B4461 - Maternal Epigenetic age Interpregnancy Interval and Adverse Pregnancy Outcomes - 15/11/2023

B number: 
Principal applicant name: 
Amanuel Gebremedhin | Curtin University (Australia)
Professor Gavin Pereira, Dr Yunsung Lee
Title of project: 
Maternal Epigenetic age, Interpregnancy Interval and Adverse Pregnancy Outcomes
Proposal summary: 

The length of time between birth and beginning of subsequent pregnancy, interpregnancy interval (IPI) is associated with an increased risk of adverse pregnancy outcomes in subsequent pregnancy, among others, preterm births, low birth weight and preeclampsia. It has also been identified as a potentially modifiable risk factors for these outcomes for planned pregnancies.
Our recent study has indicated that long IPIs (>60 months) are associated with an increased risk of complications that exceed the effects of short intervals (<6 months) after careful confounder control by matching pregnancies to the same women [1,2]. Moreover, another study, which examined the non-linear relationship between IPI and pregnancy complications by maternal age indicated that the risk of preeclampsia and gestational diabetes was greater for older mothers following long IPI. [3] However, the causal interpretations of the long IPI association remain challenging as the possibility of residual confounding cannot be ruled out.
Current guidelines on pregnancy spacing may be misinformed, overlooking the age-related risks of delayed pregnancy because pregnancy delay naturally increases maternal age. Unfortunately, there is limited research on this topic, with only two relevant studies found, [3.4] neither addressing the independent effects of biological aging, or the partition effect of pregnancy spacing (time to pregnancy, TTP and waiting) on adverse pregnancy outcomes.

Impact of research: 
This proposed research could crucially address age-related misconceptions of risk, aiding 1) improved pregnancy spacing guidelines, 2) deeper insights into age-related pregnancy risks, and 3) the development of novel methods to evaluate maternal age's impact on adverse pregnancy outcomes, thereby informing better healthcare strategies for expectant mothers. Our collaborative research team is well-positioned to undertake this project with complementary expertise in epigenetics and bioinformatics, perinatal epidemiology, and bio (statistics). We have an established history of engaging in successful collaborative projects on perinatal research and epigenetic age clock development using DNA methylation data. Reference [1]. Gebremedhin AT, Regan AK, Ball S, et al. Interpregnancy interval and hypertensive disorders of pregnancy: A population‐based cohort study. Paediatric and perinatal epidemiology. 2021;35(4):404-414. [2]. Gebremedhin AT, Regan AK, Ball S, et al. Effect of interpregnancy interval on gestational diabetes: a retrospective matched cohort study. Annals of epidemiology. 2019;39:33-38. e3. [3]. Gebremedhin AT, Tessema GA, Regan AK, Pereira G. Association between interpregnancy interval and hypertensive disorders of pregnancy: Effect modification by maternal age. Paediatric and perinatal epidemiology. 2021;35(4):415-424. [4]. Wise LA, Mikkelsen EM, Sørensen HT, et al. Prospective study of time to pregnancy and adverse birth outcomes. Fertility and sterility. 2015;103(4):1065-1073. e2. [5]. Willis SK, Hatch EE, Wesselink AK, et al. Post-partum interval and time to pregnancy in a prospective preconception cohort. Paediatr Perinat Epidemiol. May 2021;35(3):271-280. doi:10.1111/ppe.12702
Date proposal received: 
Tuesday, 14 November, 2023
Date proposal approved: 
Wednesday, 15 November, 2023
Epidemiology, Diabetes, Fertility/infertility, Hypertension, Mental health, Obesity, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Statistical methods, Ageing, Biological samples -e.g. blood, cell lines, saliva, etc., Environment - enviromental exposure, pollution, Epigenetics, Fathers, Genetic epidemiology, Mothers - maternal age, menopause, obstetrics, Nutrition - breast feeding, diet, Siblings, Birth outcomes, Blood pressure, BMI, Breast feeding, Cardiovascular, Cohort studies - attrition, bias, participant engagement, ethics, Contraception, Endocrine - endocrine disrupters