Impact of 2 years of COVID‐19 pandemic on preterm birth: Experience from a tertiary center of obstetrics in western Germany

To compare preterm birth rates and reasons before and during the COVID‐19‐pandemic using a monocentric, retrospective study.


| INTRODUC TI ON
Preterm births (PTB) are deliveries occurring before 37 weeks of pregnancy and are a leading cause of perinatal morbidity, mortality, and neurodevelopment delay. 1 The incidence of PTB in Germany has remained stable at 8%-9% since 2009. 2 There are two primary clinical etiologies of PTB: iatrogenic and spontaneous. 1Iatrogenic PTB is indicated in cases of maternal morbidity or fetal distress.Spontaneous PTB is precipitated by preterm labor or preterm prelabor rupture of membranes (PPROM). 1 The multifactorial causes include mechanisms involving infection, inflammation, uteroplacental ischemia/hemorrhage, stress, and other immunologically mediated processes, 3 yet they have not been conclusively investigated.
The COVID-19 pandemic has had a profound impact on the socioeconomic status of the population at large, as well as on maternal and neonatal outcomes throughout this period. 4The German government enforced two lockdowns, in 2020 and 2021, to reduce virus spread and prevent healthcare system overload.In addition, various measures were implemented between and after these periods to further mitigate the spread of infection. 5These factors significantly contributed to declining mental health during the pandemic, particularly affecting vulnerable populations such as patients with psychiatric disorders, individuals diagnosed with COVID-19, healthcare workers, children, and adolescents. 6Pregnant women were also affected by the situation. 6Multiple international studies have extensively examined the pandemic's impact on pregnant women and newborns, often focusing on perinatal outcomes and birth modes. 4,7wever, available data regarding PTB remain relatively sparse and present contradictory results.][10] In contrast, data from a trial conducted in Nepal indicated a substantial increase in PTB rates during the initial lockdown. 11e objective of this study is to assess the impact of the pandemic on the occurrence and underlying causes of PTB in a tertiary obstetrical center in western Germany.Additionally, we aim to analyze the influence of this period on neonatal outcomes for both term and preterm births.

| Data management
We obtained maternal and neonatal data by extracting information from digital patient records, hospital accounting data, and labor ward statistics at the tertiary obstetrical center of the University Hospital of Essen.The review period spans from January 2018 to December 2021.
To analyze the primary end-point PTB encompassing its incidence, timing, underlying causes, associated risk factors, and pregnancy complications, the study included all women delivering liveborn singletons between 22 +0 and 37 +0 weeks of pregnancy during the study period, totaling 593 cases.Prematurely born multiples or premature stillborn infants were excluded to analyze the primary end point.
The secondary end-point included stillbirth and neonatal and maternal outcomes in PTB as well as in term births (>37 +0 weeks of pregnancy) during the same period.The PTB group consisted of all 593 women, who gave birth to a liveborn singleton between 22 +0 and 37 +0 weeks of pregnancy.The term birth group consisted of all women and newborns, who were born after 37 +0 weeks of pregnancy, in the study period at our hospital (n = 4505).
The cohorts were stratified into two distinct periods: the pre-

| RE SULTS
Throughout the study period, our institution recorded a total of 6086 deliveries, with 3275 occurring pre-pandemic and 2811 during the pandemic.Among these deliveries, 593 cases of singletons born preterm and alive were observed, comprising 352 (10.7%) in the pre-pandemic group and 241 (8.6%) in the pandemic group.Notably, a decrease in the PTB rate was evident during the pandemic period COVID-19 pandemic, infant, prematurity, preterm birth, SARS-CoV-2, stillbirth, term birth compared with the pre-pandemic era (10.7% vs. 8.6%; odds ratio [OR] 0.79; 95% confidence interval 0.66-0.93)(Table 1, Figure 1).There were no significant changes noted in the stillbirth rate across all births, remaining at 0.43% before the pandemic and 0.50% during the pandemic (OR 1.17; 95% CI 0.55-2.45).
The incidence of iatrogenic terminated pregnancies within the PTB group showed a decrease from 54.4% to 49.4%, although this change was not statistically significant (P = 0.216).
It is noteworthy that the frequency of common risk factors among women who experienced PTB remained largely unchanged before and during the pandemic.These factors include gestational diabetes (12.2% vs. 13.7%;P = 0.597), a history of PTB (6.3% vs.
There were fewer spontaneous births, and an increase in elective and second-stage cesarean sections.Notably, the mean umbilical artery pH showed a slight improvement during the pandemic (7.25 vs. 7.26; P < 0.001).However, no significant differences were observed in other measured outcome parameters, such as Apgar scores and umbilical vein pH (Table 5).

