Neonatal hearing screening: modelling cost and effectiveness of hospital- and community-based screening

BACKGROUND: Children with congenital hearing impairment benefit from early detection and management of their hearing loss. These and related considerations led to the recommendation of universal newborn hearing screening. In 2001 the first phase of a national Newborn Hearing Screening Programme (NHSP) was implemented in England. Objective of this study was to assess costs and effectiveness for hospital and community-based newborn hearing screening systems in England based on data from this first phase with regard to the effects of alterations to parameter values. METHODS: Design: Clinical effectiveness analysis using a Markov Model. Outcome measure: quality weighted detected child months (QCM). RESULTS: Both hospital and community programmes yielded 794 QCM at the age of 6 months with total costs of £3,690,000 per 100,000 screened children in hospital and £3,340,000 in community. Simulated costs would be lower in hospital in 48% of the trials. Any statistically significant difference between hospital and community in prevalence, test sensitivity, test specificity and costs would result in significant differences in cost-effectiveness between hospital and community. CONCLUSION: This modelling exercise informs decision makers by a quantitative projection of available data and the explicit and transparent statements about assumptions and the degree of uncertainty. Further evaluation of the cost-effectiveness should focus on the potential differences in test parameters and prevalence in these two settings

Natural selection shaped the rise and fall of passenger pigeon genomic diversity.

The extinct passenger pigeon was once the most abundant bird in North America, and possibly the world. Although theory predicts that large populations will be more genetically diverse, passenger pigeon genetic diversity was surprisingly low. To investigate this disconnect, we analyzed 41 mitochondrial and 4 nuclear genomes from passenger pigeons and 2 genomes from band-tailed pigeons, which are passenger pigeons' closest living relatives. Passenger pigeons' large population size appears to have allowed for faster adaptive evolution and removal of harmful mutations, driving a huge loss in their neutral genetic diversity. These results demonstrate the effect that selection can have on a vertebrate genome and contradict results that suggested that population instability contributed to this species's surprisingly rapid extinction

Differentiation of the Lateral Compartment of the Cochlea Requires a Temporally Restricted FGF20 Signal

FGF20 signaling in mice is required specifically for the differentiation of cochlear outer hair cells, the cells most often damaged during age-related hearing loss

The complete genome sequence of a Neandertal from the Altai Mountains

We present a high-quality genome sequence of a Neandertal woman from Siberia. We show that her parents were related at the level of half siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neandertal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neandertals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high quality Neandertal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neandertals and Denisovans

The effectiveness of proactive telephone support provided to breastfeeding mothers of preterm infants: Study protocol for a randomized controlled trial

Background: Although breast milk has numerous benefits for infants' development, with greater effects in those born preterm (at < 37 gestational weeks), mothers of preterm infants have shorter breastfeeding duration than mothers of term infants. One of the explanations proposed is the difficulties in the transition from a Neonatal Intensive Care Unit (NICU) to the home environment. A person-centred proactive telephone support intervention after discharge from NICU is expected to promote mothers' sense of trust in their own capacity and thereby facilitate breastfeeding. Methods/design: A multicentre randomized controlled trial has been designed to evaluate the effectiveness and cost-effectiveness of person-centred proactive telephone support on breastfeeding outcomes for mothers of preterm infants. Participating mothers will be randomized to either an intervention group or control group. In the intervention group person-centred proactive telephone support will be provided, in which the support team phones the mother daily for up to 14 days after hospital discharge. In the control group, mothers are offered a person-centred reactive support where mothers can phone the breastfeeding support team up to day 14 after hospital discharge. The intervention group will also be offered the same reactive telephone support as the control group. A stratified block randomization will be used; group allocation will be by high or low socioeconomic status and by NICU. Recruitment will be performed continuously until 1116 mothers (I: 558 C: 558) have been included. Primary outcome: proportion of mothers exclusively breastfeeding at eight weeks after discharge. Secondary outcomes: proportion of breastfeeding (exclusive, partial, none and method of feeding), mothers satisfaction with breastfeeding, attachment, stress and quality of life in mothers/partners at eight weeks after hospital discharge and at six months postnatal age. Data will be collected by researchers blind to group allocation for the primary outcome. A qualitative evaluation of experiences of receiving/providing the intervention will also be undertaken with mothers and staff. Discussion: This paper presents the rationale, study design and protocol for a RCT providing person-centred proactive telephone support to mothers of preterm infants. Furthermore, with a health economic evaluation, the cost-effectiveness of the intervention will be assessed

Aggressive vs. conservative phototherapy for infants with extremely low birth weight.

