Preterm Birth and Stillbirth During the COVID-19 Pandemic in Sweden: A Nationwide Cohort Study

Letters12 January 2021Preterm Birth and Stillbirth During the COVID-19 Pandemic in Sweden: A Nationwide Cohort StudyFREEBjörn Pasternak, MD, PhD, Martin Neovius, PhD, Jonas Söderling, PhD, Mia Ahlberg, RNM, PhD, Mikael Norman, MD, PhD, Jonas F. Ludvigsson, MD, PhD, and Olof Stephansson, MD, PhDBjörn Pasternak, MD, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, Martin Neovius, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, Jonas Söderling, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, Mia Ahlberg, RNM, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, Mikael Norman, MD, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, Jonas F. Ludvigsson, MD, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this author, and Olof Stephansson, MD, PhDKarolinska Institutet, Stockholm, SwedenSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-6367 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: A recent Danish study reported that the rate of extremely preterm birth was reduced during the lockdown period of the coronavirus disease 2019 (COVID-19) pandemic; the odds ratio (OR) was 0.09 (95% CI, 0.01 to 0.40) compared with previous years (1). Given the lockdown measures, potential mechanisms might include reduced exposure to various infectious agents, physical work strain, or stress; another explanation might be an increase in stillbirth, as the Danish study was based on live births. A study from the United Kingdom reported that stillbirth was more common during the pandemic; the difference was 6.93 (CI, 1.83 to 12.0) cases per 1000 births, corresponding to a 4-fold risk increase (2).Objective: To investigate associations between being born during a period when many public health interventions aimed at mitigating the spread of COVID-19 were enforced and the risk for preterm birth and stillbirth.Methods and Findings: We conducted a nationwide cohort study of singleton births using the Swedish Pregnancy Register. This register covers 92% of all births in Sweden and includes many variables describing the mother and newborn. The study was approved by the Swedish Ethical Review Authority.We compared the risk for preterm birth and stillbirth among births from 1 April through 31 May 2020, a period when Swedish authorities had enforced a range of pandemic mitigation interventions, with births from all April through May periods in the years 2015 to 2019 combined. Adjusting for maternal age, birth country, body mass index, smoking status, and parity, we used logistic regression to estimate ORs for preterm birth and stillbirth (multinomial logistic regression for preterm birth categories; SAS software, version 9.4 [SAS Institute]). The adjusted difference (events per 1000 births) was calculated as (adjusted OR − 1) × the proportion in the comparator group.There was no association between being born in the period April to May 2020, compared with April to May 2015–2019, and risk for extremely preterm birth (adjusted OR, 0.92 [CI, 0.66 to 1.28]), very preterm birth (adjusted OR, 1.09 [CI, 0.85 to 1.40]), moderately preterm birth (adjusted OR, 0.95 [CI, 0.87 to 1.03]), or stillbirth (adjusted OR, 0.78 [CI, 0.57 to 1.06]) (Table 1). In a sensitivity analysis in which mothers with COVID-19 were excluded, results were similar to those of the main analysis (Table 2). Among mothers in the cohort, the mean number of maternal health care visits was 2.3 (SD, 1.7) in April to May 2020; the corresponding number was 2.3 (SD, 1.7) in the combined April to May 2015–2019 periods.Table 1. Main Analysis of Risk for Preterm Birth and Stillbirth in Sweden: April to May 2020 Versus April to May Periods 2015−2019Table 2. Sensitivity Analysis of Risk for Preterm Birth and Stillbirth in Sweden, Excluding Mothers With COVID-19: April to May 2020 Versus April to May Periods 2015−2019Discussion: This nationwide study did not find any associations between being born during a period when many public health interventions aimed at mitigating the spread of COVID-19 were enforced and the risk for any of the preterm birth categories or