Attitudes of maternal-fetal specialists concerning maternal-fetal surgery.

OBJECTIVE: We examined the attitudes of members of the Society for Maternal-Fetal Medicine regarding the clinical, scientific, ethical, and policy issues in maternal-fetal surgery. STUDY DESIGN: A 43-question survey was distributed to all members of the Society for Maternal-Fetal Medicine. Two mailings and one electronic mail reminder were sent, each with instructions to submit the survey either via US mail or the Internet. The survey included questions in six categories: physician demographic data, experience with maternal-fetal surgery, views on innovative therapies, scientific validation of currently used and proposed procedures, ethical issues, and future directions in public policy. RESULTS: Of the 1639 United States members sent questionnaires, 943 replied (response rate = 59%). Forty-seven percent had referred patients for open fetal surgery for nonlethal conditions, and 69% believed physicians were obligated to inform patients of this option. Seventy-eight percent believed that innovative therapies should be performed only under institutional review board-approved protocols. Although the majority of respondents believed that certain proposed benefits of open fetal surgery for myelomeningocele could offset the risks, the majority (56%) also indicated that the procedure has not been validated. Fifty-seven percent believed that a moratorium should be imposed on open fetal surgery for nonlethal conditions, such as myelomeningocele, until a multicenter-controlled clinical trial is completed. CONCLUSIONS: The use of maternal-fetal surgery for nonlethal conditions is highly controversial. The majority of maternal-fetal specialists we surveyed support further research before such procedures are integrated into clinical practice.

Toward the ethical evaluation and use of maternal-fetal surgery.

BACKGROUND: Important clinical, social, and ethical questions are associated with the evaluation and use of surgical approaches aimed at correcting fetal anatomic abnormalities. In particular, the expansion of maternal-fetal surgery to ameliorate nonlethal fetal conditions has intensified the need to address issues about the adequacy of technology assessment and the safety of those who undergo these novel procedures. APPROACH: After discussions at a multidisciplinary conference, we reviewed the development and current practices of maternal-fetal surgery and analyzed the relevant ethical issues concerning the use of maternal-fetal surgery for nonlethal conditions, focusing on the correction of myelomeningocele. FINDINGS: Characterizing nonvalidated maternal-fetal surgery procedures as "innovative therapy" blurs the boundaries between research and therapy and creates uncertainty about the obligations of clinicians and researchers. Further, maternal-fetal surgery raises ethical issues related to maternal risks and benefits, informed consent, distinguishing lethal from nonlethal conditions, withholding unproven treatments, entrepreneurship, and prioritization. RECOMMENDATIONS: To help ensure that maternal-fetal surgery will be studied and eventually applied in a scientifically and ethically sound manner, we offer several recommendations. First, innovation in maternal-fetal surgery should be conducted and evaluated as research. Second, women must be considered research subjects in these trials. Third, the informed consent process must ensure adequate comprehension and genuine voluntariness in those considering participation. Fourth, discriminatory and fearful attitudes toward individuals with disabilities should be addressed explicitly prior to making a decision to proceed with maternal-fetal surgery in an attempt to correct such disabilities. Fifth, maternal-fetal surgery should not be performed for cosmetic indications unless and until there is reliable evidence that maternal-fetal surgery can be performed safely and that long-term side effects on women and their offspring are minimal. Sixth, centers of excellence should be established for conducting research and providing maternal-fetal surgery. Seventh, funding for research on maternal-fetal surgery should be considered in the context of societal needs.

Preconceptional health care model.

During the last 10 years, there has been a movement to expand the definition of prenatal care to encompass preconceptional counseling. Major organizations throughout the world have endorsed preconceptional counseling as an integral component of care for all women contemplating pregnancy. This article will assist health care providers who interact with women of reproductive age to understand the potential benefits and limitations of preconceptional counseling and to develop an approach to that service relating to nutrition, infections, and metabolic diseases as they impact on reproductive outcome. Although there are many potential benefits of the preconception health care model, barriers to its implementation remain.

Central hemodynamic effects of oxytocin and interaction with magnesium and pregnancy in the isolated perfused rat heart.

