Reporting vaccine complications: what do obstetricians and gynecologists know about the Vaccine Adverse Event Reporting System?

BACKGROUND: Obstetrician-gynecologists are increasingly called upon to be vaccinators as an essential part of a woman's primary and preventive health care. Despite the established safety of vaccines, vaccine adverse events may occur. A national Vaccine Adverse Event Reporting System (VAERS) is a well-established mechanism to track adverse events. However, we hypothesized that many obstetrician-gynecologists are naive to the role and use of VAERS. METHODS: We devised a ten-question survey to a sample of ACOG fellows to assess their knowledge and understanding of VAERS. We performed descriptive and frequency analysis for each of the questions and used one-way analysis of variance for continuous and chi-squared for categorical variables. RESULTS: Of the 1000 fellows who received the survey, 377 responded. Only one respondent answered all nine knowledge questions correctly, and 9.2% of physicians had used VAERS. Older physicians were less familiar with VAERS in general and with the specific objectives of VAERS in particular (χ(2) = 10.7, P = .005). CONCLUSIONS: Obstetrician-gynecologist familiarity with VAERS is lacking. Only when the obstetrician-gynecologist is completely knowledgeable regarding standard vaccine practices, including the availability and use of programs such as VAERS, will providers be functioning as competent and complete vaccinators.

Labor induction for the preterm severe pre-eclamptic patient: is it worth the effort?

OBJECTIVE: The purpose of this study was to examine the success rate of labor induction in patients with severe pre-eclampsia delivered at < or = 34 weeks' gestation; to identify factors associated with its success; and to evaluate neonatal outcomes based on induction success or failure. METHODS: We identified pregnancies complicated by severe pre-eclampsia delivered at < or = 34 weeks' at our institution from 1991 to 1998. Women who underwent labor induction and had successful vaginal delivery were compared to those who underwent labor induction, but required Cesarean delivery. Multiple logistic regression analyses were performed to assess factors associated with successful induction and neonatal outcome. RESULTS: Over the 7-year study period, there were 215 patients meeting the criteria. Sixty-four (29.8%) did not undergo a labor attempt; 69 of 151 (46%) women who underwent labor induction achieved vaginal delivery. Labor induction was successful in 0%, 6.6%, 35.3% and 68.5% of cases at 24-26, 27-28, 29-31 and 32-34 weeks' gestation, respectively. By logistic regression the only factor positively associated with successful induction was gestational age at delivery (p = 0.001), while induction for non-reassuring fetal testing was inversely associated (p = 0.02). Induction attempt, failed induction and delivery mode were not associated with increased neonatal morbidity. CONCLUSIONS: In women with severe pre-eclampsia remote from term, attempted labor induction did not appear to increase neonatal morbidity, but was rarely successful at < 28 weeks.

Obstetric uses of intravenous immunoglobulin: successes, failures, and promises.

Intravenous immune globulin (IVIG) is approved for use in a number of conditions that may occur in obstetrical patients, including autoimmune thrombocytopenia and immune deficiency syndromes. IVIG also is widely used in obstetrics for nonapproved indications, such as fetal-neonatal alloimmune thrombocytopenia, antiphospholipid syndrome, and recurrent miscarriage. This review critically analyzes the use of IVIG for these indications based on the best available information. The authors conclude IVIG is effective in the management of fetal-neonatal alloimmune thrombocytopenia. IVIG appears promising as a treatment for severe fetal-neonatal alloimmune hemolysis due to antierythrocyte antibodies. A prospective multicenter trial should be undertaken. IVIG is no more effective than heparin and low-dose aspirin in the treatment of pregnancies complicated by antiphospholipid syndrome but has not been adequately evaluated in refractory cases. Finally, pending convincing studies, IVIG is not effective and should not be used for the management of recurrent miscarriage.

Adhesion development and the expression of endothelial nitric oxide synthase.

