The cost-effectiveness of universal newborn screening for bilateral permanent congenital hearing impairment : systematic review

Objective - Universal newborn hearing screening for bilateral permanent congenital hearing impairment is standard practice in many developed economies, but until there is clear evidence of cost-effectiveness, it remains a controversial use of limited health care resources. We conducted a formal systematic review of studies of newborn hearing screening that considered both costs and outcomes to produce a summary of the available evidence and to determine whether there was a need for further research.

Methods - A search was conducted of medical and nursing databases and gray literature websites by the use of multiple keywords. The titles and abstracts of studies were examined for preliminary inclusion if reference was made to newborn hearing screening, and to both costs and outcomes. Studies of potential relevance were independently assessed by 2 health economists for final inclusion in the review. Studies that met inclusion criteria were appraised by the use of existing guidelines for observational studies, economic evaluations and decision analytic models, and reported in a narrative literature review.

Results - There were 22 distinct observational or modeled evaluations of which only 2 clearly compared universal newborn hearing screening to risk factor screening for bilateral permanent congenital hearing impairment. Of these, the single evaluation that examined long-term costs and outcomes found that universal newborn hearing screening could be cost-saving if early intervention led to a substantial reduction in future treatment costs and productivity losses.

Conclusions - There are only a small number of economic evaluations that have examined the long-term cost-effectiveness of universal newborn hearing screening. This is partly attributable to ongoing uncertainty about the benefits gained from the early detection and treatment of bilateral permanent congenital hearing impairment. There is a clear need for further research on long-term costs and outcomes to establish the cost-effectiveness of universal newborn hearing screening in relation to other approaches to screening, and to establish whether it is a good long term investment.

Lack of ceruloplasmin expression alters aspects of copper transport to the fetus and newborn, as determined in mice

Copper transport and accumulation were studied in virgin and lactating C57BL/6 mice, with and without expression of ceruloplasmin (Cp), to assess the importance of Cp to these processes. One hour after i.p. injection of tracer ⁶⁴Cu, liver and kidney accounted for 80% of the radioactivity, and mammary gland 1%, while in lactating Cp+/+ mice 2–4 days post partum, uptake by mammary gland was 9-fold higher and that of liver and other organs was decreased, with ⁶⁴Cu rapidly appearing in milk. Parallel studies in Cp−/− mice (siblings from same colony) gave virtually identical results. However, their milk contained less ⁶⁴Cu, and actual copper contents determined by furnace atomic absorption were less than half those for milk from normal dams. Liver copper concentrations of pups born to Cp−/− dams also were half those of pups from wild type dams. Copper in pup brains was unaffected; but iron concentrations were reduced. We conclude that absence of Cp, while not affecting entry of exchangeable copper from the blood into the mammary gland, does have a significant effect on the availability of this metal to the newborn through the milk and in the form of stores accumulating in gestation.

Prospective evaluation of respiratory exacerbations in children with cystic fibrosis from newborn screening to 5 years of age

Background Newborn screening allows novel treatments for cystic fibrosis (CF) to be trialled in early childhood before irreversible lung injury occurs. As respiratory exacerbations are a potential trial outcome variable, we determined their rate, duration and clinical features in preschool children with CF; and whether they were associated with growth, lung structure and function at age 5 years. Methods: Respiratory exacerbations were recorded prospectively in Australasian CF Bronchoalveolar Lavage trial subjects from enrolment after newborn screening to age 5 years, when all participants underwent clinical assessment, chest CT scans and spirometry. Results 168 children (88 boys) experienced 2080 exacerbations, at an average rate of 3.66 exacerbations per person-year; 80.1% were community managed and 19.9% required hospital admission. There was an average increase in exacerbation rate of 9% (95% CI 4% to 14%; p<0.001) per year of age. Exacerbation rate differed by site (p<0.001) and was 26% lower (95% CI 12% to 38%) in children receiving 12 months of prophylactic antibiotics. The rate of exacerbations in the first 2 years was associated with reduced forced expiratory volume in 1 s z scores. Ever having a hospitalmanaged exacerbation was associated with bronchiectasis (OR 2.67, 95% CI 1.13 to 6.31) in chest CT scans, and lower weight z scores at 5 years of age (coefficient -0.39, 95% CI -0.74 to -0.05). Conclusions Respiratory exacerbations in young children are markers for progressive CF lung disease and are potential trial outcome measures for novel treatments in this age group.

Creatine pretreatment prevents birth asphyxia–induced injury of the newborn spiny mouse kidney

Background:
Acute kidney injury (AKI) is a major complication for infants following an asphyxic insult at birth. We aimed to determine if kidney structure and function were affected in an animal model of birth asphyxia and if maternal dietary creatine supplementation could provide an energy reserve to the fetal kidney, maintaining cellular respiration during asphyxia and preventing AKI.

