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Prophylactic amnioinfusion for intrapartum oligohydramnios: a meta-analysis of randomized controlled trials
Prophylactic amnioinfusion for intrapartum oligohydramnios: A metaanalysis of randomized controlled trials Catherine Pitt, MD, Luis Sanchez-Ramos, MD, Andrew M. Kaunitz, MD, and Francisco Gaudier, MD Objective: To evaluate the effectiveness of intrapartum prophylactic amnioinfusion in pregnancies complicated by oligohydramnios. Data Sources: Randomized controlled trials of prophylactic amnioinfusion in women with oligohydramnios were identified using computerized databases, index reviews, and references cited in original studies and review articles. Methods of Study Selection: We evaluated, abstracted data from, and analyzed randomized studies of prophylactic intrapartum amnioinfusion in women with oligohydramnios. In every study the group allocation was based exclusively on presence of oligohydramnios. Only published studies with clearly documented outcome data were included. The quality of each trial was evaluated for methodology, inclusion and exclusion criteria, adequacy of randomization, amnioinfusion protocols, definition of outcomes, and statistical analyses. The trials were evaluated concerning cesarean deliveries for fetal heart rate (FHR) abnormalities, overall cesarean rates, acidemia at birth, intrapartum fetal heart rate abnormalities, Apgar scores under 7 at 5 minutes, and postpartum endometritis. Tabulation, Integration, and Results: Thirty-five studies were identified, of which 14 met the inclusion criteria for this systematic review. They included 1533 patients, 793 in the amnioinfusion group, and 740 controls. Odds ratios (OR) with their 95% confidence intervals (CI) for each outcome were calculated. We calculated an estimate of the OR and risk difference for dichotomous outcomes using random and fixed-effects models. A test of homogeneity was done across studies. Women with oligohydramnios who received intrapartum amnioinfusion had lower incidence of cesarean for FHR abnormalities (OR 0.23; 95% CI 0.15, 0.35). Intrapartum amnioinfusion also was associated with lower overall rates of cesarean deliveries (OR 0.52; 95% CI 0.40, 0.68), acidemia at birth (OR 0.40; 95% CI 0.30, 0.55), FHR abnormalities during labor (OR 0.24; 95% CI 0.17, 0.34), and Apgar scores under 7 at 5 minutes (OR 0.52; 95% CI 0.29, 0.91). Postpartum endometritis rates were similar among the study groups. Conclusion: In the presence of oligohydramnios, prophyFrom the Department of Obstetrics and Gynecology and the Division of Maternal-Fetal Medicine, University of Florida Health Science Center, Jacksonville, Florida
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lactic intrapartum amnioinfusion significantly improves neonatal outcome and lessens the rate of cesarean delivery, without increasing the rate of postpartum endometritis. (Obstet Gynecol 2000;96:861– 6. © 2000 by The American College of Obstetricians and Gynecologists.)
Amniotic fluid (AF) protects the fetus by dispersing external forces directed towards the uterus equally throughout the cavity. A normal amount of AF reduces frequency and severity of umbilical cord compression from fetal movements or uterine contractions.1 In animal models, the loss of AF has been associated with variable decelerations of fetal heart rate (FHR) that resolve when fluid is replaced with saline infusion.2 Oligohydramnios frequently causes problems associated with cord compression during labor.3 Umbilical cord compression from decreased AF, resulting in variable decelerations, might be associated with fetal hypoxia, acidosis, and an increased incidence of operative deliveries.4 Moberg et al5 reported that 76% of women with premature rupture of membranes (PROM) had FHR patterns during labor that were consistent with cord compression and led to increased cesarean rates. Vintzileos et al6 also found a correlation between oligohydramnios and severe variable decelerations, lower Apgar scores, and increased perinatal mortality. Gabbe et al2 noted that infusing normal saline to restore intrauterine volume in rhesus monkeys alleviated umbilical cord compression. However, since the early 1980s, clinical studies that assessed effects of amnioinfusion on perinatal outcomes produced conflicting results.7–13 To make an unbiased assessment, this systematic review grouped multiple randomized controlled trials to examine the effects of prophylactic intrapartum amnioinfusion in the presence of oligohydramnios. The outcome of primary interest was the rate of cesarean deliveries for FHR abnormalities. Secondary outcomes included overall cesarean rates, fetal acidemia at birth, FHR abnormalities during labor, Apgar scores under 7 at 5 minutes, and postpartum endometritis.
Data Sources Studies were identified using several search strategies. We identified randomized trials of prophylactic intrapartum amnioinfusion in women with oligohydramnios using available electronic databases, references of published articles, and chapters from textbooks. Electronic databases used were Bibliographic Retrieval Service (BRS online, MacLean, VA), MEDLINE, and PubMed (National Library of Medicine, Bethesda, MD), Current Contents (Institute for Scientific Information,
0029-7844/00/$20.00 PII S0029-7844(00)01054-1
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Philadelphia, PA), and Silver Platter (Silver Platter Information Inc., Norwood, MA). Searches were conducted for literature published between January 1983 and December 1999. We selected those dates because Miyazaki and Taylor published the first major clinical trial on intrapartum amnioinfusion in 1983.3 Medical subject heading key words used for the search included “amnioinfusion,” “oligohydramnios,” and “fetal compromise.” We manually screened for references of studies and review articles for relevant citations without regard to language of publication. Published randomized controlled trials of intrapartum amnioinfusion in the presence of oligohydramnios were included in the systematic review. Abstracts were included, but unpublished trials and review articles were not.
Methods of Study Selection The investigators independently reviewed all trials identified. Inclusion criteria for this investigation were randomized clinical trials that evaluated the effect of prophylactic amnioinfusion during labor in the presence of oligohydramnios, group allocation (amnioinfusion versus no amnioinfusion) based exclusively on the presence of oligohydramnios, and clearly documented outcome data. This evaluation yielded 14 published studies4,14 –26 and one abstract (Busowski J, Pendergraft JS, Parsons M, O’Brien W. Transabdominal amnioinfusion before induction of labor. Am J Obstet Gynecol 1995;172:287) that met inclusion criteria. We evaluated the quality of the trials included in this report for adequacy of randomization schemes, blinding, methodology, inclusion and exclusion criteria, amnioinfusion protocols, definition of outcomes reported, and statistical analyses. Quality evaluation was not used as inclusion or exclusion criteria.
