Probiotic supplementation in neonates and long-term gut colonisation: A systematic review of randomised controlled trials.

BACKGROUND: Probiotic supplementation in the neonatal period results in improved gut colonisation with probiotic bacteria in the short term. There is limited information on the long-term sustainability of this colonisation. AIMS: To evaluate whether oral probiotic supplementation in the neonatal period results in sustained gut colonisation with probiotic bacteria at or beyond 6 months after its cessation. METHODS: A systematic review of neonatal probiotic randomised controlled trials (RCTs) that reported on the stool microbiota during post-discharge follow-up was carried out using guidelines of the Cochrane neonatal group. RESULTS: Four RCTs (n = 605 infants) were included in the review. The studies were heterogeneous in case selection, choice of probiotics, duration of supplementation, timing and the method of stool microbial analysis. Three RCTs (n = 471) showed the presence of intestinal probiotic bacteria at 6-12 months. The overall certainty of evidence was very low in view of small sample size, heterogeneity and identification only to the genus/species level. CONCLUSION: Low certainty of evidence suggests that probiotic supplementation in the neonatal period may result in sustained gut colonisation 6-12 months post-cessation, but not at 24 months. Adequately powered, well-designed RCTs with strain-specific assays are needed in this area.

Prevalence estimates of mental health problems in children and adolescents with intellectual disability: A systematic review and meta-analysis.

BACKGROUND: Children and adolescents with intellectual disability are at risk of developing psychiatric symptoms and disorders; yet, the estimates reported in the literature have been inconsistent, presenting a potential barrier for service planning and delivery. Sources of variability could arise from differences in measurement instruments as well as subgroup membership by severity of intellectual disability, gender and age. This systematic review aimed to address these gaps. METHOD: MEDLINE and PsycINFO databases were searched from inception to 2018 and selected studies were reviewed. Studies were included if they reported point prevalence estimates of mental health symptomology or diagnoses in a general population of 6- to 21-year-old individuals with intellectual disability. The Joanna Briggs Institute Prevalence Critical Appraisal Checklist was applied to eligible papers to appraise their scientific strength. Pooled prevalence for mental health symptomology was determined using a random-effects meta-analysis. RESULTS: A total of 19 studies were included, including 6151 children and adolescents. The pooled prevalence estimate captured by the Developmental Behaviour Checklist was 38% (95% confidence interval = [31, 46]), contrasting with 49% (95% confidence interval = [46, 51]) captured by the Child Behaviour Checklist; both rates were higher than a non-intellectual disability population. Severity of intellectual disability did not significantly influence the Developmental Behaviour Checklist risks. Insufficient data were available to conduct statistical analyses on the effects of age, gender and socioeconomic status. Of diagnosed psychiatric disorders, attention deficit/hyperactivity disorder (30%), conduct disorder (3-21%) and anxiety disorders (7-34%) were the most prevalent conditions. CONCLUSION: This review consists of the largest sample hitherto evaluated. In the intellectual disability population, mental health comorbidities could be better detected by a symptom phenotype than a psychiatric diagnostic phenotype. Crucially, future research needs to address the effect of measurement validity in the intellectual disability population. Estimated prevalence rates were high compared to the general population, indicating the importance of systematic screening, case detection and appropriate management.

Predicting Long-Term Survival Without Major Disability for Infants Born Preterm.

