Interpretation
Our data on a reduction in PTB concomitant with the COVID-19 pandemic period are concordant with those of two recent national-based studies published after the systematic review and meta-analysis of Yang and coll.,9 which concluded that a reduction in the odds of PTB was observed only in single-center studies. The first of these studies was conducted in Israel,18 on birth data from the Israel national newborn screening program and showed a 10% decline in all preterm deliveries during the COVID-19 pandemic national lockdown period. The second one, in UK,15 used administrative hospital records and found a slightly lower frequency of preterm birth rates (from 6.1% to 6.0%) during the entire pandemic period compared to pre-lockdown.
In our study, we considered events (PTB and stillbirths) up to the end of March 2021, when most mitigation strategies stopped in Italy. Most of the previous nationwide studies in Europe4,16,17 and large regional studies in other countries,19-21 were instead restricted to 2020- mostly to the first months of the year. The larger time span considered allowed us to also study women who experienced changes in care and social activities for most of or all the pregnancy. This is not trivial, as multiple factors at different times during pregnancy might have had an impact on the rate of preterm deliveries. Though there are not, so far, studies available on this interesting topic, we can speculate in accordance with others15,18 that lifestyle and behavior (more rest, working from home, reduced exposure to other respiratory pathogens), might have contributed to PTB reduction. Other possible pandemic-related changes, which are known to impact on PTB, might have been the adoption of a different and healthier diet,22 and diminished exposure to air pollution.23
Finally, the large reduction in activity of Medical Assisted Reproduction services at the beginning of the pandemic period (end of February-April 2020)24 could be responsible of the marked drop in PTB prevalence we observed in the last months of 2020.
In univariable and multivariable logistic analyses we found an inverse association between being born in the pandemic period and being late PTB, but also very PTB and extremely PTB. With the interrupted time series regression analysis we were able to demonstrate a reduction in the frequency of PTB after the lockdown only for the subgroup of late PTB, and not for the other subgroups which had much lower frequencies and thus more scattered data. Similar results were reported with this type of analysis by Been et al.16 in the Netherlands and by Bian et al.25 in China, while in Canada Shah et al.20 did not find any significant change either in the rates of all PTB or in the subgroups.
We also analyzed separately singletons and multiples; as expected for singletons, who constituted 72.9% of all PTB, we found results very similar to those of the total population, while for multiples we probably had a lower power to reach conclusive results. In detail, for multiples, all point estimates were very similar to those of singletons and below 1, indicating a reduction in PTB during the pandemic, but the CIs in the logistic analyses were wide, and encompassing the null value, especially for very preterm and extremely preterm infants. No data are available in the literature on the pattern of preterm multiples during the COVID-19 pandemic in comparison to previous years. These data would have been interesting, considering that PTB is largely represented in multiple pregnancies (in our data 61.7% of all multiples are born before 37 weeks’ GA) which are in turn associated with assisted conception which possibly decreased during the COVID-19 period. A sub analysis on multiples pregnancies would probably require an international collaboration to have larger sample sizes.
Finally, though we elected as the main analysis the unadjusted one, because we wanted to abstain to correct for variables which could not be considered “true” confounder, our results were unchanged after adjustment for many covariates considered in previous studies like maternal ethnicity /country of birth, socioeconomic background/income/ education, maternal age, parity, and pregnancy conceived with ART.15,17,19,