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Whether fetal breathing movements or gasping result in the movement of amniotic fluid substances into the distal airways remains controversial. We evaluated the effect of paralysis of the preterm rabbit fetus on the pulmonary distribution of iron dextran.Laparotomy was performed on 10 New Zealand White rabbits of 25 days' gestation (term 31 days) under general anesthesia. Fetuses in one uterine horn were given an intramuscular injection of pancuronium (1.5 mg/kg) and fetuses in the other horn were given an equal volume of normal saline solution as controls. A 1 ml volume of iron dextran (100 mg/ml) was injected into the amniotic sac of all fetuses. The laparotomy was closed, and 20 to 24 hours later the fetuses were removed by hysterotomy and assessed for paralysis. Necropsy was performed. Lungs were stained with prussian blue and evaluated histologically for the presence of iron.A total of 92 pups were delivered (49 given pancuronium, 43 given normal saline solution), of which 64 were born alive. There were no differences between groups for live births (31 pancuronium, 33 normal saline solution), pup body weight, or lung weight. Pups given normal saline solution demonstrated more breathing motions, spontaneous movement, and brown (color of iron dextran) stomach contents than did the pups given pancuronium (p0.001). At necropsy a greater number of control pups (31/33) had brown lungs grossly compared with pups given pancuronium (2/31, p0.001). Lung histologic examination showed that more control pups (29/29) had iron in the trachea and main bronchi compared with pancuronium pups (0/27, p0.001), and more control pups (29/29) had iron in the distal lung airways compared with pancuronium pups (0/27, p0.001). With use of the Optimas Image Analysis System, iron in the lungs of control pups was found to be equally distributed between right versus left lungs, upper half versus lower half lungs, and anterior versus posterior lung sections. More iron was identified in the central airways than in the periphery (p0.001).We conclude that paralysis prevents the uptake of iron dextran into the main and distal airways of the rabbit fetus. Although lung fluid production results in a net efflux of fluid, we speculate that fetal breathing movements can result in the movement of fluid into distal airways and potentially provide fetal therapy.

D espite concerted efforts toward prevention, accurate and p r o m p t diagnosis, and effective t rea tment o f p re t e rm labor, the incidence of p r e t e rm birth has not decreased over the last several decades. In fact, a l though the search for a highly effective, well tolerated tocolytic has been actively pursued, data f rom the United States indicate that the incidence o f p re t e rm birth has actually increased, f rom 9.4% to 10.7% between 1981 and 1989.1 This review will discuss the mechanism o f action o f various tocolytic drugs, some o f the problems inherent to clinical studies o f these agents, and the clinical efficacy and side effects o f commonly used tocolytics such as betaadrenergic agonists, magnesium sulfate, and prostaglandin synthesis inhibitors. Agents that have been less well investigated as tocolytics, including calcium channel blockers, oxytocin recep tor antagonists, and potassium channel stimulators, will also be discussed, but more briefly. P re te rm birth remains the leading cause of perinatal mortali ty and morbidity among nonanomalous infants. In a mult icenter study o f 33,401 neonates, 83% of neonatal deaths occurred in infants born at less than 37 weeks' gestation, and 66% of neonatal deaths occurred in infants born at less than 29 weeks' gestation. 2 However , the neonatal survival rate after 30 weeks' comple ted gestation is more than 90%. Therefore , a t tempts at inhibiting p re t e rm labor between 20 and 29 weeks' gestation are directed at improving the neonatal survival rate and reducing morbidi ty incidence, whereas at tempts at inhibition between 30 and 36 weeks are mainly directed toward reducing neonatal morbidity incidence. 3 In an assessment o f the effect of gestational age on neonatal morbidity, the incidence of respiratory distress was increased until 36 comple ted weeks o f gestation, whereas other

Objective: The purpose of this study was to review the current approaches to preventing preterm delivery. Study Design: The problem of preterm birth was assessed by reviewing the different components that play a role in preterm birth prevention, excluding infection, antibiotic treatment, and tocolytic treatment. Results: Prevention of preterm labor must initially discriminate those at risk. Positive predictive values of various approaches are currently not adequate enough to warrant intervention. Prevention modalities, in part because of poor prediction, are mostly unproved. Accurate diagnoses of preterm labor remains difficult and confuses analyses of tocolytic agents. Cervicovaginal fetal fibronectin, perhaps in combination with cervical evaluation, shows promise. Early detection programs remain controversial, but most reviews indicate that daily patient contact with high-risk patients gives cause for some optimism. Antenatal maternal glucocorticoid treatment at specific gestational ages improves neonatal outcome. Conclusion: The incidence of preterm birth is rising in the country. However, improved definition of the various components of the problem has provided an improved understanding of the problem. There is a new continuing effort and a search for new and innovative ways to address this vexing national problem.

