The obstetric and neonatal literature has obscured the historic importance of meconium. There have been contradictory opinions on the significance of fetal exposure to meconium and assertions that the immature fetus is incapable of passage of meconium. More than 50 years ago, Clifford6 observed that yellow staining of the vernix caseosa, skin, nails, and umbilical cords of newborns resulted from prolonged exposure to meconium. He hypothesized that “yellow vernix syndrome” resulted from episodes of fetal asphyxia days or weeks before labor. He suggested that “the principal cause of the prenatal asphyxia is to be found in the placenta.” In our opinion, Clifford's observation and hypothesis remain true.
We found that the degree of meconium-associated risks and the color of meconium correlate with the time the fetus has been exposed to potent soluble biologic components. The most clinically significant meconium does not have a greenish color. Long-term placental staining, ie, longer than 6 hours of fetal and placental exposure to meconium, progressively manifests as a greenish tan, muddy brown, and light tan color.
Newborns with meconium aspiration syndrome excrete dark urine that is spectrophotometrically similar to meconium.7 Two accompanying facts are that umbilical cords of affected newborns are grossly discolored by meconium and pigment is seen by light microscopy in multiple and seemingly migratory macrophages. Those pathologic appearances indicate that color intensity of excreted urine results from clearance of circulating soluble meconium components. We doubt that it results exclusively from lymphatic drainage of intrapulmonary meconium.
Reviews of articles show the substantial discordance on the incidence and significance of meconium.8,9 A review by Katz and Bowes8 found that 5% of neonates with meconium aspiration syndrome are born through thin-consistency meconium, whereas Wiswell9 found instances of 38% and 41%. The extent to which this is confusing is aptly expressed by the titles of the aforementioned contributions, respectively, “Reflections on a murky subject” and “Meconium aspiration syndrome made murkier.” Lack of placental studies and epidemiologic investigations has contributed to the confusion. In a recent article, Wiswell10 comprehensively reviewed those issues, including placental considerations.
Abramovich and Gray11 studied distribution of meconium throughout various parts of intestinal tract specimens from 31 midpregnancy fetuses. They concluded that before 16 weeks' gestation, fetuses physiologically pass meconium into the amniotic fluid. At midgestation, many fetuses are exposed to intra-amniotic microbes and cytokines, and for those and other fetuses, passage of meconium is not necessarily physiologic.
In 4709 consecutive amniocentesis specimens obtained for genetic testing in the second trimester, Allen12 found 79 cases (1.67%) with greenish meconium. The accompanying fetal mortality rate was 5.06%. Allen acknowledged that the incidence of mortality was substantially less than that reported by other investigators. We suggest that exclusion of cases in which amniotic fluid was brownish explains the low mortality rate.12 Brownish fluid in many of the excluded cases probably contained pigments of old meconium.
Because there are more stillbirths in women with cholestatic hepatopathy, Sepulveda and colleagues13 investigated how circulating maternal bile agents might be fatal to fetuses. With methods similar to ours, they found that cholic acid had a dose-dependent vasoconstrictive effect on isolated human placental chorionic veins, and they postulated that it could cause fetal asphyxia.13 Using significantly different methods, Montgomery and colleagues14 found contradictory results.1,13–15 The importance of dose-dependent considerations, however, is substantiated by Bomzon and Ljuburcic.16 They found that low concentrations of bile acids produce vasodilation, not vasoconstriction.16
Falciglia and colleagues17 reported, to their knowledge, the first case of fatal meconium aspiration syndrome in an infant born at 27 weeks' gestation. They cited other authors' findings that in utero meconium is passed in only 3% of infants of gestational ages younger than 36 weeks, an opinion that accords well with previous statement by Matthews and Warshaw,18 who stated that there was meconium staining of amniotic fluid in 251 (7.5%) of 3374 admissions and that no case was less than 34 weeks' gestation.
Combined clinical and placental findings of fetal meconium exposure provide more meaningful diagnoses than do clinical features alone. A relevant publication includes epidemiologic analysis of placental pathology and clinical features of 1252 placentally studied cases.19 That and other data provided at least three noteworthy items: meconium staining of the amniotic fluid was present in 27% of 1252 cases, as opposed to the 7.5% of the aforementioned investigators' 3374 cases;18 in our previous clinicopathologic study,19 although we had little more than a third of the cases of other investigators,18 we found in utero passage of meconium in 13 infants less than 34 weeks' gestation, whereas they reported no such cases; and we found that infants of gestational age younger than 36 weeks have an incidence of in utero meconium passage of 6.7%, compared with the incidence of 3% which Falciglia and colleagues17 cited.
The pathophysiologic mechanism by which fetuses defecate remains unknown. As stated by Resnik, in discussion of Allen's contribution,12 it used to be thought that immature fetuses do not defecate because they have insufficient motilin secreted from the intestinal tract. In samples collected from human fetuses at 19–21 weeks' gestation, motilin is present in the fetal circulation at 60% of maternal levels.20 Thus, relative to the respective amounts of intestinal tract content in mother and fetus, fetal motilin levels should be sufficient to enable discharge of meconium. As cited by Mahmoud et al,21 several hormones are known to initiate the migrating motor complex along the duodenum. Kowalewska-Kantecka22 reported that no statistically significant differences in motilin were found between preterm and term fetuses. However, term newborns who have fetal distress have a fourfold greater amount of plasma motilin in umbilical cord specimens than normal term neonates.23
Our present findings are similar to those of Baergen and colleagues.24 In meconium-induced necrotic umbilical vascular tissue from specimens of mature fetuses, they found immunocytochemically evident interleukin-1 and interleukin-1 receptor antagonist, which is important because it shows means by which cytokine and soluble meconium components achieve augmented access to fetal circulation.
Complications of fetal meconium discharge can be hazardous to immature and extremely preterm fetuses, not just to mature and postmature fetuses. In three of the four placentas available for light microscopic study, we found histopathologic signs of reduced uterine blood flow, which might have caused meconium discharge that led to umbilical vascular necrosis, substantial access of cytokine to vital organs, and, in three of the cases, fetal death. We acknowledge published hypotheses that cytokines might provide insight into mechanisms of sudden infant death syndrome.24
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© 1999 The American College of Obstetricians and Gynecologists
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