Congentital Toxoplasmosis
by Beth A. Pletcher, MD, March 1999

As more obstetricians perform routine screening for toxoplasmosis, the number of women screening positive in early pregnancy is increasing as well. Because of conflicting information about the interpretation of a positive test, the relatively high rate of false positives, and persistence of circulating IgM long after infection, many clinicians are struggling with the issue of what to do for these patients. A number of years ago when IgG and IgM screening for toxoplasmosis was just coming into vogue, there was an extremely high rate for false positive IgMs due to cross-reactivity of the assay with IgG. Over time, with improving laboratory techniques, the rate of false positivity is fortunately going down, but there remains a fair number of women who require additional diagnostic testing.

Review of the literature over the past few years (much of the data coming from European centers) has given some guidance relating to toxoplasmosis infection in pregnancy. Various antibiotic regimens have been used with some success. While there are conflicting reports and many different serologic and diagnostic methodologies employed, here are some conclusions from these articles.

  • Most prenatal infections with this protazoa occur as a result of contact with infected cats or ingestion of improperly cooked meat (beef, pork or lamb). Since most adults have asymptomatic infections, the mainstay of pregnancy screening includes measurement of toxo IgM and IgG with special attention to changes in IgG titers. Prenatal testing can be done in a number of ways and might include ultrasound, fetal blood sampling for toxo IgM or more recently detection of toxo by PCR amplification on a sample of amniotic fluid. 1

  • Large scale studies of pregnant women in the UK using both IgG and IgM measurements suggest that about 0.4% of women had a recent infection (most acquired during the first trimester) and another 7.7% represented a latent infection. 2 These numbers may be slightly higher in the US, depending upon the population, since the incidence of congenital toxoplasmosis in our newborns is estimated to be about 1%.

  • In yet another large study involving almost 36,000 pregnancies in Norway with screening throughout gestation, about 0.2% of women were found to have a primary infection and almost 11% a prior infection. The rate of primary infection increased, however, if the patient had come to Norway from another country, lived in Oslo or was tested in the first trimester. The infected patients were offered prenatal testing and in those tested, almost 1/4 had congenitally infected infants. However, the risk for transmission seemed to increase with gestational age at which the infection occurred, with transmission rates of 13%, 29% and 50% in the first, second and third trimesters respectively. Interestingly, the only clinically affected infant out of the 11 identified was born to a mother who did not receive prenatal antibiotic therapy. 3

  • In one large series of women suspected to have acquired toxoplasmosis during pregnancy and who underwent cordocentesis and/or amniocentesis for IgM/IgA/IgE or cell culture/mouse inoculation, infection was confirmed in almost 12% of newborns with only 77% of those detected prenatally. 4 Since testing did not include amniotic fluid PCR analysis for toxoplasmosis it is likely that this newer methodology would greatly improve the prenatal diagnostic rate.

  • Use of amniotic fluid PCR testing for toxo has proven to be both sensitive and specific and carries with it decreased risks for fetal loss compared to cordocentesis. In a study from Austria examining offspring of 49 patients with a confirmed infection in pregnancy, PCR correctly identified all infants with a confirmed congenital infection and all infants who were negative by PCR were also negative at one year of age regardless of whether the mother did or did not have prenatal antibiotic treatment. 5

  • Examination of the placenta also may provide some insight into toxoplasmosis in women with suspected infection who did not undergo prenatal diagnosis. In a study comparing normal placentas with placentas obtained from women whose children had congenital infection, placental culture detected almost 30% of infected infants, mouse inoculation with placental tissue increased the detection rate to 51% whereas placental tissue PCR increased the detection rate even more to almost 61%. However, with PCR analysis, there was a false positive rate of 9.5%. 6

  • Radiographic findings with congenital tosoplasmosis are inconsistent and may not be present even in the face of a true fetal infection. On the other hand, use of prenatal ultrasound may augment clinical evaluation when combined with maternal serologic testing and prenatal diagnosis. 7

  • In a study from Norway looking at outcomes and treatment for 144 women with seroconversion during pregnancy, 64 of 144 infants were eventually dignosed with congenital infections. Of these 64 infected infants, 19 had some clinical sequelae, 6 of whom had severe sequelae. Prenatal therapy with antibiotics did not appear to decrease the risk for transmission to the fetus nor did the time between diagnosis and initiation of therapy impact risk for fetal infection. As expected, the gestational age at the time of seroconversion did impact transmission risks with later infections associated with increased transmission. Treatment with antibiotics prenatally did in fact decrease the risks for sequelae (especially severe sequelae) in the newborn and the earlier the treatment was initiated, the better the outcome. 8

