Intestinal obstruction in babies exposed in utero to methylene blue.
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Biomedical subjects
Publications and source records attributed to U Nicolini.
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Fetal acid-base status was evaluated on 66 blood samples taken for rapid karyotyping from 58 growth-retarded fetuses. Before blood sampling, doppler blood flow studies of the umbilical artery showed end-diastolic frequencies to be absent in 32 fetuses (group 1) and present in 26 (group 2). Fetuses with chromosomal (n = 4) or structural (n = 8) abnormalities were excluded from subsequent analysis. Gestational age at blood sampling (27.8 [95% CI 26.5-29.1] vs 32.2 [30.4-34.1] weeks) and time from sampling to delivery (median 2 (range 0-35] vs 14 [0-77] days) were significantly lower in group 1 than group 2. There were no perinatal deaths in group 2 whereas mortality in group 1 was 65.4%. There were significant differences between the groups at blood sampling in pH, pO2, pCO2, base equivalents, and nucleated-red-cell count, but within group 1 these measurements were similar in surviving fetuses and those who died perinatally. Since acid-base determination does not predict perinatal outcome in growth-retarded fetuses, fetal blood sampling has a limited role in monitoring fetal wellbeing.
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Twelve second-trimester fetuses with cystic hygroma underwent fetal blood sampling for rapid karyotyping, haematologic evaluation, and blood gas analysis. An abnormal karyotype was found in seven cases: monosomy X in five, trisomy 21 in one, and trisomy 13 in the other. Eight of ten fetuses undergoing blood gas analysis showed hypoxaemia, five of which were growth-retarded. Nine pregnancies were terminated. Of the remaining three, only one fetus survived the perinatal period.
Two patients with severe alloimmune thrombocytopenia were managed by weekly intrauterine platelet transfusions at 25 to 36 weeks. In one patient high-dose immunoglobulin was also administered weekly to the mother, and high maternal and fetal immunoglobulin levels were achieved. Fetal platelet counts were similar in both patients. The only variable that affected fetal platelet concentration was the posttransfusion platelet count from the previous transfusion.
Fetal intravenous glucose challenge test (0.75 g/kg of estimated fetal weight) was performed at 26-33 weeks gestation in 9 patients undergoing fetal blood sampling (FBS) by ultrasound guided needling from the umbilical vein. The indication for FBS was rapid karyotyping for fetal malformations in 5 (control group) and severe intrauterine growth retardation in the remaining 4 (IUGR group). Fetal blood samples were taken before the glucose infusion and after 1, 3, 5, 10 and 15 min; glucose and insulin were assayed on each occasion and acid-base balance at 0 and 5 min. Basal fetal pO2, pH, glucose and insulin were lower in the IUGR group than in controls. Following the glucose challenge, fetal glucose levels were similar in the two groups, but in the IUGR group the latter part of the glucose curve was characterized by a slower and delayed return to basal levels. In control fetuses the insulin response following the glucose challenge peaked at 3 min while in IUGR no change in insulin concentration was detected. Fetal pO2 did not change in either group; the median change in fetal pH was significantly different between the two groups (controls: +0.01; IUGR: -0.04; P less than 0.05) and there was a significant correlation between basal pO2 and the change in fetal pH (r = 0.79) (P less than 0.02). These results support the concept of a low energy state in IUGR. Fetal glucose supplementation in IUGR is unlikely to be of benefit and may even exacerbate underlying acidosis.
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Thirteen fetuses (five twin, one triplet) were compromised by fetofetal transfusion syndrome in six pregnancies, five in the mid trimester, and one in the third trimester. This diagnosis, which was suspected because of ultrasound findings of discordant growth, discordant amniotic fluid volumes, concordant external genitalia, and monochorial placentation, was confirmed postnatally in each. Nine fetuses underwent blood sampling to aid diagnosis and assessment of fetal wellbeing. In contrast to fetofetal transfusion syndrome investigated postnatally, a difference in haemoglobin concentration of 50 g/l or more in utero was found in only one pregnancy, which was near term, although all had fetal erythroblastaemia and a difference in weight of 20% or more. In vivo confirmation of shared circulation was achieved in two pregnancies by transfusing adult Rh negative red cells into the smaller fetus and then detecting them by Kleihauer testing in blood aspirated from the larger. Invasive procedures also yielded information on fetal blood gas measurements (acidaemia in four and hypoxaemia in six) and amniotic pressure (raised in two). We suggest that comparison of haemoglobin concentrations is inaccurate in fetofetal transfusion syndrome in utero, the diagnosis of which may necessitate detection of a shared circulation using a marker such as adult red cells.
