Fetal therapy is commonly performed worldwide. Several studies reported that amnioinfusion may change intrauterine pressure and alter maternal and infant circulation, and that it improves fetal blood flow in umbilical cord compression. Unfortunately, severe maternal adverse events, such as amniotic fluid embolism by excessive amnioinfusion, were reported. In addition, although these treatments have great potential, including transabdominal amnioinfusion, they were likely avoided because of potential ethical, social, and economic issues, few poorly documented complications, and the bias against difficult-to-treat diseases.

In the field of cancer treatment, the Common Terminology Criteria for Adverse Events (CTCAE) are widely used for objectively evaluating adverse events based on the guidelines of the International Conference on Harmonization (ICH). Adverse events are defined as all undesired events, laboratory data, symptoms, and diseases that are not always related to the preceding procedures and therapy.
R. Nagai et al established an evaluation criteria for the adverse events of fetal treatment and applied them by re-assessing prospective studies of TAS procedures performed in Japan. Here, they retrospectively re-evaluated the occurrence of adverse events while performing transabdominal amnioinfusion in case series. In this study, adverse events while performing transabdominal amnioinfusion were successfully analyzed by the CTCAE for common medical indications such as TAS.
This study is a retrospective cohort study at a single tertiary perinatal center in Japan. A total of 313 procedures in 126 patients who underwent amniocentesis for transabdominal amnioinfusion at tertiary perinatal institution were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE). Adverse events were retrospectively examined using a 5-grade evaluation based on the CTCAE. Procedurally, a 21–23-G percutaneous transhepatic cholangiography drainage (PTCD) needle was advanced under ultrasound guidance into the amniotic fluid cavity with a gravity-fed infusion of warm saline solution.
No maternal deaths were recorded. Only two maternal/fetal adverse events occurred, and grade 4 fetal adverse events requiring pregnancy termination were observed in seven cases. Fetal death occurred in five cases, all with severe oligohydramnios and premature rupture of the membranes. No placental abruption or bleeding occurred before or after delivery.
Fetal therapy is a new category of treatment and has few systematic reports on adverse events; although there are reports that evaluate the effects and complications of procedures individually, they summarize the overall adverse events of the procedure without considering the effects of the procedure itself. This information is necessary to supplement data about the efficacy and safety of the treatment and to avoid generalizations.
In the present study, authors first evaluated the adverse events for the mother. Although pain caused by the procedure occurred in ≥ 95% of cases, the degree was Grade 2. There were no cases of complications of Grade 4 or higher that would make continuing pregnancy difficult. In other words, the risk is low that amnioinfusion will affect the mother who experiences difficulties in continuing pregnancy. Second, they examined the adverse events involving both the mother and fetus. One case of Grade 3 intrauterine infection was preceded by PROM, and transabdominal amnioinfusion was performed, resulting in clinical chorioamnionitis. Since maternal fever and inflammatory findings (increased white blood cell count and C-reactive protein level) were observed, the extension of pregnancy was discontinued two days after transabdominal amnioinfusion due to the possibility of maternal sepsis, and the infant was delivered. No Grade 3 or higher adverse events were found in the postpartum mothers or infants.
Study reports that amnioinfusion improves fetal blood flow impairment due to umbilical cord compression. In other words, it is easy to assume that amnioinfusion will affect fetal circulation, but a fetation in poor conditions that cannot adapt to changes in the intrauterine environment may result in fetal death. In cases requiring amnioinfusion, it is difficult to evaluate the causal relationship between the amnioinfusion procedure and adverse events because of the high risks and complex uterine environment of the original maternal and fetal conditions.
In conclusion, adverse events while performing transabdominal amnioinfusion were successfully analyzed by the CTCAE for common medical indications such as TAS.Authors also succeeded in providing new terminology for evaluating adverse events during transabdominal amnioinfusion. These results may allow obstetricians to perform transabdominal amnioinfusion in several difficult situations without the concern of causing severe adverse events for the mother and fetus.
Source: R. Nagai et al.; European Journal of Obstetrics & Gynecology and Reproductive Biology 271 (2022) 132–137