Luik III: follow-up study Neurobehavioural and cognitive effects of prenatal exposure to persistent environmental toxi

1. Luik III: follow-up study Neurobehavioural and cognitive effects of prenatal exposure to persistent environmental toxicants in three year old children (2002-2007): Preliminary results Griet Vermeir Prof. Dr. M. K. Viaene

2. Overview • Introduction • Goals • Methodology • Results • Discussion & Conclusion

3. Introduction • Several studies (Ribos-Fito et al., 2001; Struempler et al., 1985, Feldman, 1999; Burns et al., 1999; Patandin et al., 1999; …): neurobehavioural development in young children PCBs and heavy metals neg. effect

4. Goals: • The present study is part of the Environmental Health Action Program (2001-2006) in Flanders. => Cohort “neurological development” (sept 2002-march 2007). • Effects of prenatal exposure to heavy metals (Pb, Cd) and PCBs and dioxine-like compounds on neurobehavioural and cognitive development in young children. • Subgroups at risk (gender, low premorbid IQ, no breastfeeding)? (partial data only available till now) • Interactive effects of co-exposures to different chemicals? • Behaviour: a useful bio-effect parameter in follow-up studies in populations exposed to toxic agents?

5. Method • Based on inclusion criteria, the study group consisted of 200 participants (baby-mother pairs). These babies were followed until they reached the age of 3 years. • Data: • Prenatal exposure • (Postnatal exposure) • Questionnaires: concerning mother and child • Cognitive and neurobehavioural examination • Covariates (HOME,SES,family structure,intelligence mother,…)

6. Inclusion criteria • Participant biomonitoring study in Flanders • Pregnancy without complications • born at term (>36 weeks) • no major congenital abnormalities or diseases • no twins • no abnormal or asymmetrical reflexes during standard neurological screening during the first days • Flemish as their mother-tongue • Written informed consent

7. Exposure parameters • Prenatal exposure in cord blood: • Cd • Pb • PCBs (PCB 118, 170 and 28, 52, 101, 138, 153, 180) • Dioxin-like compounds (CALUX-TEQ) • HCB • DDE • (Postnatalexposure: estimates from repetitive food intake questionnaire • First year: monthly • Second year: three-monthly)

8. Tests and questionnaires concerning children

9. Test and questionnaires concerning mother

10. Covariates (1) • General information • Gender • Season of birth • Information family: • family structure, • parity, socio-economic state, • Observation home environment (HOME-score) • General health of the child: • weight, • length, • Apgar score, • medical history, • breastfeeding Test procedures: • Age of child at testing • Test leader

11. Covariates (2) • Data on mother: • age, • highest education level, • intelligence estimate, • complications during pregnancy, • medication during pregnancy and labour, • STAI: anxiety mother, • smoking, alcohol and drug use during pregnancy • Cortisol as fysiological stress parameter • Saliva samples (Salivette) • beginning and end of the first test session from mother and child • the day before the second test session (just after awakening, 30 minutes after awakening, at 1 pm and 30 minutes before going to sleep).

12. Overview measurements and examinations Information pregnancy, Postnatal depression 0 months 1 month 12 months 24 months 36 months Cord blood (Pb, Cd, PCB’s, dioxines, TSH,FT3, FT4),feeding information, covariates Cognitive and Neurobehavioural examination child, testing mother, observation home Environment Cortisol Behaviour child, emotional status mother, life-events Monthly questionnaire food intake and development Three-monthly questionnaire food intake and development

13. Selected regions

14. Practical issues • Data collection is still ongoing: until March 2007. • Data on first 102 participants: preliminary results • Not all variables processed/available: • (Postnatal exposure estimates) • Cortisol as covariate • Quality control of the general questionnaire of the Environmental Health Action Program

15. Results • All analyses were done in SPSS 12.0 • Distribution outcome variables: no transformations needed • No test leader effects (ANCOVA, p>0,100) • Stepwise lineair regression

16. Group characteristics (1)

17. Group characterictics (2) Tabel 2: group characteristics 1 CaluxTEQ-values were available only in n=71 and questionnaires of the results NEO-FFI were available in n=81 and of the STAI in n=79. *SumPCB= PCB 138+ PCB 153+ PCB 180 # Thyroid function

18. Results analyses • FT3, FT4 & TSH • PCBs & CALUX: • sum PCB • CALUX-TEQ • Heavy metals: Pb • (Pesticides: HCB & DDE)

19. Cord blood - Relationship pollutants & THs(preliminary results, in collaboration with Johan Maervoet, UIA) Multiple linear regression - Adjusted for total lipids, age mother, sex, gestational age, and alcohol consumption (n≥ 182)

20. RESULTS • FT3, FT4 & TSH • PCBs & CALUX: • sum PCB • CALUX-TEQ • Heavy metals: Pb • (Pesticides: HCB & DDE)

21. Milestones * significance does not change with STAI in the model

22. Infant behaviour at 12 months significance does not change after correction for STAI The IBQ on 24 months did not show any significant results

23. BSID: mental & motor scales # values corrected for age at time of testing ° significance does not change after correction for STAI None of the other PCB exposure parameters, Calux TEQ, DDE, HCB and Cd concentration reached (borderline) statistical significance (all p>0,1) 1 in ANCOVA analysis the relation is borderline significant in the girls group (partial eta= 0,086; p= 0,053) but not in the boys (partial eta= 0,004, p>0,100).

