The safety, acceptability, and success rates of amniocentesis in the context of preterm prelabor rupture of membranes and threatened preterm labor: a systematic review and meta-analysis

Abstract

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.

Keywords:

• PPROM
• preterm labor
• amniocentesis
• microbial invasion of the amniotic cavity
• safety

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 [1]. Challenges surrounding reporting and the standardization of definitions means that the true global incidence of preterm birth is unknown but is estimated to be around 10% of all births [2]. This equated to approximately 13 million births in the year 2020 [3], resulting in the deaths of 900,000 babies within the first 28 days of life [4].

Between 30–35% of preterm births occur for indicated maternal or fetal reasons such as pre-eclampsia (PET) or fetal growth restriction (FGR). The remainder follow spontaneous preterm labor (40–45%) or preterm prelabor rupture of membranes (PPROM) (25–30%) [5]. PPROM therefore complicates 3% of all pregnancies, of whom 50–60% will deliver within the following seven days [6]. Microbial invasion of the amniotic cavity (the presence of microorganisms and/or their nucleic acids) and/or intra-amniotic inflammation (elevation of concentrations inflammatory mediators in amniotic fluid) play an important role in these cases of preterm birth, with rates of infection inversely related to gestational age at presentation [7]. Epidemiological studies have clearly demonstrated that exposure of the fetus to intrauterine inflammation increases the risk of mortality, adverse neurological [8], pulmonary [9], and gastrointestinal outcomes. These complications include bronchopulmonary dysplasia [10,11], necrotizing enterocolitis [12], cerebral palsy [13], autism spectrum disorders [14], asthma, and others. Importantly, exposure to intra-amniotic inflammation appears to be an independent predictor of poor outcomes even in babies born at term [15].

Following PPROM or presentation in spontaneous or threatened preterm labor (tPTL), pregnancy management strategies are reactive, and aim to optimize neonatal outcome. The current standard of care in eligible patients is tocolytic therapy to delay delivery allowing administration of maternal corticosteroids to promote fetal lung maturity, magnesium sulfate infusion for neonatal neuroprotection, and maternal antibiotics to treat suspected infection. There have been no new strategies for prevention of prematurity in the last two or more decades. Indeed, effective interventions to predict and prevent preterm birth and establishing which treatments are most effective for PPROM were identified as being two of the “Top 15 UK research priorities for preterm birth” in the 2014 James Lind Alliance Priority Setting Partnership [16].

The most important reason for prevention of prematurity is to optimize fetal health and neonatal outcomes. Yet, most of the intervention trials for prematurity focus on the primary end point of gestational age at delivery. While the degree of prematurity is undoubtedly an important determinant, the longer-term infant outcomes are the most important. Pre-clinical studies in the non-human primate and rodent models suggest that targeted anti-inflammatory therapy decreases fetal inflammation and may prevent prematurity and some of the associated complications [17,18]. Maternal systemic antibiotics, the current mainstay of treatment, have only a limited efficacy in the setting of intra-amniotic inflammation and preterm labor [17,19–21]. If clinical trials with novel anti-inflammatory therapy are to be conducted, precise identification of the population who will benefit and perhaps more importantly, the population in whom novel anti-inflammatory therapies could be harmful, is critical.

Approximately 85% of women experiencing preterm birth have no identifiable risk factors for preterm birth at the beginning of their pregnancy [22], highlighting the need to find effective biomarkers before the event. Further, in women presenting with threatened preterm labor identifying the mechanisms involved and so being able to target therapy is a key and urgent clinical need and will allow us to standardize diagnostic approaches to PPROM and threatened preterm labor.

