Biomedical subjects
Publications and source records attributed to S N MacGregor.
Middle cerebral artery infarction explains some cases of congenital hemiparesis with or without neonatal stroke. The etiology of the stroke is often obscure. We describe two infants with imaging evidence of middle cerebral artery infarction whose mothers had elevated anticardiolipin antibody levels after delivery. We speculate that these antibodies may have been responsible for intrauterine thromboembolic stroke.
It has been suggested that the optical density at 450 nm may be an unreliable predictor of the severity of fetal anemia in the midtrimester of pregnancy; therefore fetal blood sampling, rather than amniotic fluid evaluation, should be performed in all isoimmunized pregnancies with elevated maternal antibody titers in the midtrimester. Potential complications of such an approach are discussed and an alternative plan of management is offered.
Twenty-six severely isoimmunized pregnancies managed exclusively with ultrasonographically guided intravascular fetal transfusions are reported. The mean gestational age plus and minus one standard deviation (+/- SD) was 26.3 +/- 3.6 weeks and the mean hematocrit (+/- SD) prior to initial transfusion was 20.6 +/- 6.7%. Four of seven hydropic fetuses and 9 of 19 without hydrops were less than or equal to 26 weeks gestation at the first transfusion. Overall survival was 85% (22/26). Survival was similar whether or not fetal hydrops was present (6/7 vs. 16/19) and whether or not the first transfusion was administered at less than or equal to 26 weeks gestation (10/13 vs. 12/13).
Pregnancies with decreased amniotic fluid volume are prediposed to umbilical cord compression and variable fetal heart rate declerations. Intrapartum amnioinfusion has been utilized in an effort to reduce cord compression. Previous studies suggested that amnioinfusion may improve the fetal metabolic state and reduce the incidence of cesarean delivery in selected patients. In this study the hypothesis was tested that intrapartum amnioinfusion will relieve cord compression in pregnancies complicated by oligohydramnios and will result in a reduced incidence of fetal intolerance to labor as well as improved fetal acid-base status at delivery. Thirty-five patients fulfilling the inclusion criteria were randomized to either the control (n = 16) or amnioinfusion treatment group (n = 19). Analysis of the data suggested that the two groups were similar for the perinatal parameters evaluated. No differences were observed in the umbilical artery blood gas analysis or incidence of cesarean section between the two groups. Intrapartum amnioinfusion does not appear to improve the perinatal outcome in pregnancies with oligohydramnios.
In 458 consecutive chorionic villus sampling (CVS) procedures, we observed a significant influence of uterine position upon sampling efficacy. Compared with anteverted (N = 243) or axial (N = 149) locations, the retroverted uterus (N = 66) was associated with a lower mean sample weight per aspiration (22, 18, and 15 mg, respectively; P less than .01) and a greater frequency of multiple-pass procedures (23, 31, and 52%, respectively; P less than .0001). To improve sampling efficiency in selected cases of uterine retroversion, we adopted a transvesical approach. When compared with transabdominal or transcervical techniques, transvesical CVS had the highest single-pass success rate (33, 33, and 60%, respectively). Only one in 30 transvesical cases required three placental passes, compared with nine of 36 retroverted uteri sampled by either transabdominal or transcervical techniques (P less than .05). The mean transvesical sample weight was 18.7 mg; at least 10 mg was retrieved in all cases. Post-procedure bleeding occurred in four instances and an additional patient suffered a spontaneous loss at 16 weeks' gestation. Aneuploidy was found in four of 30 biopsy specimens, and the remaining pregnancies either have delivered at term (N = 18) or are continuing (N = 7). Our preliminary experience suggests that selected use of this CVS method may improve sampling efficiency without increasing the incidence of complications.
Many aspects of HIV infection in pregnancy remain unclear. Subsets at increased risk for perinatal transmission, adverse pregnancy outcome, and development of symptomatic HIV infection need to be identified. For instance, relative risks may be quite different in asymptomatic HIV infected patients with T4 lymphocyte counts greater than 200 cells per cubic millimeter compared to those with either symptoms of HIV infection or T4 cell counts less than 200 cells per cubic millimeter. At present, antiviral therapeutic trials do not include pregnant women or neonates less than 3 months of age. In the future, antiviral therapy with agents, such as AZT, may reduce the risk of transplacental and intrapartum HIV transmission. Obstetricians will be involved increasingly in providing care to HIV-infected patients and educating patients in order to prevent HIV infection.
