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ObjectiveDetermining the genetic basis of speech disorders provides insight into the neurobiology of human communication. Despite intensive investigation over the past 2 decades, the etiology of most speech disorders in children remains unexplained. To test the hypothesis that speech disorders have a genetic etiology, we performed genetic analysis of children with severe speech disorder, specifically childhood apraxia of speech (CAS).MethodsPrecise phenotyping together with research genome or exome analysis were performed on children referred with a primary diagnosis of CAS. Gene coexpression and gene set enrichment analyses were conducted on high-confidence gene candidates.ResultsThirty-four probands ascertained for CAS were studied. In 11/34 (32%) probands, we identified highly plausible pathogenic single nucleotide (n = 10; CDK13, EBF3, GNAO1, GNB1, DDX3X, MEIS2, POGZ, SETBP1, UPF2, ZNF142) or copy number (n = 1; 5q14.3q21.1 locus) variants in novel genes or loci for CAS. Testing of parental DNA was available for 9 probands and confirmed that the variants had arisen de novo. Eight genes encode proteins critical for regulation of gene transcription, and analyses of transcriptomic data found CAS-implicated genes were highly coexpressed in the developing human brain.ConclusionWe identify the likely genetic etiology in 11 patients with CAS and implicate 9 genes for the first time. We find that CAS is often a sporadic monogenic disorder, and highly genetically heterogeneous. Highly penetrant variants implicate shared pathways in broad transcriptional regulation, highlighting the key role of transcriptional regulation in normal speech development. CAS is a distinctive, socially debilitating clinical disorder, and understanding its molecular basis is the first step towards identifying precision medicine approaches.

Aim This study aimed to determine the feasibility and parental acceptability of screening for congenital cytomegalovirus (cCMV) through saliva polymerase chain reaction in infants who did not pass their newborn hearing screening. Additionally, the utility (i.e. time to diagnosis and treatment) of this enhanced clinical pathway was evaluated. Methods The study was conducted through the Victorian Infant Hearing Screening Programme (VIHSP) across four maternity hospitals in Melbourne, Australia, during June 2019–March 2020. Parents were approached by VIHSP staff about obtaining a test for cytomegalovirus (CMV) at the time of their baby's second positive (‘refer’) result on the VIHSP screen. Participating parents collected a saliva swab for CMV polymerase chain reaction from their infants. Feasibility was determined by the proportion of ‘referred’ infants whose parents completed the salivary CMV screening test ≤21 days of life. Acceptability was measured through parent survey. Results Of 126 eligible families, 96 (76.0%) had salivary screening swabs taken ≤21 days of life. Most families (>92.0%) indicated that screening was acceptable, straightforward and thought testing their baby for cCMV was a good idea. One infant screened positive on day 30, was diagnosed with cCMV via confirmatory testing by day 31 and commenced valganciclovir on day 32. Conclusions Obtaining a saliva sample to screen for cCMV in infants who do not pass their newborn hearing screen is feasible and appears acceptable to parents. This targeted cCMV screening method could be an option where mothers are rapidly discharged from hospital, especially in the context of the COVID-19 pandemic.

Permanent hearing loss affects 1–3 per 1000 children in Australia1 ; this may be congenital or acquired, unilateral or bilateral, and ranges in severity from mild to profound. Hearing loss can be classified as sensorineural (SNHL), including auditory neuropathy, conductive and mixed (Table 1, Fig. 1). Australia has high-quality universal infant hearing screening, which facilitates early diagnosis and enables early intervention, hearing device fitting and timely planning for cochlear implantation if indicated.1,3 Although the National Framework for Neonatal Hearing Screening provides guidance on infant screening, and early intervention pathways are well established, aetiological investigation and medical management of newly diagnosed infants have varied. National guidelines are important to streamline management, ensure investigations are completed within relevant timeframes and reduce unnecessary stressors for families. Local and international evidence for the aetiological investigation of childhood hearing loss is heterogeneous and generally of low quality, with limited guidance on the structure or cost-effectiveness of investigations. A 2017 review recommended consensus guidelines to improve the management of hearing-impaired children,4 and both the British Association of Audiovestibular Physicians5–7 and the International Pediatric Otolaryngology Group8 have released guidelines. This position paper provides consensus recommendations for the aetiological investigation and medical management of children with SNHL, including auditory neuropathy, intended for general practitioners, paediatricians, otolaryngologists and genetic services in the Australian context.

