产前超声筛查胎儿唇裂和(或)腭裂及相关畸形

目的 评估产前超声对胎儿唇裂和(或)腭裂(简称唇腭裂)的检出率,以及合并的相关结构及染色体异常的发生情况. 方法 本研究为回顾性分析,纳入2006年1月至2010年12月在广州市妇女儿童医疗中心进行常规产前检查并分娩的单胎妊娠孕妇31 245例,于妊娠中期常规行胎儿超声筛查,发现唇腭裂的胎儿建议行染色体核型分析.所有活产新生儿及引产儿均进行口腔检查,以确诊唇腭裂,分析产前诊断的准确性. 结果 所有活产新生儿及引产儿共诊断唇腭裂48例,发生率为1.5‰(48/31 245),其中单纯唇裂占33.3％(16/48),唇裂合并腭裂占43.8％(21/48),单纯腭裂占22.9％(11/48).产前超声共发现18例单纯唇裂,其中14例与生后/引产后诊断完全相符,单纯唇裂产前超声诊断准确率为77.8％(14/18);3例分娩后发现新生儿同时合并腭裂,补充诊断为唇裂合并腭裂;1例产前超声诊断唇裂,因羊水过少引产,但引产儿无唇裂.产前超声检出18例唇裂合并腭裂,生后/引产后证实产前超声诊断均正确.2例胎儿产前超声检查正常,但新生儿检查发现单纯唇裂,均为Ⅰ度.产前超声未检出单纯腭裂,但新生儿生后诊断单纯腭裂11例.产前超声检出唇裂及唇裂合并腭裂的敏感性为86.5％(32/37),检出唇腭裂总的敏感性为66.7％(32/48),假阳性率为2.1％(1/48).产前超声诊断36例唇腭裂胎儿中10例(27.8％)合并其他结构畸形,与生后检查结果一致.产前检出18例唇裂合并腭裂胎儿中9例行染色体检查,其中 7例染色体异常.产前超声检出的36例唇腭裂胎儿中仅13例(12例单纯唇裂,1例唇裂合并腭裂)正常分娩,余23例孕妇均选择引产. 结论 产前超声筛查单纯唇裂及唇裂合并腭裂敏感性高,但难以检出单纯腭裂.单纯唇裂合并染色体异常概率低,而一旦合并腭裂,合并染色体异常及其他结构异常的风险增高.     

3个月内婴儿先天性心脏病193例回顾性分析

目的总结3个月内婴儿先天性心脏病的临床特点,提高早期诊断率。方法对193例经彩色多普勒超声心动图诊断为先天性心脏病患儿资料进行回顾性分析,其中新生儿145例,~3个月婴儿48例。结果新生儿期先天性心脏病复合畸形占21.4%（31/145）,较~3个月婴儿8.3%（4/48）明显增多,其先天性心脏病主要类型为房间隔缺损合并室间隔缺损;~3个月婴儿中以单纯畸形为主,占91.7%（44/48）,其先天性心脏病主要类型为室间隔缺损。临床表现多种、无特异性,以青紫、呼吸急促、喂养困难、心脏杂音多见,易反复呼吸道感染。结论 3个月内婴儿先天性心脏病类型多,临床表现复杂,对可疑者应尽早行超声心动图检查,早期确诊及时治疗。     

超声心动图诊断完全型心内膜垫缺损合并Ⅱ孔房缺

患儿因“发育差”，先天愚型面容。行超声心动图检查提示为先天性心脏病；完全型心内膜垫缺损并Ⅱ孔房间隔缺损。查染色体核型为21-三体。该病例提示：对可疑病例，应行全面系统检查，以明确诊断。行超声心动图检查对合并先心病完全型心内膜垫缺损的患儿常易忽视房间隔残端的观察而漏诊，应多切面仔细观察。     

彩色多普勒超声心动图检测胎儿先天性心脏病

目的　探讨彩色多普勒超声心动图检测胎儿先天性心脏病 (先心病 )的可行性。　方法　 2 96例胎儿分为两组 :14 2例有高危因素的胎儿 ,15 4例正常妊娠胎儿。应用多普勒测定胎儿心脏各切面 ,并在生后作超声心动随访。　结果　在 14 2例有高危因素的胎儿中 ,发现胎儿先心病 5例 ,其中右心发育不良综合征 1例、法洛四联症 2例、单纯性室间隔缺损 (室缺 ) 2例。漏诊 2例 ,为单纯性室缺1例及房间隔缺损 1例。 15 4例正常妊娠胎儿中未发现先心病。生后超声心动随访或引产尸检结果与产前诊断相符。　结论　彩色多普勒超声心动图在诊断胎儿先心病方面是比较准确和安全的 ,对高危孕妇需加强胎儿先心病的检测     

