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Phospholipids and creatinine in amniotic fluid in relation to gestational age. II. Complicated pregnancy.

176 samples of amniotic fluid were obtained by abdominal amniocentesis from 69 women with complicated pregnancies (toxemia, diabetes mellitus or rhesus isoimmunization) in the 27th-43rd week of pregnancy. The concentration of creatinine (172 cases), the ratio of lecithin/sphingomyelin (L/S-ratio, 155 cases) and phospholipid phosphorus (155 cases) were determined and related to gestational age. The results were compared with normal pregnancy. The mean level of creatinine in toxemia was significantly higher from the 32nd week till term (p less than 0.05) and the L/S-ratio was significantly higher (p less than 0.05) in the 34th-35th week compared with normal pregnancy. Creatinine concentration was significantly elevated in diabetic pregnancy in the 36th-37th week (p less than 0.05). Creatinine concentration tended to be low in Rh-isoimmunization. A creatinine concentration greater than or equal to 1.8 mg% and a L/S-ration greater than or equal to 2.25 always corresponded to a gestational age greater than or equal to 35th week. To get increased precision in estimating gestational age in complicated as well as in normal pregnancy the determination of both creatinine concentration and L/S-ratio in amniotic fluid is recommended.

Amniotic Fluid↗

Real-time ultrasound as an aid in intrauterine transfusion.

Real-time ultrasound was used as an aid in intrauterine transfusions for patients with Rh isoimmunization. It was preferred to fluoroscopy and x-ray control to identify the placental site and fetal abdomen and to direct the insertion and placement of the transfusion needle. The technique was used 22 times in 12 patients and resulted in increased efficiency and safety, including decreased radiation to the fetus.

Blood Transfusion, Intrauterine↗

Unconjugated estriol and 15alpha-hydroxyestriol in complicated pregnancies.

Simultaneous determinations of unconjugated estriol and 15alpha-hydroxyestriol (E4) levels in maternal serum were studied serially to ascertain the relative usefulness of these estrogens as indicators of fetal welfare. Complicated pregnancies included 16 patients with pre-eclampsia and/or hypertension, six patients with severe Rh-isoimmunization, 12 patients with diabetes mellitus, of which four had vascular disease, three patients with fetal death in utero, and three twin pregnancies. Retrospective analysis failed to indicate a clinically useful role for serum E4 determinations in the evaluation of fetal welfare during high-risk pregnancies.

Antibody Formation↗

Plasma estetrol as an index of fetal well-being.

Estetrol (15alpha-hydroxyestriol or E4) is considered to be a specific product of fetal liver and has been suggested as a good indicator of fetal well-being. The concentration of unconjugated estetrol (E4) was measured by rapid and specific radioimmunoassay in 1 ml of maternal plasma. E4 levels prior to the 18th week of pregnancy were often undetectable (smaller than 50 pg/ml). The mean plasma E4 level at term of 1.2 ng/ml was 7-fold higher than that observed at 24 weeks of gestation, and no diurnal variations were found. E4 levels in fetal plasma at term were 12-fold higher than those in maternal plasma and no fetal arterial venous differences were found. Umbilical vein but not maternal plasma levels of patients undergoing vaginal delivery were higher than those undergoing cesarean section (P smaller than 0.05) suggesting increased adrenal output of E4 precursors during labor. In patients with severe Rh-isoimmune disease plasma E4 levels were not helpful in assessing fetal well-being. However, in patients with chronic hypertension or pre-eclampsia, subnormal plasma E4 concentrations always preceded intrauterine fetal death. Plasma E4 appears to be a good indicator of fetal well-being in patients with hypertensive disease of pregnancy.

Amniotic Fluid↗

Biochemical assessment of fetal lung maturity.

The relationship between the enzyme phosphatidate phosphohydrolase (PAPase) and lecithin/sphingomyelin (L/S) ratio in amniotic fluid was evaluated in normal human pregnancies and in several pregnancies complicated by Rh isoimmunization. An increase in PAPase activity in amniotic fluid appears to parallel the increase in L/S ratio after 33 weeks gestation in normal subjects. These data suggest that amniotic fluid PAPase may originate from the fetal lung and play a role in the regulation of the synthesis os lecithin. Its usefulness as an indicator of fetal lung development requires further correlation and confirmation.

Amniotic Fluid↗

Management of late anemia in Rhesus hemolytic disease: use of recombinant human erythropoietin (a pilot study).

