Cardiovascular abnormalities in children with autosomal dominant polycystic kidney disease

It is known that adults with autosomal dominant polycystic kidney disease (ADPKD) have an increased incidence of cardiovascular abnormalities, including mitral valve prolapse. The cardiac manifestations of ADPKD in the pediatric population have not been well established. To determine the cardiac manifestations of children with ADPKD, echocardiography was performed in 154 children of 66 families in which one parent has ADPKD. Eighty-six affected children and 68 unaffected children were evaluated in a prospective, single-blinded manner by echocardiography. Affected children were defined as those with any cysts on a concurrent renal ultrasound or those predicted to be gene carriers by gene linkage analysis. A 12% incidence of mitral valve prolapse was found in the affected children compared with only 3% of the unaffected children (P < 0.05). ADPKD children, but not their unaffected siblings, demonstrate a significant correlation between left ventricular mass index and systolic blood pressure. Moreover, hypertensive ADPKD children have significantly larger left ventricular mass index than do normotensive ADPKD children. A 3.5% incidence of congenital heart disease was found in the affected group, whereas 2.9% of the unaffected children had congenital heart disease. It was concluded that systemic manifestations of ADPKD, particularly cardiovascular abnormalities, are present even in childhood and these warrant the clinician's attention.     

Birth order, sibship size, and risk of epilepsy

We examined the relation between epilepsy and birth order, using data on 1,950 probands with epilepsy and 4,636 of their full siblings without epilepsy from the Epilepsy Family Study of Columbia University. The proportion of first-born individuals appeared to be higher among probands with epilepsy than among their unaffected siblings, but this relation disappeared after we controlled for the confounding effect of sibship size. With sibship size controlled, the proportion of first-born individuals was similar to that in unaffected siblings for probands with idiopathic/cryptogenic epilepsy, generalized and partial onset seizures, and all ages at onset of epilepsy. Probands with remote symptomatic epilepsy had higher birth orders than their unaffected siblings, even after we controlled for sibship size.     

The IQ of heterozygotes for phenylketonuria (PKU). indication of a blood phenylalanine-independent action of the PKU mutant (author's transl)

The IQ of parents of phenylketonuria-(PKU-)affected children is lower than that of parents with histidinemia-affected children (control group). The difference arises almost entirely from the verbal part of the Hamburg-Wechsler test. The IQ of the parents with histidinemia-affected children shows the same distribution as that of the normal population; heterozygosity for this condition does not appear to confer any intellectual advantage. In PKU patients treated at an early age and apparently adequately, a slight, but significant decrease in IQ becomes apparent between the ages of 6 and 8 years. This slight decrease also refers mainly to the verbal IQ. At 4 years of age all PKU patients are tested with Bühler-Hetzer, as well as the Kramer test. There is a significant difference between the results in favour of the Bühler-Hetzer test, which is much less verbal. Since heterozygotes for PKU never show elevated blood phenylalanine levels and, moreover, prenatal tyrosine deficiency, as argued by others, seems highly improbable, it is supposed that the PKU gene has a more direct influence on certain ganglion cells at least, with a consequent slight, but significant lowering of the verbal IQ in heterozygotes and satisfactorily-treated homozygotes for PKU. A slightly increased intracellular phenylalanine concentration in heterozygotes and apparently adequately-treated homozygotes need not to be reflected in raised blood levels and this could be an explanation for the observed IQ lowering. But it should not be overlooked that by far the greatest part of damage in PKU patients is caused by chronic phenylalanine poisoning which is well preventable by correct dietary treatment.     

Cognitive, educational, and behavioural outcomes at 7 to 8 years in a national very low birthweight cohort

AIMS: To examine cognitive, behavioural, and educational outcomes in middle childhood among a birth cohort of very low birthweight children. METHODS: Two hundred and ninety eight survivors from a national birth cohort of 413 New Zealand very low birthweight (VLBW) children born in 1986 were assessed at 7 to 8 years of age on measures of behaviour, cognitive ability, school performance and the need for special education. These outcomes were compared with the same measures in a general population sample of over 1000 children studied at a similar age. RESULTS: The VLBW children had significantly higher rates of problems and poorer levels of functioning across all outcome measures than the general child sample. These differences persisted even after control for variability in social, family, and other characteristics of the two samples and for the degree of sensorineural disability. There was evidence of a gradient of risk with birthweight, with extremely low birthweight children having generally higher rates of problems and difficulties than other VLBW children after covariate control. CONCLUSIONS: The findings are consistent with a growing body of research evidence which suggests that premature and VLBW infants are at increased risk of longer term morbidity and functional impairment in middle childhood.     