OBJECTIVE: This study was conducted to determine whether nitric oxide (NO), a potent vasodilator and inhibitor of thrombus formation, is involved in the formation and maintenance of adhesions. METHODS: Skin, subcutaneous tissues, peritoneum and adhesions were collected from surgical patients and total RNA was isolated. Quantitative reverse transcription polymerase chain reaction (QRT-PCR) was performed to quantitate endothelial nitric oxide synthase (eNOS) and beta-actin mRNA levels. RESULTS: eNOS mRNA levels for skin, subcutaneous tissue, peritoneum and adhesions were < or = 3.12 x 10(-4), < or = 3.12 x 10(-4), 6.24 x 10(-4) and 2.5 x 10(-3) attomoles/microl, respectively. Beta-actin mRNA levels for all tissues were between 1.25 x 10(-1) and 6.25 x 10(-2) attomoles/microl. CONCLUSION: eNOS mRNA can be identified in tissue adhesions, and may therefore play a role in adhesion formation and maintenance.

Multiple brain infarcts associated with severe preeclampsia.

Posterior occipital and parietal lobe infarcts shown by computed tomography (CT) scan and magnetic resonance imaging have been associated with eclampsia. Gray-white matter, infarct-like lesions of the right basal ganglia, right posterior parietal, and left posterior parieto-occipital lobes were found by CT scan in a patient at 26 weeks gestation with severe preeclampsia and neurologic deficits. A magnetic resonance image taken 3 days postpartum had similar abnormalities, despite total resolution of the patient's symptomatology. A repeat CT scan performed 6 weeks postpartum showed complete resolution of the multiple infarctions. This is a unique case report that describes these severe brain-imaging findings in a patient with severe preeclampsia and neurologic deficits.

Detection of cytomegalovirus in the meconium of infected newborns by polymerase chain reaction.

OBJECTIVE: Congenital cytomegalovirus (CMV) infection is a leading cause of hearing loss and mental retardation throughout the world. Detection of the CMV DNA by polymerase chain reaction (PCR) offers a sensitive, rapid, and specific means of identification. Meconium, the stool formed in utero, may be an ideal specimen for CMV detection. The objective of this study was to develop a PCR-based methodology for the detection of CMV in the meconium of neonates. METHODS: Meconium was collected from 10 newborn infants (seven with positive viral cultures and three uninfected infants born to CMV-seropositive mothers). For each, DNA was isolated from meconium by organic extraction and attachment to a DNA-binding matrix, and PCR was performed using amplimers specific for the major intermediate early (MIE) and late antigenic (LA) regions of CMV. RESULTS: Gel electrophoresis demonstrated an anticipated PCR product of 250 base pairs (bp) corresponding to the MIE region of CMV in all infected and positive control meconium samples. Furthermore, a single band of 150 bp corresponding to the LA region of CMV was also amplified in several of the infected infants. Conversely, no amplification of these antigenic regions was noted in either uninfected infants born to CMV-seropositive mothers or negative controls. CONCLUSIONS: CMV is present within the meconium of infected neonates and is readily detectable by PCR.

Non-surgical management of post-cesarean endomyometritis associated with myometrial gas formation.

We present a case of post-cesarean delivery, nonclostridial endomyometritis in which uterine (myometrial) gas formation raised concern for myonecrosis and need for hysterectomy. The patient fully recovered without surgery. Myometrial gas formation in this setting and in an otherwise stable patient may be an insufficient reason for hysterectomy.

Expression and regulation of vascular endothelial growth factor in a first trimester trophoblast cell line.

Embryo implantation and development are critically dependent upon the spatial and temporal regulation of angiogenesis and localized vascular permeability. A key mediator of these effects is the endothelial cell mitogen vascular endothelial growth factor (VEGF). VEGF has been shown to promote endometrial vascular permeability, fetal vasculogenesis and placental, fetal and maternal angiogenesis. However, the mechanism through which this regulation occurs in the placenta is poorly understood. This study was conducted to determine if the pro-angiogenic cytokines, TNF-alpha and TGF-beta1, affect VEGF expression in human first trimester trophoblasts. Culture of a first trimester trophoblast cell line (HTR-8/SVneo), in the presence of either TNF-alpha or TGF-beta1, resulted in the expression of significant levels of VEGF in culture. The trophoblast cell line also showed a time-dependent and a dose-dependent increase in VEGF mRNA levels when cultured in the presence of either TNF-alpha or TGF-beta1. These results suggest that both TNF-alpha and TGF-beta1 may regulate the production of VEGF in early gestational trophoblasts and may therefore serve to modulate placental vascular permeability and angiogenesis that are necessary for embryo implantation and placentation.

