Disposition of sperm donors with resultant abnormal pregnancies.

We wished to determine how clinicians manage sperm donors whose offspring have chromosomal or structural abnormalities. A directed, multiple-choice survey was given to reproductive endocrinologists and obstetrical geneticists to assess management of sperm donors whose offspring have chromosomal or structural abnormalities. The questionnaire was completed by 66 reproductive endocrinologists and obstetrical geneticists. Abnormalities and the most common inheritance modes included: Trisomy 21 (aneuploidy, maternal origin), Turner syndrome (aneuploidy, paternal origin), cleft lip/palate (multifactorial), VATER sequence (vertebral defects, imperforate anus, tracheo-esophageal fistula, radial and renal dysplasia, sporadic inheritance), and Hurler syndrome (autosomal recessive). Response choices were: (i) remove donor from programme, (ii) inform potential recipients of prior pregnancy outcomes and continue to use donor, or (iii) further study donor to assess karyotype/mutations. Inheritance mode appeared to influence decisions to remove donors from sperm banks; however, no clear consensus was noted. Guidelines exist for screening potential gamete donors, but not for managing donors whose offspring has a chromosomal or structural abnormality. Guidelines must be developed to manage sperm donors with untoward pregnancy outcomes.

Pregnancy in transplant recipients.

A growing number of transplant recipients are women of reproductive age or children who will reach reproductive age. Thus, menstrual function and pregnancy increasingly are important issues because fertility is restored to women who were previously unable to conceive. To date, successful pregnancies have been reported in female recipients of kidney, liver, heart, pancreas-liver, bone marrow, and lung transplants. Women often become pregnant while being maintained on numerous medications, including immunosuppressive agents, and their care providers must be able to counsel and care for them. Information to date suggests that immunosuppressive medications are safe for use during pregnancy and are important in preventing maternal and fetal complications secondary to graft rejection. Although no formal guidelines have been established due to limited clinical experience, there are a few criteria that are commonly agreed on to improve the probability of a successful pregnancy outcome and the maintenance of graft function in transplant patients. Successful management of the pregnant transplant patient requires a cooperative effort between the obstetrician and transplant team.

Renal biopsy and pregnancy.

OBJECTIVE: Our aim was to review our experience with renal biopsy in pregnancy. STUDY DESIGN: We reviewed 18 renal biopsies performed during pregnancy or in the immediate postpartum period at the University of North Carolina. Indications, histopathologic findings, complications, and neonatal outcome were reviewed for each case. RESULTS: Fifteen patients underwent biopsy during the antepartum period and 3 in the postpartum period. Only 5 patients had the classic histopathologic preeclamptic lesion glomeruloendotheliosis confirmed. There were 7 identifiable renal hematomas after biopsy; 2 patients required blood transfusion. There were 4 intrauterine fetal deaths in this series; it is presumed that none were a result of the biopsy. CONCLUSION: Renal biopsy in pregnancy is a morbid procedure and should be considered only if it offers the opportunity to make a diagnosis other than severe preeclampsia in a patient remote from term.

Preeclampsia into eclampsia: toward a new paradigm.

OBJECTIVE: This study was undertaken to characterize aspects of the natural history of eclampsia. STUDY DESIGN: A retrospective analysis was performed on the records of patients with eclampsia who were delivered at two tertiary care hospitals. RESULTS: Fifty-three pregnancies complicated by eclampsia were identified. Thirty-seven of the women were nulliparous. The mean age was 22 years (range, 15-38 years). Mean gestational age at the time of seizures was 34.2 weeks' gestation (range, 22-43 weeks' gestation). Twenty-eight women had antepartum seizures (53%); 23 of the 28 had seizures at home. Nineteen women had intrapartum seizures (36%). Eight of these women had seizures while receiving magnesium sulfate, and 7 had therapeutic magnesium levels. Six women had postpartum seizures (11%), 4 >24 hours after delivery. Headache preceded seizures in 34 cases. Visual disturbance preceded seizures in 16 cases. The uric acid level was elevated to >6 mg/dL in 43 women. There were no maternal deaths or permanent morbidities. There were 4 perinatal deaths. Two patients had intrauterine fetal deaths at 28 and 36 weeks' gestation. These mothers had seizures at home. One infant died of complications of prematurity at 22 weeks' gestation and one died of respiratory complications at 26 weeks' gestation. There were 4 cases of abruptio placentae, 1 of which resulted in fetal death. Of the 53 cases of eclampsia, only 9 were potentially preventable. One of these was that of a woman who was being observed at home. The other 8 women were hospitalized and had hypertension and proteinuria. Only 7 women could be considered to have severe preeclampsia before seizure (13%), and 4 of these 7 women were receiving magnesium sulfate. CONCLUSIONS: Eclampsia was not found to be a progression from severe preeclampsia. In 32 of 53 cases (60%) seizures were the first signs of preeclampsia. In this series eclampsia appeared to be more of a subset of preeclampsia. Only 9 cases of eclampsia were potentially preventable with current standards of practice. Our paradigm for this disease, as well as our approach to seizure prophylaxis, should be reevaluated.

