A case of neonatal thrombocytopenia due to maternal Helicobacter pylori-associated immune thrombocytopenia.

Many studies in adults have suggested an association between Helicobacter pylori (H. pylori) infection and chronic immune thrombocytopenia (ITP). In adults with ITP and H. pylori infection, eradicating H. pylori is recommended as the first-line therapy. However, the association between ITP and H. pylori in children remains controversial. Diagnosing thrombocytopenia in pregnant women is challenging but crucial because maternal ITP causes neonatal ITP through transplacental transfer of immunoglobulin G, also known as passive ITP. Herein, we report a case of neonatal passive ITP due to maternal H. pylori-associated ITP. A boy was born at term with neonatal thrombocytopenia to a mother tentatively diagnosed with gestational thrombocytopenia. However, further examination suggested that maternal thrombocytopenia was associated with H. pylori, and neonatal thrombocytopenia was diagnosed as ITP due to maternal ITP. The newborn received intravenous immunoglobulin treatment, and the thrombocytopenia did not recur. The mother was examined using esophagogastroduodenoscopy, and her rapid urease test using gastric mucosa tissue samples was positive. Subsequently, she was diagnosed with H. pylori infection and received H. pylori eradication therapy, after which her platelet count remained normal. To our knowledge, this is the first reported case of neonatal passive ITP secondary to maternal H. pylori-associated ITP. This case suggests that maternal H. pylori infection can lead to the production of platelet autoantibodies, which can destroy antibody-sensitized platelets in the mother and neonate. To summarize, H. pylori infection can also cause ITP in children. Therefore, pregnant women diagnosed with H. pylori-associated ITP should receive H. pylori eradication therapy to prevent their neonates from developing passive ITP.

De novo heterozygous variants in KIF5B cause kyphomelic dysplasia.

Kyphomelic dysplasia is a heterogeneous group of skeletal dysplasias characterized by severe bowing of the limbs associated with other variable findings, such as narrow thorax and abnormal facies. We searched for the genetic etiology of this disorder. Four individuals diagnosed with kyphomelic dysplasia were enrolled. We performed whole-exome sequencing and evaluated the pathogenicity of the identified variants. All individuals had de novo heterozygous variants in KIF5B encoding kinesin-1 heavy chain: two with c.272A>G:p.(Lys91Arg), one with c.584C>A:p.(Thr195Lys), and the other with c.701G>T:p.(Gly234Val). All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. All individuals had sharp angulation of the femora and humeri, distinctive facial features, and neonatal respiratory distress. Short stature was observed in three individuals. Three developed postnatal osteoporosis with subsequent fractures, two showed brachycephaly, and two were diagnosed with optic atrophy. Our findings suggest that heterozygous KIF5B deleterious variants cause a specific form of kyphomelic dysplasia. Furthermore, alterations in kinesins cause various symptoms known as kinesinopathies, and our findings also extend the phenotypic spectrum of kinesinopathies.

Associations between size at birth and size at 6 years among preterm infants: a retrospective cohort study.

BACKGROUND: Little is known about the relationship between fetal growth and size at school age in children born prematurely. We evaluated the relationships between gestational age and anthropometric z-scores at birth and size at 6 years of age in very-low-birthweight infants born at <30 weeks' gestation. METHODS: We collected data from the medical records of 187 preterm children at birth and 6 years of age. We evaluated correlations between gestational age and z-scores for weight, body length, and head circumference at birth and z-scores for weight, height, and body mass index at 6 years of age. RESULTS: Simple regression analysis showed that, in boys and the overall group, gestational age and z-scores for weight, body length, and head circumference at birth had significant association with z-scores for weight, height, and body mass index at 6 years of age. No significant associations were found in girls, except for weight z-scores at 6 years with gestational age and head circumference z-scores at birth. Multiple regression analysis showed that gestational age and length z-score at birth were significantly and independently associated with weight and height z-score at 6 years. Gestational age was also significantly and independently associated with body mass index z-score at 6 years. CONCLUSION: Gestational age and fetal growth in length (assessed with the birth-length z-score) were associated with anthropometric z-scores at 6 years in very-low-birthweight children born at <30 weeks of gestation, especially in boys.

Urinary prostaglandin D2 metabolite excretion during the first six months of life was significantly lower in breast-fed than formula-fed infants.

