Facteurs de risque de mauvais développement psychomoteur de l’enfant au Benin

(Risk factors for poor cognitive development of children in Benin)

Michael Osei MIREKU

Supervisor: Michel COTCo-supervisor: Florence BODEAU-LIVINEC

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Background and Context

Cognitive Development

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

• 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)

(Hoque et al., 2012 and Akshoomoff, 2006 )

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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 – Antibiotherapy and 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

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Background and Context cont’d

Prevalence in Africa

57.1% among pregnant women 67.6% among preschool children

Source: WHO, 2008

Hypothesis

•Few studies on maternal folic acid deficiency and cognitive outcomes

•Few studies on lead in childhood, ID and child development

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Maternal anemia(Maternal ID)

Preterm delivery, LBW, IDA in children

Poor cognitive Development???

ID- Iron deficiency

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Objectives

Main

Specific

To identify maternal and childhood risk factors associated with poor cognitive development of children in Benin

• 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

Methods: Flow Diagram of Study

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1008 inclusions

1005 women ANC1 (IPT1)

3 exclusions :- 1 HIV+- 1 uterus malformation- 1 gestational age>28 weeks

978 women ANC2 (IPT2)37 out:- 17 refusal- 4 lost-to-follow-up- 16 migrations

27 out of the study:- 16 refusal - 7 lost-to-follow-up- 4 migrations

941 women followed until delivery

(Ouedraogo, 2012)

637 children already assessed with Mullen at one year of age (71% of follow-up) so far…..

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Study DesignSetting &

Participants

• Cohort • Allada, Benin (Rural community)• Pregnant women and their children (1 year old)

Data Collection

(concluded by Jan. 2013)

• Infants (at birth and at 1 year)• Anthropometric measurements, gender, Hb

concentration, sickle cell status, cognitive function (MSEL)…

• Maternal • Age, SES, gravidity, malaria, malnutrition,

micronutrient deficiencies, complications during pregnancy, Hb concentration (3x)…

Analysis• Stata IC11, SAS• Crude Analysis • Identify confounders using DAGS• Multivariate Analysis

Methods (2)

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Draft Time Table

Year 1Complete data collection

Primary data analysisField trip

Year 2Data analysis

Writing articles

Year 3Writing articles and PhD

manuscript

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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

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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. Acta Obstet Gynecol Scand. 91(9):1061-1068.

WHO. (2008). Worldwide prevalence of anaemia 1993–2005. 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. Thesis defence- 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.

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Thank You For Your Attention

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Definitions

Anemia • Hb concentration< 110 g / L

Micronutrients deficiencies

• 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

Ouedraogo S. 2012

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Study field

Allada

Source : http://www.ias-ch.org/siteias/static/Carte-

Benin.GIFOuedraogo S. 2012

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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)

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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)

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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

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Mothers characteristics (from Smaila Ouedraogo’s PhD)

ANC1 ANC2 DeliveryGestational age (weeks) 22,1 [21,8-22,3]** 28,9 [28,6-29,1]** 39,3 [39,1-39,5]**

Time between visits (weeks) - 6,4 [6,3-6,5]** 12,1 [11,8-12,4]**

Malaria (%) 15,1 4,0 9,6

Helminthes (%) 11,1 7,2 2,4

Hb (g / L)$ 103,2 [102,4-103,9]**

105,1 [104,4-105,8]** 111,4 [110,5-112,4]**

< 110 68,3 64,5 40,6

Iron deficiency (%) 33,3 36,3 30,7

Iron deficiency anemia (%) 24,3 26,5 13,5

Folate deficiency (%) 31,3 16,9 38,7

Vitamine B12 deficiency (%) 3,6 3,5 7,2

Inflammation (%) 20,5 12,3 34,3

Anemia in pregnancy

Cognitive function in childhood

?

Model 1 adjusted for potential confounding factors:

Total effect

Causes of anemia and cognitive function: socio-economic status, mother nutrition, prenatal infections (including malaria)

Infant nutrition (including breastfeeding), anemia and iron-deficiency at 12 months, malaria in infancy

Common causes

If question

Anemia in pregnancy

Cognitive function in childhood

?

And for or stratified by:

Potential confounding and/or intermediate factors: anemia at birth, prematurity, LBW

Model 2 adjusted for:

Potential confounding factors (as described in model 1)

Direct effect

To explore mechanisms