You are on page 1of 8

The effect of maternal fasting during Ramadan

on preterm delivery: a prospective cohort study


J Awwad, IM Usta, J Succar, KM Musallam, G Ghazeeri, AH Nassar
Department of Obstetrics and Gynaecology, American University of Beirut Medical Centre, Beirut, Lebanon
Correspondence: A Nassar, American University of Beirut Medical Centre, Department of Obstetrics and Gynaecology, PO Box 113-6044/B36,
Beirut, Lebanon. Email an21@aub.edu.lb
Accepted 29 May 2012. Published Online 25 July 2012.
Objective To determine the effect of fasting during the month of
Ramadan on the rate of preterm delivery (PTD).
Design A prospective cohort study of women with singleton
pregnancies who elected to fast and matched controls.
Setting Four medical centres in Beirut, Lebanon.
Population Women presenting for prenatal care (2034 weeks of
gestation) during the month of Ramadan, September 2008.
Methods Data were collected prospectively. The frequency of PTD
was evaluated in relation to the duration of fasting and the stage
of gestation at the time of fasting.
Main outcome measures The primary endpoint was the
percentage of pregnant women who had PTD, dened as delivery
before 37 completed weeks of gestation.
Results A total of 468 women were approached, of whom 402
were included in the study. There were no differences in smoking
history and employment. There was no difference in the
proportion of women who had PTD at <37 weeks (10.4% versus
10.4%) or PTD at <32 weeks (1.5% versus 0.5%) in the
Ramadan-fasted group and the controls, respectively. The PTD
rate was also similar in those who fasted before or during the
third trimester. The mean birthweight was lower (3094 467 g
versus 3202 473 g, P = 0.024) and the rate of ketosis and
ketonuria was higher in the Ramadan-fasted women. On
multivariate stepwise logistic regression analysis, fasting was not
associated with an increased risk of PTD (odds ratio 0.72; 95%
condence interval 0.341.54; P = 0.397). The only factor that had
a signicant effect on the PTD rate was body mass index (odds
ratio 0.43; 95% condence interval 0.200.93; P = 0.033).
Conclusions Fasting during the month of Ramadan does not seem
to increase the baseline risk of preterm delivery in pregnant
women regardless of the gestational age during which this practice
is observed.
Keywords Fasting, pregnancy, preterm delivery, Ramadan.
Please cite this paper as: Awwad J, Usta I, Succar J, Musallam K, Ghazeeri G, Nassar A. The effect of maternal fasting during Ramadan on preterm delivery:
a prospective cohort study. BJOG 2012;119:13791386.
Introduction
Pregnancy is a physiological state with particular nutri-
tional requirements critical for the achievement of optimal
maternal and neonatal outcomes. Dietary recommendations
for mothers have been established to ensure a balanced
nutritional intake for a healthy pregnancy course.
13
Circumstances that impose serious strains on the quality,
quantity and distribution of food intake are believed to
adversely affect maternal and neonatal outcomes.
Ramadan is the ninth lunar month of the Islamic
calendar and symbolises the Revelation of the holy Quran.
During this month, devout Muslims abstain from eating
and drinking from dawn to dusk for a period of
2930 days. Ramadan fasting represents a serious alteration
to routine eating and drinking habits that deserves special
consideration, namely that over one billion adherents
globally are obligated to observe this essential tenet of the
sacred law. Although the Ramadan fast is compulsory in
Islam, pregnancy may represent a relative exemption if
reasons for maternal/fetal hardship are suspected.
4
Many
Muslim women, nonetheless, still choose to fast during
their pregnancy, creating a challenge to healthcare provid-
ers who feel compelled to provide them with credible
advice. Unfortunately, a very limited literature database is
available to offer a platform for sound counselling.
Few studies have examined the untoward effects of
maternal fasting on the wellbeing of the mother and
2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2012 RCOG 1379
DOI: 10.1111/j.1471-0528.2012.03438.x
www.bjog.org
General obstetrics
fetus.
49
Signicantly lower levels of glucose, insulin, lactate
and carnitine were found in the serum of fasting moth-
ers,
6,7
with higher levels of triglycerides, non-esteried fatty
acids and 3-hydroxybutyrate. A reduction in fetal breathing
movements
8
and fetal biophysical prole
9
were also
reported in association with maternal fasting. An increased
risk of hyperemesis gravidarum
5
was further associated
with prolonged fasting. Other studies however failed to
demonstrate any undesired effects on fetuses born to fast-
ing mothers.
1016
No changes in ow velocimetry parame-
ters were found in a uterine artery Doppler study of
pregnant women during a Ramadan fast.
10,17
Similarly,
amniotic uid index, birthweight and childrens IQ were all
unaffected.
1016
There is a very limited number of studies investigating
the effects of caloric restriction on the risks of preterm
labour (PTL) and preterm delivery (PTD) in pregnant
women.
18,19
The Dutch famine in 1944/45 provides evi-
dence on the differential timing effect of poor nutrition on
low birthweight and PTD.
