ABSTRACT

OBJETIVE

To evaluate the association between the use of iron salts during the first two trimesters of gestation in non-anemic women and the development of gestational diabetes mellitus.

METHODS

The study used maternal data from the 2015 Pelotas Birth Cohort. All non-anemic women at the 24th week of gestation (n = 2,463) were eligible for this study. Gestational diabetes mellitus was self-reported by women. Crude and adjusted logistic regression were performed considering level of significance = 0.05.

RESULTS

Among the women studied, 69.7% were exposed to prophylactic iron supplementation in the first two trimesters of gestation. The prevalence of gestational diabetes mellitus among those exposed was 8.7% (95%CI: 7.4–10.1) and 9.3% (95%CI: 7.4–11.6) among those who were not exposed. Iron supplementation was not associated with increased risk of gestational diabetes mellitus in crude (OR = 0.9; 95%CI: 0,7–1,3) and adjusted analysis (OR = 1.1; 95%CI :0,8–1,6).

CONCLUSIONS

The results suggest that routine iron use in non-anemic pregnant women does not increase the risk of developing gestational diabetes. This evidence supports the existing national and international guidelines, in which prophylactic iron supplementation is recommended for all pregnant women as soon as they initiate antenatal care in order to prevent iron deficiency anemia.

Pharmacoepidemiology; Drug Utilization; Cohort Studies; Diabetes, Gestational

INTRODUCTION

Gestational diabetes mellitus (GDM) is a temporary condition characterized by hyperglycemia, which occurs due to carbohydrate and glucose intolerance¹1. World Health Organization. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: a World Health Organization Guideline. Diabetes Res Clin Pract. 2014 Mar;103(3):341-63. https://doi.org/10.1016/j.diabres.2013.10.012
https://doi.org/10.1016/j.diabres.2013.1... . It begins during pregnancy and usually disappears shortly after delivery¹1. World Health Organization. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: a World Health Organization Guideline. Diabetes Res Clin Pract. 2014 Mar;103(3):341-63. https://doi.org/10.1016/j.diabres.2013.10.012
https://doi.org/10.1016/j.diabres.2013.1... ,²2. Organização Pan-Americana de Saúde, Ministério da Saúde, Federação Brasileira das Associações de Ginecologia e Obstetrícia, Sociedade Brasileira de Diabetes. Rastreamento e diagnóstico de diabetes mellitus gestacional no Brasil. Vol. 1, Sociedade Brasileira de Diabetes. Brasília, DF: Organização Pan-Americana de Saúde; 2017 [cited 2022 June 11]. Available from: https://www.febrasgo.org.br/images/pec/CNE_pdfs/Rastreamento-Diabetes.pdf
https://www.febrasgo.org.br/images/pec/C... . Population estimates of hyperglycemia frequency in pregnancy are conflicting, because of the different criteria for GDM diagnosis, with prevalence varying from 1 to 18% of pregnant women in different populations, due to differences between guidelines²2. Organização Pan-Americana de Saúde, Ministério da Saúde, Federação Brasileira das Associações de Ginecologia e Obstetrícia, Sociedade Brasileira de Diabetes. Rastreamento e diagnóstico de diabetes mellitus gestacional no Brasil. Vol. 1, Sociedade Brasileira de Diabetes. Brasília, DF: Organização Pan-Americana de Saúde; 2017 [cited 2022 June 11]. Available from: https://www.febrasgo.org.br/images/pec/CNE_pdfs/Rastreamento-Diabetes.pdf
https://www.febrasgo.org.br/images/pec/C... ,³3. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2012 Jan;35(Suppl 1):S64-71. https://doi.org/10.2337/dc10-S062
https://doi.org/10.2337/dc10-S062... . In Latin America, for example, a GDM diagnosis is the 75 g 2-hour glucose test > 7.8 mmol/L or > 140 mg/dL. In China, > 5.1 mmol/L or > 92 mg/dL sets GDM diagnosis⁴4. Hod M, Kapur A, Sacks DA, Hadar E, Agarwal M, Di Renzo GC, et al. Initiative on gestational diabetes mellitus: a pragmatic guide for diagnosis, management, and care. Int J Gynaecol Obstet. 2015 Oct;131 Suppl 3:S173-211. https://doi.org/10.1016/S0020-7292 (15)30033-3
https://doi.org/10.1016/S0020-7292 (15)3... . In Brazil, it is recommended that the GDM diagnosis be established between the 24th and 28th week of gestation, through the oral glucose tolerance test with 75g, when at least one of the following blood glucose values is present: fasting ≥ 92 and < 126 mg/dL; 1 hour ≥ 180 mg/dl; 2 hours ≥ 153 and < 200 mg/dL²2. Organização Pan-Americana de Saúde, Ministério da Saúde, Federação Brasileira das Associações de Ginecologia e Obstetrícia, Sociedade Brasileira de Diabetes. Rastreamento e diagnóstico de diabetes mellitus gestacional no Brasil. Vol. 1, Sociedade Brasileira de Diabetes. Brasília, DF: Organização Pan-Americana de Saúde; 2017 [cited 2022 June 11]. Available from: https://www.febrasgo.org.br/images/pec/CNE_pdfs/Rastreamento-Diabetes.pdf
https://www.febrasgo.org.br/images/pec/C... .