OBJECTIVE: To describe the long-term neurodevelopmental and cognitive outcomes for children born preterm. STUDY DESIGN: In this retrospective cohort study, information on children born in Western Australia between 1983 and 2010 was obtained through linkage to population databases on births, deaths, and disabilities. For the purpose of this study, disability was defined as a diagnosis of intellectual disability, autism, or cerebral palsy. The Kaplan-Meier method was used to estimate the probability of disability-free survival up to age 25 years by gestational age. The effect of covariates and predicted survival was examined using parametric survival models. RESULTS: Of the 720 901 recorded live births, 12 083 children were diagnosed with disability, and 5662 died without any disability diagnosis. The estimated probability of disability-free survival to 25 years was 4.1% for those born at gestational age 22 weeks, 19.7% for those born at 23 weeks, 42.4% for those born at 24 weeks, 53.0% for those born at 25 weeks, 78.3% for those born at 28 weeks, and 97.2% for those born full term (39-41 weeks). There was substantial disparity in the predicted probability of disability-free survival for children born at all gestational ages by birth profile, with 5-year estimates of 4.9% and 10.4% among Aboriginal and Caucasian populations, respectively, born at 24-27 weeks and considered at high risk (based on low Apgar score, male sex, low sociodemographic status, and remote region of residence) and 91.2% and 93.3%, respectively, for those at low risk (ie, high Apgar score, female sex, high sociodemographic status, residence in a major city). CONCLUSIONS: Apgar score, birth weight, sex, socioeconomic status, and maternal ethnicity, in addition to gestational age, have pronounced impacts on disability-free survival.

Risk of Mortality into Adulthood According to Gestational Age at Birth.

OBJECTIVES: To quantify the independent risks of neonatal (0-28 days), postneonatal (29-364 days), 1- to 5- and 6- to 30-year mortality by gestational age and investigate changes in survival over time in an Australian birth cohort. STUDY DESIGN: Maternal and birth related Western Australian population data (1980-2010) were linked to the state mortality data using a retrospective cohort study design involving 722 399 live-born singletons infants. RESULTS: When compared with 39- to 41-week born infants, the adjusted risk ratio for neonatal mortality was 124.8 (95% CI 102.9-151.3) for 24-31 weeks of gestation, 3.4 (95% CI 2.4-4.7) for 35-36 weeks of gestation, and 1.4 (95% CI 1.1-1.8) for 37-38 weeks of gestation. For 24-31 weeks of gestation infants, the adjusted hazard ratio for postneonatal mortality (29-364 days) was 13.9 (95% CI 10.9-17.6), for 1- to 5-year mortality 1.4 (95% CI 0.7-3.0) and for 6- to 30-year mortality 1.3 (95% CI 0.8-2.3). The risk of neonatal and postneonatal mortality for those born preterm decreased over time. CONCLUSIONS: In Western Australia, late preterm and early term infants experienced higher risk of neonatal and postneonatal mortality when compared with their full-term peers. There was insufficient evidence to show that gestational length was independently associated with mortality beyond 1 year of age. Neonatal and postneonatal mortality improved with each decade of the study period.

Antibiotics for neonates born through meconium-stained amniotic fluid.

