Tocolysis for recurrent preterm labor using a continuous subcutaneous infusion pump.

This study attempted to determine the best method of treatment for patients with recurrent preterm labor: administration of terbutaline via an automated, programmable, subcutaneous infusion pump or oral terbutaline. In this retrospective, controlled study, 32 patients diagnosed with recurrent preterm labor, as determined by persistent uterine contractions with cervical change, were treated with a programmable infusion pump adjusted to control uterine contraction frequency to < or = 4 contractions per hour. Patients in this group were matched for age, race, parity, gestational age and cervical dilation at diagnosis of recurrent preterm labor in subjects taking oral terbutaline. The patients receiving oral terbutaline were given an average of 6.5 mg every four to six hours to maintain uterine quiescence, while those in the pump group were given basal rates of terbutaline and in addition received four to six boluses per day (< 3 mg/d total dose) to achieve this outcome. Patients using the pump were more likely to reach term and less likely to fail tocolytic therapy than were those taking oral terbutaline. The terbutaline pump appeared to be more successful in prolonging pregnancies to term after the diagnosis of recurrent preterm labor than did oral terbutaline.

Placenta praevia: does uterine activity cause bleeding?

Twenty-two women > 24 weeks' gestation with a central placenta praevia were monitored to determine if an increase in uterine activity precedes bleeding in patients with central praevias. Monitoring of all subjects began at 26.3 +/- 4.4 weeks and continued until 37 weeks (or delivery if preterm). All subjects had at least one haemorrhage, 7 women had 2, and 4 subjects had 3 episodes of bleeding. Only 3 patients delivered at term while the remainder (86%) delivered preterm. The gestational age at first episode of bleeding was 29.1 +/- 3.6 weeks and at delivery was 34.3 +/- 3.3 weeks. Nine women (41%) had an increase in uterine activity above baseline the day or the day preceding the first haemorrhage. The increase in uterine activity was not statistically significant when compared to the 6 days prior to bleeding when all 22 patients were considered.

Interval to delivery in high-risk patients: do tocolytic agents really work?

Some question whether tocolytic drugs reduce uterine activity and prolong gestation. The interval from discontinuance of tocolytics until spontaneous labor and delivery in patients (n = 69) with documented preterm labor (PTL) versus subjects receiving prophylactic tocolytic therapy (n = 41) was studied. Women with documented PTL delivered sooner after cessation of tocolytics (6.1 +/- 6.9 days) than control (C) patients (14.7 +/- 10.8 days, P less than 0.001). Also, 28 of the 69 (41%) patients in the PTL group delivered within 24 h of discontinuation of tocolysis compared to 4 (10%) in the C group (P less than 0.0004). We conclude that tocolytic therapy for documented preterm labor suppresses uterine activity and when these agents are discontinued, contractions return and labor ensues.

Home uterine activity monitoring.

Despite tremendous improvements in maternal and neonatal care, preterm delivery remains the leading cause of infant mortality. Widespread use of tocolytics and aggressive preterm labor management have had little effect on reducing the overall neonatal mortality. To improve the success of tocolysis and preterm labor management, it is critical that preterm labor be diagnosed prior to significant cervical change. At present, a combination of several components is indicated for successful preterm birth prevention programs. These should include periodic risk assessment, patient education, cervical assessment, daily contact by highly skilled perinatal nurses, daily home uterine activity monitoring, and aggressive patient management. Studies support that this approach results in early detection of preterm labor, subsequently more effective tocolytic therapy and prevention of preterm birth.

Subcutaneous tocolytic infusion therapy for patients at very high risk for preterm birth.

