Scott N. MacGregor

Cocaine use during pregnancy: Adverse perinatal outcome

Cocaine use has increased dramatically in the United States during the past decade. The life-threatening cardiovascular and central nervous system complications of cocaine have been well documented; however, few studies have examined the risks of cocaine use during pregnancy. In this report the perinatal outcome data of 70 women receiving care at the Perinatal Center for Chemical Dependence of Northwestern University, whose pregnancies were complicated by cocaine abuse, were compared with those of matched control subjects. The use of cocaine during pregnancy was associated with lower gestational age at delivery, an increase in preterm labor and delivery, lower birth weights, and delivery of small for gestational age infants.

Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients

OBJECTIVE We compared the use of aspirin alone with combined therapy (prednisone plus aspirin) in antiphospholipid antibody-positive obstetric patients with prior adverse pregnancy outcome. STUDY DESIGN Thirty-nine patients meeting specific laboratory and clinical inclusion criteria were randomized to receive either combined therapy (prednisone plus low-dose aspirin, n = 17) or aspirin alone (n = 22). The daily aspirin dose was 81 mg; prednisone was begun at 20 mg/day and increased or decreased on the basis of observed changes in serial antibody levels. Perinatal outcomes were compared between groups. Evaluation of treatment-related maternal complications and serial antibody titers was also accomplished. RESULTS Thirty-four randomized subjects were evaluable (prednisone plus low-dose aspirin, n = 12 vs aspirin only, n = 22); no perinatal losses were observed in the study cohort. Preterm delivery was experienced by significantly more patients receiving prednisone plus low-dose aspirin than aspirin only (8/12 vs 3/22, respectively; p = 0.003), and prednisone exposure appeared to be an independent risk factor for preterm birth. CONCLUSIONS The use of prednisone therapy in conjunction with low-dose aspirin does not appear to improve outcome and may provoke obstetric complications in antiphospholipid antibody-positive patients.

Interlaboratory variation in antiphospholipid antibody testing

OBJECTIVE Because of the widespread use of antiphospholipid antibody testing in the evaluation of patients with recurrent pregnancy loss, we evaluated the consistency of results among laboratories testing for anticardiolipin antibody and the lupus anticoagulant. STUDY DESIGN A questionnaire regarding methods used and samples of blood from 20 patients were sent to five university-based and five commercial facilities for antiphospholipid antibody testing. RESULTS The responses of the participating laboratories to the questionnaires revealed significant differences in methods, standardization, and units of reporting. For anticardiolipin antibody, the number of specimens found to be positive for any isotype (immunoglobulin G, M, or A) varied considerably among laboratories, with a range of 5 to 13. All laboratories were in agreement (i.e., at least one isotype was present or all were absent) for only 5 of 20 specimens (25%). In contrast, lupus anticoagulant results were more reproducible, although one facility reported results markedly discordant from the other four laboratories. CONCLUSION These observations suggest that significant interlaboratory variation exists in antiphospholipid antibody, and particularly anticardiolipin antibody, testing and might lead to unnecessary therapeutic interventions.

Sequential pathways of testing after first-trimester screening for trisomy 21

OBJECTIVE: To evaluate the performance and use of second-trimester multiple-marker maternal serum screening for trisomy 21 by women who had previously undergone first-trimester combined screening (nuchal translucency, pregnancy-associated plasma protein A, and free β-hCG), with disclosure of risk estimates. METHODS: In a multicenter, first-trimester screening study sponsored by the National Institute of Child Health and Human Development, multiple-marker maternal serum screening with alpha-fetoprotein, unconjugated estriol, and total hCG was performed in 4,145 (7 with trisomy 21) of 7,392 (9 with trisomy 21) women who were first-trimester screen-negative and 180 (7 with trisomy 21) of 813 (52 with trisomy 21) who were first-trimester screen-positive. Second-trimester risks were calculated using multiples of the median and a standardized risk algorithm with a cutoff risk of 1:270. RESULTS: Among the first-trimester screen-negative cohort, 6 of 7 (86%) trisomy 21 cases were detected by second-trimester multiple-marker maternal serum screening with a false-positive rate of 8.9%. Among the first-trimester screen-positive cohort, all 7 trisomy 21 cases were also detected in the second trimester, albeit with a 38.7% false-positive rate. CONCLUSION: Our data demonstrate that a sequential screening program that provides patients with first-trimester results and offers the option for early invasive testing or additional serum screening in the second trimester can detect 98% of trisomy 21–affected pregnancies. However, such an approach will result in 17% of patients being considered at risk and, hence, potentially having an invasive test. LEVEL OF EVIDENCE: II-2