Sibling relationship quality from birth to adolescence: the enduring contributions of friends.

The purpose of the present study was to examine continuity in sibling relationships across childhood and to evaluate the degree to which children's experiences with their friends and mothers prior to their sibling's birth predict the quality of the relationship they establish with their siblings in adolescence. Twenty-eight firstborn children, who were 48 months old at the time of their sibling's birth, were observed interacting with their siblings and friends at multiple time points. The level of positive social behaviors demonstrated in their early relationships with friends continued to predict sibling relationship quality in adolescence. Firstborn children who had more positive interactions with friends prior to their sibling's birth demonstrated more prosocial interactions with both their siblings and friends in adolescence and exhibited fewer externalizing behaviors. Longitudinal associations support the hypothesis that the social competencies that young children demonstrate in their early relationships with friends may have enduring significance for their social development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Does contiguity breed similarity? A within-family analysis of nonshared sources of IQ differences between siblings.

Hypothesized that highly contiguous siblings experience a family environment that is more alike than that experienced by siblings who are separated within the family structure (i.e., siblings with consecutive birth orders should be more alike in IQ than siblings separated by 1 or more birth orders). A dataset from the Fels Research Institute that included 538 children in 173 families (72 2-child families, 44 3-child families, 39 4-child families, and 18 families with 5 or more children). Analytic models based on a simplex birth order correlation structure and on a multiple regression model of IQ differences were developed to test the family structure relationships. Results indicate no family structure effects. It is suggested that genetic sources and 1-time events appear to be more plausible causes of the differences between siblings. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The development of sibling relationships in infancy: a short-term longitudinal study

24 infants and their preschool-aged siblings were observed in a laboratory playroom in the presence of their parents. Observations took place when the infants were 12 months old and again 6 months later. Analysis of the social behavior revealed that, at both ages, the children assumed differentiable roles in their interactions: The infants "followed" by observing and imitating while the preschoolers "led" by drawing the infants' attention and by assertive dominance. Over time, infants became increasingly willing to direct social behaviors toward their siblings. There was remarkable behavioral stability across time, with the infants' early propensities seemingly causally related to later pre-schoolers' behavior. Older girls directed more social behaviors to siblings than boys did. The amount of parent-directed behavior was affected by the number of adults present, whereas the amount of sibling-directed behavior was unaffected.     

Timing is everything: Executive functions in children exposed to elevated levels of phenylalanine.

This study addresses how the timing of a known biological insult affects the developmental progression of executive functions. The sample consisted of children exposed to elevated levels of phenylalanine, either postnatally, as in phenylketonuria (PKU; n = 46), or prenatally, as in maternal PKU (n = 15). Nonhyperphenylalaninemic siblings of children with PKU (n = 18) served as controls. Results indicated that elevated levels of phenylalanine are toxic to the neurological systems that manage executive functions and cognitive tempo. This toxicity is dose dependent, with higher levels of phenylalanine being more detrimental. Executive function difficulties noted in PKU are consistent with attention deficit hyperactivity disorder (ADHD)-inattentive type, whereas maternal PKU offspring had executive function difficulties consistent with ADHD-combined type. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of preterm birth and small gestational age on cognitive and motor development

AIMS: To determine the differential effects of preterm birth and being small for gestational age on the cognitive and motor ability of the child. METHODS: A longitudinal cohort of all infants of gestational age < or = 32 weeks born to mothers resident in the counties of Cheshire and Merseyside in 1980-1 was studied. The children were assessed at the age of 8 to 9 years using the Wechsler Intelligence Scale for Children, the Neale analysis of reading ability, and the Stott-Moyes-Henderson test of motor impairment. Adequacy of fetal growth was determined by the birthweight ratio--that is, the ratio of the observed birthweight to the expected birthweight for a given gestational age. Children with clinically diagnosed motor, learning or sensory disabilities were excluded. Information on social variables was obtained by a questionnaire completed by the parents. Of the 182 children, 158 were assessed. RESULTS: IQ was positively correlated with birthweight ratio but not with birthweight or gestational age. Motor ability was associated with birthweight, gestational age, and birthweight ratio. Reading comprehension was associated with birthweight ratio, but reading rate and accuracy were best explained by social variables and sex. IQ remained associated with birthweight ratio, after adjusting for maternal education, housing status, and number of social service benefits received. Reading ability was related to these social variables but motor ability was not. CONCLUSIONS: The effects of SGA and preterm birth differed: SGA was associated with cognitive ability, as measured by IQ and reading comprehension; motor ability was additionally associated with preterm birth. Reading rate and accuracy were not associated with SGA or preterm birth but were socially determined.     