心血管系统疾病

901713 二维伪彩色多普勒超声心动图评价新生儿先天性心脏病(附55例报告)/林其珊…∥新生儿科杂志。-1990,5(3)。-97～99 男31例,女24例,单一缺损17例(30.9％),二个以上联合缺损及复杂畸形38例(61.1％),其中青紫型先心病24例。室间隔缺损(VSD)本组22处,单一VSD仅9例。     

产前诊断唇腭裂308例回顾性研究

目的:探讨胎儿唇腭裂与染色体异常的关系,为该疾病的临床咨询及预后评估提供依据。方法:回顾性分析我院2008年1月至2016年12月所有超声诊断为唇裂/腭裂/唇腭裂的308例孕妇的产前诊断情况,比较不同类型唇腭裂的超声表型特征及染色体异常的发生率。结果:(1)超声诊断结果显示,在308例唇腭裂胎儿中非综合征型唇腭裂258例(83.77%),综合征型唇腭裂50例(16.23%),其中单纯唇裂40例(12.99%),唇裂合并腭裂266例(86.36%),单纯腭裂2例(0.65%)。(2)同意进行产前诊断137例(44.48%),染色体异常共22例(16.06%),其中23例综合征型唇腭裂中发现染色体异常共12例(52.17%),分别为13-三体8例(66.67%),18-三体2例(16.67%),三倍体2例(16.67%);而在114例非综合征型唇腭裂中发现染色体异常10例(8.77%),分别为18-三体1例,21-三体1例,标记染色体1例,发现基因微缺失微重复等遗传综合征4例(B超检查均无任何软指标及除唇腭裂外的其他结构异常),臂间倒位等染色体多态性3例。染色体基因芯片分析(CMA)检测的染色体异常检出率为16.16%(16/99),染色体核型分析异常检出率为15.79%(6/38)。(3)随访到204例患者,186例患者选择引产,18例患者出生后进行手术干预治疗。结论:唇腭裂胎儿染色体异常发生率较高,建议对所有类型唇腭裂均进行产前诊断;CMA检测可以发现除非整倍体外的拷贝数变异,建议对唇腭裂胎儿优选基因芯片进行产前诊断。     

彩色多普勒超声在胎儿先天性心脏病诊断中的应用

先天性心脏病(先心病)是一类常见的先天性疾病。通常认为,人群发病率为0·8%,而在我国围生期发生率呈上升趋势[1]。随着超声设备和技术的不断更新和进步,以及心血管胚胎学等相关基础研究的不断深入和细化,使得对先心病的自然病史的认识扩展到了胎儿阶段。因此,在胎儿期诊断先心病成为可能。二维实时超声可以显示心内结构的解剖学信息,而不能提供心脏血流动力学的情况。而彩色多普勒的应用,可以弥补二维超声的不足,可以从一个独特的角度协助诊断先心病。本文就彩色多普勒超声在胎儿先心病诊断中的应用作一介绍。1彩色多普勒超声诊断技术彩色…     

超声心动图在妊娠合并心脏病诊断中的应用

超声心动图在妊娠合并心脏病诊断中的应用赵红琴黄伟剑（温州医学院第一附属医院）孕产妇死于心脏病居非产科原因的首位［１］，常见为风湿性心脏病及先天性心脏病。超声心动图检查可鉴别先天性缺损类型、部位、程度、瓣膜病变类型及程度，心脏大小、收缩和舒张状态，肺动...     