Methods:
Pregnant spiny mice were maintained on normal chow or chow supplemented with creatine from day 20 gestation. On day 38 (term ~39 d), pups were delivered by cesarean section (c-section) or subjected to intrauterine asphyxia. Twenty-four hours after insult, kidneys were collected for histological or molecular analysis. Urine and plasma were also collected for biochemical analysis.

Results:
AKI was evident at 24 h after birth asphyxia, with a higher incidence of shrunken glomeruli (P < 0.02), disturbance to tubular arrangement, tubular dilatation, a twofold increase (P < 0.02) in expression of Ngal (early marker of kidney injury), and decreased expression of the podocyte differentiation marker nephrin. Maternal creatine supplementation prevented the glomerular and tubular abnormalities observed in the kidney at 24 h and the increased expression of Ngal.

Conclusion:
Maternal creatine supplementation may prove useful in ameliorating kidney injury associated with birth asphyxia.

Maternal dietary creatine supplementation does not alter the capacity for creatine synthesis in the newborn spiny mouse

We have previously reported that maternal creatine supplementation protects the neonate from hypoxic injury. Here, we investigated whether maternal creatine supplementation altered expression of the creatine synthesis enzymes (arginine:glycine amidinotransferase [AGAT], guanidinoaceteate methyltransferase [GAMT]) and the creatine transporter (solute carrier family 6 [neurotransmitter transporter, creatine] member 8: SLC6A8) in the term offspring. Pregnant spiny mice were fed a 5% creatine monohydrate diet from midgestation (day 20) to term (39 days). Placentas and neonatal kidney, liver, heart, and brain collected at 24 hours of age underwent quantitative polymerase chain reaction and Western blot analysis. Maternal creatine had no effect on the expression of AGAT and GAMT in neonatal kidney and liver, but mRNA expression of AGAT in brain tissues was significantly decreased in both male and female neonates born to mothers who were fed the creatine diet. SLC6A8 expression was not affected by maternal dietary creatine loading in any tissues. Maternal dietary creatine supplementation from midgestation in the spiny mouse did not alter the capacity for creatine synthesis or transport.

Zinc deficiency and its inherited disorders - A review

Zinc is an essential trace element required by all living organisms because of its critical roles both as a structural component of proteins and as a cofactor in enzyme catalysis. The importance of zinc in human metabolism is illustrated by the effects of zinc deficiency, which include a diminished immune response, reduced healing and neurological disorders. Furthermore, nutritional zinc deficiency can be fatal in newborn or growing animals. While zinc deficiency is commonly caused by dietary factors, several inherited defects of zinc deficiency have been identified. Acrodermatitis enteropathica is the most commonly described inherited condition found in humans. In several of the few cases that have been reported, this disorder is associated with mutations in the hZIP4 gene, a member of the SLC39 family, whose members encode membranebound putative zinc transporters. Mutations in other members of this family or in different genes may account for other cases of acrodermatitis in which defects in hZIP4 have not been detected. Another inherited form of zinc deficiency occurs in the lethal milk mouse, where a mutation in ZnT4 gene, a member of the SLC30 family of transmembrane proteins results in impaired secretion of zinc into milk from the mammary gland. A similar disorder to the lethal milk mouse occurs in humans. In the few cases studied, no changes in ZnT4 orthologue, hZnT4, were detected. This, and the presence of several minor phenotypic differences between the zinc deficiency in humans and mice, suggests that the human condition is caused by defects in genes that are yet to be identified. Taking into account the fact that there are no definitive tests for zinc deficiency and that this disorder can go undiagnosed, plus the recent identification of multiple members of the SCL30 and SLC39, it is likely that mutations in other genes may underlie additional inherited disorders of zinc deficiency.

Individual variation in the pup attraction call produced by female Australian fur seals during early lactation

Otariid seals (fur seals and sea lions) are colonial breeders with large numbers of females giving birth on land during a synchronous breeding period. Once pups are born, females alternate between feeding their young ashore and foraging at sea. Upon return, both mother and pup must relocate each other and it is thought to be primarily facilitated by vocal recognition. Vocalizations of thirteen female Australian fur seals (Arctocephalus pusillus doriferus) were recorded during the breeding seasons of December 2000 and 2001, when pups are aged from newborns to one month. The pup attraction call was examined to determine whether females produce individually distinct calls which could be used by pups as a basis for vocal recognition. Potential for individual coding, discriminant function analysis (DFA), and classification and regression tree analysis were used to determine which call features were important in separating individuals. Using the results from all three analyses: F0, MIN F and DUR were considered important in separating individuals. In 76% of cases, the PAC was classified to the correct caller, using DFA, suggesting that there is sufficient stereotypy within individual calls, and sufficient variation between them, to enable vocal recognition by pups of this species.

