Jennifer R. Niebyl

The inhibition of premature labor with indomethacin

We administered indomethacin orally for the treatment of premature labor in a prospective, randomized, double-blind fashion, and all infants were followed up. Indomethacin was significantly more effective than placebo in inhibition of premature labor during a 24-hour course of therapy, with treatment failure during therapy occurring in only one of 15 indomethacin-treated patients compared to nine of 15 placebo-treated patients (p less than 0.01). Mean plasma concentrations of indomethacin were approximately 0.8 micrograms/ml at both 4 and 12 hours after administration. Mean plasma levels of 15-oxo-13,14-dihydroprostaglandin F2 alpha (PGFM) were similar in the two groups before treatment, decreased markedly in the indomethacin group by 4 hours, and were not detected at 12 hours in all but the one indomethacin-treated patient who was delivered within 24 hours. Patients in the placebo group who were delivered prematurely had higher pretreatment PGFM levels (mean +/- SE, 83 +/- 18 pg/ml, n = 9) than the patients who responded to placebo (25 +/- 6 pg/ml, n = 6) (p less than 0.05). There was no difference between the indomethacin and placebo groups with respect to gestational age at delivery, birth weight, and neonatal morbidity and deaths. In particular, we found no evidence of premature closure of the ductus arteriosus, pulmonary hypertension, or increase in bleeding problems among the infants exposed to indomethacin in utero. Although no difference in neonatal outcome was observed in this small number of patients, it would seem prudent still to consider indomethacin as an experimental therapy.

Nausea and vomiting in pregnancy

This article reviews the management of nausea and vomiting in pregnancy, with attention to pharmacologic and alternative management strategies and nutritional support.

Neonatal outcome after indomethacin treatment for preterm labor

Forty-six infants exposed to indomethacin in utero for treatment for preterm labor were compared with infants from two control groups. In one control group the next consecutive patient treated with a tocolytic agent was used, and the other control group was formed by picking the next consecutive patient matched by gestational age who did not receive any tocolytic agent. There was no significant difference in Apgar scores, birth weight, or gestational age in the three groups. The incidence of neonatal complications including hypocalcemia, hypoglycemia, respiratory distress syndrome, patient ductus arteriosus, sepsis, and neonatal mortality were not significantly different in the three groups. No cases of premature closure of the ductus arteriosus or persistent fetal circulation were seen.

Cervical cancer diagnosed shortly after pregnancy: prognostic variables and delivery routes.

Objective To compare the prognoses of women diagnosed with cervical cancer during pregnancy with the prognoses of those diagnosed within 6 months after delivery and to assess the effect of vaginal delivery on recurrence risk and prognosis. Methods A matched case-control study of women with cervical cancer diagnosed during pregnancy or within 6 months of delivery was performed. Fifty-six women had cervical cancer diagnosed during pregnancy and 27 within 6 months after delivery. Controls (cervical cancer diagnosed at least 5 years since last delivery) were matched one-to-one with cases based on age, histology, stage, treatment, and time of treatment. Results Among postpartum women, four had stage IA disease, 15 had stage IB1 or IB2, and eight had stage IIA or higher disease. Eleven had radical hysterectomies and 14 had radiation therapy. Two with stage IA1 disease were treated with vaginal hysterectomies. One of seven patients who had cesareans developed a local and distant recurrence. In contrast, ten of 17 (59%) who delivered vaginally developed recurrences (P = .04). In multivariate analysis, vaginal delivery was the most significant predictor of recurrence (odds ratio [OR] 6.91; 95% confidence interval [CI] 1.45, 32.8), followed by high stage (OR 4.66; 95% CI 1.05, 20.8). The survival for patients diagnosed in the postpartum period was significantly worse than for controls. Conclusion Women diagnosed postpartum had worse survival than those diagnosed during pregnancy and were at significant risk of recurrent disease, particularly if they delivered vaginally. Therefore, pregnant women with cervical cancer should be delivered by cesarean.

The safety and efficacy of tocolytic agents for the treatment of preterm labor.

Pharmacologic inhibition of uterine contractions remains the mainstay of treatment for preterm labor despite the ongoing controversy regarding its effectiveness. A diverse variety of tocolytic medications have been proposed for clinical use, with betamimetics and magnesium sulfate being the common therapeutic agents of choice in the United States today. The clinician using these agents should be aware of the significant maternal and fetal side-effects associated with these particular medications. New classes of pharmacologic agents, including prostaglandin synthetase inhibitors, calcium channel blockers and phosphodiesterase inhibitors, have been proposed as tocolytic agents and are currently undergoing critical clinical evaluation. The purpose of this review is to provide a compilation of the available clinical studies that document the safety and efficacy of these various tocolytic agents.

