ObjectiveTo examine the environmental effects on cytosine methylation of preterm infant's DNA, because early life experiences are considered to influence the physiological and mental health of an individual through epigenetic modification of DNA.DesignA prospective cohort study, comparison of epigenetic differences in the glucocorticoid receptor (GR) gene between healthy term and preterm infants.SettingNeonatal Intensive Care Unit in a Japanese University Hospital.ParticipantsA cohort of 40 (20 term and 20 preterm) infants was recruited on the day of birth, and peripheral blood was obtained from each infant at birth and on postnatal day 4.Main outcome measuresThe methylation rates in the 1-F promoter region of the GR gene using the Mquant method.ResultsThe methylation rate increased significantly between postnatal days 0 and 4 in preterm infants but remained stable in term infants. Thus, the methylation rate was significantly higher in preterm than in term infants at postnatal day 4. Several perinatal parameters were significantly correlated with this change in the methylation rate. Logistic regression analysis revealed that methylation rates at postnatal day 4 predicted the occurrence of later complications that required glucocorticoid administration during the neonatal period. No gene polymorphism was detected within the GR promoter region analysed.ConclusionsAlthough further large-scale studies are needed to detect the environmental factors that explain the difference in epigenetic modification among infants after birth, our data show that the postnatal environment influences epigenetic programming of GR expression through methylation of the GR gene promoter in premature infants, which may result in relative glucocorticoid insufficiency during the postnatal period.

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We report a case of early onset sepsis caused by (CTX for cefotaximase and M for Munich)-type extended-spectrum β-lactamase-producing Escherichia coli (ESBL E. coli) in a preterm infant weighing 601 g. He was given meropenem and treated for endotoxin absorption with polymyxin B-immobilized fibers with only 8 mL of priming volume. The patient survived without any short-term neurological or respiratory sequelae. The choice of antibiotics is particularly important in seriously ill neonates with sepsis due to ESBL-producing organisms. Polymyxin B hemoperfusion might be an innovative therapy for severe neonatal sepsis and could improve outcome even in an extremely low-birthweight infant.

Objective:Little is known about physical constitution outcomes for very preterm infants. Here, we compare z-scores of anthropometric parameters up to 6 years of age in children born with very low birth weight (VLBW) at less than 30 weeks of gestation, with or without intrauterine growth restriction (IUGR).Design:Participants were divided into four subgroups: male (M), small for gestational age (SGA) (n = 30); M, appropriate for gestational age (AGA) (n = 59); female (F), SGA (n = 24); and F, AGA (n = 61). z-Scores of body weight (BW), body length (BL), and body mass index (BMI) were assessed at birth, 1 year corrected age, 3 years of age, and 6 years of age.Results:For boys, BW and BMI were significantly lower among SGA children than among AGA children at all assessments, but there was no difference in BL at 3 or 6 years. For girls, BW and BL were significantly lower among SGA children than among AGA children at all assessments, but no difference was detected in BMI after 1.5 years. No significant variation in the z-score of BW or BMI in either SGA group was observed after 1 year. BL z-score in all groups gradually increased until 6 years of age.Conclusion:IUGR affects BW and BMI in boys and BW and BL in girls during the first 6 years in VLBW children born at less than 30 weeks of gestation. SGA children did not catch up in BW or BMI from 1 to 6 years of age.

Background: IGF1 is a key molecule in the regulation of growth and metabolism. Low IGF1 secretion is known to cause growth restriction in childhood, as well as deregulated lipid metabolism, cardiovascular disease, and diabetes in adulthood. The IGF1 gene P2 promoter is highly methylated, resulting in low secretion of IGF1 in small infants and children. However, it is unknown when this methylation occurs. The aim of study was to clarify the point when this epigenetic program occurs during intrauterine development. We analyzed 56 preterm infants born before 32 weeks of gestation, including 19 intrauterine growth restriction (IUGR) infants whose birth weights were lower than − 2SD calculated by the Japanese datasets. We extracted genomic DNA from whole blood at birth; methylation of the six CpG sites in the IGF1 P2 promoter was analyzed by the bisulfite amplicon method using the MiSeq platform. Results: In contrast to term infants and children, the methylation of all six CpG sites positively correlated with body weight and body length at birth. IGF1 P2 promoter methylation levels were significantly reduced in all six CpG sites in infants with IUGR. Conclusions: These findings indicated that the IGF1 gene is epigenetically activated before 32 weeks of gestation in infants with IUGR and that the activated gene may become suppressed after this time point. This study may provide new insights to prevent the onset of adult diseases and to aid in nutritional management for preterm birth infants in neonatal intensive care units.