American Journal of Epidemiology Vol. 187, No.

10
© The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. DOI: 10.1093/aje/kwy091
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Advance Access publication:
May 5, 2018

Original Contribution

Ramadan Exposure In Utero and Child Mortality in Burkina Faso: Analysis of a

Population-Based Cohort Including 41,025 Children

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Anja Schoeps, Reyn van Ewijk, Gisela Kynast-Wolf, Eric Nebié, Pascal Zabré, Ali Sié,
and Sabine Gabrysch*
* Correspondence to Dr. Sabine Gabrysch, Unit of Epidemiology and Biostatistics, Institute of Public Health, Heidelberg University,
Im Neuenheimer Feld 324, 69120 Heidelberg, Germany (e-mail: sabine.gabrysch@uni-heidelberg.de).

Initially submitted November 22, 2017; accepted for publication February 21, 2018.

Ramadan exposure in utero can be regarded as a natural experiment with which to study how nutritional conditions in
utero influence susceptibility to disease later in life. We analyzed data from rural Burkina Faso on 41,025 children born
between 1993 and 2012, of whom 25,093 were born to Muslim mothers. Ramadan exposure was assigned on the basis of
overlap between Ramadan dates and gestation, creating 7 exclusive categories. We used proportional hazards regression
with difference-in-differences analysis to estimate the association between Ramadan exposure at different gestational
ages and mortality among children under 5 years of age. Under-5 mortality was 32 deaths per 1,000 child-years. Under-5
mortality among Muslims was 15% higher than that among non-Muslims (P < 0.001). In the difference-in-differences analy-
sis, the occurrence of Ramadan during conception or the first or second trimester was associated with higher under-5 mor-
tality rates among Muslims only. The mortality rates of children born to Muslim mothers were 33%, 29%, and 22% higher
when Ramadan occurred during conception, the first trimester, and the second trimester, respectively, compared with chil-
dren of non-Muslim mothers born at the same time (P = 0.01, P < 0.001, and P = 0.007). Having a Muslim mother was not
associated with mortality when the child was not exposed to Ramadan, born during Ramadan, or exposed during the third
trimester. Observance of Ramadan during early pregnancy can have detrimental consequences for the future health of the
unborn child.
child mortality; difference in differences; population-based cohort; prenatal exposure delayed effects; pregnancy;
Ramadan; sub-Saharan Africa

Abbreviations: HDSS, Health and Demographic Surveillance System; HR, hazard ratio.

Editor’s note: Invited commentaries on this article appear on
pages 2093 and 2095, and the authors’ response appears on
page 2098.
The first 9 months of life in utero are a crucial period for human
development in which future health trajectories are set, determining
physical and cognitive capabilities. Early pregnancy is a time when
the developing organism is particularly vulnerable, as this is when
organogenesis takes place, including development of the neural
and immune systems and the shaping of endocrine and metabolic
pathways (1). It is well established that some infections (including
rubella virus), certain chemicals and drugs (most famously thalido-
mide), and deficiency in certain nutrients (e.g., folate and iodine) in
early pregnancy can lead to serious fetal damage (2).
There is also a growing body of evidence that nutrients, envi-
ronmental chemicals, drugs, and infections can have more subtle
effects on the developing organism in utero, presumably through
epigenetic mechanisms. Such effects may show only later in life,
a concept referred to as “developmental origins of health and dis-
ease” (3–5). The majority of studies on the topic have come from
high- and middle-income countries and have focused on chronic
diseases in later adulthood, such as diabetes and cardiovascular
disease (6). There have been very few studies in low-income set-
tings, although it would be of great interest to better understand
developmental impacts on the immune system and infection-
related mortality (7).
When studying long-term effects of undernutrition in utero,
researchers have employed natural experiments such as famines
to avoid confounding by socioeconomic status and other factors

