Offspring IQ Research Articles

Cognitive Function in Adolescence: Testing for Interactions Between Breast-Feeding and FADS2 Polymorphisms

Breast-fed C-allele carriers of the rs174575 single nucleotide polymorphism in the fatty acyl desaturase 2 (FADS2) gene have been reported to show a 6.4 to 7 IQ point advantage over formula-fed C-allele carriers, with no effect of breast-feeding in GG carriers. An Australian sample was examined to determine if an interaction between breast-feeding and the rs174575 single nucleotide polymorphism had any effect on IQ. This hypothesis was tested in more than 700 families of adolescent twins assessed for IQ and breast-feeding, birth weight, and FADS2 polymorphisms, and parental socioeconomic status and education, and maternal FADS2 status. No significant evidence for a moderating effect on IQ of rs174575 C-carrier status and breast-feeding was found, and there no effects of maternal FADS2 status on offspring IQ. In addition, no main effects of any FADS2 polymorphisms on IQ were found when the genotype was kept as two-homozygote and one-heterozygote categories and indeed no evidence for effects of breast-feeding on IQ scores after controlling for parental socioeconomic status and education. The investigation was extended to two additional FADS2 polymorphisms (rs1535 and rs174583), but again, although these polymorphisms code alleles affecting fatty acid metabolism, no main or interaction effects were found on IQ. These results support the view that apparent effects of breast-feeding on IQ reflect differential likelihood of breast-feeding as a function of parental education and did not support the predicted interaction effect of FADS2 and breast-feeding on IQ.

Effect of birth weight, maternal education and prenatal smoking on offspring intelligence at school age

To examine the combined effect of birth weight, mothers’ education and prenatal smoking on psychometrically measured intelligence at school age 1,822 children born in 1992–1999 and attending the first six grades from 45 schools representing all of the fifteen Estonian counties with information on birth weight, gestational age and mother's age, marital status, education, parity and smoking in pregnancy, and intelligence tests were studied. The scores of Raven's Standard Progressive Matrices were related to the birth weight: in the normal range of birth weight (≥ 2500 g) every 500 g increase in birth weight was accompanied by around 0.7-point increase in IQ scores. A strong association between birth weight and IQ remained even if gestational age and mother's age, marital status, education, place of residence, parity and smoking during pregnancy have been taken into account. Maternal prenatal smoking was accompanied by a 3.3-point deficit in children's intellectual abilities. Marriage and mother's education had an independent positive correlation with offspring intelligence. We concluded that the statistical effect of birth weight, maternal education and smoking in pregnancy on offspring's IQ scores was remarkable and remained even if other factors have been taken into account.

The cost-effectiveness of universal screening in pregnancy for subclinical hypothyroidism

The purpose of this study was to determine whether routine screening for subclinical hypothyroidism during pregnancy would be cost-effective. We developed a decision analysis model to compare the cost-effectiveness of 2 screening strategies during pregnancy for subclinical hypothyroidism: (1) no routine screening of serum thyroid-stimulating hormone (TSH) levels (standard) and (2) routine screening of TSH levels. In the latter, women with subclinical hypothyroidism received thyroid hormone replacement. We assumed that thyroid hormone replacement could reduce the incidence of an offspring IQ < 85 for pregnancies with subclinical hypothyroidism. The main outcome measure was marginal cost per quality-adjusted life year (QALY) gained. Our model predicts that universal screening is the dominant strategy. For every 100,000 pregnant women who were screened, $8,356,383 are saved, and 589.3 QALYs are gained. When subclinical hypothyroidism prevalence is reduced to 0.25%, screening remains cost-effective at $21,664/QALY gained. Screening for subclinical hypothyroidism in pregnancy will be a cost-effective strategy under a wide range of circumstances.

Why do some dads get more involved than others? Evidence from a large British cohort

Previous studies in developed-world populations have found that fathers become more involved with their sons than with their daughters and become more involved with their children if they are of high socioeconomic status (SES) than if they are of low SES. This paper addresses the idea proposed by Kaplan et al. that this pattern arises because high-SES fathers and fathers of sons can make more difference to offspring outcomes. Using a large longitudinal British dataset, I show that paternal involvement in childhood has positive associations with offspring IQ at age 11, and offspring social mobility by age 42, though not with numbers of grandchildren. For IQ, there is an interaction between father's SES and his level of involvement, with high-SES fathers making more difference to the child's IQ by their investment than low-SES fathers do. The effects of paternal investment on the IQ and social mobility of sons and daughters were the same. Results are discussed with regard to the evolved psychology and social patterning of paternal behaviour in humans.

