OBJECTIVE: To estimate whether the acid-base status of neonates born to women with meconium-stained amniotic fluid varies across gestation.
METHODS: We carried out a retrospective cohort study of all pregnancies that were complicated by meconium-stained amniotic fluid in 2004. Cases were identified from a perinatal pathology database that contained data on all pregnancies complicated by meconium-stained amniotic fluid. Data abstracted from the charts included gestational age at delivery, umbilical arterial pH, birth weight, and the presence or absence of labor. Cases were stratified according to gestational age at delivery. The distribution of meconium-stained amniotic fluid across gestation was computed. The mean umbilical arterial pH values (with 95% confidence intervals) across gestation were assessed by analysis of variance.
RESULTS: The mean umbilical arterial pH in women with meconium-stained amniotic fluid did not differ across gestation. The overall incidence of meconium-stained amniotic fluid was 12.0% (766 of 6,403 deliveries). The rates of meconium-stained amniotic fluid increased from 1.2% at 32 weeks to 100% at 42 weeks.
CONCLUSION: The rising incidence of meconium-stained amniotic fluid with gestational age is consistent with the hypothesis that fetal maturation is a major etiologic factor in meconium passage. Also, the lack of variation of mean umbilical arterial pH across gestation suggests that fetal acidemia is not increased when meconium passage occurs earlier in pregnancy rather than at later gestational ages.
LEVEL OF EVIDENCE: II-3
Umbilical arterial pH values do not vary across gestation in neonates born to women with meconium-stained amniotic fluid.
From the 1 Division of Maternal-Fetal Medicine and the 2 Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School/Robert Wood Johnson University Hospital, New Brunswick, New Jersey.
Corresponding author: Yinka Oyelese, MD, Division of Maternal–Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901-1977; e-mail: YinkaMD@aol.com.
Meconium-stained amniotic fluid has been associated with poor perinatal outcomes, including low Apgar scores, meconium aspiration syndrome, increased rates of chorioamnionitis, increased incidence of neonatal intensive care admissions, and higher rates of perinatal death.1 Meconium staining of the amniotic fluid occurs in approximately 12% of pregnancies.1 However, the precise etiology of meconium passage remains unclear.2,3 Previous studies have demonstrated that the incidence of meconium-stained amniotic fluid rises with increasing gestational age.1 A study by Matthews and Warshaw4 found that 98.4% of cases of meconium-stained amniotic fluid in neonates admitted to the neonatal intensive care unit occurred at 37 weeks of gestation or later. Consequently, it is widely believed that meconium staining of the amniotic fluid, when occurring at later gestational ages, reflects maturation of the fetal autonomic nervous system. However, it is a common belief that fetal hypoxia or stress is a stimulus for fetal passage of meconium.1 Hence, labors complicated by meconium-stained amniotic fluid are typically considered high risk, with a lower threshold for cesarean delivery or other interventions, especially when meconium passage occurs earlier in gestation. Animal experiments have failed to conclusively demonstrate that hypoxia leads to meconium passage.1,4 Furthermore, studies have indicated that when meconium-stained amniotic fluid complicates labor, in the presence of reassuring fetal heart rate patterns, outcomes are similar to those labors where there is no meconium staining of the amniotic fluid.1 Therefore, the relationship between fetal hypoxemia/acidemia and meconium-stained amniotic fluid remains highly controversial.1–3
Neonatal umbilical arterial sampling for pH provides a means of objective assessment of fetal well-being at delivery.5 Furthermore, at least one previous study has shown that umbilical arterial pH values do not vary significantly between preterm and term neonates.6 The relationship between meconium passage and neonatal acid-base status across gestation has not been adequately studied.
We therefore carried out a study with the purpose of assessing the relationship between meconium-stained amniotic fluid and neonatal umbilical cord pH across gestation. We hypothesized that meconium-stained amniotic fluid is associated with lower umbilical arterial pH values at earlier gestational ages, reflecting fetal acidemia rather than a fetal maturational process.
