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Biomedical subjects

U Nicolini

Publications and source records attributed to U Nicolini.

At least 19 recordsLinked to original sources

Cystic lesions of the fetal kidney: diagnosis and prediction of postnatal function by fetal urine biochemistry.

Fetal urine was aspirated under ultrasound control from 21 large cystic renal masses in 18 pregnancies of 20 to 35 weeks gestation. None were associated with bladder or ureteric dilatation. At postnatal investigation, 12 kidneys were demonstrated to be hydronephrotic (5 with no or poor function) and 9 multicystic. Urinary concentrations of sodium (Na+), calcium (Ca++), and phosphate (PO4--) were significantly higher in the multicystic group than in the hydronephrotic, whereas urea and creatinine levels were lower. Determination of urinary PO4-- enabled differential diagnosis with no false-positive or false-negative cases. Among hydronephrotic kidneys, no biochemical parameter accurately predicted postnatal function, although creatinine was increased in all three nonfunctioning kidneys. In hydronephrotic kidneys, urinary Na+ concentration increased with advancing gestational age (r = .66; P < .02), suggesting that the duration of hydronephrosis has a negative effect on renal function.

Calcium

Mononuclear phagocyte assays, autoanalyzer quantitation and IgG subclasses of maternal anti-RhD in the prediction of the severity of haemolytic disease in the fetus before 32 weeks gestation.

In 40 cases of haemolytic disease of the fetus due to RhD immunization where the fetus required intrauterine transfusion, fetal packed cell volume was compared with the following parameters of maternal anti-D: (a) concentration, (b) IgG subclass, (c) activity in a macrophage binding assay, and (d) activity in a monocyte antibody-dependent cell mediated cytotoxicity (ADCC) assay. The anti-D concentration exceeded 4 iu/ml in all cases, correctly indicating the risk of haemolytic disease. A relationship between IgG subclass composition of the anti-D and severity of anaemia was not observed; IgG1, IgG3 and IgG1 + 3 antibodies were all detected. The ADCC assay gave the best correlation between assay results and fetal packed cell volume; high results correctly indicated fetal anaemia in 95% of cases. Macrophage binding assay results were only considered as high in 70% of cases. Overall, these results indicate that serological tests and bioassays in highly immunized mothers may not generate any information that proves more useful than ultrasonography and their previous obstetric history.

Antibody-Dependent Cell Cytotoxicity

Fetal breathing movements in oligohydramnios are not increased by aminoinfusion.

OBJECTIVE: To determine whether fetal breathing movements (FBM) in pregnancies with oligohydramnios change with restoration of amniotic fluid volume. DESIGN: A prospective experimental study. SETTING: Fetal Medicine Unit, tertiary referral hospital. SUBJECTS: 16 women with singleton pregnancies complicated by severe oligohydramnios. INTERVENTIONS: Restoration of amniotic fluid volume by transabdominal amnioinfusion. Controls comprised pregnancies in which infused fluid leaked vaginally, so that oligohydramnios was not corrected. MAIN OUTCOME MEASURES: Change in total breathing movements, change in FBM incidence derived from 40 min recordings immediately before and after amnioinfusion. RESULTS: There was no significant difference in the change in total breathing movements or in the change in incidence of FBM between the 10 pregnancies in which amniotic fluid volume was restored, and the other six in which fluid leaked after infusion and volume was not restored. In both groups, there was no significant change with infusion in number of FBM (mean change -72, 95% CI -218 to +74 in the fluid-retained group and -64, 95% CI -273 to +145 in the fluid-leaked group) and incidence of FBM (median change -2.5%, range -27 to +10 in the fluid retained group and -4.5%, range -34 to +15 in the fluid-leaked group). CONCLUSIONS: This study suggests that restitution of amniotic fluid volume in human pregnancies complicated by severe oligohydramnios does not acutely alter the incidence of FBM. These data support an increasing literature suggesting that impairment of fetal breathing is not the mechanism for oligohydramnios-related pulmonary hypoplasia.

Amnion

Midpregnancy plasma zinc in normal and growth retarded fetuses--a preliminary study.

