Identification of Nutritionally Modifiable Hormonal and Epigenetic Drivers of Positive and Negative Growth Deviance in Rural African Fetuses and Infants: Project Protocol and Cohort Description

Growth retardation (stunting, wasting and poor organ development) among children in low-income countries has major short and long-term health consequences yet very little is known about the nutritional and environmental influences on the key hormonal axes regulating child growth in these settings, nor the tempo and timing of faltering episodes. Here we describe the study protocol and provide a cohort description of the Hormonal and Epigenetic Regulators of Growth (HERO-G) study. This prospective cohort study from rural Gambia, West Africa, followed mothers and children longitudinally from pre-conception, through pregnancy, delivery, and to two years of child age A total of 251 eligible mother-infant pairs were recruited into the HERO-G study, with 206 (82%) followed up until two years of age. Women were seen at scheduled antenatal appointments at 20, 28 and 36 weeks of gestation, and at delivery, where possible. Between one week and 12 months of age, infants were visited every second day for collection of detailed anthropometry and morbidity data. Infants identified as about to enter a growth faltering episode at these visits entered a more detailed 20-day protocol, with the collection of dried blood spots, anthropometry and body composition. All infants were seen for scheduled clinic visits at 3, 6, 9, 12, 18 and 24 months of age for clinical examination and venous blood draw. Data from the HERO-G study is being used to explore three major mechanistic pathways influencing growth: 1) genome-wide investigations for signatures of epigenetic effects on any loci that might affect growth; 2) frequent anthropometric measurement coupled with non-invasive monitoring for rapid identification and interrogation of real-time faltering patterns and aetiology; 3) focused measurement of hormones and cytokines that act together in an integrated manner, both and after birth, to coordinate patterns of growth with immune activation, inflammation, and nutritional status.