The purpose of this comprehensive review is to evaluate the risk of neural tube defects (NTDs) after exposure to raltegravir during pregnancy.
Exposures to raltegravir during pregnancy reported cumulatively through 31-May-2018 to the company safety database were reviewed. This database includes all reports of pregnancy from Merck-sponsored clinical trials, spontaneous post-marketing and non-interventional data sources, including the Antiretroviral Pregnancy Registry (APR). Reports were classified as prospective (exposure report prior to knowledge of pregnancy outcome) or retrospective (report after knowledge of pregnancy outcome). Pregnancy reports were further reviewed to identify cases of NTDs. We also reviewed data from two ongoing pregnancy cohorts.
A total of 2426 pregnancies with reported outcomes were identified among women exposed to raltegravir: 1238 from the Merck safety database and 1188 from United Kingdom/Ireland and French pregnancy cohorts. Among all 2426 pregnancy reports, 1991 were prospective. No cases of NTDs were identified among the prospective pregnancy reports, of which 767 were first trimester, including 456 in the periconception period (at or within 28 days after conception). Among the 435 retrospective reports, four NTD cases per APR criteria were identified, of which only one (myelomeningocele) was among exposures in the periconception period. Given the inherent limitations and bias of retrospective reports, it is not appropriate to calculate an incidence rate.
Prospectively collected pregnancy outcome data do not suggest an association between raltegravir exposure in the periconception period and NTDs.