17-Hydroxyprogesterone caproate in triplet pregnancy: an individual patient data meta-analysis.

BACKGROUND: Preterm birth complicates almost all triplet pregnancies and no preventive strategy has proven effective. OBJECTIVE: To determine, using individual patient data (IPD) meta-analysis, whether the outcome of triplet pregnancy is affected by prophylactic administration of 17-hydroxyprogesterone caproate (17OHPc). SEARCH STRATEGY: We searched literature databases, trial registries and references in published articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) of progestogens versus control that included women with triplet pregnancies. DATA COLLECTION AND ANALYSIS: Investigators from identified RCTs collaborated on the protocol and contributed their IPD. The primary outcome was a composite measure of adverse perinatal outcome. The secondary outcome was the rate of birth before 32 weeks of gestation. Other pre-specified outcomes included randomisation-to-delivery interval and rates of birth at <24, <28 and <34 weeks of gestation. MAIN RESULTS: Three RCTs of 17OHPc versus placebo included 232 mothers with triplet pregnancies and their 696 offspring. Risk-of-bias scores and between-study heterogeneity were low. Baseline characteristics were comparable between 17OHPc and placebo groups. The rate of the composite adverse perinatal outcome was similar among those treated with 17OHPc and those treated with placebo (34 and 35%, respectively; risk ratio [RR] 0.98, 95% confidence interval [95% CI] 0.79-1.2). The rate of birth at <32 weeks was also similar in the two groups (35 and 38%, respectively; RR 0.92, 95% CI 0.55-1.56). There were no significant between-group differences in perinatal mortality rate, randomisation-to-delivery interval, or other specified outcomes. CONCLUSION: Prophylactic 17OHPc given to mothers with triplet pregnancies had no significant impact on perinatal outcome or pregnancy duration. TWEETABLE ABSTRACT: 17-Hydroxyprogesterone caproate had no significant impact on the outcome or duration of triplet pregnancy.

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis.

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

The neurobiology of stress in human pregnancy: implications for prematurity and development of the fetal central nervous system.

Adverse early experience, including prenatal maternal psychosocial stress, has the potential to negatively influence developmental processes through both physiological and behavioral mechanisms. This in turn may have adverse consequences for the mental and physical health, well-being and aging of the individual throughout the entire life-span. We have initiated a program of research on humans to examine the consequences of maternal stress and related factors in pregnancy on the length of gestation, fetal growth, and brain development. We have also investigated the physiological mechanisms that are involved. In this chapter we outline the theoretical rationale for this work and give an overview of our findings to date. These findings support a significant and independent role for behavioral processes such as maternal prenatal stress in the etiology of prematurity-related outcomes, and suggest that these effects are mediated, in part, by the maternal-placental-fetal neuroendocrine axis; specifically by placental corticotropin-releasing hormone. Using a fetal challenge paradigm as a novel method for quantifying fetal neurologic maturity in utero, we have found that the maternal environment exerts a significant influence on the fetal autonomic nervous system and on central nervous system processes related to recognition, memory and habituation. Finally, our findings provide preliminary evidence to support the notion that the influence of prenatal stress and maternal-placental hormones on the developing fetus may persist after birth, as assessed by measures of temperament and behavioral reactivity in the first 3 years of postnatal life. The implications of these studies for life-span development and health are discussed.

Corticotrophin-releasing hormone and fetal responses in human pregnancy.

