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Fetal death. A 10-year retrospective study.

Fetal death has been defined by the World Health Organization as death before complete expulsion or extraction from its mother of a product of conception, irrespective of the duration of pregnancy. Certain causes of fetal death, including syphilis, Rh isoimmunization, toxemia, and diabetes, have shown significant declines over the past several decades. However, many fetal losses continue to occur from intrauterine infections, lethal malformations, fetal growth retardation, and abruptio placentae. Fetal death with no identifiable specific cause is another consideration when dealing with these cases. Other risk factors can include maternal, sociodemographic, and medical care factors. The authors reviewed all forensic cases referred for autopsy to the Forensic Section of the Medical University of South Carolina, Medical Examiners' Office over the 10-year period 1990-1999. All cases listed as fetal death or stillbirth were included. The 42 cases were analyzed as to fetus' gestational age, sex, race, weight, location of delivery, history of prenatal care, maternal drug use, chromosomal abnormalities, cause and manner of death, and autopsy findings. The black:white ratio was approximately 2:1, and the male:female ratio was virtually 1:1. Most fetuses were older than 20 weeks' gestational age, with one third between 20 and 29 weeks. The majority were externally normal aside from maceration. Only 7.5% had congenital anomalies. Twenty-one of 38 placentas were grossly and microscopically normal. Of cases with toxicologic analysis, 21% were positive for drugs, and 17% were positive for cocaine/benzoylecgonine. The manner of death was classified as natural (28), accident (2), and undetermined (12). Few studies have reported the specific causes of fetal death, and the lack of uniformity in data collection and classification of causes of fetal death has made comparisons difficult. The authors present this retrospective study to better determine the factors leading to fetal demise in the hope of assisting death investigators in this challenging arena.

Adolescent↗

Bilateral mesial temporal sclerosis and kernicterus.

Two children with mental retardation, choreoathetosis, dystonia, and muscle rigidity are reported. They had a history of severe hyperbilirubinemia after birth as a result of Rh isoimmunization. The history and clinical picture suggested the diagnosis of kernicterus. The magnetic resonance imaging examination showed a bilateral signal intensity increase in the globus pallidus on T2-weighted images. Additionally, our patients showed symmetric bilateral hyperintensity and volume loss in the hippocampus, which is known to be another characteristic area of bilirubin deposition in kernicterus.

Child↗

Neonatal bilirubin production estimated from "end-tidal" carbon monoxide concentration.

The relationship between the pulmonary excretion rate of carbon monoxide (VECO) and the concentration of CO, in a sample of breath, drawn through a nasopharyngeal catheter at end-expiration, was assessed in 25 studies of nine preterm and 14 term infants. The VECO and this approximate end-tidal sample of CO (ETCO) correlated significantly over a wide range of CO elimination rates: VECO = 10.45 ETCO + 2.25 (n = 25, r = 0.95). The ETCO correctly predicted elevations in VECO greater than 2 SD of the mean VECO for normal infants (13.9 +/- 3.5 microliter/kg/h), with 90% sensitivity and 73% specificity (p less than 0.01). Three subjects with Rh isoimmune hemolytic disease were easily identified by the ETCO as well as the VECO. The ETCO is a simple, noninvasive measurement for rapidly identifying infants with significant hemolytic disease.

Bilirubin↗

Alpha-fetoprotein content of amniotic fluid in normal and abnormal pregnancies.

Elevation above the normal range of alpha-fetoprotein (AFP) concentration in amniotic fluid occurs in the presence of certain fetal anomalies. The value of a new method for radioimmunoassay of APF in amniotic fluid was tested by an analysis of 486 samples taken by amniocentesis at various stages of pregnancy. The normal range of concentrations during pregnancy was established by 348 samples from healthy women with normal pregnancies. This was compared with the levels found in the presence of various fetal malformations--Rh-isoimmunization, maternal diabetes, chromosomal anomalies, and fetal death in utero. The findings and their implications are discussed.

Amniotic Fluid↗

Sinusoidal fetal heart rate pattern after intrauterine transfusion.

