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

NCT ID: NCT02191683

Last Updated: 2019-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

1748 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-07-31

Study Completion Date

2018-10-31

Brief Summary

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Study Hypotheses:

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. Anaemia from conception till end of 2nd trimester is most detrimental for foetal and newborns' health, compared to 3rd trimester anaemia.
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. 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. Anaemia's impact on the risk for NCDs in the offspring may be mediated via epigenetic mechanisms, including changes in DNA methylation patterns.

Detailed Description

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Specific objectives are:

1. Characterize the health of women aged 18-40 years before conception and during pregnancy, focusing on prevalence of anaemia, infections, nutritional status, and Non-Communicable Diseases (NCDs).
2. Describe how 1st and 2nd trimester anaemia compared to 3rd trimester anaemia alters foetal growth and newborns' body composition.
3. Evaluate how 1st and 2nd trimester anaemia compared to 3rd trimester anaemia affects villous branching in the placenta, as well as uterine and umbilical artery blood flow.
4. Characterize how 1st, 2nd and 3rd trimester anaemia differentially changes the vascular endothelial growth factor A (VEGF-A)/placental growth factor (PlGF) balance and the insulin-like growth factor axis.
5. 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 in1st and 2nd trimester compared to 3rd trimester anaemia.

Outcome parameter for the pre-pregnancy study (i.): 1) Prevalence and severity of anaemia among non-pregnant Tanzanian women at fertile age and their nutritional status. 2) Incidence of conception among such women.

Outcome parameter for the pregnancy study (ii.): 1) Foetal growth rate in 2nd and 3rd trimester in offspring of anaemic mothers vs Foetal growth rate in non-anaemic mothers' offspring, 2) Comparison of anaemic mothers' vs non-anaemic mothers' newborn's body composition, placental villous branching, umbilical and uterine blood flow, VEGF-A/PlGF levels, and insulin-like growth factor axis.

For all analyses main exposure variable will be anaemia (Hb\<5mmol/L) in 1st, 2nd and/or3rd trimester of pregnancy. Confounding exposure variables will be chronic health conditions (e.g. HIV), all temporary conditions mentioned above (e.g. malaria) as well as socioeconomic status and paternal characteristics. Regression modelling using both multiple linear and logistic regressions as well as modelling for repeated measures will be used for statistical analyses. For genetic and epigenetic changes, findings in the subgroup of 180 other/newborns, remaining significant after correction for multiple comparisons, will be validated in the remaining cohort. This will enable us within one study to replicate initial findings in one representative and distinct subgroup in another larger comparable study group from an overall homogenous study. Indeed, findings surviving both corrections for multiple testing in the initial hypothesis generating array approaches, as well as being replicated in the remaining study group with single target validation techniques, are highly likely to be biological important. Possible findings from the candidate gene approach will be corrected for multiple testing and the significant results will be compared with previous findings of the same genes from studies in muscle and adipose tissue conducted by Diabetes and Metabolism, Copenhagen University Hospital.

Conditions

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Anemia and Pregnancy Metabolism and Foetal Growth Epigenetics

Study Design

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Observational Model Type

OTHER

Study Time Perspective

PROSPECTIVE

Study Groups

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Health of women before conception

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

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* not wishing to get pregnant
* being pregnant
* using family planning
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Copenhagen University Hospital, Denmark

OTHER

Sponsor Role collaborator

Aarhus University Hospital

OTHER

Sponsor Role collaborator

Lund University

OTHER

Sponsor Role collaborator

National Institute for Medical Research, Tanzania

OTHER_GOV

Sponsor Role collaborator

Department of Clinical Pathology Naestved Hospital Denmark

UNKNOWN

Sponsor Role collaborator

University of Copenhagen

OTHER

Sponsor Role lead

Responsible Party

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Ib Christian Bygbjerg

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mwelecele N Malecela, PHd

Role: STUDY_CHAIR

National Institute for Medical Research, Tanzania

Locations

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National Institute for Medical research

Korogwe, Tanga, Tanzania

Site Status

Countries

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Tanzania

References

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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.

Reference Type DERIVED
PMID: 35021220 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31014291 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30590576 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30562390 (View on PubMed)

Other Identifiers

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Strategiske Forskningsråd

Identifier Type: OTHER

Identifier Source: secondary_id

1309-00003B

Identifier Type: -

Identifier Source: org_study_id

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