Foetal Exposure and Epidemiological Transition: Role of Anaemia in Early Life for Non-communicable Diseases Later

NCT02191683 | Completed

• 2 other identifiers: 1309-00003BStrategiske Forskningsråd
• Study Type: observational
• Target: 1,748
• Locations: 1 country
• Sites: 1

Brief Summary

Study Hypotheses:

1. 1.Anaemia, which is frequent before conception as well as during early pregnancy, affects metabolism and foetal growth trajectories, influencing the risk of NCDs in the offspring.
2. 2.Anaemia from conception till end of 2nd trimester is most detrimental for foetal and newborns' health, compared to 3rd trimester anaemia.
3. 3.Anaemia from conception till end of 2nd trimester affects foetal and newborns health through poor placental development reflected in increased villous branching and changed umbilical and uterine blood flow.
4. 4.Anaemia in early pregnancy disrupts the vascular endothelial growth factor A (VEGF-A)/placental growth factor (PlGF) balance and the insulin-like growth factor (IGF) axis resulting in poor placental development, and poor health of newborns. This may be reflected in specific methylation patterns.
5. 5.Anaemia's impact on the risk for NCDs in the offspring may be mediated via epigenetic mechanisms, including changes in DNA methylation patterns.

Conditions

Anemia and Pregnancy; Metabolism and Foetal Growth; Epigenetics

Keywords

Anaemia; Pregnancy; Foetal programming; Epigenetics; Non-communicable diseases; Tanzania

Outcome Measures

Primary Outcomes (3)

• Outcome parameter for the pre-pregnancy study (i.):

  Prevalence and severity of anaemia among non-pregnant Tanzanian women at fertile age and their nutritional status.

  12 months from start

• Outcome parameter for the pregnancy study (ii.):

  Anemia's effect on foetal growth rate in 2nd and 3rd trimester measured as a) discrepancy in estimated and predicted gestational age (GA) between inclusion and antenatal visit at GA 20 weeks \& 30, b) change in z-score for foetal weight/body weight and c) gain in g/week26 at GA of 26, 32 and 37 and delivery. Newborn's body composition, placental villous branching, umbilical and uterine blood flow, VEGF-A/PlGF levels, and GFaxis. For all analyses main exposure variable are anaemia in 1st, 2nd and/or3rd trimester of pregnancy. Confounding exposure variables are chronic health conditions, temporary conditions mentioned above (e.g. malaria) and socioeconomic status and paternal characteristics. Regression modelling using multiple linear and logistic regressions and modelling for repeated measures are used for statistical analyses. Genetic and epigenetic significant changes in subgroup of 180 mother/newborns, after correction for multiple comparisons, will be validated in remaining cohort.

  31 months

• Incidence of conception among non-pregnant Tanzanian women.

  Number of women screened, with and without anaemia, respectively, who actually become pregnant within the observation period

  12 months

Study Arms (2)

Health of women before conception

Tanzanian women aged 18-40 years focusing on prevalence of anaemia, infections, nutritional status, and NCDs.

480 women during pregnancy

Describe how 1st and 2nd trimester anaemia compared to 3rd trimester anaemia alters foetal growth and newborns' body composition. Evaluate anaemia's effect on villous branching in placenta, and uterine and umbilical artery blood flow. Evaluate effect on vascular endothelial growth factor A/placental growth factor balance and insulin-like growth factor axis. Determine which markers for foetal programming such as methylation of regulatory genes related to metabolism and haematopoiesis may be discovered early after exposure to anaemia.

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Amendment October 2014: replacement of two-phase case-control study by two sub-projects, running in parallel, and following two distinct groups of women, 1) a cohort of 1500 non-pregnant women, disregarding Hb level, of whom 270 followed throughout pregnancy disregarding Hb level and gestational age at first contact, and 2) a case control study of 480 pregnant women followed from 1st trimester with a 160:160:160 ratio of women with Hb≤8g/dL: 8.1-10.9g/dL: ≥11g/dL. The Danish Council for Strategic Research notified and accepted in November 2014.

You may qualify if:

• wishing to get pregnant
• negative pregnancy test
• not using family planning

You may not qualify if:

• not wishing to get pregnant
• being pregnant
• using family planning

Sponsors & Collaborators

• University of Copenhagen: lead
• Copenhagen University Hospital, Denmark: collaborator
• Aarhus University Hospital: collaborator
• Lund University: collaborator
• National Institute for Medical Research, Tanzania: collaborator
• Department of Clinical Pathology Naestved Hospital Denmark: collaborator

Study Sites (1)

National Institute for Medical research

Korogwe, Tanga, Tanzania

Location

Related Publications (4)

• Hatem G, Hjort L, Asplund O, Minja DTR, Msemo OA, Moller SL, Lavstsen T, Groth-Grunnet L, Lusingu JPA, Hansson O, Christensen DL, Vaag AA, Artner I, Theander T, Groop L, Schmiegelow C, Bygbjerg IC, Prasad RB. Mapping the Cord Blood Transcriptome of Pregnancies Affected by Early Maternal Anemia to Identify Signatures of Fetal Programming. J Clin Endocrinol Metab. 2022 Apr 19;107(5):1303-1316. doi: 10.1210/clinem/dgac010.

  PMID: 35021220 DERIVED

• Paulsen CB, Nielsen BB, Msemo OA, Moller SL, Ekmann JR, Theander TG, Bygbjerg IC, Lusingu JPA, Minja DTR, Schmiegelow C. Anthropometric measurements can identify small for gestational age newborns: a cohort study in rural Tanzania. BMC Pediatr. 2019 Apr 23;19(1):120. doi: 10.1186/s12887-019-1500-0.

  PMID: 31014291 DERIVED

• Moeller SL, Nyengaard JR, Larsen LG, Nielsen K, Bygbjerg IC, Msemo OA, Lusingu JPA, Minja DTR, Theander TG, Schmiegelow C. Malaria in Early Pregnancy and the Development of the Placental Vasculature. J Infect Dis. 2019 Sep 26;220(9):1425-1434. doi: 10.1093/infdis/jiy735.

  PMID: 30590576 DERIVED

• Msemo OA, Bygbjerg IC, Moller SL, Nielsen BB, Odum L, Perslev K, Lusingu JPA, Kavishe RA, Minja DTR, Schmiegelow C. Prevalence and risk factors of preconception anemia: A community based cross sectional study of rural women of reproductive age in northeastern Tanzania. PLoS One. 2018 Dec 18;13(12):e0208413. doi: 10.1371/journal.pone.0208413. eCollection 2018.

  PMID: 30562390 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Periperal vein blood, umbilical cord blood, placentas

MeSH Terms

Conditions

Anemia; Noncommunicable Diseases

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mwelecele N Malecela, PHd

  National Institute for Medical Research, Tanzania

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Target Duration: 21 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 2, 2014
• First Posted: July 16, 2014
• Study Start: July 1, 2014
• Primary Completion: December 1, 2017
• Study Completion: October 1, 2018
• Last Updated: September 30, 2019

Record last verified: 2019-09

Locations

TA (1)