Carol Bower

Outcomes of Congenital Diaphragmatic Hernia: A Population-Based Study in Western Australia

Objectives. There have been many recent reports of improved survival rates for congenital diaphragmatic hernia (CDH), largely derived from institution-based data. These are often flawed by case selection bias. The objectives of this study were to document the true incidence, management, and outcomes of CDH in a geographically defined population over a 12-year period and to determine the changing trends in these over time. We also sought to ascertain the prenatal and postnatal factors associated with morbidity and death among these infants. Methods. A retrospective study of all cases of CDH in Western Australia from 1991 to 2002 was conducted. Cases were identified from 5 independent databases within the Western Australian health network, including the Western Australian Birth Defects Registry. All fetuses and neonates diagnosed with CDH in Western Australia during this period were identified, including miscarriages, stillbirths, and terminations of pregnancies in which a diagnosis of fetal CDH had been made, as well as those diagnosed postnatally. Cases not known to involve CDH until diagnosis at autopsy were also included. Infants with diaphragmatic eventration were excluded from the study. Detailed information was obtained from review of maternal and infant medical records. Results. One hundred sixteen cases of CDH were identified. Of these, 71 (61%) infants were born alive and 37 survived beyond 1 year of age (52% of live-born infants, 32% of all cases of CDH). Pregnancies involving 38 (33%) fetuses were terminated electively, 4 (3%) fetuses were aborted spontaneously, and 3 (3%) fetuses were stillborn. Another major congenital anomaly was present in 54 (47%) cases. Twenty-one (18%) cases had other anomalies that were likely to be fatal. Of all cases with an additional major anomaly, 42 (78%) died. Twenty-seven (71%) of 38 fetuses for whom the pregnancy was terminated had another major anomaly. Twenty-three (32%) live-born infants had another major anomaly (4 of which were considered fatal conditions); however, this did not affect their survival rates. Fifty-three percent of cases were diagnosed prenatally, and 49% of these pregnancies were then terminated. Of live-born infants with prenatally diagnosed CDH, 10 (33%) survived beyond 1 year of age. The gestational age at diagnosis did not affect the survival rate for live-born infants. Postnatal diagnosis occurred in 55 (47%) cases. Of these, 41 (74%) case subjects were born alive and diagnosed on clinical grounds after birth. In the remaining 14 cases, the diagnosis was made in postmortem examinations of fetuses from pregnancies that were terminated for other reasons (8 cases) or after spontaneous abortion or stillbirth (5 cases). Significant differences were found between prenatally and postnatally diagnosed live-born infants. Among live-born infants, prenatal diagnosis was associated with a significantly reduced survival rate (33%, compared with 66% for postnatally diagnosed infants). Prenatally diagnosed live-born infants were of lower birth weight and were born at an earlier gestational age. There was no statistically significant difference between the 2 groups in the onset of labor (spontaneous or induced) or in the rate of elective cesarean sections. Prenatally diagnosed live-born infants were more likely to be delivered in a tertiary perinatal center and were intubated more commonly at delivery. No difference was found in the Apgar scores at either 1 or 5 minutes between the groups. Of 71 live-born infants, 37 (52%) survived to 1 year of age. The majority of deaths occurred within the first 7 days of life (44%). Preoperative air leaks occurred for 16 (22%) infants, of whom 14 (88%) died. Factors found to predict death of live-born infants included prenatal diagnosis, right-sided hernia, major air leak, earlier gestational age at birth, lower birth weight, and lower Apgar scores at 1 and 5 minutes. Over the course of the decade, there were significant increases in the proportion of cases in which the diagnosis of CDH was made with prenatal ultrasonography and in the number of live-born infants born at the tertiary perinatal center. The mortality rate for all cases, the mortality rate for live-born infants, and the proportion of pregnancies involving prenatally diagnosed cases that were terminated electively were all greater in the later epoch but not significantly so. Conclusions. This was a comprehensive, population-based study of CDH, with full case ascertainment, large sample size, and complete outcome data for all cases. The majority of published studies of CDH examined specific patient populations, such as neonates referred to tertiary pediatric surgical centers. Invariably, those studies failed to detect the demise of cases with CDH before arrival at the referral center, whether through termination of pregnancy, in utero fetal demise, or postnatal death occurring before transfer. Exclusion of these cases from calculations of mortality rates results in significant case selection bias. In our study, 35% of live-born infants died before referral or transport. The population of infants reaching the tertiary surgical center represented only 40% of the total cases of CDH. Wide variations in reported survival rates occur throughout the literature. These differences reflect the influence of this case selection bias, as well as variable referral policies and management practices. For our study population, survival rates differed vastly depending on the subgroup analyzed. Ninety-two percent of postoperative infants survived beyond 1 year of age, as did 80% of infants who reached the surgical referral center. However, only 52% of live-born infants, 32% of all cases, and 16% of all prenatally diagnosed cases survived. Therefore, the overall mortality rate for this condition remains high, despite increased prenatal detection, transfer to tertiary institutions for delivery, and advances in neonatal care, and is influenced significantly by the rate of prenatal termination. In our study, 33% of all cases of CDH and 49% of prenatally diagnosed fetuses underwent elective termination of pregnancy. This large number of fetal terminations confounds the accurate assessment of the true outcomes of this condition.

