CHILD LUNG FUNCTION AND CARDIOVASCULAR HEALTH STUDY.

January 10, 2025 | Ongoing Project | Reading time: 8 min

Introduction

This Child Lung Function and Cardiovascular Health Study is part of a broader study named Ghana Randomised Air Pollution and Health Study (GRAPHS). The study is investigating how exposure to air pollution impacts the cardiovascular health (CVH) of children. It involves monitoring a group of children, starting from birth, to understand how early-life exposure to air pollutants affects the health of their heart as they grow.

Investigators

Kintampo Health Research Centre: Kwaku Poku Asante, MD PhD, Kaali Seyram, MD, MSc, Mujtaba Mohammed Nuhu, MPH, Osei Musah MSc, Yussif Tawfiq, MSc

Columbia University Mailman School of Public Health: Darby Jack, PhD, Steven Chillrud, PhD, Ana Navas-Acien, PhD, Kiros Berhane, PhD

Icahn School of Medicine at Mount Sinai: Alison Lee, MD, MS, Elena Colicino, PhD.

Background

Cardiovascular disease (CVD) is the leading cause of global mortality, and nearly 80% of CVD deaths occur in low- and middle-income countries (LMICs). Exposure to fine particulate matter pollution (PM2.5) is the leading environmental risk factor for CVD, and toxicity may be partially driven by metal composition. In LMICs, ~2.8 billion people are exposed daily to high levels of household air pollution (HAP) from cooking with solid fuels in inefficient stoves.

In 2019, HAP was responsible for 2.3M premature deaths and 91.5M disability-adjusted life years (DALYs) with an estimated ~43% of mortality and ~31% of DALYs attributed to CVD.Pregnant women, often the primary household cook, are highly exposed. Early life (prenatal to age 1) is a critical window of developmental plasticity when environmental exposures may harm early life cardiovascular health (CVH) and program future CVD risk. A critical step in identifying and addressing lifelong risk is characterizing exposures and mechanisms that lead to and maintain this early predisposition.

Our proposed longitudinal study leverages a birth cohort derived from a cluster-randomized stove intervention trial begun prenatally and continued through age one year. We seek to investigate the contribution of early-life HAP exposure to poorer CVH in childhood and to characterize the role that the metal composition of PM2.5 plays in the CVH effects of HAP. CVH in adolescence has been associated with adult cardiac structure and function. Thus, early life is a critical time of cardiovascular development and programming of child CVH and future disease risk.

Objectives

The objectives of this study have been categorized as follows:

Aim 1: Estimate effects of an early life LPG cookstove intervention and resulting HAP exposure changes on CVH through age 12 years. We define CVH by lower systolic BP and DBP, measured annually from age 4 to 12, better height, weight, and body mass index from birth to age 12, and lower biomarkers of CVD risk (glucose, fasting lipids) at ages 10 and 12.

a) Aim 1a. Intention-to-treat: We hypothesize that children in the LPG intervention arm will have better CVH through age 12 as compared with children in the control arm.

b) Aim 1b. Exposure-Response: We hypothesize that higher early-life PM2.5 and CO exposures will be associated with poorer CVH through age 12. Other air pollution sources resulted in heterogeneity of exposure within the study arms. We will estimate the associations between early-life HAP exposures and CVH.

Aim 2: Assess the contribution of HAP exposure to metals exposures. Here, we will evaluate associations between 1) the GRAPHS intervention arm and airborne metal concentrations measured on maternal prenatal PM2.5 filters; and 2) airborne metals and established biomarkers of metal exposures in prenatal maternal urine.

a) Aim 2a. We hypothesize that LPG intervention assignment will be associated with lower airborne metal concentrations and altered composition compared to control.

b) Aim 2b. We hypothesize that airborne metal concentrations will be associated with urine biomarkers of metal exposures.

Aim 3: Estimate the association between prenatal metal exposures and childhood CVH.

a) Aim 3a. We will assess the association of airborne metal concentrations and urine biomarkers of metal exposures with Aim 1 measures of CVH.

b) Exploratory Aim 3b: We will assess the association between study arm assignment and prenatal HAP exposure, considered separately, and CVH before and after accounting for metal concentrations (airborne or urinary metal biomarkers, separately), using mediation analyses.

Methodology

The Ghana Randomised Air Pollution and Health Study (GRAPHS), a well-designed community randomized cookstove intervention trial, is used in this study to assess the independent impact of LPG cookstoves on adult respiratory health. Liquefied Petroleum Gas (LPG) stoves and the upgraded Biolite cookstove were compared to the conventional three-stone cookstove (control arm) in GRAPHS using a cluster-randomized design.

In order to measure the effect of the clean cookstove intervention on birth weight and incident pneumonia during the first year of life, a total of 1415 maternal-infant couples were recruited and followed up over a period of four years. A subset of 800 women from the LPG, Biolite, and control arms are being followed up on in this investigation on child lung function. In this prolonged follow-up.

In this prolonged follow-up, information on exposure monitoring will be gathered for each participant four times, and information on lung function and respiratory symptoms will be gathered for each participant twice, when the children are seven and four years old, respectively. Following completion of the final lung health assessment, children who actively followed the study were recruited into the cardiovascular health study. We anticipate that n=630 children will be recruited into this research protocol at age 9, resulting in n=570 children available for the age 12 assessment.

Expected Outcomes

This study expects to produce the following outcomes:

1. We expected the statistical analysis to reveal significant negative correlations between elevated early-life PM2.5 and CO levels and cardiovascular health indicators, such as blood pressure and heart rate variability.

2. Findings may demonstrate that children exposed to different sources of air pollution exhibit varying degrees of impact on cardiovascular health, highlighting the complexity of air quality effects.

3. Development of comprehensive risk profiles for children based on their exposure history, allowing for targeted interventions and public health recommendations.

4. Lower Blood Pressure: Children in the LPG intervention group are expected to exhibit lower systolic and diastolic blood pressure readings compared to the control group.

5. Evidence generated may inform policy decisions regarding air quality regulations and the promotion of cleaner cooking technologies to protect children's cardiovascular health.

Funder: National Institute of Health (NIH).

Study Duration : Four (4) Years

Start Date : April 2023

End Date : May 2027