Two pregnancies complicated by severe Rh-isoimmunization and the development of sinusoidal fetal heart rate patterns immediately after intrauterine transfusions are presented. An intermittent sinusoidal pattern resolved, in one fetus, with sonographic evidence of delayed but complete absorption of transfused red blood cells. In contrast, the second fetus exhibited a continuous sinusoidal pattern coincident with cardiac decompensation detected by echocardiography, severe anemia, and failure to absorb transfused red blood cells. Possible pathophysiologic mechanisms for the development of sinusoidal patterns after fetal transfusions are discussed. It is concluded that a sinusoidal fetal heart rate pattern may occur after fetal transfusion and that the subsequent course of this pattern provides meaningful information about fetal condition as well as the success of intrauterine transfusion.

Adolescent↗

Bart's hydrops fetalis--clinical presentation and management--an analysis of 25 cases.

Twenty-nine hydropic infants were born in the Kandang Kerbau Hospital between 1980 and 1985, during which there were 131,658 deliveries, giving an incidence of 1 in 4,540 total births. Twenty-five of these cases were confirmed to be due to homozygous alpha thalassaemia. No case of fetal hydrops due to Rh isoimmunization was detected. The mean age of the mothers was 28.86 +/- 4.05 years (+/- SD). Eight patients had delivered 1 hydropic baby previously while 1 had a history of 2 babies with hydrops fetalis; 92% of the patients had been followed antenatally while 8% were first seen when they were admitted in labour; 25% of the patients had anaemia, 52% had polyhydramnios, 20% developed hypertension and 64% had bilateral lower limb oedema. None of the patients had concomitant hypertension, generalized oedema and proteinuria. In 4 cases of recurrent hydrops, serial ultrasound scans were performed from early pregnancy but ultrasonic features of hydrops fetalis were only seen from 27 weeks' gestation. Spontaneous labour occurred in 75% of patients at a mean of 32.3 +/- 3.3 weeks (+/- SD). All delivered vaginally and only 1 patient required abdominal decompression. Four patients required Caesarean section, 2 for failure to progress after induction of labour, 1 for major placenta praevia and the fourth for fetal distress; in the last case, diagnosis of hydrops fetalis was only made after delivery of the baby. All the babies in the series died within one hour of delivery. Homozygous alpha thalassaemia is the commonest cause of hydrops fetalis in Singapore and is an invariably fatal condition. It is associated with an increased incidence of maternal anaemia, polyhydramnios and prematurity.

Adult↗

Protein content of liquor amnii in prediction of severity of haemolytic disease of newborn.

Two series of cases of Rh isoimmunization were subjected to liquor examination for bilirubin and protein level. Series 1 comprised 298 cases for the years 1962 and 1963. Series 2 comprised 179 consecutive cases for 1967 in which preliminary selection for liquor examination had been made on the basis of previous history and maternal antibody titre.Bilirubin was measured as the liquor bilirubin ratio, and protein levels were estimated in series 1 by the Folin and Ciocalteau technique and in series 2 by a modified biuret method.Correlations with severity of haemolytic disease in the foetus was made, taking into account the stage of gestation of liquor examination. Both bilirubin and protein levels correlate with severity, but bilirubin is superior to protein. Interrelation of these measurements as bilirubin/protein ratio was inferior to bilirubin level as a method of forecasting severity.

Amniotic Fluid↗

Sonographic diagnosis of fetal hydrops.

Sonograms obtained during the 32nd and 34th weeks of a pregnancy complicated by severe Rh isoimmunization demonstrated features diagnostic of fetal-hydrops-scalp and body wall edema, ascites, hepatosplenomegaly and placental enlargement. The earliest sign that can be detected sonographically is placental enlargement.

Adult↗

Intervillous thrombosis: sonographic and pathologic correlation.

Sonographic and pathologic documentation of 7 cases of intervillous thrombosis of the placenta are presented. These lesions were demonstrated on sonography as early as 19 weeks of gestation. Since intervillous thromboses are thought to be related to Rh isoimmunization, their sonographic documentation may be of clinical importance.

Chorionic Villi↗

Amniotic fluid reverse triiodothyronine in complicated pregnancy.

