Journal of Obstetrics and Gynaecology

ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: http://www.tandfonline.com/loi/ijog20

Role of maternal serum ferritin in prediction of

preterm labour

Khaled Abdel-Malek, Mohamed Ahmed El-Halwagi, Bahaa Eldin Hammad,

Osama Azmy, Omneya Helal, Marwa Eid & Mazen Abdel-Rasheed

To cite this article: Khaled Abdel-Malek, Mohamed Ahmed El-Halwagi, Bahaa Eldin Hammad,
Osama Azmy, Omneya Helal, Marwa Eid & Mazen Abdel-Rasheed (2017): Role of maternal
serum ferritin in prediction of preterm labour, Journal of Obstetrics and Gynaecology, DOI:
10.1080/01443615.2017.1347915

To link to this article: http://dx.doi.org/10.1080/01443615.2017.1347915

Published online: 14 Sep 2017.

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 JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 2017
https://doi.org/10.1080/01443615.2017.1347915

ORIGINAL ARTICLE

Role of maternal serum ferritin in prediction of preterm labour

Khaled Abdel-Maleka , Mohamed Ahmed El-Halwagia, Bahaa Eldin Hammada, Osama Azmyb, Omneya Helala,
Marwa Eida and Mazen Abdel-Rasheedb
a
Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt; bDepartment of Reproductive Health
Research, National Research Centre, Cairo, Egypt

ABSTRACT KEYWORDS
The aim of this study was to evaluate the value of measurement of serum ferritin level in pregnant Serum ferritin; preterm
women to predict preterm labour. The study included 236 women whose haemoglobin (Hb) levels labour; premature rupture
were
10.5 gm/dl and gestational age (GA) was less than 30 weeks. Serum ferritin levels were measured of membranes
at 30 weeks of gestational age. At the end of the study, 23 women delivered with preterm premature
rupture of membrane (PPROM) and 17 women delivered before 37 weeks but without PROM (study
Downloaded by [University of Calgary] at 12:52 15 September 2017

group). The rest of the pregnant women (196 women) delivered between 37 and 40 weeks (control
group). We found a significant difference between the two groups with respect to serum ferritin level.
The cut off value of serum ferritin between the two groups was 31 ng/ml with sensitivity 92.8%, specifi-
city 99.4%, positive predictive value 97.5%, negative predictive value 98.4% and accuracy 98.3%.

IMPACT STATEMENT
 What is already known on this subject: maternal serum ferritin has been found to be elevated in
women who delivered preterm.
 What the results of this study add: In this study, we have shown that serum ferritin 31 ng/ml is
the optimal cut-point between preterm and full-term women.
 What the implications are of these findings for clinical practice and/or further research: Serum
ferritin 31 ng/ml could be proposed as a potential helpful marker to predict preterm labour.

Introduction action of prostaglandins is uterine contraction and they also

Preterm labour refers to labour between the onset of foetal
viability and the completed 37 weeks of gestation. It repre-
sents about 10% of all births and is responsible for 75% of
perinatal mortality and 50% of long-term morbidity
(Movahedi et al. 2012). The pathophysiology of preterm
labour is still largely unknown. However, there is evidence,
which indicates that subclinical infections, intrauterine infec-
tion and chronic inflammation are strong risk factors that
subsequently cause preterm labour and premature rupture of
membranes (PROM) (Kouck
y et al. 2009).
Other risk factors include history of previous preterm
labour (Ananth et al. 2006), history of previous abortion
(Swingle et al. 2009), pregnancies conceived with assisted
reproductive technologies (Dunietz et al. 2015), multifetal
gestation (Kurdi et al. 2004), vaginal bleeding in pregnancy
(Hossain et al. 2007), moderate to severe anaemia at 12 weeks
of gestation (Zhang et al. 2009), short cervix, cervical incom-
petence, previous cervical surgery (Kouck
y et al. 2009), uter-
ine problem (Chan et al. 2011), lifestyle factors such as low
socioeconomic status (Smith et al. 2007), low weight gain
(Cnattingius et al. 2013) and substance abuse during preg-
nancy (Heaman et al. 2013).
In cases of infection, microorganisms produce prostaglan-
dins either directly or via producing phospholipase A2. The
contribute to cervical softening (Romero et al. 2007).
Various biochemical markers have been developed to pre-
dict preterm labour. These markers includes foetal fibronectin
in the cervicovaginal secretions (Farag et al. 2015), human
chorionic gonadotropin in the cervicovaginal secretions (Sak
2010), maternal serum corticotropin-releasing hormone (CRH)
(Makrigiannakis et al. 2007), maternal serum alpha-fetoprotein
(AFP) at 11–13 weeks (Beta et al. 2011). This might be
explained by the status of an acute phase reaction to subclin-
ical infections that are commonly associated with preterm
labour (Movahedi et al. 2012). It has been hypothesised that
subclinical maternal infection is responsible for both the ele-
vated maternal serum ferritin levels and for spontaneous pre-
term PROM (Zhang et al. 2009).
The aim of this study was to evaluate the value of meas-
urement of serum ferritin levels in pregnant women to pre-
dict preterm labour.
Materials and methods
This cross-sectional study was conducted at outpatient clinic
and inpatient ward of Obstetrics and Gynecology department
at Kasr AL-Aini Hospital, EI-Zahraa Teaching Hospital and EI-
Sahel Teaching Hospital during the period from January 2016