Prenatal diagnosis of junctional epidermolysis bullosa associated with pyloric atresia was carried out in a couple at risk. Their two previous children had died during the first months of life of the same disorder despite surgery for the pyloric abnormality. Ultrastructural study of fetal skin biopsies obtained at 18 weeks' gestation showed dermal-epidermal separation at the lamina lucida level, while ultrasound showed marked stomach dilatation. Light microscopy of pyloric tissue obtained after termination showed the pyloric lumen to be replaced by loose connective tissue with no inflammatory reaction. Immunofluorescence studies on the skin specimens with the monoclonal antibody GB3, known to be absent in 'lethal' junctional epidermolysis bullosa skin, disclosed a marked positivity suggesting that the junctional epidermolysis bullosa in this case may be of the 'non-lethal' type.
Fetal plasma renin activity (PRA) was measured in 42 pregnancies. Compared to control fetuses, PRA was elevated in three of four hypoxemic fetuses, in two of five with hydrops and in two of five with uropathies. PRA did not change with transfusion in seven alloimmunized fetuses. This study demonstrates PRA in human fetuses and suggests that the renin-angiotensin system can respond to stimuli in fetal life.
A case of hydrops fetalis caused by massive fetomaternal hemorrhage was initially successfully treated by intrauterine intravascular transfusion. Unexplained intrauterine death occurred 2 weeks afterwards. The investigation of fetomaternal hemorrhage by fetal blood sampling and the management are discussed.
Transabdominal fetal blood sampling under ultrasonic guidance was performed at the intrahepatic vein on 214 occasions in 177 fetuses. In 72 cases, an intravascular transfusion was also attempted at the same site. In 91.1% of the samplings, more than 1 mL of pure fetal blood was obtained, and in 89.9% of transfusions, fetal hematocrit or platelet concentration was raised to a satisfactory level. Fetal bradycardia and intraperitoneal bleeding occurred in 2.3% of the cases. Among fetuses at low risk, there was only one intrauterine death, which occurred 3 weeks after the procedure, and one spontaneous abortion in a patient with twin pregnancy. In fetuses with Rh/Kell alloimmunization or perinatal alloimmune thrombocytopenia, the survival rate was 86%. Four liver enzymes were assayed in the blood of 13 fetuses that underwent transfusions at the intrahepatic vein and 13 controls in whom the site of sampling was the umbilical vein at the placental cord insertion. No differences were found between the groups at the subsequent transfusion 2-5 weeks later. The intrahepatic vein is an alternate site of sampling/transfusion when access is difficult or failure occurs at the placental cord insertion. This approach minimizes the risks of fetal blood loss, fetomaternal hemorrhage, arterial vasospasm, and cord tamponade.
Amniotic pressure was measured in 49 pregnancies with abnormal quantities of amniotic fluid. Among 17 with polyhydramnios, the pressure was always above the normal mean for gestation and exceeded the upper limit of normal in nine. In polyhydramnios, amniotic pressure correlated positively with the depth of the deepest pool (r = 0.65, P = .04) and negatively with fetal PO2 (r = -0.57, P = .03) and pH (r = -0.56, P = .04). Amniotic pressure was raised in all those with a deepest pool of greater than 15 cm, and was normal in all with a deepest pool less than 15 cm. Amniotic pressure fell significantly with drainage of amniotic fluid in those with raised pressure (mean 12.7 mmHg, 95% confidence interval 7.0-18.3; P = .002) but not in those with normal pressure (mean 0.3, 95% confidence interval -3.2 to +3.9; P = .82). Restoration of normal amniotic pressure in one pregnancy was accompanied by marked improvement in fetal acid-base status. Among 24 pregnancies with severe oligohydramnios, amniotic pressure was always below the normal mean, falling below the lower limit of normal in eight; whereas in another eight pregnancies with mild/moderate oligohydramnios, amniotic pressure was scattered evenly within the normal range. Amnioinfusion of 55-500 mL of normal saline in cases of severe oligohydramnios led to a significant rise in pressure (4.7 mmHg, 95% confidence interval 3.5-5.9; P less than .0001). We conclude that amniotic pressure is high in polyhydramnios and low in oligohydramnios. Pressure monitoring may be beneficial during amnioinfusion and therapeutic amniocentesis.
