Optimal birth weight percentile cut‐offs in defining small‐ or large‐for‐gestational‐age

Aims: It remains questionable what birth weight for gestational age percentile cut‐offs should be used in defining clinically important poor or excessive foetal growth. We aimed to evaluate the optimal birth weight percentile cut‐offs for defining small‐ or large‐for‐gestational‐age (SGA or LGA). Methods: In a birth cohort‐based analysis of 17 979 120 non‐malformation singleton live births, U.S. 1995–2001, we assessed the optimal birth weight percentile cut‐offs for defining SGA and LGA. The 25th–75th percentile group served as the reference. Primary outcomes are the risk ratios (RR) of neonatal death and low 5‐min Apgar score (<4) comparing SGA or LGA versus the reference group. More than 2‐fold risk elevations were considered clinically significant. Results: The 15th birth weight cut‐off already identified SGA infants at more than 2‐fold risk of neonatal death at pre‐term, term or post‐term, except for extremely pre‐term births <28 weeks (continuous risk reductions over increasing birth weight percentiles). LGA was associated with a reduced risk of low 5‐min Apgar score at pre‐term, but an elevated risk at term and post‐term. The 97th cut‐off identified LGA infants at 2‐fold risk of low 5‐min Apgar at term. Conclusion: The commonly used 10th and 90th birth weight percentile cut‐offs for defining SGA and LGA respectively seem largely arbitrary. The 15th and 97th percentiles may be the optimal cut‐offs to define SGA and LGA respectively.     

A 5‐HT2A/2C receptor agonist, 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane,mitigates developmental neurotoxicity of ethanol to serotonergic neurons

Prenatal ethanol exposure causes the reduction of serotonergic (5‐HTergic) neurons in the midbrain raphe nuclei. In the present study, we examined whether an activation of signaling via 5‐HT_2A and 5‐HT_2C receptors during the fetal period is able to prevent the reduction of 5‐HTergic neurons induced by prenatal ethanol exposure. Pregnant Sprague–Dawley rats were given a liquid diet containing 2.5 to 5.0% (w/v) ethanol on gestational days (GDs) 10 to 20 (Et). As a pair‐fed control, other pregnant rats were fed the same liquid diet except that the ethanol was replaced by isocaloric sucrose (Pf). Each Et and Pf group was subdivided into two groups; one of the groups was treated with 1 mg/kg (i.p.) of 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI), an agonist for 5‐HT_2A/2C receptors, during GDs 13 to 19 (Et‐DOI or Pf‐DOI), and another was injected with saline vehicle only (Et‐Sal or Pf‐Sal). Their fetuses were removed by cesarean section on GD 19 or 20, and fetal brains were collected. An immunohistological examination of 5‐HTergic neurons in the fetuses on embryonic day 20 using an antibody against tryptophan hydroxylase revealed that the number of 5‐HTergic neurons in the midbrain raphe nuclei was significantly reduced in the Et‐Sal fetuses compared to that of the Pf‐Sal and Pf‐DOI fetuses, whereas there were no significant differences between Et‐DOI and each Pf control. Thus, we concluded that the reduction of 5‐HTergic neurons that resulted in prenatal ethanol exposure could be alleviated by the enhancement of signaling via 5‐HT_2A/2C receptors during the fetal period.     

Neonatal cholestasis and glucose‐6‐P‐dehydrogenase deficiency

We report a Caucasian neonate with chronic non‐spherocytic hemolytic anemia due to a class I G6PD deficiency. A novel mutation missense mutation in exon eight of the G6PD gene was detected (c.827C>T p.Pro276Leu). Bilirubin peaked on day 5 at 24 mg/dl with a conjugated bilirubin of 17 mg/dl. Jaundice resolved within 4 weeks. A detailed work‐up failed to reveal other specific factors contributing to cholestasis. Severe hemolytic disease of the newborn may cause cholestasis even in the absence of associated primary hepato‐biliary disease. Pediatr Blood Cancer 2010;54:758–760. © 2010 Wiley‐Liss, Inc.     

