In recent years, the study of human fetal circulation by Doppler ultrasonography has advanced our understanding of fetal physiology under normal and abnormal circumstances. Two aspects of our results are interesting. Firstly, we found significant vascular vasodilatation in the splanchnic circulation of IUGR fetuses with echogenic bowel, and secondly, surprisingly none of the neonates with neonatal necrotizing enterocolitis belonged to this group.
Although many studies exist regarding Doppler flow velocimetry of splanchnic circulation in neonates,7,8,15–17 only a few studies were carried out during fetal life. The sparse data on splanchnic perfusion during human gestation may reflect the technical difficulties in obtaining flow velocities in small, fetal vessels. However, with the recent advent of high‐resolution ultrasound machines, it is now possible to determine flow velocities in most types of fetal circulation.18
Flow studies of fetal superior mesenteric artery have been reported in the normal AGA population. It was found that apart from the early stages of gestation, a relatively stable vascular resistance in the superior mesenteric artery exists throughout gestation.9 In the present study, we demonstrated a significant drop in the PI of both superior mesenteric artery and celiac trunk when compared with normal values. Mari et al (Mari G, Abuhamad A, Uerpairojkit B, Copel J. Superior mesenteric artery velocity waveform in the appropriate and small for gestational age fetus [abstract]. Ultrasound Obstet Gynecol 1996;8 Suppl 1:99) reported a similar PI reduction in the superior mesenteric artery of nine small for gestational age (SGA) fetuses, compared with 57 AGA fetuses.10 However, in a later extended study of 131 AGA fetuses (Mari G, et al, Ultrasound Obstet Gynecol 1996;8 Suppl 1:99), a converse observation was reported by the same group. A linear increase of PI was demonstrated in the superior mesenteric artery with advancing gestation, and a further increase in 17 of 41 SGA fetuses.19
Our results showed that IUGR fetuses with increased resistance in the umbilical artery and echogenic bowel had a significantly decreased PI of the superior mesenteric artery and celiac trunk. This observation merits a thorough explanation because previous animal studies have shown that in utero, stress results in reduced blood flow to the splanchnic organs on behalf of the brain circulation.20,21
The above fetal adaptive mechanism to in utero stress is known as the “sparing effect” or redistribution phenomenon, also described in human gestation by Doppler ultrasonography in the spleen, adrenal, coronary, and cerebral circulation.18,22–25 Our finding of a low PI, or a sparing effect in the superior mesenteric artery and celiac trunk, although surprising, was anecdotally reported previously by Mari et al (Mari G, et al, Ultrasound Obstet Gynecol 1996;8 Suppl 1:99) and Kilavuz and Vetter (Kilavuz O, Vetter K. The liver: The 4th preferential organ of the fetus [abstract]. Ultrasound Obstet Gynecol 1999;14 Suppl 1:79), who showed a preferential flow to the fetal liver in SGA fetuses. One possible explanation to splenic artery vasodilatation was the thought that in cases with hypoxemia, mediated erythropoietin stimulation may occur in the fetal spleen.22 However, this theory is not convincing because most fetal erythropoietin is produced by the liver, and therefore a different explanation is required. We suggest that the vasodilatation in some fetal SGA organs may be the result of hemodynamic changes, rather than the cause. If we assume that the fetal arterial bed with the placenta acts as a single chamber, any increase in umbilical artery resistance should be compensated by reciprocal vasodilatation in other fetal compartments. This has been shown in the adrenal spleen, coronary brain, and liver (Kilavuz O, et al, Ultrasound Obstet Gynecol 1999;14 Suppl 1:79).18 Therefore, the present results further confirm that the sparing effect may also be observed in the superior mesenteric artery and celiac trunk.
The main disadvantage of all previous experimental studies is that they have been performed on hypoxic animal models, which essentially differ from the chronic human in vivo situation.
The fetal arterial blood redistribution is mediated via a complex inter‐relationship between local vascular and reflex effects. It is well known that as the oxygen content of blood reduces, the fetus increases the blood flow to vital organs such as the brain, adrenal, and myocardium.21 However, local effects of changes in oxygen environment are less clearly established for other organs.26 In animal experiments, it was found that hypoxia‐induced vasodilatation at the superior mesenteric artery was not adenosine mediated.27 Recently, the role of endothelium‐derived nitric oxide has been established as a potent smooth muscle relaxing factor. In the fetus, endothelium‐derived nitric oxide produced by umbilical vascular endothelium, and in fetal sheep in utero, is capable of modulating resting umbilical vascular tone and pulmonary artery.28
In addition, it was found that at midgestation, fetal nitric oxide plays a major role in the regulation of blood flow and vascular tone across all segments of the fetal gastrointestinal tract.29 Endothelium‐derived nitric oxide, which is produced by most endothelial cells in response to hypoxemia, leads to significant smooth muscle relaxation of vascular resistance.30 In SGA fetuses, absence of or reversed diastolic flow in umbilical arteries increase the afterload, and a hypertensive state is established. This may lead to increased production of fetal endothelium‐derived nitric oxide, which stimulates vascular dilatation in the superior mesenteric artery and celiac trunk, as has been described in rats.31
Our second important observation was that none of our SGA fetuses with echogenic bowel developed neonatal necrotizing enterocolitis, despite evidence of a redistribution phenomenon reflected by increased umbilical resistance. Although previous studies have indicated increased association of SGA fetuses with Doppler abnormalities in the umbilical circulation with neonatal necrotizing enterocolitis complications, we could not support this finding.2,3 The precise etiology of neonatal necrotizing enterocolitis is unknown, and it is generally accepted that the most important etiologic factor is intestinal ischemia, or hypoperfusion leading to altered mucosal integrity.32 However, in our SGA fetuses, hypoperfusion was not evident, and on the contrary showed vasodilatation. Probably, adequate bowel perfusion was maintained, and consequently none developed neonatal necrotizing enterocolitis. The retrospective analysis of all our neonatal necrotizing enterocolitis cases in the neonatal intensive care unit further supports this observation because only one of 21 neonates was SGA. We assume that the echogenic bowel during fetal life represents a hyperperfused gut, which protects the newborn from neonatal necrotizing enterocolitis complications. However, the precise etiology of this sonographic appearance was beyond the scope of the present study. We can, therefore, conclude that SGA fetuses with echogenic bowel and increased resistance in the umbilical artery may manifest a redistribution phenomenon or splanchnic sparing effect, which was not found to be associated with development of neonatal necrotizing enterocolitis.
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