Quality of relationships in mothers and their partners in the Avon Longitudinal Study of Parents and Children.

Quality of relationship between partners is associated with a wide range of physical and psychological outcomes like anxiety and depression. There are relatively few longitudinal studies with detailed and repeated measures for quality of relationship, particularly in both partners. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a large birth cohort study in the UK with five post-partum repeated measures of quality of relationship between mothers and their partners assessed using the Intimate Bond Measure (IBM). The Measure includes two subscales named "Care" and "Control". These were measured at 2.75, 6, 9, 12, and 18 years post-partum (baseline N for mothers: 8675; baseline N for partners: 5499). The aims of this data note are to provide a comprehensive overview on the existing IBM data in ALSPAC and to describe both its strengths and limitations for future users. The internal consistency of the subscales were high (Cronbach's alpha 0.95 and 0.88 for the Care and Control subscales) in both mothers and their partners at the baseline. In the Care subscale, all 12 items were highly correlated with the overall score (r>0.62) at the baseline, but in the Control subscale there were three items that had relatively low correlations with the total subscale (r<0.46). This should be taken into account in future research. The longitudinal nature of this data on both mothers and partners will enable detailed explorations of the causes and consequences of differences in quality of relationship.

A history of asthma may be associated with grandparents' exposures to stress and cigarette smoking.

Introduction: Within human epidemiological studies, associations have been demonstrated between grandparental exposures during childhood and grandchildren's outcomes. A few studies have assessed whether asthma has ancestral associations with exposure to cigarette smoking, but results have been mixed so far. Material and methods: In this study we used four generations: (F0 great-grandparents, F1 grandparents, F2 parents, F3 study children) of the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine whether there is evidence of associations between asthma in generations F2 or F3 and exposures to severe trauma in childhood and/or active cigarette smoking during the adolescence of grandmothers and grandfathers in generations F0 and F1 respectively, or of a history of a F0 or F1 grandmother smoking during pregnancy. Results: We have shown that: a) stress exemplified by the death of a F1 grandparent's parent during the grandparents' childhood was associated with increased risk of asthma in generation F3, especially if the grandparent involved was the paternal grandmother; b) if the grandparents of generations F0 or F1 smoked during adolescence (i.e. < 17 years), their grandchildren in generations F2 and F3 were more likely to have a history of asthma; c) paternal F1 grandmother's smoking in pregnancy was associated with her F3 grandchild's asthma at age 7; d) There were differences between the results for the grandsons and granddaughters of the paternal grandmother with exposure to smoking in adolescence and with smoking in pregnancy. e) The addition of all of the individual exposure variables to the different analyses often provided a considerable increase in goodness of fit compared with only adding demographic factors associated with asthma at P < 0.10 such as social class; this was particularly true when all four exposure variables were combined in one model, suggesting possible synergistic effects between them. Discussion: We have shown associations between all four types of exposure to the grandparents to be associated with asthma in the grandchildren, such that the results both depended on whether the male or female line was involved, and the sex of the grandchildren. It was notable that the paternal grandmother was particularly involved in many of the associations. We emphasize that these are exploratory analyses, that asthma diagnostic criteria likely changed over time and may not be consistent between generations, and that the results should be tested in other cohorts.

Childhood life events of women enrolled in the Avon Longitudinal Study of Parents & Children (ALSPAC).

At the time of planning ALSPAC there was accumulating evidence that abuse and other childhood traumas were related to psychiatric problems later in life. In addition, the age at which such trauma occurred was likely to be important in influencing its long-term impact. Detailed data was therefore collected from enrolled women on traumatic events occurring during their own childhoods, along with their age at the time. The questionnaire entitled 'About Yourself' was sent out to expectant women who had enrolled in the study, which included a page in the form of a grid (an events diary) with one row per year of childhood and columns for recording where she was living at the time, who was looking after her, and any traumatic events that occurred. These free-text responses were then coded, and any events were assigned a score indicating the level of trauma the event was likely to have caused on a scale of 1 (highly traumatic) to 6 (least traumatic). This paper describes the variety of text data collected and how it was coded. The ALSPAC study has a great deal of follow-up data collected on the original respondents, as well as on their parents and grandparents, partners, offspring and their grandchildren, providing huge potential for analyses on the antecedents and outcomes of adverse childhood events across multiple generations.

Paternal health in the first 12-13 years of the ALSPAC study.