The analysis of amniotic fluid has been advocated by many to identify the mechanisms driving threatened preterm labor. The advent of next generation sequencing to identify infective organisms and profile host responses has reignited interest in the potential of amniotic fluid analysis to advance our understanding and to guide therapy. Amniocentesis is largely considered to be safe [23], but care provider concerns about complications in the setting of threatened preterm labor exist [24]. In addition, patients may also be concerned regarding the risks of amniocentesis [25]. Indeed, amniocentesis for the detection of intra-amniotic infection or inflammation is currently not discussed by either the Royal College of Obstetricians and Gynecologists or the American College of Obstetrics and Gynecology in their respective guidance for the investigation or management of preterm labor or PPROM [26,27]. These recommendations largely stem from a lack of evidence that amniocentesis will change management given current therapeutic choices, and the concern for safety. In an attempt to move the field forward, the Preterm Birth International Collaborative (PREBIC) identified the need to address the role that amniocentesis may play in guiding optimal antibiotic treatment for intra-amniotic infection, and predicting the timing of delivery in PPROM [22]. With advancements in point-of-care diagnostics, molecular microbial identification, and development of novel biologics, we posit that it will become more important in the future to tailor personalized therapies with precise risk profiles using amniotic fluid specimens.

This systematic review will critically review the data regarding safety and outcomes of amniocentesis in cases of PPROM and threatened preterm labor. This review will help inform the counseling and clinical decision-making, of patients, care providers, and researchers alike.

Methods

Protocol and registration

This systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) (Figure 1). The protocol for this review was registered with the international prospective register of systematic reviews (PROSPERO). The registration number is CRD42022352985.

Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) diagram [28].

Eligibility criteria

All English language, peer-reviewed human studies where amniocentesis was used to sample the amniotic fluid of patients presenting with threatened preterm labor (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 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.

Search strategy

A systematic review was conducted in MEDLINE, EMBASE, EMCARE, Web of Science, and SCOPUS databases using free text and Medical Subject Headings (MESH). The search strategy is available in the supporting information. Zotero software (Roy Rosenzweig Center for History and New Media, 2016, Zotero Computer Software) was used to remove duplicates from the search, and Covidence software (Veritas Health Innovation Ltd, Melbourne, Australia) was used to manage study screening and extraction.

Selection process

Two authors (DS and SS) screened all titles and abstracts independently, excluded studies deemed to be irrelevant, and then independently assessed the remaining full text articles for eligibility. Any disagreements were resolved by consensus. Studies were included where information was provided relating to any of the following: rate of uptake of amniocentesis, success rates of retrieval of amniotic fluid, safety, complications,.

Risk of bias

The Cochrane Collaboration’s tool for assessing risk of bias in randomized trials (RoB 2) was used to assess to quality of RCTs [29] (Supplementary Table 5). The quality of non-randomized trials was assessed using the Cochrane Collaboration’s ROBINS-I tool [30] (Supplementary Table 6).

Assessment of heterogeneity and data pooling

Data were assessed for heterogeneity by applying the I² test to determine whether data could be pooled. An I² value of <40% was accepted to indicate minor heterogeneity, 40–75% moderate heterogeneity, and >75% as significant heterogeneity. This analysis was performed using Review Manager (RevMan) version 5.4.

Results

Study characteristics

Fifteen studies were selected for analysis. One was a randomized control trial (RCT) [31], and one was a case-control study [32]. Of the remaining 12 studies, 5 were retrospective studies and 7 were prospective studies [33–45]. The study characteristics are summarized in Table 1.

Table 1. Characteristics of included studies.

