Since Dr. Fogh-Andersen's legendary 1942 thesis, the Danish facial cleft population has been one of the most extensively studied in terms of epidemiology and genetic-epidemiology. The etiology of cleft lip and/or palate (CLP) is still largely an enigma, and different results concerning environmental and genetic risk factors are obtained in different countries and regions. This may be due to etiological heterogeneity between settings. Therefore, an in-depth studied area with an ethnically homogeneous population, such as Denmark, has provided one of the best opportunities for progress in CLP etiological research. The present review summarizes epidemiological and genetic-epidemiological studies conducted in the 20th century Danish facial cleft population. Furthermore, analyses of sex differences, time trends and seasonality for more than 7000 CLP cases born in Denmark in the period 1936 to 1987 are presented. The review also points toward the excellent opportunities for continued etiological CLP research in Denmark in the 21st century using already established resources and an on-going prospective cohort study of 100,000 pregnant women.
BACKGROUND. The rate of recurrence of a broad range of birth defects may decrease among women who change residence after the birth of their first infant. The aim of the present study was to determine the effect of changing residence on the recurrence of congenital facial-cleft defects. METHODS. We identified 4189 women who had infants with facial-cleft defects by linking a data base comprising the records of children with facial clefts born between 1952 and 1987 with the Central Person Registry in Denmark. Among the 4189 mothers, 1902 each had additional children after the first child with a facial-cleft defect. A total of 2692 younger siblings were identified. We compared the proportion of infants with facial-cleft defects among the younger siblings between mothers who had changed municipalities or sexual partners and those who had not. RESULTS. Changing the municipality of residence did not decrease the frequency with which facial-cleft defects recurred in younger siblings. Among the 907 infants of mothers who changed municipalities but not partners, 29 (3.2 percent) had facial-cleft defects, as compared with 48 (3.4 percent) of 1425 infants of mothers who changed neither municipality nor partner (relative risk, 0.9; 95 percent confidence interval, 0.6 to 1.5). However, a change of partner reduced the recurrence risk significantly. Among 236 infants of mothers who changed partners, 1 (0.4 percent) had a facial-cleft defect, as compared with 77 (3.3 percent) of 2350 infants of mothers who did not change partners (relative risk, 0.1; 95 percent confidence interval, 0.02 to 0.9). CONCLUSIONS. Recurrence of facial-cleft defects is not linked to the residence of the mother, but having a different partner reduced a woman's risk of having a second child with this defect.
The focus of this study was to determine whether there were any significant differences in academic achievement between students with a cleft and the general population of Swedish students at the typical time of graduation from compulsory school (usually 16 years of age).
A retrospective population-based study. Data were obtained from the Swedish Medical Birth Register for the years 1973 through 1986 and were linked to the Swedish School-Grade Register.
A total of 511 individuals with cleft palate (CP), 651 individuals with cleft lip (CL), and 830 individuals with cleft lip and palate (CLP) were compared with a control group consisting of 1,249,404 individuals.
(1) Not receiving school leaving certificate; (2) odds of receiving lowest grade and reduced odds of receiving a high grade in the following subjects: (a) Mathematics, (b) English, (c) Swedish, (d) Physical Education, and (e) grade point average (GPA).
The group with cleft had higher odds of not receiving leaving certificates in comparison with the general population. They also had higher odds of receiving the lowest grade and/or reduced odds of receiving a high grade in the subjects analyzed together, with strong evidence of lower GPA in comparison with the general population. Individuals with CP were affected the most, followed by individuals with CLP; least affected were individuals with CL.
This study clearly indicates that adolescents with cleft lip and/or palate in Sweden experience significant deficits in their educational achievements in compulsory school.
Cleft lip with or without palate (CLP) can be diagnosed antenatally through ultrasound, and may be categorised as apparently isolated versus associated with other malformations. Limited data exist on the long-term outcomes following antenatal diagnosis of apparently isolated CLP.
This study examined the long-term post-natal outcomes of CLP when found in isolation antenatally, in order to determine the rates of unexpected additional anomalies, developmental delay or genetic syndromes.
A retrospective chart review of antenatal and post-natal medical charts was completed for a ten-year period between January 2000 and December 2009. At least 2 years of available post-natal clinical information was required for inclusion in the study.
A total of 97 cases of antenatally isolated CLP were ascertained. Fifteen pregnancies were terminated. Follow-up data were available for 81 liveborns, though 4 were lost to follow-up prior to 2 years of age. Twelve of the 77 children meeting study criteria were identified to have other major malformations and/or developmental disability either later in the pregnancy or post-natally. Findings included familial clefting syndromes, trisomy 21, autism spectrum disorders, brain malformations, fetal alcohol syndrome and Kabuki syndrome, among other findings. Another 11 children had additional anomalies of minor impact. Examples of findings include a perimembranous ventricular septal defect, mild unilateral optic nerve hypoplasia, mild pulmonary artery stenosis with a small atrial septal defect, and transient delays in fine and gross motor skills. No children with clefting of the lip only had major additional diagnoses.
