Amniotic fluid meconium: A fetal environmental hazard

Amniotic Fluid Meconium: A Fetal Environmental Hazard KIRK D. RAMIN, MD, KENNETHJ. THOMAS J, CARMODY,

LEVENO, MD, MARY ANN KELLY, RN, AND

PhD

Objective: To investigate the hypothesis that meconium aspiration syndrome, the major hazard of meconium during labor, may be associated with superimposed fetal acute ridemia. Methods: Umbilical artery blood gases were measured in 7816 term pregnancies with meconium in the amniotic fluid (AF) and the results were correlated with intrapartum and neonatal outcomes. Results: Sixty-nine (1%) infants developed meconium aspiration syndrome and 31 (45%) of these were in association with fetal acidemia at birth. Moreover, umbilical blood gas analysis and intrapartum events suggested that the fetal acidemia linked to meconium aspiration was an acute event rather than a long-duration process, which might be expected if meconium was itself a marker of an antecedent fetal asphyxial event. Conclusion: Meconium in the AF may be a fetal environmental hazard when acidemia supervenes rather than solely a marker of preexisting fetal compromise leading to the release of meconium. (Obstet Gynecol W&87:281-4)

Obstetrical teaching throughout this century has included the concept that meconium in the amniotic fluid (AF) is a potential warning of fetal asphyxia. In 1903, J. Whitridge Williams observed, “ . . . a characteristic sign of impending asphyxia is the escape of meconium.“’ Williams attributed the passage of meconium to I, . . . relaxation of the sphincter ani muscle induced by faulty aeration of the (fetal) blood.” This concept remains much the same in the 1993 edition of Williams Obstetrics? although the language has changed. Specifically, “ . . . hypoxia has been implicated in the evacuation of meconium from the large bowel into amnionic fluid.” This concept implies a cause and effect relationship between hypoxia and meconium. However, virtually all fetuses exposed to meconium are born in good condition.” This lack of specificity of meconium as a From the Departmmts of Obstetrics and Gynecology and Academic Comprting Semites, Uniwrsity of Texas Southwestern Medical Center, Dallas, Texns.

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marker of “impending asphyxia” accentuates the fragility of the cause and effect concept. We propose that meconium aspiration syndrome, the major hazard attributed to meconium-stained AF is, in part, a fetal environmental hazard when acidemia supervenes in the presence of meconium. Furthermore, we propose that asphyxia may not be a part of the chain of events leading to the presence of meconium in the AF.

Materials and Methods The study population included 7816 term pregnancies with meconium in the AF and delivered between January 1, 1988, and December 31, 1991. The criteria for inclusion were term (38 weeks or greater), singleton gestation, cephalic presentation, live fetus on admission, umbilical artery blood gas analysis, and birth weight at least 2500 g. We excluded women with previous cesarean deliveries, pregnancies complicated by diabetes mellitus, and infants with congenital anomalies. Throughout the study period, the prevailing obstetric practice was to perform amniotomy to assess the AF for meconium when the fetal head was judged to be safely in the pelvis and the cervix was sufficiently dilated, consistent with active labor. Intrapartum care was supervised by resident physicians, and electronic fetal monitoring was used when meconium was discovered in the AF. All births were attended by personnel trained in oral, nasal, and pharyngeal suction before delivery of the infant’s thorax. Moreover, those births complicated by meconium were routinely attended by pediatric house officers. The trachea was routinely intubated and meconium, if present, was suctioned from the lower airway. Nurses were present at each delivery and completed a perinatal data sheet. After discharge, neonatal outcomes were abstracted by research nurses who then assessed the data for consistency and completeness before electronic storage.

0029-7844/96/$15.00 SSDI 0029-7844(95)00403-3

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Figure 1. Percentage of infants who aspirated meconium from their amniotic fluid in relation to their umbilical blood pH at birth. (Mantel-Haenszel 2 analysis, P -C ,001).

