Evidence-Based Guidelines - Download as DOC by y3GCC2

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									7435b657-def7-418c-a562-73581c734aaa.doc                                                                                                          Page 7 of 25




              WORKSHEET for PROPOSED Evidence-Based GUIDELINE RECOMMENDATIONS

 Worksheet Author: Dharmapuri Vidyasagar, MD                               Home Subcommittee: AAP NRP Committee

 Author’s Home Resuscitation Council: ILCOR
                                                                           Date Submitted to Subcommittee: October 07, 2004


STEP 1: STATE THE PROPOSAL. State if this is a proposed new guideline; revision to current guideline; or deletion of current guideline.

Existing guideline, practice or training activity:
In the presence of thick meconium-stained amniotic fluid amnioinfusion may be performed to dilute the meconium in an effort to prevent meconium
aspiration syndrome.
Step 1A: Refine the question; state the question as a positive (or negative) hypothesis. State proposed guideline recommendation as a specific,
positive hypothesis. Use single sentence if possible. Include type of patients; setting (in- /out-of-hospital); specific interventions (dose, route); specific
outcomes (ROSC vs. hospital discharge).
In the presence of meconium-stained amniotic fluid, amnioinfusion should be carried out to decrease the incidence of meconium aspiration
syndrome.
Step 1B: Gather the Evidence; define your search strategy. Describe search results; describe best sources for evidence.
Terms used in search strategy: meconium, meconium-stained amniotic fluid, amnioinfusion, meconium aspiration syndrome. Clinical trials and
amnioinfusion.

List electronic databases searched (at least MEDLINE (http://igm.nlm.nih.gov/) and hand searches of journals, review articles, and books.
Medline (Pub Med); The Cochrane Database of Systematic Reviews; Science Direct; Hand searches at UIC Library.
• State major criteria you used to limit your search; state inclusion or exclusion criteria (e.g., only human studies with control group? no animal studies? N subjects
   > minimal number? type of methodology? peer-reviewed manuscripts only? no abstract-only studies?)
   Human studies published from January 1983 through October 2004. All randomized clinical trials were reviewed and included in this analysis.
   Other related articles were referenced but not included in this analysis.
• Number of articles/sources meeting criteria for further review: Create a citation marker for each study (use the author initials and date or Arabic numeral, e.g.,
“Cummins-1”). . If possible, please supply file of best references; End Note 4+ preferred as reference manager, though other reference databases
acceptable.
The search yielded the following number of citations: Meconium 4301, meconium aspiration 990, meconium stained amniotic fluid 412,
amnioinfusion 280, meconium and amnioinfusion 80, of the 80 reports on meconium and amnioinfusion 35 publications were either randomized
clinical trials, meta analysis, historic cases, or case series. These reports were included in the analysis to determine the level of evidence . They are
reviewed in detail.


                       STEP 2: ASSESS THE QUALITY OF EACH STUDY
 Step 2A: Determine the Level of Evidence. For each article/source from step 1, assign a level of evidence—based on
 study design and methodology.
     Level of                                                     Definitions
     Evidence                                            (See manuscript for full details)
      Level 1     Randomized clinical trials or meta-analyses of multiple clinical trials with substantial treatment effects

                        Wenstrom 1989; Macri 1992; Cialone 1994; Dye 1994; Eriksen 1994; Spong 1994; Hofmeyr 1998; Mahomed
                        1998; Moodley 1998; Alvarez 1999; Pierce 2000; Zhao 2000; Puertas 2001; Rathorea 2002; Hofmeyr 2002;
                        Sood 2004.
       Level 2          Randomized clinical trials with smaller or less significant treatment effects

                        Adam 1989; Sadovsky 1989; Nageotte 1991, Ilagan 1992, Glantz 2002, Shah 2004.
       Level 3          Prospective, controlled, non-randomized, cohort studies

                        Lo 1993; Khosla 1997,
       Level 4          Historic, non-randomized, cohort or case-control studies

                        De Meeus 1997; Wu 1991; Uhing 1993 ; Rogers 1995, Usta 1995 Moen 1996
       Level 5          Case series: patients compiled in serial fashion, lacking a control group
                        Hourdequin 1994;Adair 1995; Maher 1995; Wenstrom 1995;Halvax 2002
       Level 6          Animal studies or mechanical model studies

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      Level 7       Extrapolations from existing data collected for other purposes, theoretical analyses

      Level 8       Rational conjecture (common sense); common practices accepted before evidence-based guidelines




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Step 2B: Critically assess each article/source in terms of research design and methods.
  Was the study well executed? Suggested criteria appear in the table below. Assess design and methods and provide an overall
  rating. Ratings apply within each Level; a Level 1 study can be excellent or poor as a clinical trial, just as a Level 6 study could be
  excellent or poor as an animal study. Where applicable, please use a superscripted code (shown below) to categorize the primary
  endpoint of each study. For more detailed explanations please see attached assessment form.
 Component of
 Study and Rating             Excellent                 Good                   Fair                  Poor              Unsatisfactory
 Design &               Cialone 1994            Sadovsky 1989           Adam 1989
 Methods                Dye 1994 [Meta-         Wenstrom 1989           Wu 1991
                        Analysis]               Ilagan 1992             Nageotte
                        Mahomed 1998            Macri 1992              1991
                        Pierce 2000 [Meta-      Uhing 1993              Lo 1993
                        Analysis]               Spong 1994              Hourdequin
                        Puertas 2001            Eriksen 1994            1994
                        Rathorea 2002           Wenstrom 1995           Usta 1995
                        Hofmeyr 2002            Hofmeyr 1998            Rogers 1995
                        (metaanalysis)          Moodley 1998            Adair 1995
                                                Alvarez 1999            Maher 1995
                                                Zhao 2000               Moen 1996
                                                Glantz 2002             De Meeus 1997
                                                Sood 2004               Khosla 1997
                                                                          Halvax 2002
                                                                          Shah 2004

A = Return of spontaneous circulation         C = Survival to hospital discharge            E = Other endpoint
B = Survival of event                         D = Intact neurological survival
  Step 2C: Determine the direction of the results and the statistics: supportive? neutral? opposed?

 DIRECTION of study
 by results & statistics:     SUPPORT the proposal                 NEUTRAL                             OPPOSE the proposal
                              Sadovsky 1989                        Adam 1989                           Spong 1994
 Results                      Wenstrom 1989                        Nageotte 1991                       Adair 1995
                              Wu 1991                              Rogers1995                          Maher 1995
                              Ilagan 1992                          Usta 1995
                              Macri 1992                           De Meeus 1997
                              Uhing 1993                           Khosla 1997
                              Cialone 1994                         Hofmeyr 1998
                              Dye 1994                             Lo 1993
                              Eriksen 1994                         Moodley 1998
                              Hourdequin 1994
                              Wenstrom 1995
                              Moen 1996
                              Mahomed 1998
                              Alvarez 1999
                              Pierce 2000
                              Zhao 2000
                              Puertas 2001
                              Rathorea 2002
                              Hofmeyr 2002
                              Glantz 2002
                              Halvax 2002
                              Sood 2004
                              Shah 2004




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Step 2D: Cross-tabulate assessed studies by a) level, b) quality and c) direction (ie, supporting or neutral/
opposing); combine and summarize. Exclude the Poor and Unsatisfactory studies. Sort the Excellent, Good, and Fair quality
studies by both Level and Quality of evidence, and Direction of support in the summary grids below. Use citation marker (e.g. author/
date/source). In the Neutral or Opposing grid use bold font for Opposing studies to distinguish them from merely neutral studies.
Where applicable, please use a superscripted code (shown below) to categorize the primary endpoint of each study.


                                                                    Supporting Evidence
                                   Cialone 1994
                                   Dye 1994
                                   Mahomed –
                       Excellent   1998
                                   Pierce 2000
                                   Puertas 2001
 Quality of Evidence




                                   Rathorea 2002
                                   Hofmeyr 2002

                                   Wenstrom --
                                   1989
                                   Macri 1992      Sadovsky --
                        Good       Eriksen 1994    1989                            Uhing
                                                                                                   Wenstrom
                                                                                                   1995
                                   Moodley 1998    Ilagan 1992                     1993
                                   Alvarez 1999    Glantz 2002
                                   Zhao 2000
                                   Sood 2004


                                                                                                   Hourdequin
                         Fair                      Shah
                                                                                   Wu 1991         1994
                                                                                   Moen 1996       Halvax 2002
                                                   2004



                                         1                2               3                4            5                6            7              8
                                                                                   Level of Evidence
A = Return of spontaneous circulation                            C = Survival to hospital discharge              E = Other endpoint
B = Survival of event                                            D = Intact neurological survival
                                                          Neutral or Opposing Evidence


                       Excellent
 Quality of Evidence




                                   Hofmeyr 1998
                        Good       Spong 1994




                                                   Nageotte 1991     Lo 1993       De Meeus 1997
                         Fair                      Adam 1989         Khosla 1997   Usta 1995
                                                                                                   Maher 1995
                                                                                                   Adair 1995
                                                   Moodley 1998                    Rogers 1995



                                         1                2               3                4            5                6            7              8
                                                                                   Level of Evidence
A = Return of spontaneous circulation                            C = Survival to hospital discharge              E = Other endpoint
B = Survival of event                                            D = Intact neurological survival


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META-ANALYSES: to provide a basis for Step 3
 Are there two or more Level 1 studies in Step 2D that support the proposal and are statistically significant at p < 0.05? Yes.

 Do these supportive studies constitute at least one quarter of Level 1 clinical trials? Yes.
 (If the answer to both questions is “yes”, the null hypothesis is very likely to be false.)
 Do you think there are sufficient data to perform a formal meta-analysis? We have included recent metaanalysis data by Hofmeyr 2002.
 Summarize core numeric data. If you can provide a formal meta-analysis, attach the most critical tabulations, and cite the methodology used.
 Meta-analysis not conducted.

 STEP 3. DETERMINE THE CLASS OF RECOMMENDATION. Select from these summary
 definitions.
                  CLASS                                       CLINICAL DEFINITION                              REQUIRED LEVEL OF EVIDENCE
  Class I                                           • Always acceptable, safe                          • One or more Level 1 studies are present (with rare
  Definitely recommended. Definitive,               • Definitely useful                                  exceptions)
  excellent evidence provides support.              • Proven in both efficacy & effectiveness          • Study results consistently positive and compelling
                                                    • Must be used in the intended manner for
                                                      proper clinical indications.
  Class II:                                         • Safe, acceptable                                 • Most evidence is positive
  Acceptable and useful                             • Clinically useful                                • Level 1 studies are absent, or inconsistent, or lack
                                                    • Not yet confirmed definitively                     power
                                                                                                       • No evidence of harm
   • Class IIa: Acceptable and useful               • Safe, acceptable                                 • Generally higher levels of evidence
  Good evidence provides support                    • Clinically useful                                • Results are consistently positive
                                                    • Considered treatments of choice
   • Class IIb: Acceptable and useful               • Safe, acceptable                                 • Generally lower or intermediate levels of evidence
  Fair evidence provides support                    • Clinically useful                                • Generally, but not consistently, positive results
                                                    • Considered optional or alternative
                                                      treatments
  Class III:                                        • Unacceptable                                     • No positive high level data
  Not acceptable, not useful, may be                • Not useful clinically                            • Some studies suggest or confirm harm.
  harmful                                           • May be harmful.
                                                    • Research just getting started.                   • Minimal evidence is available
  Indeterminate                                     • Continuing area of research                      • Higher studies in progress
                                                    • No recommendations until                         • Results inconsistent, contradictory
                                                      further research                                 • Results not compelling

 STEP 3: DETERMINE THE CLASS OF RECOMMENDATION. State a Class of Recommendation for the Guideline Proposal.
 State either a) the intervention, and then the conditions under which the intervention is either Class I, Class IIA, IIB, etc.; or b) the condition, and then whether
 the intervention is Class I, Class IIA, IIB, etc.