Congenital hearing impairment (HI) is the most common sensory impairment and can be isolated or part of a syndrome. Diagnosis through newborn hearing screening and management through early intervention, hearing aids and cochlear implantation is well established in the Australian setting; however understanding the genetic basis of congenital HI has been missing. This population-derived cohort comprised infants with moderate-profound bilateral HI born in the 2016-2017 calendar years, detected through newborn hearing screening. Participants were recruited through an integrated paediatric, otolaryngology and genetics HI clinic and offered whole exome sequencing (WES) on a HiSeq4000 or NextSeq500 (Illumina) platform with a targeted average sequencing depth of 100x and chromosome microarray on the Illumina Infinium core exome-24v1.2 platform. Of those approached, 68% (106/156) consented to participate. The rate of genetic diagnosis was 56% (59/106), significantly higher than standard of care (GJB2/6 sequencing only), 21% (22/106). There were clinical implications for the 106 participants: 36% required no further screening, 9% had tailored screening initiated, 2% were offered treatment and 4% had informed care for a complex neurodevelopmental syndrome. WES in this cohort demonstrates the range of diagnoses associated with congenital HI and confirms the genetic heterogeneity of congenital HI. The high diagnostic yield and clinical implications emphasises the need for genomic sequencing to become standard of care.

High levels of stress and anxiety are common in children with Autism Spectrum Disorder (ASD). Within this study of school-aged children (20 male, 6 female) we hypothesised that functional hearing deficits (also pervasive in ASD) could be ameliorated by auditory interventions and that, as a consequence, stress levels would be reduced. The use of Ear-Level Remote Microphone devices and Classroom Amplification systems resulted in significantly improved listening, communication and social interaction and a reduction in physiologic stress levels (salivary cortisol) in both one-on-one and group listening situations.

There is now a growing body of research examining movement difficulties in children diagnosed with high functioning autism (HFA) and Asperger's disorder (AD). Despite this, few studies have investigated the kinematic components of movement that may be disrupted in children diagnosed with these disorders. The current study investigated rapid aiming movements in 19 individuals diagnosed with HFA, 20 individuals diagnosed with AD and 18 typically developing (TD) controls. A novel touchscreen version of a Fitts’ aiming task was administered that required participants to make 10 reciprocal aiming movements between targets. Task difficulty was manipulated by varying the size and distance between targets. Movement time in the HFA and AD groups was comparable to TD controls. Children with HFA displayed more constant and variable error across repeated aiming attempts compared to the TD group that may be attributed to deficits in feedforward online refinement of movement. These findings are in accordance with previous gait, ocular motor, upper limb and neuroimaging studies that suggest that the cerebellum may underlie movement disturbance in individuals diagnosed with HFA. Additionally, differences in the nature of upper limb motor disturbance in HFA may serve as a useful future adjunct to clinical measures.

The relationship of motor proficiency with emotional/behavioural disturbance, autistic symptoms and communication disturbance was investigated in children diagnosed with autism and Asperger’s disorder (AD). The Movement Assessment Battery for Children was used as a measure of motor impairment, and the Developmental Behavioural Checklist was used as a measure of emotional/behavioural disturbance in the following groups: AD (n = 22), high functioning autism (HFA) (n = 23), LFA (n = 8) and typically developing children (n = 20). The HFA group had more difficulty with motor items, such as ball skills and balance, than did the AD group. There were significant positive correlations between impairments in motor proficiency (in particular ball skills and balance) and emotional/behavioural disturbance, autistic symptoms and communication disturbance. These findings are consistent with the hypothesis that there are qualitative and quantitative differences in the motor profile between autism and AD. In addition, the association between motor proficiency impairment and emotional/behavioural disturbance in autism and AD emphasizes the importance for screening of co-occurring emotional/behavioural symptoms in individuals with motor difficulties. These findings have implications for the potential use of adjunct motor measures in the diagnosis and definition of autism spectrum disorders.