19
First-trimester food depriva-
tion increased the risk of PTD, whereas third-trimester
nutritional stress was associated with low birthweights.
19
Fluid restriction during the fast could theoretically provoke
contractions. Women with PTL have been reported to have
lower plasma volume than controls
20
and based on uncon-
trolled observations, intravenous hydration might decrease
contractions or delay the delivery in these women, as pro-
posed by some authors.
20,21
It has been hypothesised that
volume expansion could increase uterine blood ow, stabi-
lise decidual lysosomes and decrease prostaglandin produc-
tion.
22
In addition, it could decrease the secretion of
antidiuretic hormone from the posterior pituitary,
21,22
so
decreasing oxytocin secretion simultaneously.
21
The clinical signicance of PTD cannot be underesti-
mated because it remains the leading public health burden
in obstetric practice today. It is a major cause of neonatal
morbidity and mortality, contributing an estimated 36.5%
of infant deaths in 2005.
23
Infant survivors born
prematurely are themselves at increased risk for long-term
neurological and developmental complications.
24,25
Sharing the scientic evidence regarding the effects of
fasting on maternal and neonatal outcome is the most
appropriate approach to assist Muslim pregnant women in
making informed decisions about fasting during the month
of Ramadan. Unfortunately, the views of the medical
literature with respect to this subject remain inconclusive.
Available studies suffer many shortcomings, including small
sample size, poorly dened outcome measures, and lack of
well-matched controls. PTD has never been investigated as
an outcome measure in the context of Ramadan fasting.
The present study was therefore designed to investigate
whether fasting during Ramadan increased PTD in
pregnant women. Our null hypothesis was that daytime
fasting would be unlikely to have any measurable effect on
PTD rate in Ramadan-fasted women compared with
matched controls.
Methods
Subjects
This prospective study was conducted between the 1 and
30 September 2008 during the holy month of Ramadan in
a geographic time-zone GMT +3. Women were identied
during the course of routine prenatal care visits at four
participating medical centres representative of the socioeco-
nomic constitution of the Lebanese community during the
month of August 2008 preceding Ramadan. Eligible women
included all healthy Muslim women with singleton uncom-
plicated pregnancies who would be at 2034 weeks of
gestation at the beginning of the month of Ramadan irre-
spective of whether they would fast or not during the
month of Ramadan. Exclusion criteria consisted of the
following: conceptions by assisted reproductive technology;
pre-existing maternal medical diseases (such as chronic
hypertension, diabetes mellitus, asthma, seizures, cardiac
disease, renal disease); multiple gestations; major fetal
congenital abnormalities; polyhydramnios; obstetric com-
plications (such as gestational diabetes, pre-eclampsia,
chorioamnionitis); and previous poor obstetric outcome
(such as PTD, intrauterine fetal deaths, recurrent
pregnancy losses). The study was approved by the Institu-
tional Review Board of the American University of Beirut
Medical Centre (AUBMC). Informed consents were
provided according to the Declaration of Helsinki. Con-
senting mothers were enrolled in August and followed up
throughout the pregnancy thereafter.
Women who intended to fast were assigned to the Ram-
adan-fasted group and each fasting woman was matched
to a control non-fasting women by maternal age (1 year),
gestational age (2 weeks), parity (nulliparous versus
multiparous) and body mass index (BMI) (2 kg/m
2
). The
matching process was done sequentially within the same
clinic and on the same or the following day. Women who
intended to fast were provided with a timetable to docu-
ment days and hours of fasting. During the month of Ram-
adan, phone calls were made every fth day to monitor
individual compliance in completing the self-reported
document.
Measurements
Maternal weight and blood pressure were recorded at the
beginning and at the end of Ramadan. Maternal effects of
fasting were assessed by measuring blood concentrations of
glucose and 3b-hydroxybutyrate, and urine ketone levels.
Samples for the above measurements were collected
approximately 1 hour before breaking the fast (around
Awwad et al.
1380 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2012 RCOG
5:306:00 p.m.), both in the beginning (rst 4 days) and at
the end (last 4 days) of Ramadan. Collection was made at
home upon scheduled appointments to facilitate individual
compliance. Collected samples were then transported to the
central laboratory of AUBMC for analysis.
Glucose levels were measured using a glucometer (Accu-
Check Active; Roche Diagnostics, Basel, Switzerland).
Hypoglycaemia was dened as serum levels <3.33 mmol/l.
The 3b-hydroxybutyrate concentrations were measured by
capillary test (Optimum Betaketone test strips; Medisense,
Abingdon, Oxon, UK) to detect ketosis (1 mmol/l).
Ketonuria was measured with urine dipsticks (Multistix

)
read by Clinitek 50 (Bayer Leverkusen, North Rhine-
Westphalia, Germany) where +, ++, or +++ urine ketones
correspond to 1.5, 5, or 8 mmol/l of acetoacetate, respec-
tively. On the last visit, women were investigated for medi-
cation intake and the frequency of episodic vomiting,
diarrhoea, headache or dizziness during the month of
fasting.
