Intolerance of loud sounds in childhood: Is there an intergenerational association with grandmaternal smoking in pregnancy?

Recent research using the Avon Longitudinal Study of Parents and Children (ALSPAC) demonstrated an association between maternal grandmother smoking in pregnancy and the autistic traits of impaired social communication and repetitive behaviour in granddaughters but not grandsons, but of paternal grandmother smoking and early development of myopia in the grandchild. Here we investigate whether grandmaternal smoking in pregnancy is associated with intolerance to loud sounds. ALSPAC collected information during the index pregnancy from the study parents on the smoking habits, social and other features of their own parents. Maternal report when the child was aged 6 and 13 included hating loud sounds; at age 11 the child was tested for volume preference for listening to music through headphones. Statistical analysis compared results for grandchildren in relation to whether a parent had been exposed in utero to maternal smoking, adjusted for their grandparents' social and demographic attributes. We hypothesised that there would be sex differences in the effects of grandmaternal prenatal smoking, based on previous intergenerational studies. For 6-year-old children maternal report of intolerance to loud noise was more likely in grandsons if the maternal grandmother had smoked [adjusted odds ratio (AOR) 1.27; 95% confidence interval (CI) 1.03,1.56; P = 0.025], but less likely in girls [AOR 0.82; 95%CI 0.63,1.07] Pinteraction <0.05. If the paternal grandmother had smoked the grandchildren were less likely to be intolerant, especially girls. The objective measure of choice of volume for music through headphones showed that grandsons of both maternal and paternal smoking grandmothers were less likely to choose high volumes compared with granddaughters (P<0.05). In line with our prior hypothesis of sex differences, we showed that grandsons were more intolerant of loud sounds than granddaughters particularly at age 6, and this was confirmed by objective measures at age 11.

Grandchild's IQ is associated with grandparental environments prior to the birth of the parents.

Background. Despite convincing animal experiments demonstrating the potential for environmental exposures in one generation to have demonstrable effects generations later, there have been few relevant human studies. Those that have been undertaken have demonstrated associations, for example, between exposures such as nutrition and cigarette smoking in the grandparental generation and outcomes in grandchildren. We hypothesised that such transgenerational associations might be associated with the IQ of the grandchild, and that it would be likely that there would be differences in results between the sexes of the grandparents, parents, and children. Method. We used three-generational data from the Avon Longitudinal Study of Parents and Children (ALSPAC).  We incorporated environmental factors concerning grandparents (F0) and focussed on three exposures that we hypothesised may have independent transgenerational associations with the IQ of the grandchildren (F2): (i) UK Gross Domestic Product (GDP) at grandparental birth year; (ii) whether grandfather smoked; and (iii) whether the grandmother smoked in the relevant pregnancy. Potential confounders were ages of grandparents when the relevant parent was born, ethnic background, education level and social class of each grandparent. Results. After adjustment, all three target exposures had specific associations with measures of IQ in the grandchild. Paternal grandfather smoking was associated with reduced total IQ at 15 years; maternal grandfather smoking with reduced performance IQ at 8 years and reduced total IQ at 15.  Paternal grandmother smoking in pregnancy was associated with reduced performance IQ at 8, especially in grandsons. GDP at grandparents' birth produced independent associations of reduced IQ with higher GDP; this was particularly true of paternal grandmothers. Conclusions. These results are complex and need to be tested in other datasets. They highlight the need to consider possible transgenerational associations in studying developmental variation in populations.

Author Correction: Grandmothers' smoking in pregnancy is associated with a reduced prevalence of early-onset myopia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Grandmothers' smoking in pregnancy is associated with a reduced prevalence of early-onset myopia.

Myopia (near sightedness) is the most common vision disorder resulting in visual impairment worldwide. We tested the hypothesis that intergenerational, non-genetic heritable effects influence refractive development, using grandparental prenatal smoking as a candidate exposure. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we found that the prevalence of myopia at age 7 was lower if the paternal grandmother had smoked in pregnancy, an association primarily found among grandsons compared to granddaughters. There was a weaker, non-sex-specific, reduction in the prevalence of myopia at age 7 if the maternal grandmother had smoked in pregnancy. For children who became myopic later (between 7 and 15 years of age) there were no associations with either grandmother smoking. Differences between early and late-onset myopia were confirmed with DNA methylation patterns: there were very distinct and strong associations with methylation for early-onset but not later-onset myopia.

