The sensitivity of the Kleihauer-Betke test for placental abruption.

The Kleihauer-Betke (KB) test evaluates fetal blood in the maternal circulation, and is often used when placental abruption is suspected. At our centre, it is the protocol to perform a KB test in all suspected cases of abruption. We carried out a retrospective study of all cases of abruption that occurred at our centre over 6 years. Of the 68 confirmed cases of placental abruption, only three had positive KB tests, giving a sensitivity of only 4.4%. Thus, in the overwhelming majority of cases of confirmed abruption, the KB test was negative. Our findings indicate that the KB test has poor sensitivity for placental abruption and should not be used in the detection of abruption.

Cesarean delivery rates in Down syndrome pregnancies.

OBJECTIVES: Data on rates of cesarean delivery among pregnancies diagnosed with genetic syndromes remains limited. We examined the cesarean delivery rates for Down syndrome pregnancies over a 10-year period in the US. METHODS: We used data from the 1995-2004 US delivery data files to examine cesarean delivery rates in singleton pregnancies (at ≥20 weeks' gestation) with and without Down syndrome. We further examined if the rates of cesarean deliveries in primary and repeat cesarean deliveries among Down syndrome pregnancies differed based on the presence or absence of major structural abnormalities or stillbirth or gestational age at delivery. RESULTS: There were 35 million singleton deliveries of which 19186 were diagnosed at birth with Down syndrome (1 in 2000 births after 20 weeks gestation). The primary cesarean delivery rates were higher among Down syndrome pregnancies (17.5% in 1995 and 21.5% in 2004) compared to non-Down syndrome pregnancies (12.3% in 1995 and 16.6% in 2004). Temporal trends for cesarean deliveries were steeper among Down syndrome pregnancies with gastrointestinal and heart abnormalities than in Down syndrome cases without abnormalities. Higher cesarean delivery rates were also noted among Down syndrome pregnancies ending in third trimester live born than in control. CONCLUSION: In the US, cesarean deliveries in Down syndrome pregnancies increases over time and is greater when Down syndrome is associated with structural abnormalities and delivered during the third trimester of pregnancy.

Fetal thymus size in uncomplicated twin and singleton pregnancies.

OBJECTIVES: The main objective of this study was to determine whether fetal thymic measurements could be obtained in twins, with a secondary goal to determine whether thymic measurements from uncomplicated singleton and twin pregnancies are comparable. METHODS: The transverse diameter and perimeter of the fetal thymus were measured prospectively in 678 singleton and 56 twin pregnancies, and their relationships with gestational age were determined and compared between groups. RESULTS: Thymic measurements were possible in 757 (95.8%) of the 790 fetuses. Measurements were not possible in 19 of 678 singletons (2.8%) and in 14 of the 112 (12.5%) twins (P < 0.001). After construction of nomograms for the transverse diameter and perimeter of the fetal thymus, similar measurements were noted for singletons and twins. CONCLUSIONS: These results suggest that sonographic measurements of the thymus are feasible in twin pregnancies and that, in uncomplicated pregnancies, these measurements are similar to those noted for singletons. These findings pave the way for future studies aimed at determining the clinical utility of thymic measurements in complicated singleton and twin pregnancies.

Middle cerebral artery peak systolic velocity: a new Doppler parameter in the assessment of growth-restricted fetuses.

OBJECTIVE: The aims of this study were to determine if there is a relationship between middle cerebral artery (MCA) peak systolic velocity (PSV) and perinatal mortality in preterm intrauterine growth-restricted (IUGR) fetuses, to compare the performance of MCA pulsatility index (PI), MCA-PSV and umbilical artery (UA) absent/reversed end-diastolic velocity (ARED) in predicting perinatal mortality, to determine the longitudinal changes that occur in MCA-PI and MCA-PSV in these fetuses, and to test the hypothesis that MCA-PSV can provide additional information on the prognosis of hypoxemic IUGR fetuses. METHODS: This was a retrospective cross-sectional study of 30 IUGR fetuses (estimated fetal weight < 3(rd) percentile; UA-PI > 95% CI) in which the last MCA-PI, MCA-PSV and UA values were obtained within 8 days before delivery or fetal demise. Among the 30 fetuses, there were 10 in which at least three consecutive measurements were performed before delivery and these were used for a longitudinal study. MCA-PSV and MCA-PI values were plotted against normal reference ranges and were considered abnormal when they were above the MCA-PSV or below the MCA-PI reference ranges. RESULTS: Gestational age at delivery ranged between 23 + 1 and 32 + 5 (median, 27 + 6) gestational weeks. Birth weight ranged from 282 to 1440 (median, 540) g. There were 11 perinatal deaths. Forward stepwise logistic regression indicated that MCA-PSV was the best parameter in the prediction of perinatal mortality (odds ratio, 14; 95% CI, 1.4-130; P < 0.05) (Nagerlke R(2) = 31). In the 10 fetuses studied longitudinally, an abnormal MCA-PI preceded the appearance of an abnormal MCA-PSV. In these fetuses, the MCA-PSV consistently showed an initial increase in velocity; before demise or the appearance of a non-reassuring test in seven fetuses, there was a decrease in blood velocity. The MCA-PI presented an inconsistent pattern. CONCLUSIONS: In IUGR fetuses, the trends of the MCA-PI and MCA-PSV provide more clinical information than does one single measurement. A high MCA-PSV predicts perinatal mortality better than does a low MCA-PI. We propose that MCA-PSV might be valuable in the clinical assessment of IUGR fetuses that have abnormal UA Doppler.