Author, year, country	Study design	Study aim	No of patients	PPROM, PTL, both	Risk, uptake, success rate
Angus et al. [32] 2001, USA	Case-control	To assess whether MMP-8 levels in amniotic fluid are a useful marker of intra-amniotic infection	77	Both	No complications reported
Cobo et al. [33] 2022, Spain	Retrospective observational study	Development and validation of multivariable model of preterm birth	531	PTL	443/531 accepted amniocentesis − 88 declined
Combs et al. [34] 2014, USA	Prospective observational study	Development of a noninvasive test for microbial invasion of the amniotic cavity (MIAC)	320	PTL	Success rate 305/320 − 15 failed
Ferrazzi et al. [35] 2012, Italy	Prospective observational study	Analysis of obstetrical and neonatal outcomes in patients with AF collected within 48 h of presentation with tPTL and PPROM	40	Both	22/40 accepted amniocentesis − 17 declined
Fulova et al. [45] 2021, Czech Republic	Prospective observational cohort study	Evaluation of point-of-care IL-6 test in amniotic fluid obtained by amniocentesis in patients with PPROM	67	PPROM	Success rate 62/67 − 5 failed
Jacobsson et al. [36] 2003, Sweden	Prospective observational cohort study	Evaluation of the relationship between MIAC, IL-6, and IL-8 levels and preterm birth	58	PPROM	Success rate 53/58 − 5 failed
Kacerovsky et al. [37] 2012, Czech Republic	Prospective observational study	Evaluating whether the bacterial load of genital mycoplasmas and gestational age are related to the intra-amniotic inflammatory response.	152	PPROM	152/153 accepted − 1 declined Success rate 145/152 − 7 failed
Kacerovsky et al. [38] 2020, Czech Republic (a)	Retrospective cohort study	Evaluate if anti-microbial agents can reduce the magnitude of the intra-amniotic inflammatory response in patients with PPROM	315	PPROM	Success rate 312/315 − 3 failed
Kacerovsky et al. [40] 2020, Czech Republic (b)	Retrospective cohort study	To determine the association between MIAC and lactobacilli dominated cervical microbiota in patients with PPROM	311	PPROM	Success rate 309/311 − 2 failed
Leaños-Miranda et al. [37] 2021, Mexico	Prospective observational cohort study	Evaluate if IL-6 levels in AF collected by amniocentesis correlated with levels of intra-amniotic inflammation and adverse outcomes	452	PTL	No complications reported
Musilova et al. [43] 2017, Czech Republic (a)	Retrospective cohort study (May 2008–July 2016)	To determine the feasibility and complication rate of amniocentesis in a large cohort of women with PPROM	590	PPROM	Success rate 567/590 − 23 failed; Complication rate 4/590 (0.7%)
Musilova et al. [44] 2017, Czech Republic (b)	Prospective cohort study	To determine the relationship between maternal WCC in pregnancies complicated with PPROM and presence of MIAC	526	PPROM	525/526 accepted − 1 declined Success rate 523/526 − 3 failed;
Musilova et al. [41] 2018, Czech Republic	Retrospective cohort study (January 2016–July 2017)	Evaluation of AF pentraxins as potential biomarkers for identifying intra-amniotic inflammatory complications in PPROM	159	PPROM	Success rate 158/159 − 1 failed
Musilova et al. [42] 2019, Czech Republic	Prospective study (October 2015–September 2016)	To determine the pulsatility in the fetal portal system with respect to the presence or absence of intra-amniotic inflammation in PPROM	87	PPROM	Success rate 86/87 − 1 failed
Ovalle et al. [31] 2002, Chile	Randomized control trial	To determine whether antibiotic administration in patients with PPROM is associated with a reduction in the rates of histologically confirmed chorioamnionitis and funisitis	100	PPROM	Success rate 99/100 − 1 failed

Uptake rates of amniocentesis in cases of PPROM and threatened PTL

Four studies described the uptake rates of the amniocentesis after it was offered to patients in the context of presentation with PPROM or threatened PTL [33,35,39,44]. The pooled results included 1314 patients, with 1203 consenting to undergo amniocentesis, and 111 declining. There was significant heterogeneity (I² = 98%) within the meta-analysis. This is likely to be due to differences in the settings in which the studies were undertaken, with two centers offering amniocentesis as part of the standard clinical practice within their unit [33,39,44](Kacerovsky and Musilova are different studies from the same center), and one offering it is a part of a prospective research study [35]. In this center amniocentesis was declined in 17 of 40 patients approached, giving an acceptance rate of just 55% [35]. In comparison, the uptake rate of amniocentesis in centers where it was standard clinical practice ranged from 83.5% - >99% (Table 2).