2085 Am J Epidemiol. 2018;187(10):2085–2092

2086 Schoeps et al.
(2, 8). The most famous is the study of the Dutch Hunger Winter
of World War II, which showed that exposure to famine during
gestation, especially early gestation, increases the risk of obesity,
diabetes, coronary heart disease, breast cancer, mental illness,
and cognitive decline later in life and increases later-life mortal-
ity rates (9–13). Other research has focused on other famines
occurring during World War II, on 19th century famines, and on
more recent famines such as those that took place during the
Chinese Great Leap Forward (see Lumey et al. (8) for a review).
One study that—like our study—focused on the association
between nonfamine malnutrition and mortality exploited sea-
sonal patterns of food availability in the Gambia, linking season
of birth to smaller thymus size in children and to mortality in
young adults (7).
Another very particular natural experiment for studying the ef-
fects of undernutrition in utero is furnished by the Muslim tradition
of daytime fasting during the holy month of Ramadan. The rota-
tion of Ramadan through the year and the contrast with non-
Muslim populations in the same location provides an opportunity
to disentangle seasonal effects on fetal development (due to differ-
ent availability of nutrients, as well as environmental and infec-
tious exposures) from Ramadan effects. Studying the fetal health
impacts of intermittent maternal fasting, as occurs during Rama-
dan, would shed light on potential long-term effects of relatively
mild shocks experienced more commonly. Furthermore, effects of
Ramadan fasting are relevant in their own right, given the high
numbers of people affected each year.
Most studies of intrauterine Ramadan exposure have focused
on short-term outcomes such as low birth weight or preterm deliv-
ery, while fewer have looked beyond the immediate outcomes
and studied longer-term outcomes, including cognitive abilities,
body composition, symptoms of coronary heart disease and type
2 diabetes mellitus, and reduced work performance (14–20). To
our knowledge, there have been no studies so far on the associa-
tion between Ramadan exposure in utero and mortality outcomes
in childhood or adulthood. We hypothesized that maternal obser-
vance of Ramadan during conception and early pregnancy may
have negative impacts on the development of the fetus, leading to
higher child mortality, especially in settings with high background
levels of undernutrition among women and high infection-related
child mortality. The aim of our study was to assess the influence
of Ramadan exposure in utero at different gestational ages on
mortality among children under 5 years of age in Burkina Faso.
METHODS
Study area and population
This population-based cohort study was conducted using data
from the Nouna Health and Demographic Surveillance System
(HDSS) in northwestern Burkina Faso, which in 2012 comprised
a population of nearly 100,000 inhabitants. The Nouna HDSS
was established by an initial census carried out in 39 villages in
1992 (21). In 2000, 2 additional villages and the town of Nouna
were included, and another 17 villages followed in 2004. The
town of Nouna is a semiurban settlement with about 30,000 inhab-
itants, and the rural area around Nouna can be divided into 4 re-
gions (22). The majority of inhabitants in the Nouna HDSS are
Muslims (63%), while 32% are Christians, and a minority of
5% holds traditional beliefs. The study area is characterized
by a sub-Sahelian climate with a dry season (November–May)
and a rainy season (June–October). The majority of the popula-
tion lives by subsistence farming; literacy rates are low, and
there is seasonal food insecurity. More than one-quarter of chil-
dren between 6 and 31 months of age are wasted (21, 23).
Ramadan exposure
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During the month of Ramadan, which lasts about 30 days,
healthy adult Muslims are obliged to abstain from eating and
drinking (even water) between dawn and sunset. The Islamic lunar
calendar is approximately 11 days shorter than the Gregorian cal-
endar, so Ramadan occurs slightly earlier each year and rotates
through the Gregorian year in about 33 years. For sick people and
pregnant women, fasting during Ramadan is voluntary; however,
they are supposed to make up for this exemption by fasting
afterwards (24).
While Ramadan is likely to affect fetal health through the fast-
ing itself, other lifestyle changes taking place during Ramadan
(including increased sugar intake and changes in sleeping patterns)
may also be responsible for the association. Data from the Nouna
HDSS do not contain information on individual Ramadan fasting,
and we do not distinguish between the potential channels for asso-
ciations. We assigned Ramadan exposure in utero based on a cal-
culation of whether there was overlap between Ramadan and
gestation, utilizing the date of birth in relation to the Ramadan
dates and assuming a gestational period of 266 days, which is the
average duration of a full-term human pregnancy. Our approach
can be interpreted as an intention-to-treat analysis that helps avoid
confounding due to self-selection of women into Ramadan-
observant and nonobservant groups, which likely also differ
in other ways. We differentiated Ramadan exposure into 7 exclu-
sive categories: certainly not exposed, probably not exposed, con-
ceived during Ramadan, Ramadan starting during the first,
second, or third trimester, and born during Ramadan. Children in
the category “probably not exposed” would not have experienced
Ramadan in utero if their mothers had a normal 266-day preg-
nancy, as this would have started just after Ramadan. However, if
they were born up to 20 days postterm, they could still have been
exposed to Ramadan during conception (Figure 1).
Statistical analysis
Between 1993 and 2012, a total of 48,747 children were born
alive in the Nouna HDSS. We excluded 7,520 children for whom
the exact date of birth was unknown and 202 children for whom
information on mother’s religion was missing; this resulted in
a sample of 41,025 children for analysis.
We calculated mortality rates in children of Muslim and non-
Muslim mothers overall and stratified by the occurrence of Rama-
dan during pregnancy. Because our study period included 20 years
of observation, Ramadan did not fully rotate through the year
(from February/March in 1992 to July/August in 2012), and thus
Ramadan exposure varied by month of birth (see Web Figure 1,
available at https://academic.oup.com/aje). We used a difference-
in-differences analysis, comparing the association of Ramadan
occurrence during pregnancy with mortality between non-
Muslims and Muslims, under the assumption of a common sea-
sonal trend. The inclusion of non-Muslims in the model served
to purge any remaining seasonal mortality differences correlated
Am J Epidemiol. 2018;187(10):2085–2092