Objective To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants. Study design We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness. Results BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively. Conclusions In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years.

OBJECTIVE. The goal was to determine the prevalence and effects of slight/mild bilateral sensorineural hearing loss among children in elementary school. METHODS. A cross-sectional, cluster-sample survey of 6581 children (response: 85%; grade 1: n = 3367; grade 5: n = 3214) in 89 schools in Melbourne, Australia, was performed. Slight/mild bilateral sensorineural hearing loss was defined as a low-frequency pure-tone average across 0.5, 1, and 2 kHz and/or a high-frequency pure-tone average across 3, 4, and 6 kHz of 16 to 40 dB hearing level in the better ear, with air/bone-conduction gaps of RESULTS. Fifty-five children (0.88%) had slight/mild bilateral sensorineural hearing loss. Children with and without sensorineural hearing loss scored similarly in language (mean: 97.2 vs 99.7), reading (101.1 vs 102.8), behavior (8.4 vs 7.0), and parent- and child-reported child health-related quality of life (77.6 vs 80.0 and 76.1 vs 77.0, respectively), but phonologic short-term memory was poorer (91.0 vs 102.8) in the sensorineural hearing loss group. CONCLUSIONS. The prevalence of slight/mild bilateral sensorineural hearing loss was lower than reported in previous studies. There was no strong evidence that slight/mild bilateral sensorineural hearing loss affects adversely language, reading, behavior, or health-related quality of life in children who are otherwise healthy and of normal intelligence.

Objective: Universal Newborn Hearing Screening (UNHS) programmes have been widely implemented, but their costs, benefits and long-term logistics remain to be clearly defined. There are few rigorous evaluations of alternative strategies. In this paper, we evaluate the performance of the distraction test component of the two-tiered Victorian Infant Hearing Screening Program (VIHSP). Methods: All babies born in the State of Victoria, Australia in 1993 who survived the neonatal period were screened for the presence of risk factors for hearing loss. Those at-risk were referred for Auditory Brainstem Evoked Response (ABR) screening by a professional audiologist. All others were screened by modified distraction test at age 7–9 months. This birth cohort was followed through age 6 for diagnoses of congenital hearing loss resulting in fitting of hearing aids. Estimates of false-positives, false-negatives, sensitivity, specificity and positive predictive values were determined for the distraction test as a population screen. Ages at diagnosis and aid fitting for screen failures with hearing loss were compared with current goals. Results: For targeted (moderate or greater-aided) losses, the distraction test yielded eight (0.02%) documented false-negatives (one severe and seven moderate) and an estimated 4265 (99%) false-positives. Distraction test sensitivity was 65%, specificity 91% and PPV 0.3%. Mean age at diagnosis for distraction test failures across all severities, including mild losses, was 23 (SD 18) months with a mean age at aid fitting of 26 (SD 20) months. Conclusions: The distraction test screen generated large numbers of false-positives and a significant number of false-negatives, performing particularly poorly with moderate losses. Ages at diagnosis and aid fitting for screen failures were far older than currently accepted goals. There is little evidence that the distraction test can be made to work acceptably as a population-based screen.

