Amnioreduction safety in singleton pregnancies; systematic review and meta-analysis

Introduction

Polyhydramnios, characterized by an abnormal increase in amniotic fluid, can be attributed to maternal or fetal causes [1]. Different methods exist to identify normal and abnormal amniotic fluid volume levels [2]. The classifications of mild, moderate, and severe polyhydramnios are based on amniotic fluid index (AFI) measurements: mild is 24.0–29.9 cm, moderate is 30.0–34.9 cm, and severe is ≥35 cm. Alternatively, these classifications can also be determined by the deepest vertical pocket (DVP) dimensions: mild is 8–11 cm, moderate is 12–15 cm, and severe is ≥16 cm. [3], [4], [5]. Prenatal ultrasound identifies polyhydramnios in approximately 0.7 % of pregnancies, with severe classification accounting for 12 % of cases [4]. Pregnancies with polyhydramnios are associated with an increased risk of maternal complications, including maternal distress, cord prolapse, placental abruption, and postpartum hemorrhage [6], 7].

One method that can alleviate polyhydramnios is amnioreduction (AR). Initially described in 1933, AR was frequently used to manage twin-twin transfusion syndrome (TTTS) in monochorionic (MC) twin pregnancies and for alleviating polyhydramnios in singleton pregnancies [8], [9], [10]. There are different protocols for fluid removal amounts, removal speed, or the use of tocolytics and antibiotics. Typically, the procedure involves ultrasound-guided insertion of an 18-gauge needle, suctioning fluid, and aiming to normalize the AFI without exceeding 2.5 L at a time or 1,000 mL over 20 min [10], 11]. Amnioreduction primarily aims to lessen maternal discomfort associated with severe polyhydramnios, and in certain cases, to manage fetal complications arising from underlying anomalies, such as hydrops or sacrococcygeal teratoma [12]. While the procedure may carry peri-procedural risks, such as preterm birth [13], these events are often linked to the underlying etiology of the condition rather than the intervention itself. Overall, there is ongoing uncertainty regarding the advantages of AR in terms of extending the duration of pregnancy, reducing the preterm premature rupture of membranes (PPROM) rate, increasing the likelihood of vaginal delivery, and decreasing the occurrence of uterine atony [11], 14], 15].

In twin pregnancies, the prevalence of polyhydramnios is notably higher, primarily due to the complications of placentation [1]. To date, there is a paucity of published series on AR, with most of the available data coming from twin pregnancies complicated by TTTS, a condition with distinct pathophysiological characteristics [16], [17], [18], [19]. Fewer published studies have discussed complications of AR with singleton pregnancies [11], 12], 15], 20], 21]. The objective of our study is to conduct a systematic review and quantitative analysis of studies on adverse events related to safety following AR in singleton pregnancies, parsed by maternal and fetal measures of efficacy and risk.

Materials and methods

The Preferred Reporting Items for Systematic Reviews (PRISMA) 2020 guidelines were used to conduct this study. A protocol was submitted to the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024548134).

Results

Study selection, study characteristics, risk of bias of included studies

The process of study selection is shown in Figure 1. Study characteristics are shown in Table 1. The results of the risk of bias assessment are reported in Supplementary Table 2.

Figure 1:

Flow diagram of the study selection process.

Table 1:

Study characteristics.

Studies	Year	Country	Study period	Twin/singleton	Population, n
Piantelli et al. [24]	2004	Italy	2000–2003	Singleton	10
Dickinson et al. [11]	2014	Australia	2000–2012	Singleton	138
Kleine et al. [25]	2016	Brazil	2001–2014	Singleton	44
Ali et al. [26]	2018	India	2000–2012	Singleton	28
Erfani et al. [15]	2019	USA	2011–2018	Singleton	33
Katsura et al. [20]	2019	Japan	2017–2018	Singleton + symptomatic	18
Katsura et al. [20]	2019	Japan	2017–2018	Singleton + asymptomatic	9
Soni et al. [21]	2023	USA	2013–2021	Singleton	110
Leung et al.a [27]	2004	UK	1995–2002	Singleton/twin	37
Laoreti et al.a [12]	2024	Italy	2010–2023	65 singleton/21 twin	86

1. ^aExcluded studies due to pooled population of singleton and twin pregnancies.

Discussion

Our meta-analysis and systematic review aimed to discuss the maternal safety of amnioreduction in singleton pregnancies diagnosed with polyhydramnios (Defined as AFI ≥24 cm or DVP ≥8 cm). Although fetal mortality and mode and timing of delivery are influenced by and reflect the underlying fetal anomalies causing the polyhydramnios, our results showed that maternal complications – including placental abruption, chorioamnionitis, PPROM, and delivery within 48 h – appear to be low, highlighting the relative safety of this procedure.

In addition to safety, procedures performed during pregnancy should have demonstrable benefit such that any residual risk can be justified. In considering the risk to benefit ratio, one must consider that pregnancies with polyhydramnios have a higher prevalence of structural and congenital fetal anomalies, associated with an inherently high incidence of perinatal death [4], 5], 28]. Consequently, patients with severe polyhydramnios are often referred to specialized centers for delivery due to the risk of undetected anomalies [1]. Our included studies report a list of prenatal malformations, as summarized in Supplementary Table 1.

It is important to note that based on recommendations from multiple scientific societies [1], AR is primarily indicated for the relief of severe maternal symptoms, and appears to be the preferred option in moderate to severe cases [29], 30]. Also, considering the high rate of cesarean deliveries in pregnancies complicated by polyhydramnios, it is noticeable that AR may offer potential for vaginal birth when a Cesarean might otherwise be performed [31], 32]. The high cesarean delivery rate in cases requiring amnioreduction reflects contributions from both the amnioreduction procedure and the presence of underlying fetal anomalies, making it challenging to isolate the specific impact of each factor.

The sole previous meta-analysis examining the complications of AR in singleton pregnancies incorporated merely four small case series. However, in contrast to our study, the authors failed to reliably quantify risk due to a low confidence in the complication rate, reflecting a limited number of cases and wide heterogeneity [33]. A 5-year retrospective study from Israel reported that the isolated polyhydramnios at birth correlated with prolonged labor, placental abruption, and fetal heart rate abnormalities [34]. Several studies have indicated a heightened incidence of postpartum hemorrhage (PPH) in patients with polyhydramnios [34], 35]. On the other hand, our study demonstrated a low occurrence of placental abruption and chorioamnionitis in the AR group. This data holds significance for patient counseling and should be integrated into the informed consent process. Additionally, for healthcare providers, this study contributes insights for evidence-based practices in the side effects due to the management of pregnancies complicated by polyhydramnios.

While bolstered by inclusion of a larger number of cases and thus improved over prior analyses, our study similarly suffers from a small overall population and lack of robust assessment for causes of polyhydramnios. As the fetal safety of AR is associated with the underlying fetal anomalies causing polyhydramnios, the evaluation of fetal safety of AR per se is not theoretically possible. For whatever reason, amnioreduction in singleton gestations has become remarkably rare at our institutions, necessitating future multicenter collaboration to generate robust data and inform best practices. It is the first systematic review in over a decade to thoroughly examine the AR procedure in singleton pregnancies. Despite this limitation, our confidence in demonstrating low parsed maternal risk in largest number is significant.

In conclusion, our study demonstrated that complications – such as placental abruption, chorioamnionitis, PPROM, and delivery within 48 h – are unlikely following the AR procedure. This study serves as an initial step in compiling the safety data on AR and highlighting it as a safe option for maternal symptom relief. The prolongation of pregnancy and fetal survival should be compared with expectant management, in future studies, including appropriately and adequately powered randomized trials.