Association of assisted reproductive technology (ART) treatment and parental infertility diagnosis with autism in ART-conceived children.

STUDY QUESTION: Are assisted reproductive technology (ART) treatment factors or infertility diagnoses associated with autism among ART-conceived children? SUMMARY ANSWER: Our study suggests that the incidence of autism diagnosis in ART-conceived children during the first 5 years of life was higher when intracytoplasmic sperm injection (ICSI) was used compared with conventional IVF, and lower when parents had unexplained infertility (among singletons) or tubal factor infertility (among multiples) compared with other types of infertility. WHAT IS KNOWN ALREADY: Some studies found an increased risk of autism among ART-conceived infants compared with spontaneously-conceived infants. However, few studies, and none in the USA, have examined the associations between types of ART procedures and parental infertility diagnoses with autism among ART-conceived children. STUDY DESIGN, SIZE, DURATION: Population-based retrospective cohort study using linkages between National ART Surveillance System (NASS) data for 1996-2006, California Birth Certificate data for 1997-2006, and California Department of Developmental Services (DDS) Autism Caseload data for 1997-2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: All live born ART-conceived infants born in California in 1997-2006 (n = 42 383) with 5-year observation period were included in the study. We assessed the annual incidence of autism diagnosis documented in DDS, which includes information on the vast majority of persons with autism in California, and the association of autism diagnosis with ART treatment factors and infertility diagnoses. MAIN RESULTS AND THE ROLE OF CHANCE: Among ART-conceived singletons born in California between 1997 and 2006, the incidence of autism diagnosis remained at ∼0.8% (P for trend 0.19) and was lower with parental diagnosis of unexplained infertility (adjusted hazard risk ratio [aHRR]; 95% confidence interval: 0.38; 0.15-0.94) and higher when ICSI was used (aHRR 1.65; 1.08-2.52), when compared with cases without these patient and treatment characteristics. Among ART-conceived multiples, the incidence of autism diagnosis between 1997 and 2006 remained at ∼1.2% (P for trend 0.93) and was lower with parental diagnosis of tubal factor infertility (aHRR 0.56; 0.35-0.90) and higher when ICSI was used (aHRR 1.71; 1.10-2.66). LIMITATIONS, REASONS FOR CAUTION: Study limitations include imperfect data linkages, lack of data on embryo quality and possible underestimation of autism diagnosis cases. Limitations of the observational study design could affect the analysis by the possibility of residual confounders. Since information about ICSI use was missing for most frozen/thawed embryo transfer cycles, our findings of association of ICSI use and autism diagnosis can only be generalizable to fresh embryo transfer cycles. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides additional evidence of the association between some types of ART procedures with autism diagnosis. Additional research is required to explain the increased risk of autism diagnosis with ICSI use, as well as studies on the effectiveness and safety of ICSI.

Prevalence of autism in a United States population: the Brick Township, New Jersey, investigation.

OBJECTIVE: This study determined the prevalence of autism for a defined community, Brick Township, New Jersey, using current diagnostic and epidemiologic methods. METHODS: The target population was children who were 3 to 10 years of age in 1998, who were residents of Brick Township at any point during that year, and who had an autism spectrum disorder. Autism spectrum disorder was defined as autistic disorder, pervasive developmental disorder-not otherwise specified (PDD-NOS), and Asperger disorder. The study used 4 sources for active case finding: special education records, records from local clinicians providing diagnosis or treatment for developmental or behavioral disabilities, lists of children from community parent groups, and families who volunteered for participation in the study in response to media attention. The autism diagnosis was verified (or ruled out) for 71% of the children through clinical assessment. The assessment included medical and developmental history, physical and neurologic evaluation, assessment of intellectual and behavioral functioning, and administration of the Autism Diagnostic Observation Schedule-Generic. RESULTS: The prevalence of all autism spectrum disorders combined was 6.7 cases per 1000 children. The prevalence for children whose condition met full diagnostic criteria for autistic disorder was 4.0 cases per 1000 children, and the prevalence for PDD-NOS and Asperger disorder was 2.7 cases per 1000 children. Characteristics of children with autism in this study were similar to those in previous studies of autism. CONCLUSIONS: The prevalence of autism in Brick Township seems to be higher than that in other studies, particularly studies conducted in the United States, but within the range of a few recent studies in smaller populations that used more thorough case-finding methods.

