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Abstract Maternal obesity increases risk for bronchopulmonary dysplasia (BPD) by up to 42%. Identifying metabolic features that may contribute to the association between maternal pre-pregnancy body mass index (BMI) and BPD is critical in defining the molecular relationship between these conditions. We investigated the association between maternal obesity and BPD using newborn screen metabolites as an explanatory variable. We hypothesized that elevated pre-pregnancy BMI compared to a normal BMI referent group, is associated with increased circulating short and long-chain acylcarnitines and subsequent development of BPD. This was a retrospective study with linkage of maternal pre-pregnancy BMI, with newborn screen metabolites obtained from the California Newborn Screening Program and further linked with neonatal outcomes. Results demonstrated elevated levels of phenylalanine and proline associated with an increased risk for BPD (OR 5.3, 95% CI 1.2–23.8 and OR 5.4, 95% CI 1.3–22.3) in the obesity group compared to the referent group. Short- and long-chain acylcarnitines demonstrated a mildly increased risk for BPD in neonates of mothers with severe obesity compared to controls. The findings suggest that specific metabolites may influence the molecular conditioning that increases susceptibility to BPD.

Although most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation. An elastic net model described the relationship between GA and immunome (R=0.85, p=8.75e-14), and unsupervised clustering highlighted previously unrecognized GA-dependent immune dynamics, including decreasing basal MAP-kinase/NFκB signaling in antigen presenting cells; increasing responsiveness of cytotoxic lymphocytes to interferon-α; and decreasing frequency of regulatory and invariant T cells, including NKT-like cells and CD8+CD161+ T cells. Knowledge gained from the analysis of the neonatal immune landscape across GA provides a mechanistic framework to understand the unique susceptibility of preterm infants to both hyper-inflammatory diseases and infections.