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.

Admission to hospital of singleton children born following assisted reproductive technology (ART).

BACKGROUND: Adverse perinatal outcomes are more common in singletons born following assisted reproductive technology (ART) and this would predict an increase in hospitalization during infancy and early childhood. METHODS: We investigated hospital admissions during the first 3 years of life for all singleton children born in Western Australia between 1994 and 2000 [1328 ART, 162 350 spontaneously conceived (SC)]. RESULTS: ART infants had a significantly longer birth admission and were four times more likely to be admitted to neonatal intensive care units (NICU) than SC infants. ART children had a 60% greater risk of one or more admissions in their first year and an equal risk of admission in their second and third years. Their length of stay in hospital was longer in each age period. Maternal, infant and socio-economic confounders accounted for most of the increased admission risk in the first year. However, after adjustment, a 20% increase in the risk of admission to NICU (P < 0.05) and admission to hospital during the first year (P < 0.05) remained. CONCLUSIONS: Couples undertaking ART should be aware that ART infants are more likely to be admitted to a NICU, to be hospitalized in the first year of life and to stay in hospital longer than other children.

Co-occurrence of birth defects and intellectual disability.

This study used population-based databases to ascertain birth defects and intellectual disability (ID), defined as full IQ < 70, in children born in Western Australia during 1980-99. Of the children surviving to 1 year (n = 474 285), 4.9% had birth defects and 1.3% ID. ID was identified in 7.9% of children with birth defects. After adjusting for sex, mother's age, race, parity, plurality, birthweight and gestational age the prevalence ratio (PR) [95% confidence interval (CI)] for ID in children with birth defects compared with those with no birth defects was 7.6 [7.2, 8.0]. Those with chromosomal anomalies comprised 3.2% of the group with birth defects. The percentage ID (and PR [95% CI]) in specific categories were: Down's syndrome 97% (84.5 [79.4, 90.0]), sex chromosome anomalies 30.3% (31.0 [23.8, 40.3]), other chromosomal anomalies 64.2% (54.2 [47.2, 62.3]). Birth defects were categorised according to system in the 96.8% of children with non-chromosomal anomalies. The percentage with ID (and PR [95% CI]) for birth defects in each system were: spina bifida 18.8 (16.7 [12.2, 23.0]); nervous (except spina bifida) 38.6 (33.4 [30.3, 36.9]); cardiovascular 4.2 (4.1 [3.5, 4.8]); gastro-intestinal 2.2 (2.0 [1.5, 2.7]); urogenital 2.6 (2.4 [2.0, 2.8]; musculo-skeletal 3.6 (4.0 [3.5, 4.6]); other non-chromosomal 7.0 (7.3 [6.5, 8.3]); and multiple systems 12.3 (10.2 [8.6, 12.2]). Birth defects were present in 30.2% of children with ID (27.7% of children with mild/moderate ID (IQ 40-69) and 54% of children with severe ID (IQ < 40)). Adjusted PRs for birth defects in children with any ID, mild/moderate ID and severe ID compared with children with normal intellectual function were 6.0 [5.8, 6.3], 5.5 [5.3, 5.8] and 10.5 [9.7, 11.4] respectively. The data are useful for those providing services for children with developmental disabilities especially for predicting family support and respite and accommodation requirements for children and adults with severe ID.

Autism following a history of newborn encephalopathy: more than a coincidence?

Between June 1993 and December 1996, 276 term newborn infants with encephalopathy and 564 randomly selected term controls were enrolled in a population-based study of moderate and severe term newborn encephalopathy (NE) in Western Australia. During comprehensive neurobehavioural and cognitive follow-up of all patients and controls at 3 years and again at 5 years of age we found an unexpected but strong association between NE and autism spectrum disorders (ASDs). A diagnosis of ASD by age 5 years was reached using criteria according of the Diagnostic Statistical Manual, 4th edition. Linking records to the Western Australian Disability Services Commission Register ensured that no child in the study with ASD was missed. By age 5 years, 37 (13.4%) infants with NE and one (0.2%) control had died. Among the 239 survivors of NE, 12 (5%) were diagnosed with an ASD. Of these, 10 (4.2%) met the full criteria for autism, one had pervasive developmental disorder-not otherwise specified, and one had Asperger syndrome. Among the 563 surviving controls, five (0.8%) were diagnosed with an ASD: three with autism, one with autism/possible Asperger syndrome, and one with Asperger syndrome. Compared with the controls, the children who had experienced NE were 5.9 times (95% confidence interval 2.0-16.9) more likely to have been diagnosed with an ASD.

