Sheltering in Place and the Likelihood of Nonnatural Death.

Increasing hospitalizations for COVID-19 in the United States and elsewhere have ignited debate over whether to reinstate shelter-in-place policies adopted early in the pandemic to slow the spread of infection. The debate includes claims that sheltering in place influences deaths unrelated to infection or other natural causes. Testing this claim should improve the benefit/cost accounting that informs choice on reimposing sheltering in place. We used time-series methods to compare weekly nonnatural deaths in California with those in Florida. California was the first state to begin, and among the last to end, sheltering in place, while sheltering began later and ended earlier in Florida. During weeks when California had shelter-in-place orders in effect, but Florida did not, the odds that a nonnatural death occurred in California rather than Florida were 14.4% below expected levels. Sheltering-in-place policies likely reduce mortality from mechanisms unrelated to infection or other natural causes of death.

Selection in utero against male twins in the United States early in the COVID-19 pandemic.

OBJECTIVES: We aim to contribute to the literature reporting tests of selection in utero. The theory of reproductive suppression predicts that natural selection would conserve mechanisms, referred to collectively as selection in utero, that spontaneously abort fetuses unlikely to thrive as infants in the prevailing environment. Tests of this prediction include reports that women give birth to fewer than expected male twins, historically among the frailest of infants, during stressful times. The onset of the COVID-19 pandemic in the United States in Spring 2020 demonstrably stressed the population. We test the hypothesis that conception cohorts in gestation at the onset of the pandemic in the United States yielded fewer than expected live male twin births. METHODS: We retrieved deidentified data on the universe of live births in the United States from the National Center for Health Statistics birth certificate records. We applied Box-Jenkins time-series methods to the twin secondary sex ratio computed for 77 monthly conception cohorts spanning August 2013 to December 2019 to detect outlying cohorts in gestation at the onset of the pandemic. RESULTS: The twin secondary sex ratio fell below expected values in three conception cohorts (i.e., July, September, and October 2019, all p < .05) exposed in utero to the onset of the pandemic. CONCLUSIONS: Our results add to prior findings consistent with selection in utero. The role of selection in utero in shaping the characteristics of live births cohorts, especially during the COVID-19 pandemic, warrants further scrutiny.

Exposure to the early COVID-19 pandemic and early, moderate and overall preterm births in the United States: A conception cohort approach.

BACKGROUND: The United States (US) data suggest fewer-than-expected preterm births in 2020, but no study has examined the impact of exposure to the early COVID-19 pandemic at different points in gestation on preterm birth. OBJECTIVE: Our objective was to determine-among cohorts exposed to the early COVID-19 pandemic-whether observed counts of overall, early and moderately preterm birth fell outside the expected range. METHODS: We used de-identified, cross-sectional, national birth certificate data from 2014 to 2020. We used month and year of birth and gestational age to estimate month of conception for birth. We calculated the count of overall (<37 weeks gestation), early (<33 weeks gestation) and moderately (33 to <37 weeks gestation) preterm birth by month of conception. We employed time series methods to estimate expected counts of preterm birth for exposed conception cohorts and identified cohorts for whom the observed counts of preterm birth fell outside the 95% detection interval of the expected value. RESULTS: Among the 23,731,146 births in our study, the mean prevalence of preterm birth among monthly conception cohorts was 9.7 per 100 live births. Gestations conceived in July, August or December of 2019-that is exposed to the early COVID-19 pandemic in the first or third trimester-yielded approximately 3245 fewer moderately preterm and 3627 fewer overall preterm births than the expected values for moderate and overall preterm. Gestations conceived in August and October of 2019-that is exposed to the early COVID-19 pandemic in the late second to third trimester-produced approximately 498 fewer early preterm births than the expected count for early preterm. CONCLUSIONS: Exposure to the early COVID-19 pandemic may have promoted longer gestation among close-to-term pregnancies, reduced risk of later preterm delivery among gestations exposed in the first trimester or induced selective loss of gestations.

Expectations of non-COVID-19 deaths during the pre-vaccine pandemic: a process-control approach.

BACKGROUND: Debate over "social distancing" as a response to the pandemic includes the claim that disrupting clinical and public health programming dependent on human-to-human contact increased non-COVID-19 deaths. This claim warrants testing because novel pathogens will continue to emerge. Tests, however, appear frustrated by lack of a convention for estimating non-COVID-19 deaths that would have occurred had clinical and public health programming during the pre-vaccine pandemic remained as efficacious as in the pre-pandemic era. Intending to hasten the emergence of such a convention, we describe and demonstrate "new-signal, prior-response expectations" suggested by research and methods at the intersection of epidemiology and process control engineering. METHODS: Using German data, we estimate pre-pandemic public health efficacy by applying Box-Jenkins methods to 271 weekly counts of all-cause deaths from December 29 2014 through March 8 2020. We devise new-signal, prior-response expectations by applying the model to weekly non-COVID-19 deaths from March 9 2020 through December 26 2020. RESULTS: The COVID-19 pandemic did not coincide with more non-COVID-19 deaths than expected from the efficacy of responses to pre-pandemic all-cause deaths. CONCLUSIONS: New-signal, prior-response estimates can contribute to evaluating the efficacy of public health programming in reducing non-COVID-19 deaths during the pre-vaccine pandemic.

Patterned Outcomes, Unpatterned Counterfactuals, and Spurious Results: Perinatal Health Outcomes Following COVID-19.

