High iron levels in pregnant women were associated with an increased risk of gestational diabetes mellitus (GDM), researchers reported.

Increased hepcidin levels, particularly during the second trimester, were linked to a higher risk of GDM compared with pregnant women with normal levels (95% CI; OR 2.61; 1.07-6.39 highest versus lowest quartile) according to Shristi Rawal, PhD, of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and colleagues.

Additionally, pregnant women diagnosed with GDM had 16% higher levels of hepcidin, compared with women without GDM (6.4 versus 5.5 ng/ml; P=0.02).

As published in Diabetologia, the journal of the European Association for the Study of Diabetes, the case-controlled study also found that higher ferritin levels were correlated with a significantly increased risk of developing GDM in both the first trimester (95% CI; OR 2.43; 1.12-5.28) and second trimester (OR 3.95; 1.38-11.30).

"Iron supplementation is often recommended to pregnant women, as iron deficiency is common among pregnant women. Emerging data, however, raised potential concerns as significant associations were observed between greater iron stores and disturbances in glucose metabolism, including increased risk of type 2 diabetes, among non-pregnant individuals," Cuilin Zhang MD, PhD, senior investigator at NIHCD, told MedPage Today.



"The evidence is unclear and limited regarding the role of iron in the development of GDM, a common pregnancy complication. To address the data gap, we decided to do the study."

In addition to measuring the iron biomarkers' relationship with GDM risk, including ferritin, hepcidin, soluble transferrin receptor (sTfR), sTfR:ferritin ratio, and plasma C-reactive protein levels, the authors also aimed to follow the variances within the levels of these markers throughout the course of pregnancy.

A total of 321 women from the Eunice Kennedy Shriver NICHD Fetal Growth Studies-Singleton Cohort were involved in the study, including a sample of 107 cases of GDM matched with 214 non-GDM controls.

Oral glucose tolerance test results, gathered from the cohort's medical records, were used to identify GDM status in the participants. Current guidelines recommend that all asymptomatic pregnant women be screened for GDM at 24 weeks of gestation.

Blood tests measured the levels of plasma hepcidin, ferritin, and sTfR in all participants four times throughout pregnancy, including twice prior to a 24-week GDM diagnosis, and twice subsequently.

During the first iron level measurement during weeks 10-14 of gestation, ferritin levels in women who were to develop GDM were approximately 21% higher compared with women who did not develop GDM.

During the second blood draw at weeks 15 to 26, ferritin and hepcidin levels were both significantly higher in women who would eventually be diagnosed with GDM compared with the controls. Additionally, the sTfR:ferritin ratio was significantly lower at this time for the GDM cohort (P=0.02).

"We were not surprised by the results, which were consistent with our hypotheses," Zhang told MedPage Today. "As discussed in the paper, although iron is an essential micronutrient to the human body, due to its strong pro-oxidant properties, free iron can lead to increased oxidative stress and cellular damage, etc.
"While iron is critical to normal β-cell function and glucose homeostasis, oxidative stress from excess iron accumulation may lead to β-cell damage, impaired insulin secretion, etc."
Concentrations of only sTfR were not significantly correlated with any subsequent GDM diagnosis.

Currently, the American Congress of Obstetricians and Gynecologists recommends iron screening during pregnancy on an as-needed basis. Furthermore, the World Health Organization and the Centers for Disease Control and Prevention both recommend routine iron screening throughout the course of pregnancy.

Because the findings of the study indicated a significant relationship, especially during the second trimester prior to GDM diagnosis, between higher iron levels and subsequent GDM diagnosis, the authors recommend a clinical benefit from testing levels early in pregnancy.

Although the present study yielded strong results on a relationship that was largely unstudied, the authors highlight the fact that dietary iron intake and its relationship with GDM was not analyzed in the current study.

Zhang also noted: "In future studies, we shall simultaneously investigate the role of both iron biomarkers and dietary iron (from both food and supplement) in the development of GDM. It would be also interesting to investigate the short-term and long-term impact of maternal iron status on offspring health. We are planning to address these questions in the near future in our study cohort."