Hospitalizations from Birth to 28 Years in a Population Cohort of Individuals Born with Five Rare Craniofacial Anomalies in Western Australia.

OBJECTIVE: To describe trends, age-specific patterns, and factors influencing hospitalizations for 5 rare craniofacial anomalies (CFAs). METHODS: Data on livebirths (1983-2010; n = 721 019) including rare CFA (craniofacial microsomia, mandibulofacial dysostosis, Pierre Robin sequence, Van der Woude syndrome, and frontonasal dysplasia), episodes of death, and demographic and perinatal factors were identified from the Western Australian Register of Developmental Anomalies, Death Registrations and Midwives Notification System. Information on incident craniofacial and noncraniofacial related admissions, length of hospital stay, and intensive care and emergency-related admissions were identified using principal diagnosis and procedural codes were extracted from the Hospital Morbidity Data Collection and linked to other data sources. Associations of hospitalizations by age groups as well as demographic and perinatal factors were expressed as incidence rate ratio (IRR). RESULTS: The incident hospitalizations were 3 times as high for rare CFA (IRR 3.22-3.72) throughout childhood into adolescence than those without. Children with rare CFA had 3-4 times as many potentially preventable hospitalizations until 18 years of age than those without. Specifically, respiratory infections (IRR 2.13-2.35), ear infections (IRR 7.92-26.28), and oral health-related conditions contributed for most noncraniofacial admissions until the adolescence period. A greater incidence of noncraniofacial related hospitalizations was observed among Indigenous children, births with intrauterine growth restrictions, and families with high socioeconomic disadvantage. CONCLUSIONS: Throughout childhood, individuals with rare CFA had greater hospital service use, specifically for potentially preventable conditions, than those without. These population-level findings can inform new preventive strategies and early disease management targeted toward reducing preventable hospitalizations.

Epidemiology of Rare Craniofacial Anomalies: Retrospective Western Australian Population Data Linkage Study.

OBJECTIVE: To describe birth prevalence of rare craniofacial anomalies and associations with antenatal and perinatal factors. STUDY DESIGN: All live and stillbirths in Western Australia between 1980 and 2010 were identified from the Western Australian Birth Registrations and the Midwives Notification System (also provides information on antenatal and perinatal factors). Rare craniofacial anomalies (craniosynostosis, craniofacial microsomia, and others [Pierre Robin, Van der Woude, and Treacher Collins syndrome]) were ascertained from the Western Australian Register of Developmental Anomalies and linked to other data sources. Trends in prevalence, adjusted for sex and Indigenous status, were investigated by Poisson regression and presented as annual percent change (APC). Strengths of association of related factors were assessed using multivariable log-binomial regression adjusted for sex, Indigenous status, birth year, socioeconomic disadvantage, and remoteness and reported as risk ratios with 95% CIs. RESULTS: There was a temporal increase in prevalence of metopic synostosis (APC 5.59 [2.32-8.96]) and craniofacial microsomia (Goldenhar syndrome) (APC 4.43 [1.94-6.98]). Rare craniofacial anomalies were more likely among infants born preterm, as twins or greater-order multiples, with growth restriction, to older parents, to mothers undertaking fertility treatments, and with pre-existing medical conditions, specifically epilepsy, diabetes, or hypothyroidism. Prenatal identification of rare craniofacial anomalies was uncommon (0.6%). CONCLUSIONS: Our findings indicate a steady increase over time in prevalence of metopic synostosis and craniofacial microsomia (Goldenhar syndrome). Possible associations of fertility treatments and pre-existing maternal medical conditions with rare craniofacial anomalies require further investigation.

Longitudinal Evaluation of the Stability of Hand Function in Rett Syndrome.

