Fetal Exposure to Environmental Toxins and Attention Deficit Hyperactivity Disorder

Transcription

1 Fetal Exposure to Environmental Toxins and Attention Deficit Hyperactivity Disorder Amanda Ode PhD Student Lund University Division of Occupational and Environmental Medicine

2 Fetal Environment and Neurodevelopment Disorders in Epidemiological Research project (FENDER) Main supervisor Anna Rignell-Hydbom Co-supervisors Lars Rylander Karin Källén Peik Gustafsson Other members Per Olofsson Sten A Ivarsson Nils Haglund

3 Program 1 General overview of the project 2 Our hypothesis 3 Material and methods 4 Results 5 Discussion and conclusion 6 Future studies

4 1. General overview Attention Deficit Hyperactivity Disorder (ADHD) Common neurobehavioral disorder that affects an estimated 6-12% of school-age children Prevalence falls with age Inattention, impulsivity, and hyperactivity Genetic and environmental factors have been linked to neurobehavioral disorders

5 1. General overview Environmental toxins included in the project Perfluorinated Compounds (PFCs) Manganese Phthalates

6 1. General overview PFCs

7 1. General overview Manganese

8 1. General overview Phthalates

9 Program 1 General overview of the project 2 Our hypothesis 3 Material and methods 4 Results 5 Discussion and conclusion 6 Future studies

10 2. Our hypothesis Fetal exposure to PFCs, manganese, and phthalates is associated with ADHD

11 2. Our hypothesis Background to the hypothesis PFCs, manganese, and phthalates cross placental and fetal blood-brain barrier Animal data have shown that exposure to these toxins alter the dopaminergic system The alterations in the dopaminergic system is the major cause of ADHD symptoms High serum levels of these toxins have been linked to ADHD in school-age children

12 Program 1 General overview of the project 2 Our hypothesis 3 Material and methods 4 Results 5 Discussion and conclusion 6 Future studies

13 3. Material and methods Selection of cases and controls Cases - Children born and live in Malmö between 1978 and 2000 and followed up until diagnosed with ADHD at the department of child and adolescent psychiatry - with stored umbilical cord serum in the Malmö Maternity Unit Serum Biobank Controls - Selected from the Swedish Medical Birth Register - matched to cases for the year of birth, and maternal country of origin - with stored umbilical cord serum in the Malmö Maternity Unit Serum Biobank n=206 n=206

14 3. Material and methods Laboratory analyses PFCs and Phthalates: Liquid chromatography-tandem mass spectrometry (LC/MS/MS) Manganese: Inductively coupled plasma mass spectrometry (ICP-MS)

15 3. Material and methods Statistical analyses Wilcoxon s paired test Conditional logistic regression analysis We had an 80% chance of detecting a difference of 0.20 SD, with α value of For the analysis of the threshold effect (above the 75 th percentile), with α value of 0.05 and β value of 0.80, the lowest detectable odds ratio was 1.8

16 3. Material and methods Available variables Maternal country of birth Year of birth Maternal age Body mass index (BMI) Smoking Parity (number of previously born children) Gestational age (age of the fetus) Birth weight Sex of the infant Apgar scores

17 Program 1 General overview of the project 2 Our hypothesis 3 Material and methods 4 Results 5 Discussion and conclusion 6 Future studies

18 4. Results PFCs and ADHD PFOS PFOA Figure 1. Boxplot of the umbilical cord concentrations of perfluorooctane sulfonate (PFOS) (a) and perfluorooctanoic acid (PFOA) (b) in cases having attention deficit hyperactivity disorder and controls. The extreme values of perfluorooctanoic acid for the ADHD cases, 48 and 36 ng/ml, and for the controls, 66, 49, 31, and 23 ng/ml, are not presented in the boxplot.

19 4. Results PFCs and ADHD Table 1. The crude and adjusted odds ratio with 95% confidence interval of attention deficit hyperactivity disorder and exposure to perfluorinated compounds. Crude ADHD Diagnosis Adjusted a PFOS b 0.98 ( ) 0.98 ( ) PFOA b 0.98 ( ) 0.98 ( ) PFOS c <75% percentile % percentile 0.82 ( ) 0.81 ( ) PFOA c <75% percentile % percentile 1.03 ( ) 1.07 ( ) Abbreviations: ADHD, attention deficit hyperactivity disorder; PFOS, perfluorooctane sulfonate; PFOA, perfluorooctanoic acid a Adjusted for maternal active smoking, parity, and gestational age at birth b Odds ratio is calculated for 1 ng/ml increase in umbilical cord serum concentration c Odds ratio is calculated for PFOS and PFOA concentrations at or above the 75% percentile

20 Program 1 General overview of the project 2 Our hypothesis 3 Material and methods 4 Results 5 Discussion and conclusion 6 Future studies

21 5. Discussion Strengths Based on clinical diagnosis at the same department The analyzed blood samples were from the fetal period

22 5. Discussion Limitations Significant losses to get to the final study sample

23 5. Conclusion Our studies revealed no support for the hypothesis of an association between fetal exposure to PFCs and ADHD diagnosis in childhood However, we did not have enough power to detect weak associations between fetal exposure to PFCs and ADHD

24 Program 1 General overview of the project 2 Our hypothesis 3 Material and methods 4 Results 5 Discussion and conclusion 6 Future studies

25 6. Future studies Next step Case-control study on fetal exposure to Manganese and Phthalates and ADHD diagnosis

26 Thanks