Self-controlled case series studies: Just how rare does a rare non-recurrent outcome need to be?

The self-controlled case series method assumes that adverse outcomes arise according to a non-homogeneous Poisson process. This implies that it is applicable to independent recurrent outcomes. However, the self-controlled case series method may also be applied to unique, non-recurrent outcomes or first outcomes only, in the limit where these become rare. We investigate this rare outcome assumption when the self-controlled case series method is applied to non-recurrent outcomes. We study this requirement analytically and by simulation, and quantify what is meant by 'rare' in this context. In simulations we also apply the self-controlled risk interval design, a special case of the self-controlled case series design. To illustrate, we extract data on the incidence rate of some recurrent and non-recurrent outcomes within a defined study population to check whether outcomes are sufficiently rare for the rare outcome assumption to hold when applying the self-controlled case series method to first or unique outcomes. The main findings are that the relative bias should be no more than 5% when the cumulative incidence over total time observed is less than 0.1 per individual. Inclusion of age (or calendar time) effects will further reduce bias. Designs that begin observation with exposure maximise bias, whereas little or no bias will be apparent when there is no time trend in the distribution of exposures, or when exposure is central within time observed.

Association between maternal vitamin D status in pregnancy and neurodevelopmental outcomes in childhood: results from the Avon Longitudinal Study of Parents and Children (ALSPAC).

Seafood intake in pregnancy has been positively associated with childhood cognitive outcomes which could potentially relate to the high vitamin D content of oily fish. However, whether higher maternal vitamin D status (serum 25-hydroxyvitamin D (25(OH)D)) in pregnancy is associated with a reduced risk of offspring suboptimal neurodevelopmental outcomes is unclear. A total of 7065 mother-child pairs were studied from the Avon Longitudinal Study of Parents and Children cohort who had data for both serum total 25(OH)D concentration in pregnancy and at least one measure of offspring neurodevelopment (pre-school development at 6-42 months; 'Strengths and Difficulties Questionnaire' scores at 7 years; intelligence quotient (IQ) at 8 years; reading ability at 9 years). After adjustment for confounders, children of vitamin D-deficient mothers (<50·0 nmol/l) were more likely to have scores in the lowest quartile for gross-motor development at 30 months (OR 1·20; 95 % CI 1·03, 1·40), fine-motor development at 30 months (OR 1·23; 95 % CI 1·05, 1·44) and social development at 42 months (OR 1·20; 95 % CI 1·01, 1·41) than vitamin D-sufficient mothers (≥50·0 nmol/l). No associations were found with neurodevelopmental outcomes, including IQ, measured at older ages. However, our results suggest that deficient maternal vitamin D status in pregnancy may have adverse effects on some measures of motor and social development in children under 4 years. Prevention of vitamin D deficiency may be important for preventing suboptimal development in the first 4 years of life.

Prevalence and risk factors for reduced sound tolerance (hyperacusis) in children.

OBJECTIVE: To estimate the prevalence of reduced sound tolerance (hyperacusis) in a UK population of 11-year-old children and examine the association of early life and auditory risk factors with report of hyperacusis. DESIGN: A prospective UK population-based study. STUDY SAMPLE: A total of 7097 eleven-year-old children within the Avon longitudinal study of parents and children (ALSPAC) were asked about sound tolerance; hearing and middle-ear function was measured using audiometry, otoacoustic emissions, and tympanometry. Information on neonatal risk factors and socioeconomic factors were obtained through parental questionnaires. RESULTS: 3.7% (95% CI 3.25, 4.14) children reported hyperacusis. Hyperacusis report was less likely in females (adj OR 0.64, 95% CI 0.49, 0.85), and was more likely with higher maternal education level (adj OR 1.72, 95% CI 1.08, 2.72) and with readmission to hospital in first four weeks (adj OR 1.98, 95% CI 1.20, 3.25). Report of hyperacusis was associated with larger amplitude otoacoustic emissions but with no other auditory factors. CONCLUSIONS: The prevalence of hyperacusis in the population of 11-year-old UK children is estimated to be 3.7%. It is more common in boys.