Prevalence at Birth of Cleft Lip With or Without Cleft Palate : Data From the International Perinatal Database of Typical Oral Clefts (IPDTOC)

As part of a collaborative project on the epidemiology of craniofacial anomalies, funded by the National Institutes for Dental and Craniofacial Research and channeled through the Human Genetics Programme of the World Health Organization, the International Perinatal Database of Typical Orofacial Clefts (IPDTOC) was established in 2003. IPDTOC is collecting case-by-case information on cleft lip with or without cleft palate and on cleft palate alone from birth defects registries contributing to at least one of three collaborative organizations: European Surveillance Systems of Congenital Anomalies (EUROCAT) in Europe, National Birth Defects Prevention Network (NBDPN) in the United States, and International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) worldwide. Analysis of the collected information is performed centrally at the ICBDSR Centre in Rome, Italy, to maximize the comparability of results. The present paper, the first of a series, reports data on the prevalence of cleft lip with or without cleft palate from 54 registries in 30 countries over at least 1 complete year during the period 2000 to 2005. Thus, the denominator comprises more than 7.5 million births. A total of 7704 cases of cleft lip with or without cleft palate (7141 livebirths, 237 stillbirths, 301 terminations of pregnancy, and 25 with pregnancy outcome unknown) were available. The overall prevalence of cleft lip with or without cleft palate was 9.92 per 10,000. The prevalence of cleft lip was 3.28 per 10,000, and that of cleft lip and palate was 6.64 per 10,000. There were 5918 cases (76.8%) that were isolated, 1224 (15.9%) had malformations in other systems, and 562 (7.3%) occurred as part of recognized syndromes. Cases with greater dysmorphological severity of cleft lip with or without cleft palate were more likely to include malformations of other systems.

The effect of maternal alcohol consumption on fetal growth and preterm birth

Objective  To investigate the relationship between prenatal alcohol exposure and fetal growth and preterm birth and to estimate the effect of dose and timing of alcohol exposure in pregnancy.

Autism spectrum disorders in young children: effect of changes in diagnostic practices.

BACKGROUND It is unclear whether the increase in autism over the past two decades is a real increase or due to changes in diagnosis and ascertainment of autism spectrum disorders (ASDs), which include autism, Asperger syndrome and pervasive developmental disorder not otherwise specified (PDD-NOS). The aim of this study was to examine the trends in ASD over time in Western Australia (WA) and the possible effects and contribution of changes in diagnostic criteria, age at diagnosis, eligibility for service provision based on ASD diagnoses and changes in diagnostic practices. METHODS A population-based study was conducted among the cohort of children born in WA between 1983 and 1999 and diagnosed with ASD between the age of 2 and 8 years up to December 31, 2004. The trend in ASD diagnosis over the study period was assessed by investigating birth cohort and period effects, and examining whether these were modified by age of diagnosis. ASD diagnosis corresponding with changes in diagnostic criteria, funding and service provision over time were also investigated. A subgroup analysis of children aged <or=5 years was also conducted to examine trends in the incidence and age of diagnosis of ASD and intellectual disability (ID) and to investigate the role of changes in diagnostic practices. RESULTS The overall prevalence of ASD among children born between 1983 and 1999 and diagnosed by age 8 was 30 per 10,000 births with the prevalence of autism comprising 21 per 10,000 births. The prevalence of ASD increased by 11.9% per annum, from 8 cases per 10,000 births in 1983 to 46 cases per 10,000 births in 1999. The annual incidence of ASD, based on newly diagnosed ASD cases in each year from 1985 to 2002, increased over the study period. The increase in incidence of ASD appeared to coincide with changes in diagnostic criteria and availability of funding and services in WA, particularly for children aged <5 years. The age-specific rates of autism and PDD-NOS increased over time and the median age of diagnosis for autism decreased from 4 to 3 years of age throughout the 1990s. For children aged <or=5 years the incidence of ASD diagnosis increased significantly from 1992, with an average annual increase of 22%. Similar findings were found for autism. In the corresponding years the incidence of diagnosis of severe ID fell by 10% per annum and mild-moderate ID increased by 3% per annum. CONCLUSIONS The rise in incidence of all types of ASDs by year of diagnosis appears to be related to changes in diagnostic and service provision practices in WA. In children aged <or=5 years, diagnosis of severe ID decreased, but mild-moderate ID increased during the study period. A true increase in ASD cannot be ruled out.

