Sean O’Leary Julie Duran Christina Nelson March 29, 2011 Risk Factors Associated with Non-Receipt of Hepatitis B Vaccine in the Newborn Nursery Sean O’Leary Julie Duran Christina Nelson March 29, 2011

Disclosure No relevant financial disclosures

Background Burden of disease 43,000 new cases of hepatitis B in US annually 1 million chronically infected 2,000 to 4,000 deaths/year Early vaccination can prevent infants of infected mothers from developing hepatitis B Infants with perinatal acquisition of hepatitis B → more likely to develop chronic hepatitis B Only 50% of births to women with hepatitis B are identified for management prior to infants’ discharge MMWR Recomm Rep. 2005;54:1-31

Background Birth dose of hepatitis B vaccine is an important “safety net” for infants whose mothers are not identified as having hepatitis B Providers and hospitals may consider their populations as “low risk” for hepatitis B Close to 30% of women ages 18-34 in U.S. are foreign born, some from countries hyperendemic for hepatitis B

National Immunization Policy Cornerstone of strategy to eliminate hepatitis B: universal infant vaccination starting with a birth dose prior to discharge ACIP recommendation All hospitals develop policies to prevent perinatal hepatitis B transmission Administration of hepatitis B vaccine to all infants weighing >2 kg “On a case-by-case basis and only in rare circumstances, the first dose may be delayed until after hospital discharge …” MMWR Recomm Rep. 2005;54:1-31

Current Practice Providers and hospitals appear to have a wide variation in practices and policies Hospitals have a variety of policies: Identification of mothers who are hepatitis B + or unknown with targeted intervention The above plus a “universal birth dose” policy, such that parents of all infants are offered hepatitis B vaccine for their newborn No policy Cooper et al. Pediatrics. 2001 Dec;108(6):E98. Willis et al. Pediatrics. 2010 Apr; 125(4):704-11.

What are the risk factors associated with non-receipt of hepatitis B vaccine in the newborn nursery?

Objectives Describe hospital policies for newborn hepatitis B prevention Describe regional variation of receipt of hepatitis B vaccine Determine factors associated with non-receipt of hepatitis B vaccine in the infant, including maternal characteristics and effect of hospital policy

Study Design Retrospective cohort study 2008 Colorado Birth Certificate Registry data Policy information obtained by Perinatal Hepatitis B Prevention Unit at state health department All birth facilities (n=56) Email survey, phone calls, site visits

Population All live births in Colorado during the year 2008 (n=70,838) Exclusion criteria (n=6413): Prematurity (< 36 weeks’ gestation) < 2000 g birth weight Assisted ventilation > 6 hours Neonatal sepsis Meconium aspiration syndrome

Hospital Policy “Birth Dose” was defined as having a written policy to offer the parents of all newborn infants hepatitis B vaccine prior to discharge Hospital policy – 3 categories: No policy Policy to review maternal hepatitis B status but not including a birth dose Policy including a birth dose

Geographic Information Systems (GIS) Mapping To examine variation in receipt of hepatitis B vaccine in the newborn period State of Colorado Percent of infants who received hepatitis B vaccine prior to hospital discharge by county of residence

Statistical Analysis Multiple logistic regression with the primary outcome: non-receipt of hepatitis B vaccination Adjusted for variables chosen on basis of existing literature and expert opinion Maternal age, race/ethnicity, household income, maternal education, insurance status, hospital policy

Results: Hospital Policy Survey 56/56 (100%) birthing facilities in the state of Colorado responded to the survey

Results: Hospital Policy Percent of delivery facilities (n=56) Review maternal hepatitis B status but NO written policy to offer hepatitis B vaccine to all newborns 61% Review maternal hepatitis B status AND a written policy to offer hepatitis B vaccine to all newborns 30% No policy 9% Here are the results of the hospital policy survey.