Conceived During Ramadan
Ramadan During Trimester 1
Ramadan During Trimester 2
Jul 1, 2010 Nov 1, 2010 Mar 1, 2011 Jul 1, 2011
Figure 1. Assignment to prenatal Ramadan exposure by time of birth for children born in Nouna District, Burkina Faso, in 2011–2012. Assuming
a gestation period of 266 days, one of 7 Ramadan exposure categories was assigned to each child. The asterisks (*) indicate birth dates, while
black dots show the calculated dates of conception. The black boxes indicate the timing of Ramadan in 2010 and 2011. Mar, March; Jul, July; Nov,
November.
with Ramadan that remained after adjustment for calendar month
of birth (14). For details on the model assumptions and sensitivity
analyses, refer to Web Appendix 1.
We used 2-level multivariate Weibull proportional hazards re-
gression to estimate the association between Ramadan exposure
in utero and child survival up to age 5 years, with random inter-
cepts at the mother level. Death between birth and 5 years of age
was the event of interest. The time variable was time from birth
to death, age 5 years, loss to follow-up, or the end of the study
(December 31, 2012). After confirmation of the proportional haz-
ards assumption for the main variables of interest through the use
of Kaplan-Meier graphs, we first fitted a regression model without
considering Ramadan timing, to estimate the association between
religion and child mortality, using a binary variable indicating
whether the mother was Muslim or non-Muslim. In a second
regression model, we then added a variable indicating Ramadan
occurrence during pregnancy, as well as a term for the interaction
of Ramadan occurrence with the Muslim indicator variable. These
interaction parameters were the coefficients of interest in our
study. They can be interpreted as a comparison of mortality
between exposed and unexposed Muslims after correcting for sea-
sonality (by comparing with non-Muslims). Adjustment was
made for year of birth (continuous variable), calendar month of
birth, and region of residence. Stata version 14 (StataCorp LLC,
College Station, Texas) was used for analysis, and SAS version
9.3 (SAS Institute, Inc., Cary, North Carolina) was used for creat-
ing the figures. All P values are 2-sided.
In addition, stratified analyses were conducted for the 5 main
regions of the study area (22) and for 3 different study periods.
Besides the main outcome of under-5 mortality, we also studied
infant mortality and mortality in children aged 1–4 years. To inves-
tigate in more detail the association between being conceived dur-
ing Ramadan and mortality, we created 2 separate categories:
exposure for at least 14 days and exposure for less than 14 days.
RESULTS
Our study included 41,025 children who were born to 20,709
mothers in the Nouna HDSS between January 1993 and Decem-
ber 2012, for whom mother’s religion and the precise date of birth
were known. The majority of mothers in this sample were Muslim
(61%), while 28% were Catholic, 5% were Protestant, and 6%
had an animist religion or another religion.
Am J Epidemiol. 2018;187(10):2085–2092
Ramadan Exposure in Utero and Child Mortality 2087
Ramadan During Trimester 3
Born During Ramadan
Certainly Not Exposed
Probably Not Exposed
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Nov 1, 2011 Mar 1, 2012 Jul 1, 2012
Between 1993 and 2012, there were 4,213 deaths among chil-
dren under 5 years of age during 133,203 child-years at risk, cor-
responding to an overall mortality rate of 31.6 deaths per 1,000
child-years. Mortality rates were higher among Muslims (33.5
deaths per 1,000 child-years) than among non-Muslims (28.7
deaths per 1,000 child-years) (Table 1). Among non-Muslims,
mortality rates were somewhat lower in children who were in
utero during Ramadan as compared with children who were
not. This was most likely due to seasonal variations in mortal-
ity that were correlated with Ramadan occurrence in our sam-
ple and that were previously described in the study area (25).
This pattern was not apparent for children of Muslim mothers.
To estimate the association between Ramadan exposure in utero
and child mortality, we performed a difference-in-differences anal-
ysis to eliminate seasonal mortality differences through compari-
son with non-Muslims. In adjusted multilevel regression, children
for whom Ramadan occurred during conception or the first or sec-
ond trimester showed higher mortality rates (37%, 33%, and 25%,
respectively) than children certainly not exposed, only among
Muslims, as shown by the interaction terms (P = 0.03, P = 0.01,
and P = 0.05, respectively), while exposure during the third tri-
mester and at birth was not associated with increased mortality
(Table 2).
In the adjusted multilevel model that did not adjust for Rama-
dan occurrence during pregnancy, the mortality rate among Mus-
lims was 15% higher (95% confidence interval: 7, 24) than that
among non-Muslims (Table 3). From the model with Ramadan
interaction terms, we calculated the mortality rate ratio for Mus-
lims versus non-Muslims for each Ramadan exposure category.
Children born to Muslim mothers who experienced Ramadan in
utero during conception had a 33% higher mortality rate than chil-
dren of non-Muslim mothers in utero during the same time period
(hazard ratio (HR) = 0.97 for Muslim women vs. non-Muslim
women outside Ramadan, multiplied with HR = 1.37 for the inter-
action; P = 0.01). For trimesters 1 and 2, the increases in mortality
rates were 29% and 22% (P < 0.001 and P = 0.007), respectively
(Table 3, Figure 2). Among children exposed to Ramadan in the
third trimester, the difference in mortality between Muslims and
non-Muslims was small, and there was no increased mortality for
Muslim children born during Ramadan. Having a Muslim mother
was not associated with mortality when not exposed to Ramadan
(HR = 0.97, P = 0.74), and Ramadan occurrence was not associ-
ated with mortality among non-Muslims in the adjusted model
(Table 2).
2088 Schoeps et al.