 Intervention:          Use of amnioinfusion in women with moderate staining of amniotic fluid during labor to reduce meconium
 below the vocal cords and meconium aspiration syndrome in an infant.
 Final Class of recommendation: Class II b – acceptable and useful, fair, not consistently positive results.


REVIEWER’S PERSPECTIVE AND POTENTIAL CONFLICTS OF INTEREST: Briefly summarize your professional background, clinical
specialty, research training, AHA experience, or other relevant personal background that define your perspective on the guideline proposal. List any potential
conflicts of interest involving consulting, compensation, or equity positions related to drugs, devices, or entities impacted by the guideline proposal. Disclose any
research funding from involved companies or interest groups. State any relevant philosophical, religious, or cultural beliefs or longstanding disagreements with an
individual.
 A neonatologist with over 30 years of experience as an academic clinician, teacher and investigator, I have been keenly interested in
 the subject of neonatal respiratory problems including hyaline membrane disease (HMD), meconium aspiration syndrome (MAS)
 and neonatal resuscitation. My paper on the subject of MAS in 1975 was one of the first papers published on the subject. I have no
 conflict of interest. I am a member of the International Child Health and Perinatal Sections of the AAP.


REVIEWER’S FINAL COMMENTS AND ASSESSMENT OF BENEFIT / RISK: Summarize your final evidence integration and the rationale for
the class of recommendation. Describe any mismatches between the evidence and your final Class of Recommendation. “Mismatches” refer to selection of a class


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of recommendation that is heavily influenced by other factors than just the evidence. For example, the evidence is strong, but implementation is difficult or
expensive; evidence weak, but future definitive evidence is unlikely to be obtained. Comment on contribution of animal or mechanical model studies to your final
recommendation. Are results within animal studies homogeneous? Are animal results consistent with results from human studies? What is the frequency of
adverse events? What is the possibility of harm? Describe any value or utility judgments you may have made, separate from the evidence. For example, you
believe evidence-supported interventions should be limited to in-hospital use because you think proper use is too difficult for pre-hospital providers.
 Introduction
 The clinical problem of MAS has been a matter of serious concern to both neonatologists and perinatologists. Meconium staining of
 amniotic fluid occurs in 7-22% of live births. If this meconium-stained fluid is aspirated by the fetus before or during birth,
 meconium can obstruct the airways, cause inflammation, interfere with surfactant function and cause respiratory difficulties
 resulting in meconium aspiration syndrome (MAS). MAS occurs in 1-3% of all cases of meconium-stained amniotic fluid and in 10-
 40 % of newborns with meconium below the vocal cords. This syndrome carries a mortality rate up to 40%. Infants with severe
 MAS develop pulmonary hypertension and cardiopulmonary failure requiring ECMO. Those who survive may demonstrate residual
 neurologic deficits, therefore there is great interest in developing strategies to prevent MAS. Initial attempts were aimed at
 improving the neonatal management. Later, a perinatal approach to the problem was recommended including suctioning the
 oropharynx at birth in infants with meconium-stained amniotic fluid. Later, since the presence of thick meconium in the amniotic
 fluid was associated with a poor outcome in the infant, amnioinfusion was suggested. It is hypothesized that amnioinfusion dilutes
 the meconium, thus decreasing the potential of developing obstruction of airways and development of MAS.
 However, there is considerable discussion regarding the efficacy of amnioinfusion as an intervention to reduce the occurrence of
 MAS and its’ complications. The purpose of this study was to review the published clinical trials in the literature up to October 1,
 2004, and assess them according to their strength of evidence in relation to its efficacy.

We searched the literature using PubMed for amnioinfusion, meconium and meconium-aspiration syndrome during the period of January 1, 1983 to
October 1, 2004. We found 80 reports related to meconium and amnioinfusion. There were 3 reports of meta-analysis Dye (5 reports),
Cochrane 2001 (12 reports), Pierce 2002 (13 reports). Several reports overlapped within these three meta-analyses. Overall, the
analysis of 80 publications contained 35 reports related to amnioinfusion and meconium aspiration. Since the last meta-analysis by
Cochrene in the year 2002, we found five additional clinical trials. The current presentation consists of a review of the 35 published
reports and analysis according to their strength of support, neutrality or opposing effect. 24 of the 35 reports were in support of the
beneficial effect of AI on MAS. 11 were either neutral or opposing view.

 Supporting Reports
 Among the 23 supporting reports: 13 were of level 1 evidence (6 excellent, 7 good ) , 4 were level 2 (3 good and 1 fair) the rest 6
 belonged to Level 4 and 5 evidence. The reports of Wenstrom and Sadovsky were the earliest studies. Both reports had small
 numbers of cases. The assignment was by random allocation. Inclusion and exclusion criteria were well defined. Both studies
 showed that amnioinfusion during labor complicated by meconium was a safe and effective procedure. They showed that
 amnioinfusion led to significant decrease in the incidence of meconium below the cords and decreased meconium aspiration
 syndrome. Ilagan’s study, which is available only in abstract form, also has small numbers (38 subjects in each group).
 Amnioinfusion in this study reduced the rate of cesarean sections, and the incidence of assisted delivery, improved cord pH and
 decreased meconium below the cords. The meta-analysis by Pierce et al showed that intrapartum amnioinfusion significantly
 reduced the frequency of meconium aspiration syndrome (OR .30, 95% CI .91 --.46) of meconium below the cords and neonatal
 acidemia. They also showed significantly lower overall cesarean section rate (OR .74, CI .59-.93). They concluded that
 amnioinfusion was beneficial in preventing MAS. Hofmeyr in a meta analysis reported in Cochrane data system review concluded
 that amnio infusion was associated with a decrease in MAS other . In addition, we found reports, not included in the previous meta-
 analyses which support AI in MSAF: Uhing 1993; De Meeus 1997; Alvarez 1999, Zhao 2000, Puertas 2001 and Rathorea 2002.
 More recently (2004) Sood and Shah also reported beneficial effect of amnioinfusionin reducing MAS. In a survey by Wenstrom
 (1995) regarding the used protocol and complications of amnioinfusion, it was found that amnioinfusion performed nationwide
 using widely different protocols. Neither the method used, number of infusions performed appeared to increase the risk, many felt
 amnioinfusion was efficient. Interestingly Moen, (1996) reported that the amnioinfusion during labour significantly decreased the
 incidence of postpartum in emitiritis.
 Neutral
 There were 9 reports in this category. Some of them present supporting evidence but are not sufficiently strong on their own merit.
 For example, Adams’ report has very small numbers, (17 study vs 18 control). The De Meeus study was a retrospective study
 including historical controls. In this study amnioinfusion reduced c-section weight in infants with thick meconium. However no
 difference in meconium below the cord was found. Thus the findings of the study was nonconclusive. The report by Hofmeyr et al
 (CRAMP 1 study), was a well-designed, prospective, randomized clinical trial from South Africa. In spite of a good number of
 cases, the study did not show a significant reduction in cesarean section rates or meconium aspiration syndrome. However, when
 they pooled their data with the Zimbabwe (Cramp 2) study as well as all previous studies, they demonstrated a significant effect of
 amnioinfusion on cesarean section rate and meconium aspiration syndrome. Therefore, we identified this report as neutral. The
 report by Khosla was not a prospective randomized study. This study consisted of 25 patients who received amnioinfusion who
 were compared with 25 consecutive control subjects. In this study the incidence of cesarean section rate decreased in the

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 amnioinfusion group but neonatal parameters showed no significant difference, thus only weakly supporting the hypothesis. The
 study by Moodley also had small numbers of participants (30 in each group). In their conclusion the authors state that the decreased
 incidence of cesarean sections in the study was not statistically different. The fetal and neonatal outcomes were better in the
 amnioinfusion group but they were also not statistically significant. Nageotte et al, studied amnioinfusion in pregnancies
 complicated by oligohydraminios, they found no significance difference in neonatal outcome. There was no difference in incidence
 of meconium on gastriclavat or below cords. The study of Lo showed that amnioinfusion had decreased incidence of meconium
 below the cord, but the numbers were small (N=60) and (control=52). Roger showed that meconium aspiration in AI group was
 half data control, but it did not reach statistical significance. Further this was a retrospective study. In another study Usta, reviewed
 pregnancies complicated by moderate or thick meconium stained amniotic fluid. They also found no differences in MAS or
 meconium below cord. However, they also found higher incidence of endometritis. The above studies collectively show no
 significant of benefit of amnioinfusion, but read the concern about potential complications.
 Opposing
 There were 3 papers giving an opposing view to the hyposis. Among these the opposing paper by Spong warrants critical appraisal.
 The study was a prospective randomized controlled clinical trial. However, there was a major difference from other prospective
 randomized controlled trials. The investigators argued that the presence of meconium in the amniotic fluid in and of itself does not
 lead to aspiration. They hypothesized that meconium aspiration would occur only if there was the concomitant presence of fetal
 distress. The authors randomized 43 infants into an amnioinfusion group and 50 into a control group. However, eight patients from
 the control group received amnioinfusion when they developed signs of fetal distress. These infants were maintained in the control
 group for the analysis. In the final analysis, the authors found no overall difference in the incidence of fetal distress, operative
 deliveries, or cesarean section rates between the two groups. There were no significant differences in perinatal outcome between the
 groups. Meconium below the cords was seen in 7% of amnioinfusion versus 4% of controls. The authors surmise that it is possible
 that the amnioinfusion group is at an increased risk for meconium aspiration. They suggested that the benefit of amnioinfusion was
 more due to alleviation of fetal heart rate decelerations than due to dilution of meconium. They suggested that amnioinfusion was
 not indicated in all meconium-stained amniotic fluid cases in the absence of fetal distress. It should be noted that this is the only
 paper that takes an opposing view of amnioinfusion to prevent MAS. Mahar, presented 2 cases of amniotic fluid embolism
 following saline amniotic infusion during labour. Both had thick meconium in amniotic fluid. Thus indicating a potential
 complication of amnioinfusion. The case of the report of Adair also reported complication of uterine rupture undergoing
 amnioinfusion during trial of labour.


Preliminary draft/outline/bullet points of Guidelines revision: Include points you think are important for inclusion by the person assigned to
write this section. Use extra pages if necessary.

 Publication:        _    Chapter:             Pages:

 Topic and subheading: Prophylactic amnioinfusion for meconium-stained amniotic fluid.
          Indications for amnioinfusion
          Contraindications for amnioinfusion
          Risks of amnioinfusion

 The purpose of this worksheet was to develop evidence based guideline recommendation regarding the use of amnioinfusion to
 decrease the incidence of meconium aspiration syndrome. The existing guideline states that “In the presence of meconium stained
 amniotic fluid, amnioinfusion may be carried out, dilute the meconium in an effort to prevent MAS”.

 In view of increasing interest in prevention of MAS, we were asked to review the literature that would warrant to change the
 guidelines to “In the presence of meconium stained amniotic fluid amnioinfusion should be carried out to decrease the incidence of
 MAS”.

 Indeed the task has been challenging. Although there were large number of citations in relations to Meconium and Meconium
 Aspiration. Only 80 reports addressed the issue of meconium and amnioinfusion. Of these only 35 publications were pertinent to
 the question under study..

 Of these although 2/3rd reports(23/35) were in favor of amnioinfusion, only 17 or 50% of all reports presented strong evidence in
 favor of AI to reduce MAS. Other six were weak on the basis of small number of cases. There were 3 meta analyses conducted at
 different times (1994 Dye, 2000 Pierce and 2002 Hofmeyr) included in these reports. Each meta analysis concluded that AI was
 effective in reducing the incidence of meconium below the cord but not necessarily MAS per se, since the incidence of MAS was
 low. Thus there is difficulty in assessing the benefit of AI in reducing MAS.