During human pregnancy, maternal and fetal compartments of the human placenta produce and release corticotrophic-releasing hormone (CRH). Elevations of placental CRH are associated with decreased gestational length (including preterm delivery). The effects of elevated placental CRH on human fetal neurological development are not known. Pregnant women in the 31st and 32nd week of gestation consented to procedures for collection of blood and measurement of fetal heart rate (FHR) in response to a series of 40 vibro-acoustic stimuli (VAS). Measures of habituation and dishabituation were calculated from the FHR. All subjects were followed to delivery. Fetuses (N = 33) of women with highly elevated CRH were least responsive (p < .03) to stimulation after presentation of a novel (dishabituating) stimulus with control for parity, fetal gender, medical (antepartum) risk, and gestational length at term. In a larger sample (N = 156) a polynomial model predicted the pattern of FHR reactivity for the first 15 trials. Placental CRH concentration significantly predicted FHR reactivity after controlling for the effects of trial number, baseline FHR, inter-trial interval, and presence of uterine contractions. Increased maternal CRH levels were significantly related to the length of gestation after controlling for the effects of fetal gender, parity, and medical risk (p = .05). The relationship between length of gestation and FHR was not significant suggesting separate actions of CRH on these events. Elevated placental CRH appears to accelerate certain developmental events (gestational length) and may influence the fetal nervous system. The impaired fetal responses to novelty and increased arousal observed in this study suggest that neurological systems may be targets for placental CRH during sensitive developmental periods.

The lambda fetal heart rate pattern: an assessment of its significance in the intrapartum period.

The "lambda" fetal heart rate (FHR) pattern was first described in 1977 as a pattern involving an acceleration followed immediately by a deceleration. However, its clinical significance has not been elucidated. During 6 months, 56 patients with this pattern were identified, representing 4% of all deliveries during this period. These were compared with a control group of 500 consecutive low-risk term patients who had been monitored electronically. The lambda pattern generally appeared early in labor and lasted for a variable period of time, but rarely persisted throughout labor. The relative rates of low Apgar scores, cesarean sections, and associated nonreassuring FHR patterns were similar between the two groups. The timing or depth of the decelerative portion of the pattern did not appear to correlate with any adverse outcome. Therefore, it does not appear that the lambda pattern is associated with any adverse outcome, nor does it predict the development of other concerning FHR patterns.

Amniocentesis and the management of premature labor.

Two applications of amniocentesis for the evaluation of the patient in idiopathic premature labor, fetal lung maturity testing, and detection of occult intraamniotic infection were evaluated in a review of 59 cases. Seven patients (12%) had positive amniotic fluid cultures despite the absence of clinical signs of infection. This group presented at earlier gestational ages (29 + 2.3 versus 32 + 2.0 weeks, P less than .005) and were more likely to rupture membranes while on tocolytic therapy (four of seven versus two of 52, P less than .001) than patients whose cultures were negative. All seven patients with a positive culture delivered within 48 hours of admission, whereas 44 of 52 patients with negative cultures delivered after 48 hours (P less than .001). Increase in maternal and neonatal morbidity seemed to be related primarily to a higher cesarean section rate and earlier gestational ages at delivery in this group. Lecithin/sphingomyelin ratio was predictive of fetal lung maturity as expected. More than one-half of patients greater than 33 weeks and one-third of patients at 31 to 32 weeks demonstrated fetal lung maturity. The authors conclude that amniocentesis is an important tool in evaluating patients in preterm labor, especially with respect to making appropriate management decisions regarding tocolytic and/or corticosteroid therapy.

Premature rupture of membranes before fetal viability.

The outcome of 53 cases expectantly managed with premature rupture of membranes (PROM) before fetal viability (16 to 25 weeks) was retrospectively reviewed. Forty-one percent of patients developed amnionitis, four had prolonged hospital stays (longer than seven days), and one each had sepsis and pelvic thrombophlebitis. Twenty-two mothers (41%) had no complications. No serious long-term maternal sequelae were noted. Eighteen patients were delivered after 26 weeks, and there were 13 surviving neonates with birth weights ranging from 740 to 2170 g.

Chorioamnionitis in the preterm gestation.

Two hundred fifty-one patients with premature rupture of membranes between 28 and 34 weeks' gestation were followed prospectively to evaluate the maternal and neonatal effects of chorioamnionitis. Forty-seven (19%) developed intrauterine infection prior to delivery. Fetal tachycardia, maternal leukocytosis, and uterine contractions were not predictive of intrauterine infection in afebrile patients. In afebrile patients, however, amniocenteses positive for bacteria on Gram stains and/or with subsequent positive culture correlated with subsequent development of antenatal maternal fever. Other than an increased rate of postpartum endometritis no serious maternal complications were seen in patients with chorioamnionitis. Neonatal outcome, however, was significantly adversely affected with respect to increase in perinatal mortality, overall neonatal infection rate, and respiratory distress syndrome (RDS) in patients with maternal infection. Neither trial of labor nor duration of labor in patients with chorioamnionitis correlated with adverse neonatal outcome. However, the appearance of maternal fever prior to the onset of labor correlated more significantly with neonatal death and RDS in the newborn that did the development of maternal fever in the intrapartum period.

