Health and the use of health care services in 5‐year‐old very‐low‐birth‐weight infants

Aim: We aimed to study the effect of prematurity, time of birth and level of birth hospital on morbidity and the use of health care services at age 5. Methods: This national study included all very‐low‐birth‐weight infants (VLBWI, <32 gestational weeks or birth weight ≤1500 g) born in Finnish level II or III hospitals in 2001–2002 (n = 918), and full‐term controls (n = 381). Parental questionnaires and register data were used to compare morbidity, and the use of health care services between VLBWI and full‐term controls, and within VLBWI according to the time of birth and birth hospital level. Results: Cerebral palsy, retinopathy of prematurity, other ophthalmic problems, respiratory infections, asthma or chronic lung disease, and inguinal hernia were overrepresented in VLBWI compared with the controls. VLBWI had more outpatient and inpatient days than the controls. The time of birth and birth hospital level were not associated with the use of services or with prematurity‐related morbidity. Conclusion: Although morbidity and the use of health care services were increased in the surviving VLBWI, the average use of services was relatively small at age 5. In surviving VLBWI, the time of birth and the birth hospital level did not affect morbidity or the use of services.     

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.     

Hydrocortisone and long‐term outcomes in very‐low‐birthweight infants

Background: The long‐term effects of hydrocortisone (HDC) used for very‐low‐birthweight (VLBW) infants with chronic lung disease (CLD) are not fully understood. The aim of this study was to examine the short‐term clinical effects and long‐term impact of a physiological replacement dose of HDC on acute deterioration of CLD in VLBW infants. Methods: This prospective case–control study included 110 of the 174 VLBW infants admitted to our facility between 2003 and 2006 who were followed up to a corrected age of 18 months. Infant deaths and infants with congenital deformities were excluded from the study. The infants were classified into the following three groups: infants with CLD and treated with HDC (1–2 mg/kg/dose) due to progressive deterioration in oxygenation (CLD treatment group; n= 24); infants with CLD but not treated with HDC (CLD untreated group; n= 40); and infants without CLD (non‐CLD group; n= 46). Results: The fraction of inspired oxygen (F_IO₂) in the CLD treatment group improved significantly after treatment (P < 0.01). There were no significant differences among the three groups in terms of growth and neurodevelopmental quotient at the corrected age of 18 months following adjustment for birthweight, sex, and presence of light‐for‐date infants. There were also no significant intergroup differences in all three areas of developmental quotient. Conclusions: Physiological doses of HDC replacement are effective in treating acute deterioration in oxygenation in VLBW infants with CLD. Furthermore, this treatment modality did not adversely affect the growth and development of infants at the corrected age of 18 months.     

Report and review of described associations of Mayer‐Rokitansky‐Küster‐Hauser syndrome and Silver–Russell syndrome

Silver–Russell syndrome (SRS) and Mayer‐Rokitansky‐Küster‐Hauser (MRKH) syndrome are described in isolation. However, their co‐occurrence has only been rarely reported. Here, we present a case report of an adolescent with SRS who was diagnosed with MRKH during the evaluation of primary amenorrhoea. Multiplex ligation‐dependent probe amplification analysis showed a normal methylation pattern and normal dosage at 11p15.5. A PubMed search for all peer‐reviewed publications (original articles and reviews) using the key words Silver–Russell syndrome, Mayer‐Rokitansky‐Küster‐Hauser syndrome, genetics, hypomethylation and reproductive anomalies identified three cases of SRS with MRKH, two of which were associated with significant hypomethylation of the H19 imprinting control region of the 11p15.5 locus. This report highlights the association between SRS and MRKH. The absence of hypomethylation and normal dosage at 11p15.5 suggests these two rare entities share alternative aetiopathogenic mechanisms.     

Marked thrombocytopenia in a neonate is associated with anti‐HPA‐5b,anti‐HLA‐A31, and anti‐HLA‐B55 antibodies

Maternal antibodies against human platelet antigen (HPA) and/or human leukocyte antigen (HLA) cause fetal and neonatal alloimmune thrombocytopenia (FNAIT) in 0.09‐0.15% of live births. Severe cases account for 5‐31% and the frequency of multiple kinds of alloantibodies is 6.9‐9% of FNAIT. We present a case of severe FNAIT associated with anti‐HPA‐5b, anti‐HLA‐A31, and anti‐HLA‐B55 antibodies, successfully treated with immunoglobulin and platelet transfusion. The anti‐HLA‐B55 antibody was detected in the newborn's serum, but disappeared on the 20th day, which was followed by an increase of the platelet count. These findings suggested the potential involvement of an anti‐HLA antibody in the pathogenesis of FNAIT.     

