Influence of birth-related maternal and neonatal factors on the levels of energy metabolism mediators in infants born at 32 or fewer weeks of gestation

Abstract

Background

Energy metabolism mediators, which include the adipokines (leptin, adiponectin, ghrelin) and insulin-like growth factor 1 [IGF-1], are hormone-like proteins, produced and expressed in the placenta and fetal membranes, with properties featuring metabolic adaptation and inflammatory processes. Due to the complexity of the metabolic adaptation of preterm neonates during the transition to extrauterine life, it becomes essential to recognize the factors that influence the alteration of the adipokines and IGF-1 levels in the early postpartum stage.

This study assessed the significance of maternal-fetal-neonatal factors in predicting the levels of leptin, adiponectin, ghrelin, and IGF-1 in preterm infants born at 32 or fewer weeks of gestation, during the early stage of postnatal adaptation.

Methods

Energy metabolism mediator levels were measured in urine samples obtained from extremely (less than 28 weeks) and very (28–32 weeks) preterm infants, within 48 h after their birth, and before the initiation of enteral nutrition. The urine samples were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. The collected data included all birth-related maternal and neonatal factors such as maternal age, race/ethnicity, hypertensive disorders of pregnancy, diabetes, gravidity, parity, type of pregnancy, mode of delivery, and antenatal use of corticosteroids, antibiotics, magnesium sulfate, Apgar scores at 1 and 5 min, gestational age, and birth weight. We investigated the correlation between the levels of the tested mediators, the significance of the differences in their average levels based on the dichotomized maternal and neonatal factors, and the effect of the selected factors, in multiple regression models. Data from the regression models constructed for leptin, adiponectin, ghrelin, and IGF-1 are presented as regression coefficient β with Standard Error (SE) of β, coefficient of determination (R²), and adjusted R². Before including the factor in regression models, we tested for the multicollinearity effect. Two-sided P values <0.05 were considered statistically significant.

Results

Among the 70 studied infants, 47.1% were male, 40.6% were white, 28.6% were extremely preterm, and 18.6% were born with a weight <750 grams. Except for a mild interplay between the adiponectin and IGF-1 levels, there was no correlation between the levels of the other studied mediators. Up to 20% variation in the tested energy metabolism mediator levels was dependent on some of the birth-related maternal and neonatal characteristics. For instance, leptin levels were reduced in association with male gender (-0.493 [0.190], p < 0.02) and increased in infants born to primigravids (0.562 [0.215], p < 0.02). Adiponectin levels were increased in infants born to nulliparous as compared to multiparous women (0.400 [0.171], p < 0.03). Ghrelin levels were reduced in males (-0.057 [0.026], p < 0.04). IGF-1 levels were increased in the urine of extremely preterm neonates (0.357 [0.111], p < 0.01) and preterm infants born with an Apgar less than three at 1 min (0. 340 [p < 0.153], p < 0.04).

Conclusions

Nearly one-fifth of the variation in the urinary levels of the adipokines (leptin, adiponectin, ghrelin) and IGF-1 during the early postnatal stage in infants born at 32 or fewer weeks of gestation was predicated on one or more of the maternal and neonatal factors such as the infant’s sex, extreme preterm gestation, a low Apgar score at 1 min, or birth to nulliparous women or primigravida mothers. Further studies will be required to explain the role of energy metabolism mediators in the postnatal adaptation of preterm-born infants.

Keywords:

• Preterm birth
• maternal factors
• intrapartum/neonatal characteristics
• postpartum levels
• energy metabolism mediators

Acknowledgment

We would like to express our most sincere appreciation to the infants and their families as well as the nursing staff in the NICU for their participation and commitment to this research project.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

This research complies with the guidelines for human studies and was conducted ethically by the World Medical Association Declaration of Helsinki. The study protocols were reviewed and approved by the Institutional Review.

Parental consent

Written informed consent was obtained from the study participants’ mothers before collecting the urine samples.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [AP], upon reasonable request

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.