OBJECTIVE: To determine plasma zinc concentrations in normally and abnormally growing fetuses. DESIGN: Prospective observational study. SETTING: Fetal Medicine Unit, Queen Charlotte's Maternity Hospital. SUBJECTS: 53 pregnant women attending for fetal blood sampling at between 18 and 40 weeks gestation. 27 fetuses were normal (central group), 11 fetuses were growth retarded and 15 were malformed. MAIN OUTCOME MEASURES: Plasma zinc concentrations in maternal and fetal blood at time of fetal blood sampling. RESULTS: In normally growing fetuses, between 18 and 40 weeks gestation, there was no fall in maternal plasma zinc concentration; the fetal level fell by 36%. In 10 fetuses with symmetrical growth retardation, plasma zinc concentration tended to be low, but was not significantly different from that in the normal control fetuses. CONCLUSION: The results suggest that (i) placental transfer of zinc is an uphill secretory process and that it is a rate-limiting step in the accumulation of zinc by the fetus and (ii) in fetuses with symmetrical intrauterine growth retardation, a low plasma zinc is probably a parallel phenomenon and not necessarily an aetiological factor.

Female

Normal amniotic pressure throughout gestation.

OBJECTIVE: To characterize amniotic pressure (AP) in pregnancies with normal amniotic fluid volume. DESIGN: Observational study, mainly cross-sectional. SETTING: Fetal medicine unit within a tertiary referral hospital. SUBJECTS: Patients undergoing transamniotic invasive procedures in whom amniotic fluid volume was subjectively assessed as normal on ultrasound. Those beyond 16 weeks with a deepest vertical pool on ultrasound less than 3.0 or greater than 8.0 cm were excluded. Overall 194 pregnancies were studied on 232 occasions between 7 and 38 weeks gestation. INTERVENTIONS: Manometry readings referenced to the top of the maternal abdomen were obtained via a fluid-filled line from the needle hub and either connected to a pressure transducer (n = 190) or held vertically against a ruler (n = 42). MAIN OUTCOME MEASURES: AP in mm Hg, AP corrected for gestational age (z scores), semi-quantitative ultrasonic indices of amniotic fluid volume, clinical variables. RESULTS: AP in singleton pregnancies increased with advancing gestation (P less than 0.001), and the sigmoid-shaped regression curve plateaued in the mid-trimester. AP z scores were not influenced by volume-related phenomena such as twin gestation, the deepest vertical pool, or amniotic fluid index, nor by maternal age, parity, gravidity, fetal sex, or subsequent spontaneous preterm delivery. CONCLUSIONS: These findings suggest that AP is not principally determined by intrauterine volume. We speculate that AP, which reflects change in uterine tension as a function of radius, may instead be determined by gestation-specific anatomical and hormonal influences on gravid uterine musculature. A reference range for AP has been constructed for use in amnioinfusion and amnioreduction procedures.

Amniotic Fluid

Transvaginal sonography for fetal measurement in early pregnancy.

OBJECTIVE: To establish reference ranges for fetal size by gestation in the first trimester as indicated by cephalic, abdominal and limb measurements using transvaginal sonography. DESIGN: A prospective descriptive study. SETTING: Two antenatal clinics in Milan, Italy. SUBJECTS: 270 women with normal singleton pregnancies at 42-108 days gestation. All had regular cycles and certain dates. INTERVENTIONS: Vaginal ultrasound examination including inspection of fetal structures and lasting 5-15 min. MAIN OUTCOME MEASURES: As many of the following fetal measurements as possible according to gestational age and ease: crown-rump length (CRL), biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur and foot lengths. RESULTS: CRL was measured in 183 fetuses, BPD in 201, HC in 162, AC in 160, femur length in 133 and foot length in 62. The best description of the relation of CRL to gestational age was achieved by a quadratic function (y = -3.98 - 0.308x + 0.0117x2). Mean values thus derived were virtually identical to those obtained by Robinson & Fleming in 1975 with transabdominal static scanning. Fetal BPD, HC, AC and femur length correlated more closely with CRL than gestational age. Reference ranges (mean and 95% data intervals) were constructed for each biometrical measurement in relation to gestational age and CRL. The HC/AC and femur/foot length ratios did not show any significant variation with gestational age or CRL. CONCLUSIONS: These data may be useful in the early detection of genetic disorders affecting the growth of fetal head, trunk and limbs. Genetic and/or environmental variables play an appreciable role in the modulation of early fetal growth.

