Table 3.

Case–control studies that sought associations between iron supplementation in pregnancy and GDM.

First Author, Year of Publication	Details	Key Results	Comments
Palma, 2008 [30]	A retrospective study of 1256 pregnant women without anemia (322 who delivered a low-birth-weight baby; 934 who delivered non-low birth-weight-baby at term), attending the Marqués de Valdecilla University Hospital, Santander, Spain. Information about iron and other supplements was obtained from personal interviews and prenatal care records. A total of 91.0% of the women supplemented with iron, mainly with a daily dose of 80 mg ferrous sulfate as a single supplement. No details of baseline iron statuses were presented, although none of the women were anemic. Three sources of data for GDM were used: personal interviews (carried out within three days after delivery), clinical charts, and prenatal care records.	In the comparison of those that supplemented with iron against those that did not, no association was found between iron supplementation and GDM (4.6% of women who supplemented with iron developed GDM vs. 7.1% of women who did not supplement with iron developed GDM; risk ratio 0.65 (0.32–1.34), p = 0.2).	A woman was considered to have supplemented with iron if they took it for at least one week in pregnancy. No account of iron supplemental dose or duration (other than the above) was taken. Maternal iron supplementation was associated with a lower risk of low birth weight (odds ratio 0.58 (0.34–0.98), p < 0.05).
Bo, 2009 [31]	A study of 500 consecutive pregnant women with GDM and 500 normoglycemic women attending the Unit of Obstetrician and Gynecology of the University of Turin, Italy. Iron supplementation data were collected by interviewing. A woman was considered to have supplemented with iron if she did so for at least 2 weeks. Most (95.5%) of the 212 women that supplemented with iron (and no other micronutrients) in mid-pregnancy did so with a daily dose of 525 mg ferrous sulfate (equivalent to 105 mg elemental iron). No details were presented about baseline iron statuses or anemia.	In the comparison of those that supplemented with iron against those that did not, self-reported iron supplementation in pregnancy was associated with a higher prevalence of GDM (70.8% v. 44.4% (p < 0.001), respectively; unadjusted odds ratio 3.03 (2.18–4.20), p < 0.001; odds ratio adjusted for confounders 3.36 (1.50–7.53), p = 0.003). The duration of iron supplementation ranged from 2 to 10 weeks (with a median of 5 weeks). Only one participant was supplementing with iron prior to conception (and sensitivity analyses removing them showed no significant difference in results).	Iron supplementation in pregnancy was also significantly positively associated with increased insulin resistance and hyperglycemia, and the prevalence of the metabolic syndrome.
Jirakittidul, 2018 [32]	A retrospective study of pregnant women attending Vajira Hospital, Bangkok, Thailand for routine antenatal care. The early iron supplementation group (n = 966) was non-anemic women who started taking oral iron supplements (200 mg of ferrous fumarate; classified from hospital records) prior to 16 completed weeks of gestation, while the “control” group (n = 969) was those non-anemic women who started supplementing with iron later on in pregnancy. There was no difference in baseline hemoglobin levels between the groups.	In the comparison of those that supplemented with iron early against those that supplemented late, those that supplemented early had a higher prevalence of GDM (9.7% vs. 5.6%, respectively; risk ratio 1.83 (1.29–2.59), p < 0.001).	In this study, the control group consisted of women who supplemented their diets with iron, but only after 16 weeks’ gestation. There was no group where the women did not supplement their diets with iron.
Liu, 2018 [33]	A retrospective study of 259 women with singleton pregnancies and hemoglobin levels between 8–14 g/dL attending The People’s Hospital of Yan’an, and Affiliated Hospital of Yan’an University, Yan’an, China. The supplementary group (n = 135) took 300 mg iron/d from prior to 16 weeks’ gestation until delivery. The control group did not supplement their diets with iron.	In the comparison of those that supplemented with iron against those that did not, there was no significant difference in the prevalence of GDM (7.4% vs. 7.3%, respectively; risk ratio 1.02 (0.43–2.43), p = 1.0).	There were no reports of either the method of participant recruitment or how iron supplemental data were captured. Iron supplementation was associated with increased maternal hemoglobin levels at delivery and increased offspring birth weight.