Epidemiology of facial clefts.

Data from the Glasgow Register of Congenital Malformations were used to investigate the epidemiology of congenital facial clefts over the period 1974-85. Facial clefts were registered in 247 infants representing a prevalence of 1.56 per 1000 total births. Cleft palate was more common than cleft lip, with cleft lip and palate occupying an intermediate position. More than half of the infants with facial clefts had associated defects. Males predominated for cleft lip; females for cleft palate. Cleft lip (alone) was more common in babies born to women aged 35 years and over. Sudden declines in registered prevalence were observed in 1978 and 1985. Clefts were more common in socioeconomically deprived areas of the city. In comparison with data from elsewhere, Glasgow seems to have a low rate of cleft lip, a high rate of cleft palate, and a high rate of associated defects. Many of the findings of cleft palate in Glasgow could be explained by the interaction of an unidentified environmental teratogen with a susceptible population.     

Clinical Aspects of Cleft Lip and Cleft Palate Patients Treated at Kanazawa Medical University Hospital from 1974 to 1993*

ABSTRACT Currently, clefts of the lip, alveolus, and palate are thought to be the most common congenital malformations. In this study, we examined 1,565 cases of clefts we treated over the last 18 years, in order to summarize the clinical features and to evaluate the treatment outcomes. This study involved 589 cleft lip (CL) cases, 576 cleft lip and palate (CLP) cases, 286 cases of cleft palate (CP), 81 cases of submucous CP and 33 cases of CL and submucous CP. The familial incidence was 11.1% (174 cases). Overall, the average incidence of associated congenital abnormalities was 27.9%. Approximately half of the patients with CP alone or with submucous CP were found to have additional congenital malformations. Standeard surgical techniques for unilateral and bilateral CL cases were the Skoog's and Millard's methods, respecively, which resulted in satisfactory outcomes. As a primary operation for CP, pushback procedure was performed using a partial mucosal flap from the palate. Using this procedure 96.5% of 455 cases achieved satisfactory nasopharyngeal closure. The main objective in the treatment of CL patients is not only the repair of growing tissues but also appropriate morphological, functional and psychological reconstruction for the purpose of correcting growth inhibitory problems caused by anatomical malposition. Surgical procedures for CP patients are designed to meet several needs: correction of anatomical abnormalities of the palate and pharynx, achievement of proper nasopharyngeal closure necessary for normal phonation, prevention of growth disturbances of the maxilla, improvements in hearing and auditory tube function, and normalization of occlusion.     

Does maternal cigarette smoking during pregnancy cause cleft lip and palate in offspring?

To investigate the relationship between maternal cigarette smoking and the risk of oral clefts in offspring, we examined data from the Atlanta Birth Defects Case-Control Study, which included 238 cases of cleft lip with or without cleft palate and 107 cases of cleft palate ascertained by the Metropolitan Atlanta Congenital Defects Program from 1968 through 1980. In all, 2809 infants who served as controls were frequency matched to cases by race, period of birth, and hospital of birth. Maternal periconceptional exposures to smoking were investigated through use of a structured questionnaire. Smoking exposure was defined as reported maternal smoking during the periconceptional period (from 3 months before conception to 3 months after pregnancy began). Offspring of smoking mothers were 1.6 and 2.0 times more likely than offspring of nonsmoking mothers to have isolated cleft lip with or without cleft palate and cleft palate, respectively. On the other hand, offspring of smoking mothers were not at increased risk of having cleft palate or cleft lip with or without cleft palate that are associated with other defects. Adjustment for potential confounding variables did not alter these results. A relatively modest effect of smoking may be explained by the presence of underlying etiologic heterogeneity in oral clefts and differential susceptibility to smoking. Because of the inconsistencies in the literature on the relationship between smoking and oral clefts, these results suggest the need to refine oral clefts into more homogeneous subgroups in epidemiologic studies of these defects.     

