR=0.343,95%CI:0.134~0.881)、优生认知得分(OR=0.906,95%CI:0.836~0.981)、血清HCY水平(OR=1.734,95%CI:1.458~1.986)、异常生育史(OR=3.710,95%CI:1.217~11.308)等因素与子代CHD相关。结论 母亲MTHFR 677C/T多态性与子代CHD发生未发现关联;母亲教育程度低、家庭年收入低、异常生育史、优生认知得分低、血清HCY水平高可能增加子代CHD的发生危险。     

对数线性模型在病例-父母对照研究中的应用

介绍应用对数线性模型分析病例-父母对照研究设计的方法.以亚甲基四氢叶酸还原酶基因(MTHFR)C677T与唇腭裂的关联研究为例,应用对数线性模型分析母亲、子代基因及其交互作用与唇腭裂的关系.结果显示变异型纯合子母亲的子代发生唇腭裂的风险低于野生型纯合子母亲的子代,S2=0.43 (95％CI:0.19 ～ 0.95),未发现唇腭裂与子代基因及母子交互作用相关.应用对数线性模型分析病例-父母对照研究设计的方法尤其适用于妊娠期疾病与源于胚胎时期疾病等的病因学研究.     

母亲孕前BMI和孕期增重与子代孤独症之间关系的研究

目的 探讨母亲孕前BMI和孕期增重与子代孤独症之间的关系。方法 选取2013－2014年经医疗机构确诊的181例1～5岁孤独症儿童为病例组,采用1 ∶ 1病例对照研究方法选择同地区、同性别、同年龄发育正常的儿童作为对照组。按母亲孕前BMI值分为低、正常和高3组,孕期增重根据美国医学研究所标准分为低、正常和高3组,采用SPSS 18.0软件进行χ²检验和logistic回归分析。结果 两组儿童年龄和性别分布均衡(χ²=0.434,P >0.05)。病例组母亲孕前BMI平均值为(21.28±3.80)kg/m²,高于对照组的(19.87±2.83)kg/m²,差异有统计学意义(χ²=9.580,P< 0.05);病例组母亲高BMI人数(10.5%)多于对照组(2.8%);随着孕前BMI增加,子代孤独症患病风险逐渐增大,高BMI组子代孤独症发病风险是正常BMI组的3.7倍(OR=3.71,95%CI:1.34～10.24);病例组正常BMI母亲孕期增重过度(44.1%)高于对照组(33.9%);病例组高BMI母亲孕期增重过度(52.6%)明显高于对照组(20.0%),正常BMI(χ²=8.690,P< 0.05)和高BMI(χ²=4.775,P< 0.05)母亲孕期增重过度与孤独症发病有关。logistic回归分析显示,母亲孕前高BMI(调整前OR=1.89,95%CI:1.26～2.85;调整后OR=1.52,95%CI:1.19～2.27)和孕期增重过度(调整前OR=1.63,95%CI:1.08～1.25;调整后OR=1.64,95%CI:1.21～2.21)是子代孤独症发生的危险因素。结论 母亲孕前超重/肥胖和孕期增重过度与子代孤独症发生有一定的关系,可能是孤独症的危险因素。     

孕期妇女膳食指南依从性指数与子代先天性心脏病的关系

目的 研究孕期妇女膳食指南依从性指数（CDGCI_PW）与子代先天性心脏病（先心病）的关系。方法 在陕西省西安市开展以医院为基础的病例对照研究,采用半定量食物频率问卷调查孕妇整个孕期的饮食情况。应用修订的CDGCI_PW评分评估孕期膳食质量,运用logistic回归分析其与子代先心病的关系,采用受试者工作特征曲线（ROC）构建CDGCI_PW对子代先心病患病的预测模型。结果 共纳入1 422名研究对象,病例组474名,对照组948名。病例组CDGCI_PW评分M（Q₁,Q₃）为46.0（26.0,65.0）分低于对照组60.0（40.0,77.0）分,两组间差异有统计学意义（P<0.001）。与CDGCI_PW评分Q₁组相比,CDGCI_PW评分Q₂、Q₃和Q₄组的子代总先心病发生风险均降低（OR=0.60,95%CI：0.43~0.83;OR=0.64,95%CI：0.45~0.89;OR=0.29,95%CI：0.19~0.44）（趋势检验P<0.001）。CDGCI_PW评分每增加10分,子代总先心病的发生风险降低17%（OR=0.83,95%CI：0.79~0.88）。构建ROC预测的曲线下面积为0.793（95%CI：0.768~0.818）,约登指数最大处的灵敏度为0.740、特异度为0.725。结论 本研究提示改善妇女孕期膳食质量可降低子代先心病的发生风险。     

