key: cord-0757501-kc5wcv99
authors: Muin, Dana A.; Neururer, Sabrina; Falcone, Veronica; Windsperger, Karin; Helmer, Hanns; Leitner, Hermann; Kiss, Herbert; Farr, Alex
title: Antepartum stillbirth rates during the COVID‐19 pandemic in Austria: A population‐based study
date: 2021-10-31
journal: Int J Gynaecol Obstet
DOI: 10.1002/ijgo.13989
sha: 3d3091dc847884e69f53f63e8849d6c93f6bb96a
doc_id: 757501
cord_uid: kc5wcv99

BACKGROUND: The coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 has had dramatic effects on the pregnant population worldwide, increasing the risk of adverse perinatal outcomes. OBJECTIVE: To assess the incidence of antepartum stillbirth (aSB) during the COVID‐19 pandemic in Austria. METHODS: We collected epidemiological data from the Austrian Birth Registry and compared the rate of aSB (i.e., fetal death at or after 24(+0) gestational weeks) during the pandemic period (March–December 2020) and in the respective pre‐pandemic months (2015–2019). RESULTS: In total, 65 660 pregnancies were included, of which 171 resulted in aSB at 33.7 ± 4.8 gestational weeks. During the pandemic, the aSB rate increased from 2.49‰ to 2.60‰ (P = 0.601), in contrast to the significant decline in preterm deliveries at or before 37 gestational weeks from 0.61‰ to 0.56‰ (relative risk [RR] 0.93; 95% confidence interval [CI] 0.91–0.96; P < 0.001). During the first lockdown, the aSB rate significantly increased from 2.38‰ to 3.52‰ (P = 0.021), yielding an adjusted odds ratio of 1.57 (95% CI 1.08–2.27; P = 0.018). The event of aSB during the COVID‐19 pandemic was strongly related with increased fetal weight and maternal obesity. CONCLUSION: In Austria, there has been an overall increase in the incidence of aSB during the pandemic with a significant peak during the first lockdown.

In March 2020, the World Health Organization declared coronavirus disease 2019 (COVID-19)-caused by the the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-a global pandemic 1 and ever since, the disease has had profound direct and indirect effects on the pregnant population worldwide. On the one hand, the direct effects of SARS-CoV-2 have caused a wide spectrum of symptoms in pregnant women in the case of infection, leading to a mild to severe maternal disease with increased risk for pulmonary disease and need for intensive care. 2, 3 On the other hand, placental infections threaten fetal well-being, contributing to both placental dysfunction and vertical transmission to the fetus. 4 The indirect effect of the pandemic may hypothetically involve the individual's adoption of poor lifestyle habits due to social distancing, lockdowns, and redundancy, fostering unfavorable behaviors, such as smoking, high-caloric intake, and becoming more sedentary. 5 Also health-seeking behavior rapidly decreased, resulting in less frequent clinical check-ups. Lastly, closures and reductions in the public healthcare system with disruptions to follow-up visits and regular obstetric monitoring significantly impacted the management of both low-and high-risk pregnancies. 6 We hypothesized that the restrictions in healthcare services and changes in prenatal care in Austria during the pandemic have negatively impacted perinatal outcomes, as reflected by the prevalence of antepartum stillbirth. We, therefore, conducted a population-based study to assess the antepartum stillbirth rate-defined as fetal death at or after 24 +0 gestational weeks, during the pandemic (March-December 2020) and in the pre-pandemic era (matched months 2015-2019).

The Austrian Birth Registry prospectively collects maternal demographic and perinatal data from the obstetrical database ViewPoint (General Electric Company) of all maternity units in Austria, including registered home deliveries. For this study, we retrieved data from the Austrian Birth Registry during two distinct time periods: from March 16, 2020 to April 13, 2020 (reflecting the first lockdown phase in Austria), and from March 1, 2020 to December 31, 2020 (reflecting the pandemic era in Austria). Data were compared with the analogue periods between 2015 and 2019. We included all singleton live and stillborn deliveries at or after 24 +0 gestational weeks. We excluded multiple pregnancies, intrapartum and perinatal deaths, and stillborn fetuses following late terminations of pregnancy and those with congenital anomalies (Figure 1 ).