Tabulation and Integration Data were extracted independently from each of the selected studies by one of two authors (CP or FLG). Main outcomes measured and the data abstraction form were determined before studies were evaluated. Any identified uncertainties regarding data abstraction were resolved after consultation with the senior author (LSR). Outcomes examined included cesarean deliveries for FHR abnormalities, cesarean delivery rates, acidemia at birth, FHR abnormalities during labor, Apgar scores under 7 at 5 minutes, and rates of postpartum endometritis. Fetal heart rate abnormalities included intrapartum variable decelerations. Acidemia at birth was defined as an umbilical artery pH less than 7.20 in nine trials4,14 –16,18 –21,27 and less than 7.10 in two.23,25 Not all included trials evaluated each of the main outcomes;
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therefore, specific outcome analyses were based on a variable number of studies. Although most trials defined oligohydramnios as an AF index (AFI) under five, a single study defined it as an index of ten or less.21 Amnioinfusion protocols used mainly transcervical approaches; however, two studies reported transabdominal infusions.23 (Busowski J, Pendergraft JS, Parsons M, O’Brien W. Transabdominal amnioinfusion prior to induction of labor. Am J Obstet Gynecol 1995;172:287). All protocols included initial administrations of normal saline or lactated Ringer’s solution ranging from 250 to 1000 mL, infused in 20 – 60 minutes, followed by various maintenance infusion schemes until delivery or when certain AFIs were achieved. Data analyses were done with EGRET computerized software package (Epidemiological Statistics Software, Statistics and Epidemiology Research Corporation, Seattle WA). To pool dichotomous outcomes, we calculated an estimate of the odds ratio (OR) and risk difference (defined as the incidence of the outcome in the treatment group minus the incidence of the outcome in the comparison group) using a random effects model (DerSirmonian and Laird)27 and a Mantel-Haenszel fixed-effects model.28 No substantial difference was noted in the results obtained with either method, so only the fixed-effects results are reported. To determine the ability to combine the individual trials evaluated, we did a formal test of homogeneity across studies.29 In a further evaluation of homogeneity of effects, we plotted data with the rate of outcome variables in the comparison groups on the X axis and in the amnioinfusion groups on the Y axis as suggested by L’Abbe et al.30 We also examined publication bias through visual inspection of a funnel plot whereby ORs were plotted against study sample sizes.31 The number needed to treat (the number of patients who need to be treated to prevent one event) was calculated as an estimate of clinical benefit. The number needed to treat is equal to 1/(control event rate—treatment event rate).
Results We identified 35 publications of intrapartum amnioinfusion in women with oligohydramnios. We excluded 21 publications. Sixteen were either retrospective studies or review articles. One study evaluated neonatal outcomes in women with oligohydramnios, but maternal data were already included as a separate publication, so that study11 was excluded. Another study included preliminary data that was later published in a larger clinical trial.22 Three publications involved antepartum amnioinfusion and were excluded.32–34 Therefore, 14 randomized controlled trials on intrapartum amnioinfusion in women with oligohydramnios form
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the basis of this report.3,14 –21,23–26 (Busowski J, Pendergraft JS, Parsons M, O’Brien W. Transabdominal amnioinfusion prior to induction of labor. Am J Obstet Gynecol 1995;172:287). In included trials, allocation to amnioinfusion or comparison groups was based only on the presence of oligohydramnios. Nine of the trials were done in the United States4,14 –20 (Busowski J, Pendergraft JS, Parsons M, O’Brien W. Transabdominal amnioinfusion prior to induction of labor. Am J Obstet Gynecol 1995;172:287), two in China,24,26 and one each in Italy,23 Spain,22 and Sweden.25 A total of 1533 women were enrolled in the trials, 793 to amnioinfusion and 740 to comparison groups. The number randomized to amnioinfusion groups ranged from 16 –100, with comparison groups generally of similar size (15–130). Trial design features are shown in Table 1. The trials demonstrate heterogeneity in study design with respect to end-points evaluated and amnioinfusion protocols. Compared with women allocated to comparison groups, those who received amnioinfusion had lower cesarean rates for FHR abnormalities during labor (OR 0.23; 95% CI 0.15, 0.35) (Table 1). Only four of 13 individual trials evaluated showed significant differences in overall cesarean rates. However, after pooling data from all publications, significantly lower cesarean rates were noted among women who received intrapartum amnioinfusion (OR 0.52; 95% CI 0.40, 0.68) (Table 2). A lower incidence of fetal acidemia was found in the group who received amnioinfusion (OR 0.40; 95% CI 0.30, 0.55) (Table 3). The incidence of fetal heart rate abnormalities during labor also was significantly lower in the amnioinfusion group (OR 0.24; 95% CI 0.17, 0.34) (Table 4). There was a small but significant difference in
Table 1. Intrapartum Amnioinfusion and Cesarean for Fetal Heart Rate Abnormalities Study
Amnioinfusion group n
0/60 (0.0%) Wu26 Strong14 1/30 (3.3%) Owen15 2/43 (4.6%) Schrimmer16 7/175 (4.0%) Nageotte17 2/50 (4.0%) MacGregor4 6/19 (31.6%) Macri18 2/85 (2.3%) Chauhan19 2/21 (9.5%) Ogundipe20 4/56 (7.1%) Busowski 0/16 (0.0%) Vergani23 2/39 (5.1%) Persson4/60 (6.7%) Kjerstadius25 Totals 32/654 (4.9%)
Comparison group n
Odds ratio (95% CI)
8/58 (13.8%) 4/30 (13.3%) 9/57 (15.8%) 25/130 (19.2%) 4/26 (15.4%) 6/16 (37.5%) 17/85 (20.0%) 1/17 (5.9%) 6/60 (10.0%) 2/15 (13.3%) 10/40 (25.0%) 14/52 (26.9%)
0.05 (0.00, 0.87) 0.22 (0.02, 2.14) 0.26 (0.05, 1.27) 0.17 (0.07, 0.42) 0.23 (0.04, 1.35) 0.77 (0.19, 3.12) 0.10 (0.02, 0.43) 1.68 (0.14, 20.33) 0.69 (0.18, 2.59) 0.16 (0.01, 3.71) 0.16 (0.03, 0.80) 0.19 (0.06, 0.63)
106/586 (18.1%)
0.23 (0.15, 0.35)*
CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X211 ⫽ 11.10, P ⫽ .44.