Novel mutations identified in exon 7 of phenylalanine hydroxylase gene in Chinese

Exon 7 of the phenylalanine hydroxylase (PAH) gene was analyzed in 45 children affected with classic phenylketonuria (PKU) from northern China by using PCR-single strand conformation polymorphism (PCR-SSCP) technique and DNA direct sequencing. Six missense mutations (i.e. R243Q, R241H, G247V, L249H, P254I and G257V) and one silent mutation (V245V) were identified. The latter three missense mutations were demonstrated as novel mutations in comparison with the PAH mutation Database. One missense mutation (R241H) was first documented in Chinese. Our results showed population and regional differences in the PAH mutation distribution and suggest that there is more than one founding population for PKU in China. The finding of novel mutations will enhance our capability in molecular diagnosis of PKU.     

Thinness at birth in a northern industrial town

OBJECTIVE: To determine whether babies in an area of Britain with unusually high perinatal mortality have different patterns of fetal growth to those born elsewhere in the country. DESIGN: Measurement of body size in newborn babies. SETTING: Burnley (perinatal mortality in 1988 15.9/1000 total births) and Salisbury (perinatal mortality 10.8/1000 total births), England. SUBJECTS: Subjects comprised 1544 babies born in Burnley, Pendle, and Rossendale Health District, and 1025 babies born in Salisbury Health District. MAIN OUTCOME MEASURES: Birthweight, length, head, arm and abdominal circumferences, and placental weight were determined. RESULTS: Compared with babies born in Salisbury, Burnley babies had lower mean birthweight (difference 116 g, 95% confidence interval (CI) 77,154), smaller head circumferences (difference 0.3 cm, 95% CI 0.2, 0.4), and were thinner as measured by arm circumference (difference 0.3 cm, 95% CI 0.3, 0.4), abdominal circumference (difference 0.5 cm, 95% CI 0.4, 0.6) and ponderal index (difference 0.8 kg/m3, 95% CI 0.6, 1.0). The ratio of placental weight to birthweight was higher in Burnley (difference 0.6%, 95% CI 0.4, 0.9). These differences were found in boys and girls and did not depend on differences in duration of gestation or on the different ethnic mix of the two districts. Mothers in Burnley were younger, shorter in stature, had had more children, were of lower social class, and more of them smoked during pregnancy than mothers in Salisbury. These differences did not explain the greater thinness of their babies. CONCLUSIONS: Babies born in Burnley, an area with high perinatal mortality, are thin. The reason is unknown. Poor maternal nutrition is suspected because Burnley babies have a higher ratio of placental weight to birthweight. The greater thinness at birth of Burnley babies could have long term consequences, including higher rates of cardiovascular disease.     

Cost of care for a geographically determined population of low birthweight infants to age 8-9 years. I. Children without disability

AIM: To determine the extra cost of healthcare associated with low birthweight, in a cohort study of a geographically defined population in five health districts that comprise Merseyside. METHODS: The study comprised all children of birthweight < or = 1500 g and a 10% random sample of those weighing 1501-2000 g, without clinical disability, born in 1980 and 1981 to mothers resident in Merseyside, and their controls, matched by age, sex, and school class, followed up to age 8-9 years. RESULTS: The cost of care associated with the initial admission to the neonatal special/intensive care unit and subsequent use of hospital and family practitioner services was assessed. There were 641 survivors without disability and 227 non-survivors who weighed < or = 2000 g at birth. The mean cost of neonatal care per low birthweight child was 13 times greater than for a control child. For children weighing < or = 1000 g at birth, neonatal costs were 55 times greater than for the control children. Low birthweight children continue to use hospital and family practitioner services more intensively than controls to age 8-9 years. CONCLUSION: Low birthweight children used hospital and family practitioner services more intensively throughout the follow up period. Whether the increased use of health services persists into adolescence and adulthood is yet to be determined.     