OBJECTIVE: To investigate the longitudinal stability of hand function in Rett syndrome and to analyze further the relationships between stability of hand function and genotype, age, and walking ability. STUDY DESIGN: Longitudinal video data of functional abilities of individuals with genetically confirmed Rett syndrome were collected by families of individuals registered with the Australian Rett Syndrome Database. A total of 120 individuals provided 290 recordings from which 170 observation pairs were available for comparison. The Rett Syndrome Hand Function Scale was used to classify a level of hand function observed in each video on a range from unable to grasp, pick up, and hold objects to skillful manipulation of large and small objects. RESULTS: Approximately one-third of the population lost some hand function over time. Younger children (<6 years) rather than adults were at greater risk of deterioration in hand function. Clinical severity, as indicated by walking ability or genotype, played a lesser role. There was no identified pattern between genotype and the stability of hand function skills. Rather, mutations associated with milder (p.Arg133Cys, p.Arg294∗) and greater (p.Arg106Trp, p.Thr158Met) clinical severity were both associated with greater risks of decline. CONCLUSIONS: Genotype was a lesser predictor of loss of hand function beyond the early regression period, and younger children were particularly vulnerable to further loss of hand function compared with adults.

Risk of Hospitalizations Following Gastrostomy in Children with Intellectual Disability.

OBJECTIVE: To examine the frequency of hospital admissions before and after gastrostomy insertion in children with severe intellectual disability. STUDY DESIGN: We conducted a retrospective cohort study using linked health administrative and disability data from Western Australia (WA) and New South Wales (NSW). Children born between 1983 and 2009 in WA and 2002 and 2010 in NSW who had a gastrostomy insertion performed (n = 673 [WA, n = 325; NSW, n = 348]) by the end of 2014 (WA) and 2015 (NSW) were included. Conditional Poisson regression models were used to evaluate the age-adjusted effect of gastrostomy insertion on acute hospitalizations for all-cause, acute lower respiratory tract infections (LRTI), and epilepsy admissions. RESULTS: The incidence of all-cause hospitalizations declined at 5 years after procedure (WA cohort 1983-2009: incidence rate ratio, 0.70 [95% CI, 0.60-0.80]; WA and NSW cohort 2002-2010: incidence rate ratio, 0.63 [95% CI, 0.45-0.86]). Admissions for acute LRTI increased in the WA cohort and remained similar in the combined cohort. Admissions for epilepsy decreased 4 years after gastrostomy in the WA cohort and were generally lower in the combined cohort. Fundoplication seemed to decrease the relative incidence of acute LRTI admissions in the combined cohort. CONCLUSIONS: Gastrostomy was associated with health benefits including reduced all-cause and epilepsy hospitalizations, but was not protective against acute LRTI. These decreases in hospitalizations may reflect improved delivery of nutrition and medications.

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 Developmental Disorders in Children of Immigrant Mothers: A Population-Based Data Linkage Evaluation.

OBJECTIVES: To evaluate the prevalence and risks of developmental disability (autism spectrum disorder, intellectual disability, and cerebral palsy) in Western Australian children of different groups of foreign-born women. STUDY DESIGN: Western Australian population-based linked data of 764 749 singleton live births from 1980 to 2010 were used to compare disability outcomes among children of foreign-born, Australian-born non-Indigenous, and Indigenous women. The risk of disability was assessed using multinomial logistic regression. RESULTS: Overall, the prevalence of any disability was lowest for the children of foreign-born mothers. From 1980 to 1996 but not from 1997 to 2010, children born to mothers from foreign-born low-income countries had an increased relative risk of autism spectrum disorder with intellectual disability, and children born to foreign-born mothers from upper-middle-income countries had an increased risk of cerebral palsy with intellectual disability. After adjusting for smoking, the relative risks of intellectual disability and cerebral palsy with intellectual disability were markedly decreased in children of Australian-born Indigenous mothers. CONCLUSIONS: Although we did not find among children born to foreign-born women an increased prevalence across all the measured developmental outcomes, we did observe an increased risk of autism spectrum disorder with intellectual disability and cerebral palsy with intellectual disability for mothers of some foreign-born groups. Our findings related to smoking in the Indigenous population underscore its possible role on the causal pathway to intellectual disability. Maternal migration is considered a factor on the causal pathway to intellectual disability. Maternal migration may be either a risk or a protective factor on the causal pathway to developmental disabilities and the direct role of migration is inconclusive in our study.

Impact of Gastrostomy Placement on Nutritional Status, Physical Health, and Parental Well-Being of Females with Rett Syndrome: A Longitudinal Study of an Australian Population.

