Research Article: Relationships among Common Illness Symptoms and the Protective Effect of Breastfeeding in Early Childhood in MAL-ED: An Eight-Country Cohort Study

Date Published: March 29, 2018

Publisher: The American Society of Tropical Medicine and Hygiene

Author(s): Stephanie A. Richard, Benjamin J. J. McCormick, Jessica C. Seidman, Zeba Rasmussen, Margaret N. Kosek, Elizabeth T. Rogawski, William Petri, Anuradha Bose, Estomih Mduma, Bruna L. L. Maciel, Ram Krishna Chandyo, Zulfiqar Bhutta, Ali Turab, Pascal Bessong, Mustafa Mahfuz, Laura E. Caulfield.


Children in low-income countries experience multiple illness symptoms in early
childhood. Breastfeeding is protective against diarrhea and respiratory infections,
and these illnesses are thought to be risk factors of one another, but these
relationships have not been explored simultaneously. In the eight-site MAL-ED study,
1,731 infants were enrolled near birth and followed for 2 years. We collected
symptoms and diet information through twice-weekly household visits. Poisson
regression was used to determine if recent illness history was associated with
incidence of diarrhea or acute lower respiratory infections (ALRI), accounting for
exclusive breastfeeding. Recent diarrhea was associated with higher risk of incident
diarrhea after the first 6 months of life (relative risk [RR] 1.10, 95% confidence
interval [CI] 1.04, 1.16) and with higher risk of incident ALRI in the 3- to 5-month
period (RR 1.23, 95% CI 1.03, 1.47). Fever was a consistent risk factor for both
diarrhea and ALRI. Exclusive breastfeeding 0–6 months was protective against
diarrhea (0–2 months: RR 0.39, 95% CI 0.32, 0.49; 3–5 months: RR 0.83,
95% CI 0.75, 0.93) and ALRI (3–5 months: RR 0.81, 95% CI 0.68, 0.98). Children
with recent illness who were exclusively breastfed were half as likely as those not
exclusively breastfed to experience diarrhea in the first 3 months of life. Recent
illness was associated with greater risk of new illness, causing illnesses to cluster
within children, indicating that specific illness-prevention programs may have
benefits for preventing other childhood illnesses. The results also underscore the
importance of exclusive breastfeeding in the first 6 months of life for disease

Partial Text

Children in low-income countries are exposed to numerous infections in early life either
concurrently or within a short timeframe because of high rates of infectious diseases
and pathogens in their environments, poor nutritional status, and immune function, and
lack of access to health care. Studies of childhood illness often focus on a specific
disease in a population,1 and mortality
studies often attribute a single cause of death, even if multiple illnesses were
present.2 Comorbidities in
low-income populations have not been fully explored, nor has the distribution of
illnesses over time.

The MAL-ED study was conducted at eight different sites from November 2009 to February
2014: Bangladesh (Dhaka: BGD), India (Vellore: INV), Nepal (Bhaktapur: NEB), Pakistan
(Naushehro Feroze: PKN), Brazil (Fortaleza: BRF), Peru (Loreto: PEL), South Africa
(Venda: SAV), and Tanzania (Haydom: TZH).15 Children were enrolled within 17 days of birth and visited twice a
week by well-trained fieldworkers who collected daily information about symptoms using
harmonized and standardized data collection forms.16 Field workers asked caregivers if the child was ill or had any
symptoms for each day since the last visit. On average, caregivers were visited in their
homes 99 times per year (means at the sites ranged from 92 to 101 visits per year) to
inquire about the last 3 days. Symptom prevalence per child was calculated as the sum of
days with a symptom divided by the days followed in the study, multiplied by 100.

The MAL-ED study is a comprehensive cohort study that collected detailed data on a
variety of symptoms across the first 2 years of life in eight disparate sites. Symptoms
were not evenly distributed among the children in the eight study populations. The
majority of illness symptoms (80%) were concentrated in around half of the children and
although the distribution of diarrhea followed that of all grouped illnesses, ALRI were
more highly concentrated in as few as 8% of children. Both BRF and SAV had the most
skewed concentration of symptoms in the fewest children, but equally had the fewest
reported days of illness. This is unlikely to reflect any disparity between maternal and
trained fieldworker reports, which were highly correlated in most sites. Most of the
symptoms existed on their own or along with one other symptom; three or more concurrent
symptoms were seen on 14% of the days with any symptoms, with the highest percentages in
PKN and TZH (Supplemental
Figure 1).




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