OBJECTIVE: Our purpose was to determine the cardiac effects of oxytocin in the isolated perfused rat heart model and to see whether pregnancy or pharmacologic levels of magnesium modifies the hormone's action. STUDY DESIGN: Hearts were excised from 30 female Sprague-Dawley rats (15 pregnant, 15 nonpregnant) and attached to a Langendorf's apparatus. Heart rate, left ventricular systolic pressure, and contractility were measured. Hearts were exposed serially to 2, 4, and 6 mU/ml concentrations of oxytocin. The experiment was repeated in 15 pregnant animals at a magnesium level of 5 mEq/L. RESULTS: Hearts from pregnant rats had lower heart rates than did hearts from nonpregnant animals. Oxytocin exposure diminished heart rate but increased left ventricular systolic pressure and contractility in a dose-dependent manner. Pregnancy did not alter this response. Magnesium levels of 5 mEq/L reversed the effects of oxytocin on contractility and left ventricular systolic pressure. CONCLUSION: Oxytocin is a negative chronotropic and positive inotropic agent in hearts from pregnant and nonpregnant rats. Magnesium reserves the positive inotropic effects of oxytocin.

Central hemodynamic effects of recombinant human relaxin in the isolated, perfused rat heart model.

OBJECTIVE: To determine the cardiac effects of relaxin in the isolated, perfused rat heart model, and to see if pregnancy modifies the hormone's actions. METHODS: Hearts were excised from 18 female Sprague-Dawley rats (ten pregnant, eight nonpregnant) and attached to a Langendorff apparatus. Left ventricular systolic pressure, heart rate, and contractility were measured. Hearts were exposed serially to 0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 ng/mL concentrations of recombinant human relaxin. RESULTS: Hearts from pregnant rats had lower heart rates than those from nonpregnant animals. Relaxin increased heart rate, left ventricular systolic pressure, and contractility in a dose-dependent fashion. Pregnancy did not modify this response. CONCLUSION: Recombinant human relaxin is a potent inotropic and chronotropic agent. The effects coupled with the physiologic increase of relaxin during human pregnancy indicate that relaxin may be involved in the cardiovascular changes of pregnancy.

The impact of a preconceptional health promotion program on intendedness of pregnancy.

The objective for this study was to determine whether a brief preconceptional health promotion program for low-income women attending family planning clinics impacts on intendedness of pregnancy. In this prospective study, we examined data on 1378 women presenting for prenatal care at three local health departments. Each of the departments offers a standardized preconceptional health promotion program in its family planning clinics. Comparisons were undertaken for 456 women who had been exposed to the family planning preconception program, 309 women who had attended the family planning clinics but had not been exposed to the program, and 613 women who were unknown to the health department before beginning prenatal care. Women exposed to information on preconceptional health during routine family planning visits, the experimental group, had a 51.8% (p = 0.064) greater likelihood of identifying their pregnancies at intended than a group known to the local health departments' family planning programs but unexposed to the intervention. Furthermore, the experimental group had a 64.2% (p = 0.0009) greater likelihood of intendedness than a comparison group not known to the health departments before the initiation of prenatal care. Our study indicates that an introductory program of preconceptional health promotion which is targeted to women not planning a pregnancy in the immediate future is associated with a higher rate of intendedness in subsequent pregnancies. Expansion of similar preconceptional programs in family planning clinics may prove a useful approach for promoting intendedness of pregnancy in low-income women.

Effects of cocaine administration during early organogenesis on prenatal development and postnatal growth in mice.

