Intrauterine growth restriction affects z-scores of anthropometric parameters during the first 6 years in very low-birth-weight-children born at less than 30 weeks of gestation.

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.

The extent of DNA methylation anticipation due to a genetic defect in ICR1 in Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is a representative imprinting disorder. Gain of methylation at imprinting control region 1 (ICR1-GOM), leading to the biallelic expression of IGF2 and silencing of H19, is one of the causative alterations in BWS. Twenty percent of BWS patients with ICR1-GOM have genetic defects in ICR1. Evidence of methylation anticipation in familial BWS patients with ICR1 genetic defects has been reported. However, the precise methylation pattern and extent of anticipation in these patients remain elusive. In addition, although age-related IGF2-DMR0 hypomethylation has been reported in the normal population, the period of its occurrence is unknown. In this study, we analyzed 10 sites (IGF2-DMR0, IGF2-DMR2, CTCF binding sites 1-7, and the H19 promoter) within the IGF2/H19 domain in familial BWS patients harboring a pathogenic variant in ICR1. We found that sites near the variant had relatively higher methylation in the first affected generation and observed methylation anticipation through maternal transmission in the next generation. The extent of anticipation was greater at sites far from the variant than nearby sites. The extended and severe GOM might be due to the insufficient erasure/demethylation of pre-acquired ICR1-GOM in primordial germ cells or during the preimplantation stage. In the normal population, age-related IGF2-DMR0 hypomethylation occurred; it became established by young adulthood and continued to old age. Further studies are needed to clarify (1) the precise mechanism of anticipation in patients with familial BWS and (2) the mechanism and biological significance of constitutive hypomethylation of IGF2-DMR0 and/or other imprinted differentially methylated regions.

Postnatal relative adrenal insufficiency results in methylation of the glucocorticoid receptor gene in preterm infants: a retrospective cohort study.

Background: To investigate the relationship between early-life stress and glucocorticoid receptor (GR) gene methylation, which may result in long-lasting neurodevelopmental impairment, we performed a longitudinal analysis of the methylation ratio within the GR gene promoter 1F region using next-generation sequencing in preterm infants.Cell-free DNA was extracted from the frozen serum of 19 preterm birth infants at birth and at 1 and 2 months after birth. All were admitted to the neonatal intensive care unit of Juntendo University Shizuoka Hospital between August 2014 and May 2016 and suffered from chronic lung disease (CLD).Through bisulfite amplicon sequencing using an Illumina Miseq system and Bismark-0.15.0 software, we identified the rate of cytosine methylation. Results: Patients' sex and body weight standard deviation were extracted as the associated independent variables at birth. Sex, glucocorticoid administration for treating CLD, and postnatal invasive procedures (surgical operation and blood sampling) were extracted as the associated independent variables at 1 month. Methylation rates increased significantly between postnatal 1 and 2 months at 9 of the 39 CpG sites. Postnatal glucocorticoid administration to treat circulatory collapse was the most-associated independent variable with a positive regression coefficient for a change in methylation rate at these nine CpG sites. It also influenced the methylation ratio at 22 of the 39 CpG sites at 2 months of age. The standard deviation (SD) score at birth was extracted as an independent variable, with a negative regression coefficient at 9 of the 22 CpG sites together with glucocorticoid administration. Conclusions: The results of this study indicate that a prenatal environment that results in intrauterine growth restriction and postnatal relative adrenal insufficiency requiring glucocorticoid administration leads to GR gene methylation. That, in turn, may result in neurodevelopmental disabilities.

Correlations between feeding type and blood ionized magnesium levels in Japanese preterm infants.

Although magnesium (Mg) contents are different between breast milk and formula, few studies have investigated the blood Mg level in breast fed or formula fed preterm infants. We examined the influence of feeding type on serum Mg and whole blood ionized Mg (iMg) levels in preterm infants soon after birth. We included 115 preterm infants born between gestational weeks 32 and 35. Infants were separated into two groups: breast milk (BM) dominant group (n = 30) receiving ≥70% of Mg intake from BM and mixed-fed (MF) group (n = 85) receiving ≥30% of Mg intake from formula. Blood levels of Mg, iMg, Ca, and iCa at day 1 of age and at discharge from the hospital were compared between the groups. No differences in the Mg and iMg levels at day 1 of age were observed between the two groups. The Mg and iMg levels at discharge were significantly lower (P < 0.05) in the BM group than in the MF group; 0.86 (interquartile range 0.81-0.91) versus 0.91 (0.86-0.99) mmol/L and 0.46 (0.41-0.51) versus 0.52 (0.47-0.57) mmol/L, respectively. There were no differences in the Ca and iCa levels between the two groups. By stepwise multiple regression analysis, the percentage of BM intake was a significant independent predictor of the Mg and iMg levels. The feeding type influenced serum Mg and blood iMg levels in preterm infants soon after birth. Further studies are needed to investigate the influence of Mg on growth and the optimal range of blood Mg levels.