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To determine the influence of the autonomic nervous system on the circulation of normal and growth-retarded fetal lambs we measured the responses of heart rate and arterial blood pressure to parasympathetic (atropine 0.2 mg/kg) and beta-adrenergic (propranolol 1.0 mg/kg) blockade in the last quarter of gestation. The heart rate response to parasympathetic blockade increased with gestational age in both normal and growth-retarded fetuses but in the growth-retarded fetuses there was a significantly greater response to parasympathetic blockade than in control fetuses from 121 days' gestation to term. The heart rate response to beta-adrenergic blockade did not change with gestational age in normal fetuses. From 131 days' gestation to term the heart rate response to beta-adrenergic blockade in growth-retarded fetuses was significantly higher than in normal fetuses. The systemic arterial blood pressure responses to parasympathetic or beta-adrenergic blockade were similar in growth-retarded and normal fetuses. These results indicate an increased parasympathetic and beta-adrenergic influence on the heart of fetuses whose growth has been retarded. It may also suggest a more generalized increase in parasympathetic and sympathetic tone affecting other organs and systems in the growth-retarded fetal lambs.

A study to measure the pressor activity which is generated in incubated plasma of pregnant and nonpregnant rabbits was performed by means of a recently modified bioassay technique. It was found that plasma of normal pregnant rabbits generated significantly higher amounts of active pressor principle (APP) than those generated by plasma of nonpregnant rabbits. The possible relevance of these results to blood pressure regulation during normal and abnormal pregnancies is discussed.

We studied the fetal pituitrary-adrenal axis in 9 growth retarded fetal lambs by serially measuring plasma glucocorticoids and ACTH concentrations from 115 to 140 days of gestation and adrenal blood flow at 138 days of gestation. At each gestational age period studied, plasma glucocorticoid and ACTH concentrations were similar in both growth retarded and control fetuses (Figs. 1, 2). However, ACTH concentration tended to be higher in the last 20 days of gestation in the growth retarded fetuses. This resulted in a significantly lower glucocorticoid/ACTH ratio between 121 to 130 days of gestation in the growth retarded fetal lambs as compared to the control fetuses (212 +/- 111 vs. 1042 +/- 257). The glucocorticoid/ACTH ratio in the growth retarded fetuses became similar to the ratio of the control fetuses at 131 to 140 days (445 +/- 145 vs. 554 +/- 182). Adrenal blood flow was significantly increased at term in the the growth retarded fetuses (535 +/- 87 vs. 302 +/- 40 ml/min/100g). These data indicate that the pattern of maturation of the fetal adrenal gland in the growth retarded fetal lamb is similar to that of the normal sized fetus. Because of the increased adrenal blood flow observed at 138 days of gestation, there is a suggestion of a decreased sensitivity to ACTH in these animals.

The changes in cardiac output, pulse rate, mean arterial pressure, and mammary blood flow were observed during pregnancy and nursing in a chronically instrumented rabbit preparation. Nursing and suckling were found to be associated with significant changes in cardiac output and mammary blood flow. These changes included a progressive increase in cardiac: output during pregnancy. In addition, nursing animals had a significantly higher cardiac output than did nonnursing animals. Mammary blood flow was found to increase significantly prior to delivery and reached peak values at 2 weeks after delivery. The relationship between these changes and variables such as litter size, hormonal status, and puerperal stage is discussed in light of the possible physiologic mechanisms which control adaptation during nursing.

Lactate and pyruvate concentration differences across the fetal umbilical circulation and the maternal uterine circulation were measured in a chronic sheep preparation. Significant gains in lactate in both the fetal and maternal circulations were observed. The lactate taken up by the fetus would account for 32% of fetal oxygen consumption if oxidized. There was no significant change in pyruvate concentration across the fetal umbilical circulation; however, pyruvate was gained by maternal uterine blood.

