Co‐causation of reduced newborn size by maternal undernutrition, infections, and inflammation

Abstract

More than 20 million babies are born with low birthweight annually. Small newborns have an increased risk for mortality, growth failure, and other adverse outcomes. Numerous antenatal risk factors for small newborn size have been identified, but individual interventions addressing them have not markedly improved the health outcomes of interest. We tested a hypothesis that in low‐income settings, newborn size is influenced jointly by multiple maternal exposures and characterized pathways associating these exposures with newborn size. This was a prospective cohort study of pregnant women and their offspring nested in an intervention trial in rural Malawi. We collected information on maternal and placental characteristics and used regression analyses, structural equation modelling, and random forest models to build pathway maps for direct and indirect associations between these characteristics and newborn weight‐for‐age Z‐score and length‐for‐age Z‐score. We used multiple imputation to infer values for any missing data. Among 1,179 pregnant women and their babies, newborn weight‐for‐age Z‐score was directly predicted by maternal primiparity, body mass index, and plasma alpha‐1‐acid glycoprotein concentration before 20 weeks of gestation, gestational weight gain, duration of pregnancy, placental weight, and newborn length‐for‐age Z‐score (p < .05). The latter 5 variables were interconnected and were predicted by several more distal determinants. In low‐income conditions like rural Malawi, maternal infections, inflammation, nutrition, and certain constitutional factors jointly influence newborn size. Because of this complex network, comprehensive interventions that concurrently address multiple adverse exposures are more likely to increase mean newborn size than focused interventions targeting only maternal nutrition or specific infections.

Breast Milk Cytokines and Early Growth in Gambian Infants

“…Higher levels of specific pro-inflammatory BM cytokines were negatively associated with WAZ at the final visit in our cohort, although the relationship was weak and clinical significance remains as yet unclear. The relationship between a pro-inflammatory environment and poor weight gain, both in the fetus and infant, has been previously described (46, 51–54). More specifically, the importance of TNFα and IL6 to early infant growth has already been suggested by Fields et al (47).…”

Effect of Diarrheal Illness During Pregnancy on Adverse Birth Outcomes in Nepal

“…This has been demonstrated for malaria [31, 32], but no such studies exist for common diarrheal pathogens. Inflammation resulting from infection may also play a role through impaired growth pathways and reduced nutritional transfer from mother to fetus [11, 33, 34].…”

“…Studies of diarrhea during pregnancy (1) have examined only women who were hospitalized for diarrheal illness or (2) have focused on specific etiologies such as listeria or typhoid, which are known to cause severe disease in pregnant women [4–9]. Community-based studies that have included women who were not hospitalized have generally examined infant neurocognitive outcomes and growth [4, 10, 11].…”

Poor Birth Outcomes in Malaria in Pregnancy: Recent Insights Into Mechanisms and Prevention Approaches

“…In addition, undernutrition during pregnancy may also affect placental size and its functional capacity, given that maternal weight and gestational weight gain are both mediators of placental weight. All three factors were positively correlated to birthweight ( 89 ). Furthermore, both MiP and maternal undernourishment have been reported to impair trophoblast invasion and migration, as well as increase uterine artery resistance ( 50 , 90 , 91 ).…”