Meta‐analysis of physiological effects of skin‐to‐skin contact for newborns and mothers

Background: Skin‐to‐skin care has been adopted all over the world, although physiological changes during or after it have not been evaluated very well. The purpose of the present study was therefore to investigate whether skin‐to‐skin contact for newborn babies and their mothers affects body temperature, heart rate and oxygen saturation of the babies. Methods: Studies investigating body temperature, heart rate and oxygen saturation of babies during and/or after skin‐to‐skin contact were systematically searched and reviewed. Meta‐analyses to examine the effects and meta‐regression analyses to investigate correlations between the effects and birthweight, duration of the care, environmental temperature, and resources of the setting, were conducted. Results: A total of 23 studies were included. Meta‐analyses showed evidence of an increase in body temperature (weighted mean difference [WMD] 0.22°C, P < 0.001) and a decrease in saturation of babies (WMD ?0.60%; P= 0.01) during skin‐to‐skin care, compared with those before skin‐to‐skin care. Increase in body temperature was more evident in middle–low‐income settings (WMD, 0.61°C, P < 0.001) than high‐income settings (WMD 0.20°C, P < 0.001). Both the positive effect on body temperature and the negative effect on saturation were more marked in cold environments than where the environmental temperature was higher (WMD 0.18°C, P < 0.001; WMD ?0.82%, P= 0.02). Conclusion: Skin‐to‐skin care is effective in increasing the body temperature of babies, especially where resources are limited and the environment is cold. Decreased oxygen saturation of the babies, however, warrants further prospective studies to confirm the findings.     

A meta‐analysis of nutrition interventions on mental development of children under‐two in low‐ and middle‐income countries

Interventions to improve nutritional status of young children in low‐ and middle‐income countries (LMIC) may have the added benefit of improving their mental and motor development. This meta‐analysis updates and goes beyond previous ones by answering two important questions: (1) do prenatal and postnatal nutritional inputs improve mental development, and (2) are effects on mental development associated with two theoretically interesting mediators namely physical growth and motor development? The meta‐analysis of articles on Medline, PsycINFO, Global Health and Embase was limited to randomized trials in LMICs, with mental development of children from birth to age two years as an outcome. The initial yield of 2689 studies was reduced to 33; 12 received a global quality rating of strong. Of the 10 prenatal and 23 postnatal nutrition interventions, the majority used zinc, iron/folic acid, vitamin A or multiple micronutrients, with a few evaluating macronutrients. The weighted mean effect size, Cohen's d (95% CI) for prenatal and postnatal nutrition interventions on mental development was 0.042 (?0.0084, 0.092) and 0.076 (0.019, 0.13), respectively. Postnatal supplements consisting of macronutrients yielded an effect size d (95% CI) of 0.14 (0.0067, 0.27), multiple micronutrients 0.082 (?0.012, 0.18) and single micronutrients 0.058 (?0.0015, 0.12). Motor development, but not growth status, effect sizes were significantly associated with mental development in postnatal interventions. In summary, nutrition interventions had small effects on mental development. Future studies might have greater effect if they addressed macronutrient deficiencies combined with child stimulation and hygiene and sanitation interventions.     

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.     

Non‐immediate‐reading skin tests and prolonged challenges in non‐immediate hypersensitivity to beta‐lactams in children

Background

A minority of children reporting non‐immediate reactions to beta‐lactams (BLs) are allergic. Allergy workup usually includes late‐reading (48‐72 hours) skin tests (ST) and short (1‐3 days) drug provocation tests (DPT), regardless of the chronology of the index reaction. The sensitivity of hyper‐late‐reading (≥6‐7 days) ST and of prolonged DPT for the diagnosis of non‐immediate hypersensitivity to BLs is yet to be determined.

Objectives

To establish the diagnostic values of late‐reading ST and hyper‐late‐reading ST and of prolonged DPT in children reporting non‐immediate reactions to BLs.

Methods

Prospective assessment of children reporting non‐immediate reactions to BLs with late‐ and additional hyper‐late‐reading intradermal (ID) and patch tests, and if negative, with prolonged DPT.

Results

Five hundred and fifty children reporting reactions to a single or several BLs (674 suspected BLs) were included. Non‐immediate hypersensitivity to BLs was diagnosed in 63 children (11.5%), reporting 66 reactions (9.8%), based on responses in ST (n = 17, 25.8%: 5 to ID, 8 to patch tests, and 4 to both tests), DPT (n = 43, 65.2%), and clinical history (n = 6, 9.1%), including 3/9 children with severe cutaneous adverse reactions. Skin test positivity was observed after the 6‐7th day in 14/17 children, and DPT positivity after a median time of 3 days. No severe reaction was observed after ST or during prolonged DPT.

Conclusion

Additional hyper‐late‐reading of ST enhanced their positivity. However, their overall sensitivity remained weak, especially in non‐severe cases. Prolonged DPT are safe and may improve the performance of DPT in the diagnosis of non‐immediate hypersensitivity to BLs.     

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.