GDM is responsible for many consequences in maternal-fetal health in the short and long term²2. Organização Pan-Americana de Saúde, Ministério da Saúde, Federação Brasileira das Associações de Ginecologia e Obstetrícia, Sociedade Brasileira de Diabetes. Rastreamento e diagnóstico de diabetes mellitus gestacional no Brasil. Vol. 1, Sociedade Brasileira de Diabetes. Brasília, DF: Organização Pan-Americana de Saúde; 2017 [cited 2022 June 11]. Available from: https://www.febrasgo.org.br/images/pec/CNE_pdfs/Rastreamento-Diabetes.pdf
https://www.febrasgo.org.br/images/pec/C... . The most common consequences among children are the increased risk of fetal macrosomia, neonatal hypoglycemia, shoulder dystocia, and hyperinsulinemia at birth. Mothers with GDM are at increased risk of preeclampsia, gestational hypertension, cesarean section, and polyhydramnios. In addition, there is an increased risk of fetal malformations, abortion, neonatal and perinatal mortality, as well as an increased risk of maternal mortality⁵5. Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008 May;358(19):1991-2002. https://doi.org/10.1056/NEJMoa0707943
https://doi.org/10.1056/NEJMoa0707943... ,⁶6. Reece EA, Leguizamón G, Wiznitzer A. Gestational diabetes: the need for a common ground. Lancet. 2009 May;373(9677):1789-97. https://doi.org/10.1016/S0140-6736 (09)60515-8
https://doi.org/10.1016/S0140-6736 (09)6... . In the long term, the effect of GDM on mothers is the elevated risk for the development of metabolic syndrome and type 2 diabetes⁶6. Reece EA, Leguizamón G, Wiznitzer A. Gestational diabetes: the need for a common ground. Lancet. 2009 May;373(9677):1789-97. https://doi.org/10.1016/S0140-6736 (09)60515-8
https://doi.org/10.1016/S0140-6736 (09)6... . In addition, there is a greater risk of GDM in future pregnancies, which also burdens the public health sector. For the child, the risk of developing childhood obesity and metabolic syndrome almost doubles compared to children born from non-diabetic mothers, and there is also a higher risk of fetal malformation⁶6. Reece EA, Leguizamón G, Wiznitzer A. Gestational diabetes: the need for a common ground. Lancet. 2009 May;373(9677):1789-97. https://doi.org/10.1016/S0140-6736 (09)60515-8
https://doi.org/10.1016/S0140-6736 (09)6... .