Cocaine use has been associated with adverse developmental effects in humans. However, clinical reports both confirm and deny an association between cocaine use and malformations. Similarly, differences in species and strain, as well as route and timing of cocaine administration, have added to the difficulties in determining the teratogenicity of cocaine in animal models. This study was undertaken to compare the effects of dose, route, and timing of cocaine administration in ICR mice during early organogenesis. A single intraperitoneal (ip) administration of cocaine ( > or = 60 mg/kg) on Day 9 of gestation (plug day = 1) produced maternal lethality. The predominant developmental effect of cocaine administration was an increase in the percentage of litters exhibiting an enlarged renal pelvis. Despite a high incidence of affected pups at these doses, the enlargement was not severe. These results, in agreement with previous reports, provide further evidence that the developing urogenital system is sensitive to cocaine administration. When cocaine was administered using a subcutaneous route, pup weights were greater and the incidence of enlarged renal pelvis was lower than when an ip route was used. To better mimic human binge cocaine abuse, the toxicity of a "split dose" was determined. A 60 mg/kg dose was administered using one administration of 60 mg/kg, two treatments of 30 mg/kg, or three administrations of 20 mg/kg with 1 hr separating the treatments. The incidence of enlarged renal pelvis was similar when cocaine was administered as one or two but was decreased when cocaine was administered as three treatments. Both the route and split-dose studies suggest that high-peak serum concentrations are required to perturb development. There were no differences in the incidence or severity of enlarged renal pelvis when cocaine was administered on Day 8, 9, or 10 or on all 3 days of gestation. This suggested that the increase in enlarged renal pelvis may not be a specific teratogenic effect of cocaine administration but may be a delay of normal development induced by cocaine exposure during this early period of organogenesis. To address this hypothesis, cocaine was administered on Day 9 using an ip route and the pups were allowed to be naturally born. In pups whose mothers received cocaine there was an increase in postnatal deaths and a trend toward a reduction in pup body weight/litter at Postnatal Day 21. However, when renal morphology was assessed on Postnatal Day 21 no abnormal kidneys were seen. This supports the hypothesis that enlarged renal pelvis produced by cocaine administration during early organogenesis represents a developmental delay and not a persistent teratogenic defect. These studies suggest that high peak cocaine concentrations are required to delay normal kidney morphogenesis in mice.

Breast-feeding education of obstetrics-gynecology residents and practitioners.

OBJECTIVE: Our purpose was to assess breast-feeding education, knowledge, attitudes, and practices among resident and practicing obstetrician-gynecologists. STUDY DESIGN: A mailed survey was administered to a national sample of resident and practicing obstetrician-gynecologists. RESULTS: Response rates were 64% for residents and 69% for practitioners. Residency training included limited opportunity for direct patient interaction regarding breast-feeding; 60% of practitioners recommended that training devote more time to breast-feeding counseling skills. Only 38% of residents reported that obstetric faculty presented breast-feeding topics; more common sources were nursing staff and other residents. Practitioners rated themselves as more effective in meeting the needs of breast-feeding patients than were residents; prior personal breast-feeding experience was a significant influence on perceived effectiveness. Almost all respondents agreed that obstretician-gynecologists have a role in breast-feeding promotion, but significant deficits in knowledge of breast-feeding benefits and clinical management were found. CONCLUSION: Residency training and continuing education programs should create opportunities to practice breast-feeding promotion skills and emphasize management of common lactation problems.

Preconception care: a means of prevention.

Preconceptional health promotion should provide a prevention framework for interactions with all women of childbearing potential. Preconceptional counselling is properly directed by specialists in the field of obstetrics and gynaecology, but a multispecialty effort may be needed to achieve adequate information for decision-making. Preconceptional health care offers an important opportunity for physicians involved in women's health to expand a primary care and a primary prevention focus. The obstetrician or gynaecologist is not only involved in acute diagnosis and treatment plans but also in disease prevention, risk and behaviour modification and counselling, which are integral parts of primary prevention and co-ordinated women's health care.

National assessment of physicians' breast-feeding knowledge, attitudes, training, and experience.