Tocolytic magnesium sulfate exposure and risk of cerebral palsy among children with birth weights less than 1,750 grams.

The authors examined the relation between intrapartum magnesium sulfate exposure and risk of cerebral palsy in a case-control study of low birth weight children designed to control for confounding by the clinical indications for magnesium in pregnancy. Case children (n = 97) included all singleton children with cerebral palsy who were born in 1985-1989 in Atlanta, Georgia with a birth weight less than 1,750 g and whose mothers had not had a hypertension-related disease during pregnancy. Control children (n = 110) were randomly selected from the infant survivors using identical selection criteria. Data on magnesium sulfate exposure, labor and delivery, and infant characteristics were abstracted from hospital records. The authors found no association between exposure to magnesium sulfate and cerebral palsy risk (odds ratio = 0.9; 95% confidence interval: 0.3, 2.6) either in all children or in subgroups with varying likelihoods for exposure to magnesium. However, the association did vary by birth weight, with a protective effect being seen in children born weighing less than 1,500 g and an elevated risk in children with birth weights of 1,500 g or more; all confidence intervals included 1.0 except for the combined <1,500 g group. Several ongoing randomized clinical trials of magnesium and cerebral palsy may shed more definitive light on this relation.

Aetiology of childhood vision impairment, metropolitan Atlanta, 1991-93.

Data from the population-based Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP) were used to describe the underlying causes of vision impairment (VI; corrected visual acuity in the better eye of 20/70 or worse) in young children (n = 228) in metropolitan Atlanta in 1991-93. Children with VI were identified through record review at multiple educational and medical sources. Children were categorised as having isolated VI or multiple disabilities (i.e. VI plus one or more of four additional developmental disabilities) and as having low vision (visual acuity 20/70-20/400) or blindness (visual acuity worse than 20/400). Medical conditions abstracted from MADDSP sources were reviewed to determine the probable aetiology of a child's VI. Aetiologies were assigned to one of three developmental time periods: prenatal, perinatal, or postnatal. Prenatal aetiologies were identified in 43% of the children; 38% of the prenatal aetiologies were genetic. Perinatal aetiologies were found in 27% of the children. Postnatal aetiologies were rare. Prenatal aetiologies were more common in children with isolated VI; perinatal and postnatal aetiologies were more common in children with multiple disabilities. Children with prenatal aetiologies tended to have less severe vision loss than did children with perinatal or postnatal aetiologies. The distribution varied by birthweight, but did not differ significantly by sex or race.

American Academy of Pediatrics. Committee on Children With Disabilities. Care coordination: integrating health and related systems of care for children with special health care needs.

Care coordination is a process that links children with special health care needs and their families to services and resources in a coordinated effort to maximize the potential of the children and provide them with optimal health care. Care coordination often is complicated because there is no single entry point to multiple systems of care, and complex criteria determine the availability of funding and services among public and private payers. Economic and sociocultural barriers to coordination of care exist and affect families and health care professionals. In their important role of providing a medical home for all children, primary care pediatricians have a vital role in the process of care coordination, in concert with the family.

The descriptive epidemiology of infantile spasms among Atlanta children.

PURPOSE: To determine the population-based epidemiology of infantile spasms (IS) among Atlanta children. METHODS: By using data from a cross-sectional, population-based surveillance system that included 21 EEG laboratories, we identified children born in 1975-1977 in metropolitan Atlanta with IS. Cumulative incidence up to age 2 years was estimated from the number of children with IS born in the study area in 1975-1977, and age-specific prevalence was calculated from the number of children previously diagnosed with IS who lived in the study area at age 10 years. Data regarding coexisting disabilities were available from the surveillance system for developmental disabilities. RESULTS: The cumulative incidence of IS was 2.9/10,000 live births; half of the children with IS had cryptogenic IS. The age-specific prevalence of IS was 2.0/10,000 among 10-year-old children. Eighty-three percent of 10-year-old children with a history of IS had mental retardation (MR, IQ < or =70); 56% of children with a history of IS had profound MR (IQ <20). Developmental outcome did not differ between the children with cryptogenic IS and those with symptomatic IS. Among the 10-year-old children with profound MR who were living in Atlanta at age 10 years, 12% had a history of IS. Fifty percent of children with IS developed Lennox-Gastaut syndrome (LGS) before age 11 years. CONCLUSIONS: The syndrome of IS is rare in the general population, yet a significant percentage of all children with profound MR and severe childhood epilepsy syndromes in the general population have a history of IS.