Patients with multiple gestations or recalcitrant preterm labor are at very high risk for preterm birth in spite of adequate tocolysis. Subcutaneous infusion of tocolytic medications on an ambulatory basis has been used in several small series and has effectively prolonged gestation. This retrospective analysis presents data from 992 patients at very high risk for preterm delivery who were prescribed this therapy. The amount of tocolytic medication was individualized by utilizing the patient's volume of distribution and clearance. Pharmacists adjusted the dosage based on uterine activity strips received by nursing personnel. The average basal rate was .073 +/- .020 mg/h. Patients received an average of seven scheduled boluses per day and 1.54 +/- .93 unscheduled boluses per week (.25 +/- .03 mg each). The therapy extended the gestation a mean of 38 +/- 23 days and average gestational age at delivery was 36.3 +/- 2.6 weeks with a mean birthweight of 2759 +/- 681 g. This study, utilizing a large number of patients, confirms earlier reports that for women at very high risk for preterm delivery subcutaneous tocolytic infusion therapy is beneficial. Prospective studies evaluating such treatment on a randomized basis are indicated.

Administration of heparin by subcutaneous infusion with a programmable pump.

Heparin has a short half-life (8 to 12 hours) and therefore must be administered by continuous infusion or by intermittent subcutaneous injection. Intermittent subcutaneous injection may lead to fluctuation in the levels of anticoagulation attained. In correcting this deficiency, the programmable automated subcutaneous infusion pump in conjunction with weekly home nursing visits has been used. Eight pregnant women with documented deep venous thrombosis or embolic events before pregnancy who received such therapy were studied. Eight similar subjects who received intermittent subcutaneous injection, matched for age, parity, site of deep venous thrombosis, and days on a regimen of heparin therapy, served as the control group. The mean daily dose of heparin by subcutaneous infusion pump was higher (29,445 vs 13,822 U), resulting in smoother, more therapeutic heparinization (mean partial thromboplastin time, 20.6 vs 10.4 seconds above control) when compared with the intermittent subcutaneous injection group (p less than 0.05, p less than 0.007). There were two complications (hematoma, site infection) in the intermittent subcutaneous injection group while none occurred in the subcutaneous infusion pump group. When used in concert with weekly home visits, the subcutaneous infusion pump method of administration allowed more even control of anticoagulation, appeared to result in fewer complications (although not statistically significant), and subjectively was better received by patients than the intermittent subcutaneous injection technique.

Home uterine activity monitoring is associated with a reduction in preterm birth.

The value of home uterine activity monitoring plus perinatal nursing support in the prevention of preterm birth among high-risk patients has been demonstrated by several studies. Other reports with less stringent guidelines and less intensive nursing contact have questioned the contribution of home uterine activity monitoring and perinatal nursing support to a preterm birth prevention program. In this large, prospective, randomized multicenter study, patients were assigned to receive either daily monitoring and nursing contact or a preterm birth prevention program including intensive education and more frequent prenatal visits. Among the monitored patients, there was a significant increase in early detection of preterm labor (2 cm or less), successful tocolysis, and prolongation of pregnancy to term. Thirty-one percent of these diagnoses of preterm labor resulted from evaluation of increased uterine activity without associated patient-perceived symptoms. We conclude that a program of daily uterine activity monitoring and perinatal nursing support results in earlier diagnosis of preterm labor and subsequently more effective tocolysis.

Uterine activity compared with symptomatology in the detection of preterm labor.

The relative contribution of uterine activity obtained by home monitoring with a guard ring tocodynamometer compared with seven specific signs and symptoms reported during patient/nurse contact as an aid in detecting preterm labor has not been studied. In this prospective, multicenter study, patients at risk for developing early labor who were randomized to receive home uterine activity monitoring and perinatal nursing support were assessed. The initiator of provider contact (uterine activity detected on routine transmission, patient-perceived signs and symptoms of preterm labor during perinatal nurse contact, or both) resulting in a diagnosis of preterm labor was recorded. Contraction data were then analyzed for an association with preterm labor. There was a strong association of increased uterine activity (four or more contractions per hour) on a repeat monitoring strip with preterm labor (P less than .001). Among patients diagnosed with preterm labor, 31% had increased uterine activity detected on a routine transmission without patient-reported signs and symptoms, compared with 24% who were diagnosed as the result of patient-reported symptoms without increased uterine activity. Daily objective uterine activity data alone have greater incremental value over and above other signs and symptoms as an aid to the physician in diagnosing preterm labor.

