Reduction in Infant Cardiac Deaths in US States Implementing Policies to Screen Newborns for Critical Congenital Heart Disease Matthew Oster, MD, MPH Washington, DC September 21, 2018 The findings and conclusions in this presentation have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy.

Objective To estimate the effect of CCHD newborn screening policies on infant deaths from congenital heart disease in the United States

Study Design Difference-in-difference analysis This method compares changes in outcomes following the introduction of a policy in groups with the policy and without the policy Can be used to assess outcomes of policies adopted at different times by state or local governments The method assumes similar pre-policy trends in outcomes and attributes different post-introduction trends, after controlling for state-specific factors, to policy

Data Source and Outcomes Data source: Period Linked Birth-Infant Death Data files from National Center for Health Statistics All births and infant deaths through end of 2013 by state of birth Underlying and multiple causes of death from death certificates classified using ICD-10 codes Two outcome measures – counts of infant deaths from 24 hours to under 6 months due to CCHD or due to other/unspecified CHD

Estimation Approach State screening policies by month of birth Mandate implemented Non-mandatory Mandate adopted but not yet implemented Voluntary screening policy Poisson regression models State screening policy in place at beginning of birth month Log of number of births in month in state Adjusted for state factors

CCHD Screening Policies as of June 1, 2013 States first adopted CCHD screening policies in mid-2011 7 states implemented mandates by June 1, 2013 2 states implemented mandates during August 2011-January 2012 5 implemented mandates during July 1, 2012-June 1, 2013 13 states adopted but did not yet implement mandates by June 1, 2013 4 other states adopted voluntary screening policies by June 1, 2013 Birth months through June 2013 included to allow for 6 months of death records

States That Implemented Screening Mandates by June 1, 2013 Date adopted Date implemented Connecticut May 2012 January 1, 2013 Delaware May 1, 2013 Indiana May 2011 January 1, 2012 Maryland May 19, 2011 September 1, 2012 New Hampshire June 2012 August 11, 2012 New Jersey June 2, 2011 August 31, 2011 Tennessee March 1, 2012 May 31, 2013 West Virginia April 5, 2012

Trends in CCHD Early Infant Death Rates, 2007-2012

Changes in Infant Deaths from CCHD or CHD During January 1, 2007-June 1, 2013.   All states States with no policy implemented States with mandatory policy States with non-mandatory policy Characteristic Before enactment Between enactment and implementation After implementation After enactment CCHD deathsa per 100,000 births 9.8 10.0 8.3 7.8 4.5 10.6 Other CHD deathsa per 100,000 births 13.5 13.4 12.0 11.5 8.5 14.8 13.8

Changes in Infant Deaths from CCHD or CHD During January 1, 2007-June 1, 2013.   All states States with no policy implemented States with mandatory policy States with non-mandatory policy Characteristic Before enactment Between enactment and implementation After implementation After enactment CCHD deathsa per 100,000 births 9.8 10.0 8.3 7.8 4.5 10.6 Other CHD deathsa per 100,000 births 13.5 13.4 12.0 11.5 8.5 14.8 13.8

Changes in Infant Deaths from CCHD or CHD During January 1, 2007-June 1, 2013.   All states States with no policy implemented States with mandatory policy States with non-mandatory policy Characteristic Before enactment Between enactment and implementation After implementation After enactment CCHD deathsa per 100,000 births 9.8 10.0 8.3 7.8 4.5 10.6 Other CHD deathsa per 100,000 births 13.5 13.4 12.0 11.5 8.5 14.8 13.8

Decline in death rate (%) (95% confidence interval) Adjusted Percent Declines in Rates of CCHD and Other CHD Deaths Due to Mandatory Screening Policies   Decline in death rate (%) (95% confidence interval) Age range of deaths CCHD deaths Other CHD deaths 24 hours to <6 months 33.4% 21.4% (10.6% - 50.3%) (6.9% - 33.7%) Sensitivity analyses – timing of mandate Implemented Aug 2011-June 2012 19.7% (3.1% – 37.1%) 21.7% (8.7% - 32.9%) Implemented July 2012-June 2013 53.6% 21.0% (36.0% - 66.3%) (0.3% - 37.4%) Adjusted for state-specific effects such as race, plurality, income, and unemployment rate

Key Findings – Effects of Screening Policies Relative reductions in CCHD and Other CHD deaths compared to births in months with no state policy, adjusted for state factors and time trends Mandatory screening CCHD deaths to age 6 months fell by one-third (33.4%) Other CHD deaths fell by one-fifth (21.4%) Both changes were statistically significant Non-mandatory screening No reductions in CCHD or other CHD deaths (<5% difference, not statistically significant)

Extrapolation to Universal CCHD Screening in US Potential reduction in annual deaths for US as a whole Recognized CCHD deaths: 120 (95% CI: 38–181)/year Other CHD deaths: 117 (95% CI: 38-185)/year May represent undiagnosed or unrecorded CCHD deaths

Limitations and Next Steps Small numbers of state birth-months exposed to state mandates Limited to information provided on death certificate CCHD vs. Other CHD We used most recent data that were made available by NCHS. Updated analyses with more recent data are ongoing.

Broader limitations Effect is limited to policy only Does not necessarily reflect practice Unknown: What is actual effect of hospital implementation?

Conclusions Mandatory policies for CCHD screening using pulse oximetry had a significant impact on infant deaths Estimate ~120 fewer infant deaths/year in US due to recognized CCHD with a universal mandatory screening policy Estimate ~117 fewer infant deaths/year in US due to “other CHD” with a universal mandatory screening policy These estimates may help inform policy decisions in other countries

Thank you Rahi Abouk, PhD William Paterson University, Cotsakos College of Business Scott Grosse, PhD Elizabeth Ailes, PhD Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities

Regression Results: Effects of CCHD Screening Policies   Poisson regression coefficient (95% confidence interval) Explanatory variable CCHD deaths Other CHD deaths Mandatory CCHD screening -0.406 -0.241 (-0.699, -0.112)* (-0.410, -0.071)* Non-mandatory CCHD screening -0.065 -0.016 (-0.244, 0.114) (-0.233, 0.201)

Tests of Non-Parallel Trends Hypothesis Regression coefficients on linear time interacted with the screening policy variables (mandatory and non-mandatory vs. no policy) Mandatory screening: -0.001 (95% CI: -0.008 to 0.006) Non-mandatory screening: -0.043 (95% CI: -0.221 to 0.136)

Falsification Analysis Infant deaths for other leading causes substituted for CCHD/CHD – all confidence intervals overlap zero Cause of death Coefficient (95% CI) for the effect of mandatory CCHD screening Coefficient (95% CI) for the effect of non-mandatory CCHD screening Sudden infant death syndrome   0.139 (-0.088, 0.367) 0.090 (-0.059, 0.239) Bacterial sepsis of newborn 0.158 (-0.192, 0.507) 0.082 (-0.070, 0.234) Maternal and placental complications 0.216 (-0.370, 0.803) 0.359 (-0.050, 0.768) Short gestation and low birth weight -0.171 (-0.483, 0.142) -0.056 (-0.207, 0.095)