Prevalence and phenotype consequence of FRAXA and FRAXE alleles in a large, ethnically diverse, special education-needs population.

We conducted a large population-based survey of fragile X (FRAXA) syndrome in ethnically diverse metropolitan Atlanta. The eligible study population consisted of public school children, aged 7-10 years, in special education-needs (SEN) classes. The purpose of the study was to estimate the prevalence among whites and, for the first time, African Americans, among a non-clinically referred population. At present, 5 males with FRAXA syndrome (4 whites and 1 African American), among 1,979 tested males, and no females, among 872 tested females, were identified. All males with FRAXA syndrome were mentally retarded and had been diagnosed previously. The prevalence for FRAXA syndrome was estimated to be 1/3,460 (confidence interval [CI] 1/7,143-1/1,742) for the general white male population and 1/4, 048 (CI 1/16,260-1/1,244) for the general African American male population. We also compared the frequency of intermediate and premutation FRAXA alleles (41-199 repeats) and fragile XE syndrome alleles (31-199 repeats) in the SEN population with that in a control population, to determine if there was a possible phenotype consequence of such high-repeat alleles, as has been reported previously. No difference was observed between our case and control populations, and no difference was observed between populations when the probands were grouped by a rough estimate of IQ based on class placement. These results suggest that there is no phenotype consequence of larger alleles that would cause carriers to be placed in an SEN class.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. I. Birth defects and developmental disorders.

Members of the workgroup on birth defects and developmental disorders discussed methods to assess structural anomalies, genetic changes and mutations, fetal and infant mortality, functional deficits, and impaired fetal and neonatal growth. Tier 1 assessments for all five adverse reproductive outcomes consist of questionnaires and reviews of medical records rather than laboratory testing of biologic specimens. The work-group members noted a role for neurodevelopmental testing and for limited genetic studies, such as karyotyping in Tier 2 assessments. Emerging methodologies to identify chromosomal aberrations, DNA adducts, and repair inhibition were reserved for Tier 3.

Reported biomedical causes and associated medical conditions for mental retardation among 10-year-old children, metropolitan Atlanta, 1985 to 1987.

This report describes biomedical causes of mental retardation (MR) among school-age children and associated medical conditions in children for whom no cause was reported. This study involved 715, 10-year-old children with MR (intelligence quotient [IQ] 70 or less) born between 1975 and 1977. We determined biomedical causes of MR using a hierarchical approach based on the timing of the event (i.e. prenatal, perinatal, or postneonatal). Among children with no identified biomedical cause the occurrence of associated medical conditions was examined. No reported biomedical cause could be found in 78% of children with MR (87% mild, IQ 50 to 70; 57% severe, IQ < 50). Prenatal causes were present in 12%, perinatal causes in 6%, and postneonatal causes in 4%. On the basis of these findings it was concluded that intensive use of public health prevention strategies can reduce the number of children who receive a diagnosis of MR.

Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children.

PURPOSE: To determine the prevalence and descriptive epidemiology of Lennox-Gastaut Syndrome (LGS) among metropolitan Atlanta children. METHODS: We conducted a population-based study of LGS as part of the Metropolitan Atlanta Developmental Disabilities Study (MADDS) using a multiple-source surveillance system for epilepsy and developmental disabilities. Children were defined as having LGS if they had onset of multiple seizure types before age 11 years, with at least one seizure type resulting in falls, and an EEG demonstrating slow spike-wave complexes (<2.5 Hz). Mental retardation (MR) was not used as a diagnostic criterion. RESULTS: The lifetime prevalence of LGS at age 10 years was 0.26/1,000. Ninety-one percent of those with LGS had MR (IQ < or = 70), and 39% had a history of infantile spasms (IS). A comparison of children with LGS and those with multiple seizure types without slow spike-wave complexes demonstrated that those with LGS were more likely to have MR, history of IS, and multiple disabilities (MR, cerebral palsy, blindness, hearing impairment). Seventeen percent of all children in Atlanta with profound MR (IQ < 20) had LGS. CONCLUSIONS: LGS accounts for only 4% of all childhood epilepsy, yet is a significant contributor to childhood morbidity.