Results: Hospital Policy Percent of delivery facilities (n=56) Review maternal hepatitis B status but NO written policy to offer hepatitis B vaccine to all newborns 61% Review maternal hepatitis B status AND a written policy to offer hepatitis B vaccine to all newborns 30% No policy 9% 61% of the facilities had a policy to review maternal hepatitis B status but without a written policy to offer hepatitis B vaccine to all newborns.

Results: Hospital Policy Percent of delivery facilities (n=56) Review maternal hepatitis B status but NO written policy to offer hepatitis B vaccine to all newborns 61% Review maternal hepatitis B status AND a written policy to offer hepatitis B vaccine to all newborns 30% No policy 9% 30% had…

Results: Hospital Policy Percent of delivery facilities (n=56) Review maternal hepatitis B status but NO written policy to offer hepatitis B vaccine to all newborns 61% Review maternal hepatitis B status AND a written policy to offer hepatitis B vaccine to all newborns 30% No policy 9% And finally, 9% had…

State of Colorado. Percent of Infants Who Received Hepatitis B Vaccine, by County Percent Receiving Vaccine This is a map of the state of Colorado with percentage of infants who received vaccine by county.

State of Colorado. Percent of Infants Who Received Hepatitis B Vaccine, by County Percent Receiving Vaccine Note the scale on the right. The lighter yellow color signifies newborn hepatitis B birth dose rates of under 20% whereas the dark red color at bottom indicates rates of over 80%.

State of Colorado. Percent of Infants Who Received Hepatitis B Vaccine, by County Percent Receiving Vaccine For your reference, Denver and the rest of the Front Range of Colorado is located in the upper middle portion of the map, where the majority of the state lives, and mostly has rates in the 40 to 80% range. The rest of the state is fairly rural…

State of Colorado. Percent of Infants Who Received Hepatitis B Vaccine, by County Percent Receiving Vaccine And in these rural areas, we were able to show a four fold variation in receipt of hepatitis B vaccine. Note the red areas in the lower right portion of the map – this is the rural southeast of Colorado – had among the highest rates, over 80%,

State of Colorado. Percent of Infants Who Received Hepatitis B Vaccine, by County Percent Receiving Vaccine while other rural areas had rates less than 20%, in the lighter yellow color. Due to the limits of our dataset, we were unable to explore this further, but we suspect it may be associated with hospital policy.

Overall Vaccination Rate 61.2% of newborns in cohort received hepatitis B vaccine prior to hospital discharge

Maternal Demographic Characteristics + Hep B Vaccine, n=39,703 No Hep B Vaccine, n=24,722 Maternal age, years – mean (SD) 27.3 (6.1) 28.7 (6.1) Race/Ethnicity, % White, Non-Hispanic Hispanic Black, Non-Hispanic Asian Native American/Alaskan Other/Unknown 56% 30% 5% 3% 1% 64% 22% 4% Marital Status, % Married Never Married Divorced 72% 26% 2% 79% 20% Here are the characteristics of our study population, showing demographic characteristics based on whether or not an infant received a hepatitis B vaccine.

Maternal Demographic Characteristics + Hep B Vaccine, n=39,703 No Hep B Vaccine, n=24,722 Maternal age, years – mean (SD) 27.3 (6.1) 28.7 (6.1) Race/Ethnicity, % White, Non-Hispanic Hispanic Black, Non-Hispanic Asian Native American/Alaskan Other/Unknown 56% 30% 5% 3% 1% 64% 22% 4% Marital Status, % Married Never Married Divorced 72% 26% 2% 79% 20% To walk you through these next few slides, columns are divided into infants who received a hepatitis B vaccine and those that did not.

Maternal Demographic Characteristics + Hep B Vaccine, n=39,703 No Hep B Vaccine, n=24,722 Maternal age, years – mean (SD) 27.3 (6.1) 28.7 (6.1) Race/Ethnicity, % White, Non-Hispanic Hispanic Black, Non-Hispanic Asian Native American/Alaskan Other/Unknown 56% 30% 5% 3% 1% 64% 22% 4% Marital Status, % Married Never Married Divorced 72% 26% 2% 79% 20% 100% …with the columns adding up to 100% for each category.

