BACKGROUND: The impact of Prader-Willi syndrome (PWS) domain gene expression on the growth of healthy children is not well understood. This study investigated associations between PWS domain gene expression in umbilical cord tissue and prenatal and postnatal growth, considering potential sex differences. METHODS: Relative gene expression of paternally expressed MAGEL2, NDN, and SNURF-SNRPN, and the small nucleolar RNAs SNORD116 and SNORD115 were determined by real-time quantitative polymerase chain reaction in umbilical cord tissue from 122 healthy newborns (59 girls and 63 boys). Gene expression levels were correlated with auxological measures at birth, infancy, and childhood (ages 2, 4, and 6 years). RESULTS: MAGEL2, NDN, SNORD116, and SNORD115 expression in the umbilical cord was negatively associated with birth weight, length, and placental weight (P <
0.001). Postnatally, these genes were positively associated with weight and length at 3 months (P <
0.001) and weight gain from birth to ages 1, 2, and 4 years (P <
0.01). Negative associations at birth were stronger in girls (P <
0.001), while positive associations during infancy and childhood were stronger in boys (P <
0.001). MAGEL2, SNORD116, and SNORD115 expression predicted early-postnatal growth, explaining the higher growth rate in boys compared to girls and accounting for sex differences up to 1.5 kg in weight and 3 cm in height during infancy. CONCLUSIONS: Paternally expressed PWS domain gene expression in the umbilical cord was negatively associated with prenatal growth and positively with early-postnatal growth in healthy infants. This gene expression may predict early human postnatal growth and promote the well-known sex dimorphism in growth. These results can also help in understanding the etiology of PWS, which remains unclear.