ORIGINAL ARTICLE

Serum Ferritin and Iron/TIBC of Pregnant Women

Attending Nnamdi Azikiwe University Teaching
Hospital, Nnewi, Anambra State, Nigeria: A
Longitudinal Study
Oluchi Aloy-Amadi1, Augustine U. Akujobi2, Johnkennedy Nnodim1, Joy Ndudim-Dike1,
Amaka Edward1, Michael Anokwute3
1
Department of Medical Laboratory Science, Imo State University, Owerri, Imo State, Nigeria, 2Department
of Optometry, Imo State University, Owerri, Imo State, Nigeria, 3Department of Haematology and Blood
Transfusion, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria

ABSTRACT

Background: During pregnancy, serum ferritin level is decreased because of the increased need of iron which triggers
ferritin mobilization from its stores. Iron is needed during pregnancy to expand the red blood cell mass and for fetal
and placental growth. Aim: The study was aimed at determining the levels of serum ferritin and serum iron/TIBC of
pregnant women at different trimesters and comparing them with that of non-pregnant women. Methods: One hundred
and sixty apparently healthy pregnant women attending antenatal clinic at Nnamdi Azikiwe University Teaching
Hospital, Nnewi at booking in their first trimesters constituted the study population. Similarly, 160 age-matched non-
pregnant women were used as the control groups. Five milliliters of venous blood were collected from each subject by
means of a hypodermic needle and syringe. One milliliter of blood was aliquoted into potassium CDTA container and
used for malaria parasite screening. The remaining 4 ml was placed into gel tubes and used for screening for HIV I
and II, Hepatitis B surface Antigen (HBSAg), Hepatitis C virus (HCV), Veneral Disease Research Laboratory (VDRL),
and for serum ferritin and Iron. The same procedures were conducted on same pregnant women at the second and third
trimesters. At the second trimester, only 156 pregnant women were followed up, while 140 women completed the
study at the last trimester. Results: Serum ferritin (ng/ml) and serum iron (µg/dl) were significantly decreased from
the first trimester (28.83 ± 19.39) and (74.18 ± 23.92), second (23.76 ± 18.74) and (67.77 ± 17.22), and to the third
(20.45 ± 18.42) and (61.23 ± 17.35) (F=10.2, P < 0.001) and (F = 21.9, P < 0.001), respectively. On the other hand,
TIBC increased significantly from the first trimester (349.50 ± 52.69), second (364.67 ± 54.53), and to the third (374.40
± 55.40) (F = 10.9, P < 0.001), respectively. When compared to non-pregnant controls, the serum ferritin and iron in
the first (28.83 ± 19.39) and (74.18 ± 23.92), second (23.76 ± 18.74) and (67.77 ± 17.22), and third (20.45 ± 18.42)
and (61.23 ± 17.35) trimester were significantly decreased compared to the non-pregnant controls (39.67 ± 54.70) and
(80.78 ± 38.19) (F = 14.2, P < 0.001) and (F = 33.7, P < 0.001), respectively. The TIBC in the first (349.50 ± 52.69),
second (364.67 ± 54.53), and third (374.40 ± 55.40) trimesters showed a significant increase compared to the controls
(338.37 ± 57.68) (F = 17.1, P < 0.001), respectively. Conclusion: This study showed that levels of serum ferritin and
serum iron/TIBC in pregnant women are altered in pregnancy. Therefore, there is need to monitor pregnancies at risk
to prevent adverse outcomes.

Key words: Longitudinal, pregnancy, serum ferritin, serum iron/TIBC

Address for correspondence:

Oluchi Aloy-Amadi, Department of Medical Laboratory Science, Imo State University, Owerri, Imo State, Nigeria.
Tel.: 
https://doi.org/10.33309/2638-7697.030203 www.asclepiusopen.com
© 2020 The Author(s). This open access article is distributed under a Creative Commons Attribution (CC-BY) 4.0 license.

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 Aloy-Amadi, et al.: Serum Ferritin and Iron/TIBC of Pregnant Women: A Longitudinal Study

