1. The impact of malaria in pregnancy on changes in blood pressure in children over the first year of life OO Ayoola#**, OO Omotade*, I Gemmell, PE Clayton & JK Cruickshank # Endocrine Sciences & Cardiovascular Medicine, University of Manchester, * College of Medicine, University of Ibadan ** Wellcome Trust Research Training Fellowship awarded to Dr Ayoola

2. Background Excess preponderance of hypertension and associated CV complications in African adults Hypertension and its complications in West Africa occur at younger ages; (Ezenwaka C, Atherosclerosis 1997; Cruickshank et al J Hypert 2001) For normal weight boys, prevalence of systolic BP (>90 th percentile, <95 th percentile) higher in black than white boys aged 1-17 yrs (Rosner et al Hypertension 2009)

3. Bogalusa Heart Study: multiple regression on systolic BP at 15-17y (n= 182, Af.Am 92) 95 % CI Standard beta coefficients P value Birth weight-8.6 to 4.1 - 0.36 <0.01 Height0.27 to 0.57 0.38<0.01 BMI0.30 to 0.85 0.3<0.01  WT 0-4y -1.3 to –0.3 - 0.25 0.01 SBP at 4y 0.08 to 0.44 0.19<0.01 NB. Ethnic difference in 15y BP ‘accounted for’ by b’weight etc. Cruickshank et al Circulation 2005;111:1932-37

4. Falciparum malaria HYPER-endemic across (West) Africa co-exist with non-communicable diseases which are rapidly replacing traditional infections more frequent and severe in pregnancy causing maternal anaemia, and low birth weight (LBW) babies accounts for 5–12% of all LBW, 35% of preventable LBW and contributes to 75,000– 200,000 infant deaths each year (Steketee, Am J Trop Med, 1996)

5. Histological appearances of normal and malaria-infected placenta (A)normal and (B) malaria-infected showing parasites and monocyte-macrophage infiltrates Rogerson et al, Lancet Infect Dis 2007

6. LBW and catch up growth associated with increased risks of hypertension in later life…… Bansal et al, J Hypert 2008 March Weight Gain from Birth to 3 months & Rise in Systolic BP

7. Questions Is early origins hypothesis relevant to endemic High Blood Pressure (BP) in West Africa? Are the effects of malaria in pregnancy on birth size and early growth related to the pattern of BP change in the first year of life?

8. ** Wellcome Trust Research Training Fellowship awarded to Dr Ayoola Ibadan Maternal malaria, Infant Growth & Blood Pressure project **

9. Methods Standardised anthropometry and BP measures by Trained Nurses team with 2 monthly re- validation in mothers through pregnancy, at delivery and postnatally in babies at birth, 3 and 12 months. BPs by ‘Datascope’,validated for mothers and infancy; 3 measures and mean of last 2 readings analysed

10. Malaria parasite examination and definition Thick blood smears for malaria parasites through pregnancy, at delivery, cord blood, 3 and 12 months Defined as: asexual blood stages of Plasmodium falciparum during any pregnancy visit or at delivery, in the placenta or cord blood Women grouped into 2: –a)‘No Malaria’ (MP No) - no parasites detected throughout pregnancy or delivery – b) ‘Malaria present’ (MP Yes) - parasites present at least once during pregnancy and/or at delivery. Analysis: t-tests / multiple regression

11. Infant recruitment and follow-up from birth till one year of age 318 babies measured at all time-points = birth, 3 and 12 months 436 births – 399 at 3 months – 380 at 1 year

12. n = 318 BOYS n = 173 GIRLS n = 145 Mean MP NO n = 86 MP YES n = 87 MP NO n = 72 MP YES n = 73 Weight (kg)2.992.872.88 2.80 Length (cm)49.148.5 48.1 BMI (kg/m 2 )12.3412.1912.2312.1 Effect of Malaria on birth size and BP BIRTH SBP (mmHg)70.968.6 75.870.4* SBP/W24.124.426.725.6 SBP/L1.451.421.561.47

13. n = 318 BOYS n = 173 GIRLS n = 145 Mean MP NO n = 86 MP YES n = 87 MP NO n = 72 MP YES n = 73 Weight (kg) 6.14 5.84*5.525.40 Length (cm) 61.50 61.0460.4159.73 BMI (kg/m 2 )16.1615.6*15.1215.1 SBP (mmHg)90.190.2 89.589.6 SBP/W15.015.7*16.517.0 SBP/L1.461.481.491.50 Effect of Malaria on Growth and BP 3 months *p <0.03

14. n = 318 BOYS n = 173 GIRLS n = 145 Mean MP NO n = 86 MP YES n = 87 MP NO n = 72 MP YES n = 73 Weight (kg) 8.79 8.40* 7.917.94 Length (cm) 74.22 73.56 72.772.5 BMI (kg/m 2 ) 15.8815.47 14.9415.08 SBP (mmHg)90.189.9 88.889.0 SBP/W10.410.9*11.4 SBP/L1.211.22 1.23 Effect of Malaria on Growth and BP 12 months *p <0.01

15. Variable SBP ß 95% CI P-value R 2 0 - 12 months Sex (boy/girl) -4.399-7.72 to -1.08 0.01 Malaria status 3.6350.32 to 6.95 0.03 Length SDS 0-3 -1.984 -3.56 to -0.40 0.014 Weight SDS 0-12 2.406 0.98 to 3.84 0.001 Baby’s malarial status at 3 months -6.394-15.6 to 2.81 0.17 Baby’s malarial status at 12 months -0.720-7.38 to 5.940.83 0.10 Determinants of change in infant BP from birth to one year

16. 12 MONTHS n = 318 BOYS n = 173 BP Percentile MP NO n = 86 MP YES n = 87 <95 th 80 74 >95th 6 13 Comparison of Infant BP by Maternal malaria with US BP percentiles at age 1 year (X 2 = 5.53, p= 0.02) OR of having hypertension in boys exposed to maternal malaria = 2.95, (X 2 = 4.226, p=0.04) GIRLS n = 145 MP NO n = 72 MP YES n = 73 67 66 5 7 (X 2 =1.79,p= 0.2)

17. Conclusions Babies exposed to maternal malaria were smaller, shorter and thinner at birth and failed to catch up over their first year. Findings were more pronounced in boys. SBP adjusted for weight higher in boys exposed to maternal malaria Mean SBP change in infancy higher in exposed children particularly girls

18. Conclusions Hence potentially important role for intrauterine exposure to malaria in influencing early BP Follow-up continuing to elucidate contribution of these factors to their later BP profiles

19. Acknowledgements Professor JK Cruickshank Professor PE Clayton Professor O Omotade and others at University of Ibadan Nursing Team of ICGV Cardiovascular and Endocrine Research Team at University of Manchester