CONTACT Khaled Abdel-Malek profkhaled@hotmail.com 137 Abdul Aziz Al-Saud, Al-Manial, Cairo, Egypt
ß 2017 Informa UK Limited, trading as Taylor & Francis Group
 2 K. ABDEL-MALEK ET AL.

to June 2016. Sample size was calculated and was found to Table 1. Comparison between preterm and full-term as regard demographic
information.
be 217 at minimum according to total birth, incidence of pre-
term labour (10%), maximum deviation (± 4%) and confidence Preterm Full-term
Mean ± SD Mean ± SD p value
level (95). A total of 255 pregnant women were seen and
Age 29 ± 5.3 28.9 ± 5.1 .958
examined during the routine antenatal care. Only 236 women Parity 2.58 ± 0.7 2.56 ± 0.6 .883
were chosen from the pregnant women whose haemoglobin BMI 27.5 ± 4.7 29.8 ± 3.6 .093
Gestational age at delivery 33.45 ± 1.58 38.86 ± 1
(Hb) level was
10.5 gm/dl and gestational age (GA) before
p value ¼ Level of significance.
30 weeks based on the last menstrual period. Women were Statistically not significant (p
.05).
asked about symptoms of previous genital and urinary tract
infection, previous preterm labour and previous cervical oper-
Table 2. Comparison between preterm and full-term as regard medical data.
ation. Women were excluded from the study if they had any
Preterm Full-term
of the following criteria: Hb <10.5 g, poly-hydramnios, mul-
tiple pregnancy, foetal congenital anomalies, uterine anoma- N ¼ 40 % N ¼ 196 % p value
lies, cervical dilation more than 3 cm or cervical effacement History of pelvic inflammatory disease
No 12 30 29 14.8 .206
more than 50%. Diabetic, cardiac and hepatic women were Yes 28 70 167 85.2
also ruled out from the study. History of urinary tract infection
No 8 20 10 5.1 .249
At 30 weeks of gestational age, blood samples were col-
Yes 32 80 186 94.9
lected from the 236 pregnant women with the inclusion crite-
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Pervious preterm labour

ria. Blood samples were left to clot and then centrifuged to Yes 11 27.5 39 19.9 .527
No 29 72.5 157 80.1
separate serum, which was kept in Eppendorf tubes at Surgical history
20  C until the time of the assay of serum ferritin. Turbid History of cervical cerclage 5 12.5 29 14.8 .353
and hemolysed samples were discarded. Serum ferritin levels History of cervical cautery 8 20 10 5.1
No 27 67.5 157 80.1
were measured by enzyme immunoassay techniques using
p value ¼ Level of significance.
kits provided from quorum EIA ferritin enzyme-immunoassay. Statistically not significant (p
.05).
All the participants were informed about this test and con-
sent was taken from all of them.
Table 3. Comparison between preterm and full-term as regard Hb and ferritin
Complete antenatal care for all the pregnant women was level.
done. At the end of study, 23 women delivered with preterm Preterm Full-term
premature rupture of membrane (PPROM) and 17 women Mean ± SD Mean ± SD p value
delivered before 37 weeks, but without PROM (study group). Hb (gm/dl) 11.1 ± 0.7 11.0 ± 0.8 .565
Serum ferritin (ng/ml) 76.3 ± 29.4 20.2 ± 5.0 <.001
The rest of the pregnant women (196 women) delivered
SD: Standard deviation.
between 37 and 40 weeks (control group).
p value ¼ Level of significance.
Statistically highly significant (p < .001).
Statistically not significant (p
.05).
Study design
but there was significant difference between the two groups
This was a cross-sectional study. It was approved by the with respect to serum ferritin level. The mean level of serum
Medical Research Ethics committee of the National Research ferritin in preterm was 76.3 ± 29.4 while in full-term was
Centre, Cairo, Egypt, under registration number 16-005. All 20.2 ± 5, so there was statistical difference between the two
the participants were informed about this test and a written groups (Table 3).
consent was taken from each of them. Both the groups were divided according to the gravidity
to study the influence of increased gravidity on both Hb and
Statistical analysis ferritin levels. There was no significant difference with respect
to Hb and ferritin levels among preterm cases in both primi-
The clinical and laboratory data were revised, coded, tabu- gravida group and multigravida group, and no significant dif-
lated and introduced to a PC using Statistical package for ference among full-term cases in both primigravida group
Social Science (SPSS 15.0.1 for Windows; SPSS Inc, Chicago, IL, and multigravida group (Table 4). ROC curve (Figure 1)
2001). Statistical analysis was done to obtain mean, range, revealed the cut off value of serum ferritin between the two
Student’s t-test and Chi square tests. groups was 31 ng/ml with sensitivity 92.8%, specificity 99.4%,
positive predictive value 97.5%, negative predictive value
98.4% and accuracy 98.3%.
Results
The demographic date (age, parity, BMI and gestational age
Discussion
at delivery) for both the groups were shown in Table 1. There
was no significant difference between preterm and full-term Normally from the second trimester, serum ferritin starts to
groups regarding history of pelvic inflammatory disease, his- decline. Maternal serum ferritin at the time of delivery may
tory of urinary tract infection, previous preterm labour and reach 1/3rd the value found in the infant cord sample. Now it
history of cervical surgical (Table 2). There was also no signifi- is well-established that ferritin can increase markedly when
cant difference with respect to Hb between the two groups, there is physiologic stress in acute or chronic infection, with

