Family studies on the effects on offspring ’ s body size and blood pressure

Introduction: Increasing maternal weight gain during pregnancy, gestational weight gain (GWG), is associated with several adverse outcomes in the child, e.g. high birth weight, childhood overweight and obesity, as well as adult blood pressure (BP). Studies have also shown that specific periods of pregnancy might be more sensitive in terms of influencing these outcomes. However, the aforementioned associations could be explained by genetic and/or environmental factors which are shared between the mother and child. As far as we know, no studies have examined to what extent these genetic and environmental factors explain the variation in GWG. Aims: The overall aim of this PhD thesis was therefore to investigate the possible associations between GWG and the children’s birth weight and body mass index (BMI) during childhood (study 2), and BP during early adulthood (study 3), while taking environmental and genetic factors shared between the mother and child into account (within the twin/sibling pairs). The current thesis also aimed at exploring how much of the variation in GWG which is determined by genetic (the heritability) and both unique and common environmental factors (study 1). Methods and Results: Study 1 was a register-based twin study with Swedish female monozygotic (MZ) and dizygotic (DZ) twin pairs with children born 1982-1989 and 19922010. Genetic factors accounted for 43% of the variation in GWG in the first pregnancy (N = 694 twin mother-pairs) and 26% in the second pregnancy (N = 465 twin mother-pairs). Unique environmental factors explained the remaining variation in GWG. Studies 2 and 3 were both prospective cohort studies, where study 2 was based on a data-collection of Swedish MZ twin mothers born 1962 to 1975 and their children (N = 82 twin mother-pairs), and study 3 was register-based and included Swedish male sibling pairs born 1982-1989 (N = 4908 brother pairs). In study 2, the results indicated that total, and possibly also second and third trimester weight gain, were associated with birth weight in the offspring within the twin pairs in the fully adjusted model. In terms of GWG and offspring weight and BMI during infancy and childhood, no associations were found. In study 3, no significant associations were found between GWG and systolic BP, or diastolic BP, or the offspring’s risk of hypertension, neither within nor between the sibling pairs. Conclusions: This thesis shows that the total GWG, and specifically weight gain during the second and third trimester, seem to be positively associated with offspring birth weight, but no effects were seen for BMI during infancy and childhood. However, due to the limited sample size, this requires further investigation. Moreover, no association was found between total GWG and the male sibling pairs’ BP at the age of 18 years. The variation in GWG seems to be largely explained by the mother’s unique environment during pregnancy and to a smaller degree by genetic factors. LIST OF SCIENTIFIC PAPERS 1. Elina Scheers Andersson, Karri Silventoinen, Per Tynelius, Ellen Aagaard Nohr, Thorkild I.A. Sørensen and Finn Rasmussen. Heritability of gestational weight gain – a Swedish register-based twin study. Twin Res Hum Genet 2015 Aug 18(4): 410-418. 2. Elina Scheers Andersson, Karri Silventoinen, Per Tynelius, Ellen Aagaard Nohr, Thorkild I.A. Sørensen and Finn Rasmussen. Totaland trimesterspecific gestational weight gain and offspring birth and early childhood weight: A prospective cohort study on monozygotic twin mothers and their offspring. Twin Res Hum Genet 2016 Aug 19(4): 367-376. 3. Elina Scheers Andersson, Per Tynelius, Ellen Aagaard Nohr, Thorkild I.A. Sørensen and Finn Rasmussen. No association of maternal gestational weight gain with offspring blood pressure and hypertension at age 18 years in male sibling-pairs: a prospective register-based cohort study. PLoS ONE 2015 March 20. 10(3) (Available from: http://journals.plos.org/plosone/article? id=10.1371/journal.pone.0121202) These papers will be referred to by their numbers (1-3) in the text. CONTENTS 1 Background . 1 1.1 Gestational weight gain (GWG) . 1 1.1.1 Historical background . 1 1.1.2 Descriptive epidemiology . 2 1.1. 3 Components and pattern . 4 1.1. 4 Determinants . 5 1.1. 5 Health consequences . 8 1.2 Familial confounding . 11 2 Aims . 13 2.1 Overall aims . 13 2.2 Specific research questions . 13 3 Material and Methods. 15 3.1 Study populations . 15 3.1.1 National registers and register-linkages . 15 3.1.2 Recruitment and data collection for study 2 . 18 3.2 Study variables and definitions . 22 3.2.1 Exposures . 22 3.2.2 Outcomes . 22 3.2. 3 Covariates . 22 3.3 Statistical analysis. 24 3.3.1 Family studies. 24 3.4 Ethical considerations . 28 4 Results . 30 4.1 Heritability of GWG (Study 1) . 30 4.2 GWG and offspring weight at birth and BMI during childhood (Study 2) . 31 4.3 GWG and offspring blood pressure in young adulthood (Study 3) . 33 5 Discussion . 35 5.1 Heritability of GWG (Study 1) . 35 5.1.1 Main findings . 35 5.1.2 Results in relation to previous research . 35 5.1. 3 Methodological considerations . 36 5.1. 4 Interpretations and Implications . 37 5.2 GWG and offspring weight at birth and BMI during childhood (study 2) . 38 5.2.1 Main findings . 38 5.2.2 Results in relation to previous research . 38 5.2. 3 Methodological considerations . 39 5.2. 4 Interpretations and Implications . 40 5.3 GWG and offspring blood pressure in young adulthood (study 3) . 41 5.3.1 Main findings . 41 5.3.2 Results in relation to previous research . 41 5.3.3 Methodological considerations . 42 5.3.4 Interpretations and Implications . 43 6 Conclusions . 44 6.1 Future research . 44 7 Acknowledgements . 46 8 References . 49 LIST OF ABBREVIATIONS