Investigating Possible Trans/Intergenerational Associations With Obesity in Young Adults Using an Exposome Approach.

Animal experiments demonstrate ways in which an exposure in one generation can be reflected in a variety of outcomes in later generations. In parallel human observational studies have shown associations between grandparental and parental exposures to cigarette smoking and/or nutrition and growth and survival of the grandchild. These studies have controlled for just a few confounders selected ad hoc. Here we use an exposome approach (using all available measures of exposure) to determine trans/inter-generational factors that may be important in studying environmental factors associated with fat mass in young human adults. The study takes advantage of the rich data available in the Avon Longitudinal Study of Parents and Children (ALSPAC). We test associations with features of grandparents (G0) and the childhood of the parents (G1) of 24-year olds (G2). We hypothesized that intergenerational associations would be revealed, particularly with exposure to cigarette smoke, and that these would vary with the sexes of all three generations. The study exposome analyzed 172 exposures to the maternal line and 182 to the paternal line. A series of stepwise regression analyses reduced the initial 40 unadjusted factors (P < 0.05) to eight independent features on the maternal line, and of 26 on the paternal line to five. We found strong associations between the father starting to smoke cigarettes regularly before age 11 and increased fat mass in his adult children (unadjusted = +7.82 [95% CI +2.75, +12.90] Kg; adjusted = +11.22 [+5.23, +17.22] Kg); this association was stronger in male offspring. In addition, when the paternal grandmother had smoked in pregnancy her adult granddaughters, but not grandsons had elevated mean fat mass (interaction with sex after adjustment, P = 0.001). The exposome technique identified other factors that were independently associated with fat mass in young adults. These may be useful in identifying appropriate confounders in other more proximal analyses, but also may identify features that may be on epigenetic pathways leading to increased fat mass in subsequent generations. We acknowledge that the results need to be replicated in other cohorts and encourage further linkage of outcomes with previous generational exposures, particularly along the paternal line.

Maternal Prenatal External Locus of Control and Reduced Mathematical and Science Abilities in Their Offspring: A Longitudinal Birth Cohort Study.

A personality scale that identifies individuals' general attitude to what happens to them as largely a matter of luck or fate or of powerful others (externality) or whether they feel they can influence the consequences (internality) is known as locus of control (LOC). A continuous scale can distinguish those who are more external from those who are more internal. Lower scholastic achievement is associated with externality and higher achievement with internality, but little is known about the association of parental LOC on children's academic performance. Data collected within the Avon Longitudinal Study of Parents and Children (ALSPAC) are analyzed to assess associations between mothers' LOC orientation, measured during pregnancy, and their children's abilities in mathematics and science reasoning. We found that maternal external LOC is associated with lower scores for her child assessed by tests measuring mental arithmetic as well as understanding of mathematical and scientific concepts. Additionally, we determined the extent to which three separate sets of factors previously found to positively influence the developing child's ability mediate these findings: (a) perinatal and infant exposures, such as prenatal smoking, binge drinking, consumption of oily fish, and postnatal breast feeding; (b) parenting attitudes and strategies; and (c) the interface of the parents with their child's school. The three factors identify at least 50% of the mechanism by which maternal externality is associated with poor academic outcomes in her child and may be candidates for further investigation as possible intervention targets.

The relationship between parental locus of control and adolescent obesity: a longitudinal pre-birth cohort.