The management of (Rhesus) hemolytic disease of the fetus and newborn includes intrauterine transfusions to prevent the development of hydrops, treatment of the possible hyperbilirubinemia in the immediate postnatal period, and treatment of late anemia. Low levels of serum erythropoietin due to suppression of the bone marrow by multiple intrauterine transfusions is a suggested mechanism for this anemia. The aim of our study was to test whether recombinant human erythropoietin reduced the need for erythrocyte transfusions in these infants. Twenty infants with Rhesus isoimmunization were blindly randomized to treatment and control groups at the 2nd wk of life. The number of intrauterine and exchange transfusions and demographic data were similar in both groups. The infants in the treatment group received recombinant human erythropoietin, s.c. 200 U/kg of body weight three times a week for a period of 6 wk, whereas the infants in the control group received a placebo for the same period. In the treatment group, the mean number of erythrocyte transfusions was significantly lower than that of the control group (1.8 versus 4.2). The reticulocyte counts and Hb levels rose earlier in the treatment group. The platelet and neutrophil counts were similar in both groups throughout the study. This study demonstrates that recombinant human erythropoietin treatment decreases the need for erythrocyte transfusions in the late anemia of infants with Rh isoimmunization. Considering the risks of blood transfusions, this decrease in the donor exposure is worthwhile.

Anemia, Hemolytic↗

Bacteriolytic activity of amniotic fluid.

Bacteriolytic activity and lecithin concentration were measured in amniotic fluid samples from both normal and pathologic pregnancies, including conditions such as severe Rh isoimmunization, placental dysfunction, preeclampsia, and diabetes. The bacteriolytic activity increased threefold from the 25th gestational week to term, after which a slight reduction was found. No difference was found between pathologic and normal pregnancies. No correlation was found between lecithin content and bacteriolytic activity. Samples from pregnancies in which the infant developed respiratory distress syndrome had low lecithin concentrations but showed normal bacteriolytic activities.

Amniotic Fluid↗

Fetal-maternal transfusion following early abortion.

Therapeutic abortion has been a major potential source of Rh isoimmunization. Popularization of early termination necessitates reconfirmation of established policies. This study involved 75 patients, selected at random, in whom pre- and post-abortion blood smears were studied for fetal-maternal hemorrhage. Results showed that this may occur even in early suction termination. The significance of these findings was discussed in relation to the cost-effectiveness and the dosage of anti-Rho (D) globulin administered to patients.

Abortion, Therapeutic↗

Severe Rh disease--poor outcome is not inevitable.

Most centers report only moderate success in the intrauterine treatment of severe Rh-isoimmune hemolytic disease. For the hydropic fetus, the prognosis is poor. Innovations in the assessment, treatment, and follow-up of the severely affected fetus have yielded more encouraging results. Among the 24 fetuses receiving a refined management plan, instituted in June, 1980, survival rates were 100% in the nonhydropic fetus and 75% in the hydropic fetus. Improved fetal evaluation by means of extensive real-time ultrasonography allows more exact assessment of stage of disease, safer performance of intrauterine transfusion, and a direct picture of the fetal response to treatment. The intrauterine transfusion procedure differs in many aspects from those used in other centers and is notable mostly because of the absence of traumatic fetal death since the present program began. This improvement and the absence of neonatal death have resulted in 92% survival rate among the fetuses transfused. The success of this integrated team approach suggests revision of the pessimism toward the fetus with severe Rh disease.

Blood Transfusion, Intrauterine↗

Fetal intestinal obstruction: necessity for percutaneous umbilical blood sampling to assess the severity of Rh sensitization.

Investigation into the severity of hemolytic disease due to Rh isoimmunization may be complicated by concurrent amniotic fluid contamination with bile. We have presented a case in which a prenatal sonogram showed evidence of fetal intestinal obstruction, which was subsequently confirmed postpartum by exploratory laparotomy. Since intrauterine regurgitation of bile occurs with intestinal obstruction distal to the papilla of Vater, percutaneous umbilical blood sampling is necessary to discern the presence and severity of hemolytic disease as indicated by an abnormal spectrophotometric absorption pattern.

Adult↗

Assessment of size of small volume feto-maternal bleeds. A new method of quantification of the Kleihauer technique.

The risk of Rh-isoimmunization is probably related to the volume of foeto-maternal bleeding. With the Kleihauer technique foetal cells may be detected in maternal blood, but estimation of the size of foetal bleed the cells represent is at present difficult and open to serious error.A new method of quantifying the technique by using a standard volume of maternal blood, and a simple machine for the preparation of comparable blood films, is described. The new method eliminates many of the errors of previous techniques, and should be capable of automation for large-scale screening programmes.

Erythroblastosis, Fetal↗

Epidemiology of fetal death in Latin America.

