The last 20 years has seen an exponential increase in rates of overweight and obesity around the world (1,2). Women of childbearing age have not been spared in this epidemic and approximately one-third of US (2) and one-fifth of UK (3) women are obese. Obesity prevalence among women aged 12–44 years in the US doubled between 1976 and 2004 and the number having a body mass index (BMI) ≥40 tripled (4). In the decade following 1993, a 70% increase in pre-pregnancy obesity was reported in a study of nine US states (5).
Coinciding temporally with this epidemic has been an increasing interest in how exposures in pregnancy can affect the long-term health and development of the offspring of these gestations. The process by which persistent physiological alterations in offspring result from intrauterine conditions is referred to as foetal programming (6). Indeed, a large number of studies that attest to the importance of the intrauterine environment suggest that it can ‘programme’ or affect later risk of obesity (7), hypertension (8) and even depression (9) in offspring independent of genetic and socioeconomic confounders.
The presence of maternal obesity in pregnancy creates an intrauterine environment that is suboptimal for both the mother and her foetus and is a major modifiable contributor to adverse maternal and child health outcomes. Pre-pregnancy obesity is a risk factor for diabetes mellitus (DM), hypertension, thromboembolic disease and asthma in pregnancy (10). At delivery, obese women are 20% more likely than normal weight women to suffer perinatal haemorrhage and three times more likely to develop an infection (11). They are less likely to breastfeed (12) and are more prone to lactation delay and failure than normal weight women (13). Obese mothers are also twice as likely to give birth to macrosomic infants who themselves have higher rates of birth trauma and perinatal asphyxia (14). In the longer term, pre-pregnancy obesity is associated with a number of adverse health outcomes for the mother including cardiovascular and metabolic disease (11) and the offspring of these pregnancies appear more likely to be obese (7) and suffer from the metabolic syndrome (15).
The cardiovascular and endocrine systems may not be the only ones whose functioning is affected or ‘programmed’ by obesity in pregnancy. In fact, a recent systematic review suggests that infants born to mothers who were obese were at increased risk of central nervous system (CNS) developmental problems including neural tube defects, spina bifida and hydrocephaly (16).
If maternal obesity does adversely affect neurodevelopmental outcomes in offspring later in life, it is not clear if this occurs via a direct programming effect or if obesity simply serves as a marker of the actual pre- or post-natal causal factors. The foetal programming hypothesis would posit that the intrauterine exposures accompanying maternal obesity would alone be sufficient to produce long-term adverse effects on offspring neurodevelopment. Such an effect could occur via the dys-regulation of maternal hormonal or immune systems, or even nutrient excesses. Alternatively, pregnancy obesity could be linked to neurodevelopmental outcomes via a number of indirect or non-causal pathways. For example, obesity in pregnancy might simply be a marker of problems known to affect overweight mothers and that also influence foetal neurodevelopment such as folate (17) or vitamin D deficiency (18). Pregnancy exposures common to obese women including increased rates of DM (10), exposure to traumatic events in pregnancy and/or perinatal depression could also be responsible (19). Moreover, the effects of pregnancy obesity on the offspring's cognitive, emotional and behavioural development might not be because of pre-natal exposures but rather mediated post-natally by obstetric complications or child health problems such as obesity or DM. Finally, genetic and/or environmental confounders might be responsible for observed associations. Maternal cognitive problems (20), maladaptive personality traits (21), frank psychiatric disorder (22) or even exposure to poverty (23) might not only increase a mother's risk of obesity, but also affect the risk of foetal neurodevelopmental problems independent of the intrauterine state associated with maternal obesity.
Given the potential for maternal obesity during pregnancy to affect CNS development, coupled with the fact that it may be a modifiable risk factor for CNS problems makes this area particularly worthy of study. As a result, we systematically reviewed extant studies to determine if the offspring of women who were overweight or obese prior to or during pregnancy had higher rates of neurodevelopmental problems in childhood, adolescence and adulthood than those born to mothers with a BMI in the normal range. We anticipated that the offspring of women who were overweight and obese would manifest higher levels of problems than those born to women with normal BMIs.