Discharge of newborns with risk factors of severe hyperbilirubinemia: description of a hospital at home-based care monitoring and phototherapy.

Neonatal jaundice is common and associated with delay in hospital discharge and risk of neurological sequelae if not treated. The objectives of the study were to report on our experience of the monitoring and treatment of neonatal jaundice in a home care setting and its feasibility and safety for neonates with high risk of severe hyperbilirubinemia. The 2-year study has been led in the greater Paris University Hospital At Home (Assistance Publique-Hôpitaux de Paris). The device of the intervention was the Bilicocoon® Bag, a light-emitting diode sleeping bag worn by the neonate when the total serum bilirubin value exceeds intensive phototherapy threshold, according to the guidelines from the American Academy of Pediatrics. One hundred and thirty-nine neonates had participated in the intervention and 39 (28%) were treated by phototherapy at home, as continuation of inpatient phototherapy or started at home. Seventy-five percent of the sample had more than two risk factors for development of severe hyperbilirubinemia. Twenty five percent of the cohort who received phototherapy at home had lower gestational age (p < 0.014) and had younger age at discharge from maternity (p < 0.09). Median length of stay in hospital at home was 5 days. Two patients needed readmission in conventional hospital (1%) for less than 24 h. In multivariate model, the length of stay decreased with the higher gestational age (p < 0.001) and increased significantly with the older age at discharge, the birth weight < 10th percentile, and a treatment by phototherapy at home.    Conclusion: Hospital at home, which is a whole strategy using an effective and convenient phototherapy device combined with a specialized medical follow-up, could be an alternative to conventional hospitalization for neonates at high risk of severe jaundice. The maternity discharge is facilitated, the mother-infant bonding can be promoted, and the risk of conventional rehospitalization is minimal, while guaranteeing the safety of this specific care. What is Known: • Managing neonatal jaundice is provided in conventional hospital with phototherapy. • Neonatal jaundice increases the risk of prolonged hospitalization or readmission. What is New: • Phototherapy is feasible in hospital at home for neonates with high risk of severe hyperbilirubinemia. • The care pathway of neonates from conventional hospital to hospital at home is described.

Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease.

Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-ß4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-ß4 abundance was confirmed with ELISA. Knockout of thymosin-ß4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin ß4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable.

Phylodynamic and phylogeographic patterns of the HIV type 1 subtype F1 parenteral epidemic in Romania.

In the late 1980s an HIV-1 epidemic emerged in Romania that was dominated by subtype F1. The main route of infection is believed to be parenteral transmission in children. We sequenced partial pol coding regions of 70 subtype F1 samples from children and adolescents from the PENTA-EPPICC network of which 67 were from Romania. Phylogenetic reconstruction using the sequences and other publically available global subtype F sequences showed that 79% of Romanian F1 sequences formed a statistically robust monophyletic cluster. The monophyletic cluster was epidemiologically linked to parenteral transmission in children. Coalescent-based analysis dated the origins of the parenteral epidemic to 1983 [1981-1987; 95% HPD]. The analysis also shows that the epidemic's effective population size has remained fairly constant since the early 1990s suggesting limited onward spread of the virus within the population. Furthermore, phylogeographic analysis suggests that the root location of the parenteral epidemic was Bucharest.

Performance of HIV-1 DNA or HIV-1 RNA tests for early diagnosis of perinatal HIV-1 infection during anti-retroviral prophylaxis.

OBJECTIVE: To compare performance of testing for human immunodeficiency virus (HIV)-1 DNA and HIV-1 RNA for diagnosis of HIV-1 infection in infants receiving preventive antiretroviral therapy. STUDY DESIGN: This substudy of the French multicenter prospective cohort of neonates born to HIV-infected mothers, included 1567 infants tested for HIV with polymerase chain reaction (PCR) in a single laboratory, receiving post-natal prophylaxis, not breastfed, and having simultaneous HIV-1 DNA and RNA results before 45 days. The performance of PCR was assessed in reference to the 6-month HIV-1 RNA result. RESULTS: Specificity of both HIV-1 RNA and HIV-1 DNA PCR was 100% at all ages (except 99.8% for DNA at birth); sensitivity was 58% (RNA) and 55% (DNA) at birth, and 89% at 1 month, 100% at 3 months for both, and 100% at 6 months (DNA). Concordance between HIV-1 DNA and RNA results was 0.78 and 0.81 (Kappa) at birth and 1 month and 100% at 3 and 6 months. Type of maternal and neonatal prophylaxis had no effect on sensitivity, but influenced viral load. CONCLUSION: The performances of testing for HIV-1 DNA and RNA were similar with 100% sensitivity at 3 months. At 1 month during prophylaxis, 11% of infected children had negative PCR results.

