Mediation effect of cord blood cortisol levels between maternal prepregnancy body mass index and birth weight: a hospital-based cross-sectional study

Abstract

Background: Changes in maternal weight affect the maternal and fetal hypothalamicpituitary-adrenal (HPA) axis, influencing birth weight and contributing to the fetal origin of adult diseases (Barker's hypothesis). This study primarily focused on cord blood cortisol levels and identified the association between maternal pre-pregnancy body mass index (pre-BMI) and birth weight. It also assessed cord blood lipid profile changes related to maternal pre-BMI, birth weight, and cord blood cortisol levels.Purpose: To study the mediation effect of cord blood cortisol level between maternal pre-BMI and birth weight and its correlation with cord blood lipid profile.Methods: A total of 169 maternal-neonatal pairs were included at two tertiary care centers.Mediation analysis was used to estimate the extent of the association between maternal weight changes and birth weight. Results:For each unit increase in maternal pre-BMI, birth weight increased by 90.50 g; for every kilogram increase in gestational weight, birth weight increased by 128.44 g. No considerable mediation effect of cortisol was found between pre-BMI and gestational weight gain or between rate of weight gain and birth weight. Pre-BMI and birth weight had a significant negative correlation with high-density lipoprotein-cholesterol (HDL-C) levels, i.e., HDL-C was decreased by 1.1 mg/dL for every unit increase in BMI (P=0.017) and for every 100-g increase in birth weight, HDL-C decreased by 0.6 mg/dL (P=0.046). A significant positive correlation was found between cord blood lipid profile and cortisol levels, especially HDL-C (P=0.041). Conclusion: Cord blood cortisol levels did not mediate the association between maternal weight change and birth weight. A positive correlation was noted between cord blood cortisol A c c e p t e d A r t i c l e 3 levels and HDL-C level. Cord blood HDL-C level was negatively correlated with maternal pre-BMI and birth weight.

Pregestational Prediabetes Induces Maternal Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation and Results in Adverse Fetal Outcomes: Influences on HPA Axis and Development

“…Studies have also shown that excessive fetal exposure to GCs is associated with the downregulation of fetal glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) and impairment of the feedback regulation of the HPA axis in both infancy and adulthood [5,13,40,41]. Cross-sectional research has indicated a connection between low birth weight and disrupted functioning of the HPA axis, leading to elevated levels of GC in adulthood [10,[42][43][44]. In addition, the association between low birth weight and the development of T2DM was first reported in studies by Hales et al, who demonstrated a several-fold increase in the incidence of glucose intolerance and T2DM in adult men who were born with low birth weight compared with those born with normal birth weight [39,45].…”

Does cord blood cortisol have a mediating effect on maternal prepregnancy body mass index and birth weight?

“…Thus, the possibility has been raised that maternal or fetal blood cortisol levels may mediate the relationship between maternal pre-BMI or GWG and birth weight. Therefore, Selvam et al [ 7 ] conducted a hospital-based cross-sectional study to investigate whether cord blood cortisol mediates pre-BMI or GWG and birth weight after assuming cortisol as a hormone representing the HPA axis. The authors reported that the mediation effect of cord blood cortisol on maternal pre-BMI or GWG and birth weight was not statistically significant [ 7 ].…”

“…Therefore, Selvam et al [ 7 ] conducted a hospital-based cross-sectional study to investigate whether cord blood cortisol mediates pre-BMI or GWG and birth weight after assuming cortisol as a hormone representing the HPA axis. The authors reported that the mediation effect of cord blood cortisol on maternal pre-BMI or GWG and birth weight was not statistically significant [ 7 ]. Jin et al [ 8 ] analyzed all steroid hormones in the maternal-placental-fetal unit and found that corticosterone had a partial mediating effect of 3.48% and cortisol and corticosterone had a mediating effect of 4.33% and 5.38%, respectively, when the GWG was higher than the Institute of Medicine’s recommendation.…”

“…However, few studies have examined the change in cord blood lipid profile and maternal pre-BMI, birth weight, and cord blood cortisol. Therefore, Selvam et al [ 7 ] investigated changes in the cord blood lipid profile according to maternal pre-BMI, birth weight, and cord blood cortisol as secondary outcomes. In this study, cord blood high-density lipoprotein cholesterol (HDL-C) levels were negatively correlated with both pre-BMI and birth weight and positively correlated with cord blood cortisol.…”

“…In contrast, Mandraha et al [ 9 ] reported that LGA, SGA, or LBW neonates showed statistically significant higher levels of lowdensity lipoprotein cholesterol, very-low-density lipoprotein cholesterol, triglyceride, and cholesterol except HDL-C than appropriate for gestational age neonates. Although Selvam et al [ 7 ] reported that cortisol levels decrease due to maternal and fetal HPA axis dysfunction and maternal obesity and HDL-C concentrations decrease due to HPA axis dysregulation, further animal studies and large-scale multi-center studies are needed to support this claim due to inconsistent results of previous studies.…”