Offspring Intelligence Research Articles

Maternal hypothyroxinemia and effects on cognitive functioning in childhood: how and why?

Exposure to maternal hypothyroxinemia during pregnancy, which is characterized by low free T4 but normal thyroid-stimulating hormone (TSH) levels, can negatively affect the foetus. This review provides an overview of present findings concerning the association between maternal hypothyroxinemia during pregnancy and childhood cognitive functioning. Possible causes of maternal hypothyroxinemia and potential mechanisms underlying this association are also discussed. Clinical and epidemiological studies suggest that maternal hypothyroxinemia in the first half of pregnancy but not later in pregnancy impairs cognitive development in infancy and childhood. Animal models confirm that the first half of pregnancy may constitute a sensitive period in which maternal hypothyroxinemia alters neurogenesis and causes neuronal migration errors in the developing foetal brain. However, observational studies in humans cannot demonstrate causality of the association between hypothyroxinemia and neurodevelopment. In the only completed randomized trial of antenatal thyroid screening and subsequent levothyroxine treatment of mild maternal subclinical thyroid dysfunction, including hypothyroxinemia, the interventions did not affect offspring intelligence quotient (IQ). More randomized trials are needed investigating whether screening for hypothyroxinemia and its treatment earlier in the first trimester of pregnancy can improve child cognitive functioning or prevent neurodevelopmental changes. Long-term observational studies should identify molecular, neuroanatomical and neurophysiological factors involved in the association between maternal hypothyroxinemia and offspring cognitive functioning. Information on such mechanisms can be used for the development of innovative prevention and intervention studies that address maternal hypothyroxinemia and its potential consequences.

High FSH decreases the developmental potential of mouse oocytes and resulting fertilized embryos, but does not influence offspring physiology and behavior in vitro or in vivo

Do different concentrations of FSH in the assisted reproductive technology (ART) procedure in vitro or in vivo affect the developmental competence of oocytes, the embryos and the offspring conceived from these embryos? Improper FSH treatment (200 IU/l in vitro, 10 IU/ml in vivo and 200 IU/ml in vivo) impairs the development competence of oocyte and embryo, but does not influence offspring physiology and behavior. Exogenous FSH has been widely used in the field of ART. However, the effects of different concentrations of FSH on the developmental competence of oocytes, embryos and the offspring conceived from these embryos, are still unknown. In a prospective study, a total of 45 mice at 8-10 weeks of age were primed in vivo with different dosages of FSH (9 mice in the 10 IU/ml, 10 mice in the 50 IU/ml, 10 mice in the 100 IU/ml and 16 mice in the 200 IU/ml groups). Fresh MII oocytes were retrieved from ovaries: this was designated as in vivo group. Thirty six mice at 8-10 weeks of age were sacrificed by cervical dislocation to obtain ovaries without FSH treatment (9 mice in the 0 IU/l, 9 mice in the 50 IU/l, 8 mice in the 100 IU/l and 10 mice in the 200 IU/l groups), and then the immature oocytes were collected from these ovaries and cultured in vitro matured medium supplemented with 0, 50, 100 and 200 IU/l FSH: this was designated as in vitro group. Spindle assembly of matured MII oocytes was stained via an immunofluorescence method and the oocytes ratio of normal spindle was analyzed. The developmental competence of the resulting fertilized embryos in the pre- and post-implantation stages was examined in in vitro and in vivo groups. Furthermore, physiological index, including reproductive potential and body weight, of the offspring was investigated by mating experiments and behavior index, including learning, memory, probing and intelligence, was tested by Morris water maze in in vitro and in vivo groups. In the in vitro groups, the oocyte maturation competence, normal spindle assembly, blastocyst formation and implantation, as well as viable pup production were all impaired in the group treated with 200 IU/l FSH (P < 0.05). No differences were observed among the other three groups (P > 0.05). In the in vivo groups, 10 IU/ml FSH but not 200 IU/ml treatment influenced blastocyst formation and viable pup production (P < 0.05), although the high proportion of spindle assembly abnormality was only observed in the 200 IU/ml FSH treatment group (P < 0.05). Furthermore, there were no significant differences in terms of physiological index (reproductive potential and body weight) and behavior index (learning, memory, probing and intelligence) in offspring from in vitro and in vivo groups (P > 0.05). The mouse model was used in this study. The results of the mouse follicle growth and oocyte development in responding to different concentrations of FSH are not 100% transferable to human, because of the physiological differences between mouse and human. The findings indicated that FSH application in the field of ART is safe to the resulted offspring, but it should be more carefully used for each women in ART cycles because the inappropriate FSH concentration would decrease the oocyte developmental competence. This work was partially supported by the Ministry of Science and Technology of China Grants (973 program; 2011CB944504), the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China (30825038), the National Natural Science Funds for Young Scholar (31000661) and by the Joint Research Fund for Overseas, Hong Kong and Marco Scholars (31128013/C120205). None of the authors has any conflicts of interest.

