International Journal of Reproduction, Contraception, Obstetrics and Gynecology

Anushree N et al. Int J Reprod Contracept Obstet Gynecol. 2023 Aug;12(8):2394-2398

www.ijrcog.org pISSN 2320-1770 | eISSN 2320-1789

DOI: https://dx.doi.org/10.18203/2320-1770.ijrcog20232278
Original Research Article

Serum ferritin level and its association with gestational diabetes

mellitus in pregnancy
Anushree N.*, Sujatha Prabhu, Sana Fathima

Department of Obstetrics and Gynecology, ESICMC PGIMSR and Model Hospital, Rajajinagar, Bengaluru,
Karnataka, India

Received: 26 April 2023

Revised: 08 June 2023
Accepted: 09 June 2023

*Correspondence:
Dr. Anushree N.,
E-mail: anukonasale@gmail.com

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Short term as well as long term effects of GDM on both the mother and the child are preventable if
screening and diagnosis are done at an early stage. Efforts have been made to try and identify clinical and biochemical
markers that could predict GDM. Ferritin, an acute phase reactant is one such protein. This study was undertaken to
know if there is an association between serum ferritin level and GDM in pregnancy.
Methods: A prospective study conducted in the Department of OBG, ESIC-MC-PGIMSR from January 2020 to June
2021. 388 gravid women satisfying the inclusion criteria were enrolled for the study after obtaining an informed written
consent and maternal serum ferritin was assayed between 24 to 28 weeks of gestation and was statistically analysed.
Results: Both group demographic characters were matched and they were also matched for Hb% thereby eliminating
anaemia, a confounding factor for the study. The mean serum ferritin level in GDM group was 46.4 ng/ml and in non-
GDM group was 37.3 ng/ml (p<0.001). With ROC (Receiver operator characteristics curve) the cut off value of serum
ferritin is 34.7 ng/ml with 95% CI, with sensitivity of 71% and specificity of 63%.
Conclusions: In this study S. ferritin value of >34.7 ng/ml at 24-28 weeks of gestation, there is 63% risk of developing
GDM. Thus, we conclude that elevated serum ferritin level could be used as a biochemical marker for prediction of
GDM.

Keywords: Gestational diabetes, Serum ferritin, Haemoglobin, Inflammation, Acute phase reactant

INTRODUCTION type 2 diabetes with persistent glucose intolerance

developed later.
Gestational diabetes mellitus (GDM) is ‘any degree of
glucose intolerance that either starts during pregnancy or The incidence of GDM is increasing globally and presently
is newly diagnosed in pregnancy’ according to ACOG it is 20-27% of all pregnancies. Modern lifestyle, changes
(American college of obstetrics and gynaecology) and The in diet, increased obesity, reduced physical activity,
International association of diabetes and pregnancy study increased prevalence of metabolic syndrome, older age at
groups (IADPSG).1 It is also defined as carbohydrate child birth lead to increased GDM incidence. History of
intolerance of variable severity with onset or first diabetes in family and Indian ethnicity are additional risk
recognition during pregnancy, according to WHO factors.2 Gestational diabetes mellitus is an important
guidelines. It also includes women, whose glucose cause of perinatal morbidity and mortality. Short term as
tolerance becomes normal after pregnancy and those with well as long term effects on the health of both mother and
the child due to GDM is preventable if screening and