The aim of this study was to report the incidence, prevalence and clinical characteristics of congenital hearing loss sufficient to require hearing aid fitting in the first 6 years of life for the 1993 birth cohort of the state of Victoria (population 4.4 million), Australia. In 1993, 64,116 infants born in the state of Victoria survived the neonatal period. Subjects included all children with congenital hearing loss for which hearing aids were fitted, at any time up to and including 31 December 1999, when the youngest member of the cohort reached 6 years of age. Data on the degree, type and etiology of hearing loss were available from the Australian Hearing database for all subjects. Sociodemographic and health data were available from the Victorian Infant Hearing Screening Program (VIHSP) and parent questionnaires. The known prevalence of identified congenital hearing loss increased as the cohort aged. By the time the youngest member had reached the age of 6 years, 134 children (78 boys, 56 girls) had been fitted with hearing aids for permanent congenital hearing loss of any degree (2.09/1000). Fifty-four (40%) of these had known mild losses (20-40 dB HL). The prevalence of known moderate or greater loss (> 40 dB HL) was 1.12/1000; the data suggest that over 90% could have been detectable by neonatal hearing screening. A further seven children from the birth cohort were fitted with hearing aids due to acquired forms of hearing loss (0.11/1000). The etiology was known in only 57 (43%) congenital cases, with known non-syndromal genetic causes accounting for 21 (37%) of these. This study reports on the prevalence of congenital hearing loss requiring hearing aid fitting for an entire birth cohort. These data indicate the possible yield from neonatal screening, and hence the likely benefit of such screening. For a large proportion of cases, the etiology remains unknown. These data have implications for health service delivery and illustrate the usefulness of a population database in monitoring the prevalence of congenital hearing loss.

Introduction The aetiology of congenital hearing loss is heterogeneous, and in many infants a genetic cause is suspected. Parents face a diagnostic odyssey when searching for a cause of their infant’s hearing loss. Through the Melbourne Genomics Health Alliance, a prospective cohort of infants will be offered whole-exome sequencing (WES) with targeted analysis in conjunction with chromosome microarray to determine the genetic causes of congenital hearing loss. Parents will also be offered the opportunity to receive additional results from their infant’s WES. Methods Eligible infants will be identified through the Victorian Infant Hearing Screening Program and offered an appointment in a paediatrician-run clinic, a genetics assessment and enrolment in the Victorian Childhood Hearing Impairment Longitudinal Databank. If parents consent to WES, genes causing deafness will be analysed and they can choose to obtain additional findings. For the additional results component, a modified laboratory protocol has been designed for reporting of results in the absence of a relevant phenotype. Parents’ experience of being offered WES will be evaluated using surveys. Discussion This project will provide descriptive analysis of the genetic aetiology of congenital hearing loss in this cohort and may provide data on genotype–phenotype correlations. Additionally, choices regarding additional findings will be analysed. Participants will represent a diverse cross section of the population, increasing the ability to generalise results beyond the study group. Evaluation surveys will allow analysis of preferences around counselling, usefulness of a decision aid and adequacy of information provision.

To evaluate both monaural and binaural processing skills in a group of children with autism spectrum disorder (ASD) and to determine the degree to which personal frequency modulation (radio transmission) (FM) listening systems could ameliorate their listening difficulties.Auditory temporal processing (amplitude modulation detection), spatial listening (integration of binaural difference cues), and functional hearing (speech perception in background noise) were evaluated in 20 children with ASD. Ten of these subsequently underwent a 6-week device trial in which they wore the FM system for up to 7 hours per day.Auditory temporal processing and spatial listening ability were poorer in subjects with ASD than in matched controls (temporal: P = .014 [95% CI -6.4 to -0.8 dB], spatial: P = .003 [1.0 to 4.4 dB]), and performance on both of these basic processing measures was correlated with speech perception ability (temporal: r = -0.44, P = .022; spatial: r = -0.50, P = .015). The provision of FM listening systems resulted in improved discrimination of speech in noise (P.001 [11.6% to 21.7%]). Furthermore, both participant and teacher questionnaire data revealed device-related benefits across a range of evaluation categories including Effect of Background Noise (P = .036 [-60.7% to -2.8%]) and Ease of Communication (P = .019 [-40.1% to -5.0%]). Eight of the 10 participants who undertook the 6-week device trial remained consistent FM users at study completion.Sustained use of FM listening devices can enhance speech perception in noise, aid social interaction, and improve educational outcomes in children with ASD.