Higher risk of orofacial clefts in children born to mothers with angina pectoris: A population‐based case‐control study

Previously an unexpected association of maternal angina pectoris (MAP) during pregnancy with a higher risk of orofacial clefts in their children was found. There were three objectives of this study: (i) to evaluate the validity of MAP‐diagnoses in the previous study and the recent history of mothers with MAP in a follow‐up study; (ii) to estimate the prevalence of other congenital abnormalities in the offspring of mothers with MAP; and (iii) to analyze the possible effect of confounders for the risk of orofacial clefts. The large dataset of population‐based Hungarian Case‐Control Surveillance System of Congenital Abnormalities, 1980–1996 was evaluated including 22 843 cases with congenital abnormalities and 38 151 controls without any defect. Twenty‐two cases (0.10%) and 12 controls (0.03%) were born to mothers with medically recorded MAP (odds ratio [OR] with 95% confidence interval [CI]: 3.7, 1.8–7.3). Of 22 cases, six had isolated cleft lip ± palate (OR with 95% CI: 13.3, 4.9–35.9) and two were affected with isolated cleft palate (OR with 95% CI: 10.5, 2.3–47.6). The diagnosis of MAP was confirmed in seven women visited at home in 2009–2010, two had recent myocardial infarction and five were smokers. There was no higher risk for other congenital abnormalities. In conclusion the higher risk of orofacial clefts was confirmed in the children of mothers with MAP and smoking may trigger the genetic predisposition of both MAP and orofacial clefts. However, the number of cases was limited and therefore further studies are needed to confirm or reject this theoretically and practically important observation.     

Monitoring of Congenital Malformations in Tottori, 1974–1983*

ABSTRACT The prevalence and distribution of the congenital malformed infants and the neurocutaneous syndrome patients who were born in Tottori Prefecture, Japan between 1974 and 1983 were reported. The average prevalence of 581 cases with congenital malformations at birth was 1.21 per 100 births (live and stillbirths), which was similar to other populations in Japan. The prevalence values of cleft lip, cleft palate and cleft palate with cleft lip in Tottori was somewhat higher than in Kanagawa and Osaka districts. Frequencies of tuberous sclerosis, Sturge-Weber syndrome and neurofibromatosis in live births were about 1:22,000,1:65,000 and 1:2,200, respectively. These data in Japanese population were considered to be about the same as those reported in Caucasian populations.     

Epidemiological Approaches to Identify Risk Factors for Human Congenital Malformations: Descriptive and Analytical Epidemiology of Cleft Lip and/or Palate in Japan*

Abstract This paper described three major epidemiological approaches to explore etiological clues to and risk factors for human congenital malformations, taking cleft lip and/or palate as an example. (1) An analysis of mortality statistics demonstrated an apparently downward trend of infant mortality from cleft lip and/or palate over the recent three decades in Japan. This particular finding was found to be plausibly ascribable to changing clinical assignment of causes of death from “cleft lip and/or palate” to “congenital heart diseases” or “multiple anomalies, syndromes or chromosome abnormalities”, when previous reports on incidence rate and autopsy series were examined. (2) A case-control study of 194 infants with cleft lip and/or palate (cases) and 194 normal infants (controls), who were matched to cases for sex, maternal age to within one year, birth order and residential area, yielded the following major findings, (a) A significantly increased risk was associated with parental highest educational attainment of less than 19 years, parental occupation of unskilled/service workers, positive family history of cleft lip and/or palate, positive past history of artificial abortion, maternal smoking habits at first trimester, and maternal episodes at first trimester of suffering from any diseases and of ingesting any drugs, (b) A significantly decreased risk was linked with frequent maternal intake at first trimester of such animal proteins as meats, fishes and shells, eggs and milk, (c) Maternal drinking habits and radiation exposures, and frequent maternal ingestion of Japanese/black tea were not associated. (d) Maternal coffee drinking at first trimester significantly elevated the risk, but turned to be unrelated when maternal smoking habits were statistically corrected. (3) A cohort study of approximately 10,000 pregnants, which is ongoing from April 1989 in Nagoya and aims to disclose the associations of parental life-style habits with general pregnancy outcomes including major congenital malformations, was briefly discussed.     

Epidemiology of facial clefting.