BACKGROUND: Approximately 1 in 10 pregnancies is affected by meconium passage at delivery, which can result in meconium aspiration syndrome (MAS). MAS can cause respiratory complications and, very rarely, death. Antibiotics have been prescribed for neonates exposed to meconium in amniotic fluid, with the intention of preventing infection due to potential bacterial contaminants. OBJECTIVES: We conducted this review to assess the efficacy and safety of antibiotics for:1. prevention of infection, morbidity, and mortality among infants born through meconium-stained amniotic fluid (MSAF) who are asymptomatic at birth; and2. prevention of infection, morbidity, and mortality among infants born through MSAF who have signs and symptoms compatible with meconium aspiration syndrome (MAS). SEARCH METHODS: We performed a literature search using the following databases: MEDLINE (1966 to July 2016); Embase (1980 to July 2016); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to July 2016); and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 7) in the Cochrane Library. We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials that compared antibiotics administered via any route versus placebo or no treatment for prevention of infection among neonates exposed to MSAF, or who developed MAS. We excluded cohort, case control, and any other non-randomised studies and applied no language restrictions. We included studies of term and preterm infants, and we included studies examining use of any antibacterial antibiotics. We included studies that reported on any outcomes of interest. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of included trials by reviewing information provided in study reports and obtained by personal communication with study authors. We extracted data on relevant outcomes, estimated effect size, and reported values as risk ratios (RRs), risk differences (RDs), and mean differences (MDs), as appropriate. We conducted subgroup analyses for treatment of MAS and for prophylaxis (asymptomatic neonates exposed to meconium). MAIN RESULTS: Four randomised controlled studies including a total of 695 participants were eligible for inclusion. Three studies evaluated neonates with MAS, and one study assessed asymptomatic neonates exposed to meconium in amniotic fluid. These studies exhibited varying degrees of methodological rigour: Two studies were at low risk of bias, and two were at unclear risk. We graded evidence derived from these studies as low quality. We downgraded overall evidence owing to the large number of participants lost to follow-up in one trial, the small sample sizes of all trials, and unclear methodological details provided for two trials.The primary outcome was risk of early- and late-onset neonatal sepsis. Antibiotics did not decrease the risk of sepsis in neonates with a diagnosis of MAS (RR 1.54, 95% confidence interval (CI) 0.27 to 8.96; RD 0.00, 95% CI -0.02 to 0.03; 445 participants, three studies; I² = 0%) nor in asymptomatic neonates exposed to meconium in amniotic fluid (RR 0.76, 95% CI 0.25 to 2.34; RD -0.01, 95% CI -0.07 to 0.04; 250 participants, one study; I² = 0%). Results show no significant differences in mortality or duration of stay in hospital between groups given antibiotics and control groups of symptomatic and asymptomatic neonates. One study in asymptomatic neonates reported a significant reduction in duration of mechanical ventilation for the control group compared with the antibiotic group (MD 0.26, 95% CI 0.15 to 0.37; 250 participants, one study; I² = 0%). AUTHORS' CONCLUSIONS: Upon review of available evidence, we found no differences in infection rates following antibiotic treatment among neonates born through meconium-stained fluid and those with meconium aspiration syndrome. The overall quality of evidence is low owing to the small number of included studies. Well-controlled studies of adequate power are needed.

One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates.

BACKGROUND: Animal studies and trials in older children and adults suggest that a 'one dose per day' regimen of gentamicin is superior to a 'multiple doses per day' regimen. OBJECTIVES: To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates. SEARCH METHODS: Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3) in the Cochrane Library (searched 8 April 2016), MEDLINE (1966 to 8 April 2016), Embase (1980 to 8 April 2016), and CINAHL (December 1982 to 8 April 2016). SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing one dose per day ('once a day') compared to multiple doses per day ('multiple doses a day') of gentamicin to newborn infants. DATA COLLECTION AND ANALYSIS: Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Eleven RCTs were included (N = 574) and 28 excluded. All except one study enrolled infants of more than 32 weeks' gestation. Limited information suggested that infants in both 'once a day' as well as 'multiple doses a day' regimens showed adequate clearance of sepsis (typical RR 1.00, 95% CI 0.84 to 1.19; typical RD 0.00, 95% CI -0.19 to 0.19; 3 trials; N = 37). 'Once a day' gentamicin regimen was associated with fewer failures to attain peak level of at least 5 µg/ml (typical RR 0.22, 95% CI 0.11 to 0.47; typical RD -0.13, 95% CI -0.19 to -0.08; number needed to treat for an additional beneficial outcome (NNTB) = 8; 9 trials; N = 422); and fewer failures to achieve trough levels of 2 µg/ml or less (typical RR 0.38, 95% CI 0.27 to 0.55; typical RD -0.22, 95% CI -0.29 to -0.15; NNTB = 4; 11 trials; N = 503). 'Once a day' gentamicin achieved higher peak levels (MD 2.58, 95% CI 2.26 to 2.89; 10 trials; N = 440) and lower trough levels (MD -0.57, 95% CI -0.69 to -0.44; 10 trials; N = 440) than 'multiple doses a day' regimen. There was no significant difference in ototoxicity between two groups (typical RR 1.69, 95% CI 0.18 to 16.25; typical RD 0.01, 95% CI -0.04 to 0.05; 5 trials; N = 214). Nephrotoxicity was not noted with either of the treatment regimens. Overall, the quality of evidence was considered to be moderate on GRADE analysis, given the small sample size and unclear/high risk of bias in some of the domains in a few of the included studies. AUTHORS' CONCLUSIONS: There is insufficient evidence from the currently available RCTs to conclude whether a 'once a day' or a 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However, data suggest that pharmacokinetic properties of a 'once a day' gentamicin regimen are superior to a 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There was no change in nephrotoxicity or auditory toxicity. Based on the assessment of pharmacokinetics, a 'once a day regimen' may be superior in treating sepsis in neonates of more than 32 weeks' gestation.