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 There are other variables to be considered. Not all studies were intended to study the effect of AI on MAS. Some studies were
 aimed at improving oligohydramios and others were to decrease fetal heart decelaration. MAS or meconium below the cord was a
 secondary finding in all the reports reviewed.

 While the supporting evidence was found in 2/3 rd of the reports only 50% had showed level I and II evidence.

 Among the opposing or neutral reports two papers are very strong level I (Spong ,1994 and Hofmeyr,1998). Nine others were “fair”
 varying from level 2 to 5. It is also interesting to note that studies coming from developing countries where fetal monitoring has not
 yet reached high degree of sophistication, AI was shown to decrease MAS (Khosla 1997 Mohamed 1998 , Rathorea 2002, , Sood
 2004, Shah 2004).
 Wenstrom’s survey in USA in 1997 also suggested that AI was beneficial in reducing MAS. However there many variations in the
 protocols used among the institutions across the country.

 Overall the evidence suggests that AI is relatively safe and clinically useful but has intermediate evidence in its effectiveness
 to reduce MAS. Therefore the recommendation of level IIb is given.

 Because of many variables involved in the AI studies, there is a need for prospective controlled studies to delineate multiple
 confenders such as oligohydramios, fetal deceleration, fetal distress, previous C/S, effect of labor, etc.

 INDICATIONS FOR AI : Oligohydramios, fetal deceleration, thick meconium in the amniotic fluid.

 CONTAINDICATIONS : Active labor, previous C-section, infection.

 RISKS OF AI: Amniotic fluid embolism, endometrites,uterine rupture.




Attachments:
       Printed (paper) bibliography; and on diskette using a reference manager. It is recommended that the bibliography be printed in annotated
        format. This will include the article abstract and any notes you would like to make providing specific comments on the quality,
        methodology and/or conclusions of the study.
       Key figures or tables from evidence-based analysis
       Full hard copies of most critical cited papers




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                                                                 Citation List
         Citation Marker                                                             Full Citation*

SUPPORTING:
{Sadovsky, 1989 #1}                         Sadovsky Y, Amon E, Bade ME, Petrie RH. Prophylactic amnioinfusion during labor complicated by
                                            meconium: a preliminary report. Am J Obstet Gynecol 1989;61:613-617.
                                            Wenstrom KD, Parsons MT. The prevention of meconium aspiration in labor using amnioinfusion.
{Wenstrom, 1989 #2}                         Obstet Gynecol 1989;73:647-651.
                                            Wu B, Sun L, Tang L. Intrapartum amnioinfusion for replacement of meconium-stained amniotic fluid to
{Wu, 1991 #3}                               prevent meconium aspiration syndrome. Chinese Medical Journal 1991;104(3):221-224.

{Ilagan NB, 1992 #21}                       Ilagan NB, Kazzi GM, Shankaran S, Liang KC, Womack SJ, Bronsteen RA, Quigg MH. Transcervical
                                            amnioinfusion for the prevention of neonatal meconium aspiration. Pediatr Res 1992;31(4):205A.

                                            Macri CJ, Schrimmer DB, Leung A, Greenspoon JS, Paul RH. Prophylactic amnioinfusion improves
{Macri, 1992 #4}                            outcome of pregnancy complicated by thick meconium and oligohydramnios. Am J Obstet Gynecol
                                            1992;67:117-121.
                                            Uhing MR, Bhat R, Philobos M, Raju TN. Value of amnioinfusion in reducing meconium aspiration
{Uhing, 1993 #6}                            syndrome. Am J Perinatol 1993;10(1):43-45.
{Cialone, 1994 #7}                          Cialone PR, Sherer DM, Ryan RM, Sinkin RA, Abramowicz JS. Amnioinfusion during labor
                                            complicated by particulate meconium-stained amniotic fluid decreases neonatal morbidity. Am J Obstet
                                            Gynecol 1994; 170:842-849.
                                            Dye T, Aubry R, Gross S, Artal R. Amnioinfusion and the intrauterine prevention of meconium
{Dye, 1994 #8}                              aspiration. Am J Obstet Gynecol 1994;171(6):1601-1605.
{Eriksen, 1994 #9}                          Eriksen N, Hostetter M, Parisi V. Prophylactic amnioinfusion in pregnancies complicated by thick
                                            meconium. Am J Obstet Gynecol 1994;170:344.
                                            Hourdequin P, Kauffmann E, Gabriel R, Jotterand AD, Chatelet-Cheront C, Quereux C, Delcroix M.
(Hourdequin et al., 1994)                   Amnio-infusion during labor: experience and review of the literature Obstet Gynecol. 1994 May;83(5 Pt
                                            2):851-4.

(Wenstrom, Andrews, Maher                  Wenstrom K, Andrews WW, Maher JE. Amnioinfusion survey: prevalence, protocols, and
1995)                                       complications. Obstet Gynecol 1995 86: 572-6.

(Moen, Besinger, Tomich,Fisher,             Moen MD, Besinger RE, Tomich PG, Fisher SG. Effect of amnioinfusion on the incidence of postpartum
1996).                                      endometritis in patients undergoing cesarean delivery.
                                            Aust N Z J Obstet Gynaecol. 1996 Nov;36(4):407-10.



                                            Mahomed K, Mulambo T, Woelk G, Hofmeyr GJ, Gulmezoglu AM. The Collaborative Randomised
{Mahomed, 1998 #14}
                                            Amnioinfusion for Meconium Project (CRAMP): 2. Zimbabwe. Br J Obstet Gynaecol 1998;105:309-313.
                                            Alvarez M, Puertas A, Suarez AM, Herruzo A, Miranda JA. Transcervical amnioinfusion in deliveries
{Alvarez M, 1999 #22}                       with meconium-stained amniotic fluid. Amnioinfusion transcervical en partos con liquido amniotico
                                            tenido de meconio, Prog Obstet Ginecol 1999;42:365-372.

                                            Pierce J, Gaudier FL, Sanchez-Ramos L. Intrapartum amnioinfusion for meconium-stained fluid: meta-
{Pierce, 2000 #16}                          analysis of prospective clinical trials. Obstet Gynecol 2000 Jun;95(6 Pt 2):1051-1056.


{Zhao, 2000 #17}                            [Zhao S, Ai L, Zhang H. Significance of amnioinfusion and amniotic fluid exchange under continuous
                                            internal fetal heart rate monitoring for management of fetal distress during labor.] Zhonghua Fu Chan Ke
                                            Za Zhi 2000;35(1):20-22.


{Puertas, 2001 #18}                         Puertas A, Carillo MP, Molto L, Alvarez M, Sedeno S, Miranda JA. Meconium-stained amniotic fluid in
                                            labor: a randomized trial of prophylactic amnioinfusion. Eur J Obstet Gynecol Reprod Biol 200
                                            Glantz JC, Letteney DL. Pumps and warmers during amnioinfusion: is either necessary? Eur J Obstet


                                                                       15- 15
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(Glantz, Letteney, 2002)                   Gynecol Reprod Biol. 2002 Sep 10;104(2):105- 1;99:3337.

                                           Rathorea AM, Singh R, Ramji S, Tripathi R. Randomised trial of amnioinfusion during labour with
{Rathorea, 2002 #19}                       meconium stained amniotic fluid. BJOG 2002 Jan;109(1):17-20.

                                       Hofmeyr, GJ (2002) Amnioinfusion for meconium-stained liquor in labor. Cochrane Database Sys
(Hofmeyr, 2002 )                    Rev(1):CD000014.


(Halvax , Szabo , Vizer ,           Halvax L, Szabo I, Vizer M, Csermely T, Ertl T. Simultaneous use of intrapartum fetal pulse oximetry and
Csermely , Ertl 2002)               amnioinfusion in meconium stained amniotic fluid. Eur J Obstet Gynecol Reprod Biol 2002 104(2):105-8.



                                    Shah AA. Effect of amnioinfusion for meconium stained amniotic fluid on perinatal outcome.
( Shah 2004).                       J Pak Med Assoc. 2004 Jun;54(6):322-5.

                                    S
Sood , Dimple , Aggarwal , Faridi   ood MC, Dimple D, Aggarwal N, Faridi MM. Amnioinfusion in thick meconium . Indian J Pediatr 2004;
2004.                               71:677-681.




NEUTRAL:
                                           Adam K, Cano L, Moise KJ. The effect of intrapartum amnioinfusion on the outcome of the fetus with
                                           heavy meconium stained amniotic fluid. Proceedings of 9th Annual Meeting of the Society of Perinatal
{Adam K, 1989 #20}                         Obstetricians, New Orleans, Louisiana, USA 1989; 438.
(Nageotte, Bertucci et al., 1991)          Nageotte MP, Bertucci L, Towers CV, Lagrew DL, Modanlou H.Prophylactic amnioinfusion in
                                           pregnancies complicated by oligohydramnios: a prospective study. Obstet Gynecol. 1991 May; 77(5):
                                           677-80.
                                           Lo KWK & Rogers M. A controlled trial of amnioinfusion: the prevention of meconium aspiration in
{Lo, 1993 #5}
                                           labour. Aust NZ J Obstet Gynaecol 1993;33(1):51-54.


                                           Rogers MS, Lau TK, Wang CC, Yu KM. Amnioinfusion for the prevention of meconium aspiration
(Rogers et al., 1995)                      during labour. Obstet Gynecol. 1995 Aug;86(2):230-4.


                                           Usta IM, Mercer BM, Sibai BM. Risk factors for meconium aspiration syndrome. Gynecol 1995 85(2)
                                            237-241
(Usta et al., 1995)

                                           De Meeus JB, D’Halluin G, Bascou V, Ellia F, Magnin G. Prophylactic intrapartum amnioinfusion: a
{De Meeus, 1997 #11}                       controlled retrospective study of 135 cases. J Gynecol Obstet Biol Reprod 1997;26(6):610-616.


                                           Khosla AH, Sangwan K, Ahuja SD. Prophylactic amnioinfusion during labour complicated by
                                           meconium. Aust NZ J Obstet Gynaecol 1997;37(3):294296.
{Khosla, 1997 #12}



                                           Hofmeyr GJ, Gulmezoglu AM, Buchmann E, Howarth GR, Shaw A, Nikodem VC, Cronje H, de Jager
{Hofmeyr, 1998 #13}                        M, Mahomed K. The Collaborative Randomised Amnioinfusion for Meconium Project (CRAMP): 1.
                                           South Africa. Br J Obstet Gynaecol 1998;105:304-308.


                                           Moodley J, Matchaba P, Payne AJ. Intrapartum amnioinfusion for meconium-stained liquor in
                                           developing countries. Tropical Doctor 1998;28:31-34.
{Moodley, 1998 #15}




                                                                     15- 16
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OPPOSING:
                                           Spong CY, Ogundipe OA, Ross MG. Prophylactic amnioinfusion for meconium stained amniotic fluid.
                                           Am J Obstet Gynecol 1994;170:285.
{Spong, 1994 #10}

                                           Adair CD, Sanchez-Ramos L, Kaunitz AM, Briones D. A trial of labor complicated by uterine rupture
                                           following amnioinfusion. South Med J. 1995 Aug;88(8):847-8.
(Adair, Sanchez-Ramos , Kaunitz
Briones 1995).

                                           Maher JE, Wenstrom KD, Hauth JC, Meis PJ. Amniotic fluid embolism after saline amnioinfusion: two
                                           cases and review of the literature. J Reprod Med. 1995 May;40(5):383-6.