OBJECTIVE: Previous reports have demonstrated that physician counseling can improve rates of breast-feeding initiation and duration but suggest that physicians are ill-prepared for this role. It is unclear whether residency training for pediatricians, obstetrician/gynecologists, and family physicians provides the knowledge and skills necessary for effective breast-feeding promotion. DESIGN: Survey. PARTICIPANTS: A national random sample of 3115 residents and 1920 practicing physicians in pediatrics, obstetrics/gynecology, and family medicine. OUTCOMES: Assessment of breast-feeding knowledge, attitudes, training, and experience. RESULTS: Overall response rate was 68%. All groups demonstrated significant deficits in knowledge of breast-feeding benefits and clinical management; for example, less than 50% of residents chose appropriate clinical management for a breast-fed jaundiced infant or a breast abscess. Practicing physicians performed slightly better, but still more than 30% chose incorrect advice for mothers with low milk supply. Residents reported that their breast-feeding instruction consisted mainly of didactic lecture, not patient experience. Only 55% of senior residents recalled even one instance of precepting related to breast-feeding, and less than 20% had demonstrated breast-feeding techniques at least five times during residency. Regarding preparation for breast-feeding counseling, more than 50% of all practicing physicians rated their residency training as inadequate. Overall, physician involvement in breast-feeding promotion was endorsed by 90% of respondents, yet only half rated themselves as effective in counseling breast-feeding patients. The greatest predictor of physician self-confidence was previous personal or spousal breast-feeding experience. CONCLUSIONS: In this national sample of residents and practicing physicians in three specialties, physicians were ill-prepared to counsel breast-feeding mothers. Deliberate efforts must be made to incorporate clinically based breast-feeding training into residency programs and continuing education workshops to better prepare physicians for their role in breast-feeding promotion.

Pregnancy in a patient with eosinophilic granulomatosis of the lung: a case report.

BACKGROUND: There are three syndromes of histiocytosis X: eosinophilic granulomatosis of the lungs, Hand-Schüller-Christian disease, and Letterer-Siwe disease. Although there have been five case reports of Hand-Schüller-Christian disease in pregnancy, we found none describing pregnancy in patients with eosinophilic granulomatosis. CASE: We present a report of eosinophilic granulomatosis of the lungs in pregnancy. The patient's pregnancy was complicated by fetal growth retardation (FGR) and oligohydramnios, but resulted in the delivery of a healthy infant. Her pulmonary disease remained stable. CONCLUSION: Pregnancy does not appear to exacerbate pulmonary eosinophilic granulomatosis. In this patient, pregnancy was complicated by FGR and oligohydramnios. This case report may be valuable in counseling patients with eosinophilic granulomatosis who are currently pregnant or contemplating pregnancy.

Estrogen mediates the pregnancy-enhanced cardiotoxicity of cocaine in the isolated perfused rat heart.

OBJECTIVE: To determine whether pregnancy enhances cocaine toxicity in the isolated perfused whole rat heart model and whether this enhanced toxicity can be simulated by pre-treatment with either estrogen or progesterone. METHODS: Hearts excised from 65 female Sprague-Dawley rats were attached to a Langendorff apparatus for measurement of left ventricular systolic pressure, heart rate, and contractility. Before excision, the animals were assigned to one of five groups: 1) nonpregnant, 2) pregnant, 3) nonpregnant pretreated with progesterone, 4) nonpregnant pretreated with estrogen, and 5) nonpregnant pretreated with estrogen and progesterone. Each group was exposed serially to the following cocaine concentrations: 5 x 10(-6), 1 x 10(-5), and 6 x 10(-5) mol/L. RESULTS: Heart rate declined at all doses of cocaine (9.2, 6.9, and 31.0%, respectively). The lowest dose of cocaine had positive inotropic effects, with a 23.2% increase in left ventricular pressure and a 15.3% increase in contractility. Exposure to the two higher doses resulted in negative inotropic effects (a 24.8% decrease in left ventricular pressure and a 39.7% decrease in contractility for the highest dose). Although pre-treatment with estrogen, alone or with progesterone, resulted in responses similar to those seen in pregnant animals, progesterone pre-treatment alone failed to do so. CONCLUSIONS: Cocaine displayed cardiotoxicity in isolated rat hearts similar to that in other animal models. This toxicity was enhanced by pregnancy. We were able to simulate changes by pretreating the animals with estrogen. Perhaps the enhanced cardiotoxicity of cocaine in pregnancy is partially mediated by estrogen.

Group B streptococci: results of a protocol of antepartum screening and intrapartum treatment.