TBX1基因多态性与先天性心脏病的相关性

目的探讨TBX1基因多态性与先天性心脏病(先心病)的相关关系。 方法选择2004-10—2005-03在哈尔滨医科大学附属第二医院住院的先心病患儿99例，对照组96名(与先心病患儿年龄相近的健康儿童)。应用小剂量DNA提取技术及采用ABI Prism SNaPshot方法,检测了先心病患儿和对照组儿童的TBX1基因多态性。 结果经χ2检验，TBX1基因各基因型频率在对照组、先心病组之间均无显著性差异(P>005)；各等位基因频率在两组人群中差异均无显著性意义(P>005)。 结论未发现TBX1基因多态性与先天性心脏病之间存在相关关系。     

142例胎儿唇腭裂的超声诊断与遗传因素分析

目的探讨胎儿唇腭裂的影像学特征与遗传基础。方法142例病例均接受产前超声系统检查,经过两级医生检查及会诊做出最终诊断。同时收集活产胎儿的胎儿脐带或引产胎儿的大腿肌肉组织,进行全基因组测序(whole genome sequening,WGS),以发现染色体数目异常和拷贝数异常(copy number variations,CNVs)。结果142例孕妇年龄分布为21~41岁,孕周为12~35周。142例胎儿中,男性94例,女性48例,男女比例为1∶0.51。根据唇腭裂的类型,单纯唇裂有84/142例(59.15%),唇裂合并其他系统畸形情况有31/142例(21.83%)。单纯唇腭裂有14/142例(9.86%),唇腭裂合并其他系统畸形情况有13/142例(9.15%)。9.2%(13/142)的胎儿有染色体数目异常,8.4%(12/142)的胎儿检出了致病性CNV。结论对CNVs的检测可以增加胎儿腭裂的遗传检测诊断率,在临床中应重视检测致病性CNVs。     

Protective effect of hyperemesis gravidarum for nonsyndromic oral clefts

OBJECTIVE: To evaluate whether hyperemesis gravidarum is associated with a decreased risk for nonsyndromic oral clefts and to examine the relationship between hyperemesis gravidarum, birth weight, and gestational age. METHODS: This was a population-based, matched case-control study of 1950 subjects with oral clefts (1368 with cleft lip with or without cleft palate; 582 with cleft palate) collected from the Hungarian Congenital Abnormality Registry and 1955 controls identified from the National Birth Registry. RESULTS: Fewer mothers of newborns with oral clefts had early-onset hyperemesis gravidarum than did mothers of controls (cleft lip with or without cleft palate: 83 cases and 121 controls, odds ratio [OR] = 0.67, 95% confidence interval [CI] 0.50, 0.89; cleft palate: 42 cases and 64 controls, OR = 0.63, 95% CI 0.42, 0.94). The use of dimenhydrinate was more common among mothers of subjects with cleft palate (OR = 2.47, 95% CI 1.11, 5.49), whereas iron seemed to have a protective effect against this condition (OR = 0.26, 95% CI 0.09, 0.80). Gestational age and birth weight were not significantly associated with hyperemesis gravidarum. CONCLUSION: This study suggests that hyperemesis gravidarum provides a protective effect against risk to oral clefts in newborns.     

10. Easily identifiable congenital malformations

Summary. At birth, the prevalence of easily identifiable congenital malformations was 14 per 1000 babies. Polydactyly was very common and cleft lip/cleft palate very rare as they are in other black populations. The prevalence of neural-tube defects was only 1.6 per 1000 babies and there was little to indicate that the socially disadvantaged were any more vulnerable than those with better living standards. As a group, congenital malformations contribute very little towards the poor maternal and fetal outcomes in Zaria.     

综合征性神经管缺陷3 798例分析

目的：探讨综合征性神经管缺陷（neural tube defects,NTDs）的发生形式和伴发畸形谱。方法：中国出生缺陷监测网采用以医院为基础的监测方法,收集1987-1995年间,孕28周到产后7d,伴各种出生缺陷的围产儿资料,包括活产、死胎和死产。结果：3498例综合征性NTDs,无脑、脊柱裂和脑膨出分别为997例、2394例和407例。伴发肌肉、骨骼系统,面、耳、颈部和泌尿生殖系统畸形的围产儿分别为51.3％,19.6％和9.3％。前5位高发畸形分别是马蹄内翻足、唇腭裂（唇裂合并腭裂）、腹裂、足外翻、足月睾丸未降。神经管缺陷的裂联合征（schisis-association）中,NTDs合并总唇裂（唇裂 唇裂合并腭裂）占67.5％,无脑合并腭裂占8.3％,无脑合并脐膨出占6.6％。综合征性NTDs患儿低出生体重儿发生率为36.9％,围产期病死率为71.2％,产前诊断率为33.1％。结论：为1/3的NTDs可伴发其他畸形。综合征性NTDs儿病死率高,预后差。     