Maternal Demographic Characteristics + Hep B Vaccine, n=39,703 No Hep B Vaccine, n=24,722 Maternal age, years – mean (SD) 27.3 (6.1) 28.7 (6.1) Race/Ethnicity, % White, Non-Hispanic Hispanic Black, Non-Hispanic Asian Native American/Alaskan Other/Unknown 56% 30% 5% 3% 1% 64% 22% 4% Marital Status, % Married Never Married Divorced 72% 26% 2% 79% 20% The first thing to note on this slide is that mothers of infants who did not receive hepatitis B vaccine were slightly older than mothers of infants who did receive the vaccine.

Maternal Demographic Characteristics + Hep B Vaccine, n=39,703 No Hep B Vaccine, n=24,722 Maternal age, years – mean (SD) 27.3 (6.1) 28.7 (6.1) Race/Ethnicity, % White, Non-Hispanic Hispanic Black, Non-Hispanic Asian Native American/Alaskan Other/Unknown 56% 30% 5% 3% 1% 64% 22% 4% Marital Status, % Married Never Married Divorced 72% 26% 2% 79% 20% Regarding race/ethnicity, note that there was a higher percentage on non-Hispanic white mothers whose infants did not receive the vaccine, and the converse was true for Hispanic mothers: the percentage of mothers whose infants received the vaccine was higher than those that did not.

Maternal Demographic Characteristics + Hep B Vaccine, n=39,703 No Hep B Vaccine, n=24,722 Insurance, % Medicaid Private Self-Pay Other/Unknown‡ 40 47 4 9 26 65 3 6 This slide shows maternal insurance status. ‡ ‘Other’ category includes Medicaid pending, Child Health Plan, Veterans Administration, Correctional Facility, Unknown, etc.

Maternal Demographic Characteristics + Hep B Vaccine, n=39,703 No Hep B Vaccine, n=24,722 Insurance, % Medicaid Private Self-Pay Other/Unknown‡ 40 47 4 9 26 65 3 6 Here, we see that for those that received the hepatitis B vaccine, the percentage was higher for Medicaid and lower for private insurance when compared to those that did not receive it. ‡ ‘Other’ category includes Medicaid pending, Child Health Plan, Veterans Administration, Correctional Facility, Unknown, etc.

Non-Receipt Hepatitis B Vaccine: Household Income These next 3 slides will illustrate in a descriptive manner, percentages of infants who did not receive HBV vaccine. There are some mental gymnastics here, as I am presenting somewhat of a double negative, so bear with me. The bigger bars on these slides are showing the percentages of non-receipt, so smaller is better. This slide illustrates that as household income increases, the percentage of infants who received HBV decreases.

Non-Receipt of Hepatitis B Vaccine: Maternal Education This slide shows [title]. Here, we see that as maternal education increases, the percent of newborns not given hepatitis B vaccine also increases.

Non-Receipt of Hepatitis B Vaccine: Hospital Policy This slide illustrates non-receipt of HBV by hospital policy. Again, smaller is better. Note that the percentage of infants who did not receive HBV is lowest for hospitals with policies that include a birth dose…

Non-Receipt of Hepatitis B Vaccine: Hospital Policy This slide illustrates [title]. Note that the percentage of infants who did not receive HBV is lowest for hospitals with policies that include a birth dose, followed by hospitals with no hepatitis b policy at all, and the highest percentage of non-receipt was in the hospitals that had policies but did not include a universal birth dose in that policy.

Non-Receipt of Hepatitis B Vaccine: Hospital Policy followed by hospitals with no hepatitis b policy at all,

Non-Receipt of Hepatitis B Vaccine: Hospital Policy and the highest percentage of non-receipt was in the hospitals that had policies but did not include a universal birth dose in that policy.