 (Maher JE, Wenstrom KD, Hauth
JC, Meis PJ.1995)




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ABSTRACTS (By Year of Publication):

SUPPORTING EVIDENCE:

Sadovsky Y, Amon E, Bade ME, Petrie RH. Prophylactic amnioinfusion during labor complicated by meconium: a
preliminary report. Am J Obstet Gynecol 1989;61:613-617.
     Objective: To evaluate the safety and efficacy of prophylactic amnioinfusion in the management of labor
     complicated by meconium. Methods: Random allocation with sealed envelopes. Inclusion criteria: Patients in
     labor with more than trace meconium on membrane rupture. Additional inclusion criteria: Singleton
     pregnancy, vertex presentation, ≥34 weeks’ gestation, anticipate time to delivery >1 hour. Exclusion criteria:
     Fetal malpresentation, multiple gestation, fetal malformation, polyhydramnios, chorioamnionitis, cord prolapse,
     any situation that necessitated urgent intervention, and maternal heart disease. Intervention: Study subjects
     (n=19) received amnioinfusion with normal saline warmed to 37C, 600 ml during the first hour, then 180
     ml/hr. The infusion was topped before delivery. Comparison was made with a control group (n=21). Outcome:
     Significantly lower rate of neonatal acidemia (pH <7.20 in 16% amnioinfusion vs 38% control and base deficit
     >10 mmol/L in 5% amnioinfusion vs 10% control); decreased incidence of more than trace amount of
     meconium below the vocal cords (amnioinfusion 0% vs control 29%); decreased need for positive pressure
     ventilation (amnioinfusion 16% vs control 48%). Conclusion: Amnioinfusion during labor complicated by
     meconium is a simple and apparently safe procedure, and effectively decreases the frequency of thick
     meconium, the frequency of neonatal acidemia, the frequency of more than trace meconium below the vocal
     cords, and the need for positive pressure ventilation. Comments: No study or control neonates developed


                                                                    15- 17
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     meconium aspiration syndrome. Numbers are too small to allow for adequate analysis. Final Assignment
     Level 2, good, support.

Wenstrom KD, Parsons MT. The prevention of meconium aspiration in labor using amnioinfusion. Obstet Gynecol
1989;73:647-651.
     Objective: To evaluate the efficacy of amnioinfusion in improving outcome and decreasing the incidence of
     meconium below the cords, and therefore meconium aspiration syndrome, in infants born to patients laboring
     with thick meconium. Methods: Computer-generated, randomized treatment assignment sequence. Inclusion
     criteria: “Pea soup,” thick, particulate meconium. Exclusion criteria: Initial temperature >100.4F, signs of
     chorioamnionitis, any indications of fetal distress (fetal tachycardia, bradycardia, late decelerations, or severe
     variable decelerations), initial fetal scalp pH <7.20. Intervention: Study subjects (n=36; initially 41 but 5
     patients did not receive infusion for various reasons) received amnioinfusion with 1000 ml normal saline over
     20-40 minutes initially, and repeated every 6 hours until delivery. Study subjects compared with control group
     (n=44). Outcome: Significantly fewer 1 minute Apgar scores <7 (amnioinfusion 11/36 vs control 23/44);
     significantly lower incidence of operative delivery (amnioinfusion 6/36 vs control 15/44); less meconium
     below the cords (amnioinfusion 2/36 vs control 16/44); decreased incidence of meconium aspiration syndrome
     (amnioinfusion 0/36 vs control 3/44). Conclusion: Amnioinfusion is a simple, inexpensive, and safe technique
     that reduces the incidence of meconium below the cords and improves obstetric outcome in patients laboring
     with thick meconium. Comments: AI group had fewer low one-minute Apgar scores, less meconium below the
     vocal cords, lower operative delivery rate. Neonatologists were blinded. Final Assignment: Level 1, good,
     support.

Wu B, Sun L, Tang L. Intrapartum amnioinfusion for replacement of meconium-stained amniotic fluid to prevent
meconium aspiration syndrome. Chinese Medical Journal 1991;104(3):221-224.
     Methods: Retrospective study. Inclusion criteria: MSAF in term patients in cephalic presentation. Exclusion
     criteria: Other signs of fetal distress or indication for cesarean section. Intervention: Study subjects (n=73)
     received IAR (intrapartum amnioinfusion for replacement) with warmed normal saline at rate of 15-20 ml/min.
     After infusion of 1st 500 ml of saline, MSAF equal to ½ of infused volume let out, then another 500 cc infused
     and MSAF evacuated again until color of fluid nearly clear. Compared with control group (n=104) who
     received routine care. Outcome: Meconium became clear in 72/73 cases. Incidence of neonatal asphyxia in
     cases with heavy MSAF much lower in IAR group (P<0.005); decreased incidence of MAS (amnioinfusion
     1/73 vs control 10/104); cesarean section rate lower in IAR, especially for fetal distress (P<0.05). Final
     Assignment: Level 4, fair, support.

Ilagan NB, Kazzi GM, Shankaran S, Liang KC, Womack SJ, Bronsteen RA, Quigg MH. Transcervical amnioinfusion for
the prevention of neonatal meconium aspiration. Pediatr Res 1992;31(4):205A.

     Methods: Random allocation. Inclusion criteria: Patients in active labor with thick, tenacious, pea-soup,
     opaque meconium. Exclusion criteria: Malpresentation; multiple gestation; chorioamnionitis. Intervention:
     Study subjects received amnioinfusion with 500 ml normal saline (n=38) and compared with control group
     (n=40). Outcome: Increased spontaneous vaginal delivery (amnioinfusion 30/38 vs control 14/40);
     significantly decreased cesarean section rate (amnioinfusion 6/38 vs control 19/40); decreased assisted delivery
     (amnioinfusion 2/38 vs control 7/40); increased cord pH (amnioinfusion 7.31  0.04 vs control 7.27  0.06);
     lower incidence 1” Apgar score ≤6 (amnioinfusion 6/38 vs control 13/40); decreased meconium below cords
     (amnioinfusion 6/38 vs control 20/40). Conclusion: Amnioinfusion decreases the incidence of meconium
     below the vocal cords, decreases the frequency of neonatal acidemia and decreases the rate of cesarean section.
     Final Assignment: Level 2, good, support.

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;67:117-121.
     Objective: The use of amnioinfusion in labors with the presence of thick meconium and oligohydramnios will
     not decrease the incidence of fetal distress, cesarean delivery, meconium aspiration or meconium aspiration

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     syndrome. Methods: Random allocation by computer; sealed envelopes. Inclusion criteria: Singleton
     pregnancy, vertex presentation, ≥37 weeks’ gestation, estimated fetal weight ≥2500 gm, cervical dilation of
     ≤5 cm, normal baseline fetal heart rate (FHR), the presence of at least one acceleration of ≥15 seconds
     duration and ≥15 beats above baseline, artificially or spontaneously ruptured membranes, thick meconium,
     amniotic fluid index ≤5 cm. Exclusion criteria: Abnormal FHR patterns including baseline tachycardia >160
     bpm or bradycardia <120 bpm, persistent late decelerations, moderate or severe variable decelerations, vaginal
     bleeding, non-vertex presentation, chorioamnionitis, fetal anomalies, uterine anomalies, contraindication to
     labor. Intervention: Study subjects received amnioinfusion with 500 ml normal saline warmed to 37C infused
     by gravity flow over 20-30 minutes (n=85). If post-infusion AFI <5 cm, additional 500 ml infused. If
     subsequent AFI >5 cm and <10 cm, additional 250 ml infused. Study subjects were compared with control
     group (n=85). Outcome: Significant reduction in rate of fetal distress (amnioinfusion 3/85 vs control 19/85);
     significant reduction in rate of cesarean section for fetal distress (amnioinfusion 2/85 vs control 17/85);
     decreased incidence of meconium aspiration (amnioinfusion 4/85 vs control 33/85) and meconium aspiration
     syndrome (amnioinfusion 0/85 vs control 5/85). Conclusion: Prophylactic amnioinfusion was associated with
     decreased incidence of fetal distress, decreased presence of meconium below the vocal cords, and an absence of
     meconium aspiration syndrome. Final Assignment: Level 1, good, support.

Uhing MR, Bhat R, Philobos M, Raju TN. Value of amnioinfusion in reducing meconium aspiration syndrome. Am J
Perinatol 1993;10(1):43-45.
     Methods: Retrospective review of 436 pregnancies complicated by thick, meconium-stained amniotic fluid.
     Intervention: Of 436 patients, 110 received amnioinfusion. Outcome: Decreased incidence of meconium in
     trachea (amnioinfusion 18.2% vs untreated 29.1%); decreased incidence of respiratory distress (amnioinfusion
     2.7% vs 10.1%); decreased incidence of MAS (amnioinfusion 1.8% vs untreated 5.5%). Final Assignment:
     Level 4, good, support.

Cialone PR, Sherer DM, Ryan RM, Sinkin RA, Abramowicz JS. Amnioinfusion during labor complicated by particulate
meconium-stained amniotic fluid decreases neonatal morbidity. Am J Obstet Gynecol 1994; 170:842-849.
     Objective: To evaluate the efficacy of prophylactic amnioinfusion in decreasing neonatal morbidity associated
     with labor complicated by particulate meconium-stained amniotic fluid and to assess potential complications of
     the procedure. Methods: Random allocation by computer-generated, randomized treatment assignment.
     Sample size was determined assuming a 33% incidence of meconium below the vocal cords on the basis of
     control populations in previous studies. Expected reduction to 17%. To achieve an error of 0.1, 90 patients
     were required. Inclusion criteria: Laboring term and post-term with uncomplicated antenatal course; singleton,
     vertex presentation at >36 weeks’; moderate or thick meconium-stained amniotic fluid. Exclusion criteria: any
     obstetric risk factor other than meconium staining. Intervention: Study subjects (n=47) received
     amnioinfusion with normal saline at room temperature at rate of 600 ml over 1 hour, followed by infusion of
     150 ml/hr, until fully dilated, compared with control group (n=58). Outcome: Significant decrease in incidence
     of meconium below the vocal cords (amnioinfusion 2/47 vs control 36/58); significantly increased umbilical
     arterial pH (amnioinfusion 7.29  0.01 vs control 7.25  0.009); decreased meconium concentration between
     rupture of membranes and delivery (amnioinfusion 46/46 vs control 15/58); decreased incidence of repetitive
     moderate and severe variable decelerations during labor; reduced incidence of meconium aspiration syndrome
     (amnioinfusion 1/47 vs control 8/58). Conclusion: Amnioinfusion may prevent the development or reduce the
     severity of meconium aspiration syndrome in some susceptible neonates and should be considered as an
     addition to the intrapartum management of patients with particulate meconium-stained amniotic fluid.
     Comments: Neonatal team was blinded. All infants underwent aggressive obstetric/pediatric management
     including endotracheal suction at the time of delivery. Study was unique in that it was specifically designed to
     include only those subjects who had a single obstetric risk factor (i.e. thick meconium). “Meconiumcrit” was
     performed as described by Trimmer and Gilstrap and weight percent of solid component of meconium was
     determined on all samples. This paper is one of the only to demonstrate the serial change in the consistency of
     meconium in the amniotic fluid throughout labor and delivery. This study also shows that even in the absence
     of obstetrical risk factors, the presence of variable decelerations was higher in the control group (9.1% in AI)
     and 60% in control group ( p<0.001), suggesting that meconium staining alone is not detrimental to the infant

                                                         15- 19
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     unless there is fetal distress. These findings seem similar to SPONG (1994). Significant differences were found
     in meconium below the cords (2/47 vs. 36/58 p<.001), umbilical pH (7.29+ .01 vs 7.25+ .009 p<.05), MAS
     1/47 vs 8/58 p<.05). Conclusion: Amnioinfusion should be considered in addition to intrapartum management
     of patients with particulate material. Final Assignment: Level 1, excellent support.

Dye T, Aubry R, Gross S, Artal R. Amnioinfusion and the intrauterine prevention of meconium aspiration. Am J Obstet
Gynecol 1994;171(6):1601-1605.
     Objective of study: Evaluated the published literature on the effectiveness of amnioinfusion in decreasing the
     incidence of meconium below the vocal cords and MAS among women with more than trace meconium-
     stained amniotic fluid. Methods: Literature search conducted to evaluate clinical trials of amnioinfusion in
     preventing MAS. 5 trials were found that met certain basic design criteria, i.e. prospective study design.
     Inclusion criteria: Meconium-stained amniotic fluid. Intervention: Study subjects received amnioinfusion
     (n=247) and compared with controls (n=260). Outcome: Patients who received AI were less likely to have
     meconium below the vocal cords and less likely to have MAS than were infants without AI. Conclusion:
     Amnioinfusion is effective intervention for prevention of MAS. Final Assignment: Level 1, excellent,
     support.