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diagnosis are done at an early stage.2 There is no specific Screening for GDM
biochemical test that can predict the risk of developing
GDM other than blood sugars tests which can screen and All pregnant women enrolled for the study, irrespective of
diagnose GDM like oral glucose challenge test their last meal were given 75 gm anhydrous glucose
(OGCT)/Oral glucose tolerance test (OGTT). Despite dissolved in 300 ml water to be consumed orally at one
years of research, there is still no agreement regarding time or within 5-10 minutes. A plasma standardised
optimal GDM screening.3 Recent studies have shown a glucometer was used to evaluate blood sugar 2 hours after
positive correlation between elevated serum ferritin the oral glucose load. The threshold blood sugar level of
concentration with insulin resistance and diabetes, and its more than or equal to 140 mg/dl was taken as cut off for
association has also been described in gestational diabetes diagnosis of GDM as per diabetes in pregnancy society of
mellitus (GDM).4 Thus, the present study was to evaluate India (DIPSI) criteria. All patients received antepartum
association between serum ferritin level and GDM in and intrapartum care as per the institutional protocol. All
pregnant women. of them subsequently underwent repeat screening test for
GDM at 32 to 34 weeks. Patients diagnosed as GDM was
METHODS advised and prepared for frequent prenatal care visits,
metabolic control requiring Medical Nutritional Therapy
Study design, sample size and source of data (MNT), self-monitoring of blood glucose and Insulin
therapy and counselled regarding the risk of potential fetal
Current study is a prospective study, 388 pregnant women and neonatal complications and the need for routine
attending antenatal clinic in the department of obstetrics surveillance of fetal well-being. All the data were entered
and gynaecology, ESIC-MC-PGIMSR, Rajajinagar, in a pretested proforma and analysed using SPSS software.
Bangalore, between January 2020 to June 2021(18
Months) were enrolled in the study. RESULTS

Inclusion criteria In the present study 388 gravid women, whose serum
ferritin level was estimated at 24 to 28 weeks were
Pregnant women willing to give informed written consent, followed up with repeat screening for GDM in third
Gestational age 24 to 28 weeks as calculated by LMP and trimester, among them 77 (19.7%) were diagnosed with
dating scan GDM during the follow up period.

Exclusion criteria
Age (yrs)
Pregnant women with Anaemia (Hb <11gm/dl), pre- 30.0 28.0 27.0
eclampsia, type 1 and type 2 diabetes, haematological 25.0
disorders (sickle cell anaemia, hemoglobinopathies, 20.0
Mean

thalassemia), liver disorders (haemochromatosis, 15.0

hepatitis), any local and systemic infections, autoimmune 10.0
disorder (SLE, rheumatoid arthritis).
5.0
0.0
Method of collection of data
GDM Non GDM

All patients satisfying the inclusion criteria were enrolled

for the study. Each participant was clinically evaluated Figure 1: Mean age distribution among study groups.
with detailed obstetric, menstrual and medical history.
General physical examination, systemic examination and Age distribution
obstetric examination were performed and accurate
gestational age was assessed by noting the last menstrual The mean age of patients in GDM group was 28.0 years
date and confirmed by early trimester dating scan. All of and in non-GDM group was 27.0 years. The p value being
them underwent serum ferritin estimation and oral glucose 0.087, statistically insignificant. Hence both groups were
tolerance test (OGTT) at 24-28 weeks. comparable with respect to maternal age.

Serum ferritin estimation Parity distribution

Venous blood samples were obtained from the subjects Number of primigravida’s in GDM group and in non-
enrolled for the study between 24-28 weeks gestation to GDM group were 33.8% and 44.7% respectively.
measure serum ferritin level by chemi-luminescent Multigravidas were 66.2% in GDM and 55.3% in non-
immune-assay (CLIA) on ACCESS TWO with Beckman GDM, p value is 0.082, statistically insignificant, therefore
Coulter. It was done in fully automated analyser. The the parity distribution was comparable in both groups.
serum ferritin was measured in ng/ml.

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Serum ferritin distribution

PARITY
70.0% 66.2% The mean serum ferritin level of patients in GDM group
was 46.4 and in non-GDM group was 37.3. The p value
60.0% 55.3% being 0.001, statistically significant. Hence serum ferritin
is a risk factor for GDM.
50.0% 44.7%
40.0% 33.8% In comparison with proportions of serum ferritin level <30
GDM
ng/dl, 148 (85.5%) were non-GDM and 25 (14.5%) were
30.0% Non GDM GDM, between 30-60 ng/dl, 88 (79.3%) were non-GDM
20.0% and 23 (20.7%) were GDM, between 60-90 ng/dl 68
(76.4%) were non-GDM and 21 (23.6%) were GDM and
10.0% with S. Ferritin level of >90 ng/dl, 7 (46.7%) were non-
GDM and 8 (53.3%) were GDM. P value being (<0.001)
0.0%
PRIMI MULTI statistically significant, it infers that higher the serum
ferritin level greater the risk for development of GDM.