Polyunsaturated fatty acid levels in blood during pregnancy, at birth and at 7 years: their associations with two common FADS2 polymorphisms.

Minor alleles of polymorphisms in the fatty acid desaturase (FADS) gene cluster have been associated with reduced desaturation of the precursor polyunsaturated fatty acids (FAs) in small studies. The effects of these polymorphisms during progressive developmental stages have not previously been reported. Data from blood samples for 4342 pregnant women, 3343 umbilical cords reflecting the newborn's blood supply and 5240 children aged 7 years were analysed to investigate the associations of polyunsaturated FAs with rs1535 and rs174575-two polymorphisms in the FADS2 gene. Strong positive associations were observed between the minor G allele for these two markers, especially rs1535, and the substrates linoleic (18:2n-6) and α-linolenic (18:3n-3) acid. Negative associations were observed for the more highly unsaturated FAs such as arachidonic acid (20:4n-6), timnodonic acid (EPA, 20:5n-3) and cervonic acid (DHA, 22:6n-3). Bivariable genetic associations using the mother and child genotypes suggested that the newborn metabolism had a greater capacity to synthesize the more highly unsaturated omega-6 FAs than the more highly unsaturated omega-3 FAs. Nevertheless, despite the immaturity of the neonate, there was evidence that synthesis of DHA was occurring. However, by 7 years, no associations were observed with the maternal genotype. This suggested that the children's FA levels were related only to their own metabolism with no apparent lasting influences of the in utero environment.

Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC).

BACKGROUND: As a component of thyroid hormones, iodine is essential for fetal brain development. Although the UK has long been considered iodine replete, increasing evidence suggests that it might now be mildly iodine deficient. We assessed whether mild iodine deficiency during early pregnancy was associated with an adverse effect on child cognitive development. METHODS: We analysed mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort by measuring urinary iodine concentration (and creatinine to correct for urine volume) in stored samples from 1040 first-trimester pregnant women. We selected women on the basis of a singleton pregnancy and availability of both a urine sample from the first trimester (defined as ≤13 weeks' gestation; median 10 weeks [IQR 9-12]) and a measure of intelligence quotient (IQ) in the offspring at age 8 years. Women's results for iodine-to-creatinine ratio were dichotomised to less than 150 µg/g or 150 µg/g or more on the basis of WHO criteria for iodine deficiency or sufficiency in pregnancy. We assessed the association between maternal iodine status and child IQ at age 8 years and reading ability at age 9 years. We included 21 socioeconomic, parental, and child factors as confounders. FINDINGS: The group was classified as having mild-to-moderate iodine deficiency on the basis of a median urinary iodine concentration of 91·1 µg/L (IQR 53·8-143; iodine-to-creatinine ratio 110 µg/g, IQR 74-170). After adjustment for confounders, children of women with an iodine-to-creatinine ratio of less than 150 µg/g were more likely to have scores in the lowest quartile for verbal IQ (odds ratio 1·58, 95% CI 1·09-2·30; p=0·02), reading accuracy (1·69, 1·15-2·49; p=0·007), and reading comprehension (1·54, 1·06-2·23; p=0·02) than were those of mothers with ratios of 150 µg/g or more. When the less than 150 µg/g group was subdivided, scores worsened ongoing from 150 µg/g or more, to 50-150 µg/g, to less than 50 µg/g. INTERPRETATION: Our results show the importance of adequate iodine status during early gestation and emphasise the risk that iodine deficiency can pose to the developing infant, even in a country classified as only mildly iodine deficient. Iodine deficiency in pregnant women in the UK should be treated as an important public health issue that needs attention. FUNDING: None.

Umbilical cord PUFA are determined by maternal and child fatty acid desaturase (FADS) genetic variants in the Avon Longitudinal Study of Parents and Children (ALSPAC).