24. Observation toy preference * significance does not change after correction for STAI In girls, no effects of any of the exposure parameters were found on toy preference.

25. Child behaviour Checklist CBCL 24: no effect. * significance does not change after correction for STAI

26. Child behaviour Checklist

27. BSID: interaction sumPCB*Pb values corrected for age at time of testing ° significance does not change after correction for STAI 1 in ANCOVA analysis, the relation is borderline significant in the girls group (partial eta= 0,081; p= 0,065) but not in the boys (partial eta= 0,006, p>0,100). 2 in ANCOVA analysis, the relation is borderline significant in the girls group (partial eta= 0,088; p= 0,057) but not in the boys (partial eta= 0,038, p>0,100).

28. CBCL: interaction effect * significance does not change after correction for STAI

29. Summary PCBs & CALUX (1) • Sum PCB: • Lower score on Mental Development Index (BSID) • More masculin play behaviour, less gender-specific behaviour (Boys only) • Less affective problems • Easier to sooth at 12 months • Crawling & First Steps Alone at later age

30. Summary PCBs & CALUX (2) • CALUX-TEQ: • less sleeping problems • less emotional reactivity • Interaction sumPCB*PB has surplus effect: • On BSID: even lower Mental Development Index (Girls might be more vulnerable) • (On BSID: Motor Development Index: Girls might be more vulnerable) • On CBCL: even less affective problems

31. RESULTS • FT3, FT4 & TSH • PCBs & CALUX: • sum PCB • CALUX-TEQ • Heavy metals: Pb • (Pesticides: HCB & DDE)

32. Milestones * significance does not change with STAI in the model

33. Infant behaviour * significance does not change with STAI in the model

34. SON IQ * significance does not change after correction for STAI None of the PCB exposure parameters, Calux TEQ, DDE, HCB, and Cd concentration reached (borderline) statistical significance (all p>0,1)

35. Mother-child interaction

36. SON IQ: interaction effects * significance does not change after correction for STAI in ANCOVA analysis, the relation is not significant in boys or girls separately.

37. Summary Pb & Cd • Lower intelligence (SON-IQ): • Total IQ • Reasoning IQ • SON-IQ: Pb*sum PCB • Mother-child interaction: • More difficult to give structure and set limits? • IBQ 12 months: higher activity level • IBQ 24 months: decreased duration of orienting (sustained attention) • Milestones: pulling oneself up later?

38. Other exposure parameters • No significant effects were found with Cd. • No relation was found between sumPCB, Calux TEQ, Cd.

39. Other outcome variables • PSAI: not analysed due to interpretation problems of the official scoring system • GBO and RTOS= no relation with any of the exposure parameters

40. Conclusion (1) • Effects of prenatal exposure to heavy metals (Pb) and PCBs and dioxine-like compounds on neurobehavioural and cognitive development in young children: • Pb: reproduction from literature • PCBs: • developmental index (BSID)=> reproduction literature • gender-specificity => relatively new (suggested in literature) • Subgroups at risk: only partial data available • Gender-effects that were suggested: • Gender specificity • IQ-related (comprehension & reasoning) (partial data only available till now)? Knowing that PCBs are endocrine disruptors, this isn’t surprising. Interference of sex-hormones prenatally might have different effects in boys and girls. As a consequence, the cognitive functions will develop in a different way.

41. Conclusion (2) • Interactive effects of co-exposures to different chemicals? • Structurally different chemicals might have a more pronounced effect (on IQ) in co-exposure • Behaviour: a useful bio-effect parameter in follow-up studies in populations exposed to toxic agents: • Gender specific behaviour: very stable parameter and relatively easy to obtain.

42. Collaborators • Openbaar Psychiatrisch Ziekenhuis • Prof. Dr. M.K. Viaene • Lic. Psych Griet Vermeir • Rita Verachtert • Mieke Thijs • Jan Laenen • Natalie Verelst • KULeuven, Faculteit Psychologie • Prof. B. Van Den Bergh • Ine Nijs • Lien Van Laer • Veerle Nullens • UIA, Department Pharmaceutical sciences • Prof. A. Covaci • Lic Pharm Johan Maervoet • UGent, Radiotherapy and Nuclear Medicine • Prof. Dr. N. Van Laerebeke • Joan Govaerts • All collaborators of Environmental Health Action Program