Studies in animal models and human pregnancies suggest that severe fetal anemia and/or replacement of fetal with adult blood result in decreased pH, increased base deficit, and hyperlactacidemia. Similar changes have been noted in growth-retarded, nonanemic fetuses, and we therefore hypothesized that isoimmunized fetuses requiring intrauterine transfusions might have diminished growth. We longitudinally studied growth patterns in 17 isoimmunized fetuses by noting biparietal diameter and head and abdominal circumference measurements at each transfusion. The distributions of these measurements above and below the 25th, 50th, and 75th percentiles derived from our general obstetric population were compared at the initial transfusion and the last ultrasonogram performed before delivery. Birth weights also were noted and their distribution around the 25th, 50th, and 75th percentiles was compared to the expected distribution. For each ultrasonographic parameter, the distribution of measurements at the last ultrasonogram before delivery was not significantly different from the distribution at the initial ultrasonogram. The birth weight distribution also was not significantly different than the expected distribution. Thus we were unable to demonstrate slowing of fetal growth in our severely isoimmunized pregnancies.
Prior studies have identified a correlation between the rate of fetal loss (subsequent to chorionic villus sampling) and the operator's level of experience. However, centers performing only modest numbers of procedures during the initial phase of their programs have reported loss rates similar to those of the more active diagnostic units. Our personal experience would suggest that a "learning curve" for chorionic villus sampling does exist but that fetal loss may be an insensitive end point with which to evaluate the impact of cumulative performance. In an attempt to quantify the learning curve that we have appreciated subjectively, a detailed analysis of our initial experience with chorionic villus sampling was undertaken. Between May 1988 and August 1989, a total of 185 procedures were accomplished consecutively by one operator and form the basis for this analysis. Transcervical (n = 82) and transabdominal (n = 103) techniques were used for posterior and anterior-fundal placental locations, respectively. Three pregnancy losses occurred and insufficient material for analysis was retrieved in five patients. We observed a significant reduction in the required number of placental aspirations during the study interval (p less than 0.001). When analyzed separately, consecutive performances of the transabdominal technique demonstrated a significant reduction in the mean number of placental passes (p less than 0.00001) along with more efficient sampling (increased sample weight/aspiration attempt; p less than 0.01). Although the fetal loss rate is a critical measure of safety and may directly be related to operator experience, other measures of expertise (e.g., single-pass success rate) may be more appropriate indicators of competence and may be useful to centers wishing to initiate their own chorionic villus sampling programs.
In an investigation of the effects of intrauterine, intravascular transfusions (IUT) on fetal and neonatal hemolysis and erythropoiesis, 12 fetuses who received IUT for treatment of severe isoimmunization had serial measurements of hemoglobin concentration, Kleihauer-Betke stains to detect fetal hemoglobin-containing erythrocytes, and determination of plasma erythropoietin (EPO) concentration before each IUT, at birth, and postnatally. Reticulocyte counts and sensitizing antibody titers were measured in five fetuses. Mean values before the first IUT, before the final IUT, and at birth were as follows: hemoglobin level, 6.1, 9.1, and 11.3 gm/dl; reticulocyte count, 22.7%, 0.5%, and 0.9%; fetal hemoglobin-containing erythrocytes, 100%, 1.6%, and 1.5%; and EPO level, 12, 56, and 756 mU/ml, respectively. Only one neonate required exchange transfusion. In the first month postnatally, all infants had a profound anemia. All but one infant required simple blood transfusions postnatally. Before the first postnatal transfusion, mean hemoglobin concentration was 6.2 gm/dl, mean reticulocyte count was 0.8%, mean erythropoietin concentration was 23 mU/ml, and the sensitizing antibody titer remained markedly elevated. Except for the surge of EPO at birth, EPO levels did not rise prenatally or postnatally unless marked anemia (hemoglobin level less than 5 gm/dl) occurred. These observations suggest that the intrauterine and postnatal anemia in fetuses who receive IUTs may be explained both by hemolysis of newly formed erythrocytes by circulating antibody, which typically persisted for more than a month after birth, and by suppressed erythropoiesis.
