Diagnostic Complexities in Congenital Tuberculosis: Insights From Preterm Twins Conceived via In Vitro Fertilization and a Literature Review.

Abstract

Congenital tuberculosis (CTB) poses significant diagnostic challenges, particularly in preterm infants. This case report describes the discordant clinical presentation of CTB in dizygotic twins conceived via in vitro fertilization (IVF) and born at 31⁺⁶ weeks' gestation. Both twins presented with nonspecific symptoms (fever and respiratory distress) on postnatal day (PND) 31 and 25, respectively, but followed distinct clinical courses: Twin 1 developed disseminated disease with facial palsy and central nervous system (CNS) involvement, whereas Twin 2 presented with a cervical mass and bone destruction. Diagnosis was markedly delayed, with confirmation on PND 99 and 98, respectively, and initially mistaken for sepsis or histiocytosis. Definitive diagnosis was achieved through next-generation sequencing (NGS) and Xpert Mycobacterium tuberculosis/Rifampicin (Xpert MTB/RIF) assays. The twins were treated with a 14-month antitubercular regimen including linezolid. Their asymptomatic mother was subsequently diagnosed with latent genital TB-a likely contributor to her primary infertility-and received standard therapy with isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA), and ethambutol (EMB). At follow-up (chronological age 2 years), both twins showed adequate catch-up growth and normal visual function. This case illustrates that CTB can manifest as phenotypically diverse and disseminated disease in preterm IVF twins following reactivation of maternal latent infection. It also provides a clinical paradigm linking female genital tuberculosis (FGTB) pathogenesis-mediated by Th1/Th17-driven endometrial damage-to infertility, IVF-associated immunosuppressive reactivation, and congenital transmission. These findings highlight the potential value of considering latent TB screening in women undergoing infertility evaluation, particularly before IVF, to prevent severe maternal and neonatal outcomes. However, given that these observations are derived from a single case report, larger studies are warranted to establish definitive screening recommendations.