The existence of a major gene (or genes) that contributes significantly to the familial clustering of cleft lip with or without cleft palate (CL(P)) has been suggested by genetic epidemiology studies and supported by patient-control genotype association studies with a candidate gene. Here we present an analysis of the familial recurrence risk data for isolated cleft palate (CP) and show that an oligogenic model with six genes of equal effect fits the data best. The discrimination between alternative models is, however, poor and a major locus that explains half of the familial recurrence is plausible. The prospects for identification of susceptibility loci for CP are discussed.
OBJECTIVE: Infants with cleft lip and palate may often have other associated congenital defects although the reported incidence and the types of associated malformations vary between different studies. The purpose of this investigation was to assess the prevalence of associated malformations in a geographically defined population. METHODS: The prevalence of associated malformations in infants with clefts were collected prospectively between 1975 to 1992 on all infants born in greater Stockholm, Sweden. The patient records were also compared with data from the National Malformation Registry and other hospital records if any. RESULTS: Of the 616 cleft infants (367 boys, 249 girls) born during this period, 21% had associated malformations that either required follow-up or treatment. Associated malformations were more frequent in infants who had both cleft lip and palate (28%) than in infants with isolated cleft palate (22%) or infants with isolated cleft lip (8%). Malformations of the upper or lower limbs or the vertebral column were the most common other anomalies and accounted for 33% of all associated defects. Twenty-four percent of associated malformations were in the cardiovascular system and congenital heart disease was the most common isolated associated malformation. Fifteen percent of all associated malformations were multiple and they were frequently associated with mental retardation or chromosomal anomalies. Twenty-two percent of infants with associated malformations were born preterm, compared with an expected 5% incidence of preterm delivery in Sweden. CONCLUSION: A more extensive cleft seems to be associated with a higher risk for associated malformations. Although many associated congenital defects can be detected at a physical examination, the high prevalence of congenital heart disease (16 times that of general population) may justify a routine echocardiographic screening.
By January 1998, most of Canada's cereal grain products were being fortified with folic acid. Among 336963 women who underwent antenatal maternal serum screening, the prevalence of orofacial clefts did not change from before (1.15 per 1000) to after (1.21 per 1000) food fortification (prevalence ratio, 1.06; 95% confidence interval, 0.86-1.30).
To determine the prevalence of dental caries and enamel defects in 5- and 10-year-old Swedish children with cleft lip and/or palate (CL(P)) in comparison to non-cleft controls.
The study group consisted of 139 children with CL(P) (80 subjects aged 5 years and 59 aged 10 years) and 313 age-matched non-cleft controls. All children were examined by one of two calibrated examiners. Caries was scored according to the International Caries Detection and Assessment System (ICDAS-II) and enamel defects as presence and frequency of hypoplasia and hypomineralization.
The caries prevalence among the 5-year-old CL(P) children and the non-cleft controls was 36% and 18%, respectively (p
OBJECTIVE: The aim of this project was to assess whether any changes in the birth prevalence of cleft lip with/without cleft palate (CL[P]) occurred in Denmark during the period 1988 through 2001. In this period an official recommendation of a supplementation of folic acid to pregnant women was introduced; furthermore, smoking among pregnant women decreased considerably. DESIGN AND SETTINGS: There are few places in which ecological studies of oral clefts are possible. Denmark provides a particularly good setting for this kind of study because of a high ascertainment and a centralized registration of subjects with cleft over the last 65 years. PARTICIPANTS: Cleft occurrence in Denmark from 1936 to 1987 has previously been reported. Here we extend the study to include all live-born children with oral clefts born in Denmark in 1988 through 2001. Among a total of 992,727 live births, 1332 children with CL(P) were born during this period. RESULTS AND CONCLUSIONS: The birth prevalence of CL(P) in Denmark has previously been found to be constant in the period 1962 through 1987, with a frequency of 1.4 to 1.5 per 1000 live births. This study showed a similar occurrence in 1988 through 2001 (birth prevalence = 1.44 per 1000 live births, 95% confidence interval = 1.37 to 1.52). The introduction of folic acid and the decrease in smoking prevalence among pregnant women do not seem to have reduced the birth prevalence. This may be due to noncompliance with the folic acid recommendation and/or only a weak causal association between folic acid and smoking and occurrence of CL(P).