Classification of small-for-gestational age births: weight-by-gestation standards of second birth conditional on the size of the first

Percentiles of weight-by-gestational age were constructed for first and second births, based on linked sibship-data from the Medical Birth Registry of Norway. Standards were made for weight-by-gestational age of second births conditional on whether the first birth was small-for-gestational age (SGA) or large-for-gestational age (LGA). These standards were compared with the conventional, cross-sectional standard of all second births. The relevance of the conditional standards was assessed on the basis of perinatal mortality, using logistic regression analyses. When applying cross-sectional standards of second births, more than 30% of the births following a SGA first birth were classified as SGA, compared with only 1.7% following an LGA first births. The overall risk for a perinatal loss in second births following a SGA first birth was twice that among second births following a LGA first birth. When second births were themselves categorised as SGA or non-SGA using the cross-sectional standards, the mortality among the SGA second births was such that the risk was 4 to 5 times higher following LGA first births compared with SGA first births. When conditional standards were applied to define SGA among second births, the risk relation between the subgroups (defined by classification of first birth) corresponded to the observed overall risk pattern. An unconditional SGA classification conceals important differences between clinically distinct subgroups.     

The relationship between maternal birthweight and gestational age in twins and singletons and those of their offspring in Norway

In order to elucidate whether maternal plurality affects offspring intrauterine growth, the relationship between birthweight and gestational age of twins and singletons and those of their first singleton liveborn children in Norway was studied using data from the Medical Birth Registry. The population-based sample consisted of 49 698 mother–offspring pairs (48 842 with singleton and 856 with twin-mothers). In bivariate analyses, no significant differences in mean birthweight and gestational age of offspring of twin and singleton mothers were found, although the mean birthweight and gestational age of the twin-mothers themselves were significantly lower than those of singletons (819 g and 14 days respectively). In multiple regression analysis, the expected birthweight of offspring was 230.3 g (95% CI: 193.2–267.4 g) higher when the mother was a twin than when the mother was a singleton, when controlling for non-standardised maternal birthweight. When adjusting for relative maternal birthweight ( z -score), the association between maternal plurality and offspring birthweight was not statistically significant. The results suggest that being born as a twin has no substantial consequences on offspring growth in utero and show that mean differences in birthweight between twins and singletons should be standardised when both groups are included in multivariate studies.     

Genetic variants in IRF6 and the risk of facial clefts: single-marker and haplotype-based analyses in a population-based case-control study of facial clefts in Norway

Mutations in the gene encoding interferon regulatory factor 6 (IRF6) underlie a common form of syndromic clefting known as Van der Woude syndrome. Lip pits and missing teeth are the only additional features distinguishing the syndrome from isolated clefts. Van der Woude syndrome, therefore, provides an excellent model for studying the isolated forms of clefting. From a population-based case-control study of facial clefts in Norway (1996-2001), we selected 377 cleft lip with or without cleft palate (CL/P), 196 cleft palate only (CPO), and 763 control infant-parent triads for analysis. We genotyped six single nucleotide polymorphisms within the IRF6 locus and estimated the relative risks (RR) conferred on the child by alleles and haplotypes of the child and of the mother. On the whole, there were strong statistical associations with CL/P but not CPO in our data. In single-marker analyses, mothers with a double-dose of the 'a'-allele at rs4844880 had an increased risk of having a child with CL/P (RR=1.85, 95% confidence interval: 1.04-3.25; P=0.036). An RR of 0.38 (95% confidence interval: 0.16-0.92; P=0.031) was obtained when the child carried a single-dose of the 'a'-allele at rs2235371 (the p.V274I polymorphism). The P-value for the overall test was <0.001. In haplotype analyses, several of the fetal and maternal haplotype relative risks were statistically significant individually but were not strong enough to show up on the overall test (P=0.113). Taken together, these findings further support a role for IRF6 variants in clefting of the lip and provide specific risk estimates in a Norwegian population.     

Fecundability among women with type 1 and type 2 diabetes in the Norwegian Mother and Child Cohort Study

Aims/Hypothesis  

We assessed the effects of type 1 diabetes and type 2 diabetes on fecundability (as manifest by increased time-to-pregnancy [TTP]) in a large cohort of pregnant women.     

Exposure to dental amalgam restorations in pregnant women

Lygre GB, Björkman L, Haug K, Skjærven R, Helland V. Exposure to dental amalgam restorations in pregnant women. Community Dent Oral Epidemiol 2010; 38: 460–469. © 2010 John Wiley & Sons A/S Abstract – Objectives: The Norwegian Mother and Child Cohort Study (MoBa) started in 1999 to identify environmental factors that could be involved in mechanisms leading to disease. Questions have been raised about potential risks to the fetus from prenatal exposure to mercury from amalgam fillings in pregnant women. The aim of the present study was to identify factors potentially associated with amalgam fillings in pregnant women participating in the Norwegian Mother and Child Cohort Study (MoBa). An additional aim was to obtain information about dental treatment in the cohort. Methods: Total of 67 355 pregnancies from the MoBa study were included in the present study. Information regarding age, education, smoking habits, alcohol consumption, weight, and height for the women was obtained from a questionnaire that was filled in at the 17th week of pregnancy. In another questionnaire, which was sent to all participants in the 30th week of pregnancy, the women reported types of dental treatment during pregnancy, total number of teeth, and number of teeth with amalgam fillings. The self‐assessed number of teeth and number of teeth with amalgam fillings were validated in an external sample of 97 women of childbearing age. Results: Odds ratio for having more than 12 teeth with amalgam fillings increased considerably with age. Other significant risk factors for having high exposure to amalgam were low education, high body mass index (BMI), and smoking during pregnancy. Women with the lowest levels of education had a twofold increased odds ratio of having more than 12 teeth filled with amalgam compared with women who had more than 4 years of university studies. According to the results from the validation of self‐assessed number of teeth with amalgam fillings, the information obtained was reliable. Conclusion: Age, education, smoking habits, and BMI were associated with amalgam exposure.     