/

- 6.99

7.00

7.10

7.20

7.25

2 7.31

UMBILICAL ARTERY BLOOD pH

Meconium aspiration syndrome was diagnosed in infants with clinical and radiographic evidence of this complication. All these infants had dyspnea, tachypnea, and the need for supplemental oxygen by 6 hours of life, as well as diffuse, irregular patchy infiltrates on the chest radiographs. Infants with meconium below the vocal cords but no clinical evidence of disease were not considered to have suffered aspiration syndrome. Statistical analyses were performed using 2 or Fisher exact tests and Mantel-Haenszel 2 test for trend with the SAS/STAT statistical program (SAS Institute, Inc., Cary, NC). P 5 .05 was considered significant.

Results During the 4-year study period, 59,216 women were delivered at our hospital and 8136 (14%) had meconiurn-stained AF. Of these, 7816 pregnancies met the inclusion criteria for this study. Data concerning the viscosity, ie, thick versus moderate or thin, were not available in our data base because these descriptions were considered imprecise and difficult to define carefully. The demographics of the study group were not statistically different from those of the general obstetric population at Parkland Hospital, ie, approximately 46% were Hispanic, 33% were African-American, and 18% were white. Twenty-nine percent of the women were less than 19 years old; 4% were 35 or older. A slight majority (52%) of the women were parous, and 89% of those studied were of 38-41 weeks’ gestation; approx-

182 Ramin et al

Meconium

Enzknmental

Hazard

imately 11% were more than 42 weeks. More importantly, there was no statistical difference in the number of gestations 42 weeks or greater between those pregnancies complicated by meconium and no aspiration and those with meconium aspiration (854 [ll%l and ten [15%1, respectively). As shown in Figure 1, the incidence of neonatal meconium aspiration syndrome was related to umbilical artery blood pH values in virtually all the categories analyzed. These data suggest that meconium aspiration syndrome is significantly (P < .OOl) associated with fetal pH values less than 7.20, and, conversely, infrequent with higher umbilical artery blood pH values. Using the umbilical artery blood pH threshold of 7.19 or less to represent fetal acidemia associated with meconium aspiration in this study, we analyzed the pattern or classification of fetal acidemia in relation to the aspiration syndrome.4 Approximately 45% (n = 31) of the total infants who developed meconium aspiration syndrome (n = 69) were acidemic at birth. These infants typically had blood gas patterns suggestive of an acute process: 27 (87%) of these infants had respiratory or mixed blood gas patterns. Specifically, 87% had blood gas patterns that included hypercarbia (carbon dioxide pressure [PCO,] at least 65 mmHg). Eight hundred twenty-one (11%) of those infants with meconiumstained AF and who did not suffer meconium aspiration syndrome had hypercarbia, compared with 22 (32%) of those with meconium aspiration syndrome (P < .OOl). The common analgesic practice during the study period was to administer intravenous meperidine to

Obstetrics & Gynecology

those women in labor. Sixty-eight (1%) of those women whose AF was meconium-stained but whose infant did not suffer from meconium aspiration syndrome received a labor epidural, compared with none of those giving birth to infants with meconium aspiration syndrome (not statistically different). Complications during labor and delivery were analyzed in relation to the development of meconium aspiration syndrome; these results are summarized in Table 1. Importantly, meconium aspiration syndrome was associated with correlates of fetal jeopardy during labor or delivery. For example, fetal heart rate (FHR) abnormalities, cesarean delivery for nonreassuring FHR patterns, as well as forceps delivery to expedite birth, were significantly associated with meconium aspiration syndrome. Duration of labor, need for oxytocin stimulation, hypertension in labor, and cesarean delivery for dystocia were all unrelated to meconium aspiration syndrome. Similarly, chorioamm ‘onitis (defined as maternal temperature 38C or more during labor) was not significantly related to meconium aspiration. Logistic regression analysis of these outcomes revealed that cesarean delivery for nonreassuring FHR patterns, forceps delivery, and FHR abnormalities were the most likely correlates of neonatal meconium aspiration syndrome. Table 2 shows the condition of the infant at birth in relation to subsequent development of meconium aspiration as well as selected indices of neonatal outcome. Meconium aspiration was significantly increased in those infants with very low Apgar scores and who required assisted ventilation in the delivery room. Sim-

Table 1. Labor and Delivery Complications in Relation to the Development of Neonatal Meconium