Association between offspring intelligence and parental mortality: a population-based cohort study of one million Swedish men and their parents

Background:An inverse association of IQ with mortality has been observed in previous studies. Analyses of associations between offspring’s IQ and parental mortality in biological and non-biological family relations may shed...

Memory deficits in children with and at risk for anxiety disorders

There are limited data on the neurocognitive correlates of childhood anxiety disorders. The objective of this study was to examine whether visual and verbal memory deficits of nonemotional stimuli are (1) a shared feature of three common childhood anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) or whether these deficits are restricted to specific anxiety disorders, and (2) present in offspring who possess at least one of the following established risk factors for anxiety disorders, parental history of panic disorder (PD), or major depressive disorder (MDD). One hundred and sixty offspring, ages 9-20 years, were recruited from parents with lifetime diagnoses of PD, MDD, PD plus MDD, or neither illness. Different clinicians blindly administered semistructured diagnostic interviews to offspring and parents. Verbal and visual memory subtests of the Wide Range Assessment of Memory and Learning were administered to offspring. The results showed that offspring with ongoing social phobia demonstrated reduced visual but not verbal memory scores compared to those without social phobia when controlling for offspring IQ, separation anxiety disorder, and generalized anxiety disorder. No other offspring anxiety disorder predicted memory performance. Neither parental PD nor parental MDD was associated with offspring memory performance. These findings are relevant to understanding the phenomenology of childhood anxiety disorders and may provide insights into the neural circuits underlying these disorders.

Maternal smoking during pregnancy and offspring IQ

Breslau et al. 1 report that a strong association between maternal smoking during pregnancy and the IQ of the offspring is eliminated by adjustment for various maternal characteristics. The final model (model 4 in tables 5 and 6) includes low birthweight as one of the characteristics adjusted for. Since maternal smoking during pregnancy may affect the prevalence of low birthweight, inclusion of low birthweight in the model may be regarded as possible over adjustment. It would be interesting to know whether the main conclusion would still remain if adjustment was made only for maternal IQ, education, and urban/rural residence and not for low birthweight.

Maternal smoking during pregnancy and offspring IQ

Maternal smoking in pregnancy lowers birthweight. It is unclear, however, whether smoking during pregnancy lowers offspring IQ, and, if it does, whether it is through the smoking effect on fetal growth. Representative samples of low birthweight (<2500 g) and normal birthweight children born in 1983-85 from inner-city and suburban communities in southeast Michigan, USA were assessed at ages 6, 11, and 17, using Wechsler intelligence tests. Smoking during pregnancy was ascertained from mothers at the first assessment; and smoking at any time was ascertained at the first and second assessment. Generalized estimating equation models were used, with children's IQ at all three assessments as outcomes (n = 798). Without adjustment, offspring of mothers who smoked during pregnancy scored 6.8 IQ points lower than offspring of mothers who never smoked, on average. Low birthweight children scored 5.4 IQ points lower than normal birthweight children, on average. The statistical association of maternal smoking with offspring IQ was confounded by maternal characteristics, chiefly, maternal cognitive ability as measured by IQ and education; adjustment for these factors eliminated the association. By contrast, adjustment for maternal IQ and education as well as smoking during pregnancy had a negligible effect on the low birthweight-related IQ deficit. Low birthweight did not mediate the association of smoking and lowered IQ in offspring. Maternal smoking during pregnancy is a proxy for a matrix of vulnerabilities for adverse child cognitive development and has no direct causal effect on child's IQ. The relationship of low birthweight and IQ is independent of maternal smoking and maternal cognitive abilities.

Paternal age and intelligence: implications for age-related genomic changes in male germ cells

A robust association between advancing paternal age and schizophrenia risk is reported, and genetic changes in the germ cells of older men are presumed to underlie the effect. If that is so, then the pathway may include effects on cognition, as those with premorbid schizophrenia are reported to have lower intelligence. There are also substantial genetic influences on intelligence, so de novo genetic events in male germ cells, which accompany advancing paternal age, may plausibly influence offspring intelligence. An association of paternal age with IQ in healthy adolescents may illuminate the mechanisms that link it to schizophrenia. We examined the association of paternal age and IQ scores using the Israeli Army Board data on 44 175 individuals from a richly described birth cohort, along with maternal age and other potential modifiers. A significant inverted U-shaped relationship was observed between paternal age and IQ scores, which was independent from a similar association of IQ scores with maternal age. These relationships were not significantly attenuated by controlling for multiple possible confounding factors, including the other parent's age, parental education, social class, sex and birth order, birth weight and birth complications. Overall, parental age accounted for approximately 2% of the total variance in IQ scores, with later paternal age lowering non-verbal IQ scores more than verbal IQ scores. We found independent effects of maternal and paternal age on offspring IQ scores. The paternal age effect may be explained by de novo mutations or abnormal methylation of paternally imprinted genes, whereas maternal age may affect fetal neurodevelopment through age-related alterations in the in-utero environment. The influence of late paternal age to modify non-verbal IQ may be related to the pathways that increase the risk for schizophrenia in the offspring of older fathers.