Eriksen N, Hostetter M, Parisi V. Prophylactic amnioinfusion in pregnancies complicated by thick meconium.
Am J Obstet Gynecol 1994;170:344.

         Objective of study: Prophylactic Intrapartum amnioinfusion in pregnancies complicated by thick
         meconium will not decrease the incidence of fetal distress, cesarean section for fetal distress, or
         meconium below the vocal cords. Methods: Computer randomization with use of sealed envelopes.
         Inclusion criteria: Patients in active labor at >36 weeks’ gestation with thick meconium-stained
         amniotic fluid. Exclusion criteria: Malpresentation; multiple gestation; cervical dilatation ≥7 cm; fetal
         distress on admission; chorioamnionitis. Intervention: Study subjects received amnioinfusion with 800
         ml normal saline at room temperature over 1 hour, followed by infusion of 180 ml/hr (n=65) and
         compared with control group (n=59). Outcome: Decreased incidence of meconium below the vocal
         cords (amnioinfusion 1/65 vs control 8/59); 2 cases of meconium aspiration syndrome occurred in
         control patients but none receiving amnioinfusion. No significant difference in incidence of fetal
         distress (amnioinfusion 16/65 vs control 8/59) or cesarean section for fetal distress (amnioinfusion 7/65
         vs control 7/59). Conclusion: Prophylactic amnioinfusion in patients with thick meconium decreases
         the incidence of meconium below the vocal cords and may have a subsequent impact on diminishing
         the incidence of meconium aspiration syndrome if a larger study were undertaken. Final Assignment:
         Level 1, good, support.


         Hourdequin P, Kauffmann E, Gabriel R, Jotterand AD, Chatelet-Cheront C, Quereux C, Delcroix M.
         Amnio-infusion during labor: experience and review of the literature Obstet Gynecol. 1994 May;83(5
         Pt 2):851-4

                 OBJECTIVES: Evaluation of amnioinfusion results during labour in case of thick meconium
         amniotic fluid or in case of oligo-hydramnios associated with variable deceleration of the fetal heart
         response. PATIENTS AND METHODS: Prospective non randomized study. Amnioinfusion was
         applied to 47 cases of thick meconial amniotic fluid and to 18 cases of variable fetal heart decelerations
         associated with oligo-hydramnios. Obstetrical and neonatal data were compared with a similar group
         without amnioinfusion (n = 32). RESULTS: Comparing both groups shows that amnioinfusion offers a
         better fetal well-being during labour, according to Kreb's fetal heart evaluation during labour (8.53 +/-
         1.06 vs 6.56 +/- 0.35--p < 0.01), lows the cesarean section rate (8.5% vs 31.2%--p < 0.01).


                                                         15- 20
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         Amnioinfusion is also associated with a higher Apgar's score at one minute after delivery (9.4 +/- 0.8 vs
         8.7 +/- 1.7--p = 0.01) and a lower rate of thick meconium inhalation (13.7% vs 40.7%--p < 0.01). There
         was no difference for children's first days of life. We found no serious complication following
         amnioinfusion. CONCLUSION: We confirm general agreement about amnioinfusion, according to
         international literature. Amnioinfusion needs an acute care to prevent classically described
         complications. In case of thick meconial amniotic fluid or variable decelerations associated with oligo-
         hydramnios, amnioinfusion during labour offers a better fetal well-being.Comments: This non
         randomized study consisted of small number of cases of AI in two different groups, one with meconium
         stained amniotic fluid and other with oligohydronious. Level 5, fair, supportive



         Wenstrom K, Andrews WW, Maher JE. Amnioinfusion survey: prevalence, protocols, and
         complications. Obstet Gynecol 1995 86: 572-6.

         OBJECTIVE: To determine whether amnioinfusion is associated with labor and delivery
         complications, and whether complication type and reported incidence are related to infusion method.
         METHODS: Questionnaires regarding amnioinfusion experience were sent to every academic
         obstetrics and gynecology department in the United States (78 maternal-fetal medicine fellowship
         directors or, if the department did not have a fellowship, 206 residency directors). A literature review
         on amnioinfusion was also performed. RESULTS: Seventy-six percent of fellowship directors and
         62% of residency directors responded to our survey, representing 644,910 deliveries per year and at
         least 22,833 amnionfusions per year. A wide variety of infusion protocols were reported. Forty-nine
         centers reported at least one associated complication; none was significantly associated with any of the
         various aspects of the many protocols (P > .05). The mean number (+/- standard error of the mean) of
         amnioinfusions performed annually was similar between centers that did (261 +/- 48) and did not (154
         +/- 29) report complications (P = .06). The literature review suggested that amnioinfusion is efficacious
         and relatively safe. CONCLUSION: Amnioinfusion is performed nationwide according to widely
         varying protocols with few associated complications. Neither the method employed nor the number of
         infusions performed appears to significantly increase the risk of having a complication.Comments:
         Level 5, good, support.



Moen MD, Besinger RE, Tomich PG, Fisher SG. Effect of amnioinfusion on the incidence of postpartum
endometritis in patients undergoing cesarean delivery.
Aust N Z J Obstet Gynaecol. 1996 Nov;36(4):407-10.

         We reviewed records from 251 consecutive cesarean deliveries performed over a six-month period to
         evaluate the effect of amnioinfusion during labor on the incidence of postpartum endometritis in
         patients who delivered by cesarean section. One hundred fifty-four patients were excluded because they
         were not in labor, were at less than 35 weeks' gestation or received antibiotics during labor. Twenty-
         three of the remaining 97 patients received amnioinfusion during labor and represented the study group.
         Seventy-four patients did not receive amnioinfusion during labor and were used as controls. The
         incidence of postpartum endometritis in the amnioinfusion group was 13%, while the incidence in the
         group not receiving amnioinfusion was 38% (relative risk, 0.34; 95% confidence interval, 0.13-0.88; P
         = .026). Amnioinfusion during labor appears to significantly decrease the incidence of postpartum
         endometritis in patients subsequently undergoing cesarean delivery


                                                      15- 21
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         Comment: The study was NOT INTENDED TO STUDY THE EFFECT OF AI ON MAS. It mainly
         indicates that amnioinfusion reduced postpartum endometritis Final assignment: Level 4, fair,
         support.

     :




     .

Mahomed K, Mulambo T, Woelk G, Hofmeyr GJ, Gulmezoglu AM. The Collaborative Randomised Amnioinfusion for
Meconium Project (CRAMP): 2. Zimbabwe. Br J Obstet Gynaecol 1998;105:309-313.
     Methods: Random allocation by consecutively-numbered, sealed, opaque envelopes in computer-generated
     random sequence. Inclusion criteria: Patients in labor “during office hours” at ≥37 weeks’ gestation with
     singleton in cephalic presentation and with moderate or heavy meconium staining of amniotic fluid.
     Intervention: Study subjects received amnioinfusion with 500 ml normal saline over 30 min, then 500 ml at 2
     ml/min.(n=325) and compared with control group (n=336). Outcome: Significantly decreased incidence of
     meconium aspiration syndrome (amnioinfusion 10/323 or 3.1% vs control 42/329 or 12.8%); significant
     reductions in several measures of perinatal morbidity including: decreased incidence of 5 min Apgar score <7
     (amnioinfusion 9/324 vs control 27/336); less NICU admissions (amnioinfusion 41/321 vs control 76/332);
     decreased need for neonatal ventilation (amnioinfusion 10/320 vs control 34/332) and decreased incidence of
     hypoxic ischemic encephalopathy (amnioinfusion 1/320 vs control 14/329) in amnioinfusion group.
     Conclusion: The results show striking improvements in perinatal outcome for women randomly allocated to
     receive amnioinfusion for meconium staining of the amniotic fluid. Further, no complications related to
     amnioinfusion were observed. Final Assignment: Level 1, excellent, support.

     .

Alvarez M, Puertas A, Suarez AM, Herruzo A, Miranda JA. Transcervical amnioinfusion in deliveries with meconium-
stained amniotic fluid. Amnioinfusion transcervical en partos con liquido amniotico tenido de meconio, Prog Obstet
Ginecol 1999;42:365-372.
     Methods: Random allocation utilizing number list. Inclusion criteria: active labor; meconium stained
     amniotic fluid. Exclusion criteria: other than cephalic presentation; multiple pregnancy; gestation <37 weeks,
     fetal heart rate abnormality; fetal anomaly incompatible with life; cord prolapse; placental abruption, placenta
     previa; transmissible infection; uterine scar. Intervention: amnioinfusion 600 ml of normal saline at 37C
     infused over one hour, followed by 180 ml per hour (n=40) compared with control group (n=45). Outcomes:
     Reduced cesarean section rate for fetal distress (amnioinfusion 1/40 vs control 8/45); reduced cesarean section
     when meconium concentration >10% (amnioinfusion 5/40 vs control 15/45); decreased incidence of meconium
     below cord (amnioinfusion 4/40 vs control 14/45); decreased incidence of variable decelerations
     (amnioinfusion 13/40 vs control 32/45). Final Assignment: Level1, good, support.

Pierce J, Gaudier FL, Sanchez-Ramos L. Intrapartum amnioinfusion for meconium-stained fluid: meta-analysis of
prospective clinical trials. Obstet Gynecol 2000 Jun;95(6 Pt 2):1051-1056.
     Methods: Meta-analysis of prospective clinical trials published in English between January 1980 and
     December 1998. Utilized computerized databases, references of published articles, and chapters from
     textbooks. Inclusion criteria: moderate to thick meconium-stained fluid treated during labor according to each
     institution’s protocol. Criteria for selection of studies: prospective trials that evaluated the effect of
     prophylactic amnioinfusion during labor with moderate to thick meconium-stained AF, group allocation
     (amnioinfusion vs controls) based exclusively on meconium-stained AF during labor, not on other indications



                                                         15- 22
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     for amnioinfusion, and clearly documented outcome data. Search yielded 11 published studies and two
     abstracts, for total of 13 studies (8 trials in US; 1 in Hong Kong; 1 in India; 2 in South Africa; 1 in Zimbabwe).
     A total of 1924 women (950 received amnioinfusion during labor and 974 controls). Intervention:
     Amnioinfusion protocols included an initial administration of saline solution, ranging from 500 to 1000 ml,
     infused in 20-60 minutes. This was followed by various maintenance infusion procedures until delivery, or
     when a certain AF index was attained. Outcome: Outcomes examined included meconium below the vocal
     cords immediately after birth, meconium aspiration syndrome, fetal acidemia at birth (umbilical artery pH
     <7.20), cesarean delivery rates and postpartum endometritis. Decreased Incidence of meconium below vocal
     cords at birth (amnioinfusion 27/555 or 4.9% vs control 132/576 or 22.9%). Decreased incidence of meconium
     aspiration syndrome (amnioinfusion 24/950 or 2.5% vs control 83/974 or 8.5%). Decreased incidence of fetal
     acidemia at birth (amnioinfusion 41/348 or 11.8% vs control 90/363 or 24.8%). Decreased cesarean delivery
     rate (amnioinfusion 184/932 or 19.7% vs control 231/951 or 24.3%). Conclusion: In cases of meconium-
     stained amniotic fluid, amnioinfusion significantly improves neonatal outcome and lowers the rate of cesarean
     delivery and does not increase the rate of postpartum endometritis. Comments: Neonatal health care providers
     masked in only 6 of 13 studies. Lack of masking for treatment allocations could potentially influence neonatal
     care providers regarding diagnoses of neonatal outcomes. Specific outcome analyses were based on a variable
     number of studies because not all trials evaluated each variable. Review limited to published clinical trials and
     abstracts. Since studies with no difference in outcomes are less likely to be published, this review may be
     biased toward statistically significant events. However, would need any subjects with negative results to negate
     their findings so unlikely that bias affected the study. Final Assignment: Level 1, excellent, support.

[Zhao S, Ai L, Zhang H. Significance of amnioinfusion and amniotic fluid exchange under continuous internal fetal heart
rate monitoring for management of fetal distress during labor.] Zhonghua Fu Chan Ke Za Zhi 2000;35(1):20-22.
     Objective: To discuss the significance of amnioinfusion and amniotic fluid exchange under continuous internal
     fetal heart rate monitoring for fetal distress. Methods: Prospective controlled. Inclusion criteria: Frequent
     variable deceleration and meconium stained amniotic fluid during labor. Intervention: Study subjects (n=68)
     received amnioinfusion and amniotic fluid exchange. Compared with control group (n=68) who received
     oxygen, change of position and intravenous fluids. Outcome: In study group, variable decelerations
     disappeared or relieved in 62/68 vs control 20/68 (P = 0.01); significantly lowered cesarean section rate
     (amnioinfusion 14.7% vs control 47.1%); significant decrease in neonatal asphyxia (amnioinfusion 7.4% vs
     control 48.5%); decreased incidence of meconium aspiration syndrome. Comments: This paper has a
     disadvantage since it was published in foreign language. The information given in the English abstract is
     inadequate to be definitive but the authors although the final conclusion suggests that amnioinfusion is
     beneficial in the prevention of fetal distress and meconium aspiration. Final Assignment: Level 1, good
     support.

Puertas A, Carillo MP, Molto L, Alvarez M, Sedeno S, Miranda JA. Meconium-stained amniotic fluid in labor: a
randomized trial of prophylactic amnioinfusion. Eur J Obstet Gynecol Reprod Biol 2001;99:33-37.
     Methods: Randomized controlled trial. Randomly assigned to receive amnioinfusion or no amnioinfusion
     according to list of randomly-generated numbers in a sealed envelope assigned to each woman. Even numbers
     received amnioinfusion. Inclusion criteria: ruptured membranes and moderate or thick meconium in the
     amniotic fluid. Other inclusion criteria: uncomplicated pregnancy, term gestation, no uterine scarring,
     cervical dilatation <6 cm, single fetus in vertex presentation, no signs of alteration in fetal heart rate (fetal
     distress), no vaginal bleeding, no indications of vertically transmissible infectious disease. Intervention:
     Amnioinfusion with 0.9% saline at room temperature via an infusion pump set at 600 ml/h during the first hour
     and 180 ml/hr subsequently until full dilatation or until basal uterine pressure increased to 20 mmHg (n = 103)
     compared with control group (n = 103). Outcome: Increased frequency of spontaneous vaginal deliveries
     (amnioinfusion 72/103 vs control 51/103) and reduced cesarean section rate (amnioinfusion 12/103 vs control
     24/103); increased AFI 60 min post-amnioinfusion (amnioinfusion 11.5  3.2 vs control 7.7  3.8); lower
     frequency of neonatal acidosis, i.e. arterial pH <7.20 (amnioinfusion 18/103 vs 31/103); less meconium below
     cords, i.e. “more than a trace” of meconium below cords (amnioinfusion 11/103 vs control 30/103); decreased
     frequency of variable fetal heart rate decelerations (amnioinfusion 54/103 vs control 73/103); lower frequency


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     of late decelerations (amnioinfusion 3/103 vs control 10/103) and late variable decelerations (amnioinfusion
     13/103 vs control 35/103). Comments: Calculated “meconiumcrit” by centrifugation at 2500 rpm for 10 min
     rather than at 1000 rpm used by Trimmer and Gilstrap. May have led to greater compaction of the meconium so
     data are not directly comparable with Timmer and Gilstrap’s classification. Neonatologists but not obstetricians
     blinded to group allocation. Frequency of meconium aspiration syndrome was too low (amnioinfusion 3/103 vs
     control 4/103) to reach significance. Amnioinfusion was stopped due to uterine hypertonia in 17/103 subjects;
     none required intervention and uterine tone spontaneously returned to normal. Final Assignment: Level 1,
     excellent, support.

         Glantz JC, Letteney DL. Pumps and warmers during amnioinfusion: is either necessary? Eur J Obstet
         Gynecol Reprod Biol. 2002 Sep 10;104(2):105-

         OBJECTIVE: To determine if there is evidence from published reports that the use of infusion pumps
         or solution warmers during amnioinfusion is beneficial. DATA SOURCES: We identified all English-
         language amnioinfusion reports published since 1983 through Medline and references. METHODS OF
         STUDY SELECTION: Fourteen prospective papers with at least 40 subjects were identified. DATA
         EXTRACTION AND SYNTHESIS: For the amnioinfusion and control groups in each study, odds
         ratios (OR) were calculated for cesarean delivery, fetal distress, meconium below the cords, low 5-
         minute Apgar score, and endometritis. Cumulative ORs were calculated using the Mantel-Haenszel
         inverse variance method. This process was repeated after separation into pump-gravity and warmed-
         unwarmed groups. Multiple regression analyses were performed. Amnioinfusion improved the ability
         of the fetus to tolerate labor (fetal distress OR 0.40), decreased the incidence of meconium below the
         cords (OR 0.16), and decreased the rate of cesarean delivery (OR 0.56). There were no demonstrable
         benefits associated with the use of warmers or pumps. In multiple regression analysis, infusion pumps
         were associated with a significantly increased risk of fetal distress (P = .01). CONCLUSION: The use
         of amnioinfusion is associated with a decreased risk of fetal distress, meconium below the vocal cords.
         And cesarean delivery. To date there is no demonstrable benefit using the infusion pumps or solution
         warmers during amnioinfusion. Comment: The major thrust of the study was to evaluate the use of
         pumps and warmers during amnioinfusion. The findings regarding the effect of amnioinfusion on
         meconium aspiration was secondary. No meta analysis on the effect of AI on MAS was studied. Meta
         analysis of 8 studies showed reduction in meconium below vocal cords (OR 0.16, 95% CI o.o7- 0.36)
         no effect on 5 min Apgar score < 7, 5 studies (OR 0.55, 95% CI 0.19-1.62) and endometrics (OR 0.457,
         CI 95%CI 22-1.53). Meta-analysis on MAS not done. Level 2, good, support.

Rathorea AM, Singh R, Ramji S, Tripathi R. Randomized trial of amnioinfusion during labour with meconium stained
amniotic fluid. BJOG 2002 Jan;109(1):17-20.
     Objective: To assess the effect of amnioinfusion during labor with meconium stained amniotic fluid on
     cesarean section rate and perinatal outcome. Methods: Computer-generated random number sequence.
     Allocation concealment done using sequentially numbered sealed opaque envelopes. Inclusion criteria:
     Patients in labor at ≥37 weeks’ gestation, singleton fetus with cephalic presentation and moderate or thick
     meconium in amniotic fluid or “meconium of >10%. Exclusion criteria: Chorioamnionitis, indication for
     immediate delivery (cord prolapse, severe fetal bradycardia), fetal congenital anomaly, Antepartum
     hemorrhage, polyhydramnios, maternal cardiac or pulmonary disease. Intervention: Study subjects received
     amnioinfusion with 500 ml normal saline over 30 minutes (n=100) and compared with control group (n=100).
     Outcomes: Decreased cesarean section rate; significant decrease in incidence of meconium at the vocal cords;
     improvement in 1 minute Apgar scores, respiratory distress and fewer admissions to the NICU compared with
     the controls. Conclusion: Amnioinfusion in an under-resourced labor ward decreases cesarean section rates and
     fetal morbidity. Comments: The sample size was inadequate to address the issue of meconium aspiration
     syndrome. Final Assignment: Level 1, excellent, support.



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     Hofmeyr GJ. For meconium-stained liquor in labour. Cochrane Database Syst Rev (1): CD000014. 2002.

         Background: Amnioinfusion aims to prevent or relieve umbilical cord compression during labour by
         infusing a solution into the uterine cavity. It is also thought to dilute meconium when present in the
         amniotic fluid and so reduce the risk of meconium aspiration. However, it may be that the mechanism
         of effect is that it corrects oligohydramnios (reduced amniotic fluid), for which thick meconium
         staining is a marker. Objectives: The objective of this review was to assess the effects of
         amnioinfusion for meconium-stained liquor on perinatal outcome. Search strategy: The Cochrane
         Pregnancy and Childbirth Group trials register (October 2001) and the Cochrane Controlled Trials
         Register (Issue 3, 2001) was searched. Selection criteria: Randomized trials comparing amnioinfusion
         with no amnioinfusion for women in labour with moderate or thick meconium-staining of the amniotic
         fluid. Data collection and analysis: Eligibility and trial quality were assessed by one reviewer. Main
         results: Twelve studies, most involving small numbers of participants, were included. Under standard
         perinatal surveillance, amnioinfusion was associated with a reduction in the following: heavy
         meconium staining of the liquor (relative risk 0.03, 95% confidence interval 0.01 to 0.15); variable fetal
         heart rate deceleration (relative risk 0.65, 95% confidence interval 0.49 to 0.88); and reduced caesarean
         section overall (relative risk 0.82, 95% confidence interval 0.69 to 1.97). No perinatal deaths were
         reported. Under limited perinatal surveillance, amnioinfusion was associated with a reduction in
         the following: meconium aspiration syndrome (relative risk 0.24, 95% confidence interval 0.12 to
         0.48); neonatal hypoxic ischemic encephalopathy (relative risk 0.07, 95% confidence interval 0.01 to
         0.56) and neonatal ventilation or intensive care unit admission (relative risk 0.56, 95% confidence
         interval 0.39 to 0.79); there was a trend towards reduced perinatal mortality (relative risk 0.34, 95%
         confidence interval 0.11 to 1.06). Reviewer’s conclusions: Amnioinfusion is associated with
         improvements in perinatal outcome, particularly in settings where facilities for perinatal surveillance
         are limited. The trials reviewed are too small to address the possibility of rare but serious maternal
         adverse effects of amnioinfusion. Level 1, excellent, support.

         Halvax L, Szabo I, Vizer M, Csermely T, and Ertl T. Simultaneous use of intrapartum fetal pulse
         oximetry and amnioinfusion in meconium stained amniotic fluid. Eur J Obstet Gynecol Reprod Biol
         2002104(2):105-8.

         OBJECTIVE: Fetal pulse oximetry is a minimally invasive, simple technique which continuously helps
         to reflect in utero well-being. The presence of meconium in the amniotic fluid may be a clinical sign of
         fetal hypoxemia. Amnioinfusion has a beneficial effect on the incidence of meconium aspiration
         syndrome (MAS), and the presence of meconium below the level of the vocal cords. STUDY DESIGN:
         We studied the impact of amnioinfusion combined with fetal pulse oximetry on the incidence of
         meconium aspiration syndrome and operative delivery. RESULTS: The retrospective analysis revealed
         that the presence of meconium below the level of vocal cords was significantly reduced. The frequency
         of cesarean section is decreased, however, it did not reach statistical significance. CONCLUSION:
         Fetal pulse oximetry may be used in combination with amnioinfusion and cardiotocography (CTG) to
         reduce the risk of meconium aspiration syndrome and the number of instrumental deliveries and
         improve perinatal outcome. Comment: The major aim of this retrospective study was to assess the
         impact of fetal pulse oximetry in AI on MAS. Level 5, fair, supportive of amnioinfusion reducing
         MAS. Amnioinfusion was used in combination with fetal pulse oximetry. The use of this combination
         may be limited in countries with limited resources. Comments: Level 5, fair, support.