Objective. To determine the growth and physical outcome at 2 years of age for children born after assisted reproductive techniques in the state of Victoria. Design. Using a case-matched control study between January 1991 and July 1993, 314 children (196 singletons, 47 sets of twins, 8 sets of triplets) conceived after in vitro fertilization (IVF) and related techniques at the Monash IVF and Royal Women's Hospital Reproductive Biology Unit and 150 control children (113 singletons, 17 sets of twins, 1 set of triplets) randomly selected from the general population using the Victorian Perinatal Data Collection Unit records were enrolled to be examined for minor dysmorphic and major organ abnormalities. Singleton and twin cases were matched for plurality and gestation and date of birth. Triplets were not matched. Results. IVF status was not a significant independent factor for physical outcomes, including malformation rates, nor for days of hospitalization postdischarge and operations. There was no significant interaction between IVF status and mean percentiles for weight and head circumference. The IVF group had a greater mean length percentile. Twins in both groups had significantly poorer physical outcomes than singletons on some measures. Conclusion. This study did not demonstrate an independent IVF effect on the growth and physical outcome of children at 2 years of age when matched for plurality and gestation. The poor outcomes where noted were related to the effects of multiple births. These findings must be viewed in context of the response rates and therefore representativeness of the data. The need for longitudinal studies is demonstrated.

OBJECTIVE: To determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. STUDY DESIGN: Participants were VLBW (500-1250 g) children enrolled in the Caffeine for Apnea of Prematurity randomized trial between 1999 and 2004. We investigated the relationships between 4 potential social advantages: higher maternal education, higher paternal education, caregiver employment, and 2 biologic parents in the same home--and gain in cognitive scores. Cognitive assessments were performed at the corrected ages of 18 months (Mental Development Index score on the Bayley Scales of Infant Development II) and 5 years (Full Scale IQ on the Wechsler Preschool and Primary Scale of Intelligence III). Cognitive gain was computed by subtracting each individual 18-month Mental Development Index score from the corresponding Full Scale IQ at 5 years. RESULTS: Data were available for 1347 children. Mean (SD) cognitive scores were 90.8 (15.7) at 18 months and 98.9 (14.5) at 5 years. Multivariable regression showed that higher maternal education, higher paternal education, and caregiver employment had independent and additive effects of similar size on cognitive gain (P < .001); the mean cognitive gain between 18 months and 5 years increased by 3.6 points in the presence of each of these advantages. When all 3 were present, cognitive scores improved on average by 10.9 points compared with children without any of these advantages. CONCLUSION: In VLBW children, a count of 3 social advantages strongly predicts gains in cognitive scores across the preschool years.

BACKGROUND: There is a lack of information on prevalence, cause and consequences of slight/mild bilateral sensorineural hearing loss (SNHL) in children. We report the first systematic genetic analysis of the GJB2 gene in a population-derived sample of children with slight/mild bilateral SNHL. METHODS: Hearing tests were conducted in 6240 Australian elementary school children in Grades 1 and 5. 55 children (0.88%) were found to have a slight/mild sensorineural hearing loss. 48 children with slight/mild sensorineural hearing loss and a matched group of 90 children with normal hearing participated in a genetic study investigating mutations in the GJB2 gene, coding for connexin 26, and the presence of the del(GJB6-D13S1830) and del(GJB6-D13S1854) deletions in the GJB6 gene, coding for connexin 30. RESULTS: Four of 48 children with slight/mild sensorineural hearing loss were homozygous for the GJB2 V37I change. The four children with homozygous V37I mutations were all of Asian background and analysis of SNPs in or near the GJB2 gene suggests that the V37I mutation arose from a single mutational event in the Asian population. DISCUSSION: Based on the prevalence of carriers of this change we conclude that V37I can be a causative mutation that is often associated with slight/mild sensorineural hearing loss. No other children in the slight/mild hearing loss group had a hearing loss related to a GJB2 mutation. One child with normal hearing was homozygous for the R127H change and we conclude that this change does not cause hearing loss. Two children of Asian background were carriers of the V37I mutation. Our data indicate that slight/mild sensorineural hearing loss due to the GJB2 V37I mutation is common in people of Asian background.