BACKGROUND: To identify risk factors associated with fetal death, and to measure the rate and the risk of fetal death in a large cohort of Latin American women. METHODS: We analyzed 837,232 singleton births recorded in the Perinatal Information System Database of the Latin American Center for Perinatology and Human Development (CLAP) between 1985 and 1997. The risk factors analyzed included fetal factors and maternal sociodemographic, obstetric, and clinical characteristics. Adjusted relative risks were obtained, after adjustment for potential confounding factors, through multiple logistic regression models based on the method of generalized estimating equations. RESULTS: There were 14,713 fetal deaths (rate=17.6 per 1000 births). The fetal death risk increased exponentially as pregnancy advanced. Thirty-seven percent of all fetal deaths occurred at term, and 64% were antepartum. The main risk factors associated with fetal death were lack of antenatal care (adjusted relative risk [aRR]=4.26; 95% confidence interval, 3.84-4.71) and small for gestational age (aRR=3.26; 95% CI, 3.13-3.40). In addition, the risk of death during the intrapartum period was almost tenfold higher for fetuses in noncephalic presentations. Other risk factors associated with stillbirth were: third trimester bleeding, eclampsia, chronic hypertension, preeclampsia, syphilis, gestational diabetes mellitus, Rh isoimmunization, interpregnancy interval<6 months, parity > or =4, maternal age > or =35 years, illiteracy, premature rupture of membranes, body mass index > or =29.0, maternal anemia, previous abortion, and previous adverse perinatal outcomes. CONCLUSIONS: There are several preventable factors that should be dealt with in order to reduce the gap in fetal mortality between Latin America and developed countries.

Adolescent↗

Passive antibody and the immune response. Factors which determine enhancement and suppression.

The isoimmune response of fowl inoculated with RBC coated with antibody was investigated. Anti-B antiserum from a single animal was used to coat different donor type RBC. With each donor type RBC the immune response to the coated determinants is suppressed. Enhancement of the immune response to noncoated determinants occurs when they are products of an allelic gene or belong to a different blood group system. Coating some B antigen determinants suppresses the response to noncoated determinants of the same antigen, i.e., determinants which are products of the same B gene. Varying the quantity of passive antibody revealed that the degree of suppression and the degree of enhancement are negatively correlated. These findings support the concept that antibody-coated determinants function as carrier for noncoated determinants, provided a certain physical association exists between them. A further interpretation of these studies is that in certain situations an antibody to one antigen may interfere with events which lead to an immune response to a different antigen. The possibility, that the protection afforded by ABO incompatibility against Rh isoimmunization is because of a similar phenomenon, is discussed. A hypothesis is presented which states that where the immune response to certain antigens behaves as a dominantly inherited trait, and is associated with histocompatibility type, the nonresponder animals possess an antibody (perhaps cell bound) which interferes with the response to determinants for which it does not have specificity. Responders are assumed to lack this antibody because it has specificity for their major histocompatibility antigens.

Animals↗

Inhibition of synthesis of fetal hemoglobin by an isoleucine analogue.

Reticulocytes from newborn infants with Rh isoimmune hemolytic disease actively incorporated radioactive amino acids in vitro into hemoglobins F and A. Approximately 50% of the reticulocytes appeared capable of synthesis of both of these hemoglobins within the same cell, as demonstrated by the selective elution technique of Betke and Kleihauer. An isoleucine analogue, L-O-methylthreonine, inhibited the incorporation of a variety of amino acids into hemoglobin F, without significantly affecting the synthesis of hemoglobin A. The inhibition was prevented upon concomitant addition of L-isoleucine to the medium. These observations suggest that an independent biosynthetic apparatus is present in the cell for the synthesis of each of these two hemoglobins. Because isoleucine is present only in the gamma chains of hemoglobin F, the inhibitory effect of the analogue on the synthesis of this hemoglobin must represent a selective effect on the production of gamma chains.

Fetal Hemoglobin↗

Fetal movements in human pregnancies in the third trimester.

Fetal movements (FM) were measured using a real-time B-scan method in 50 women in the third trimester. One hundred ninety-five observations were made. The number of FM per 20-minute observation period was similar in normal, diabetic, and hypertensive pregnancies and in patients with placenta previa, but was significantly lower in patients with Rh isoimmunization and an affected fetus. The number of FM did not vary with gestational age, mode of delivery, or birth weight and was significantly increased in patients either with a reactive nonstress test (NST) or in the presence of fetal breathing movements (FBM). Fetal movements were absent before delivery in 4 patients: In 3, the fetus died in utero and in the other a positive contraction stress test (CST) was observed. Conversely, in 2 other fetuses who died in utero, FM were observed during the last examination before death. In both, the cause of fetal death was related to an acute change. No relationship between FM and neonatal death was observed. These data suggest FM monitoring may be helpful in evaluating antepartum fetal condition.