Impact of the Phenylalanine Hydroxylase Gene on Maternal Phenylketonuria Outcome

The aim of the present study was to examine to what extent maternal and offspring phenylalanine hydroxylase (PAH) genotypes in conjunction with maternal IQ and dietary control during pregnancy are related to cognitive development in offspring of women with phenylketonuria (PKU). PAH gene mutations were determined in 196 maternal PKU subjects and their offspring. The women were grouped according to PAH genotype, which predicts the metabolic phenotype (severe PKU, mild PKU, and mild hyperphenylalaninemia [MHP]). IQ was determined in both the mothers (Wechsler Adult Intelligence Scale-Revised at >18 years) and their children (Wechsler Intelligence Scale for Children-Revised at > or = 6-7 years of age). According to PAH genotypes, 62% of the women exhibited severe PKU, 19% exhibited mild PKU, and 19% exhibited MHP. Maternal IQ increased, and the assigned phenylalanine (Phe) levels decreased with decreasing severity of PAH genotype. In offspring of mild maternal PKU, multiple regression analysis showed offspring IQ to be significantly related to maternal IQ but not to Phe exposure during pregnancy, which was <750 micromol/L in all cases of mild PKU. In offspring of mothers with severe PKU and average Phe exposure during pregnancy of 360 to 750 micromol/L, multiple regression analysis revealed both maternal IQ and Phe exposure to be significant predictors of offspring IQ. When average Phe exposure was <360 micromol/L, cognitive development was normal (mean IQ: 105), whereas an average Phe exposure of >750 micromol/L severely depressed offspring IQ (mean IQ: 56) in this group regardless of maternal IQ. It could not be documented that the offspring PAH genotype affects cognitive development. Female individuals with severe PKU should be offered a diet for a lifetime. If good metabolic control is established, then women with PKU will have children with IQ scores that are not influenced by their disease.

Pregnancy Experiences in the Woman With Mild Hyperphenylalaninemia

A major issue in maternal phenylketonuria (MPKU) has been whether maternal non-PKU mild hyperphenylalaninemia (MHP) is teratogenic. Such untreated pregnancies and their outcomes are presented on this report. Enrolled pregnancies in which the untreated prepregnancy assigned phenylalanine level (APL) was no more than 600 micro mol/L were included in the Maternal PKU Collaborative Study and were followed according to protocol. Forty-eight enrolled women with non-PKU MHP had mean APL 408 +/- 114 micromol/L. They had a total of 58 pregnancies that resulted in live births. Fifty were untreated. Maternal phenylalanine (Phe) levels in the untreated pregnancies decreased during pregnancy for average Phe exposure of 270 +/- 84 micromol/L, virtually identical to the level of 269 +/- 136 micromol/L in the 8 treated pregnancies. Birth measurements in the 50 offspring from untreated pregnancies were within normal limits with z scores of -0.25 for weight, 0.28 for length, and -0.63 for head circumference, although birth head circumference was negatively correlated with maternal APL (r = -0.30). Only 1 offspring had congenital heart disease. Offspring IQ was 102 +/- 15 compared with 96 +/- 14 in the mothers with untreated pregnancies and with 109 +/- 21 in control offspring. Maternal non-PKU MHP no more than 600 micromol/L does not require dietary therapy. The naturally lower Phe level during pregnancy seems to protect against teratogenesis.

Cognitive and Behavioral Development in Maternal Phenylketonuria Offspring

To assess cognitive and behavioral outcome in treated maternal phenylketonuria (PKU) offspring. In this prospective, longitudinal study, 228 children who were born to mothers with treated PKU or untreated mild hyperphenylalaninemia were compared with 70 control subjects at 7 years of age. Offspring cognitive outcome negatively correlated with the number of gestational weeks that elapsed until maternal metabolic control was achieved (r = -0.61). Behavioral outcome was similarly affected. Postnatal measurement of stimulation in the home was also related to offspring IQ. Children who are born to mothers who have PKU and attain metabolic control before or very early in pregnancy seem to begin life with undiminished potential. Delay in attainment of maternal metabolic control is associated with declines in offspring developmental outcome. The postnatal environment also significantly affects outcome. Interventions to improve dietary compliance before and throughout pregnancy as well as interventions to improve the postnatal home environment may reduce the risks associated with maternal PKU.

