Michael Osei MIREKU Supervisor: Michel COT Co-supervisor: Florence BODEAU-LIVINEC

1. Facteurs de risque de mauvais développement psychomoteur de l’enfant au Benin(Riskfactors for poor cognitive development of children in Benin) Michael Osei MIREKU Supervisor: Michel COT Co-supervisor: Florence BODEAU-LIVINEC

2. Background and Context Cognitive Development • Neurological and psychological development of a child • Motor (Gross and Fine) • Language (Receptive and Expressive) • Visual Reception • Measurement • Bayley Scales of Infant Development (BSID) • Mullen Scales of Early Learning (MSEL) • (Hoqueet al., 2012 and Akshoomoff, 2006 ) Risk factors • Genetic Disorders- Sickle cell anemia • (Thompson et al., 2002) • Childhood under nutrition • Iron deficiency/ Anemia in children • Preterm births and low birth weight (LBW) • Environmental factors • Socio-economic factors

3. Background and Context cont’d Anemia Etiology • Genetics – Sickle cell, G6PD deficiency disease • Infections – Malaria, Helminthes, HIV • Nutritional – Iron, Folate, Vit. B12 deficiencies Health Consequences • Increased risk of maternal morbidity and mortality (Schmiegelow et al., 2012) • Infant mortality, Low birth weight, Preterm birth Control and Prevention • Genetics – Antibiotherapyand analgesics • Infections –Artemesin-based drugs, ITMNs, Albendazole-based drugs • Nutritional – Iron, Folate, Vit. B12 supplements G6PD (Glucose-6-phosphate dehydrogenase) ITMNs-Insecticide treated mosquito nets

4. Background and Context cont’d Prevalence in Africa 57.1% among pregnant women 67.6% among preschool children Source: WHO, 2008

5. Hypothesis Preterm delivery, LBW, IDA in children • Few studies on maternal folic acid deficiency and cognitive outcomes • Few studies on lead in childhood, ID and child development ??? Maternal anemia (Maternal ID) Poor cognitive Development ID- Iron deficiency

6. Objectives Main To identify maternal and childhood risk factors associated with poor cognitive development of children in Benin Specific • To determine : • the effect of maternal anemia and maternal iron deficiency on the cognitive development of children in Benin at age 1 year • the effect of maternal folic acid deficiency on the cognitive development of children in Benin at age 1 year • the impact of lead exposure on the cognitive development of children in Benin at age 1 year

7. Methods: Flow Diagram of Study 1008inclusions 3exclusions : - 1HIV+ - 1uterus malformation - 1gestationalage>28 weeks 1005women ANC1 (IPT1) 27 out of the study: - 16refusal - 7lost-to-follow-up - 4 migrations 978womenANC2 (IPT2) 37 out: - 17refusal - 4lost-to-follow-up - 16 migrations 941womenfolloweduntildelivery (Ouedraogo, 2012) 637 children already assessed with Mullen at one year of age (71% of follow-up) so far…..

8. Methods (2) Study Design Setting & Participants • Cohort • Allada, Benin (Rural community) • Pregnant women and their children (1 year old) • Infants (at birth and at 1 year) • Anthropometric measurements, gender, Hbconcentration, sickle cell status, cognitive function (MSEL)… • Maternal • Age, SES, gravidity, malaria, malnutrition, micronutrient deficiencies, complications during pregnancy, Hb concentration (3x)… Data Collection (concluded by Jan. 2013) Analysis • Stata IC11, SAS • Crude Analysis • Identify confounders using DAGS • Multivariate Analysis

9. Draft Time Table

10. Relevance of Study • Second study on the association between maternal anemia and cognitive development after only one small existing study . (Vaughn et.al, 1986) • Help inform policy makers on appropriate interventions during pregnancy • Contribute to the growing knowledge on risk factors of cognitive development in children

