Long Term Outcome of Severe Anaemia in Malawian Children

Severe anaemia is a common, frequently fatal, condition in African children admitted to hospital, but its long term outcome is unknown. Early reports that survivors may be at risk of additional late morbidity and mortality may have significant implications for child survival in Africa. We assessed the short and long term outcome of severe anaemia in Malawian children and identified potential risk factors for death and further severe anaemia. For 18 months, we followed up children (6-60 months old) presenting to hospital with severe anaemia (haemoglobin <or=5 g/dl) and their hospital and community controls with the aim to compare all cause mortality and severe anaemia recurrence rates between the groups, and to identify risk factors for these adverse outcomes. A total of 377 cases, 377 hospital controls and 380 community controls were recruited. Among cases, the in-hospital mortality was 6.4% and post-discharge all cause mortality was 12.6%, which was significantly greater than in hospital controls (2.9%) or community controls (1.4%) (Log rank test, p <0.001). The incidence of recurrence of severe anaemia among the cases was 0.102 per child-year (95% Confidence Interval 0.075-0.138), and was significantly higher than the 0.007 per child-year (95% CI 0.003-0.015) in the combined controls (p <0.0001). HIV was the most important risk factor both for post-discharge mortality (Hazard Ratio 10.5, 95% CI 4.0-27.2) and for recurrence of severe anaemia (HR 5.6, 95% CI 1.6-20.1). Severe anaemia carries a high 'hidden' morbidity and mortality occurring in the months after initial diagnosis and treatment. Because severe anaemia is very common, this is likely to contribute importantly to overall under-five mortality. If not adequately addressed, severe anaemia may be an obstacle to achievement of the Millennium development goal No.4 on child survival. Strategies to diagnose and properly treat HIV infected children early most likely will reduce the high post-discharge mortality in severe anaemi

Risk factors for recurrence of severe anaemia among cases.

1<p>number of children included in Univariate model;</p>2<p>Hazard Ratio;</p>3<p>Confidence Interval;</p>4<p>number of children included in the multivariable Cox Proportional Hazards model was 307. All variables with a univariate HR p-value ≤0.1 and important confounders (age, sex, residency, HIV) were included in the multivariable model. The other factor not presented in the table but included in the model was undernutrition;</p>5<p>age was entered as a continuous variable in the model;</p>6<p>not applicable</p

Baseline characteristics of severe anaemia cases by outcome.

1<p>mean (SD);</p>3<p><i>p<0.0001</i> between Survivors and All deaths or post-discharge mortality</p

Unadjusted (in black) and adjusted (in red) Hazard Ratios of main risk factors for post-discharge all cause mortality among severely anaemic children (<i>cases</i>).

<p>Unadjusted (in black) and adjusted (in red) Hazard Ratios of main risk factors for post-discharge all cause mortality among severely anaemic children (<i>cases</i>).</p

Baseline characteristics by study group.

1<p>mean (sd);</p>2<p>Haemoglobin;</p>3<p>blood cultures were not done on community controls</p

All cause mortality and morbidity by study group.

1<p>per child-year (95% Confidence Interval);</p>2<p>median (range);</p>3<p>assuming that all children loss to follow-up survived;</p>4<p>all severe anaemia episodes were admitted to hospital and transfused;</p>5<p>incidence based on number of episodes of severe anaemia;</p>6<p>assuming that all children lost to follow-up did not have a severe anaemia episode;</p>7<p>presented to study clinic due to illness;</p>8<p>any asexual parasites/µL blood;</p>9<p>number of children with at least one re-admission to hospital</p

Survival curve showing the time to post-discharge death and the events versus number at risk of severely anaemic children (<i>cases</i>) and hospital and community controls during the follow-up period.

<p>Survival curve showing the time to post-discharge death and the events versus number at risk of severely anaemic children (<i>cases</i>) and hospital and community controls during the follow-up period.</p

Risk factors for post-discharge all cause mortality among cases.

1<p>number of children included in Univariate model;</p>2<p>Hazard Ratio;</p>3<p>Confidence Interval;</p>4<p>number of children included in the multivariable Cox Proportional Hazards model was 272. All variables with a univariate HR p-value ≤0.1 and important confounders (age, sex, residency, HIV) were included in the multivariable model. Other factors not presented in the table that were included in the model were history of a previous transfusion, Hb at admission;</p>5<p>age was entered as a continuous variable in the model;</p>6<p>not applicable;</p>7<p>weight-for-height;</p>8<p>height-for-age</p