INTRODUCTION These two proteins play essential roles in vertebrate

metabolism, respectively oxygen transport by blood and

F
erritin is a protein that performs an iron storage oxygen storage in muscles. To maintain the necessary
function in mammals. It is found mainly in the liver, levels, human iron metabolism requires a minimum of iron
spleen, and bone marrow and to a lesser extent in the diet.[6]
throughout the tissues. The concentrations of serum ferritin
present a close correlation with total reserves of iron in Iron requirements are greater in pregnancy than in the non-
the body. This protein can, therefore, be used as a reliable pregnant state. Although iron requirements are reduced in
estimator of iron reserves in the organism. During gestation, the first trimester because of the absence of menstruation,
levels of serum ferritin fall by 50%. This is a consequence they steadily increase thereafter. The total requirement
of the normal heme-iron dilution process during pregnancy, of a 55 kg woman is approximately 1000 mg. Translated
and also of the extraction of iron by the fetus.[1] The utility of into daily needs, the requirement is approximately 0.8 mg
ferrotherapy during gestation is still a matter of controversy. Fe in the first trimester, and > 6 mg in the third trimester.
Some studies have found beneficial effects for the mother Absorptive behavior changes accordingly; a reduction
including lower rate of anemia Karimi et al., 2000, and for in iron absorption in the first trimester is followed by a
the fetus where higher levels of ferritin have been found progressive rise in absorption throughout the remainder of
in newborns when the mothers received iron supplements pregnancy. The amounts that can be absorbed from even an
during their pregnancy.[2] Serum ferritin is considered as a optimal diet, however, are less than the iron requirements in
better parameter to detect latent iron deficiency especially later pregnancy and stores of ≥300 mg if she is to meet her
before the change of red cell morphology and red cell indices. requirements fully.[7]
A high degree of correlation has been shown between serum
ferritin and bone marrow iron stores. In the stage of latent iron Iron deficiency continues to be the leading single nutritional
deficiency (absence of storage iron), as assessed by marrow deficiency in the world, despite considerable efforts to
iron content, serum ferritin concentration is decreased, but decrease its prevalence.[8]
the transferrin saturation, serum iron, and Hb levels may
remain unchanged.[3] Women in developing countries are always in a state of
precarious iron balance during their reproductive years.
During pregnancy, low serum ferritin concentrations in Their iron stores are not well developed because of poor
the presence of normal hemoglobin indicate deficient iron nutritional intake, recurrent infections, menstrual good loss,
stores. Such females are prone to develop overt iron deficient and repeated pregnancies.[9] During the first two trimesters
anemia. In pregnancy, serum ferritin concentration is the of pregnancy, iron deficiency anemia increases the risk for
maximum at 12–16 weeks of gestation, and then the levels preterm labor, low birth weight babies, and infant mortality
start decreasing as the pregnancy advances. Low serum and predicts iron deficiency in infants after 4 months of
ferritin levels during second and third trimesters predict low age.[10] It is estimated that anemia accounts for 3.7% and
hemoglobin levels in late pregnancy.[4] Serum ferritin levels 12.8% of maternal deaths during pregnancy and childbirth in
showed significantly lowest values in second trimester, with Africa and Asia, respectively.[11]
slight increase again in third trimester. Increasing gravity
had no significant effect on serum ferritin levels.[4] Iron This study was aimed at determining the levels of serum
stores that are elevated in pregnancy are associated with ferritin and serum iron/TIBC of pregnant women attending
preterm delivery, pre-eclampsia, and gestation diabetes Nnamdi Azikiwe University Teaching Hospital, Nnewi
mellitus. Women with ferritin levels that are elevated for (NAUTH), Anambra State, Nigeria.
the third trimester of pregnancy (>41 ng/ml) have a gravity
increased risk of preterm and very preterm delivery that has MATERIALS AND METHODS
been attributed to intrauterine infection. Another plausible
mechanism for high ferritin levels is failure of the maternal Study area
plasma volume to expand. The research study was conducted at NAUTH, Nnewi, from
January to December, 2016.
Ferritin production is increased with infection and
inflammation as part of the acute phase response. In the Subjects
presence of infection, macrophages produce inflammatory The study constituted of 160 apparently healthy pregnant
cytokines that generate reactive oxygen species, releasing women who presented for booking at the antenatal clinic of
free iron ferritin.[5] NAUTH in their first trimesters. Their ages were between
20 and 40 years. They were enrolled after ethical approval
The body of an adult human contains about 4 g (0.005% from NAUTH and written informed consent from the
body weight) of iron, mostly in hemoglobin, and myoglobin. pregnant women was obtained. Similarly, 160 age-matched

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 Aloy-Amadi, et al.: Serum Ferritin and Iron/TIBC of Pregnant Women: A Longitudinal Study