Table 1. Numbers of Live Births, Numbers of Child Deaths, and Mortality Before 5 Years of Age, by Prenatal Ramadan Exposure and Religion,
Among 41,025 Children From Nouna District, Burkina Faso, 1993–2012

Muslims Non-Muslims
Ramadan Exposure Category Live Births No. of Child- No. of Child U5M Live Births No. of Child- No. of Child U5M
No. % Years Deaths Ratea No. % Years Deaths Ratea

Certainly not exposed 2,837 11.3 9,263 297 32.1 1,936 12.2 6,488 208 32.1

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Probably not exposed 1,467 5.9 4,778 169 35.4 933 5.9 3,124 99 31.7
Conceived during Ramadan 2,150 8.6 6,983 252 36.1 1,338 8.4 4,485 119 26.5
Exposed during trimester 1 5,981 23.8 20,070 681 33.9 3,573 22.4 12,122 319 26.3
Exposed during trimester 2 6,058 24.1 19,183 632 32.9 3,791 23.8 11,960 319 26.7
Exposed during trimester 3 4,261 17.0 13,248 425 32.1 2,755 17.3 8,650 252 29.1
Born during Ramadan 2,339 9.3 7,586 262 34.5 1,606 10.1 5,263 179 34.0
Total 25,093 81,111 2,718 33.5 15,932 52,092 1,495 28.7

Abbreviation: U5M, under-5 mortality.

a
Number of deaths per 1,000 child-years.

In sensitivity analyses separating mortality during infancy from ratios for infant mortality were 1.23 (P = 0.05) for first-
mortality later in childhood, Ramadan exposure during conception trimester Ramadan occurrence and 1.17 (P = 0.13) for second-
was associated with 68% higher infant mortality among Muslims trimester Ramadan occurrence. In children aged 1–4 years,
than among non-Muslims (HR = 1.68, P = 0.004), while hazard Ramadan exposure during the first (HR = 1.34, P = 0.002) and

Table 2. Effect of Prenatal Ramadan Exposure on Mortality Before 5 Years of Age (Difference-in-Differences
Analysis) Among 41,025 Children From Nouna District, Burkina Faso, 1993–2012

Parametera and Exposure Category HR 95% CI P Value

Ramadan
Conceived vs. certainly not 0.86 0.69, 1.09 0.22
Trimester 1 vs. certainly not 0.88 0.73, 1.06 0.17
Trimester 2 vs. certainly not 0.91 0.76, 1.10 0.35
Trimester 3 vs. certainly not 0.92 0.76, 1.11 0.37
Born vs. certainly not 1.05 0.86, 1.29 0.63
Probably not vs. certainly not 0.99 0.77, 1.26 0.92
Mother is Muslim (yes vs. no) 0.97 0.81, 1.17 0.77
Ramadan × Muslim mother interactionb
Conceived vs. certainly not 1.37 1.03, 1.82 0.03
Trimester 1 vs. certainly not 1.33 1.06, 1.67 0.01
Trimester 2 vs. certainly not 1.25 1.00, 1.57 0.05
Trimester 3 vs. certainly not 1.10 0.87, 1.40 0.43
Born vs. certainly not 1.02 0.79, 1.34 0.86
Probably not vs. certainly not 1.14 0.83, 1.56 0.42
Year of birth (linear; per year since 1993) 0.96 0.95, 0.96 <0.001
Region of residence
Central vs. Nouna town 1.39 1.22, 1.58 <0.001
Northeast vs. Nouna town 1.94 1.74, 2.16 <0.001
Southeast vs. Nouna town 1.24 1.09, 1.40 0.001
Southwest vs. Nouna town 1.88 1.69, 2.09 <0.001

Abbreviations: CI, confidence interval; HR, hazard ratio.

a
Model: difference-in-differences analysis with a random intercept for mother; results were additionally adjusted for
month of birth (estimates not displayed).
b
Interaction terms.

Am J Epidemiol. 2018;187(10):2085–2092
 Ramadan Exposure in Utero and Child Mortality 2089

Table 3. Mortality Before 5 Years of Age in Muslims Compared With Non-Muslims, by Prenatal Ramadan Exposure,
Among 41,025 Children From Nouna District, Burkina Faso, 1993–2012

Prenatal Ramadan Exposure Calculationa HR 95% CI P Value

Total (not considering Ramadan) b

1.15 1.07, 1.24 <0.001
Ramadan exposure categoryc
Certainly not exposed —d 0.97 0.81, 1.17 0.74

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Probably not exposed 0.97 × 1.14 1.11 0.86, 1.43 0.43
Conceived during Ramadan 0.97 × 1.37 1.33 1.06, 1.66 0.01
Ramadan during trimester 1 0.97 × 1.33 1.29 1.12, 1.49 <0.001
Ramadan during trimester 2 0.97 × 1.26 1.22 1.06, 1.40 0.007
Ramadan during trimester 3 0.97 × 1.11 1.07 0.91, 1.26 0.39
Born during Ramadan 0.97 × 1.02 1.00 0.82, 1.21 0.98

