Effectiveness of Adaptation of the Dose of Iron Supplementation in Pregnancy on Maternal-child Health. (ECLIPSES)

NCT03196882 | Completed Phase 4 DMC

• 3 other identifiers: IJG-FER-20122012-005480-28PI12/02777
• Study Type: interventional
• Target: 704
• Locations: 1 country
• Sites: 2

Brief Summary

Currently, there is no consensus regarding iron supplementation dose that is most beneficial for maternal and offspring health during gestation. This deficit, or excess, of iron prejudices the mother-child wellbeing. Therefore the hypotheses are that an iron supplementation adapted to values of hemoglobin at the start of the pregnancy will would be more effective in preventing iron deficiency, without increasing the risk of hemoconcentration by the end of pregnancy. This would be helped optimize mother-child health status. The aims of the study are to determine the highest level of effectiveness of iron supplementation adapted to hemoglobin (Hb) levels in early pregnancy, which would be optimum for mother-child health. To accomplish this objective a Randomized Clinical Trial (RCT) triple-blinded was designed. The study is structured as a RCT with 2 strata, depending on the Hb levels before week 12 of gestation. Stratum 1: If Hb from 110 to 130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 80 mg/d. Stratum 2: If Hb \>130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 20 mg/d. This study will be conducted in non-anemic pregnant women at early gestation stage, and their subsequent newborns. The data recollected to mothers will be: socio-economic data, clinical history, food item frequency, lifestyle and emotional state, and adherence to iron supplement prescription. In addition, biochemical measured will be Hemoglobin, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). In children, the data collected will be: ultrasound fetal biometry, anthropometric measurements, and temperament development Should conclusive outcomes be reached, the study would indicate the optimal iron supplementation dose required to promote maternal and infant health. These results would contribute towards developing guidelines for good clinical practice.

Conditions

Anemia Ferropenic; Risk of Hemoconcentration (Iron Levels >130g/L)

Keywords

pregnancy; iron; hemoglobin; supplementation; neurodevelopment; newborn; anemia; clinical trial

Outcome Measures

Primary Outcomes (3)

• Anemia

  \- Anemia is defined as Hb \<110 g/L in the 1st and 3rd trimester, Hb \<110 in 2nd trimester (Centers for Disease Control and Prevention, 1998).

  at week 36 of gestation (3rd visit of study)

• ferropenic anemia

  \- Ferropenic anemia is defined as: Hb \< the normal limit, and serum ferritin (SF) \<15 μg/L (WHO, 2007)

  at week 36 of gestation (3rd visit of study)

• Risk of hemoconcentration

  \- Hemoconcentration risk is defined as: Hb \>130 g/L in the 2nd and /or3rd trimester (Peña-Rosas y Viteri, 2009).

  at week 36 of gestation (3rd visit of study)

Secondary Outcomes (4)

• C282Y polymorphisms of HFE gene

  Blood analysis at 12 weeks of gestation.

• Anthropometric parameters of newborn.

  At birth

• Neurorconductual development of newborn (Bayley Scales)

  40days post-partum

• H63D polymorphisms of HFE gene

  Blood analysis at 12 weeks of gestation.

Study Arms (4)

Stratum 1: 40 mg/day of iron

ACTIVE COMPARATOR

Ferrimanitol ovoalbumin. 40mg of iron in a sachet (powder for oral solution) by mouth, every 24 hours from 12th week of gestation to partum Stratum 1: If the levels of Hb are situated between 110 and 130 g/L, the individual will be randomly assigned to an iron dose supplement of 40 (medium supplementation) or 80 mg/d (high supplementation)

Drug: 40mg/day of iron

Stratum 1: 80 mg/day of iron

EXPERIMENTAL

Ferrimanitol ovoalbumin. 80mg of iron in a sachet (powder for oral solution) by mouth, every 24 hours from 12th week of gestation to partum Stratum 1: If the levels of Hb are situated between 110 and 130 g/L, the individual will be randomly assigned to an iron dose supplement of 40 (medium supplementation) or 80 mg/d (high supplementation)

Drug: 80mg/day of iron

stratum 2: 40 mg/day of iron

ACTIVE COMPARATOR

Ferrimanitol ovoalbumin. 40mg of iron in a sachet (powder for oral solution) by mouth, every 24 hours from 12th week of gestation to partum Stratum 2: If the levels of Hb are \>130 g/L, the individual will be randomly assigned to an iron dose supplement of 40 (medium supplementation) or 20 mg/d (low supplementation)

Drug: 40mg/day of iron

stratum 2: 20 mg/day of iron

EXPERIMENTAL

Ferrimanitol ovoalbumin. 20mg of iron in a sachet (oral solution) by mouth, every 24 hours from 12th week of gestation to partum Stratum 2: If the levels of Hb are \>130 g/L, the individual will be randomly assigned to an iron dose supplement of 40 (medium supplementation) or 20 mg/d (low supplementation)

Drug: 20mg/day of iron

Interventions

40mg/day of iron DRUG

Ferrimanitol ovalbumin granulated. Powder for oral solution. The doses of 40 mg per day of elemental iron correspond to 300 mg ferrimanitol ovoalbumin

Also known as: PROFER 40 mg

Stratum 1: 40 mg/day of iron; stratum 2: 40 mg/day of iron

20mg/day of iron DRUG

Ferrimanitol ovalbumin granulated Powder for oral solution. The doses of 20 mg per day of elemental iron correspond to 150 mg ferrimanitol ovoalbumin

Also known as: FERROPROTINA

stratum 2: 20 mg/day of iron

80mg/day of iron DRUG

Ferrimanitol ovalbumin granulated. Powder for oral solution The doses of 80 mg per day of elemental iron correspond to 600 mg ferrimanitol ovoalbumin.