Prenatal detection of facial clefts

OBJECTIVES: To determine (1) the antenatal detection rate for isolated cleft lip and/or cleft palate during the routine anomaly scan; (2) the correlation between prenatal diagnosis and postnatal findings, and (3) the association of apparently isolated cleft lip and/or cleft palate with other anomalies, in particular chromosomal abnormalities. METHOD: A population-based retrospective analysis of all cases of isolated cleft lip and/or cleft during an 8-year period in an academic teaching hospital in the UK. RESULTS: Thirty-nine cases of isolated cleft lip and/or cleft palate were identified among deliveries at the hospital. Twenty-eight cases had a routine anomaly scan. Fourteen cases were detected prenatally (sensitivity 50%). None of the isolated cleft palates was detected, while 14 of 20 cases of cleft lip (70%) were detected. One of the isolated cases of cleft lip was associated with trisomy 21, while 3 of the isolated cleft palate cases were associated with the Pierre Robin syndrome. In all cases, an antenatal diagnosis of cleft was confirmed following delivery or post-mortem examination (specificity 100%). CONCLUSIONS: Ultrasound is a useful tool in screening for cleft lip with or without cleft palate, but not for cleft palate alone. Even with an isolated cleft lip, there is an increased risk of chromosomal abnormality. The role of prenatal education and support is extremely important in the preparation of prospective parents and can help alleviate the shock which occurs when there is an unexpected cleft at birth.     

出生缺陷影响因素的病例对照研究

目的 探讨出牛缺陷的影响因素.方法 2009年4月1日-2010年3月31日,选择在青岛市妇女儿童医疗保健中心、青岛大学医学院附属医院、青岛市市立医院等75家医疗保健机构、孕龄为13周至产后7 d内发现的缺陷儿为出生缺陷组;选取同期无出生缺陷的健康新生儿作为对照组.采用病例对照研究方法,利用出生缺陷三级监测网络信息,以专门设计的出生缺陷影响因素病例对照调查表,对两组胎婴儿的父母进行问卷调查.结果 (1)青岛市妇女儿童医疗保健中心等75家医疗保健机构分娩围产儿数77 231例,其中分娩围产期出生缺陷儿466例,围产儿出生缺陷发生率为60.34/万.前6位的出生缺陷病因依次是先天性心脏病112例、总唇裂(唇裂、唇裂合并腭裂)85例、多指(趾)53例、神经管畸形38例、先天性脑积水37例、肢体短缩28例,共计353例,占全部出生缺陷儿的54.48%(353/648).(2)出生缺陷组母亲的大专及以上文化程度(25.6%)低于对照组(30.0%),两组比较,差异有统计学意义(P<0.05).(3)出生缺陷组中父母经常被动吸烟、经常饮酒、饲养宠物的比例高于对照组,两组比较,差异有统计学意义(P<0.05).(4)出生缺陷组母亲孕期有害化学物质及有害物理因素接触率(分别为13.9%及20.5%)与对照组(分别为1.1%及11.7%)比较,差异有统计学意义(P<0.01).出生缺陷组母亲孕期患感冒(34.3%)、发热(13.1%)及服用药物(33.8%)的发生率高于对照组(分别为13.5%、1.5%及9.9%),两组比较,差异有统计学意义(P<0.01).出生缺陷组母亲孕期有不良精神因素刺激的发生率(11.3%)高于对照组(1.4%),两组比较,差异有统计学意义(P<0.01).(5)出生缺陷组中有家族遗传病史者有19例(2.9%,19/648),对照组中无.两组比较,差异有统计学意义(P<0.01).出牛缺陷组中母亲有异常生育史者有89例(13.7%,89/648),对照组有31例(4.8%,31/650).两组比较,差异有统计学意义(P<0.01).(6)多因素条件logistic回归分析显示,母亲孕期接触有害化学物质(OR=13.46)、孕期患病(OR=3.37)、孕期服药(OR=2.20)、不良精神凶素刺激(OR=5.44)、孕期挑食与偏食(OR=1.90)、孕期贫血(OR=1.52)、多胎(OR=4.40)及父亲饮酒(OR=1.55)是出生缺陷发生的主要危险因素,而孕期补充钙、铁等微量元素及营养素是保护性因素(OR=0.45).结论 (1)主要出生缺陷疾病依次是先天性心脏病、唇裂、多指(趾)、神经管畸形、先天性脑积水及肢体短缩.(2)母亲孕期接触有害化学物质、孕期患病、孕期服药、不良精神因素刺激、孕期挑食与偏食、孕期贫血、多胎及父亲饮酒是出生缺陷发生的主要危险因素;而孕期补充钙、铁等微量元素及营养素是保护性凶素.(3)减少和控制孕期主要危险因素是预防出生缺陷的重要环节.

