Balance Ability in 7- and 10-Year-Old Children
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Open Access Research BMJ Open: first published as 10.1136/bmjopen-2015-009635 on 30 December 2015. Downloaded from Balance ability in 7- and 10-year-old children: associations with prenatal lead and cadmium exposure and with blood lead levels in childhood in a prospective birth cohort study Caroline M Taylor,1 Rachel Humphriss,2,3 Amanda Hall,2,3 Jean Golding,1 Alan M Emond1 To cite: Taylor CM, ABSTRACT et al Strengths and limitations of this study Humphriss R, Hall A, . Objectives: Most studies reporting evidence of Balance ability in 7- and 10- adverse effects of lead and cadmium on the ability to ▪ year-old children: Data were collected prospectively in a popula- balance have been conducted in high-exposure groups associations with prenatal tion-based study. lead and cadmium exposure or have included adults. The effects of prenatal ▪ The number of participants was large compared and with blood lead levels in exposure have not been well studied, nor have the with several comparable studies. childhood in a prospective effects in children been directly studied. The aim of the ▪ Measures of Pb and Cd do not necessarily birth cohort study. BMJ Open study was to identify the associations of lead (in utero reflect lifetime exposure. 2015;5:e009635. and in childhood) and cadmium (in utero) exposure ▪ Balance measures have a poor test–retest doi:10.1136/bmjopen-2015- with the ability to balance in children aged 7 and reliability. 009635 10 years. Design: Prospective birth cohort study. ▸ Prepublication history Participants: Maternal blood lead (n=4285) and and additional material is cadmium (n=4286) levels were measured by INTRODUCTION available. To view please visit inductively coupled plasma mass spectrometry in Balance, or postural stability, is defined as the journal (http://dx.doi.org/ women enrolled in the Avon Longitudinal Study of the ability to keep the centre of gravity over 10.1136/bmjopen-2015- http://bmjopen.bmj.com/ Parents and Children (ALSPAC) during pregnancy. 1 009635). the base of support. The maintenance of Child lead levels were measured in a subsample of 582 balance underpins the ability to carry out Received 4 August 2015 of ALSPAC children at age 30 months. nearly all daily activities. Balance impairment Revised 10 November 2015 Main outcome measures: Children completed a in adults is also a major cause of falls and of Accepted 2 December 2015 heel-to-toe walking test at 7 years. At 10 years, the fall-related injuries, such as hip fracture, children underwent clinical tests of static and dynamic which can cause isolation and make it diffi- balance. Statistical analysis using SPSS V.19 included cult to live independently. The control of logistic regression modelling, comparing categories of balance is complex and is dependent on ≥5 vs <5 µg/dL for lead, and ≥1 vs <1 µg/L for on September 23, 2021 by guest. Protected copyright. cadmium. sensory inputs from the vestibular and visual Results: Balance at age 7 years was not associated systems, neural processing centres in the central nervous system, and motor inputs 1Centre for Child and with elevated in utero lead or cadmium exposure (adjusted OR for balance dysfunction: Pb 1.01 (95% from the proprioceptive centre. Functional Adolescent Health, School of fi Social and Community CI 0.95 to 1.01), n=1732; Cd 0.95 (0.77 to 1.20), damage or de cits in any of these systems Medicine, University of n=1734), or with elevated child blood lead level at can lead to balance dysfunction, which can Bristol, Bristol, UK age 30 months (adjusted OR 0.98 (0.92 to 1.05), be associated with low self-esteem, anxiety 2 School of Social and n=354). Similarly, neither measures of static nor and loss of confidence in children.2 Community Medicine, dynamic balance at age 10 years were associated University of Bristol, Bristol, Lead and cadmium are toxic metals: the with in utero lead or cadmium exposure, or child effects of lead on neurocognitive and behav- UK lead level. 3Children’s Hearing Centre, ioural functions in children are well docu- Conclusions: These findings do not provide any – University Bristol NHS mented,3 5 but those of cadmium are less Foundation Trust, Bristol, UK evidence of an association of prenatal exposure to lead 6–8 or cadmium, or lead levels in childhood, on balance clear. Lead passes freely through the pla- Correspondence to ability in children. Confirmation in other cohorts is centa, so that the ratio of fetal to maternal Dr Caroline M Taylor; needed. blood lead is about 0.8, although the pla- [email protected] centa can act as a partial barrier to Taylor CM, et al. BMJ Open 2015;5:e009635. doi:10.1136/bmjopen-2015-009635 1 Open Access BMJ Open: first published as 10.1136/bmjopen-2015-009635 on 30 December 2015. Downloaded from cadmium.9 The fetus is particularly