Systematic review of interventions for children with Fetal Alcohol Spectrum Disorders

BackgroundChildren with Fetal Alcohol Spectrum Disorders (FASD) may have significant neurobehavioural problems persisting into adulthood. Early diagnosis may decrease the risk of adverse life outcomes. However, little is known about effective interventions for children with FASD. Our aim is to conduct a systematic review of the literature to identify and evaluate the evidence for pharmacological and non-pharmacological interventions for children with FASD.MethodsWe did an electronic search of the Cochrane Library, MEDLINE, EMBASE, PsychINFO, CINAHL and ERIC for clinical studies (Randomized controlled trials (RCT), quasi RCT, controlled trials and pre- and post-intervention studies) which evaluated pharmacological, behavioural, speech therapy, occupational therapy, physiotherapy, psychosocial and educational interventions and early intervention programs. Participants were aged under 18 years with a diagnosis of a FASD. Selection of studies for inclusion and assessment of study quality was undertaken independently by two reviewers. Meta-analysis was not possible due to diversity in the interventions and outcome measures.ResultsTwelve studies met the inclusion criteria. Methodological weaknesses were common, including small sample sizes; inadequate study design and short term follow up. Pharmacological interventions, evaluated in two studies (both RCT) showed some benefit from stimulant medications. Educational and learning strategies (three RCT) were evaluated in seven studies. There was some evidence to suggest that virtual reality training, cognitive control therapy, language and literacy therapy, mathematics intervention and rehearsal training for memory may be beneficial strategies. Three studies evaluating social communication and behavioural strategies (two RCT) suggested that social skills training may improve social skills and behaviour at home and Attention Process Training may improve attention.ConclusionThere is limited good quality evidence for specific interventions for managing FASD, however seven randomized controlled trials that address specific functional deficits of children with FASD are underway or recently completed.

Craniosynostosis in Western Australia, 1980–1994: A population-based study

A craniomaxillofacial unit was established recently in Western Australia, and a study was carried out to provide some baseline characteristics of primary craniosynostosis in Western Australia and to investigate whether there has been any significant temporal change in birth prevalence. A case control study was conducted, using cases identified from a population-based register of birth defects, and a random sample of all births without a birth defect formed the control group. All subjects were born in Western Australia over the period 1980-1994 inclusive. The prevalence of craniosynostosis over the period 1980-1994 in Western Australia was 5.06 per 10,000 births. There was a significant linear increase in lambdoid synostosis over this period of 15.7% per year. Craniosynostosis was significantly more common among male infants, infants born preterm (<37 weeks gestation), breech presentation or presentations other than vertex, and infants born to fathers 40 years of age or older, even after accounting for known autosomal dominant syndromes. Other major birth defects were found in 11.2% of children with nonsyndromic craniosynostosis. Only 43 children (25.3%) with craniosynostosis were reported to have been seen by a geneticist. Thus, the prevalence of craniosynostosis in Western Australia is among the lowest reported. There is no current explanation for the increase in lambdoid synostosis. The increased risk of so-called nonsyndromic craniosynostosis with paternal age raises the possibility of undiagnosed new dominant mutations. This, along with the excess of other birth defects in children with craniosynostosis emphasises the need to ensure that these families are offered genetic counseling.

On the twin risk in autism.

Autism is considered by many to be the most strongly genetically influenced multifactorial childhood psychiatric disorder. In the absence of any known gene or genes, the main support for this is derived from family and twin studies. Two recent studies (Greenberg et al. 2001; Betancur et al. 2002) suggested that the twinning process itself is an important risk factor in the development of autism. If true, this would have major consequences for the interpretation of twin studies. Both studies compared the number of affected twin pairs among affected sib pairs to expected values in two separate samples of multiplex families and reported a substantial and significant excess of twin pairs. Using data from our epidemiological study in Western Australia, we investigated the possibility of an increased rate of autism in twins. All children born between 1980 and 1995 with autism, Asperger syndrome, or pervasive developmental disorder not otherwise specified (PDD-NOS) were ascertained. Of the 465 children with a diagnosis, 14 were twin births (rate 30.0/1,000) compared to 9,640 children of multiple births out of a total of 386,637 births in Western Australia between 1980 and 1995 (twin rate weighted to number of children with autism or PDD per year 26.3/1,000). These data clearly do not support twinning as a substantial risk factor in the etiology of autism. We demonstrate that the high proportion of twins found in affected-sib-pair studies can be adequately explained by the high ratio of concordance rates in monozygotic (MZ) twins versus siblings and the distribution of family size in the population studied. Our results are in agreement with those of two similar studies by Croen et al. (2002) in California and Hultman et al. (2002) in Sweden.