125例新生儿先天性甲状腺功能减低症围产因素分析

目的 探讨围产期相关因素与先天性甲状腺功能减低(甲减)症(CH)的关系。方法采用病例对照研究。选择2012年1月至2013年12月在福建省新生儿疾病筛查中心诊断为CH的新生儿125例为病例组,按1:3比例随机选择非CH的新生儿为对照组。采用单因素及二项分类logistic同归模型分析CH的围产期相关危险因素。结果 单因素分析显示,病例组中母亲妊娠期高血压、妊娠期糖尿病、妊娠合并甲状腺疾病、高龄产妇的发生率高于对照组,差异有统计学意义(均P<0.05);病例组新生儿在女性、早产儿、过期儿、低出生体重儿、巨大儿、双胎及多胎、伴发其他出生缺陷和感染的发生率均高于对照组,差异有统计学意义(均P<0.05)。多因素logistic回归分析显示,高龄产妇(OR=2.518,95%CI:1.186~5.347)、妊娠期糖尿病(OR=1.904,95%CI:1.190~3.045)、妊娠合并甲减(OR=12.883,95%CI:2.055~80.751)或甲亢(OR=30.797,95%CI:3.309~286.594)、早产儿(OR=4.238,95%CI:1.269~14.155)、过期儿(OR=12.799,95%CI:1.257~130.327)、低出生体重儿(OR=3.505,95%CI:1.059~11.601)、巨大儿(OR=3.733,95%CI:1.415~9.851)、双胎及多胎(OR=5.493,95%CI:1.701~17.735)、伴发其他出生缺陷(OR=3.665,95%CI:1.604~8.371)和胎儿窘迫(OR=3.130,95%CI:1.317~7.440)为新生儿CH的高危因素(均P<0.05)。结论 新生儿CH与母亲孕龄、妊娠期糖尿病、妊娠合并甲状腺疾病以及新生儿出生体重、胎龄、胎数、胎儿窘迫、伴发其他出生缺陷等有一定关系,应加强围孕期保健,减少高危因素,降低CH发病率。     

膳食模式对社区管理2型糖尿病患者血糖控制影响的研究

目的 了解膳食对社区管理2型糖尿病（T2DM）患者血糖控制的影响，为实施针对糖尿病患者的防治策略和措施提供依据。方法 于2015年在常熟市和武汉市随机抽取8个社区，对进行社区管理的T2DM患者进行问卷调查、身体测量和血糖检测。研究采用因子分析获得膳食模式。并分别以FPG、餐后2 h血糖控制是否达标为因变量，进行非条件多因素logistic回归分析影响因素。结果 最终共纳入1 818名T2DM患者，患者FPG控制率为57.59%（95%CI：55.30%~59.86%），餐后2 h血糖控制率为24.90%（95%CI：22.93%~26.91%）；因子分析得到5种膳食模式：动物性食物模式、水果-水产-薯类模式、蔬菜-谷物模式、蛋-奶-豆模式和油盐模式。非条件多因素logistic回归分析显示，调整其他因素后，FPG达标概率降低与动物性食物模式（OR=0.71，95%CI：0.52~0.98）、水果-水产-薯类模式（OR=0.71，95%CI：0.51~0.97）相关，餐后2 h血糖达标概率降低与水果-水产-薯类模式（OR=0.60，95%CI：0.40~0.90）相关，FPG和餐后2 h血糖达标概率增加均与蔬菜-谷物模式（OR=1.41，95%CI：1.03~1.94；OR=1.68，95%CI：1.13~2.51）、蛋-奶-豆模式（OR=1.75，95%CI：1.25~2.46；OR=1.56，95%CI：1.00~2.42）有关。与蛋-奶-豆模式Q₄组相比，膳食模式组合（水果-水产-薯类模式Q₄组、蔬菜-谷物模式Q₂组、蛋-奶-豆模式Q₃组）FPG控制达标可能性更高（OR=6.79，95%CI：1.15~40.23，P=0.035）；与蔬菜-谷物模式Q₄组相比，膳食模式组合（水果-水产-薯类模式Q₄组、蔬菜-谷物模式Q₃组、蛋-奶-豆模式Q₂组、油盐模式Q₂组）餐后2 h血糖控制达标可能性更高（OR=12.78，95%CI：1.26~130.05，P=0.031）。结论 搭配得当的膳食模式及膳食模式组合更有利于武汉市和常熟市社区管理T2DM患者的FPG和餐后2 h血糖控制，应加强患者营养教育，提高患者食物搭配能力。     

