Aims and Objectives

To determine whether children of women who were overweight or obese at the time of pregnancy are more likely to receive high ratings of ADHD symptoms as compared to children of women who were normal weight. Importantly, use of the ALSPAC data will allow us to extend previous work by testing potential mechanisms, e.g. maternal dietary intake during pregnancy and child weight, as well as examining longitudinal associations across childhood.

Background

Overweight and obesity are significant public health concerns. Prevalence is continuously escalating and by 2030 it is estimated that as many as 2.16 billion and 1.12 billion adults world-wide will be overweight and obese, respectively (Kelly et al., 2008). Women entering pregnancy are more likely than ever to be overweight or obese, with well-documented deleterious health consequences for both mother and child. Less is, however, known about the possible consequences for child mental health.

The concept of maternal weight in programming of mental health problems in the offspring has been studied primarily from the perspective of underweight and low weight gain in pregnancy. Famine studies in the Netherlands and China show that low maternal weight at the beginning of pregnancy is a risk factor for neurodevelopmental disorders in the adult offspring. Fetal brain development is dependent on maternal energy supply (Hay & Sparks, 1985). Due to the obesity epidemic, recent work has examined mental health consequences for the offspring as a function of maternal overweight/obesity in pregnancy (Rodriguez, 2010a). We were first to report an association between maternal pre-pregnancy overweight/obesity and symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in children (Rodriguez et al., 2008).

ADHD, a neurodevelopmental disorder, is very common and has an estimated world-wide prevalence of 5%. The core symptoms of inattention and hyperactivity are associated with impairment even at sub-clinical levels (Rodriguez et al., 2007). Thus, ADHD and its symptoms pose a public health concern due to the documented negative ramifications to the individual, family, and society.

Our first report showed an association between maternal pre-pregnancy overweight/obesity and core symptoms of ADHD combining data from three prospective cohorts from Sweden, Finland, and Denmark with a pooled sample size of over 12,000 children. The finding was confirmed in another Swedish prospective cohort of younger children using the full symptom description of ADHD (Rodriguez, 2010a). Further, this work also showed a significant association with child negative affect. It was possible to adjust for many confounding factors including maternal depression, stress, socio-demographics, as well as ADHD symptoms in both parents. One possibility that the Rodriguez (2010a) paper examined was whether the child's own weight accounted for the association. This is a plausible link because previous research has pointed to the contribution of maternal pre-pregnancy weight in the programming of child weight (Rodriguez, 2010b). Although the results did not show that child weight accounted for the association, the question remains opened because child weight was assessed as within or outside the normal range, thus it is unknown whether child body mass index (BMI) mediates or accounts for the association.

Hypotheses:

1) Children born to mothers who were overweight or obese at pregnancy will have higher risk of child behavior problems, specifically those related to ADHD according to teachers and mothers.

2) Children exposed to maternal obesity in utero will have consistent behavior problems across childhood.

3) Children's own weight will not mediate the association between prenatal exposure to maternal obesity and child behavior problems.

Methodology

Design: A longitudinal prospective study with contrast groups.

Participants: This study is based on data collected from the Avon Longitudinal Study of Parents and Children, ALSPAC (Golding et al., 2001). ALSPAC is a longitudinal birth cohort study, which enrolled all pregnant women living within Avon, England, due to give birth between the 1st April 1991 and 31st December 1992. It is estimated that approximately 85-90% of those eligible for inclusion chose to participate and the sample has been shown to be representative of the UK population. The core ALSPAC sample consists of 14,541 pregnancies, 69 of which had unknown birth outcomes. Data was obtained on the remaining 14,272 via postal questionnaires. For the purpose of this study women will be excluded if they did not respond to the 12 week questionnaire (2,019) or if they had multiple births (208).

Predictor: Prepregnancy maternal BMI will be calculated using the standard formula (weight in kg/height in m2) and rounded to nearest whole number. Maternal pre-pregnancy BMI will be analyzed as continuously and categorically according to the standard classification of the WHO guidelines for overweight and obesity: normal weight (20-24.99), underweight (15-19.99), overweight (25-29.99) and obese (>= 30).

Outcomes: The main outcome measures will be teacher reports of child behavior at ages 8 and 11 years using the Strengths and Difficulties Questionnaire (Goodman, 2000), a widely-used general screener for psychiatric disorders in community samples. One subscale is devoted to ADHD symptoms.

To assess whether children's own weight contributes to ADHD symptoms we will use data collected yearly on physical development (weight) up to the age of 11 years.

Confounders: Participants reported socio-demographic data, including age, occupation, marital status as well as smoking via self-report at 12 weeks gestation. We will also include psychosocial factors such as maternal anxiety and depression during pregnancy. Birth outcomes such as birth weight and gestational age will be included in the model.

Data Analysis: The hypotheses will be tested using linear and logistic regression analyses in which maternal pre-pregnancy BMI is used to predict behavioral outcomes in childhood. All of the central analyses will include covariates. Data available at several time-points will be initially analysed cross-sectionally; longitudinal and growth modelling will be used as a subsequent step. With the available sample sizes, small to moderate group differences in continuous outcomes can be detected with a power of 90% at the 5% test level. Analyses will take into account missing data.

The results offered by this study will not only provide an opportunity for replication in an independent sample in another geographical region, but more importantly will provide an opportunity for extension and examination of potential mediation by child weight as well as longitudinal analysis of child behavior problems across childhood.

REFERENCES

Golding J, Pembrey M, Jones R. ALSPAC--the Avon Longitudinal Study of Parents and Children. I. Study methodology. Paediatric and Perinatal Epidemiology 2001;15(1):74-87.

Goodman R, Ford T, Simmons H, Gatward R, Meltzer H. Using the Strengths and Difficulties Questionnaire (SDQ) to screen for child psychiatric disorders in a community sample. Br J Psychiatry. 2000;177:534-9.

Hay WW, Jr., Sparks JW. Placental, fetal, and neonatal carbohydrate metabolism. Clin Obstet Gynecol. 1985;28(3):473-85.

Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes. 2008;32(9):1431-7.

Rodriguez A. Is prenatal exposure to maternal obesity linked to child mental health? In: Bagchi D, editor. Global View

on Childhood Obesity: Current Status, Consequences and Prevention: Elsevier; 2010, pp157-166.

Rodriguez A. Maternal pre-pregnancy obesity and risk for inattention and negative emotionality in children. J Child Psychol Psychiatry. 2010a;51(2):134-43.

Rodriguez A. Is prenatal exposure to maternal obesity linked to child mental health? In: Bagchi D, editor. Global View on Childhood Obesity: Current Status, Consequences and Prevention: Elsevier; 2010b.

Rodriguez A, Miettunen J, Henriksen TB, Olsen J, Obel C, Taanila A, et al.Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from three prospective pregnancy cohorts. Int J Obes (Lond). 2008;32(3):550-7.