The pandemic preterm paradox: A test of competing explanations.

Epidemiologists have long argued that side effects of the stress response include preterm birth. Research reports that fear of lethal infection stressed pregnant persons at the outset of the COVID-19 pandemic and that "shutdowns" and "social distancing" impeded access to social support and prenatal care. The decline in preterm births in high-income countries, including the United States (US), during the early months of the pandemic therefore poses a paradox for science. Explanations of this "pandemic preterm paradox" remain untested. We apply time-series modeling to data describing 80 monthly conception cohorts begun in the US from July 2013 through February 2020 to determine which of 3 explanations most parsimoniously explains the paradox. We infer that "prior loss," or the argument that an increase in spontaneous abortions and stillbirths depleted the population of fetuses at risk of preterm birth, best explains data currently available. We describe the implications of these results for public health practice.

Scarring In Utero: An Attempt to Validate With Data Unconfounded by Migration and Medical Care.

BACKGROUND: "Scarring in utero" posits that populations exposed to injurious stressors yield birth cohorts that live shorter lives than expected from history. This argument implies a positive historical association between period life expectancy (i.e., average age at death in year t) and cohort life expectancy (i.e., average lifespan of persons born in year t). Tests of the argument have not produced consistent results and appear confounded by autocorrelation, migration, and access to medical care. Here we test whether, as predicted by scarring in utero, sex-specific period and cohort life expectancy appear positively related among Swedes born from 1751 through 1800. If scarring has ever influenced longevity, we should detect signals of its effects in these cohorts because, unlike other populations with known life span, they aged in place and unlikely benefitted from increased access to efficacious medical care. METHODS: We use Box-Jenkins methods to control autocorrelation and measure associations. RESULTS: Contrary to the scarring hypothesis, we find an inverse association between period and cohort life expectancy. Our findings imply that, among males, variation in injurious stress on the population predicted changes in cohort life span ranging from a gain of approximately 67 weeks to a loss of about 45 weeks of life and among females from a gain of approximately 68 weeks to a loss of about 38 weeks of life. CONCLUSION: Epidemiologists trying to understand and explain temporal variation in cohort life expectancy should view the scarring argument with greater skepticism than currently found in the literature.

Racial disparities in law enforcement/court-ordered psychiatric inpatient admissions after the 2008 recession: a test of the frustration-aggression-displacement hypothesis.

BACKGROUND: Societies under duress may selectively increase the reporting of disordered persons from vulnerable communities to law enforcement. Mentally ill African American males reportedly are perceived as more threatening relative to females and other race/ethnicities. We examine whether law enforcement/court order-requested involuntary psychiatric hospitalizations increased among African American males shortly after ambient economic decline-a widely characterized population stressor. METHODS: We identified psychiatric inpatient admissions requested by law enforcement/court orders from 2006 to 2011 across four US states (Arizona, California, New York, North Carolina). Our analytic sample comprises 13.1 million psychiatric inpatient admissions across 95 counties over 72 months. We operationalized exposure to economic downturns as percent change in monthly employment in a metropolitan statistical area (MSA). We used zero inflated negative binomial and linear fixed effects regression analyses to examine psychiatric inpatient admissions requested by law enforcement/court orders following regional employment decline over a time period that includes the Great Recession of 2008. FINDINGS: Declines in monthly employment precede by one month a 6% increase in psychiatric hospitalizations requested by law enforcement/court order among African American males (p < 0.05), but not among other race/sex groups. Estimates amount to an excess of 2554 involuntary admissions among African American males statistically attributable to aggregate-level employment decline. CONCLUSIONS: Economic downturns may increase involuntary psychiatric commitments among African American males. Our findings underscore the unique vulnerability of racial/ethnic minorities during economic contractions.

Excess Injury Mortality in Washington State During the 2021 Heat Wave.

PUBLIC HEALTH IMPLICATIONS: Under global warming scenarios, heat waves of this magnitude will become much more common. Adaptation and planning efforts are needed to protect residents of the historically temperate Pacific Northwest for a range of health outcomes. (Am J Public Health. 2023;113(6):657-660. https://doi.org/10.2105/AJPH.2023.307269).

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.

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.

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.

The 2016 Presidential Election and Prenatal Care Utilization Among Foreign-born Hispanic Pregnant People.