An analysis was performed of patients with facial clefts notified between 1960 and 1982 to the Liverpool Congenital Malformations Registry. From 1960-82 there were 325 727 births in the area surveyed and 544 cases of facial clefting were notified. When 88 patients with recognised syndromes and multiple congenital anomalies were excluded, the overall prevalence of facial clefts alone was 1.4 per 1000 total births. This group was then classified further into 137 cases of cleft lip alone, 166 cases of cleft lip and palate, and 153 cases of cleft palate alone. The prevalence of these groups per 1000 total births is 0.42, 0.51, and 0.47 respectively. There were some fluctuations in annual prevalence with rises being observed in the mid and late 1960s and mid and late 1970s. There was a noticeable male predominance in the cleft lip and cleft lip and palate groups of 1.52:1 and 1.98:1 respectively, with a 1:1 ratio in the cleft palate group. There were no significant differences in birthweight and mean maternal age in the three groups. In the cleft palate group, however, there was a significant trend towards an increase in the frequence of conception in the second half of the year. There was a maternal history of epilepsy in 4.4% of the cleft lip and 3% of the cleft lip and palate groups but only in 1 patient (0.6%) in the cleft palate group. The study illustrates the importance of environmental factors in the aetiology of facial clefting.     

Congenital malformations among infants whose mothers had gestational diabetes or preexisting diabetes

BACKGROUND: Diabetes type 1 is associated with an increased risk for infant congenital malformations. It is debated whether this is true also at gestational diabetes. AIMS: To study occurrence of congenital malformations in infants whose mothers had preexisting or gestational diabetes. STUDY DESIGN: A register study covering over 1.2 million Swedish births in 1987-1997 based on the Swedish health registries. SUBJECTS: We identified from the Medical Birth Registry 3864 infants born of women with preexisting diabetes and 8688 infants born of women with gestational diabetes. OUTCOMES MEASURES: Congenital malformations identified in the Medical Birth Registry, the Registry of Congenital Malformations, and the Hospital Discharge Registry. The rates of congenital malformations among these infants was compared with the population rates. RESULTS: At preexisting diabetes, the total malformation rate was 9.5% while the rate at gestational diabetes was similar to the population rate, 5.7%. At preexisting diabetes, certain conditions were more common than expected: orofacial clefts, cardiovascular defects, oesophageal/intestinal atresia, hypospadias, limb reduction defects, spine malformations, and polydactyly. For some of these conditions, an excess was found also for infants whose mothers had gestational diabetes. Infants with multiple malformations were in excess at preexisting diabetes but not at gestational diabetes but the specific type of malformations involved were similar in the two diabetes groups. CONCLUSIONS: It is suggested that in the group of gestational diabetes exists a subgroup with an increased risk for a diabetes embryopathy, perhaps due to preexisting but undetected diabetes type 2.     

Delayed detection of cleft palate: an audit of newborn examination

Aims

To identify prevalence of delayed detection of cleft palate, and associated factors that could lead to improved identification at neonatal clinical examination.

Methods

Audit of hospital notes, parental questionnaire incorporating open ended questions, and telephone questionnaire of junior doctors in the referring hospitals incorporating fixed choice questions.

Results

Of 344 cleft palate patients without cleft lip or submucous cleft palate, the day the cleft was detected was recorded in 92%. Delayed detection, after the first day, was 28% overall, distributed as 37% with isolated cleft palate and 23% with syndromic cleft palate. Narrow V shaped clefts were more likely to be delayed in detection compared with broad U shaped clefts, as were soft palate clefts compared with hard palate clefts. Five with isolated cleft palates were not detected until after the first year. Babies born at home were unlikely to be detected on day 1. Symptoms were significantly increased in the delayed detection group for feeding problems and nasal regurgitation. A telephone questionnaire of trainee paediatricians in referring units revealed that digital examination was more commonly practised than visual inspection, and few recalled receiving specific instruction on examination of the palate.

Conclusion

Delayed detection of cleft palate was not uncommon, and the features of those more likely to be missed suggested digital examination was related. Trainee doctors and midwives should be instructed to inspect visually using a light and tongue depressor, then digitally if submucous cleft palate is suspected.     

非综合征型唇腭裂易感基因位点研究进展

非综合征型唇腭裂是一种常见的出生缺陷,病因复杂,目前普遍认为是遗传因素和环境因素共同作用的结果.先天性唇腭裂易感基因是自全基因组测序以来的研究热点,筛选出的众多候选基因正不断被基因位点多态性检测、病例对照研究、Meta分析等方法验证,但结果迥异.该文就近年来研究较多的非综合征型唇腭裂易感基因以及环境因素与唇腭裂相互关系方面的研究进展展开综述.     