Another prevalent problem during pregnancy is iron deficiency anemia, which reaches 42.0% of all pregnant women⁷7. Zhu Y, Zhang C. Prevalence of gestational diabetes and risk of progression to type 2 Diabetes: a global perspective. Curr Diab Rep. 2016 Jan;16(1):7. https://doi.org/10.1007/s11892-015-0699-x
https://doi.org/10.1007/s11892-015-0699-... . In this sense, current guidelines from World Health Organization (WHO) and Brazilian Ministry of Health recommend, in addition to an adequate diet, a prophylactic (routine) iron supplementation for all pregnant women, in order to fulfill the physiological needs for this mineral⁸8. World Health Organization. Guideline: daily iron and folic acid supplementation in pregnant women. Geneva: World Health Organization; 2012.,⁹9. Ministério da Saúde (BR). Secretaria de Atenção à Saúde. Departamento de Atenção Básica. Atenção ao pré-natal de baixo risco. Brasília, DF: Ministério da Saúde, 2013.. However, this universal prophylactic supplementation has been questioned, because according to some authors, high iron intake may increase the risk of GDM, especially for women with normal hemoglobin levels in early pregnancy¹⁰10. Helin A, Kinnunen TI, Raitanen J, Ahonen S, Virtanen SM, Luoto R. Iron intake, haemoglobin and risk of gestational diabetes: a prospective cohort study. BMJ Open. 2012 Sep;2(5):e001730. https://doi.org/10.1136/bmjopen-2012-001730
https://doi.org/10.1136/bmjopen-2012-001... ,¹¹11. Milman N. Iron prophylaxis in pregnancy: general or individual and in which dose? Ann Hematol. 2006 Dec;85(12):821-8. https://doi.org/10.1007/s00277-006-0145-x
https://doi.org/10.1007/s00277-006-0145-... , which has been reported as an independent risk factor for DMG¹²12. Lao TT, Chan LY, Tam KF, Ho LF. Maternal hemoglobin and risk of gestational diabetes mellitus in Chinese women. Obstet Gynecol. 2002 May;99(5 Pt 1):807-12. https://doi.org/10.1016/s0029-7844 (02)01941-5
https://doi.org/10.1016/s0029-7844 (02)0... .

Findings regarding the association between the use of iron salts and the development of gestational diabetes are new and still inconclusive, therefore, further studies on this topic are necessary. This study aims to evaluate the association between the use of iron salts in non-anemic women in early pregnancy and the development of GDM in a birth Cohort in which mothers were followed up since the antenatal period.

METHODS

This paper uses data from antenatal and perinatal studies from the 2015 Pelotas’ Birth Cohort (C2015), which was conducted in the city of Pelotas in southern Brazil. The study invited all women living in the urban area of Pelotas who gave birth, including stillbirths, in the city’s five maternity hospitals between January 1 and December 31, 2015.

Mothers were interviewed at the maternity hospital a few hours after delivery and answered a standardized questionnaire. They answered questions about the antenatal period: demographic, socioeconomic, biological and behavioral issues, along with characteristics of pregnancy, delivery, and medication use, including folic acid, iron salts, and other vitamins and minerals. Furthermore, 75% of mothers who participated in the perinatal study were followed by this cohort since the antenatal period. More details on the study can be found in the cohort profile paper¹³13. Hallal PC, Bertoldi AD, Domingues MR, Silveira MF, Demarco FF, Silva IC, et al. Cohort Profile: The 2015 Pelotas (Brazil) Birth Cohort Study. Int J Epidemiol. 2018 Aug;47(4):1048-1048h. https://doi.org/10.1093/ije/dyx219
https://doi.org/10.1093/ije/dyx219... .

The analyses in this article were performed with all mothers from the perinatal follow-up who were eligible for this study (n = 2,463) (Figure). Anemic pregnant women before 24th week of gestation (with a record of at least one hemoglobin test < 11 g/dL in their antenatal card) were not included in the analyses.

