Antenatal steroids suppress growth in the fetus and newborn. Although weight deficits are regained by weaning, studies show that intrauterine growth restriction with postnatal "catch-up" growth is a risk factor for hypertension, insulin resistance, and ischemic heart disease in adult life, with multigenerational consequences. We tested the hypothesis that fetal exposure to betamethasone suppresses fetal growth in the F1 pups and their untreated F2 offspring. Timed pregnant rats received a single two-dose course of intramuscular betamethasone (0.25 mg/kg/day) on days 17 and 18 of gestation. Matched controls received equivalent volumes sterile normal saline. The first-generation (F1) offspring were studied at term, P21, and P70, or mated at P60 to produce the following subgroups: (1) saline male/saline female (SM/SF), (2) betamethasone (B) male/BFemale (BM/BF), (3) BM/SF, and (4) SM/BF. The unexposed second-generation (F2) offspring were examined at birth and P70. Growth, neurological outcomes, and growth factors were determined. At birth, the F1 pups exposed to B were significantly growth suppressed compared with the controls, with correspondingly lower blood glucose, insulin, IGF-I, corticosterone, and leptin levels and delayed neurological outcomes. Catchup growth occurred at P21, surpassing that of the control group. By P70, growth was comparable, but glucose was higher, insulin was lower, and memory was retarded in the B group, and transmitted to the unexposed F2 offspring of B-exposed rats. Antenatal betamethasone has sustained metabolic and neurological effects that may impact the unexposed offspring. Whether these intergenerational effects reverse in future generations remain to be determined.
Keywords: Antenatal betamethasone; Growth hormone; Insulin; Insulin-like growth factor I; Intergenerational effects; Leptin; Neurological outcomes.