The concentrations of reverse triiodothyronine (3,3',5'-T3 or rT3) in amniotic fluid (AF) were measured by radioimmunoassay in 81 patients with various complications of pregnancy and in 39 normal pregnant patients at equivalent gestational age. In normal pregnancy, AFrT3 concentrations decreased with advancing gestational age. At 21-25, 26-30, 31-35, and 36-40 weeks of normal pregnancy, AFrT3 concentrations (mean +/- SE) were 353 +/- 62 (n = 6), 131 +/- 49 (n = 7), 94 +/- 25 (n = 14), and 93 +/- 5 (n = 20) ng/dl, respectively (ranges: 200-600, 57-350, 66-135, and 50-135). Both normal and supranormal values of AFrT3 were found in patients with complicated pregnancy. In patients with RH isoimmune disease, higher than normal AFrT3 concentrations were associated with seriously affected or gravely ill fetuses wheras normal AFrT3 concentrations predicted a more favorable outcome. There was a good correlation between AFrT3 and AF pigment (deltaOD450) levels (r = 0.70, P less than 0.001). In complicated pregnancy other than erythroblastosis fetalis, AFrT3 concentrations were not of any prognostic significance, and there was no correlation between AFrT3 and lecithin/spingomyelin ratio. The data suggest that AFrT3 determination may help in the assessment of the fetal condition in erythroblastosis fetalis.

Amniotic Fluid↗

Amniotic fluid concentrations of iodothyronines and thyrotropin do not reliably predict fetal thyroid status in pregnancies complicated by maternal thyroid disorders or anencephaly.

In this study we report measurements of amniotic fluid (AF) concentrations of iodothyronines and TSH in 69 normal and 16 complicated pregnancies. The latter group included 2 women with untreated hyperthyroidism, 1 patient with untreated hypothyroidism, 5 hyperthyroid patients who received propylthiouracil (3 with Graves' disease, 1 with a multinodular goiter, and 1 with chronic thyroiditis), 3 women with Graves' disease who were hypothyroid after treatment, but who were receiving replacement therapy, and 5 anencephalic pregnancies. AF hormone levels could not be correlated with either maternal or cord serum values, neonatal serum measurements, and/or the clinical status of the infant. AF TSH and T4 levels were markedly elevated in 1 patient with Graves' disease and severe Rh isoimmunization and in 2 pregnancies complicated by anencephaly without identifiable pituitary tissue in the fetus. We conclude that measurements of AF concentrations of thyroid hormones and TSH do not reliably predict fetal or neonatal thyroid status.

Amniotic Fluid↗

Transplacental transfer of morphine in man.

The transplacental transfer of morphine and morphine-3-glucuronide (M3G) was studied in five cases of suspected Rh-isoimmunization. Ultrasound-guided fetal blood sampling from the umbilical vein was carried out as a diagnostic procedure before intrauterine blood transfusion. Morphine was given as a parenteral premedication to the mother at a dose of 0.13-0.20 mg/kg bw. Fetal blood was sampled 5-74 minutes after the morphine administration. These five women were investigated on 14 different occasions. The plasma concentrations of morphine and M3G were measured in blood samples collected simultaneously from mother and fetus. The feto-maternal ratio of morphine was 0.96 at five minutes and remained close to 1.0 in most samples taken later. At 12 minutes the ratio of M3G was less than 0.002 and between 0.2 and 0.6 in the later samples. The feto-maternal plasma ratios of morphine and M3G did not change over the studied period in one woman investigated five times between gestational weeks 26 and 32. This is the first time transplacental transfer of morphine has been quantified in man. Our results demonstrate a rapid transplacental passage and equilibration of morphine between mother and fetus.

Female↗

Accuracy of the serological ELISA test compared with the polymerase chain reaction for the diagnosis of cytomegalovirus infection in pregnancy.