stillbirth.This study did not confirm previously reported data from Denmark and the United Kingdom (1, 2). A difference between ours and the Danish study was the sample size, where our study was based on a total of 17 661 births during April to May 2020, of which 43 were extremely preterm. In the Danish study, there was 1 case of extremely preterm birth among 5162 births during the 1-month risk period. As opposed to the single-center study of stillbirth from the United Kingdom, ours was nationwide. Low event numbers and single-center designs may be sensitive to random variation. Given the observed estimates for stillbirth in the current study, further research is warranted to investigate the possibility of a decreased risk.These findings should be interpreted in the context of the COVID-19 mitigation strategy used in Sweden. Although society was not completely closed, Swedish authorities enforced many policies—all in action April to May 2020—to mitigate the spread of COVID-19, such as promotion of general hygiene measures and social distancing (including remote working), ban of nonessential travel, prohibition of gatherings of more than 50 people, and closure of upper secondary schools and universities. In effect, Sweden is estimated to have reached a reproduction number of severe acute respiratory syndrome coronavirus 2 infection below 1.0 by mid-April (3). Further, Sweden has also seen abrupt ends of the influenza and calicivirus seasons (contrasting with the smoother epidemiologic curves observed in previous seasons) (4, 5), supporting the notion that the pandemic public health interventions had substantial effects on the transmission of contagious infectious diseases. Still, given the harder lockdown enforced in Denmark, it is possible that differences in pandemic interventions lead to different effects on extremely preterm birth rates.References1. Hedermann G, Hedley PL, Bækvad-Hansen M, et al. Danish premature birth rates during the COVID-19 lockdown. Arch Dis Child Fetal Neonatal Ed. 2021;106:93-95. [PMID: 32788391] doi:10.1136/archdischild-2020-319990 CrossrefMedlineGoogle Scholar2. Khalil A, von Dadelszen, Draycott T, et al. Change in the incidence of stillbirth and preterm delivery during the COVID-19 pandemic. JAMA. 2020. [PMID: 32648892] doi:10.1001/jama.2020.12746 CrossrefMedlineGoogle Scholar3. Public Health Agency of Sweden. Country: estimation of the reproduction number. Article in Swedish. Accessed at www.folkhalsomyndigheten.se/contentassets/4b4dd8c7e15d48d2be744248794d1438/riket-skattning-av-det-momentana-reproduktionstalet-2020-08-03.pdf on 14 August 2020. Google Scholar4. Public Health Agency of Sweden. Calicivirus report week 15, 2020. Article in Swedish. Accessed at www.folkhalsomyndigheten.se/contentassets/0ad710ef377e4de6938e84b3a0ad7766/calicivirus-veckorapport-2020-v15_ny.pdf on 14 August 2020. Google Scholar5. Public Health Agency of Sweden. The influenza season 2019–2020. Article in Swedish. Accessed at www.folkhalsomyndigheten.se/globalassets/statistik-uppfoljning/smittsamma-sjukdomar/veckorapporter-influensa/2019-2020/influensasasongen-2019-2020-sasongssammanfattning-final-v3.pdf on 14 August 2020. Google Scholar Comments 0 Comments Sign In to Submit A Comment Alex Farr; Veronica Falcone; Michael WagnerMedical University of Vienna, Vienna, Austria5 February 2021 Preterm Birth and Stillbirth During the COVID-19 Pandemic in Sweden: A Nationwide Cohort Study To the Editor: With great interest, we have read the recent article by Björn Pasternak and colleagues entitled “Preterm Birth and Stillbirth During the COVID-19 Pandemic in Sweden: A Nationwide Cohort Study”.1 The authors analyzed data of the Swedish Pregnancy Register to determine if preterm birth, and stillbirth rates have changed during the SARS-CoV-2 pandemic. This question is important, as previously published studies from Denmark,2 as well as from the UK3, have reported a decrease in preterm birth rates and higher stillbirth rates during the ongoing coronavirus disease (COVID-19) pandemic, which limited services during pregnancy, labour, and childbirth worldwide. The authors did not detect a significant change in preterm