OBJECTIVES: To investigate whether parental external locus of control (ELOC) measured in pregnancy is related to obesity in their adolescent offspring and whether the child's own ELOC measured at age 8 contributes. To determine whether associations are due to types of behaviour used by externally oriented participants. SUBJECTS/METHODS: Longitudinal pre-birth cohort study (Avon Longitudinal Study of Parents & Children (ALSPAC)) set in south-west England. Families whose adolescent offspring had their fat mass measured using DXA scans at any of ages 9, 11, 13, 15 or 17 (range, n = 7329 at 9 to n = 4850 at 17). The primary outcome measures were mean fat mass, and obesity measured as ≥85th centile of fat mass at each age. RESULTS: We found that parent and child externality was associated with greater fat mass [e.g., mean difference at age 15 associated with maternal ELOC was 1.70 kg (+1.17, +2.24), paternal ELOC 1.49 kg (+0.89, +2.09) and child's ELOC 1.50 kg (+0.93, +2.06) (P < 0.0001)]. Further analyses showed that factors associated with parent behaviour such as smoking in pregnancy, failure to breast feed, and early introduction of solids accounted for a third of the excess fat mass associated with maternal externality, whereas aspects of diet and energetic activity in later childhood were not. Further analyses demonstrated that the child's own ELOC only became independently important for adolescent obesity from age 13, whereas the mothers' and to a lesser extent the fathers' ELOC were associated at each age. CONCLUSIONS: There is increased interest in determining factors that may be involved in the aetiology and maintenance of excessive weight in adolescents. We demonstrate that parental locus of control is a promising candidate. We suggest interventions to change parents' locus of control towards internality in pregnancy might have long-term preventative benefits on the likelihood of obesity in the offspring.

Events associated with stability and change in adult locus of control orientation over a six-year period.

Although locus of control (LOC) has been the focus of thousands of studies we know little about how or if it changes over time and what is associated with change. Our lack of knowledge stems in part from the past use of cross-sectional and not longitudinal methodologies to study small numbers of participants from non-representative populations. The purpose of the present study was to use a longitudinal design with a large representative population to provide relevant information concerning the stability and change of adult LOC. Before the birth of their child, and again six years later, mothers and their partners participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) completed LOC tests and structured stressful events surveys. Analyses revealed that stresses experienced in relationships with spouses, friends and family, financial stability and job security, and illness/smoking were associated with changes in LOC. Results suggest substantial variation of LOC within spousal/parent dyads and moderate stability of LOC over time for both men and women. Stressors associated with change in LOC may be possible candidates when considering interventions to modify LOC expectancies.

Are the early childhood antecedents of men's external locus of control similar to those of their female partners?

Background: The concept of locus of control of reinforcement was introduced by Julian Rotter and has been the focus of intense research for nearly half a century.  Surprisingly little research has been directed at clarifying antecedents of locus of control (LOC) orientations in adult men apart from a few small studies. We previously identified a number of independent antecedents associated with women's LOC, including features of their parents and early childhood. This raised the question as to whether these factors were also associated with the development of LOC in men. Methods: To identify antecedents of LOC orientations in a representative population of women we previously analysed information concerning characteristics of their parents and their own childhood experiences using pregnant women taking part in the Avon Longitudinal Study of Parents and Children (ALSPAC).  Here we use the same design to determine whether their male partners have similar antecedents of LOC orientation. As previously, we use a hypothesis-free exposome technique using all available information on the parents and childhood of the individuals. Results: We show that men had many of the same antecedent characteristics as the women - in particular, their mother's year of birth and father's social group, being exposed to cigarette smoke prenatally, starting to smoke regularly before the age of 11, and having a friend die were all associated with being external. Associations of internality common to both were warm maternal care, being breast fed, being born in an area other than that where they currently live, attending boarding school and having a parent admitted to hospital. Conclusions: In general, the antecedents of male external and internal personalities have many similarities to those of women, thus providing some features to inform the possible theoretical background as to how LOC might develop over time.

Grand-maternal smoking in pregnancy and grandchild's autistic traits and diagnosed autism.

Although there is considerable research into the genetic background of autism spectrum disorders, environmental factors are likely to contribute to the variation in prevalence over time. Rodent experiments indicate that environmental exposures can have effects on subsequent generations, and human studies indicate that parental prenatal exposures may play a part in developmental variation. Here we use the Avon Longitudinal Study of Parents and Children (ALSPAC) to test the hypothesis that if the mother or father (F1) had been exposed to their own mother's (F0) smoking during pregnancy, the offspring (F2) would be at increased risk of autism. We find an association between maternal grandmother smoking in pregnancy and grand daughters having adverse scores in Social Communication and Repetitive Behaviour measures that are independently predictive of diagnosed autism. In line with this, we show an association with actual diagnosis of autism in her grandchildren. Paternal grandmothers smoking in pregnancy showed no associations.