Maternal phenylketonuria in Western Australia: pregnancy outcomes and developmental outcomes in offspring.

To examine the outcomes of phenylketonuric (PKU) pregnancies in Western Australia including birth characteristics and cognitive and behavioural outcomes in offspring. A cross-sectional study of women and their offspring who were identified from the Western Australian Maternal PKU Program (WAMPKUP) from 1991 to 2000 was carried out. Cognitive assessments (K-BIT or Griffiths scales) were conducted on women and their children, and behavioural assessments (CBCL) were conducted on the children. Thirty pregnancies by nine women were registered on the WAMPKUP between 1991 and 2000. There were 16 live births, with one preterm delivery at 32 weeks. There were no congenital abnormalities. Five of the nine mothers and their nine children (aged 18 months-10 years) participated in developmental assessments. A linear relationship was shown between lower maternal IQ scores and later attainment of metabolic control in pregnancy (rs = -0.828; P = 0.01). There was significant correlation between lower offspring IQ scores and later attainment of metabolic control in pregnancy (rs = -0.734; P = 0.02). Correlation between maternal and offspring cognitive scores was not significant. Four of nine (44%) children rated in the clinical range for behavioural problems. Compared to children with no behavioural difficulties, these children had lower cognitive abilities (P = 0.05) and maternal metabolic control during pregnancy was poor (P = 0.05). Poor metabolic control in pregnancy is associated with poorer cognitive outcomes and increased behavioural difficulties in offspring of mothers with PKU. The results have implications for the implementation of appropriate dietary measures before conception in PKU pregnancies, and indicate a need for the establishment of multidisciplinary teams to follow up individuals with PKU to communicate the importance of pregnancy planning, to manage PKU pregnancies, and to follow up the offspring.

A longitudinal investigation of social causation and social selection processes involved in the association between socioeconomic status and psychiatric disorders.

Social causation theory and social selection theory have been put forth to explain the finding that low socioeconomic status (SES) is associated with risk for psychiatric disorders. The predictions of both theories were investigated using data from a community-based longitudinal study. Psychosocial interviews were administered to 736 families from 2 counties in New York State in 1975, 1983, 1985-1986, and 1991-1993. Results indicated that (a) low family SES was associated with risk for offspring anxiety, depressive, disruptive, and personality disorders after offspring IQ and parental psychopathology were controlled, and (b) offspring disruptive and substance use disorders were associated with risk for poor educational attainment after offspring IQ and parental psychopathology were controlled. These findings indicate that social causation and social selection processes vary in importance among different categories of psychiatric disorders.

Maternal non-phenylketonuric mild hyperphenylalaninemia.

Unlike maternal phenylketonuria (PKU) which produces severe birth defects when untreated during pregnancy, maternal non-PKU mild hyperphenylalaninemia (MHP) has a less severe impact but whether it is benign or may have long-term consequences for offspring has been unclear. From an international survey of maternal MHP we obtained information about 86 mothers (blood phenylalanine (Phe) 150-720 mumol/l), their 219 untreated pregnancies and 173 offspring. Spontaneous fetal loss and congenital anomalies were no more frequent than normally expected. Median Z-scores for birth length and birth head circumference and offspring IQ (100), however, were significantly lower for maternal Phe > 400 mumol/l than for maternal Phe < 400 mumol/l, in which the median offspring IQ was 108. Data on maternal MHP from the prospective Maternal PKU Collaborative Study (MPKUCS) are as yet incomplete but seem to be conforming to the general pattern of the international survey. We conclude that maternal blood Phe levels above 400 mumol/l in maternal MHP are associated with lower birth measurements and slightly lower offspring IQ. It would seem that dietary intervention to lower the maternal Phe levels to below 400 mumol/l might be indicated in maternal MHP pregnancies with the higher blood Phe levels.