The changes in the maternal circulation following administration of ritodrine hydrochloride were investigated in chronically prepared pregnant sheep. Low infusion rates of ritodrine (see text) elevated the maternal heart rate and cardiac output and decreased peripheral vascular resistance. Stroke work fell while minute work increased. The distribution of uterine blood flow did not change, as measured with microspheres. Simultaneously measured fetal cardiac output and umbilical blood flow were not altered. When ritodrine infusion rates (see text) were increased there was a slight but significant decrease in uterine perfusion pressure, and an increase in uterine vascular resistance with uterine blood flow decreasing. These changes were observed when the ewes were not in labor, and similar changes were again recovered with ewes in labor despite the simultaneous inhibition of uterine contractions. Selective beta blockade with practolol during ritodrine administration decreased the maternal tachycardia without affecting cardiac output, peripheral vascular resistance, or uterine vascular resistance.

To determine the association between levels of major basic protein and onset of preterm labor, plasma levels of major basic protein were measured in 13 women from weeks 22 to 41 of gestation. Twelve of the 13 women studied experienced spontaneous onset of labor. All of these women demonstrated a late rise in serum levels of major basic protein characterized by an increase in concentration of 156% ± 14%. A temporal association between a rise in concentrations of major basic protein and the onset of preterm labor, which was successfully treated with tocolytic agents, was observed in three patients. Increases in major basic protein began 3 to 4 weeks before delivery. The rise in levels of major basic protein was absent in one patient who was delivered of her infant at 30 weeks' gestation after induction of labor with oxytocin. Analysis of these data indicate that a protein marker is associated with the onset of human labor not only at term but also preterm.

There has been an awareness throughout the history of civilization that runting may occur in various animal species, particularly those of a polytocous reproductive nature. However, it was only three decades ago that McBurney helped focus attention on the problem of human fetal growth retardation with his manuscript entitled The Undernourished Full—Term Infant. 1 He reported his observations of 69 term infants born with birth weights less than 2500 g, thus introducing the concept of fetal intrauterine growth retardation. However, little attention was paid to aberrations of fetal growth until 1963 when Gruenwald presented his concept of chronic placental insufficiency2 and Lubchenco defined a small—for—date infant [small—for—gestational—age (SGA) infant] as one whose birth weight is below the 10th percentile for a specific gestational age.3 Gruenwald’s and Lubchenco’s reports initiated a surge of interest in intrauterine fetal growth retardation (IUGR), and it quickly became evident that there was an attendant increased morbidity and mortality for the fetus, neonate, and surviving adult. The overall effect of these investigations was to stimulate research in the broader disciplines of fetal growth and development.

It is now well recognized that a priming agent without untoward effects on mother or fetus is highly desirable when an indicated induction is required in the face of an unripe cervix. There appears to be a potential role for Laminaria, estrogens, relaxin, and various forms and routes of administration of prostaglandins because efficacy has been reported with all of these methods. With careful selection of patients and judicious fetal monitoring, there are multiple reasonable modes available, although an ideal priming agent has not yet emerged.

This report describes a procedure for investigation of the pathophysiology of fetal growth retardation in the sheep. In ewes with single fetuses (96 to 125 day's gestation) a polyvinyl catheter was inserted into a distal branch of the uterine artery supplying the pregnant horn and cdvanced retrograde to the main uterine artery. Catheters were also placed in fetal blood vessels. Gradual embolization of the uteroplacental vascular bed was accomplished by injecting carbonised microspheres, 15 μ in diameter, into the uterine artery daily, if fetal blood gases were normal. When compared with control fetuses, the embolication group showed a mean decrease of 30 per cent in weight, variable decreases in certain organ weights, and a significant increase in the brain-to-liver weight ratio. In the embolization group, mean fetal Po 2 decreased 11 and 18 per cent, respectively, in each of the last two weeks of the study.

A rapid, simple inexpensive test has been devised to determine whether pulmonary surface-active material (surfactant) is present in amniotic fluid. The test depends on the ability of the pulmonary surfactant to generate stable foam in the presence of ethanol. Analysis of 138 samples of amniotic fluid showed that an appreciable titer of the surfactant appears on the average at 33 weeks' estimated gestation but that the time of appearance is variable from 25 weeks to term. When test results were sorted into three zones (clearly negative, intermediate, and clearly positive) infants of 12 of 12 patients with clearly negative tests had severe respiratory-distress syndrome or transitional respiratory distress, whereas those of 68 of 68 patients with clearly positive tests were free of respiratory distress. In 13 cases with intermediate tests eight of the infants showed mild to severe respiratory difficulty. The test has high predictive value for respiratory-distress syndrome when applied to uncontamina...