Hospital admissions and gestational age at birth: 18 years of follow up in Western Australia.

BACKGROUND: Infants born moderate to late preterm are twice as likely to be rehospitalised within the first few weeks following discharge from the birth admission. It is not understood how rehospitalisation risk changes with age or how risks have changed over time. METHODS: A retrospective birth cohort study of all live, singleton births in Western Australia 1 January 1980-31 December 2010, without congenital anomalies, followed to 18 years of age. Rehospitalisation rates for gestational age categories (<28, 28-31, 32-33, 34-36, 37-38 and ≥42 weeks) were compared with term births (39-41 weeks) using negative binomial regression. To assess whether rehospitalisation risk changed with age or over time, analyses were conducted for different age intervals and for 5-year birth cohorts. RESULTS: Rehospitalisation rates were higher up to 18 years for all preterm and early term categories including early term (37-38 weeks) [130.2/1000 person-years at risk (pyr); 95% confidence interval 129.1, 131.4]; late preterm (34-36 weeks) (164.2/1000 pyr; 161.1, 167.4), and post-term (≥42 weeks) (115.3/1000 pyr; 111.7, 119.0) compared with term births (109.1/1000 pyr; 108.5, 109.7). The effect of gestational age on rehospitalisation was highest during the first year of life and declined by adolescence [e.g. 34-36 weeks: rate ratio = 2.10 (2.04, 2.15) for 29 days-1 year; 1.14 (1.11, 1.18) for 12-18 years]. The risk of rehospitalisation up to 1 year of age has declined since 1980, except for those born <32 weeks. CONCLUSIONS: Rehospitalisation risk is greater for singleton children born at all gestational ages compared with those born full term. This effect of gestational age on rehospitalisation is highest in the first year post-discharge, but has almost disappeared by adolescence.

Probiotic Supplementation in the Neonatal Age Group and the Risk of Hospitalisation in the First Two Years: A Data Linkage Study from Western Australia.

BACKGROUND: Probiotic supplementation in preterm neonates is standard practice in many centres across the globe. The impact of probiotic supplementation in the neonatal age group on the risk of hospitalisation in infancy has not been reported previously. METHODS: Infants born < 32 + 6 weeks of gestation in Western Australia were eligible for inclusion. We conducted a retrospective cohort study comparing data from before probiotic supplementation (Epoch 1: 1 December 2008-30 November 2010, n = 1238) versus after (Epoch 2: 1 June 2012-30 May 2014, n = 1422) on the risks of respiratory- and gastrointestinal infection-related hospitalisation. A subgroup analysis of infants born < 28 weeks of gestation was analysed separately for similar outcomes. RESULTS: Compared to Epoch 1, an 8% reduction in incidence of hospitalisation up to 2 years after birth was observed in Epoch 2 (adjusted incidence rate ratio (IRR) of 0.92; 95% confidence interval (CI); 0.87-0.98), adjusted for gestational age, smoking, socioeconomic status, and maternal age. The rate of hospitalisation for infants born < 28 weeks of gestation was comparable in epochs 1 and 2. CONCLUSION: Infants exposed to probiotic supplementation in the neonatal period experience a reduced risk of hospitalisation in the first two years after discharge from the neonatal unit.

Maternal prebiotic supplementation during pregnancy and lactation modifies the microbiome and short chain fatty acid profile of both mother and infant.