non-pregnant women consisting of NAUTH staff and health significance was calculated using post hoc test to analyze the
science students were used as the control groups. results of the experimental data. Differences were considered
significant at P < 0.05.
METHODOLOGY
RESULTS
This research was a cohort study and was carried out at
the antenatal clinic of NAUTH, Nnewi, from January to Table 1 shows mean levels of serum Ferritin and serum iron/
December, 2016. All pregnant women who presented for TIBC of pregnant women at different trimesters.
booking for antenatal care in their first trimester were
recruited for the study and were enrolled after providing Table 2 shows mean values of serum ferritin, serum iron, and
their informed consent. Questionnaires were administered TIBC in pregnant women compare to non-pregnant women.
to them to obtain their medical and obstetrics history.
Ultrasound scan was used to confirm the pregnancy and its The mean level of serum ferritin in the control subjects
duration. (39.67 ± 54.70) was significantly increased statistically when
compared to the first (28.83 ± 19.39), second (23.76 ± 18.74),
At the first trimester visit and at subsequent trimesters, the and third (20.45 ± 18.42) trimesters (F = 14.2, P <  0.001).
blood pressure was measured. The weight and height were Similarly, the serum, iron mean levels in the controls
also measured and used to calculate the body mass index (80.78 ± 23.19) were significantly increased compared to the
(BMI). Five millimeters of venous blood were collected from first trimesters (74.18 ± 23.92), second (67.77 ± 17.22), and
each subject by means of a hypodermic needle and syringe. third (61.23 ± 17.35) trimesters (F = 33.7, P < 0.001).
One milliliter of blood was aliquoted into potassium EDTA
container and used for screening for malaria parasite. However, the TIBC mean level in the controls (338.37 ±
57.69) was significantly increased statistically compared to
The remaining 4 ml was put into gel tubes and used for the first (349.50 ± 52.69), second (364.67 ± 54.53), and third
screening for HIV I and II, Hepatitis B Surface Antigen (374.40 ± 55.40) (F = 17.1, P < 0.001).
(HBsAg), Hepatitis (Virus (HCV), Veneral Disease Research
Laboratory (VDRL), and for serum ferritin and iron. Post hoc analysis
Serum ferritin in the first (28.83 ± 19.39), second
After the screening exercise, pregnant women who were not (23.76 ± 18.74), and third (20.45 ± 18.42) trimesters showed
eligible were excluded. One hundred and sixty apparently a statistically significant decrease when compared to the
healthy pregnant women were enrolled in the study as the control subjects (39.67 ± 54.70) (P = 0.003 and <0.001).
test group, while an equivalent number of age-matched non- A non-statistically significant decrease was seen when
pregnant women served as controls. Pregnancy test was to the second trimester (23.76 ± 18.74) was compared to the
confirm they were not pregnant. The same procedures were first (28.83 ± 19.39) (P = 0.375), and the third trimester
conducted on same pregnant women at the second and third (20.45 ± 18.42) (P = 0.720), but a statistically significant
trimesters. 156 pregnant women were followed up at the decrease was observed when the third trimester (20.45 ±
second trimester, while only 140 completed the study. 18.42) was compared to the first (28.83 ± 19.39) (P = 0.040).

Results from pregnant women were compared across the Serum iron showed a statistically significant decrease when
trimesters and comparisms were also made with the non- the first (74.18 ± 23.92), second (67.77 ± 17.22), and third
pregnant controls. (61.23 ± 17.35) trimesters were compared to the control
subjects (80.78 ± 38.19) (P = 0.07 and <0.001). Similarly,
Ethical approval a statistically significant reduction was observed when the
The ethical approval was obtained from the ethics review second trimester (67.77 ±17.22) was compared to the first
Committee of Nnamdi Azikiwe University Teaching Hospital (74.18 ± 23. 92) (P = 0.010), and the third (61.23 ± 17.35)
(NAUTH), Nnewi, and written informed consent was (P = 0.008), and when the third trimester (61.23± 17.35) was
obtained from the pregnant women before sample collection. compared to the first (74.18 ± 23.92) (P < 0.001). However,
TIBC in first trimester (349.50 ± 52.69) showed a statistically
Statistical analysis insignificant increase when compared to the controls (338.37
Statistical analysis was performed using computer software ± 57.68) (P = 0.174), but a statistically significant increase
Statistical Package for the Social Sciences (SPSS). One- in the second (364.67 ± 54.53) and third (374.40 ± 55.40),
way analysis of variance was used to compare between compared to the controls (338.37 ± 57.68). A statistically
pregnant women at all trimesters and non-pregnant women significant increase was also observed when the second
(Independent ANOVA), and for comparisons across the (364.67 ± 54.53) and third (374.40 ± 55.40) were compared
trimesters (the repeated measure ANOVA). Statistical to the first (349.50 ± 52.69) (P = 0.028 and <0.001). On the

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 Aloy-Amadi, et al.: Serum Ferritin and Iron/TIBC of Pregnant Women: A Longitudinal Study

Table 1: Mean values of serum ferritin and serum iron/tibc of pregnant woman at different trimesters
(mean±SD)
Trimester Serum ferritin (ng/ml) Serum iron (µg/dl) TIBC (µg/dl)
First trim N=160 28.83±19.39 74.18±23.92 349.50±52.69
Second trim N=156 23.76±18.74 67.77±17.22 364.67±54.53
Third trim N=140 20.45±18.42 61.23±17.35 374.40±55.40
F (P-value) 10.2 (<0.001)* 21.9 (<0.001)* 10.9 (<0.001)*
Post hoc
1st versus 2nd 0.019* 0.003* 0.014*
2 versus 3
nd rd
0.179 0.002* 0.166
1 versus 3
st rd
<0.001* <0.001* <0.001*
Significant at P<0.05

