Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat. RESULTS: Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n=235; placebo, n=223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n=21) vs 16.1% (n=36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P=0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P=0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P=0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P=0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P=0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P=0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P=0.01). There were no differences in the incidence of treatment-related adverse events between the groups. CONCLUSIONS: The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.

Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester. METHODS: This was a planned, but modified, secondary analysis of our multinational, multicenter, randomized, placebo-controlled trial, in which women were randomized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo. Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation. Treatment continued until either delivery, 37 weeks of gestation or development of preterm rupture of membranes. Maternal and neonatal outcomes were evaluated for the subset of all randomized women with cervical length < 28 mm at enrollment. The primary outcome was preterm birth at

Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Preterm birth is the leading cause of perinatal morbidity and mortality worldwide. Treatment of preterm labor with tocolysis has not been successful in improving infant outcome. The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth. The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth. METHODS: This randomized, double-blind, placebo- controlled, multinational trial enrolled and randomized 659 pregnant women with a history of spontaneous preterm birth. Between 18 + 0 and 22 + 6 weeks of gestation, patients were assigned randomly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery, 37 weeks' gestation or development of preterm rupture of membranes. The primary outcome was preterm birth at

Antiretroviral therapy during pregnancy. Beyond AZT (ZDV).

Although zidovudine (ZDV) monotherapy remains the standard for the prevention of mother-to-child transmission, it may now be inadequate therapy for treatment of the mother. The safety and efficacy of the newer therapeutic agents have yet to be established during pregnancy; however, the need to maintain maternal health mandates that clinicians understand the benefits and limitations of antiretroviral therapy beyond ZDV.

Pitfalls in the diagnosis of nonconjoined monoamniotic twins.

The morbidity and mortality of monoamniotic twins are high. Despite recent advances in imaging, the definitive diagnosis of monoamniotic twins remains elusive. When monoamniotic twins are suspected, the optimal antepartum management is uncertain. A false-positive diagnosis of monoamniotic twins by computed tomographic amniography was investigated. By a Medline search the literature on monoamnionicity from 1966 to January 1994 was reviewed. All reports including diagnostic methods and management of monoamniotic twins were reviewed. All five previous case reports of computed tomographic amniography correctly identified amnionicity in cases in which amnionicity was unclear. Four cases confirmed monoamnionicity and one case excluded monoamnionicity. Four recent series that used ultrasonography revealed a low predictive accuracy (9% to 25%) for the establishment of monoamnionicity when intervening membranes were absent. One recent prospective series revealed a positive predictive value of 80% among five monoamniotic twin pairs with the use of first-trimester ultrasonography. The methods available to diagnose monoamniotic twins are improving. The complications that result from a false-positive diagnosis are discussed and the management and diagnosis of monoamniotic twins are reviewed.

Parturients infected with human immunodeficiency virus and regional anesthesia. Clinical and immunologic response.

BACKGROUND: It is estimated that 1.5 million Americans are infected with the human immunodeficiency virus (HIV-1), and the consequences of HIV infection are a leading cause of death in women aged 15-44 yr. Thus, HIV-1 disease, or acquired immunodeficiency syndrome, occurs with increasing frequency in the parturient, and there is little information concerning the risks of regional anesthesia. Fear of spreading infection to the central nervous system or adverse neurologic sequelae have led some clinicians to advise against regional anesthesia. Thus, this study was undertaken to evaluate the possible problems or risks associated with regional anesthesia in parturients infected with HIV-1 and to determine whether anesthesia affected the clinical course of the disease. METHODS: The clinical course and immunologic function of 30 parturients infected with HIV-1 were evaluated prospectively. Extensive medical and laboratory evaluation before delivery and 4-6 months postpartum was undertaken. Medical problems related to HIV-1 disease and use of antiviral drugs also were monitored. The anesthetic management was dictated by the clinical situation and the patient's wishes were careful postpartum follow-up to evaluate possible neurologic changes or infection. RESULTS: Regional anesthesia was administered in 18 parturients, and 12 received small doses of opioids or no analgesia. There were no changes in the immunologic parameters studied (CD4+, p24, beta 2 microglobulins), and HIV-1 disease remained stable in the peripartum period. There were no infections, complications, or neurologic changes in the peripartum period. Sixty-eight percent of the infants were HIV-1-negative and, in 21% of infants, the HIV-1 status was indeterminate (probably negative). CONCLUSIONS: This prospective study of parturients infected with HIV-1 demonstrated that regional anesthesia can be performed without adverse sequelae. There were no neurologic or infectious complications related to the obstetric or anesthetic course. The immune function of the parturient was stable in the peripartum period. Although the number of patients studied was small, with careful medical evaluation, regional anesthesia is an acceptable choice in the parturient infected with HIV-1.

AIDS (HIV) risk assessment in an inner-city women's clinic.