Abstract：

Objective To investigate the influence factors of birth defects. Methods The congenital malformational fetuses born from 13 week of gestation to 7 days after birth were selected as the study group between April 1st, 2009 and March 31st, 2010. The health born fetuses were set as control in the same period. Case-control and the three-level of monitor network of birth defects were used in the study in the participating 75 hospitals (Qingdao Women and Children's Medical Center, Affiliated Hospital of Medical College Qingdao University, Qingdao Municipal Hospital, etc.) . The study and control group's parents were interviewed by an uniformed questionnaire which was designed specially with influence factors of birth defects. Results (1) There are 466 congenital malformational fetuses in the total of 77 231 fetuses collected in 75 hospitals. The congenital malformational rate accounts for about 6. 034‰. The top six defect diseases were congenital heart disease (112 cases) , total harelip (cleft lip; cleft lip with palate; 85 cases) ,polydactyly (53 cases) , neural tube defects (38 cases) , congenital hydrocephalus (37 cases) and limb reduction defect (27 cases) in turn, which amounts to 353 cases (54.48% , 353/648). (2) Their mother education level in the birth-defect group (25. 6%) were significantly lower than that in control group (30. 0% , P < 0. 05). (3) The rate of passive smoking, drinking, raising pets of the parents in birth-defect group were significantly higher than that in control group (P < 0. 05). (4) The rate of exposure to harmful chemical and physical factors of mothers in birth defects group (13.9% and 20. 5% , respectively) was higher than that in control group (1.1% and 11.7% , respectively) , the difference between which were significant (P < 0. 01) . The rate of disease (34. 3%) , fever (13. 1%) , taking drugs (33. 8%) in pregnancy period in birth defect group were higher than that in control group (13. 5% , 1.5% and 9. 9% ,respectively) , the difference between which were significant (P <0. 01). The rate of bad moral irritation to the mother in pregnancy in birth defect group (11. 3%) was significantly higher than that in control group (1.4% , P<0.01). (5) There were 19 cases (2.9% , 19/648) with family heredity medical history in birth defect group, but there were none in the control group, the difference between which were significant (P<0. 01). There were 89 cases (13.7% , 89/648) with unusual birth history of their mothers in birth defect group, but there were 31 cases (4. 8% , 31/650) in control group, the difference between which were significant (P<0. 01). (6) Conditional Logistic Regression model was used for univalent and multivariate analysis. The results showed that main influence factors were identified as having important effect on birth defects, including mothers' exposure to harmful chemical factors (OR=13. 46) , disease (OR=3. 37) ,taking drugs (OR=2. 20) , exposure to bad moral irritation (OR=5. 44) , food-choosy (OR=1. 90) ,anemia (OR=1. 52) in gestational period, polyembryony (OR=4. 40) , father drinking (OR=1. 55) .While it was protective factors to supplement microelements such as the calcium iron and nutrient, etc. in pregnancy period (OR=0. 45). Conclusions First, the main birth defects were congenital heart disease, total harelip (cleft lip; cleft lip with palate) , polydactyly, neural tube defects, congenital hydrocephalus and limb reduction defect in turn. Second, the main influence factors identified as having important effect on birth defects were mothers' exposure to harmful chemical factors, ill, taking drugs, exposure to bad moral irritation, food-choosy, anemia in gestational period, polyembryony, father drinking. But it is protective factors to supplement microelements such as the calcium iron and nutrient, etc. in pregnancy period. Finally, it is the important part to prevent the birth defects by reducing and controlling dangerous factors in pregnancy period.     