Abdomen

Fetal urine biochemistry: an index of renal maturation and dysfunction.

OBJECTIVE: To construct a reference range for fetal urinary sodium, potassium, urea, creatinine, calcium and phosphate with gestation and to assess to what extent these biochemical indices are modified in fetuses with lower urinary tract obstruction. DESIGN: Prospective descriptive study. SETTING: Royal Postgraduate Medical School London. SUBJECTS: 24 women between 17 and 35 weeks gestation with an ultrasound diagnosis of fetal lower urinary tract obstruction, with or without renal dysplasia and a control group of 26 women between 16 and 33 weeks gestation with normal amniotic fluid volume and fetal anatomy. INTERVENTIONS: Fetal urine samples (1-100 ml) were aspirated from the control fetuses either before termination of pregnancy (n = 9) or at the time of intrauterine transfusion for Rh alloimmunization (n = 17). The fetuses with obstructive uropathy had urine samples aspirated on one occasion (n = 14) or serially (n = 10). MAIN OUTCOME MEASURES: Relation between urine biochemistry and renal damage ascertained clinically or at postmortem. RESULTS: In the control group, urinary sodium and phosphate decreased and creatinine increased significantly with gestational age, consistent with increasing fetal glomerular filtration rate and progressive maturation of tubular function. Urinary sodium and calcium were significantly higher in fetuses with renal dysplasia compared with those with lower urinary tract obstruction but normal renal histology or normal clinical outcome. Serial urinary samples from fetuses with obstructive uropathy showed more pronounced deviation from the normal with increasing gestation in all fetuses with renal dysplasia. The highest sensitivity in the detection of renal dysplasia was shown by urinary calcium (100%) whereas urinary sodium showed the best specificity (80%). CONCLUSION: Renal damage is the direct effect of urinary obstruction, rather than an association so that treatment should start as soon as possible. Urinary biochemistry may be helpful in the management of these patients.

Electrolytes

Relief of presumed compression in oligohydramnios: amnioinfusion does not affect umbilical artery Doppler waveforms.

The suggestion that amnioinfusion improves umbilical artery Doppler indices of downstream resistance in oligohydramnios by relieving cord compression was investigated by obtaining waveforms before and immediately after amnioinfusion in 16 pregnancies with severe oligohydramnios. There was no significant difference in the change in umbilical artery pulsatility index (PI) between 11 pregnancies in which amniotic fluid volume was restored (mean delta PI = -0.07, 95% confidence interval -0.17 to +0.07), and 5 pregnancies in which immediate vaginal leakage of infused fluid prevented restitution of amniotic fluid volume. Fetal heart rate did not change significantly in either group. End-diastolic frequencies did not return with restitution of amniotic fluid volume in the 2 pregnancies in which they were absent before infusion (absent in 1, reverse in 1). This study suggests that restitution of amniotic fluid volume in human pregnancies complicated by severe oligohydramnios does not acutely alter the umbilical artery PI.

Amnion

Prenatal pericardiocentesis: its role in the management of intrapericardial teratoma.

A fetus with intrapericardial teratoma had a large pericardial effusion diagnosed by echocardiography. Cardiac tamponade, a common cause of fetal death, was averted by intrauterine pericardiocentesis. Planned obstetric and neonatal management permitted surgical treatment before cardiorespiratory distress developed. The tumor was completely excised and the infant is asymptomatic.

Adult

Further predictors of renal dysplasia in fetal obstructive uropathy: bladder pressure and biochemistry of 'fresh' urine.