AIM: The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and breast milk is considered to provide the optimal source of infant nutrition. This pilot study from September 2013 to May 2015 examined the effect of breastfeeding on prostaglandin metabolism in healthy term infants. METHODS: Urine samples were collected from 19 infants at one month of age in the Juntendo University Hospital, Tokyo, Japan. The 13 infants in the breast-fed group received less than 540 mL/week of their intake from formula, and the other six were exclusively fed on formula. At six months, we sampled 14 infants: nine breast-fed and five receiving formula. The infants were from normal single pregnancies and free from perinatal complications. We analysed urinary prostaglandin metabolites-tetranor prostaglandin E2 metabolite (t-PGEM) and tetranor prostaglandin D2 metabolite (t-PGDM)-using liquid chromatography tandem-mass spectrometry. RESULTS: Urinary t-PGDM excretion at one and six months was significantly lower in breast-fed infants than formula-fed infants. However, urinary t-PGEM excretion at one and six months was not significantly different between the groups. CONCLUSION: Our study showed that the type of feeding in early infancy affected prostaglandin metabolism in healthy term infants.

Influence of i.v. lipid emulsion on lipoprotein subclass in preterm infants.

BACKGROUND: Lipid emulsions given i.v. are normally rapidly metabolized by apoprotein recruited from high-density lipoprotein (HDL) particles in the blood. Very low-birthweight infants (VLBWI), however, have a low rate of lipid clearance from the blood, and therefore lipid emulsions must be given carefully to minimize the risk of hyperlipidemia. The purpose of this study was to evaluate the influence of i.v. lipid emulsion on lipoprotein subclass profile in VLBWI during the early postnatal period. METHODS: Forty-six VLBWI who had been given different doses of lipid emulsion in the first few days after birth were enrolled in the present study. Triglyceride and cholesterol content of each lipoprotein subclass was measured at 3 weeks after birth, and their correlation with the total dose of lipid emulsion was calculated. RESULTS: There was no correlation between the total dose of lipid emulsion and the triglyceride and cholesterol content in any subclasses of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL). There was a significant negative correlation between the total dose of lipid emulsion and the triglyceride content in very large (P < 0.05, r = -0.32), large (P < 0.01, r = -0.47) and medium HDL (P < 0.05, r = -0.34) particles; and the cholesterol content in large (P < 0.01, r = -0.47) and medium HDL (P < 0.01, r = -0.4) particles. CONCLUSION: Lipid emulsion influenced the triglyceride and cholesterol content of HDL particles in VLBWI, suggesting that lipid emulsion can affect lipid metabolism in this infant population in the early postnatal period.

Long-term renal tubular damage in intrauterine growth-restricted rats.

BACKGROUND: Intrauterine growth restriction (IUGR) has been shown to be associated with increased risk of renal disease or hypertension in later life. Glomerular dysfunction, however, has mainly been reported, and limited information is available to link IUGR with renal tubular damage. The aim of this study was therefore to investigate urinary markers of tubular damage in a rat model of IUGR induced by bilateral uterine artery ligation. METHODS: Pregnant Sprague-Dawley rats underwent bilateral uterine artery ligation, while the control group underwent sham surgery. RESULTS: Birthweight was reduced, and urinary ß2-microglobulin (ß2-MG)-, cystatin C (Cys-C)-, and calbindin-to-creatinine ratios were significantly higher at weeks 4 and 8 in the IUGR group compared with the control group. These urinary markers were not significantly different at week 16 between the two groups. Increased excretion of urinary ß2-MG, Cys-C, and calbindin was observed in IUGR rats at ≥8 weeks of age. CONCLUSION: Children born with IUGR are at increased risk for renal tubular damage.

Relationship between insulin-like growth factor 1, leptin and ghrelin levels and catch-up growth in small for gestational age infants of 27-31 weeks during neonatal intensive care unit admission.