MATERIALS AND METHODS
We carried out a retrospective cohort study of all women at Saint Peter's University Hospital, New Brunswick, New Jersey, in the year 2004, who had meconium-stained amniotic fluid during labor or delivery. Institutional review board approval was obtained for this study. According to existing protocols, all women who were noted to have meconium-stained amniotic fluid, either in labor or at the time of delivery, routinely had their placentas sent off for pathology. The diagnosis of meconium-stained amniotic fluid was a clinical one made by visual observation of green, yellow, or brown staining of the amniotic fluid in labor. It was also standard protocol to perform sampling of the umbilical arteries for gases and pH at each delivery. Immediately after each affected delivery, a segment of the umbilical cord was doubly clamped, and a sample of umbilical arterial blood was taken in a heparinized syringe. This sample was then put on ice and immediately sent to the laboratory for pH and gas analysis.
We identified cases for this study from the perinatal pathology database. This database contains, among other data, information about all pregnancies complicated by meconium-stained amniotic fluid. The medical records of the patients were retrieved and reviewed, and data was abstracted. Cases were stratified according to gestational age at delivery. The primary outcomes assessed were the umbilical arterial pH, base excess, Apgar scores, birth weight, and the presence or absence of labor. We compared these outcomes across gestational age in weekly strata from 32 to 42 weeks.
The incidence of gestational age-specific meconium passage was derived by dividing the number of cases of meconium-stained amniotic fluid cases at each week in gestation by the total number of live births at that gestational age. In a similar fashion, the distribution of umbilical cord pH across gestational age (35–42 weeks) was assessed by analysis of variance. Test for linear trend in the incidence of meconium-stained amniotic fluid across gestational age was assessed.7 Differences in pH and base excess by gestational age (less than 38 versus 38 weeks or more) were compared using t test, and differences in Apgar scores by gestational age were compared using the Kruskal-Wallis test. All statistical tests were two-tailed, and P<.05 was considered to denote statistical significance. All analyses were performed using SAS 9.1 (SAS Institute, Cary, NC).
Of the total of 6,403 deliveries, 766 (12.0%, 95% confidence interval [CI] 11–13%) were complicated by meconium-stained amniotic fluid. Charts were available for review in 740 of these cases. Sixty-four patients did not have umbilical arterial pH results available; therefore, our analysis was performed on the 676 patients who had umbilical arterial pH values in their charts. The rate of meconium-stained amniotic fluid increased with gestational age, from 1.2% at 32 weeks to 38.7% at 41 weeks, and reached a peak of 100% at 42 weeks (Fig. 1). Patient demographics are shown in Table 1. Among the 676 women with meconium-stained amniotic fluid whose records were available, 28.1% (95% CI 24.8–31.6%) were delivered by cesarean. Thirty-nine percent (95% CI 32.3–46.0%) of the cesarean deliveries were for nonreassuring fetal heart rate tracings.
Mean umbilical arterial pH values were similar for women with meconium-stained amniotic fluid who underwent labor and those who had cesarean deliveries without labor (Table 2). There was only case of meconium passage before 35 weeks; this was at 32 weeks. The mean umbilical cord arterial pH did not vary across gestation (Fig. 2). When we compared deliveries complicated by amniotic stained fluid with gestational ages greater than or less than 38 weeks of gestation, there was no statistically significant difference in umbilical arterial pH or base excess (Table 2). Similarly, there were no statistically significant differences between pH and base excess values for patients delivered with and without labor (Table 2)
Finally, to evaluate significant acidemia, we specifically examined cases where the umbilical arterial pH values were less than 7.2 and less than 7.1 (Fig 3). These values were selected based on previous studies defining fetal acidemia based on neonatal umbilical arterial pH values.8 No patients at less than 37 weeks had an umbilical arterial pH less than 7.1 (Fig. 3A). The distribution pattern of umbilical arterial pH values less than 7.2 was fairly uniform from 36 to 42 weeks (Fig. 3B).
We found an incidence of meconium-stained amniotic fluid of 12%, similar to that found in previous studies.1 We also found that the incidence of meconium-stained amniotic fluid increased with gestational age, lending support to the hypothesis that meconium passage is a physiologic event that is in large part due to developmental maturation of the fetal autonomic nervous system.
Contrary to our expectations, we found that the umbilical arterial pH values were similar in women with meconium-stained amniotic fluid across gestation. We had hypothesized that women with meconium-stained amniotic fluid at earlier gestational ages would have lower umbilical arterial pH values, reflecting a possible hypoxemic or acidemic insult being responsible for the meconium-stained amniotic fluid, rather than normal fetal maturation. Our findings agree with those of Scott and colleagues9 who reported no association of meconium passage in preterm deliveries with fetal acidosis. In fact, the distribution of pH values less than 7.1 was fairly uniform, and was limited to cases where the gestational age was 38 weeks or greater, and no cases of pH less than 7.2 occurred before 36 weeks of gestation.
