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.
The aetiology of abortions and calf mortality in 65 Danish cattle herds consisting of both dairy and beef breeds during a 1-year period is described. All observed aborted foetuses, still-born calves, and calves dying before 6 months of age were necropsied, and relevant microbiological examinations were performed. A total of 240 calves and 66 abortions were submitted corresponding to a calf mortality rate of 7%. The abortion frequency could not be calculated. 43% of the calves died at day 0, while 22% were aborted, 15% died during the first week of life, 9% died from 1 to 4 weeks of age, and 11% died at the age of 1 to 6 months. The most common cause was neonatal pulmonic atelectasis (stillbirth) followed by foetal infections, pneumonia, and septicaemia.
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.
Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment.
Among 77,885 twins in the Danish Twin Registry, 155 of the most BW-discordant MZ twin pairs (median BW difference 0.5 kg) were assessed using a 2 h oral glucose tolerance test with sampling of plasma (p-)glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. HOMA for beta cell function (HOMA-ß) and insulin resistance (HOMA-IR), and also insulin sensitivity index (BIGTT-SI) and acute insulin response (BIGTT-AIR), were calculated. Subgroup analyses were performed in those with: (1) double verification of BW difference; (2) difference in BW >0.5 kg; and (3) no overt metabolic disease (type 2 diabetes, hyperlipidaemia or thyroid disease).
No intra-pair differences in p-glucose, insulin, C-peptide, incretin hormones, HOMA-ß, HOMA-IR or BIGTT-SI were identified. p-Glucose at 120 min was higher in the twins with the highest BW without metabolic disease, and BIGTT-AIR was higher in those with the highest BW although not in pairs with a BW difference of >0.5 kg.
BW-discordant MZ twins provide no evidence for a detrimental effect of low BW on glucose metabolism in adulthood once genetic factors and rearing environment are controlled for.
In the county of Fyn (about 500,000 inhabitants) which is a well defined and representative 10% sample of the total Danish population, 15 total birth cohorts were scrutinized for the occurrence of anorectal malformations (ARM). All the patients were followed until the age of 7 or death. In a total of 96,073 births, 29 cases were observed; one concordant monozygotic pair was counted as one case. The study showed the point prevalence at birth to be 3.0 per 10,000; almost the same frequency has been found in Sweden whereas other figures from Europe and North America are lower. Children with ARM have in general a poor prognosis, largely due to the many associated anomalies. In this material, 11 of 12 isolated ARM cases survived until age 7, but five of these had significant handicaps. Out of 17 probands with associated anomalies, only seven survived until age 7, all of them having some handicap. This group of patients spent at least 15 times more days in hospital than an age-matched group from the same region until age 7, and they underwent a considerable number of operations. The study showed an increased frequency of chromosome anomalies among children with ARM.
Thirty-four mothers to infants seriously infected with group B streptococci (GBS) were investigated for G1m (1) and G3m(5) allotype markers. The frequency of Gm (1, -5) was 14.7%, of Gm(1,5) 20.6% and Gm (-1, 5) 64.7%. There was a marked deficit Gm (1) individuals and the distribution significantly differed from that in the normal Swedish populations.
To investigate whether the frequency of carriers of mutations in the HFE gene associated with hereditary hemochromatosis diminishes with age as an indication that HFE mutations are associated with increased mortality. It is of value in the debate concerning screening for hereditary hemochromatosis to determine the significance of heterozygosity.
Genotyping for mutations in exons 2 and 4 of the HFE gene using denaturing gradient gel electrophoresis in 1784 participants aged 45 to 100 years from 4 population-based studies: all 183 centenarians from the Danish Centenarian Study, 601 people aged 92 to 93 years from the Danish 1905 Cohort, 400 aged 70 to 94 years from the Longitudinal Study of Aging Danish Twins, and 600 aged 45 to 67 years from a study of middle-aged Danish twins.
All participants (N=1784) were screened for mutations in exon 4, and a trend toward fewer heterozygotes for the C282Y mutation-the mutation most often associated with hereditary hemochromatosis-was found. This was significant for the whole population (P=.005) and for women (P=.004) but not for men (P=.26). A group of 599 participants was screened for mutations in exon 2, and there was no variation in the distribution of mutations in exon 2 in the different age groups.
In a high-carrier frequency population like Denmark, mutations in HFE show an age-related reduction in the frequency of heterozygotes for C282Y, which suggests that carrier status is associated with shorter life expectancy.
Comment In: Arch Intern Med. 2002 May 27;162(10):1196-712020197
Behavior genetic designs and analysis can be used to address issues of central importance to demography. We use this methodology to document genetic influence on human fertility. Our data come from Danish twin pairs born from 1953 to 1959, measured on age at first attempt to get pregnant (FirstTry) and number of children (NumCh). Behavior genetic models were fitted using structural equation modeling and DF analysis. A consistent medium-level additive genetic influence was found for NumCh, equal across genders; a stronger genetic influence was identified for FirstTry, greater for females than for males. A bivariate analysis indicated significant shared genetic variance between NumCh and FirstTry.