For the “gestational diabetes mellitus” outcome, self-reports were considered. The mothers answered the following question: “Did you have diabetes during pregnancy?” followed by another question: “Did you have diabetes before pregnancy?” Pregnant women who had diabetes before pregnancy (n = 44) were excluded. Self-reported information about mother’s knowledge of GDM in the immediate postpartum was validated through a study previously carried out in Pelotas’ maternity, with high specificity (99.0%, 95%CI: 98.1–99.6) and good sensitivity 73.0% (95%CI: 55.9–86.2)¹⁴14. Dode MA, Santos IS. [Validity of self-reported gestational diabetes mellitus in the immediate postpartum]. Cad Saude Publica. 2009 Feb;25(2):251-8. Portuguese. https://doi.org/10.1590/S0102-311X2009000200003
https://doi.org/10.1590/S0102-311X200900... .

The variables used in the analysis as possible confounding factors were: maternal age (collected in complete years and categorized as ≤ 19, 20–29, 30–46); ethnicity (self-reported by mothers as white, black or other); parity (total number of deliveries, including stillbirths and current pregnancy; later categorized as 1, 2, 3, or 4 or more); mother’s schooling (number of years of study, later categorized into four groups: 0–4, 5–8, 9–11, and 12 or more years), and family income expressed in local currency and converted into a multiple of minimum wage at the time of the perinatal interview (categorized as ≤ 1, 1.1–3.0, 3.1–6.0, 6.1– 10, and > 10). The ‘minimum wage’ is the measure of the legal minimum monthly salary for formal employees in Brazil.

Family history of diabetes mellitus was reported by mothers at the 24-month follow-up, pre-pregnancy body mass index (BMI) was calculated by dividing pre-pregnancy weight by the square of maternal height, then categorized according to WHO criteria¹⁵15. World Health Organization. Obesity and overweight. 2021 [cited 2022 Aug 10]. Available from: https://www.who.int/gho/ncd/risk_factors/overweight/en/
https://www.who.int/gho/ncd/risk_factors... : underweight (< 18.5 kg/m²); normal (18.5–24.9 kg/m²); overweight (25.0–29.9 kg/m²); or obese (≥ 30 kg/m²) and smoking in pregnancy was considered as “yes” when the mother reported smoking at least one cigarette a day, for at least 30 days.

Information regarding supplement use was taken from the following questions: “Have you used or are you currently using any vitamin, calcium, folic acid or iron salts since you became pregnant?” If the answer was “yes,” the drug names were then questioned and for each reported drug a question about the trimester of use was asked: “In which trimester of pregnancy did you use this drug?” (1^st trimester, 2^nd trimester, 3^rd trimester).

From these questions, it was possible to generate the main exposure used in our analyses: “use of prophylactic iron in the first and / or second trimester of pregnancy,” prophylactic iron formulated using only iron compounds or combing them with other active substances, provided that iron was the main compound present. All analyses were performed in Stata software 15.0. Sample description was performed according to exposure and outcome (GDM) using the chi-square test. The association of iron supplements use with GDM development was evaluated by logistic regression.

The regression followed a previously established hierarchical conceptual model, which comprises three levels. The distal level included sociodemographic variables and family history of diabetes; the second level included pre-gestational BMI, parity and smoke; and the proximal level included the use of iron salts. Variables with p < 0.20 were kept in the model to control confounding factors. For all statistical analyses, the significance threshold was set at p < 0.05.

The Universidade Federal de Pelotas, School of Physical Education Ethics Committee, approved the study protocol (522.064). All mothers signed an informed consent form before being interviewed.