BACKGROUND & AIMS: Improving maternal gut health in pregnancy and lactation is a potential strategy to improve immune and metabolic health in offspring and curtail the rising rates of inflammatory diseases linked to alterations in gut microbiota. Here, we investigate the effects of a maternal prebiotic supplement (galacto-oligosaccharides and fructo-oligosaccharides), ingested daily from <21 weeks' gestation to six months' post-partum, in a double-blinded, randomised placebo-controlled trial. METHODS: Stool samples were collected at multiple timepoints from 74 mother-infant pairs as part of a larger, double-blinded, randomised controlled allergy intervention trial. The participants were randomised to one of two groups; with one group receiving 14.2 g per day of prebiotic powder (galacto-oligosaccharides GOS and fructo-oligosaccharides FOS in ratio 9:1), and the other receiving a placebo powder consisting of 8.7 g per day of maltodextrin. The faecal microbiota of both mother and infants were assessed based on the analysis of bacterial 16S rRNA gene (V4 region) sequences, and short chain fatty acid (SCFA) concentrations in stool. RESULTS: Significant differences in the maternal microbiota profiles between baseline and either 28-weeks' or 36-weeks' gestation were found in the prebiotic supplemented women. Infant microbial beta-diversity also significantly differed between prebiotic and placebo groups at 12-months of age. Supplementation was associated with increased abundance of commensal Bifidobacteria in the maternal microbiota, and a reduction in the abundance of Negativicutes in both maternal and infant microbiota. There were also changes in SCFA concentrations with maternal prebiotics supplementation, including significant differences in acetic acid concentration between intervention and control groups from 20 to 28-weeks' gestation. CONCLUSION: Maternal prebiotic supplementation of 14.2 g per day GOS/FOS was found to favourably modify both the maternal and the developing infant gut microbiome. These results build on our understanding of the importance of maternal diet during pregnancy, and indicate that it is possible to intervene and modify the development of the infant microbiome by dietary modulation of the maternal gut microbiome.

Biracial couples and adverse birth outcomes: a systematic review and meta-analyses.

BACKGROUND: Differences in birth outcomes such as low birthweight (LBW), preterm births (PTB), stillbirth, differences in birthweight in Black vs. White race are well known. Infants born to biracial parents (mother and father from either Black or White races) also experience higher adverse birth outcomes. OBJECTIVE: To systematically review and meta-analyze birth outcomes among parents of mixed racial background compared to parents of same race. SEARCH STRATEGY: Medline, Embase, CINAHL and bibliographies of identified articles were searched for English language studies. SELECTION CRITERIA: Studies reporting association between parental mixed racial status and LBW, PTB, or small-for-gestational age (SGA) outcomes were included. DATA COLLECTION AND ANALYSES: After exclusion of duplicate cohorts in different publications, data from White mother-Black father (WMBF), Black mother-White father (BMWF) and Black mother-Black father (BMBF) groups were compared with the White mother-White father (WMWF) group. RESULTS: Eight English language studies from of 26 335 596 singleton births were included and reviewed. Compared to the WMWF group, the adjusted odds ratio (95% confidence intervals) were: (a) low birthweight; 1.21 (1.10-1.33) for WMBF, 1.75(1.64-1.87) for BMWF, and 2.08 (1.81-2.38) for BMBF; (b) preterm births; 1.17 (1.05-1.31) for WMBF, 1.37 (1.18-1.59) for BMWF, and 1.78 (1.59-2.00) for BMBF; and (c) stillbirths; 1.43 (0.92-2.21) for WMBF, 1.51 (1.09-2.08) for BMWF, and 1.85 (1.47-2.32) for BMBF. CONCLUSION: Biracial status of parents was associated with higher risk for adverse pregnancy outcomes than both White parents but lower than both Black parents, with maternal race having a greater influence than paternal race on pregnancy outcomes.

Do adults born preterm deliver preterm babies? A record linkage study from Western Australia.

