Oligohydramnios is a debilitating condition characterized by an amniotic fluid index of $\le$5 cm or the deepest vertical pocket of $\le$2 cm. It has been shown to be correlated with a series of perinatal morbidities at after 34 weeks of gestation, including low birth weight, fetal acidosis, limb deformities, pulmonary hypoplasia and respiratory distress syndrome [1]. The reported overall newborn survival rate was only 10.2% in those with severe oligohydramnios during the second trimester [2]. Oligohydramnios can be caused by a wide variety of etiologies, including preterm premature rupture of the membranes (PPROM) and conditions with reduced secretion of the amniotic fluid.

Managing oligohydramnios in the second trimester is often challenging. Previous reports have shown that antepartum transabdominal amnioinfusion (TA) may be of potential therapeutic utility for oligohydramnios by re-expanding the amniotic fluid volume [3]. Moreover, TA can enhance the quality of ultrasonographic images, leading to an increased diagnostic yield. Conversely, studies, predominantly in cases with PPROM, have reported that TA does not appear to improve neonatal outcomes and may be linked to potential complications, such as chorioamnionitis and placental abruption [4, 5].

Accordingly, we present our experience with TA in managing patients with oligohydramnios in the second trimester for heterogeneous etiologies. The aim of the current study is to (1) evaluate the safety profiles of TA, (2) assess whether TA improves the detection rate of fetal anomalies.

Oligohydramnios can be found in idiopathic cases or in complicated pregnancies. Impaired regulatory mechanisms accompanied by fetal anomalies, PPROM, fetal growth restriction and impaired placental function are the common etiologies for oligohydramnios [6]. Previous research has indicated that oligohydramnios complicates 32% of fetuses with severe urinary tract anomalies [7]. Similarly, the current study found that 68.87% of cases with severe oligohydramnios were complicated by fetal abnormalities. An additional 19 cases of fetal malformations were detected post-TA by ultrasonography or magnetic resonance imaging, suggesting that TA is a valuable procedure for severe oligohydramnios in the second trimester, enabling detection of fetal anomalies through detailed imaging examinations.

Our results support the notion that TA is a relatively safe procedure with limited complications, which is in line with the reports from Chhabra’s [8] and Wenstrom’s groups [9]. In a retrospective analysis of 313 TA procedures in 126 patients with oligohydramnios, Nagai et al. [10] found that fetal/maternal adverse events occurred in two cases and fetal adverse events requiring pregnancy termination in only seven cases. To minimize the risk of adverse events, all TA procedures should be performed by a multidisciplinary team of operators with extensive experience.

Amnioinfusion can be performed intrapartum or antepartum, as well as for diagnostic or therapeutic purposes [11]. In recent years, antepartum TA has been used primarily for prenatal diagnosis. Based on our analysis, we suggest that TA can enhance the detection of fetal anomalies through an ultrasonographic scan. Earlier studies demonstrated that diagnostic amnioinfusion helped improve the visualization rate of fetal structures from 51% to 77% [12]. Similarly, the detection rate of fetal anomalies significantly increased from 33.80% pre-TA to 60.56% post-TA in the current study. Moreover, magnetic resonance imaging has been demonstrated to improve diagnostic accuracy in certain abnormalities that are otherwise difficult to diagnose due to fetal position and oligohydramnios [13]. Of note, TA ensures better perinatal outcome by prolonging the duration of pregnancy. Several studies have been conducted where women who underwent a subsequent series of TA reached a higher gestational week with a lower rate of perinatal mortality [14, 15].

Whether TA improves perinatal outcomes remains an open question as previous studies report conflicting results. For instance, Turhan et al. [16] and van Kempen et al. [17] both reported that TA in patients with oligohydramnios showed similar perinatal outcomes as those managed expectantly, whereas significant effects of TA on latency period and neonatal outcomes in pregnant women complicated with PPROM have also been reported [18, 19]. In the present study, eight neonates were successfully delivered with pregnancies prolonged up to 63–119 days. In the eight cases of severe oligohydramnios with no obvious associated fetal anomalies, adequate amniotic fluid volume was achieved by repeated TA, thus reducing the incidence of pulmonary hypoplasia and increasing the latency of pregnancy. However, it should be noted that all the women in the no-TA group opted for pregnancy termination. Ideally, a control group of pregnant women with severe oligohydramnios who were managed conservatively would have provided the best comparison. However, due to the tolerability for abortion in China, obtaining such control group would be extremely difficult. Therefore, we believe that TA may be most effective in neonates without fetal structural anomalies.

We acknowledge that most previous studies examining the effectiveness of TA have been conducted in patients with oligohydramnios caused by PPROM. Porat et al. [20] suggest that the latency period from PROM to delivery increased, and the rate of pulmonary hypoplasia and neonatal death decreased after TA. Conversely, in a study with 58 cases of PROM, some researchers found no statistically significant differences between weekly serial TA and no intervention [5]. The etiologies for oligohydramnios in the present study were heterogeneous and thus probably more representative. Nonetheless, the number of PPROM cases in the current study was small and all cases opted for pregnancy termination.

Pulmonary hypoplasia can be secondary to oligohydramnios in PPROM, in which the normal development of lungs is hindered by the lack of amniotic fluid and chronic compression. Moreover, the severity of pulmonary hypoplasia has been observed to be intimately associated with the timing of occurrence of oligohydramnios [21]. Several prior studies [22, 23] reported that fetoscopic endoluminal tracheal occlusion, an experimental prenatal procedure that reversibly block the trachea of the fetus, may improve lung development and increased neonatal outcomes in PPROM before 22 weeks of gestation. Regrettably, this procedure is still in its infancy in China and it requires stringent protocols and extensive experience.

Undoubtedly, additional large, randomized controlled trials are necessary to investigate the benefits of therapeutic TA. However, there are inherent difficulties in designing such studies predominantly due to the ethical and practical difficulties in obtaining the control group. Despite all these, our preliminary experience demonstrates that TA is technically feasible and safe. We believe that more informative decisions could be made following TA that provides enhanced visualization of fetal structures. In the future, such large-scale studies may help establish guidelines for managing oligohydramnios in the second trimester.

In summary, this study showed that TA demonstrates promise in increasing the diagnostic efficiency and enhancing the probability of fetal survival. Given the retrospective nature of this analysis, larger prospective multi-center studies are necessary to conclusively determine the safety and efficacy of TA for severe oligohydramnios.

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Conception and design: YLW; Administrative support: YLW; Provision of study materials or patients: YLW, WG; Collection and assembly of data: WG; Data analysis and interpretation: XZ, YW, RH, LG; Manuscript writing: All authors. All authors read and approved the final manuscript. All authors have participated sufficiently in the work to take public responsibility for appropriate portions of the content and agreed to be accountable for all aspects of the work in ensuring that questions related to its accuracy or integrity.

The study was approved by institutional ethics board of Ethics Committee of International Peace Maternity & Child Health Hospital (approval number: GKLW2019-72). Written informed consents were waived due to the retrospective nature of this study.

We express our sincere gratitude to the colleagues of our unit for their valuable support.

This work was supported by grants from National Natural Science Foundation of China (81971401) and Shanghai Science and Technology Commission (21Y11906600, 18140902501).

The authors declare no conflict of interest.