Fetal supply with long-chain PUFA (LC-PUFA) during pregnancy is important for brain growth and visual and cognitive development and is provided by materno-fetal placental transfer. We recently showed that maternal fatty acid desaturase (FADS) genotypes modulate the amounts of LC-PUFA in maternal blood. Whether FADS genotypes influence the amounts of umbilical cord fatty acids has not been investigated until now. The aim of the present study was to investigate the influence of maternal and child FADS genotypes on the amounts of LC-PUFA in umbilical cord venous plasma as an indicator of fetal fatty acid supply during pregnancy. A total of eleven cord plasma n-6 and n-3 fatty acids were analysed for association with seventeen FADS gene cluster SNP in over 2000 mothers and children from the Avon Longitudinal Study of Parents and Children. In a multivariable analysis, the maternal genotype effect was adjusted for the child genotype and vice versa to estimate which of the two has the stronger influence on cord plasma fatty acids. Both maternal and child FADS genotypes and haplotypes influenced amounts of cord plasma LC-PUFA and fatty acid ratios. Specifically, most analysed maternal SNP were associated with cord plasma levels of the precursor n-6 PUFA, whereas the child genotypes were mainly associated with more highly desaturated n-6 LC-PUFA. This first study on FADS genotypes and cord fatty acids suggests that fetal LC-PUFA status is determined to some extent by fetal fatty acid conversion. Associations of particular haplotypes suggest specific effects of SNP rs498793 and rs968567 on fatty acid metabolism.

Influences on child fruit and vegetable intake: sociodemographic, parental and child factors in a longitudinal cohort study.

OBJECTIVE: To examine the sociodemographic, parental and child factors that predict fruit and vegetable consumption in 7-year-old children. DESIGN: Diet was assessed using three 1d unweighed food diaries. The child's daily fruit and vegetable consumption was calculated by summing the weight of each type of fruit, fruit juice and vegetable consumed. The various others factors measured were assessed by a questionnaire at different time points. SETTING: The Avon Longitudinal Study of Parents and Children (ALSPAC). SUBJECTS: A total of 7285 children aged 7 years residing in the south-west of England during 1999-2000. RESULTS: Median daily fruit and vegetable consumption (201 g) was below the recommendations for this age group (320 g). Girls ate more fruit and vegetables per unit energy (30.3 g/MJ) than boys (26.7 g/MJ; P =< 0.001). The predictors of fruit and vegetable consumption were mostly similar. Fruit and vegetable consumption was associated with maternal consumption, maternal education status and parental rules about serving fruit/vegetables every day, food expenditure per person and whether the child was choosy about food. Vegetable consumption was also associated with the other characteristics of the child, such as whether the child enjoyed food and whether the child tried a variety of foods. CONCLUSIONS: Children are not eating recommended amounts of fruit and vegetables, particularly boys. Consumption of fruit and vegetables appears to be influenced by parental rules about daily consumption and parental consumption and by the child's choosiness. Parent's actions could influence this. These findings may prove useful for those planning healthy eating campaigns for children.

Growth and body composition in children who are picky eaters: a longitudinal view.

BACKGROUND/OBJECTIVES: Picky eating may be associated with higher risk of being underweight and poor growth over time or conversely, being overweight. Our aim was to investigate if children identified as picky eaters showed differences in height, weight and body composition from their non-picky peers. SUBJECTS/METHODS: Picky eaters were identified in the Avon Longitudinal Study of Parents and Children cohort at 3 years of age. Height and weight were measured on seven occasions (age 7-17 years). Body composition was measured on five occasions by dual-energy x-ray absorptiometry (age 9-17 years). Participants were classified as thin/normal/overweight or obese at each age point using body mass index (BMI) classifications. Data were analysed with adjusted multiple regression analysis and mixed-design repeated measures ANOVA. RESULTS: There was a main effect of being a picky child on height and weight (and on BMI and lean mass index (LMI) in boys) (lower in the picky children, all p ≤ 0.044), but not on percentage body fat or fat mass index (and not on BMI and LMI in girls) (all p > 0.2). The mean heights, weights and BMIs of picky eaters were consistently above the 50th centiles of reference growth charts. More than two-thirds of picky eaters were not thin at any age point. However, being a picky eater was predictive of being thin at a few age points. CONCLUSIONS: The growth trajectories of children who were picky eaters were reassuring. The prevalence of thinness amongst some picky eaters is notable, suggesting that some children may need specific early identification, intervention and growth surveillance.