Central hemodynamic effects of an oxytocin receptor antagonist (atosiban) in the isolated, perfused rat heart.

OBJECTIVE: Atosiban is a selective oxytocin receptor antagonist capable of inhibiting oxytocin-induced contractility of the uterus. Trials of this agent in intact animals and women as a tocolytic agent for preterm labor have shown atosiban to be devoid of cardiac effects. This is in contrast to other tocolytic agents, which have profound hemodynamic effects. We conducted this study to determine the cardiac effect of atosiban in the isolated, perfused rat heart model. METHODS: Hearts were excised from 60 female Sprague-Dawley rats and attached to a Langendorff apparatus. Left ventricular systolic pressure, heart rate, and contractility were measured. Hearts from half of the animals were exposed serially to 300 micrograms/min, 600 micrograms/min, and 1200 micrograms/min of atosiban. The remaining hearts formed the control group and were exposed to aerated Krebs solution. RESULTS: There were no significant differences between hearts exposed to atosiban and hearts within the control group for heart rate, left ventricular systolic pressure, and contractility. P values ranged from .12 to .73. CONCLUSIONS: Using a classic physiologic model to study cardiac performance and drug effects, we were unable to detect any central hemodynamic effects of atosiban. This is in contrast to oxytocin, which we previously studied and found negative chronotropic and positive ionotropic effects.

Urinary incontinence in pregnancy and the puerperium: a prospective study.

OBJECTIVE: Pregnancy and childbirth are commonly thought to be associated with the development of urinary incontinence and lower urinary tract symptoms. The purpose of this study was to assess the relationship, if any, between pregnancy and the development of lower urinary tract symptoms. STUDY DESIGN: A prospective study of lower urinary tract symptoms was carried out in a cohort of pregnant women who answered a series of symptom questionnaires and kept a 24-hour bladder chart on which frequency of urination and volumes voided were recorded throughout pregnancy and for 8 weeks after birth. RESULTS: A total of 123 women participated in the study. Mean daily urine output (P =.01) and the mean number of voids per day (P =.01) increased with gestational age and declined after delivery. Episodes of urinary incontinence peaked in the third trimester and improved after birth (P =.001). White women had higher mean voided volumes and fewer voiding episodes than did black women. Ingestion of caffeine was associated with smaller voided volumes and greater frequency of urination. CONCLUSION: Pregnancy is associated with an increase in urinary incontinence. This phenomenon decreases in the puerperium. Pregnancy and childbirth trauma are important factors in the development of urinary incontinence among women. These findings warrant further investigation.

Peripartum cardiomyopathy: a review of the literature.

UNLABELLED: Peripartum cardiomyopathy (PPCM) is a poorly characterized, rare form of cardiomyopathy. The etiology of PPCM is unknown, but viral, autoimmune, and idiopathic causes may contribute. The presentation is similar to other forms of congestive heart failure; the diagnosis of PPCM should not be considered until other causes of cardiac dysfunction are ruled out. Echocardiography is central to diagnosis. Early diagnosis and initiation of treatment are essential to optimize pregnancy outcome. Intensivists and anesthesiologists should be consulted to assist with management in complicated cases. Management of PPCM is essentially supportive. Prognosis is poor, although cardiac transplant is improving prognosis and should be considered when conventional therapy fails. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to understand the typical presentation of peripartum cardiomyopathy including adverse outcome predictors, to understand how to make the diagnosis of PPCM and how to manage it, and to understand the natural history of the disease.