The Avon Longitudinal Study of Parents and Children (ALSPAC) collected information from the enrolled pregnancy onwards to identify features of the environment in which the study child was brought up. Among data collected were features concerning the health of the mothers' partners - generally the study father. This was an important feature since the father's physical and mental health can have a long-term effect on the family. In this Data Note we describe the data available on the father's health from pregnancy until 12 years after the offspring was born. Not only is this a valuable addition to the environmental information available for studies of the child's development and the mental health of the mother over time, but it will provide a useful description of the father himself during adulthood.

Associations between autistic traits and early ear and upper respiratory signs: a prospective observational study of the Avon Longitudinal Study of Parents and Children (ALSPAC) geographically defined childhood population.

OBJECTIVE: To determine whether early ear and upper respiratory signs are associated with the development of high levels of autistic traits or diagnosed autism. DESIGN: Longitudinal birth cohort: Avon Longitudinal Study of Parents and Children (ALSPAC). SETTING: Area centred on the city of Bristol in Southwest England. Eligible pregnant women resident in the area with expected date of delivery between April 1991 and December 1992 inclusive. PARTICIPANTS: 10 000+ young children followed throughout their first 4 years. Their mothers completed three questionnaires between 18-42 months recording the frequency of nine different signs and symptoms relating to the upper respiratory system, as well as ear and hearing problems. OUTCOME MEASURES: Primary-high levels of autism traits (social communication, coherent speech, sociability, and repetitive behaviour); secondary-diagnosed autism. RESULTS: Early evidence of mouth breathing, snoring, pulling/poking ears, ears going red, hearing worse during a cold, and rarely listening were associated with high scores on each autism trait and with a diagnosis of autism. There was also evidence of associations of pus or sticky mucus discharge from ears, especially with autism and with poor coherent speech. Adjustment for 10 environmental characteristics made little difference to the results, and substantially more adjusted associations were at p<0.001 than expected by chance (41 observed; 0.01 expected). For example, for discharge of pus or sticky mucus from ears the adjusted odds ratio (aOR) for autism at 30 months was 3.29 (95% CI 1.85 to 5.86, p<0.001), and for impaired hearing during a cold the aOR was 2.18 (95% CI 1.43 to 3.31, p<0.001). CONCLUSIONS: Very young children exhibiting common ear and upper respiratory signs appear to have an increased risk of a subsequent diagnosis of autism or demonstrated high levels of autism traits. Results suggest the need for identification and management of ear, nose and throat conditions in autistic children and may provide possible indicators of causal mechanisms.

The beneficial role of personality in preserving well-being during the pandemic: A longitudinal population study.

BACKGROUND: The COVID-19 pandemic resulted in increased rates of mental health problems. We examined the possible role of the personality characteristic, Locus of Control (LOC), in moderating pandemic-induced stress. METHODS: The UK-based Avon Longitudinal Study of Parents & Children (ALSPAC), 7021 adults (mean ages: women 57.6 (SD = 4.48); partners 60.5 (SD = 5.36)) responded to a 2020 questionnaire which included a generalised measure of LOC. Between March 2020-January 2021, questionnaires focussed on the pandemic were administered, which included measures of mental health. Over 60 % of respondents completed questionnaires at three timepoints of interest. RESULTS: In those with an internal LOC higher rates of positive well-being and reduced likelihood of anxiety and depression were shown compared to those who were external, e.g. after adjustment for socioeconomic/demographic factors mean differences in well-being score for internal compared with external women was +2.01 (95%CI +1.02,+2.10) p = 0.0001; for their partners +2.52 (95%CI +1.22,+3.82) p = 0.0002. External women were more likely than internals to have depression (adjusted OR 3.41 [95%CI 1.77,6.57] p < 0.0005. LIMITATIONS: Attrition is a problem in this 30-year-old longitudinal cohort. Those still participating are more likely to have higher education and SES levels, be female and have an internal LOC. This population suffers from a lack of ethnic diversity. CONCLUSIONS: Having an internal LOC positively moderated the effects of pandemic-induced stress on the frequency of anxiety and depression in middle-age. Programmes geared to raise internality and coping strategies may have long-term benefits on well-being in stressful situations, especially for women and frontline health professionals.

Measures of puberty in the Avon Longitudinal Study of Parents and Children (ALSPAC) offspring cohort.