Table 2: Mean values of serum ferritin, serum iron, and TIBC in pregnant women compare to non-pregnant
women (mean±SD)
Control/Trimester Serum ferritin (ng/ml) Serum iron (µg/dl) TIBC (µg/dl)
Control c
39.67±54.70 80.78±38.19 338.37±57.68
n=160
First Trim 28.83±19.39 74.18±23.92 349.50±52.69
n=160
Second Trim 23.76±18.74 67.77±17.22 364.67±54.53
n=156
Third Trim 20.45±18.42 61.23±17.35 374.40±55.40
n=140
F (P-value) 14.2 (<0.001)* 33.7 (<0.001)* 17.1 (<0.001)*
Post hoc
Control/Trimester Serum ferrintin (ng/ml) Serum iron (µg/dl) TIBC (µg/dl)
C versus 1 st
0.003* 0.007* 0.174
C versus 2nd <0.001* <0.001* <0.001*
C versus 3rd <0.001* <0.001* <0.001*
1 versus 2
st nd
0.375 0.010* 0.028*
2nd versus 3rd 0.720 0.008* 0.282
1 versus 3
st rd
0.040* <0.001* <0.001*
C=Control. *Significant at P<0.05. Trim=Trimester

other hand, a non-statistically significant increase was seen from its stores. This is in line with the work done by
when the third trimester (374.40 ± 55.40) was compared to Namama,[12] who showed that levels of serum ferritin were
the second (364.67 ± 54.43) (P = 0.282). decreased in pregnancy compared to that in non-pregnancy,[13]
also showed that non-pregnant women had more iron
DISCUSSION stores, therefore had less need for iron than their pregnant
counterparts. The higher iron need in pregnancy triggered its
This study has shown that serum ferritin decreased mobilization from its stores. During pregnancy, there is an
significantly in pregnancy as compared to the non-pregnant immense stress on iron metabolism and it frequently induces
women. iron deficiency which is characterized, by a reduced ferritin
level.[4] Furthermore, some of the pregnant women started
The decrease may be because during pregnancy there is pregnancy with low iron stores, hence the reason for low
increased need of iron which triggers ferritin mobilization ferritin in pregnancy compared to the controls.

 Clinical Research in Obstetrics and Gynecology  •  Vol 3  •  Issue 2  •  2020

 Aloy-Amadi, et al.: Serum Ferritin and Iron/TIBC of Pregnant Women: A Longitudinal Study

Ferritin is an acute phase reactant protein and is sometimes development (Bothwell, 2000). There is a significant increase
found elevated independent of the iron status during illness in the amount of iron required to increase the red cell mass,
and inflammation. According to Bain et al.,[14] serum ferritin expand the plasma volume and allow for the growth of the
decreases in early pregnancy and usually remains low fetal-placental unit.[18]
throughout pregnancy, even when supplementary iron is
given. Pregnancy is commonly associated with urinary tract Total iron binding capacity (TIBC) was insignificantly
infections and some occult infections. In such individuals, increased in the first trimester, but increased significantly in
high serum ferritin levels are likely to be seen despite iron the second and third trimesters compared to non-pregnant
deficiency.[15] women. When compared across the trimesters, the values
increased from the first to the third trimester. This agrees
Ferritin progressively decreased from the first to the with the work done by Amah-Tariah et al. and Chaudari et
third trimester. This could be due to increased demand for al. Okwara et al.[13,16,19] TIBC is known to be increased in
fetal growth and development as pregnancy progressed. pregnancy and during iron overload.[20]
This disagrees with the study done by Naghmi et al. and
Namama[4,12] who showed that ferritin decreased from first CONCLUSION
to second trimester with a slight rise in the third trimester. It
is in line with Okwara et al.,[13] who stated that serum ferritin The findings have shown that, by longitudinal analysis,
declined progressively from first to the third trimester. serum ferritin and serum iron were decreased with increased
The immense stress on iron metabolism during pregnancy in gestational age, while TIBC was increased as pregnancy
frequently induces iron deficiency, hence the reduction in progressed. Furthermore, serum ferritin and serum iron were
ferritin level. This also implies a progressive mineral transfer decreased in each trimester compared to the non-pregnant
from the mother to the fetus. Serum ferritin also showed controls, whereas TIBC was increased in all the trimesters
significantly lowest values in the third trimesters. compared to the controls. Therefore, there is need to monitor
pregnancies at risk to prevent adverse outcomes.
The demand for iron is variable during the three trimesters
and the practice of iron supplementation is also not uniform.
Furthermore, the decrease in serum ferritin level may be
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