Prenatal magnesium sulfate exposure and the risk for cerebral palsy or mental retardation among very low-birth-weight children aged 3 to 5 years.

OBJECTIVE: To examine the relationship between prenatal magnesium sulfate exposure and the risk for cerebral palsy (CP) or mental retardation (MR) among very low-birth-weight (VLBW; <1500 g) children. Secondarily, to investigate the effect of prenatal magnesium sulfate exposure on VLBW infant mortality. DESIGN: Cohort study with follow-up to 1 year of age; a subset followed up to 3 to 5 years. SETTING: Twenty-nine Georgia counties, including the 5-county Atlanta metropolitan area. PARTICIPANTS: All VLBW births (N=1097) occurring during 2 years (1986-1988); all metropolitan Atlanta VLBW neonates who survived infancy (N=519). MAIN OUTCOME MEASURES: Infant mortality as determined from vital statistics records. Development of CP or MR by 3 to 5 years of age among metropolitan Atlanta VLBW survivors as determined from the Metropolitan Atlanta Developmental Disabilities Surveillance Program. RESULTS: For the entire cohort, there was no association between prenatal magnesium sulfate exposure and infant mortality (adjusted rate ratio, 1.02; 95% confidence interval [CI], 0.83-1.25). Among Atlanta-born survivors, those exposed to magnesium sulfate had a lower prevalence of CP or MR than those not exposed (CP: magnesium sulfate, 0.9%, no magnesium sulfate, 7.7%, crude odds ratio [OR], 0.11, 95% CI, 0.02-0.81; MR: magnesium sulfate, 1.8%, no magnesium sulfate, 5.8%, crude OR, 0.30, 95% CI, 0.07-1.29). Multivariable adjustment had no appreciable effect on the ORs for CP or MR, but the CIs included 1.0. CONCLUSIONS: A reduced risk for CP, and possibly MR, among VLBW children is associated with prenatal magnesium sulfate exposure. The reduced risk for childhood CP or MR does not appear to be due to selective mortality of magnesium sulfate-exposed infants.

Prevalence of selected developmental disabilities in children 3-10 years of age: the Metropolitan Atlanta Developmental Disabilities Surveillance Program, 1991.

PROBLEM/CONDITION: Serious developmental disabilities affect approximately 2% of school-age children and are lifelong conditions that incur substantial financial and societal costs. REPORTING PERIOD: January 1991-December 1991. DESCRIPTION OF SYSTEM: The Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP) monitors the prevalence of four serious developmental disabilities--mental retardation, cerebral palsy, vision impairment, and hearing impairment--among children 3-10 years of age in the five-county metropolitan-Atlanta area. Children who have at least one of the four developmental disabilities are ascertained through annual review of records at schools, hospitals, and other sources. RESULTS AND INTERPRETATION: During 1991, rates for mental retardation varied by age, race, and sex; rates ranged from 5.2 per 1,000 children to 16.6 per 1,000 children. Regardless of the absolute rate of mental retardation in each of the age-, race-, and sex-specific categories, severe mental retardation (i.e., an intelligence quotient of <50) accounted for one third of all cases. The overall crude rate of cerebral palsy was 2.4 per 1,000 children; however, the rate was higher among black children (3.1 per 1,000 children) than among white children (2.0 per 1,000 children). The rate of moderate to severe hearing impairment was 1.1 per 1,000 children, and the rate of vision impairment was 0.8 per 1,000 children. Rates of hearing impairment were higher among black males than among children in the other race and sex groups, whereas rates for vision impairment varied only slightly between these groups. The rates of the developmental disabilities were not adjusted for possible confounding factors (e.g., maternal education, family income, and various medical conditions). Consequently, the variation in rates may reflect social or other characteristics unique to the study population. ACTIONS TAKEN: MADDSP data will be used to direct early childhood intervention efforts to reduce the prevalence of these four developmental disabilities. MADDSP data also are being used to measure progress toward the year 2000 national objectives for the prevention of serious mental retardation.