Habitual levels of physical activity influence bone mass in 11-year-old children from the United Kingdom: findings from a large population-based cohort.

UNLABELLED: We examined the influence of habitual levels of physical activity on bone mass in childhood by studying the relationship between accelerometer recordings and DXA parameters in 4457 11-year-old children. Physical activity was positively related to both BMD and bone size in fully adjusted models. However, further exploration revealed that this effect on bone size was modified by fat mass. INTRODUCTION: Exercise interventions have been reported to increase bone mass in children, but it is unclear whether levels of habitual physical activity also influence skeletal development. MATERIALS AND METHODS: We used multivariable linear regression to analyze associations between amount of moderate and vigorous physical activity (MVPA), derived from accelerometer recordings for a minimum of 3 days, and parameters obtained from total body DXA scans in 4457 11-year-old boys and girls from the Avon Longitudinal Study of Parents and Children. The influence of different activity intensities was also studied by stratification based on lower and higher accelerometer cut-points for moderate (3600 counts/minute) and vigorous (6200 counts/minute) activity, respectively. RESULTS: MVPA was positively associated with lower limb BMD and BMC adjusted for bone area (aBMC; p < 0.001, adjusted for age, sex, socio-economic factors, and height, with or without additional adjustment for lean and fat mass). MVPA was inversely related to lower limb bone area after adjusting for height and lean mass (p = 0.01), whereas a positive association was observed when fat mass was also adjusted for (p < 0.001). Lower limb BMC was positively related to MVPA after adjusting for height and lean and fat mass (p < 0.001), whereas little relationship was observed after adjusting for height and lean mass alone (p = 0.1). On multivariable regression analysis using the fully adjusted model, moderate activity exerted a stronger influence on lower limb BMC compared with light activity (light activity: 2.9 [1.2-4.7, p = 0.001]; moderate activity: 13.1 [10.6-15.5, p < 0.001]; regression coefficients with 95% confidence intervals and p values). CONCLUSIONS: Habitual levels of physical activity in 11-year-old children are related to bone size and BMD, with moderate activity exerting the strongest influence. The effect on bone size (as reflected by DXA-based measures of bone area) was modified by adjustment for fat mass, such that decreased fat mass, which is associated with higher levels of physical activity, acts to reduce bone size and thereby counteract the tendency for physical activity to increase bone mass.

Associations of size at birth and dual-energy X-ray absorptiometry measures of lean and fat mass at 9 to 10 y of age.

BACKGROUND: Birth weight has been positively associated with risk of overweight in later life. However, little information exists on how weight and length at birth are associated with subsequent lean and total body fat. OBJECTIVE: We investigated the association between weight and length at birth and body composition and fat distribution in childhood. DESIGN: Body composition was measured by using dual-energy X-ray absorptiometry in 9-10-y-old subjects (n = 3006 boys and 3080 girls). Weight and length at birth were measured or taken from hospital records. RESULTS: Birth weight was positively associated with both lean body mass (LBM) and total body fat at 9-10 y of age in both sexes. LBM rose by 320 g per 1-SD increase in birth weight (P < 0.001), and total body fat rose by 2.5% (P = 0.001), but birth weight was unassociated with the fat-to-lean mass ratio (FLR). Ponderal index (PI) at birth (ie, weight/length3) was positively associated with LBM, total body fat, and the FLR in both sexes; the FLR increased by 2.7% in boys (P = 0.021) and by 5.0% in girls per 1-SD increase in PI (P < 0.001). Weight and length at birth did not predict central adiposity; although trunk fat had a strong positive association with PI at birth, this association disappeared after adjustment for total body fat. CONCLUSIONS: Higher PI at birth is associated with both higher fat and lean mass in childhood but also with an increase in the FLR. PI at birth is a better predictor of subsequent adiposity than is birth weight.