Table 2. Details of the studies reporting uptake rates.

Study	Setting	Number	Uptake rate (%)
Cobo et al. [33]	Standard practice	531	83.5
Ferrazzi et al. [35]	Prospective study	40	55
Kacerovsky et al. [39]	Standard practice	153	>99
Musilova et al. [44]	Standard practice	526	>99

Success rate of amniocentesis in cases of PPROM and threatened PTL

Eleven studies described the success rates of amniocentesis (Table 3). Those providing definitions of a “successful” amniocentesis are included in Table 3. Due to the proximity of the publication years of several of the papers the authors were contacted by email for clarification to ensure that cases were not counted twice. Data from one of the retrospective cohort studies [44] was almost completely presented in one of their prospective studies [42], and partly included patients in another five studies [38,40–43]. After removal of duplicate cases the results therefore included 1792 cases. There was significant heterogeneity (I² = 85%) within the meta-analysis. Success rates were high in cases of PPROM and ranged from 91.5% to 100%. It is worth noting that in the largest cohort reporting success rates, a collection of 0.5 ml of amniotic was deemed to be a successful amniocentesis [44]. All these cases were PPROM, and therefore potentially technically more challenging. However, high success rates of >99% were still achieved. The two operators in this study had success rates of 99.6% and 99.3%. These rates were reached after an initial 116 and 59 procedures, respectively. After this period each operator had only one failed amniocentesis in 273 and 142 cases, respectively. Success rates ranged between 90.2% to 100% in cases of tTPL; however, in 66 of the cases of tPTL, no information is provided on what was classed as a “successful” amniocentesis [32].

Table 3. Details of the studies reporting their success rates, reasons for failure where applicable, and definition of a successful amniocentesis.

Study	PPROM/PTL/both	Number (*)	Success rate (%)	Reasons for failed cases	Successful amniocentesis volume
Angus et al. [32]	PTL (n = 66) PPROM (n = 11)	77	100	No reported failures	Not mentioned
Combs et al. [34]	PTL	338	90.2	No mention	15 ml
Fulova et al. [45]	PPROM	67	92.5	“Marked oligohydramnios”	Not mentioned
Jacobsson et al. [36]	PPROM	58	91.5	“Inadequate fluid for testing”	30–50 ml
Kacerovsky et al. [39]	PPROM	152	95.6	“Amniocentesis failure”	“Approximately 5 ml”
Kacerovsky et al. [38] (a)	PPROM	273 (20)	99	“Amniocentesis failure”	“Approximately 5 ml”
Kacerovsky et al. [40] (b)	PPROM	311 (212)	99	“Failed due to anhydramnios”	3ml
Musilova et al. [43] (a)	PPROM	590	96	“Amniocentesis failed”	0.5 ml
Musilova et al. [44] (b)	PPROM	525 (103)	99.9	All oligohydramnios with AFI <1	0.5 ml
Musilova et al. [41]	PPROM	158 (63)	99.9	“Amniocentesis failure”	2–3 ml
Ovalle et al. [31]	PPROM	100	99	“Failure to retrieve fluid”	Not mentioned

Note: The (*) indicates the number of individual cases in the publication that are not included in the retrospective analysis [43].

Complications rates of amniocentesis in cases of PPROM and threatened PTL

Three studies reported risks associated with amniocentesis in the context of PPROM or threatened PTL (Table 4). The pooled results included 1119 cases, and minor heterogeneity was noted (I² = 34%) indicating heterogeneity may not be important within the meta-analysis. The overall complication rate was 0.35% with four reported complications (two umbilical cord punctures and two chorionic plate fetal vessel injuries), none of which resulted in a change of management of the patient, the need for emergency delivery, or in lasting harm to the mother or fetus. These complications are classified as “Grade 2 (moderate) Fetal procedural haemorrhage” using the Maternal and Fetal Adverse Event Terminology (MFAET) [46]. There were no reports of fetal injury or demise. There were no reported maternal complications, including no infectious or hemorrhagic complications across all studies.