A case of posterior urethral valve syndrome is presented. Four weeks after a normal 24-week ultrasound examination, diminished amniotic fluid, megacystis, and renal hyperechogenicity were observed. A repeat ultrasound examination at 30 weeks' gestation identified oligohydramnios and increased renal echogenicity. These findings prompted the performance of a percutaneous cystocentesis to assess fetal renal function indirectly. The specimen was evaluated for osmolality and sodium and chloride concentrations. The urine electrolyte concentrations (sodium 115 mEq/L; chloride 93 mEq/L) and the osmolality (230 mOsm/L) were elevated, suggesting impaired renal function and a poor prognosis. Despite these findings, aggressive management was used, including administration of antenatal corticosteroids and elective preterm delivery. A percutaneous cystocentesis was required during the infant's initial resuscitation, followed by a difficult urethral catheterization. Ultimately, a vesicostomy performed on day 4 of life was associated with prompt return of renal function (serum creatinine 0.7 mg/dL at the time of discharge). At 6 months of age, normal renal function has been documented and the vesicostomy has been closed. This case demonstrates the potential limitations of available prognostic criteria in evaluating fetal urinary obstruction and residual renal function. In selected cases (when the onset of obstruction is documented in the third trimester), refinement of these prognostic criteria may be indicated. Similar cases may be best managed by preterm delivery and prompt postnatal decompression.
In initiating a chorionic villus sampling (CVS) protocol, we relied upon placental locations as the determinant in the choice of technique. An anterior or fundal location prompted a transabdominal (TA) CVS, while the transcervical (TC) approach was reserved for posterior placentas. A coaxial needle system was used for TA CVS (18-gauge, 15-cm guide needle and 20-gauge, 20-cm sampling needle), while TC CVS was accomplished with a 5.8-French, 27-cm polyethylene catheter. Between July 1988 and February 1989 our initial 118 procedures were performed for 115 consecutive pregnancies using this protocol. Testing indications and antenatal characteristics of the TA (n = 56) and TC (n = 63) groups were similar. One procedure failure occurred in the TC group, and a single aspiration was sufficient in 59% of the cases (TA, 30/55; TC, 39/63). In TC procedures an increased aggregate sample weight was observed as compared to TA cases (25.8 g vs. 16.9 g, respectively; P less than .001). This difference was not attributable to an increased number of placental aspirations in TC cases. One abnormal karyotype was observed (45X), and four pregnancy losses occurred (TC, 3; TA, 1). Using placental location to determine the choice of CVS technique appears to be feasible and may be associated with a lower failure rate during a facility's initial experience (when compared to reliance upon one technique alone). Trials comparing the safety of these two methods should consider placental location an independent variable before randomization.
We examined the prevalence of marijuana use in a group of pregnant women using a qualitative, rapid urine screen to detect marijuana metabolites. Between July 1, 1987, and Aug 15, 1987, 322 consecutive patients underwent an anonymous urine toxicology screen at the time of admission to the labor-and-delivery unit. Patients were identified only by a consecutive number and by their age, race, marital status, gravidity, parity and obstetric service (clinic vs. private). The prevalence of positive urine toxicologic screens for marijuana was 19.9% among the study population (64 positive tests among 322 women screened). The prevalence was greater among the clinic patients than the private patients (52 of 161, or 32.3%, vs. 12 of 161, or 7.5%, respectively). The distribution of race and marital status among the marijuana-positive and -negative groups were also significantly different. Specifically, the proportions of black and single women were higher among the marijuana-positive group. Our findings suggest that marijuana use is common in our obstetric patients. The possible association between marijuana use during pregnancy and perinatal morbidity, as well as the unreliable nature of patient drug histories, may support the use of rapid, inexpensive screening techniques, especially if general screening is considered.
The frequency of cocaine abuse during pregnancy has increased markedly in recent years. Cocaine abuse during pregnancy has been associated with significant perinatal morbidity and mortality. In this study a large population of pregnant women were tested for drug use at the time of their admission to the hospital for labor and delivery. During the study period a total of 138 (8%) of 1776 patients who were delivered of infants had positive urine toxicologic screening tests for cocaine. Moreover, the prevalence of peripartum cocaine abuse increased considerably during the study period. The perinatal outcomes of the 138 patients whose urine samples yielded positive test results for cocaine were compared with those of the 88 control patients with negative results. Cocaine use was associated with lower gestational age at delivery and higher incidences of preterm delivery, premature rupture of the membranes, and small-for-gestational-age infants. When compared with control infants, infants of mothers who used cocaine had more instances of neonatal morbidity and longer hospitalizations. In this study peripartum cocaine abuse was common, increased during the study period, and was associated with perinatal morbidity.