Pregnancy in women heterozygous for MCT8 mutations: risk of maternal hypothyroxinemia and fetal care.

CONTEXT: Monocarboxylate transporter 8 (MCT8 or SLC16A2) mutations cause X-linked Allan-Herndon-Dudley syndrome. Heterozygous females are usually asymptomatic, but pregnancy may modify thyroid function and MCT8 is expressed in the placenta, suggesting that maternal and fetal abnormalities might develop even in the absence of MCT8 fetal mutation. Genetic counseling is so far based on X-linked transmission, and prenatal diagnosis is rarely performed. OBJECTIVE: To describe thyroid function and the prenatal diagnosis in pregnant mothers harboring heterozygous MCT8 mutations and management of the persistent maternal hypothyroxinemia. Patients Two women heterozygous for MCT8 mutations (c.1690G>A and c.1393-1G>C) were monitored throughout pregnancy. METHODS: Prenatal diagnosis included sex determination, direct MCT8 sequencing, and familial linkage analysis. Ultrasonography and hormonal assays for maternal thyroid function evaluation were performed serially during pregnancy. Neonatal thyroid hormonal status was assessed. RESULTS: None of the three fetuses (two males and one female) carried MCT8 mutations. One of the two heterozygous mothers revealed gestational hypothyroxinemia, prompting early levothyroxine (l-T4) therapy until delivery. The second heterozygous mother showed normal thyroid function but was preventively traited by l-T4 and all of the three neonates had normal thyroid hormone levels and thyroid gland at birth, suggesting advantages of prenatal care and/or compensatory mechanisms. CONCLUSION: Heterozygous MCT8 women should be monitored for requirement of l-T4 therapy to prevent fetal and neonatal hypothyroidism and to avoid risk of potential cognitive delay due to gestational hypothyroxinemia. Moreover, when the disease-causing mutation is known and/or the first child is affected, prenatal diagnosis for male fetuses should be assessed early for MCT8 mutations by direct sequencing.

LTR real-time PCR for HIV-1 DNA quantitation in blood cells for early diagnosis in infants born to seropositive mothers treated in HAART area (ANRS CO 01).

HIV-1 diagnosis in babies born to seropositive mothers is one of the challenges of HIV epidemics in children. A simple, rapid protocol was developed for quantifying HIV-1 DNA in whole blood samples and was used in the ANRS French pediatric cohort in conditions of prevention of mother-to-child transmission. A quantitative HIV-1 DNA protocol (LTR real-time PCR) requiring small blood volumes was developed. First, analytical reproducibility was evaluated on 172 samples. Results obtained on blood cell pellets and Ficoll-Hypaque separated mononuclear cells were compared in 48 adult HIV-1 samples. Second, the protocol was applied to HIV-1 diagnosis in infants in parallel with plasma HIV-RNA quantitation. This prospective study was performed in children born between May 2005 and April 2007 included in the ANRS cohort. The assay showed good reproducibility. The 95% detection cut-off value was 6 copies/PCR, that is, 40 copies/10(6) leukocytes. HIV-DNA levels in whole blood were highly correlated with those obtained after Ficoll-Hypaque separation (r = 0.900, P < 0.0001). A total of 3,002 specimens from 1,135 infants were tested. The specificity of HIV-DNA and HIV-RNA assays was 100%. HIV-1 infection was diagnosed in nine infants before age 60 days. HIV-DNA levels were low, underlining the need for sensitive assays when highly active antiretroviral therapy (HAART) has been given. The performances of this HIV-DNA assay showed that it is adapted to early diagnosis in children. The results were equivalent to those of HIV-RNA assay. HIV-DNA may be used even in masked primary infection in newborns whose mothers have received HAART.

Alkylammonium-based protic ionic liquids. Part I: Preparation and physicochemical characterization.

Novel alkylammonium-cation-based protic acid ionic liquids (PILs) were prepared through a simple and atom-economic neutralization reaction between an amine, such as diisopropylmethylamine, and diisopropylethylamine, and a Brønsted acid, HX, where X is HCOO-, CH 3COO-, or HF2-. The density, viscosity, acidic scale, electrochemical window, temperature dependency of ionic conductivity, and thermal properties of these PILs were measured and investigated in detail. Results show that protonated alkylammonium such as N-ethyldiisopropyl formate and N-methyldiisopropyl formate are liquid at room temperature and possess very low viscosities, that is, 18 and 24 cP, respectively, at 25 degrees C. An investigation of their thermal properties shows that they present a wide liquid range up to -100 degrees C and a heat thermal stability up to 350 degrees C. Alkylammonium-based PILs have a relatively low cost and low toxicity and show a high ionic conductivity (up a 8 mS cm(-1)) at room temperature. They have wide applicable perspectives for fuel cell devices, thermal transfer fluids, and acid-catalyzed reaction media and catalysts as replacements of conventional inorganic acids.