Table 4. Details of the studies reporting complications.

Study	PPROM/PTL/both	Number	Complications
Angus et al. [32]	PTL (n = 66) PPROM (n = 11)	77	0
Leaños-Miranda et al. [37]	PTL (intact membrane)	452	0
Musilova et al. [44]	PPROM	590	4 (0.6%)

Risk of bias

Assessing the risk of bias for the included studies presented an issue. Only one of the included studies, a retrospective cohort study, had the main aim of assessing the safety of amniocentesis in cases of PPROM [44]. The remaining studies utilized amniocentesis in this context to collect amniotic fluid for use in a wider context e.g. correlating amniotic fluid characteristics with perinatal outcomes, and accordingly resulted in a heterogenous group. However, these studies contained within them information relating to the uptake, safety, and success of rates of amniocentesis which were extracted for the purposes of this systematic review.

Of the 15 studies one was a randomized control trial, and another was a prospective case-control study. The remainder were cohort studies with no control population principally because amniocentesis was offered as standard clinical care in these institutions. All studies demonstrated robust follow up, collecting birth information for >80% of cases in all circumstances, with many collecting data on 100% of cases.

The assessment of the RCT study using the RoB 2 tool is reported in Supplementary Table 5, and the studies assessed using ROBINS-I reported in Supplementary Table 6. Overall, the cohort studies were found to have a low risk of bias. Equally the RCT was deemed to have a low risk of bias.

Table 5. Summary characteristics of the studies with details of uptake rates, success rates, safety data and complications.

Study ID	Date range	Selection	Approached	Eligible	Declined	Accepted	Consented	Amniocentesis	Complications
Angus et al. [32]	NI	NI	NI	NI	NI	77	77	77	0
Cobo et al. [33]	2012–2018	Consecutive	531	446	88	358	358	358	NI
Combs et al. [34]	Sept 2007–Nov 2009	NI	338	338	NI	320	320	305	NI
Ferrazzi et al. [35]	Nov 2009–Oct 2011	NI	40	40	17	23	23	23	NI
Fulova et al. [45]	May 2015–Sept 18	NI	67	67	0	67	67	62	NI
Jacobsson et al. [36]	1996–2001	NI	58	58	0	58	58	53	NI
Kacerovsky et al. [37]	July 2008–Oct 2010	Consecutive	174	153	1	152	152	145	NI
Kacerovsky et al. [38]	January 2014–May 2019	Retrospective analysis	317	315	0	315	315	312	NI
Kacerovsky et al. [40](Lactobacilli)	Aug 2015–Dec 2018	Retrospective analysis	356	311	0	311	311	309	NI
Leaños-Miranda et al. [37]	Jan 2016–July 2019	Consecutive	452	452	0	452	452	452	0
Musilova et al. [43] (WCC)	Feb 2012–June 2017	Consecutive	526	526 (479) − 42 excluded after amnio	1	525	525	523	NI
Musilova et al. [44]	May 2008–July 2016	Retrospective analysis	595	595	5	590	590	567	4
Musilova et al. [41]	NI	Retrospective analysis	159	159	0	159	159	158	NI
Ovalle et al. [31]	Oct 1991–Jan 1996	Consecutive	NI	100	NI	100	100	99	NI

Given that time frames of recruitment, selection processes, rates of acceptance of amniocentesis, and success rates are all relevant pieces of information for those planning to conduct studies, including clinical trials, this information has been included below (Table 5). Information on complication rates has been included for completion.

Discussion

Key findings

In this systematic review of the uptake, safety and outcomes of amniocenteses performed in cases of PPROM or threatened PTL, we found an overall complication rate of 0.35%. In all cases the complications were moderate Grade 2 and did not result in a change in pregnancy management. The largest retrospective study that was reviewed was the only one to report complications, detailing four cases of complication out of a series of 590. In these cases, there were two umbilical vessel punctures, and two chorionic plate vessel injuries. All four injuries resulted in “temporary, sonographically apparent bleeding into the amniotic cavity” but none of the cases required emergency delivery. The same series expressly stated that there were no maternal complications and no cases of placental abruption, fetal injury, hypoxia, or anemia, and no emergency births associated with amniocentesis [44].

