Maternal cortisol and stress are associated with birth outcomes, but are not affected by lipid-based nutrient supplements during pregnancy: an analysis of data from a randomized controlled trial in rural Malawi

An estimated 15% of children are born low birth weight and 11% are born preterm globally. Complications from preterm birth are responsible for 35% of the world's 3.1 million neonatal deaths and are a leading cause of under-5 mortality worldwide. Risk factors for smaller size at birth or shortened duration of gestation include poor nutrition during pregnancy, infections, and maternal stress. Maternal multiple micronutrient (MMN) supplements have been found to result in a small increase in birth weight of 22 g and an increase in the duration of gestation. Lipid-based nutrient supplements (LNS) provided during pregnancy have been evaluated for their effects on birth outcomes and early childhood growth in several studies. In impoverished communities, malnutrition is compounded by physical and psychosocial stressors that may further compromise pregnancy. Acute or chronic psychosocial experiences and biologic measures of serum or salivary cortisol concentrations have been associated with shortened duration of gestation and intrauterine growth restriction. Cortisol is a regulatory hormone involved in the hypothalamic-pituitary-adrenal axis (HPA) response to stress as well as in the fetal-placental-maternal neuroendocrine system regulating the maintenance of pregnancy and the timing of parturition. Cortisol and corticotropin-releasing hormone (CRH) concentrations rise exponentially over the course of pregnancy due to a positive feedback mechanism via the placenta. Elevated cortisol concentration is negatively associated with IGF-1 activity and is involved in fetal growth and maturation. Despite the physiologic explanations for a normal rise in cortisol during pregnancy, higher than expected increases in cortisol and CRH concentrations have important short- and long-term negative functional consequences on the health of the pregnancy and the offspring in later life. A three-armed, randomized controlled trial was conducted in rural Malawi to evaluate the effects of LNS, MMN, or iron-folic acid tablets (IFA) on birth outcomes. The trial enrolled 1391 women in early pregnancy and measured salivary cortisol concentration at 28 weeks and 36 weeks gestation. The results showed that there were no significant differences in mean cortisol concentrations by intervention group at 28 weeks or 36 weeks gestation. Cortisol concentrations were negatively associated with duration of gestation and birth weight, but not associated with length-for-age or head circumference-for-age z-scores. Perceived stress at 36 weeks was significantly associated with shorter newborn length-for-age z-scores.