Fusobacterium: anaerobic occult amnionitis and premature labor.

Fusobacterium species are well established pathogens. Before the advent of effective anaerobic antimicrobial therapy, they were associated with prolonged, often fatal courses. Previously, fusobacterium had not been identified as a common perinatal pathogen. Three cases of occult amnionitis due to Fusobacterium are presented. Review of five series of occult amnionitis revealed 23 cases. In seven (30.4%), Fusobacterium was isolated. In 14 (60.8%), an anaerobic species was isolated. The average gestational age of patients from whom anaerobes were grown was 29.0 weeks. Of those that grew no anaerobes, the average gestational age was 32.3 weeks (P less than .05). The overall rate of maternal febrile morbidity was 35%. Fusobacterium accounted for 50% of the febrile cases while accounting for only 30.4% of the total cases.

Late abruptio placenta in trauma patients: implications for monitoring.

A case report is presented in which abruptio placenta occurs five days after trauma. This is a very rare occurrence. The high incidence of abruption occurring after severe trauma is reviewed, and the importance of continuous fetal monitoring for at least 48 hours after admission to the hospital is stressed.

Laparoscopic tubal sterilization using thermal coagulation.

A technique using a low-voltage, rechargeable battery pack and a cautery hook assembly for thermal coagulation and division of the fallopian tube under laparoscopic visualization has been evaluated in 393 patients. The procedure is quick, easy to perform, and electrically safe. The gross extent of the burn to the fallopian tube by thermal coagulation and division was compared with that done by high-frequency unipolar electrocoagulation and division. The difference in the mean total gross tubal burn produced by the 2 methods is not statistically significant. The variance of total tubal burn in individual cases within each group is significantly greater in the electrocoagulation group. The authors assume that pregnancy rates in patients undergoing thermal coagulation and division will be no different than those reported in patients in the electrocoagulation and division group. Two hundred of the patients have been followed from 12 to 33 months and no method-failure pregnancies have occurred.

PIP: A new technique, utilizing thermal coagulation provided by a low 6 voltage rechargeable battery pack and disposable cautery hook assembly, was used in performing laparoscopic tubal sterilization on 393 patients during 1975-1977 and found to be a safe and effective procedure. No major complications or burns occurred. 51% of the patients were followed for 12-33 months and no pregnancies attributable to method failure occurred. In order to assess the degree of burn damage resulting from thermal coagulation as compared to burn damage associated with high frequency unipolar electrocautery, 10 patients had the right tube cauterized by thermal coagulation and the left tube by electrocautery. Surgical specimens from both tubes were histologically examined. No significant differences in total gross burn area were observed; however, variation in the degree of individual burns was greater for the high frequency electrocoagulation specimens. For patients interested in the possibility of tubal reanastomosis this variation might be crucial. The surgical procedures involved in using thermal coagulation are described and a table presents the gross burn measurements for both the electrocoagulation and thermal coagulation specimens.

Placenta accreta: a problem of increasing clinical significance.

Placenta accreta in association with placenta previa and previous cesarean delivery is a condition of increasing clinical significance. A case report of a woman with placenta percreta is presented. Risk factors, incidence, and management are discussed. Recommendations for preoperative and intraoperative management are presented.

Fetal maturity cascade: a rapid and cost-effective method for fetal lung maturity testing.