Reproductive risk factors for epilepsy among ten-year-old children in metropolitan Atlanta.

The elements of a woman's reproductive history that may be associated with her risk of having a child who develops epilepsy have not been well described. To examine these possible associations, we used a multiple-source case ascertainment method to identify ten-year-old children with epilepsy who were living in the metropolitan Atlanta area in 1985-87; same-age control children were selected from public schools. To obtain reproductive history and other information, we interviewed 107 mothers of children with epilepsy and 408 mothers of control children. Twenty-nine children with a known intrauterine or postnatal aetiology were excluded from the analysis. We computed adjusted odds ratios for reproductive history characteristics, controlling for the race of the child, maternal education, census block group income, maternal pregnancy history and family history of a developmental disability. Our analyses indicated that mothers of children with epilepsy not only had more previous live births, but more previous adverse reproductive outcomes including spontaneous abortions, very low birthweight infants and infants with birth defects. The risk was especially strong for maternal history of a child with a birth defect. The specific types of birth defects reported in excess include central nervous system defects (specifically spina bifida) and Down's syndrome.

The relationship between idiopathic mental retardation and maternal smoking during pregnancy.

OBJECTIVES: Smoking has been linked to small cognitive, achievement, and behavioral deficits but has not been associated with more severe cognitive impairments. This investigation evaluated the relationship between maternal smoking during pregnancy and idiopathic mental retardation (MR). METHODS: Data on maternal smoking during pregnancy were obtained during face-to-face interviews with the mothers of 221 children with idiopathic MR and the mothers of 400 children attending public school. All children had been born in the five-county metropolitan Atlanta area in 1975 or 1976 and were living in the area when they were 10 years of age. We used exposure odds ratios (ORs) to assess the relationship between maternal smoking and MR, controlling for sex, maternal age at delivery, race, maternal education, economic status, parity, and alcohol use. RESULTS: Maternal smoking during pregnancy was associated with slightly more than a 50% increase in the prevalence of idiopathic MR (adjusted OR, 1.6; 95% confidence interval, 1.0-2.4), and children whose mothers smoked at least one pack a day during pregnancy had more than a 75% increase in the occurrence of idiopathic MR (OR, 1.9; 95% confidence interval, 1.0-3.4). This increase was neither accounted for by other sociodemographic risk factors for MR nor explained by an increase in the prevalence of low birth weight among the children of smokers. CONCLUSIONS: Our data suggest that maternal smoking may be a preventable cause of mental retardation.

Low birthweight and the risk for mental retardation later in childhood.

Data from the population-based Metropolitan Atlanta Developmental Disabilities Study were used in a case-control study to assess the association between low birthweight and mental retardation (intelligence quotient < or = 70) among 10-year-old children who were born in 1975 or 1976. Children with mental retardation were identified from existing records at multiple sources and control children were selected from public school rosters. Data on birthweight and other covariates (sex, birth order, maternal age, maternal race, maternal education and gestational age) came from birth certificates. We used multiple logistic regression modelling to obtain adjusted odds ratios for mental retardation, with normal birthweight children (those weighing > or = 2500 g) as the referent group. For low birthweight children as a whole, the odds ratio for mental retardation was 2.8 (95% CI 1.9-4.2). The risk was higher for very low birthweight (< 1500 g) children than for moderately low birthweight (1500-2499 g) children, and higher for severe mental retardation (intelligence quotient < 50) than for mild mental retardation (intelligence quotient 50-70). Adding gestational age to the models revealed that normal birthweight children who were born preterm also were at increased risk of having mental retardation at age 10 years.

Prevalence of epilepsy and epileptic seizures in 10-year-old children: results from the Metropolitan Atlanta Developmental Disabilities Study.