OBJECTIVES: To evaluate how age-related trends in nutritional status, physical health, and parental well-being in females with Rett syndrome may be related to gastrostomy placement and to examine the impact of the procedure on mortality. STUDY DESIGN: We included 323 females from the Australian Rett Syndrome Study and analyzed their demographic, genetic, and child and parental health data collected from over 6 waves of follow-up questionnaire between 2000 and 2011. We used mixed-effects models to estimate the association between repeated measures of outcomes and age, gastrostomy placement and their interaction and Cox proportional hazards regression models to estimate relative risks of mortality for individuals with gastrostomy. RESULTS: Nearly one-third (30.3%) of the cases underwent gastrostomy placement. Nutritional status based on weight, height, and body mass index (BMI) improved over time, and BMI was greater in individuals with gastrostomy placement than in those without (adjusted ß = 0.87, 95% CI 0.02-1.73). There was no association between gastrostomy placement and individual's physical health outcomes or parental physical and mental health, nor did the age trend of these outcomes vary by gastrostomy insertion status. Nevertheless, among those at risk of suboptimal weight, the all-cause mortality rate was greater in those who had gastrostomy placement compared with those who had not (hazard ratio 4.07, 95% CI 1.96-8.45). CONCLUSION: Gastrostomy placement was associated with improvement in BMI in females with Rett syndrome, but its long-term impact on individuals and their families is unclear.

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.

Twenty-Five Year Survival of Children with Intellectual Disability in Western Australia.

OBJECTIVES: To investigate survival up to early adulthood for children with intellectual disability and compare their risk of mortality with that of children without intellectual disability. STUDY DESIGN: This was a retrospective cohort study of all live births in Western Australia between January 1, 1983 and December 31, 2010. Children with an intellectual disability (n = 10 593) were identified from the Western Australian Intellectual Disability Exploring Answers Database. Vital status was determined from linkage to the Western Australian Mortality database. Kaplan-Meier product limit estimates and 95% CIs were computed by level of intellectual disability. Hazard ratios (HRs) and 95% CIs were calculated from Cox proportional hazard regression models adjusting for potential confounders. RESULTS: After adjusting for potential confounders, compared with those without intellectual disability, children with intellectual disability had a 6-fold increased risk of mortality at 1-5 years of age (adjusted HR [aHR] = 6.0, 95%CI: 4.8, 7.6), a 12-fold increased risk at 6-10 years of age (aHR = 12.6, 95% CI: 9.0, 17.7) and a 5-fold increased risk at 11-25 years of age (aHR = 4.9, 95% CI: 3.9, 6.1). Children with severe intellectual disability were at even greater risk. No difference in survival was observed for Aboriginal children with intellectual disability compared with non-Aboriginal children with intellectual disability. CONCLUSIONS: Although children with intellectual disability experience higher mortality at all ages compared with those without intellectual disability, the greatest burden is for those with severe intellectual disability. However, even children with mild to moderate intellectual disability have increased risk of death compared with unaffected children.

Improved Survival in Down Syndrome over the Last 60 Years and the Impact of Perinatal Factors in Recent Decades.

OBJECTIVE: To calculate the survival of people with Down syndrome over the past 60 years and the influence of major perinatal factors by using linked population-based data. STUDY DESIGN: A data linkage between 2 Western Australian (WA) data sets (the Register for Developmental Anomalies and the Intellectual Disability Exploring Answers database) was used to identify 772 children born with Down syndrome in WA from 1980-2010. Perinatal and mortality data were extracted from the WA Midwives Information System and WA death registrations and compared with the remaining WA population born during that same era. An additional 606 children with Down syndrome living in WA prior to 1980 were available from a disability services database and were used for predicting survival into adulthood. RESULTS: Overall, for cases born 1953-2010, 88% (95% CI 86%, 90%) survived to 5 years of age, 87% (95% CI 85%, 89%) to 10 years, and 83% (95% CI 80%, 85%) to 30 years. Children live-born with Down syndrome were significantly more likely (all P > .001) to have mothers older than 35 years (32.7% vs 13.4%), a gestational age less than 37 weeks (23.8% vs 7.9%), a cesarean delivery (28.9% vs 23.0%), and a birth weight less than 2500 g (20.4% vs 6.1%). Down syndrome survival was reduced in the presence of a cardiovascular defect, younger gestational age, low birth weight, or earlier birth years. CONCLUSIONS: Improved survival for children born with Down syndrome over the last 60 years has occurred incrementally, but disparities still exist for children who are preterm or have low birth weight.