Aspiration Syndrome

Labor and delivery outcome(s) Fetal heart rate abnormality Oxytocin stimulation Length of labor 2-h second stage 12 h or longer Cesarean delivery All Fetal distress Dystocia Hypertension in labor Forceps delivery Shoulder dystocia

Infants with meconium in the AF and no MAS (N = 7747)

fnfants with meconium intheAF and MAS (N = 69)

PI

2501 (32%) 1739 (23%)

47 (68%) 14 (20%)

C.001 NS

132 (2%) 1237 (16%)

2 (3%) 8(12%)

NS NS

1101 (14%)

36 (52%) 23 (33%) 8(12%)

.COl .OOl

12(17%)

NS

12 (17%)

.03

l(l%)

NS

435 (6%) 586 (8%) 787 (10%)

711 (9%) t?4(1%)

AF = amniotic fluid; MAS = meconium aspiration syndrome. * ,$ and Fisher exact test (two-tailed), as indicated.

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NS

Table 2. Condition of Newborns at Delivery and Subsequent Neonatal Morbidity

Outcome Apgar scores 53 at I min 53at5min Ventilation at birth+ Seizure(s)

first 24 h

Deaths

Infants with meconium in the AF and no MAS (N = 7747)

Infants with meconium in the AF and MAS (N = 69)

97 (1.3%)

12 (17%)

c.001

10 (0.1%) 715 (9%)

3 (4%) 29 (42%)

c.002

11 (0.1%) 4 (0.05%)

5 (7%) 4 (6%)

<.ool <.OQl

‘z.001

AF = amniotic fluid; MAS = meconium aspiration syndrome. * ,$ analysis and Fisher exact test &wo-tailed), as indicated. + Assisted with ambu bag.

ilarly, neonatal seizures and deaths were significantly increased (P < .OOl) in those infants diagnosed to have meconium aspiration syndrome. All four neonatal deaths in infants with meconium aspiration syndrome were attributable to aspiration. The remaining four neonatal deaths of infants delivered from meconiumstained AF but without aspiration syndrome were attributed to group B streptococcal sepsis (n = 21, asphyxia (n = 11, and unexplained subarachnoid hemorrhage (n = 1).

Discussion Obstetrical texts from the 17th through the 19th centuries reported meconium passage as a sign of fetal death or impending death. 5 Several more recent report&j7 have also described meconium as a marker of fetal compromise. However, obstetricians have also long realized that the detection of meconium in the AF during labor is problematic in the prediction of fetal asphyxia. In a recent review in the obstetrical literature, Katz and Bowes6 emphasized the prognostic uncertainty of meconium by referring to the topic as a “murky subject.” Indeed, although 1242% of human labors are complicated by meconium, few such labors are linked to infant mortality.3,6 In a recent investigation from our institution, meconium was found to be a “low risk” obstetrical hazard because the perinatal mortality attributable to meconium was one death per 1000 live births.3 Three theories have been suggested to explain fetal passage of meconium and may partially explain the tenuous connection between the detection of meconium and infant mortality. The pathologic explanation proposes that fetuses pass meconium in response to hypoxia and that meconium therefore signals antecedent fetal compromise.’ Alternatively, intrauterine passage

