Perinatal lipocalin-2 profile at the extremes of fetal growth.

BACKGROUND: Lipocalin-2 (LCN-2) has been identified as an osteoblast-secreted hormone regulating immunity, inflammation and metabolic homeostasis and has emerged as a diagnostic and prognostic biomarker for acute kidney injury in neonates. We investigated the impact of fetal growth on antepartum maternal serum, cord serum and breast milk LCN-2 concentrations and the associations of the latter with perinatal parameters. METHODS: Maternal serum, cord serum and breast milk LCN-2 concentrations were measured by ELISA in samples from 80 mothers who delivered 40 appropriate (AGA), 20 large for gestational age (LGA) and 20 intrauterine growth restricted (IUGR) neonates, classified by customized weight centiles. LCN-2 concentrations were associated with birth weight, customized centile, gender, maternal age and delivery mode. RESULTS: Antepartum maternal serum LCN-2 concentrations were significantly higher in women delivering AGA infants compared to the other two groups. Cord blood LCN-2 concentrations were significantly higher compared to maternal ones; furthermore, they were significantly elevated in the IUGR group compared to the LGA one (p = .019). Lowest concentrations were detected in breast milk, which did not differ between the three growth groups. A negative correlation was documented between cord blood LCN-2 concentrations and customized centiles (r: -0.304, p = .007). CONCLUSIONS: The higher cord serum LCN-2 concentrations, compared to maternal ones, may point to its fetal origin and potential role in intrauterine growth. The negative correlation of cord LCN-2 concentrations with customized centiles, possibly implies reduced nephron endowment/subclinical kidney damage in IUGR neonates. The extremely low LCN-2 breast milk concentrations could imply that the secretion of LCN-2 from maternal circulation to breast milk is not influenced by factors leading to intrauterine growth pathology.

Inhibitors of osteoblastogenesis in early human milk and maternal serum: evidence for protective properties of mother's milk on bone.

Objective: Lactation is associated with a dramatic increase of maternal bone turnover, leading to a reversible bone loss. Early life nutrition may influence later osteoporosis risk. Proteins synthesized by the group of wingless (Wnt) genes are key mediators of osteoblastogenesis and bone formation. We aimed to investigate maternal milk and serum concentrations of the inhibitors of the Wnt signaling pathway, Dickkopf-1 (DKK-1) and sclerostin.Material and methods: In 80 women, maternal milk and serum concentrations of DKK-1 and sclerostin were determined by ELISA on the 3rd-4th day postpartum. Concentrations were associated with various maternal, gestational and neonatal characteristics.Results: DKK-1 and sclerostin were detectable in early milk [mean ± SD: 817.17 ± 259.61 pg/mL, median (range) 258.04 (2452.40-53.17) pg/mL, respectively] at significantly lower concentrations than in maternal serum [mean ± SD: 3375.36 ± 416.75 pg/mL, median (range) 16 200.54 (58 832.00-3012.60) pg/mL, respectively], (p < .000). Maternal milk sclerostin concentrations positively correlated with respective serum ones (r = 0.599, p = .000). Maternal serum and milk sclerostin concentrations positively correlated with maternal body mass index (r = 0.37, p = .001 and r =0.38, p = .000, respectively), while maternal serum sclerostin concentrations were higher in primiparas (p = .002).Conclusion: DKK-1 and sclerostin are present in early human milk at significantly lower concentrations, compared with maternal serum, probably contributing to the short- and long-term benefits of mother's milk for bone health. Moreover, the large amounts of both substances in maternal serum may represent disruption of the Wnt cascade, contributing to the well-known lactation-associated bone loss, which seems to be greater in primiparas and obese mothers.

Cord blood fatty acid-binding protein-4 levels are upregulated at both ends of the birthweight spectrum.

AIM: Fatty acid-binding protein-4 (FABP4) is an adipokine associated with obesity and signs of the metabolic syndrome. We aimed to investigate at birth in term neonates with normal and abnormal intrauterine growth concentrations of FABP4 and associate them with various perinatal parameters. METHODS: Serum cord blood FABP4 levels were prospectively determined by ELISA in 80 singleton term appropriate-for-gestational-age (AGA), intrauterine growth-restricted (IUGR) and large-for-gestational-age (LGA) neonates. RESULTS: Compared to the AGA group, cord blood FABP4 levels were increased in the IUGR and LGA groups. Additionally, they were higher in early-term than full-term neonates. A significant U-shaped correlation was recorded between serum FABP4 levels and birthweight. A significant negative correlation between cord blood FABP4 and gestational age in the whole study population was noted. CONCLUSION: Cord blood FABP4 levels were significantly higher at the extremes of foetal growth at term and negatively correlated with gestational age, being increased in early-term versus full-term neonates. Further longitudinal studies with larger sample sizes are required to elucidate FABP4 implication in foetal growth and its association with future adverse cardiometabolic outcomes in the offspring.

Preadipocyte factor-1 in maternal, umbilical cord serum and breast milk: The impact of fetal growth.

BACKGROUND/OBJECTIVE: To study the concentrations of preadipocyte factor-1 (Pref-1) -an inhibitor of adipocyte differentiation, implicated in adipose tissue metabolism, late metabolic disorders and fetal growth- in maternal and umbilical cord serum, as well as maternal milk and correlate above concentrations with intrauterine growth and other perinatal parameters. MATERIAL AND METHODS: Pref-1 concentrations were determined by ELISA in antepartum maternal and umbilical cord serum, as well as day 3 to 4 postpartum breast milk, deriving from 80 women, who delivered 40 appropriate (AGA), 20 large for gestational age (LGA) and 20 intrauterine growth restricted (IUGR) neonates, classified by the use of customized birth-weight standards adjusted for significant determinants of fetal growth. RESULTS: Umbilical cord serum Pref-1 concentrations were significantly higher than antepartum maternal ones (p < 0.001), while breast milk concentrations were the lowest (p < 0.001 concerning umbilical serum, p < 0.001 concerning maternal serum). Umbilical cord serum Pref-1 concentrations were significantly lower in the LGA group than in the AGA one (p = 0.044). Breast milk and maternal serum Pref-1 concentrations did not differ between the three intrauterine growth groups. Maternal serum and breast milk Pref-1 concentrations did not correlate with maternal age, body mass index before and after gestation, birth weight, body length, and customized centile. A positive weak correlation was recorded between maternal serum and milk Pref-1 concentrations (r = 0.238, p = 0.034). CONCLUSIONS: Pref-1 concentrations in umbilical cord serum are higher than in antepartum maternal serum, probably pointing to its fetal origin and role in intrauterine growth. Breast milk concentrations, being extremely low, and possibly implying infant protection from metabolic disorders, positively correlate with maternal serum ones, conceivably suggesting a transfer of the substance from the circulation to the breast. Umbilical cord serum Pref-1 concentrations were lower in LGA fetuses/neonates, as compared to respective AGA ones.