Variables Associated with Non-Receipt of Hepatitis B Vaccine Characteristic Unadjusted OR Adjusted OR* 95% CI Age 1.04 1.01 1.01, 1.02 Race/Ethnicity White, Non-Hispanic Hispanic Black, Non-Hispanic Asian American Indian/Alaskan 1.57 Ref 1.10 1.46 1.27 1.14 0.97 0.96 1.42 1.09, 1.19 -- 0.89, 1.06 0.87, 1.06 1.20, 1.68 Household Income < $15,000 $15,000-$24,999 $25,000-$34,999 $35,000-$49,999 $50,000-$74,999 $75,000 + 1.23 1.49 1.74 2.10 2.37 1.15 1.13 1.38 1.66 1.51 1.06, 1.25 1.03, 1.24 1.25, 1.52 1.49, 1.85 1.31, 1.74 These next two slides present the results of our multivariate analysis. *Adjusted for: maternal age, race, household income, education, insurance, hospital policy, marital status, and gestational age (all significant)

Variables Associated with Non-Receipt of Hepatitis B Vaccine Characteristic Unadjusted OR Adjusted OR* 95% CI Age 1.04 1.01 1.01, 1.02 Race/Ethnicity White, Non-Hispanic Hispanic Black, Non-Hispanic Asian American Indian/Alaskan 1.57 Ref 1.10 1.46 1.27 1.14 0.97 0.96 1.42 1.09, 1.19 -- 0.89, 1.06 0.87, 1.06 1.20, 1.68 Household Income < $15,000 $15,000-$24,999 $25,000-$34,999 $35,000-$49,999 $50,000-$74,999 $75,000 + 1.23 1.49 1.74 2.10 2.37 1.15 1.13 1.38 1.66 1.51 1.06, 1.25 1.03, 1.24 1.25, 1.52 1.49, 1.85 1.31, 1.74 The most notable piece on this slide is that the adjusted ORs generally increase with increasing income, showing that when controlling for other factors, increasing income is associated with non-receipt of hepatitis B vaccine. *Adjusted for: maternal age, race, household income, education, insurance, hospital policy, marital status, and gestational age (all significant)

Variables Associated with Non-Receipt of Hepatitis B Vaccine Characteristic Unadjusted OR Adjusted OR* 95% CI Education 8th Grade or Less 9th-12th Grade, No Diploma Some College Bachelor’s Degree Master’s Degree Doctorate or Professional Degree Ref 1.22 1.48 2.24 2.84 2.73 1.15 1.13 1.38 1.66 1.51 -- 1.06, 1.25 1.03, 1.24 1.25, 1.52 1.49, 1.85 1.31, 1.74 Insurance Medicaid Private Self-Pay 2.05 1.20 1.06 0.99 1.40, 1.55 0.96, 1.17 0.92, 1.06 Hospital Policy No Policy Policy Without Birth Dose Policy Including Birth Dose 1.64 2.38 1.39 2.21 1.32, 1.47 2.13, 2.30 This slide shows more variables included in our logistic regression. *Adjusted for: maternal age, race, household income, education, insurance, hospital policy, marital status, and gestational age (all significant).

Variables Associated with Non-Receipt of Hepatitis B Vaccine Characteristic Unadjusted OR Adjusted OR* 95% CI Education 8th Grade or Less 9th-12th Grade, No Diploma Some College Bachelor’s Degree Master’s Degree Doctorate or Professional Degree Ref 1.22 1.48 2.24 2.84 2.73 1.15 1.13 1.38 1.66 1.51 -- 1.06, 1.25 1.03, 1.24 1.25, 1.52 1.49, 1.85 1.31, 1.74 Insurance Medicaid Private Self-Pay 2.05 1.20 1.06 0.99 1.40, 1.55 0.96, 1.17 0.92, 1.06 Hospital Policy No Policy Policy Without Birth Dose Policy Including Birth Dose 1.64 2.38 1.39 2.21 1.32, 1.47 2.13, 2.30 Here, we see an impressive effect of maternal education on the adjusted Ors, with increasing maternal education showing increasing odds of non-receipt of hepatitis B vaccine. *Adjusted for: maternal age, race, household income, education, insurance, hospital policy, marital status, and gestational age (all significant).