Association of blood pressure in adolescence with birthweight

AIMS: To compare the blood pressure of very low birthweight infants with that of normal birthweight controls in adolescence. METHODS: A cohort of all infants of birthweight < or = 1500 g born to women resident in the county of Merseyside in 1980-1 was followed up at age 15 years with age, sex, and school matched controls. Growth indices and blood pressures were measured under standard conditions. The smoking history of mothers and children and their status for several socioeconomic variables were documented. In a matched pairs analysis systolic and diastolic blood pressures were compared for cases and controls before and after adjusting for height, weight, and body mass index. RESULTS: There were 172 singleton 15 year old survivors of birthweight < 1500 g out of 40,321 live births of Merseyside residents in 1980-1. Of the 172 survivors, 128 (74%) who had no clinical disability and 11 (6%) with a clinical disability but attending normal schools, were assessed with individually matched age, sex, and school controls. Twenty three (13%) had a clinical disability and were attending special schools; these were assessed without controls. Ten (6%) children refused or were unavailable for assessment. The systolic blood pressure was significantly higher in cases than in controls; the mean of the difference was 3.2 mm Hg. The diastolic blood pressure was also higher in the cases, but the difference was not significant. The controls were significantly heavier (4.4 kg), taller (4.0 cm), with larger head circumference (1.5 cm) than the cases. The difference in body mass index was not significant. Adjusting for height, weight, or body mass index increased the difference in systolic blood pressure between cases and controls. There were no significant differences in the socioeconomic variables, but what differences did exist favoured the controls. There was also a higher prevalence of smoking among the children and the mothers of the cases than the controls. CONCLUSIONS: The study supports the hypothesis that in adolescents variation in systolic blood pressure has its origins in fetal development. Some of the variation could be attributed to socioeconomic differences.     

Father's effect on infant birth weight

OBJECTIVE: We sought to determine whether paternal size at birth and during young adulthood influences the birth weight of the offspring. STUDY DESIGN: This historic cohort study followed up girls born in Copenhagen during 1959 to 1961. Their pregnancies in 1974 to 1989 were traced through the Danish Population Register, and the Personal Identification Numbers of the fathers of the children were obtained. Paternal birth weight was obtained from midwifery records and adult stature from military draft records. RESULTS: Compared with fathers who weighed at least 4 kg at birth, fathers who weighed 3 to 3.99 kg at birth had infants who were 109 gm lighter, and fathers who weighed <3 kg had infants who were 176 gm lighter after adjustment for maternal birth weight and adult stature, smoking, and medical and socioeconomic factors. After adjustment, fathers in the lowest quartile of adult body mass index had infants that were 105 gm lighter than those of fathers in the highest quartile. Both paternal birth weight and adult body mass index exhibited significant trends in association with infant birth weight. CONCLUSION: Independently of maternal size, the father's physical stature, particularly his own size at birth, influences the birth weight of his children.     

Consistency of mothers' behavior toward infant siblings.

Examined how similarly mothers behave toward infant siblings in 50 families in which mothers were videotaped while interacting with each of 2 siblings when each child was 12 mo old. The average age difference between siblings was 35 mo. Maternal behavior was assessed from the videotapes during feeding and free play. Factor analysis yielded 3 factors: Affection, Verbal Attention, and Control. Results indicate that the mothers behaved very similarly toward their 2 siblings at the same age in infancy: The consistency of maternal behavior toward the siblings approached the reliability of the measures. Although results might differ for older children, and for siblings of different ages, the data suggest that differential maternal treatment of children of the same age in infancy is unlikely to be a major source of the marked individual differences that have been observed within pairs of siblings. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of smoking cessation during pregnancy on preterm delivery and low birthweight

BACKGROUND: Evidence exists that maternal cigarette smoking is associated with preterm birth. Our purpose was to investigate the relation between maternal smoking cessation at different points during pregnancy and the preterm delivery rate and low birthweight. METHODS: Data from the 1988 National Health Interview Survey were analyzed. The study included women who gave birth to children within 6 years of the 1988 interview date (N = 4876). Preterm delivery and infant low birthweight were the main outcome measures. These measures were compared with maternal smoking status during pregnancy. Logistic regression models were computed to control for maternal age at the time of birth, parity, race, and total family income. RESULTS: Women who did not smoke cigarettes during pregnancy were less likely to give birth prematurely (5.9% vs 8.2%, P = .003) or give birth to a low-birthweight baby (5.5% vs 8.9%, P < .001) than women who smoked at some time during the year before giving birth. A significant association existed between maternal smoking status and both preterm delivery and low birthweight. Compared with those who smoked beyond the first trimester, those who quit smoking within the first trimester had reductions in the proportion of preterm deliveries (6.7% vs 9.1%) and low birthweight infants (7.9% vs 9.6%). CONCLUSIONS: Low birthweight and preterm delivery are reduced in women who stop smoking in the first trimester of pregnancy.     

