The FOETALforNCD project: how does anaemia before and during pregnancy affect the newborn’s health short and long-term

This blog post was written by Christentze Schmiegelow¹, Daniel Minja², John Lusingu², Ib Bygbjerg³

Approximately three quarters of individuals with non-communicable diseases (NCDs) live in low and middle-income countries (LMICs) (1). Whilst traditional behavioural risk-factors of NCDs such as an unhealthy diet and limited physical activity also apply to LMIC populations (2), the increased susceptibility to NCDs in these regions may be partially determined by events or conditions which occur during foetal development.

An adverse event during pregnancy, which results in a nutritionally restricted environment in the womb, may programme the foetus to adapt to an environment with limited nutritional access, in preparation for the expected nutritional conditions outside the womb (3). However this adaptation may result in an environmental mismatch whereby exposure to sufficient, but not necessarily excessive, nutrition cannot be aptly handled later in life, leading to an increased risk of cardiometabolic diseases.

Early pregnancy is potentially a key time-point for foetal programming; although poor maternal or paternal health before conception could also play a role in the adaptive programming of the foetus (4). One potential mechanism of foetal programming is through epigenetic changes of the foetus’ DNA. A restricted nutritional environment in the mother’s womb may down-regulate foetal growth. This process averts abortion of the foetus or premature birth, at the expense of the birth weight of the newborn (5). One mechanism might be through the insertion of a methyl group in the foetus’ regulator genes. Regulator genes which may be targeted for down-regulation include those responsible for insulin production. The silencing of insulin production may be permanent and beneficial after birth if the newborn grows up in poor nutritional conditions; however, increases in nutritional access and energy intake later in life may increase the risk of developing cardio-metabolic diseases.

Anaemia in expecting mothers is another potential exposure during pregnancy which may lead to foetal programming and reduced birth weight. In LMICs, 40-60% of pregnant women are anaemic. Anaemia in pregnancy is associated with decreased birth weight (6); however, the process by which the condition affects foetal growth is not well established. Poor placental development in early pregnancy may play a pivotal role in these scenarios (7-9).

The FOETALforNCD project, funded by the Danish Council for Strategic Research, aims to investigate how anaemia affects placental and newborn health, and the potential link between foetal programming and increased risk of NCDs in later life. The project got key-funding from the Danish Council for Strategic Research, and granted approval by the Tanzanian National Ethics Committee.

The project recruited and followed 1570 women in Tanzania, before (1415) and during different stages of pregnancy (538), between July 2014 and December 2016. Haemoglobin was measured at every contact. Causes of anaemia, maternal nutritional status and general health were characterized before and during pregnancy, and at birth. Micronutrient status and blood markers of placental and foetal growth were also measured. Foetal growth and placental development were evaluated using ultrasound and Doppler flow measurements. The newborns’ health were evaluated at delivery and at 1 month of age. The placenta which was collected at birth, will be investigated at a later date using stereology.

We plan to investigate maternal, paternal, and cord blood for epigenetic markers of foetal programming for cardio-vascular and metabolic development, and potential indicators of cardio-metabolic diseases. These markers will be linked to maternal, placental, foetal, and newborn health. Using these measurements we will also try to identify the time-point of highest vulnerability for anaemia during pregnancy.

This project aims to shed light on the role of anaemia on placental development, intrauterine growth, and foetal programming. The results of our study will help to guide health interventions against anaemia in order to reduce the risk of NCDs in LMICs and globally.

FOETALforNCD Consortium:

Global Health, Department of Public Health, University of Copenhagen, Denmark (3)
Centre for Medical Parasitology, University of Copenhagen & Copenhagen University Hospital, Denmark (1)
Diabetes and Metabolism, Department of Endocrinology, Copenhagen University Hospital, Denmark
Department of Gynaecology and Obstetrics, Aarhus University Hospital, Denmark
Diabetes and Endocrinology, Department of Clinical Science, Lund University, Sweden
National Institute for Medical Research, Tanga Centre, Tanzania (2)
Department of Clinical Pathology, Naestved Hospital, Denmark

Reference List
(1) World Health Organisation. Global Health Estimates: Deaths by Cause, Age, Sex, and Country, 2000-2012. 2014. Geneva. Ref Type: Report

(2) Nakagami T, Qiao Q, Carstensen B, Nhr-Hansen C, Hu G, Tuomilehto J et al. Age, body mass index and Type 2 diabetes-associations modified by ethnicity. Diabetologia 2003; 46(8):1063-1070.

(3) Hales CN, Barker DJ. The thrifty phenotype hypothesis. Br Med Bull 2001; 60:5-20.

(4) Pembrey M, Saffery R, Bygren LO. Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research. J Med Genet 2014; 51(9):563-572.

(5) Bouchard L. Epigenetics and fetal metabolic programming: a call for integrated research on larger cohorts. Diabetes 2013; 62(4):1026-1028.

(6) Rahman MM, Abe SK, Rahman MS, Kanda M, Narita S, Bilano V et al. Maternal anemia and risk of adverse birth and health outcomes in low- and middle-income countries: systematic review and meta-analysis. Am J Clin Nutr 2016; 103(2):495-504.

(7) Haider BA, Olofin I, Wang M, Spiegelman D, Ezzati M, Fawzi WW. Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis. BMJ 2013; 346:f3443.

(8) Rijken MJ, Papageorghiou AT, Thiptharakun S, Kiricharoen S, Dwell SL, Wiladphaingern J et al. Ultrasound evidence of early fetal growth restriction after maternal malaria infection. PLoS ONE 2012; 7(2):e31411.

(9) Xiong X, Buekens P, Alexander S, Demianczuk N, Wollast E. Anemia during pregnancy and birth outcome: a meta-analysis. Am J Perinatol 2000; 17(3):137-146.