Effect of a bone marrow microenvironment on the ex-vivo expansion of umbilical cord blood progenitor cells.

Progenitor cells (CD34(+)) can be isolated from umbilical cord blood and used to correct or reconstitute various cell lines within the haematopoietic and endothelial cell lineage. The main disadvantage of this procedure relates to the low volume of blood that can be collected after the umbilical cord has been clamped, which limits the number of progenitor cells available for treatment. This limitation, however, can be overcome by expanding CD34(+) cells ex vivo. Our aim was to perform a controlled study to determine if the ex-vivo proliferation of umbilical cord CD34(+) cells is enhanced when they are placed in a system that mimics the bone marrow microenvironment. For this purpose, CD34(+) cells were isolated from umbilical cord blood using a magnetic cell sorting kit and seeded in platforms containing different cocktails of cytokines with and without a three-dimensional (3D) biomatrix. Results from this study suggest that the number of viable cells can double after 1 week in any of the culture platforms and that the 3D biomatrix does not enhance cell proliferation.

A study to determine if acute maternal and fetal hyperglycemia/insulinemia induces leptin production during pregnancy.

BACKGROUND: In pregnant primates, the effect of post-prandial hyperglycemic or insulinemic states on leptin production is not known. Our goal was to conduct a controlled study using an established pregnant baboon model ( PAPIO ANUBIS) to determine whether acute glucose changes would have an effect on maternal or fetal plasma leptin levels. METHODS: Two animals were operated on at 138 and 140 days of gestation (term approximately 184 days) by placing 4 cannulae in the maternal aorta, inferior vena cava, fetal carotid artery, and the amniotic cavity. At 145 and 150 days, glucose infusions were started via the maternal femoral vein. Animal 1 received 7.5 gm of glucose over a 2-hour period at 145 th day. Animal 2 received 20 gm of glucose over a 1-hour period at 150th day. Both animals remained ad libitum throughout the experiments. Maternal and fetal blood samples were obtained from the arterial lines before the glucose infusion and at half hour intervals to include 30 minutes post-infusion. RESULTS: Significant changes from baseline concentrations were observed for maternal and fetal glucose and insulin concentrations in response to both glucose challenges. Maternal and fetal plasma leptin concentrations did not correlate with glucose or insulin changes. CONCLUSION: This preliminary study demonstrated that in primates, acute changes in circulating maternal or fetal glucose or insulin concentration do not affect maternal or fetal plasma leptin concentrations. These results suggest that alterations in leptin secretion by the maternal-placental-fetal unit may only occur in pathological states.

Low pregnancy-associated plasma protein-a at 10(+1) to 14(+6) weeks of gestation and a possible mechanism leading to miscarriage.

OBJECTIVE: To compare pregnancy-associated plasma protein-A (PAPP-A) serum levels at 10(+1) to 14(+6) weeks gestation in groups of patients with different obstetrical outcomes. PATIENTS AND METHODS: The medical records of women who had consented to donate blood for biochemical research purposes while their pregnancies were uncomplicated were reviewed to define the clinical groups. After the clinical groups were defined, the donated maternal serum samples were thawed and PAPP-A measured by ELISA. ANOVA was used to compare mean values within groups. RESULT: All groups had similar gestational ages at blood donation (overall mean 12.5 weeks; no difference in gestational age was found within groups, p = 0.18). The overall PAPP-A serum level was 2.01 mIU/ml with only the spontaneous abortion group having a statistical different PAPP-A level (0.09 mIU/ml; p < 0.001). CONCLUSION: These data suggest that those women who experienced spontaneous abortions had significantly different mean PAPP-A serum levels at 10(+1) to 14(+6) weeks gestation. Several lines of evidence suggest that downregulation of insulin-like growth factor-II availability due to a decreased PAPP-A serum level may be the cause of spontaneous abortion in these women.

Use of recombinant human erythropoietin (EPO-alfa) in a mother alloimmunized to the Js(b) antigen.