The inhibition of labor subsequent to premature rupture of the membranes remains controversial. To evaluate the possibility that diminished amniotic fluid volume impacts on the latent period in patients receiving tocolytic therapy after premature rupture of the membranes, we reviewed our recent clinical experience with premature rupture of the membranes and the use of tocolytic agents. Between January 1985 and June 1988, 70 singleton pregnancies with premature rupture of the membranes between 25 and 34 weeks of gestation without prior tocolytic therapy were included. Ritodrine (n = 22), magnesium sulfate (n = 37), or both agents (n = 11) were administered and followed by oral terbutaline if tocolysis was achieved. Ultrasonographic examination was performed after admission and patients were grouped on the basis of estimates of residual amniotic fluid volume. Fourteen patients had adequate fluid volume; 20 had diminished fluid volume, and 36 had oligohydramnios. Patients with adequate fluid volume had a significantly longer interval between tocolytic therapy and delivery when compared with the other two categories (analysis of variance, p less than 0.001), and proportionately more patients remained undelivered for greater than 1 week (adequate 8 of 14 vs. diminished 3 of 20 and oligohydramnios 3 of 36; p less than 0.001). In the 18 patients with premature rupture of the membranes before 30 weeks' gestation, adequate fluid volume was associated with the longest latent period (adequate 14.0 days; diminished 12.6 days, and oligohydramnios 2.8 days; analysis of variance, p less than 0.05). We conclude that tocolytic therapy is of little benefit in the presence of oligohydramnios. If additional prospective studies of tocolytic efficacy in pregnancies complicated by premature rupture of the membranes are undertaken, inclusion of residual amniotic fluid volume as an independent variable before randomization should be considered.
Fetal blood sampling and intravascular transfusion via cordocentesis allow more precise fetal evaluation and treatment in isoimmunized pregnancies. However, the timing of repeat transfusion has remained empiric. In this report we review our experience with fetal transfusions in isoimmunized pregnancies to evaluate the ability to predict fetal hematocrit decline and thereby determine the optimum timing for repeat transfusions. Between March 1986 and March 1988, 60 intravascular fetal transfusions were performed in 20 patients. Fetal transfusions were excluded from analysis if blood samples were unable to be obtained before and after transfusion, as well as at the beginning of the next transfusion or birth. Fifty-three procedures were analyzed. Two equations were used to predict the fetal hematocrit at the subsequent transfusion. The difference between observed and predicted hematocrits at the beginning of a subsequent transfusion or birth was -0.9% +/- 5.8% with equation 2, which was the more accurate formula in the majority of fetuses. Prediction of fetal hematocrit decline may be used to determine the optimum timing of repeat transfusion.
The prenatal diagnosis and antepartum management of congenital diaphragmatic hernia and anterior abdominal wall defects are reviewed. In addition, the intrapartum and neonatal considerations and management strategies are discussed.
Cocaine abuse during pregnancy has been associated with increased perinatal morbidity and mortality regardless of the quantity or quality of prenatal care. In this study, we tested the hypothesis that among cocaine-abusing women delivering at the same institution, those receiving comprehensive prenatal care have better perinatal outcome than those receiving little or no prenatal care. Between January 1, 1984 and July 1, 1987, 120 pregnant women who abused cocaine received multidisciplinary prenatal care in the Perinatal Center for Chemical Dependence of Northwestern University (group 1). During this same period, we identified 21 cocaine-abusing parturients at our institution who were not enrolled in the Perinatal Center for Chemical Dependence and who received little or no prenatal care (group 2). Control subjects were selected from the general obstetric population for comparison. Data from these two groups were compared with each other and with matched control pregnancies. Group 2 pregnancies had lower mean gestational age at delivery, lower mean birth weight, and a higher incidence of preterm delivery than group 1 pregnancies. Furthermore, groups 1 and 2 were significantly different from control pregnancies for these parameters. We conclude that comprehensive prenatal care may improve outcome in pregnancies complicated by cocaine abuse; however, the perinatal morbidity associated with cocaine abuse cannot be eliminated solely by improved prenatal care.
Direct intravascular fetal transfusion under ultrasound guidance allows precise evaluation of both fetal anemia and adequacy of therapy. In addition, the change in hematocrit after transfusion may be used to estimate the circulatory fetoplacental blood volume. In this study we present the estimates of fetoplacental blood volume calculated at the time of intravascular fetal transfusions. Between March 1986 and March 1988, 60 intravascular fetal transfusions were performed in 20 patients. The 56 procedures in which fetal hematocrits were obtained both before and after transfusion were analyzed. The mean fetoplacental blood volume before transfusion was 94.0 ml/kg. Furthermore, the fetoplacental blood volume per kilogram fetal weight decreased with advancing gestation. These estimates of fetoplacental blood volume and changes relative to gestational age may be useful in the treatment of the severely isoimmunized fetus. Reliance on the more recently generated fetoplacental blood volumes may allow more accurate predictions of transfusion volumes and estimation of the hematocrit after transfusion.