Blood Melatonin in Breast Milk-Fed Preterm Infants: Longitudinal Biomonitoring to 38 Weeks’ Postmenstrual Age (ProMote Study)

TL;DR

The study tracks melatonin levels in preterm infants fed breast milk, finding significant individual variation without clear patterns linked to birth time, age, or weight.

Contribution

This is the first longitudinal study to assess morning blood melatonin in breast milk-fed preterm infants up to 38 weeks PMA.

Findings

Melatonin concentrations showed substantial individual variability among preterm infants.

No consistent differences in melatonin levels were found based on time of birth, PMA, or weight-for-gestational-age.

Umbilical cord melatonin levels were low and not significantly influenced by gestational age at birth.

Abstract

Background/Objectives: Melatonin, produced by the placenta and pineal gland, regulates circadian timing and has antioxidant and immunomodulatory actions. After birth, neonatal secretion is low and its circadian pattern matures over months; evidence in preterm neonates is mixed. We longitudinally monitored morning blood melatonin from birth to 38 weeks’ postmenstrual age (PMA) in breast milk-fed preterm neonates, assessing differences by time of birth (day vs. night), PMA, and weight-for-gestational-age (WfGA). Methods: A prospective NICU cohort, conducted within the ProMote study. In total, 132 preterm neonates were recruited from 112 mothers. For infants ≥33 weeks’ GA, three samples were obtained: umbilical cord (available in 94; otherwise at the first NICU admission), day of life (DOL) 4–7, and DOL 10–14; for infants <33 weeks’ GA, an additional sample at 35–36 weeks’ PMA. Melatonin was measured by ELISA. Primary analyses used raw melatonin concentrations in linear mixed-effects models; sensitivity analyses checked robustness. Results: A final sample comprised 122 neonates. Concentrations were low to modest with wide between-neonate variation and no monotonic change across PMA. Mixed models showed no consistent differences by time of birth and no stable WfGA effect; occasional PMA-specific contrasts did not recur at adjacent time points. Umbilical cord concentrations were low, and gestational age at birth did not materially influence levels at a given PMA. Sensitivity analyses led to the same inference. Conclusions: In breast milk-fed preterm neonates, morning serum melatonin from 26–38 weeks’ PMA shows substantial individual variability without consistent differences by time of birth, PMA, or WfGA.

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