With reported prevalence rates of 4-9 cases per 1,000 children, childhood epilepsy is a major public health concern. Reported prevalence rates vary, mainly because researchers often use different epilepsy definitions. In addition, total prevalence may be underestimated if incomplete case-ascertainment methods are used. We used a multiple-source case-ascertainment method that included obtaining information from electroencephalogram laboratories to estimate the prevalence of epilepsy and to classify seizure types among 10-year-old children. In the metropolitan Atlanta (GA, U.S.A.) area, we found a lifetime prevalence of childhood epilepsy of 6 per 1,000 (95% confidence interval, 5.5-6.5) 10-year-old children. However, using capture-recapture analysis, this prevalence may be as high as 7.7 per 1,000. Proportionately more boys than girls had epilepsy. The prevalence did not vary appreciably by race. Partial seizures, including secondarily generalized seizures, were the most common seizure type (58%). Of the children with epilepsy, 35% had another developmental disability (mental retardation, cerebral palsy, visual impairment, or hearing impairment). An accurate estimate of the public health burden of childhood epilepsy and determination of possible risk factors for idiopathic epilepsy both depend on conducting complete community-based case ascertainment and obtaining detailed clinical data.

The administrative prevalence of mental retardation in 10-year-old children in metropolitan Atlanta, 1985 through 1987.

OBJECTIVES: In this study, data from the Metropolitan Atlanta Developmental Disabilities Study were used to determine the administrative prevalence (i.e., the number of children previously identified for service provision) of mental retardation among 10-year-old children during the years 1985 through 1987. METHODS: Children with mental retardation (intelligence quotient [IQ] of 70 or lower) were identified by review of records from multiple sources, with the public schools as the primary source. RESULTS: The overall administrative prevalence of mental retardation was 12.0 per 1000 children. The rate for mild mental retardation (IQ of 50 to 70) was 8.4 per 1000 and the rate for severe mental retardation (IQ lower than 50) was 3.6 per 1000. The prevalence was higher in Black children than in White children (prevalence odds ratio [POR] = 2.7) and in boys than in girls (POR = 1.4). Children with severe mental retardation had more coexisting disabilities than did children with mild mental retardation. CONCLUSIONS: The mental retardation prevalence rates reported here, especially the race-specific rates, may reflect social and demographic features unique to the metropolitan Atlanta area and therefore should be used with caution in making comparisons with other populations.

Mild mental retardation in black and white children in metropolitan Atlanta: a case-control study.

OBJECTIVES: This study assessed differences in the prevalence of mild mental retardation, defined as an intelligence quotient (IQ) from 50 to 70, between Black and White children. METHODS: A case-control study design was used. Ten-year-old children with mental retardation were identified from multiple sources. Information on race, sex, maternal age, birth order, economic status, and maternal education was abstracted from birth certificates of 330 case children and 563 control children (public school students). RESULTS: The crude Black-White odds ratio (OR) was 2.6, but it was reduced to 1.8 after the other five covariates were controlled. The disparity was largest among children whose mental retardation was first diagnosed when they were 8 to 10 years old (adjusted OR = 2.5). We found no significant difference in the occurrence of mild mental retardation between Black and White children diagnosed before the age of 6 years (adjusted OR = 1.2). Black children had a higher prevalence of mild mental retardation within all strata of the other five covariates. CONCLUSIONS: Five sociodemographic factors accounted for approximately half of the excess prevalence of mild mental retardation among Black children. Possible reasons for the residual difference are discussed.

Variation in the influence of selected sociodemographic risk factors for mental retardation.

OBJECTIVES: This study explored the utility of subdividing mental retardation into groups based on the presence of other neurological conditions. METHODS: Data were abstracted from birth certificates as part of a case-control study of mental retardation among 10-year-old children. The study sample included 458 case children and 563 control children selected from public schools. Case children were subdivided on the basis of intelligence quotient (IQ) score and the presence of other neurological conditions. RESULTS: Other neurological conditions were more common with severe mental retardation than with mild mental retardation. Regardless of IQ level or the presence of other neurological conditions, boys were more likely than girls to have mental retardation. Older mothers were more likely than younger mothers to have a child with mental retardation accompanied by another neurological condition. High birth order, Black race, and low maternal education were associated with a higher prevalence of isolated mental retardation. CONCLUSIONS: These findings suggest that sociodemographic risk factors for mental retardation vary according to the presence of other neurological conditions and that subdivisions based on medical or physical criteria may be useful in epidemiologic studies of mental retardation.