PMID- 33327931 OWN - NLM STAT- MEDLINE DCOM- 20210830 LR - 20220506 IS - 1866-1955 (Electronic) IS - 1866-1947 (Print) IS - 1866-1947 (Linking) VI - 12 IP - 1 DP - 2020 Dec 16 TI - Stunting and lead: using causal mediation analysis to better understand how environmental lead exposure affects cognitive outcomes in children. PG - 39 LID - 10.1186/s11689-020-09346-x [doi] LID - 39 AB - BACKGROUND: Many children in Bangladesh experience poor nutritional status and environmental lead exposure, both of which are associated with lower scores on neurodevelopmental assessments. Recent studies have suggested that part of lead's adverse effects on neurodevelopment are caused in part by lead's effect on growth. New statistical methods are now available to evaluate potential causal pathways in observational studies. This study used a novel statistical method to test the hypothesis that stunting, a measure of linear growth related to poor nutrition, is a mediator and/or an effect modifier of the lead exposure's adverse effect on cognitive development. METHODS: Participants were 734 children from a longitudinal birth cohort established in rural Bangladesh to study the health effects of prenatal and early childhood environmental metal exposures. Lead exposure was estimated using umbilical cord blood samples obtained at birth and blood obtained via venipuncture at age 20-40 months. Stunting was determined using the World Health Organization's standards. Neurodevelopment was assessed at age 20-40 months years using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). We evaluated the effect of lead on stunting and whether the effect of lead on cognitive scores is modified by stunting status in multivariable regression analyses. We then conducted a novel 4-way mediation analysis that allows for exposure-mediator interaction to assess how much of the effect of lead on cognitive scores is explained by the pathway through stunting (mediation) and how much is explained by the interaction between lead and stunt (effect modification). RESULTS: Stunting was not a mediator of the effect of lead in our analyses. Results suggested effect modification by stunting. In an area of Bangladesh with lower lead exposures (median umbilical cord blood lead concentration, 1.7 mug/dL), stunting modified the relationship between prenatal blood lead concentrations and cognitive score at age 2-3 years. A 1-unit increase in natural log cord blood lead concentration in the presence of stunting was associated with a 2.1-unit decrease in cognitive scores (beta = - 2.10, SE = 0.71, P = 0.003). This interaction was not found in a second study site where lead exposures were higher (median umbilical cord blood lead concentration, 6.1 mug/dL, beta = - 0.45, SE = 0.49, P = 0.360). CONCLUSIONS: We used a novel method of mediation analysis to test whether stunting mediated the adverse effect of prenatal lead exposure on cognitive outcomes in Bangladesh. While we did not find that stunting acted as mediator of lead's effect on cognitive development, we found significant effect modification by stunting. Our results suggest that children with stunting are more vulnerable to the adverse effects of low-level lead exposure. FAU - Gleason, Kelsey M AU - Gleason KM AD - Department of Medicine, Robert Larner M.D. College of Medicine, Burlington, VT, USA. FAU - Valeri, Linda AU - Valeri L AD - Department of Biostatistics, Columbia Mailman School of Public Health, New York, NY, USA. FAU - Shankar, Anuraj H AU - Shankar AH AD - Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. FAU - Obrycki, John F AU - Obrycki JF AUID- ORCID: 0000-0003-4450-9194 AD - Department of Neurology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. FAU - Ibne Hasan, Md Omar Sharif AU - Ibne Hasan MOS AD - Dhaka Community Hospital, Dhaka, Bangladesh. FAU - Mostofa, Golam AU - Mostofa G AD - Dhaka Community Hospital, Dhaka, Bangladesh. FAU - Quamruzzaman, Quazi AU - Quamruzzaman Q AD - Dhaka Community Hospital, Dhaka, Bangladesh. FAU - Wright, Robert O AU - Wright RO AD - Department of Preventive Medicine, Icahn School of Medicine at Mt. Sinai, New York, NY, USA. AD - Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Christiani, David C AU - Christiani DC AD - Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. FAU - Bellinger, David C AU - Bellinger DC AD - Department of Neurology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. AD - Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. FAU - Mazumdar, Maitreyi AU - Mazumdar M AD - Department of Neurology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. maitreyi.mazumdar@childrens.harvard.edu. AD - Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. maitreyi.mazumdar@childrens.harvard.edu. LA - eng GR - U54 HD90255/Eunice Kennedy Shriver National Institute of Child Health and Human Development/International GR - R01 ES015533/ES/NIEHS NIH HHS/United States GR - P30 ES000002/ES/NIEHS NIH HHS/United States GR - T42 OH008416/NH/NIH HHS/United States GR - R01 ES026317/ES/NIEHS NIH HHS/United States GR - U54 HD090255/HD/NICHD NIH HHS/United States GR - P42 ES016454/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20201216 PL - England TA - J Neurodev Disord JT - Journal of neurodevelopmental disorders JID - 101483832 RN - 2P299V784P (Lead) SB - IM MH - Bangladesh MH - Child, Preschool MH - *Cognition MH - Female MH - *Growth Disorders/chemically induced MH - Humans MH - Infant MH - Infant, Newborn MH - *Lead/adverse effects MH - *Mediation Analysis MH - Pregnancy PMC - PMC7745460 OTO - NOTNLM OT - Bangladesh OT - Bayley Scales of Infant Development OT - Blood lead OT - Cognitive development OT - Mediation analysis OT - Stunting COIS- The authors declare that they have no competing interests. EDAT- 2020/12/18 06:00 MHDA- 2021/08/31 06:00 PMCR- 2020/12/16 CRDT- 2020/12/17 05:30 PHST- 2020/01/06 00:00 [received] PHST- 2020/11/18 00:00 [accepted] PHST- 2020/12/17 05:30 [entrez] PHST- 2020/12/18 06:00 [pubmed] PHST- 2021/08/31 06:00 [medline] PHST- 2020/12/16 00:00 [pmc-release] AID - 10.1186/s11689-020-09346-x [pii] AID - 9346 [pii] AID - 10.1186/s11689-020-09346-x [doi] PST - epublish SO - J Neurodev Disord. 2020 Dec 16;12(1):39. doi: 10.1186/s11689-020-09346-x.