The obstetrician-gynecologist's role in vaccine-preventable diseases and immunization.

OBJECTIVE: To assess by survey the immunization role currently played obstetrician-gynecologists in the state of Michigan. METHODS: Masked questionnaires requesting demographic, knowledge-based, practice, and attitudinal data were sent to 850 ACOG-registered fellows. RESULTS: Three hundred sixty-five physicians responded, 313 of whom were in active practice. Most were male (70%) and graduated from medical school between 1970 and 1989 (68%). The majority provided both obstetric and gynecologic services. The minority (47%) specifically identified themselves as primary care providers. Only 15% of respondents considered screening for vaccine-preventable diseases to be outside the realm of routine obstetric-gynecologic care. In practice, however, 19% did not screen their obstetric patients for any vaccine-preventable diseases, and only 10% assessed their patients for all nine vaccine-preventable diseases listed in the questionnaire. In gynecologic patients, almost 40% of physicians did not assess for any vaccine-preventable disease. A wide range in knowledge level was identified concerning vaccine-preventable diseases, immunization recommendations, and vaccine safety. CONCLUSION: These data show a discrepancy between perceived responsibilities and actual practice patterns of obstetrician-gynecologists regarding vaccine-preventable diseases and the immunization of women. Limitations in current knowledge and practical concerns specific to vaccine administration contribute to this disparity.

Effect of imiquimod on cytokine induction in first trimester trophoblasts.

OBJECTIVES: Imiquimod (IQ) is used clinically for the topical treatment of external genital warts. IQ is an immune response modifier and induces the expression of interferon-alpha and other cytokines in human Peripheral Blood Monocytes (PBMC). Trophoblasts have been previously shown to express inflammatory cytokines upon lipopolysaccharide (LPS) stimulation. The objective of this study was to evaluate the ability of IQ to induce transcription of cytokines in trophoblasts. METHODS: A transformed human first trimester trophoblast cell line, HTR-8/SVneo, was cultured in DMEM containing IQ at concentrations of 0 to 5.0 microg/ml. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) viability assays were conducted to control for any drug-induced cell death. Total RNA was isolated from trophoblasts at 0, 8 and 24 hours of culture and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was conducted using specific amplimers for the inflammatory cytokines interleukin (IL)-1alpha, IL-1beta, IL-6 and IL-8. RT-PCR of beta-actin was performed to control for equal RNA loading. RESULTS: RT-PCR was unable detect an increase in either IL-1alpha, IL-1beta, IL-6 or IL-8 mRNA in first trimester trophoblasts cultured in the presence of 0 to 5.0 microg/mL of IQ for up to 24 hours. RT-PCR confirmed equal RNA loading and MTT viability assays did not show loss of cell viability at concentrations of IQ up to 5.0 microg/ml. CONCLUSIONS: IQ, at the concentrations tested, did not induce the transcriptional expression of inflammatory cytokines in human first trimester trophoblasts. These data suggest that IQ would not induce the expression of inflammatory cytokines in placental trophoblasts.

Mathematic modeling of forces associated with shoulder dystocia: a comparison of endogenous and exogenous sources.

OBJECTIVE: A mathematic model was developed to estimate the compressive pressure on the fetal neck overlying the roots of the brachial plexus by the symphysis pubis during a shoulder dystocia event. The induced pressure was calculated for both exogenous (clinician applied) and endogenous (maternal and uterine) forces during the second stage of labor. STUDY DESIGN: Intrauterine pressure and clinician-applied force data were taken from the existing literature. A free-body diagram was generated and equilibrium equations were used to calculate the contact pressure between the base of the fetal neck and the symphysis pubis during a shoulder dystocia event. RESULTS: Clinician-applied traction to the fetal head (exogenous force) led to an estimated contact pressure of 22.9 kPa between the fetal neck and the symphysis pubis. In contrast, uterine and maternal expulsive efforts (endogenous forces) resulted in contact pressures that ranged from 91.1 to 202.5 kPa. The estimated pressures resulting from endogenous forces are 4 to 9 times greater than the value calculated for clinician-applied forces. CONCLUSION: Neonatal brachial plexus injury is not a priori explained by iatrogenically induced excessive traction. Spontaneous endogenous forces may contribute substantially to this type of neonatal trauma.

Colonoscopic release of the incarcerated gravid uterus.

BACKGROUND: Incarceration of the gravid uterus occurs in the early second trimester in approximately one in 3000 pregnancies. If conventional manual attempts at restoring the uterine fundus to the anterior position are unsuccessful, correction by an invasive laparotomy procedure is necessary. We describe a minimally invasive technique to dislodge the incarcerated gravid uterus. TECHNIQUE: Gravid patients with an incarcerated uterus refractory to manual reduction are administered sedation, and one to two enemas. After sedation, manual reduction is attempted again. If unsuccessful, a colonoscope is passed above the level of the uterine fundus generating external anterior forces, which dislodge the uterus from beneath the sacral promontory. EXPERIENCE: The procedure was performed six times in five patients. One patient required a second procedure because of recurrence of the condition. All procedures were successful. No pregnancy losses occurred after the procedure, and no complications of colonoscopy were encountered. CONCLUSION: Colonoscopic release of the incarcerated gravid uterus is an option when attempts at manual reduction fail. This procedure may avoid laparotomy to correct this condition.

Transvaginal ultrasound-guided aspiration of pelvic abscesses.

OBJECTIVE: To assess the utility of a less invasive approach to the care of women with a pelvic abscess, we retrospectively reviewed the outcome of women with pelvic abscesses managed by transvaginal ultrasound-guided aspiration. METHODS: A retrospective analysis of 27 pelvic abscesses in 22 consecutive women undergoing transvaginal drainage, including 13 tuboovarian abscesses (TOAs) and 14 postoperative abscesses (POAs). All patients received broad-spectrum intravenous antibiotics from the time infection was diagnosed to resolution of signs and symptoms. Chart review and examination of ultrasound files were utilized to extract demographic clinical, laboratory, and outcome data. RESULTS: The mean age for the study group was 30 years old. Mean duration from diagnosis to drainage was 5.6 days (TOA) and 2.0 days (POA), P < 0.01. The mean diameter of the abscesses was 86 mm. The volume of purulent material drained ranged from 70-750 mL. Perceived adequacy of drainage was correlated with lack of abscess septation. Cultures for aerobic and anaerobic pathogens were positive in 51% of cases (79% POA versus 23% TOA, P < 0.05) with 1.9 organisms/ positive culture. Transvaginal drainage was successful in 25 of 27 abscesses. No complications were reported. CONCLUSION: In skilled hands, transvaginal guided aspiration of pelvic abscess is a highly successful technique with minimal risk to the patient. Follow-up studies are needed to assess the long-term sequelae, such as frequency of infertility, ectopic pregnancy, and chronic pelvic pain.

Partner notification of sexually transmitted disease in an obstetric and gynecologic setting.

OBJECTIVE: To survey obstetrician-gynecologists regarding current approaches to partner notification of women with sexually transmitted diseases (STDs) and to relate reported practices to state requirements. METHODS: An anonymous questionnaire was sent to community, hospital-employed, and university-based physicians within a single health care system. The survey was designed to assess physician demographics, knowledge, and attitudes about partner notification of women with STDs. RESULTS: One hundred eight (49%) of 222 surveys were returned. Respondents were 36% private practitioners, 38% hospital-employed, and 23% university faculty physicians. Although most correctly identified the importance of partner notification for several STDs, they (63 of 108, 58%, confidence interval [CI] 50%, 67%) could not identify all of those conditions. Most respondents (84 of 108, 78%, CI 69%, 85%) were unaware of all required reportable STDs and the state's preferred method of partner notification. The vast majority of respondents (96 of 108, 89%, CI 82%, 94%) relied on women to notify their partners of the STD. CONCLUSION: Educational efforts are needed to increase physician awareness of required reportable STDs and the role of partner notification and treatment in disease control. Physicians need to be aware of state regulations for partner notification when they are in practice. Development of standard algorithms for partner notification and treatment might be needed.

