Background Following the Thalidomide disaster, the Medical Birth Registry of Norway (MBRN) was established in 1967, with epidemiological surveillance of congenital anomalies as one main aim. Limb reduction defects (LRD) constitute a rare and heterogeneous anomaly group, where correct registration and classification is important for surveillance and research. We aimed at reviewing and recoding LRD cases in the MBRN using the same classification system for all years, and evaluate time trends, characteristics and risk factors, 1970–2016. Methods After reviewing and recoding LRD cases using International Classification of Diseases (ICD), 10 th version, for all years, time trends, association with major anomalies, risk factors and infant outcomes were calculated. Generalized linear models for the binomial family with log link gave relative risks (RR) with 95% confidence intervals (CI). Classification of LRD as suggested by European surveillance of congenital anomalies (EUROCAT) was attempted. Results Overall LRD prevalence, 1970–2016, was 4.4 per 10 000, slightly increasing during 1970–1981, followed by relatively stable rates. There were more defects in upper than lower limbs. Defects in hands/fingers were most common, but unspecific descriptions prevented classification of LRD according to EUROCAT. A majority of cases had associated anomalies, the most common being other limb defects, followed by cardiac defects and anomalies in the nervous and digestive systems. From 1999, 26% of LRD cases were terminated, more than 90% of these had associated major anomalies. Stillbirth, neonatal and infant mortality were higher among infants with LRD, also related to associated anomalies. Pre-gestational diabetes was associated with a more than three times increased risk of offspring total LRD, while no association with maternal epilepsy was found. Taking folate/multivitamin supplements before and/or during pregnancy was associated with lower risk of offspring LRD (adjusted RR 0.7; 95% CI 0.6–0.9), while daily smoking did not significantly increase the risk. Conclusion The MBRN now has information on LRD coded by ICD-10 from 1970, but information is not specific enough to use other recommended classification systems. Collecting radiographic descriptions and/or more details from hospital records would improve the quality of the registry data. Taking folate supplements before/during pregnancy may reduce the risk of offspring LRD.

Potocki-Shaffer syndrome (PSS) is a contiguous gene syndrome caused by 11p11.2 deletions. PSS is clinically characterized by intellectual disability, craniofacial anomalies, enlarged parietal foramina, and multiple exostoses. PSS occasionally shows autism spectrum disorder, epilepsy, and overgrowth. Some of the clinical features are thought to be associated with haploinsufficiency of two genes in the 11p11.2 region; variants affecting the function of ALX4 cause enlarged parietal foramina and EXT2 lead to multiple exostoses. However, the remaining clinical features were still yet to be linked to specific genetic alterations. In this study, we identified de novo truncating variants in an 11p11.2 gene, PHF21A, in three cases with intellectual disability and craniofacial anomalies. Among these three cases, autism spectrum disorder was recognized in one case, epilepsy in one case, and overgrowth in two cases. This study shows that PHF21A haploinsufficiency results in intellectual disability and craniofacial anomalies and possibly contributes to susceptibility to autism spectrum disorder, epilepsy, and overgrowth, all of which are PSS features.

Objective To investigate intergenerational recurrence of breech delivery, with a hypothesis that both women and men delivered in breech presentation contribute to increased risk of breech delivery in their offspring. Design Population based cohort study for two generations. Setting Data from the medical birth registry of Norway, based on all births in Norway 1967-2004 (2.2 million births). Participants Generational data were provided through linkage by national identification numbers, forming 451 393 mother-offspring units and 295 253 fatheroffspring units. We included units where both parents and offspring were singletons and offspring were first born, forming 232 704 mother-offspring units and 154 851 father-offspring units for our analyses. Main outcome measure Breech delivery in the second generation. Results Men and women who themselves were delivered in breech presentation had more than twice the risk of breech delivery in their own first pregnancies compared with men and women who had been cephalic presentations (odds ratios 2.2, 95% confidence interval 1.8 to 2.7, and 2.2, 1.9 to 2.5, for men and women, respectively). The strongest risks of recurrence were found for vaginally delivered offspring and were equally strong for men and women.

The general reduction in mean birth weight among first born mothers was not observed in the next generation. We suggest that first born mothers have the same biologically potential for achieving similar sized offspring as later born mothers, and that social factors account for the inverse relation.

There is increasing interest in the associations between parental birthweight and gestational age with their perinatal outcomes. We investigated perinatal mortality risk in offspring in relation to maternal and paternal gestational age and birthweight. We used population-based generational data from the Medical Birth Registry of Norway, 1967-2006. Singletons in both generations were included, forming 520,794 mother-offspring and 376,924 father-offspring units. Perinatal mortality in offspring was not significantly associated with paternal gestational age or birthweight, whereas it was inversely associated with maternal gestational age. A threefold increased risk in perinatal mortality was found among offspring of mothers born at 28-30 weeks of gestation relative to offspring of mothers born at term (37-43 weeks) (relative risk: 2.9, 95% CI 1.9, 4.6). There was also an overall association between maternal birthweight and offspring perinatal mortality. Relative risk for mothers whose birthweight was <2000 g was 1.5 (95% CI 1.1, 1.9), relative to mothers whose birthweight was 3500-3999 g. However, confined to mothers born at >or=34 weeks of gestation, the birthweight association was not significant. Weight-specific perinatal mortality in offspring was dependent on the birthweight of the mother and the father, that is, offspring who were small relative to their mother's or father's birthweight had increased perinatal mortality. In conclusion, a mother's gestational age, and not her birthweight, was significantly associated with perinatal mortality in the offspring, while there was no such association for the father.