J.C.P. Kingdom

Elaboration of stem villous vessels in growth restricted pregnancies with abnormal umbilical artery Doppler waveforms

Objective To assess the elaboration of placental stem villous vessels from pregnancies complicated by intrauterine growth restriction (IUGR) with absent end–diastolic flow velocity detected prior to delivery in the umbilical artery.

Villous Development and the Pathogenesis of IUGR

Successful human pregnancy depends upon a coordinated series of events in developmental biology - not only of the embryo, but also of the placenta. The initial events in placentation involve the formation of a spheroidal trophoblastic shell that functions as a barrier to the diffusion of oxygen during embryogenesis until the end of the first trimester (see Chs 6,12 and [1]). By contrast the embryonic placental circulation perfuses the placental villi from 7 postmenstrual weeks of gestation. Diffusion of oxygen to the embryo appears less important in these circumstances, which is in marked contrast to the situation in the third trimester when adequate oxygen transfer to the fetus depends on well-developed uteroplacental and fetoplacental vascular beds. This chapter describes the development of placental villi during normal pregnancy, leading to a discussion of the evidence supporting the concept of villous maldevelopment in IUGR. For more detailed discussion of this topic the reader is referred to one of the following specialised texts [2–4].

Atrial natriuretic peptide counteracts the vasoconstrictor effects of 5-hydroxytryptamine, U46619 and endothelin-1 in the human umbilical artery

A role for atrial natriuretic peptide (ANP) in maintaining low vascular resistance within the fetoplacental circulation was investigated using isolated strips of human umbilical artery (HUA). Physiological levels of ANP significantly reduced the isometric contractile response of the HUA to U46619 (a stable thromboxane A2 mimetic), to 5-hydroxytryptamine and to endothelin-1, though no effect on agonist sensitivity could be demonstrated. These data suggest that ANP may modify vascular tone in vivo thereby counterbalancing several humoral factors which act to increase vascular resistance within the fetoplacental circulation.

Contractile responses of the human umbilical artery from pregnancies complicated by intrauterine growth retardation

The contractile properties of the umbilical artery to oxygen, U46619 (a stable thromboxane A2 mimetic) and 5-hydroxytryptamine (5-HT) were studied in normal term (> or = 37 weeks) and preterm (< 34 weeks) pregnancies, and in a group of pregnancies complicated by intrauterine growth retardation (IUGR). Isometric contractile responses in the preterm group to oxygen were reduced when compared with the term group, though no differences were found between these groups in the responses to either U46619 or 5-HT. In the IUGR group the responses to oxygen did not differ from gestationally matched normal pregnancies, though among those cases delivered preterm, the finding of absent end-diastolic flow velocity in the umbilical artery prior to delivery was associated with markedly diminished responses to oxygen. These data indicate the development of oxygen-induced contractions in the umbilical artery as pregnancy advances, which may fail to function in the severely growth-retarded fetus.