In vivo and in vitro characterization of the sequence requirement for oligomer formation of Ca2+/calmodulin-dependent protein kinase IIalpha

A family was identified with 5 of 6 siblings and 3 other immediate family members who had developed chronic fatigue syndrome (CFS) as adults. All 8 met criteria for the CFS case definition as recommended by the Centers for Disease Control and Prevention. Sixty-eight blood samples were obtained over a period of 2 years from 20 family members (8 affected, 12 unaffected) and 8 normal controls. All blood samples were tested for NK activity in 4-h 51Cr-release assays and for the number of circulating CD3-CD56(+) and CD3-CD16(+) by flow cytometry. NK activity of the affected immediate family members (cases, n = 8) was significantly lower (P = 0.006, two-sided) than that of the concurrently tested normal controls. The results for unaffected family members were intermediate between these two groups, and the pairwise comparison of unaffected family members to either cases or controls showed no statistically significant difference (P = 0.29, two-sided). No differences were seen between the groups in the absolute number of CD3-CD56(+) or CD3-CD16(+) lymphocytes in the peripheral blood. Familial CFS was associated with persistently low NK activity, which was documented in 6/8 cases and in 4/12 unaffected family members. In the family with 5 of 6 siblings who had documented CFS, 2 of their offspring had pediatric malignancies. Low NK activity in this family may be a result of a genetically determined immunologic abnormality predisposing to CFS and cancer.     

Barriers to completion of healthcare proxy forms: a qualitative analysis of ethnic differences

To determine whether history of chronic lung disease (CLD) in children born at very low birthweight (VLBW) confers additional risk for impaired health, growth, and neurodevelopment, 17 VLBW children born in 1984 who had CLD (requiring supplemental oxygen more than 30 days after birth) in infancy and 28 VLBW children who did not have CLD were assessed at age 7 years. Assessments included a medical history, standard physical and neurological examinations, pulmonary-function tests, and tests of neuropsychological and psychoeducational functioning. Health status did not differ between the groups. In contrast, children with CLD did not perform as well in neuropsychological and psychoeducational assessments. Although CLD confers little added risk to health, it seems to add significantly to risks for poor school performance that are known to be associated with very low birthweight.     

A family study of autism: cognitive patterns and levels in parents and siblings

First-degree relatives of 99 autism probands and of 36 Down's syndrome controls were assessed with standardised tests of intellectual functioning, reading, and spelling. Higher mean verbal IQ scores, and discrepancies in favour of verbal scores, were characteristic of autism relatives. No consistent differences were found on performance scales, reading, and spelling tests. Among autism relatives, siblings affected with the broad phenotype of autism had significantly lower IQ scores and poorer reading and spelling performances than unaffected siblings. However, the small size of the cognitive difference and the lack of a distinctive cognitive profile indicates that standardised cognitive measures used in this study are unlikely to improve the operationalised definition of the broad phenotype of autism. The slightly superior verbal performance of relatives in the autism group might represent some form of heterozygote advantage.     

Adoption and Cognitive Development: A Meta-Analytic Comparison of Adopted and Nonadopted Children's IQ and School Performance.

This meta-analysis of 62 studies (N=17,767 adopted children) examined whether the cognitive development of adopted children differed from that of (a) children who remained in institutional care or in the birth family and (b) their current (environmental) nonadopted siblings or peers. Adopted children scored higher on IQ tests than their nonadopted siblings or peers who stayed behind, and their school performance was better. Adopted children did not differ from their nonadopted environmental peers or siblings in IQ, but their school performance and language abilities lagged behind, and more adopted children developed learning problems. Taken together, the meta-analyses document the positive impact of adoption on the children's cognitive development and their remarkably normal cognitive competence but delayed school performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)