Antibody Formation↗

Intravenous immunoglobulins in rhesus hemolytic disease.

OBJECTIVE: To evaluate the role of intravenous immunoglobulins in Rh hemolytic disease of newborn. METHODS: The study included all DCT positive Rh isoimmunized babies admitted in the unit from August 2000 to February 2001. Intravenous immunoglobulins in the dose of 500 mg/kg on day 1 and day 2 of life in addition to the standard therapy. Babies who received IVIG were compared with those who did not receive IVIG for the peak bilirubin levels, duration of phototherapy, number of exchange transfusions, discharge PCV and the need for blood transfusions for late anemia till 1 months of age. RESULTS: A total of 34 babies were eligible for the study. 8 babies received IVIG and 26 babies only standard treatment. The mean maximum bilirubin levels were significantly lower in the IVIG group compared to the group who received NO IVIG (16.52 +/- 2.96 Vs 22.72 +/- 8.84, p=0.004). Five babies in the IVIG group (62.5%) and 23 babies in the NO IVIG group required exchange transfusions (88.5%, p=0.014). 12 of the 26 babies in the NO IVIG group required multiple exchange transfusions while none of the babies in IVIG group required more one exchange transfusion (p=0.03). The mean duration of phototherapy was 165 +/- 109 hours in the IVIG group as against 119 +/- 56 hours in the NO IVIG group (p=0.29). Blood transfusion for anemia was more common in the IVIG group (37.5% Vs 11.5% p=0.126) though the packed cell volumes at discharge were similar in both the groups (39.5 +/- 11 Vs 40 +/- 5.1, P=0.92). CONCLUSION: Intravenous immunoglobulins is effective in decreasing the maximum bilirubin levels and the need for repeated exchange transfusions in Rh hemolytic disease of newborn. There is however an increased need for blood transfusions for late anemia in the babies treated with IVIG.

Erythroblastosis, Fetal↗

The plasma estradiol as an index of fetoplacental function.

A radioligand assay has been developed for the measurement of unconjugated 17beta-estradiol in as little as 0.01 ml of pregnancy plasma employing rabbit uterine cytosol as specific binder and activated charcoal as nonspecific absorbant. Large numbers of samples could be processed simultaneously at relatively little expense and results were obtainable within 3 hr. The procedure was sensitive to 1 ng/ml. No diurnal or positional variations were found. Values from 250 unselected normal patients showed a constantly rising mean plasma E(2) from 18 to 35 wk gestation from 4.5 to 14 ng/ml. From 35 to 40 wk, mean E(2) rose only to 15 ng/ml and the range of values increased substantially. When 22 normal pregnant subjects were followed serially, rising levels of plasma E(2) were found with no significant fall ever seen. By contrast, patients exhibiting fetal distress generally had falling or reduced E(2) levels. However, 3 cases of Rh isoimmunization had elevated or normal E(2) concentrations even after clearcut evidence of fetal demise. A decrease of 45% in E(2) concentration was associated with intraamniotic instillation of hypertonic saline prior to delivery supporting the view that placental conversion of maternal adrenal precursors is responsible for about half of the E(2) production in pregnancy. The postpartum clearance of endogenous E(2) was measured and found to fit a two compartment model with mean half-time of 22 min and 7 hr. Follicular phase levels of E(2) were attained by 35 hr postpartum. The concentration of unconjugated E(2) in pregnancy plasma correlated as well with the state of the placenta as other placental hormone measurements and holds promise of being a rapid, inexpensive, and reliable method of following patients with high-risk pregnancies in a variety of clinical settings.

Abortion, Induced↗

Acute nonlymphocytic leukemia after transient myeloproliferative disorder in a patient with Down syndrome.

An infant with Down syndrome (DS) and RH isoimmunization developed transient myeloproliferative disorder (TMD) during the neonatal period. At 16 months she presented with acute nonlymphocytic leukemia (ANLL). Cytogenetic studies during TMD showed trisomy 21 only but new abnormalities emerged during ANLL. She is now in complete remission 5 years after diagnosis. Patients with TMD have either trisomy 21 or mosaic 21 in blood and bone marrow but in phenotypically normal children this cell line disappears with resolution of the TMD. A review of the literature indicates that there are no clinical, hematological, or cytogenetic differences between DS children with TMD who subsequently develop acute leukemia and those who do not. However, the leukemia in the former group may differ in presentation, type, and possibly survival time from other DS children who develop leukemia de novo.

Bone Marrow↗