OBJECTIVE: Our purpose was to evaluate and report the results of a protocol for the identification and treatment of all group B streptococcal carriers. STUDY DESIGN: In 1991 we instituted a protocol of antepartum cultures for group B streptococci on all pregnant women who attended clinics at the University of North Carolina Hospitals. Cultures were obtained from the lower third of the vagina and rectum at 24 to 28 weeks' gestation. Women with positive cultures were treated with intravenous antibiotics in labor. Women with signs of chorioamnionitis (through intrapartum assessment) were also treated in labor, regardless of carrier status. RESULTS: During the first 2 years of this protocol 1681 women were delivered. Forty percent of the women were from the private practice, 32% were black, and 62% were married. The group B streptococcal carriage rate was 14%. During the period of evaluation there were no infants infected with group B streptococci and no adverse reactions or complications among women who were treated with antibiotics. CONCLUSION: We found antepartum screening and intrapartum chemoprophylaxis of all group B streptococcal carriers to be an acceptable and effective protocol for reducing perinatal group B streptococcal infections.

Central hemodynamic effects of cocaine and ritodrine in the isolated, perfused rat heart.

OBJECTIVE: To explore the cardiac interactions of cocaine and ritodrine in pregnancy. METHODS: Using the isolated, perfused rat-heart model, hearts from pregnant Sprague-Dawley rats were exposed to increasing concentrations of ritodrine: 25, 50, 100, and 250 ng/mL. Hearts of half of the animals, the experimental group, were exposed to cocaine (5 x 10(-6) mol/L). Left ventricular systolic pressure, heart rate, and contractility were measured. RESULTS: Ritodrine had marked positive inotropic and chronotropic effects. Cocaine exposure resulted in smaller increases in all indices. CONCLUSION: Cocaine blunted but did not obliterate the cardiac stimulatory effects of ritodrine in this model.

The bioethics of human fetal tissue research and therapy: moral decision making of professionals.

OBJECTIVE: We investigated the decision making of professionals regarding the ethical acceptability of using human fetal tissue from elective abortion for research or therapy. STUDY DESIGN: We surveyed 390 professionals from 20 European countries on their ethical beliefs regarding the scientific and medical use of human fetal tissue from elective abortion. We assessed the importance of basic medical ethics and beliefs regarding the morality of abortion and fetal rights to their decision making. RESULTS: Sixty-six percent of 198 responding professionals believed that use of fetal tissue from elective abortion was ethically acceptable. Beliefs regarding the morality of elective abortion and fetal exploitation overwhelmingly influenced individual ethics regarding fetal tissue research or therapy. CONCLUSION: Ethical decision making is a dynamic process and individuals are not altogether consistent in their beliefs. The important public policy issues raised in this study concern the rights of the dead fetus, whether these rights are exploited through fetal tissue therapy, and whether women's right of authority over the disposition of aborted fetal tissue is abdicated.

PIP: In 1990, 390 professionals involved or interested in reproductive health issues from 20 European countries were randomly selected to participate in this study in collaboration with the Institute for Bioethics at Maastricht, the Netherlands. The group of scientists, physicians, public health officials, lawyers, philosophers, theologians, and ethicists were mailed an English-language, self-administered questionnaire. Surveys were completed by 198 professionals (51% response rate) from 20 European countries. 66% (n = 118) of the professionals believed that the therapeutic use of human fetal tissue from elective abortion was ethically acceptable, whereas 34% (n = 60) did not. Bivariate analysis showed that 87% (n = 47) of those who believed that life begins at or after viability and 90% (n = 60) of those who believed elective abortion was morally acceptable found the use of fetal tissue for research and therapy ethically acceptable. 137 did not believe that the potential medical benefits arising from fetal tissue therapy outweighed any moral problem associated with the abortion. Even so, 61% (n = 82) holding that position believed that the therapeutic use of fetal tissue from selective abortion was ethically acceptable. However, about half the sample stated that they were not knowledgeable about animal studies research on fetal tissue therapy in the treatment of Parkinson disease. Of the 68% (n = 113) who supported fetal tissue therapy generally, only 80 (70%) of these would continue to do so if research showed that fetal tissue therapy offered only temporary relief rather than actual cure. Consequently, 48% would support fetal tissue therapy in humans under these conditions. None of the multiple regression analysis variables measuring demographics or the concepts of beneficence, justice, abortion morality generally, or the use of scientific evidence remained significant. The only significant variables associated with an increased likelihood of approving the use of fetal tissues were ones representing the value and belief concepts of fetal rights, concerns over second-trimester abortion, respect for autonomy of the mother, and nonmaleficence.

