Original Article
Vasoconstrictive activity of meconium stained amniotic fluid in the human placental vasculature

https://doi.org/10.1016/S0301-2115(99)00099-8Get rights and content

Abstract

Objective: The purpose of this study was to study was to determine the effect of meconium stained amniotic fluid on the vasculature of isolated perfused human placental cotyledon. Study Design: Isolated placental cotyledons were dually perfused. Fetal perfusion pressure was used as an index of vascular resistance. Meconium stained amniotic fluid (MSAF) was collected from patients after artificial rupture of membranes in term gestation. A dilution of meconium (1:2; 1:4; 1:8; 1:16) was performed. Optical density (OD) of MSAF varied between 0 and 35.0 units/g as determined by spectrophotometry. Bolus injections of 1.0 ml of MSAF at different concentrations were injected into the fetal circulation. Heated and dialyzed MSAF after adequate dilution and evaluation of optical density were injected into fetal circulation in separate experiments. Results: Analysis of variance (ANOVA) and paired t-test were used for statistical analysis. Bolus injections of MSAF into the fetal circulation resulted in a concentration-dependent increase in perfusion pressure. MSAF with the highest OD resulted in a greater change in perfusion pressure as compared to more dilute MSAF (P=0.0001). After high OD amniotic fluid injections the provoked contractions lasted longer compared to dilute MSAF (P=0.006). MSAF after dialyzation did not exhibit any vasoconstrictive effect. Conclusion: Meconium is a vasoconstrictive agent in the fetal-placental vasculature and has a concentration dependent effect.

Introduction

Meconium stained amniotic fluid (MSAF) has well known adverse effects on neonatal survival and neurologic outcome in term or post-term infants [1], [2]. In addition, it is an independent risk factor for cerebral palsy among preterm infants, regardless of gestational age [3].

Two possible mechanisms may explain the association between MSAF and fetal or newborn brain damage. A higher incidence of subclinical chorioamnionitis and microbial invasion of the amniotic cavity has been described in patients with MSAF. Therefore the risk of cytokine-induced perinatal ischemic brain damage is increased [4], [5]. Another mechanism may be related to the vasoconstrictive effect of meconium on the feto-placental vasculature [6], [7].

Recently, it has been suggested that meconium or substances within meconium are capable of penetrating and diffusion through Wharton’s jelly and may induce histopathologic vascular changes in human umbilical arteries and veins [8].

The vasoactive effect of meconium on the human umbilical cord and its blood vessels has been previously demonstrated [6], [7], [9]. It is possible that this vasoactive effect may be one of the several primary causes of neonatal complications, such as persistent fetal circulation, necrotizing enterocolitis and renal failure occurring more frequently in conjunction with MSAF. These complications are likely to be initiated as a result of the vasoconstrictive effect of meconium on placenta, umbilical cord, and other fetal vessels [6], [9]. However, no data are available that directly examine the influence of meconium on vascular activity of the feto-placental unit. The aim of this study was to evaluate the effect of meconium on the feto-placental vasculature using in vitro, dually perfused, term placentas.

Section snippets

Materials and methods

Placentas (n=16) from uncomplicated term pregnancies were collected immediately after either vaginal or cesarean delivery. The perfusion experiments were performed using the method of Schneider and Huch [10]. Placentas were taken to the laboratory where a fetal artery and fetal vein from a single cotyledon were cannulated, within 20 min of delivery. Following successful establishment of the fetal circulation, the placenta was mounted in a perfusion chamber, and the maternal circulation was

Results

The mean basal pressure in the control placentas was higher than in the experimental placenta, although it did not reach statistical significance (50.2±10.7 mm Hg versus 48.8±9.7 mm Hg, P=0.8).

Fig. 1 displays the changes in pressure at various optical densities. Bolus infusion of MSAF resulted in a significant dose-dependent increase in perfusion pressure. The MSAF with the highest optical density demonstrated the greatest change in perfusion pressure. (42.8±11.7 mm Hg for OD of 24–35 U/g vs.

Comment

The presence of MSAF is an ominous sign, especially when it occurs in preterm labor and delivery [3], [4]. There is considerable evidence that the presence of meconium in amniotic fluid increases the odds for birth asphyxia, subsequent brain damage and neonatal mortality [2], [6], [7]. Meconium staining of amniotic fluid is reported in 12 to 20% of live births and in many of these cases represents a response of the fetus to the stress of labor [12].

Meconium passage may be in response to hypoxia

Acknowledgments

The authors are grateful to Els and Martin Wyler for sponsoring the establishment of The Placenta Perfusion Laboratory, in which the present study was performed.

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