Urine was aspirated on two consecutive days from the dilated bladder of nine fetuses with lower urinary tract obstruction. Gestational age ranged from 17 to 35 weeks. Renal dysplasia was diagnosed histologically in four fetuses, whereas the other five had normal renal histology or only partial dysplasia. Urinary sodium (Na+) and osmolality (Osm) decreased significantly in the second urine sample 1 day after bladder emptying (median decrease: Na+ = -11.3 per cent; Osm = -13.3 per cent). Although there were no significant differences between fetuses with or without renal dysplasia, normalization of an initially raised urine Na+ concentration occurred at the second sample in a fetus with partially normal renal histology, thus correcting a false-positive diagnosis of dysplasia. Bladder pressure was measured at the time of the first urine sampling in seven fetuses and in a further eight with bladder outlet obstruction undergoing a single urine aspiration at 18-28 weeks. Bladder pressure was increased above the reference range in 8 of 15 fetuses with urinary obstruction, but there was no correlation between pressure and the degree of impairment of renal function. Although no conclusive clinical guidelines can be drawn from this study for the evaluation of fetal renal function, these findings suggest that, in lower urinary tract obstruction, tubular reabsorption is impeded by the standing pressure in the urinary tract and that improvement of renal function may occur following relief of obstruction.

Electrolytes

Edwards' syndrome after the replacement of cryopreserved-thawed embryos.

A case of Edwards' syndrome after the replacement of frozen-thawed embryos is reported. The presence of cardiac abnormalities and limb deformities raised the suspicion of chromosomal abnormality. The diagnosis of trisomy 18 was made by cytogenetic analysis of fetal blood from the umbilical vein. The chromosomal nondisjunction might have been spontaneous or because of freezing and thawing. If it occurred as a result of freezing and thawing, it is more likely that this was at the first cleavage division rather than the second meiotic division because the embryos were frozen at the late pronuclear stage. Unfortunately, there were no karyotypic markers in the couple's chromosomes to time the nondisjunction. The wisdom of using donor oocytes in an ovum donation program from patients with long-standing infertility is questioned.

Abnormalities, Multiple

Changes in concentrations of cortisol, dehydroepiandrosterone sulphate and progesterone in fetal and maternal serum during pregnancy.

OBJECTIVE: In fetuses, adrenal steroids have been implicated in organ maturation and in some species in initiation of labour. The fetal adrenal gland differs from the adult in its complement of steroid metabolizing enzymes. This study sought to examine the changes in peripheral cortisol, progesterone and dehydroepiandrosterone sulphate (DHEAS) in unstressed fetuses during pregnancy. DESIGN: Paired maternal and fetal samples were collected from 47 patients. Fetal blood samples were collected by transabdominal needling. All fetuses were appropriately grown for age which ranged from 18 to 41 weeks. MEASUREMENTS: Hormones were measured using specific, validated immunoassays. RESULTS: Fetal progesterone (mean, 822 nmol/l; 95% data intervals 196-1449 nmol/l) varied considerably between individuals but there was no significant change in serum concentration with gestational age, nor was there any difference between male and female fetuses. There was a small, but significant (y = 0.339x2 - 13.5x + 231; r = 0.72, P = 0.0001) rise in cortisol in the fetal circulation from 32 to 41 weeks gestational age, whereas the mean fetal DHEAS concentration decreased linearly with gestational age from 4.1 mumol/l at 18 weeks to 2.6 mumol/l at 41 weeks (r = -0.41; P = 0.007). Mean progesterone concentration in the maternal serum increased linearly from 98 nmol/l at 18 weeks to 783 nmol/l at 41 weeks. In the fetus there was a significant correlation between progesterone and cortisol concentrations. CONCLUSIONS: These results are compatible with the proposed role of cortisol in fetal lung maturation, confirm high levels of progesterone in the fetus from an early stage of gestation, and provide further evidence for placental progesterone being the precursor of fetal cortisol.

Adrenal Cortex Hormones

Fetal liver dysfunction in Rh alloimmunization.