Simplified method of feeding infants born with cleft palate with or without cleft lip.

Most infants born with a cleft palate with or without cleft lip are undergrown and have histories of difficult feeding. For the past two years, all of the infants born with isolated cleft palate with or without cleft lip, referred to the Boston Floating Cleft Palate Clinic, were fed using a simplified method. A standard nipple that was cross cut and a standard glass baby bottle were used. The infants were fed in the sitting position and burped frequently. Data indicating that nutrition in these infants is adequate as judged by weight gain was provided.     

Emotion self-regulation in preschool-aged children with and without orofacial clefts

Emotion self-regulation is an important developmental task in the preschool period that is related to children's emotional and behavioral adjustment in early childhood. Emotion self-regulation and its relation to later adjustment has not been studied in children born with orofacial clefts, despite their risk for externalizing and internalizing behavior problems. Eighty-three 5-year-old children with cleft lip and palate, isolated cleft palate, or no cleft condition were videotaped during a laboratory disappointment situation. Results showed that children in the cleft group expressed less disappointment than children in the comparison group. Longitudinal analyses revealed that parenting stress measured when the children were 2 years of age predicted Expressed Disappointment at age 5 years, which, in turn, predicted severity of behavior problems at age 7 years. Although tentative, results indicate that control over mild negative affect may be a protective factor for children with clefts, buffering the effects of early stress on the development of later behavioral and emotional problems. Thus, interventions that reduce parenting stress and enhance children's emotion regulation strategies may decrease the risk for later psychological problems in this population.     

Clinical Analysis of the Cleft Patterns of Lip and Palate

The patterns in the cleft lip and palate were classified in great detail, and the point of center of the clefts in this disease was speculated. The purpose of the present study was to establish the basic data for classifications of epidemiological surveys in the future. The subjects were 377 patients with cleft lips and palates who visited the Second Department of Oro-Maxillo-Facial Surgery, Aichi-Gakuin University Hospital. The models of cleft lip and palate divided into 17 segments prepared for an analysis of cleft patterns. And as consequence, the following results were obtained.     

Three-dimensional ultrasonographic imaging of fetal tooth buds for characterization of facial clefts.

The purpose of this prospective study was to investigate whether the antenatal characterization of fetal facial clefts can be improved by three-dimensional ultrasonographic visualization of fetal tooth buds. Between January 1996 and June 1998, seventeen consecutive fetuses with facial clefts were examined for fetal maxillary tooth buds in the cleft area using three-dimensional multiplanar reconstruction. It was possible in all cases to classify the clefts either as cleft lip alone or unilateral cleft lip and palate or bilateral cleft lip and palate. Three-dimensional computed tomography and histological jaw sections of three stillborn infants were produced in order to examine the correlation between the sonographic, radiographical and histological findings. The prenatal characterization of the facial clefts by means of a visualization of the tooth buds showed to be accurate postnatally in all cases. The sonographic proof of tooth buds might gain increasing importance as this technique seems to facilitate and improve the prenatal classification of suspected facial clefts.     

Cleft lip and palate in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin: a morphological in vivo study

It is well-known that TCDD (2,3,7,8, tetrachloridedibenzo-p-dioxin) induces cleft palates (CPs) in pregnant C57BL mice. However, it is unclear if TCDD is a possible teratogen for cleft lip. We examined maxillofacial malformations including cleft lip in three animal strains: A/J mice, C57BL/6J mice and ICR mice. The A/J mouse develops cleft lip and palate spontaneously at a 5-10% rate. TCDD was administered in olive oil on gestation day (GD) 12.5 with gastric tubes at 10 microg/kg, 20 microg/kg, or 40 microg/kg to examine the dose-response, and on a single day from GD 8.5-14.5 to examine the timing effects of TCDD administration on lip and palate formation. Furthermore, the palatal shelf movements during GD 8.5-14.5 were observed with a stereoscopic microscope. All embryos had cleft palates when the TCDD was administered just before palatogenesis (GD11.5-GD12.5). With respect to the TCDD effects, there were large differences among the strains. In the A/J mice, the difference between a lethal dose and a dose that could induce a cleft palate was close. Cleft lips were not induced, even when the TCDD was given just before labiogenesis. Morphologically, both palatal shelves contacted perfectly along their lengths, but separated and formed cleft palates. In conclusion, TCDD is a strong inducer of cleft palates, and interferes with the fusion phase of the secondary palate, but has no effect on the lip.     