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of meconium may represent normal physiologic maturation of the fetal gastrointestinal tract under neural control.’ Third, meconium passage could also occur due to vagal stimulation from common but transient umbilical cord entrapment and resultant increased peristalsis.‘o Thus, fetal release of meconium could also represent physiologic processes rather than pathologic events. In the study now reported, and including almost 8000 pregnancies with meconium in the AF, meconium aspiration syndrome was significantly associated with fetal acidemia at birth. Other significant correlates of the aspiration syndrome included indices of fetal jeopardy, such as cesarean delivery, forceps to expedite delivery, and intrapartum FHR abnormalities. Similarly, indices of the infant condition at birth, to include depressed Apgar scores and the need for assisted ventilation in the delivery room, also implicated fetal compromise during labor or delivery. Our analysis of fetal acidemia based on umbilical blood gases suggested that the fetal compromise associated with meconium aspiration syndrome was an acute event because most acidemic fetuses had abnormally increased PC02 rather than the pure metabolic acidemia that might be expected with fetal events preceding the immediate circumstances of birth. Interestingly, hypercarbia in fetal lambs has been shown to induce fetal gasping and resultant increased inhalation of AF.“,‘* Moreover, Jovanovic and NguyenI observed that meconium gasped into the fetal lungs caused aspiration syndrome only in asphyxiated experimental animals. Therefore, our results could be used to hypothesize that the pathophysiology of meconium aspiration syndrome includes, but is not limited to, fetal hypercarbia, which stimulates fetal respiration leading to intrauterine aspiration of meconium into the alveoli, and lung parenchymal damage secondary to acidemiainduced alveolar cell damage in the presence of meconium. Therefore, the results of this study could be interpreted to implicate meconium in the AF as a fetal hazard when acidemia supervenes rather than a result of fetal compromise. In this pathophysiologic scenario, meconium in the AF is a fetal environmental hazard rather than a marker of preexistent fetal compromise. However, the pathophysiologic sequence now proposed does not account for approximately one-half of our cases of meconiurn aspiration syndrome because these neonates were not acidemic at birth. Thus, the pathophysiologic scenario now proposed for meconium aspiration syndrome cannot be taken as the exclusive explanation. Other unidentified factors are operative in at least 50% of cases of newborn meconium aspiration syndrome. We conclude that the high incidence of meconium observed in the AF during labor often represents fetal passage of gastrointestinal contents in conjunction with

l&3

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Meconium Environmental Hazard

normal physiologic processes. Such meconium, however, can become an environmental hazard when fetal acidemia supervenes. Clearly, prevention of fetal acidemia in the presence of AF meconium should be an obstetric goal. Unfortunately, our results suggest that such fetal acidemia occurs acutely and is therefore unpredictable and probably unpreventable.

References 1. Williams JW. Wiams obstetrics. 1st ed. New York, London: D Appleton & Co., 1903. 2. Cunningham FG, MacDonald PC, Gant NF, Leveno KJ, Gilstrap LC III. Williams obstetrics. 19th ed. Norwalk, Connecticut: Appleton L Lange, 1993. 3. Nathan L, Leveno KJ, Carmody TJ, Kelly MA, Sherman ML. Meconium: A 1990s perspective on an old obstetric hazard. Obstet Gynecol 1994;83:329-32. 4. American College of Obstetricians and Gynecologists. Assessment of fetal and newborn acid-base status. ACOG technical bulletin, no. 127. Washington, DC: American College of Obstetricians and Gynecologists, 1989. 5. Schulze M. The significance of the passage of meconium during labor. Am J Obstet Gynecol 1925;10:83-8. 6. Katz VL, Bowes WA. Meconium aspiration syndrome: Reflections on a murky subject. Am J Obstet Gynecol 1992;166:171-83. 7. Yeomans ER, Gilstrap LC III, Leveno KJ, Burris JS. Meconium in the amniotic fluid and fetal acid base status. Obstet Gynecol 1989;73:175-8. 8. Walker J. Foetal anoxia. J Obstet Gynaecol Br Commonw 1953;61: 162-80. 9. Mathews TG, Warshaw JB. Relevance of the gestational age distribution of meconium passage in utero. Pediatrics 1979;64: 38-l. 10. Hon EH, Bradfield AM, Hess OW. The electronic evaluation of the fetal heart rate. Am J Obstet Gynecol 1961;82:291-300. 11. Dawes GS, Fox HE, Leduc BM, Liggins GC, Richards RT. Respiratory movements and rapid eye movement sleep in the foetal lamb. J Physiol 1972;220:119-43. 12. Boddy K, Dawes GS, Fisher R, Pinter S, Robinson JS. Foetal respiratory movements, electrocortical and cardiovascular responses to hypoxaemia and hypercapnia in sheep. J Physiol 1974;243:599-618. 13. Jovanovic R, Nguyen HT. Experimental meconium aspiration in guinea pigs. Obstet Gynecol 1989;73:652-6.

Address reprint requests to: Kenneth J. Leveno, MD Department of Obstetrics and Gynecology University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75235-9032

ReceivedJune 5, 1995. Receivedin revised form September 7, 1995. Accepted September12, 1995. Copyright 0 1996 by The American College of Obstetricians Gynecologists. Published by Elsevier Science Inc.

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