Risk assessment and antibody testing are potential modalities through which interventions to reduce heterosexual and perinatal transmission of human immunodeficiency virus (HIV) can occur. More than 98% of women attending inner-city adult gynecology, adult contraception and teen family planning clinics successfully completed self-administered HIV (AIDS) risk assessment questionnaires and received individual counseling, risk-reduction education and referral for antibody testing. Fourteen percent of the women (671/4,802) reported at least one HIV risk factor. Multiple sexual partners and intravenous drug use were the most commonly reported HIV risk factors in this population.

Seroprevalence and epidemiologic correlates of human immunodeficiency virus infection in women with acute pelvic inflammatory disease.

As the number of women with acquired immunodeficiency syndrome (AIDS) continues to rise in the United States, it becomes important to target preventive interventions as effectively as possible toward those groups at highest risk of acquiring human immunodeficiency virus (HIV) infection. We analyzed the prevalence of serum antibody to HIV in 333 women admitted to the Gynecology Service at San Francisco General Hospital with acute pelvic inflammatory disease in the years 1985-1988. The proportion of women with HIV infection in our sample rose incrementally over this 4-year period, from 0 to 6.7%. A history of intravenous (IV) drug use conferred a 23-fold risk of HIV seropositivity. In contrast, markers of the level of sexual activity did not correlate significantly with the presence of HIV infection, although the power to detect such an association was limited by the small sample size. An intensification of educational efforts directed at IV drug-using women in San Francisco is necessary to prevent further increases in the rate of HIV infection and further spread into the heterosexual population.

Substance abuse in pregnancy.

The number of women who abuse drugs during pregnancy is unknown, but as many as 375,000 infants may be affected. Although some substances appear to result in less damage than others, it is impossible to differentiate individual effects because of the common use of multiple substances. The potential for synergy among substances with similar physiologic effect is an additional factor. The immediate perinatal effects of substance abuse are often obvious; it is the long-term effects that we have only recently begun to examine. These long-term effects will involve both the individual and society.

Isolation of Chlamydia trachomatis from sexually abused female adolescents.

Cultures for Chlamydia trachomatis were obtained from 127 female adolescents (13-17 years of age) evaluated for reported sexual abuse. The rate of positive cultures for C trachomatis in this population was 14% (18 of 127). Neisseria gonorrhoeae was found in 12% (15 of 127) of these patients. All but two of the culture-positive patients admitted sexual activity before the abuse, and it is likely that most of the infections were acquired during this previous sexual activity. Concomitant infection with N gonorrhoeae was found in seven adolescents positive for C trachomatis. No adolescents in this study exhibited a positive VDRL. Victims of abuse should be tested for both gonococcal and chlamydial infection. These data show that if antibiotic prophylaxis is used for the sexually abused adolescent, it should be directed against both C trachomatis and N gonorrhoeae.

Management of twin pregnancy: the vaginal route is still safe.

To investigate the effect of method of delivery on the outcome of twin pregnancies, we reviewed all deliveries at our institution over the 10 years from 1976 to 1985. Two hundred six pairs were delivered, with a mean gestational age of 34 weeks (range 20 to 43 weeks) and a mean weight of 2116 gm (range 220 to 3800 gm). The mean gestational age at diagnosis of the twin pregnancy was 23 weeks. Nineteen (4.6%) infants were stillborn, and 36 (8.7%) died in the neonatal period. Cesarean section was used to deliver both twins in 66 cases. The method of delivery for the remaining 142 cases was vaginal-vertex, 85 (61%), vaginal-breech, 40 (29%), cesarean section, 13 (9%), and version and extraction, 2 (1%). The four most common indications for cesarean section for both twins were previous cesarean section, breech presentation, abnormal labor, and fetal distress. The indications for the 13 cesarean sections after vaginal delivery of twin A were fetal distress, cord prolapse, high presenting part, and footling breech. The impact of the method of delivery was investigated by comparing outcome variables between twin pairs. No significant differences were noted for perinatal mortality, need for resuscitation, duration of newborn hospital stay, and trauma. There were significant differences in the 1- and 5-minute Apgar scores in the vaginal delivery group. These differences were clinically minor, tending toward mild acidemia, and were unaffected by route or method of delivery.

Management of the pregnant woman infected with the human immunodeficiency virus.

A significant number of the one to two million adults in the United States infected with the human immunodeficiency virus (HIV) are women of childbearing age. It is estimated that approximately 50% of HIV-infected pregnant women will transmit the virus to their fetuses or neonates. Obstetricians and gynecologists must be prepared to care for HIV-infected pregnant women. Comprehensive management includes clinical and psychosocial care in the antepartum, intrapartum, and postpartum periods. Referrals and/or consultations with other providers are often appropriate. Infection control policies must be uniform for all patients because not all HIV-infected patients will be so identified.

Beta-adrenergic receptors and cyclic adenosine monophosphate generation in human fetal lung.

