Association of Maternal First Trimester Serum Levels of Free-Beta Human Chorionic Gonadotrophin and Hypospadias: A Population-Based Study.

Abstract

PURPOSE\nThe Human Chorionic Gonadotrophin (hCG) stimulates fetal testosterone production and contributes to normal development of male genitalia. Using population-based data, we hypothesized that differences in maternal free beta-hCG (hCGb) may be associated with hypospadias.\n\n\nMATERIALS AND METHODS\nData were obtained from the Paris Registry of Congenital Malformations (REMAPAR) (2011-2016). The initial study population included 3,172 pregnant women who gave birth to a singleton live born male infant with a congenital malformation. After exclusion of cases with unknown hCGb and those with chromosomal or genetic abnormalities, the study population included 194 boys with isolated hypospadias and 1,075 controls. For cases with operative note (N=125), we obtained data on type of (proximal/distal) hypospadias. Using quantile regression, we compared median values of multiple of median (MoM) hCGb measured for first trimester Down syndrome screening (10th-13th gestational weeks) for overall, as well as by type of hypospadias versus controls. We also took into account possible effects of placental dysfunction (maternal age, intrauterine growth retardation and preterm births) as potential factors of confusion.\n\n\nRESULTS\nOverall, the median hCGb MoM was comparable for women who had an infant with hypospadias versus controls (0.99 versus 0.95, p=0.3). However, proximal hypospadias was associated with a statistically significant higher median MoM than distal hypospadias or unspecified (1.49 versus 0.92 versus 1.05, p=0.02). The estimates were comparable after adjustment for placental dysfunction.\n\n\nCONCLUSIONS\nOur findings support the hypothesis that an alteration in maternal hCGb levels is associated with hypospadias. However, this association appears to be limited to proximal hypospadias.