Iron is the main component of hemoglobin and myoglobin (iron and oxygen binding protein respectively found in the blood and muscle) that plays a key role in oxygen transport, storage and use. Iron is also involved in the synthesis of hormone and other enzymes.
Iron deficiency is the most widespread nutritional deficiency in the world and the most common cause of anemia during pregnancy (1, 2).
Maternal nutritional status directly affects fetal growth and development. Mild anemia is a common issue during pregnancy as your body needs more blood to support your growing fetus and placenta. Iron deficiency may cause anemia by decreasing the capacity to carry oxygen by the hemoglobin resulting in lack of oxygen in the mother and fetus (3). This may lead to fetal hypoxia, premature birth and even perinatal or maternal mortality (4).
There is a lack of studies determining the potential contribution of iron deficiency to miscarriage.
Recent work including 1568 pregnant women (5) showed that iron levels gradually decreased as the pregnancy progressed. One third of pregnant women have iron deficiency during the first and second trimester, this rate increased up to 43% during the last trimester.
A lower iron concentration has been found in women who miscarried (6.96 mmol/L) as compared to control patient (7.59 mmol/L, uneventful, full term healthy pregnancy). Although the difference seen was minor, it was statistically significant (meaning that the slight difference seen was real). Further, zinc was also found in lower concentration in the miscarriage group (72.67 µmol/L) when compared to the control group (83.25 µmol/L).
Nevertheless, from this observational study, we cannot conclude that a minor iron deficiency as the one
seen or even the more accentuated zinc deficiency correlating with the occurrence of a miscarriage, could be a cause for miscarriage.
There is no causative relation between an iron deficiency and a miscarriage.
Iron is stored in almost all tissues of the body in the form of a protein, namely ferritin. While ferritin is a biomarker of inflammation (6-7), it is also a good biomarker of thyroid function.
A recent study showed a close correlation between serum ferritin levels and thyroid activity (8).
In this study, enrolling n=50 diagnosed hypothyroid patients and n= 50 healthy control individuals, serum ferritin levels were shown to be reduced in hypothyroid patients (21.08 ng/mL) as compared to controls (59.89 ng/mL).
In parallel, elevated serum ferritin levels were observed in hyperthyroid patients affected by Grave’s disease (9).
Interestingly, thyroid hormones regulate ferritin expression by a feedback loop mechanism.
In a study including patients affected by Hashimoto’s thyroiditis with low ferritin levels, the administration of L-T4 therapy (levothyroxine), restoring an euthyroid function, significantly increases ferritin levels (10).
Inversely, the synthesis of thyroid hormones by the enzyme thyroperoxidase requires iron so the depletion of iron store (low ferritin levels) may accentuate the decrease of free T3 and T4 levels (thyroid hormones) although the autoimmune mechanisms (chronic inflammation in the case of Hashimoto’s thyroiditis) are the principal causes of the low production of thyroid hormones.
As mentioned previously, ferritin levels could be altered by inflammation and for an accurate interpretation, free iron and CRP levels should also be evaluated.
The take home message is to consider an iron deficiency (as seen by low ferritin levels) as a marker of a possible autoimmune
condition such as Hashimoto’s thyroiditis (hypothyroidism) and ferritin levels could be restored with adequate therapy (levothyroxine).
While in this patients population higher risk of miscarriage has been reported (11), the principal cause is the autoimmune condition itself and not low ferritin levels that are just a biomarker of the thyroid function
Again, in overall healthy individuals, iron deficiency could not be consider as a risk factor for miscarriage based on published scientific data.
References:
1- Stoltzfus R, Dreyfuss M. Guidelines for the use of iron supplements to prevent and treat iron deficiency anaemia. ILSI Press, 1998.
2- 2. World Health Organization. Micronutrient deficiencies: iron deficiency anaemia. www.who.int/nutrition/topics/ida/en/.
3- Narasinga BS. Anaemia and micronutrient deficiency. Natl Med J India. 2003. 16 Suppl 2: 46-50.
4- Murray-Kolb LE, Chen L, Chen P, Shapiro M, Caulfield L. CHERG iron report: maternal mortality, child mortality, perinatal mortality, child cognition, Iron and estimates of prevalence of anemia due to iron deficiency. CHERG Iron Report 2013.
5- Shen PJ, Gong B, Xu FY, Luo Y. Four trace elements in pregnant women and their relationships with adverse pregnancy outcomes. Eur Rev Med Pharmacol Sci. 2015 Dec;19(24):4690-7.
6- Cho MR, Park JK, Choi WJ, Cho AR, Lee YJ. Serum ferritin level is positively
associated with insulin resistance and metabolic syndrome in postmenopausal
women: A nationwide population-based study. Maturitas. 2017 Sep; 103:3-7.
7- Kim T, Streja E, Soohoo M, Rhee CM, Eriguchi R, Kim TW, Chang TI, Obi Y, Kovesdy CP, Kalantar-Zadeh K. Serum Ferritin Variations and Mortality in Incident Hemodialysis Patients. Am J Nephrol. 2017 Jul 14;46(2):120-130.
8- Sachdeva A, Singh V, Malik I, Roy PS, Madaan H, Nair R. Association between serum ferritin and thyroid hormone profile in hypothyroidism. Int J Med Sci Public Health. 2015; 4(6): 863-865.
9- Saïd R. [Hyperthyroidism: a cause of serum ferritin elevation]. Rev Med Interne. 2000 Dec;21(12):1129-31. French.
10- Takamatsu J, Majima M, Miki K, Kuma K, Mozai T. Serum ferritin as a marker of thyroid hormone action on peripheral tissues. J Clin Endocrinol Metab. 1985
Oct;61(4):672-6.
11- Zhang Y, Wang H, Pan X, Teng W, Shan Z. Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: A systematic review and meta-analysis. PLoS One. 2017 Apr 17;12(4): e0175708.
References