BACKGROUND: Infants born preterm at <37 + 0 weeks of gestation experience systemic complications later in adulthood. However, the risk of adults born preterm delivering preterm babies themselves is not well investigated. METHODS: Midwives Notifications of births for the Western Australian population from 1980 to 2010 were obtained. A retrospective cohort study of 958,729 live-born singletons infants was conducted. Logistic regression was used to estimate odds ratios of preterm birth for preterm born parents compared to term born parents. Adjustment was made for socioeconomic status (quintiles of an area level disadvantage score), parity, maternal age, and ethnicity. RESULTS: A total of 876,755 term and 81,974 preterm babies were born during the study period. Information on the preterm birth status of the mother or father was available for 138,123 children. Of these, 1555 (12.08%) children were born preterm to parents born preterm (either of the two parents were preterm), 11,504 (9.22%) preterm children were born to parents born at term, 11,319 term children were born to parents born preterm and 113,254 term children were born to parents born at term. 68,915 (8.39%) preterm children were born where parents' whose gestational age was unknown. The unadjusted and adjusted odds ratios with and 95% confidence intervals (CI) for the odds of preterm born adults delivering preterm child were 1.35 (1.29-1.42, p < .0001) and 1.25 (1.18-1.32, p < .0001) respectively. The adjusted odds ratio (with 95% CI) for Aboriginal vs Caucasian adults was 1.96 (1.91-2.01, p < .0001). CONCLUSION:  In Western Australia delivering a preterm child is 25% greater when the parent was born preterm than when the parent was born at term in Western Australia. The effect appears to be transgenerational.

Study Protocol for a Randomised Controlled Trial Investigating the Effects of Maternal Prebiotic Fibre Dietary Supplementation from Mid-Pregnancy to Six Months' Post-Partum on Child Allergic Disease Outcomes.

Infant allergy is the most common early manifestation of an increasing propensity for inflammation and immune dysregulation in modern environments. Refined low-fibre diets are a major risk for inflammatory diseases through adverse effects on the composition and function of gut microbiota. This has focused attention on the potential of prebiotic dietary fibres to favourably change gut microbiota, for local and systemic anti-inflammatory effects. In pregnancy, the immunomodulatory effects of prebiotics may also have benefits for the developing fetal immune system, and provide a potential dietary strategy to reduce the risk of allergic disease. Here, we present the study protocol for a double-blinded, randomised controlled trial investigating the effects of maternal prebiotics supplementation on child allergic disease outcomes. Eligible pregnant women have infants with a first-degree relative with a history of medically diagnosed allergic disease. Consented women are randomised to consume either prebiotics (galacto-oligosaccharides and fructo-oligosaccharides) or placebo (maltodextrin) powder daily from 18-20 weeks' gestation to six months' post-partum. The target sample size is 652 women. The primary outcome is infant medically diagnosed eczema; secondary outcomes include allergen sensitisation, food allergies and recurrent wheeze. Breast milk, stool and blood samples are collected at multiple timepoints for further analysis.

One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates.

