Determinants of Neonatal Anemia in Women Carrying Multiples

Determinants of Neonatal Iron Homeostasis in Women Carrying Multiples

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Anemia

Detailed 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.

• Study Type: Observational
• Enrollment (Estimated): 350

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14642
      • Strong Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women (n = 100-125) carrying multiples (twins, triplets and quadruplets)

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Pregnant women carrying multiples; Healthy pregnant women carrying twins, triplets and quadruplets will be recruited.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Neonatal iron status at birth	Cord blood hematological measures will be evaluated	Umbilical cord blood will be collected at birth
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Cornell University
• Collaborators: University of Rochester
• Investigators: Principal Investigator: Kimberly O'Brien, PhD, Cornell University

Publications and helpful links

General Publications

• Delaney KM, Guillet R, Fleming RE, Ru Y, Pressman EK, Vermeylen F, Nemeth E, O'Brien KO. Umbilical Cord Serum Ferritin Concentration is Inversely Associated with Umbilical Cord Hemoglobin in Neonates Born to Adolescents Carrying Singletons and Women Carrying Multiples. J Nutr. 2019 Mar 1;149(3):406-415. doi: 10.1093/jn/nxy286.
• 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.
• 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.
• 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.
• Delaney KM, Guillet R, Pressman EK, Caulfield LE, Zavaleta N, Abrams SA, O'Brien KO. Iron absorption during pregnancy is underestimated when iron utilization by the placenta and fetus is ignored. Am J Clin Nutr. 2020 Sep 1;112(3):576-585. doi: 10.1093/ajcn/nqaa155.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): December 1, 2017
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: April 12, 2012
• First Submitted That Met QC Criteria: April 19, 2012
• First Posted (Estimated): April 23, 2012

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia
• Other Study ID Numbers: OSP 64155

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO