1. Aetna considers amnioinfusion medically necessary for any of the following indications:

   1. Prophylactic treatment of oligohydramnios, or
   2. Reduction of variable decelerations of the fetal heart rate because of cord compression during labor, or

   3. Treatment of preterm premature rupture of membranes.

2. Aetna considers amnioinfusion experimental and investigational for facilitation of external cephalic version, prevention of meconium aspiration syndrome, and all other indications because of insufficient evidence in the peer-reviewed literature.

Amnioinfusion is a procedure in which normal saline or lactated Ringer's solution is infused into the uterine cavity to replace amniotic fluid.  It is used to treat problems known to be associated with decreased intra-amniotic volume, including prophylactic treatment of oligohydramnios and treatment of severe variable decelerations during labor.

Amnioinfusion has also been used to reduce the risk of meconium aspiration during labor in women with moderate or thick meconium fluid.  However, a multi-center randomized controlled clinical trial found no benefit to amnioinfusion for this indication.  In a prospective, multi-center, randomized controlled study (n = 1,975), Fraser et al (2005) examined if amnioinfusion in women who have thick meconium staining of the amniotic fluid reduces the risk of perinatal death, moderate or severe meconium aspiration syndrome, or both.  Women in labor at 36 or more weeks of gestation who had thick meconium staining of the amniotic fluid were stratified according to the presence or absence of variable decelerations in fetal heart rate and then randomly assigned to amnioinfusion or to standard care.  The composite primary outcome measure was perinatal death, moderate or severe meconium aspiration syndrome, or both.  Perinatal death, moderate or severe meconium aspiration syndrome, or both occurred in 44 infants (4.5 %) of women in the amnioinfusion group and 35 infants (3.5 % of women in the control group (relative risk [RR], 1.26; 95 % confidence interval [CI]: 0.82 to 1.95).  Five perinatal deaths occurred in the amnioinfusion group, and 5 in the control group.  The rate of cesarean delivery was 31.8 % in the amnioinfusion group and 29.0 % in the control group (RR, 1.10; 95 % CI: 0.96 to 1.25).  These investigators concluded that for women in labor who have thick meconium staining of the amniotic fluid, amnioinfusion did not reduce the risk of moderate or severe meconium aspiration syndrome, perinatal death, or other major maternal or neonatal disorders.

In an editorial that accompanied the article by Fraser et al, Ross (2005) stated that “Given the lack of benefit of amnioinfusion in the study by Fraser et al, what might the clinician do to prevent the meconium aspiration syndrome?  Although routine intrapartum oropharyngeal and nasopharyngeal suctioning of term infants born through meconium-stained amniotic fluid is a mainstay of current therapy, it has recently been shown not to prevent the meconium aspiration syndrome.  Better understanding of how the maturation of the motility of the fetal colon accounts for the timing of the passage of meconium and its stimulation by fetal stress (thought to be mediated, in part, by means of the hypoxia-induced release of placental corticotropin-releasing factor) ultimately may lead to future therapeutic interventions …. the article by Fraser et al provides strong evidence that amnioinfusion is not warranted to prevent this syndrome in women with thick meconium staining of the amniotic fluid”.

The ACOG Committee on Obstetric Practice (2006) stated that based on available literature, routine prophylactic amnioinfusion for meconium-stained amniotic fluid is not recommended.  Prophylactic use of amnioinfusion for meconium-stained amniotic fluid should be performed only in the setting of additional clinical studies.  Data are not available on if amnioinfusion for fetal heart rate decelerations in the presence of meconium-stained amniotic fluid reduces meconium aspiration syndrome or other meconium-associated morbidities.  However, amnioinfusion remains a reasonable approach in the treatment of repetitive variable decelerations, regardless of amniotic fluid meconium status.

There is evidence supporting the use of amnioinfusion in pregnancies complicated by preterm premature rupture of membranes (pPROM).  In a randomized controlled study, Tranquilli et al (2005) assessed the role of transabdominal amnioinfusion in improving the perinatal outcomes of pregnancies complicated by pPROM.  Women with singleton pregnancies complicated by pPROM, between 24 + 0 and 32 + 6 weeks of gestation were randomized 24 hours after admission to the hospital, to expectant management with transabdominal amnioinfusion or expectant management only.  Main outcome measures were effects of transabdominal amnioinfusion on pPROM-delivery interval and on perinatal outcomes.  Of the 65 women with pPROM, 34 met the inclusion criteria.  Seventeen women were assigned to amnioinfusion (the amnioinfusion group), and the other 17 to expectant management.  Compared with the control group (median: 8 days; range of 3 to 14), the pPROM-delivery period was significantly longer in women who underwent amnioinfusion (median of 21 days; range of 15 to 29) (p < 0.05).  Women with amnioinfusion were less likely to deliver within 7 days since pPROM (RR: 0.18; range of 0.04 to 0.69, 95 % CI) or within 2 weeks (RR: 0.46; range of 0.21 to 1.02, 95 % CI).  In the amnioinfusion group the neonatal survival was significantly higher at each gestational age (p < 0.01, Yates's correction for Log Rank Test) with a reduction in pulmonary hypoplasia.  These researchers concluded that compared with standard expectant management, the treatment with transabdominal amnioinfusion after pPROM resulted in significant prolongation of pregnancy and better neonatal outcomes.

