Data relating to prenatal lead exposure and child IQ at 4 and 8 years old in the Avon Longitudinal Study of Parents and Children

As part of the Avon Longitudinal Study of Parents and Children (ALSPAC), measures of child IQ were collected by trained psychologists. The Wechsler Pre-school and Primary Scale of Intelligence – Revised UK edition (WPPSI) was used at age 4 years in a subsample of children enrolled in ALSPAC (the Children in Focus cohort), chosen at random from the last 6 months of ALSPAC births (about 10% of the participants). At age 8 years all children enrolled in the main cohort were invited to complete a short form of the Wechsler Intelligence Scale for Children (WISC)-III UK. Prenatal blood lead (B-Pb) concentrations were measured by inductively-couple plasma mass spectrometry in samples from women at a median gestation age of 11 weeks. Child blood lead was measured by atomic absorption spectrometry in samples from children attending the Children in Focus clinic at age 30 months. Maternal reports at 32 weeks’ gestation were used to generate data on a range of potential confounders. The data were used to determine the associations between prenatal exposure to lead and child IQ at 4 and 8 years. The effect of child B-Pb at 3 years as a moderator of these associations was tested. (For results, please see doi:10.1016/j.neuro.2017.07.003 Taylor et al., (2017)).


Subject area
Human Biology More specific subject area

Child development
Type of data Value of the data The ALSPAC dataset contains information on a large number of children in a geographically defined population whose development was monitored to age 24-25 years old at present (2017)).
The data provide a basis for early identification of adverse effects of environmental exposures (metals and other toxicants). The data allow detailed analyses of family and social circumstances and their associations with child development.

Data
In this paper, we describe data on child IQ at 4 and 8 years, prenatal B-Pb concentrations and child B-Pb concentrations at age 2.5 years (see Tables).
The ALSPAC study website contains details of all the data that are available through a fully searchable data dictionary:http:// www.bris.ac.uk/alspac/researchers/data-access/data-dictionary/. Data can be obtained by bona fide researchers after application to the ALSPAC Executive Committee (http://www.bristol.ac.uk/ alspac/researchers/access/).

Prenatal samples
Whole blood samples were collected in acid-washed heparin vacutainers (Becton and Dickinson) by midwives as early as possible in pregnancy. Midwives' participation in collecting the bloods was voluntary, dependent on time available and consequently was only obtained in two of the three Health Authority areas of the recruitment region. Altogether 4484 samples were collected at a median gestational age of 11 weeks (range 1-42 weeks, mode 10 weeks, interquartile range 9-13 weeks). The social background of the women who gave the samples did not differ from the rest of the ALSPAC population apart from being slightly older and more educated (Taylor et al., 2013). Samples were stored at 4 C at the collection site and then sent to the central Bristol laboratory within 0-4 days. These samples were kept at room temperature for up to 3 h during transfer, and were stored at 4 C as whole blood in the original tubes for 18-19 years before being sent for analysis.
The method of assay of lead has been described in detail elsewhere (Taylor et al., 2013). In brief, the laboratory of Robert Jones at the Centers for Disease Control and Prevention (CDC) developed methods to prepare the samples for analysis of whole blood lead (CDC method 3009.1). Clotted whole blood was digested to remove all clots before being analysed using inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). Two levels of bench quality control (QC) materials, as well as a blind QC material, were used for daily quality control.
There were 4484 samples available for lead assays of which 4285 were successfully analysed (tube/vial broken n = 7, suspect sample n = 3, quantity not sufficient for repeat testing n = 67, lab error n = 122). One of the samples had a lead concentration below the limit of detection of the assay (0.24 mg/dL). For this sample, in consideration of the distribution of the lead concentrations, a value of 0.7 times the limit of detection value (limit of detection/ p 2) was considered to be a better estimate of the value than taking a midpoint (Hornung and Reed, 1990;Centers for Disease Control and Prevention, 2005). The mean level was 3.67 AE 1.47 (range 0.29-19.14, median 3.41) mg/dL.

Child samples
A randomly selected sample of parents whose babies were born within the last 6 months of enrollment into ALSPAC were invited to bring their children to a research clinic (Children in Focus, CiF) at  No evidence for supralinear dose-response relationship or lower limit of level of concern Taylor et al. (2017) Prenatal blood lead Child IQ at 4 and 8 years No associations with child IQ Table 3 Other publications on prenatal and child lead measures in ALSPAC.