BACKGROUND: Animal studies and trials in older children and adults suggest that a one dose per day regimen of gentamicin is superior to a multiple doses per day regimen. OBJECTIVES: To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates. SEARCH METHODS: Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, April 2011), MEDLINE (1966 to April 2011), EMBASE 1980 to April 2011, and CINAHL (December 1982 to April 2011). Abstracts of the Society for Pediatric Research were searched from 1980 to 2010 inclusive. SELECTION CRITERIA: All randomised or quasi randomised controlled trials comparing one dose per day ( 'once a day') compared to multiple doses per day ( 'multiple doses a day') of gentamicin to newborn infants < 28 days of life. DATA COLLECTION AND ANALYSIS: Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Eleven studies were included (N = 574) and nineteen excluded. All infants in both 'once a day' as well as 'multiple doses a day' regimen showed adequate clearance of sepsis [typical RD 0.00 (95% CI - 0.19 to 0.19); 3 trials; N = 36]. For the other primary outcome measures relating to gentamicin pharmacokinetics 'once a day' dosing of gentamicin was superior. 'Once a day' gentamicin regimen was associated with less failures to attain peak level of at least 5 µg/ml [typical RR 0.22 (95% CI 0.11 to 0.47); 9 trials; N = 422] and less failures to achieve trough levels of < 2 µg/ml [typical RR 0.38 (95% CI 0.27 to 0.55); 11 trials N = 503] compared to 'multiple doses a day' regimen.Ototoxicity and nephrotoxicity were not noted with either of the treatment regimens. AUTHORS' CONCLUSIONS: There is insufficient evidence from the currently available RCTs to conclude whether 'once a day' or 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However, data suggests that pharmacokinetic properties of 'once a day' gentamicin regimen are superior to 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There is no change in nephrotoxicity or auditory toxicity. Based on this assessment of pharmacokinetics, 'once a day regimen' may be superior in treating neonatal sepsis in neonates greater than 32 weeks gestation.

Use of laryngeal mask airway in near-term and term neonates during resuscitation: is it effective and safe?

A scenario where laryngeal mask airway was used for successful resuscitation of a late preterm neonate after failed bag and mask ventilation and unsuccessful endotracheal intubation is presented. A summary of available evidence regarding the safety and efficacy of the use of laryngeal mask airway during neonatal resuscitation is also presented.

Literacy and Numeracy Underachievement in Boys and Girls With ADHD.

Objective: The aim was to determine literacy and numeracy outcomes, among children with and without ADHD by gestational age and gender. Method: De-identified linked population data from the Western Australian Monitoring of Drugs of Dependence System and Western Australian Literacy and Numeracy Assessment databases, and the Midwives Notification System used information on 6,819 children with ADHD compared with 14,451 non-ADHD children. Results: A total of 23% of boys and 28% of girls with ADHD had numeracy scores below the benchmark in School Year 3, compared with 11% of children without ADHD. These differences were also evident for reading, writing, and spelling through primary school. Children with ADHD and reduced gestational age were at a greater risk of not meeting numeracy and reading benchmarks, compared with children born at term. Conclusion: Children with ADHD are disadvantaged from an early age in key areas of learning, and this risk increased with reduction in gestational age at birth.

Introducing the ORIGINS project: a community-based interventional birth cohort.

Objectives Non-communicable diseases (NCDs) pose the greatest threat to human health globally. The dramatic rise in early onset NCDs - such as childhood obesity, the allergy epidemic and an increasing burden of mental ill health in children and youth - reflect the profound early impact of modern environments on developing systems. The ORIGINS Project is a research platform enabling world class investigation of early antecedent pathways to NCDs, and how to curtail these. As well as facilitating strategic long-term research capacity, ORIGINS is a pipeline for short-term productivity through a series of clinical trials, early interventions, mechanistic studies, and targeted research questions to improve maternal and paternal health and the early environment. Methods ORIGINS is a decade-long collaborative initiative between the Joondalup Health Campus (JHC) and the Telethon Kids Institute (TKI) to establish a Western Australian (WA) birth cohort of 10,000 families, enrolled during pregnancy. It is currently funded to follow up participating children and their families to five years of age. Comprehensive data and biological samples are collected from participants at up to 15 different timepoints, from the first antenatal clinic visit. In the process, ORIGINS is creating a major research platform, consisting of an extensive, world class biobank and databank. Of key strength and novelty, ORIGINS includes a series of harmonised nested sub-projects integrated with clinical and diagnostic services and providing real-time feedback to improve the health of individuals and the community. Conclusions At its core, ORIGINS aims to improve the health and quality of life of the next generation through improved pathways to optimise the early environment and reduce adversity by promoting primary prevention, early detection and early intervention. This dynamic, interactive, community-based project not only provides novel research capacity, productivity, collaboration and translational impact on future generations - it is also anticipated to have flow on benefits for community engagement, cohesion and purpose. This will provide a sentinel example for tailored replication in other communities around the world as part of interconnected grass root strategies to improve planetary health.