One hundred ninety-three amniotic fluid samples were tested for fetal lung maturity using a maturity cascade scheme involving the sequential use of, in order, the shake test, fluorescence polarimetry, and lecithin: sphingomyelin (L:S) ratio. If any of these tests indicated maturity, the sequence was terminated and no further test was performed, and the fetus was considered mature. Seventy percent of the tests yielded mature values and of these, 85 (63%) required a shake test only, 37 (27%) had a shake test and a fluorescence polarimetry, and only 14 (10%) required all three tests. From these 193 amniocenteses, 111 patients delivered within 72 hours of the procedure. One of 94 infants had respiratory distress syndrome after a mature test (1% false maturity) and ten of 17 had respiratory distress syndrome after an immature cascade (41% falsely immature). This approach saves time and cost and by confirming immaturity with multiple tests only when necessary and may improve predictability of neonatal respiratory distress syndrome.

Oxytocin challenge test: achieving the desired goals.

The desired goals of the oxytocin challenge test (OCT) are preventing stillbirth and avoiding unnecessary premature intervention. To effectively reduce stillbirth the test should be done on a significant proportion of those fetuses who would subsequently succumb in utero. To analyze whether or not the OCT is achieving these goals. 5351 deliveries over a 2-year period at the University of California, Irvine, Medical Center were studied retrospectively. Four hundred and thirty of these patients had 823 OCTs performed. There were ten positive and 19 suspicious tests, and five neonatal deaths in these two groups. In patients who were studied with OCTs only one stillbirth occurred (in a patient who was noncompliant). During the same period, all stillbirths were reviewed. In the group in which stillbirth occurred, it was determined that 11 or 35% of the patients had indications for antepartum testing but were not tested. All 11 of these patients were transferred to the University hospital or had no prenatal care. It is suggested that these stillbirths may have been prevented had appropriate prenatal care allowed identification of patients for antepartum testing.

The use of amniocentesis in patients with premature rupture of membranes.

A prospective study was conducted to evaluate the usefulness of amniocentesis in patients with premature rupture of membranes (PROM) for the prediction of occult or impending intrauterine infection and the assessment of fetal maturity. Fifty-nine patients with PROM between 28 and 35 weeks' gestation, without apparent infection, were evaluated sonographically for possible amniocentesis. Thirty patients had successful amniocenteses for a success rate of 51%. Fifteen patients had a mature lecithin/sphingomyelin (L/S) ratio and were delivered immediately without respiratory distress syndrome (RDS) or other neonatal complications. All amniotic fluids were evaluated by Gram stains and cultures. Nine of the 30 patients had positive cultures, with a high incidence of subsequent development of amnionitis and other infectious morbidity. In the 21 patients with negative cultures, there were 19 without any infectious morbidity. Amniocentesis appears in this study to be a useful method for selecting the patients who have mature fetuses and/or who are more likely to develop amnionitis.

Fetal heart rate patterns and fetal distress in fetuses with congenital anomalies.

Over a 3-year period at the Long Beach Women's Hospital, where electronic FHR (fetal heart rate) monitoring was routine, there were 8622 live births, including 41 infants born with major congenital malformations. The neonatal death rate in these malformed infants was 44%; 17 were delivered by cesarean section, 11 of which were performed because of fetal distress. There were no characteristic FHR patterns that would specifically identify major congenital malformations. There was a significantly increased incidence of prematurity, breech presentation, and cesarean section delivery in the congenital malformation group as compared to the overall population delivering at the Women's Hospital. The clinical implications of these observations are discussed.

Fetal heart rate patterns and fetal distress in patients with preterm premature rupture of membranes.

Two hundred sixty-seven consecutive patients with preterm premature rupture of membranes (PROM) and 130 consecutive patients with idiopathic premature labor and intact membranes between 28 and 35 weeks' gestation were compared. A significantly higher incidence of cesarean section for fetal distress was found in patients with PROM (7.9%) compared with patients with premature labor (1.5%) (P less than .05). Fetal distress occurred with similar frequency in patients with and without chorioamnionitis. Analysis of electronic fetal heart rate patterns in patients with fetal distress revealed that 16 of 21 patients (76%) with PROM had patterns consistent with umbilical cord compression. A significant difference was found in neonatal mortality rates between the PROM group (4.5%) and the premature labor group (0) (P less than .05). The neonatal death rate in patients with fetal distress (three of 12) was significantly higher than in patients without distress (nine of 385) (P less than .01). It is suggested that the increased incidence of fetal distress in patients with preterm PROM may represent the loss of the protection of the umbilical cord that amniotic fluid normally provides.

