The association between high levels of luteinizing hormone and proliferative retinopathy of prematurity in female preterm infants

Background: Luteinizing hormone (LH) and human chorionic gonadotropin (hCG), generally considered reproductive hormones, have potent proangiogenic properties. Both of these hormones and their joint receptor (CG/LH receptor) are found in the human eye. We hypothesized that an excess of these hormones is associated with proliferative retinopathy of prematurity (P-ROP).

Methods: Dried blood spots (DBS) were used to perform a cross-sectional study of infants (gestational age of <26 weeks) with and without P-ROP, born in Michigan between August 1, 2012, and March 15, 2015. The DBS were collected at 1 week and 4 weeks of age from 45 preterm infants (27 no-ROP and 18 P-ROP). The DBS were linked to hospital records and then deidentified. ICD-9 codes were used to identify P-ROP cases. Hormones levels were measured via electrochemiluminescence assays on the Meso Scale Discovery platform. Associations between hormone levels at 1 and 4 weeks of age and the presence or absence of P-ROP were assessed.

Results: In female infants, we noted a trend toward higher LH levels in ROP cases at week 1 (P = 0.11) and significantly higher LH levels in cases at week 4 (P = 0.03). In male infants, no ROP-related differences in LH levels were found at either time point. For hCG levels, no associations with P-ROP were found in either sex at either time point.

Conclusions: The association of high LH with P-ROP in female but not male infants raises the possibility that there are sex-specific hormonal determinants of aberrant retinal angiogenesis.