Stillbirth risk prediction using machine learning for a large cohort of births from Western Australia, 1980-2015.

Quantification of stillbirth risk has potential to support clinical decision-making. Studies that have attempted to quantify stillbirth risk have been hampered by small event rates, a limited range of predictors that typically exclude obstetric history, lack of validation, and restriction to a single classifier (logistic regression). Consequently, predictive performance remains low, and risk quantification has not been adopted into antenatal practice. The study population consisted of all births to women in Western Australia from 1980 to 2015, excluding terminations. After all exclusions there were 947,025 livebirths and 5,788 stillbirths. Predictive models for stillbirth were developed using multiple machine learning classifiers: regularised logistic regression, decision trees based on classification and regression trees, random forest, extreme gradient boosting (XGBoost), and a multilayer perceptron neural network. We applied 10-fold cross-validation using independent data not used to develop the models. Predictors included maternal socio-demographic characteristics, chronic medical conditions, obstetric complications and family history in both the current and previous pregnancy. In this cohort, 66% of stillbirths were observed for multiparous women. The best performing classifier (XGBoost) predicted 45% (95% CI: 43%, 46%) of stillbirths for all women and 45% (95% CI: 43%, 47%) of stillbirths after the inclusion of previous pregnancy history. Almost half of stillbirths could be potentially identified antenatally based on a combination of current pregnancy complications, congenital anomalies, maternal characteristics, and medical history. Greatest sensitivity is achieved with addition of current pregnancy complications. Ensemble classifiers offered marginal improvement for prediction compared to logistic regression.

Congenital Mycoplasma pneumoniae pneumonia in a neonate.

A fatal case of vertical transmission of Mycoplasma pneumoniae manifesting as congenital pneumonia in a neonate is presented. The diagnosis was based on the detection of DNA by polymerase chain reaction on the neonatal nasopharyngeal aspirates and placenta and rising titers of maternal anti Mycoplasma antibodies by complement fixation test.

Cytomegalovirus-associated ileal stricture in a preterm neonate.

Gastrointestinal (GI) manifestations of post-natally acquired cytomegalovirus (CMV) in preterm neonates can vary from mild diarrhoea to severe necrotising enterocolitis. However, the suspicion of CMV-related GI disease remains low. Mild CMV disease localised to the GI tract may go undiagnosed initially until a more obvious complication such as strictures manifest. A case of CMV-associated enteritis in an extremely preterm neonate is presented. The diagnosis was established after the histopathology of the surgical specimen showed the presence of CMV inclusion bodies. Testing the stool specimen for CMV to establish the diagnosis when the pathology is limited to the GI tract is also discussed.

Antenatal steroid administration in medically uncomplicated pregnancy beyond 37 weeks of gestation for the prevention of neonatal morbidities prior to elective caesarean section: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Elective caesarean section is associated with an increased risk of respiratory morbidity and admission to special care nursery even at full-term gestation. AIM: To systematically review the efficacy of antenatal steroid administration to prevent neonatal morbidity at full-term. Only randomised and quasirandomised controlled trials were selected. METHODS: Standardised methodology as described by the Cochrane neonatal review group was used for data collection and analysis. RESULTS: A total of three randomised controlled trials (N = 2740 patients) were included in the review. Meta-analysis of the published data was carried out. A significant decrease in the risk of respiratory distress syndrome (odds ratio (OR) 0.40 (95%CI: 0.23-0.71, p < 0.001), risk of transient tachypnoea of newborn (OR 0.37 (95%CI: 0.25-0.56, p < 0.00001)), risk of admission to special care nursery (OR 0.53 (95%CI: 0.37-0.76, p < 0.0007)) were observed. CONCLUSION: Although antenatal steroid administration prior to elective caesarean section demonstrated significant benefit in the prevention of neonatal morbidities; however, one need to be cautious before it can be routinely administered because of the paucity of long-term safety data.