or stillbirth rates during the pandemic, when many public health interventions aimed at mitigating the spread of COVID-19. The available data on the effects of limited obstetrical services during pregnancy, labor and childbirth that occurred worldwide during the pandemic’s first wave are sparse. Herewith, we want to contribute to the ongoing discussion by confirming the findings of Pasternak et al.1 for Austria. Data from the Austrian Perinatal Registry, obtained from all 82 obstetrical departments in the country, showed that the preterm birth rate among singleton liveborn newborns was 5.7% during the first term 2020, compared to 6.0% for the same time period of the 5 years before, which was not statistically significant (p=0.507). We also found that the differences between the stillbirth rates in 2020 and those of the 5 years before were not statically significant. Pasternak et al.1argued that their contradictory results might be due to different strategies during the pandemic, but enforcement of lockdown orders, as well as access to antenatal care, was more restricted in Austria than in Sweden. To conclude, data from our nationwide perinatal registry, which is similar to the Swedish registry, are in line with the data of Pasternak et al.1, showing no significant difference with regard to preterm birth and stillbirth between the pandemic and the pre-pandemic period. It should be critically analyzed whether regional purposes have caused this discrepancy to the available literature. This underlines the urgent need for epidemiologic studies in this field, which should question our current perinatal management, in order maintain and optimize high-quality perinatal care in the future. We would then have drawn a good lesson from this terrible pandemic. Acknowledgments The authors thank Sabrina Neururer from the Austrian Perinatal Registry for her analysis, as well as Angelika Berger and Herbert Kiss from the Medical University of Vienna for their enduring support. References Pasternak B, Neovius M, Söderling J, et al. Preterm Birth and Stillbirth During the COVID-19 Pandemic in Sweden: A Nationwide Cohort Study. Ann Intern Med. 2021 Jan 12. doi: 10.7326/M20-6367 [online ahead of print]. Hedermann G, Hedley PL, Baekvad-Hansen M, et al. Danish premature birth rates during the COVID-19 lockdown. Arch Dis Child Fetal Neonatal Ed. 2021 Jan;106(1):93-95. doi: 10.1136/archdischild-2020-319990. Epub 2020 Aug 11. Khalil A, von Dadeszen P, Draycott T, et al. Change in the Incidence of Stillbirth and Preterm Delivery During the COVID-19 Pandemic. JAMA 2020 Jul 10;324(7):705-706. doi: 10.1001/jama.2020.12746 [online ahead of print]. Roy K PhilipDivision of neonatology, Department of Paediatrics, School of Medicine University of Limerick and UL Hospitals, Limerick, Ireland15 February 2021 Prematurity rates in response to COVID-19 lockdown around the world: why is it variable? Dear Editor, Pasternak et al in their article, “Preterm Birth and Stillbirth During the COVID-19 Pandemic in Sweden: A Nationwide Cohort Study”, described a well conducted Registry analysis and observed no reduction in births of extreme preterm (EP, <28 weeks) or very preterm (VP, 28-32 weeks) infants during lockdown.1 While initial reports from Denmark, Ireland, Netherlands, UK, Canada, Australia and USA suggested an intriguing reduction of EP and VP births during the first COVID-19 lockdown2; reports from low- and middle-income countries (LMIC),3 and recent large multi-ethnic cohorts from USA4, did not concur with earlier European papers. Perhaps limitations of initial studies being addressed would have yielded more diverse results. Is lockdown teaching new perinatal lessons? Answers potentially reside in the implementation of ‘biggest natural socio-environmental experiment of modern times’ namely ‘COVID-19 lockdown’ and the preexisting population characteristics to which mitigation measures were applied to.2 Even assuming that the summative mitigation measures would have an impact on EP and VP pregnancies to progress towards higher gestations, following assumptions have to be operational for a favorable outcome, 1. Established maternal wellbeing