PMID- 30057028 OWN - NLM STAT- MEDLINE DCOM- 20190806 LR - 20190806 IS - 1618-131X (Electronic) IS - 1438-4639 (Linking) VI - 222 IP - 1 DP - 2019 Jan TI - Prenatal mercury exposure and child neurodevelopment outcomes at 18 months: Results from the Mediterranean PHIME cohort. PG - 9-21 LID - S1438-4639(18)30084-1 [pii] LID - 10.1016/j.ijheh.2018.07.011 [doi] AB - INTRODUCTION: Neurotoxicity due to acute prenatal exposure to high-dose of mercury (Hg) is well documented. However, the effect of prenatal exposure to low Hg levels on child neurodevelopment and the question about "safety" of fish-eating during pregnancy remain controversial. International comparisons of Hg concentrations in mother-child biological samples and neurodevelopmental scores embedded in birth cohort studies may provide useful evidence to explore this issue. MATERIALS AND METHODS: The Mediterranean (Italy, Slovenia, Croatia, and Greece) cohort study included 1308 mother-child pairs enrolled in the Public Health Impact of long-term, low-level, Mixed Element exposure in a susceptible population EU Sixth Framework Programme (PHIME). Maternal hair and venous blood, cord blood and breast milk samples were collected, and total Hg (THg) levels were measured. Demographic and socioeconomic information, lifestyles and nutritional habits were collected through questionnaires at different phases of follow-up. Children at 18 months of age underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Multivariate linear and logistic regressions were performed, for each country, to assess the association between THg and BSID-III scores, obtaining adjusted beta coefficients and odds ratios (ORs). These values were used to conduct a meta-analysis, to explore possible heterogeneity among countries and to obtain combined estimates of the association between THg exposure and BSID-III scores. RESULTS: Median THg (ng/g) was: 704 in maternal hair, 2.4 in maternal blood, 3.6 in cord blood, and 0.6 in breast milk. THg concentrations were highest in Greece and lowest in Slovenia. BSID-III neurodevelopmental scores were higher in Croatia and Slovenia. The meta-analysis of multivariate linear models found an overall positive association between language composite score and receptive communication scaled score and increasing THg in maternal hair (n = 1086; beta = 0.55; 95%CI: 0.05-1.05 and n = 1075; beta = 0.12; 95%CI: 0.02-0.22, respectively). The meta-analysis of logistic regression models showed that the overall adjusted OR between THg in cord blood and suboptimal gross motor score was borderline significant (n = 882; OR = 1.03; 95%CI: 1.00-1.07). Heterogeneity was found across the four sub-cohorts for language composite score in maternal blood, and for fine motor scaled score in cord blood and breast milk. Language composite score and THg concentrations in maternal venous blood were positively related (n = 58; beta = 4.29; CI95% (-0.02, 8.60)) in Croatia and an increase of 1 ng/g of THg in maternal venous blood was associated with a reduced risk for children to fall in the lowest quintile of language score by 31% (n = 58; OR = 0.69; CI 95%: 0.37, 1.01). The comparison of beta coefficients obtained by multiple linear regression model showed an inverse association between fine motor score and THg concentrations in cord blood for Croatia (n = 54; beta = -0.53; CI 95%: -1.10, 0.04) and Slovenia (n = 225; beta = -0.25; CI 95%: -0.49, -0.01). In Slovenia THg level in breast milk was associated with suboptimal fine motor performance (n = 195; OR = 5.25; CI 95%: 1.36, 21.10). CONCLUSIONS: This study showed an inverse relation between THg levels and developmental motor scores at 18 months, although the evidence was weak and partially internally and externally inconsistent. No evidence of detrimental effects of THg was found for cognitive and language outcomes at these concentrations and age. CI - Copyright (c) 2018 Elsevier GmbH. All rights reserved. FAU - Barbone, Fabio AU - Barbone F AD - Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", via dell'Istria, 65/1, 34137, Trieste, Italy. Electronic address: fabio.barbone@burlo.trieste.it. FAU - Rosolen, Valentina AU - Rosolen V AD - Department of Medical Area, University of Udine, via Colugna 50, 33100, Udine, Italy. Electronic address: valentina.rosolen@uniud.it. FAU - Mariuz, Marika AU - Mariuz M AD - Department of Medical Area, University of Udine, via Colugna 50, 33100, Udine, Italy. Electronic address: marika.mariuz@uniud.it. FAU - Parpinel, Maria AU - Parpinel M AD - Department of Medical Area, University of Udine, via Colugna 50, 33100, Udine, Italy. Electronic address: maria.parpinel@uniud.it. FAU - Casetta, Anica AU - Casetta A AD - Department of Medical Area, University of Udine, via Colugna 50, 33100, Udine, Italy. Electronic address: anica.casetta@uniud.it. FAU - Sammartano, Francesca AU - Sammartano F AD - Department of Medical Area, University of Udine, via Colugna 50, 33100, Udine, Italy. Electronic address: francesca.sammartano@uniud.it. FAU - Ronfani, Luca AU - Ronfani L AD - Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", via dell'Istria, 65/1, 34137, Trieste, Italy. Electronic address: luca.ronfani@burlo.trieste.it. FAU - Vecchi Brumatti, Liza AU - Vecchi Brumatti L AD - Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", via dell'Istria, 65/1, 34137, Trieste, Italy. Electronic address: liza.vecchibrumatti@burlo.trieste.it. FAU - Bin, Maura AU - Bin M AD - Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", via dell'Istria, 65/1, 34137, Trieste, Italy. Electronic address: maura.bin@burlo.trieste.it. FAU - Castriotta, Luigi AU - Castriotta L AD - Institute of Hygiene and Clinical Epidemiology Academic Hospital of Udine, via Colugna 50, 33100, Udine, Italy. Electronic address: luigi.castriotta@asuiud.sanita.fvg.it. FAU - Valent, Francesca AU - Valent F AD - Institute of Hygiene and Clinical Epidemiology Academic Hospital of Udine, via Colugna 50, 33100, Udine, Italy. Electronic address: francesca.valent@asuiud.sanita.fvg.it. FAU - Little, D'Anna Latesha AU - Little DL AD - Azienda per I'Assistenza Sanitaria n. 5 Friuli Occidentale, via Piave 54 33170 Pordenone (PN), Italy. Electronic address: danna.little@aas5.sanita.fvg.it. FAU - Mazej, Darja AU - Mazej D AD - Jozef Stefan Institute, Jamova 39 SI-1000, Ljubljana, Slovenia. Electronic address: darja.mazej@ijs.si. FAU - Snoj Tratnik, Janja AU - Snoj Tratnik J AD - Jozef Stefan Institute, Jamova 39 SI-1000, Ljubljana, Slovenia; International Postgraduate School Jozef Stefan, Jamova 39 SI-1000, Ljubljana, Slovenia. Electronic address: janja.tratnik@ijs.si. FAU - Miklavcic Visnjevec, Ana AU - Miklavcic Visnjevec A AD - Jozef Stefan Institute, Jamova 39 SI-1000, Ljubljana, Slovenia. Electronic address: anamiki41@gmail.com. FAU - Sofianou, Katia AU - Sofianou K AD - Institute of Child Health, "Aghia Sophia" Children's Hospital, Thivon & Papadiamantopoulou, Goudi, 115 27, Athens, Greece. Electronic address: katsofkat@hotmail.com. FAU - Spiric, Zdravko AU - Spiric Z AD - Green Infrastructure Ltd., Fallerovo Setaliste 22, 10.000, Zagreb, Croatia. Electronic address: zdravko_spiric@hotmail.com. FAU - Krsnik, Mladen AU - Krsnik M AD - University Medical Centre Ljubljana, Slovenia. Electronic address: mladen.krsnik@kclj.si. FAU - Osredkar, Josko AU - Osredkar J AD - University Medical Centre Ljubljana, Slovenia. Electronic address: josko.osredkar@kclj.si. FAU - Neubauer, David AU - Neubauer D AD - University Medical Centre Ljubljana, Slovenia. Electronic address: david.neubauer@kclj.si. FAU - Kodric, Jana AU - Kodric J AD - University Medical Centre Ljubljana, Slovenia. Electronic address: jana.kodric@kclj.si. FAU - Stropnik, Stasa AU - Stropnik S AD - University Medical Centre Ljubljana, Slovenia. Electronic address: stasa.stropnik@kclj.si. FAU - Prpic, Igor AU - Prpic I AD - The Clinical Hospital Center of Rijeka, Kresimirova 42, 51000, Rijeka, Croatia. Electronic address: igor.prpic@medri.uniri.hr. FAU - Petrovic, Oleg AU - Petrovic O AD - The Clinical Hospital Center of Rijeka, Kresimirova 42, 51000, Rijeka, Croatia. Electronic address: oleg@kbc-rijeka.hr. FAU - Vlasic-Cicvaric, Inge AU - Vlasic-Cicvaric I AD - The Clinical Hospital Center of Rijeka, Kresimirova 42, 51000, Rijeka, Croatia. Electronic address: inge_v_c@yahoo.com. FAU - Horvat, Milena AU - Horvat M AD - Jozef Stefan Institute, Jamova 39 SI-1000, Ljubljana, Slovenia; International Postgraduate School Jozef Stefan, Jamova 39 SI-1000, Ljubljana, Slovenia. Electronic address: milena.horvat@ijs.si. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20180726 PL - Germany TA - Int J Hyg Environ Health JT - International journal of hygiene and environmental health JID - 100898843 RN - FXS1BY2PGL (Mercury) MH - Adult MH - Child Development/*drug effects MH - Environmental Exposure/adverse effects MH - Female MH - Humans MH - Infant MH - Mercury/blood/*toxicity MH - Neurodevelopmental Disorders/*chemically induced MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Young Adult OTO - NOTNLM OT - Bayley scales of infant and toddler development OT - Child neurodevelopment OT - Cohort study OT - Developmental motor scales OT - Fish OT - Mercury EDAT- 2018/07/31 06:00 MHDA- 2019/08/07 06:00 CRDT- 2018/07/31 06:00 PHST- 2018/02/16 00:00 [received] PHST- 2018/07/13 00:00 [revised] PHST- 2018/07/19 00:00 [accepted] PHST- 2018/07/31 06:00 [pubmed] PHST- 2019/08/07 06:00 [medline] PHST- 2018/07/31 06:00 [entrez] AID - S1438-4639(18)30084-1 [pii] AID - 10.1016/j.ijheh.2018.07.011 [doi] PST - ppublish SO - Int J Hyg Environ Health. 2019 Jan;222(1):9-21. doi: 10.1016/j.ijheh.2018.07.011. Epub 2018 Jul 26.