维生素D受体基因多态性与妊娠期糖尿病关系的病例对照研究

目的 探讨维生素D受体（VDR）基因多态性与妊娠期糖尿病（GDM）之间的关系,为GDM的机制研究提供线索与依据。方法 采用病例对照研究设计,以2012年3月1日至2014年7月30日在山西医科大学第一医院产科分娩的孕妇为研究对象,其中334例被诊断为GDM,按年龄、妊娠时间及居住地1∶1匹配相应健康对照。对研究对象进行DNA基因分型,剔除基因分型缺失率>10%者,最终323例病例和320例对照纳入研究。在共显性、显性、隐性和等位基因遗传模型下,通过非条件logistic回归分析VDR基因位点多态性和GDM之间的关系,并采用Haploview软件分析单倍型与GDM之间的关系。结果 在基因水平上,VDR基因与GDM发病风险有关（P<0.05）。在调整孕前BMI、糖尿病家族史后,rs7967152位点在共显性（AC vs. AA,OR=1.58,95%CI：1.13~2.21）、显性（AC+CC vs. AA,OR=1.58,95%CI：1.15~2.18）和等位基因（C vs. A,OR=1.41,95%CI：1.10~1.82）遗传模型下与GDM风险升高有关;rs2238140位点在共显性（AA vs. GG,OR=2.24,95%CI：1.19~4.20）、显性（GA+AA vs. GG,OR=1.48,95%CI：1.07~2.03）和等位基因（A vs. G,OR=1.43,95%CI：1.11~1.83）遗传模型下与GDM风险升高有关。在共显性和显性遗传模型下,孕妇携带rs2853564位点AG基因型、AG+GG基因型（OR=1.46,95%CI：1.04~2.05;OR=1.45,95%CI：1.05~2.00）与携带AA基因型相比,是GDM的危险因素;孕妇携带rs2853566位点AG基因型、AG+GG基因型（OR=1.43,95%CI：1.03~2.00;OR=1.41,95%CI：1.02~1.94）与携带AA基因型相比,是GDM的危险因素。在VDR基因内由rs1544410、rs7967152组成的单倍型区块,其GC单倍型与是GDM的危险因素（OR=1.50,95%CI：1.15~1.97）。结论 VDR基因rs7967152、rs2238140、rs2853564、rs2853566位点多态性和区块（rs1544410、rs7967152）GC单倍型与GDM的发病风险升高有关。     

陕西省新生儿体表先天畸形的影响因素分析

目的 探讨陕西省新生儿体表先天畸形的影响因素。方法 采用分层多阶段随机抽样方法,通过问卷调查2010-2013年陕西省孕满28周且结局明确的育龄妇女及其生育子女的相关信息,采用多因素logistic回归分析新生儿体表先天畸形的影响因素。结果 多因素logistic回归分析结果显示,妊娠期肝内胆汁淤积症（OR=21.76,95%CI：4.46～106.25）、不良孕产史（OR=11.88,95%CI：9.14～15.45）、家族出生缺陷史（OR=6.15,95%CI：2.66～14.23）、双胎（OR=5.74,95%CI：3.34～9.86）、母亲为工人（与其他职业比,OR=2.47,95%CI：1.30～4.68）或农民（与其他职业比,OR=1.91,95%CI：1.14～3.20）、产检<4次（与产检>7次者比,OR=1.84,95%CI：1.28～2.64）、职业危险暴露（OR=1.74,95%CI：1.26～2.42）、母亲来自关中地区（与陕北地区者比,OR=1.65,95%CI：1.20～2.28）、母亲居住农村（OR=1.75,95%CI：1.13～2.71）、围孕期使用药物（OR=1.64,95%CI：1.26～2.13）是体表先天畸形的危险因素,而母亲围孕期服用铁剂（OR=0.46,95%CI：0.21～0.99）是体表先天畸形的保护因素。结论 母亲来自关中地区、农村、农民或工人、不良孕产史、家族出生缺陷史、双胎、产检<4次、职业危险暴露、使用药物、妊娠期患肝内胆汁淤积症可能增加新生儿体表先天畸形的罹患风险。     