Abbreviations: CI, confidence interval; HR, hazard ratio.

a
Calculation of stratum HRs from the baseline HR and the interaction HR.
b
Survival analysis without Ramadan exposure (with a random intercept for mother; results were adjusted for year
of birth, month of birth, region of residence, season at death, and sex of child).
c
Based on the full model shown in Table 2.
d
This value corresponds to the estimate for “mother is Muslim (yes vs. no)” as displayed in Table 2.

second (HR = 1.25, P = 0.02) trimesters was associated with a
strong increase in mortality, but the association of Ramadan expo-
sure during conception (HR = 1.11, P = 0.48) with mortality
was weaker.
When analyses were stratified by region of residence, the
increased mortality rate in children exposed to Ramadan in utero
was visible in all regions, with the strongest associations being
seen in the Northeast and the Southwest, the regions with the high-
est child mortality. Because of the lower sample sizes, regional es-
timates were not significant at the 5% level, except for Ramadan
exposure in the first or second trimester in the Southwest region,
which had the largest number of children. Stratification by year of

2.0
Hazard Ratio

1.0

0.5
Certainly Probably Conceived Trimester 1 Trimester 2 Trimester 3 Born
Not Not During During During During During
Exposed Exposed Ramadan Ramadan Ramadan Ramadan Ramadan
Ramadan Exposure

Figure 2. Mortality under 5 years of age according to prenatal Ramadan exposure among children of Muslim mothers compared with children of
non-Muslim mothers who were in utero during the same time period, Nouna District, Burkina Faso, 1993–2012. The hazard ratios were derived
from an adjusted multilevel model (see Tables 2 and 3) that included 25,093 children born to Muslim mothers and 15,932 children born to non-
Muslim mothers in Nouna District. They were calculated by dividing the under-5 mortality rates of Muslims by the under-5 mortality rates of non-
Muslims. A hazard ratio of 1.3 means that under-5 mortality among Muslims was 30% higher than that among non-Muslims; a hazard ratio of 1.0
means that the mortality of Muslims and non-Muslims was the same; and hazard ratios below 1 signify lower mortality among Muslims. Vertical lines
display 95% confidence intervals.