A sheep preparation was developed for studying fetoplacental and neonatal blood volumes using isotope dilution techniques. Fetoplacental blood volume was measured in 46 fetal lambs (gestational age 112 to 146 days) using radioactive iodinated human serum albumin ( 125 I-RISA). In 28 of the 46 animals, blood volume was also computed using 125 I-RISA and maternal red cells labeled with radiochromium ( 51 Cr). Blood volume averaged 156.1 ml/kg of fetal weight with the single-label method and 134.7 ml/kg with the double-label method. Blood volumes measured in 17 neonatal lambs with the single-label technique averaged 110.0 ml/kg, and with the double-label technique in 10 animals averaged 104.0 ml/kg. Placental blood volume, determined by subtracting the neonatal blood volume from the fetoplacental blood volume, although varying from animal to animal, was independent of fetal weight and remained relatively constant during the last fourth of gestation.

The cardiovascular effects of alphaMSH and related peptides have not been studied extensively. Although there are some observations of adult animals, no studies have been conducted of the fetal and neonatal circulation. Therefore we examined the responses to an i.v. bolus of 75 micrograms of alphaMSH on heart rate (HR) mean arterial pressure (MAP), aortic blood flow (ABF), and stroke volume (SV) in 9 newborn lambs (15 to 27 days) and in fetal sheep (110 to 133 days gestation). An increase in ABF and decrease in MAP was observed following alphaMSH injection in the fetus (140 ± 38 to 158 ± 40 ml/Kg/min, p 0.005 and 41.7 ± 1.8 to 39.0 ± 1.6 mm Hg p 0.0125 respectively) (mean ± SE). There was no significant modification of fetal HR or SV. In the newborn, there was an increase in ABF (257 ± 25 to 326 ± 33 ml/Kg/min, p 0.005) and HR (106 ± 8 to 122 ± 10 beats/min, p 0.005) and a decrease in MAP (73 ± 4 to 69 ± 5, p 0.005) after alphaMSH injection. There was no modification of the SV in the newborn lamb. Beta blockade with propranolol (lmg/Kg) did not prevent the rise in ABF and HR observed after the same dose of alphaMSH in the newborn lamb. These results indicate that alphaMSH is able to increase the left ventricular output in the newborn and fetal sheep and its mechanism of action is not through beta adrenergic receptor (Supported by NIH Grant HLO6285 and HD06619).

IUGR fetal lambs with chronic hypoxemia are particularly susceptible to additional acute stress. We therefore studied the cardiovascular responses of 6 IUGR fetuses to superimposed acute hypoxemia. IUGR was produced by daily embolization of the uteroplacental vascular bed. Additional acute fetal hypoxemia (PaO211 torr) was produced by the ewe breathing a 10% O2,and nitrogen gas mixture. Fetal cardiac output (CO) and its distribution was measured using radioactive microspheres. Basal umbilical blood flow (Q) was reduced in the IUGR fetuses (132±18 ml · min-1 · kg-1; mean ± SE), and kidneys, and adrenal Q (ml × min-1 × 100 g-1) elevated. During the acute hypoxemic episodse, Q increased to myocardium (478 ± 209 to 732 ± 248) and to the brain (238 ± 79 to 295 ± 69) with a trend to further increase in adrenal blood flow (588 ± 88 to 1001 ± 329). These increased organ Q changes were similar to those occurring in normal fetuses but reached greater absolute levels.There was also a decrease in Q to the gut, kidneys and carcass, but no change in CO nor the depressed umbilical Q. The Q to the carcass in the IUGR fetus during acute hypoxemia is greater than the Q observed in the normal fetus. The inability of the IUGR fetus to increase their abnormally low umbilical Q, plus its inability to reduce the carcass Q,as the normal fetus does, may account for the increased mortality rate observed in the IUGR fetus under acute hypoxemia.

