Abundances of placental imprinted genes CDKN1C, PHLDA2 and IGF-2 are related to low birth weight and early catch-up growth in full-term infants born small for gestational age

Children born small for gestational age (SGA) generally have a catch-up growth and rapid weight gain in the first years of life, which is a high risk of insulin resistance and cardiovascular diseases later in life. It was reported that the level of imprinted genes IGF-2, CDKN1C and PHLDA2 regulates placental growth. We assessed these imprinted genes expression levels in placental tissue and their influences on catch-up growth of full-term SGA infants. The protein and mRNA levels of placental CDKN1C, PHLDA2 and IGF-2 were analyzed in 29 full-term SGA and 29 full-term infants born appropriate for gestational age (AGA) using quantitative RT-PCR and Western blot assay, respectively. Catch-up growth was indicated by increased standard deviation score (ΔSDS) of weight at 1, 3 and 6 months relative to birth weight (BW). Correlations between indicated variables were evaluated using Pearson correlation coefficient analysis. Compared to AGA infants, CDKN1C and PHLDA2 levels were significantly increased, whereas IGF-2 was significantly reduced in SGA infants. The value of ΔSDS was significantly higher in SGA than that in AGA infants. For SGA status, Pearson analysis shows i) a negative correlation of CDKN1C and PHLDA2 abundances with BW, and a positive correlation of IGF-2 with BW, ii) no correlation between the three imprinted gene abundances and placental weight (PW), and between PW and BW, iii) a positive correlation of PHLDA2 abundance with CDKN1C, and iv) a positive correlation of CDKN1C and PHLDA2 abundances with ΔSDS, and a negative correlation of IGF-2 with ΔSDS at 1, 3 and 6 months. Taken together, increased CDKN1C and PHLDA2 and reduced IGF-2 abundances in placental tissue were related to BW and early period catch-up growth in full-term SGA infants. Placental CDKN1C, PHLDA2 and IGF-2 level monitoring may be useful for predicting and preventing the development of SGA.