11. References Hoque MM, Ahmed NU, Khan FH, Jahan R, Yasmeen HN, Chowdhury MA. (2012) Breastfeeding and cognitive development of children: assessment at one year of age. Mymensingh Med J. 21(2):316-21. Akshoomoff N. (2006) Use of the Mullen Scales of Early Learning for the Assessment of Young Children with Autism Spectrum Disorders. Child Neuropsychol. 12(4-5): 269-277 Schmiegelow C, Minja D, Oesterholt M, Pehrson C, Suhrs HE, Bosteom S, Lemnge M, Magistrado P, Rasch V, Lusingu J, Theander TG, Nielsen BB. (2012).Factors associated with and causes of perinatal mortality in northeastern Tanzania. ActaObstetGynecol Scand. 91(9):1061-1068. WHO. (2008). Worldwideprevalenceof anaemia1993–2005. Pp 8-10 Thompson RJ Jr., Gustafson KE, Bonner MJ, Ware RE. (2002). Neurocognitive development of young children with sickle cell disease through three years of age. J. Pediatr. Psychol. 27 (3):235-244. Ouedraogo S. Thesisdefence- UPMC in 2012 Vaughn J, Brown J, Carter JP. (1986).The effects of maternal anemia on infant behavior. Journal of the National Medical Association. 78(10) : 963-968.

12. Thank You For Your Attention

13. Definitions Anemia • Hb concentration< 110 g / L • Inflammation : • CRP ≥ 6mg/mL • Iron deficiency: • ferritin < 12 µg / L ou 12 µg/L ≥ ferritin ≤ 30 µg/L et CRP+ • Folate deficiency: • folate < 6,6 ng / L • Vitamine B12 deficiency : • vitamine B12 < 150 pg / L • Iron deficiency anemia: • Anemia+iron deficiency • Micronutrients deficiencies Ouedraogo S. 2012

14. Study field Allada Source : http://www.ias-ch.org/siteias/static/Carte-Benin.GIF Ouedraogo S. 2012

15. Methods: Cohort of pregnanct women MiPPAD and APEC (PI: Michel Cot) Birth cohort study in Benin 1005 pregnant women included in a trial funded by the European Commission comparing 2 IPTp: sulfadoxine–pyrimethamine and mefloquine Study of risk factors for anemia during pregnancy (malaria, helminths, iron deficiency, folate deficiency, vitamine B12 deficiency)

16. Variables in pregnant women At the time of recruitment: parity, gestational age, MUAC (middle upper-arm circumference), maternal weight and height and demographic and socio-economic data Malaria (parasite density and placental infection), other parasitizes (helminthes), multiple pregnancy, urinary tract infection, sickle cell disease, micronutrients deficiency, under nutrition (body mass index), poor antenatal care Anemia: Anemia will be defined as hemoglobin <110 g/l and severe anemia as hemoglobin <80 g/l Iron-deficiency anemia: serum ferritin C-reactive protein (CRP)

17. Variables in infants At 1, 9 and 12 months (within the trial): Mortality Anthropometric measurements Blood assessments: malaria, other infections, nutrition, Hb, ferritin, helminthes, folic acid, vitamin B12 At 12 months (within the R21): Development assessment MSEL: Mullen Scales of Early Learning, Ten Questions Questionnaire Maternal depression, parent-child interaction (HOME), maternal non-verbal IQ (Raven) Blood lead

18. Mothers characteristics (from SmailaOuedraogo’s PhD)

19. Model 1 adjusted for potential confounding factors: If question Causes of anemia and cognitive function: socio-economic status, mother nutrition, prenatal infections (including malaria) ? Anemia in pregnancy Cognitive function in childhood Total effect Common causes Infant nutrition (including breastfeeding), anemia and iron-deficiency at 12 months, malaria in infancy

20. To explore mechanisms Model 2 adjusted for: Potential confounding factors (as described in model 1) And for or stratified by: Potential confounding and/or intermediate factors: anemia at birth, prematurity, LBW ? Cognitive function in childhood Anemia in pregnancy Direct effect