Path analysis of IQ during infancy and early childhood and an index of the home environment in the Colorado Adoption Project

A parent-offspring adoption path model, which includes a measured index of the home environment, was formulated to assess the extent to which relationships between the environmental index and children's behavior are mediated by genetic and environmental influences of the parents. In addition to the direct effect of the home environment on children's behavior, three types of indirect effects mediated by parental phenotype are considered: a pure environmental effect, a pure genetic effect, and a combined environmental-genetic effect. To illustrate its application, the model was fitted to parental and offspring IQ data collected in the Colorado Adoption Project and an environmental index based on Caldwell and Bradley's (1978) Home Observation for Measurement of the Environment (HOME). Four sets of data, including the HOME index and offspring IQ measured longitudinally at 1, 2, 3, and 4 years of age, were analyzed. The results suggest that in infancy (ages 1 and 2), the HOME reveals a direct environmental effect on children's IQ as well as indirect effects mediated via parental IQ. Surprisingly, during early childhood (ages 3 and 4), the relationship between the HOME and children's IQ is due only to indirect parental mediation. Moreover, other than at year 1, the mediation is purely genetic.

The Safety of Aspartame-Reply

In Reply.— Drs Levy and Waisbren abandon the linear relationship between the IQ of offspring and maternal plasma phenylalanine concentration that they previously reported 1 ; this relationship was significant ( r = -.82; P 2 have analyzed these data by linear regression to demonstrate the 10.5-point drop in IQ of the baby for each 250-μmol/L increment in maternal blood phenylalanine level. The issue of whether these data demonstrate that the deleterious effects on brain function caused by hyperphenylalaninemia follow a linear or threshold pattern is as yet unsettled. The fundamental question is whether plasma concentrations on the order of 200 μmol/L have harmful effects on the human central nervous system. This is important now because normal people may achieve this concentration of blood phenylalanine through excessive of aspartame. Drs Levy and Waisbren indicate that the intake of 10 mg/kg of aspartame products represents ingestion of large amounts

The Safety of Aspartame

To the Editor.— In Letter to the Editor, Dr Pardridge 1 interpreted our data 2 on effects of maternal hyperphenylalaninemia on offspring IQ as indicating a 10.5-point drop in the IQ of babies born of mothers with 250-μmol/L increments in the blood phenylalanine This is an inaccurate interpretation of the data, as we have previously pointed out. 3 By categorizing the information in Fig 1 of our report according to the maternal plasma phenylalanine levels represented in our sample, we obtained the following mean IQ scores for offspring: This does not represent 10.5-point drop in IQ of offspring for each 250-μmol/L increment in the maternal plasma phenylalanine level. In fact, the mean IQ of 119 for offspring at maternal plasma phenylalanine levels of 200 to 300 μmol/L—which are higher than the plasma phenylalanine levels that normal individuals or those who carry the gene for phenylketonuria have even

Familiality estimates from restricted samples

In a recent paper here, Benbow, Zonderman, and Stanley (1983) report that the coefficient of regression of offspring IQ on parental IQ is much lower among the gifted than in the population at large. Thus, Benbow, Stanley, Kirk, and Zonderman conclude in a second paper, the gifted resemble their parents less than do people in general. In this paper, I show that this result is an artifact of the particular estimator of the regression coefficient employed by Bendoq, Zonderman, and Stanley. The leastsquares estimator, which they employ, is severely biased downward, if the sample on the dependent variable is restricted to the upper tail of the distribution, and this is precisely the nature of Benbow et al.'s sample. That is to say, in a bivariate normal distribution with constant regression coefficient, samples restricted to values of the dependent variable (here, child's IQ) above a certain value will always produce a lower regression coefficient than unrestricted samples drawn from the entire but same distribution. I introduce an unbiased estimator that can be calculated from the sample statistics reported in the Benbow, Zonderman, and Stanley article and find that the coefficient of regression of gifted child's IQ on parental IQ is, in fact, higher than the regression coefficients reported in the literature for unrestricted samples. That is, Benbow et al.'s data suggest that the gifted in fact resemble their parents more than do persons in general.

The Louisville Twin Study: Developmental Synchronies in Behavior

The Louisville Twin Study includes nearly 500 pairs of twins and their siblings who have participated in a longitudinal study of mental development, beginning in infancy and extending to adolescence. The results show that individual differences beginning in infancy and extending to adolescence. The results show that individual differences in intelligence progressively stabilized by school age, and each child followed a distinctive pattern of spurts and lags in mental development. Monozygotic twins became increasingly concordant over ages and matched each other closely for developmental trends. By contrast, dizygotic twins regressed to an intermediate level of concordance, comparable with that found for siblings and parent-offspring sets. A comprehensive home assessment was performed to identify the home/family variables that contributed to mental development. The overall results pointed to a strong developmental thrust in the growth of intelligence, which was principally guided by an intrinsic genetic ground plan. Qualitative features of home and family did, however, add significantly to prediction of offspring IQ. The results are interpreted in the context of Waddington's developmental model, and some recent advances in neurobiology and genetics are surveyed for their implications for developmental behavior genetics.