Maternal Antibodies to Herpes Virus Antigens and Risk of Gastroschisis in Offspring

• Published in: American journal of epidemiology 2016-12, Vol.184 (12), p.902-912
• Main Authors: Werler, Martha M, Parker, Samantha E, Hedman, Klaus, Gissler, Mika, Ritvanen, Annukka, Surcel, Heljä-Marja
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Viral - blood; Case-Control Studies; Cohort Studies; Congenital Abnormalities - epidemiology; Cytomegalovirus Infections - blood; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - immunology; Epstein-Barr Virus Infections - blood; Epstein-Barr Virus Infections - complications; Epstein-Barr Virus Infections - immunology; Female; Finland - epidemiology; Gastroschisis - epidemiology; Gastroschisis - etiology; Herpesviridae Infections - blood; Herpesviridae Infections - complications; Herpesviridae Infections - immunology; Humans; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulin M - blood; Immunoglobulin M - immunology; Infant, Newborn; Logistic Models; Male; Maternal Age; Medical Record Linkage; Odds Ratio; Original Contributions; Pregnancy; Pregnancy Complications, Infectious - immunology; Pregnancy Complications, Infectious - virology; Prevalence; Registries; Risk Factors; Young Adult
• ISSN: 0002-9262; 1476-6256
• DOI: 10.1093/aje/kww114

Gastroschisis risk is highest in offspring of young women and is increasing in prevalence, suggesting that exposures that are increasingly common among younger females may be causal. Some infections by viruses in the herpes family are more common in the earlier childbearing years and have been increasing in prevalence over time. Data from the Finnish Maternity Cohort were linked to Finnish malformation and birth registers (1987-2012) for this study, a nested case-control study of mothers of offspring with gastroschisis and age-matched controls. Maternal antibody responses in early pregnancy (mean gestational age = 11.1 weeks) to Epstein Barr virus (EBV), herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), and cytomegalovirus were measured. Conditional logistic regression models were used to estimate odds ratios (and 95% confidence intervals) for high immunoglobulin reactivity. Odds ratios for high immunoglobulin M (IgM) reactivity to EBV-viral capsid antigen and HSV-1 or HSV-2 (as indicators of recent infection) were 2.16 (95% confidence interval (CI): 0.97, 4.79) and 1.94 (95% CI: 0.74, 5.12), respectively. For higher immunoglobulin G (IgG) reactivity to EBV-viral capsid antigen and HSV-2 IgG, odds ratios were 2.16 (95% CI: 0.82, 5.70) and 2.48 (95% CI: 1.50, 4.10), respectively. Reactivities to HSV-1 IgG, cytomegalovirus IgM, or cytomegalovirus IgG did not appear to increase gastroschisis risk. Primary EBV infection was not associated with gastroschisis, but observed associations with both IgM and IgG reactivities to EBV and HSV suggest that reactivations may be risk factors for it.