During the past ten to 15 years, maternal-fetal medicine has seen the publication of several books aimed at providing the subspecialist with a comprehensive text/reference work. These attempts, however, have more often than not missed the mark because of incomplete content, inadequate depth beyond that found in textbooks of obstetrics, excessively specialized chapters by multiple contributors focused on their own research, or a nonobstetric perinatal perspective. Contrary to their predecessors, Creasy and Resnik have masterfully encompassed the boundaries of the subspecialty in their textbook, Maternal-Fetal Medicine: Principles and Practice . This work is logically separated into four parts: early fetal development and the environment, diagnostic modalities in maternal-fetal medicine, maternal and fetal pathophysiology, and the neonate. Each part is subdivided into chapters written by leaders in the field, many of whom are both scientists and practicing academic obstetric perinatologists. The flavor is, therefore, distinctly practical with as firm a basis in

Growth retarded fetuses are considered to be under chronic stress due to lack of oxygen and nutrients. Since FGR lambs have proportionally a large adrenal weight and a small thymus, both suggestive signs of increased adrenal activity, we measured the total corticosteroid levels in this syndrome. Growth retardation was produced in 7 chronically catheterized fetal lambs by embolization of the maternal uterine bed with non radioactive microspheres. Fetal femoral artery pH was (mean±SE) 7.38±0.008; PO2 18.41±0.61 torr; PCO2 46.62±1.19 torr and hematocrit 36.64±0.68%. Total corticosteroid was measured by RIA serially in fetal femoral arterial plasmas from 113 to 141 days gestation. Mean corticosteroid concentration (ng/ml) in FGR lambs were 4.92±1.0 (n=10), 7.44±1.3 (n=11), 20.75±5.42 (n=17) at 110-120, 121-130 and 131 to 141 days gestation respectively. These values are not significantly different from control animals, (5.21±1.02, n=10; 7.22±0.75, n=5; 13.75±3.12, n=4; respectively). These results indicate that placental embolization enough to cause fetal growth retardation is not a stimulus for enhanced fetal adrenal activity nor accelerates fetal adrenal maturation.

In Reply. — We agree with Dr Goodlin's statement that "an obstetrician's primary obligations are to the mother." In the rare case, such as the one we reported, in which the mother is dead but the fetus remains alive, existing maternal requests should not by themselves dictate management. Fetal and neonatal benefit should be the primary concern. The case that Dr Goodlin cites is one in which refusal of surgical intervention by a living, though terminally ill mother was overridden by the courts.1This represents a clear violation of the autonomy of the pregnant woman. Two interesting hypothetical scenarios are presented by Drs Wear, Dillon, and Lee. The first of these concerns the case in which "the family refuses maintenance when extended support... would markedly enhance... fetal survival." While acknowledging that in most cases the father of the fetus will be the appropriate decision maker after death of the

A prospective, interinstitutional comparative trial was undertaken to examine the efficacy, safety, and pharmacodynamics of different administration routes of ritodrine hydrochloride for the management of preterm labor. Forty-five subjects between 20 and 36 weeks' gestation received either intravenous (n = 24) or intramuscular (n = 21) therapy. Successful tocolysis occurred in 14 of 21 (67%) patients in the group treated intramuscularly and in 16 of 24 (67%) patients in the group treated intravenously. A greater mean dose (8.6 versus 3.3 mg/hour) and a higher mean serum concentration (38.9 versus 24.7 micrograms/ml) were needed to achieve successful tocolysis in the intravenous group as compared with the intramuscular group. Patients who did not respond to tocolytic therapy in both groups had levels of ritodrine in the blood either equivalent to or greater than those of subjects who were successfully treated. Analysis of ritodrine levels in the successfully treated intramuscular group demonstrated significant differences in blood levels depending on muscle group used. These differences can be at least partially attributed to higher mean doses administered to patients receiving vastus lateralis injections as compared with those receiving gluteal muscle injections. The results suggest that intramuscular administration of ritodrine is an efficacious and safe route of drug delivery. Additional studies are needed to better define dose-response curves for the intramuscular administration of ritodrine hydrochloride.