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Table 2. Intrapartum Amnioinfusion and Overall Cesarean Rate Study
Amnioinfusion group n
Comparison group n
Odds ratio (95% CI)
4/60 (6.7%) 14/58 (24.1%) 0.22 (0.07, 0.73) Wu26 Strong14 4/30 (13.3%) 6/30 (20.0%) 0.62 (0.15, 2.45) Owen15 8/43 (18.6%) 17/57 (29.8%) 0.54 (0.21, 1.40) Schrimmer16 25/175 (14.3%) 36/130 (27.7%) 0.44 (0.25, 0.77) Nageotte17 7/50 (14.0%) 7/26 (26.9%) 0.44 (0.14, 1.44) MacGregor4 10/19 (52.6%) 7/16 (43.7%) 1.43 (0.38, 5.44) Macri18 13/85 (15.3%) 25/85 (29.4%) 0.43 (0.20, 0.92) Chauhan19 4/21 (19.0%) 3/17 (17.7%) 1.10 (0.21, 5.75) Ogundipe20 12/56 (21.4%) 10/60 (16.7%) 1.36 (0.54, 3.46) Vergani23 5/39 (12.8%) 12/40 (30.0%) 0.34 (0.11, 1.09) Wang24 9/39 (23.1%) 8/39 (20.5%) 1.09 (0.37, 3.19) Persson-Kjerstadius25 8/60 (13.3%) 15/52 (28.8%) 0.38 (0.15, 0.99) Mino21 3/100 (3.0%) 10/100 (10.0%) 0.28 (0.07, 1.04) Totals 112/777 (14.4%) 170/710 (23.9%) 0.52 (0.40, 0.68)* CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X212 ⫽ 13.35, P ⫽ .34.
the incidence of 5-minute Apgar scores under 7 in women who received intrapartum amnioinfusion (OR 0.52; 95% CI 0.29, 0.91) (Table 5). Amnioinfusion improved fetal outcomes and decreased cesarean deliveries but did not increase the risk of postpartum endometritis (OR 0.60; 95% CI 0.36, 1.01) (Table 6). The numberneeded-to-treat analysis is shown in Table 7. Amnioinfusion in five women was required to prevent one case of FHR abnormalities, whereas 42 required treatment to prevent one newborn with an Apgar score under 7 at 5 minutes. With the exception of acidemia at birth, tests of homogeneity showed that the studies were not heterogeneous for the various outcomes. For most outcomes
Table 3. Intrapartum Amnioinfusion and Acidemia at Birth Study
Amnioinfusion Comparison group n group n
Odds ratio (95% CI)
0/17 (0.0%) 5/18 (27.7%)0.07 (0.00, 1.38) Strong14 Owen15 13/39 (33.3%) 10/55 (18.2%)2.25 (0.87, 5.85) Schrimmer16 14/175 (8.0%) 39/130 (30.0%)0.20 (0.10, 0.39) MacGregor4 3/19 (15.8%) 3/16 (18.8%)0.81 (0.14, 4.72) Macri18 7/85 (8.2%) 31/85 (36.5%)0.16 (0.06, 0.38) Chauhan19 2/19 (10.5%) 1/12 (8.3%) 1.29 (0.10, 16.04) Ogundipe20 4/56 (7.1%) 5/60 (8.3%) 0.85 (0.21, 3.32) Busowski 0/16 (0.0%) 3/15 (20.0%)0.11 (0.01, 2.29) Vergani23† 1/22 (4.5%) 4/22 (18.2%)0.21 (0.02, 2.10) Persson-Kjerstadius25† 3/60 (5.0%) 2/52 (3.8%) 1.32 (0.21, 8.15) Mino21 22/100 (22.0%) 36/100 (36.0%)0.50 (0.27, 0.94) Totals 69/608 (11.4%) 139/565 (24.6%)0.40 (0.30, 0.55)* CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X210 ⫽ 27.87, P ⫽ .002. Acidemia was defined as an umbilical artery pH less than 7.20 except in two studies (†) where it was defined as less than 7.10.
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Table 4. Intrapartum Amnioinfusion and Fetal Heart Rate Abnormalities Study
Amnioinfusion group n
Comparison group n
Odds ratio (95% CI)
Strong14 Owen15 Schrimmer16 MacGregor4 Macri18 Chauhan19 Vergani23 Wang24 Mino21 Totals
16/30 (53.3%) 8/43 (18.6%) 14/175 (8.0%) 4/19 (21.1%) 3/85 (3.5%) 5/19 (26.3%) 2/37 (5.4%) 3/39 (7.7%) 4/100 (4.0%) 59/547 (10.8%)
21/30 (70.0%) 19/57 (33.3%) 34/130 (26.2%) 12/16 (75.0%) 19/85 (22.4%) 8/17 (47.1%) 14/33 (42.4%) 17/39 (43.6%) 9/100 (9.0%) 153/507 (30.2%)
0.49 (0.17, 1.41) 0.46 (0.18, 1.18) 0.24 (0.12, 0.48) 0.09 (0.02, 0.43) 0.13 (0.04, 0.45) 0.40 (0.10, 1.62) 0.08 (0.02, 0.38) 0.11 (0.03, 0.41) 0.42 (0.12, 1.42) 0.24 (0.17, 0.34)*
CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X28 ⫽ 10.64, P ⫽ .22.
analyzed, funnel plot analyses produced plot shapes incompatible with publication bias.
Discussion This systematic review showed that prophylactic intrapartum amnioinfusion in women with oligohydramnios significantly decreases FHR abnormalities, acidemia at birth, and rates of cesarean deliveries. The lower overall rate of cesarean delivery among women with oligohydramnios who received prophylactic amnioinfusion largely was caused by fewer cesarean deliveries for FHR abnormalities. Amnioinfusion also was associated with reduction in several adverse maternal and perinatal outcomes without increasing the incidence of postpartum endometritis. Hofmeyer et al10 reviewed the effectiveness of amnioinfusion in several clinical settings. They evaluated
Table 5. Intrapartum Amnioinfusion and Apgar Scores Under 7 at 5 Minutes Study
Amnioinfusion Comparison group n group n
1/30 (3.3%) 0/30 (0.0%) Strong14 Owen15 1/43 (2.3%) 1/57 (1.8%) Schrimmer16 6/175 (3.4%) 9/130 (6.9%) Nageotte17 2/50 (4.0%) 2/26 (7.7%) Macri18 0/85 (0.0%) 8/85 (9.4%) Chauhan19 1/19 (5.3%) 0/12 (0.0%) Busowski 0/16 (0.0%) 1/15 (6.7%) Vergani23 3/39 (7.7%) 4/40 (10.0%) Wang24 1/39 (2.6%) 0/39 (0.0%) Persson-Kjerstadius25 3/60 (5.0%) 5/52 (9.6%) Mino21 0/100 (0.0%) 0/100 (0.0%) Totals 18/656 (2.7%) 30/586 (5.1%)
Odds ratio (95% CI) 3.00 (0.12, 76.58) 1.33 (.08, 21.94) 0.48 (0.17, 1.38) 0.50 (0.07, 3.77) 0.05 (0.00, 0.94) 2.03 (0.08, 53.87) 0.29 (0.01, 7.76) 0.75 (0.16, 3.59) 3.08 (0.12, 77.91) 0.49 (0.11, 2.18) excluded 0.52 (0.29, 0.91)*
CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X28 ⫽ 6.17, P ⫽ .72.