The liver enzymes, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP), were measured in the blood of 25 fetuses with severe Rh alloimmunization at the time of their first, second and third intravascular transfusions and in 17 comparison fetuses. In the comparison group, GGT increased with advancing gestation (r = 0.7; P = 0.002), whereas ALP, AST and ALT did not correlate with gestational age. Rh hydropic fetuses (n = 8) had higher blood ALT levels than the comparison fetuses (P = 0.008) had significantly increased transaminases when compared with non hydropic fetuses (n = 17). In hydropic fetuses, AST correlated with the nucleated red cell count before transfusion (r = 0.94; P = less than 0.0001). Fetal transaminases were no longer increased in hydropic fetuses by the second (AST) or third (ALT) transfusion. In both hydropic and non hydropic fetuses, GGT increased by the second transfusion (median percentage change +85%, range -83% to +596%; P = 0.003). The rise in fetal GGT was transitory and correlated with the increase in fetal haematocrit at the first transfusion (r = 0.58; P = 0.006). This study reports liver dysfunction secondary to extramedullary erythropoiesis in Rh alloimmunization and implicates portal hypertension for the rise in fetal GGT with transfusion.

Alanine Transaminase

Direct antenatal fetal electrocardiographic waveform analysis.

OBJECTIVE: To establish a technique for continuous recording of fetal electrocardiograms (ECG) for waveform analysis in the antenatal period. DESIGN: Prospective descriptive study. SETTING: Fetal Medicine Unit, Queen Charlotte's and Chelsea Hospital, London, UK. SUBJECTS: 35 women undergoing antenatal fetal blood sampling. INTERVENTIONS: One end of an insulated Cooner wire was attached to the sampling needle and the other to an automatic ECG-ST waveform analyser. MAIN OUTCOME MEASURES: ECG signals were obtained with the needle in the fetal abdomen during intrahepatic umbilical vein sampling or aspiration of fetal urine but not when it was in the placental cord insertion. RESULTS: Continuous recording of the T/QRS ratio was obtained for a total of 166 min (mean 8 min per fetus) from 20 fetuses (16-38 weeks). The T/QRS ratio had no correlation with gestational age and fetal heart rate and was similar to values described in term fetuses in labour. CONCLUSIONS: The technique described can identify ST waveform changes and may be useful in the investigation of fetal cardiac arrhythmias, intrauterine growth retardation and in monitoring fetal transfusions.

Electrocardiography

Fetal blood sampling from the intrahepatic vein for rapid karyotyping in the second and third trimesters.

One hundred and twelve fetuses with structural anomalies (n = 84), intrauterine growth retardation (n = 21) or amniotic fluid volume disorders (n = 7) detected by ultrasound underwent blood sampling from the intrahepatic vein for rapid karyotyping. The procedure was successful in 95.5%. 12.5% of the fetuses had an abnormal karyotype. Fetal bradycardia was observed in two fetuses (1.8%) and intraperitoneal bleeding in three (2.7%). There were three procedure-related losses but these were not due to the intrahepatic vein sampling itself. Fetal blood sampling is the method of choice for rapid karyotyping in the second and third trimesters, and the intrahepatic vein is an alternate site when access is difficult or failure to sample occurs at the placental cord insertion. Additional advantages of fetal blood sampling at the intrahepatic vein include absence of cord complications, reduced risk of fetal blood loss and fetomaternal haemorrhage, and the lack of need to confirm the fetal origin of the sample.

Blood Specimen Collection

Acute twin-twin transfusion: a possible mechanism for brain-damaged survivors after intrauterine death of a monochorionic twin.

Intrauterine death of one twin in monochorionic pregnancies is associated with increased mortality and morbidity for the survivor. This has been attributed to the consequences of intrauterine disseminated intravascular coagulation (DIC) initiated by the dead twin. We describe a case in which the fetal cerebral and renal lesions typically found in survivors occurred without any derangement in coagulation. Instead, acute twin-twin transfusion was suggested by the presence of severe anemia in the surviving fetus at delivery. We suggest that the lesions frequently found in the survivors are often due to acute hemodynamic and ischemic changes resulting from acute twin-twin transfusion at the time of intrauterine death, rather than to late-onset DIC. This hypothesis has an important implication for future management: Intervention must occur before intrauterine death if neurologic sequelae in the survivor are to be prevented.

Brain Diseases