Umbilical Cord Blood Leptin and IL-6 in the Presence of Maternal Diabetes or Chorioamnionitis

Abstract

Diabetes during pregnancy is associated with elevated maternal insulin, leptin and IL-6. Within the placenta, IL-6 can further stimulate leptin production. Despite structural similarities and shared roles in inflammation, leptin and IL-6 have contrasting effects on neurodevelopment, and the relative importance of maternal diabetes or chorioamnionitis on fetal hormone exposure has not been defined. We hypothesized that there would be a positive correlation between IL-6 and leptin with progressively increased levels in pregnancies complicated by maternal diabetes and chorioamnionitis. To test this hypothesis, cord blood samples were obtained from 104 term infants, including 47 exposed to maternal diabetes. Leptin, insulin, and IL-6 were quantified by multiplex assay. Factors independently associated with hormone levels were identified by univariate and multivariate linear regression. Unlike IL-6, leptin and insulin were significantly increased by maternal diabetes. Maternal BMI and birth weight were independent predictors of leptin and insulin with birth weight the strongest predictor of leptin. Clinically diagnosed chorioamnionitis and neonatal sepsis were associated with increased IL-6 but not leptin. Among appropriate for gestational age infants without sepsis, IL-6 and leptin were strongly correlated (R=0.6, P<0.001). In summary, maternal diabetes and birth weight are associated with leptin while chorioamnionitis is associated with IL-6. The constraint of the positive association between leptin and IL-6 to infants without sepsis suggests that the term infant and placenta may have a limited capacity to increase cord blood levels of the neuroprotective hormone leptin in the presence of increased cord blood levels of the potential neurotoxin IL-6.

Significance of Umbilical Cord Leptin Profile during Pregnancy in Gestational Diabetes Mellitus—A Systematic Review and Meta-Analysis

“…It is shown that cord leptin profile levels were significantly higher in women with GDM than in the control group (SMD = 0.59, 95% CI = 0.37 to 0.80, p < 0.001). This finding is consistent with previous studies in this regard [15,[31][32][33][34], in contrast with the absence of differences objectified by other authors [35][36][37]. On the other hand, lower cord leptin levels than maternal levels, with no differences between women with and without GDM, have been found by Mosavat M et al [38].…”

“…Nevertheless, some authors have detected significant differences among clinical-analytical variables of interest. A significant association between cord leptin levels and maternal BMI has been reported between mothers with [15,34,42] and without GDM [43]. Shang et al [32] have communicated that cord plasma leptin levels are inversely correlated with HOMA-IR in women with GDM.…”

“…The log cord serum leptin profile was independently associated with length and birth weight in multivariable linear regression analysis after adjustment for potentially confounding factors. Also, in GDM, cord blood leptin levels have been positively correlated with birth weight [34,42]. Higher levels were present in macrosomia compared to normal birth weight newborns [32], while lower levels were present in SGA infants with either stunting only or wasting only [47].…”

Hormonal Determinants of Growth and Weight Gain in the Human Fetus and Preterm Infant

“…Very little is known about the impacts of gestational diabetes on fetal hormones prior to delivery. Increasing maternal glucose levels are associated with increased cord blood c -peptide levels ( Table 3 ), even if the criteria for gestational diabetes are not met [ 278 , 279 , 280 , 281 ]. Similarly, among pregnant women with or without gestational diabetes, cord blood leptin levels rise in association with increasing maternal fasting blood sugar levels [ 262 , 279 , 280 , 281 ].…”

“…Increasing maternal glucose levels are associated with increased cord blood c -peptide levels ( Table 3 ), even if the criteria for gestational diabetes are not met [ 278 , 279 , 280 , 281 ]. Similarly, among pregnant women with or without gestational diabetes, cord blood leptin levels rise in association with increasing maternal fasting blood sugar levels [ 262 , 279 , 280 , 281 ]. Cord blood leptin and leptin per kg of infant weight are higher in newborns of mothers with gestational diabetes compared to normal pregnancies [ 216 ].…”