We designed experiments to determine whether beta-adrenergic receptors are present and functional in human fetal lung during the 2nd trimester of gestation. To determine the presence of beta receptors, characterize their binding sites, and assess changes in receptor with gestational age, we performed radioligand binding assays with the specific, high-affinity beta antagonist, 125I-iodocyanopindolol, in membrane particulates from the lungs of 2nd trimester abortuses (15-23 wk). Binding of 125I-iodocyanopindolol was saturable and of high affinity (dissociation constant = 40 pM). Binding was stereoselective as determined by competition studies with (-) and (+) stereoisomers of propranolol. Agonist affinities (isoproterenol greater than epinephrine much greater than norepinephrine) were consistent with a predominance of beta-2 receptors; this predominance was confirmed by competition studies with the specific beta-2 receptor antagonist ICI 118-551 (75% beta-2, 25% beta-1). The concentration of beta-adrenergic receptors increased with gestational age. To assess the functional coupling of the beta receptors, we tested the ability of receptor occupancy to activate adenylate cyclase. For this assay, we incubated minced human fetal lung with beta agonists and determined the amount of cAMP generated. beta Agonists stimulated cAMP generation more than 2-fold. We conclude that beta-adrenergic receptors are present and functional in human fetal lung as early as the 2nd trimester.

Failure to demonstrate decreased beta-adrenergic receptor concentration or decreased agonist efficacy in term or preterm human parturition.

Iodine 125-labeled iodocyanopindolol, a radioactive beta-adrenergic antagonist, bound to particulate preparations of pregnant human myometrium in a manner compatible with binding to the beta-adrenergic receptor. Studies with a specific beta 2-antagonist, IPS 339, indicated that 72% of receptors present were of the beta 2-subtype. Quantitative studies of beta-receptor concentrations in myometrium from women at term indicated no change in receptor concentration during labor. Similarly, there was no difference in beta-receptor concentration in myometrium from women in labor or before labor between 28 and 34 weeks of gestation. Concentrations of the beta-receptor were not different at any stage of gestation assayed. Isoproterenol competition for iodocyanopindolol binding was used to examine efficacy of receptor agonist interactions in myometrium from women at term, in labor, or before labor and from women in preterm labor. There was no difference in high-affinity binding, an index of efficacy, in any of the groups examined.

Screening for carbohydrate intolerance in pregnancy: a comparison of two tests and reassessment of a common approach.

The usefulness of glycosylated hemoglobin as a prenatal screening test for carbohydrate intolerance was studied in 806 consecutive subjects by correlating glycosylated hemoglobin to 1-hour post-50 gm Glucola plasma glucose levels, 3-hour oral glucose tolerance tests, and perinatal and maternal outcomes. Sixty-seven subjects whose 1-hour post-50 gm Glucola plasma glucose levels were greater than or equal to 150 mg/100 ml underwent 3-hour oral glucose tolerance tests; 12 were diagnostic of carbohydrate intolerance. Compared to carbohydrate-tolerant control subjects, gravid patients with carbohydrate intolerance were older, more obese, had higher 1-hour post-50 gm Glucola plasma glucose and glycosylated hemoglobin levels, and infants with increased birth weight percentiles, depressed 5-minute Apgar scores, and an increased incidence of shoulder dystocia and perinatal mortality. Three of 10 carbohydrate-intolerant patients who were evaluated post partum were found to have previously undiagnosed diabetes. Division of measurements of 1-hour post-50 gm Glucola plasma glucose and glycosylated hemoglobin into normal, borderline, and suspicious groups demonstrated a reduction in discriminatory capability of glycosylated hemoglobin as compared to the 1-hour post-50 gm Glucola plasma glucose. We conclude that laboratory screening for carbohydrate intolerance should be a standard element of the prenatal evaluation; gravid patients found to have carbohydrate intolerance should be reevaluated post partum to rule out overt diabetes, and the 1-hour post-50 gm Glucola plasma glucose test is the preferred means of routine screening for carbohydrate intolerance in pregnancy.

Glycosylated hemoglobin as a screening test for carbohydrate intolerance in pregnancy.

The usefulness of glycosylated hemoglobin as a prenatal screening test for carbohydrate intolerance was studied in 806 consecutive subjects by correlating glycosylated hemoglobin to 1-hour post-50 gm Glucola plasma glucose (1 degree G) levels, and 3-hour oral glucose tolerance tests (3 degrees GTT). Sixty-seven subjects whose 1 degree G greater than or equal to 150 mg/100 ml received a 3 degrees GTT; 12 were diagnostic of carbohydrate intolerance. Compared to carbohydrate-tolerant controls, carbohydrate-intolerant gravid patients had higher 1 degree G (p less than 0.001) and glycosylated hemoglobin (p less than 0.05) levels. Linear regression analysis of 1 degree G and glycosylated hemoglobin demonstrated r = 0.35 (p less than 0.0001). Compared to the glycosylated hemoglobin test, the 1 degree G screening test has greater specificity, sensitivity, and predictive value for a positive diagnosis. Consequently, the 1 degree G is a better routine screening test for carbohydrate intolerance than is glycosylated hemoglobin.