Erythropoietin (EPO) is a glycoprotein hormone and the principal regulator of erythropoiesis in the fetus, newborn, and adult. EPO-alfa is erythropoietin manufactured by recombinant human DNA technology (rhEPO). After counseling, a pregnant woman with anti-Js(b) in her serum was started on rhEPO (600 U/Kg, biweekly) to prevent anemia secondary to serial donations of her blood for fetal transfusions. After a total of 25 rhEPO infusions and autologous donation of 8 units of whole blood, maternal hemoglobin prior to the elective cesarean section at 37 weeks was 11.3 gm/dL. Serum EPO concentration was determined in paired maternal and fetal blood samples, before ultrasound guided intravascular transfusions, in this alloimmunized Js(b)-negative and another Rh(D) alloimmunized pregnancy to determine possible correlations between maternal and fetal serum EPO. rhEPO prevented anemia in a patient who donated 8 units of blood from 18-37 weeks of pregnancy without inducing adverse biological effects such as hypertension or thrombotic complications in the placenta. Data presented in this study suggest that EPO does not cross the human placenta.

Current concepts of fetal growth restriction: part II. Diagnosis and management.

OBJECTIVE: To update diagnostic concepts and management strategies of fetal growth restriction (FGR). DATA SOURCE: An English literature search was conducted for pertinent articles related to FGR from 1976 to 1997 including original research articles, review articles, and book chapters. METHODS OF STUDY SELECTION: In part II, clinical studies involving both diagnostic and therapeutic approaches to the management of FGR were included. Throughout the study period, the evolution of concepts is demonstrated. TABULATION, INTEGRATION, AND RESULTS: Diagnostic methods including two- and three-dimensional ultrasound for diagnosis of fetal structural abnormalities, organ volumetry, and estimating fetal weight are presented. Clinical tools to assess fetal well-being such as nonstress tests, contraction stress tests, biophysical profile scores, and Doppler blood flow velocimetry of fetal circulation and funicentesis are discussed. Correlations between these indirect fetal evaluations and fetal blood biochemical parameters obtained by funicentesis are also reviewed. Finally, various therapeutic approaches, especially timing of delivery of growth-restricted fetuses, are formulated. CONCLUSION: We suggest that both diagnostic and therapeutic approaches to FGR should be modified. With the current development of technology, newly available three-dimensional ultrasound might offer more precise diagnostic data than conventional two-dimensional ultrasonography in the near future. From current concepts of pathophysiology of FGR, morphometric measurement abnormality alone should not be a basis for intervention. Combined use of morphometric measurements and functional evaluation tests and good clinical judgment using flexibility and individualization are the key elements in successful management of FGR.

Current concepts of fetal growth restriction: part I. Causes, classification, and pathophysiology.

OBJECTIVE: To update basic concepts and management strategies of fetal growth restriction (FGR). DATA SOURCE: An English literature search was conducted for pertinent articles related to FGR from 1976 to 1997. Original research articles, review articles, and book chapters were reviewed. METHODS OF STUDY SELECTION: This study was divided into two parts. For this article, both human data and animal data pertinent to understanding causative factors, pathogenesis, clinical type, and pathophysiology were included. To perform a meaningful comparison, the concept of investigators and their methods of investigation were critically compared between the two study periods: 1976-1985 and 1986-1997. TABULATION, INTEGRATION, AND RESULTS: Older concepts involving basic principles of FGR based on animal models during the first study period were integrated with new research findings obtained from human FGR during the second study period. By comparative analysis of older animal data and new human data, current concepts of FGR were synthesized. CONCLUSION: Fetal growth restriction affects a heterogenous group of infants. Despite development of new technology for investigation, many older basic concepts related to FGR are still fundamentally sound. However, new investigations directly performed on human fetuses are a useful expansion of the older concepts.

Extracoelomic fluid osmometry and electrolyte composition during early gestation in the baboon.

OBJECTIVE: Access to extracoelomic fluid offers the opportunity to assess and potentially treat genetic disorders early in pregnancy. We have been using the pregnant baboon as a model to develop techniques and evaluate the feasibility of sampling extracoelomic fluid. The aim of this study was to determine the osmolality, oncotic pressures, and electrolyte composition of the baboon's extracoelomic fluid between days 39 and 41 of gestation and to compare them with those of maternal blood. STUDY DESIGN: The optimal time to perform the coelocentesis procedure was determined in 14 timed pregnant baboons. Six coelocenteses were then performed in aseptic conditions, under continuous transvaginal ultrasonographic guidance and avoiding the amniotic or yolk sacs. Between 3 and 5 mL extracoelomic fluid was aspirated from each baboon with a 10-mL syringe. Only 1 attempt at sampling was performed for each of the 6 animals. Pregnancies were tracked by transabdominal ultrasonographic evaluations on postprocedure day 3 and then weekly until day 140 of pregnancy. Oncotic pressures and biochemical measurements were determined with 1 mL extracoelomic fluid and 1 mL heparinized maternal venous blood. RESULTS: Data analysis suggests that maternal blood and extracoelomic fluid have similar osmolalities and concentrations of electrolytes but different colloid osmotic pressures (P <.001). CONCLUSION: This nonhuman primate model can be used to gain some insight into the physiologic changes in the composition of the extracoelomic fluid and to evaluate the safety of the coelocentesis procedure. The data suggest that the chorion laeve behaves as a semipermeable membrane at 40 days' gestation.

