Introduction: Whether patients with neurofibromatosis (NF) are at higher risk for adverse pregnancy outcomes is an important but understudied clinical question. The Nationwide Inpatient Sample (NIS)(1) is a large administrative database representing a 20% stratified sample of all nonfederal US hospital discharges, and is well suited for studying a rare disease in a younger patient population. We hypothesized that adverse outcomes of pregnancy might occur at a higher rate in NF due to the higher prevalence of nerve sheath tumors and vascular disorders.

Methods: Using the NIS, we conducted a retrospective cohort study of pregnant patients with NF. We constructed a logistic regression model for the primary outcome of pre-eclampsia and the secondary outcomes of preterm labor, C-section, and cerebrovascular disease, adjusting for age, diabetes, hypertension, renal disease, multiple births, prior C-section, year, and race. Outcomes and covariates were defined using NIS variables and ICD-9-CM diagnosis and procedure codes.

Results: We identified 889 patients with neurofibromatosis type 1 (NF1) and 46 patients with neurofibromatosis type 2 (NF2) among approximately 10 million admissions in pregnant women between 1998 and 2008. NF1 was associated with a higher risk of pre-eclampsia (odds ratio [OR] 2.41), preterm labor (OR 1.75), C-section (OR 1.71), and cerebrovascular disease during pregnancy (OR 13.9, p<0.0001 for all outcomes). For NF2, only the risk of pre-eclampsia was elevated (OR 4.9, p=0.001), although small sample size warrants caution in interpreting a negative finding.

Conclusions: NF1 was associated with a higher risk of vascular complications of pregnancy. The biological mechanism of this association is unclear, but may relate to an underlying vasculopathy that has been reported in NF1 patients(2). Pre-eclampsia is a complex disorder of endothelial dysfunction associated with higher risk and earlier onset of hypertension. Clarifying this association will improve understanding of the mechanisms of vascular risk in NF1.

Patient Care: This study addresses a previously neglected but important clinical question, one that frequently arises in the care of female patients with NF. The findings will help educate the primary care providers, obstetricians, geneticists, neurologists, and neurosurgeons who jointly manage these complex patients. Knowing that patients with NF1 may have a higher risk of vascular complications of pregnancy will enable patients and physicians to target these risks through preventative care and early intervention. Finally, we hope our work will improve understanding of the mechanisms of vascular risk in NF, particularly in NF1.

Learning Objectives: 1. To show how a large administrative database can be used to investigate important clinical questions about rare diseases and outcomes. 2. To educate clinicians who encounter patients with NF, including neurosurgeons, about the potential risks of pregnancy in this population. 3. To encourage multidisciplinary collaboration in the care of patients with a complex multisystem genetic disorder.

References: 1. Nationwide Inpatient Sample: description at http://www.hcup-us.ahrq.gov/nisoverview.jsp. 2. Rasmussen SA, Yang Q, Friedman JM. Mortality in neurofibromatosis 1: an analysis using U.S. death certificates. Am J Hum Genet 2001 68(5):1110-1118.