By Rebecca Kofod Vinding
Chariman: Anders Juul
Opponent: Ellen Aagaard Nøhr
Opponent: Jovanna Dahlgren
The increased prevalence of overweight children cannot be explained by changes in genetic factors, since the great increase has occurred over a short period of time, the causes must be sought in environmental exposures (1,2). Identification of these exposures are important as preventive steps against development of obesity, type 2 diabetes and cardiovascular diseases (3). We have focused on two exposures in this thesis. Firstly, caesarean section (CS) which has had an increase in prevalence the last decades (4). Two recent meta-analyses have shown associations between delivery by CS and obesity in the off-spring in both child- and adulthood (5,6). Secondly, we have focused on maternal dietary n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) during pregnancy, since it is an important determinant of adequate child development and health (7). In humans, both observational studies on dietary intake of fish as well as randomized trials of fish oil supplementation in pregnancy have shown longer gestation and higher birth weight in children born to women with a high n-3 LCPUFA intake (8–11). The increased birth weight could solely be caused by the prolonged duration of pregnancy (9,12), but could also be explained by an increased intrauterine growth rate. Animal studies have shown that n-3 LCPUFA supplementation both in pregnancy and the postnatal period affects the proliferation and differentiation of pre-adipocytes, which could theoretically have a positive impact on later adiposity through inhibition of fat tissue development (13,14). However, in humans randomized trials with n3 LCPUFA supplementation in pregnancy and/or lactation have shown ambiguous results regarding anthropometric outcomes later in childhood (15–17)
The thesis consists of the following papers:
I. Cesarean Section and Body Mass Index at 6 months and into Childhood Rebecca Kofod Vinding, MD, Tobias Steen Sejersen, MD, Bo L Chawes, MD, DMSc, Klaus Bønnelykke, MD, PhD, Thora Buhl, MD, PhD, Hans Bisgaard MD, DMSc and Jakob Stokholm, MD, PhD. Pediatrics 2017, May
II. Fish oil supplementation increases pregnancy duration and intrauterine growth. Randomized controlled trial Rebecca Kofod Vinding, MD, Jakob Stokholm, MD, PhD, Astrid Sevelsted, MSc, Bo L. Chawes, MD, DMSc, Klaus Bønnelykke, MD, PhD, Malin Barman, PhD, Bo Jacobsson, MD, PhD and Hans Bisgaard, MD, DMSc. Submitted Pediatrics
III. Fish-oil supplementation in pregnancy causes a proportional increase in lean mass, bone mass and fat mass at 6 years: A Randomized, Controlled, Double-Blind, Clinical Trial. Manuscript ready for submission Rebecca Kofod Vinding, MD, Jakob Stokholm, MD, PhD, Astrid Sevelsted, MSc, Tobias Sejersen, MD, Bo Chawes, MD, PhD, DMSc, Klaus Bønnelykke, MD, Jonathan Thorsen, MD, PhD, Laura D Howe, PhD, Martin Krakauer, MD, PhD, Thora Buhl, MD, PhD and Hans Bisgaard, MD, DMSc
We examined the development of Body Mass Index (BMI) from birth through childhood in children with different delivery mode, to determine if CS were associated with differences in childhood growth and obesity. We collected height/length and weight measurements prospectively from term children until 5 years in COPSAC2010 and 13 years in COPSAC2000, furthermore dualenergy X-ray absorptiometry (DXA) scans were performed at age 3.5 years and 7 years.
We analysed the effect of n-3 LCPUFA supplementation in pregnancy on intrauterine growth, gestational age and birth weight. The study was a double-blinded, RCT. The pregnant women received capsules containing either 2.4 g of n-3 LCPUFA or control daily from pregnancy week 24 until one week after birth. We found that n-3 LCPUFA compared to control was associated with a longer duration of pregnancy, a higher birth weight and an increased intrauterine growth.
We examined the effect of n-3 LCPUFA supplementation in pregnancy on childhood anthropometrics outcomes. The study was nested in the above-mentioned intervention study. We used prospectively collected height/length and weight to examine the development of BMI from birth through 6 years of age. At 6 years we evaluated the cross sectional effect on height, weight, BMI, head and waist measurements. We used data from DXA scans at 3.5 years and 6 years. We found that the n-3 LCPUFA group had a significantly higher mean z-score BMI from 1 week to 6 years of age compared to the controls, leading to a significantly higher z-score BMI at age 6 years and a larger waist circumference.
Supplementation with n-3 LCPUFA in pregnancy led to increased BMI in childhood with sustained elevated BMI from age 1 year till 6 years. We saw no difference in fat percentage but a proportional increase in lean mass, fat mass and bone mass at 6 years. Our findings confirm that n-3 LCPUFA affects fetal programing leading to changed growth during childhood. Further studies are needed to establish the long-term health implications of our findings.