# 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.

## Key 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.