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 COT
Co-supervisor: Florence BODEAU-LIVINEC
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)
(Hoque et al., 2012 and Akshoomoff, 2006 )
• Genetic Disorders- Sickle cell anemia
(Thompson et al., 2002)
Risk factors
•
•
•
•
•
Childhood under nutrition
Iron deficiency/ Anemia in children
Preterm births and low birth weight (LBW)
Environmental factors
Socio-economic factors
2
Background and Context cont’d
Anemia
Etiology
Health
Consequences
Control and
Prevention
• Genetics – Sickle cell, G6PD deficiency disease
• Infections – Malaria, Helminthes, HIV
• Nutritional – Iron, Folate, Vit. B12 deficiencies
• Increased risk of maternal morbidity and mortality
(Schmiegelow et al., 2012)
• Infant mortality, Low birth weight, Preterm birth
• 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
3
Background and Context cont’d
Prevalence in Africa
57.1% among pregnant women
67.6% among preschool children
Source: WHO, 2008
4
Hypothesis
Preterm delivery, LBW, IDA in children
Maternal anemia
(Maternal ID)
???
Poor cognitive Development
•Few studies on maternal folic acid deficiency and cognitive
outcomes
•Few studies on lead in childhood, ID and child development
ID- Iron deficiency
5
Objectives
Main
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
Specific
• 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
6
Methods: Flow Diagram of Study
1008 inclusions
1005 women ANC1 (IPT1)
978 women ANC2 (IPT2)
3 exclusions :
- 1 HIV+
- 1 uterus malformation
- 1 gestational age>28 weeks
27 out of the study:
- 16 refusal
- 7 lost-to-follow-up
- 4 migrations
37 out:
- 17 refusal
- 4 lost-to-follow-up
- 16 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…..
7
Methods (2)
Study Design
Setting &
Participants
Data
Collection
(concluded by Jan.
2013)
Analysis
• Cohort
• Allada, Benin (Rural community)
• Pregnant women and their children (1 year old)
• 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)…
•
•
•
•
Stata IC11, SAS
Crude Analysis
Identify confounders using DAGS
Multivariate Analysis
8
Draft Time Table
Year 1
Complete data collection
Year 2
Year 3
Primary data analysis
Data analysis
Field trip
Writing articles
Writing articles and PhD
manuscript
9
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
10
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.
11
12
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+
Micronutrients
deficiencies
• Folate deficiency:
• folate < 6,6 ng / L
• Vitamine B12 deficiency :
• vitamine B12 < 150 pg / L
• Iron deficiency anemia:
• Anemia+iron deficiency
Ouedraogo S. 2012
13
Study field
Allada
Source : http://www.iasch.org/siteias/static/Carte-Benin.GIF
Ouedraogo S. 2012
14
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)
15
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)
16
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
17
Mothers characteristics (from Smaila Ouedraogo’s PhD)
ANC1
ANC2
Delivery
22,1 [21,8-22,3]**
28,9 [28,6-29,1]**
39,3 [39,1-39,5]**
-
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
103,2 [102,4103,9]**
68,3
105,1 [104,4-105,8]**
111,4 [110,5-112,4]**
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
Gestational age (weeks)
Time between visits (weeks)
Hb (g / L)$
< 110
18
Model 1 adjusted for potential
confounding factors:
Causes of anemia and cognitive
function: socio-economic status,
mother nutrition, prenatal
infections (including malaria)
Anemia in
pregnancy
?
If question
Cognitive function in
childhood
Total effect
Common
causes
Infant nutrition (including
breastfeeding), anemia and
iron-deficiency at 12 months,
malaria in infancy
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
?
Anemia in
pregnancy
Direct effect
Cognitive function in
childhood