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Ben Schwartz is Associate Editor, Contemporary OB/GYN.
A recent study looked at whether a cost-effective finger-prick whole-blood test for toxoplasmosis can reliably detect the presence of the parasite Toxoplasma gondii. PLUS: Cell-free DNA (cfDNA) tests are increasingly being offered to women in the first trimester of pregnancy but results from a recent study suggest cfDNA tests may not significantly reduce miscarriage risk.
A recent study in PLOS Neglected Tropical Diseases looked at whether a cost-effective finger-prick whole-blood test for toxoplasmosis can reliably detect the presence of the parasite, Toxoplasma gondii(T. gondii). In toxoplasmosis cases, timely intervention is imperative since the fetus is at most risk for contracting the disease in the third trimester. However, conventional serologic testing can be cost-prohibitive and necessary equipment is not always available.
The researchers recruited participants from the National Collaborative Chicago-Based Congenital Toxoplasmosis Study (NCCCTS) as well as obstetrical patients in Chicago and Morocco. Participants provided whole blood via fingerstick. A total of 205 individuals (244 samples) were included in the study and had their serologic status for T. gondiiassessed using the whole blood-variant test and results were confirmed using either their NCCCTS records or through concurrent standard laboratory testing. Overall, 101 samples proved seropositive, including five from acutely infected individuals who had IgM/IgG antibodies against T. gondii, while 143 samples were seronegative. The authors defined seropositive as having detectable anti-Toxoplasma immunoglobulin G (IgG) and/or immunoglobulin M (IgM).
The whole blood test was found highly sensitive and specific with a sensitivity of 100% (95% CI: 96.41%-100%) and specificity of 100% (95% CI: 97.45%-100%). The authors found 100% concordance with whole-blood, serum variant, and reference testing as well.
The authors believe there are several advantages to their point-of-care test. The test is much more convenient and less invasive than conventional serologic testing. It also has the potential to have greater availability given its low cost. It is also much quicker with results available for interpretation within 20-30 minutes. There are some noted disadvantages, however. It requires initial, alternative testing for those who are seropositive to distinguish IgG from IgM and requires follow-up testing for seroconversion when used for screening during gestation. The required fingerstick may cause discomfort for the patient and may also need to be performed multiple times in cases with technical difficulties. There is also some training involved in performing and interpreting the test. However, the authors believe that the high sensitivity and specificity of the test as well as its low cost can help reduce morbidity and mortality from congenital toxoplasmosis.
Do cfDNA tests reduce miscarriage rates?
Cell-free DNA (cfDNA) tests are increasingly being offered to women in the first trimester of pregnancy. One argument for use of this modality is to decrease the number of invasive testing and the associated risk for miscarriage. But results from a recent study appearing in JAMA suggest cfDNA tests may not significantly reduce miscarriage risk.
The randomized, multicenter, clinical trial included 1997 women (mean age=36.2 years) who had a risk of Down syndrome between 1 in 5 and 1 in 250 based on first trimester combined screening or sequential combined screening. These women were assessed at 57 centers throughout France between April 2014 and April 2017. The women were randomized to either cfDNA testing followed by invasive testing when cfDNA tests were positive (n=1015) or direct invasive testing (n=982). All the women included in the study were believed to have a higher likelihood of an affected fetus based on maternal age and other clinical factors identified during the first trimester screens.
The authors found that the cfDNA screening and confirmatory tests were able to reliably identify trisomy 21 cases but miscarriage rates prior to 24 weeks gestation were similar in women from both the cfDNA and invasive arms of the study (8[0.8%] vs 8 [0.8%] miscarriages; risk difference, -0.3%; 1-sided 95% CI, -0.68% to ∞, P=.47). On average, miscarriages occurred at a median of 19.9 (IQR, 16.9-21.1) weeks’ gestation in cfDNA testing and 19.9 (IQR, 18.8-22) weeks’ gestation. However, the researchers also noted that 751 (76.5%) of women in the invasive group went on to have amniocentesis or CVS compared to just 84 (8.3%) women in the cfDNA group. Overall, there were 28 (2.8%) and 49 (5%) chromosomal abnormalities diagnosed in the cfDNA and invasive testing groups, respectively.
The authors note some limitations to their study. Although the invasive testing rate was lower following cfDNA tests, the high false-positive rate (5.6%) in the group was much higher than the average 0.1% published in earlier studies. Cell-free DNA testing was also only performed for trisomy 21, while the potential for cfDNA to rule out other chromosomal anomalies is likely to improve in the near future, this expanded use was not employed in this study. It’s also possible that the study may have been underpowered to identify potentially clinically important reductions in miscarriages with cfDNA testing. The authors believe that while miscarriage results were similar in both groups, cfDNA tests still hold value since patient safety is still a main priority. The number of invasive procedures was far lower in the cfDNA group and invasive procedures have been associated with extremely rare but severe outcomes, such as maternal septicemia and death.