A heritable cause of cleft lip and palate—Van der Woude syndrome caused by a novel IRF6 mutation. Review of the literature and of the differential diagnosis

Background  

Orofacial clefts are common congenital malformations usually characterized by a multifactorial etiology. These heterogeneous defects comprise cleft lip (CL), CL with cleft palate (CL/P), and cleft palate, sometimes observed in recognizable syndromes, with mendelian, chromosomal, or environmental pathogenesis. The Van der Woude syndrome is a mendelian CL/P, accounting for about 2% of all cases and caused by mutations in the interferon regulatory factor 6 (IRF6) gene, located on 1q32.2 chromosome.     

Incidence and Familial Occurrence of the Congenital Anomalies of the Face, Hand and Foot

We made an epidemiological study of congenital anomalies of the face, hand and foot in newborns from 1973 to 1992 in Miyagi Prefecture which has a population of about two million. In these twenty years 579,766 babies were born in Miyagi Prefecture. Out of these newborns 3,416 babies with 3,759 congenital anomalies of the face, hand and foot were registered. Of all registered congenital anomalies, face anomalies were most commonly encountered, followed by hand and foot anomalies. Among face anomalies, in order of frequency, accessory ear was the most common, next cleft lip with or without cleft palate, cleft palate alone, cryptotia and microtia. The occurrence ratio per 10,000 live births was 9.6 in accessory ear, 6.7 in cleft lip, 6.1 in cleft lip with cleft palate, 4.2 in cleft palate alone, 2.9 in cryptotia, and 1.8 in microtia. In hand and foot anomalies, polydactyly was the most common and syndactyly the next. Incidence ratio of polydactyly was 5.8 in the hand and 6.4 in the foot. Polydactyly was the most frequent in the preaxial ray in the hand and in the postaxial ray in the foot. About half of cases of postaxial polydactyly the foot was associated with syndactyly between the fourth and fifth toe. In addition, we reported on variation of the incidence ratio and familial occurrence of congenital anomalies of the face, hand and foot.     

Postoperative speech development based on cleft types in children with cleft palate

BACKGROUND: The purpose of this historical cohort study was to compare the speech development of children with three types of cleft palate while controlling for some confounding factors. METHODS: Subjects included 28 children with bilateral cleft lip and palate (BCLP), 74 with unilateral cleft lip and palate (UCLP), 33 with isolated cleft palate (ICP), and 168 normal control children. Children with cleft palate attended a speech clinic in Fukuoka, had attained adequate velopharyngeal function after palatoplasty carried out within 18 months after birth, and had no syndromic diseases, persistent hearing loss, mental retardation, or central nervous system problems. RESULTS: Children with BCLP began using two-word sentences later than other children (3 months, P<0.01). However, the difference based on sex was also statistically significant. Female patients started using two-word sentences earlier than male patients (2 months, P<0.01). Children with BCLP had lower verbal scores on the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) than other children (12.4-14.9 points, P<0.01). There was no significant difference based on sex. CONCLUSIONS: The results of this research indicate the following: speech development of children with ICP and UCLP was similar to that of normal children; however, speech development of children with BCLP was delayed compared with other children with or without cleft palate.     

Noncardiac Malformations at Major Congenital Heart Defects

Using the Swedish Cardiology Registry and the Registry of Congenital Malformations, and after excluding infants with a known chromosomal anomaly, data on 397 infants (15%) born during the period 1981–1990 with a major cardiac defect and at least one noncardiac malformation were analyzed. No clear-cut association appeared between specific heart defects and major groups of noncardiac malformations except for a possible relation between spleen anomalies and endocardial cushion defects. Specific associations also appeared between common truncus and limb reduction defects and between transposition of the great vessels and situs inversus. However, the small numbers of infants in the latter groups and the large number of tested hypotheses make it difficult to exclude chance associations.