Denition of endpoints
Gestational age was calculated based on the last menstrual
period or rst-trimester ultrasonography whenever appro-
priate. The primary endpoint was the percentage of
pregnant women who had PTD, dened as delivery before
37 completed weeks of gestation. Secondary endpoints
included the percentage of women with conrmed hypo-
glycaemia, ketosis, ketonuria, those with deliveries before
32 weeks of gestation, and birthweight <2500 g and
<1500 g. Small-for-gestational-age was dened as birth-
weight <10th centile for gestational age for singletons.
The frequency of PTD was evaluated in relation to the
duration of fasting (15 days versus >15 days) and the
stage of gestation at the time of fasting (rst/second versus
third trimester). Matching for maternal age, parity and
BMI was carried out to control for previously established
risk factors for PTD. Additional variables such as smoking
and employment, considered confounders for PTD, were
also collected.
Statistical analysis
Based on the yearly statistics from the Department of
Obstetrics and Gynaecology at AUBMC and worldwide
estimates of PTD rate of approximately 10%,
20
a total sam-
ple size of 398 pregnant women (199 in the fasting group
and 199 in the control group) was needed for the detection
of a two-fold increase in the rate of PTD (from 10% to
20%), under the assumptions of a type I error (two-sided)
of 5% and a power of at least 80%. Considering a dropout
rate of 10%, the total number of women required was esti-
mated to be 440 (220 in each arm).
Statistical analysis was performed using spss statistical
package version 13 (SPSS Inc., Chicago, IL, USA). Cate-
gorical data were compared using a chi-square test.
Otherwise, the two-tailed Fisher exact test was used if the
expected cell frequencies were small. Continuous variables
were compared using two-tailed Students t-test if
assumptions of normality and homogeneity of variances
appeared to be reasonable or the Wilcoxon rank-sum test.
Multivariate stepwise logistic regression analysis was per-
formed to examine the inuence of confounding variables
on the PTD: fasting, maternal age (<35 and 35 years); nul-
liparity, BMI (<25 kg/m
2
and 25 kg/m
2
); employment, and
smoking. A P-value of <0.05 was considered statistically sig-
nicant. Data that were considered completely missing at
random were deleted using the listwise approach.
Results
Of 468 women interviewed, 427 (91.2%) agreed to partici-
pate in the study. After excluding 12 women for early with-
drawal and 13 for missing data, the analysis was run on
402 women (201 Ramadan-fasted and 201 controls). The
mean number of fasting days was 22 9 (median 26; range
130). No signicant differences were found in the baseline
demographic characteristics between the two groups
(Table 1).
Table 1. Maternal characteristics of the Ramadan-fasted and
control (non-fasting) groups
Ramadan-fasted
group
(n = 201)
Control
group
(n = 201) P value
Age (years)* 29.7 5.2 30.0 5.4 0.529
Gestational age
at recruitment
(weeks)*
27.0 4.7 26.9 4.9 0.672
Body mass index
(kg/m
2
)*
24.8 4.3 24.3 3.6 0.252
Gravidity**
Primigravida 54/200 (27) 69/201 (34.3) 0.171
Gravida 2 146/200 (73) 132/201 (65.7)
Parity**
Nulliparous 91/200 (45.5) 86/201 (42.8) 0.282
Primiparous 46/200 (23) 60/201 (29.8)
Para 2 63/200 (31.5) 55/201 (27.4)
Miscarriage**
Zero 115/200 (57.5) 136/201 (67.6) 0.115
12 77/200 (38.5) 58/201 (28.9)
3 8/200 (4) 7/201 (3.5)
Smoker** 19/183 (10.4) 9/175 (5.1) 0.099
Employed** 47/191 (24.6) 51/190 (26.8) 0.648
*Data presented as mean standard deviation.
**Data presented as n (%).
Maternal fasting effects on preterm delivery
2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2012 RCOG 1381
The proportion of women who had PTD was compara-
ble between the fasting and control groups (Table 2).
However, the caesarean delivery rate was signicantly lower
in Ramadan-fasted women (28.4% versus 39.3%; P =
0.027) and their neonates had a signicantly lower mean
birthweight compared with those born to controls (3094
467 versus 3202 473 g; P = 0.024). When evaluating the
obstetric effects of fasting in relation to the stage of gesta-
tion, no differences were found in the occurrence of PTD
whether women fasted during the rst/second trimester or
third trimester (12/106 versus 9/95, P = 0.844). Moreover,
the duration of fasting did not appear to inuence the end-
points measured. Fasting for 15 days or for >15 days did
not affect signicantly the percentage of women who had
PTD (7/51 versus 14/150; P = 0.535).