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Table 6. Intrapartum Amnioinfusion and Postpartum Endometritis Study
Amnioinfusion group n
Comparison group n
Odds ratio (95% CI)
Wu26 Owen15 Schrimmer16 MacGregor4 Macri18 Ogundipe20 Mino21 Totals
3/60 (5.0%) 1/43 (2.3%) 7/175 (4.0%) 4/19 (21.0%) 8/85 (9.4%) 3/56 (5.3%) 01/100 (0.0%) 26/538 (4.8%)
8/58 (13.8%) 11/57 (19.0%) 10/130 (7.7%) 1/16 (6.2%) 9/85 (10.6%) 1/60 (1.7%) 0/100 (0.0%) 40/506 (7.9%)
0.33 (0.08, 1.31) 0.10 (0.01, 0.80) 0.50 (0.18, 1.35) 4.00 (0.40, 40.10) 0.88 (0.32, 2.39) 3.34 (0.34, 33.08) excluded 0.60 (0.36, 1.01)*
CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X25 ⫽ 9.01, P ⫽ .11.
nine clinical trials of intrapartum amnioinfusion for umbilical cord compression and found a reduction in overall rates of cesarean deliveries and specifically of cesarean deliveries for “fetal distress.” Two systematic reviews in the Cochrane Library35,36 compared amnioinfusion in women with oligohydramnios. The first included two trials that compared prophylactic versus therapeutic amnioinfusion in laboring women.38 The second reviewed 12 trials in which some participants had evidence of intrapartum infection or had variable decelerations before randomization.36 Those reviews also differ from our meta-analysis with regard to amnioinfusion in the control groups. A single trial in our review used amnioinfusion for women randomized to the comparison group. In the study by Ogundipe et al, 22% of controls received amnioinfusion when variable decelerations developed.20 We limited our meta-analysis to randomized controlled trials because they are the most reliable method of assessing efficacy of therapeutic interventions. However, studies are more likely to be published if they Table 7. Number-needed-to-treat Analysis of Prophylactic Amnioinfusion for Oligohydramnios
Outcome Cesarean for FHR abnormalities Overall cesarean rate Acidemia at birth Intrapartum FHR abnormalities Apgar score under 7 at 5 minutes Postpartum endometritis
Amnioinfusion Comparison group group 32/654 (4.9%) 112/777 (14.4%) 69/608 (11.4%) 59/547 (10.8%) 18/656 (2.7%) 26/538 (4.8%)
106/586 (18.1%) 170/710 (23.9%) 139/565 (24.6%) 153/507 (30.2%) 30/586 (5.1%) 40/506 (7.9%)
Number needed to treat (95% CI) 8 (6, 10) 11 (7, 18) 8 (6, 11) 5 (4, 7) 42 (21, 500) 32 (16, 1000)
CI ⫽ confidence interval; FHR ⫽ fetal heart rate.
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show statistically significant findings. A review in which only published articles are analyzed might be biased toward larger or statistically significant effects or both, and erroneous conclusions might result. It is unlikely that bias of that nature was a factor in our systematic review because several studies showed similar results between amnioinfusion and comparison groups. Unpublished trials with negative results would have to include a large number of women to negate our findings. Funnel plot analyses indicated no obvious publication bias.31 Two important issues related to meta-analysis are quality of the studies and heterogeneity. Based on thorough evaluation and assessment of each trial, the included studies were of high quality. Excessive heterogeneity in systematic reviews, degree of incompatibility in the quantitative results among trials included in the meta-analysis, might decrease validity of this approach. Although absolute homogeneity among studies might appear desirable, it could also preclude generalization to a larger population. Nonetheless, understanding the sources of heterogeneity remains important. We found significant heterogeneity for only one outcome, fetal acidemia at birth. The pooled results found the incidence of acidemia at birth significantly decreased in women who received intrapartum amnioinfusion. Among all studies assessed, the proportion of subjects who experienced acidemia at birth ranged from 0 –30.2% and 3.8 –36.5% in the amnioinfusion and comparison groups, respectively. That broad range likely indicates uncertainty in the definition of acidemia. The finding of significant heterogeneity for fetal acidemia at birth is likely the result of two studies with higher rates of acidemia for those assigned to the comparison group (no amnioinfusion).15,25 However, even after removing the two studies with discrepant results, subgroup analysis for that outcome showed significant differences in favor of prophylactic amnioinfusion. Differences in inclusion criteria and interventions were noted and could have affected our overall findings. For example, three studies15,21,27 did not quantify degree of oligohydramnios, or included subjects with AFIs no more than 10 cm. Two studies used transabdominal rather than transcervical amnioinfusion.23,27 Subgroup analysis excluded three studies (oligohydramnios definition) and two studies (transabdominal amnioinfusion). Excluding those studies did not alter our overall results. Although amnioinfusion has proved effective in reducing perinatal morbidity, concerns exist regarding its safety. A recent survey of United States teaching hospitals found that many methods of amnioinfusion are used, and all appear safe.37 Although most obstetricians
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consider amnioinfusion safe, some express concerns it might increase rates of infectious morbidity. Complications reported include uterine rupture, increased basal uterine tone, hypertonus, fetal bradychardia, umbilical cord prolapse, placental abruption, AF embolism, and maternal morbidity and death. Fortunately, those are rare and apparently unrelated to the specific protocol followed.38 The numbers of women undergoing amnioinfusion in randomized trials are far too small to be able to evaluate the possibility of those unusual complications.
