**Background:** Preterm birth is associated with altered growth patterns and increased risk of cardiometabolic diseases. Breast milk (BM) contains appetite-regulating hormones that may influence neonatal growth, but differences between term and preterm BM and their impact on growth are not fully understood. This study aimed to compare BM levels of ghrelin, resistin, leptin, insulin, peptide YY, and gastrointestinal peptide (GIP) between women with term and preterm labor, assess their association with neonatal growth in the first month, and evaluate the influence of maternal body composition and diet on these hormones.
**Methods:** This observational, longitudinal study enrolled 48 women (30 term, 18 preterm) at Hospital Clínico San Carlos (Madrid, Spain) from September 2019 to March 2020. BM samples were collected at days 7, 14, and 28 of lactation. Maternal body composition (BMI, body fat %, muscle %) was measured by bioimpedance at days 7 and 28. Maternal diet was assessed via 72-hour dietary recall at the same time points. BM hormones were analyzed using U-Plex Ultra-Sensitive MSD kits (insulin, leptin, ghrelin, GIP, peptide YY) and a Single Spot R-Plex assay (resistin). Neonatal anthropometrics (weight, length, head circumference) were obtained from medical records at birth and days 7, 14, 28. Growth velocities were calculated using Patel's model. Linear regression models (adjusted for sex and maternal fat mass) assessed associations between BM hormones and neonatal growth. Mixed models (with woman-by-day as random effect) evaluated associations of maternal body composition and diet with BM hormones.
**Key Results:** BM from women with preterm labor had significantly lower ghrelin levels but higher insulin, leptin, resistin, GIP, and peptide YY compared to term women (all p<0.05). Over the first month, resistin decreased, while GIP and peptide YY increased; insulin showed an interaction effect (decreasing in preterm, stable in term). In term neonates, weight gain was positively associated with BM insulin at day 7 (β not explicitly reported) and negatively with peptide YY at days 7 and 28. Length gain in term infants was positively associated with insulin at day 7. Head circumference in term infants was negatively associated with peptide YY at days 7 and 28. In preterm neonates, weight and length gain were positively associated with BM ghrelin at day 14 (β not explicitly reported). No associations were found for head circumference in preterm infants. At day 7, women with preterm labor had significantly higher BMI (28.8 vs. 24.7 kg/m², p=0.036), higher body fat % (42.4% vs. 35.9%, p=0.021), and lower muscle % (24.6% vs. 26.1%, p=0.033) compared to term women; these differences were not significant at day 28. Dietary intakes were similar between groups except for lower PUFA intake at day 28 in preterm women (11.6 vs. 14.2 g, p=0.026). In mixed models, among preterm women, BMI and body fat % were positively associated with BM ghrelin (β=7.7±0.8 and β=5.6±1.9, respectively). Protein and fiber intake were positively associated with BM ghrelin in preterm women (β=2.6±1.1 and β=1.8±0.5). In term women, fiber intake was negatively associated with BM peptide YY (β=-0.2±0.1). No associations were found between maternal anthropometry and BM hormones in term women.
**Clinical Implications:** This study demonstrates that preterm labor alters the hormonal profile of breast milk, with lower ghrelin levels that are positively associated with growth in preterm infants. Maternal body composition (higher fat mass) and dietary components (protein and fiber) are linked to higher BM ghrelin in preterm mothers, suggesting that optimizing maternal nutrition and body composition could improve BM hormonal content and support growth in premature infants. The findings also highlight that BM insulin and peptide YY influence growth in term infants differently. The negative impact of antenatal corticosteroids on growth through BM hormones warrants further investigation. These results support the importance of monitoring diet and body composition in mothers who deliver preterm to enhance the hormonal quality of their breast milk.