Associations of maternal weight gain in pregnancy with offspring cognition in childhood and adolescence: findings from the Avon Longitudinal Study of Parents and Children.

An association of gestational weight gain (GWG) with offspring cognition has been postulated. We used data from the Avon Longitudinal Study of Parents and Children, a United Kingdom prospective cohort (1990 through the present) with a median of 10 maternal weight measurements in pregnancy. These were used to allocate participants to 2009 Institute of Medicine weight-gain categories and in random effect linear spline models. Outcomes were School Entry Assessment score (age, 4 years; n = 5,832), standardized intelligence quotient assessed by Wechsler Intelligence Scale for Children (age, 8 years; n = 5,191), and school final-examination results (age, 16 years; n = 7,339). Offspring of women who gained less weight than recommended had a 0.075 standard deviation lower mean School Entry Assessment score (95% confidence interval: −0.127, −0.023) and were less likely to achieve adequate final-examination results (odds ratio = 0.88, 95% confidence interval: 0.78, 0.99) compared with offspring of women who gained as recommended. GWG in early pregnancy (defined as 0–18 weeks on the basis of a knot point at 18 weeks) and midpregnancy (defined as 18–28 weeks on the basis of knot points at 18 and 28 weeks) was positively associated with School Entry Assessment score and intelligence quotient. GWG in late pregnancy (defined as 28 weeks onward on the basis of a knot point at 28 weeks) was positively associated with offspring intelligence quotient and with increased odds of offspring achieving adequate final-examination results in mothers who were overweight prepregnancy. Findings support small positive associations between GWG and offspring cognitive development, which may have lasting effects on educational attainment up to age 16 years.

Paternal Age in Relation to Offspring Intelligence in the West of Scotland Twenty-07 Prospective Cohort Study

BackgroundThe adverse effects of advancing maternal age on offspring's health and development are well understood. Much less is known about the impact of paternal age.MethodsWe explored paternal age-offspring cognition associations in 772 participants from the West of Scotland Twenty-07 study. Offspring cognitive ability was assessed using Part 1 of the Alice Heim 4 (AH4) test of General Intelligence and by reaction time (RT).ResultsThere was no evidence of a parental age association with offspring RT. However, we observed an inverse U-shaped association between paternal age and offspring AH4 score with the lowest scores observed for the youngest and oldest fathers. Adjustment for parental education and socioeconomic status somewhat attenuated this association. Adjustment for number of, particularly older, siblings further reduced the scores of children of younger fathers and appeared to account for the lower offspring scores in the oldest paternal age group.ConclusionWe observed a paternal age association with AH4 but not RT, a measure of cognition largely independent of social and educational experiences. Factors such as parental education, socioeconomic status and number of, particularly older, siblings may play an important role in accounting for paternal age-AH4 associations. Future studies should include parental intelligence.