After a data check for integrity and consistency, all patient data were de-identified and the database was frozen before analysis.

In Austria, the government issued three lockdown phases to reduce the spread of SARS-CoV-2. The first lockdown was undertaken from March 16 to April 13, 2020 (i.e.,, 27 days), the second lockdown was from November 17 to December 6, 2020 (i.e., 19 days), and the third lockdown was from December 26, 2020 to February 7, 2021 (i.e., 41 days). As the first lockdown was the most tight and severe phase in this country, our analyses refer to this phase only.

Categorical data are presented as absolute (n) and relative (%) frequencies. We compared categorical data with the χ 2 test, and continuous data with an unpaired t test. Log-binomial regression and logistic regression were performed to assess risk ratios (RR) and odds ratios (OR). All ratios and difference measures are accompanied by a 95% confidence interval (CI). A two-sided P value less than 0.05 represents statistical significance. The analyses were performed using STATA 16 (StataCorp LLC, College Station, TX, USA). 

Patients and the public were not involved in the design, conduct, reporting, interpretation, and dissemination of the results of this study. During the pandemic and in comparison with the preceding years, the total pregnant female population was older (30.7 ± 5.3 years; P < 0.001), had a higher BMI (24.3 ± 5.3; P < 0.001), and a higher parity (25.8% versus 22.8%; P < 0.001). Likewise, mean newborn weight and length were higher during the pandemic than in the previous years (3364 ± 546 g vs. 2247 ± 521 g and 50.9 ± 3.3 cm vs. 50.7 ± 2.7 cm, respectively; P < 0.001).

The rate of preterm delivery at or before 37 gestational weeks decreased from 6.1% to 5.6% (RR 0.93; 95% CI 0.90-0.96) during the pandemic compared with the pre-pandemic era (P < 0.001), the stillbirth rate increased from 2.49‰ to 2.60‰ (RR 1.1; 95% CI 1.06-1.17; P = 0.601; Table 1 ).

In particular, during the first lockdown phase, the risk of experiencing stillbirth increased to RR 1.48 (95% CI 1.06-1.06; P = 0.022), and to RR 1.56 (95% CI 1.08-2.27; P = 0.018) after adjustment for maternal age, BMI, and nicotine consumption (Table 2) between March and April 2020, compared with the preceding years (P = 0.021; Figure 2 ). Table 3 shows the fetal and maternal characteristics in antepartum stillbirth events during the pandemic and pre-pandemic eras.