Am J Epidemiol. 2018;187(10):2085–2092
2090 Schoeps et al.
birth showed that the measures of association of Ramadan expo-
sure with mortality during trimesters 1 and 2 were comparable
between the 3 study periods (1993–1999, 2000–2006, and
2007–2012) and the association for being conceived dur-
ing Ramadan was stronger during the most recent period.
Among children exposed to Ramadan during conception, the
association was stronger in children exposed for 14 days or more
(HR = 1.45, P = 0.04). It was weaker and not significant for chil-
dren exposed for less than 14 days (HR = 1.27, P = 0.21).
DISCUSSION
Using 20 years of surveillance data from northwestern Burki-
na Faso, we detected a strong association between having been
exposed to Ramadan in utero and under-5 mortality. This associ-
ation was present from conception to the second trimester, and
particularly strong during early pregnancy, when the mortality
rate of children born to Muslim mothers was around 30% higher
than that among children of non-Muslim mothers born at the
same time. The 15% higher mortality seen in children of Mus-
lim mothers overall was entirely explained by Ramadan expo-
sure, as having a Muslim mother was not associated with
mortality when the pregnancy occurred outside of Ramadan.
For our analysis, we assigned children of Muslim mothers as
being exposed to Ramadan without having actual information on
maternal fasting, as in an intention-to-treat analysis. Use of this
approach avoids confounding by health issues associated with
decreased fasting adherence and increased child mortality. How-
ever, if a substantial proportion of Muslim women did not adhere
to Ramadan fasting during pregnancy, our results would underes-
timate the true association due to nondifferential misclassification.
Another source of misclassification is pregnancy duration. For
the Ramadan exposure assignment, we assumed a gestational age
of 266 days for all children. There are, however, natural variations
in gestational age at birth, and only about 50% of children are born
within 7 days of the estimated due date (26). Some children born
at higher gestational ages will have been classified as not exposed
to Ramadan, even though they were actually exposed during con-
ception. To ensure that our comparison category was “certainly
not exposed to Ramadan,” we created a separate category of chil-
dren “probably not exposed,” capturing possible exposure in very
early pregnancy among children born 1–20 days postterm. A dif-
ferent issue is children who were born early—that is, who were in
utero for less than 266 days. These children might have been as-
signed Ramadan exposure during conception or the beginning of
trimester 1, even though they were actually not exposed to Rama-
dan at all. The categorization of the certainly-not-exposed children
(born just before Ramadan) was not affected by this, because a
shorter gestation would not lead to an overlap with Ramadan.
Thus, any misclassification of pregnancy duration would only
have led to an attenuation of the measures of association.
If some women planned their pregnancies to avoid an overlap
with Ramadan, this could have introduced bias. If this group was
less vulnerable for some reason, this could have artificially
increased our estimates. Such behavior should be more likely in
Muslim women, because there is less reason for non-Muslims to
avoid an overlap with Ramadan. Our sensitivity analyses provided
no evidence for such pregnancy planning (Web Appendix 1), and
previous research comparing Muslims who were pregnant during
a Ramadan with those who were not found no differences in edu-
cation, smoking behavior, health, or income (14–16, 19, 27), sug-
