Roger K. Freeman

Advanced maternal age: the mature gravida.

A 3-year study of women ages 35 years and older who were delivered at Womens Hospital of Long Beach from January 1, 1981, to December 31, 1983, was performed to study the risks involved with advanced maternal age. The study group included 1023 women who were 35 years and older, and they were divided into parous and nulliparous groups. A control group consisting of 5343 women aged 20 to 25 years was used for comparison. Each group was analyzed for the following parameters: pregnancy complications, labor complications, delivery factors, and neonatal outcome. The results show very few statistical differences in the factors analyzed. On the basis of this 3-year study it appears that pregnancies in women of advanced maternal age in the 1980s who are delivered in a modern tertiary care center may be of no higher risk for adverse outcome than pregnancies in younger parturients.

Clinical experience with the oxytocin challenge test

Abstract The oxytocin challenge test may provide information regarding fetal well-being which is helpful to the obstetrician. In this study, there were 65 negative tests on 43 patients, and those fetuses with negative tests uniformly did well, if there were no congenital anomalies or complications in the mechanics of delivery. There were 21 positive tests on 15 patients. A positive test was significant in that it confirmed the clinical impression that the fetus was existing in a markedly unfavorable environment, heralded a fall in maternal estriol excretion and, in 3 instances, signified impending intrauterine death. Loss of beat-to-beat variability of the fetal heart rate may increase the ominous prognosis of a positive test. In instances where the 24 hour urinary estriol excretion is chronically low and therefore of questionable value in timing delivery, the test provides a physiologic stress to the fetus, the response to which may reflect the degree of fetoplacental respiratory reserve. Or, when a positive oxytocin challenge test occurs in the face of normal 24 hour estriol production, the likelihood of subsequent fetal deterioration seems high.

Clinical experience with the amniotic fluid lecithin/sphingomyelin ratio

Abstract Amniotic fluid lecithin/sphingomyelin (L/S ratios were measured in 425 pregnancies and restrospectively correlated with neonatal pulmonary performance. L/S ratios of 2.0 and greater, a value reached at about 34 weeks of gestation, were associated with 3.7 per cent morbidity from idiopathic respiratory distress syndrome (RDS) and a 0.3 per cent mortality rate from hyaline membrane disease (HMD) among 347 newborn infants. A 63 per cent morbidity from RDS and 23 per cent mortality rate from HMD, however, were found among 48 newborn infants delivered within 72 hours of having an L/S ratio of less than 2.0. The association of an L/S ratio greater than 2.0 with a low incidence of RDS and virtual absence of HMD substantiates the value of this method as a predictor of fetal pulmonary maturity.

Estriol in pregnancy: IV. Normal concentrations, diurnal and/or episodic variations, and day-to-day changes of unconjugated and total estriol in late pregnancy plasma☆

Normal values of unconjugated, total, and immunoreactive (measured without extraction) plasma estriol (E3) have been determined from radioimmunoassay data obtained in 217 uncomplicated third-trimester pregnancies. Small but significant diurnal variations in unconjugated and total plasma E3 have been observed in a study comprising 12 women who were hospitalized during late pregnancy for diabetes, toxemia, or placenta previa. The late morning decreases in unconjugated and the afternoon/evening decreases in total plasma E3 concentrations, averaging some 10 to 15 per cent, were overshadowed by considerable episodic fluctuations and may thus be clinically irrelevant. Day-to day changes of unconjugated and total plasma E3 concentrations in late pregnancy were similar and smaller than changes in urinary E3 measurements. The urinary E3/creatinine ratio, however, reducing inadequacies of 24 hour urine collections, varied less than unconjugated or total plasma E3. The data suggest that a decrease in unconjugated or total plasma E3 must exceed 40 to 45 per cent of the mean of the three preceeding determinations if it is to be considered a signal of fetal distress.

Baseline fetal heart rate characteristics as an indicator of fetal status during the antepartum period

A retrospective study was designed to determine whether the baseline fetal heart rate (FHR), recorded before oxytocin infusion, would have any correlation with the outcome of the oxytocin challenge test (OCT).

Lecithin/sphingomyelin ratio in pregnancies complicated by diabetes mellitus

The amniotic fluid lecithin/sphingomyelin (L/S) ratio was determined in 182 pregnancies complicated by Classes B and C diabetes and in 28 patients with Classes D, F, and R diabetes. These data were retrospectively correlated with the occurrence of the respiratory distress syndrome (RDS) or hyaline membrane disease (HMD). Only four cases of RDS and two cases of HMD were observed in 200 patients with an L/S ratio of 2.0 or greater prior to delivery. This 3 per cent incidence of complications is no higher than that of the nondiabetic population in our institution. Seven of 10 neonates with an antenatal L/S ratio of 1.5 to 1.9 developed RDS. An L/S ratio of 2.0 or more appears to be reliable predictor of fetal pulmonary maturity even in pregnancies complicated by diabetes mellitus.

