Foetal Exposure and Epidemiological Transition: The Role of Anaemia in Early Life for Non-Communicable Diseases in Later Life
Anaemia and non-communicable diseases (NCDs) are major health problems in the developing world. This project investigates if anaemia, in particularly Hb <8 g/dL, in early pregnancy or even before, may programme the foetus towards increased risk for NCDs when growing up in a society in fast transition.
Anaemia and non-communicable diseases (NCDs) are major health problems in the developing world. "Westernization" of life-style e.g. more refined food with higher content of sugar and saturated fat, sedentary life and smoking and alcohol consumption leading to obesity, are well-known risk factors for NCDs such as type 2 diabetes (T2DM), hypertension and their complications. However, obesity is not present in about half of those affected by T2DM and hypertension in Sub-saharan Africa and South-east Asia.
Hales & Barker (1991), hypothesized that low birth-weight (LBW) due to adverse events in foetal life may programme the child to become "thrifty", e.g. saving energy. This may be beneficial, when hard work, scarce food and repeated infection prevail, but less so when living conditions change, i.e. when getting urbanized and/or more "westernized". "Thrifty" individuals may be more prone to NCDs even without being obese.
Hales & Barker’s hypothesis has now been shown to operate in adults born to undernourished mothers, including Dutch during WWII, Chinese during the ‘big hunger’ and more recently Indians. Also Danish studies of monozygote twins have clearly shown that the smaller baby is at higher risk for NCD.
It has been speculated that the 1st and 2nd trimester in pregnancy is the key time point for foetal programming predisposing to NCD. Furthermore, anaemia might have the most detrimental effects on foetal growth and placental development at this time-point.
Despite both NCD and anaemia being highly prevalent in low and middle income countries whether anaemia before and during pregnancy affects foetal programming has not been investigated.
- Characterize the health of women aged 18-40 years before conception and during pregnancy, focusing on prevalence of anaemia, infections, nutritional status, and NCDs.
Describe how 1st/2nd trimester anaemia compared to 3rd trimester anaemia alters foetal growth and newborns’ body composition.
Evaluate how 1st and 2nd trimester anaemia compared to 3rd trimester anaemia affects villous branching, as well as uterine and umbilical artery blood flow.
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 (IGF) axis.
Determine which markers for foetal programming such as methylation of regulatory genes related to metabolism and haematopoiesis may be disclosed early after exposure to anaemia in1st and 2nd trimester compared to 3rd trimester anaemia.
In Korogwe District, Tanga Region northeastern Tanzania, a cohort and a case control study involving non-pregnant and pregnant women are ongoing.
In the cohort study, 1500 non-pregnant women irrespective of their haemoglobin (Hb) levels will be followed. The first 270 women who become pregnant will be followed throughout pregnancy, irrespective of their Hb levels and gestational age (GA) at the time the pregnancy is identified. In the case control study, 480 pregnant women will be enrolled in the 1st trimester (GA≤14 weeks) on a 1:1:1 basis with an Hb≤8.0g/dL (moderate-severe anaemia) (160 women); Hb 8.1-10.9 g/dL (mild-moderate anaemia) (160 women); Hb ≥11.0g/dL (non-anaemic) (160 women), respectively, using Hemocue Hb point-of-care and will be followed until delivery.
Korogwe District Hospital will be the focal point at which foetal growth and placental development will be evaluated using ultrasound and Doppler flow measurements as well as blood markers throughout pregnancy. Causes of anaemia, nutritional status and general health will be characterized before and during pregnancy, and the newborns’ health and body composition measured at delivery. Women, foetal, newborn, and placental health will be linked to epigenetic markers of foetal programming for NCDs in cord blood and placental tissue.
This project will shed light on the role of anaemia before and during pregnancy on placental development, intrauterine growth and foetal programming, including epigenetic changes.
The project will be managed by a consortium consisting of the following units:
- Centre for Medical Parasitology
University of Copenhagen & Copenhagen University Hospital, Denmark
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
The National Institute for Medical Research (NIMR) as part of the umbrella consortium Joint Malaria Programme (JMP) in Tanzania and Department of Clinical Pathology, Naestved Hospital, Denmark will be affiliated partners. Another cooperative partner will be the District Medical Officer in Korogwe.
Funded by The Danish Council for Strategic Research. The grant received is DKK 17,945,000. The project will run for 3½ years, and it includes 2 PhDs, and 3 postdocs (incl. a PhD and a postdoc from Tanzania).
For inquiries regarding this research project please contact the principal investigators:
|Ib C. Bygbjerg||University of Copenhagen|
|Christentze Schmiegelow||University of Copenhagen|
|Dirk Lund Christensen||University of Copenhagen|
|Leif Groop||Lund University|
|Louise Grunnet||Copenhagen University Hospital, Rigshospitalet|
|Lise Grupe Larsen|
|Birgitte Bruun Nielsen||Aarhus University|
|Thor Theander||University of Copenhagen|
|Allan Vaag||Steno Diabetes Center, Copenhagen|