RESULTS

Of the 2,463 mothers who participated in this study, about half were aged between 20 and 29 years (48%), most had white skin (75.8%), and more than nine years of schooling (72.1%). The predominant family income was 1.1 to 3 minimum wages (46%), and most mothers (47%) had pre-gestational BMI considered normal by WHO criteria¹⁵15. World Health Organization. Obesity and overweight. 2021 [cited 2022 Aug 10]. Available from: https://www.who.int/gho/ncd/risk_factors/overweight/en/
https://www.who.int/gho/ncd/risk_factors... . More than half of women were in their first pregnancy (52.7%), had no family history of gestational diabetes (55.5%) and were non-smokers (86.6%) (Table 1).

Women eligible for this study did not differ from women participating in the perinatal C2015 study regarding the analyzed characteristics (Table 1).

Of all women in the analyzed sample (n = 2,463), 69.7% were exposed to iron supplementation in the first and / or second trimester of pregnancy. GDM prevalence was higher among pregnant women who were older (12.8%); less educated (13.7%); had a family income between 1.1 and 3.0 minimum / monthly salaries (10.2%); pre-pregnancy BMI ≥ 30 (16.9%); 4 or more children (12.6%) and a family history of diabetes (12.5%) (Table 2).

The prevalence of self-reported GDM in the entire cohort (n = 4,270) was 8.5% (95%CI: 7.6–9.3), and among those eligible for this study it was 8.8% (95%CI : 7.7–10.0), 8.6% (95%CI: 7.3–10.0) being among those who were exposed to iron supplements and 9.2% (95%CI: 8.9–9.2) among those who were not (Table 2).

The use of iron salts in the first or second gestational trimester showed no positive association with GDM both in the crude analysis (OR = 0.9; 95%CI: 0.6–1.3) and in the analysis adjusted for skin color, age, education, family income, pre-gestational BMI, parity, family history of diabetes mellitus, and smoking during pregnancy (OR = 1.1; 95%CI: 0.8–1.5) (Table 3).

A subset of analyses was performed for data corresponding to the first trimester of pregnancy (up to 12^th weeks). Results were similar to those derived from the main analyses (including the first and/or second trimester (OR_a = 1.2; 95%CI: 0.8–1.7) (Table 3).

DISCUSSION

This study showed that, among non-anemic women, prophylactic use of iron in the first and/or second trimester of pregnancy was not an independent risk factor for the development of GDM.

Published evidence on this subject is controversial. Previous observational studies have suggested that higher stores of iron might be associated with glucose metabolism disorders and an increase in the risk of GDM¹⁶16. Nastaran SA, Nourossadat K, Abbas HF, Hamid AM. Hemoglobin level during the first trimester of pregnancy in gestational diabetes. Ginekol Pol. 2012 Dec;83(12):929-33.. This relation is biologically plausible, because iron has a high oxidation-reduction capacity and its free form can catalyze the formation of free radicals, causing cell damage, a process that is also known as oxidative stress. Another suggested mechanism involves the formation of hydroxyl radicals, which can damage the cell membranes of pancreatic ß cells, affecting insulin synthesis and secretion, associated with pregnancy-induced insulin resistance²¹21. Casanueva E, Viteri FE. Iron and oxidative stress in pregnancy. J Nutr. 2003 May;133(5 Suppl 2):1700S-8S. https://doi.org/10.1093/jn/133.5.1700S
https://doi.org/10.1093/jn/133.5.1700S... ,²²22. Liu Q, Sun L, Tan Y, Wang G, Lin X, Cai L. Role of iron deficiency and overload in the pathogenesis of diabetes and diabetic complications. Curr Med Chem. 2009;16(1):113-29. https://doi.org/10.2174/092986709787002862
https://doi.org/10.2174/0929867097870028... . Excessive iron deposition in muscles may also decrease glucose uptake²²22. Liu Q, Sun L, Tan Y, Wang G, Lin X, Cai L. Role of iron deficiency and overload in the pathogenesis of diabetes and diabetic complications. Curr Med Chem. 2009;16(1):113-29. https://doi.org/10.2174/092986709787002862
https://doi.org/10.2174/0929867097870028... .