Objectives: This study details the incidence, by gestational age and birth weight, of specific neonatal morbidities in singleton neonates without major congenital anomalies. Study Design: Data were prospectively collected on all deliveries at five tertiary centers in the United States during the years 1983 through 1986. Pregnancies were meticulously dated and the gestational ages of the neonates at delivery were confirmed by Dubowitz score. Results: The incidence of respiratory distress syndrome gradually decreases with increasing gestational age until 36 weeks. A marked decrease in the incidence of necrotizing enterocolitis, patent ductus arteriosus, intraventricular hemorrhage, and sepsis occurs after 32 completed weeks. The number of days of mechanical ventilation for respiratory distress syndrome and newborn stay in the tertiary care facility also were significantly reduced after 32 weeks. Conclusions: The incidence of both respiratory distress syndrome and patent ductus arteriosus is markedly decreased by both increasing gestational age and birth weight. The incidence of grade III and IV intraventricular hemorrhage, necrotizing enterocolitis, and sepsis virtually vanishes after 34 weeks. These data relating neonatal morbidities to gestational age are important to the obstetrician in the critical decision regarding the timing of delivery and to the parents, who can benefit from a realistic prediction of the neonatal course.

Patient and staff education concerning the subtle signs and symptoms that precede a clinical diagnosis of preterm labor have not been well established. Therefore we interviewed 100 patients for the presence or absence of various symptoms and signs during the 7 days preceding diagnosis of preterm labor. An additional 100 patients without preterm labor matched for gestation were chosen at random as control subjects. A history of increased uterine contractions, menstrual cramps, constant backache, constant pelvic pressure, increased amount and consistency and color change of vaginal discharge, and increased frequency of urination were present with a statistically significant higher frequency in patients with preterm labor compared with controls. Twenty-nine percent of patients did not report any uterine contractions and only half described them as painful. Fewer than 50% of the women reported contractions as frequently as every 10 minutes or more.

Severe cardiovascular complications occurred in eight of 160 patients treated with terbutaline for preterm labor. Associated corticosteroid therapy and twin gestations appear to be predisposing factors. Potential mechanisms of the pathophysiology are briefly discussed.

The distribution of uterine blood flow (UBF) in the chronically instrumented pregnant term rabbit was examined before and after indomethacin infusion. A significant fall in placental but not myometrial blood flow was observed. The fall in placental blood flow was significantly higher in placentas which were implanted in the midsection of the uterine horn than in those implanted in both ends of the horn. The results suggest that different physiologic mechanisms may regulate the blood flows in the placenta and the myometrium.

In previous studies, both purified porcine relaxin and prostaglandin F2 alpha, have been applied vaginally in the human to promote cervical ripening near term. In this study, the histologic changes in the cervix induced by these locally applied hormones are described in a rabbit model. Similar histologic changes occurred following treatment with relaxin or prostaglandin F2 alpha and these changes were comparable with those seen in the cervix following the spontaneous onset of labor in control rabbits. The main histologic features were a dissolution of the collagen bundles and an apparent increase in the ground substance. However, a unique giant cell infiltrate was seen in the relaxin-treated rabbits and the control rabbits in spontaneous labor. The nature and possible function of these giant cells are discussed. The similarity of the general morphologic changes in the cervix induced by relaxin and prostaglandin F2 alpha supports the concept that these hormones may act (either in sequence or separately) to activate the same collagenolytic system to produce the same effect in cervical connective tissue rather than act in parallel to produce separate or complementary structural changes.

Fifty pregnant women at term, with a cervix unfavorable for induction, were electively induced with intravenous oxytocin after priming with either oral prostaglandin E2 or a placebo. Oral PGE2 was effective in increasing the Bishop score and in inducing labor prior to the induction, but did not increase the incidence of successful inductions.50 pregnant women were included in a double-blind study aimed at determining whether oral prostaglandin E2 (PGE2) can effectively prime an unripe cervix prior to oxytocin induction of labor. Study participants ranged in age from 20-37 years and were 36-41 weeks pregnant. Patients were randomly assigned to receive either PGE2 or a placebo. 2 tablets were administered at 3 hour intervals for 3 doses. Oxytocin infusion began 9-11 hours after the 3rd dose of oral medication and was increased until adequate uterine contractions were induced. No difference in the frequency of contractions was seen in the 2 groups during priming; however, PGE2 patients showed a 2 point advance in Bishop score, which was significantly greater than the 0.7 change in the control group. The most striking finding was that 6 women in the PGE2 group, compared with 1 in the placebo group, went into active labor during the priming phase and delivered without induction. Oxytocin failed to induce effective labor in 9 patients in each group. There was no difference between the 15 control and 10 PGE2 patients successfully induced in terms of duration or dosage of oxytocin. However, the more inducible patients in the PGE2 group may have begun labor before oxytocin induction, rendering the groups less equivalent for the induction part of the study. These results suggest that oral PGE2 priming results in an easier course to delivery, although not in a higher incidence of successful induction. It is recommended that the PGE2-oxytocin induction regimen be studied in patients at various stages of induction, perhaps with an increased dosage of PGE2 or a shorter interval between dosages.