Clinical high-risk designation does not predict excess fetal-maternal hemorrhage.

During a 5-year period, an enzyme-linked antiglobulin test was used to screen and quantitate fetal-maternal hemorrhage in 789 consecutive D-negative mothers who were delivered of D-positive babies. Six hundred seventy-two patients (85.2%) had no detectable fetal-maternal hemorrhage, and 117 patients (14.8%) had a detectable fetal-maternal hemorrhage. Eight of the 789 (1%) had a fetal-maternal hemorrhage greater than 30 ml and required more than one vial of Rh immune globulin. Two patients with fetal-maternal hemorrhage of 29 and 30 ml also received additional Rh immune globulin. Each case was reviewed for the presence of high-risk features that are thought to predict patients at risk for fetal-maternal hemorrhage. Patients having a cesarean section or complicated vaginal delivery were considered to be in a group at high risk for fetal-maternal hemorrhage, while those with a spontaneous vaginal delivery were considered not to be at risk for fetal-maternal hemorrhage. Thirty-two of 237 patients (13.5%) in the risk group and 82 of 552 patients (15.3%) in the group not at risk had detectable fetal-maternal hemorrhage. The incidence of fetal-maternal hemorrhage for these two groups was not statistically different (p greater than 0.50 by chi 2 analysis). If only patients in the risk group had been screened for fetal-maternal hemorrhage, then five of 10 (50%) who required more than one vial of Rh immune globulin would have been undertreated and at risk for developing anti-D antibodies. In addition, newborn birth weight, Apgar scores, and hematocrits were examined for 13 cases of fetal-maternal hemorrhage of greater than or equal to 21 ml, and none of these characteristics could be used to predict patients at risk for fetal-maternal hemorrhage. Therefore, no maternal or newborn characteristics could be identified that would reliably predict patients at risk for fetal-maternal hemorrhage. We conclude that all D-negative patients with D-positive babies should continue to be screened for fetal-maternal hemorrhage to identify those patients requiring more than one vial of Rh immune globulin.

The association of anti-P and early abortion

The current report details the serologic findings in a case reported previously of a P1k woman, para 0 gravida 13, who was treated during her fourteenth pregnancy with plasmapheresis to reduce the anti‐P titer. These studies suggest that anti‐P can induce early abortion in Pk women and that the abortions are immunologically mediated. Further, this case supports the disputed proposal that the anti‐P component of anti‐PP1Pk is responsible for pregnancy loss in p women.

Drug therapy during pregnancy.

Fetal dysmorphic syndromes have been described with exposure to most commonly used anticonvulsants, most recently carbamazepine (Tegretol, Ciba-Geigy, Basel, Switzerland). Fetal genetic susceptibility may determine which infants are affected. Long-term use of heparin in pregnancy may cause significant osteoporosis, which appears to be reversible. Pharmacokinetic studies of ritodrine have resulted in recommendations for more appropriate infusion regimens, including a role for intramuscular therapy for patients undergoing maternal transport. Nifedipine shows promise as a tocolytic with fewer side effects than ritodrine but equivalent efficacy. Indomethacin is also an effective tocolytic, and clinically significant side effects have not been seen with 48 hours or less of treatment. Indomethacin has also been used successfully for treatment of polyhydramnios.

Pregnancy following total hysterectomy

Abstract Twenty-one cases of pregnancy following total hysterectomy are reviewed. Fourteen followed vaginal and seven followed abdominal hysterectomies. Twelve presented as immediate postoperative complications (the early ectopic) and nine presented many months or years later (the late ectopic). The clinical course was typical for ectopic pregnancy but therapy was delayed because this diagnosis was rarely considered. In the early cases the surgery had been done between days 16 and 19 of the menstrual cycle. The embryonic sizes suggested that the fertilized ovum had been in the tube at the time of the hysterectomy and its passage had been blocked by the tubal ligature. The patients were treated for presumed postoperative infection despite normal temperatures and leukocyte counts. A tender adnexal mass was noted only after several weeks, in contrast to the usual earlier presentation of inflammatory masses. Pregnancy test was positive in the two cases tested.

Folic acid and prevention of birth defects

Don C Van Dyke* MD, Professor of Pediatrics, Divisions of Developmental Disabilities and Medical Genetics, The Children’s Hospital of Iowa; Phyllis J Stumbo RD LD PhD, Assistant Research Scientist, Clinical Research Center, The University of Iowa Hospitals and Clinics; Mary J Berg PharmD, Professor, College of Pharmacy, The University of Iowa; Jennifer R Niebyl MD, Professor, Director, Department of Obstetrics and Gynecology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.