Late First-Trimester Invasive Prenatal Diagnosis: Results of an International Randomized Trial

OBJECTIVE: To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11–14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening. METHODS: We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies. RESULTS: We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P = .07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P = .02) overall and in week 13 (P = .03, relative risk = 4.65), but data were insufficient to determine this risk in week 14. CONCLUSION: Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss. LEVEL OF EVIDENCE: I

The clinical significance of a single umbilical artery as an isolated finding on prenatal ultrasound

Objective To evaluate the perinatal outcome in fetuses with single umbilical artery detected on targeted prenatal ultra-sound without other anomalies. Methods During a 3.5-year period, an isolated single umbilical artery was suspected on prenatal ultrasound examination in 57 fetuses evaluated at two referral centers. Targeted imaging to rule out concurrent fetal anomalies was normal in all cases. Pregnancy and perinatal outcome data were retrieved by review of the medical records or from conversations with referring physicians. Complete follow-up was available in 50 cases. Results A two-vessel umbilical cord was confirmed at birth in 50 neonates. The mean gestational age at delivery was 38.6 ± 2.8 weeks; the mean birth weight was 3202.8 ± 835.8 g. Seventeen patients (34%) underwent genetic amniocentesis, and all fetuses had a normal karyotype. The only neonate ascertained to have a congenital anomaly after birth was diagnosed with total anomalous pulmonary venous return. This neonate underwent a corrective surgical procedure and is thriving with no apparent problems at 3.5 years of age. There were no perinatal deaths. Conclusion In the absence of additional sonographically detectable anomalies, an isolated single umbilical artery does not seem to affect clinical outcome and therefore should not alter routine obstetric management.

Effects of intravascular, intrauterine transfusion on prenatal and postnatal hemolysis and erythropoiesis in severe fetal isoimmunization

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.

Isolated hyperechoic fetal bowel: significance and implications for management.

OBJECTIVE The objective of this study was to determine the significance of isolated hyperechoic fetal bowel. STUDY DESIGN Forty-five cases with prospective, ultrasonographic diagnosis of isolated hyperechoic fetal bowel were reviewed. Fetal variables, including aneuploidy, deoxyribonucleic acid studies for cystic fibrosis, congenital infection, growth retardation, and intrauterine death were reported. RESULTS Thirty-four of the 45 cases (76%) resulted in live-born infants without detected abnormalities. However, hyperechoic bowel was associated with cystic fibrosis in two cases (4%), congenital infection in two cases (4%), and fetal alcohol syndrome in one case. Termination of pregnancy was elected in three cases and intrauterine fetal death occurred in three cases (7%). Growth retardation was observed in five of 39 (13%) live-born infants. CONCLUSION Isolated hyperechoic fetal bowel is associated with significant pathologic disorders. Women whose fetuses are diagnosed as having isolated hyperechoic bowel should be offered additional prenatal diagnostic options, including maternal serologic studies for congenital infection, fetal karyotype, and deoxyribonucleic acid testing for cystic fibrosis. In addition, continuing ultrasonographic evaluation of fetal growth and antenatal biophysical assessment should be considered.

Cordocentesis: an appraisal of risks.

Fetal blood sampling via cordocentesis is being used with increasing frequency. Between March 1986 and February 1988, we performed 58 intravascular transfusions (64 attempts) and 27 fetal blood samplings (28 attempts) guided by ultrasonography. The complication rates for intravascular transfusion and fetal blood sampling were 9.4% (6 of 64) and 7.1% (2 of 28), respectively. The procedure-related mortality rates were 4.7% (3 of 64) and 0%. We caution that the potential complications be seriously considered when appropriate patients are selected for cordocentesis. Additionally, we recommend that cordocentesis be performed only in tertiary care centers by personnel skilled in both ultrasonography and prenatal diagnosis.

Enhanced sensitization after cordocentesis in a rhesus-isoimmunized pregnancy

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.