CONTEXT: The most frequently used methods for detecting antibodies are the indirect immunofluorescence test and the enzymatic immunoassay (ELISA). The polymerase chain reaction is a molecular biology technique in which the production of large amounts of specific DNA fragments is induced from very low concentrations of complex substrates aloowing the detection of very low amounts of viral particles. OBJECTIVE: To assess the accuracy of serological/ELISA tests in comparison with the polymerase chain reaction in maternal blood to diagnose cytomegalovirus infection. DESIGN: A descriptive study was performed. SETTING: High-risk outpatient clinic of Campinas University (Unicamp). PARTICIPANTS: We selected 243 pregnant women. All of them had been indicated for blood sampling because of suspicions of cytomegalovirus infection and also because of other infections. MAIN MEASUREMENTS: The group was tested for cytomegalovirus. Serological tests were run and compared to the polymerase chain reaction, which was considered to be the gold standard. Status analyses were done using Fisher's exact test, via the SAS software. RESULTS: The previous cytomegalovirus infection rate was 94.6%. The main reasons for inclusion in the study were fetal nervous system malformation (25.5%), maternal toxoplasmosis (25.5%) and Rh isoimmunization (14.8%). Only two women were included because of positive serological immunoglobulin M test for cytomegalovirus. The sensitivity and specificity of the serological tests were 94% and 6% for immunoglobulin G. CONCLUSION: Serological tests had lower sensitivity in comparison with the polymerase chain reaction test when diagnosing cytomegalovirus infection. The consequences of positive polymerase chain reaction and negative immunoglobulin M in women remain unknown.

Adult↗

[Persistent neonatal hyperbilirubinemia resulting from Gilbert's syndrome in association with RhD hemolytic disease].

OBJECTIVE: To report on an infrequent association of pathologies causing considerable increase in bilirubin production and a significant decrease in its excretion. DESCRIPTION: The third pregnancy of an RhD negative woman. Her first child was normal and delivered to term and did not receive Rhogam. The second pregnancy was problematic due to Rh isoimmunization. She delivered a child to term, who required three exchange transfusions, but died on the 8th day of life. The third child was delivered at term, ORh positive, direct Coombs positive and had stump bilirubin of 6.5 mg/dl and hematocrit at 44%. Five hours after birth the child was jaundiced. Phenobarbital and intensive phototherapy were introduced. Hyperbilirubinemia was soon controlled, but relapsed whenever phototherapy was discontinued. On the 10th day of life the child received a transfusion for significant anemia. As jaundice persisted to the 13th day, associated Gilbert syndrome was considered and DNA sequence analysis was requested. The test demonstrated a mutant homozygote genotype UDPT1A1[TA]7TAA. Phototherapy remained necessary until the 17th day of life and she was discharged from hospital the following day, after bilirubinemia had been controlled. She returned for follow-up and exhibited normal growth and neurological development. COMMENTS: This case demonstrates the significance of increased bilirubin production/decreased bilirubin excretion causing intense hyperbilirubinemias and, in the absence of vigorous treatment, kernicterus. The effectiveness of intense phototherapy has also been demonstrated, reducing the risks of more aggressive treatments such as exchange transfusion. It also provides evidence of the importance of bilirubinemia follow-up until complete resolution.

Adult↗

Marker proteins in the particulate fraction of third-trimester amniotic fluid.

The present clinical evaluation of fetal lung maturity relies largely on the determination of the amniotic surfactant phospholipids phosphotidylglycerol, lecithin, and sphingomyelin, but there are many false negatives as well as false positives among diabetics. The use of other components of lung surfactant, namely, the hydrophobic surfactant proteins (SPs) has long been suggested as an alternative to the classical assay, but tests based on the detection of immunoreactive SP-A have not proved superior or supplanted phospholipid ratios as an index. This report investigates the proteins in a fraction of third-trimester human amniotic fluid (the particulate fraction) enriched in the SP complexes that form the surfactant monolayer. The proteins were analyzed by two-dimensional polyacrylamide gel electrophoresis and visualized by silver staining and immunoblotting. Eight proteins are of particular interest. Three novel proteins (termed AFPP-1, AFPP-4, and AFPP-8) and the alpha-fetoprotein/human serum albumin complex (AFPP-7) can be detected throughout the 28- to 38-week gestational window. The protein that is referred to as AFPP-2 could be identified as SP-A on the basis of immunologic cross-reactivity as well as size and charge characteristics. The time course of appearance of AFPP-2 was also followed in patients with Rh isoimmunization syndrome and was found to be the same as that seen for SP-A. The SP-A was detected as at least five major charged isoforms with multiple subisoforms of different molecular weight and can be distinguished from a related set of proteins (AFPP-5) that appear with a different time course but are possible precursors. Two other proteins (AFPP-3, AFPP-6), which are detectable inconsistently bear some similarity to others reported previously but not extensively characterized. These results define both constant and variable proteins of the particulate fraction of the amniotic fluid and indicate that certain protein isoforms are changing throughout the third trimester. These data enhance the possibility of the utilization of these proteins as markers of lung maturity in conditions such as maternal diabetes.