AIM: Poor post-natal growth is related to later morbidity and poor cognitive development in preterm infants. We investigated the relationship between plasma insulin-like growth factor 1 (IGF-1), leptin, active ghrelin levels and post-natal growth in preterm infants small for gestational age (SGA). METHODS: Plasma IGF-1, leptin and active ghrelin levels were measured at birth and at 2, 4, 6 and 8 weeks after birth in 42 very low birthweight (VLBW) infants (born between 27 and 31 weeks of gestation), including 14 SGA infants with extrauterine growth restriction (EUGR), 6 SGA infants without EUGR and 22 appropriate-for-gestational-age infants. RESULTS: At birth, IGF-1 levels in SGA infants without EUGR did not differ significantly from those in SGA infants with EUGR. However, IGF-1 levels in SGA infants without EUGR were as high as those observed in appropriate-for-gestational-age infants and were significantly different from those in SGA infants with EUGR at 4 and 8 weeks of age. Leptin and ghrelin levels did not differ significantly among the three groups at any time point. CONCLUSION: IGF-1 is related to catch-up growth in SGA VLBW infants during neonatal intensive care unit admission; however, this does not appear to be the case for leptin and ghrelin. IGF-1 level monitoring may be useful for predicting EUGR in preterm VLBW infants.

Association of zinc and copper with clinical parameters in the preterm newborn.

BACKGROUND: Given that preterm infants are born at a time of rapid fetal growth, they are at risk of deficiency of essential nutrients for brain development, including zinc (Zn) and copper (Cu). This study evaluate the relationship between serum Cu or Zn, gestational age (GA) and anthropometric parameters at birth in preterm infants. METHODS: This was a retrospective study of infants <35 weeks' GA from January 2010 to August 2012. We collected the data from medical records of 59 preterm infants at birth with regard to GA, anthropometric parameters, and serum Cu and Zn levels. Correlation of Cu, Zn, and GA with anthropometric parameters at birth was then done. RESULTS: Zn was inversely correlated with GA, bodyweight (BW), body length (BL), and head circumference (HC), and Cu was inversely correlated with the standard deviation (SD) score for BW, BL, and HC. On stepwise multiple regression analysis, GA was a significant independent predictor of Zn level, and HC SD score was a significant independent predictor of Cu level. CONCLUSIONS: Prematurity influences Zn, and intrauterine head growth restriction influences Cu at birth in preterm infants. Further research is needed to evaluate the relationship between intrauterine growth restriction and brain Cu metabolism.

Effect of insulin-like growth factor-I during the early postnatal period in intrauterine growth-restricted rats.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period. METHODS: Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed. RESULTS: Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA. CONCLUSIONS: No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period.

Evaluation of kidney dysfunction and angiotensinogen as an early novel biomarker of intrauterine growth restricted offspring rats.

BACKGROUND: Few studies have addressed the growing concerns of chronic kidney diseases in children with intrauterine growth restriction (IUGR). Therefore, the purpose of this study was to evaluate long-term kidney dysfunction and determine if urinary angiotensinogen (AGT) was suitable as a novel early biomarker for kidney dysfunction in IUGR offspring. METHODS: Pregnant rats underwent bilateral uterine artery ligation, and as a control group, sham surgeries were performed. RESULTS: The birth weight was reduced, the urinary AGT to creatinine ratio was significantly higher at week 20, and urinary protein levels were significantly higher at week 32 in IUGR rats than in control rats. On the other hand, the histological findings at week 32 revealed long-term kidney dysfunction, more severe glomerulosclerosis, and greater glomerular diameters in IUGR rats. Moreover, AGT mRNA expression and immunohistological staining were significantly increased in IUGR rats; this suggests that the intrarenal renin-angiotensin system (RAS) contributes to renal dysfunction of IUGR offspring. CONCLUSION: Urinary AGT elevation prior to urinary protein levels suggests that AGT is an early biomarker. At week 32, kidney dysfunction was severe in IUGR rats and intrarenal RAS appeared to be one of the causes.

Measurement of cytokine levels in cerebrospinal fluid over time in neonatal Enterococcal meningitis.

Enterococcus faecalis is rarely involved in neonatal meningitis. Several studies have indicated that the cytokines related to bacterial infection may induce nerve cell damage; therefore, the cytokine levels in cerebrospinal fluid (CSF) could represent a valuable hallmark for rapid recognition of the disease and evaluation of the degree of neurological involvement. We analyzed cytokine levels in the CSF of a neonate with E. faecalis meningitis over time. Tumor necrosis factor-α (TNF-α) tended to be elevated during the acute phase of infection, and then decreased during the convalescent stage after treatment. CSF inflammatory cytokine measurement may provide important clues for predicting the development of complications in the host because some of these cytokines, such as TNF-α, can injure neurons.