Differential diagnosis and treatment of cheilognathopalatoschises

Cleft lip, alveolous and palate is the second frequent malformation in Europe with an incidence of 1 : 500. Pertaining to ontogeny it must be differentiated between cleft lip and alveolous and cleft palate. Cleft lip and cleft lip and alveolous can occur unilateral, right or left, or bilateral. Cleft bony palate can also occur unilateral, right or left, or bilateral, but cleft velum only in the median plane. Diagnostic and treatment of cleft lip and palate call for interdisciplinary cooperation between gynecologist/obstetrician, cranio-maxillo-facial surgeon, pediatrician, otorhinolaryngologist, orthodontist and logopedist. The schedule of primary cleft surgery in Germany is marked by a more-stage concept, in which at the end of the second year of life cleft lip and palate except cleft alveolous should be closed up. Despite of most careful surgery patients with cleft lip and palate can show functional and aesthetic disturbances. The functional disorders can affected masticatory function, speech, hearing and nasal breathing. Aesthetics disorders can be concerned to skeletal or soft tissue deformities of lip and nose. Operative corrections of bone and soft tissue can rehabilitate these patients entirely from functional and aesthetic view.     

A population-based case-control teratologic study of ampicillin treatment during pregnancy

OBJECTIVE: This was a study of the association between ampicillin treatment during pregnancy and prevalence of different congenital abnormalities. STUDY DESIGN: The paired analysis of case patients with congenital abnormalities and matched population control subjects was performed in the population-based Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Of 38,151 pregnant women who had babies without any defects (population control group), 2632 (6.9%) had been treated with ampicillin. Of 22,865 pregnant women who had offspring with congenital abnormalities (case patients), 1643 (7.2%) had been treated with ampicillin (crude odds ratio, 1.0; 95% confidence interval, 0.7-1.2). Of 812 mothers who were delivered of babies affected by Down syndrome (patient control subjects), 61 (7.5%) had ampicillin treatment, and these were also compared with the case group. RESULTS: The prevalence of ampicillin use during the second and third months of gestation, which is the critical period for most major congenital abnormalities, showed significant difference in the case-control pair analysis only for cleft palate (odds ratio, 4.2; 95% confidence interval, 1.4-16.3). This possible association was confirmed by the analysis of medically recorded ampicillin use and by the comparison of ampicillin treatment between the group with cleft palate and the patient control subjects. CONCLUSION: Treatment with ampicillin during pregnancy may pose little if any teratogenic risk in human beings. Only a higher prevalence of cleft palate was found after the ampicillin treatment during the second and third months of gestation. The lack of an experimental animal model and the lack of consistency with previous epidemiologic studies may indicate that even this apparent risk is not real and instead is a chance association; further investigation is therefore necessary.     

Alpha-tocopherol levels in mothers of children with cleft lip or with cleft lip and palate

OBJECTIVES: Environmental factors may play equally critical role as genes in facial embryogenesis. It was suggested that cleft palate occurring in association with cleft lip may result from environmental factors that affect development of both the lip and the palate. Cleft lip forms from the third through seventh week of embryonic development. During these period fetal nutrition is histotrophic, pressure of oxygen is low, genes for antioxidant enzymes are supressed and alpha-tocopherol play an essential role in the fetal tissues antioxidant capacity. Cleft palate forms from the fifth through twelfth weeks of gestation, when hemonutrition and antioxidant enzymes are developing, and hypothetical deficiency of tocopherol is not so crucial. AIM: The goal of the study was to investigate concentrations of alpha-tocopherol in women who gave birth to a child with cleft lip and mothers of children with cleft lip and palate. MATERIAL AND METHODS: Blood samples from 31 healthy mothers of children with isolated cleft lip (CL) and 29 healthy mothers of children with isolated cleft lip and palate (CLP) were collected. Fasting plasma alpha-tocopherol concentrations were measured by the high performance liquid chromatography. Kolmologorov-Smirnov test with Lilefors correction and k-means cluster analysis were applied to determine differences between the groups of women. RESULTS: We found that alpha-tocopherol concentrations were lower in CL compared to CLP, but the difference did not achieve level of statistical significantly (medians: 15.8 micromol/L vs. 20.0 micromol/L; p = 0.066). There were identified three clusters of alpha-tocopherol concentrations: 14.0 micromol/L (19CL+8CLP), 19.6 micromol/L (8CL+13CLP), and 21.1 micromol/L (4CL+8CLP). The distribution of results to the clusters was dependent on type of the orofacial cleft (chi squared = 6.95 with 2 degrees of freedom, p = 0,031). CONCLUSIONS: Analysis for environmental risk factors should be performed separately for cleft lip and cleft lip and palate because these two conditions appear to be etiologically distinct. The role of a higher periconceptional intake of alpha-tocopherol in reduction of risk of giving birth to a child with cleft lip requires further research.