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Premature baby

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Impact of COVID-19 lockdown on the rate of very premature births

6 minutes

16/11/2020

Prof. Roy K Philip, FRCPI, MD, MBA

Impact of COVID-19 lockdown on the rate of very premature births: intriguing observations, some answers and more questions

World population has witnessed serious consequences of COVID-19 pandemic; some directly posed by the SARS-CoV-2 virus itself and the others from humanity’s limitations to cope with the societal ramifications of the illness per se or the mitigation measures initiated by Governments to combat the spread of the virus. In the midst of these maladies, observing closely one could also see a few rays of hope that emerged as a by-product of societal response to the COVID-19 pandemic. One such observation is a change in the rate of premature births, particularly involving extremely low birthweight (ELBW, <1,000 gm) and very low birthweight (VLBW, <1,500 gm) babies during the COVID-19 lockdown in various countries.

Our report from Limerick, Ireland in early June 2020 was one of the first studies in the world suggesting such an intriguing observation and a concurrent Danish study also posted similar findings.1,2 While Irish study observed an unprecedented 73% reduction of VLBW infants during the first four months of 2020 compared to the previous twenty years, Danish research reported over 90% reduction of extremely premature births in comparison to the previous five years.1,2 Two independent pre-prints that appeared in the literature with almost identical outcome from two European research groups triggered considerable interest from the scientific community as well the media. Newspapers and broadcasters from around the world, including The New York Times and BBC reported the rather unexpected and unprecedented results and the potential merits if the findings were to be replicated through larger studies from other geographical locations as well.3,4 What is so interesting in such a small epidemiological observation and why is it potentially so significant?

Prematurity (born <37 weeks of gestational age) accounts for approximately 1 in 10 births or over 15 million annually in the world, contributing significantly to neonatal morbidity and mortality.5 Global annual rate of preterm mortality approximate 1 million with over 80% contributed by developing and resource limited countries.5,6 Neonatal death (within 28 days of birth) is the single biggest contributor of under-five mortality globally and according to United Nations (UN) the most important factor to address in order to achieve the sustainable development goals (SDGs) for children.7 Even with all the advances in antenatal, midwifery, obstetric and neonatal care, it is worth noting that the rate of prematurity did not come down over the last three decades, in fact only increased in many parts of the world.8,9

In this context, we have analysed the summative socio-environmental impact of COVID-19 mitigation measures imposed by Irish Government and the behavioral modifications adopted by pregnant women that potentially influenced their wellbeing and that of unborn infants during the lockdown period.1 In many countries, even prior to the lockdown, practice of social distancing, enhanced hand hygiene measures and face mask usage were promoted. Lockdown itself was in effect a unique social experiment that controlled so many socio-environmental confounding variables that otherwise would not have happened in modern societies for many decades and would not be reproduced even through the implementation of a rigorous research protocol. For understandable reasons the healthcare delivery of pregnant women in modern medicine is primarily centered on hospital-based observations, monitoring and timely interventions. While this is extremely important and must continue, perhaps we as a society should give sufficient and deserving thrust to the family centered, culturally rooted and socio-environmentally modifiable factors that might offer invaluable adjunct benefits to maternal wellbeing and possibly nurture foetal growth towards the nature’s intended due maturity date.10

baby in incubator with nurse

Since the initial reports of reduction of births involving extremely premature and very low birthweight infants during the COVID-19 lockdown, maternity units from various countries published similar observations.2,3,11 However, a few reports have also suggested negative outcomes such as increase in stillbirth rate, increase in premature births and worsening maternal morbidity indices.12 What could be the reason for such a variation in outcomes? Perhaps the answer is in exploring the socio-economic background or pre-intervention characteristics of the population to which the COVID-19 lockdown mitigation measures were applied to, what supports were offered to pregnant women during the lockdown for the timely access to critical obstetric and perinatal services, what socio-environmental factors could have been modified in a given society as well as the behavioral modifications adopted by a given population in response to the imposed measures.1,11