Dental associations with blood mercury in pregnant women.

OBJECTIVES: There is curiosity concerning the source of mercury that is absorbed into the mother's blood and which may affect the developing fetus. This study therefore sets out to determine the extent to which dental amalgam (DA) may contribute to total blood mercury (TBHg) levels of pregnant women in the UK. METHODS: Whole blood samples and information on diet and socio-demographic factors were collected from pregnant women (n = 4484) enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). The whole blood samples were assayed for total mercury levels using inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS), and the women were retrospectively asked about features of their dental care during the pregnancy. Linear regression was used to estimate the relative contributions of DA to TBHg levels (log-transformed) based on R(2) values, compared to the results from dietary and socio-demographic variables. RESULTS: The contribution to the variance of the mothers' TBHg levels by dental variables was 6.47%, a figure comparable to the 8.75% shown for seafood consumption in this population. Dietary and dental variables explained 20.16% of the variance, with socio-demographic variables contributing only a further 3.40%. The number of amalgams in the mouth at the start of pregnancy accounted for most of the variance in dental variables. CONCLUSIONS: Dental amalgam contributes a comparable amount of variance in TBHg to seafood consumption in this population. However, because the measures of DA exposure were imprecise, these findings are likely to be an underestimate. There is no evidence to date in the literature that fetal exposures to mercury from maternal DAs have adverse effects on the developing child, but long-term studies are warranted.

Preconception and prenatal environmental factors associated with communication impairments in 9 year old children using an exposome-wide approach.

Although speech and language deficits are common in children and strongly associated with poor educational and social outcomes, little attention has been paid to the antecedents. In this study we used the information from the Avon Longitudinal Study of Parents and Children to examine preconception and prenatal environmental risk factors that were related to communication difficulties in children using the Children's Communication Checklist (CCC). We used an exposome-wide approach to identify environmental factors univariably associated with the CCC. Taking account of the False Discovery rate, we used a P value of 0.000157 to identify 621 of 3855 items tested. These were then subjected to a series of stepwise linear regression analyses, firstly within 10 domains: personal characteristics, health, development, education, socio-economic variables, lifestyle, home and social environments, life events and chemical and other exposures; and then with the predictive variables from each domain. The final model consisted of 19 variables independently associated with the communication scale. These variables suggested 6 possible mechanisms: stressors primarily associated with socio-economic disadvantage although other lifestyle choices such as a social network of family or friends can ameliorate these effects; indicators of future parenting skills primarily associated with aspects of parental personality; aspects of the home environment; poor maternal health with a novel finding concerning maternal hearing loss; and maternal education which was partially mediated by the child's IQ. Finally, there may be a mechanism via the maternal diet in pregnancy in particular the consumption of fatty or processed foods. This is the subject of ongoing investigation.

Effects on childhood body habitus of feeding large volumes of cow or formula milk compared with breastfeeding in the latter part of infancy.