广州市1991－2013年艾滋病相关死亡影响因素分析

目的 分析广州市艾滋病病毒感染者和艾滋病患者(HIV/AIDS)中艾滋病相关死亡的影响因素,为采取相应的措施提供依据。方法 利用国家艾滋病综合防治信息系统中1991－2013年广州市疫情资料,使用Cox风险比例模型分析艾滋病相关死亡的影响因素。结果 广州市HIV/AIDS病例中,报病时病程阶段为AIDS(HR=2.717,95%CI:2.039～3.621)、由医疗机构诊疗发现(HR=1.516,95%CI:1.159～1.981)、未接受过CD₄⁺T淋巴细胞检测(HR=4.866,95%CI:3.674～6.444)、符合治疗标准未治疗(HR=12.213,95%CI:8.467～17.616)、报病时年龄40岁以上的病例发生艾滋病相关死亡的风险更高。另外,不符合治疗标准而未治疗的病例发生艾滋病相关死亡的风险也高于接受抗病毒治疗的病例(HR=1.936,95%CI:1.145～3.272)。结论 及早发现HIV/AIDS病例,接受CD₄⁺T淋巴细胞检测和抗病毒治疗可降低HIV/AIDS的死亡风险,延长生存时间。     

Exploring the effects of methylenetetrahydrofolate reductase gene variants C677T and A1298C on the risk of orofacial clefts in 261 Norwegian case-parent triads

Folic acid and the methylenetetrahydrofolate reductase (MTHFR) gene have both been implicated in the etiology of orofacial clefts. The authors selected 261 case-parent triads (173 cases with cleft lip with or without cleft palate (CL/P) and 88 cases with cleft palate only (CPO)) from a Norwegian population-based study of orofacial clefts (May 1996-1998). A case-parent triad design was used to examine whether MTHFR variants C677T and A1298C, and their haplotypes, are risk factors for orofacial clefts. Among CL/P cases, the child's genotype at C677T or A1298C did not influence the risk. However, children of mothers carrying the C677T variant allele had a lower risk of CL/P. For CPO, children carrying the C677T variant allele had about a twofold increased risk, whereas the mother's genotypes did not contribute to the risk. The haplotype-based transmission/disequilibrium test showed that except for 677T/1298A (p = 0.06), none of the other haplotypes showed evidence of excess transmission to the offspring. The authors also explored interaction of C677T with maternal use of folic acid among children with CPO. Surprisingly, the risk associated with the child's carrying either CT or TT was higher (fourfold) when the mother used folic acid. These findings suggest a possible role of MTHFR and folic acid in the causation of orofacial clefts, but the strength and direction of these effects remain to be clarified.     

Does the interaction between maternal folate intake and the methylenetetrahydrofolate reductase polymorphisms affect the risk of cleft lip with or without cleft palate?

Periconceptional folic acid supplementation may reduce the risk of cleft lip with or without cleft palate (CL(P)). Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methyltetrahydrofolate, the predominant circulating form of folate. To determine the effect of MTHFR C677T and MTHFR A1298C genotypes and haplotypes on CL(P) risk and the interaction with maternal periconceptional dietary folate and folic acid supplement intake, the authors conducted a case-control triad study in the Netherlands (1998-2000) among 179 CL(P) and 204 control families. Infant and parental MTHFR C677T and MTHFR A1298C genotypes and haplotypes were not associated with CL(P) risk in the case-control and transmission disequilibrium test analyses. Mothers carrying the MTHFR 677TT genotype and who either did not use folic acid supplements periconceptionally or had a low dietary folate intake, or both, had an increased risk of delivering a CL(P) child (odds ratio (OR) = 5.9, 95% confidence interval (CI): 1.1, 30.9; OR = 2.8, 95% CI: 0.7, 10.5; OR = 10.0, 95% CI: 1.3, 79.1, respectively). No supplement use, low dietary folate intake, and maternal MTHFR 1298CC genotype increased the risk of CL(P) offspring almost sevenfold (OR = 6.5, 95% CI: 1.4, 30.2). Thus, the detrimental effect of low periconceptional folate intake on the risk of giving birth to a CL(P) child was more pronounced in mothers with the MTHFR 677TT or MTHFR 1298CC genotype.     