The likelihood of hypoglycaemia was similar between the
fasting and control groups both at the beginning and at the
end of Ramadan (Table 3). Ketosis and ketonuria were
more frequent among Ramadan-fasted women compared
with controls (Table 3). Ramadan-fasted women had a sig-
nicantly lower mean increase in maternal weight com-
pared with controls at the end of the fasting month
(1.6 2.2 kg versus 2.3 2.0 kg; P = 0.001). They were
also more likely to report episodes of vomiting (P =
0.011), diarrhoea (P = 0.004) and dizziness (P = 0.001)
throughout the same month (Table 4).
On multivariate stepwise logistic regression analysis,
none of the factors studied had a signicant effect on the
PTD rate except for BMI (odds ratio 0.43; 95% condence
interval 0.200.93; P = 0.033). Fasting was not associated
with an increased risk of PTD (odds ratio 0.72; 95%
condence interval 0.341.54; P = 0.397).
Discussion
The ndings of the present study showed that Ramadan
fasting during the month of September in a geographic
time zone GMT +3 did not increase the risk of PTD in a
cohort of healthy Lebanese pregnant women with single-
tons between 20 and 34 weeks of gestation. A PubMed
search of the English literature from 1980 to August 2011
using the key words fasting, Ramadan, preterm labour
and preterm delivery, reveals this study to be the rst to
determine the effect of Ramadan fasting on PTD during
the course of pregnancy. Data generated consequently add
valuable information to the existing body of knowledge
that will be useful to the counselling process of pregnant
women interested in fasting during this holy month.
Our ndings are in contrast with several human and ani-
mal studies that evaluated various patterns of experimental
caloric deprivation and the risks of PTD. Meal pattern vari-
ations for instance were shown to inuence the frequency
of PTD in pregnant women. Siega-Riz et al.
26
reported that
Table 2. Primary and secondary end-points in the Ramadan-fasted
and control (non-fasting) groups
Ramadan-fasted
group
(n = 201)
Controls
group
(n = 201) P value
Gestational age at
delivery (weeks)*
38.2 1.7 38.4 1.5 0.499
Preterm delivery**
<37 weeks 21 (10.4) 21 (10.4) 1.000
<32 weeks 3 (1.5) 1 (0.5) 0.623
Small for gestational
age**
11/195 (5.6) 12/194 (6.2) 0.820
Birthweight (g)* 3094 467 3202 473 0.024
Birthweight <2500 g** 12/195 (6.2) 7/194 (3.6) 0.353
Birthweight <1500 g** 1/195 (0.5) 2/194 (1.0) 0.623
Caesarean delivery** 57/201 (28.4) 79/201 (39.3) 0.027
*Data presented as mean standard deviation.
**Data presented as n (%).
Table 3. Maternal laboratory data of Ramadan-fasted and control
(non-fasting) groups
Ramadan-fasted
group
Control
group P value
Hypoglycaemia* 48/150 (32) 32/141 (22.7) 0.076
Hypoglycaemia** 38/99 (38.4) 21/82 (25.6) 0.068
Ketosis* 17/150 (11.3) 7/141 (5.0) 0.048
Ketosis** 15/99 (15.1) 5/82 (6.1) 0.053
Ketonuria* 18/141 (12.8) 6/137 (4.4) 0.013
Ketonuria** 12/82 (14.6) 2/79 (2.5) 0.006
All data presented as n (%).
*Data collected during the rst 4 days of Ramadan.
**Data collected during the last 4 days of Ramadan.
Table 4. Signs and symptoms reported by Ramadan-fasted and
control (non-fasting) groups during the month of Ramadan
Ramadan-fasted
group
(n = 201)
Control
group
(n = 201) P value
Weight gain (kg)* 1.6 2.2 2.3 2.0 0.001
Vomiting** 10/200 (5.0) 1/200 (0.5) 0.011
Diarrhoea** 9/200 (4.5) 0 0.004
Headache** 5/201 (2.5) 3/201 (1.5) 0.724
Dizziness** 17/201 (8.5) 2/201 (1.0) 0.001
Systolic pressure* 110 10 110 11 0.678
Diastolic pressure* 68 8 67 10 0.158
*Data presented as mean standard deviation.
**Data presented as n (%).
Awwad et al.
1382 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2012 RCOG
women who ate fewer than three meals and two snacks per
day had a 30% higher risk for PTD compared with preg-
nant women who met this frequency. Pregnant women
who abstained from eating for >13 hours per day had a
three-fold greater risk of delivering preterm at <34 weeks
of gestation (TS Herrmann, unpublished data from 1999).
Improving the nutritional status of pregnant women was
therefore proposed by some as a means of reducing the risk
of PTD.
27,28
Few animal studies also indicate that food
deprivation of 1248 hours during late gestation upregu-
lates corticotrophin-releasing hormone (CRH) messenger
RNA (mRNA) in various regions of the rodent brain
29,30
and triggers preterm birth.
31,32
Similarly, work in sheep
conrmed that acute undernutrition in early gestation
triggered PTD.
33
Herrmann et al.
34
found that a 13-hour
fast in 237 pregnant women increased signicantly mater-
nal CRH concentrations compared with fasts of shorter
duration. An inverse linear relationship between maternal
CRH concentrations and gestational age at delivery was
also established.