Effects of Tobacco Smoking in Pregnancy on Offspring Intelligence at the Age of 5

The aim of the study was to examine the effects of tobacco smoking in pregnancy on children's IQ at the age of 5. A prospective follow-up study was conducted on 1,782 women, and their offspring were sampled from the Danish National Birth Cohort. At 5 years of age, the children were tested with the Wechsler Preschool and Primary Scale of Intelligence-Revised. Parental education, maternal IQ, maternal alcohol consumption in pregnancy, the sex and age of the child, and tester were considered core confounders, but the full model also controlled for prenatal paternal smoking, maternal age and Bodymass Mass Index, parity, family/home environment, postnatal parental smoking, breast feeding, the child's health status, and indicators for hearing and vision impairments. Unadjusted analyses showed a statistically significant decrement of 4 points on full-scale IQ (FSIQ) associated with smoking 10+ cigarettes per day compared to nonsmoking. After adjustment for potential confounders, no significant effects of prenatal exposure to tobacco smoking were found. Considering the indisputable teratogenic effects of tobacco smoking, these findings should be interpreted with caution. Still, the results may indicate that previous studies that failed to control for important confounders, particularly maternal intelligence, may be subject to substantial residual confounding.

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.

Contrasting Effects of Maternal and Paternal Age on Offspring Intelligence

Both maternal and paternal ages are increasing in the developed world. The average age of mothers at time of childbirth has increased from 26.4 years in 1974 to 29.3 years in 2002, while the average age of fathers has increased from 29.2 years in 1980 to 32.1 years in 2002 [1]. This increase in the average parental age is most likely due to the societal trend for couples to delay starting a family for career or financial reasons. The concept of the female “biological clock” (the effect of increasing maternal age on reducing fertility) is well known and is a source of anxiety for many women [2]. In contrast, the consequences of increasing paternal age on fertility and other adverse reproductive outcomes are rarely discussed [3].

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...

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.

A dose‐response relationship between maternal smoking during late pregnancy and adult intelligence in male offspring

An association between maternal smoking during pregnancy and cognitive and behavioural development has been observed in several studies, but potential effects of maternal smoking on offspring adult intelligence have not been investigated. The objective of the present study was to investigate a potential association between maternal smoking during pregnancy and offspring intelligence in young adulthood. Adult intelligence was assessed at the mean age of 18.7 years by a military draft board intelligence test (Borge Priens Prove) for 3044 singleton males from the Copenhagen Perinatal Cohort with information regarding maternal smoking during the third trimester coded into five categories (about 50% of the mothers were smokers). The following potential confounders were included as covariates in multivariable analyses: parental social status and education, single mother status, mother's height and age, number of pregnancies, and gestational age. In separate analyses, birthweight and length were also included as covariates. Maternal cigarette smoking during the third trimester, adjusted for the seven covariates, showed a negative association with offspring adult intelligence (P=0.0001). The mean difference between the no-smoking and the heaviest smoking category amounted to 0.41 standard deviation, corresponding to an IQ difference of 6.2 points [95% confidence interval 0.14, 0.68]. The association remained significant when further adjusted for birthweight and length (P=0.007). Both unadjusted and adjusted means suggested a dose-response relationship between maternal smoking during pregnancy and offspring adult intelligence. When subjects with missing data were excluded, essentially the same results were obtained in the reduced sample (n=1829). These results suggest that smoking during pregnancy may have long-term negative consequences on offspring adult intelligence.