Also known as: PROFER 80 mg

Stratum 1: 80 mg/day of iron

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult woman
• ICS belonging to
• Pregnant less than 12 weeks gestation,
• To understand the Spanish or Catalan
• Sign the informed consent
• Without anemia (Hb \<110 d / dL) in the pre-analytical at 12 weeks

You may not qualify if:

• Multiple or risk pregnancy.
• Taking iron supplements containing 10mg iron than in the previous three months
• Pregnant women with hypersensitivity to the active substance, hypersensitivity to egg proteins or intolerant to fructose or galactose.
• chronic or severe pre-existing disease that affects the nutritional development, such as cancer, diabetes mellitus and other metabolic diseases, malabsorptive diseases such as Crohn's disease, ulcerative colitis, gastro-duodenal ulcers, and liver diseases such as chronic hepatitis, liver cirrhosis and chronic pancreatitis.
• Immunosuppression: chronic HIV infection, transplant, neutropenic, or patients receiving immunosuppressive therapy.

Sponsors & Collaborators

• Victoria Arija Val: lead
• University Rovira i Virgili: collaborator
• Catalan Institute of Health: collaborator
• Hospital Universitari Joan XXIII de Tarragona.: collaborator
• Carlos III Health Institute: collaborator

Study Sites (2)

Atención a la Salud Sexual y Reproductiva (ASSIR)- REUS- Altebrat

Reus, Tarragona, Spain

Location

Atención a la Salud Sexual y Reproductiva (ASSIR)- Tarragona Valls

Tarragona, Spain

Location

Related Publications (7)

• Aranda N, Ribot B, Garcia E, Viteri FE, Arija V. Pre-pregnancy iron reserves, iron supplementation during pregnancy, and birth weight. Early Hum Dev. 2011 Dec;87(12):791-7. doi: 10.1016/j.earlhumdev.2011.06.003. Epub 2011 Jun 30.

  PMID: 21723050 BACKGROUND

• Recommendations to prevent and control iron deficiency in the United States. Centers for Disease Control and Prevention. MMWR Recomm Rep. 1998 Apr 3;47(RR-3):1-29.

  PMID: 9563847 BACKGROUND

• Hernandez-Martinez C, Canals J, Aranda N, Ribot B, Escribano J, Arija V. Effects of iron deficiency on neonatal behavior at different stages of pregnancy. Early Hum Dev. 2011 Mar;87(3):165-9. doi: 10.1016/j.earlhumdev.2010.12.006. Epub 2011 Jan 22.

  PMID: 21256683 BACKGROUND

• Pena-Rosas JP, Viteri FE. Effects and safety of preventive oral iron or iron+folic acid supplementation for women during pregnancy. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD004736. doi: 10.1002/14651858.CD004736.pub3.

  PMID: 19821332 BACKGROUND

• Ribot B, Aranda N, Viteri F, Hernandez-Martinez C, Canals J, Arija V. Depleted iron stores without anaemia early in pregnancy carries increased risk of lower birthweight even when supplemented daily with moderate iron. Hum Reprod. 2012 May;27(5):1260-6. doi: 10.1093/humrep/des026. Epub 2012 Feb 21.

  PMID: 22357769 BACKGROUND

• Cendra-Duarte E, Canals J, Becerra-Tomas N, Mateu-Fabregat J, Bullo M, Arija V. Dietary glycemic index and load during pregnancy and offspring behavioral outcomes: exploring sex differences. Eur J Pediatr. 2025 Feb 6;184(2):178. doi: 10.1007/s00431-025-06005-y.

  PMID: 39909936 DERIVED

• Iglesias-Vazquez L, Gimeno M, Coronel P, Caspersen IH, Basora J, Arija V. Maternal factors associated with iron deficiency without anaemia in early pregnancy: ECLIPSES study. Ann Hematol. 2023 Apr;102(4):741-748. doi: 10.1007/s00277-023-05123-7. Epub 2023 Feb 15.

  PMID: 36790457 DERIVED

Related Links

• World Health Organization (WHO). Iron and folate supplementation. Standards for maternal and neonatal care. Integrated Management of Pregnancy and Childbirth (IMPAC). Geneva: WHO, 2007; pp. 1-6.

MeSH Terms

Conditions

Anemia

Interventions

Iron

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Victoria Arija, MD Professor

  Institut d'Investigació en Atenció Primària, IDIAP Jordi Gol i Gurina, Catalonia, Spain - Nutrition and Public Health Unit, Rovira i Virgili University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be triple blind: the participant, the health-care professional, and the investigator-statistician. The treatment drug will be administered "blind" i.e. the doses are not identifiable since the packaging has the same format, presentation, and visual characteristics. For Stratum 1, the treatments will be designated as A or B, and for Stratum 2 they will be designated as C or D. The laboratory of MEIJI TEDEC FARMA, SA will be responsible for manufacturing, packaging and labeling the study medications. Only MEIJI TEDEC FARMA, SA and the Clinical Pharmacology Service of the Vall d'Hebron Hospital in Barcelona will know the distribution codes and the composition of each of the treatments.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD

Model Details: Multi-centered, parallel groups, controlled, triple blind, randomized clinical trial (RCT) subdivided in 2 strata as a function of the hemoglobin (Hb) levels at the start of the pregnancy: Stratum 1: If Hb from 110 to 130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 80 mg/d. Stratum 2: If Hb \>130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 20 mg/d. The study is structured as a RCT with 2 stratum, depending on the Hb levels before week 12 of gestation. In each stratum there are two arms of intervention. Total 4 arms.

Study Record Dates

• First Submitted: June 15, 2017
• First Posted: June 23, 2017
• Study Start: July 10, 2013
• Primary Completion: January 30, 2017
• Study Completion: January 30, 2017
• Last Updated: June 23, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)