Fat emulsion given to very low-birthweight infants increases urinary L-FABP.

BACKGROUND: In premature infants, many factors influence the function of renal tubules, such as asphyxia, respiratory disorders, use of high-concentration oxygen, hypotension, and drug treatment. When tubular ischemia and oxidative stress develop due to renal microcirculatory pathology, urinary L-type fatty acid-binding protein (L-FABP) level increases. METHODS: Urinary L-FABP level was measured over time in very low-birthweight infants (VLBWI), and the effect of fat emulsion on L-FABP level was investigated. Thirty-one VLBWI were divided into two groups with regard to treatment with fat emulsion: the lipid group (n = 20) and the control group (n = 11). Urinary L-FABP was measured before (0-3 days of age), during (7-14 days of age), and after fat emulsion treatment (21-28 days of age) in the two groups. RESULTS: Median urinary L-FABP level before treatment was 459 ng/mgCr (range, 22.7-5100 ng/mgCr; mean, 1067 ± 1570 ng/mgCr) and 797 ng/mgCr (range, 69-3900 ng/mgCr; mean, 1066 ± 1188 ng/mgCr) in the lipid and control groups, respectively, showing no significant difference. Median urinary L-FABP level was 624 ng/mgCr (range, 50-2050 ng/mgCr; mean ± SD, 799 ± 655 ng/mgCr) and 273 ng/mgCr (range, 31-987 ng/mgCr; mean ± SD, 359 ± 323 ng/mgCr) at 7-14 days of age, respectively, showing that the level was significantly higher in the lipid group. At 21-28 days of age, the median level was 462 ng/mgCr (range, 49-1867 ng/mgCr; mean ± SD, 557 ± 534 ng/mgCr) and 130 ng/mgCr (range, 20-993 ng/mgCr; mean ± SD, 290 ± 329 ng/mgCr), respectively, showing that L-FABP level tended to be higher in the lipid group. CONCLUSIONS: Fat emulsion treatment induced a significant increase in urinary L-FABP level, suggesting that fat emulsion affected the proximal tubule in VLBWI.

Oxidative stress early in infancy and neurodevelopmental outcome in very low-birthweight infants.

BACKGROUND: Reactive oxygen species may be involved in serious diseases in premature infants. The objective of this study was to assess the relationship between neurodevelopmental outcome and oxidative stress marker level in the urine of very low-birthweight (VLBW) infants. METHODS: Spot urine samples were collected from 35 VLBW infants. Urinary excretion of 8-hydroxy-2″-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and 8-iso-prostaglandin F2α (8-isoPGF), a marker of lipid peroxidation, was measured at 1, 2, 4, and 6 weeks of age. Neurodevelopmental outcome at 18 months' corrected age was assessed using the Bayley Scales of Infant Development (BSID)-II. RESULTS: Significant correlations were found between urinary 8-OHdG at 2 and 4 weeks and the Mental Development Index of the BSID-II. No significant correlation was found between urinary 8-isoPGF and indices of the BSID-II. CONCLUSIONS: In VLBW infants, urinary 8-OHdG level correlated with mental development rather than psychomotor development at 18 months' corrected age; urinary 8-OHdG might be a predictive marker of neurodevelopmental outcome in VLBW infants.

The impact of cyclooxygenase inhibitor use on urinary prostaglandin metabolites in preterm infants.