Aims: To determine key themes from parents’ comments on paths to diagnosis and intervention for their children with hearing loss, following introduction of at-risk neonatal hearing screening and modification of distraction test screening for infants not at-risk. Methods: Parents of children born in 1993 in Victoria, Australia, who were eligible for screening via the Victorian Infant Hearing Screening Program and who were subsequently diagnosed with a permanent congenital hearing loss and fitted with hearing aids prior to the year 2000 were asked to complete a semi-structured questionnaire shortly after aid fitting. Two researchers independently analysed parent comments using the constant comparative method. Results: Parents of 82 children (61%) replied to the questionnaire. Themes analysis revealed a generally positive response to neonatal ABR screening, with a mixed response to the distraction test; powerful emotions experienced by parents at diagnosis including denial and shock; frustration arising from delays in diagnosis, and communication difficulties with providers. Special difficulties testing children with other medical and developmental problems, confusion about tympanostomy tube insertion, and difficulty with wearing hearing aids were also reported. Some children had experienced problems in the school setting. Experience of post-diagnostic services was generally positive. Conclusions: Parents need greater support both during the testing of screen failures and at the time of diagnosis. Providers need more training in how to communicate findings to parents, particularly at times when parents are experiencing strong emotions. Parents need more strategies to enable hearing aid wearing in very young children. Some children with additional medical, developmental, and behavioural problems need specialised approaches to testing.

The aim of this study was to report the incidence, prevalence and clinical characteristics of congenital hearing loss sufficient to require hearing aid fitting in the first 6 years of life for the 1993 birth cohort of the state of Victoria (population 4.4 million), Australia. In 1993, 64,116 infants born in the state of Victoria survived the neonatal period. Subjects included all children with congenital hearing loss for which hearing aids were fitted, at any time up to and including 31 December 1999, when the youngest member of the cohort reached 6 years of age. Data on the degree, type and etiology of hearing loss were available from the Australian Hearing database for all subjects. Sociodemographic and health data were available from the Victorian Infant Hearing Screening Program (VIHSP) and parent questionnaires. The known prevalence of identified congenital hearing loss increased as the cohort aged. By the time the youngest member had reached the age of 6 years, 134 children (78 boys, 56 girls) had been fitted with hearing aids for permanent congenital hearing loss of any degree (2.09/1000). Fifty-four (40%) of these had known mild losses (20-40 dB HL). The prevalence of known moderate or greater loss (40 dB HL) was 1.12/1000; the data suggest that over 90% could have been detectable by neonatal hearing screening. A further seven children from the birth cohort were fitted with hearing aids due to acquired forms of hearing loss (0.11/1000). The etiology was known in only 57 (43%) congenital cases, with known non-syndromal genetic causes accounting for 21 (37%) of these. This study reports on the prevalence of congenital hearing loss requiring hearing aid fitting for an entire birth cohort. These data indicate the possible yield from neonatal screening, and hence the likely benefit of such screening. For a large proportion of cases, the etiology remains unknown. These data have implications for health service delivery and illustrate the usefulness of a population database in monitoring the prevalence of congenital hearing loss.