BACKGROUND: Few studies have evaluated the relationship between adequate and timely prenatal care among immigrant pregnant people and the recent political climate, including the 2016 election and associated campaigns. OBJECTIVES: We examine whether the 2016 presidential election was associated with changes in prenatal care utilization among US foreign-born Hispanic pregnant people. RESEARCH DESIGN: Interrupted time series. SUBJECTS: All foreign-born Hispanic and US-born non-Hispanic White people delivering singleton infants from 2008 to 2017 who resided in the 23 states that fully implemented the 2003 version of the birth certificate before January 2008 (n=12,397,503). MEASURES: We examine the relationship between the presidential election and changes in the odds of inadequate or late/no prenatal care among immigrant Hispanic pregnant people, as well as trends in prenatal care utilization before the election. RESULTS: Our results show no unexpected changes in receipt of inadequate prenatal care, and late/no prenatal care, among the 7 monthly conception cohorts exposed to the election before the third trimester. However, we detected increases in the odds of both inadequate care and late/no prenatal care among foreign-born Hispanic pregnant people in June 2015 and January 2016, respectively. These upward level shifts persisted through the remainder of our time series ending with the cohort conceived around December 2016. CONCLUSIONS: The worsening shifts in prenatal care utilization we observe may serve as a bellwether for worsening outcomes among immigrant women and their families. Research is therefore urgently needed to investigate the determinants and consequences of these concerning trends.

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.

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.

Sildenafil and suicide in Sweden.

Much theory asserts that sexual intimacy sustains mental health. Experimental tests of such theory remain rare and have not provided compelling evidence because ethical, practical, and cultural constraints bias samples and results. An epidemiologic approach would, therefore, seem indicated given the rigor the discipline brings to quasi-experimental research. For reasons that remain unclear, however, epidemiologist have largely ignored such theory despite the plausibility of the processes implicated, which engender, for example, happiness, feelings of belonging and self-worth, and protection against depression. We use an intent-to-treat design, implemented via interrupted time-series methods, to test the hypothesis that the monthly incidence of suicide, a societally important distal measure of mental health in a population, decreased among Swedish men aged 50-59 after July 2013 when patent rights to sildenafil (i.e., Viagra) ceased, prices fell, and its use increased dramatically. The test uses 102 pre, and 18 post, price-drop months. 65 fewer suicides than expected occurred among men aged 50-59 over test months following the lowering of sildenafil prices. Our findings could not arise from shared trends or seasonality, biased samples, or reverse causation. Our results would appear by chance fewer than once in 10,000 experiments. Our findings align with theory indicating that sexual intimacy reinforces mental health. Using suicide as our distal measure of mental health further implies that public health programming intended to address the drivers of self-destructive behavior should reduce barriers to intimacy in the middle-aged populations.

Stillbirth as left truncation for early neonatal death in California, 1989-2015: a time-series study.

BACKGROUND: Some scholars posit that attempts to avert stillbirth among extremely preterm gestations may result in a live birth but an early neonatal death. The literature, however, reports no empirical test of this potential form of left truncation. We examine whether annual cohorts delivered at extremely preterm gestational ages show an inverse correlation between their incidence of stillbirth and early neonatal death. METHODS: We retrieved live birth and infant death information from the California Linked Birth and Infant Death Cohort Files for years 1989 to 2015. We defined the extremely preterm period as delivery from 22 to < 28 weeks of gestation and early neonatal death as infant death at less than 7 days of life. We calculated proportions of stillbirth and early neonatal death separately by cohort year, race/ethnicity, and sex. Our correlational analysis controlled for well-documented declines in neonatal mortality over time. RESULTS: California reported 89,276 extremely preterm deliveries (live births and stillbirths) to Hispanic, non-Hispanic (NH) Black, and NH white mothers from 1989 to 2015. Findings indicate an inverse correlation between stillbirth and early neonatal death in the same cohort year (coefficient: -0.27, 95% CI of - 0.11; - 0.42). Results remain robust to alternative specifications and falsification tests. CONCLUSIONS: Findings support the notion that cohorts with an elevated risk of stillbirth also show a reduced risk of early neonatal death among extremely preterm deliveries. Results add to the evidence base that selection in utero may influence the survival characteristics of live-born cohorts.

Male-to-Female Ratios, Race/Ethnicity, and Spontaneous Preterm Birth among 11 Million California Infants.

OBJECTIVE: An observed disparity in population-scale data are a larger number of males among preterm births (PTBs). We investigated spontaneous PTB risk among women of various race/ethnic groups in combination with infants' sex. STUDY DESIGN: This observational study was conducted in > 10 million California births (1991-2012) using birth certificates linked with maternal and infant hospital discharge data. RESULTS: Male-to-female ratios among term (37-42 weeks) infants exhibited the narrow ratio range 1.02 to 1.06 across race/ethnic groups. Such ratios among spontaneous PTBs were generally larger for all race/ethnic groups except non-Hispanic blacks. For blacks, ratios tended to be lower and similar to their term birth counterpart, 1.03. Hazard ratios adjusted for maternal age and education for non-Hispanic blacks were 0.99 (95% confidence interval [CI] 0.90-1.09), 1.01 (95% CI 0.95-1.08), 0.98 (95% CI 0.94-1.03), and 1.03 (95% CI 1.01-1.05), respectively, for gestational week groupings of 20 to 23, 24 to 27, 28 to 321, and 32 to 36. Hazard ratios for non-Hispanic whites for the same groupings were 1.08 (95% CI 0.98-1.18), 1.13 (95% CI 1.07-1.19), 1.21 (95% CI 1.17-1.25), and 1.18 (95% CI 1.17-1.19). CONCLUSION: Why male-to-female ratios are similar across gestational ages in blacks but substantially higher in other race/ethnic groups is theoretically considered relative to inflammation, stress, and other influences.

