1. S T A T E N S S E R U M I N S T I T U T Michael Howitz (how@ssi.dk) 1, Jacob Brunbjerg Simonsen 2, Tyra Grove Krause 1, John Robbins 3, Rachel Scheerson 3, Kåre Mølbak 1 and Mark A. Miller 4 1) Department of Epidemiology, Statens Serum Institut, Copenhagen, Denmark 2) Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark 3) Laboratory of Developmental and Population Studies, National Institute of Child Health and Human Development, Bethesda, USA 4. Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, USA Risk of adverse birth outcome after group B meningococcal disease – Two population based cohort studies Introduction Systemic group B Neisseria meningitidis (GBM) disease induces antibodies that react in-vitro with polysialated neural cell adhesion molecules, which is abundant present in fetal brain tissue. For this reason, concern has been raised that vaccine-induced IgG specific to capsular polysaccharide of GBM may elicit an autoimmune reaction that may affect birth outcome. As antibodies towards GBM may cross the placental barrier, we investigated whether women with a previous systemic GBM disease experienced pregnancy complications or if their offspring had increased risk of birth defects. Methods Data were obtained from four national registries to form two cohort designs, with the entire Danish population and ten individual matched persons per case as reference populations. Cohort I included 1,422 women with confirmed GBM disease 1974-2005 followed until child birth, registered pregnancy complication or end of the follow-up period. Cohort II included 502 children born by women with a GBM disease 1977-2005 followed for any registered birth defects or diseases within the first three years of life. Conclusion Our results do not support the hypothesis that GBM is associated with immunoreactive disease that may affect the course of pregnancy or the health of the offspring, and are in line with previous findings that GBM diseased persons are at no increased risk of autoimmune disease. Results Overall we found no increased risk of induced abortion, stillbirths, pre- term birth (<37 gestational week) and low birth weight (<2,500 grams) among women with a previous GBM disease. Their children had likewise no increased risk of birth defects (OR 1.00, 95% CI 0.53-1.90) or disease within the first three years of life (HR 0.94, 95% CI 0.79-1.12). Table 1. Age and county of residence adjusted odds ratio (OR) for selected pregnancy outcomes for females with previous group B or group C meningococcal disease, 1974-2005 7 – 8 November 2007, London, UK Meningitis Research Foundation’s International Conference Acknowledgements Financial support. The Fogarty International Center and the Institute of Health and Human Development of the National Institutes of Health. Pregnancy measures B OR (95% CI) yes/no C OR (95% CI) yes/no B/C ratio OR (95% CI) Background population yes/no Induced abortion or stillbirth? 1.18 (0.90-1.55) 90/227 1.37 (0.90-2.08) 38/86 0.90 (0.57-1.41) Ref 266,673/846,816 Born before ge- stational week 37? 0.95 (0.53-1.71) 12/213 0.83 (0.30-2.25) 4/82 1.16 (0.36-3.70) Ref 45,773/775,290 Birthweight below 2,500 grams? 0.66 (0.27-1.61) 5/222 1.05 (0.33-3.34) 3/83 0.62 (0.15-2.66) Ref 28,383/816,944 Small for gestati- onal age at birth? 0.64 (0.39-1.04) 17/208 0.68 (0.32-1.48) 7/79 0.94 (0.38-2.36) Ref 63,299/493,534 ICD-10 and ICD-8 codes for birth defects B OR (95% CI) Cases/referents C OR (95% CI) Cases/referents B/C ratio OR (95% CI) Q00.0-QQ52.9, 740.00-752.09; Q54.0-Q64.9, 752.20-755.59; Q66.0-Q99.9, 755.79-759.99 1.14 (0.80-1.62) 41/290 1.11 (0.65-1.89) 18/122 1.00 (0.53-1.90) ICD-10 and ICD-8 codes for all diseases studied B HR (95% CI) Cases/referents C HR (95% CI) Cases/referents B/C ratio HR (95% CI) A00.0-N99.9; 000.0-629.99, 680.00-738.99 0.94 (0.79-1.12) 182/1386 0.91 (0.70-1.19) 74/546 1.06 (0.78-1.45) Table 2. Comorbidity adjusted odds ratio (OR) for birth defects among children born of mothers with a previous group B or group C meningococcal disease, 1974-2005 Table 3.Comorbidity adj. hazards ratio (HR) of disease within the first three life years among children born of mothers with a previous group B or group C meningococcal disease, 1974-2005