It is not uncommon for obstetricians to be more aggressive in the management of labors complicated by meconium-stained amniotic fluid at earlier gestations, with earlier recourse to cesarean delivery, due to the belief that the meconium passage at these early gestational ages is indicative of fetal distress or hypoxemia. Our findings do not support this belief and would suggest that pregnancies whose labors are complicated by meconium-stained amniotic fluid at earlier gestational ages could be managed in a similar fashion as those where meconium-stained amniotic fluid occurs later in gestation.
This study has some limitations. The incidence of meconium-stained amniotic fluid at earlier gestational ages was low, and therefore the numbers were relatively small. However, this problem is likely to occur in any study of meconium staining of the amniotic fluid; 95% of cases occur at 37 weeks or more.4 We conducted a post hoc power analysis under 2 scenarios: 1) The study had a power of 79.1% with a type I error of 5% to detect a linear trend toward increasing umbilical arterial pH across gestational age (as shown in Fig. 1); and 2) our study had 90.6% power with a type 1 error of 5% to detect a difference in pH at less than 38 weeks of gestation (mean pH 7.27) and at 38 weeks or more (mean pH 7.22). Furthermore, meconium was not graded as light, medium, or thick, nor was a distinction made between patients who had meconium-stained amniotic fluid in early labor and those who developed it intrapartum. A recent study found lower Apgar scores, umbilical arterial pH values, and increased rates of meconium aspiration syndrome in women in whom there was a change from light meconium staining of the amniotic fluid to thick meconium staining during labor.10 Our study design did not permit us to reliably determine the timing of any intrapartum changes in meconium characteristics.
We could not exclude some low-grade hypoxic insult (with associated acidemia) that increased with gestational age being responsible for the increased incidence of meconium-stained amniotic fluid with increased gestational age. Our hypothesis that the increased meconium incidence with increasing gestation is a maturational process assumes that there are no differences in umbilical cord pH values between pregnancies with and those without meconium-stained amniotic fluid. A previous study that compared umbilical arterial pH values and levels of fetal erythropoietin (a marker for chronic hypoxia) between neonates born with and those born without meconium passage found no differences in umbilical arterial pH values between the groups, but did find significantly elevated levels of fetal erythropoietin in those neonates where there was meconium passage.11 Those findings suggest that meconium passage may be associated with chronic low-level hypoxia that may not be reflected in umbilical arterial pH values. However, that study did not examine pH or fetal erythropoietin across gestation. Unfortunately, we were unable to obtain data on those pregnancies of similar gestational ages that were not affected by meconium-stained amniotic fluid.
Finally, the impact of confounding by indication cannot truly be assessed. For instance, the rate of meconium-stained amniotic fluid at 42 weeks was 100%, higher than had previously been reported. However, there were only 12 women who did reach 42 weeks. It is possible that if pregnancies had been allowed to continue, the rate of meconium at 42 weeks may have been lower. It is also possible that cases where meconium was detected earlier were more likely to have been managed more aggressively, affecting our results.
The umbilical arterial pH only evaluates fetal acid-base status at the time of birth. Thus, we cannot exclude with confidence any transient antepartum or intrapartum acid-base status abnormalities that had resolved by the time of delivery. Although we did not compare umbilical arterial pH values with women who did not have meconium-stained amniotic fluid, this would not have helped to address our objective of determining whether meconium passage earlier in gestation is associated with differences in acid-base status. In spite of the aforementioned limitations, our study has strengths of reasonable numbers and a consistent policy of umbilical arterial sampling for pH and identification of all pregnancies complicated by meconium-stained amniotic fluid.
In conclusion, we have confirmed increased rates of meconium-stained amniotic fluid with advancing gestation and have demonstrated that deliveries that are complicated by meconium-stained amniotic fluid at earlier gestations do not have lower umbilical arterial pH values than those where the meconium staining occurs at term. We believe our findings may be helpful in understanding the physiology and pathophysiology of meconium passage. In addition, there is no clear evidence that the presence of meconium in isolation is an indication for changing obstetric management.
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© 2006 The American College of Obstetricians and Gynecologists
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