Twins born following assisted reproductive technology: perinatal outcome and admission to hospital

BACKGROUND Compared with spontaneously conceived (SC) singletons, adverse perinatal outcome, neonatal intensive care unit (NICU) admission and hospital admission in infancy are more common in those born following Assisted Reproductive Technology (ART). Similar comparisons for twins have shown conflicting results. METHODS We investigated perinatal outcome and hospital admission during the first 3 years of life for all twin children born in Western Australia between 1994 and 2000 [700 ART, 4097 SC]. RESULTS ART twins had a greater risk of adverse perinatal outcome including preterm birth, low birthweight and death compared with SC twins of unlike-sex. In their first year of life, ART twins had a longer birth admission; were 60% more likely to be admitted to a NICU; and had a higher risk of hospital admission. The increased risk of hospital admission continued in the second and third year but was not statistically significant in the third year. CONCLUSIONS Couples undertaking ART should be aware that in addition to the known increased perinatal risks associated with a twin birth, ART twins are more likely than SC twins to be admitted to a NICU and hospitalized in the first 3 years of life.

Physical and Mental Health in Mothers of Children with Down Syndrome

OBJECTIVE To identify the relationship between characteristics of the child with Down syndrome and the health of their mother. STUDY DESIGN Families with a child/young adult with Down syndrome (<25 years) provided information related to the health of the child, functioning and behavior, and the health and well-being of the mother (n = 250). RESULTS The mean physical health score of mothers was 50.2 (SD = 9.6). Factors associated with lower mean physical health scores were as follows: child having a current heart problem (P = .036), a higher body mass index (P = .006), and higher (poorer) scores on the Developmental Behavior Checklist. Better physical health scores were seen in mothers whose children required no help/supervision in learning new skills (P = .008) and domestic tasks (P = .014). The mean mental health score of mothers was 45.2 (SD = 10.6), significantly lower than the norm of 50 (P < .0001). Associated child factors included current ear problems (P = .079), muscle/bone problems (P = .004), >4 episodes of illness in past year (P = .016), and higher scores on the DBC (P < .0001). CONCLUSIONS The most important predictors of maternal health were childrens behavioral difficulties, everyday functioning and current health status. Mothers of children with Down syndrome appear to experience poorer mental health and may require greater support and services to improve behavior management skills for their child and their own psychological well-being.

Environmental risk factors by gender associated with attention-deficit/hyperactivity disorder.

BACKGROUND: Early environmental risk factors associated with attention-deficit/hyperactivity disorder (ADHD) have been increasingly suggested. Our study investigates the maternal, pregnancy, and newborn risk factors by gender for children prescribed stimulant medication for treatment of ADHD in Western Australia. METHODS: This is a population-based, record linkage case–control study. The records of all non-Aboriginal children and adolescents born in Western Australia and aged <25 years who were diagnosed with ADHD and prescribed stimulant medication (cases = 12 991) were linked to the Midwives Notification System (MNS) to obtain maternal, pregnancy, and birth information. The control population of 30 071 children was randomly selected from the MNS. RESULTS: Mothers of children with ADHD were significantly more likely to be younger, be single, have smoked in pregnancy, have labor induced, and experience threatened preterm labor, preeclampsia, urinary tract infection in pregnancy, or early term delivery irrespective of the gender of the child, compared with the control group. In the fully adjusted model, a novel finding was of a possible protective effect of oxytocin augmentation in girls. Low birth weight, postterm pregnancy, small for gestational age infant, fetal distress, and low Apgar scores were not identified as risk factors. CONCLUSIONS: Smoking in pregnancy, maternal urinary tract infection, being induced, and experiencing threatened preterm labor increase the risk of ADHD, with little gender difference, although oxytocin augmentation of labor appears protective for girls. Early term deliveries marginally increased the risk of ADHD. Studies designed to disentangle possible mechanisms, confounders, or moderators of these risk factors are warranted.