Metabolic gestational age assessment in low resource settings: a validation protocol

Abstract

Preterm birth is the leading global cause of neonatal morbidity and mortality. Reliable gestational age estimates are useful for quantifying population burdens of preterm birth and informing allocation of resources to address the problem. However, evaluating gestational age in low-resource settings can be challenging, particularly in places where access to ultrasound is limited. Our group has developed an algorithm using newborn screening analyte values derived from dried blood spots from newborns born in Ontario, Canada for estimating gestational age within one to two weeks. The primary objective of this study is to validate a program that derives gestational age estimates from dried blood spot samples (heel-prick or cord blood) collected from health and demographic surveillance sites and population representative health facilities in low-resource settings in Zambia, Kenya, Bangladesh and Zimbabwe. We will also pilot the use of an algorithm to identify birth percentiles based on gestational age estimates and weight to identify small for gestational age infants. Once collected from local sites, samples will be tested by the Newborn Screening Ontario laboratory at the Children’s Hospital of Eastern Ontario (CHEO) in Ottawa, Canada. Analyte values will be obtained through laboratory analysis for estimation of gestational age as well as screening for other diseases routinely conducted at Ontario’s newborn screening program. For select conditions, abnormal screening results will be reported back to the sites in real time to facilitate counseling and future clinical management. We will determine the accuracy of our existing algorithm for estimation of gestational age in these newborn samples. Results from this research hold the potential to create a feasible method to assess gestational age at birth in low- and middle-income countries where reliable estimation may be otherwise unavailable.

Unlocking the global health potential of dried blood spot cards

“…Upon receipt, the samples were visually assessed for quality and considered unsatisfactory if there was insufficient blood, serum rings, or if the sample was clotted, layered, or otherwise overtly damaged. A detailed study protocol can be found here [10].…”

“…NSO screens for over thirty priority diseases using immunoassays, enzyme assays, high performance chromatography, liquid chromatography-mass spectrometry (LC-MS/MS), Flow Injection Analysis Tandem Mass Spectrometry (FIA-MS/MS), and quantitative real time PCR (qPCR) [10,11]. Sample receipt and analysis were integrated into the existing NSO workflow.…”

“…Sample receipt and analysis were integrated into the existing NSO workflow. Further details on analytes measured can be found here [4,5,10]. Priority analysis times were put in place for all biochemical testing and hemoglobinopathy screening, with the goal of completing analysis of priority conditions within 14 days of birth.…”

Real world external validation of metabolic gestational age assessment in Kenya

“…A detailed study protocol has previously been published which describes the study sites and provides further details on sample collection and processing [17]. The Kenya study site is located in Kisumu at the KEMRI Centre for Global Health Research, with field sites located in Siaya County, where a maternal-infant demographic surveillance program followed a prospective cohort of pregnant women and their infants in two community hospitals: Siaya County Referral Hospital (SCRH) and Bondo sub-County Hospital (BSCH).…”

A novel way of determining gestational age upon the birth of a child

“…Further validation of this approach is necessary to determine to what extent local factors may affect metabolic profiles, which in turn could impact the accuracy and generalisability of metabolic-derived estimates of GA. We are currently in the process of implementing and further evaluating this approach to GA estimation in multiple low-resource settings in sub-Saharan Africa and South Asia, including Kenya, Zambia, Zimbabwe, and Bangladesh [ 8 ]. Heel prick and/or cord blood samples are being obtained from infants in these sites and sent to Newborn Screening Ontario laboratories for further analysis.…”