Estriol in pregnancy: II. Daily urinary estriol assays in the management of the pregnant diabetic woman

Abstract Some 1,300 daily 24 hour urinary estriol (E3) and creatinine (C) determinations were carried out in 60 hospitalized pregnant diabetic women. Pregnancy was allowed to continue until spontaneous labor ensued unless there were signs of fetal jeopardy, based upon a significant drop in E3 excretion, or maternal indications. There were no intrauterine fetal deaths, and only one neonatal death occurred during this nonintervention policy. Patient-to-patient differences in E3 excretion were greater among diabetic gravidas than in normal women. In diabetic patients there was only a fair correlation between E3 excretion and birth weight (r = 0.41). Day-to-day variations of E3 excretion were appreciable, averaging 15.7 per cent. A decrease in E3 excretion was judged “significant” when this drop exceeded 35 per cent of the mean E3 excretion of the 3 preceding days and when this drop also was paralleled by a concomitant fall in the E3/C ratio. By these criteria, E3 excretion fell “significantly” in 14 of the 60 pregnancies studied. Had E3 been determined only twice weekly, 9 of these 14 falls would have been missed or detected with delay. In pregnant diabetic subjects, urinary E3 assays should be carried out daily if the obstetric management is based upon E3 determinations.

Antenatal Testing – A Reevaluation: Executive Summary of a Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop

In August 2007, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health Office of Rare Diseases, the American College of Obstetricians and Gynecologists, and the American Academy of Pediatrics cosponsored a 2-day workshop to reassess the body of evidence supporting antepartum assessment of fetal well-being, identify key gaps in the evidence, and formulate recommendations for further research. Participants included experts in obstetrics and fetal physiology and representatives from relevant stakeholder groups and organizations. This article is a summary of the discussions at the workshop, including synopses of oral presentations on the epidemiology of stillbirth and fetal neurological injury, fetal physiology, techniques for antenatal monitoring, and maternal and fetal indications for monitoring. Finally, a synthesis of recommendations for further research compiled from three breakout workgroups is presented.

Estriol in pregnancy. V. Unconjugated and total plasma estriol in the managements of pregnant diabetic patients.

Abstract Sixty-two consecutive diabetic women hospitalized from one to eight weeks prior to delivery were included in this study. Some 1,100 simultaneous unconjugated plasma estriol, total plasma estriol, 24 hour urinary estriol, and creatinine assays were performed on an almost daily schedule. Clinical management was based upon a weekly oxytocin challenge test and daily 24 hour urinary estriol and creatinine determinations. Twenty patients had spontaneous onset of labor and 32 were delivered electively at 38 weeks while three were delivered for maternal and seven for fetal indications. Gestational age at delivery averaged 38 weeks and ranged from 35 to 42 weeks. A total of 840 day-to-day variations of unconjugated plasma estriol, total plasma estriol, and the urinary estriol/creatinine ratio were computed as the per cent rise or fall from the highest mean of three consecutive preceding values. Observed were 369, 419, and 428 decreases in unconjugated plasma estriol, total plasma estriol, and urinary estriol/creatinine, respectively, averaging 12.8 ± 9.6 (S.D.), 13.4 ± 10.1, and 14.4 ± 10.6 per cent. One stillbirth occurred, which was preceded by a 42 per cent decrease in unconjugated plasma estriol but unheralded by either a drop in total plasma estriol or the urinary estriol/creatinine ratio. There were fewer falls of more than 40 per cent unassociated with perinatal morbidity and death with unconjugated plasma estriol (No. = 3) than with total plasma estriol (No. = 8) and urinary estriol/creatinine (No. = 8). These data suggest that unconjugated plasma estriol is the most predictive test among presently available estriol assays for managing the pregnant diabetic patient.

Estriol assays in obstetrics

Abstract Estriol-6-(O-carboxymethyl) oxime (E 3 -6-CMO) and estriol-4-azobenzoic acid (E 3 -4-ABA) were coupled to BSA and compared with regard to antigenicity and antiserum specificity as well as suitability for radioimmunoassay (RIA) of unconjugated and total plasma estriol (E 3 ) and, if possible, of immunoreactive E 3 in unextracted plasma. Anti-E 3 titers were consistently higher in response to E 3 -6-CMO-BSA than to E 3 -4-ABA-BSA. Antisera against E 3 -6-CMO-BSA cross-reacted up to 220% with 6-oxoestriol, but exhibited ring D specificity comparable to that observed with sera against E 3 -4-ABA-BSA which cross-reacted with estriol-3-sulfate (E 3 -3S) and estriol-3-glucosiduronate (E 3 -3G) considerably more than E 3 -6-CMO-BSA antisera. RIAs for unconjugated and total E 3 in third trimester pregnancy plasma were established utilizing either type of antiserum for unconjugated E 3 . The specificity of both types of antisera sufficed to render purification of E 3 extracts prior to RIA superfluous. Anti-E 3 -4-ABA-BSA sera facilitated the RIA of immunoreactive E 3 in 10 μl of unextracted plasma measuring unconjugated E 3 plus E 3 -3S and E 3 -3G. All three assays could be performed with an inter-assay coefficient of variation of 10% or less. Normal values for unconjugated and total plasma E 3 , measured in 300 women with uncomplicated pregnancies, averaged 6.9, 10.7 and 16 ng/ml and 98, 135 and 196 ng/ml at 30–32, 33–36 and 37–40 weeks of gestation, respectively. Unconjugated E 3 averaged 8.8% of total plasma E 3 concentrations. Immunoreactive plasma E 3 concentrations, on the average, were 6 times larger than unconjugated E 3 and amounted to about 50% of total plasma E 3 levels.