  • A retrospective review of cases of congenital toxoplasmosis looking at treatment regimens of spiramycin alone vs. alternating cycles of spiramycin and pyrimethamine-sulfonamide showed no significant differences in the rate of fetal infection (transmission) or the occurrence of symptoms or overt disease in the newborn between these two protocols. 9

  • One recent report of a congenital toxo infection in a newborn whose mother was infected before conception raises the issue of an appropriate disease free period prior to conception. From this study a recommendation was made to advise women with a primary toxo infection to wait six to nine months before considering pregnancy. 10

  • In a 1997 article in Obstetrics and Gynecology the issue of the value of routine toxoplasmosis screening in pregnancy was examined. This group looked at three different approaches to screening: a) no testing in pregnancy, b) targeted screening when fetal anomalies were noted and c) screening all pregnant women. They concluded that although approach "c" would decrease the incidence of congenital toxoplasmosis compared to "a" and "b", it would cause 18.5 pregnancy losses from invasive prenatal testing for each child with congenital toxoplasmosis prevented. Even if all fetuses identified as being affected were terminated, there would still be 12.1 pregnancy losses for each case of congenital toxo avoided. 11

Based upon all of this recent data, what is the most reasonable approach to patient care in this setting? In our practice, women who screen positive for toxoplasmosis by IgG and IgM serology will be offered additional testing through a laboratory doing more sensitive assays using IgA and Ig ratios to try to more accurately pinpoint the time of primary infection. We feel this is necessary because of the still significant chances of a false positive IgM result coupled with the prolonged production of IgM after a primary infection. It is also important to take a focused exposure history including: cats in the household, exposure to cat litter, ingestion of undercooked or raw meat and exposure to soil through gardening outside. Some women may have been screened in another pregnancy in the past and if those results are available, you may be able to avoid further testing if she was identified as positive in the distant past. If further testing confirms a primary infection during or just prior to pregnancy, then prenatal testing and antibiotic therapy should be considered. The most sensitive prenatal test seems to be the amniotic fluid PCR analysis, but amniotic fluid culture/mouse inoculation and or cordocentesis for fetal IgM determination are still being offered in some centers. The fetal risks with cordocentesis compared to amniocentesis alone need to be considered as well. For patients who test positive, a detailed discussion needs to take place and if termination is not an option, therapy with spiramycin should be offered. This medication has, in the recent past, been difficult to obtain in the US, but remains the mainstay of treatment and appears as effective as other regimens as outlined in the articles cited above. Although ultrasound examination of the fetus may augment the prenatal diagnosis of congenital toxoplasmosis, for many affected fetuses the sonogram may be normal, even when the infants are clinically affected at birth. Referral to a trained perinatologist is certainly a reasonable course of action when this diagnosis is made prenatally. The decision to offer routine screening to all prenatal patients remains controversial and needs to be made by each clinician in practice. If a provider did not feel that toxo screening should be offered to all patients, it might be practical to offer screening to those patients who are identified as high risk. These patients might include women who have cats in their home (and the cats have not been recently tested for toxo), women who have traveled outside of the US recently and those who acknowledge ingestion of raw or undercooked meats. Screening only women who are identified to be at risk by virtue of an abnormal sonogram will surely miss a large number of infected fetuses and clearly no screening (as advocated in the 1997 article cited above) will also miss infected women. Over time we may also look to ACOG for guidance on this issue; it already has a Technical Bulletin on the subject. For each clinician the ultimate decision to screen patients is a personal choice and must take into account varying patient populations and optimal patient care.

  1. Semin Perinatol 1998 Aug; 22(4):332-8

  2. J Infect 1998 Mar; 36(2):1189-96

  3. J Clin Microbiol 1998 Oct; 36(10):2900-6

  4. Prenat Diagn 1997 Nov; 17(11):1047-54

  5. Eur J Clin Microbiol Infec Dis 1998 Dec; 17(12):853-8

  6. Placenta 1998 Sep; 19(7):545-9

  7. Pediatr Radiol 1997 Feb; 27(2):133-8

  8. Am J Obstet Gynecol 1999 Feb; 180(2 Pt 1):410-5

  9. Am J Reprod Immunol 1998 May; 39(5):335-40

  10. Prenat Diagn 1998 Oct; 18(10):1079-81

  11. Obstet Gynecol 1997 Sep; 90(3):457-64