Introduction
Preterm birth, defined as birth before 37 weeks of gestation, is the leading cause of death of children under the age of five years worldwide. Globally there has been no change in the preterm birth rate between 2010 and 2020, when rates were calculated to be 9.8% and 9.9% of all livebirths, respectively. The analysis of amniotic fluid has been advocated by many to identify the mechanisms driving threatened preterm labor. Amniocentesis is largely considered to be safe, but care provider concerns about complications in the setting of threatened preterm labor (tPTL) exist. This systematic review will critically review the data regarding safety and outcomes of amniocentesis in cases of PPROM and tPTL and help in the counseling and clinical decision-making of patients and care providers alike.

Methods
This systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA). All English language, peer-reviewed human studies where amniocentesis was used to sample the amniotic fluid of patients presenting with tPTL or PPROM and published between January 1990 and March 2022 were included. Data on the uptake rates, success rates, and safety profile associated with amniocentesis in this context of tPTL or PPROM were analyzed as part of the systematic review. Included studies compromised of randomized control trials, cohort studies, and case-control studies. Conference abstracts and abstracts with no full text were excluded.

Results
10,215 studies were returned after searches were conducted in MEDLINE, EMBASE, EMCARE, Web of Science, and SCOPUS databases using free text and Medical Subject Headings (MESH). 399 studies were assessed for eligibility with 15 studies being included in the final review. The main reason for exclusion from the review was an absence of safety data. Four studies gave information on uptake rates of amniocentesis in cases of PPROM and tPTL, with a range of 55% in an observational study to >99% in centers offering it as part of routine care. Eleven studies detailed success rates of amniocentesis, with all centers reporting >90% success rates. However, in some centers, a “successful” amniocentesis was deemed to be a retrieval of >0.5 ml. Three studies reported risks associated with amniocentesis. There were four reported complications (all transitory) in a series of 1119 cases (0.35%).

Discussion
This systematic review found that amniocentesis in cases of PPROM or threatened preterm labor is a safe and feasible procedure. These data should give care providers confidence to counsel patients appropriately.