Determinants of Neonatal Anemia in Women Carrying Multiples

Anemia Clinical Trial

Official title:

Determinants of Neonatal Iron Homeostasis in Women Carrying Multiples

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01582802
• Other study ID #: OSP 64155
• Status: Active, not recruiting
• Start date: July 2011
• Est. completion date: December 2023

Study information

• Verified date: July 2023
• Source: Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Multiple births in the United States are rapidly increasing in large part due to assisted reproductive technologies. Recent data indicate that multiple births now comprise 3-4.5% of all births in the United States. Pregnant women are at risk for iron (Fe) deficiency anemia yet there are virtually no data on Fe status in women carrying multiples and current recommendations do not necessitate Fe screening among this high risk group. Maternal anemia is known to increase the risk of adverse birth outcomes including preterm birth and low birth weight. Moreover, the developing brain is increasingly recognized to be susceptible to Fe insufficiency in utero and growing data support that suboptimal Fe stores at birth are associated with long-term irreversible cognitive deficits in the offspring. To address these gaps in knowledge the investigators will monitor weight gain, hematological measures, Fe status indicators and serum hepcidin across pregnancy in approximately 120 women carrying twins and triplets. Determinants of maternal anemia will be identified. Neonatal hematological measures will be assessed in cord blood from each neonate at birth for assessment of hematological measures, Fe status and hepcidin. Determinants of neonatal anemia will be identified. Inflammatory markers will be measured in all blood samples and related to outcomes. Stable iron isotopes will be given to a subset of women to assess maternal Fe absorption and fetal Fe uptake.

Description:

Pregnant women (n=100-125) carrying multiples (twins and triplets) will be identified when entering prenatal care. Women will be invited to participate in a longitudinal study of Fe homeostasis across pregnancy and at delivery in the maternal / neonatal dyad. In all maternal and cord blood samples obtained, whole blood will be analyzed for hemoglobin, hematocrit, reticulocyte count, erythrocyte count, mean corpuscular hemoglobin, mean corpuscular Hb concentration, mean corpuscular volume, and red cell distribution width using standard procedures. Circulating Fe status indicators (serum iron, ferritin, C-reactive protein, IL-6, erythropoietin, transferrin receptor and hepcidin) and serum folate and vitamin B12 will be measured. Distributions of each variable will be examined and associations among variables will be explored. Multiple linear regression models will be constructed to examine specific relations between a) determinants of Fe deficiency anemia in the mother; b) Fe status indicators in the mother vs. those in the neonate; c) Fe status indicators in the mother and neonate with placental Fe binding proteins; and d) neonatal Fe status between siblings.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 350
• Est. completion date: December 2023
• Est. primary completion date: December 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 19 Years to 45 Years

Eligibility

Inclusion Criteria:

• The investigators anticipate that the majority of these women will be recruited early in gestation because many of these pregnancies are a result of assisted reproductive technology.

• Eligible volunteers will be otherwise healthy and have no diagnosed, preexisting medical conditions known to impact iron homeostasis

Exclusion Criteria:

• Hemoglobinopathies,

• Preexisting diabetes,

• Malabsorption diseases

Related Conditions & MeSH terms

• Anemia

Locations

Country	Name	City	State
United States	Strong Memorial Hospital	Rochester	New York

Sponsors (2)

Lead Sponsor	Collaborator
Cornell University	University of Rochester

Country where clinical trial is conducted

United States, 

References & Publications (3)

Ru Y, Pressman EK, Cooper EM, Guillet R, Katzman PJ, Kent TR, Bacak SJ, O'Brien KO. Iron deficiency and anemia are prevalent in women with multiple gestations. Am J Clin Nutr. 2016 Oct;104(4):1052-1060. doi: 10.3945/ajcn.115.126284. Epub 2016 Aug 31. — View Citation

Ru Y, Pressman EK, Guillet R, Katzman PJ, Bacak SJ, O'Brien KO. Predictors of anemia and iron status at birth in neonates born to women carrying multiple fetuses. Pediatr Res. 2018 Aug;84(2):199-204. doi: 10.1038/s41390-018-0044-6. Epub 2018 Jun 15. — View Citation

Ru Y, Pressman EK, Guillet R, Katzman PJ, Vermeylen F, O'Brien KO. Umbilical Cord Hepcidin Concentrations Are Positively Associated with the Variance in Iron Status among Multiple Birth Neonates. J Nutr. 2018 Nov 1;148(11):1716-1722. doi: 10.1093/jn/nxy151. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maternal iron status	Maternal hematological measures will be evaluated	Biochemical measures will be obtained whenever women have blood drawn across pregnancy (there are no fixed time points for sampling). These will be obtained over an approximate 36 week interval
Primary	Neonatal iron status at birth	Cord blood hematological measures will be evaluated	Umbilical cord blood will be collected at birth
Primary	Determinants of inter- and intra-uterine variance of neonatal iron status	ICC will be evaluated for iron status biomarkers	Umbilical cord blood will be collected at birth
Secondary	Effect of maternal Fe status on placental iron transporter expression	protein and RNA expression of iron transporters will be evaluated	Participants will be followed over the course of gestation from approximately week 12 of pregnancy until term
Secondary	Maternal iron absorption and Fe57 enrichment in cord blood	net quantity of isotope in newborns will be determined	Participants will be given 10 mg of stable iron between week 27-32 of gestation. Blood will be drawn 2 weeks post-dosing and maternal and umbilical cord blood will be obtained at delivery