Journal of Trace Elements in Medicine and Biology 29 (2015) 39–46
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Review
Colder-to-warmer changes in children’s blood lead concentrations are related to previous blood lead status: Results from a systematic review of prospective studies Gerard Ngueta a,b,∗ , Catherine Gonthier a , Patrick Levallois a,b,c a
Population Health and Optimal Health Practices Research Unit, Research Center of CHU of Quebec, Laval University, Quebec, QC, Canada Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Quebec, QC, Canada c National Public Health Institute of Quebec, QC, Canada b
a r t i c l e
i n f o
Article history: Received 12 March 2014 Accepted 18 July 2014 Keywords: Season Blood lead levels Children Prospective studies
a b s t r a c t Objective: To estimate the extent of changes in mean BLLs from colder to warmer months, in children aged 1–5 years with different status of lead in colder months. Methodology: We performed a systematic review using an in-house algorithm developed in MEDLINE, EMBASE, Web of Science, and CINHAL. Search was performed between November 2012 and July 2013, and data evaluation and extraction were subsequently conducted. The mean BLLs observed in the warmer months was divided by the one observed in the colder months to obtain the warmer-to-colder ratio (WCR). Study-specific WCRs were pooled using the fixed-effects method of Mantel–Haenszel to estimate the combined WCR. Results: From 4040 papers initially identified, eight cohort studies were considered relevant for inclusion. The combined WCR was inversely related to the BLLs observed during colder months. The values were 1.25 (95% CI: 0.90–1.60), 1.06 (95% CI: 0.92–1.19), and 0.95 (95% CI: 0.51–1.39) for children showing baseline BLLs of 0.10) nor in those with children aged more
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G. Ngueta et al. / Journal of Trace Elements in Medicine and Biology 29 (2015) 39–46
Fig. 1. Flow chart of study selection and elimination process. Table 1 Estimate of warmer-to-colder ratio (WCR). Authors
Children’s age and sample size
Definition of season
Mean (standard deviation) of ambient temperaturea
Blood collection
WCRb
Reigart and Whitlock [26] McCusker [11]
Colder (Oct–Feb) warmer (July–Sept) NA
Colder: 13.3 (4.4) warmer: 26.7 (1.5) Winter: 0.1 (2.5) summer: 24.7 (0.8)
NA
Baghurst et al. [17]
3.3 years (mean) N = 82c 10 months-12 years winter cohort N = 116 summer cohort N = 30 6–60 months N = 646
Colder (April–Oct) Warmer (Nov–March)
Colder: 17.8 (4.2) warmer: 29.7 (2.5)
Capillary blood
U.S.EPA [24]
0–24 months N = 249
Winter: 4.1 (1.6) summer: 24.0 (0.5)
Umbilical cord blood
Berglund et al. [18]
1–3 years N = 16e
Summer (June, July, August) winter (Feb, March) NA
1.060‡ 1.252‡‡ Cohort A: 1.220* Cohort B: 0.947 Cohort C: 0.785* Cohort D: 0.867 Cohort E: 0.823* 6 months of age: 1.065 15 months of age: 1.111** 24 months of age: 1.014 36 months of age: 1.080** 48 months of age: 1.063* 60 months of age: 1.035 3.57d
Venous blood
1.200*
Nichani et al. [20]
0–15 years N = 71
Oct-Nov 1992: 2.4 (2.2); Feb 1993: −2.8 (1.0) Dec–Jan: 26.1 (2.1) March–May: 29.2 (0.9) June–Aug: 28.7 (1.2)
Capillary blood
1.247***
Kemp et al. [19]
1–8 years N = 142
Winter: 5.0 (1.7) Summer: 23.3 (4.9)
Venous blood
1–3-year-old 1.324** 4–8 year-old 1.130**
Strand et al. [23]
12–24 months N = 250
Unknownf
Venous blood
Spring/fall ratio: 1.266***
a
Winter season (non-monsoon: Dec 2002–Jan 2003), Summer (March–May 2003), Rainy (June–Aug 2003), Winter (Dec–March) Summer (July–Sept) NA ◦
Venous blood
As recorded by the local station during the period of study (expressed in C). b p-value of seasonal effect was reported when available; Authors reported seasonal changes in geometric mean of BLLs as being statistically significant, * p < 0.05, ** p < 0.01 or *** p < 0.001. c Only children included in long-term follow-up. d Authors did not report the p-value for seasonal effect. e Only children from Stockholm with BLLs greater than percentile 75 of blood lead distribution were followed. f Authors did not specify cities where the study was conducted; ‡ for children with elevated free erythrocyte porphyrins ‡‡ for children with elevated free erythrocyte porphyrins NA, Not available; BLLs, Blood lead levels.
G. Ngueta et al. / Journal of Trace Elements in Medicine and Biology 29 (2015) 39–46
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Fig. 2. Warmer-to-colder ratio (WCR) by blood lead (BLLs) during colder months with (A) and without (B) the extreme value from US. EPA study (x = 2,13; y = 3,53).
than 3 years (21 = 0.23, p > 0.10). The WCRs were similar when studies were grouped by the place of study or the date of study. However, the general trend was toward an increase of combined WCRs in children with BLLs 3 years 2 Date of study ≤ 1996 2 >1996 3 Place of study Northern countries 3 Others 2 Mean blood lead concentrations during colder seasons 1 30 g dL−1 ) are reported to have low levels of serum 25-hydroxyvitamin D, and low 1,25-dihydroxyvitamin-D [8–10]. The formation of these metabolites begins in the skin (promoted by the sunlight exposure) and is completed in the liver and kidney [32]. Given that the synthesis of the active form of vitamin D (1,25-dihydroxyvitamin-D) mainly occurs in the kidney, the inverse association between BLLs and 1,25-dihydroxyvitamin-D is plausible and may be mediated by the proximal tubular dysfunction in children with excessive lead exposure. In support of this hypothesis, previous studies suggest that renal dysfunction could occur in children exposed to lead [35]. Although the evidence of renal toxicity of lead at low-level (