34
It is plausible then to assume that CRH
pathways may be involved in the pathogenesis of starva-
tion-induced PTD, possibly stimulating placentalfetal
signalling during late gestation to hasten fetal delivery from
a potentially adverse environment. These experimental
starvation models nevertheless may not always be represen-
tative of a 15-hour Ramadan fast. It is likely that the nature
of stressors associated with energy deprivation during reli-
gious fasting expresses a different pattern of manifestations
on the obstetric outcome.
The metabolic adaptation to energy restriction in humans
involves the release of ketoacids, b-hydroxybutyric acid, and
acetoacetic acid to replace glucose as the primary substrate
in tissues. Transient ketonuria and ketonaemia may occur
during pregnancy as a result of caloric restriction and also
secondary to hypohydration. Ketones were described to
affect amniotic uid volume and composition in sheep,
35
and potentially to cause damage to the neurological system
of rodents.
36
Felig and Lynch
37
suggested that pregnant
women were more vulnerable to heightened ketonaemia
and hypoglycaemia after a brief period of fasting (12 hours)
compared with non-pregnant ones. The term accelerated
starvation was coined by Metzger et al.
38
who conrmed
these ndings following 16 hours of fasting. Hizli et al.
17
in
a casecontrol design of 56 Ramadan-fasting pregnant
women concurred with the above. On the other hand,
Dikensoy et al.
39
could not detect signicant ketonaemia or
ketonuria in pregnant women after a 13- to 14-hour daily
fast. The ndings of the present study revealed that a
15-hour fast resulted in an increased likelihood of ketonuria
and ketosis in pregnant women, but failed to correlate these
ndings with a higher rate of PTD.
The most widely used indicator of maternal nutritional
status during pregnancy is birthweight. Our study showed
a signicant reduction in birthweight in the Ramadan-
fasted group. Weight nonetheless provides a limited per-
spective on fetal growth and development during gestation.
Data from the 1944/45 Dutch famine provide valuable
information on the effects of severe energy rationing on
birthweights. A daily energy restriction of 400800 kcal/
person/day from a baseline of 1800 kcal for 7 months
resulted in a signicant drop in birthweights only when it
coincided with the third-trimester of pregnancy.
40
A retro-
spective cohort study of neonates born to 284 mothers
who fasted in Ramadan during their pregnancy did not
show any signicant effects on birthweights.
13
Similarly, a
casecontrol study revealed that fasting in 56 pregnant
women did not affect birthweight compared with pregnant
controls.
17
Reviewing studies that evaluate the effects of
Ramadan fasting on maternal and fetal health, we found
only one that matches closely our study in relation to the
characteristics of the fasting period.
41
In that respect, both
were performed during September 2008 and within the
same geographic time zone GMT +3. Unlike the ndings
of the present study however, Ozturk et al.
41
in their
prospective controlled design, showed no signicant
differences in maternal weight gain and birthweights
among 42 Ramadan-fasted pregnant women compared with
non-fasting controls.
41
The Turkish study nevertheless
suffered a major limitation related to the small number of
women studied. The lower birthweight in our study could
have contributed to the lower caesarean delivery rate in the
Ramadan-fasted group.
The majority of reported health-related ndings in
relation to fasting and energy deprivation are complex and
often contradictory.
42
Energy deprivation may be either: (i)
elective, often reective of a real-time social experience
such as religious fasting; (ii) experimental, targeted to
measure specic physiological outcome measures; or (iii)
compulsory, best exemplied by catastrophic real-life
events, such as famine. Fundamental differences exist
among these three patterns of energy deprivation, in terms
of the magnitude of caloric deprivation, temporal charac-
teristics, individual background energy reserves, and conse-
quently bodily physiological adjustments. Elective caloric
stress, being self-imposed and predictive, is normally asso-
ciated with episodic replenishment of individual energy
reserves. It should be differentiated from the non-repetitive
highly standardised experimental type occurring in the
context of healthy individual energy reserves, and the
cumulative coercive compulsory type leading to the
progressive erosion of individual energy reserves.
The non-obstetric medical literature provides a wealth of
data evaluating the effects of religious fasting on health,
and shows that changes in energy balance are not
consistent between communities observing a Ramadan fast.
As would be expected during this period, several studies
Maternal fasting effects on preterm delivery
2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2012 RCOG 1383
reported either reduced daily energy intake
43,44
or demon-
strated an overall energy balance.
45,46
Contrary to any pre-
diction nonetheless, few studies reported on a paradoxical
increase in the daily energy intake during Ramadan leading
to an overall weight gain.
4749
In a survey of Saudi families,
59.5% of women reported weight gain and 79.4% increased
their food expenditure during Ramadan.