Prenatal diagnosis and perinatal management of fetal sacrococcygeal teratoma.

Sacrococcygeal teratoma is the most common fetal neoplasm, with an incidence of 1 in 40,000 births. Fetuses with this malformation are at risk for significant perinatal morbidity and mortality. We identified nine fetuses with sacrococcygeal teratomas that were diagnosed antenatally and managed at the University of North Carolina Hospitals over a 7-year period. We retrospectively reviewed the charts of mothers and infants and recorded data concerning perinatal and surgical management. Six infants survived the neonatal period. All infants diagnosed after 20 weeks' gestation survived. Fetal hydrops developed in three fetuses, all of whom died. Inadequate ventilation secondary to prematurity was a contributing factor in each lethal case. Diagnosis at an early gestational age, development of fetal hydrops, and premature delivery predicted a poor prognosis. When possible, we recommend that delivery be delayed to allow for fetal development. Stabilization of the infant should be attempted before resection of the teratoma.

Prenatal diagnosis and perinatal management of fetal sacrococcygeal teratoma.

Sacrococcygeal teratoma is the most common fetal neoplasm, with an incidence of 1 in 40,000 births. Fetuses with this malformation are at risk for significant perinatal morbidity and mortality. We identified nine fetuses with sacrococcygeal teratomas that were diagnosed antenatally and managed at the University of North Carolina Hospitals over a 7-year period. We retrospectively reviewed the charts of mothers and infants and recorded data concerning perinatal and surgical management. Six infants survived the neonatal period. All infants diagnosed after 20 weeks' gestation survived. Fetal hydrops developed in three fetuses, all of whom died. Inadequate ventilation secondary to prematurity was a contributing factor in each lethal case. Diagnosis at an early gestational age, development of fetal hydrops, and premature delivery predicted a poor prognosis. When possible, we recommend that delivery be delayed to allow for fetal development. Stabilization of the infant should be attempted before resection of the teratoma.

Management of cervical cerclage after preterm premature rupture of membranes.

The optimal management of preterm premature rupture of membranes (PPROM) in a patient with a cerclage is controversial. The issues are whether the latency period between rupture of membranes and delivery is decreased if the cerclage is removed and whether there is an increased rate of maternal or neonatal infection if the cerclage is kept in place. The data are sparse in directing management of women with prophylactic cerclages placed earlier in their pregnancies who rupture membranes. Latency seems to be increased if the cerclage is kept in place, but maternal and neonatal infectious morbidity is increased also. In women at early gestational ages, keeping the cerclage in place may be warranted until labor ensues. In more advanced gestations, it seems preferable to immediately remove the cerclage upon diagnosis of PPROM.

Cystic fibrosis and the National Institutes of Health consensus statement: are obstetrician-gynecologists ready to comply?

OBJECTIVE: To determine if obstetrician-gynecologists are ready to comply with the April 1997 National Institutes of Health (NIH) consensus statement regarding carrier screening for cystic fibrosis. METHODS: A multiple-choice questionnaire was mailed to all active North Carolina nonfederal physicians with a primary specialty of obstetrics and gynecology. Ten questions surveyed the participants' knowledge about cystic fibrosis. RESULTS: Two hundred eighty-six surveys were returned for a response rate of 30.4%. The respondents differed in their knowledge base depending on their specialty, age, and number of years of experience as a physician. The youngest physicians and the least experienced yielded the highest percentage correct. The questions most frequently answered correctly dealt primarily with clinical information about cystic fibrosis, whereas the questions most often answered incorrectly dealt with carrier frequency and testing information. CONCLUSION: The obstetrics-gynecology community is not yet prepared to comply with the NIH Consensus Statement to offer cystic fibrosis carrier screening to couples preconceptionally or prenatally. Further education is necessary before obstetrician-gynecologists can counsel patients adequately.

Prenatal diagnosis and perinatal management of fetal sacrococcygeal teratoma.