BACKGROUND: There is limited evidence on the association between the clinical course of patent ductus arteriosus (PDA) and prostaglandin (PG) metabolites. This study aimed to determine the influence of PDA treatment on urinary PG metabolite excretion in very-low-birth-weight (VLBW) infants. METHODS: Urine samples were collected from 25 VLBW infants at 1, 3, and 7 days of age. Infants were separated into two groups: a PDA-treated group that received a cyclooxygenase-2 (COX) inhibitor (n = 12) and a control group that did not receive a COX inhibitor during the first 7 days after birth (n = 13). Urinary PG metabolite tetranor prostaglandin E2 metabolite (t-PGEM) and tetranor prostaglandin D2 metabolite (t-PGDM) levels were analyzed using liquid chromatography-tandem mass spectrometry. RESULTS: Urinary t-PGEM excretion levels were not significantly different between the groups at 1, 3, and 7 days of age. Urinary t-PGDM excretion levels at 1 day of age were higher in PDA-treated infants than in control infants (median [interquartile range]: 5.5 [2.6, 12.2] versus 2.1 [1.0, 3.9] ng/mg creatinine; p = 0.017); however, among PDA-treated infants, the levels were significantly lower at 3 and 7 days than at 1 day of age (5.5 [2.6, 12.2] versus 3.4 [1.7, 4.5] and 4.0 [1.7, 5.3] ng/mg creatinine, respectively; p < 0.05). The urinary t-PGDM excretion level in the control group did not significantly differ among the time points. CONCLUSION: PDA and COX inhibitor administration affected PG metabolism in VLBW infants. Our results indicated that urinary t-PGDM excretion was significantly associated with PDA-treatment in preterm infants.

Use of Head and Chest Circumference Ratio as an Index of Fetal Growth Retardation in Preterm Infants.

We evaluated the relationship between fetal growth in preterm babies using the head circumference (HC)/chest circumference (CC) ratio and other anthropometric parameters at birth and at school age. Data were collected from 187 very low birth weight (VLBW) children born at less than 30 weeks of gestational age (GA) at birth and at 6 years. We assessed the correlation between the HC/CC ratio and body weight (BW), body length (BL), and HC z-scores at birth, and BW, body height (BH), and body mass index (BMI) z-scores at 6 years. Multiple regression analysis showed that BW z-score, BL z-score, and HC z-score at birth were significantly associated with HC/CC at birth. The BMI z-score at 6 years was also significantly associated with HC/CC at birth. The HC/CC ratio at birth is a reliable parameter for evaluating fetal growth restriction and a possible predictor of physical growth in VLBW children.

Growth Trajectories during the First 6 Years in Survivors Born at Less Than 25 Weeks of Gestation Compared with Those between 25 and 29 Weeks.

We aimed to determine the differences in the growth trajectories of the youngest gestational survivors (<25 weeks' gestation) up to 6 years of age compared to those of older gestational ages. Preterm infants were divided into two groups: 22−24 weeks' gestation (male (M) 16, female (F) 28) and 25−29 weeks' gestation (M 84, F 59). Z-scores of body weight (BW), body length (BL), and body mass index (BMI) were derived from Japanese standards at 1, 1.5, 3, and 6 years of corrected age. Comparisons between the two groups by sex were made using the Wilcoxon test and linear regression analysis to examine the longitudinal and time-point associations of anthropometric z-scores, the presence of small for gestational age (SGA), and the two gestational groups. BW, BL, BMI, and z-scores were significantly lower in the 22−24 weeks group at almost all assessment points. However, there were no significant differences in BW, BL, BMI, and z-scores between the two female groups after 3 years. BMI z-scores were significantly associated with the youngest gestational age and the presence of SGA at all ages in males, but not in females. The youngest gestational age had a greater influence in males on the z-score of anthropometric parameters up to 6 years of age.

Analysis of Factors Associated With Body Mass Index at Ages 18 and 36 Months Among Infants Born Extremely Preterm.