Fetal intraperitoneal infusion of saline was performed in two patients with severe oligohydramnios at 24 and 25 weeks' gestation in order to enhance visualization of intra-abdominal organs. Renal agenesis was easily diagnosed. The technique can be considered as an alternative to artificial instillation of amniotic fluid in the differential diagnosis of conditions associated with severe oligohydramnios.
A technique is described for measuring pressure within the amniotic cavity and within fetal vessels and/or body compartments. Two saline-filled catheters were connected at one end to needles inserted during indicated invasive procedures and at the other to silicon strain gauge transducers. In 36 pregnancies with normal liquor volume, stable intra-amniotic pressure (IAP, range 1-14 mmHg) increased with gestation (r = 0.48, p less than 0.01). In pregnancies complicated by severe oligohydramnios, IAP was less than or equal to 1 mm Hg and rose to normal levels with saline amnioinfusion. Raised IAP (range 17-26 mm Hg), found in pregnancies with gross polyhydramnios, fell with drainage of amniotic fluid. Subtraction manometry was used to determine supra-amniotic pressure within the intervillus space, umbilical vein, umbilical artery, abdominal and thoracic cavities, and the urinary tract in normal and/or pathological fetuses. Low intravesical and intrapelvicalyceal pressures (median 6.5, range 2-10 mm Hg) were noted in fetuses with obstructive uropathies. Intrauterine subtraction manometry appears to be a useful tool in the understanding of fetal pathophysiology and may be of clinical benefit in the therapeutic drainage and infusion of amniotic fluid and in the assessment of certain fetal disease states.
Intraperitoneal and umbilical vein pressure readings were obtained during intrauterine transfusion in patients with Rh alloimmunization. In 15 nonacidotic fetuses, mean umbilical vein pressure before transfusion (4.5 mm Hg, SD = 2.3) increased by 4.6 mm Hg (delta umbilical vein pressure confidence intervals +2.8 to +6.4; p less than 0.0001) with transfusion. delta Umbilical vein pressure correlated positively with the increase in hematocrit level (r = 0.55; p less than 0.05) and negatively with gestational age (r = -0.58; p less than 0.05). Basal umbilical vein pressure was raised in the only acidotic fetus, whereas delta umbilical vein pressure was 0. Intraperitoneal pressure was recorded in 11 fetuses before and after transfusion, five of which were associated with fetal heart rate changes or preexisting ascites. Basal intraperitoneal pressure (2.5 mm Hg, confidence intervals 1.4 to 3.6) was significantly lower than basal umbilical vein pressure (confidence intervals, 3.2 to 5.8; p less than 0.02). In uncomplicated intraperitoneal transfusions, intraperitoneal pressure rose significantly (delta intraperitoneal pressure = +5.8; confidence intervals 2.9 to 8.8; p less than 0.005). In four transfusions associated with fetal bradycardia or tachycardia, delta intraperitoneal pressure (range, 16 to 26) was greater than in uncomplicated transfusions (range, 1 to 9). delta Intraperitoneal pressure was 0 in the fetus with ascites. These results implicate increases in umbilical vein pressure and intraperitoneal pressure in immediate complications of intrauterine transfusion, and support a role for intraperitoneal pressure monitoring during intraperitoneal transfusion.
Insulin was measured in the blood collected in utero from three midtrimester anencephalic fetuses. The hyperinsulinism found could be due to an underutilization of glucose in the absence of most of the brain and could be responsible for the relatively normal growth in anencephaly despite the absence of the hypothalamohypophysial axis.