Hicks (2005) noted that the benefit of amnioinfusion in women with previous cesarean deliveries is unclear.  Theoretically, rapid increases in intra-uterine volume would lead to a higher risk of uterine rupture.  The author concluded that the use of amnioinfusion in women with previous cesarean delivery who are undergoing a trial of labor may be a safe procedure, but confirmatory large, controlled prospective studies are needed before definitive recommendations can be made.

A Cochrane review (Hofmeyr, 2004) found no randomized controlled studies of transabdominal amnioinfusion for external cephalic version at term.  Adama van Scheltema and colleagues (2006) assessed the effectiveness of antepartum transabdominal amnioinfusion to facilitate external cephalic version after initial failure.  Women with a structurally normal fetus in breech lie at term, with a failed external cephalic version and an amniotic fluid index (AFI) less than 15 cm, participated in this study.  After tocolysis with indomethacin, a transabdominal amnioinfusion was performed with an 18-G spinal needle.  Lactated Ringers solution was infused until the AFI reached 15 cm, with a maximum of 1 liter.  External cephalic version was performed directly afterward.  A total of 7 women participated in the study.  The gestational age of the women was between 36(+4) weeks and 38(+3) weeks, and 3 women were primiparous.  The AFI ranged from 4 cm to 13 cm.  A median amount of 1,000 ml Ringers solution (range of 700 ml to 1,000 ml) was infused per procedure.  The repeat external cephalic versions after amnioinfusion were unsuccessful in any of the patients.  The authors concluded that amnioinfusion does not facilitate external cephalic version.

Xu et al (2007) evaluated if amnioinfusion (AI) reduces meconium aspiration syndrome (MAS) and other indicators of morbidity in babies born to women with meconium-stained amniotic fluid (MSAF).  Randomized trials comparing AI with no AI for women in labor with MSAF were reviewed.  Trial quality was evaluated using pre-established criteria.  The following morbidity indicators were assessed: MAS, 5-min Apgar score less than 7, arterial cord pH less than 7.2, and cesarean section.  Studies were stratified according to the level of peripartum surveillance (standard versus limited).  Typical RRs with their 95 % CI were calculated for each outcome using a random effects model.  In clinical settings with standard peripartum surveillance, no evidence that AI reduced the risk of MAS (RR 0.59, 95 % CI: 0.28 to 1.25), 5-min Apgar score less than 7 (RR 0.90, 95 % CI: 0.58 to 1.41), or cesarean delivery (RR 0.89, 95 % CI: 0.73 to 1.10) was found.  In clinical settings with limited peripartum surveillance, AI appeared to reduce the risk of MAS (RR 0.25, 95 % CI: 0.13 to 0.47).  The authors concluded that in clinical settings with standard peripartum surveillance, the evidence does not support the use of AI for MSAF.  In settings with limited peripartum surveillance, where complications of MSAF are common, AI appears to reduce the risk of MAS.  However, the authors stated that this finding requires confirmation by further studies.

Engel and colleagues (2008) evaluated the effect of intra-partum AI in the presence of MSAF.  Women with MSAF were assigned to receive AI (n = 93) or no-AI (n = 128).  The trials were evaluated for fetal distress syndrome, route of delivery, fetal acidemia, Apgar score at 1 and 5 mins, MAS, post-partum endometritis, as well as maternal hospital stays.  Amnioinfusion in cases of meconium-stained fluid did not improve the number of fetal distress symptoms during fetal heart rate monitoring.  Amnioinfusion was associated with a significant decrease of neonatal acidemia although it did not improve Apgar score.  The authors concluded that AI was not associated with reduction in the incidence of neonatal outcome and puerperial complications.