gesting that Muslims generally do not plan their pregnancies in
such a way that they avoid overlap with a Ramadan.
The majority of studies on the association between Ramadan
fasting and health of the offspring have focused on immediate
outcomes such as birth weight and preterm delivery and have
mostly found no associations (28–32). Even though low birth
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weight is associated with increased child mortality (33), the
effect of Ramadan fasting on child mortality presumably does
not act via birth weight but through an impact on the developing
immune system, which is in line with the impacts of seasonality
on thymus size reported from the Gambia (6). While undernutri-
tion in utero can lead to intrauterine growth restriction that is
measurable as low birth weight, as well as to epigenetic changes
influencing later disease risk (9), the systems affected and the
time(s) at which this shows in life will depend on the types of
nutrients missing and the exact timing of undernutrition during
pregnancy. For example, persons exposed to the Dutch Hunger
Winter in early pregnancy had normal birth weight but suffered
from a higher burden of disease as adults (9).
Previous studies on long-term outcomes showed that chil-
dren who were exposed to Ramadan in utero had lower aca-
demic performance (14, 15) and were more likely to suffer
from learning disabilities (27), suggesting an impact on the
developing nervous system. There is also evidence from Indo-
nesia linking Ramadan exposure in utero to adult body size
(17), to lower nurse-rated general adult health, and to higher
prevalence of slow-healing wounds and chest pain (symptoms
indicative of diabetes and coronary heart disease) (19).
In line with our study, the great majority of studies on long-
term outcomes of Ramadan exposure showed stronger associa-
tions if children were exposed early in pregnancy, during the
time of conception and the first trimester (14, 17, 20, 34). This
is biologically plausible and consistent with our knowledge on
fetal programming (1, 35). An alternative explanation for the
stronger associations in early pregnancy is a higher adherence
to fasting during this time, especially when women are not yet
aware of the pregnancy (28, 34).
In pregnant women, fasting leads to increases in levels of free
fatty acids and ketones and decreases in blood glucose after a rela-
tively short period of time (12–18 hours), a process called “accel-
erated starvation” (36). Because of its location close to the equator,
the durations of fasting periods in Burkina Faso are roughly con-
stant over the years (around 13 hours). At the same time, preexist-
ing undernutrition and physical labor in a hot climate may
exacerbate fasting effects. Intermittent exposure to decreased glu-
cose and increased ketone levels, the balance of calories from pro-
teins and carbohydrates, and deficiencies in crucial micronutrients
can be responsible for adverse effects on fetal health (35). From
our data, however, it is impossible to say whether the association
between Ramadan and mortality is due to the lack of food and
water intake during the daytime or due to other lifestyle changes
related to Ramadan, such as overall reduced calorie intake,
increased sugar and fat intake, decreased intake of micronutrient-
rich foods, changes in sleeping patterns, or other factors.
The developing immune system is particularly vulnerable to
maternal malnutrition in the first trimester through a range of
mechanisms: micronutrient deficiencies directly affecting thymus
development and hematopoiesis, impaired maternal immune
Am J Epidemiol. 2018;187(10):2085–2092