AST‐to‐platelet ratio index in non‐invasive assessment of long‐term graft fibrosis following pediatric liver transplantation

Long‐term graft fibrosis occurs in the majority of pediatric liver transplant recipients. Serial biopsies to monitor graft health are impractical and invasive. The APRI has been evaluated in pediatric liver disease, but not in the context of post‐transplantation fibrosis. We aimed to investigate the validity of APRI as a predictor of long‐term graft fibrosis in pediatric liver transplant recipients. This was a retrospective, observational study of a cohort of children who underwent liver transplantation at King's College Hospital between 1989 and 2003, with a relevant dataset available. Protocol liver biopsies were performed at 10‐yr follow‐up and fibrosis was graded using the Ishak scoring system, with S3‐6 denoting “significant fibrosis.” APRI was calculated concurrently with biopsy. A total of 39 asymptomatic patients (20 males; median age at transplant, 1.43 yr) underwent protocol liver biopsies at a median of 10.39 yr post‐transplantation. APRI was associated with significant fibrosis (p = 0.012). AUROC for APRI as a predictor of significant fibrosis was 0.74 (p = 0.013). The optimal cutoff APRI value for significant fibrosis was 0.45 (sensitivity = 0.67; specificity = 0.79; PPV = 0.67; NPV = 0.79). APRI appears to be a useful non‐invasive adjunct in the assessment of significant graft fibrosis in the long‐term follow‐up of pediatric liver transplant survivors.     

Bed‐sharing among six‐month‐old infants in western Sweden

Aim: In spite of several reports of an increased risk of sudden infant death syndrome (SIDS) in connection with bed‐sharing, it is not an uncommon practice. The aim of this study was to examine bed‐sharing at 6 months of age and the factors that are associated with bed‐sharing. Methods: Our cohort comprised 8176 randomly chosen families. At 6 month of age, the families received an invitation to the study, with a questionnaire, which was completed by 5605 families (response rate 68.5%). Results: Of the families, 19.8% bed‐shared. In the multivariate analysis, we found a correlation between breast‐feeding and bed‐sharing (breast‐feeding at 6 months: OR 1.94; 95% CI 1.56, 2.41). Moreover, we found an association with 3+ nightly awakenings at 6 months (2.70; 2.20, 3.32). It was more common to share a bed if the parent was single (2.04; 1.19, 3.51) and less common if the infant was bottle‐fed in the first week (0.70; 0.54, 0.90). Never using a pacifier was associated with a higher frequency of bed‐sharing. Conclusion: We found a correlation between breast‐feeding and bed‐sharing as well as between sleeping problems and a single parent. A lower percentage of infants sleeping in the parental bed were seen in association with formula feeding in the first week after birth.     

Fatal graft‐versus‐host disease after living‐donor liver transplantation from an HLA‐DR‐mismatched donor

Acute GVHD is a rare complication after liver transplantation that has a high mortality rate. We experienced an infant case complicated with acute GVHD. An 8‐month‐old infant with biliary atresia underwent LDLT with a graft obtained from his mother. Their HLAs showed a donor‐dominant one‐way match, not at HLA‐DR but at HLA‐A, HLA‐B, and HLA‐C (recipient; A 31/33, B 51/54, C 1/14, DR 9/11, donor; A 31/‐, B 51/‐, C 14/‐, DR 8/11). The patient exhibited a high fever, skin rash, and diarrhea, and was diagnosed with acute GVHD based on the blood chimerism test. Despite immunosuppression treatment with prednisolone and tacrolimus, plasma exchange, blood transfusion including cord blood transplantation, and antibiotics, the child died on postoperative day 126. Donor‐dominant one‐way matching at HLA class 1 can be a high‐risk factor for acute GVHD despite HLA class 2 mismatching.     

