Jose Villar1,2, María C Restrepo-Méndez1,2, Rose McGready3,4, Fernando C Barros5, Cesar G Victora6, Shama Munim7, Aris T Papageorghiou1,2, Roseline Ochieng8, Rachel Craik1, Hellen C Barsosio9,10, James A Berkley11, Maria Carvalho8, Michelle Fernandes1,12, Leila Cheikh Ismail1,13, Ann Lambert1,2, Shane A Norris14, Eric O Ohuma1,15, Alan Stein16,17, Chrystelle O O Tshivuila-Matala1,14,18, Krina T Zondervan1,19, Adele Winsey1, Francois Nosten3,4, Ricardo Uauy20, Zulfiqar A Bhutta21, Stephen H Kennedy1,2. 1. Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom. 2. Oxford Maternal and Perinatal Health Institute, Green Templeton College, University of Oxford, Oxford, United Kingdom. 3. Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand. 4. Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom. 5. Programa de Pós-Graduação em Saúde e Comportamento, Universidade Católica de Pelotas, Pelotas, Brazil. 6. Programa de Pós-Graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, Brazil. 7. Division of Women and Child Health, Department of Obstetrics and Gynaecology, Aga Khan University, Karachi, Pakistan. 8. Faculty of Health Sciences, Aga Khan University, Nairobi, Kenya. 9. KEMRI Coast Centre for Geographical Medicine and Research, University of Oxford, Kilifi, Kenya. 10. KEMRI Centre for Global Health Research, Liverpool School of Tropical Medicine, Liverpool, United Kingdom. 11. KEMRI Wellcome Trust Research Programme, Nairobi, Kenya. 12. Faculty of Medicine, Department of Paediatrics, University of Southampton, Southampton, United Kingdom. 13. Clinical Nutrition and Dietetics Department, University of Sharjah, Sharjah, United Arab Emirates. 14. SAMRC Developmental Pathways For Health Research Unit, Department of Paediatrics and Child Health, University of the Witwatersrand, Johannesburg, South Africa. 15. Maternal, Adolescent, Reproductive and Child Health Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom. 16. Department of Psychiatry, University of Oxford, Oxford, United Kingdom. 17. MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. 18. Health, Nutrition and Population Global Practice, World Bank Group, Washington, DC. 19. Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. 20. Department of Nutrition and Public Health Interventions Research, London School of Hygiene and Tropical Medicine, London, United Kingdom. 21. Center for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada.
Abstract
Importance: The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures. Objective: To examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years. Design, Setting, and Participants: The INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020. Exposures/Interventions: Preterm-birth phenotypes. Main Outcomes and Measures: Infant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool. Results: A total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype. Conclusions and Relevance: Results of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity.
Importance: The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures. Objective: To examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years. Design, Setting, and Participants: The INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020. Exposures/Interventions: Preterm-birth phenotypes. Main Outcomes and Measures: Infant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool. Results: A total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype. Conclusions and Relevance: Results of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity.
Authors: Roberto Frenquelli; Marc Ratcliff; Jimena Villar de Onis; Michelle Fernandes; Fernando C Barros; Jane E Hirst; Aris T Papageorghiou; Stephen H Kennedy; Jose Villar Journal: Front Neurosci Date: 2022-04-18 Impact factor: 5.152