Figure 2: Distribution of parity among study groups.

Hb%
Gestational age 14.0 12.2 11.7
12.0
The mean gestation age for serum ferritin assay in both
GDM and non-GDM group was 27.1 years and 25.1 years 10.0
respectively (p=0.277), infers that both the groups were
Mean
8.0
matched for GA. 6.0
4.0
GA 2.0
30.0 27.1 0.0
25.1 GDM Non GDM
25.0
20.0
Figure 4: Mean Hb distribution.
Mean

15.0
10.0 S.FERRITIN
5.0 46.4
50.0
0.0 37.3
40.0
GDM Non GDM
30.0
Mean

Figure 3: Mean gestational age at the time of serum 20.0

ferritin assay.
10.0
Hemoglobin 0.0
GDM Non GDM
The mean Hb in both GDM and non-GDM group were
12.2 gm% and 11.7 gm% (p=0.665). Infers that both the
groups were matched for Hb %. Figure 5: Mean serum ferritin distribution among
study groups.

Table 1: Comparison of proportions of serum ferritin with GDM.

S. Ferritin
Outcome <30 30-60 60-90 >90 P value
N % N % N % N %
Non GDM 148 85.5% 88 79.3% 68 76.4% 7 46.7%
GDM 25 14.5% 23 20.7% 21 23.6% 8 53.3% <0.001*
Total 173 100.0% 111 100.0% 89 100.0% 15 100.0%
Note: p value* significant at 5% level of significance (p<0.05).

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Table 2: ROC analysis. levels, which causes hyperinsulinemia. This

hyperinsulinemia glycates transferrin receptors, thereby
Std. P 95% CI causing increases free iron, in-turn there is overall increase
Parameters AUC in ferritin synthesis. Hyperinsulinemia adds to this
Error value Lower Upper
S. ferritin 0.595 0.038 0.01* 0.52 0.669 oxidative stress by causing increased iron levels.13
*p value significant at 5% level of significance (p<0.05) Glycated transferrin in diabetic state is unable to bind iron,
which leads to storage of elevated free iron in the form of
Table 3: Specificity and sensitivity determined ferritin. Ferritin production is triggered by the presence of
through ROC analysis. iron. As serum ferritin levels are increased in the states of
insulin resistance and hyperinsulinemia, GDM which is
Cut-off associated with insulin resistance, should have the
Parameters Sensitivity Specificity possibility of elevated serum ferritin levels. This increase
value
S. ferritin 34.7 71% 63% in serum ferritin levels manifests even before the
symptoms of insulin resistance develops and GDM
The AUC for serum ferritin is 60% (p<0.01). The cut-off manifests. So, measuring serum ferritin levels early in the
value to predict GDM among pregnant women is >34.7 pregnancy just before the period of development of GDM,
ng/ml with sensitivity of 71% and specificity of 63%. This could guide us to a better awareness about the possibility
infers that in pregnant women with serum ferritin value of of developing GDM.14 Thereby reducing the morbidity
>34.7 ng/ml there is 63% chance that they will develop concerned with GDM. This study included 388 gravid
gestational diabetes. women attending the antenatal clinic, meeting the
inclusion criteria. serum ferritin level and OGTT were
done at 24-28 weeks of gestation, antenatal follow-up of
patients done, with 77 (19.8%) were diagnosed with GDM
in the current pregnancy. 44 (57%) were on medical
nutrition therapy and 33 (43%) were on insulin.