Sacrococcygeal teratoma is the most common fetal neoplasm, with an incidence of 1 in 40,000 births. Fetuses with this malformation are at risk for significant perinatal morbidity and mortality. We identified nine fetuses with sacrococcygeal teratomas that were diagnosed antenatally and managed at the University of North Carolina Hospitals over a 7-year period. We reviewed retrospectively the charts of mothers and infants and recorded data concerning perinatal and surgical management. Six infants survived the neonatal period. All infants diagnosed after 20 weeks' gestation survived. Fetal hydrops developed in three fetuses, all of whom died. Inadequate ventilation secondary to prematurity was a contributing factor in each lethal case. Diagnosis at an early gestational age, development of fetal hydrops, and premature delivery predicted a poor prognosis. When possible, we recommend that delivery be delayed to allow for fetal development. Stabilization of the infant should be attempted before resection of the teratoma.

Prenatal diagnosis of mosaic trisomy 13: a case report.

While the clinical features associated with full trisomy 13 have been well characterized, the clinical outcome associated with mosaic trisomy 13 is much less clear. The medical literature reports a broad range of possible clinical outcomes from severe mental retardation and birth defects to normal intelligence. There is no consensus about the typical phenotype in these cases. This makes genetic counselling after prenatal diagnosis of mosaic trisomy 13 particularly difficult. Some of the medical literature attempts to correlate the percentage of trisomic cells in peripheral blood leukocytes or skin fibroblasts with clinical outcome. There have not been case reports correlating the percentage of trisomic amniocytes and clinical outcome. We report the prenatal diagnosis of mosaic trisomy 13 by amniocentesis in which no prenatal ultrasound abnormalities were noted, and autopsy was normal with the exception of the presence of a small ventricular septal defect.

Perinatal outcomes in women with systemic lupus erythematosus.

OBJECTIVE: Pregnancies of women with systemic lupus erythematosus (SLE) were studied to assess the effects interaction of this disease and pregnancy. STUDY DESIGN: Charts of pregnant women with a discharge diagnosis of lupus were reviewed. Inclusion criterion was SLE diagnosed by the criteria of the American College of Rheumatology. All patients were cared for at the University of North Carolina Hospitals, a tertiary level university center. RESULTS: Between January 1988 and June 1995, we participated in the care of 21 women with the diagnosis of SLE. Their obstetric histories included a total of 56 pregnancies spanning 19 years. Obstetric histories were divided into pregnancies occurring before the patient was diagnosed with lupus and those pregnancies occurring after she had been given the diagnosis. The diagnosis of lupus was made during the course of five pregnancies; those five were categorized as occurring after diagnosis. Of the pregnancies that occurred before a woman's diagnosis of SLE, 46% resulted in live births, 36% ended in spontaneous abortion, and 18% ended in an intrauterine fetal demise. Among pregnancies occurring after the diagnosis of SLE, 85% resulted in live birth, 10% in spontaneous abortion, 3.3% in intrauterine fetal demise, and 3.3% in neonatal death. Of all live births, 53% were delivered before 37 weeks' gestation. The most common causes of maternal morbidity were joint involvement (n = 8) and dermatologic disorders (n = 6). Other clinical manifestations of SLE included nephritis (n = 5), hypertension (n = 4), pleuritis (n = 3), and thrombocytopenia (n = 3). One maternal death occurred as a result of pulmonary disease. Four pregnancies were complicated by preeclampsia. Seven patients were hospitalized during their pregnancies for lupus-related complications. CONCLUSIONS: Substantial fetal, neonatal, and maternal risks still exist for pregnant women with lupus.

Does epidural analgesia cause dystocia?