Shah AA. Effect of amnioinfusion for meconium stained amniotic fluid on perinatal outcome.
J Pak Med Assoc. 2004 Jun;54(6):322-5.


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         Objective: To see the effect of amnioinfusion on perinatal outcome in cases of meconium staining of liquor.
         Methods This study was conducted in department of Obstetrics and Gynecology, unit 1, Jinnah Postgraduate
         Medical Centre, Karachi, from 1st January 1998 to 31st December 2000. Four hundred patients were included in
         this study, assigning 200 for amnioinfusion and 200 as control. All patients were matched in both the groups
         with respect to age, antenatal booking, parity, gestational age, stage of labour, color of amniotic fluid and fetal
         birth weight. Both the groups were found to be comparable. Results: The rate of Caesarean section was found to
         be 37% in amnioinfusion group, which collaborates with other international studies. The fetal outcome was
         better i.e. 91% alive and healthy, after amnioinfusion due to dilution of meconium stained amniotic fluid with
         physiological solutions. The perinatal outcome was recorded by Apgar score at 5 minutes. The perinatal
         morbidity and mortality both were significantly lowered and was found to be 6% as compared to 14% in control,
         which was also noticed by less number of admissions in nursery i.e. 12% and perinatal deaths. The incidence of
         meconium aspiration syndrome was found to be 56% in control and was reduced to 22% after amnioinfusion in
         the other arm of the study. Conclusion These results are very encouraging and suggestion can be safely made
         that in future amnioinfusion will be the ideal method of preventing fetal distress due to meconium stained
         amniotic fluid.
         Reviewers Conclusions: Reviewer could not access the original full length paper. (waiting for the inter library
         loan). Based on the information given in the abstract the study design is not clear regarding randomization,
         exclusion criteria and end points. However the results were in favor of amnioinfusion in the prevention of
         meconium aspiration syndrome. Level 2, fair, support.

Sood MC, Dimple D, Aggarwal N, Faridi MM. Amnioinfusion in thick meconium. Indian J Pediatr 2004; 71:677-681.

        Objective: To evaluate the effectiveness of transcervical amnioinfusion for meconium stained amniotic fluid
        during labor. Method: Women at term and in early labor presenting with meconium were randomized to receive
        transcervical saline amnioinfusion or given normal obstetrical care with no amnioinfusion. Patients were
        assigned to each group by a coin toss. Criteria for inclusion into the study were: 1) Singleton pregnancies, 2)
        Vertex presentation, 3) gestational age >37 weeks, and 4) cervical dilation <5cm and adequate pelvis.
        Amnioinfusion was carried out using standard technique. Informed consent was obtained and all patients
        received a single dose of broad spectrum antibiotic intravenously. All women in labor were monitored
        electronically. C-section was carried out if fetal distress was noted. Infants were also examined for the presence
        of meconium levels. The following findings were documented. Chest x-rays were obtained in all infants within
        one hour after birth. The following factors were analyzed: 1) FHR changes, 2) Rate of operative delivery, 3)
        Presence of meconium below the cord 4) MAS by chest x-ray, 5) postpartum complications in mother in first 48
        hours. Results: A total of 199 women were enrolled in the study. Three were excluded due to vaginal bleeding.
        Of the remaining 196, 100 were assigned to the control group and 96 were assigned to the amnioinfusion group.
        FHR deceleration: Persistent deceleration was noted in 26% of the study group and 56% of the control group
        (p<.07). In the study group CTG were revealed in 40% of cases whereas only in 11% of the control group. The
        amnioinfusion group had 87% vaginal births as compared to only 58% in the control group. The incidence of c-
        section was 12% in the study group versus 42% in the control group. The differences persisted when analyzed
        by parity. N priigravida 33% C-section in study group and 52% in control group among the multigravida) % C-
        section but 19% in control. Maternal outcomes analysis showed that in study group the atony was seen in 6 of 96
        patients in the amnioinfusion group and only one of 100 in the control group. Neonatal outcome: Lower
        meconium below the vocal cord was seen in study group MAS was also markedly reduced 6.3% in infusion
        group vs. 20% in control group (p<.005). Perinatal mortality did not decrease significantly. Duration of nursery
        stay was no different. C-sections dropped from 68% to 13%. The authors concluded that amnioinfusion reduced
        significantly the fetal heart rate deceleration, c-sections rate, in infants the incidence of MAS and hospital stay.
        Authors concluded that the amnioinfusion decreases MAS significantly. They also emphasized the effect of
        meconium aspiration in decreasing the rate of c-sections, which is important to developing countries.
        Conclusion: Supports the hypothesis. Weakness: Study design and randomization not adequate. Reviewers’
        Conclusion: The findings of the study show that amnioinfusion in addition to decreasing the incidence of MAS
        it also decreases the C-section rate and hospital rate. Comments: Level 1, good, support.

NEUTRAL:

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Adam K, Cano L, Moise KJ. The effect of Intrapartum amnioinfusion on the outcome of the fetus with heavy meconium
stained amniotic fluid. Proceedings of 9th Annual Meeting of the Society of Perinatal Obstetricians, New Orleans,
Louisiana, USA 1989; 438.
     Methods: Random allocation. Inclusion criteria: heavily meconium-stained amniotic fluid. Intervention:
     amnioinfusion 1000 ml administered once (n = 17) versus control group (n=18). Outcomes: Meconium
     aspiration syndrome, meconium below the cords, cesarean section for fetal distress. Comments:
     Neonatologists were blinded but obstetricians were not. The numbers are too small for adequate analysis. Final
     Assignment: Level 2, fair.

Nageotte MP, Bertucci L, Towers CV, Lagrew DL, Modanlou H.Prophylactic amnioinfusion in pregnancies
complicated by oligohydramnios: a prospective study. Obstet Gynecol. 1991 May;77(5):677-80.

Prophylactic amnioinfusion was assessed in term and post-dates pregnancies with decreased amniotic fluid
volume. Subjects were randomly assigned to one of three groups: amnioinfusion with warmed saline solution,
room-temperature saline, or control. Patients receiving prophylactic amnioinfusion had a significant decrease
in both the frequency and severity of variable decelerations in the first stage of labor (P = .006) and in the
average total number of variable decelerations in the first and second stages of labor (P = .01) compared with
controls. There was no observed effect on newborn serum electrolyte levels with amnioinfusion, nor was there
any apparent benefit of infusion of warmed saline compared with room-temperature saline. In contrast to
premature gestations with oligohydramnios, prophylactic amnioinfusion was not associated with a significant
improvement in mean umbilical arterial and venous pH or a significant decrease in cesarean delivery for fetal
distress (P = .09). This is perhaps because the term fetus has an enhanced ability to tolerate recurrent episodes
of heart rate decelerations without demonstrating the rapid metabolic changes seen in the premature fetus.
Comments: Level 2, fair, neutral.

Lo KWK & Rogers M. A controlled trial of amnioinfusion: the prevention of meconium aspiration in labour. Aust NZ J
Obstet Gynaecol 1993;33(1):51-54.
     Objective: To examine the effect of amnioinfusion on the incidence of MAS, perinatal asphyxia and obstetrical
     intervention amongst patients with moderate and thick meconium-stained amniotic fluid. Methods:
     Prospective, non-randomized study. Inclusion criteria: Patients in labor with more than trace meconium
     (moderate or thick). Additional inclusion criteria: Singleton pregnancy, vertex presentation, ≥37 wks
     gestation, normal fetal heart rate pattern, anticipated time to delivery >2 hours (cervical dilation <8 cm).
     Exclusion criteria: Malpresentation; multiple gestation; fetal malformation, polyhydramnios,
     chorioamnionitis, cord prolapse, vaginal bleeding, moderate or severe variable or late decelerations, significant
     maternal disease. Intervention: Each patient received amnioinfusion or was part of control group based on
     their own decision. Study subjects (n=60) received amnioinfusion with normal saline at room temperature; one
     liter infused at rate of 10-15 ml/min. Infusion stopped when completed or on reaching 2nd stage of labor or
     when cesarean section performed. Amnioinfusion repeated after 4 hrs if patient remained undelivered.
     Compared with control group (n=52). Outcome: No significant differences in cesarean section rates but was a
     trend towards a lower incidence of total operative deliveries (P = 0.01) and cesarean sections (P = 0.04) in
     amnioinfusion groups when only cases of fetal distress were considered. Significantly lower rate of neonatal
     acidemia (P = 0.009); significant improvement in 5 minute Apgar score; and significantly decreased incidence
     of meconium below the vocal cords (P = 0.02). Conclusion: Amnioinfusion benefits the patient in terms of a
     reduction in need for operative delivery for fetal distress and results in improved neonatal outcomes.
     Comments: Study was not randomized; patients allowed to choose amnioinfusion or no amnioinfusion. Final
     Assignment: Level 3, fair, neutral.

Rogers MS, Lau TK, Wang CC, Yu KM. Amnioinfusion for the prevention of meconium aspiration during
labour. Obstet Gynecol. 1995 Aug;86(2):230-4.


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         The aim of this observational study is to review the outcome of prophylactic intrapartum amnioinfusion
         (AI) in pregnancies complicated by moderate to thick meconium-stained liquor (MSL). The labour and
         neonatal outcome of all 298 AIs performed over a 3-year period were compared to a matched-control
         group of patients whose labour was complicated by moderate or thick MSL but without AI. The
         incidence of moderate or thick meconium below the vocal cords of the neonate were significantly lower
         in the AI group (6.4% and 3.4%) compared with the control group (15.4% and 6.7%). The incidence of
         meconium aspiration syndrome in the AI group was half (1.7%) that of the control group (3.7%),
         although the difference did not reach statistical significance. There was a significant higher incidence of
         cardiotocographic abnormalities in the AI group (30.5% versus 14.7%), with higher incidences of
         Caesarean section and operative vaginal deliveries. The reduction in the incidence and thickness of
         meconium after AI was not accompanied by any statistically significant reduction in adverse fetal
         outcomes such as low Apgar scores, cord pH values, admissions to and duration of admission to the
         neonatal unit, or the incidence of meconium-aspiration syndrome. Comment: No significant
         differences in MAS, low Apgar scores between the two groups. Supportive of reducing meconium
         below cords and opposing for cardiotocographic abnormalities. Level 4, fair neutral

Usta IM, Mercer BM, and Sibai BM. Risk factors for meconium aspiration syndrome. Gynecol 1995 85(2)
237-241

OBJECTIVE: To identify potential predictors of meconium aspiration syndrome (MAS) in pregnancies
complicated by moderate or thick meconium-stained amniotic fluid (AF). METHODS: In the period 1990-
1993, 937 vertex singleton pregnancies with moderate or thick meconium-stained AF were delivered; of these,
39 neonates developed MAS and 898 did not. The two groups were compared retrospectively according to
maternal findings, pregnancy outcome, and neonatal complications, using univariate analysis (P < .05
considered significant) and stepwise multiple logistic regression analysis to identify independent significant
factors for prediction of MAS and to calculate odds ratios (OR) and 95% confidence intervals. RESULTS:
The two groups had a similar mean gestational age at delivery and birth weight. They also had similar
incidences of post-dates pregnancies, small and large for gestational age infants, and amnioinfusion use.
Univariate analysis identified significant differences between the two groups in 13 variables, two of which
were excluded from logistic analysis because of inadequate data. Logistic regression analysis identified only
six variables with independent, statistically significant effects on MAS: admission for induction with
nonreassuring fetal heart tracing (OR 6.9), need for endotracheal intubation and suctioning below the vocal
cords (OR 4.9), 1-minute Apgar score of 4 or less (OR 3.1), present cesarean delivery (OR 3.0), and previous
cesarean delivery (OR 2.5). Cigarette smoking was associated with a lower risk for MAS (OR 0.07). The
presence of at least one of the five risk factors had a sensitivity of 92%, a specificity of 56%, a positive
predictive value of 8%, and a negative predictive value of 99% for MAS. CONCLUSION: Considering the
high negative predictive value of the test, infants without any risk factors will not develop MAS and thus can
be safely allowed to room with their mothers. Furthermore, this model helps to identify infants who may
benefit from 24-hour observation and in counseling women about the neonatal risk for developing MAS.
Comment: This retrospective analysis of 937 singletons with meconium stained AF WAS NOT INTENDED
to study the effect of AI or its complications. However authors found no difference in MAS with
amnioinfusion. No differences in MAS meconium below cords. They found amnioinfusion group had higher
incidence of endometritis and fetal heart abnormalities. Level 4, fair, neutral.