The epidemiologic literature estimating the indirect or secondary effects of the coronavirus disease 2019 (COVID-19) pandemic on pregnant people and gestation continues to grow. Our assessment of this scholarship, however, leads us to suspect that the methods most commonly used may lead researchers to spurious inferences. This suspicion arises because the methods do not account for temporal patterning in perinatal outcomes when deriving counterfactuals, or estimates of the outcomes had the pandemic not occurred. We illustrate the problem in 2 ways. First, using monthly data from US birth certificates, we describe temporal patterning in 5 commonly used perinatal outcomes. Notably, for all but 1 outcome, temporal patterns appear more complex than much of the emerging literature assumes. Second, using data from France, we show that using counterfactuals that ignore this complexity produces spurious results. We recommend that subsequent investigations on COVID-19 and other perturbations use widely available time-series methods to derive counterfactuals that account for strong temporal patterning in perinatal outcomes.

Twinning during the pandemic: Evidence of selection in utero.

BACKGROUND AND OBJECTIVES: The suspicion that a population stressor as profound as the COVID-19 pandemic would increase preterm birth among cohorts in gestation at its outset has not been supported by data collected in 2020. An evolutionary perspective on this circumstance suggests that natural selection in utero, induced by the onset of the pandemic, caused pregnancies that would otherwise have produced a preterm birth to end early in gestation as spontaneous abortions. We test this possibility using the odds of a live-born twin among male births in Norway as an indicator of the depth of selection in birth cohorts. METHODOLOGY: We apply Box-Jenkins methods to 50 pre-pandemic months to estimate counterfactuals for the nine birth cohorts in gestation in March 2020 when the first deaths attributable to SARS-CoV-2 infection occurred in Norway. We use Alwan and Roberts outlier detection methods to discover any sequence of outlying values in the odds of a live-born twin among male births in exposed birth cohorts. RESULTS: We find a downward level shift of 27% in the monthly odds of a twin among male births beginning in May and persisting through the remainder of 2020. CONCLUSIONS AND IMPLICATIONS: Consistent with evolutionary theory and selection in utero, birth cohorts exposed in utero to the onset of the COVID-19 pandemic yielded fewer male twins than expected. LAY SUMMARY: Our finding of fewer than expected male twin births during the onset of the COVID-19 pandemic provides more evidence that evolution continues to affect the characteristics and health of contemporary populations.

Changes in preterm birth and caesarean deliveries in the United States during the SARS-CoV-2 pandemic.

BACKGROUND: Preliminary studies suggest that the SARS-CoV-2 pandemic and associated social, economic and clinical disruptions have affected pregnancy decision-making and outcomes. Whilst a few US-based studies have examined regional changes in birth outcomes during the pandemic's first months, much remains unknown of how the pandemic impacted perinatal health indicators at the national-level throughout 2020, including during the 'second wave' of infections that occurred later in the year. OBJECTIVES: To describe changes in monthly rates of perinatal health indicators during the 2020 pandemic for the entire US. METHODS: For the years 2015 to 2020, we obtained national monthly rates (per 100 births) for four perinatal indicators: preterm (<37 weeks' gestation), early preterm (<34 weeks' gestation), late preterm (34-36 weeks' gestation) and caesarean delivery. We used an interrupted time-series approach to compare the outcomes observed after the pandemic began (March 2020) to those expected had the pandemic not occurred for March through December of 2020. RESULTS: Observed rates of preterm birth fell below expectation across several months of the 2020 pandemic. These declines were largest in magnitude in early and late 2020, with a 5%-6% relative difference between observed and expected occurring in March and November. For example, in March 2020, the observed preterm birth rate of 9.8 per 100 live births fell below the 95% prediction interval (PI) of the rate predicted from history, which was 10.5 preterm births per 100 live births (95% PI 10.2, 10.7). We detected no changes from expectation in the rate of caesarean deliveries. CONCLUSIONS: Our findings provide nationwide evidence of unexpected reductions in preterm delivery during the 2020 SARS-CoV-2 pandemic in the US. Observed declines below expectation were differed by both timing of delivery and birth month, suggesting that several mechanisms, which require further study, may explain these patterns.

Sex-specific deaths in Norway and Sweden during the COVID-19 pandemic: Did mandates make a difference?

AIMS: To determine whether differences between Norway's and Sweden's attempts to contain SARS-CoV-2 infection coincided with detectably different changes in their all-cause mortality sex ratios. Measuring temporal variation in the all-cause mortality sex ratio before and during the pandemic in populations exposed to different constraints on risky behavior would allow us to better anticipate changes in the ratio and to better understand its association with infection control strategies. METHODS: I apply time Box-Jenkins modeling to 262 months of pre-pandemic mortality sex ratios to arrive at counterfactual values of 10 intra-pandemic ratios. I compare counterfactual to observed values to determine if intra-pandemic ratios differed detectably from those expected as well as whether the Norwegian and Swedish differences varied from each other. RESULTS: The male to female mortality sex ratio in both Norway and Sweden increased during the pandemic. I, however, find no evidence that the increase differed between the two countries despite their different COVID-19 containment strategies. CONCLUSION: Societal expectations of who will die during the COVID-19 pandemic will likely be wrong if they assume pre-pandemic mortality sex ratios because the intra-pandemic ratios appear, at least in Norway and Sweden, detectably higher. The contribution of differences in policies to reduce risky behavior to those higher ratios appears, however, small.

Non-COVID-19 deaths after social distancing in Norway.

Lay persons and policy makers have speculated on how national differences in the imposition of social distancing to reduce SARS CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has affected non-COVID-19 deaths. No rigorous estimation of the effect appears in the scholarly literature. We use time-series methods to compare non-COVID-19 deaths in Norway during its 9 weeks of mandated social distancing to those expected from history as well as from non-COVID-19 deaths in relatively less restricted Sweden. We estimate that 430 fewer Norwegians than expected died from causes other than COVID-19. We argue that failing to account for averted non-COVID-19 deaths will lead to an underestimate of the benefits of social distancing policies.