Relation of Prenatal Phenylalanine Exposure to Infant and Childhood Cognitive Outcomes: Results From the International Maternal PKU Collaborative Study

The primary aims of this study were to model the form of the relation between prenatal exposure to phenylalanine (Phe) and measures of offspring intellectual development and to estimate the developmental relations of maternal demographic, pregnancy-related, and perinatal variables on offspring intelligence during infancy and childhood. The participants were the 413 children and their mothers from the International Maternal PKU Collaborative Study. Results supported a nonlinear relation between prenatal Phe exposure and offspring cognitive outcomes, with damage to the developing fetus if average Phe levels are above approximately 360 micromol/L. Moreover, prenatal Phe exposure had a strong effect on offspring outcomes at 1 year of age and was the only one of the background, pregnancy-related, or perinatal variables to influence directly offspring outcomes at 2, 4, and 7 years of age. The present study was able to document the importance of prenatal exposure to Phe for predicting offspring cognitive outcomes in the presence of other predictors of these outcomes.

Correlations between Antepartum Maternal Metabolism and Intelligence of Offspring

It is not clear to what extent maternal metabolism during pregnancy affects the cognitive and behavioral function of the offspring by altering brain development in utero. To investigate this question, we correlated measures of metabolism in pregnant diabetic and nondiabetic women with the intellectual development of their offspring. The study included 223 pregnant women and their singleton offspring: 89 women had diabetes before pregnancy (pregestational diabetes mellitus), 99 had the onset of diabetes during pregnancy (gestational diabetes mellitus), and 35 had normal carbohydrate metabolism during their pregnancy. We correlated measures of maternal glucose and lipid metabolism (fasting plasma glucose levels, hemoglobin A1c levels, episodes of hypoglycemia, episodes of acetonuria, and plasma beta-hydroxybutyrate and free fatty acid levels) with two measures of intellectual development in the offspring--the mental development index of the Bayley Scales of Infant Development, given at the age of two years, and the Stanford--Binet Intelligence Scale, given at the ages of three, four, and five years and expressed as an average of the three scores. After correction for socioeconomic status, race or ethnic origin, and patient group, the children's mental-development-index scores at the age of two years correlated inversely with the mothers' third-trimester plasma beta-hydroxybutyrate levels (r = -0.21, P less than 0.01); the average Stanford-Binet scores correlated inversely with third-trimester plasma beta-hydroxybutyrate (r = -0.20, P less than 0.02) and free fatty acid (r = -0.27, P less than 0.002) levels. No other correlations were significant. Including various perinatal events (e.g., prematurity and acidemia) in the analyses did not alter the results. Maternal diabetes during pregnancy may affect behavioral and intellectual development in the offspring. The associations between gestational ketonemia in the mother and a lower IQ in the child warrant continued efforts to avoid ketoacidosis and accelerated starvation in all pregnant women.

Longitudinal, prospective evaluations of intelligence in children at risk.

Data are presented from the intellectual assessment of 153 children at two test periods in the St. Louis Risk Research Project. At phase I (1967-72) the Wechsler tests of intelligence were administered to offspring in families with one schizophrenic parent, one parent with affective disorder, one parent with schizoaffective disorder, one physically ill parent, or to offspring with two normal parents (mean age, 8 years). At phase II (1975-78) the intelligence of offspring was tested again at a mean age of 16 years. Differences between children as a function of parental diagnoses were assessed using a repeated measures analysis of covariance. The analyses yielded significant time effects. A time-by-parental-diagnosis effect was found for Verbal IQ, with children of parents with schizophrenia, affective disorder, or physical illness all showing a greater decrease in their scores at the second testing than offspring in the other groups. Offspring of psychotic mothers had lower IQ scores than those of psychotic fathers. Children of schizophrenics and children of schizoaffectives had the lowest stability in IQ scores from the first to the second testing.

The effects of teenaged motherhood and maternal age on offspring intelligence.

Abstract Causal models of the effects of maternal age on offspring intelligence were generated using three large data sets. The direct and indirect effects of two components of maternal age, teenage motherhood and linear maternal age, were investigated separately for white and black children. The intervening variables investigated as routes of indirect effect were family structure, parental education, parental employment, family income, and family size. The findings indicate that there are no direct effects of teenage maternity on offspring intelligence, and that the observed negative relationship is primarily attributable to parental education. In contrast, the overall effect of maternal age, while very small and positive, is primarily direct, that is, not mediated by any of the social or economic conditions included in the model. The consistency of these findings and the impact on children's intelligence of the other variables included in the model are demonstrated and discussed.