Authors
Exposure Results Golding et al. (1998) Child blood lead Documentation of child blood lead level Taylor et al. (2013) Prenatal blood lead Environmental factors predicting prenatal blood lead level Taylor et al. (2014b) Prenatal blood lead Documentation and review of prenatal blood levels and international levels of concern Warrington et al. (2015) Maternal blood lead Association with polymorphism in ALAD age 30 months. Parental consent for a venous blood sample was obtained from 81% of the 1135 children in the CiF group. A venous blood sample was collected in lead-free tubes from 71% (n = 653) of clinic attenders; 69 samples had insufficient volume for analysis, leaving 582 samples for analysis. The blood lead concentration was measured at Southampton General Hospital, UK, by atomic absorption spectrometry using micro-sampling flame atomisation. Details of the quality control procedures have been published (Chandramouli et al., 2009 (Wechsler, 1990) at a research clinic for children in the CiF subsample. All cores scales were administered. The children were also given a digit span test of short term memory, devised and standardised by Professor Susan Gathercole (research psychologist).
Inter-rater reliability was ensured as follows. The testers were overseen by Steve Gibbs, a tester with long experience of psychometric testing with ALSPAC. He observed each tester, met with the group regularly to discuss the precise administration of each test, and supervised and checked their scoring. Each tester scored four videos of tests and interindividual scores were compared.
The WPPSI comprises ten subtests: five verbal and five performance. The verbal subtest scores were combined to make up the verbal IQ, and the performance scores combined to make up the performance IQ. The ten subtest scores were combined to produce a full-scale IQ score. Following each child's session, which usually lasted 50-60 min, the parent or carer was given a short questionnaire asking whether the child's behaviour and performances was typical, and if not, how and why.
If a child completed fewer than four subtests on the performance scale then the final performance IQ score was not calculated (and therefore not the full-scale score either). If, however, the child completed four out of the five subtests, the mean of the four subtests was calculated and imputed for the subtest not completed, so that a performance score could be computed. This prorating is standard WPPSI practice. Identical rules applied to the verbal score. Thus, some children, although not completing a subtest, had a score for that subtest.

IQ at 8 years
Mental development at age 8 years was measured by the Wechsler Intelligence Scale for Children WISC-III UK (Wechsler et al., 1992) at a research clinic for all children enrolled in the ALSPAC cohort. A short form of the measure was employed, where alternate items were used for all subtests, with the exception of the coding subtest which was administered in full. Hence the length of the sessions was reduced and the children were less likely to become tired. The WISC comprises five verbal subtests (Information, Similarities, Arithmetic, Vocabulary, Comprehension) and five performance subtests (picture completion, coding, picture arrangement, block design, object assembly). The children were also given the forwards and backwards digit span task (a measure of short-term memory). The verbal subtest scores were combined to make up the verbal IQ and the performance scores were combined to make the performance IQ. The ten subtest scores were combined to produce a full-scale (total) IQ score.
Inter-rater reliability was ensured as follows: the testers were trained psychologists, who were overseen by Dr Claire Bell, a senior psychologist with long experience of psychometric testing within the study. She observed each tester, and met with the group regularly to discuss the precise administration of each subtest and checked their scoring. The task was made as reassuring and unstressful for the child as possible, with the tester explaining that the child would be playing lots of games: looking at pictures, doing puzzles, making patterns and answering some questions. It was explained that some of the things might get quite difficult but not to worry as they were the same things we would ask older children to play. All children were encouraged to have a go at things, even if they thought they were just guessing.
Raw scores were calculated according to the items used in the alternate item form of the WISC. This was achieved by summing the individual items within each subtest and multiplying by 2 for picture completion, information, arithmetic, vocabulary, comprehension and picture arrangement; multiplying by 5/3 for similarities, multiplying by 3/2 for object assembly and block design, thus, making the raw scores comparable to those that would have been obtained had the full test been administered (the raw score for the coding subtest was calculated in the standard way as the full subtest was administered). It is because of this multiplication that some of the scores do not follow a smooth distribution.
For a small number of cases, scores could be imputed where a tester or computer error had been made and such a score would otherwise have been missing. Dr Bell made such decisions on a case by case basis.

Questionnaire assessments
The ALSPAC study included the distribution of questionnaire by mail to the pregnant woman for self-completion and return in a pre-paid envelope at 32 weeks' gestation. Table 6 Effect sizes of selected variables in model 3 in Table 2 in Taylor et al., 2017 (R 2   Maternal characteristics by 5 or >5 mg/dl (n (%)) (complete cases at age 8 years

Publications
Publications on associations of prenatal exposures with child IQ in the ALSPAC cohort are shown in Table 1. Publications on associations of prenatal lead with measures of child development are shown in Table 2. Other publications using the prenatal and child lead measures are shown in Table 3.

Associations with prenatal lead
In our parallel paper (Taylor et al., 2017) we show that prenatal lead exposure was not associated with adverse effects on child IQ at age 4 or 8 years in ALSPAC. There was, however, some evidence to suggest that boys are more susceptible than girls to prenatal exposure to lead. Here we show: (i) Characteristics of ALSPAC participants included and excluded in the study (complete cases) (Table 4) (ii) Maternal characteristics by B-Pb 5 or >5 mg/dl (n (%)) (complete cases at age 8 years) (Table 5) (iii) Effect sizes of selected variables in model 3 in Table 2 of the parallel paper (Taylor et al., 2017) (R 2 ) (complete cases) (   Model 3: adjusted for sex, actual age at testing, maternal education, smoking in pregnancy, alcohol in pregnancy, maternal age, parity, time resident in Avon, housing tenure, household crowding, family adversity index, weighted life events score. a n = 1823. b R 2 for 20th imputation.
involvement in the study design nor in the collection, analysis and interpretation of the data.

Completing financial interests
The authors have no competing interests.

Ethics approval
Ethics approval for the study was obtained from the ALSPAC Ethics and Law Committee and Local Research Ethics Committees.