Transient anomalies in genital appearance in some extremely preterm female infants may be the result of foetal programming causing a surge in LH and the over activation of the pituitary-gonadal axis

Aim Animal studies have linked foetal programming with the development of the polycystic ovarian syndrome, and metabolic syndrome, in adulthood. The objective is to describe the investigation of four extreme-premature female infants born between 25 and 29 weeks' gestation with apparent genital abnormalities in association with unusually high androgens and gonadotrophins, to postulate a cause and to raise awareness of pitfalls in assessment of these infants. Methods Clinical examination and biochemical evaluation of four infants referred for apparent congenital ambiguity. Results Female gender was assigned at birth. Chromosome analysis confirmed 46XX, urine steroid profiles demonstrated no evidence of congenital adrenal hyperplasia and only the expected levels of foetal adrenal steroids.Elevated LH (up to 162 IU/l), testosterone (up to 2·6 nmol/l), delta4 androstenedione (up to > 35 nmol/l) and dehydro-epiandrosterone sulphate (DHEAS) (up to 26·6 µmol/l) were seen in all four infants. These decreased over time but were significantly different from a control population of premature infants of similar gestational age. Conclusions We postulate that the clinical pattern of apparent clitoral enlargement in some extremely premature infants may reflect true temporary virilization due to an unusually high (or excessive) LH surge, in turn causing high foetal androgens. Foetal programming of gonadotrophin excess is probably the primary cause of androgen increase, in turn causing virilization, in some extreme-premature infants. These may potentially be a group at future risk of polycystic ovary or metabolic syndrome, however, further work needs to be conducted to substantiate this hypothesis.