BACKGROUND: There is controversy over whether a lack of breastfeeding is related to obesity development. OBJECTIVE: We examined the effects of feeding different types of milk in late infancy on childhood growth. DESIGN: A cohort of 1112 term, singleton children (born in 1992) from the Avon Longitudinal Study of Parents and Children, United Kingdom, were studied prospectively. Food records collected at 8 mo of age were used to define the following 5 mutually exclusive feeding groups on the basis of the type and amount of milk consumed: breast milk (BM), <600 mL formula milk/d (FMlow), ≥600 mL formula milk/d (FMhigh), <600 mL cow milk/d (CMlow), and ≥600 mL cow milk/d (CMhigh). Weight, height, and BMI were measured at 14 time points from birth to 10 y of age, and SD scores (SDSs) were calculated. Dietary energy and macronutrient intakes were available at 7 time points. RESULTS: CMhigh children were heavier than were BM children from 8 mo to 10 y of age with weight differences (after adjustment for maternal education, smoking, and parity) ≥0.27 SDSs and an average of 0.48 SDSs. The maximum weight difference was at 18 mo of age (0.70 SDS; 95% CI: 0.41, 1.00 SDS; P = <0.0001). CMhigh children were taller at some ages (25-43 mo; P < 0.01) and had greater BMI SDSs from ≥8 mo of age (at 9 y of age; P = 0.001). FMhigh children were heavier and taller than were BM children from 8 to 37 mo of age. There were marked dietary differences between milk groups at 8 mo of age, some of which persisted to 18 mo of age. Adjustments for current energy and protein intakes did not attenuate the growth differences observed. CONCLUSIONS: The feeding of high volumes of cow milk in late infancy is associated with faster weight and height gain than is BM feeding. The feeding of bottle-fed infants with high volumes of cow milk in late infancy may have a persisting effect on body habitus through childhood.

Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy.

Postpartum depression (PPD) affects up to 19% of women, negatively impacting maternal and infant health. Reductions in plasma oxytocin levels have been associated with PPD and heritability studies have established a genetic contribution. Epigenetic regulation of the oxytocin receptor gene (OXTR) has been demonstrated and we hypothesized that individual epigenetic variability at OXTR may impact the development of PPD and that such variability may be central to predicting risk. This case-control study is nested within the Avon Longitudinal Study of Parents and Children and included 269 cases with PPD and 276 controls matched on age group, parity, and presence or absence of depressive symptoms in pregnancy as assessed by the Edinburgh Postnatal Depression Scale. OXTR DNA methylation (CpG site -934) and genotype (rs53576 and rs2254298) were assayed from DNA extracted from blood collected during pregnancy. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of elevated symptoms of PPD with genotype, methylation, and their interaction adjusted for psychosocial factors (n = 500). There was evidence of an interaction between rs53576 and methylation in the OXTR gene amongst women who did not have depression prenatally but developed PPD (p interaction = 0.026, adjusted for covariates, n = 257). Those women with GG genotype showed 2.63 greater odds of PPD for every 10% increase in methylation level (95% CI: 1.37, 5.03), whereas methylation was unrelated to PPD amongst "A" carriers (OR = 1.00, 95% CI: 0.58, 1.73). There was no such interaction among women with PPD and prenatal depression. These data indicate that epigenetic variation that decreases expression of OXTR in a susceptible genotype may play a contributory role in the etiology of PPD.

Birth weight is positively related to bone size in adolescents but inversely related to cortical bone mineral density: findings from a large prospective cohort study.

To examine the influence of intrauterine environment on subsequent bone development, we investigated the relationship between birth weight and cortical bone parameters, and the role of puberty, bone resorption and insulin as possible mediators. Bone outcomes were obtained from mid-tibial pQCT scans performed at age 15.5 years in 1960 males and 2192 females from the ALSPAC birth cohort. Birth weight was positively related to periosteal circumference (PC) [beta=0.40 (0.34, 0.46)], which was largely but not completely attenuated after adjustment for height and weight [beta=0.07 (0.02, 0.12)] (SD change in outcome per 1 kg increase in birth weight with 95% CI). Based on our height and weight adjusted model, the association was stronger in females compared to males (P=0.02 for gender interaction), and persisted in 2842 participants with equivalent results at age 17.7 years. Conversely, birth weight was inversely related to cortical bone mineral density (BMDC) at age 15.5 years after adjusting for height and weight [beta=-0.18 (-0.23, -0.13)], with a stronger association in males compared to females (P=0.01 for gender interaction), but an equivalent association was not seen at 17.7 years. In further analyses performed on data from age 15.5 years, the association between birth weight and PC was unaffected by adjustment for puberty (Tanner stage at age 13.5 years), bone resorption (fasting beta-carboxyterminal cross linking telopeptide (ßCTX) at age 15.5 years) or insulin (fasting insulin at age 15.5 years). In contrast, the association with BMDC was attenuated by approximately 30% after adjustment for puberty or bone resorption, and by 50% after adjustment for both factors combined. We conclude that the inverse relationship between birth weight and BMDC is in part mediated by effects of puberty and bone resorption, which may help to explain the transitory nature of this association, in contrast to the more persisting relationship with PC.