Spontaneous resolution of hypofibrinogenemia in a triplet gestation associated with second trimester in utero death of two fetuses.

Multiple gestations are increasing in frequency secondary to assisted reproductive technologies; therefore, it will become increasingly important to know how to manage a multiple pregnancy in which an in utero fetal death has occurred. This case report describes the spontaneous resolution of maternal hypofibrinogenemia associated with the deaths of two fetuses in a triplet gestation. A 29-year-old woman with a triplet gestation had in utero death of two monoamniotic fetuses between 15 and 17 weeks' gestation. Maternal plasma fibrinogen levels were obtained weekly and were initially in the normal range for pregnancy. At 31 weeks' gestation, the fibrinogen level decreased to 239 mg/dl and reached a nadir of 150 mg/dl 11 days later. Although the patient received no treatment, her fibrinogen level increased to 307 mg/dl over the next 4 days and then remained above 260 mg/dl for the rest of her pregnancy. At 35 weeks' gestation, a healthy 2090 gm female was delivered. The infant is alive and well and developing normally. When there is an in utero death of one fetus of a multiple gestation in the second or early third trimester, some authors advocate heparinization to reverse maternal coagulopathy; others describe spontaneous resolution of hypofibrinogenemia. The role of heparin in treating hypofibrinogenemia remains unclear. Hypofibrinogenemia may resolve spontaneously without exposing the patient to the potentially serious risks associated with heparin therapy.

Do nifedipine and verapamil potentiate the cardiac toxicity of magnesium sulfate?

We hypothesized that verapamil and nifedipine would potentiate the cardiac toxicity of magnesium in a dose-dependent manner. The hypothesis was tested in the isolated perfused rat heart model (Langendorff's apparatus) with Sprague-Dawley rats. After excision of hearts, each heart was exposed to increasing doses of verapamil and nifedipine followed by magnesium sulfate. Heart rate, contractility, and left ventricular systolic pressure were measured. Nifedipine and verapamil infusion in this model caused dose-dependent decreases in all three parameters measured (p values 0.05 to 0.01). The addition of magnesium sulfate potentiated these dose-dependent decreases (p values 0.01 to 0.0002). Nifedipine and verapamil caused similar depression at equivalent doses. Nifedipine and verapamil cause dose-dependent cardiac depression that is potentiated by the addition of magnesium sulfate in the isolated perfused rat heart. Caution is called for when magnesium sulfate and calcium channel blockers are administered in combination.

The pharmacokinetics of recombinant human relaxin in nonpregnant women after intravenous, intravaginal, and intracervical administration.

The pharmacokinetics of recombinant human relaxin (rhRlx) after intravenous (iv) bolus administration and the absorption of rhRlx after intracervical or intravaginal administration were determined in nonpregnant women. The study was conducted in two parts. In part I, 25 women received 0.01 mg/kg rhRlx iv. After a minimum 7-day washout period, these women were dosed intracervically (n = 10) or intravaginally (n = 15) with 0.75 or 1.5 mg rhRlx, respectively, in 3% methylcellulose gel. Part II was a double-blind, randomized, three-way crossover study in 26 women. At 1-month intervals, each woman received one of three intravaginal treatments consisting of 0 (placebo), 1, or 6 mg rhRlx in 3% methylcellulose gel. The serum concentrations of relaxin following iv administration were described as the sum of three exponentials. The mean (+/- SD) initial, intermediate, and terminal half-lives were 0.09 +/- 0.04, 0.72 +/- 0.11, and 4.6 +/- 1.2 hr, respectively. Most of the area under the curve was associated with the intermediate half-life. The weight-normalized clearance was 170 +/- 50 mL/hr/kg. The observed peak concentration was 98 +/- 29 ng/mL, and the weight-normalized initial volume of distribution was 78 +/- 40 mL/kg, which is approximately equivalent to the serum volume. If central compartment elimination was assumed, the volume of distribution at steady state (Vss/W) was 280 +/- 100 mL/kg, which is approximately equivalent to extracellular fluid volume. Vss/W could be as large as 1300 +/- 400 mL/kg without this assumption.(ABSTRACT TRUNCATED AT 250 WORDS)