The infant feeding activity and nutrition trial (INFANT) an early intervention to prevent childhood obesity : cluster-randomised controlled trial

Background : Multiple factors combine to support a compelling case for interventions that target the development of obesity-promoting behaviours (poor diet, low physical activity and high sedentary behaviour) from their inception. These factors include the rapidly increasing prevalence of fatness throughout childhood, the instigation of obesity-promoting behaviours in infancy, and the tracking of these behaviours from childhood through to adolescence and adulthood. The Infant Feeding Activity and Nutrition Trial (INFANT) aims to determine the effectiveness of an early childhood obesity prevention intervention delivered to first-time parents. The intervention, conducted with parents over the infant's first 18 months of life, will use existing social networks (first-time parent's groups) and an anticipatory guidance framework focusing on parenting skills which support the development of positive diet and physical activity behaviours, and reduced sedentary behaviours in infancy.

Methods/Design : This cluster-randomised controlled trial, with first-time parent groups as the unit of randomisation, will be conducted with a sample of 600 first-time parents and their newborn children who attend the first-time parents' group at Maternal and Child Health Centres. Using a two-stage sampling process, local government areas in Victoria, Australia will be randomly selected at the first stage. At the second stage, a proportional sample of first-time parent groups within selected local government areas will be randomly selected and invited to participate. Informed consent will be obtained and groups will then be randomly allocated to the intervention or control group.

Discussion : The early years hold promise as a time in which obesity prevention may be most effective. To our knowledge this will be the first randomised trial internationally to demonstrate whether an early health promotion program delivered to first-time parents in their existing social groups promotes healthy eating, physical activity and reduced sedentary behaviours. If proven to be effective, INFANT may protect children from the development of obesity and its associated social and economic costs.

Serotonin discontinuation syndrome following utero exposure to antidepressant medication : prospective controlled study

Objectives: The aim of the present study was to examine neonatal symptoms previously reported to be associated with exposure to antidepressant medication in late pregnancy in a group of infants exposed to antidepressants, using a prospective and controlled design.

Method: A prospective case-control study recruited 27 pregnant women taking antidepressant medication and 27 matched controls who were not taking antidepressant medication in pregnancy. Of the 27 women taking medication, 25 remained on medication in the third trimester and, of these, 23 women had complete data available. In pregnancy and after delivery women were assessed with the Beck Depression Inventory-II and a purpose-designed questionnaire. After delivery mothers were asked a set of nine questions pertaining to symptoms of discontinuation in their newborn and questions about pregnancy and delivery complications.

Results: There was an increased risk of discontinuation symptoms in neonates exposed to antidepressant medication in late pregnancy and an association with higher dose medication. The study group were found to be significantly more likely to display behaviour such as crying, jitteriness, tremor, feeding, reflux and sneezing and sleep for <3 h after a feed. They also had significantly higher rates of jaundice and admissions to the special care nursery.

Conclusions: Exposure to antidepressants in late pregnancy is associated with a range of symptoms in the neonate that are consistent with the effects of exposure to antidepressants in late pregnancy. The clusters of symptoms most highly correlated are the gastrointestinal and central nervous system symptoms. These finding helps to identify the common symptoms associated with a neonatal serotonin discontinuation syndrome.

Influences on fecundity in Australian fur seals (Arctocephalus pusillus doriferus)

Recovery of the Australian fur seal (Arctocephalus pusillus doriferus) population has been slower than that of other fur seals, perhaps due to nutritional constraints on fecundity. However, the population doubled in recent decades, suggesting that reproductive rates may have changed. Pregnancy rates and birthrates were estimated and the influences of maternal age, size, condition, and lactation status were investigated over 3 consecutive breeding seasons (2003–2005). Mid-gestation pregnancy rate, estimated from plasma progesterone concentrations, was 84% ± 3% (mean ± SE) and was negatively influenced only by age (P< 0.001). Birthrate, estimated from observations of females with newborn offspring during the breeding season, was 53% 6 3% (mean ± SE) and was influenced negatively by lactation status (P = 0.035). The difference between pregnancy rates and birthrates suggests that a high degree of late-gestation abortion occurs, especially in younger females. Lactation status was not influenced by any variables, and the high rate (86% ± 2%; mean ± SE) suggests that many offspring are suckled beyond the typical weaning period. Although relationships between reproductive rates and body condition were not found, the results are consistent with a nutritional stress hypothesis. The recent increase in population growth is not due to increased fecundity, which remains low compared to other otariids. Paradoxically, high pregnancy rates were observed in young females (3 years), suggesting that rapid maturity is adaptive for benthic foragers.