Sex-specific associations of insulin-like peptides in cord blood with size at birth

Objective: Insulin-like peptides (insulin, IGF-1, IGF-2) are essential regulators of foetal growth. We assessed the role of these peptides for birth size in a sex-specific manner. Design: Cross-sectional cohort analysis. Patients and Measurements: In 369 neonates, cord blood insulin, C-peptide, IGF-1 and IGF-2 levels were measured. Outcomes were placenta weight, birthweight, length and ponderal index. In linear regression models, the association of insulin-like peptides with growth outcomes was assessed, adjusted for gestational age and delivery mode. Interaction between insulin-like peptides and neonatal sex was assessed. Results: No sex differences in levels of insulin-like peptides were observed. Significant interactions were found of sex with IGF-1 for birthweight, and of sex with C-peptide for all outcomes, except ponderal index. The association of IGF-1 (ng/mL) with birthweight was stronger and only significant in males (beta coefficient 3.30 g; 95%CI 1.98-4.63 in males and 1.45 g; −0.09-2.99 in females). Associations of C-peptide (ng/mL) with growth outcomes were stronger and only significant in females (placenta weight females: 181.3 g; 109.3-253.3; P <.001, males: 29.8 g; −51.5-111.1; P =.47, birthweight females: 598.5 g; 358.3-838.7: P <.001, males: 113.7 g; −154.0-381.4; P =.40). Associations of IGF2 with birthweight were similar in males and females. No associations were found with ponderal index. Conclusions: C-peptide and IGF-1 in cord blood associate with birthweight, length and placenta weight in a sex-specific manner, with stronger associations of C-peptide levels with placenta weight, birthweight and length in females and stronger associations of IGF-1 levels with birthweight in males