Intelligence and Family Size: Another Look

gence on fertility and of household size on offspring's intelligence remain the subject of public debate. Most recently, attention has centered on the decline in Scholastic Aptitude Test scores and the possible effects of the postwar baby boom. These concerns suggest that economists would do well to introduce intelligence into the household utility maximization model used to explain differential fertility. We attempt to do this here.

Congenital malformations and other reproductive hazards from environmental chemicals.

From a number of disasters which have already occurred throughout the world, it is known that the reproductive process in both animals and man may be severely affected by chemicals. The range of effects that might occur include not only foetal death or malformation, but also effects on the subsequent development, behaviour, intelligence and reproductive capacity of offspring which appear otherwise normal at birth. The special sensitivity of the foetus to some environmental carcinogens is also discussed. Some of the problems in screening for such effects in animals are mentioned along with the need for adequate monitoring programmes to detect reproductive toxicity both from industrial exposure to chemicals and from more general environmental exposure.

Prenatal progesterone II. Its role in the treatment of pre-eclamptic toxaemia and its effect on the offspring's intelligence: a reappraisal

Dalton's results concerning the beneficial effect of progesterone supplementation in preventing pre-eclamptic toxaemia [16] and in enhancing intellectual potential [17,18] were reappraised. We could find no evidence in the data that progesterone supplementation was any better at preventing preeclamptic toxaemia than treating the disorder symptomatically. Nor could we find any convincing evidence that excess progesterone enhances development at 1 yr of age, academic attainment at 9–10 yr of age, or success in school leaving examinations and improves the chances of continuing further full-time education after leaving school.

Measured intelligence in offspring of oral and nonoral contraceptive users

A study has been made of measures of intelligence of 210 children (5 to 8 years of age) born to mothers who used oral and nonoral contraceptives pregestationally. Ninety-six of these children were born to mothers who used oral contraceptives, and one hundred and fourteen were born to mothers who used vaginal contraceptive methods. The intelligence of the children was measured in the form of the full-scale I.Q. score by the Wechsler Intelligence Scale for Children (WISC) adapted and normalized for Puerto Rico by the Puerto Rico Department of Education. A three-factor analysis of variance was performed on the dota collected for comparison of the two groups. It was observed that there was no significant difference between the average I.Q. scores of children born to mothers using oral contraceptives and those born to the mothers using nonoral contraceptives. The average I.Q. in children of the oral contraceptive group was 85.04 and that in children of the nonoral contraceptive group was 85.54. Distributions for both groups were also found to be similar. No significant differences between means were observed for sex, age, and interactions with the exception of the age and sex interaction, where, again, no specific, meaningful trend could be established. The average I.Q. in the sample fell very close to the center of the “normal” range of the WISC, Puerto Rican adaptation. The results of the study do not offer any evidence as to the effect of the use of oral contraceptives on the intelligence measure (by the WISC) of the offspring born to mothers using them pregestationally. The children under study, on an average, are of “normal” intelligence as measured by the Puerto Rican intelligence standards.

The Effect of Mothers' Diets on the Intelligence of Offspring. A Study of the Influence of Vitamin Supplementation of the Diets of Pregnant and Lactating Women on the Intelligence of Their Childern

The Effect of Mothers' Diets on the Intelligence of Offspring. A Study of the Influence of Vitamin Supplementation of the Diets of Pregnant and Lactating Women on the Intelligence of Their Childern

Social Environment as a Modifying Factor in the Correlation between Maternal Age and Intelligence of Offspring

Social Environment as a Modifying Factor in the Correlation between Maternal Age and Intelligence of Offspring