Objective To investigate the possibility that children born after ICSI were at increased risk for neurodevelopmental delay. Design Retrospective case-control study. Setting IVF clinic. Patient(s) Fifty-eight singleton children born after ICSI and 38 normally conceived singleton children (controls), matched for relevant sociodemographic characteristics, from Australia and 208 case-patients and 221 controls from the United Kingdom. Main outcome measure(s) Antenatal and perinatal, and sociodemographic characteristics; physical health, including congenital abnormalities; and neurodevelopment by using the Griffiths scales of mental development. Result(s) Eighty-five percent of case-patients and 96% controls were assessed at a mean age of 13 months. Neurodevelopmental scores were similar in all children. Perinatal outcome was similar, apart from more caesarean sections in the case-patients. Rates of congenital anomalies were similar (5.6% among case-patients vs. 5.7% among controls). Children from fathers with oligozoospermia showed no extra problems. Children born after ICSI in the United Kingdom and Australia were similar. Conclusion(s) Children conceived after ICSI did not differ from their naturally conceived peers in physical health or development at ages up to 15 months.

Aims: To determine whether a two tier universal infant hearing screening programme (population based risk factor ascertainment and universal distraction testing) lowered median age of diagnosis of bilateral congenital hearing impairment (CHI) >40 dB HL in Victoria, Australia. Methods: Comparison of whole population birth cohorts pre and post introduction of the Victorian Infant Hearing Screening Program (VIHSP). All babies surviving the neonatal period born in Victoria in 1989 (pre-VIHSP) and 1993 (post-VIHSP) were studied. (1) Pre-1992: distraction test at 7–9 months. (2) Post-1992: infants with risk factors for CHI referred for auditory brain stem evoked response (ABR) assessment; all others screened by modified distraction test at 7–9 months. Results: Of the 1989 cohort (n = 63 454), 1.65/1000 were fitted with hearing aids for CHI by end 1995, compared with 2.09/1000 of the 1993 cohort (n = 64 116) by end 1999. Of these, 79 cases from the 1989 cohort (1.24/1000) and 72 cases from the 1993 cohort (1.12/1000) had CHI >40 dB HL. Median age at diagnosis of CHI >40 dB HL for the 1989 birth cohort was 20.3 months, and for the 1993 cohort was 14.2 months. Median age at diagnosis fell significantly for severe CHI but not for moderate or profound CHI. Significantly more babies with CHI >40 dB HL were diagnosed by 6 months of age in 1993 than in 1989 (21.7% v 6.3%). Compared to the six years pre-VIHSP, numbers aided by six months were consistently higher in the six years post-VIHSP (1.05 per 100 000 births versus 13.4 per 100 000 births per year). Conclusions: VIHSP resulted in very early diagnosis for more infants and lowered median age of diagnosis of severe CHI. However, overall results were disappointing.

OBJECTIVE To determine (1) the prevalence and nature of connexin 26 mutations in a cohort of Australian children with non-syndromic hearing loss, and (2) the carrier frequency of the common connexin 26 mutation (35delG) in the general population. DESIGN A cohort, case-finding study. Mutation analysis was performed on DNA extracted from white blood cells, buccal cells, or Guthrie blood spots. SETTING A hearing loss investigation clinic and a deafness centre in two Australian capital cities, 1 January 1998 to 31 October 2000. PARTICIPANTS (1) 243 children (age range, 4 weeks to 16 years; median, 4 years), attending hearing loss clinics in Sydney and Melbourne; (2) 1000 blood samples obtained from anonymous Guthrie card blood spots collected in 1984 [corrected] by the Victorian Clinical Genetics Service as part of the newborn screening program. MAIN OUTCOME MEASURES (1) The prevalence and types of connexin 26 mutations in a cohort of children with prelingual deafness; (2) the carrier frequency of the common connexin 26 mutation, 35delG, in the general population. RESULTS Connexin 26 mutations were identified and characterised in 52 (21%) of the 243 children; 14 different mutations, including four previously unreported mutations (135S, C53R, T123N and R127C), were identified. The common 35delG mutation was found in 56 of the 104 alleles (ie, 86 of the connexin 26 alleles in which a mutation was positively identified). The mutations V371 and M34T were also relatively common. The carrier frequency of connexin 26 mutations and of the common 35delG connexin 26 mutation in the Victorian population was estimated to be 1 in 54 and 1 in 100, respectively. CONCLUSIONS Mutations in the connexin 26 gene (especially the 35delG mutation) are a common cause of prelingual hearing loss in Australia.