However, three randomized controlled trials, performed in hospitals and primary care services in China (n = 1,164)²³23. Chan KK, Chan BC, Lam KF, Tam S, Lao TT. Iron supplement in pregnancy and development of gestational diabetes: a randomised placebo-controlled trial. BJOG. 2009 May;116(6):789-97. https://doi.org/10.1111/j.1471-0528.2008.02014.x
https://doi.org/10.1111/j.1471-0528.2008... , Finland (n = 2,912)²⁴24. Kinnunen TI, Luoto R, Helin A, Hemminki E. Supplemental iron intake and the risk of glucose intolerance in pregnancy: re-analysis of a randomised controlled trial in Finland. Matern Child Nutr. 2016 Jan;12(1):74-84. https://doi.org/10.1111/mcn.12139
https://doi.org/10.1111/mcn.12139... and the United Arab Emirates (n = 960)²⁵25. Ouladsahebmadarek E, Sayyah-Melli M. SiminTaghavi, Abbasalizadeh S, Seyedhejazie M. The effect of supplemental iron elimination on pregnancy outcome. Pak J Med Sci. 2011;27:641-5., found no significant difference in GDM incidence between control and experimental women. The daily iron dose in the experimental group ranged from 30mg to 60mg administered during the first and second gestational trimesters²⁴24. Kinnunen TI, Luoto R, Helin A, Hemminki E. Supplemental iron intake and the risk of glucose intolerance in pregnancy: re-analysis of a randomised controlled trial in Finland. Matern Child Nutr. 2016 Jan;12(1):74-84. https://doi.org/10.1111/mcn.12139
https://doi.org/10.1111/mcn.12139... ,²⁵25. Ouladsahebmadarek E, Sayyah-Melli M. SiminTaghavi, Abbasalizadeh S, Seyedhejazie M. The effect of supplemental iron elimination on pregnancy outcome. Pak J Med Sci. 2011;27:641-5.. In the control group, two studies used placebo²⁴24. Kinnunen TI, Luoto R, Helin A, Hemminki E. Supplemental iron intake and the risk of glucose intolerance in pregnancy: re-analysis of a randomised controlled trial in Finland. Matern Child Nutr. 2016 Jan;12(1):74-84. https://doi.org/10.1111/mcn.12139
https://doi.org/10.1111/mcn.12139... and one used a lower dosage of iron and a frequency of use lower than that of the experimental group²⁵25. Ouladsahebmadarek E, Sayyah-Melli M. SiminTaghavi, Abbasalizadeh S, Seyedhejazie M. The effect of supplemental iron elimination on pregnancy outcome. Pak J Med Sci. 2011;27:641-5.. It should be noted that one of the randomized clinical trials cited²³23. Chan KK, Chan BC, Lam KF, Tam S, Lao TT. Iron supplement in pregnancy and development of gestational diabetes: a randomised placebo-controlled trial. BJOG. 2009 May;116(6):789-97. https://doi.org/10.1111/j.1471-0528.2008.02014.x
https://doi.org/10.1111/j.1471-0528.2008... reported poor adherence to supplementation, which is a reality among pregnant women, mainly due to iron supplementation’s undesirable adverse effects²⁶26. Titilayo A, Palamuleni ME, Omisakin O. Sociodemographic factors influencing adherence to antenatal iron supplementation recommendations among pregnant women in Malawi: Analysis of data from the 2010 Malawi Demographic and Health Survey. Malawi Med J. 2016 Mar;28(1):1-5. https://doi.org/10.4314/mmj.v28i1.1
https://doi.org/10.4314/mmj.v28i1.1... , a fact that may alter the results of this and other researches, underestimating this compound’s real effect.