The response of bovine beta‐lactoglobulin‐specific T‐cell clones to single amino acid substitution of T‐cell core epitope

Cow’s milk is one of the most common food allergens in the first year of life, with approximately 2.5% of infants experiencing an allergic reaction to it. Beta‐lactoglobulin (BLG) is one of the major allergens in cow’s milk. Previously, we reported that four of six T‐cell clones (TCC) which were established from cow’s milk allergy patients recognized BLGp97‐117 as the core sequence and also recognized BLG in association with the human leucocyte antigen (HLA)‐DRB1*0405 allele. Using two of these four TCCs, we evaluated the T‐cell response to BLG peptides with single amino acid substitution or deletion and identified BLGp102‐112 as the minimum essential region in BLGp97‐117. In the alanine‐scan assay, the proliferative responses of TCCs to pE108A disappeared, and the proliferative responses of TCCs to pC106A decreased. In the analog peptide proliferation assay, pY102S had retained some T‐cell response to the two TCCs. Collecting these results, we propose a motif for the interaction between the HLA‐DRB1*0405 allele and antigen peptide, and suggest that BLGp105‐108 are important residues to retain the TCR/BLG‐peptide/HLA complex. pY102A and pY102S are partial agonists for the T‐cell receptor. These peptides might be considered as candidate peptides for the modification of the T‐cell response to BLG in cow’s milk allergy.     

Maternal selenium,copper and zinc concentrations in pregnancy associated with small‐for‐gestational‐age infants

Pregnancy during adolescence increases the risk of adverse pregnancy outcome, especially small‐for‐gestational‐age (SGA) birth, which has been linked to micronutrient deficiencies. Smoking has been shown to be related to lower micronutrient concentrations. Different ethnicities have not been examined. We used a subset from a prospective observational study, the About Teenage Eating study consisting of 126 pregnant adolescents (14–18‐year‐olds) between 28 and 32 weeks gestation. Micronutrient status was assessed by inductively coupled mass spectrometry. Smoking was assessed by self‐report and plasma cotinine, and SGA was defined as infants born <10th corrected birthweight centile. The main outcome measures were as follows: (1) maternal plasma selenium, copper and zinc concentrations in adolescent mothers giving birth to SGA vs. appropriate‐for‐gestational‐age (AGA) infants; and (2) comparison of micronutrient concentrations between women of different ethnicities and smoking habits. The plasma selenium {mean ± standard deviation (SD) [95% confidence interval (CI)]} concentration was lower in the SGA [n = 19: 49.4 ± 7.3 (CI: 45.9, 52.9) µg L^?1] compared with the AGA [n = 107: 65.1 ± 12.5 (CI: 62.7, 67.5) µg L^?1; P < 0.0001] group. Smoking mothers had a lower selenium concentration compared with non‐smokers (P = 0.01) and Afro‐Caribbean women had higher selenium concentrations compared with White Europeans (P = 0.02). Neither copper nor zinc concentrations varied between groups. Low plasma selenium concentration in adolescent mothers could contribute to the risk of delivering an SGA infant, possibly through lowering placental antioxidant defence, thus directly affecting fetal growth. Differences in plasma selenium between ethnicities may relate to variation in nutritional intake, requiring further investigation.     

Current human T‐cell lymphotropic virus type 1 mother‐to‐child transmission prevention status in Kagoshima

The aim of this study was to assess the current human T‐cell lymphotropic virus type 1 (HTLV‐I) mother‐to‐child transmission (MTCT) prevention system in Kagoshima Prefecture. We investigated the rate of carrier pregnant women from obstetrics facilities in Kagoshima by mail in 2012 and compared our results with previous study results. We interviewed carrier pregnant women about their choices for infant nutrition, and we interviewed midwives about the follow‐up system. In 2012, 8719 screening tests were performed, covering 58.1% of all pregnant women in Kagoshima; the rate of carrier pregnant women was 1.3%. Of 59 carriers, 39 chose short‐term breast‐feeding. The HTLV‐I carrier rate among pregnant women in Kagoshima has declined. The current HTLV‐I MTCT prevention system in Kagoshima is effective, but not sufficient. To bring the nutrition methods to completion, various types of support are needed. Further studies will elucidate many unsolved problems concerning MTCT.