Background: When studying the development of children through the preteen years into adolescence, it is often important to link features of their physical and mental health to the stage of puberty at the time. This is complex since individuals vary substantially in the ages at which they reach different pubertal milestones. Methods: The Avon Longitudinal Study of Parents and Children (ALSPAC) is an ongoing longitudinal cohort study based in southwest England that recruited over 14000 women in pregnancy, with expected dates of delivery between April 1991 and December 1992. From 1999, information on puberty was collected using a number of different methods : (a) A series of annual questionnaires were administered when the index children were aged between eight and 17 years; these were mainly concerned with the physical changes associated with puberty; (b) identification of the age at peak height growth using the SITAR methodology; and (c) retrospective information from the girls on their age at onset of menstruation (menarche). Results: The advantages and disadvantages of each method are discussed. Conclusions: The data are available for analysis by interested researchers.

Maternal reports of morbidity during the index ALSPAC pregnancy.

Within the ALSPAC (Avon Longitudinal Study of Parents and Children) resource, information concerning the health of the mother during pregnancy is available from three sources: (i) computerised data collected by midwives after the delivery of the baby, known as the STORK database; (ii) data abstracted by ALSPAC staff from detailed medical obstetric records, and (iii) reports by mothers during pregnancy, and shortly after delivery using structured questionnaires completed at home. In this Data Note we focus on source (iii), and detail the information obtained from these mothers concerning their health, signs and symptoms together with medications and supplements taken during pregnancy. We also describe how the data can be accessed.

The benefits of fish intake: Results concerning prenatal mercury exposure and child outcomes from the ALSPAC prebirth cohort.

Health advice to pregnant women concerning consumption of mercury-containing foods has resulted in anxiety, with subsequent avoidance of fish consumption during pregnancy. However, seafood contains many nutrients crucial for children's growth and development. Longitudinal studies in the Seychelles, where fish is a major component of the diet, have not demonstrated harmful cognitive effects in children with increasing maternal mercury levels. Is the same true in a more developed country (the UK) where fish is eaten less frequently? We review publications using data collected by the Avon Longitudinal Study of Parents and Children (ALSPAC) to address this topic. Total mercury levels were measured in maternal whole blood and umbilical cord tissue. Offspring were followed throughout childhood, especially their cognitive development. No adverse associations were noted. Significantly beneficial associations with prenatal mercury levels were shown for total and performance IQ, mathematical/scientific reasoning, and birthweight in fish-consuming vs non-fish consuming mothers. These beneficial findings are similar to those observed in the Seychelles where fish consumption is high and prenatal Hg levels are x10 higher than US levels. Government recommendations should be reviewed to emphasise the beneficial value of fish consumption during pregnancy. DATA AVAILABILITY: ALSPAC data access is through a system of managed open access. The steps below highlight how to apply for access to the data included in this paper and all other ALSPAC data. If you have any questions about accessing data, please email: alspac-data@bristol.ac.uk.

Grandmaternal smoking during pregnancy is associated with differential DNA methylation in peripheral blood of their grandchildren.

The idea that information can be transmitted to subsequent generation(s) by epigenetic means has been studied for decades but remains controversial in humans. Epidemiological studies have established that grandparental exposures are associated with health outcomes in their grandchildren, often with sex-specific effects; however, the mechanism of transmission is still unclear. We conducted Epigenome Wide Association Studies (EWAS) to test whether grandmaternal smoking during pregnancy is associated with altered DNA methylation (DNAm) in peripheral blood from their adolescent grandchildren. We used data from a birth cohort, with discovery and replication datasets of up to 1225 and 708 individuals (respectively, for the maternal line), aged 15-17 years, and tested replication in the same individuals at birth and 7 years. We show for the first time that DNAm at a small number of loci in cord blood is associated with grandmaternal smoking in humans. In adolescents we see suggestive associations in regions of the genome which we hypothesised a priori could be involved in transgenerational transmission - we observe sex-specific associations at two sites on the X chromosome and one in an imprinting control region. All are within transcription factor binding sites (TFBSs), and we observe enrichment for TFBS among the CpG sites with the strongest associations; however, there is limited evidence that the associations we see replicate between timepoints. The implication of this work is that effects of smoking during pregnancy may induce DNAm changes in later generations and that these changes are often sex-specific, in line with epidemiological associations.

Paternal grandmother's smoking in pregnancy is associated with extreme aversion to bitter taste in their grandchildren.