Variations in the risk of disability pension in Norway 1970-99. A gender-specific age-period-cohort analysis

AIMS: A study was undertaken to investigate whether cohort or period effects could explain the varying and generally increasing incidence of disability pension in Norway between 1970 and 1999. METHODS: The study used data from a complete national register of new disability cases in Norway, including all cases of disability pension in the 16-60 age group categorized according to age and gender for each year from 1970 to 1999. The population at risk was defined for each year from census data and number of individuals already receiving disability pension. Data were organized in five-year age groups, five-year time periods and corresponding overlapping nine-year birth cohorts. Age- and gender-specific rates were displayed graphically for periods and cohorts. Separate Poisson regression models were fitted for age periods and age cohorts. Finally a combined age, period, and cohort model was applied. RESULTS: The overall incidence was 7.4/1,000 non-disabled persons per year for women and 6.0/1,000 for men. For women 52.1% of the cases were in the 51-60 age group, whereas the corresponding figure for men was 57.6%. Statistical analysis showed an increasing trend for both genders, more pronounced for women than men. All time periods deviated significantly from the trend, either upwards or downwards. Age-cohort models showed less variation, but recent cohorts had higher than expected rates, especially for men. CONCLUSIONS: Further studies should investigate why Norwegian women were more affected by the period effects than men. An increasing incidence of disability pension among recent cohorts is a major challenge for the Norwegian welfare system.     

Recurrence of gestational age in sibships: implications for perinatal mortality.

The authors studied the extent to which preterm birth and perinatal mortality are dependent on the gestational ages of previous births within sibships. The study was based on data collected by the Medical Birth Registry of Norway from 1967 to 1995. Newborns were linked to their mothers through Norway's unique personal identification number, yielding 429,554 pairs of mothers and first and second singleton newborns with gestational ages of 22-46 weeks, based on menstrual dates. Siblings' gestational ages were significantly correlated (r = 0.26). The risk of having a preterm second birth was nearly 10 times higher among mothers whose firstborn child had been delivered before 32 weeks' gestation than among mothers whose first child had been born at 40 weeks. However, perinatal mortality in preterm second births was significantly higher among mothers whose first infant had been born at term, compared with mothers whose firstborn child was delivered at 32-37 weeks. Since perinatal mortality among preterm infants is dependent on the gestational age in the mother's previous birth, a common threshold of 37 weeks' gestation for defining preterm birth as a risk factor for perinatal death may not be appropriate for all births to all mothers.     

Parent-offspring body mass index associations in the Norwegian Mother and Child Cohort Study: a family-based approach to studying the role of the intrauterine environment in childhood adiposity

In the present study, the authors investigated the role of the intrauterine environment in childhood adiposity by comparing the maternal-offspring body mass index (BMI) association with the paternal-offspring BMI association when the offspring were 3 years of age, using parental prepregnancy BMI (measured as weight in kilograms divided by height in meters squared). The parent-offspring trios (n = 29,216) were recruited during pregnancy from 2001 to 2008 into the Norwegian Mother and Child Cohort Study conducted by The Norwegian Institute of Public Health. Data from self-administered questionnaires were used in linear regression analyses. Crude analyses showed similar parental-offspring BMI associations; the mean difference in offspring BMI was 0.15 (95% confidence interval: 0.13, 0.16) per each 1-standard-deviation increase in maternal BMI and 0.15 (95% confidence interval: 0.13, 0.17) per each 1-standard-deviation increase in paternal BMI. After all adjustments, the mean difference in offspring BMI per each 1-standard-deviation increment of maternal BMI was 0.12, and the mean difference in offspring BMI per each 1-standard-deviation increment of paternal BMI was 0.13. There was no strong support for heterogeneity between the associations (P > 0.6). In conclusion, results from the present large population-based study showed similar parental-offspring BMI associations when the offspring were 3 years of age, which indicates that the maternal-offspring association may be explained by shared familial (environmental and genetic) risk factors rather than by the intrauterine environment.     

Epidemiology of cleft palate alone and cleft palate with accompanying defects

The epidemiology of cleft palate with multiple defects is often thought to be different from that of cleft palate alone, but there are few empirical data on this question. We explored this in a population-based data set created by combining data from two sources: the 1.8 million live births recorded from 1967 to 1998 in the Norwegian Birth Registry, and the two Norwegian surgical centers that repair cleft palate. Accompanying defects were identified from either source. Stratified analysis and logistic regression were used to assess relative risks by covariates. Of 1,431 babies with cleft palate, 31 % had another birth defect recorded by one or both sources. Prevalence of isolated cleft palate was steady over time, while cleft palate with other defects increased substantially. Girls had a higher risk of isolated cleft palate (relative risk 1.4; 95% confidence interval, 1.2–1.6) but not of cleft palate accompanied by other defects (1.1; 0.88–1.3). Older parents and parents who were first cousins had no increased risk of isolated cleft palate, but were twice as likely as others to have a baby with cleft palate accompanied by other defects. Risk factors differ between cases of cleft palate with and without accompanying defects.