In our study, no differences were found in GDM prevalence between women exposed and not exposed to the supplement, as in the study of Chan et al.²³23. Chan KK, Chan BC, Lam KF, Tam S, Lao TT. Iron supplement in pregnancy and development of gestational diabetes: a randomised placebo-controlled trial. BJOG. 2009 May;116(6):789-97. https://doi.org/10.1111/j.1471-0528.2008.02014.x
https://doi.org/10.1111/j.1471-0528.2008... , which did not find increased GDM incidence in the exposed group. The analysis of the study association may be limited due to lack of information regarding dosage, adherence, frequency of use and exposure time. Dosage information would be useful for qualifying the exposure variable (use of iron salts), considering “yes” as a response only for compounds with prophylactic dosage. Knowledge of adherence to iron salt compounds would allow a better selection of women eligible for the study, and exposure time would be useful for estimating dose-response effect.

Regardless of the findings concerning the relationship between the occurrence of GDM and iron use, it is a fact that GDM has been increasing in several countries as a result of population growth, increased maternal age, lack of physical activity and, especially, of the increased prevalence of obesity²2. Organização Pan-Americana de Saúde, Ministério da Saúde, Federação Brasileira das Associações de Ginecologia e Obstetrícia, Sociedade Brasileira de Diabetes. Rastreamento e diagnóstico de diabetes mellitus gestacional no Brasil. Vol. 1, Sociedade Brasileira de Diabetes. Brasília, DF: Organização Pan-Americana de Saúde; 2017 [cited 2022 June 11]. Available from: https://www.febrasgo.org.br/images/pec/CNE_pdfs/Rastreamento-Diabetes.pdf
https://www.febrasgo.org.br/images/pec/C... . Our findings confirm this trend, presenting a prevalence of self-reported gestational diabetes almost three times higher (8.5%; 95%CI: 7.8– 9.6) when compared with another birth cohort study conducted in the year 2004, also in the city of Pelotas, with 4,231 pregnant women, which found a 3.0% self-reported prevalence of gestational diabetes (95%CI: 2.53–3.64)²⁷27. Dode MA, Santos IS. [Risk factors for gestational diabetes mellitus in the birth cohort in Pelotas, Rio Grande do Sul State, Brazil, 2004]. Cad Saude Publica. 2009 May;25(5):1141-52. Portuguese. https://doi.org/10.1590/S0102-311X2009000500021
https://doi.org/10.1590/S0102-311X200900... . It is known that there are many divergences between the diagnostic criteria used for the GDM diagnosis, but between 2004 and 2015 there were no changes in the diagnostic test cut-offs in the Brazilian Ministry of Health recommendations⁹9. Ministério da Saúde (BR). Secretaria de Atenção à Saúde. Departamento de Atenção Básica. Atenção ao pré-natal de baixo risco. Brasília, DF: Ministério da Saúde, 2013..

It should be noted, among the limitations of this study, that many pregnant women had only one or two hemoglobin results in the antenatal card, which means that pregnant women who only had one recorded hemoglobin test with a normal result (non-anemic) were eligible for our study. However, they may have developed anemia later and such information was not registered in the card. On the other hand, the use of information from antenatal records completed by health professionals who followed these pregnant women was a positive aspect and considered indispensable for defining which women were eligible for the study, since these results enabled the identification of non-anemic pregnant women according to the gestational trimester, which guaranteed the temporality of the study association.

The fact that information about the use of iron was only self-reported and that there were no questions about the dose and precise time of treatment can be considered other limitations of this study. Furthermore, the control variable “family history of diabetes” was only collected from the third month of the children’s 24-month follow-up, which resulted in a high number of missing information (27.4%).

Among the positive aspects of the study, we highlight the fact that all pregnant women who had a hospital delivery in the municipality were interviewed within one year, and the small number of refusals, which allows the generalization of the results to other pregnant women under the same conditions of our sample.

CONCLUSIONS

Our study showed that iron supplementation in non-anamic pregnant women is not related with the development of GDM, which meets current national and international guidelines, whose recommendation is the routine supplementation to all pregnant women as soon as they start antenatal care to prevent iron deficiency anemia.

REFERENCES

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