Increased rate of miscarriage during second wave of <scp>COVID</scp>‐19 pandemic in India

The lack of reliable data on the risk of miscarriage due to coronavirus disease 2019 (COVID-19) is a concern for both patients and obstetricians. A recent meta-analysis demonstrated an increased risk of adverse pregnancy outcome in low-to-middle-income countries (LMICs) when compared with high-income countries1. The second wave of the COVID-19 pandemic was reported to be more fatal than the first wave, with increased disease severity and maternal mortality2. However, the impact of the second wave of COVID-19 in India on the rate of miscarriage is unknown. We report on the incidence of miscarriage in a cohort of pregnant and postpartum women with COVID-19 (n = 1630) admitted to BYL Nair Charitable Hospital (NCH), Mumbai, India, between 1 April 2020 and 4 July 2021, during the first (1 April 2020 to 31 January 2021) and second (1 February 2021 to 7 July 2021) waves of the COVID-19 pandemic (Figure 1). Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed using reverse transcription polymerase chain reaction of nasopharyngeal swabs, as per the national testing guidelines. The data of the cohort admitted during the COVID-19 pandemic were compared to those of 11 952 women admitted prior to the pandemic between 1 October 2016 and 30 September 2018. This prepandemic period was selected due to uninterrupted obstetric and gynecological services and data availability. Miscarriage was defined as spontaneous pregnancy loss before 20 weeks of gestation or delivery of a dead fetus weighing less than 500 g. Intrauterine fetal demise (IUFD) was defined as in-utero death of a fetus that was confirmed by ultrasound before delivery. The study was approved by the ethics committees of TNMC (ECARP/2020/63) and ICMR-NIRRH (IEC no. D/ICEC/Sci-53/55/2020) and registered with the Clinical Trial Registry of India (CTRI#2020-025423). The rate of miscarriage per 1000 births was significantly higher during the second wave of the COVID-19 pandemic than that during the first wave (82.6 vs 26.8; P < 0.001) or the prepandemic period (odds ratio, 1.7 (95% CI, 1.16–2.59); P = 0.006). The rate of miscarriage per 100 admissions during the second wave of the COVID-19 pandemic was also significantly higher than that during the first wave (P < 0.004) or the prepandemic period (P = 0.003) (Table 1). During the prepandemic period, the rate of miscarriage was significantly higher in the months February to July (in 2017 and 2018) (55.7 per 1000 births) compared with the months April to January (in 2016, 2017 and 2018) (42.8 per 1000 births) (P = 0.004). Even so, the rate of miscarriage during the second wave of the COVID-19 pandemic (February–July 2021) was significantly higher compared with the same months in the prepandemic period in 2017 and in 2018 at NCH (P = 0.044) (Tables S1 and S2). The rate of IUFD was significantly higher during the COVID-19 pandemic compared with that during the prepandemic period (P = 0.006). The incidence of first- and second-trimester IUFD during the COVID-19 pandemic was higher compared with that in the prepandemic period, but the difference did not reach statistical significance (P = 0.09). The rate of second-trimester miscarriage was significantly higher during the COVID-19 pandemic as compared to the prepandemic period (P < 0.001) (Table 1). A higher number of symptomatic women with COVID-19 and miscarriage were reported during the first wave (7/22 (31.8%)) as compared to the second wave (5/28 (17.9%)) of the COVID-19 pandemic. During the second wave of the COVID-19 pandemic, 96.4% (27/28) of women with miscarriage conceived spontaneously, as compared to a rate of 77.3% (17/22) during the first wave (P = 0.07). Our study demonstrates that the risk of miscarriage during the second wave of the COVID-19 pandemic was three times higher compared with the first wave of the pandemic and two times higher compared with the prepandemic period. Although seasonal variation was observed and the rate of miscarriage was higher during February–July compared to April–January in the prepandemic period, we observed a significantly higher rate of miscarriage during the same months in the second wave of the COVID-19 pandemic. This is the first study to report on the increased rate of miscarriage during the second wave of the COVID-19 pandemic in India. The observed increased risk of miscarriage in women with COVID-19 supports the findings of a study conducted in Turkey3 but is in contrast to the findings of the studies from the USA4 and Canada5. The findings of our study support the observations that COVID-19 could disproportionately affect pregnant women in LMICs1 and women from an Asian ethnic background. The increased miscarriage rate during the second wave of the pandemic could be due to the high infectivity and virulence of the Delta (B.1.617.2) variant of SARS-CoV-2, which was reported to be responsible for the second wave in India6, leading to more IUFDs in both trimesters. Higher COVID-19 rates, fewer antenatal care visits, reduced access to nutritious food and travel restrictions during the second wave could also account for the increased rate of miscarriage during the second wave of the pandemic. However, further studies are required to demonstrate the causal link between fetal death and COVID-19. Limitations of this study include the lack of SARS-CoV-2 testing of products of conception and data on genome sequencing of SARS-CoV-2 strains. In conclusion, our study provides evidence to support counseling of women wishing to become pregnant during the ongoing COVID-19 pandemic and of those who become infected during the first trimester of pregnancy. In our study, COVID-19 appeared to be associated with an increased risk of miscarriage, especially during the second wave of the pandemic. Our findings are important for public health policy, especially for prioritizing the vaccination of pregnant women in India and other LMICs in light of the predicted third wave of the COVID-19 pandemic. We thank Dr Periyasamy Kuppusamy for his assistance in statistical analysis. The study was funded by intramural grant of ICMR-NIRRH (No. ICMR-NIRRH/RA/1070/05-2021). R.K.G. is an awardee of the DBT Wellcome Trust India Alliance Clinical and Public Health Intermediate Fellowship (Grant no. IA/CPHI/18/1/503933). Data available on request due to privacy/ethical restrictions Table S1 Seasonal variation in the rate of miscarriage observed prior to vs during the COVID-19 pandemic Table S2 Number of births and miscarriages in the evaluated period prior to the COVID-19 pandemic (1 October 2016 to 31 September 2018), overall and according to month Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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