49
The behavioural
response of Muslims to religious requirements therefore
does not appear to be uniform across cultures. A process
of overcompensation could be driven by binge eating or
modication of caloric sources and food preferences. The
current design did not account for the total daily energy
intake of the pregnant Lebanese women throughout the
study. Yet, the signicantly lower weight gain found in the
current study in association with Ramadan fasting points
to a likely decrease in maternal daily caloric intake. It
should be noted that body mass measurements are not the
best index of energy intake, because they can be con-
founded by a negative water balance as a result of hypohy-
dration
43
and a signicant fall in daily energy expenditure
secondary to decreased habitual activity prole.
In the present study, we acknowledge some limitations.
Because Ramadan is a lunar month, it may occur in any
season of the year. The daily duration of the fast may
therefore vary from 10 to 19 hours depending on the sea-
son and the geographic location, being much shorter the
nearer one is to the equator. For this reason, the usefulness
of our ndings is more relevant to pregnant women who
observe Ramadan around September in a time zone GMT
+3. Furthermore, the study design did not account for the
daily caloric intake of the women studied, which renders
the comparison with other studies more difcult. Also, it
did not address alterations in food quality which could
profoundly affect gut metabolism potentially inuencing
the risk of PTD via modulation of local and systemic
inammatory markers. Although the sample size of preg-
nant women enrolled in this study is much larger than the
majority of comparable studies, it is only capable of detect-
ing a two-fold or greater increase in PTD rates, i.e. 10 to
20% PTD rate. Considering that preterm birth is a complex
entity with multiple predisposing factors, no single alter-
ation in behaviour during pregnancy may be held account-
able alone for any signicant increase in PTD rate.
Consequently, failing to reject the null hypothesis does not
necessarily imply equivalence. At the other end, we also
recognise several strengths to this study. (i) The prospective
controlled nature of the design involved a rigid process of
patient matching by recruiting controls who matched study
women at every level of known confounding variables, i.e.
maternal age, gestational age, parity and BMI. In addition,
the control population was restricted to Muslim women so
the unexposed group could have counterfactually been part
of the exposed group. (ii) The endpoint measured had not
been previously investigated in the context of a Ramadan
fast, namely PTD. (iii) A rigorous follow-up system of
study women was adopted to reduce recall bias. It con-
sisted of contacting women by phone every fth day to
reinforce personal compliance in completing timetable
sheets. (iv) A home collection service was designed to
ensure that blood and urine samples were promptly
obtained as previewed by the study design. This approach
reduced noncompliance and dropouts as a result of fatigue
and dehydration from food and uid deprivation.
Conclusions
In conclusion, the ndings of the present study showed
that Ramadan fasting during the month of September in a
geographic time zone GMT +3, did not increase maternal
risk for preterm delivery in healthy singleton pregnancies
>20 weeks of gestation, despite a smaller gain in maternal
weight, increased incidence of ketosis and ketonuria, and
signicant reduction in birthweight.
Since behavioural responses of Muslims to religious
requirements are not always uniform, further research is
greatly needed to investigate underlying cultural back-
grounds and dietary habits, and evaluate their effects on
maternal and fetal wellbeing. It is also important not to
overlook the fact that the effects of fasting on pregnancy may
not always be immediate. Concerns that carryover metabolic
consequences could continue late into adulthood are real. In
that respect, the present data alone may not be sufcient to
ascertain that Ramadan fasting is safe during pregnancy.
Whether the signicant effect on birthweight is clinically
relevant can only be conrmed by longitudinal studies to
assess the effects of poor fetal growth on the origin of adult
diseases according to the Barker Hypothesis.
50
The build-
up of similar research is highly valuable in offering health-
care providers new insights on addressing this issue, and
providing directions to drive best practices in the future.
Disclosure of interest
None of the authors of this manuscript have conicts of
interest with this research.
Contribution to authorship
JA provided guidance regarding the study question, and
helped with the writing up and editing of the article. IMU
conducted the statistical analyses and helped with editing
of the article. JS helped in data collection, entry and called
women to arrange for collection of their blood and urine
samples. KMM helped with the analysis, as well as the edit-
ing of the article. GG provided expert guidance on the arti-
cle and helped in editing. AHN conceived the idea,
developed the study objectives, and led the preparation of
the article, including writing and editing.
Awwad et al.
1384 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2012 RCOG
Details of ethics approval
This study was approved by the Institutional Review Board
at the American University of Beirut on 15 January 2008.
Funding
This study was funded by a grant from the Medical
Practice Plan at the American University of Beirut, Beirut,
Lebanon. (Principal investigator: Anwar H. Nassar, MD).
The funding agency did not play any role in any aspect of
the study.
Acknowledgements
We are grateful to Dr Dima Dandashi who helped in the
recruitment of the women and in data entry, and to Miss
Suad Katerji, the Laboratory Reception Supervisor, and her
team who visited the women participating in this study at
their homes to secure blood and urine samples. j
References
1 Theobald HE. Eating for pregnancy and breast-feeding. J Fam Health
Care 2007;17:459.
2 Stover J. Nutritional management of pregnancy in chronic kidney
disease. Adv Chronic Kidney Dis 2007;14:21214.
