ObjectiveTo investigate early nutrition and growth of preterm monochorionic diamniotic（MCDA） twins combined with selective intrauterine growth restriction（sIUGR） and explore the potential role of DNA methylation in regulating extrauterine growth. MethodsTwenty-four pairs of preterm MCDA twins combined with sIUGR hospitalized in the Department of Neonatology of The First Affiliated Hospital of Sun Yat-sen University from March 2019 to February 2022 were enrolled， divided into larger twins group（n=24） and smaller twins group （n=24） according to birth weight. The comparison of daily nutritional intakes， the incidence of neonatal complications and physical growth from birth to 24 months of corrected age between two groups was performed using t-test， analysis of ANOVA， Chi-square test or Fisher's exact test. Differential DNA methylation analysis was performed using the methylation microarrays and differentially methylated site was validated using pyrosequencing method. ResultsThere were no significant differences in the daily intake of carbohydrate， protein， fat and energy between two groups （all P＞0.05）. There were no significant differences in the incidence of asphyxia， neonatal respiratory distress syndrome， bronchopulmonary dysplasia， retinopathy of prematurity and necrotizing enterocolitis between two groups （all P＞0.05）. Z-scores for weight， length and head circumference were significantly lower in the smaller twins group compared with the larger twins group from birth to 24 months of corrected age（all P =0.000）. Difference in Z-scores for weight and length at term， 6 months， 12 months of corrected age did not differ significantly from that at birth（all P＞0.05） while difference in Z-scores for weight and length between the twins at 18 months and 24 months of corrected age were significantly lower than that at birth （P = 0.009， P = 0.032， P = 0.026， P = 0.004）. Difference in Z-scores for head circumference at 6 months， 12 months， 18 months， 24 months of corrected age were significantly lower than at birth （P = 0.001， others P = 0.000） except at term（P＞0.05）. The differences in weight， length and head circumference between the twins at term， 6 months， 12 months， 18 months and 24 months of corrected age significantly reduced （P = 0.001， P = 0.007， P = 0.001， others P = 0.000）. Eighteen differentially methylated sites were identified and the methylation level of NFATC1 gene in the smaller twins group was significantly higher than that in the larger twins group（P = 0.043）. ConclusionMCDA twins combined with sIUGR shares similar early nutrition and neonatal complications， while smaller twins at 24 months of corrected age grow faster than larger twins， which might be related to a higher methylation level of NFATC1 gene in smaller twins.

Objective To assess the growth of monochorionic diamniotic (MCDA) twins discordant for birth weight during their first 24 months of life.Methods Clinical data and growth parameters from birth to 24 months of age of 31 pairs(62 cases) of birth weight-discordant MCDA twins (≥ 25％ difference in birth weight) who were born alive in the First Affiliated Hospital,Sun Yat-sen University between January 1,2010 and June 30,2016 were retrospectively analyzed.Each pair of twins was divided into the large birth weight group (31 cases) and the small birth weight group (31 cases).All datas were statistically analyzed with Chisquare test,paired t test,analysis of variance or LSD-t test.Results (1) The incidence of birth defects and hypoproteinemia in the small birth weight group were higher than that in the large birth weight group [29.0％ (9/31) vs 0.0％ (0/31),54.8％ (17/31) vs 25.8％ (8/31);x2=8.319 and 5.429;both P ＜ 0.05].(2) The standard deviation scores (SDS) of weight,length and head circumference at birth and 1,6,12,18 and 24 months of age of the small birth weight group were lower than those of the large birth weight group [birth:(-2.00 ± 0.66) vs (-0.04±0.60),(-1.83±1.13) vs (-0.37±0.83),(-1.42±1.03) vs (0.17±0.84),t=17.214,8.390 and 7.759;1 month:(-1.77±0.81) vs (-0.60±0.65),(-2.36±1.20) vs (-0.94±0.74),(-1.71±1.26) vs (-0.44± 1.09),t=9.424,9.059 and 7.197;6 months (-1.00±0.84) vs (-0.09±0.56),(-1.31 ± 1.22) vs (-0.04±0.80),(0.30±1.51) vs (1.11 ± 1.20),t=-7.578,7.988 and 6.091;12 months:(-0.34±1.06) vs (0.47±0.79),(-1.00±0.92) vs (-0.14±0.73),(-0.16±0.76) vs (0.49±0.58),t=5.747,7.155 and 5.664;18 months:(-0.06±0.95) vs (0.74±0.66),(-0.92± 1.07) vs (-0.24±0.92),(-0.32±0.72) vs (0.29±0.66),t=6.153,4.496 and 3.877;24 months:(0.20±0.79) vs (0.88±0.62),(-0.66±0.59) vs (0.01 ±0.67),(-0.37±0.60) vs (0.34±0.68),t=5.317,4.800 and 4.905;all P ＜ 0.001].However,the changes in SDS (△ SDS) of weight,length and head circumference from birth to 24 months of age and the incidence of △ SDS ＞ 0.67 were significantly higher in the small birth weight group than those in the large birth weight group [△SDS:(2.20± 1.10) vs (0.92±0.91),(1.17± 1.21) vs (0.37± 1.14),(1.05± 1.07) vs (0.16±0.89),t=8.422,3.918 and 3.547,all P ＜ 0.001;△SDS ＞ 0.67:93.5％ (29/31) vs 61.3％ (19/31),61.3％ (19/31) vs 35.5％ (11/31),61.3％ (19/31) vs 29.0％ (9/31),x2=9.226,4.133 and 6.53 1,all P ＜ 0.05].(3) The difference in SDS for weight,length and head circumference between the large and small birth weight twins at 24 months of age were significantly lower than those at birth [(0.68 ± 0.71) vs (1.95 ± 0.63),(0.67 ± 0.77) vs (1.46± 0.97),(0.71 ± 0.80) vs (1.60±1.15);all P ＜ 0.05].Conclusions Growth differences are found between birth weight-discordant MCDA twins all the way to 24 months of age from birth at a reduced trend.