| DISCUSS ION
This study aimed to evaluate the impact of the COVID-19 pandemic on PTB rates and causes.Our institution witnessed a notable 19.6% reduction in PTB rates during this period.Although the underlying causes for PTB changed, the risk factors remained consistent.
Additionally, the distribution by gestational age showed consistency throughout.
Been et al. 9 reported similar findings from the Netherlands, showing reduced PTB rates nationwide after the introduction of restrictive measures.In contrast to this and to our results, a Danish study by Hedermann et al. 12 analyzed 31 180 singleton births occurring annually between March 12 and April 14 from 2015 to 2020, revealing differing outcomes.Their study's overall PTB rate did not change during the lockdown.However, extremely PTB (<28 weeks of gestation) showed a clear reduction. 12In a study from Ireland, the authors came to a similar conclusion focusing on birth weight.In 30 705 births from one institution, the proportion of babies lighter than 1500 g dropped from 8.18 per 1000 in 2001-2019 to 2.17 per 1000 in 2020 (P = 0.022). 13single-center study from London (UK) explored pregnancy outcomes between 1681 births occurring before and 1718 births occurring during the pandemic until June 2020.Stillbirths increased from 1.2 per 1000 births to 7.0 per 1000 births (P = 0.01), with no significant change in PTB rate. 14The stillbirths were not in SARS-CoV-2-infected patients.Despite this, the possibility of asymptomatic infection cannot be completely ruled out in every instance.
In our cohort, stillbirths arose but without statistical significance (stillbirths among all births 0.43% vs. 0.50%, P = 0.68; stillbirths among preterm born infants 0.7% vs. 1.3%;P = 0.318).We presume that some of these stillbirths might be due to asymptomatic/unknown infection, because SARS-CoV-2 increases the risk of stillbirth. 15In addition, different virus types could have influenced the stillbirth rate and the PTB differently, 16 because different virus types are associated with different disease burden. 17e present study did not just cover the beginning of the pandemic as the compared studies 8-10,12-14 did, but covered the e Maternal diseases including women whose early delivery was indicated, e.g. because of carcinomas, deterioration of general maternal condition due to previous illness, states of exhaustion or therapy-refractory pregnancy cholestasis.f Fetal diseases including diabetic fetopathy, fetal hydrops, anencephaly, macrosomia, and fetal bradycardia.
pandemic from its beginning until the end of 2021, when the Delta variant was dominant.
In our institution, the Alpha variant showed the highest PTB rate at 10.9%, followed by the initial lockdown period when the wild-type was predominant, resulting in a PTB rate of 9.2%.Subsequently, the Delta variant gained prevalence, coinciding with a decrease in the PTB rate to 7.5%.Favre et al. 16 studied outcomes of 2055 unvaccinated SARS-CoV-2-positive pregnant women between March 2020 and September 2022, focusing on different virus variants (pre-Delta, Delta, Omicron periods).The Delta variant showed a significantly higher risk of severe maternal adverse outcomes (6.5%; 7 of 262; 95% CI 3.8%-10.2%).Additionally, the PTB rate was highest during the Delta period (13.7% [Delta] vs. 9.3% [pre-Delta] vs.

11.0% [Omicron]
).These findings align with observations in the unvaccinated general population, showing higher hospitalization and emergency room presentation rates during the Delta variant compared with the pre-Delta periods. 17The contradicting decrease in PTB rates in our institution during the Delta variant could be related to the fact that previous studies only included unvaccinated individuals.In our study, we did not specifically account for vaccination status or SARS-CoV-2 infection, although the outcomes could potentially have been influenced by vaccination status.Torche and Nobles 18 reported a protective effect of vaccination in relation to premature birth.This aspect might have played a role in our research setting, especially considering that since September 2021, the German Standing Vaccination Committee (STIKO) at the Robert Koch Institute explicitly included pregnant and unvaccinated breastfeeding women as target groups for COVID-19 vaccination in the official recommendation. 19e meta-analysis conducted by Chmielewska et al. 4 pandemic group (January 1, 2018 to December 31, 2019) and the pandemic group (January 1, 2020 to 31 December, 2021).As the data were retrospectively collected from existing patient records, obtaining informed consent from study participants was deemed unnecessary.The study received approval from the local ethics committee-the Ethik Kommission of the University Hospital of Essen, Robert-Koch-Strasse 9-11, 45 147 Essen, Germany, (No. 21-10 462-BO) and adhered to the guidelines outlined in the Declaration of Helsinki.

4 F I G U R E 2
also underscored this trend, reinforcing the consistency of our findings with the observed reductions or stable PTB rates during the pandemic in high-resource settings such as the USA and Denmark, even when considering the impact of the Delta variant.The authors demonstrated notable decreases in PTB rates specifically within highincome countries.They suggested that alterations in healthcare delivery and shifts in population behaviors might be influential factors contributing to these observed reductions.Reasons for prematurity.TA B L E 3 Preterm birth depending on weeks of gestation.a Abbreviations: CI, confidence interval; HELLP, hemolysis, elevated liver enzymes and low platelet count; IUGR, intrauterine growth restriction OR, odds ratio; PPROM, preterm prelabor rupture of membranes; PTB, preterm birth; SGA, small for gestational age.
20Values are number (percentage).Given the recognized risk factors and pathophysiologic aspects associated with PTB, 1 an expectation might have been for an increase in PTB rates during the pandemic.For instance, stress and anxiety, well established as risk factors for PTB, were notably heightened during the pandemic.6Furthermore,prenatalcarehas faced challenges during the pandemic.Townsend et al.,20in a meta-analysis, TA B L E 4 Pregnancy complications among preterm births.a a Values are number (percentage). T B L E 5 Neonatal outcomes in term births. aAbbreviations: CI, confidence interval; OR, odds ratio.a Data are presented as mean ± standard deviation or as number (percentage).