Fetal outcome in murine Lyme disease

Lyme disease is an inflammatory syndrome caused by infection with Borrelia burgdorferi. Although this syndrome has important implications for human pregnancy, little is known about gestational infection with B. burgdorferi. Fetal death occurred in 33 of 280 gestational sacs (12%) in 39 C3H/HeN female mice infected by intradermal injection of B. burgdorferi 4 days after mating (acute infection), compared with 0 of 191 sacs in 25 control mice (P = 0.0001). Forty-six percent of acutely infected mice suffered at least one fetal death, compared with none of the control animals (P = 0.0002). There were no fetal deaths in 18 C3H/HeN mice infected 3 weeks prior to mating (chronic infection). A sensitive PCR technique detected B. burgdorferi DNA in the uteri of acutely infected mice but did not detect DNA in the uteri of controls or chronically infected mice. Spirochete DNA was only rarely detected in fetal tissues, and its presence was not required for fetal death. The inclusion of an internal competitive PCR target indicated that the lack of B. burgdorferi sequences in fetal DNA was not due to the presence of a PCR inhibitor. Histologic analysis of gestational tissues from infected animals demonstrated nonspecific pathology consistent with fetal death. These findings indicate an association between murine fetal death and acute infection with B. burgdorferi early in gestation but not with chronic infection. Our data suggest that fetal death is due to a maternal response to infection rather than fetal infection. These findings could provide an explanation for observations in humans in which sporadic cases of fetal death in women infected with B. burgdorferi during pregnancy have been reported, while previous infection has not been associated with fetal death.