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

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 (>90th percentile, <95th percentile) higher in black than white boys aged 1-17 yrs

(Rosner et al Hypertension 2009)

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

Height 0.27 to 0.57 0.38 <0.01

BMI 0.30 to 0.85 0.3 <0.01

DWT 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

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)

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

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

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?

**Wellcome Trust Research Training Fellowship awarded to Dr Ayoola

Ibadan Maternal malaria, Infant Growth & Blood Pressure project **

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

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

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

n = 318 BOYS

n = 173 GIRLS n = 145

Mean MP NO n = 86

MP YESn = 87

MP NO n = 72

MP YESn = 73

Weight (kg) 2.99 2.87 2.88 2.80Length (cm) 49.1 48.5 48.5 48.1BMI (kg/m2) 12.34 12.19 12.23 12.1

Effect of Malaria on birth size and BPBIRTH

SBP (mmHg) 70.9 68.6 75.8 70.4*

SBP/W 24.1 24.4 26.7 25.6SBP/L 1.45 1.42 1.56 1.47

n = 318 BOYS

n = 173 GIRLS n = 145

Mean MP NO n = 86

MP YESn = 87

MP NO n = 72

MP YESn = 73

Weight (kg) 6.14 5.84* 5.52 5.40Length (cm) 61.50 61.04 60.41 59.73BMI (kg/m2) 16.16 15.6* 15.12 15.1

SBP (mmHg) 90.1 90.2 89.5 89.6

SBP/W 15.0 15.7* 16.5 17.0SBP/L 1.46 1.48 1.49 1.50

Effect of Malaria on Growth and BP3 months

*p <0.03

n = 318 BOYS

n = 173 GIRLS n = 145

Mean MP NO n = 86

MP YESn = 87

MP NO n = 72

MP YESn = 73

Weight (kg) 8.79 8.40* 7.91 7.94Length (cm) 74.22 73.56 72.7 72.5BMI (kg/m2) 15.88 15.47 14.94 15.08

SBP (mmHg) 90.1 89.9 88.8 89.0

SBP/W 10.4 10.9* 11.4 11.4SBP/L 1.21 1.22 1.22 1.23

Effect of Malaria on Growth and BP12 months

*p <0.01

Variable SBP

ß 95% CI P-value R2

0 - 12 months

Sex (boy/girl) -4.399 -7.72 to -1.08 0.01

Malaria status 3.635 0.32 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 5.94 0.83 0.10

Determinants of change in infant BP from birth to one year

12 MONTHS

n = 318 BOYS

n = 173BP Percentile

MP NO n = 86

MP YESn = 87

<95th 80 74

>95th 6 13

Comparison of Infant BP by Maternal malariawith US BP percentiles at age 1 year

(X2 = 5.53, p= 0.02)

OR of having hypertension in boys exposed to maternal malaria = 2.95, (X2 = 4.226, p=0.04)

GIRLS n = 145

MP NO n = 72

MP YESn = 73

67 66

5 7

(X2 =1.79, p= 0.2)

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

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

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