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Biomedical subjects

S S Grant

Publications and source records attributed to S S Grant.

14 recordsLinked to original sources

Prediction of pregnancy outcome with single versus serial maternal serum alpha-fetoprotein tests.

OBJECTIVE: The purpose of our study was to determine whether the trend of three maternal serum alpha-fetoprotein samples was more predictive of pregnancy outcome than the initial sample in the evaluation of patients with unexplained alpha-fetoprotein elevations. STUDY DESIGN: A total of 432 patients with unexplained elevation of their first two maternal serum alpha-fetoprotein samples had a third sample drawn. Pregnancy outcomes were determined. Patients were grouped for analysis according to the level of the initial sample, the final sample, and the trend of three samples. Statistical analysis was by chi 2 and logistic regression, with p < 0.05 considered significant. RESULTS: The initial maternal serum alpha-fetoprotein was most predictive of preterm delivery (p < 0.001), size small for gestational age (p < 0.001), and intrauterine fetal death (p = 0.009). Neither the final value nor the trend of three values was as prognostic. CONCLUSION: The first maternal serum alpha-fetoprotein is the best predictor of pregnancy outcome. Obtaining a second sample to confirm the elevation is appropriate, but additional samples provide minimal information.

Female

Management of fetal hemolytic disease by cordocentesis. I. Prediction of fetal anemia.

Between January 1985 and November 1990, 128 pregnancies complicated by maternal red blood cell alloimmunization were referred to our Fetal Diagnosis and Treatment Unit. We examined the premise that an evaluation of fetal blood would accurately identify fetuses at risk of requiring antenatal transfusion therapy. Two hundred seventy-two diagnostic cordocenteses were performed. Criteria for the timing of repeat cordocenteses were developed retrospectively on the basis of the fetal hematocrit values, reticulocyte counts, and direct Coombs' test results of the first 84 pregnancies. These criteria were tested and confirmed prospectively on the next 44 pregnancies. On the basis of the first blood sample, four hematologic patterns (and their distributions) were identified in the 98 antigen-positive fetuses. Pattern 1: fetuses at low risk of having significant antenatal anemia (hematocrit less than 30%) (n = 11, 11%). These fetuses had normal hematocrit values and reticulocyte counts coupled with negative or trace-positive direct Coombs' test. No fetus in this group had significant antenatal anemia. Pattern 2: fetuses at intermediate risk of having anemia (n = 29, 31%). Pattern 2 fetuses had normal hematocrit values and either direct Coombs' titers of more than trace less than or equal to 2+ and normal reticulocyte counts or low reticulocyte counts (less than 2.5th percentile for gestation). Twenty-one percent (n = 6) of fetuses in pattern 2 had significant antenatal anemia. Patterns 3 and 4: fetuses at greatest risk of having severe anemia. These fetuses had normal hematocrit values associated with either reticulocyte counts greater than 97.5th percentile for gestation or a direct Coombs' test greater than or equal to 3+ (pattern 3, n = 49, 50%) or both, or a mild anemia (greater than 30% but less than 2.5th percentile for gestation) (pattern 4, n = 9, 10%). Eighty percent (n = 39) of fetuses with pattern 3 and 90% (n = 8) with pattern 4 developed a hematocrit value less than 30%. We conclude that evaluation of fetal hemolytic disease with a fetal blood specimen permits the identification of fetuses at high risk of having antenatal anemia.

Amniocentesis

The association between fetal karyotype and mean corpuscular volume.

To determine whether elevated fetal mean corpuscular volume is characteristic of a chromosome abnormality or fetal disease, 22 fetuses with chromosome abnormalities, 31 with uteroplacental insufficiency, 50 undergoing their first cordocentesis for hemolytic disease, and 50 control fetuses were identified. Chromosomally abnormal fetuses had a significantly higher mean corpuscular volume than the control fetuses. Among fetuses with chromosome abnormalities, the mean corpuscular volume for trisomic or triploid fetuses was significantly higher than for fetuses with other chromosome abnormalities. An elevated mean corpuscular volume was also associated with uteroplacental insufficiency, intrauterine growth retardation, and hemolytic disease. It correlated significantly with gestational age (p less than 0.002 in all cases) in all groups except trisomy or triploidy. In addition, it correlated with hematocrit in the hemolytic disease group (r = -0.60, p less than 0.0001) and with PO2 in fetuses with intrauterine growth retardation (r = -0.43, p = 0.005) from all causes including uteroplacental insufficiency. Trisomic or triploid fetuses showed no such relationships and therefore appear to have escaped the normal control mechanisms for erythropoiesis. One in 12 fetuses with an elevated mean corpuscular volume had trisomy or triploidy, whereas no fetus with trisomy or triploidy had a normal mean corpuscular volume. Thus an unexpectedly elevated fetal mean corpuscular volume in a patient undergoing cordocentesis for reasons other than evaluation of fetal chromosomes would appear to warrant further karyotypic analysis.

