Worldwide, the prevalence of obesity has reached epidemic proportions. In Denmark one third of all pregnant women are overweight and 12 % are obese. Perhaps even more concerning, a dramatic rise in the prevalence of childhood overweight and obesity has also been evident over recent decades. The obesity epidemic is not simply a consequence of poor diet or sedentary lifestyles. Obesity is a multifactorial condition in which environmental, biological and genetic factors all play essential roles. The Developmental Origins of Health and Disease (DoHaD) hypothesis has highlighted the link between prenatal, perinatal and early postnatal exposure to certain environmental factors and subsequent development of obesity and non-communicable diseases. Maternal obesity and excessive gestational weight gain, resulting in over-nutrition of the fetus, are major contributors to obesity and metabolic disturbances in the offspring. Pregnancy offers the opportunity to modify the intrauterine environment, and maternal lifestyle changes during gestation may confer health benefits to the child. The overall aim with this PhD thesis was to study the effects of maternal obesity on offspring body size and metabolic outcomes, with special emphasis on the effects of lifestyle intervention during pregnancy. The thesis is based on a literature review, description of own studies and three original papers/manuscripts (I, II and III). In paper I, we used data from the Danish Medical Birth Registry. The aim of this paper was to examine the impact of maternal pregestational Body Mass Index (BMI) and smoking on neonatal abdominal circumference (AC) and weight at birth and to define reference curves for birth AC and weight in offspring of healthy, non-smoking, normal weight women. Data on 366,886 singletons were extracted and analyzed using multivariate linear regressions. We found that birth AC and weight increased with increasing pregestational BMI and decreased with smoking. Reference curves were created for offspring of healthy, non-smoking mothers with normal pregestational BMI. Paper II and III are based on an offspring follow-up of a randomized controlled trial (RCT) with 360 obese pregnant women. The intervention during pregnancy consisted of two major components: dietary advice and physical activity. The intervention resulted in a small, but significant difference in gestational weight gain compared to the control group. A number of 301 completed the trial and were eligible for the follow-up. We managed to include 157 mother and child dyads in the follow-up, which was conducted in Odense University Hospital and Aarhus University Hospital, Skejby between February 2010 and November 2012. At that time the children were in the ages 2.5-3 years. In addition to the children from the RCT, a group of 97 children born to lean mothers were included as an external reference group. The follow-up consisted of a clinical examination with anthropometric measures, DEXA scans and fasting blood samples for evaluation of metabolic outcomes. In paper II the effect of the maternal intervention on offspring body composition and anthropometric outcomes was studied. The primary outcome was BMI Z-score and secondary outcomes were: body composition values by DEXA (fat mass, lean mass and fat percentage), BMI, percentage of overweight or obese children and skin fold thicknesses. We found no significant differences in offspring outcomes between randomized groups of the preceding RCT. Neither was any differences detected between offspring of the RCT or the external reference group born to lean mothers. Paper III focused on the metabolic outcomes in the offspring. We additionally studied the predictive values of birth weight (BW) and birth abdominal circumference (BAC) on metabolic risk factors. We found that both BAC and BW were significantly associated with several risk factors in early childhood. All metabolic measurements in RCT offspring were similar, and no differences were detected between the RCT offspring and the external reference group of offspring of lean mothers. Lifestyle intervention in obese pregnant women has the potential to modify the intrauterine environment and confer long-term benefits to the child. In this follow-up study, lifestyle intervention in pregnancy did not result in changes in offspring body composition or metabolic risk factors at 2.8 years. This might be due to a limited difference in gestational weight gain between follow-up attendees. When comparing offspring of obese women with offspring of normal weight mothers all outcomes were similar. We speculate that obese mothers entering a lifestyle intervention RCT regardless of the intervention have a high motivation to focus on healthy lifestyle during pregnancy, which makes it difficult to determine the effects of the randomized lifestyle intervention compared to an unselected control group of obese women. Our studies (paper I and III) on birth abdominal circumference show that abdominal size at birth is a good predictor of later adverse metabolic profile. Abdominal circumference at birth may reflect visceral adiposity and this measurement together with birth weight are strongly associated to later adverse metabolic outcome. Future studies should be performed in other populations to confirm this.