3 Kunz LH, King JC. Impact of maternal nutrition and metabolism on
health of the offspring. Semin Fetal Neonatal Med 2007;12:717.
4 Robinson T, Raisler J. Each one is a doctor for herself: Ramadan fast-
ing among pregnant Muslim women in the United States. Ethn Dis
2005;15:S199103.
5 Rabinerson D, Dicker D, Kaplan B, Ben-Rafael Z, Dekel A. Hypereme-
sis gravidarum during Ramadan. J Psychosom Obstet Gynaecol
2000;21:18991.
6 Malhotra A, Scott PH, Scott J, Gee H, Wharton BA. Metabolic
changes in Asian Muslim pregnant mothers observing the Ramadan
fast in Britain. Br J Nutr 1989;61:66372.
7 Prentice AM, Prentice A, Lamb WH, Lunn PG, Austin S. Metabolic
consequences of fasting during Ramadan in pregnant and lactating
women. Hum Nutr Clin Nutr 1983;37:28394.
8 Mirghani HM, Weerasinghe SD, Smith JR, Ezimokhai M. The effect
of intermittent maternal fasting on human fetal breathing move-
ments. J Obstet Gynaecol 2004;24:6357.
9 Mirghani HM, Weerasinghe DS, Ezimokhai M, Smith JR. The effect
of maternal fasting on the fetal biophysical prole. Int J Gynaecol
Obstet 2003;81:1721.
10 Mirghani HM, Salem M, Weerasinghe SD. Effect of maternal fast-
ing on uterine arterial blood ow. J Obstet Gynaecol Res 2007;
33:1514.
11 Kamyabi Z, Naderi T. The effect of Ramadan fasting on amniotic
uid volume. Saudi Med J 2004;25:456.
12 Kiziltan G, Karabudak E, Tuncay G, Avsar F, Tuncay P, Mungan O,
et al. Dietary intake and nutritional status of Turkish pregnant
women during Ramadan. Saudi Med J 2005;26:17827.
13 Kavehmanesh Z, Abolghasemi H. Maternal Ramadan fasting and
neonatal health. J Perinatol 2004;24:74850.
14 Salleh H. Ramadan fasting among pregnant women in Muar district,
Malaysia and its association to health outcomes. Malays J Reprod
Health 1989;7:6983.
15 Cross JH, Eminson J, Wharton BA. Ramadan and birth weight at full
term in Asian Moslem pregnant women in Birmingham. Arch Dis
Child 1990;65:10536.
16 Azizi F, Sadeghipour H, Siahkolah B, Rezaei-Ghaleh N. Intellectual
development of children born of mothers who fasted in Ramadan
during pregnancy. Int J Vitam Nutr Res 2004;74:37480.
17 Hizli D, Yilmaz SS, Onaran Y, Kafali H, Danisman N, Mollamahmuto-
glu L. Impact of maternal fasting during Ramadan on fetal Doppler
parameters, maternal lipid levels and neonatal outcomes. J Matern
Fetal Neonatal Med 2011;1(8272) (Epub ahead of print).
18 Hobel C, Culhane J. Role of psychosocial and nutritional stress on
poor pregnancy outcome. J Nutr 2003;133:1709S17S.
19 Stein Z, Susser M. The Dutch famine, 19441945, and the reproduc-
tive process II. Interrelations of caloric rations and six indices at birth.
Pediatr Res 1975;9:706.
20 Goodlin RC, Quaife MA, Dirksen JW. The signicance, diagnosis,
and treatment of maternal hypovolemia as associated with fetal/
maternal illness. Semin Perinatol 1981;5:16374.
21 Bieniarz J, Burd L, Motew M, Scommegna A. Inhibition of uterine
contractility in labor. Am J Obstet Gynecol 1971;111:8749.
22 Guinn DA, Goepfert AR, Owen J, Brumeld C, Hauth JC. Manage-
ment options in women with preterm uterine contractions: a ran-
domized clinical trial. Am J Obstet Gynecol 1997;177:81418.
23 Mathews TJ, MacDorman MF. Infant mortality statistics from the
2005 period linked birth/infant death data set. Natl Vital Stat Rep
2008;57:132.
24 Marlow N, Wolke D, Bracewell MA, Samara M. Neurologic and
developmental disability at six years of age after extremely preterm
birth. N Engl J Med 2005;352:919.
25 Saigal S, Doyle LW. An overview of mortality and sequelae of pre-
term birth from infancy to adulthood. Lancet 2008;371:2619.
26 Siega-Riz AM, Herrmann TS, Savitz DA, Thorp JM. The frequency
of eating during pregnancy and its effect on preterm delivery. Am
J Epidemiol 2001;153:64752.
27 Hobel CJ, Siega-Riz AM. The West Los Angeles preterm birth pre-
vention project: a reassessment of interventions. Prenat Neonatal
Med 1998;3:1614.
28 Kafatos AG, Vlachonikolis IG, Codrington CA. Nutrition during preg-
nancy: the effects of an educational intervention program in Greece.
Am J Clin Nutr 1989;50:9709.