The demographic characteristics of both the groups were

well matched. In present study there was no statistical
significance in Hb values (p=0.665) between 2 groups,
which is similar to studies done by Soheilykhah et al (p=
0.70) and Islam et al (p=0.222).6,15 This eliminated anemia
as a confounding factor, minimizing the error and
strengthening the present study. The mean serum ferritin
concentration in GDM and non-GDM groups were 46.4
ng/mL and 37.3 ng/ml (p<0.001). Serum ferritin levels are
significantly elevated in GDM group which was similar to
studies done by Sumathy et al (p<0.001), Soheilykhah et
al (p=0.01) and Islam et al (p<0.001).3,6,15 ROC (Receiver
Figure 6: ROC distribution curve. operator characteristics curve) obtained in our study with
the cut off value for serum ferritin as marker of
Table 4: Baseline demographic characteristics in the development of GDM is 34.7 ng/ml with 95% CI. The
present study. sensitivity and specificity being 71% and 63%
respectively. This infers that in pregnant women with
Non P serum ferritin value of >34.7 ng/ml there is 63% chance
Variables GDM
GDM value that they will develop Gestational diabetes (2 out of 3
N 77 311 NA women with serum ferritin level of >34.7 can develop
Age (years) GDM). Among these 388 pregnant women in this study,
28.0±5.2 27.0±4.4 0.087
Mean±SD 77 were diagnosed with GDM in the current pregnancy. 44
Parity Primi 33.8 44.7 were on medical nutrition therapy and 33 were on insulin
0.082
(%) Multi 66.2 55.3 therapy. out of 77 who developed GDM, about 21 had S.
Gestational age 27.1 25.1 0.277 ferritin values between 60-90 ng/ml, and 8 had values
Haemoglobin above 90 ng/ml and in these 8 women with serum ferritin
12.2 11.7 0.665
(gm%) >90, 6 were started on insulin. This implies that high serum
ferritin levels had required the need of insulin for their
DISCUSSION blood sugar control. Among 21 who had serum ferritin
level 60-90ng/ml, about 12 had the need of insulin and
Insulin is responsible for redistribution of transferrin remaining 9 just needed MNT for their adequate blood
receptors to cell surface, which in turn causes insulin sugar control. The p value of this association is <0.001,
dependent GLUT and IGF II to co-localise on adipocytes. which was significant.
Insulin action in the liver is inhibited by Increased iron

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Limitations 6. Soheilykhah S, Mojibian M, Jannati Moghadam M.

Serum ferritin concentration in early pregnancy and
Limitations of current study were, our study being a time risk of subsequent development of gestational diabetes:
bound study with smaller sample size, the future research A prospective study. Int J Reprod Biomed. 2017;
is required with adequate sample size to conclude that if 15(3):155-60.
serum ferritin level could be used as a biochemical marker 7. Bowers KA, Olsen SF, Bao W, Halldorsson TI, Strøm
for prediction of GDM. M, Zhang C. Plasma Concentrations of Ferritin in
Early Pregnancy Are Associated with Risk of
CONCLUSION Gestational Diabetes Mellitus in Women in the Danish
National Birth Cohort. J Nutr. 2016;146(9):1756-61.
In the present study with cut-off for serum ferritin level 8. Goldenberg RL, Tamura T, DuBard M, Johnston KE,
being 34.7ng/ml with 95% CI, sensitivity of 71% and Copper RL, Neggers Y. Plasma ferritin and pregnancy
specificity of 63%, we conclude that elevated serum outcome. Am J Obstet Gynecol 1996;175:1356-9.
ferritin level is associated with development of GDM. It is 9. Scholl TO. High third-trimester ferritin concentration:
advantageous as it is cost effective and widely done association with very preterm delivery, infection, and
biochemical test in most laboratories. maternal nutritional status. Obstet Gynecol. 1998;92:
161-6.
Funding: No funding sources 10. Entman SS, Richardson LD, Killam AP. Elevated
Conflict of interest: None declared serum ferritin in the altered ferrokinetics of toxemia of
Ethical approval: The study was approved by the pregnancy. Am J Obstet Gynecol. 1982;144:418-22.
Institutional Ethics Committee 11. Raman L, Pawashe AB, Yasodhara P.
Hyperferritinemia in pregnancy-induced hypertension
an eclampsia. J Postgrad Med. 1992;38:65-7.
12. Prasad DKV, Sheela P, Kumar AN, Kumar NL, Deedi
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