Transient neonatal liver disease after maternal antenatal intravenous Ig infusions in gestational alloimmune liver disease associated with neonatal haemochromatosis.

OBJECTIVES: Neonatal haemochromatosis is a rare gestational disease that results in severe foetal liver disease with extrahepatic iron overload, sparing the reticuloendothelial system. Recurrence can be prevented with intravenous immunoglobulin (IVIG) infusions during pregnancy, supporting an alloimmune aetiology. The aim of the study was to assess the effect of antenatal treatment with IVIG infusion on the outcome of pregnancies in women with a history of documented neonatal haemochromatosis likely owing to gestational alloimmune disease and to analyse IVIG tolerance. METHODS: From 2004 to 2012, 8 pregnant women were treated with IVIG at 1 g/kg body weight weekly from 18 weeks' gestation until birth in a prospective multicentre study. RESULTS: All 8 neonates born to the treated women survived. Five developed mild neonatal liver disease with hepatomegaly (n = 1), hyperechogenic liver (n = 2), abnormal liver function tests (n = 1), raised serum ferritin (n = 3) and α-fetoprotein (n = 5) levels, or mild iron overload on liver magnetic resonance imaging (n = 1). Ferritin and α-fetoprotein levels normalised before 14 days and 2 months, respectively. A per-mother-basis analysis comparing outcomes of treated (n = 8) and untreated (n = 9) gestations showed a significant improvement in the survival of neonates with gestational IVIG therapy (survival 8/8 vs 0/9, P < 0.001). Adverse effects of IVIG infusion occurred in 5 mothers leading to discontinuation of treatment in 1 case. Preterm neonates born before 37 weeks' gestation had a decreased risk of neonatal liver disease (P = 0.04). CONCLUSIONS: Antenatal treatment with IVIG infusion in women at risk for gestational alloimmune disease recurrence improves the outcome of pregnancies despite mild signs of transient neonatal liver disease.

Assessment of implementation of a standardized parenteral formulation for early nutritional support of very preterm infants.

INTRODUCTION: Parenteral nutrition (PN) plays an important role in the nutritional support of very preterm newborns. It has been suggested that a high proportion of PN orders could be standardized. In 2002, we implemented in our unit the preparation of three standardized formulations for PN adapted to the nutritional requirements of premature infants<32 weeks. Following this change of practice, a retrospective observational study was conducted to evaluate the relevance of the implemented standardized PN regime. Twenty premature inborn infants<32 weeks gestation who had received standardized (STD) PN in 2003 were matched for 20 infants who had received individualized (IND) PN in 2001. Adequacy of nutrition was assessed by comparing daily intravenous nutrient intake and biochemical parameters during the first week. Amino-acid intakes on day 3 were higher in the STD group (1.5+/-0.2 g/kg/d vs. 0.9+/-0.5, p<0.001), and the calcium phosphate intakes were better balanced. The cumulated intake of amino acids for the first week was greater in the STD group (+20% ; p=0.0003). Biochemical parameters were similar in both groups. Insulin infusions were less frequent in the STD group (p<0.06). CONCLUSION: Standardized parenteral formulations provided higher early intakes of amino acid and glucose, a better calcium phosphate ratio, and a greater amount of amino-acid intakes during the first week while maintaining the same biochemical parameters. This strategy forms part of an approach concerning quality control and the respect of good professional practice for the preparation of parenteral nutrition solutions.

Identification of human herpesvirus 6 variants A and B by primer-specific real-time PCR may help to revisit their respective role in pathology.