Alkylammonium-based protic ionic liquids. II. Ionic transport and heat-transfer properties: fragility and ionicity rule.

The physicochemical characterization of six alkylammonium-based protic ionic liquids (PILs) is presented. These compounds were prepared through a simple and atom-economic neutralization reaction between a tertiary amine and a Brønsted acid, HX, where X- is HCOO-, CH3COO-, HF2-. The temperature dependency and the effect of added water on properties such as density, viscosity, ionic conductivity, and the thermal comportment of these PILs were measured and investigated. The results allowed us to classify them according to a classical Walden diagram and to appreciate their great "fragility". PILs have applicable perspectives in replacements of conventional inorganic acids for fuel cell devices and thermal transfer fluids.

Altered heterochromatin organization after perinatal exposure to zidovudine.

BACKGROUND: Zidovudine (3'-azido-3'-deoxythymidine, AZT), administered to pregnant women alone or in combination with other antiretroviral drugs, greatly reduces the mother-to-child transmission of HIV-1. The potential genotoxicity of these molecules is underestimated and wide-ranging evaluation of its biological and clinical consequences is required. METHODS: We investigated the nuclear organization of constitutive heterochromatin, a major domain participating in epigenetic regulation, in uninfected infants born to HIV-1-infected mothers treated with zidovudine and/or other nucleoside reverse transcriptase inhibitors (NRTIs) during pregnancy. We studied the organization of chromosome 1 heterochromatin (1q12) in peripheral leukocytes of 25 HIV-1-uninfected children (newborn to 9 years old): children born to HIV-1-infected mothers exposed to zidovudine and/or other NRTIs (n=15), children born to HIV-1-infected mothers not exposed to any NRTIs (n=6) and children born to HIV-1-uninfected mothers (n=4). RESULTS: Results differed significantly between NRTI-exposed and -unexposed children. By contrast, there was no difference between NRTI-unexposed children born to HIV-1-infected mothers and children born to HIV-uninfected mothers. The anomaly persisted in lymphocytes cultured for 48 h. There was no evidence of abnormal DNA methylation, a major feature of constitutive heterochromatin and associated with the loss of its structure. In a complementary sample of children, analysis of chromosome 11 and 16 heterochromatin suggests that the defect affects most of the other heterochromatic sites of the human genome. The heterochromatin defect persists long after the end of the exposure and appears in leukocytes of both myeloid and lymphoid lineages, suggesting that haematopoietic stem cells are affected.

Early multitherapy including a protease inhibitor for human immunodeficiency virus type 1-infected infants.

BACKGROUND: To assess tolerance and efficacy of early multitherapy including a protease inhibitor for infants perinatally infected with HIV. METHODS: Observational study of tolerance and clinical and immunovirologic evolution in HIV-infected infants treated before the age of 1 year in the French Perinatal Study. RESULTS: Thirty-one infants were included. The median age was 3.7 months at initiation of multitherapy. Clinical stage was C (n = 8), B (n = 5) or A/N (n = 18). The median HIV RNA viral load was 5.8 log copies/ml, and the median CD4 cell percentage was 29%. Median follow-up of treatment was 27 months. Of 31 infants 15 experienced mild to moderate adverse events. No infant had clinical or immunologic progression. The median change in viral load was -2.7 log copies/ml after 3 months, -2.0 log after 12 months and -1.7 log after 24 months of treatment. The proportion of infants with a viral load below 500 copies/ml decreased from 53% at 6 months to 18% at 24 months of treatment. The virologic response was not correlated with viral load at baseline. However, the slope of the viral load decrease during the first month of treatment was predictive of the virologic response at 3 and 6 months. Fourteen infants with a viral load of >500 copies/ml after 6 months of treatment displayed viruses with antiretroviral resistance mutations in reverse transcriptase and/or protease genes. CONCLUSIONS: Despite the absence of clinical or immunologic progression, the high frequency of virologic failure associated with genotypic resistance reveals the difficulties associated with implementing antiretroviral multitherapy in infants. Suboptimal doses of protease inhibitor could be a factor contributing to treatment failure.