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17. Nageotte MP, Bertucci L, Towers CV, Lagrew DL, Modanlou H. Prophylactic amnioinfusion in pregnancies complicated by oligohydramnios: A prospective study. Obstet Gynecol 1991;77:677– 80. 18. Macri CJ, Schrimmer DB, Leung A, Greenspoon JS, Paul RH. Prophylactic amnioinfusion improves outcome of pregnancy complicated by thick meconium and oligohydramnios. Am J Obstet Gynecol 1992;167:117–21. 19. Chauhan SP, Rutherford SE, Hess LW, Morrison JC. Prophylactic intrapartum amnioinfusion for patients with oligohydramnios—A prospective randomized study. J Reprod Med 1992;37:817–20. 20. Ogundipe OA, Spong CY, Ross MG. Prophylactic amnioinfusion for oligohydramnios: A reevaluation. Obstet Gynecol 1994;84: 544 – 8. 21. Mino M, Puertas A, Miranda JA, Herruzo AJ. Amnioinfusion in term labor with low amniotic fluid due to rupture of membranes: A new indication. Eur J Obstet Gynecol Reprod Biol 1999;82:29 –34. 22. Mino M, Puertas A, Herruzo JA, Miranda JA. Amnioinfusion in labor induction of term pregnancies with rupture of the membranes and low amniotic fluid. International J Gynecol Obstet 1998;61:135– 40. 23. Vergani P, Ceruti P, Strobelt N, Locatelli A, D’Oria P, Mariani S. Transabdominal amnioinfusion in oligohydramnios at term before induction of labor with intact membranes: A randomized clinical trial. Am J Obstet Gynecol 1996;175:465–70. 24. Wang CC, Rogers MS. Lipid Peroxidation in cord blood: A randomised sequential pairs study of prophylactic saline amnioinfusion for intrapartum oligohydramnios. Br J Obstet Gynecol 1997;104:1145–51. 25. Persson-Kjerstadius N, Forsgren H, Westgren M. Intrapartum amnioinfusion in women with oligohydramnios. A prospective randomized trial. Acta Obstet Gynecol Scand 1999;78:116 –9. 26. Wu BT. Intrapartum amnioinfusion in patients with oligohydramnios. Chung Hua Fu Chan Ko Tsa Chih 1989;24:2– 4. 27. DerSirmonian R, Laird N. Meta-analysis in clinical trials. Controlled Clinical Trials 1986;7:177– 88. 28. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959;22: 719 – 48. 29. Breslow NE, Day NE. Statistical methods in cancer research. Vol. 1, No. 32. The analysis of case control studies. Lyon, France: IARC Scientific Publications, 1980. 30. L’Abbe KA, Detsky AS, O’Rourke K. Meta-analysis in clinical research. Ann Int Med 1987;107:224 –33.
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31. Egger M, Davey Smith G, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629 –34. 32. Garzetti GG, Ciavanttini A, De Cristofaro F, La Marca N, Arduini D. Prophylactic transabdominal amnioinfusion in oligohydramnios for preterm premature rupture of membranes: Increase of amniotic fluid index during latency period. Gynecol Obstet Invest 1997;44:249 –54. 33. Gramallini D, Piantelli G, Delle Chiaie L, Rutolo S, Vadora E. Amnioinfusion in the management of oligohydramnios. 1998;26: 293–301. 34. Nageotte MP, Freeman RK, Garite TJ, Dorchester W. Prophylactic intrapartum amnioinfusion in patients with preterm premature rupture of membranes. Am J Obstet Gynecol 1985;153:557– 62. 35. Hofmeyr GJ. Prophylactic versus therapeutic amnioinfusion for oligohydramnios in labour. The Cochrane Library, Vol 1. Oxford: Update Software, 2000. 36. Hofmeyr GJ. Amnioinfusion for umbilical cord compression in labour. The Cochrane Library, Vol 1. Oxford: Update Software, 2000. 37. Wenstrom K, Andrews WW, Maher JE. Amnioinfusion survey: Prevalence, protocols, and complications. Obstet Gynecol 1995;86: 572– 6. 38. Posner MD, Ballagh SA, Paul RH. The effect of amnioinfusion on uterine pressure and activity: A preliminary report. Am J Obstet Gynecol 1990;163:813– 8.
Address reprint requests to:
Luis Sanchez-Ramos, MD University of Florida Health Science Center Department of Obstetrics and Gynecology 653-1 West 8th Street Jacksonville, FL 32209 E-mail: [email protected]
Received April 13, 2000. Received in revised form July 13, 2000. Accepted August 17, 2000. Copyright © 2000 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
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lactic intrapartum amnioinfusion significantly improves neonatal outcome and lessens the rate of cesarean delivery, without increasing the rate of postpartum endometritis. (Obstet Gynecol 2000;96:861– 6. © 2000 by The American College of Obstetricians and Gynecologists.)
Amniotic fluid (AF) protects the fetus by dispersing external forces directed towards the uterus equally throughout the cavity. A normal amount of AF reduces frequency and severity of umbilical cord compression from fetal movements or uterine contractions.1 In animal models, the loss of AF has been associated with variable decelerations of fetal heart rate (FHR) that resolve when fluid is replaced with saline infusion.2 Oligohydramnios frequently causes problems associated with cord compression during labor.3 Umbilical cord compression from decreased AF, resulting in variable decelerations, might be associated with fetal hypoxia, acidosis, and an increased incidence of operative deliveries.4 Moberg et al5 reported that 76% of women with premature rupture of membranes (PROM) had FHR patterns during labor that were consistent with cord compression and led to increased cesarean rates. Vintzileos et al6 also found a correlation between oligohydramnios and severe variable decelerations, lower Apgar scores, and increased perinatal mortality. Gabbe et al2 noted that infusing normal saline to restore intrauterine volume in rhesus monkeys alleviated umbilical cord compression. However, since the early 1980s, clinical studies that assessed effects of amnioinfusion on perinatal outcomes produced conflicting results.7–13 To make an unbiased assessment, this systematic review grouped multiple randomized controlled trials to examine the effects of prophylactic intrapartum amnioinfusion in the presence of oligohydramnios. The outcome of primary interest was the rate of cesarean deliveries for FHR abnormalities. Secondary outcomes included overall cesarean rates, fetal acidemia at birth, FHR abnormalities during labor, Apgar scores under 7 at 5 minutes, and postpartum endometritis.
Data Sources Studies were identified using several search strategies. We identified randomized trials of prophylactic intrapartum amnioinfusion in women with oligohydramnios using available electronic databases, references of published articles, and chapters from textbooks. Electronic databases used were Bibliographic Retrieval Service (BRS online, MacLean, VA), MEDLINE, and PubMed (National Library of Medicine, Bethesda, MD), Current Contents (Institute for Scientific Information,
0029-7844/00/$20.00 PII S0029-7844(00)01054-1
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Philadelphia, PA), and Silver Platter (Silver Platter Information Inc., Norwood, MA). Searches were conducted for literature published between January 1983 and December 1999. We selected those dates because Miyazaki and Taylor published the first major clinical trial on intrapartum amnioinfusion in 1983.3 Medical subject heading key words used for the search included “amnioinfusion,” “oligohydramnios,” and “fetal compromise.” We manually screened for references of studies and review articles for relevant citations without regard to language of publication. Published randomized controlled trials of intrapartum amnioinfusion in the presence of oligohydramnios were included in the systematic review. Abstracts were included, but unpublished trials and review articles were not.
Methods of Study Selection The investigators independently reviewed all trials identified. Inclusion criteria for this investigation were randomized clinical trials that evaluated the effect of prophylactic amnioinfusion during labor in the presence of oligohydramnios, group allocation (amnioinfusion versus no amnioinfusion) based exclusively on the presence of oligohydramnios, and clearly documented outcome data. This evaluation yielded 14 published studies4,14 –26 and one abstract (Busowski J, Pendergraft JS, Parsons M, O’Brien W. Transabdominal amnioinfusion before induction of labor. Am J Obstet Gynecol 1995;172:287) that met inclusion criteria. We evaluated the quality of the trials included in this report for adequacy of randomization schemes, blinding, methodology, inclusion and exclusion criteria, amnioinfusion protocols, definition of outcomes reported, and statistical analyses. Quality evaluation was not used as inclusion or exclusion criteria.