Blood Volume

Relationship between second trimester maternal serum alpha-fetoprotein and umbilical artery Doppler velocimetry and their association with preterm delivery.

One explanation for an abnormal maternal serum alpha-fetoprotein (MSAFP) may be an abnormal placenta. A specimen for MSAFP and a series of umbilical artery waveforms were obtained prior to amniocentesis from 144 consecutive women referred for either maternal age (n = 85), a persistently elevated MSAFP unassociated with a structural abnormality (n = 42), or a low MSAFP (n = 17). Almost 50% of deliveries before 37 weeks and 60% of neonatal birthweights below the tenth percentile occurred in the high MSAFP group. We observed that the systolic-diastolic ratio (S/D), pulsatility index, and resistance index tended to be higher in women referred for an elevated MSAFP. Confining analyses to the elevated MSAFP group, the MSAFP in multiples of the median correlated with birthweight independent of the gestational age at delivery (p less than 0.001). In addition, the S/D related directly to MSAFP (p less than 0.03) and indirectly to the gestational age at delivery (p less than 0.04). None of these relationships was observed in the groups of women referred for either maternal age (who had a normal MSAFP) or a low MSAFP. Employing a stepwise multiple linear regression, we found that the gestational age at delivery could be predicted during the midsecond trimester using a combination of the umbilical artery S/D and MSAFP. When the analyses and predictions were limited to subjects whose MSAFP still exceeded 2 multiples of the median at the time of amniocentesis, the positive predictive value for preterm delivery was 100% and the negative predictive value was 93%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Management of fetal hemolytic disease by cordocentesis. II. Outcome of treatment.

Forty-eight of 128 pregnancies complicated by maternal red blood cell alloimmunization (49%) received a total of 142 intravascular transfusions (range, 1 to 7) for treatment of severe anemia (hematocrit, less than or equal to 30%). Thirteen fetuses (27%) had hydrops when therapy was initiated. The overall survival rate was 96%. Eighty-five percent of survivors received two or more transfusions before delivery. The mean gestational age at initiation of therapy was 28 weeks (range, 18 to 36 weeks). Bleeding from uterine and umbilical cord puncture sites was not of clinical significance. The most common complication was fetal bradycardia (8%). Simple intravascular transfusion resulted in the replacement of fetal red blood cells with adult red blood cells and suppression of fetal erythropoiesis. By the completion of the second transfusion, on average, less than 1% of circulating red blood cells were fetal. Within 3 weeks of the second transfusion, the mean reticulocyte count was less than 1%. The rate at which the fetal hematocrit declined after a transfusion (exclusive of the first) was inversely related to gestational age (r = -0.84, p less than 0.0001), permitting a 4- to 5-week interval between transfusions after 32 weeks' gestation. A total of 78% of surviving neonates were delivered at term. Neonates transfused more than once antenatally required less phototherapy (75.8 +/- 54 vs 165 +/- 101 hours, p less than 0.003) and, when delivered at term, fewer hospital days (4.8 +/- 2 vs 8.6 +/- 6 days, p = 0.01) compared with those transfused once. We conclude that the treatment of fetal anemia by intrauterine simple intravascular transfusion permits a term delivery in the majority of cases and is associated with high perinatal survival and low perinatal morbidity.

Blood Transfusion, Intrauterine

Gastroschisis and omphalocele: does either antenatal diagnosis or route of delivery make a difference in perinatal outcome?

