Association Between Pandemic Influenza A(H1N1) Vaccination in Pregnancy and Early Childhood Morbidity in Offspring

Abstract

IMPORTANCE Several studies investigating potential adverse effects of the pandemic A(H1N1) vaccine have supported that influenza A(H1N1) vaccination does not increase the risk for major pregnancy and birth adverse outcomes, but little is known about possible adverse effects in offspring of A(H1N1)-vaccinated mothers beyond the perinatal period and into early childhood. OBJECTIVE To evaluate whether pandemic influenza A(H1N1) vaccination in pregnancy increases the risk for early childhood morbidity in offspring. DESIGN, SETTING, AND PARTICIPANTS Register-based cohort study comprising all live-born singleton children in Denmark from pregnancies overlapping the A(H1N1) influenza vaccination campaign in Denmark, from November 2, 2009, to March 31, 2010. From a cohort of 61 359 pregnancies, offspring exposed and unexposed to the influenza A(H1N1) vaccine during pregnancy were matched 1:4 on propensity scores. EXPOSURE Vaccination in pregnancy with a monovalent inactivated AS03-adjuvanted split virion influenza A(H1N1)pdm09 vaccine (Pandemrix; GlaxoSmithKline Biologicals). MAIN OUTCOMES AND MEASURES Rate ratios of hospitalization in early childhood until 5 years of age. Hospitalization was defined as (1) first inpatient hospital admission, (2) all inpatient hospital admissions, and (3) first hospital contact for selected diseases, which included individual infectious diseases and individual neurologic, autoimmune, and behavioral conditions. RESULTS The mean (SD) age at end of follow-up was 4.6 (0.40) years for the 61 359 children included in the study. In the cohort, the mothers of 55 048 children were unvaccinated, 349 mothers were vaccinated in the first trimester, and 5962 mothers were vaccinated in the second or third trimesters. Children exposed in the first trimester were not more likely to be hospitalized in early childhood than unexposed children (hospitalization rates per 1000 person-years, 300.6 for exposed vs 257.5 for unexposed; rate ratio, 1.17; 95% CI, 0.94-1.45). Similarly, children exposed in the second or third trimester were not more likely to be hospitalized in early childhood than unexposed children (hospitalization rates per 1000 person-years, 203.6 for exposed vs 219.3 for unexposed; rate ratio, 0.93; 95% CI, 0.87-0.99). This 7% decreased risk was primarily a result of reduced risks for infectious disease-related hospitalizations. CONCLUSIONS AND RELEVANCE To our knowledge, this is the most comprehensive study to date of potential adverse effects manifesting after the perinatal period. We detected no increased risk for early childhood morbidity. These results support the safety profile of the influenza A(H1N1) vaccine used in pregnancy.

Flu vaccination in pregnancy

“…No elevated risk was found for cancer, infections, neurodevelopmental problems, chronic diseases, or all cause morbidity or mortality in the children of vaccinated mothers. This is consistent with results from other studies based on large health databases and national registries 1314151617. The message is clear: influenza vaccination during pregnancy is, by all available evidence, safe for mother and offspring.…”

Schizophrenia and Influenza at the Centenary of the 1918-1919 Spanish Influenza Pandemic: Mechanisms of Psychosis Risk

“…Some authors consider the fact that influenza vaccination is not recommended in the first trimester in some countries as cause for concern, leaving women and the developing foetus vulnerable during a critical neurodevelopmental window (228). Epidemiologically, first trimester (or any other trimester) pandemic influenza vaccination does not appear to be associated with increased childhood morbidity (229). Although neurodevelopmental outcome data are largely lacking, some mouse models suggested that influenza vaccination early in pregnancy can indeed promote behavioral function and neurogenesis in the offspring, and confer protection from the effects of MIA with LPS (230,231).…”

Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study

“…The main strength of our study was the availability of a population based birth registry with detailed clinical information on pregnancy and birth, receipt of the 2009 pH1N1 influenza vaccine during pregnancy, 44 and linkage to health administrative databases permitting follow-up for health outcomes up to 5 years of age. We cannot dismiss the possibility of residual confounding of our findings due to an inability to include unmeasured or unknown confounders in the propensity scores.…”

“… 37 Although substantial evidence now supports the safety of maternal influenza immunization with respect to birth outcomes (for example, preterm birth, congenital anomalies), 38 39 40 41 42 43 few studies have assessed pediatric health outcomes beyond the first six months of life. 44 45 46 47 48 49 The lack of information on longer term health outcomes in children following influenza vaccination during pregnancy may be a potential barrier to achieving higher uptake and has been identified as an evidence gap for maternal immunization policy globally. 50 51 In this study, we evaluated the relation between 2009 pandemic H1N1 (pH1N1) influenza vaccination during pregnancy and pediatric health outcomes in the first five years of life.…”