BACKGROUND: Human herpesvirus 6 (HHV-6) isolates are classified into two variants, termed HHV-6A and HHV-6B, on the basis of distinct genetic, antigenic and biological characteristics, but the specific pathogenicity of each variant remains poorly understood. OBJECTIVES: To design a rapid, sensitive and specific real-time variant-specific PCR (VS-PCR) method to differentiate both variants in biological specimens. STUDY DESIGN: The VS-PCR was adapted from a real-time PCR assay, based on TaqMan technology, previously developed for the genome quantitation of both HHV-6 variants [Gautheret-Dejean A, Manichanh C, Thien-Ah-Koon F, Fillet AM, Mangeney N, Vidaud M, et al. Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients. J Virol Meth 2002;100:27-35], a consensual reverse primer (Taq2) being changed into two variant-specific primers named H6A and H6B. This method was applied to a large set of biological specimens obtained in different pathological contexts. RESULTS: The sensitivity threshold was about 10 copies/well for HHV-6A-specific PCR (PCR-A) and 1 copy/well for HHV-6B-specific PCR (PCR-B). Both assays showed a linear dynamic range from 10 to 100,000 copies of HHV-6 DNA. Regarding the specificity and the capacity of discrimination of each assay, one variant could be detected and identified in the presence of more than 1000 times higher concentrations of the other variant in virus mixtures. The comparison of the results obtained with this VS-PCR with those previously obtained with a classic PCR method allowed us to validate our new technique on a wide panel of biological samples, including numerous patients with severe HHV-6-related symptoms. The high prevalence of HHV-6B was confirmed in healthy individuals and immunocompromised patients. HHV-6A was identified in distinct samples from several patients exhibiting neurological disorders. CONCLUSIONS: We developed a new VS-PCR assay, able to differentiate HHV-6A and HHV-6B in biological samples, even in the case of mixed infections. Our study confirms the wide prevalence of HHV-6B and highlights the potential greater neuropathogenic role of HHV-6A in immunocompromised patients and young infants.

The role of 24 h pH-recording in pediatric otolaryngologic gastro-esophageal reflux disease.

The purpose of this study was to investigate the role of 24 h pH monitoring for the diagnosis of otolaryngologic including rhinologic manifestations of gastro-esophageal reflux (GER) in children and if possible to correlate the results with the efficacy of medical treatment. This is a retrospective study of 72 children from January 1997 to December 1999. The children were separated into three groups according to the main symptoms (although association of symptoms was frequent): rhinologic (n=28), laryngotracheal (n=28) and pharyngeal-otologic (n=16). With the classical gastroenterologic criterion (> or =4.2% of total time at pH < 4), the pH monitoring was positive in 56% of the patients. However, this criterion does not seem to be sensitive for otolaryngologic gastro-esophageal reflux disease (GERD) because multiple daytime short reflux episodes are often involved. Indeed, the pH monitoring was positive in 75% of the patients (82% in the rhinologic group) when a number of 40 episodes in 24h was also taken into account. The success rate of medical treatment was about 80% in case of positive pH recording. This study underlines that GER is an important factor in pediatric otolaryngologic diseases.

Transnasal endoscopic treatment of choanal atresia without prolonged stenting.

OBJECTIVE: To analyze the outcome of transnasal endoscopic repair of choanal atresia (CA) in children without prolonged nasal stenting after surgery. DESIGN: Retrospective study. SETTING: Academic tertiary care children's hospital. PATIENTS: Forty children aged 3 days to 15 years (mean age, 41 months) who presented with unilateral (n = 26) or bilateral (n = 14) CA and underwent surgery between August 1996 and December 1999. INTERVENTION: All children underwent transnasal endoscopy with telescopes, endoscopic instruments, and a microdebrider. Nasal tubes in neonates or infants and nasal packing in older children were always removed after 2 days. Systematic revision endoscopy was performed with the patients under local or general anesthesia on days 6 to 10. All patients were then clinically and endoscopically monitored for nasal obstruction and healing during a mean follow-up period of 18 months. RESULTS: There were 16 patients with associated malformations, including 6 cases of CHARGE association (a malformative syndrome that includes coloboma, heart disease, CA, retarded development, genital hypoplasia, and ear anomalies, including hypoplasia of the external ear and hearing loss), and 14 patients (9 with bilateral CA) with a history of previous choanal surgery (4 transnasal, 4 laser, and 6 transpalatine). Postoperatively, 32 patients (80%) had normal nasal patency and a satisfactory choanal diameter, and 8 (20%) had restenosis or complete choanal closure. Six underwent a second procedure, with success. The results in all children who had been previously treated with laser or transpalatine surgery were successful. The last patient, who presented with severe Treacher Collins syndrome, is still tracheotomized. There were no significant postoperative complications. One patient died of congenital cardiopathy 6 months after surgery. CONCLUSIONS: Transnasal endoscopic repair of CA is a safe and successful technique. The use of powered instrumentation and routine postoperative revision endoscopy seems to avoid prolonged nasal stenting.