In a Cochrane review, Hofmeyr and Xu (2010) evaluated the effects of AI for meconium-stained liquor on perinatal outcome.  These investigators searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2009).  Randomized trials comparing AI with no AI for women in labor with moderate or thick meconium-staining of the amniotic fluid were included.  Two review authors assessed eligibility and trial quality, and extracted data, independently.  A total of 13 studies of variable quality (4,143 women) were included.  Subgroup analysis was performed for studies from settings with limited facilities to monitor the baby's condition during labor and intervene effectively, and settings with standard peripartum surveillance.  For settings with standard peripartum surveillance, there was considerable heterogeneity for several outcomes.  There was no significant reduction in the primary outcomes MAS, perinatal death or severe morbidity, and maternal death or severe morbidity.  There was a reduction in cesarean sections (CSs) for fetal distress but not overall.  Meconium below the vocal cords diagnosed by laryngoscopy was reduced, as was neonatal ventilation or neonatal intensive care unit admission, but there was no significant reduction in perinatal deaths or other morbidity.  Planned sensitivity analysis excluding trials with greater risk of bias resulted in an absence of benefits for any of the outcomes studied.  Settings with limited peripartum surveillance: 2 studies (855 women) were included.  In the AI group there was a reduction in CS for fetal distress and overall; MAS (RR 0.25, 95 % CI: 0.13 to 0.47), and neonatal ventilation or neonatal intensive care unit admission; and a trend towards reduced perinatal mortality (RR 0.37, 95 % CI: 0.13 to 1.01).  In one of the studies, meconium below the vocal cords was reduced and, in the other, neonatal encephalopathy was reduced.  The authors concluded that AI is associated with substantive improvements in perinatal outcome only in settings where facilities for perinatal surveillance are limited.  It is unclear if the benefits are due to dilution of meconium or relief of oligohydramnios.  In settings with standard peripartum surveillance, some non-substantive outcomes were improved in the initial analysis, but sensitivity analysis excluding trials with greater risk of bias eliminated these differences.  Amnioinfusion is either ineffective in this setting, or its effects are masked by other strategies to optimize neonatal outcome.  The trials reviewed were too small to address the possibility of rare but serious maternal adverse effects of AI.

Breech presentation is associated with increased complications.  Turning a breech baby to head-first presentation using external cephalic version (ECV) attempts to reduce the chances of breech presentation at birth, and reduce the adverse effects of breech vaginal birth or caesarean section.  Tocolytic drugs and other methods have been used in an attempt to facilitate ECV.  In a Cochran review, Cluver et al (2012) evaluated interventions such as tocolysis, fetal acoustic stimulation, regional analgesia, trans-abdominal amnioinfusion or systemic opioids on ECV for a breech baby at term.  These investigators searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 30, 2011) and the reference lists of identified studies.  Randomized and quasi-randomized trials comparing the above interventions with no intervention or other methods to facilitate ECV at term were selected for analysis.  These researchers assessed eligibility and trial quality.  Two review authors independently assessed for inclusion all potential studies identified as a result of the search strategy and independently extracted the data using a designed data extraction form.  The author included 25 studies, providing data on 2,548 women.  They used the random-effects model for pooling data due to clinical heterogeneity in the included studies in the various comparisons.  The overall quality of the evidence was reasonable, but a number of assessments had insufficient data to provide an answer with any degree of assurance.  Tocolytic drugs, in particular beta stimulants, were effective in increasing cephalic presentations in labor (average risk ratio (RR) 1.38, 95 % confidence interval (CI): 1.03 to 1.85, 8 studies, 993 women) and in reducing the number of caesarean sections (average RR 0.82, 95 % CI: 0.71 to 0.94, 8 studies, 1,177 women).  No differences were identified in fetal bradycardias (average RR 0.95, 95 % CI: 0.48 to 1.89, 3 studies, 467 women) although the review was under-powered for assessing this outcome.  These investigators identified no difference in success, cephalic presentation in labor and caesarean sections between nulliparous and multiparous women.  There were insufficient data comparing different groups of tocolytic drugs.  Sensitivity analyses by study quality agreed with the overall findings.  Regional analgesia in combination with a tocolytic was more effective than the tocolytic alone in terms of increasing successful versions (assessed by the rate of failed ECVs, average RR 0.67, 95 % CI: 0.51 to 0.89, 6 studies, 550 women) but there was no difference identified in cephalic presentation in labor (average RR 1.63, 95 % CI: 0.75 to 3.53, 3 studies, 279 women) nor in caesarean sections (average RR 0.74, 95 % CI: 0.40 to 1.37, 3 studies, 279 women) or fetal bradycardia (average RR 1.48, 95 % CI: 0.62 to 3.57, 2 studies, 210 women).  There were insufficient data on the use of vibro-acoustic stimulation, amnioinfusion or systemic opioids.  The authors concluded that t beta stimulants, to facilitate ECV, increased cephalic presentation in labor and birth, and reduced the caesarean section rate in both nulliparous and multiparous women, but there were insufficient data on adverse effects.  Calcium channel blockers and nitric acid donors had insufficient data to provide good evidence.  The authors recommended betamimetics for facilitating ECV.  There is scope for further research.  The possible benefits of tocolysis to reduce the force required for successful version and the possible risks of maternal cardiovascular side effects, need to be addressed further.  Further trials are needed to compare the effectiveness of routine versus selective use of tocolysis, the role of regional analgesia, fetal acoustic stimulation, amnioinfusion and the effect of intravenous or oral hydration prior to ECV.  Although randomized trials of nitroglycerine are small, the results are sufficiently negative to discourage further trials.