Relationship of uterine contractility to preterm labor.

An increased uterine contraction rate is associated with preterm labor. The contraction rate in individual patients, however, has not been evaluated critically as to its predictive value in forecasting early labor. In this randomized multicenter study, 105 patients at high risk for preterm delivery monitored their contraction rate at home on a daily basis. An analysis was conducted to determine the association of at least four contractions per hour on a routine strip followed by at least four contractions per hour on a repeat tracing with subsequent preterm labor. Using this threshold, 70% of the patients were correctly classified. This contraction rate resulted in a sensitivity of 57%, a specificity of 80%, a positive predictive value of 72%, and a negative predictive value of 68%. A threshold rate of at least four contractions per hour on a remonitor strip identifies a patient at increased risk for preterm labor (P = .003).

Cost effectiveness of ambulatory uterine activity monitoring.

A cost analysis is presented comparing 34 patients who received uterine activity monitoring versus 33 patients who attempted to detect uterine activity by palpation. All patients were at high risk for preterm delivery and were given the same educational information and prenatal care regarding signs and symptoms of preterm labor. The results revealed an increase in newborn days (640) and cost to those patients who were in the self-palpation group ($13,364) compared to monitored parturients (268 days and $8,633). The difference was attributed to neonatal morbidity from an increased number of preterm deliveries greater than 26 weeks but less than 37 weeks (P = 0.04). The increase in NICU days was significant (P = 0.03). No difference in normal newborn costs for infants delivered after greater than 33 weeks could be detected between the two groups, but morbidity was increased among control infants delivering between 34 and 36 weeks. Uterine activity monitoring to prevent preterm birth appears to be medically effective and reduces cost.

Prostaglandin E2 induction of abortion and fetal demise.

Prostaglandin E2 (PGE2) suppositories have been shown to be active contractile agents and are effective in uterine evacuation for mid-trimester abortion or fetal demise. In this study, 85 patients were treated with vaginal PGE2 suppositories. When laminaria were used in patients with closed cervices, and compared to those who had minimal cervical dilatation, there was no difference in the time from induction to expulsion. Ninety-three percent of the 85 patients aborted successfully within 24 h. In each of the seven "failures", three or less suppositories were used prior to a dilatation and evacuation procedure. In this study, 81% of the abortions were complete, and in one-third of the remaining patients dilatation and curettage was performed just after delivery of the fetus. The incidence of minor side-effects ranged from 12 to 21%, and there were no major complications. It is concluded that the use of vaginal prostaglandin E2 suppositories for induction of mid-trimester abortion or fetal demise in the third trimester is safe and effective.

PIP: Prostaglandin (PG) E2 suppositories have been shown to be effective in uterine evacuation for mid-trimester abortion. At the University of Mississippi Medical Center, vaginal PGE2 suppositories have been used routinely to effect termination of pregnancies following fetal death at any age and in the majority of therapeutic abortions performed at over 14 weeks' gestation. This study evaluated the results of PGE2 treatment in 85 patients seen at the center during an 18-month period, the majority (65%) of whom were delivered because of fetal death. Prior to the procedure, 55% of these patients had a closed cervix and laminarias were inserted. The average time from induction with PGE2 to expulsion of the fetus was 9.3 hours (range, 1.4-23.2 hours), with no significant difference between the groups with and without laminaria unless the cervix was dilated more than 2 cm at the time of admission. 94% of study subjects required 3 or fewer suppositories to effect delivery. Of the 85 patients, 78 (91%) aborted successfully within 24 hours. There were no major complications; the incidence of minor side effects ranged from 12% (for diarrhea) to 21% (for hyperpyrexia). Overall, these findings suggest that medical induction using prostaglandins is a safe, convenient method of evacuating the uterus, particularly in the case of fetal death after 20 weeks. The minor side effects such as nausea and vomiting, fever, diarrhea, headache, and chills can be reduced when patients are premedicated with anti-emetics and antidiarrheal preparations. Moreover, these side effects may be further decreased by the use of newer compounds, such as the 15-methylated prostaglandins, that are believed to induce less reaction in the gastrointestinal tract.