Assessment of the risk of fetal loss after the coelocentesis procedure using a baboon model.

OBJECTIVES: The aims of this study were to gain some insight with regard to the safety of the coelocentesis procedure and, to determine pH, pCO2, and base excess status of the extracoelomic fluid 40 days after fertilization. METHODS: Twenty-eight timed-mated baboons from the breeding colony of the Biological Resource Laboratory at the University of Illinois at Chicago were studied. The initial 19 animals were used to determine the ultrasonographic relations between the different compartments of the gestational sac from 38 to 62 days of pregnancy. Under aseptic conditions, in 9 animals coelocenteses were then performed, under continuous transvaginal ultrasound guidance to avoid the amniotic or yolk sacs. Extracoelomic fluid (1-5 ml) was aspirated using 10-ml syringes. Only one attempt of sampling was performed in each of the 9 animals. Extracoelomic fluid pH, pCO2, and base excess were compared with maternal femoral venous blood. Pregnancies were followed by transabdominal ultrasound evaluations on day 3 after the procedure and weekly until day 140 after fertilization. RESULTS: Extracoelomic fluid could be aspirated easily using a 20-gauge needle. Only one pregnancy loss was detected within 3 days after the procedure. No complications occurred in the remaining 8 pregnancies. Extracoelomic fluid pH (7.45 +/- 0.01) and pCO2 (39.9 +/- 2.4 mm Hg) were significantly different from maternal femoral venous blood pH (7.41 +/- 0.01) and pCO2 (47.1 +/- 1.4 mm Hg; p < 0.02), while base excess values were similar. CONCLUSIONS: This preliminary study performed at 40 days after fertilization in the baboon model suggests that the coelocentesis procedure is technically simple and presents a relatively low risk to mother and fetus if a 20-gauge needle is used and the amount of aspirated extracoelomic fluid is <3 cm3. At this gestational age, the extracoelomic fluid is more alkalotic than maternal femoral venous blood.

Ultrasonically dense amniotic fluid in early pregnancy in asymptomatic women without vaginal bleeding. A report of two cases.

BACKGROUND: During the second trimester of pregnancy, the presence of free-floating particles in the amniotic fluid on ultrasonography has been associated with aggregates of cells or fetal blood and with unexplained elevation of maternal serum alpha-fetoprotein and the later development of abruptio placentae and fetal distress. During the third trimester, particulate amniotic fluid is thought to represent meconium or vernix. CASES: An unusual, ultrasonically dense appearance of the amniotic fluid was noted prior to 18 weeks of pregnancy in two asymptomatic women who carried exencephalic fetuses. In both cases, prenatal evaluation of the amniotic fluid suggested that the free-floating particles were due to the presence of blood. CONCLUSION: A detailed ultrasonographic evaluation should be undertaken should dense amniotic fluid be detected early in pregnancy because this sign may help in the early diagnosis of fetuses with congenital malformations likely to bleed.

Altered newborn gender distribution in patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG).

OBJECTIVE: to determine if the sex ratio (male/female) is altered in infants born to patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG). STUDY DESIGN: Between 2/1/90 and 1/3/91, 3,116 patients underwent prenatal screening using second-trimester maternal serum alpha-fetoprotein (MSAFP), MShCG, and maternal serum unconjugated estriol (MSuE3). Among these, there were 132 patients with low second-trimester MShCG (< 0.4 MoM), normal MSAFP and MSuE3. The gender distribution of these term, normal newborns was compared to that of 237 controls, matched for race, maternal age, and referral source and delivered at term to mothers with normal mid-trimester MSAFP, MSuE3, and MShCG. The gender distribution of these two groups of newborns was also compared to that of 78 term newborns from the same obstetrical population delivered to mothers with second-trimester MShCG > 2.5 MoM and normal MSAFP and MSuE3. All patients had a complete obstetrical history. RESULTS: Forty-nine percent of the controls were male vs. 62% of the group with slow second-trimester MShCG (P < .01). Within the group with low MShCG, 59% of infants were male when the MShCG was between 0.19 and 0.4 MoM (A) and 80% when the MShCG was < 0.2 MoM (B) (control vs. A vs. B P < .005). The sex ratio in the high-MShCG group was similar to control. CONCLUSION: The data suggest that gender distribution is different from normal in patients with low mid-trimester MShCG.