Prenatal impacts on health through fetal programming

 

The most sensitive period of human life is the time in utero, when organs are formed, the neural and immune system develop and endocrine and metabolic pathways are shaped. Following the seminal work by David Barker, recent years have seen a growing literature investigating how circumstances during pregnancy affect offspring health throughout the life course. As a fetus goes through critical development phases, exposures to environmental circumstances can result in permanent changes to its physiology and have life-long implications for health, presumably through epigenetic mechanisms. The study field sprouting from the fetal programming theory has become known as the “Developmental Origins of Health and Disease” (DOHaD).

When studying long-term effects of undernutrition in utero, researchers have employed natural experiments such as famines to avoid confounding by socioeconomic status and other factors. The most famous is the Dutch Hunger Winter study which showed that exposure to famine during gestation, especially early gestation, increases the risk for obesity, diabetes, coronary heart disease, breast cancer, mental illness and cognitive decline later in life. Fewer studies have used actual experiments, i.e. randomized interventions that aimed to improve prenatal nutrition. We plan to investigate the impact of the Food and Agricultural Approaches to Reducing Malnutrition (FAARM) cluster-randomized trial in Bangladesh on the epigenome of the children conceived during the trial.

A very particular natural experiment to study the effects of nutrition in utero is furnished by the Muslim tradition of daytime fasting during the holy month of Ramadan. The rotation of Ramadan through the year and the contrast to non-Muslim populations in the same location provides an opportunity to disentangle seasonal effects on fetal development (due to different availability of nutrients, as well as environmental and infectious exposures) from Ramadan effects. Any Ramadan impact on long-term health would of course depend on the particular dietary changes happening in that particular context.

Due to climate change, rainfall levels are changing in many regions worldwide, which has adverse effects on harvest quality and thus nutrient availability in poor rural populations of low- and middle-income countries who directly depend on agriculture for their livelihoods. As rainfall shocks occur quasi-randomly, these have also been used to study early life impacts on health.

The phenotypic plasticity in utero through epigenetic changes allows organisms to quickly adapt to changes in their environment. This Predictive Adaptive Response (PAR) can be beneficial when prenatal circumstances adequately predict postnatal environments. If circumstances during gestation strongly differ from the environment after birth (e.g. Dutch Famine: plenty of high-caloric food in post-war Netherlands), the PAR is likely harmful. We plan to study this match or mismatch of pre- and postnatal circumstances, i.e. how the interaction between the two is shaping health.


Using data from Burkina Faso, Bangladesh, The Gambia, Indonesia and elsewhere, this project aims to:

  • Describe prenatal food and nutrient availability changes due to quasi-random exposures such as Ramadan occurrence or rainfall patterns
  • Assess the influence of a dietary diversification intervention among young women on the epigenome of their offspring
  • Assess the influence of Ramadan exposure in utero at different gestational ages on child mortality in low-income settings
  • Examine the interactions between prenatal exposure to adverse nutritional circumstances and later-life exposures on health and development outcomes


Project team:


External collaborators:


Funding:

New DFG project (2021-2024): How do prenatal and postnatal circumstances interact in shaping health? An interdisciplinary approach using quasi-experiments


Publications:

Seiermann AU, Al-Mufti H, Waid JL, Wendt AS, Sobhan S, Gabrysch S. (2021) Women's fasting habits and dietary diversity during Ramadan in rural Bangladesh. Maternal and Child Nutrition, 17(3): e13135

Schoeps A, van Ewijk R, Kynast-Wolf G, Nebié E, Zabré P, Sié A, Gabrysch S. (2018): Ramadan exposure in utero and child mortality in Burkina Faso: Analysis of a population-based cohort including 41,025 children. American Journal of Epidemiology; 187(10):2085-2092.

Gabrysch S, Van Ewijk R (2018). Authors’ Response to Commentaries. American Journal of Epidemiology, 187(10): 2098-2099.