Prevention of preterm birth by ambulatory assessment of uterine activity: a randomized study.

Tocodynamometry, used on an ambulatory basis, has been shown to detect uterine activity. The objective of this study was to assess the effectiveness of ambulatory tocodynamometry in the early identification of preterm labor. In this investigation 67 women at risk for preterm labor were randomly divided into two groups: 34 received a uterine activity monitor while 33 patients used palpation. Approximately two thirds of the study sample developed preterm labor. Upon diagnosis of preterm labor, parturients in the control group had cervical dilatation of less than 3 cm (p less than 0.001) and effacement of greater than 50% more often than the monitored group (p less than 0.01). As a result there was a significant decrease in the number of patients who responded to tocolytic therapy in the unmonitored group. Among those with preterm labor the time gained in utero was greater in the monitored group (8.2 +/- 2.7 weeks) compared to the control group (4.2 +/- 2.9 weeks) (p less than 0.05). Subsequently 29 of 34 monitored patients attained term (36 completed gestational weeks) versus only 18 of the 33 patients in the unmonitored group (p less than 0.01). Although the sample size is relatively small, uterine activity monitoring in these very high risk patients resulted in an increased number of suitable candidates for tocolysis and allowed a significantly greater percentage of women to reach term.

Plasma prolactin concentrations and pregnancy-induced hypertension.

Human prolactin (PRL) has been related to various pathologic disorders known to be associated with osmoregulation and hypertension. In this study, we compared changes in plasma PRL concentrations in normal pregnant patients to those in patients with severe pregnancy-induced hypertension (PIH). Comparison of plasma PRL concentrations collected antepartum, at delivery, and 48 hours postpartum failed to distinguish women with PIH from those without. Only women with PIH, however, showed a significant rise in systemic PRL concentrations between admission to the study and delivery. Antepartum abnormalities in plasma PRL concentrations associated with PIH may not have been detected because of diurnal variations in PRL secretion.

Comparison of two prostaglandins used to terminate midtrimester pregnancy.

One of the most widely used methods of pregnancy termination has involved the use of prostaglandin drugs. Vaginal suppositories containing prostaglandin E2 (PGE2) have been used successfully by many investigators. Because of problems with a long delay between induction and abortion, as well as minor side effects, other prostaglandin agents have been tested. In our study, 17 matched patients given PGE2 vaginal suppositories to induce abortion were compared with a similar group in whom the methyl ester of prostaglandin F2 alpha ( MPGF2 alpha) was used. There was no statistically significant difference between the two groups in side effects, number of patients requiring curettage, or placental expulsion time. Patients treated with PGE2 had a shorter fetal expulsion time (P less than .001), and there were no major complications in either group. It appears from these data that multiple PGE2 vaginal suppositories are equal to or better than the newer single MPGF2a suppository followed by intramuscular injections when used for second trimester terminations.

Comparative efficacy of ibuprofen, indomethacin, and placebo in the treatment of primary dysmenorrhea.

Forty-two women with primary dysmenorrhea were successfully enrolled in a double-blind, three-way crossover study in which each patient received either ibuprofen (Motrin), indomethacin (Indocin), or a placebo during each of three successive painful menstrual cycles. Thirty-one patients successfully completed the study. The results showed that ibuprofen and indomethacin were superior to the placebo in their ability to relieve pain and that patients preferred ibuprofen to indomethacin. Ibuprofen was significantly superior to the placebo regarding the number of patients who could pursue normal daily function, whereas indomethacin was not. Four patients reported side effects, all during the indomethacin cycle.