In addition to the safety profile of amniocentesis in this systematic review we demonstrate that success rates of the procedure are consistently high (>90%) across all units reporting data. This includes units in which the procedure was not performed as part of standard clinical practice and therefore demonstrates the likely feasibility of implementing amniocentesis as an intervention.

This systematic review also demonstrates that uptake rates of amniocentesis in cases of PPROM and threatened PTL ranged widely between units. Uptake rates of 57.5% in a center conducting a prospective observational research study compare starkly to uptake rates of over 99% in centers where amniocentesis is part of standard clinical practice [35,43]. Accepting routine clinical care and agreeing to take part in an interventional clinical study are not directly comparable; however, this information may need to be borne in mind by investigators who plan to conduct clinical trials using amniocentesis.

Despite the reassuring findings of this systematic review, consideration must also be given to the fact that amniocentesis in these cases may fail (although reported failure rates were low), may cause injury (however transient), and may not be acceptable to patients or care providers. Amniocentesis in the assessment of PPROM and threatened PTL should only be carried out as part of prospectively registered randomized control trials with appropriate reporting systems in place. If these studies show the value of amniocentesis, then it may be adopted into standard clinical practice.

Strengths and weaknesses

The overall complication rate of 0.35% found in this systematic review related purely to fetal complications at the time of amniocentesis. There were no maternal complications, with specific mention made of no hemorrhagic complications at the time of amniocentesis, and no infectious complications thereafter. Delivery data was provided across all studies, but the focus was on fetal outcomes, with no mention of maternal obstetric complications at the time of birth. Of the 399 full-text articles reviewed, 252 (63.2%) were excluded because of an absence of safety data for either the mother or fetus.

This systematic review examines 3698 cases of amniocentesis in the setting of tPTL and PPROM; however, 2053 of these cases related to one research group, with a small number of highly skilled practitioners. These centers saw success rates of >99% providing useful information as to the low rate of complications in the hands of experienced operators.

Generalizability of findings

This systematic review includes cases from eight different countries across both experimental and clinical scenarios. Therefore, it is likely that these results can be applied to amniocentesis performed outside of the reviewed studies. We do note, however, that the majority of amniocenteses in this review were conducted by two experience operators which may over-estimate expected success rates in other units. To address this issue, we have detailed the number of procedures they undertook prior to achieving their overall quoted success rates. Where heterogeneity was found to be high (uptake rates and success rates) we have chosen not to pool the data to create a composite outcome, instead the data has been reported as ranges.

Conclusion

This systematic review found that amniocentesis in cases of PPROM or threatened preterm labor is a safe and feasible procedure. Where reported, transient moderate complications occurred in 0.35% of cases, and success rates of greater than 90% were observed across all studies, even in the theoretically more complex situation of PPROM. These data should give care providers confidence to counsel patients appropriately. However, it was noted that uptake rates of amniocentesis in experimental situations was as low as 57.5%. Investigators should keep this information in mind when planning clinical trials involving amniocentesis. Finally, we note that studies involving amniocentesis in these clinical situations often do not report the uptake, success, or risks of the procedure which may result in an underestimation of these variables due to under-reporting. Consistent, prospective reporting should be encouraged.

Acknowledgments

The authors wish to thank Professor Marian Kacerovsky for his helpful personal communications. during the preparation of this manuscript. University Hospital Hradec Kralove Charles University, Faculty of Medicine in Hradec Kralove, Czechia.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, DS, upon reasonable request.

Additional information

Funding

DJS receives funding from the Westminster Medical School Research Trust. There are no other funding sources for the creation of this systematic review.