Tabulation and Integration Data were extracted independently from each of the selected studies by one of two authors (CP or FLG). Main outcomes measured and the data abstraction form were determined before studies were evaluated. Any identified uncertainties regarding data abstraction were resolved after consultation with the senior author (LSR). Outcomes examined included cesarean deliveries for FHR abnormalities, cesarean delivery rates, acidemia at birth, FHR abnormalities during labor, Apgar scores under 7 at 5 minutes, and rates of postpartum endometritis. Fetal heart rate abnormalities included intrapartum variable decelerations. Acidemia at birth was defined as an umbilical artery pH less than 7.20 in nine trials4,14 –16,18 –21,27 and less than 7.10 in two.23,25 Not all included trials evaluated each of the main outcomes;
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therefore, specific outcome analyses were based on a variable number of studies. Although most trials defined oligohydramnios as an AF index (AFI) under five, a single study defined it as an index of ten or less.21 Amnioinfusion protocols used mainly transcervical approaches; however, two studies reported transabdominal infusions.23 (Busowski J, Pendergraft JS, Parsons M, O’Brien W. Transabdominal amnioinfusion prior to induction of labor. Am J Obstet Gynecol 1995;172:287). All protocols included initial administrations of normal saline or lactated Ringer’s solution ranging from 250 to 1000 mL, infused in 20 – 60 minutes, followed by various maintenance infusion schemes until delivery or when certain AFIs were achieved. Data analyses were done with EGRET computerized software package (Epidemiological Statistics Software, Statistics and Epidemiology Research Corporation, Seattle WA). To pool dichotomous outcomes, we calculated an estimate of the odds ratio (OR) and risk difference (defined as the incidence of the outcome in the treatment group minus the incidence of the outcome in the comparison group) using a random effects model (DerSirmonian and Laird)27 and a Mantel-Haenszel fixed-effects model.28 No substantial difference was noted in the results obtained with either method, so only the fixed-effects results are reported. To determine the ability to combine the individual trials evaluated, we did a formal test of homogeneity across studies.29 In a further evaluation of homogeneity of effects, we plotted data with the rate of outcome variables in the comparison groups on the X axis and in the amnioinfusion groups on the Y axis as suggested by L’Abbe et al.30 We also examined publication bias through visual inspection of a funnel plot whereby ORs were plotted against study sample sizes.31 The number needed to treat (the number of patients who need to be treated to prevent one event) was calculated as an estimate of clinical benefit. The number needed to treat is equal to 1/(control event rate—treatment event rate).
Results We identified 35 publications of intrapartum amnioinfusion in women with oligohydramnios. We excluded 21 publications. Sixteen were either retrospective studies or review articles. One study evaluated neonatal outcomes in women with oligohydramnios, but maternal data were already included as a separate publication, so that study11 was excluded. Another study included preliminary data that was later published in a larger clinical trial.22 Three publications involved antepartum amnioinfusion and were excluded.32–34 Therefore, 14 randomized controlled trials on intrapartum amnioinfusion in women with oligohydramnios form
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the basis of this report.3,14 –21,23–26 (Busowski J, Pendergraft JS, Parsons M, O’Brien W. Transabdominal amnioinfusion prior to induction of labor. Am J Obstet Gynecol 1995;172:287). In included trials, allocation to amnioinfusion or comparison groups was based only on the presence of oligohydramnios. Nine of the trials were done in the United States4,14 –20 (Busowski J, Pendergraft JS, Parsons M, O’Brien W. Transabdominal amnioinfusion prior to induction of labor. Am J Obstet Gynecol 1995;172:287), two in China,24,26 and one each in Italy,23 Spain,22 and Sweden.25 A total of 1533 women were enrolled in the trials, 793 to amnioinfusion and 740 to comparison groups. The number randomized to amnioinfusion groups ranged from 16 –100, with comparison groups generally of similar size (15–130). Trial design features are shown in Table 1. The trials demonstrate heterogeneity in study design with respect to end-points evaluated and amnioinfusion protocols. Compared with women allocated to comparison groups, those who received amnioinfusion had lower cesarean rates for FHR abnormalities during labor (OR 0.23; 95% CI 0.15, 0.35) (Table 1). Only four of 13 individual trials evaluated showed significant differences in overall cesarean rates. However, after pooling data from all publications, significantly lower cesarean rates were noted among women who received intrapartum amnioinfusion (OR 0.52; 95% CI 0.40, 0.68) (Table 2). A lower incidence of fetal acidemia was found in the group who received amnioinfusion (OR 0.40; 95% CI 0.30, 0.55) (Table 3). The incidence of fetal heart rate abnormalities during labor also was significantly lower in the amnioinfusion group (OR 0.24; 95% CI 0.17, 0.34) (Table 4). There was a small but significant difference in
Table 1. Intrapartum Amnioinfusion and Cesarean for Fetal Heart Rate Abnormalities Study
Amnioinfusion group n
0/60 (0.0%) Wu26 Strong14 1/30 (3.3%) Owen15 2/43 (4.6%) Schrimmer16 7/175 (4.0%) Nageotte17 2/50 (4.0%) MacGregor4 6/19 (31.6%) Macri18 2/85 (2.3%) Chauhan19 2/21 (9.5%) Ogundipe20 4/56 (7.1%) Busowski 0/16 (0.0%) Vergani23 2/39 (5.1%) Persson4/60 (6.7%) Kjerstadius25 Totals 32/654 (4.9%)
Comparison group n
Odds ratio (95% CI)
8/58 (13.8%) 4/30 (13.3%) 9/57 (15.8%) 25/130 (19.2%) 4/26 (15.4%) 6/16 (37.5%) 17/85 (20.0%) 1/17 (5.9%) 6/60 (10.0%) 2/15 (13.3%) 10/40 (25.0%) 14/52 (26.9%)
0.05 (0.00, 0.87) 0.22 (0.02, 2.14) 0.26 (0.05, 1.27) 0.17 (0.07, 0.42) 0.23 (0.04, 1.35) 0.77 (0.19, 3.12) 0.10 (0.02, 0.43) 1.68 (0.14, 20.33) 0.69 (0.18, 2.59) 0.16 (0.01, 3.71) 0.16 (0.03, 0.80) 0.19 (0.06, 0.63)
106/586 (18.1%)
0.23 (0.15, 0.35)*
CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X211 ⫽ 11.10, P ⫽ .44.