Cocaine intoxication presenting as preeclampsia and eclampsia.

OBJECTIVE: To relate the clinical presentation of acute cocaine intoxication in the third trimester to preeclampsia and eclampsia. METHODS: Eleven women presented to Long Beach Memorial Women's Hospital and the University of California, Irvine Medical Center with hypertension and clinical symptoms of headache, blurred vision, abdominal pain, or seizures in the third trimester of pregnancy. Each had a positive urine drug screen for cocaine. The laboratory evaluation for preeclampsia included a complete blood count, platelet count, uric acid, aspartate aminotransferase, alanine aminotransferase, creatinine, and urine for protein content. RESULTS: All women had a diastolic blood pressure of at least 90 mmHg, which returned to the normal range 45-90 minutes after admission. Each presented with one or more symptoms associated with preeclampsia, which ultimately improved as the drug wore off. In addition, all laboratory evaluations for preeclampsia were negative. CONCLUSION: If a patient presents in the third trimester with hypertension and clinical symptoms of preeclampsia that rapidly improve shortly after admission, cocaine intoxication should be considered as the possible source.

Fetal fibronectin: a method for detecting the presence of amniotic fluid.

OBJECTIVE: To determine whether fetal fibronectin is a sensitive test for the detection of amniotic fluid (AF) in women with rupture of the membranes. METHODS: In a multicenter clinical trial, pooling, ferning, and nitrazine tests were compared with fetal fibronectin in 339 women at term (study group) with a clinical history of rupture of the membranes and in 67 women at term receiving routine prenatal care (controls). Ruptured membranes was diagnosed if any two of the standard tests were positive. Fetal fibronectin in the cervicovaginal secretions was determined using a qualitative enzyme-linked immunosorbent assay test. Fetal fibronectin was considered positive at 50 ng/mL. RESULTS: The sensitivity of fetal fibronectin in the women with ruptured membranes was 98.2%. No controls had ruptured membranes based on standard test results, but 13 women had fetal fibronectin present. The mean (+/- standard error) interval between sampling and delivery was significantly less in the women positive for fetal fibronectin (169.3 +/- 45.8 hours) than in those with no detectable fetal fibronectin (333.4 +/- 29.0 hours). CONCLUSION: Fetal fibronectin is a sensitive test for detection of AF in the vagina and compares favorably to standard tests. Its low specificity suggests that the assay may detect an alteration in membrane integrity. In addition, in patients without rupture of the membranes, the interval between sampling and delivery is significantly shorter if fetal fibronectin is present. We speculate that the presence of fetal fibronectin in cervicovaginal secretions may be a marker for impending labor in gravidas without gross rupture of the membranes.

Development and experience of a university-based, freestanding birthing center.

OBJECTIVE: To describe our experience with a freestanding birthing center established in conjunction with a university medical center, and to determine the safety and effectiveness of such a program. METHODS: The University of California Irvine Medical Center opened a freestanding birthing center 2 miles from the hospital. The unit provides prenatal, labor, delivery, postpartum and well-baby care 24 hours/day. All direct patient care is provided by certified nurse-midwives. Data were collected prospectively to provide a descriptive account and to evaluate maternal and perinatal morbidity and mortality to determine the safety and efficacy of this approach. RESULTS: During the first 20 months of operation, the University of California Irvine Birthing Center cared for 1830 patients. Approximately 90% were indigent, 85% were Hispanic, and 35% were nulliparas. Of the total patients, 12% were transferred antenatally for high-risk conditions and 19% were transferred intrapartum. The cesarean rate for all patients was 10% (6.5% for those whose intrapartum care began at the birthing center). The perinatal mortality rate was six per 1000. Neonatal morbidity rates, neonatal intensive care unit admissions, and maternal complications were not greater than expected. CONCLUSION: The first 20 months of experience with a university-based, freestanding birthing center suggests that this alternative is safe for delivering obstetric and newborn care to low-risk patients.