Tania Siahanidou

Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations

Objective The phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY). To date, mutation screening has been limited to patients with a family history consistent with MODY. In this study, we investigated the prevalence of HNF4A mutations in a large cohort of patients with diazoxide responsive hyperinsulinemic hypoglycemia (HH). Subjects and methods We sequenced the ABCC8, KCNJ11, GCK, GLUD1, and/or HNF4A genes in 220 patients with HH responsive to diazoxide. The order of genetic testing was dependent upon the clinical phenotype. Results A genetic diagnosis was possible for 59/220 (27%) patients. KATP channel mutations were most common (15%) followed by GLUD1 mutations causing hyperinsulinism with hyperammonemia (5.9%), and HNF4A mutations (5%). Seven of the 11 probands with a heterozygous HNF4A mutation did not have a parent affected with diabetes, and four de novo mutations were confirmed. These patients were diagnosed with HI within the first week of life (median age 1 day), and they had increased birth weight (median +2.4 SDS). The duration of diazoxide treatment ranged from 3 months to ongoing at 8 years. Conclusions In this large series, HNF4A mutations are the third most common cause of diazoxide responsive HH. We recommend that HNF4A sequencing is considered in all patients with diazoxide responsive HH diagnosed in the first week of life irrespective of a family history of diabetes, once KATP channel mutations have been excluded.

Circulating levels of adiponectin in preterm infants

Objective: To determine circulating levels of adiponectin in preterm infants and examine possible associations with anthropometric measurements, weight gain, and leptin and insulin levels. Design: Prospective study. Setting: A university hospital neonatal care unit. Study population: 62 preterm (mean (SD) gestational age 32.0 (2.1) weeks) and 15 full-term infants (reference group). Interventions: Blood samples taken at discharge (40.9 (14.8) days of life) from the preterm infants and at a comparable postnatal age in full-term infants. All infants were fed the same commercial formula, but in nine preterms the formula contained long-chain polyunsaturated fatty acids (LCPUFAs). Main outcome measures: Serum levels of adiponectin, leptin and insulin. Associations of adiponectin levels were tested only in the preterm group. Results: Serum levels of adiponectin were lower in preterm (40.9 (14.8) μg/ml) than full-term infants (53.1 (16.0) μg/ml, p<0.01). However, after adjustment for body weight, the influence of prematurity on adiponectin levels was no longer significant. In preterm infants, adiponectin levels independently correlated with being born small for gestational age (SGA) (β = −0.35, p = 0.01), weight gain (β = 0.28, p = 0.03) and LCPUFA-supplemented formula (β = 0.34, p = 0.009). Serum adiponectin levels did not correlate with insulin or leptin levels. However, insulin levels were higher in preterm than in full-term infants after adjustment for body weight. Conclusions: Adiponectin levels are lower in preterm infants at discharge than full-term infants probably due to decreased adiposity. The levels are influenced by being born SGA, weight gain and, possibly, by dietary LCPUFAs. The importance of these findings in the development of insulin or leptin resistance in children born prematurely needs to be further studied.

HNA-1d: a new human neutrophil antigen located on Fcγ receptor IIIb associated with neonatal immune neutropenia.

Neonatal immune neutropenia (NIN) is a rare, but potentially life‐threatening, disorder caused by maternal alloantibodies recognizing paternal neutrophil antigens on fetal cells. Alloantibodies directed against the human neutrophil alloantigen system (HNA)‐1 located on Fcγ receptor IIIb (FcγRIIIb) are most frequently implicated in NIN. In this report, we describe two cases of NIN with alloantibodies against FcγRIIIb, which did not match one of the known HNA‐1a, ‐1b, or ‐1c specificities, but define a new antigen, HNA‐1d.