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Table 2. Intrapartum Amnioinfusion and Overall Cesarean Rate Study
Amnioinfusion group n
Comparison group n
Odds ratio (95% CI)
4/60 (6.7%) 14/58 (24.1%) 0.22 (0.07, 0.73) Wu26 Strong14 4/30 (13.3%) 6/30 (20.0%) 0.62 (0.15, 2.45) Owen15 8/43 (18.6%) 17/57 (29.8%) 0.54 (0.21, 1.40) Schrimmer16 25/175 (14.3%) 36/130 (27.7%) 0.44 (0.25, 0.77) Nageotte17 7/50 (14.0%) 7/26 (26.9%) 0.44 (0.14, 1.44) MacGregor4 10/19 (52.6%) 7/16 (43.7%) 1.43 (0.38, 5.44) Macri18 13/85 (15.3%) 25/85 (29.4%) 0.43 (0.20, 0.92) Chauhan19 4/21 (19.0%) 3/17 (17.7%) 1.10 (0.21, 5.75) Ogundipe20 12/56 (21.4%) 10/60 (16.7%) 1.36 (0.54, 3.46) Vergani23 5/39 (12.8%) 12/40 (30.0%) 0.34 (0.11, 1.09) Wang24 9/39 (23.1%) 8/39 (20.5%) 1.09 (0.37, 3.19) Persson-Kjerstadius25 8/60 (13.3%) 15/52 (28.8%) 0.38 (0.15, 0.99) Mino21 3/100 (3.0%) 10/100 (10.0%) 0.28 (0.07, 1.04) Totals 112/777 (14.4%) 170/710 (23.9%) 0.52 (0.40, 0.68)* CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X212 ⫽ 13.35, P ⫽ .34.
the incidence of 5-minute Apgar scores under 7 in women who received intrapartum amnioinfusion (OR 0.52; 95% CI 0.29, 0.91) (Table 5). Amnioinfusion improved fetal outcomes and decreased cesarean deliveries but did not increase the risk of postpartum endometritis (OR 0.60; 95% CI 0.36, 1.01) (Table 6). The numberneeded-to-treat analysis is shown in Table 7. Amnioinfusion in five women was required to prevent one case of FHR abnormalities, whereas 42 required treatment to prevent one newborn with an Apgar score under 7 at 5 minutes. With the exception of acidemia at birth, tests of homogeneity showed that the studies were not heterogeneous for the various outcomes. For most outcomes
Table 3. Intrapartum Amnioinfusion and Acidemia at Birth Study
Amnioinfusion Comparison group n group n
Odds ratio (95% CI)
0/17 (0.0%) 5/18 (27.7%)0.07 (0.00, 1.38) Strong14 Owen15 13/39 (33.3%) 10/55 (18.2%)2.25 (0.87, 5.85) Schrimmer16 14/175 (8.0%) 39/130 (30.0%)0.20 (0.10, 0.39) MacGregor4 3/19 (15.8%) 3/16 (18.8%)0.81 (0.14, 4.72) Macri18 7/85 (8.2%) 31/85 (36.5%)0.16 (0.06, 0.38) Chauhan19 2/19 (10.5%) 1/12 (8.3%) 1.29 (0.10, 16.04) Ogundipe20 4/56 (7.1%) 5/60 (8.3%) 0.85 (0.21, 3.32) Busowski 0/16 (0.0%) 3/15 (20.0%)0.11 (0.01, 2.29) Vergani23† 1/22 (4.5%) 4/22 (18.2%)0.21 (0.02, 2.10) Persson-Kjerstadius25† 3/60 (5.0%) 2/52 (3.8%) 1.32 (0.21, 8.15) Mino21 22/100 (22.0%) 36/100 (36.0%)0.50 (0.27, 0.94) Totals 69/608 (11.4%) 139/565 (24.6%)0.40 (0.30, 0.55)* CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X210 ⫽ 27.87, P ⫽ .002. Acidemia was defined as an umbilical artery pH less than 7.20 except in two studies (†) where it was defined as less than 7.10.
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Table 4. Intrapartum Amnioinfusion and Fetal Heart Rate Abnormalities Study
Amnioinfusion group n
Comparison group n
Odds ratio (95% CI)
Strong14 Owen15 Schrimmer16 MacGregor4 Macri18 Chauhan19 Vergani23 Wang24 Mino21 Totals
16/30 (53.3%) 8/43 (18.6%) 14/175 (8.0%) 4/19 (21.1%) 3/85 (3.5%) 5/19 (26.3%) 2/37 (5.4%) 3/39 (7.7%) 4/100 (4.0%) 59/547 (10.8%)
21/30 (70.0%) 19/57 (33.3%) 34/130 (26.2%) 12/16 (75.0%) 19/85 (22.4%) 8/17 (47.1%) 14/33 (42.4%) 17/39 (43.6%) 9/100 (9.0%) 153/507 (30.2%)
0.49 (0.17, 1.41) 0.46 (0.18, 1.18) 0.24 (0.12, 0.48) 0.09 (0.02, 0.43) 0.13 (0.04, 0.45) 0.40 (0.10, 1.62) 0.08 (0.02, 0.38) 0.11 (0.03, 0.41) 0.42 (0.12, 1.42) 0.24 (0.17, 0.34)*
CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X28 ⫽ 10.64, P ⫽ .22.
analyzed, funnel plot analyses produced plot shapes incompatible with publication bias.
Discussion This systematic review showed that prophylactic intrapartum amnioinfusion in women with oligohydramnios significantly decreases FHR abnormalities, acidemia at birth, and rates of cesarean deliveries. The lower overall rate of cesarean delivery among women with oligohydramnios who received prophylactic amnioinfusion largely was caused by fewer cesarean deliveries for FHR abnormalities. Amnioinfusion also was associated with reduction in several adverse maternal and perinatal outcomes without increasing the incidence of postpartum endometritis. Hofmeyer et al10 reviewed the effectiveness of amnioinfusion in several clinical settings. They evaluated
Table 5. Intrapartum Amnioinfusion and Apgar Scores Under 7 at 5 Minutes Study
Amnioinfusion Comparison group n group n
1/30 (3.3%) 0/30 (0.0%) Strong14 Owen15 1/43 (2.3%) 1/57 (1.8%) Schrimmer16 6/175 (3.4%) 9/130 (6.9%) Nageotte17 2/50 (4.0%) 2/26 (7.7%) Macri18 0/85 (0.0%) 8/85 (9.4%) Chauhan19 1/19 (5.3%) 0/12 (0.0%) Busowski 0/16 (0.0%) 1/15 (6.7%) Vergani23 3/39 (7.7%) 4/40 (10.0%) Wang24 1/39 (2.6%) 0/39 (0.0%) Persson-Kjerstadius25 3/60 (5.0%) 5/52 (9.6%) Mino21 0/100 (0.0%) 0/100 (0.0%) Totals 18/656 (2.7%) 30/586 (5.1%)
Odds ratio (95% CI) 3.00 (0.12, 76.58) 1.33 (.08, 21.94) 0.48 (0.17, 1.38) 0.50 (0.07, 3.77) 0.05 (0.00, 0.94) 2.03 (0.08, 53.87) 0.29 (0.01, 7.76) 0.75 (0.16, 3.59) 3.08 (0.12, 77.91) 0.49 (0.11, 2.18) excluded 0.52 (0.29, 0.91)*
CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X28 ⫽ 6.17, P ⫽ .72.