Ritodrine hydrochloride was administered parenterally to pregnant ewes during spontaneous or oxytocin-induced uterine activity. The effects of ritodrine on the uterus and cardiovasculature were assessed both with and without simultaneous administration of either alpha or beta blockade. Ritodrine was found to be an effective inhibitor of both spontaneous and induced uterine activity. Ritodrine did cause maternal tachycardia but no significant hypotension. Alpha-adrenergic blockade did not influence the effects of ritodrine. Beta blockade with propranolol reversed the uterine and cardiovascular effects of ritodrine, whereas beta blockade with practolol reversed the cardiovascular effects without interfering with the inhibition of uterine activity produced by ritodrine.

The response of the fetal circulation to beta adrenergic stimulation with ritodrine hydrochloride has been investigated by long-term monitoring of the fetal lamb in utero. Ritodrine was infused intravenously either into the ewe or directly into the fetus, and cardiovascular and acid-base responses were measured. Fetal cardiac output and its distribution were measured with the use of radionuclide-labeled microspheres. The output of each ventricle also was measured by means of long-standing implanted electromagnetic flow transducers around the ascending aorta or pulmonary trunk during infusion of ritodrine at various rates into the fetus. Infusion of ritodrine (1.9 mcg. per kilogram per minute) into the ewe caused no change in fetal heart rate, blood pressure, cardiac output, or umbilical blood flow, but did cause an increase in fetal adrenal and myocardial blood flow. Ritodrine infused directly into the fetus produced a marked increase in fetal heart rate and a minimal change in cardiac output. There were no significant changes in fetal or maternal acid-base balance during the ritodrine infusions.

Seventy patients with preterm labor and intact membranes were initially treated with ritodrine hydrochloride to delay preterm delivery. Tocolysis beyond 24 hours was achieved in 59 patients. Fifty-five of the 59 patients were then placed on either oral ritodrine or placebo as maintenance therapy in a randomized double-blind manner. If preterm labor recurred, the sequence of intramuscular and then oral treatment was repeated. The number of days gained after initiation of intramuscular treatment was similar in both groups (oral ritodrine = 34 days, oral placebo = 36 days). In those 55 patients receiving oral treatment, there was a smaller number of relapses requiring repeat intramuscular treatment in the oral ritodrine group (1.11 in the ritodrine patient vs. 2.71 in the placebo patient, p less than 0.05), and the mean interval between beginning oral treatment and the first relapse/delivery was 5.8 days in the oral placebo group and 25.9 in those receiving oral ritodrine (p less than 0.05). Cardiovascular side effects, notably maternal tachycardia and palpitations were frequent but well tolerated. The results suggest that oral ritodrine maintenance will decrease the incidence of recurrent preterm labor in patients who have had initial successful tocolysis.

Plasma concentrations of albumin and fibrinogen and arterial hematocrits were determined during the last third of gestation in growth-retarded and control fetal lambs. The mean fetal plasma albumin concentration increased slightly as term approached and was not significantly different in the two groups. The mean plasma fibrinogen concentration did not change in the control fetuses, but was significantly elevated in the growth-retarded fetuses, as was the mean arterial hematocrit. The theoretical implications of these findings relative to capillary blood flow are discussed.

Preterm labor and delivery remain a significant problem in contemporary obstetric practice. Although the exact cause remains unclear, it is most likely to be multifactorial in nature. No satisfactory screening tool or marker currently exists to firmly establish the diagnosis of impending labor. However, epidemiologic and historical variables associated with preterm delivery show some promise in this regard and are currently being evaluated in preterm prevention programs. Appropriate management of preterm labor mandates early recognition of subtle signs and symptoms; successful therapy is dependent on this issue. The approach to the clinical management of the patient in preterm labor used at our institution is described. Therapy with beta-adrenergic receptor agonists is currently the recommended pharmacologic treatment of this disorder. A review of other tocolytic agents and their usefulness in the management of preterm labor are presented.

Cardiac output and mammary blood flow distribution prior to and after suckling were studied in 10 nursing rabbits by means of radionuclide-labeled microspheres. Suckling was followed by a 5.8% rise in cardiac output and a 20.4% rise in mammary blood flow. Determinations of intraglandular blood flow distribution have shown that there was a 43% increase in blood flow to the glands suckled from as compared to a 22.7% rise to the contralateral untouched glands and a 4.9% rise in the remainder of untouched glands. The conclusion is that a local mechanism may be involved in the regulation of mammary blood flow in the nursing rabbit.

Thirty-eight women were treated over 353 menstrual cycles with an intramuscular contraceptive preparation of 150 mg of dihydroxyprogesterone acetophenide in combination with 10 mg of estradiol enanthate. Treatment consisted of one injection “monthly”. This compound proved to be an effective antifertility agent. Persistent menstrual irregularities of varying degree, was seen in every subject followed for more than 5 cycles, and was severe enough in 26% of the study group to cause cessation of therapy. The subject acceptance of this preparation was not enthusiastic, and it seems unlikely that it will supplant other contraceptive modes for the majority of the populace.