Parental, prenatal, and neonatal associations with ball skills at age 8 using an exposome approach.

There is little consistency in the literature concerning factors that influence motor coordination in children. A hypothesis-free "exposome" approach was used with 7359 children using longitudinal information covering 3 generations in regard to throwing a ball accurately at age 7 years. The analyses showed an independent robust negative association with mother's unhappiness in her midchildhood (6-11 years). No such association was present for study fathers. The offspring of parents who described themselves as having poor eyesight had poorer ability. This hypothesis-free approach has identified a strong negative association with an unhappy childhood. Future studies of this cohort will be used to determine whether the mechanism is manifest through differing parenting skills, or a biological mechanism reflecting epigenetic effects.

Dependence of deodorant usage on ABCC11 genotype: scope for personalized genetics in personal hygiene.

Earwax type and axillary odor are genetically determined by rs17822931, a single-nucleotide polymorphism (SNP) located in the ABCC11 gene. The literature has been concerned with the Mendelian trait of earwax, although axillary odor is also Mendelian. Ethnic diversity in rs17822931 exists, with higher frequency of allele A in east Asians. Influence on deodorant usage has not been investigated. In this work, we present a detailed analysis of the rs17822931 effect on deodorant usage in a large (N∼17,000 individuals) population cohort (the Avon Longitudinal Study of Parents and Children (ALSPAC)). We found strong evidence (P=3.7 × 10(-20)) indicating differential deodorant usage according to the rs17822931 genotype. AA homozygotes were almost 5-fold overrepresented in categories of never using deodorant or using it infrequently. However, 77.8% of white European genotypically nonodorous individuals still used deodorant, and 4.7% genotypically odorous individuals did not. We provide evidence of a behavioral effect associated with rs17822931. This effect has a biological basis that can result in a change in the family's environment if an aerosol deodorant is used. It also indicates potential cost saving to the nonodorous and scope for personalized genetics usage in personal hygiene choices, with consequent reduction of inappropriate chemical exposures for some.

Maternal fatty acids in pregnancy, FADS polymorphisms, and child intelligence quotient at 8 y of age.

BACKGROUND: Brain tissue is selectively enriched with highly unsaturated fatty acids (FAs). Altering the maternal FA status in pregnancy may improve fetal neural development with lasting consequences for child development. OBJECTIVE: We explored whether maternal FAs in erythrocytes, either measured directly or indirectly by maternal FADS genetic variants, are associated with child intelligence quotient (IQ). DESIGN: Linear regression analyses, adjusted for 18 confounders, were used to investigate the associations in 2839 mother-child pairs from the population-based Avon Longitudinal Study of Parents and Children cohort. RESULTS: Low levels of arachidonic acid (20:4n-6) were associated with lower performance IQ (-2.0 points; 95% CI: -3.5, -0.6 points; P = 0.007, increased R² = 0.27%), high levels of osbond acid (22:5n-6) were associated with verbal IQ (-1.8 points; 95% CI: -3.2, -0.4 points; P = 0.014, R² = 0.20%), and high levels of adrenic acid (22:4n-6) were associated with verbal IQ (-1.7 points; 95% CI:-3.1, -0.3 points; P = 0.016, R² = 0.19%). There was some evidence to support a negative association of low docosahexaenoic acid (DHA; 22:6n-3) with full-scale IQ (R² = 0.15%). Novel weak associations were also observed for low levels of osbond acid (R² ≤ 0.29%) and FADS variants with opposite effects for intron variants and variants in the promoter region such as rs3834458 (R² ≤ 0.38%). CONCLUSIONS: These results support the positive role of maternal arachidonic acid and DHA on fetal neural development, although the effects on child IQ by 8 y of age were small (0.1 SD), with other factors contributing more substantially. The endogenous synthesis of these FAs by FADS genes, especially FADS2, may also be important. The replication of these results is recommended.