vulnerable to the census surveys.23 Further details of ALSPAC are available effects of these metals because of high rates of cell div- at http://www.bris.ac.uk/alspac. ision and development. The development of the inner ear and vestibular function spans the whole of the Collection, storage and analysis of blood samples period of gestation (eg, the membranous labyrinth is Maternal blood samples complete by week 7 with development of the bony laby- Whole blood samples were collected in trace-element- rinth from weeks 9 to 23; the vestibular apparatus is in free vacutainers (Becton and Dickinson, Oxford, UK) by an adult-like form by week 25, and is active by week 32; midwives as early as possible in pregnancy. The median vestibular ganglions develop from week 12 and reach gestational age at the time of blood sampling was maturity at week 39, etc10). Thus, prenatal exposure to 11 weeks. The IQR was 9–13 weeks, and 93% of the lead and cadmium may have adverse effects on the samples were collected at <18 weeks of gestation. Whole development of the inner ear, and hence, on vestibular blood samples were stored in the original tube at 4°C at function and balance ability in later childhood. the collection site before being transferred to the It was noted in the 1980s that children who survived central Bristol laboratory within 1–4 days. Samples were acute lead encephalopathy had ataxia and experienced at ambient temperature during transfer (up to 3 h). difficulties in maintaining postural balance.11 This led to They were then stored at 4°C until analysis. Samples a series of studies in children with somewhat more mod- were analysed for lead and cadmium using inductively erate levels of lead exposure (5.0–20.7 µg/dL) showing coupled plasma mass spectrometry in standard mode that the child’s lead level was associated with balance by R Jones at the Centers for Disease Control and – dysfunction and sway oscillation.12 16 To the best of our Prevention (CDC), Bethesda, Maryland, USA (CDC knowledge, there are no reports of the effect of Method 3009.1). Quality control was monitored as out- cadmium on balance ability in children. However, a lined in Golding et al.24 The analyses were completed on recent study of lead and cadmium levels in adults in the 4285 samples for lead and 4286 for cadmium. One US National Health and Nutrition Examination Survey sample had a lead level below the limit of detection found preliminary evidence of an association of lead (0.29 µg/dL); 1119 samples were below the lower limit and cadmium with balance and vestibular function.17 In of detection for cadmium (0.20 µg/L). These samples addition, altered postural balance response has been were assigned a value of 0.7 times the lower limit of reported in adult workers occupationally exposed to detection (LOD/√2).25 26 – lead18 20 and cadmium.21 These results require confirm- ation in other cohorts and particularly in children. Child blood samples The aims of our study were to investigate the associa- Details of the selection of the subsample of children and tions of in utero exposure to lead and cadmium, and analysis of the blood samples have been reported previ- 327 lead levels in children, and on balance in childhood ously in detail. In brief, a 10% randomly selected http://bmjopen.bmj.com/ using data obtained from the Avon Longitudinal Study subsample of parents whose babies were born in the last of Parents and Children (ALSPAC). 6 months of the ALSPAC study were invited to attend a research clinic (Children in Focus, CIF). At age 30 months, parental consent was sought for a venous METHODS blood sample, and was given by 81% of the 1135 chil- fi We rst modelled associations of in utero exposure to dren in the CIF group. The sample was drawn into lead- lead and cadmium, using maternal blood levels during free tubes from 653 (71%) of children attending the pregnancy, with clinical measures of balance (dynamic fi clinic. However, 69 samples were insuf cient, leaving 582 on September 23, 2021 by guest. Protected copyright. and static) at 7 and 10 years of age. We also investigated samples for analysis. Analysis was by atomic absorption associations with questionnaire items related to balance spectrometry (Southampton General Hospital, UK) with repeated at 30, 42 and 81 months, and further items at appropriate quality controls. 10 years. We also modelled the associations of child levels of lead with the balance variables. Balance variables Clinic measures The ALSPAC study Full details of the balance outcomes including details of The study sample was derived from the ALSPAC study, a the measurements and validity have previously been population-based study investigating environmental and published.28 In brief, at age 7 years, the heel-to-toe genetic influences on the health, behaviour and devel- walking test of the Movement Assessment Battery for opment of children.