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.

Reproductive suppression and longevity in human birth cohorts.

OBJECTIVES: Reproductive suppression refers to, among other phenomena, the termination of pregnancies in populations exposed to signals of death among young conspecifics. Extending the logic of reproduction suppression to humans has implications for health including that populations exposed to it should exhibit relatively great longevity. No research, however, has tested this prediction. METHODS: We apply time-series methods to vital statistics from Sweden for the years 1751 through 1800 to test if birth cohorts exposed in utero to reproductive suppression exhibited lifespan different from expected. We use the odds of death among Swedes age 1 to 9 years to gauge exposure. As the dependent variable, we use cohort life expectancy. Our methods ensure autocorrelation cannot spuriously induce associations nor reduce the efficiency of our estimates. RESULTS: Our findings imply that reproductive suppression increased the lifespan of 24 annual birth cohorts by at least 1.3 years over the 50-year test period, and that 12 of those cohorts exhibited increases of at least 1.7 years above expected. CONCLUSIONS: The best available data in which to search for evidence of reproductive suppression in humans support the argument that populations subjected to environments dangerous for children yield birth cohorts that exhibit unexpectedly great longevity.

Collective Optimism and Selection Against Male Twins in Utero.

Scholarly literature claims that health declines in populations when optimism about investing in the future wanes. This claim leads us to describe collective optimism as a predictor of selection in utero. Based on the literature, we argue that the incidence of suicide gauges collective optimism in a population and therefore willingness to invest in the future. Using monthly data from Sweden for the years 1973-2016, we test the hypothesis that the incidence of suicide among women of child-bearing age correlates inversely with male twin births, an indicator of biological investment in high-risk gestations. We find that, as predicted by our theory, the incidence of suicide at month t varies inversely with the ratio of twin to singleton male births at month t + 3. Our results illustrate the likely sensitivity of selection in utero to change in the social environment and so the potential for viewing collective optimism as a component of public health infrastructure.

Sun Smoke in Sweden: Perinatal Implications of the Laki Volcanic Eruptions, 1783-1784.

BACKGROUND: The Icelandic volcano Laki erupted from June 1783 through January 1784. It produced 122 megatons of sulfur dioxide, particulate matter, and acid rain and contributed to one of the coldest winters on record in Western Europe. Although uncontrollable volcanic eruptions continue, few studies have investigated their perinatal health implications. METHODS: Using the Human Mortality Database, we assessed the association between the Laki event and the secondary sex ratio, infant mortality rates, and the number of births from 1751 to 1800 with time-series models that controlled for temporal trends. RESULTS: The secondary sex ratio decreased 3% below expected levels in 1784 (95% CI = -4%, -1%). Both female and male infant mortality rates exceeded expectation in 1785, by 54% (95% CI = 25%, 83%) and 37% (-1%, 74%), respectively. We observed little change in female live births but a reduction in male live births in 1784. CONCLUSIONS: Our findings are consistent with the hypothesis that the large-scale Laki volcanic eruptions of 1783-1784 resulted in adverse perinatal health outcomes in Sweden.

Separating the Bruce and Trivers-Willard effects in theory and in human data.

OBJECTIVES: Theories of reproductive suppression predict that natural selection would conserve mechanisms that abort the gestation of offspring otherwise unlikely to thrive in prevailing environments. Research reports evidence among humans of at least two such mechanisms-the Trivers-Willard and Bruce Effects. No literature, however, compares the mechanisms nor estimates their relative contribution to observed characteristics of human birth cohorts. We describe similarities and differences between the Trivers-Willard and Bruce Effects and explore high quality historical data from Sweden to determine which mechanism better describes temporal variation in the ratio of males to females in birth cohorts. METHODS: We measure Trivers-Willard exposures with the death rate among women of reproductive age. We measure Bruce exposures with the death rate among children. We use time-series regression methods to estimate the relative contribution of the Trivers-Willard and Bruce Effects to temporal variation in historical Swedish secondary sex ratio data. RESULTS: We find that the Bruce Effect appears to be a better predictor of the secondary sex ratio than does the Trivers-Willard Effect. CONCLUSIONS: Attempts to identify mechanisms by which reproductive suppression affects fetal loss and characteristics of human birth cohorts should consider the Bruce Effect as an alternative to the Trivers-Willard Effect.