Identifying birth defects in automated data sources in the Vaccine Safety Datalink.

PURPOSE: The Vaccine Safety Datalink (VSD), a collaboration between the Centers for Disease Control and Prevention and several large healthcare organizations, aims to monitor safety of vaccines administered in the USA. We present definitions and prevalence estimates for major structural birth defects to be used in studies of maternal vaccine safety. METHODS: In this observational study, we created and refined algorithms for identifying major structural birth defects from electronic healthcare data, conducted formal chart reviews for severe cardiac defects, and conducted limited chart validation for other defects. We estimated prevalence for selected defects by VSD site and birth year and compared these estimates to those in a US and European surveillance system. RESULTS: We developed algorithms to enumerate >50 major structural birth defects from standardized administrative and healthcare data based on utilization patterns and expert opinion, applying criteria for number, timing, and setting of diagnoses. Our birth cohort included 497 894 infants across seven sites. The period prevalence for all selected major birth defects in the VSD from 2004 to 2013 was 1.7 per 100 live births. Cardiac defects were most common (65.4 per 10 000 live births), with one-fourth classified as severe, requiring emergent intervention. For most major structural birth defects, prevalence estimates were stable over time and across sites and similar to those reported in other population-based surveillance systems. CONCLUSIONS: Our algorithms can efficiently identify many major structural birth defects in large healthcare datasets and can be used in studies evaluating the safety of vaccines administered to pregnant women. Copyright © 2017 John Wiley & Sons, Ltd.

Assessing the safety of influenza immunization during pregnancy: the Vaccine Safety Datalink.

The influenza vaccine can reduce maternal and neonatal morbidity and mortality and thus is recommended for all pregnant women. However, concerns regarding safety of influenza vaccine remain a barrier to vaccination. We describe ongoing analyses of influenza vaccine safety during pregnancy within the Vaccine Safety Datalink that includes the evaluation of acute events, adverse pregnancy and birth outcomes, and congenital anomalies. In addition, we highlight unique challenges and strategies for the study of vaccine safety among pregnant women with the use of large linked databases.

Birth and early developmental screening outcomes associated with cannabis exposure during pregnancy.

OBJECTIVE: To compare birth and early developmental screening outcomes for infants with and without in utero cannabis exposures. STUDY DESIGN: Observational cohort of women receiving prenatal care within a large health system, live birth between October 1, 2015 and December 1, 2017, and at least one infant visit. Cannabis exposure was through routine urine toxicology screen. Preterm birth, small for gestational age (SGA) birth, birth defects, and early developmental screening outcomes were assessed from birth and electronic health record data. RESULTS: Of 3435 women, 283 (8.2%) had a positive urine toxicology screen. In utero cannabis exposure was associated with SGA birth, adjusted rate ratio (aRR) 1.69 (95% confidence interval [CI]: 1.22-2.34). Abnormal 12-month developmental screens occurred in 9.1% of infants with in utero cannabis exposure vs. 3.6% of those with negative maternal screens, aRR 1.90 (95% CI: 0.92-3.91). Additional birth outcomes were not associated with in utero cannabis exposure. CONCLUSIONS: Exposure to cannabis during pregnancy may adversely impact fetal growth.

Safety of guidelines recommending live attenuated influenza vaccine for routine use in children and adolescents with asthma.

OBJECTIVE: Evaluate whether a guideline recommending Live Attenuated Influenza Vaccine (LAIV) for children 2 years and older with asthma increased risks for lower respiratory events (LREs), within 21 or 42 days of vaccination, as compared to standard guidelines to administer Inactivated Influenza Vaccine (IIV) in children with asthma. METHODS: This was a pre/post guideline retrospective cohort study of children ages 2-17 years with asthma and receiving one or more influenza vaccines in two large medical groups from 2007 to 2016. Both groups recommended IIV in the pre-period; in 2010, one group implemented a guideline recommending LAIV for all children, including those with asthma. Main outcomes were medically attended LREs within 21 and 42 days after influenza immunization. Analysis used a generalized estimating equation regression to estimate the ratio of rate ratios (RORs) comparing pre/post events between LAIV guideline and control group. RESULTS: The cohort included 7851 influenza vaccinations in 4771 children with asthma. Among patients in the LAIV guideline group, the proportion receiving LAIV increased from 23% to 68% post-guideline implementation, versus an increase from 7 to 11% in the control group. Age and baseline asthma severity adjusted ROR showed no increase in LREs, primarily asthma exacerbations, following implementation of the LAIV guideline: overall aROR (95% Confidence Interval): 0.74 (0.43-1.29) for LRE within 21 days of vaccination, 0.77 (0.53-1.14) for LRE within 42 days of vaccination. For the subset of children ages 2-4 years aROR: 0.92 (0.34-2.53) for LRE within 21 days of vaccination and 0.94 (0.49-1.82) for LRE within 42 days of vaccination; for children 5-18 years aROR (95% CI): 0.58 (0.26-1.30) for LRE within 21 days of vaccination and 0.67 (0.37-1.23) for LRE within 42 days. CONCLUSION: In a large cohort of children with asthma, a guideline recommending LAIV rather than IIV did not increase LREs following vaccination.

Maternal safety of trivalent inactivated influenza vaccine in pregnant women.

OBJECTIVE: To estimate the risks for medically attended events occurring within 42 days of receiving trivalent inactivated influenza vaccine and to evaluate specific risks of first-trimester vaccination. METHODS: This retrospective observational cohort study compared rates of medically attended adverse events in trivalent inactivated influenza-vaccinated and unvaccinated pregnant women in the Vaccine Safety Datalink. Using a Poisson distribution and log link, we calculated maternal adjusted incident rate ratios for composite safety outcomes for the full cohort and the subset vaccinated during the first trimester. RESULTS: The cohort included 75,906 vaccinated (28.4% in the first trimester) and 147,992 unvaccinated women matched by age, site, and pregnancy start date. In the first 3 days after vaccination, trivalent inactivated influenza vaccine was not associated with increased risk of specified medically attended events, including allergic reactions, cellulitis, and seizures (full cohort adjusted incident rate ratio 1.12, 95% confidence interval [CI] 0.81-1.55; P=.48; first-trimester adjusted incident rate ratio .97, 95% CI 0.53-1.78; P=.93). In the first 42 days, no incident cases of Guillain-Barré syndrome, optic neuritis, transverse myelitis, or Bells palsy were identified. Trivalent inactivated influenza vaccine was not associated with thrombocytopenia (full cohort adjusted incident rate ratio 0.90, 95% CI 0.68--1.19; P=.45; first-trimester adjusted incident rate ratio 0.56, 95% CI 0.22-1.39; P=.21) or an acute neurologic event (full cohort adjusted incident rate ratio 0.92, 95% CI 0.54-1.6; P=.75; first-trimester adjusted incident rate ratio 1.05, 95% CI 0.46-2.38; P=.91). CONCLUSIONS: Receipt of trivalent inactivated influenza vaccine during pregnancy was not associated with increased risk of adverse events in the 42 days after vaccination, supporting its safety for the mother.