De Meeus JB, D’Halluin G, Bascou V, Ellia F, Magnin G. Prophylactic Intrapartum amnioinfusion: a controlled
retrospective study of 135 cases. J Gynecol Obstet Biol Reprod 1997;26(6):610-616.
Methods: controlled retrospective; each group compared to historical control group. Inclusion criteria
   Oligohydramnios (amniotic fluid index ≤5) or particulate meconium-stained amniotic fluid. Exclusion criteria:
   breech presentation, chorioamnionitis, uterine bleeding, gestational age <36 weeks, multiple pregnancy and


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     fetal distress requiring prompt delivery or cesarean section. From 3/1/93 until 6/30/95, 4031 women delivered
     at University Hospital of Poitiers. From this population, 135 subjects were prospectively included in
     prophylactic AI (amnioinfusion) program during labor (71 for oligohydramnios – group 1 [G1]; 64 for
     particulate meconium-stained amniotic fluid – group 2 [G2]). Historical control group of 121 subjects
     retrospectively identified from 3363 patients who delivered between 1/1/91 and 12/31/92 and fulfilled the
     following criteria: oligohydramnios or particulate meconium-stained amniotic fluid during labor, age, parity,
     gestation age, occurrence of pregnancy disorders (preeclampsia, intrauterine growth retardation and preterm
     labor), induction of labor for pathology and duration of labor. 57 subjects with AFI ≤5 (control group 1 [CG1])
     and 64 subjects with particulate meconium-stained amniotic fluid (control group 2 [CG2]) were selected.
     Interventions: amnioinfusion with 500 ml warmed normal saline at 37C during 20-30 min when cervical
     dilatation was >2 cm. AFI assessed hourly and if <10 cm, 250 ml normal saline re-infused. Oligohydramnios
     and thick meconium groups studied separately. Mean amnioinfusion volume was 893 ml in G1 and 734 ml in
     G2. Outcome: reduced cesarean section rate oligohydramnios group 1 (8/71 or 11.3%) vs CG1 (14/71 or
     24.5%). Decreased assisted delivery rate particulate meconium-stained group 2 (15.5%) vs CG2 (25.35%).
     One infant from G2 (1.6%) had meconium below vocal cords vs six in CG2 (9.4%) which was not statistically
     significant but had a P value of 0.05. Comments: For patients who were treated with amnioinfusion for
     oligohydramnios, the overall cesarean section rate was decreased. However, authors could not confirm data
     with regard to cesarean section rate for fetal distress. For patients presenting with thick meconium,
     amnioinfusion resulted in a significant decrease in cesarean section rate. Final Assignment: Level 4, fair,
     neutral.

Khosla AH, Sangwan K, Ahuja SD. Prophylactic amnioinfusion during labour complicated by meconium. Aust NZ J
Obstet Gynaecol 1997;37(3):294296.
 Objective: To evaluate the safety and efficacy of amnioinfusion in labor complicated by meconium stained
              amniotic fluid. Methods: Prospective non-randomized study. Inclusion criteria: Meconium-
              stained amniotic fluid. Additional inclusion criteria: Singleton pregnancy at ≥36 weeks’
              gestation, cervical dilatation ≥4 cm, normal fetal heart rate pattern, absence of medical or
              obstetrical complications. Intervention: Study subjects received amnioinfusion with 500 ml
              normal saline, administered via infant feeding tube inserted through cervix; infused via
              intravenous set attached to saline bottle (n=25) and compared with control group (n=25). AFI
              measured before and after procedure; if post-infusion AFI <10, additional 250 ml of normal
              saline infused. Outcome: Significant decrease in cesarean section rate (amnioinfusion 4% vs
              control 28%); significantly effective in dilution of meconium stained amniotic fluid (thick
              meconium at initial rupture of membranes in 19/25 study vs 14/25 control subjects; at delivery,
              thick meconium seen in 6/25 study vs 16/25 control subjects); mean AFI increased by 9.5 cm
              post-amnioinfusion in women with an initial AFI <6 (mean AFI was 3.4 cm and increased to
              12.9 cm after amnioinfusion in the study group while mean AFI in control group was 2.9 cm at
              start of study). No significant difference in neonatal outcome was seen after amnioinfusion (no
              significant improvement in Apgar scores at one and five minutes; no significant difference in
              incidence of meconium on gastric lavage or below the vocal cords; 3/25 babies in study group
              vs 4/25 babies in control group were clinically diagnosed with meconium aspiration syndrome).
              Conclusion: The incidence of cesarean section was decreased but neonatal parameters showed
              no significant difference in the amnioinfusion group. Final Assignment: Level 3, fair, neutral.

Hofmeyr GJ, Gulmezoglu AM, Buchmann E, Howarth GR, Shaw A, Nikodem VC, Cronje H, de Jager M, Mahomed K.
The Collaborative Randomised Amnioinfusion for Meconium Project (CRAMP): 1. South Africa. Br J Obstet Gynaecol
1998;105:304-308.
 Objective: To evaluate the efficacy of amnioinfusion for meconium stained amniotic fluid during labor.
              Methods: Participants allocated by sealed, consecutively-numbered, opaque envelopes in
              computer-generated random sequence. The investigators conducted a multi-center randomly


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                   controlled trial which included 4 urban academic hospitals in South Africa. Obstetric
                   surveillance included the use of electronic fetal heart rate monitoring in most cases. Inclusion
                   criteria: Women in labor at ≥37 weeks’ gestation with singleton cephalic presentation and
                   moderate or heavy meconium stained amniotic fluid. Intervention: Study subjects received
                   amnioinfusion with normal saline at room temperature at 15 ml/min for 800 ml, then maintained
                   at 3 ml/min for the duration of labor (n=176) and compared with control group (n=176).
                   Outcome measure: Cesarean section rate, incidence of MAS and perinatal Outcome: The
                   cesarean section rate did not decrease (RR 0.98, 95% CI 0.76 – 1.26). MAS was lower than
                   expected (RR 0.67, 95% CI 0.19 – 2.33). There were no significant differences in subsidiary
                   outcomes. Comments: Meta-analysis of pooled data from 7 studies performed prior to this
                   report and 2 CRAMP studies revealed significant reductions in the cesarean section rate as well
                   as the incidence of MAS. Conclusion: BASED ON POOLED DATA, BUT NOT ON THE
                   STUDY’S OWN DATA, THE USE OF AMNIOINFUSION IN MECONIUM-STAINED
                   AMNIOTIC FLUID REDUCED THE INCIDENCE OF MAS. Final Assignment: Level1,
                   good, neutral

Moodley J, Matchaba P, Payne AJ. Intrapartum amnioinfusion for meconium-stained liquor in developing countries.
Tropical Doctor 1998;28:31-34.
 Objective: To determine whether amnioinfusion during the Intrapartum period for meconium-stained
              amniotic fluid decreases cesarean section rates for fetal distress and decreases perinatal
              morbidity. Methods: Random allocation using sealed envelopes. Inclusion criteria: Term
              patients in active labor, dilated 8 cm with meconium staining of amniotic fluid that had normal
              fetal heart rate patterns on presentation. Exclusion criteria: Medical or surgical conditions,
              chorioamnionitis, previous cesarean section. Intervention: Study subjects (n=30) received
              amnioinfusion with normal saline at 15 ml/min until a volume of one liter was infused. This was
              repeated if delivery did not occur within 4 hours. Comparison made with control group (n=30).
              Outcome: Mean pH of umbilical arterial blood significantly higher in study group
              (amnioinfusion 7.30 vs control 7.23); fewer patients in study group developed HIE or
              meconium aspiration syndrome (amnioinfusion 3/30 vs control 7/30) but was not statistically
              significant; cesarean section for fetal distress was performed on fewer patients in the
              amnioinfusion group (3/30 vs control 7/30). Conclusion: Amnioinfusion is an effective
              treatment for improving perinatal outcome in pregnancies complicated by meconium stained
              amniotic fluid. Final Assignment: Level 2, fair, neutral


 OPPOSING:
Spong CY, Ogundipe OA, Ross MG. Prophylactic amnioinfusion for meconium stained amniotic fluid. Am J Obstet
Gynecol 1994;170:285.


         Objective: To determine the benefit of prophylactic amnioinfusion for meconium compared with
         standard care, incorporating therapeutic amnioinfusion for variable decelerations. Methods: Computer-
         generated random number sequence. Inclusion criteria: Singleton, vertex presentation at ≥37 weeks’
         gestation with moderate to heavy meconium and no variable FHR decelerations. Exclusion criteria:
         Light meconium; prenatally diagnosed fetal malformations, maternal temperature >100.4F on
         admission, evidence of fetal distress. Intervention: Study subjects (n=43) received amnioinfusion with
         600 ml normal saline bolus followed by 3 ml/min. If variable decelerations developed in patients in the
         control group, they received an identical amnioinfusion (occurred in 8/50). Study subjects compared to


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         control group (n=50). Outcome: Neither meconium present below the vocal cords nor meconium
         aspiration syndrome was statistically different between the two groups. There was a higher, though not
         statistically significant, incidence of maternal chorioamnionitis-endometritis in the amnioinfusion
         group (amnioinfusion 7/43 or 16% vs control 4/50 or 8%). Arterial cord pH <7.20 and admission to
         Level 2 or 3 nurseries were not significantly different. Conclusion: Prophylactic amnioinfusion in term
         pregnancies did not improve perinatal outcome and increased the risk for chorioamnionitis-
         endometritis. Final Assignment: Level 1, good, oppose.


Adair CD, Sanchez-Ramos L, Kaunitz AM, Briones D. A trial of labor complicated by uterine rupture
following amnioinfusion. South Med J. 1995 Aug;88(8):847-8.

         Amnioinfusion has become accepted in the management of intrapartum cord compression, meconium-
         stained fluid, and oligohydramnios. Limited experience exists regarding amnioinfusion in patients
         undergoing a trial of labor after cesarean section and its potential complications. We report a case of
         trial of labor in which uterine rupture occurred following intrapartum amnioinfusion. This case
         demonstrates the need for careful attention to amnioinfusion volumes and administration in patients
         with a previous cesarean section.Comment: This is a single case report highlighting that amnioinfusion
         is not without complications especially in a setting of a previous C-section. Level 5, fair, opposing.


Maher JE, Wenstrom KD, Hauth JC, Meis PJ. Amniotic fluid embolism after saline amnioinfusion: two cases
and review of the literature. J Reprod MetHE d. 1995 May;40(5):383-6.

BACKGROUND: Amnioinfusion is an intrapartum intervention with proven benefit in certain clinical
situations. It is thought to be a safe treatment with few adverse effects. CASES: Two cases of fatal amniotic
fluid (AF) embolism occurred in women who were treated during labor with a saline amnioinfusion. In both
cases, amnioinfusion was administered after finding thick meconium staining of the AF. In addition to the
amnioinfusion, common factors in these cases and three previously reported AF embolisms associated with
amnioinfusion are the presence of rapid labor, meconium-stained fluid, or both. CONCLUSIONS: Amniotic
fluid embolism is a rare cause of maternal morbidity and mortality. It is not known whether amnioinfusion
increases the rate of its occurrence in laboring patients. Comment: This is an important report of complication
of AI. However authors state no change in clinical practice is warranted on basis of this report. Future studies
must look for this complication. Level 5, fair, opposing




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