Amniotic Fluid↗

A case of recurrent infantile polycystic kidney associated with hydrops fetalis.

Nonimmune hydrops fetalis is becoming a predominant form of fetal hydrops due to the declining incidence of immune hydrops fetalis triggered by Rh isoimmunization. Infantile polycystic kidney appeared to be related to hydrops fetalis whether it is causal or merely coincidental and may represent another entry to differential diagnoses. Infantile polycystic kidney was diagnosed by an elevated maternal serum alpha-fetoprotein (AFP) value coupled with an ultrasonographic abnormality scanned as a multicystic mass with ascites in the fetal abdomen antenatally. This study presents a case of infantile polycystic kidney that resulted in a stillborn baby with hydrops fetalis and extensive placental calcification; it was the first case in Korea in which nonimmune hydrops fetalis was associated with infantile polycystic kidney in consecutive siblings by autosomal recessive inheritance in one family. In addition, this paper comprehensively reviews the incidence, etiology, prenatal diagnosis and proper management of nonimmune hydrops fetalis.

Adult↗

Human chorionic somatommamotropin (HCS) and pregnancy. Its relation with insulin.

Plasma HCS levels have been measured in normal and pathological pregnant women. In the normal group HCS levels increased from 6--8 weeks till 33-34 weeks and then felt significantly. HCS pattern in prediabetic and chemical diabetic pregnant women was similar to the normal group. However HCS levels in chemical diabetics were significantly higher during the first two trimesters. HCS levels increased in twin pregnancy, diminished in cases of eclampsia, hypertension, fetal growth retardation, mole and blighted ovum, and disappeared after intrauterine death. Nothing could be deduced from the obese and Rh-isoimmunization groups. It is confirmed the value of HCS determination as an index of placental maturation. Also, insulin/HCS ratio may be of some aid in the study of carbohydrate intolerance in pregnancy.

Adolescent↗

[The antioxidants (coenzyme Q10) in materno-fetal physiopathology].

BACKGROUND: Coenzyme Q10 (ubidecarenone) is a torpeniod molecule mainly located in bacterial and mitochondrial membranes. It is a part of a specific enzyme system and acts primarily on the transport of electrons in the mitochondrial respiratory chain. It performs an antioxidant action. We studied both fetal and maternal coenzyme Q10 plasma levels in physiological conditions and also in the presence of some pathologies. METHODS: As regards the maternal side, we selected 483 pregnancies, performing 615 blood samples, and divided them into four groups: A: physiological pregnancies; B: spontaneous abortions; C: threatened abortions; D: threatened late abortions and threatened pre-term deliveries. We then selected 61 pregnancies which differed from the previous ones and determined Q10 levels in fetal samples obtained by cordocentesis. We divided a control group from pathological groups: intra-uterine growth retardation (IUGR); Rh-isoimmunization (with intra-uterine transfusion), non immune fetal hydrops, fetal malformations. Coenzyme Q10 levels were determined in only one laboratory by high-performance liquid chromatography (HPLC). Coenzyme Q10 concentrations were expressed as mg/ml, the data as the mean + SD. Statistical analysis was performed employing a linear regression model and the student "t"-test. RESULTS: After working out a normality curve of CoQ10 levels in maternal blood, we noticed that the levels of Coenzyme Q10 were low in spontaneous abortions, in threatened late abortions and in threatened pre-term deliveries. We determined the value of 0.3 mg/ml as a cutoff to differentiate the fetal from the adult values. Moreover, CoQ10 values turned out to be increased only in fetuses affected by non-immune fetal hydrops. CONCLUSIONS: Accordingly, we can say that maternal CoQ10 plasma levels can be considered as a marker of pathological uterine contractile activity. There is a substantial increase in CoQ10 fetal plasma levels in fetuses affected by hypoxic hypoxia and also in those affected by non-immune fetal hydrops.

Abortion, Spontaneous↗