Variables Associated with Non-Receipt of Hepatitis B Vaccine Characteristic Unadjusted OR Adjusted OR* 95% CI Education 8th Grade or Less 9th-12th Grade, No Diploma Some College Bachelor’s Degree Master’s Degree Doctorate or Professional Degree Ref 1.22 1.48 2.24 2.84 2.73 1.15 1.13 1.38 1.66 1.51 -- 1.06, 1.25 1.03, 1.24 1.25, 1.52 1.49, 1.85 1.31, 1.74 Insurance Medicaid Private Self-Pay 2.05 1.20 1.06 0.99 1.40, 1.55 0.96, 1.17 0.92, 1.06 Hospital Policy No Policy Policy Without Birth Dose Policy Including Birth Dose 1.64 2.38 1.39 2.21 1.32, 1.47 2.13, 2.30 Finally, the highest odds ratio for non-receipt of hepatitis B vaccine was found in hospital policy. Having a written policy to offer hepatitis B vaccine to all newborns was the referent group. Having a policy to review maternal hepatitis B status but not a birth dose policy had an odds ratio of 2.21. The interpretation of this is that after controlling for other factors such as race, household income, and maternal education, the odds of an infant not receiving hepatitis B vaccine are two-fold higher in hospitals without a birth dose policy compared to those that have one. *Adjusted for: maternal age, race, household income, education, insurance, hospital policy, marital status, and gestational age (all significant).

Summary of Results Only about 1/3 of hospitals in Colorado were following ACIP recommendation to have a written policy for a birth dose of hepatitis B vaccine Wide regional variation in receipt of hepatitis B vaccine in newborn nurseries in Colorado

Summary of Results ↑ Maternal education and income = ↓ hepatitis B vaccination rates Hospital policy without universal birth dose = ↑ odds of non-receipt of hepatitis B vaccine Infants born in hospitals without a universal birth dose policy → half as likely to receive hepatitis B vaccine As maternal education and income increase, likelihood of receiving hepatitis B vaccine decreases After controlling for maternal characteristics, a hospital policy that does not include a provision for a birth dose is associated with a higher odds of non-receipt of hepatitis B vaccine compared to hospitals with such a policy Infants born in such hospitals are half as likely to receive hepatitis B vaccine when compared to infants born in hospitals with a birth dose policy

Limitations Based on one year of data (2008) Sample size was large Based only on data from Colorado Birth certificate data Possibly subject to misclassification bias Unable to account for all potential confounders Individual physician practices, vaccine refusal

Conclusions An “opt out” policy for receiving hepatitis B vaccine appears much more effective than an “opt in” policy Hospitals that have policies that do not include a birth dose should not consider that they are effectively preventing infants from acquiring hepatitis B Hospitals and state governments should adopt written policies stating that parents of all infants are offered hepatitis B vaccine prior to discharge

Future Directions Will we ever get to a point where hepatitis B vaccination is as routine as Vitamin K and eye ointment, with occasional refusals?

Acknowledgments Children’s Outcomes Research Program Colorado Department of Public Health and Environment Amy Warner Kirk Bol Department of Health and Human Services, Health Resources and Services Administration, National Research Service Award T32HP10006 Children’s Outcomes Research Program Allison Kempe, MD, MPH Michaela Brtnikova, PhD Colorado School of Public Health Dennis Lezotte, PhD Ned Calonge, MD, MPH Jill Norris, PhD