Background There have been reports suggesting that children born after in-vitro fertilisation by intracytoplasmic sperm injection (ICSI) are at increased risk of neurodevelopmental delay. We have undertaken a case-control study of this issue.Methods We studied 208 singleton children conceived by ICSI and a control group of 221 normally conceived singleton children. Children were recruited from 22 fertility centres and local nurseries throughout the UK. Controls were selected to match cases as closely as possible for social class, maternal educational attainment, region, sex, and race. The primary outcome measure was neurodevelopmental scoring; secondary measures were perinatal outcomes, postnatal health, and congenital abnormalities. A single examiner assessed all the children.Findings A follow-up rate of 90% for the ICSI group was achieved at a mean age of 17 months. No difference between the study children and controls was found in mean neurodevelopmental scores (98.08 [SD 10.93] vs 98.69 [9.99]) or any subscales on the Griffiths' scales of mental development. Perinatal outcome was similar apart from a higher rate of caesarean section (73 [35.1%] vs 53 [24.0%], p=0.015) and a lower mean birthweight (3163 [SD 642] vs 3341 [606] g, p=0.013) in the study group. Rates of major congenital abnormality were also similar overall (ten [4.8%] study vs ten [4.5%] control), although there were significantly more congenital anomalies among children born to fathers with oligozoospermia than in other children.Interpretation This population study did not show any significant difference between children conceived after ICSI and their naturally conceived peers in terms of physical health and development.

Genetic hearing impairment affects approximately 1/2000 live births. Mutations in one gene, GJB2, coding for connexin 26 cause 10%-20% of all genetic sensorineural hearing loss. Mutation analysis in the GJB2 gene and audiology were performed on 106 families presenting with at least one child with congenital hearing loss. The families were recruited from a hospital-based multidisciplinary clinic, which functions to investigate the aetiology of sensorineural hearing loss in children and which serves an ethnically diverse population. In 74 families (80 children), the aetiology was consistent with non-syndromic recessive hearing loss. Six different connexin 26 mutations, including one novel mutation, were identified. We show that GJB2 mutations cause a range of phenotypes from mild to profound hearing impairment and that loss of hearing in the high frequency range (4000-8000 Hz) is a characteristic feature in children with molecularly diagnosed connexin 26 hearing impairment. We also demonstrate that this type of audiology and high frequency hearing loss is found in a similar-sized group of deaf children in whom a mutation could only be found in one of the connexin 26 alleles, suggesting connexin 26 involvement in the aetiology of hearing loss in these cases. In our study of the M34T mutation, only compound heterozygotes exhibited hearing loss, suggesting autosomal recessive inheritance.

This study was designed to look in detail at the paths to diagnosis for a group of 197 children with congenital sensorineural hearing impairment (SNHI), who were diagnosed between 1989 and 1991 in the state of Victoria, Australia. Despite the existence of universal infant screening at 7-9 months by distraction test or questionnaire, the median age at diagnosis for the study group was 18.0 months, with median age at aid fitting of 20.8 months, and median age at commencement of specialised intervention programmes of 22.3 months. Parent questionnaires completed for 143 (73%) of these children showed that 49% had known risk factors for hearing loss yet only 20% of them had been referred for audiological assessment before the 7-9 month screen. Only 63% of those eligible for the 7-9 month screen had received it. Of those children who were screened by distraction test 46% passed as did 57% of those screened by questionnaire. Twenty four parents (17%) described how they had initially 'denied' their own observations of their infants' abnormal hearing behaviour. When concerns were raised with professionals, 10% of parents were falsely reassured without audiological assessment. Detection methods are failing through a combination of poor screen test efficacy, incomplete population coverage, and parental and professional denial.