Shoulder dystocia.

Shoulder dystocia is an infrequent and unexpected emergency requiring rapid and deft solution. Identifiable risk factors include maternal diabetes, fetal macrosomia (especially in the presence of diabetes), and maternal history of previous delivery of a large infant. Other reported risk factors include arrest and protraction disorders of labor and midpelvic operative delivery; however, more than 50% of shoulder dystocia occurs in instances without identifiable risk factors, and permanent neonatal injury is thus unpredictable. Therefore, all personnel in the delivery suite must be well versed in the timely and appropriate application of corrective measures. Although most instances of shoulder dystocia cannot be predicted, the judicious use of CS delivery in diabetic patients with expected birth weights of more than 4250 g should reduce the risk of shoulder dystocia in this subgroup of patients. A trial of labor for nondiabetic patients with suspected fetal macrosomia is recommended because predicting actual birth weights in this population remains difficult.

Single daily dosing of gentamicin: pharmacokinetic comparison of two dosing methodologies for postpartum endometritis.

OBJECTIVE: We compared the pharmacokinetics of two methods for dosing gentamicin for the treatment of postpartum endometritis with the goal of achieving adequate peak serum concentrations (>12 mg/L) and prolonged trough levels below 2 mg/L. METHODS: Group-I subjects (n = 5) received intravenous gentamicin, 5 mg/kg per total body weight over 60 min., with a maximum dose of 500 mg. Group-II subjects (n = 17) were dosed intravenously according to the following formula: Dose = desired peak concentration (fixed at 14 mg/L) * (volume of distribution, i.e., 0.35 L/kg) * adjusted body weight (in kilograms). Serum gentamicin levels were obtained 1 hr. and 8-12 hr. after infusion of the second dose. Pharmacokinetic parameters for the subjects in each group were calculated according to standard formulas. RESULTS: Subjects in Group I had significantly higher doses and peak drug concentrations (P < 0.01), while in Group II, 76% of patients had peak levels less than desired (<12 mg/L). Both groups maintained trough levels of <2 mg/L in excess of 12 hr. CONCLUSIONS: Changing to the adjusted body weight formula for Group I, while maintaining a dose between 4 and 5 mg/kg, would reduce excessive peak concentrations. Using a calculated volume of distribution of 0.4 L/kg in Group II would improve peak serum concentrations to the desired levels. Both dosing regimens ensure adequate aminoglycoside pharmacokinetic parameters and avoid the need for monitoring serial serum drug concentrations, provided the expected clinical response is also achieved. While the first dosing formula is simpler to calculate, the second dosing formula allows for more individualized dosing considerations.

High levels of maternal serum human chorionic gonadotropin in Down syndrome pregnancies: the possible role of a transcription factor on chromosome 21.

Increased levels of human chorionic gonadotropin (hCG) are used as markers for Down syndrome (DS) screening of low-risk populations. The pathophysiology for increased hCG levels remains unknown. In general, hCG synthesis is limited by the rate of beta-chain formation. In the placenta, 2 of a total of 6 hCG beta-genes are expressed. We hypothesized that in DS, a transcriptional factor may upregulate beta-chain transcription by interacting with the beta5-promoter. Primary cell cultures of skin fibroblasts from both normal and DS midtrimester fetuses were established and transfected with the beta5-promoter linked to the chloramphenicol-acetyl-transferase reporter gene. The chloramphenicol-acetyl-transferase activity was measured. Three of six DS-derived cell cultures showed a three-fold increase in acetylation. The increase in hCG promoter activity in DS-derived fibroblasts suggests a possible role for a transcriptional factor located on the human chromosome 21 by either directly or indirectly interacting with the beta5-promoter.