Association of sociodemographic characteristics of children with intellectual disability in Western Australia.

The social determinants of intellectual disability (ID) are poorly understood, particularly in Australia. This study has investigated sociodemographic correlates of ID of unknown cause in Western Australian born children. Using record linkage to the Western Australian Maternal & Child Health Research Database, maternal sociodemographic characteristics of children with ID (of unknown cause) born between 1983 and 1992 (n = 2871) were compared with those of children without ID (n = 236,964). Socioeconomic indices for areas based on the census district of mother's residence were also included in the analysis. Aboriginal mothers (OR = 2.83 [CI: 2.52, 3.18]), teenagers (OR = 2.09 [CI: 1.82, 2.40]) and single mothers (OR = 2.18 [CI: 1.97, 2.42]) were all at increased risk of having a child with mild or moderate ID. Children of mothers in the most socioeconomically disadvantaged 10% had more than five times the risk of mild and moderate ID compared with those in the least disadvantaged 10% (OR = 5.61 [CI: 4.42, 7.12]). Fourth or later born children were also at increased risk (OR = 1.82 [CI: 1.63, 2.02]). The results of the study have implications both for further aetiological investigation as well as service provision for children with ID. Furthermore, many of the sociodemographic correlates identified in this study, particularly in the mild/moderate category of ID, are potentially modifiable, opening up opportunities for primary prevention.

Perinatal factors and the development of autism: a population study.

BACKGROUND: Autism is considered to have a genetic basis, although exposure to certain stimuli in the prenatal period has been implicated to be causal in some cases. Some investigations have shown an association with obstetric complications but findings have been inconsistent owing to differences in sampling and methods. OBJECTIVE: To examine the association of obstetric factors with autism spectrum disorders for a cohort of children, using obstetric data contained in a statutory database collected at the time of birth. DESIGN: Subjects born in Western Australia between 1980 and 1995 and diagnosed with an autism spectrum disorder by 1999 were included as cases (n = 465). Siblings of the cases (n = 481) and a random population-based control group (n = 1313) were compared with the cases on obstetric information contained in the Maternal and Child Health Research Database of Western Australia. RESULTS: Compared with control subjects, cases had significantly older parents and were more likely to be firstborn. Case mothers had greater frequencies of threatened abortion, epidural caudal anesthesia use, labor induction, and a labor duration of less than 1 hour. Cases were more likely to have experienced fetal distress, been delivered by an elective or emergency cesarean section, and had an Apgar score of less than 6 at 1 minute. Cases with a diagnosis of autism had more complications than those with pervasive developmental disorder not otherwise specified or Asperger syndrome. Nonaffected siblings of cases were more similar to cases than control subjects in their profile of complications. CONCLUSIONS: Autism is unlikely to be caused by a single obstetric factor. The increased prevalence of obstetric complications among autism cases is most likely due to the underlying genetic factors or an interaction of these factors with the environment.

An investigation into sub-telomeric deletions of chromosome 22 and pervasive developmental disorders.

Deletions of the sub-telomeric region of chromosome 22 have been associated with mental retardation, developmental delay, and autistic behaviors. This study investigated sub-telomeric anomalies of chromosome 22 using fluorescent in situ hybridization (FISH) probes in 82 subjects diagnosed with autism and atypical autism. No microdeletions were detected in this group. Similar FISH analyses were undertaken on two children with developmental delay, who were ascertained to be ring 22 during routine cytogenetic investigations. One subject was shown to have a microdeletion in the sub-telomeric region tested. Both children met the social and communication cut off for autism on the ADI and but did not meet the cut off for restrictive and repetitive behaviors. Only one of the two children met the criteria for PDD on the ADOS.

Prevalence of intellectual disability in Western Australia.

Record linkage of multiple sources was used to ascertain children with intellectual disability born in Western Australia between 1983 and 1992. The prevalence was 14.3 per 1000, 10.6 per 1000 for children with mild or moderate and 1.4 per 1000 for those with a severe level of intellectual disability. Prevalence was greater in males (prevalence ratio 1.6) and in children of Aboriginal mothers (prevalence ratio 2.3). Although prevalence of intellectual disability has been found to vary according to study location, method of ascertainment and criteria used, these estimates are similar to estimates from several recent studies.

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.