Dietary predictors of maternal prenatal blood mercury levels in the ALSPAC birth cohort study.

BACKGROUND: Very high levels of prenatal maternal mercury have adverse effects on the developing fetal brain. It has been suggested that all possible sources of mercury should be avoided. However, although seafood is a known source of mercury, little is known about other dietary components that contribute to the overall levels of blood mercury. OBJECTIVE: Our goal was to quantify the contribution of components of maternal diet to prenatal blood mercury level. METHODS: Whole blood samples and information on diet and sociodemographic factors were collected from pregnant women (n = 4,484) enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). The blood samples were assayed for total mercury using inductively coupled plasma dynamic reaction cell mass spectrometry. Linear regression was used to estimate the relative contributions of 103 dietary variables and 6 sociodemographic characteristics to whole blood total mercury levels (TBM; untransformed and log-transformed) based on R2 values. RESULTS: We estimated that maternal diet accounted for 19.8% of the total variation in ln-TBM, with 44% of diet-associated variability (8.75% of the total variation) associated with seafood consumption (white fish, oily fish, and shellfish). Other dietary components positively associated with TBM included wine and herbal teas, and components with significant negative associations included white bread, meat pies or pasties, and french fries. CONCLUSIONS: Although seafood is a source of dietary mercury, seafood appeared to explain a relatively small proportion of the variation in TBM in our UK study population. Our findings require confirmation, but suggest that limiting seafood intake during pregnancy may have a limited impact on prenatal blood mercury levels.

Autism spectrum disorder and autistic traits in the Avon Longitudinal Study of Parents and Children: precursors and early signs.

OBJECTIVE: To chart the emergence of precursors and early signs of autism spectrum disorder (ASD) and autistic traits in the Avon Longitudinal Study of Parents and Children, a prospective longitudinal cohort study of the surviving offspring of 14,541 pregnant women from southwestern England with an expected delivery date between April 1991 and December 1992. METHOD: Parents' contemporaneous reports of their infant's development (241 questionnaire responses collected up to 30 months of age) were examined in relation to the diagnosis of autism spectrum disorder by age 11 years (n = 86) and a measure of autistic traits, derived by factor analysis. RESULTS: Among the children later diagnosed with ASD, concerns about vision and hearing were more often reported in the first year, and differences in social, communication, and fine motor skills were evident from 6 months of age. Repetitive behaviors and differences in play, imitation, and feeding habits were reported in the second year. Differences in temperament emerged at 24 months of age and bowel habit by 30 months. All of these early signs were strongly associated with the presence of autistic traits in the rest of the population and these differences were often evident in the first year of development. Over the first 30 months of development, the best predictors of both later ASD and autistic traits included the Social Achievement and Communication scores from the Denver Developmental Screening Test, measures of communicative skills (Vocabulary and Combines Words) from the MacArthur Infant Communicative Development Inventories, and a repetitive behavior score. CONCLUSIONS: Precursors, early signs, and other developmental differences were reported in the first year of development among children from the general population who later developed autism spectrum disorder and subtler autistic traits. Other differences emerged and unfolded as development progressed. The findings confirm the long-held suspicion that early differences underscore the multifaceted nature of autism spectrum disorder and the broader autism phenotype, and highlight the centrality of impairments in social communication skills.