Subcutaneous fat necrosis associated with severe hypocalcaemia in a neonate

Subcutaneous fat necrosis (SFN) of the newborn is an uncommon disorder of the adipose tissue, mostly affecting full-term or post-term newborns who experience perinatal distress. The lesions of SFN typically occur during the first six weeks of life; they are usually self-limited and no specific therapy is required. The disorder may be rarely complicated with hypercalcaemia. We present the case of a neonate with perinatal asphyxia who manifested SFN followed by hypocalcaemia instead of hypercalcaemia and a biochemical profile of pseudohypoparathyroidism four weeks after the eruption of skin lesions. The infant was treated with alfacalcidiol. Blood biochemistry was normalized within one week and serum parathyroid hormone levels declined to normal over the next two months. It is suggested that perinatal asphyxia was the common etiopathogenetic factor for the development of both SFN and pseudohypoparathyroidism.

Safety and pharmacokinetics of oseltamivir for prophylaxis of neonates exposed to influenza H1N1.

Oseltamivir was administered at 1.0 mg/kg b.i.d. to 13 neonates exposed to influenza H1N1. No influenza, neurologic, or laboratory adverse effects occurred. The mean Cmax values for oseltamivir and oseltamivir carboxylate were found to be lower than those reported for children 1 to 5 years old, whereas Tmax values were similar to children 1 to 5 years old. Age and gender were found to significantly affect oseltamivir clearance.

Eosinophilic gastroenteritis complicated with perforation and intussusception in a neonate.

Eosinophilic gastroenteritis (EG) is a disease characterized by marked eosinophilic infiltration of the gastrointestinal tract, an absence of vasculitis, and a peripheral eosinophilia in approximately 50% of patients (1). EG is included in a standardized diagnostic classification scheme of gastrointestinal diseases of infants and children resulting from adverse immunologic reactions to foods (1). Kaijser originally described this disorder in 1937. The prevalence of this disease in the general population is unknown. Clinical symptoms are related to the gastrointestinal region involved (esophagus, stomach, small intestine, colon) and to the predominant layer affected (mucosa, muscularis, serosa). Eosinophilic infiltration of the mucosal layer causes inflammation; that of the muscular layer leads to thickening and rigidity, provoking symptoms of obstruction; whereas infiltration of the serosa results in ascites (2). The disease is distinguished into allergic eosinophilic esophagitis, gastritis, or gastroenterocolitis according to the anatomic region affected (1). Eosinophilic infiltration of the gastric antrum is typical in eosinophilic gastritis or gastroenterocolitis and may result in gastric outlet obstruction (1). Intestinal perforation and intussusception are rare complications of the disease (3). Even though patients of all ages can be affected, a few cases of neonates with EG, without complications, have been reported (4–6). We describe a male neonate who presented typical symptoms of EG on the first day of life and whose condition was complicated by perforation of the antral wall and ileoileal intussusception.

Circulating Adiponectin in Preterm Infants Fed Long-Chain Polyunsaturated Fatty Acids (LCPUFA)-Supplemented Formula—A Randomized Controlled Study

Adiponectin has potent insulin-sensitizing effects, improves lipid metabolism, and potentially protects against the development of metabolic syndrome. Thus, increasing adiponectin levels in preterm infants at risk for developing metabolic syndrome may be of special interest. The aim of this study was to examine the effects of dietary long-chain polyunsaturated fatty acids (LCPUFA) on serum adiponectin and lipid concentrations in preterm infants. Adiponectin and lipid levels of 60 healthy preterm infants [gestational age 32.7 (1.9) wk] randomly assigned to be fed either 1) a formula containing LCPUFA [arachidonic and docosahexanoic] (+LCPUFA group) or 2) the same formula without LCPUFA (−LCPUFA/control group), were determined at mean (SD) 33.8 (11.7) d. Adiponectin and HDL-C concentrations were significantly higher in the +LCPUFA group than in controls (p = 0.002 and p = 0.01, respectively); whereas, triglyceride levels were lower (p = 0.06). Adiponectin correlated positively with HDL-C levels and negatively with triglyceride levels in the +LCPUFA group but not in the controls. In conclusion, circulating adiponectin concentrations were higher in preterm infants fed a formula containing LCPUFA than infants fed an LCPUFA-free formula and they correlated with lipidemic profile.