Although there are many examples in the experimental literature of an environmental exposure in one generation impacting the phenotypes of subsequent generations, there are few studies that can assess whether such associations occur in humans. The Avon Longitudinal Study of Parents and Children (ALSPAC) has, however, been able to determine whether there are associations between grandparental exposures and their grandchildren's development. Several of our studies, including sensitivity to loud noise, have shown associations between a grandmother smoking in pregnancy and the phenotype of the grandchild. These results were mostly specific to the sex of the grandchild and to whether the prenatal (i.e. during pregnancy) smoking occurred in the maternal or paternal grandmother. Here, we have used ancestral data on prenatal smoking among the grandmothers of the ALSPAC index children to examine possible effects on the grandchild's ability to detect the bitter taste of PROP (6 n-propylthiouracil), distinguishing between the 10% deemed 'extreme tasters', and the rest of the population (total N = 4656 children). We showed that grandchildren whose paternal (but not maternal) grandmothers had smoked in pregnancy were more likely than those of non-smoking grandmothers to be extreme tasters [odds ratio (OR) 1.28; 95% confidence interval (CI) 1.03, 1.59] and that this was more likely in granddaughters (OR 1.42; 95% CI 1.03, 1.95) than grandsons (OR 1.18; 95% CI 0.88, 1.60). This pattern of association between paternal foetal exposure and the granddaughter's development has been found with several other outcomes, suggesting that investigations should be undertaken to investigate possible mechanisms.

Human transgenerational observations of regular smoking before puberty on fat mass in grandchildren and great-grandchildren.

Previously, using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) we showed that sons of fathers who had started smoking regularly before puberty (< 13 years) had increased fat mass during childhood, adolescence, and early adulthood. We now show that if the paternal grandfather had started smoking pre-puberty, compared with later in childhood (13-16 years), his granddaughters, but not grandsons, had evidence of excess fat mass at two ages: mean difference + 3.54 kg; (P with 1-tailed test) = 0.043 at 17 years, and + 5.49 kg; (P1 = 0.016) at age 24. When fathers of maternal grandfathers had started smoking pre-puberty, their great-granddaughters, but not great-grandsons, had excess body fat: + 5.35 kg (P1 = 0.050) at 17, and + 6.10 kg (P1 = 0.053) at 24 years. Similar associations were not found with lean mass, in a sensitivity analysis. To determine whether these results were due to the later generations starting to smoke pre-puberty, further analyses omitted those in subsequent generations who had smoked regularly from < 13 years. The results were similar. If these associations are confirmed in another dataset or using biomarkers, this will be one of the first human demonstrations of transgenerational effects of an environmental exposure across four generations.

The external housing environment of participants in the Avon Longitudinal Study of Parents and Children (ALSPAC): a resource for studies of influences on health.

Background: Early life environmental health exposures related to housing can have a significant impact on an individual's physical and mental health and physical development. Housing exposures can fall into two main areas - a representation of social circumstances and physical conditions. Methods: During pregnancy and post-delivery, self-completion questionnaires concerning the housing environment were administered to the ALSPAC (Avon Longitudinal Study of Parents & Children) study mothers and their partners until the study offspring were aged 18. Data collected included types of housing, housing tenure, numbers of rooms in the home, whether shared or sole use of kitchen and indoor flushing toilet, household moves, Council Tax band, difficulties in affording rent/mortgage and becoming homeless. Here we also describe the historic development of housing in the Bristol and surrounding Avon areas. Results: Data collected included the tenure (e.g., owned/rented) of the home, its size (indexed by the number of rooms), the presence of over-crowding (measured by the number of residents per room), presence of amenities, and frequency of household moves. This information was collected on over 13,000 women during pregnancy >8000 at age 10 and >4000 at 18 years. Council Tax bands were asked at 10 and 18 years. Conclusions: This is the first of two Data Notes on the housing type and housing circumstances of the families enrolled in ALSPAC. The second Data Note will detail their internal housing conditions. The data provides an excellent resource for researchers when considering the influences of housing on physical and mental health and development.

Demographic and socioeconomic predictors of religious/spiritual beliefs and behaviours in a prospective cohort study (ALSPAC) in Southwest England: Results from the parental generation.