Importance: The development of neonatology has been associated with improved survival among infants born extremely preterm, and understanding their long-term outcomes is becoming increasingly important. However, there is little information on body mass index (BMI) among these children. Objective: To determine factors associated with BMI at ages 18 months and 36 months among infants born extremely preterm. Design, Setting, and Participants: This retrospective, multicenter cohort study was conducted using data from the Neonatal Research Network Japan database for 8838 infants born at gestational ages 23 to 28 weeks with data on BMI at 18 months and 36 months. Data were analyzed from April 2018 through June 2021. Exposures: BMI and BMI z score at ages 18 months and 36 months were regressed with gestational age, intrauterine growth restriction (IUGR) status, and complications during pregnancy and the neonatal period separately by presence of multiple pregnancy and sex. Main Outcomes and Measures: BMI and BMI z score at ages 18 months and 36 months. Results: Among 16 791 eligible infants born extremely preterm, 8838 infants were included in the analysis. There were 7089 infants born from single pregnancies (mean [SD] gestational age, 26.0 [1.6] weeks; 3769 [53.2%] boys; mean [SD] birth weight, 847 [228] g) and 1749 infants born from multiple pregnancies (mean [SD] gestational age, 26.3 [1.5] weeks; 903 [51.6%] boys; mean [SD] birth weight, 860 [217] g). In single pregnancies, every week of increased gestational age was associated with an increase in BMI of 0.21 (95% CI, 0.17-0.25) among boys and 0.20 (95% CI, 0.15-0.25) among girls at age 18 months and 0.21 (95% CI, 0.18-0.24) among boys and 0.21 (95% CI, 0.18-0.24) among girls at age 36 months. There was an interaction association between gestational age and IUGR among boys at age 36 months, with a decrease in the change associated with gestational age of 0.12 (95% CI, 0.05-0.19). Every week of increased gestational age in single pregnancies was associated with an increase in BMI z score of 0.14 (95% CI, 0.17-0.21) among boys and 0.17 (95% CI, 0.13-0.21) among girls at age 18 months and 0.19 (95% CI, 0.16-0.22) among boys and 0.17 (95% CI, 0.15-0.20) among girls at age 36 months. Among single pregnancies, IUGR was associated with a decrease in BMI among boys (0.59 [95% CI, 0.23-0.95]) and girls (0.75 [95% CI, 0.39-1.11]) and BMI z score among boys 0.85 [95% CI, 0.25-0.95)] and girls (0.67 [95% CI, 0.36-0.97] at age 18 months and BMI among boys (0.44 [95% CI, 0.17-0.18]) and girls (0.84 [95% CI, 0.55-1.12]) and BMI z score among boys (0.46 [95% CI, 0.21-0.71]) and girls (0.77 [95% CI, 0.53-1.01]) at age 36 months. In multiple pregnancies, IUGR was associated with a decrease in BMI z score at age 36 months among boys (0.26 [95% CI, 0.42-0.89]) and girls (0.29 [95% CI, 0.22-0.79]). In single pregnancies intraventricular hemorrhage (IVH) was associated with a decrease in BMI of 0.47 (95% CI, 0.21-0.73) among boys and 0.42 (95% CI, 0.13-0.71) among girls at age 18 months and 0.53 (95% CI, 0.32-0.74) among boys and 0.31 (95% CI, 0.07-0.54) among girls at age 36 months. IVH was associated with a decrease in BMI z score in single pregnancies of 0.63 (95% CI, 0.20-0.41) among boys and 0.35 (95% CI, 0.12-0.60) among girls at age 18 months and 0.53 (95% CI, 0.34-0.71) among boys and 0.30 (95% CI, 0.11-0.50) among girls at age 36 months. Similar associations were seen in multiple pregnancies. Conclusions and Relevance: This study found that gestational age, the presence of IUGR and multiple pregnancy, and IVH complications were associated with infant BMI at ages 18 months and 36 months. These findings suggest that these complicating factors should be considered when setting growth targets and nutrition strategies for infants born extremely preterm.

Choline-related metabolites influenced by feeding patterns in preterm and term infants.

Objective: This study was performed to examine the choline status on term and preterm infants using urinary metabolome analysis.Material and methods: Samples were collected from 19 term and 20 preterm infants between 15 days and 1 month, respectively. The infants were separated into four groups: the term-breast group (TB, n = 13), the term-formula group (TF, n = 6), the preterm-breast (PB, n = 11), and the preterm-mixed group (PM, n = 9). Urinary metabolome analysis was performed using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS). We also performed metabolome analysis of the infant formulas.Results: Urinary excretion of choline metabolites (choline, N,N-dimethylglycine, sarcosine, and betaine) was significantly higher in TB than TF infants (p < .05). Choline, betaine, and sarcosine excretion was not significantly different between the PB and TB infants. Choline and N,N-dimethylglycine excretion was significantly higher in PM than PB infants. Choline metabolites excretion was also significantly higher in PM than TF infants. Choline and betaine levels were significantly higher in the preterm than term formula used in this study.Conclusions: The type of feeding in early infancy affects choline metabolism. Metabolome analysis is useful for assessing choline metabolism to modify the contents of infant formulas also in preterm infants.

IGF1 gene is epigenetically activated in preterm infants with intrauterine growth restriction.

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.

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.