transfer altering the fetal immune system’s trajectory, and mater-
nal glucocorticoids suppressing fetal thymus and lymphocyte
development as well as influencing the development of the
fetal hypothalamic-pituitary-adrenal axis (37). Especially in
sub-Saharan Africa, where infectious diseases (pneumonia, diar-
rhea, malaria) are still a major cause of under-5 mortality (38), al-
terations in the functioning of the immune system can be expected
to influence child survival.
Our finding that periconceptional Ramadan exposure was
most strongly linked to mortality, and mainly to infant mortality
rather than later child mortality, could mean that impacts incurred
during the embryo’s formative phase are particularly severe and
kill earlier or that they disrupt immune mechanisms that are im-
portant for maternal immune transfer, which is particularly rele-
vant in infancy before vaccination takes effect. However, given
our limited statistical power in subanalyses, results of the stratified
analyses should not be overinterpreted. To shed more light on the
mechanisms involved, it would be helpful to study cause-specific
mortality and to investigate epigenetic changes where such data
are available. Finally, because sex differences in immune response
and in fetal programming are common (39–42), we plan to inves-
tigate effect modification by child sex as soon as newer years of
surveillance data become available.
In conclusion, we found that Ramadan exposure in early preg-
nancy leads to a 30% increase in child mortality in rural Burkina
Faso, a setting where infectious causes of child mortality domi-
nate. This suggests that changes in nutrient intake and/or lifestyle
which are far less dramatic than those that occur during a famine
or hunger season can have long-lasting detrimental effects on
child health, which might act through impacts on immune system
development (6).
Besides its contribution to knowledge on the developmental
origins of disease and causes of child mortality, our finding is rele-
vant for the 1.6 billion Muslims globally, tens of millions of whom
get pregnant each year. According to Islam, pregnant women
are exempt from fasting during Ramadan if they are worried
about their health or the health of their unborn child (24), but it
has been shown in several settings that many women still fast
(43–47). Conception and early pregnancy seem to be the most
vulnerable periods, which complicates matters, as it would imply
abstaining from fasting while trying to get pregnant and in a
period when women may not yet want to reveal their pregnancy
status. Furthermore, our finding may be important to women of
other faiths who fast and to all women, because meal-skipping and
dieting during pregnancy are common in nonreligious pregnant
women as well (18, 48, 49). Even though the effect of Ramadan
fasting on child mortality is probably restricted to high-mortality
settings, long-term health and cognitive effects may also affect
people in high-income settings.
ACKNOWLEDGMENTS
Author affiliations: Unit of Epidemiology and
Biostatistics, Institute of Public Health, Heidelberg
University, Heidelberg, Germany (Anja Schoeps, Gisela
Kynast-Wolf, Sabine Gabrysch); Gutenberg School of
Management and Economics, Johannes Gutenberg
University, Mainz, Germany (Reyn van Ewijk); and Centre
Am J Epidemiol. 2018;187(10):2085–2092
Ramadan Exposure in Utero and Child Mortality 2091
de Recherche en Santé de Nouna, Nouna, Burkina Faso (Eric
Nebié, Pascal Zabré, Ali Sié).
This work benefitted from support provided by the
German Research Foundation to R.v.E. (grant 260639091)
and to the Nouna Health and Demographic Surveillance
System (research grant SFB 544 (“Control of Tropical
Infectious Diseases”), 1999–2011).
Conflict of interest: none declared.
Downloaded from https://academic.oup.com/aje/article-abstract/187/10/2085/4993217 by Universitas Diponegoro user on 25 January 2019
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