Background: We explored associations between possible demographic and socioeconomic causes of religious/spiritual beliefs and behaviours (RSBB) in the parental generation of the Avon Longitudinal Study of Parents and Children (ALSPAC). Methods : We used a prospective birth cohort study (ALSPAC) in Southwest England with 14,157 enrolled mothers and 14,154 associated partners. Three RSBB outcome measures collected during pregnancy were examined: religious belief (belief in God/a divine power; yes/not sure/no), religious affiliation (Christian/none/other) and religious attendance (frequency of attendance at a place of worship). Multiple demographic and socioeconomic exposures were assessed (23 in mothers and 22 in partners). We explored age-adjusted associations between each exposure and outcome using multinomial regression, in addition to exposure-age interactions. Results: Many demographic and socioeconomic factors were associated with RSBB, including age, ethnicity, marital status, education, income and deprivation. Overall, higher socioeconomic position was associated with increased levels of RSBB, particularly regarding religious attendance. For instance, compared to mothers with the lowest level of educational attainment, a degree-level education was associated with a six-fold increase in the relative risk ratio of religious attendance at least once a week, relative to not attending at all (RRR=5.90; 95% CI=[4.44; 7.86]). The magnitude of these associations often varied by outcome, e.g., income was associated with religious attendance, but only weakly with religious affiliation. Although results were demographically and socially patterned, overall effect sizes were relatively small, with a largest pseudo- R 2 value of 2.4%. Patterns of association were similar for mothers and partners. Conclusion: The observed positive association between socioeconomic position and RSBB is contrary to much previous theoretical and empirical work. Potential reasons for these differences are discussed, including cross-cultural variation in religiosity and state support, and differences between RSBB measures. This descriptive paper can also help inform future studies using these data regarding the consideration of appropriate confounders.

Regular smoking of male ancestors in adolescence and fat mass in young adult grandchildren and great-grandchildren.

Background: Previous studies using the Avon Longitudinal Study of Parents and Children (ALSPAC) have shown that if men commenced smoking prior to the onset of puberty their sons, their granddaughters and great-granddaughters were more likely to have excess fat (but not lean) mass during childhood, adolescence and early adulthood. In this study we assess associations between ancestral smoking during adolescence (ages 11-16 years) with fat and lean mass of subsequent generations at two ages. Methods: We analysed data on exposures of grandparents and great-grandparents collected by ALSPAC. The outcomes were the fat masses of their grandchildren and great-grandchildren measured at ages 17 and 24. Measures of lean mass were used as controls. Adjustment was made for 8-10 demographic factors using multiple regression. Results: We found associations between adolescent smoking of the paternal grandfathers and the adjusted fat mass of their grandchildren, but no associations with the grandchildren's lean mass. Grandchildren at age 17 had an average excess fat mass of +1.65 [95% CI +0.04, +3.26] Kg, and at age 24 an average excess of +1.55 [95% CI -0.27, +3.38] Kg. Adolescent smoking by the maternal grandfather showed similar, but weaker, associations: at 17 an average excess fat mass of +1.02 Kg [95% CI -0.20, +2.25] Kg, and at 24 an average excess of +1.28 [95% CI -0.11, +2.66] Kg. There were no pronounced differences between the sexes of the children. For the great-grandparents there were few convincing results, although numbers were small. Conclusions: We have shown associations between grandfathers' smoking in adolescence and increased fat (but not lean) mass in their children. Confirmation of these associations is required, either in a further data set or by demonstrating the presence of supportive biomarkers.

Demographic and socioeconomic predictors of religious/spiritual beliefs and behaviours in a prospective cohort study (ALSPAC) in Southwest England: Results from the offspring generation.

Background: We explored associations between possible demographic and socioeconomic causes of religious/spiritual beliefs and behaviours (RSBB) in the offspring generation of the Avon Longitudinal Study of Parents and Children (ALSPAC). Methods: We examined approximately 4,450 offspring aged 28 years with RSBB data from a prospective birth cohort study (ALSPAC) in Southwest England. Three RSBB outcome measures were assessed: religious belief (belief in God/a divine power; yes/not sure/no), religious affiliation (Christian/none/other) and religious attendance (frequency of attendance at a place of worship). We explored age- and sex-adjusted associations between 35 demographic and socioeconomic exposures and each of the three RSBB outcomes using multinomial regression. Exposure-sex interactions were also examined. Results: Some sociodemographic factors were associated with RSBB in this cohort; for instance, being female and from an ethnicity other than White were associated with increased religiosity across all domains. For many other exposures, however, associations were frequently null or inconsistent, often depending on the specific exposure and outcome combination. As an example, higher educational attainment was associated with higher rates of religious attendance, but not with religious belief or affiliation; in contrast, higher income was associated with lower levels of religiosity. No consistent interactions between sex and the exposures on RSBB were found. Effect sizes were also rather weak, with most pseudo- R 2 values below 0.5% and a maximum of 1.2%. Conclusions: The results highlight that several demographic and socioeconomic factors are associated with RSBB in this cohort. However, the number of these associations, and their magnitude, is smaller than comparable results from the parental generation of these offspring, suggesting that patterns of sociodemographic factors associated with RSBB differ between these generations. In addition to describing these associations, this paper will help inform future studies using these data, particularly regarding the choice of potential sociodemographic confounders.