STUDY OBJECTIVE: To analyze the effects of epidural analgesia for labor when dystocia occurs. DESIGN: Retrospective cohort study. SETTING: Academic health center. PATIENTS: 641 low risk, nulliparous women in spontaneous labor. INTERVENTIONS: 406 (63%) women received epidurals analgesia and 253 (37%) did not. Sixty women (9.4%) required an abdominal delivery for dystocia. MEASUREMENTS AND MAIN RESULTS: Women receiving epidural analgesia were more likely to be white, receive care from an attending physician, need labor augmentation, and deliver a heavier infant. Multivariate analysis identified five variables predictive of dystocia and abdominal delivery: pitocin augmentation odds ratio (O.R.) = 3.9 (2.0 to 7.6), duration of labor more than 20 hours O.R. = 2.4 (1.3 to 4.4), high epidural dose O.R. = 2.2 (1.2 to 4.1), birthweight over 4,000 grams O.R. = 2.0 (1.0 to 4.2), and early placement of epidural O.R. = 1. 9 (1.0 to 3.5). Repeating the regression after excluding the 20 women who developed abnormal labor prior to epidural placement (18 of 20 women had protracted dilatation) demonstrated that pitocin augmentation O.R. = 4.0 (1.8 to 4.), high epidural dose O.R. = 3.0 (1.9 to 6.2), duration of labor greater than 20 hours O.R. = 2.7 (1.3 to 5.7), and birthweight over 4,000 grams O.R. = 2.1 (0. 9 to 4.8) were associated with dystocia. CONCLUSION: Epidural analgesia appears to be a marker of abnormal labor rather than a cause of dystocia. High concentration anesthetics and epinephrine should be avoided, as they may influence labor. Randomized, controlled trials of this technique will be difficult to do; our work should reassure patients and their clinicians that epidural analgesia does not adversely affect labor.

Risk of preeclampsia in second-trimester triploid pregnancies.

OBJECTIVE: To determine the magnitude of the risk and the predictive clinical characteristics for development of preeclampsia when triploidy is diagnosed in the second trimester. METHODS: A retrospective analysis of databases maintained by the cytogenetics laboratories at the University of Iowa and University of North Carolina was performed to identify all cases of triploidy. We examined the karyotype, maternal serum screening (particularly the hCG level), ultrasound results, and evidence of maternal hypertensive disease. RESULTS: Seventeen cases of triploidy were identified between 1987 and 1996. Preeclampsia or hypertension complicated six of these cases with onset between 15 and 22.5 weeks' gestation. In these six cases, the serum hCG level was extremely high. Serum screening results were available in seven cases in which preeclampsia did not develop, and the hCG levels were under 0.09 multiples of the median in five of the seven cases. In all six cases in which preeclampsia or hypertension developed, there was sonographic evidence of placentomegaly. Sonographic findings in 16 of 17 cases revealed fetal growth restriction, oligohydramnios, fetal anomalies, placentomegaly, or a combination of these. CONCLUSION: In our series of pregnancies complicated by triploidy, the risk of developing preeclampsia or hypertension in the second trimester was 35%. It appears that elevated serum hCG levels and placentomegaly are associated with a higher risk of preeclampsia but low hCG levels are not. This information is important in counseling patients who are hesitant to terminate a pregnancy purely for a fetal abnormality, even if the anomaly is lethal.

A guide to the safety of CNS-active agents during breastfeeding.

For most agents with CNS activity, there are limited data regarding their safety in breastfeeding. Any decision to institute treatment for a neurological or psychiatric disorder must weigh the benefits of maternal treatment against the potential harm to the breastfeeding mother of withholding medication which may improve her illness. For the neonate, one must balance the risk of medication exposure against the benefit of receiving breast milk. Most tricyclic antidepressants can be used in lactating women. Because of the limited data, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors should only be used with due consideration of the potential adverse effects. Breastfeeding is best avoided by women who require lithium therapy, because of both the immature excretory systems in the infant and relatively high doses received by the infant. There is little information about the safety of antipsychotic medications in breastfeeding. Concerns include toxicity and abnormal neurological development in the infant. These agents may be used with caution. Most agents which cause depression of the CNS, including opiates and sedatives, can be used in small doses and for short courses in breastfeeding mothers. Most anticonvulsants can be used in lactating women. Reference texts and consultation with experts are useful adjuncts to discussion of the risks and benefits of therapy with the patient. The scope of this review is limited to drugs with therapeutic uses, thus drugs of abuse are not discussed, nor are caffeine and alcohol (ethanol).

Prenatal diagnosis using fetal cells from the maternal circulation.

Current prenatal diagnosis relies on invasive methods such as amniocentesis and chorionic villus sampling. Because these methods carry a low, but finite risk of pregnancy loss, noninvasive genetic screening techniques are the focus of intense research. Isolating fetal cells from maternal blood for genetic analysis is the least invasive method currently being investigated. We discuss the various methods that have been used to isolate these cells. Nucleated red blood cells have emerged as the ideal fetal cell type. This is because they have the DNA material necessary for genetic analysis, they are consistently present in maternal blood, they can be easily identified based on their morphology, and they have a definite gestational life span.