Table 4. Comparison between primigravida group and multigravida group as regard Hb and ferritin level among preterm and full-term cases.
Preterm
Primigravida Multigravida
Mean ± SD Mean ± SD
Hb (gm/dl) 10.9 ± 0.7 11.2 ± 0.7
Serum ferritin (ng/ml) 70.3 ± 32.9 79.1 ± 42.4
SD: Standard deviation.
p value ¼ Level of significance.
Statistically not significant (p
.05).
Downloaded by [University of Calgary] at 12:52 15 September 2017
Figure 1. ROC curve revealed that the cut off value of serum ferritin between
two groups was 31 ng/ml with sensitivity 92.8% and specificity 99.4%.
tissue damage or in the presence of liver disease or cancer.
Ferritin in these cases reflects a status of an acute phase reac-
tion rather than being an indicator of nutritional status
(Movahedi et al. 2012).
In this study, serum ferritin was highly-elevated in women
who had preterm labour (76.3 ± 29.4 ng/ml) in comparison to
those women with full term labour (20.2 ± 5 ng/ml). These
results are supported by the result obtained by Saha et al.
(2000). They compared the maternal serum ferritin in the two
groups of pregnant women. The study group consisted of 50
pregnant women who had preterm labour, and control group
consisted of 50 pregnant women who delivered at full-term.
Serum ferritin was found to be elevated in patients with pre-
term labour and preterm premature rupture of membranes
(23.24 ± 12.13 ng/ml and 29.44 ± 28.41 ng/ml, respectively),
while serum ferritin in control group was 8.69 ± 3.7 ng/ml.
Xiao et al. (2002) have published similar results. They
studied the maternal serum ferritin concentrations in 312
cases of preterm delivery and 424 women who had full-term
labour. They found a two-fold increased risk of preterm pre-
mature rupture of membranes among women with ferritin
concentrations above 64.5 ng/ml compared with women
whose concentrations were less than 26 ng/ml.
Our results also are in agreement with those reported by
Movahedi et al. (2012). They observed that elevated serum
ferritin concentrations during the second trimester were pre-
dictive of preterm delivery. Regarding the best cut-off point
JOURNAL OF OBSTETRICS AND GYNAECOLOGY 3
Full-term
Primigravida Multigravida
p value Mean ± SD Mean ± SD p value
.293 10.7 ± 0.7 11.2 ± 0.8 .179
.515 21.8 ± 6.3 19.2 ± 3.9 .271
for the serum ferritin level to predict preterm labour, ROC
curve revealed that the serum ferritin values of more than
22.5 ng/ml was the optimal cut-point, yielded the best com-
bination with sensitivity of 78.3% and specificity of 83%. In
our study, the cut off value of serum ferritin between the
two groups was 31 ng/ml with sensitivity 92.8%, specificity
99.4%, positive predictive value 97.5%, negative predictive
value 98.4% and accuracy 98.3%.
However, our results are not in agreement with the results
reported by Weintraub et al. (2005), who reported that mean
serum ferritin concentrations were not significantly different
among patients with preterm and full-term deliveries, and no
significant correlation was found between serum ferritin con-
centrations and gestational age at birth. Yet, it is possible
that the relatively small study sample did not enable the
authors to reach statistical significance.
In this study, there was no significant difference between
the primigravida and multigravida women with respect to Hb
and ferritin levels. This means that the gravidity and parity of
the women have no influence on Hb and ferritin levels. These
results are not in agreement with Da Silva et al. (2003) who
reported that the risk of preterm labour was significantly
higher among very young primigravida. This discrepancy may
be because his target group in primigravida was mothers
aged less than 18 years.
Conclusions
Serum ferritin is highly elevated in cases of preterm labour,
so it could be proposed as a potential helpful marker to pre-
dict preterm labour.
Disclosure statement
The authors declare no conflict of interest.
Funding
Cairo University, [10.13039/501100002386].
ORCID
Khaled Abdel-Malek http://orcid.org/0000-0003-4824-3039
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