29 Brady LS, Smith MA, Gold PW, Herkenham M. Altered expression of
hypothalamic neuropeptide mRNAs in food-restricted and food-
deprived rats. Neuroendocrinology 1990;52:4417.
30 Suemaru S, Hashimoto K, Hattori T, Inoue H, Kageyama J, Zensuke
O. Starvation-induced changes in rat brain corticotropin releasing
factor (CRF) and pituitary-adrenocortical response. Life Sci
1986;39:11616.
31 Fowden AL, Ralph MM, Silver M. Nutritional regulation of uteroplac-
ental prostaglandin production and metabolism in pregnant ewes and
mares during late gestation. Exp Clin Endocrinol 1994;102:21221.
32 Binienda Z, Massmann A, Mitchell MD, Gleed RD, Figueroa JP, Nath-
aielsz PW. Effect of food withdrawal on arterial blood glucose and
plasma 12,14-dihydro-15-keto-prostaglandin F2a concentrations and
nocturnal myometrial electromyographic activity in the pregnant rhe-
sus monkey in the last third of gestation: a model for preterm
labour? Am J Obstet Gynecol 1989;160:74650.
33 Bloomeld FH, Oliver MH, Hawkins P, Campbell M, Phillips DJ,
Gluckman PD, et al. A periconceptional nutritional origin for nonin-
fectious preterm birth. Science 2003;300:606.
34 Herrmann TS, Siega-Riz AM, Hobel CJ, Aurora C, Dunkel-Schetter C.
Prolonged periods without food intake during pregnancy increase
risk for elevated maternal corticotropin-releasing hormone concen-
trations. Am J Obstet Gynecol 2001;185:40312.
35 Ross MG, Sherman DJ, Ervin MG, Castro R, Humme J. Maternal
dehydrationrehydration: fetal plasma and urinary responses. Am
J Physiol 1988;255:E6749.
Maternal fasting effects on preterm delivery
2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2012 RCOG 1385
36 Bhasin S, Shambaugh GE 3rd. Fetal fuels V. Ketone bodies inhibit
pyrimidine biosynthesis in fetal rat brain. Am J Physiol 1982;243:
E2349.
37 Felig P, Lynch V. Starvation in human pregnancy: hypoglycemia,
hypoinsulinemia, and hyperketonemia. Science 1970;170:9902.
38 Metzger BE, Ravnikar V, Vileisis RA, Freinkel N. Accelerated starva-
tion and the skipped breakfast in late normal pregnancy. Lancet
1982;???:58892.
39 Dikensoy E, Balat O, Cebesoy B, Ozkur A, Cicek H, Can G. Effect of
fasting during Ramadan on fetal development and maternal health.
J Obstet Gynaecol Res 2008;34:4948.
40 Stein AD, Zybert PA, Van de Bor M, Lumey LH. Intrauterine famine
exposure and body proportions at birth: the Dutch Hunger Winter.
Int J Epidemiol 2004;33:8316.
41 Ozturk E, Balat O, Ugur MG, Yazicioglu C, Pence C, Erel O, et al.
Effect of Ramadan fasting on maternal oxidative stress during the
second trimester: a preliminary study. J Obstet Gynaecol Res 2011;
7:72933.
42 Trepanowski JF, Bloomer RJ. The impact of religious fasting on
human health. Nutr J 2010;9:57.
43 Leiper JB, Molla AM. Effects on health of uid restriction during
fasting in Ramadan. Eur J Clin Nutr 2003;57:5308.
44 Rolfes SR, Pinna K, Whitney E. Understanding Normal and Clini-
cal Nutrition, 7th edn. Belmont, CA: Thomson Wadsworth,
2006.
45 Yucel A, Degirmenci B, Acar M, Albayrak R, Haktanir A. The effect
of fasting month of Ramadan on the abdominal fat distribution;
assessment by computed tomography. Tohoku J Exp Med 2004;3:
17987.
46 Beltaifa L, Bouguerra R, Ben Slama C, Jabrane H, El-Khadhi A, Ben
Rayana MC, et al. Food intake and anthropometrical and biological
parameters in adult Tunisians during fasting at Ramadan. East Med-
iterr Health J 2002;8:60311.
47 Gharbi M, Akrout M, Zouari B. Food intake during and outside Ram-
adan. East Mediterr Health J 2003;9:13140.
48 Adlouni A, Ghalim N, Benslimane A, Lecerf JM, Saile R. Fasting dur-
ing Ramadan induces a marked increase in high-density lipoprotein
cholesterol and decrease in low-density lipoprotein cholesterol. Ann
Nutr Metab 1997;41:2429.
49 Bakhotmah BA. The puzzle of self-reported weight gain in a month
of fasting (Ramadan) among a cohort of Saudi families in Jeddah,
Western Saudi Arabia. Nutrition J 2011;10:84.
50 Barker DJP. Fetal origins of coronary heart disease. BMJ 1995;
311:1714.
Awwad et al.
1386 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology 2012 RCOG