BACKGROUND: It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less). METHODS: We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments. RESULTS: Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P\u3c0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g. CONCLUSIONS: Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.

Early Infant Morbidity in the City of São Paulo, Brazil

BACKGROUND: Early infant morbidities may produce adverse outcomes in subsequent life. A low Apgar score is a convenient measure of early infant morbidity. We study determinants of early infant morbidity (sex, plurality, mode of delivery, prior losses, gestational age, prenatal care and birth weight, parity and maternal age, race, maternal education and community development) for the 1998-birth cohort, City of São Paulo, Brazil. METHODS: This study identified all deliveries that took place in the City of São Paulo during 1998. Information was extracted from 209,628 birth records. We used multivariate logistic regression to assess the effect of each independent variable on Apgar score less than seven at one minute and Apgar score less than seven at five minutes. RESULTS: Low birth weight, prematurity and community development were found to be strong predictors of morbidity. Maternal education showed strong negative correlation with both Apgar scores. The negative correlations between maternal schooling and Apgar scores were observed after prenatal care, parity and maternal age were included in the model. Unmeasured proximate factors may thus be the true source of disparity between educational groups. Children of very young adolescent mothers had lower Apgar scores at one minute (but not at five minutes) than those born to mothers 15 to 19. Parity one or higher was associated with decreased odds of low Apgar scores. Cesarean section and operative delivery were associated with higher odds of early infant morbidity. CONCLUSION: Education may allow mothers to have better care in the peripartum period. More educated mothers may be more likely to recognize certain morbidities through the pregnancy period and the monitoring of such morbidities yields better infant outcomes. Also, having less than seven prenatal care visits was found to predict early infant morbidity and one way to increase the use of such services is to focus on aspects of care that may lead to easier accessibility and continuity of prenatal care. Physicians should inform mothers about the risks associated with high number of children for a next infant and also about the risks for the infant associated with unnecessary cesarean sections. Special attention should be paid to adolescent mothers, since much of their increased risk is likely to be minimized by counseling

Newborn Genetic Screening for Hearing Impairment: A Preliminary Study at a Tertiary Center

Universal newborn hearing screening (UNHS) is of paramount importance for early identification and management of hearing impairment in children. However, infants with slight/mild, progressive, or late-onset hearing impairment might be missed in conventional UNHS. To investigate whether genetic screening for common deafness-associated mutations could assist in identifying these infants, 1017 consecutive newborns in a tertiary hospital were subjected to both newborn hearing screening using a two-step distortion-product otoacoustic emissions (DPOAE) screening and newborn genetic screening (NGS) for deafness. The NGS targeted 4 deafness-associated mutations commonly found in the Taiwanese population, including p.V37I (c.109G>A) and c.235delC of the GJB2 gene, c.919-2A>G of the SLC26A4 gene, and mitochondrial m.1555A>G of the 12S rRNA gene. The results of the NGS were then correlated to the results of the NHS. Of the 1017 newborns, 16 (1.6%) had unilateral DPOAE screening failure, and 22 (2.2%) had bilateral DPOAE screening failure. A total of 199 (19.6%) babies were found to have at least 1 mutated allele on the NGS for deafness, 11 (1.1%) of whom were homozygous for GJB2 p.V37I, 6 (0.6%) compound heterozygous for GJB2 p.V37I and c.235delC, and 1 (0.1%) homoplasmic for m.1555A>G, who may potentially have hearing loss. Among them, 3 babies, 5 babies, and 1 baby, respectively, passed the NHS at birth. Comprehensive audiological assessments in the 9 babies at 3 months identified 1 with slight hearing loss and 2 with mild hearing loss. NGS for common deafness-associated mutations may identify infants with slight/mild or potentially progressive hearing impairment, thus compensating for the inherent limitations of the conventional UNHS