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.

Long-Term Fine Particulate Matter Concentrations and Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2: Differential Relationships by Socioeconomic Status Among Pregnant Individuals in New York City.

We aimed to determine whether long-term ambient concentrations of fine particulate matter (particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5)) were associated with increased risk of testing positive for coronavirus disease 2019 (COVID-19) among pregnant individuals who were universally screened at delivery and whether socioeconomic status (SES) modified this relationship. We used obstetrical data collected from New-York Presbyterian Hospital/Columbia University Irving Medical Center in New York, New York, between March and December 2020, including data on Medicaid use (a proxy for low SES) and COVID-19 test results. We linked estimated 2018-2019 PM2.5 concentrations (300-m resolution) with census-tract-level population density, household size, income, and mobility (as measured by mobile-device use) on the basis of residential address. Analyses included 3,318 individuals; 5% tested positive for COVID-19 at delivery, 8% tested positive during pregnancy, and 48% used Medicaid. Average long-term PM2.5 concentrations were 7.4 (standard deviation, 0.8) µg/m3. In adjusted multilevel logistic regression models, we saw no association between PM2.5 and ever testing positive for COVID-19; however, odds were elevated among those using Medicaid (per 1-µg/m3 increase, odds ratio = 1.6, 95% confidence interval: 1.0, 2.5). Further, while only 22% of those testing positive showed symptoms, 69% of symptomatic individuals used Medicaid. SES, including unmeasured occupational exposures or increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to concurrent social and environmental exposures, may explain the increased odds of testing positive for COVID-19 being confined to vulnerable pregnant individuals using Medicaid.

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.

The association of COVID-19 infection in pregnancy with preterm birth: A retrospective cohort study in California.

INTRODUCTION: Our understanding of the association between coronavirus disease 19 (COVID-19) and preterm or early term birth among racially and ethnically diverse populations and people with chronic medical conditions is limited. METHODS: We determined the association between COVID-19 and preterm (PTB) birth among live births documented by California Vital Statistics birth certificates between July 2020 and January 2021 (n=240,147). We used best obstetric estimate of gestational age to classify births as very preterm (VPTB, <32 weeks), PTB (< 37 weeks), early term (37 and 38 weeks), and term (39-44 weeks), as each confer independent risks to infant health and development. Separately, we calculated the joint effects of COVID-19 diagnosis, hypertension, diabetes, and obesity on PTB and VPTB. FINDINGS: COVID-19 diagnoses on birth certificates increased for all racial/ethnic groups between July 2020 and January 2021 and were highest for American Indian/Alaska Native (12.9%), Native Hawaiian/Pacific Islander (11.4%), and Latinx (10.3%) birthing people. COVID-19 diagnosis was associated with an increased risk of VPTB (aRR 1.6, 95% CI [1.4, 1.9]), PTB (aRR 1.4, 95% CI [1.3, 1.4]), and early term birth (aRR 1.1, 95% CI [1.1, 1.2]). There was no effect modification of the overall association by race/ethnicity or insurance status. COVID-19 diagnosis was associated with elevated risk of PTB in people with hypertension, diabetes, and/or obesity. INTERPRETATION: In a large population-based study, COVID-19 diagnosis increased the risk of VPTB, PTB, and early term birth, particularly among people with medical comorbidities. Considering increased circulation of COVID-19 variants, preventative measures, including vaccination, should be prioritized for birthing persons. FUNDING: UCSF-Kaiser Department of Research Building Interdisciplinary Research Careers in Women's Health Program (BIRCWH) National Institute of Child Health and Human Development (NICHD) and the Office of Research on Women's Health (ORWH) [K12 HD052163] and the California Preterm Birth Initiative, funded by Marc and Lynn Benioff.

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.