An endocrine model for the diagnosis of intrauterine growth retardation as demonstrated by the determination of total estrogen and pregnandiol 24-hour urinary excretion in 222 at risk pregnancies.
A reliable method for surveillance of chronic impairment of nutritive placental function is described. The techniques are simple, tested for their reliability, without need for isotopes or special apparatus and hence inexpensive. Using 222 pregnancies at risk it is shown that the simultaneous determination of a fetal (estrogen) and a placental (pregnandiol) parameter makes the early diagnosis of intrauterine growth retardation possible. Estrogen diagnosis alone has a reliability of 90.1% with 1.8% falsely pathological and 8.1% falsely normal findings (Tab. I). Simultaneous pregnandiol determinations increase the number of falsely pathological findings to 8.1% but reduce that of falsely normal ones to 2.7%. No small for date (SGA) infants are found here. It consists of 5 cases of imminent (3 times actual) premature delivery and one postmature one. Hence our technique indicates the risk of intrauterine growth retardation in all cases but not the risk of premature or postmature delivery. Early diagnosis (from week 20) indicates that impairment of placental function as indicated by decreased pregnandiol excretion, occurs weeks or months earlier than decreased estrogen excretion (Fig. 1). This can be explained only by assuming that the rate of estrogen excretion is usually not dependent on the placenta but on the capacity of the fetal adrenals and liver. Thus our results indirectly confirm those of others who claim that the fetus can synthetize estrogen precursors without the need for placental pregnenolon by using acetate. Thus it appears that the synthetic pathway is independent of the placenta at the beginning plays a quantitative role also. Since the placenta can form aromatic compounds even when its nutritive function is severely impaired, our finding is further proof that estrogen excretion reflects fetal and not fetoplacental well-being. It follows that pathological estrogen excretion indicates fetal injury that has already occurred. The requirement that a sensitive parameter of placental function be hence determined in time is met by pregnandiol assays. Low pregnandiol excretion often precedes low estrogen excretion which leads to a SGA infant, indicating that pregnandiol excretion is closely correlated to placental nutritive function. Synthetic reactions in the fetus require energy and hence depend on the placenta. Normal estrogen excretion frequently observed in the presence of prolonged decreased pregnandiol excretion must hence indicate that the fetus can compensate for placental insufficiency. In the placenta this can be demonstrated by hyperplasia of the capillaries. This is reflected in the undulating excretion of pregnandiol (Fig. 1), where compensation (new vessel formation) and depression (lesion of vessels) make these contradictory placental processes "visible". The functional unity  of the fetus and the placenta is finally also demonstrated by the fact that each prolonged compensatory phase of the placenta is reponded to by the fetus with a clearly compensatory excretion of estrogen (Fig. 1)...
D000328:Adult; D004967:Estrogens / Q000652:urine*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis*; D006128:Growth; D006801:Humans; D010922:Placenta Diseases / Q000175:diagnosis*; D010925:Placental Function Tests; D010927:Placental Insufficiency / Q000175:diagnosis*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011276:Pregnanediol / Q000652:urine*; D012306:Risk
D004967:Estrogens; D011276:Pregnanediol