You Are What Your Mother Ate: Diet, Pregnancy Outcome And Lifelong Health

Published on 24 June 2009 in Food, health and wellbeing

Introduction

The incidence of babies born at the birth weight extremes is steadily increasing in the UK and is of concern because the associated complications for mother and child are a major drain on NHS resources. Low birth weight babies (<2500g, 7.8% of births), most of whom are born prematurely, are 40 times more likely to die within the first year of life, and surviving babies have a high risk of mental, visual and aural impairment, autism and cerebral palsy. High birth weight babies (>4000g, 11% of births) are at increased risk of stillbirth, heart and neural tube defects and birth injuries. For the mothers of these babies there is also a greater incidence of gestational diabetes, hypertension, operative delivery and post-partum haemorrhage. As well as these immediate complications of pregnancy there are compelling and robust epidemiological relationships between these extremes of birth weight and the subsequent development of diabetes, obesity, immune dysfunction, osteoporosis, stroke and cardiovascular disease. This suggests that the prevention of these diseases should begin during pregnancy.

The nutritional status and dietary intake of the mother plays an important and potentially modifiable role in avoiding birth weight extremes and optimising life long health but clearly one size will not fit all. Nutritional risk factors for low birth weight and premature delivery include short inter-pregnancy intervals, low pre-pregnancy weights, insufficient gestational weight gain, multi-fetal pregnancies and a young maternal age. At the other end of the nutritional spectrum a high maternal body mass index (BMI) and excessive pregnancy weight gain are variously associated with an increased incidence of stillbirth, fetal macrosomia and more rarely fetal growth restriction. Appropriate maternal nutrition is imperative for ensuring a favourable pregnancy outcome in all these vulnerable groups and is the focus of our research.

Key Points

• Maternal dietary intake can influence the growth and nutrient transfer function of the placenta and is the major determinant of fetal growth and weight at birth.
   
• Both over and undersupply of nutrients to the fetus can alter the pattern of prenatal growth and have life time health consequences.
   
• Mothers are more likely to comply with dietary advice during pregnancy than at any other stage of the life cycle, but that advice must be appropriate for her age, physiology and nutritional status at the time of conception.
   
• It is imperative that dietary advice during pregnancy has a sound and specific scientific evidence base for each of the known nutritionally vulnerable groups.
   
• Establishing cause and effect of the route to altered prenatal growth, metabolism and life long health requires use of clinically relevant animal models which replicate the key features of adverse pregnancy outcomes in the target human cohorts.

Research Undertaken

Our specific interest is in the nutritional antecedents of poor pregnancy outcome in young adolescent girls since premature delivery of low birth weight babies predominates in this group and adolescent pregnancies account for 1 in 10 births in the UK and 1 in 5 births worldwide. We have developed specific adolescent sheep paradigms. Relative to the human, the sheep is the model of choice because of the ability to study singleton pregnancies, comparable maternal size and adiposity, equivalent birth weight, and similar organogensis for all major organ systems. Furthermore sheep have a relatively long gestation length and the fetal circulation can be catheterised to directly measure fetal nutrient uptakes and metabolism in utero. These animal models are providing the scientific evidence base instigating and informing human studies here in the UK and internationally.
 
Our animal studies show that

• Overnourishing young adolescents to promote high gestational weight gains during pregnancy results in major placental growth restriction and premature delivery of very low birth weight lambs. This model also recapitulates the key features of human intrauterine growth restriction irrespective of maternal age.
   
•  Reduced placental angiogenesis and uterine blood flow are an early defect in pregnancies which will ultimately result in fetal growth restriction.
   
• Undernourishing young adolescents to prevent maternal body growth also modestly reduces birth weight, primarily due to direct limitation of nutrient supply to the fetus rather than alterations in placental development.
   
• Low maternal weight and adiposity at conception reduce birth weight by ~500g irrespective of subsequent gestational weight gain.
   
• High rather than low gestational weight gains are most detrimental to fetal growth.
   
• The main genes involved in appetite and energy balance in postnatal life are present in the early fetal brain and are sensitive to changes in nutrient supply. Moreover growth restricted fetuses display normal metabolic responses to short term increases in fetal fuel supply and anabolic hormone concentrations. 
   
• When born into a calorie rich environment, low birth weight offspring exhibit rapid compensatory catch-up growth, altered carbohydrate and fat metabolism and increased adiposity. Preliminary evidence suggests that some but not all of these programmed effects are amenable to postnatal dietary modification.  

Policy Implications

For adolescent pregnancies;

• Low maternal weight and adiposity at conception and gestational intakes at both ends of the nutritional spectrum negatively influence pregnancy outcome in young putatively growing adolescents by different mechanisms.
   
• Counter-intuitively, hugely increasing the energy and protein intake in still growing adolescents to promote higher gestational weight gains is highly unlikely to benefit the fetus and could well be detrimental to pregnancy outcome.
   
• Maternal adaptations to varying nutrient supply are likely to differ in still-growing versus adult humans and therefore impact on their optimal nutritional management and obstetrical care.

For all vulnerable pregnancies;

• Doppler ultrasound to measure placental size and utero-placental blood flows has potential to identify at risk human pregnancies at an early stage and target resources to those who need it most.
   
• Small improvements in the growth trajectory of growth restricted fetuses are likely to increase gestation length, birth weight and survival without handicap. Novel approaches are currently being evaluated in our ovine paradigms.
   
• The presence and nutritional sensitivity of the main genes involved in postnatal appetite and energy balance in fetal life provide one plausible route for the prenatal programming of obesity.
   
• As 20% of pregnant women are obese, there is an urgent requirement to assess the mechanisms underlying the contrasting pregnancy outcomes typical of this population and to provide recommendations for diet and gestational weight change that are safe for mother and child. 

Author

Dr Jacqueline Wallace Jacqueline.Wallace@abdn.ac.uk

Topics

Food, health and wellbeing

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