Some of the known and non-modifiable reasons increasing the rate of prematurity such as history of previous premature births, multiple pregnancies and maternal illnesses have attracted considerable research already.13 Even after studying preterm premature rupture of membranes (PPROM), intra-amniotic inflammation, infectious mediators, immunological markers and variations in vaginal microbiota for many years, it is not yet clearly understood what exactly triggers the biological cascade leading to premature births.14,15,16 Our study and a few that followed prompt us to opt for a more holistic, family centered, primary care focused and socially rooted approach to influence the modifiable risk-factors that could be triggering premature birth. Based on previously published primary research, these modifiers include: better maternal nutrition, less work related stress, less commuting and associated stress, less of physically demanding and prolonged out of hours work, reduction of exposure to common infectious agents, reduced exposure to environmental pollution, optimal sleep and appropriate exercise, better partner support, prevention of intimate partner violence (domestic violence), optimal maternal immunizations, avoidance of cigarette smoke and alcohol as well as illicit drugs.17,18,19,20,21,22 Which one factor contributes the most is not yet understood, however the summative or cumulative effects of such socio-environmental modifiers potentially played a role in our observed reduction of prematurity.1,10,11

These findings also raise some socially challenging and difficult questions as well:

  • When should maternity leave commence to optimally benefit infant and mother?

  • How much of stress evoking or physically demanding prolonged work or out-of-hours work or commuting should pregnant women be expected to do, while also ensuring optimal foetal wellbeing?

  • Is it worth pursuing with some of the proven infection avoidance measures during pregnancy, even after the pandemic?

Our work and that of others that immediately followed would not be sufficient to answer these questions that could challenge the prevailing societal norms; however we should still pursue our search for the real reasons behind the enigma of premature births.1,2,11 International studies are already underway to understand and enlighten us regarding the true magnitude of the suggested possibilities, reasons behind the observed variations well as the evidence to support a causal relationship.

Conflicts of interest: None to report.

References
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1. Philip RK, Purtill H, Reidy E, Daly M, Imcha M, McGrath D, O’Connell NH, Dunne CP. Reduction in preterm births during the COVID-19 lockdown in Ireland: a ‘natural experiment’ allowing analysis of data from the prior two decades. medRxiv https://doi:10.1101/2020.06.03.20121442.

2. Hedermann G, Hedley PL, Beakvad-Hansen M, Hjalgrim H, Rostgaard K, Poorisrisak P, Breindahl M, Melbye M, Hougaard DM, Christansen M, Lausten-Thomsen U. Changes in premature birth rates during the Danish nationwide COVID-19 lockdown: a nationwide register-based prevalence proportion study. medRxiv 2020 https://doi.org/10.1101/2020.05.22.20109793.

3. Preston E. During coronavirus lockdowns, some doctors wondered: where are the preemies? The New York Times, 2020. Available: https://www.nytimes.com/2020/07/19/health/coronavirus-premature-birth.html (Accessed 8th November 2020)

4. BBC World News. What’s behind a drop in premature births during a lockdown? Available: https://www.bbc.co.uk/sounds/play/w3cszcc3 (Accessed 23rd July 2020)

5. Liu L, Oza S, Hogan D, Chu Y, Perin J, Zhu J, et al. Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016;388(10063):3027-35.

6. Harrison MS, Goldenberg RL. Global Burden of Prematurity. Semin Fetal Neonatal Med. 2016;21(2):74-9.

7. Ashorn P, Black RE, Lawn JE, Ashorn U, Klein N, Hofmeyr J, Temmerman M, Askari S. The Lancet Small Vulnerable Newborn Series: science for a healthy start. The Lancet 2020;396:743-745.

8. Purisch SE, Gyamfi-Bannerman C. Epidemiology of Preterm Birth. Semin Perinatol. 2017;41(7):387-391. doi: 10.1053/j.semperi.2017.07.009.

9. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and Causes of Preterm Birth. Lancet. 2008;371(9606):75-84. doi: 10.1016/S0140-6736(08)60074-4.

10. Philip RK, Purtill H, Reidy E, Daly M, Imcha M, McGrath D, O’Connell NH, Dunne CP. Unprecedented reduction in births of very low birthweight (VLBW) and extremely low birthweight (ELBW) infants during the COVID-19 lockdown in Ireland: a ‘natural experiment’ allowing analysis of data from the prior two decades. BMJ Global Health. 2020;5:e003075.

11. Been JV, Ochoa LB, Bertens LCM, Schoenmakers S, Steegers EA, Reiss IK. Impact of COVID-19 mitigation measures on the incidence of preterm birth: a national quasi-experimental study. The Lancet Public Health. 2020. doi. 10.1016/S2468-2667(20)30223-1

12. Khalil A, von Dadelszen P, Draycott T, Ugwumadu A, O’Brien P, Magee L. Changes in the incidence of preterm delivery during the COVID-19 pandemic. JAMA 2020;324:75-84.

13. Frey HA, Klebanoff MA. The Epidemiology, Etiology, and Costs of Preterm Birth. Semin Fetal Neonatal Med. 2016;21(2):68-73. doi: 10.1016/j.siny.2015.12.011.

14. Muñoz-Pérez VM, Oritz MI, Carino-Cortes R, Fernandez-Martinez E, Rocha-Zavaleta L, Bautista-Avila M. Preterm Birth, Inflammation and Infection: new alternative Strategies for Their Prevention. Curr Pharm Biotechnol. 2019;20(5):354-365. doi: 10.2174/1389201020666190408112013.

15. Govindaswami B, Jagatheesan P, Nudelman M, Narasimhan SR. Prevention of Prematurity: Advances and Opportunities. Clin Perinatol. 2018;45(3): 579-595. doi: 10.1016/j.clp.2018.05.013.

16. Zeitlin J, Szamotulska K, Drewniak N, Mohangoo AD, Chalmers J, Sakkeus L, Irgens L, Gatt M, Gissler M, Blondel B, Euro-Peristat Preterm Study Group. Preterm Birth Time Trends in Europe: A Study of 19 Countries. BJOG. 2013;120(11):1356-65. doi: 10.1111/1471-0528.12281.

17. Staneva A, Bogossian F, Pritchard M, Wittkowski A. The effects of maternal depression, anxiety and perceived stress during pregnancy on preterm birth: A systematic review. Women Birth. 201528(30;179-93. doi: 10.1016/j.wombi.2015.02.003.

18. Hall JS, Ferguson SA, Turner AI, Robertson SJ, Vincent GE, Aisbett B. The effect of Working On-Call on Stress Physiology and Sleep: A Systematic Review. Sleep Med Rev. 2017;33:79-87. doi: 10.1016/j.smrv.2016.06.001.

19. Bonzini M, Coggon D, Godfrey K, Inskip H, Crozier S, Palmer KT. Occupational Physical Activities, working Hours and Outcome of Pregnancy: Findings From the Southampton Women’s Survey. Occup Environ Med. 2009;66(10):685-90. doi: 10.1136/oem.2008.043935.

20. Meijer WJ, van Noortwijk AGA, Bruinse HW, Wensing AMJ. Influenza Virus Infection in Pregnancy: A Review. Acta Obstet Gynecol Scand. 2015;94(8):797-819. doi: 10.1111/aogs.12680.

21. Watson LF, Taft AJ. Intimate Partner Violence and the Association With very Preterm Birth. Birth. 2013;40(1):17-23. doi: 10.1111/birt.12024.

22. Bergin N, Murtagh J, Philip RK. Maternal Vaccination as an Essential Component of Life-course Immunization and Its Contribution to Preventive Neonatology. Int J Environ Res Public Health. 2018;15(5):847. doi: 10.3390/ijerph15050847.

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