Out of 137 articles, 5 articles met our inclusion criteria. These articles included a total of 22 fetuses with circular shunt in which NSAIDs were used to attempt ductal constriction [10, 11, 12, 13, 14] (Table 1). Through screening, 120 articles were removed due to irrelevance. Seventeen full-text articles were assessed and twelve were excluded due to being undesired study design or did not meet our eligibility criteria of NSAID use for intervention.
Ductal constriction was confirmed by echocardiography across all 5 studies. Gill et al. and Torigoe et al. also utilized fetal cardiac MRI to evaluate for ductal constriction. Freud et al. defined ductal constriction as visible narrowing and flow acceleration with a peak velocity > 2 m/s and/or increase in diastolic flow with pulsatility index < 1.9. Gill et al. defined it as visible DA narrowing and normalization of the umbilical artery flow. Torigoe et al. defined it as visible narrowing as well as increased doppler flow gradients from the baseline. Finally, Lopes et al. and Powel et al. did not specify criteria used to define constriction of the DA. All the above-mentioned criteria were used to adjust NSAID therapy based on individual fetal response and disease progression.
Of the 22 fetuses that received NSAID therapy, 82% achieved ductal constriction. Freud et al. were able to achieve ductal constriction in 12 of 15 (80%) fetuses receiving therapy. In a case series by Torigoe et al., three of four fetuses were able to achieve the same outcome with NSAIDs. Cumulatively, 4 of the 22 fetuses were resistant to NSAID therapy, even with high doses of indomethacin. Of the 18 fetuses able to achieve ductal constriction, only 1 experience fetal death (about 6%). By comparison, of the 4 fetuses unable to achieve ductal constriction, 2 (50%) experience fetal death.
Of the 22 fetuses, at least 59% experienced oligohydramnios at some point during therapy. However, in the case report by Gill et al., the presence of oligohydramnios was not stated.
The therapeutic regimen for each study is summarized in Table 2. However, it is important to note that therapy response differed in each fetus and was titrated accordingly. Of the fetuses able to achieve ductal constriction, 56% were unable to wean therapy to ibuprofen and needed to continue indomethacin to maintain ductal constriction. Of those able to achieve ductal constriction, 8 were able to discontinue indomethacin therapy while 14 were unable to do so.
Of the 22 fetuses identified in these studies, 10 (45%) presented with hydrops at some point. The main point of treatment was aimed at reduction of this unfavorable outcome. Notably, of the 10 fetuses with hydrops, 50% had resolution with prenatal NSAID therapy (Table 1).