Genetic variation of infant reduced folate carrier (A80G) and risk of orofacial defects and congenital heart defects in China

PURPOSE: This study was designed to investigate whether the risks of congenital heart defects (CHD) and orofacial defects were influenced by a polymorphism of the offspring's RFC1 or by an interaction between the RFC1 gene and maternal periconceptional use of folic acid. METHODS: A case-control study was conducted. A total of 82 families with a child affected by cleft lip with or without cleft palate (CLP), 67 families with a child-affected by CHD, and 100 nonmalformed control families were genotyped using PCR-RFLP. RFC1 G allele was tested through family-based association test. RESULTS: Among mothers who did not use folic acid, the risks of 4.03 (95% CI = 1.33-12.77) for the G80/G80 genotype and 4.14 (95% CI = 1.06-16.82) for the G80/A80 genotype were observed relative to the A80/A80 genotype for CHD offspring. In family-based association tests (FBAT), offspring carrying the G allele for RFC1 is at increased risk for CHD (Z = 2.140, p < .05). No significant association was found between either RFC1 genotype or maternal folic acid supplementation and the risks of CLP. CONCLUSIONS: Our findings suggest that the RFC1 G allele is likely to be an important candidate gene in folate transport and to be associated with risk for CHD. This study found modest evidence for a gene-nutrient interaction between offspring RFC1 genotype and periconceptional intake of folic acid on the risk of congenital heart defects.     

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。     

肥胖相关基因多态性与妊娠期糖尿病发病风险的关系

目的 探讨肥胖相关（FTO）基因及多态性位点与妊娠期糖尿病（GDM）发病风险的关系,为GDM机制研究提供线索与依据。方法 以2012年3月1日至2014年7月30日在山西医科大学第一医院产科分娩的孕妇为研究对象,将诊断为GDM的孕妇作为病例组,并按年龄、妊娠时间及居住地1：1频数匹配非GDM孕妇作为对照组,最终纳入324例病例和318例对照,提取孕妇外周血DNA并进行基因分型,应用min P检验和非条件logistic回归分析FTO基因及多态性位点与GDM发病风险的关系。结果 min P法结果显示,FTO基因与GDM发病风险无关（P>0.05）。在调整糖尿病家族史、孕前BMI且调整多重比较后,非条件logistic回归分析结果显示,在FTO基因的多态性位点中,携带rs11075995位点TT基因型与AA基因型孕妇相比（OR=0.59,95% CI：0.35～0.89）,携带rs3826169位点GG基因型与携带AA基因型孕妇相比（OR=0.59, 95% CI：0.35～0.88）,携带rs74245270位点GA基因型（OR=0.69,95% CI：0.49～0.98）、GA或AA基因型（OR=0.70,95% CI：0.50～0.97）与GG基因型孕妇相比,均是GDM的保护因素;相反,携带rs74018601位点GA基因型（OR=1.51,95% CI：1.07～2.12）、GA或AA基因型（OR=1.46,95% CI：1.06～2.02）与GG基因型孕妇相比,携带rs7205009位点AA基因型（OR=1.83,95% CI：1.18～2.86）、GA或AA基因型（OR=1.53,95% CI：1.08～2.19）与携带GG基因型孕妇相比,携带rs9888758位点AG基因型与携带AA基因型孕妇相比（OR=1.43,95% CI：1.02～2.00）,均是GDM的危险因素。结论 FTO基因rs11075995、rs3826169、rs74245270、rs74018601、rs7205009与rs9888758位点多态性与GDM的发病风险有关。     

Smoking and the risk of oral clefts: exploring the impact of study designs

BACKGROUND: Maternal cigarette smoking is a suspected cause of oral clefts, although this association has not been firmly established. We used case-crossover, case-time-control, and bidirectional case-crossover designs to supplement findings from a case-control study of maternal smoking and oral clefts among offspring in a large birth registry. METHODS: Data are from the Swedish Medical Birth Registry. From 1983 through 1997 there were 678 recorded cases of cleft palate and 1175 cases of cleft lip with or without palate. Maternal smoking status was ascertained in early pregnancy. Controls for the case-control study were a random sample of infants born without a cleft; controls for the case-crossover designs were nonmalformed infants born to case mothers. RESULTS: Cleft palate was positively associated with maternal smoking in all study designs, whereas cleft lip with or without cleft palate was associated with smoking only in the case-control design. In the case-control design, the odds ratios for cleft palate were 1.2 (95% confidence interval = 1.0-1.5) for women who smoked 1 to 9 cigarettes per day and 1.4 (1.1-1.8) for women who smoked 10+ cigarettes per day. In the case-time-control analysis, the odds ratio for cleft palate with maternal smoking was 3.2 (1.3-7.4) and in the bidirectional case-crossover design, the odds ratio was 2.2 (1.1-4.1). CONCLUSIONS: An association between smoking and cleft palate was supported by all designs, whereas that between smoking and cleft lip with or without cleft palate was not. Case-only designs are a viable option in birth registries and may yield more information than a case-control design alone.     

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.