Postnatal Gestational Age Estimation Using Newborn Metabolic Profiles: A Validation Study in Matlab, Bangladesh

Background: Accurate preterm birth data are necessary for population health surveillance and to guide preterm birth initiatives. Gestational age is not routinely or accurately documented in many low-resource nations, however. Metabolic testing of newborn dried blood spots has been used to develop algorithms that yield accurate preterm birth estimates in North America. This study sought to validate published gestational age estimation models in infants born in Bangladesh. Methods: This was a prospective cohort study nested within the Preterm and Stillbirth Study, Matlab. The gestational age of all infants was confirmed by first trimester ultrasound. Cord blood and heel-prick blood spots were collected and analyzed at a provincial newborn screening facility in Ottawa, Canada. The performance of previously-published gestational age algorithms developed from heel-prick data to derive gestational age and preterm birth estimates was evaluated. Findings: 1036 cord blood and 487 heel-prick samples were collected from 1069 unique newborns. When applied to heel-prick metabolic profiles, published algorithms correctly estimated gestational age to within 1.07 weeks and accurately estimated gestational age to within 2 weeks for 94.3% of infants. Model performance was modestly reduced when applied to cord blood samples and accurately estimated gestational age to within 2 weeks for 90.3% of infants. Areas under the curve for distinguishing preterm births from term births were 0.945 (95%CI 0.890-0.999) for heel-prick samples and 0.894 (95%CI 0.853-0.935) for cord blood data. Interpretation: Metabolic gestational age dating provides accurate population-level estimates of gestational age and preterm birth burden. Models are effective on data obtained from both heel prick and cord blood, with the latter as a potentially more feasible option for deriving preterm birth estimates in low resource settings. Funding: This study was supported by the Bill & Melinda Gates Foundation [OPP1141535]. Declaration of Interest: The authors report no conflicts of interest Ethical Approval: Mothers provided informed consent for their infants to be included in the PreSSMat birth cohort and to have clinical data, cord blood and newborn heel prick samples collected and analysed. The present study was approved by the Research Review and Ethical Review Committees of the International Centre for Diarrhoeal Disease Research, Bangladesh (PR-16039). Approvals were also obtained from the Research Ethics Boards of the Ottawa Health Science Network (20160219-01H), and the Children’s Hospital of Eastern Ontario (16/20E).