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Table 6. Intrapartum Amnioinfusion and Postpartum Endometritis Study
Amnioinfusion group n
Comparison group n
Odds ratio (95% CI)
Wu26 Owen15 Schrimmer16 MacGregor4 Macri18 Ogundipe20 Mino21 Totals
3/60 (5.0%) 1/43 (2.3%) 7/175 (4.0%) 4/19 (21.0%) 8/85 (9.4%) 3/56 (5.3%) 01/100 (0.0%) 26/538 (4.8%)
8/58 (13.8%) 11/57 (19.0%) 10/130 (7.7%) 1/16 (6.2%) 9/85 (10.6%) 1/60 (1.7%) 0/100 (0.0%) 40/506 (7.9%)
0.33 (0.08, 1.31) 0.10 (0.01, 0.80) 0.50 (0.18, 1.35) 4.00 (0.40, 40.10) 0.88 (0.32, 2.39) 3.34 (0.34, 33.08) excluded 0.60 (0.36, 1.01)*
CI ⫽ confidence interval. * Pooled odds ratio and 95% confidence interval. Heterogeneity X25 ⫽ 9.01, P ⫽ .11.
nine clinical trials of intrapartum amnioinfusion for umbilical cord compression and found a reduction in overall rates of cesarean deliveries and specifically of cesarean deliveries for “fetal distress.” Two systematic reviews in the Cochrane Library35,36 compared amnioinfusion in women with oligohydramnios. The first included two trials that compared prophylactic versus therapeutic amnioinfusion in laboring women.38 The second reviewed 12 trials in which some participants had evidence of intrapartum infection or had variable decelerations before randomization.36 Those reviews also differ from our meta-analysis with regard to amnioinfusion in the control groups. A single trial in our review used amnioinfusion for women randomized to the comparison group. In the study by Ogundipe et al, 22% of controls received amnioinfusion when variable decelerations developed.20 We limited our meta-analysis to randomized controlled trials because they are the most reliable method of assessing efficacy of therapeutic interventions. However, studies are more likely to be published if they Table 7. Number-needed-to-treat Analysis of Prophylactic Amnioinfusion for Oligohydramnios
Outcome Cesarean for FHR abnormalities Overall cesarean rate Acidemia at birth Intrapartum FHR abnormalities Apgar score under 7 at 5 minutes Postpartum endometritis
Amnioinfusion Comparison group group 32/654 (4.9%) 112/777 (14.4%) 69/608 (11.4%) 59/547 (10.8%) 18/656 (2.7%) 26/538 (4.8%)
106/586 (18.1%) 170/710 (23.9%) 139/565 (24.6%) 153/507 (30.2%) 30/586 (5.1%) 40/506 (7.9%)
Number needed to treat (95% CI) 8 (6, 10) 11 (7, 18) 8 (6, 11) 5 (4, 7) 42 (21, 500) 32 (16, 1000)
CI ⫽ confidence interval; FHR ⫽ fetal heart rate.
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show statistically significant findings. A review in which only published articles are analyzed might be biased toward larger or statistically significant effects or both, and erroneous conclusions might result. It is unlikely that bias of that nature was a factor in our systematic review because several studies showed similar results between amnioinfusion and comparison groups. Unpublished trials with negative results would have to include a large number of women to negate our findings. Funnel plot analyses indicated no obvious publication bias.31 Two important issues related to meta-analysis are quality of the studies and heterogeneity. Based on thorough evaluation and assessment of each trial, the included studies were of high quality. Excessive heterogeneity in systematic reviews, degree of incompatibility in the quantitative results among trials included in the meta-analysis, might decrease validity of this approach. Although absolute homogeneity among studies might appear desirable, it could also preclude generalization to a larger population. Nonetheless, understanding the sources of heterogeneity remains important. We found significant heterogeneity for only one outcome, fetal acidemia at birth. The pooled results found the incidence of acidemia at birth significantly decreased in women who received intrapartum amnioinfusion. Among all studies assessed, the proportion of subjects who experienced acidemia at birth ranged from 0 –30.2% and 3.8 –36.5% in the amnioinfusion and comparison groups, respectively. That broad range likely indicates uncertainty in the definition of acidemia. The finding of significant heterogeneity for fetal acidemia at birth is likely the result of two studies with higher rates of acidemia for those assigned to the comparison group (no amnioinfusion).15,25 However, even after removing the two studies with discrepant results, subgroup analysis for that outcome showed significant differences in favor of prophylactic amnioinfusion. Differences in inclusion criteria and interventions were noted and could have affected our overall findings. For example, three studies15,21,27 did not quantify degree of oligohydramnios, or included subjects with AFIs no more than 10 cm. Two studies used transabdominal rather than transcervical amnioinfusion.23,27 Subgroup analysis excluded three studies (oligohydramnios definition) and two studies (transabdominal amnioinfusion). Excluding those studies did not alter our overall results. Although amnioinfusion has proved effective in reducing perinatal morbidity, concerns exist regarding its safety. A recent survey of United States teaching hospitals found that many methods of amnioinfusion are used, and all appear safe.37 Although most obstetricians
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consider amnioinfusion safe, some express concerns it might increase rates of infectious morbidity. Complications reported include uterine rupture, increased basal uterine tone, hypertonus, fetal bradychardia, umbilical cord prolapse, placental abruption, AF embolism, and maternal morbidity and death. Fortunately, those are rare and apparently unrelated to the specific protocol followed.38 The numbers of women undergoing amnioinfusion in randomized trials are far too small to be able to evaluate the possibility of those unusual complications.
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Address reprint requests to:
Luis Sanchez-Ramos, MD University of Florida Health Science Center Department of Obstetrics and Gynecology 653-1 West 8th Street Jacksonville, FL 32209 E-mail: [email protected]
Received April 13, 2000. Received in revised form July 13, 2000. Accepted August 17, 2000. Copyright © 2000 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Obstetrics & Gynecology