Impact of Postpartum Influenza Vaccination of Mothers and Household Contacts in Preventing Febrile Episodes, Influenza-like Illness, Healthcare Seeking, and Administration of Antibiotics in Young Infants During the 2012–2013 Influenza Season

BACKGROUND Influenza is associated with an increased risk for serious illness, hospitalization, and mortality in infants aged <6 months. However, influenza vaccines are not licensed for administration in this age group. The study evaluated the effectiveness of postpartum influenza vaccination of mothers and household members in infants. METHODS The influenza vaccine was offered to mothers and household members of neonates born or hospitalized in 3 hospitals prior to the 2012-2013 season. Mothers were contacted every 2 weeks during the influenza season, and data regarding the onset of fever and/or respiratory symptoms in infants, healthcare seeking, hospitalization, and administration of antibiotics were collected. RESULTS The study group consisted of 553 mothers who delivered 573 neonates. The influenza vaccine was administered to 841 of 1844 (45.6%) household contacts. Vaccination coverage rates ranged between 41.9% for neonates siblings and 49% for mothers. Five hundred thirty infants were analyzed for vaccine effectiveness. For outcomes in the infant, postpartum maternal vaccination had 37.7% effectiveness against acute respiratory illness (ARI), 50.3% against a febrile episode, 53.5% against influenza-like illness (ILI), 41.8% against related healthcare seeking, and 45.4% against administration of antibiotics. Multiple logistic regression analyses showed that maternal influenza vaccination was significantly associated with a decreased probability for febrile episodes, ARIs, and/or ILIs in infants, related healthcare seeking, and/or administration of antibiotics during the influenza season. Vaccination of other household contacts had no impact. CONCLUSIONS Maternal postpartum vaccination against influenza was associated with a significant reduction of influenza-related morbidity, healthcare seeking, and antibiotic prescription in infants during the influenza season.

Serum lipids in preterm infants fed a formula supplemented with nucleotides.

Background The effect of dietary nucleotides on lipid metabolism has been the subject of clinical studies with conflicting results. We measured serum triglycerides, total cholesterol (total-C), and lipoprotein cholesterol levels (HDL-C, LDL-C, and VLDL-C) in preterm neonates fed formula with and without nucleotide supplements. Methods This prospective, randomized, controlled study included 150 healthy preterm neonates (gestational age, 33.0 ± 1.9 weeks) matched for gestational age, birth weight, and gender. Subjects were assigned at birth to receive either a standard milk formula supplemented with nucleotides (group F-NT) or the same formula without nucleotides (group F). Serum was obtained before discharge (29.1 ± 10.0 days of life) and triglycerides, total-C, and HDL-C were determined enzymatically. LDL-C and VLDL-C were estimated by the Friedewald formula. For statistical analysis t test, Mann Whitney-U test, two-way ANOVA, and &khgr;2 test were used, as appropriate. The influence of several factors on serum lipid levels was evaluated by linear regression analysis. Results Serum triglycerides, total-C, and VLDL-C levels did not differ between groups. HDL-C levels (median; 25th–75th percentiles) were significantly higher (P < 0.001) in group F-NT (48.0 mg/dL; 40.5–57.0 mg/dL) than in group F (34.5 mg/dL; 27.2–44.0 mg/dL). On the contrary, LDL-C levels (median; 25th-75th percentiles) were significantly lower (P < 0.001) in group F-NT (39.0 mg/dL; 26.0–54.0 mg/dL) than in group F (65.0 mg/dL; 41.0–73.0 mg/dL). In the multiple regression analysis, nucleotide supplementation was identified as one of the controlled independent factors influencing serum HDL-C and LDL-C levels. Conclusions Preterm neonates fed from birth with formula supplemented with nucleotides have significantly higher HDL-C and lower LDL-C serum levels than do neonates fed unsupplemented formula. The clinical relevance of these results remains to be elucidated.

Pasteurella multocida Infection in a neonate: evidence for a human-to-human horizontal transmission.

Pasteurella multocida is usually transmitted by animal contact; however, in a significant proportion of cases, no animal exposure can be identified. Although vertical transmission has been identified in neonates, horizontal human-to-human spread has not been documented. A case of neonatal sepsis and meningitis resulting from horizontal transmission of P. multocida is described.