Ancestral smoking and developmental outcomes: a review of publications from a population birth cohort†.

The adverse effects on the child of maternal smoking in pregnancy is well-recognized, but little research has been carried out on the possible non-genetic effects of ancestral smoking prior to the pregnancy including parental initiation of cigarette smoking in their own childhoods or a grandmother smoking during pregnancy. Here, we summarize the studies that have been published mainly using data from the Avon Longitudinal Study of Parents and Children. We demonstrate evidence that ancestral smoking prior to or during pregnancy can often be beneficial for offspring health and both ancestor- and sex-specific. More specifically, we report evidence of (i) adverse effects of the father starting to smoke pre-puberty on his son's development; (ii) beneficial effects on the grandson if his maternal grandmother had smoked in pregnancy; and (iii) mainly adverse effects on the granddaughter when the paternal grandmother had smoked in pregnancy. The ancestor- and sex-specificity of these results are consistent with earlier studies reporting associations of health and mortality with ancestral food supply in their parents' and grandparents' pre-pubertal childhoods.

Maternal prenatal vitamin B12 intake is associated with speech development and mathematical abilities in childhood.

Deficiencies of many nutrients in pregnancy have adverse effects on fetal brain development with consequent impaired cognitive function in childhood. However, it is unclear whether deficiencies of vitamin B12 prenatally are harmful to the developing fetus. We therefore used the Avon Longitudinal Study of Parents and Children to test the hypothesis that cognitive outcomes in childhood are reduced if their mothers consumed a diet low in vitamin B12 during pregnancy. A detailed exposome analysis was used to identify 9 factors independently associated with low vitamin B12 intake. These were taken into account in each of 26 outcome analyses. Results showed that the children of women with the lowest 10% intake of B12 were at increased risk of poor vocabulary at 24 months, reduced ability at combining words at 38 months, poor speech intelligibility at 6 years, poor mathematics comprehension at school years 4 and 6 (ages 8-9 and 10-11 years), and poor results on the national mathematics tests (age 13). There were no such significant adjusted associations for reading or spelling abilities, or for verbal or full-scale IQ (Intelligence Quotient) at 8 or at 15. Thus, we have confirmed that there are adverse effects on the child's development if the pregnant woman has a low intake of vitamin B12, and we have shown that these are specific to certain speech and mathematical abilities.

Unexpected Associations between the Number of FRAXE Repeats in Boys and Evidence of Diabetes in Their Mothers and Maternal Grandmothers.

The FRAXE section of the FMR2 gene, located on the X chromosome, contains varying numbers of trinucleotide repeats; boys with over 200 repeats tend to have mild cognitive impairments, though this is rare. Little is known, however, concerning the phenotypes of individuals with smaller numbers of repeats. Here we answer the research question as to whether the health of ancestors of boys from whom the relevant X chromosome was inherited differed in any way according to the number of FRAXE repeats. Numbers of FRAXE repeats in 5057 boys from the Avon Longitudinal Study of Parents and Children (ALSPAC) were assessed. The distribution was bimodal, with the second smaller distribution starting at 22 repeats. We tested whether possession of 22+ repeats was associated with differences in the health of mothers (who share the X chromosome) and maternal grandmothers (half of whom share it). Female ancestors of boys with >21 repeats compared with <22 showed that maternal grandmothers (MGM) and mothers (M) had an increased risk of diabetes: MGM Type I odds ratio (OR) 2.40 [95%CI: 1.07,5.38]; MGM Type II OR 1.61 [0.96,2.70]; M OR 1.95 [0.96,3.94] using self-reported questionnaire measures. These results were confirmed from maternal medical records which revealed an increased level of diabetes [OR 2.40 (1.16,4.96)] and an increased risk of repeated glycosuria during pregnancy [OR 1.60 (1.08,2.36)]. We tested numbers of FRAXA repeats and showed no such associations, indicating that the findings were not associated with triploid repeats in general. If these findings are replicated elsewhere, there are at least three possible interpretations: (i) maternal diabetes/prediabetes results in an increased number of FRAXE repeats; (ii) women with high numbers of FRAXE repeats are at increased risk of diabetes; or (iii) some common factor, e.g. genomic instability, results in both diabetes and increased repeats.