Results
A total of 362,129 live births (351,139 singletons and 10,990 multiples) occurred during the pandemic period, and 1,117,172 live births (1,079,259 singletons and 37,913 multiples) during the historical period. The number and percentage of PTB in different categories of GA and of stillbirths in the two periods are presented in Table 1, together with unadjusted and adjusted overall OR of adverse perinatal outcomes based on meta-analysis. The pandemic period compared with the historical period was associated with a reduced risk for PTB (< 37 weeks’ GA), late PTB (32-36 weeks’ GA), very PTB (< 32 weeks’ GA), and extremely PTB (< 28 weeks’ GA), with very similar estimates in unadjusted and adjusted analyses. No association was instead found for stillbirths. Forest plots for unadjusted estimates are reported in Figures 1a-1d (for liveborn PTB) and S Figure 1 (for stillbirths), while those for adjusted estimates are reported in S Figures 2-6.
Singletons contributed 72.9% of all PTB, and in these the associations remained very similar to those in the whole population of neonates; for PTB the unadjusted OR was 0.92 [95% CI: 0.89; 0.95], for late PTB: 0.92 [95% CI: 0.89; 0.96], for very PTB: 0.88 [95% CI 0.84; 0.92], and for extreme PTB: 0.92 [95% CI: 0.85;1.00]. (S Figures 7-14)
Multiples represented 3.3% of all births and contributed 27.1% of all PTB; in all classes of PTB point estimates were not very different from those of singletons, but with wider CIs which encompassed the null value: PTB unadjusted OR: 0.93 [95% CI: 0.84;1.03]; late PTB: 0.94 [95% CI: 0.84; 1.04], very PTB: 0.90 [95% CI: 0.78; 1.4], and extreme PTB: 0.77 [95% CI: 0.58; 1.01]. (S Figures 15-22).
The interrupted time series regression analyzed 38 months before lockdown and 13 months after it, showing a decreasing trend in the overall percentage of PTB in the three years before the pandemic superimposed to a biannual seasonal oscillation. The de-seasonalized trend (estimated relative change of PTB percentage) was -0.17% per month, 95% CI: -0.26%; -0.09%. A further reduction of PTB prevalence (estimated relative change -4.2% compared with the previous period, 95%CI: -8.4%; 0.0%) after lockdown and other mitigation strategies was demonstrated (Figure 2), in addition to the continuing decreasing trend.
The comparison between the counterfactual scenario and actual trend after lockdown confirmed the drop in PTB prevalence (estimated mean decrease = -3.8%, 95%CI: -7.5%, -0.1%), which was particularly marked in the last months of 2020. (Figure S 23)
Similar results were found for the subclass of late PTB (trend in frequency before the pandemic: -0.14% per month, 95% CI: -0.22%; -0.06%; further change after lockdown: -4.3%, 95%CI: -8.4%; -2.9%), but not for very or extremely PTB, which had much lower frequencies and more scattered data (S Figures 24-26).
Interrupted time series analysis in singletons mirrored the results of the whole population (Figures S27-S30); no interruption was detected for multiple births (data not shown).