The route of delivery for the fetus with an abdominal wall defect is controversial. This investigation proposed two null hypotheses: 1) The prognosis for the fetus with an abdominal wall defect is not affected by the timing of the diagnosis (antenatal or postnatal); and 2) the route of delivery does not affect fetal outcome. Sixty-one pregnancies complicated by either fetal gastroschisis (33) or omphalocele (28) delivered between December 1979 and January 1989 were reviewed. Seventy-one percent of the fetuses with gastroschisis and 59% with omphalocele were born vaginally. Gestational age at delivery, incidence of meconium staining, days to first neonatal oral feeding, percentage of neonates with one-stage closure of their defect, and percent of neonates with a birth weight less than the tenth percentile for gestational age were similar in fetuses with gastroschisis and with omphalocele, whether diagnosed antenatally or at birth. Significantly lower birth weights and longer neonatal hospitalizations were noted in the infants with omphalocele diagnosed antenatally compared with those diagnosed at birth (P less than .03), but no such differences were seen with gastroschisis. The route of delivery did not affect outcome for either defect. All fetuses born with gastroschisis and 87% with omphalocele free of associated lethal abnormalities were discharged alive. We conclude that the antenatal diagnosis of gastroschisis is not associated with either worse disease or a poorer outcome, though this may not be true for omphalocele. The good outcome with a high vaginal delivery rate suggests the need for a randomized trial of vaginal and cesarean delivery for fetal gastroschisis and omphalocele.

Abdominal Muscles

Prenatal diagnosis of fetal hyperthyroidism using funipuncture.

Women with Graves disease who are euthyroid as a result of ablative therapy still produce thyroid-stimulating antibodies that can cross the placenta. The fetuses of such patients are at risk of hyperthyroidism. We found that fetal blood sampling for the measurement of fetal endocrine function was useful in two patients for both diagnostic and therapeutic purposes. It may be especially helpful for situations in which maternal and fetal endocrine functions are dissimilar.

Adult

Achondrogenesis type II (Langer-Saldino) in association with jugular lymphatic obstruction sequence.

The prenatal diagnosis of achondrogenesis in association with cystic hygroma is described. Ultrasound findings of severe short-limbed dwarfism, decreased vertebral ossification, and normal ossification of the calvarium were all consistent with achondrogenesis type II. Although the unusual finding of associated cystic hygroma raised the suspicion of a concurrent chromosome abnormality, the karyotype of both fetal lymphocytes and fetal fibroblasts was normal. Autopsy confirmed dilated lymphatic channels in the basal endothelial layer of the skin, cystic hygroma, and coarctation of the aorta. Although previously unreported, we suggest that the features of this case of achondrogenesis indicate an association with lymphatic stasis and jugular lymphatic obstruction sequence in this syndrome.

Adult

Expression of collagenase IV (basement membrane collagenase) activity in murine tumor cell hybrids that differ in metastatic potential.

Expression of a basement membrane collagen-degrading metalloprotease activity (collagenase IV) was studied in a series of murine cell hybrids derived from fusions between highly metastatic cells (B16-F10RR) or moderately metastatic cells (UV-2237RR) and tumorigenic cells (K-1735 clone 16) or normal cells [peritoneal macrophages (PEC) or C3H mouse embryo fibroblasts (C3H-F)]. The collagenase IV activity of the parent cells and the hybrids was assayed in vitro and compared to the metastatic propensity of the same cells evaluated in both syngeneic (C57BL/6 X C3H/HeN)F1 mice and BALB/c nude mice. The level of collagenase IV activity secreted by the parent lines correlated with their metastatic capacity. The highly metastatic B16-F10RR line secreted the highest enzyme activity, whereas the tumorigenic but nonmetastatic K-1735 clone 16 and the normal parents PEC and C3H-F secreted the lowest enzyme activity. The enzyme activity was completely inhibited with EDTA. The hybrid derived from fusion of cells from two metastatic cell lines as well as hybrids derived from a metastatic and a nonmetastatic tumor cell line expressed higher levels of collagenase IV activity than either parent, and this expression was associated with a high ability to produce metastases in both nude and syngeneic mice. Fusion of metastatic cells with normal cells produced hybrid cells that exhibited suppression of both collagenase IV activity and metastatic capacity. Collagenase IV activity and metastatic propensity can, therefore, be altered by somatic cell hybridization; in the series of hybrids examined in these experiments the expression of type IV collagen-degrading metalloprotease activity and the metastatic ability were closely correlated, which suggests that collagenase IV activity and other properties required for metastasis are genetically linked.

Animals

Reduction in amniocentesis risks using a real-time needle guide procedure.

Rates of complications associated with a second trimester genetic amniocentesis were studied in 918 patients, and complete infant follow-up was obtained. In 903 singleton pregnancies and 15 twin gestations, the procedure was performed under continuous sector scanning guidance through an attached needle guide. Eight fetal deaths in the 903 cases occurred at less than 28 weeks after amniocentesis (0.89%), none within two weeks after the procedure. Only one fluid was visibly blood contaminated. Comparisons are made with other series from the literature.

Amniocentesis