indices, antenatal medical care and equity for timely access to perinatal care being in situ and sustained through the lockdown, 2. Gestational age from 20 weeks (lower cutoff for stillbirths) to 32 weeks (upper cutoff for VP) getting sufficient temporal exposure to ‘a lockdown with net maternal support’, potentially offering fetus with yet unidentified factors for sustenance in the intrauterine milieu, and 3. Whether maternal stress factors, nutrition, infection or environmental pollutant exposure had increased, decreased or remained unchanged through lockdown. Identical COVID-19 contingency measures could have variable socio-environmental impact in different populations. While Sweden adopted mitigation measures as part of their lockdown from 1st April to 31st May 2020,1 the Government Stringency Index5 was lower than in many other countries that described the reduction of EP and VP births during the 1st phase of pandemic. As the results of international perinatal epidemiological collaborative projects become available, and if birth cohorts and countries are stratified for analysis; one could speculate that the reduction of EP and VP births during the first COVID-19 lockdown could be limited to regions or countries sharing certain socioeconomic norms, similarities in healthcare access, population characteristics and human development index, on to which COVID-19 mitigation measures were applied to, and adopted by society. References: Pasternak B, Neovius M, Söderling J, et al. Preterm Birth and Stillbirth During the COVID-19 Pandemic in Sweden: A Nationwide Cohort Study. Ann Intern Med. 2021 Jan 12. doi: 10.7326/M20-6367 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 Glob Health. 2020 Sep;5(9):e003075. doi: 10.1136/bmjgh-2020-003075. PMID: 32999054; PMCID: 118 PMC7528371. Ashish KC, Gurung R, Kinney MV, et al. Effect of the COVID-19 pandemic response on intrapartum care, stillbirth, and neonatal mortality outcomes in Nepal: a prospective observational study. Lancet Glob Health. 2020;8(10):e1273-e1281. Main EK, Chang SC, Dhurjati R, et al. Singleton preterm birth rates for racial and ethnic groups during the coronavirus disease 2019 pandemic in California. Am J Obs Gynae 2020. doi: 10.1016/j.ajog.2020.01.026 Blavatnik School of Government and University of Oxford. Bsg.ox.ac.uk. Coronavirus Government response Tracker 2020. Available at: https://www.bsg.ox.ac.uk/research/research-projects/coronavirus-government-response-tracker [Accessed: 14th February 2021] Disclosures: No conflict of interest to disclose. Author, Article, and Disclosure InformationAuthors: Björn Pasternak, MD, PhD; Martin Neovius, PhD; Jonas Söderling, PhD; Mia Ahlberg, RNM, PhD; Mikael Norman, MD, PhD; Jonas F. Ludvigsson, MD, PhD; Olof Stephansson, MD, PhDAffiliations: Karolinska Institutet, Stockholm, SwedenFinancial Support: The study was supported by the Swedish Society of Medicine (grant SLS-937994) and NordForsk (grant 105545). Drs. Pasternak and Stephansson are supported by Karolinska Institutet Strategic Research Area Epidemiology investigator grants. The funding sources had no role in the conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-6367.Reproducible Research Statement: Study protocol and statistical code: Available from Dr. Pasternak. Data set: Not available.Corresponding Author: Björn Pasternak, MD, PhD, Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, 17176 Stockholm, Sweden; e-mail, bjorn.pasternak@ki.se.This article was published at Annals.org on 12 January 2021. 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in maternal, reproductive and child health: Results of an international surveyPerinatal Outcomes During the COVID-19 Pandemic in Ontario, CanadaPregnancy Outcome during the First COVID 19 Lockdown in Vienna, Austria June 2021Volume 174, Issue 6 Page: 873-875 Keywords Birth Cohort studies COVID-19 Disclosure Odds ratio Preterm birth Prevention, policy, and public health Research design Stillbirths Upper respiratory tract infections ePublished: 12 January 2021 Issue Published: June 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. 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