The event of antepartum stillbirth during the pandemic was strongly related to increased fetal weight (RR 1.00, 95% CI 1.00-1.00; P < 0.001) and obesity class III (i.e., BMI ≥ 40.0: RR 2.54, 95% stillbirths in 265 women with SARS-CoV-2 infection, 7 the incidence of stillbirth among women affected by COVID-19 has been extrapolated to 11.5 per 1000 total births, reflecting a three-fold increase compared with the national rate of 4.1 per 1000 live births in the UK. 8 As a reaction to gather more robust evidence, institutional, regional and national data have been analyzed. In a large Londonbased tertiary referral center, the comparison of antepartum stillbirths (above 22 weeks of gestation and excluding terminations of pregnancy) from October 2019 to January 2020 and February to June 2020 resulted in a four-fold institutional increase in the local stillbirth rate from 1.19‰ to 6.98‰ (OR 5.79, 95% CI 1.54-10.1; 9 with a constantly high incidence of 14.2‰ throughout the following months. 10 To counterbalance these local data, a further UK study assessed regional and national hospitalization data from England, including antepartum stillbirths above 24 weeks of gestation, during the pandemic from April to June 2020 and in the pre-pandemic period between 2016 and 2019, concluding neither a regional nor a national increase in stillbirth rates in England. 11 These data support the findings of another institutional study from the UK showing no statistical difference in rates of stillbirths or decrease in preterm births. 12 Further data published on stillbirth rates in Europe continued to reflect the conflicting evidence. A regional study from Italy observed a three-fold increase from 1.07‰ to 3.23‰ between March and May 2020 versus 2019. 13 In contrast, in Denmark, stillbirth rates declined from a pre-pandemic rate of 3.3‰ to 2.7‰ during the lockdown from April to May 2020 (adjusted OR 0.78, 95% CI 0.57-1.06) with no compensatory increase in the rate of preterm delivery. 14 Likewise, Spanish data confirm no increase either (OR 0.9, 95% CI 0.37-2.18) 15 as do the population data from Germany, showing a pre-pandemic stillbirth rate of 4.24‰ between January and July 2019 compared with 4.15‰ between the respective months during the COVID-19 pandemic. 16 Recent meta-analyses on population stillbirth rates during the pandemic and historical cohorts from the pre-pandemic era show that, in high-income countries, stillbirth rates, unrelated to maternal SARS-CoV-2 infection, remained stable, as shown in the synthesis of 21 studies from 18 countries (OR 1.08, 95% CI 0.94-1.23; P = 1.23; adjusted OR 1.06, 95% CI 0.81-1.38); in a further 14 studies from nine countries (OR 1.38, 95% CI 0.94-2.02; P = 0.099; I 2 = 52%) 18 ; or another analysis including 12 studies (OR 1.113, 95% CI 0.834-1.485). 19 In accordance with our findings, an increase in birth weight was reported by six studies (mean difference 17 g, 95% CI 7-28 g) during the pandemic period. 17 However, we agree that the incidence of antepartum stillbirth is still alarmingly high, and that "there has never been a more urgent time" to conceal the direct and indirect drivers of increased stillbirth rates during the pandemic. 20 The major strength of our study is the high quality of its validated data derived from a nationwide birth registry. Our strict inclusion and exclusion criteria resulted in a homogeneous and concise cohort of antepartum fetal deaths only, excluding late terminations of pregnancy and fetal congenital malformations, which may have led to stillbirth irrespective of the pandemic. Furthermore, the present study design comparing two distinct time periods, reduced potential seasonal variances that could influence the overall stillbirth rates.

Our study is limited by its retrospective design with potentially missing data, errors in maternal data collection across study sites, and the failure to control for recall bias. Of note, we lack insight into the exact causes of fetal death in individual cases, and also, no data were available on the maternal SARS-CoV-2 infection status before, during, and after the event of stillbirth. However, for the latter, the low numbers of pregnant women in Austria who had COVID-19 during the study period, and particularly during the first lockdown phase, need to be considered. In conclusion, in Austria, there has been an overall rise in the antepartum stillbirth rate during the COVID-19 pandemic. Particularly during the first lockdown phase, there has been a significant incidence peak, associated with maternal and fetal weight. This should be considered with regard to future perinatal management, in order to maintain high-quality perinatal care during the ongoing COVID-19 pandemic.

DAM acknowledges the support of Prof. DDr. J.C. Huber.

The authors have no conflicts of interest.

We confirm that all authors fulfilled all conditions required for authorship, as all authors contributed to the conception, planning, and carrying out of the research. DAM and AF conceived the study. DAM wrote the first draft of this paper. DAM, KW, HK, and AF designed the study. SN, HH, and HL acquired the data. DAM, SN, and HL conducted the statistical analyses. All authors contributed to critically TA B L E 3 Fetomaternal characteristics of stillbirth events in Austria from March to December, and from March to April, respectively, during the pandemic period and the preceding years a 

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Antepartum stillbirth rates during the COVID-19 pandemic in Austria: A population-based study