Giorgio Pardi

Insemination of HIV-negative women with processed semen of HIV-positive partners

Many HIV-discordant couples want to have children so much that they are willing to abandon condom-protected sexual intercourse irrespective of the risks. Previous testing in our laboratory showed that gradient centrifugation followed by a swim-up procedure effectively removed HIV-1-infected cells from the semen of HIV-seropositive men. 85 HIV-discordant couples were screened for fertility; 29 women were found suitable for a timed insemination course with the processed semen of their HIV-seropositive partner. None of the inseminated women seroconverted, and 17 pregnancies were achieved in 15 women. All 10 babies born to these mothers remain HIV seronegative. The findings may help in the counselling of such couples and also give them hope of having healthy babies.

Association between the Activity of the System A Amino Acid Transporter in the Microvillous Plasma Membrane of the Human Placenta and Severity of Fetal Compromise in Intrauterine Growth Restriction

Primarily, our objectives were to compare system A amino acid transporter activity in the microvillous plasma membrane (MVM) of placentas from normally grown (appropriate for gestational age, AGA) and intrauterine growth-restricted (IUGR) fetuses delivered during the third trimester, as a whole and in relation to the severity of IUGR. Ten AGA and 16 IUGR pregnancies were studied at the time of elective cesarean section performed between 28 and 40 wk of gestation. Severity of IUGR pregnancies was assessed primarily by Doppler velocimetry and fetal heart rate monitoring. Placental MVM vesicles were prepared, and system A activity in these was measured. The transporter activity was significantly lower in IUGR compared with AGA pregnancies. Within the IUGR group system A activity was only significantly lower, compared with AGA, in cases that presented with a reduction in umbilical blood flow. We conclude that placental MVM system A activity is lower in IUGR compared with AGA pregnancies delivered during the third trimester. System A activity is related to the severity of IUGR.

Umbilical amino acid concentrations in normal and growth-retarded fetuses sampled in utero by cordocentesis

Fetal plasma amino acid concentrations were obtained by cordocentesis at midgestation in 11 normal (appropriate for gestational age) fetuses and at late gestation in 12 small-for-gestational-age fetuses, and at cesarean section in 14 normal term infants. In normal fetuses total molar amino acid concentrations and fetal/maternal total molar concentration ratios did not change significantly between the second and third trimesters. Fetal and maternal concentrations of most amino acids were significantly correlated at both midgestation and late gestation. Small-for-gestational-age fetuses had significantly lower concentrations of total alpha-aminonitrogen; this was mainly because of a reduction of the branched chain amino acids valine, leucine, and isoleucine, and of lysine and serine. Maternal arterial concentrations of phenylalanine, arginine, histidine, and alanine were elevated in small-for-gestational-age pregnancies. Thus there are only minor changes in amino acid concentrations between midgestation and late gestation in normal fetuses with a constant fetal/maternal ratio. In small-for-gestational-age infants a significant reduction in alpha-aminonitrogen and in most essential amino acids was demonstrable in utero weeks before delivery.

The incidence of complications after caesarean section in 156 HIV-positive women

ObjectiveTo investigate the risks of post-operative complications in HIV-positive mothers who undergo a caesarean section (CS) because the delivery cannot be safely accomplished by the vaginal route or to protect the infant from viral infection. DesignIn a multicentre study, we reviewed the incidence, and type of post-operative complications in 156 HIV-positive women who underwent a CS. These results were compared with those observed in an equal number of HIV-uninfected women who matched for the indication requiring a caesarean delivery, the stage of labour, the integrity or rupture of membranes, and the use of antibiotic prophylaxis. SettingSeven teaching hospitals providing obstetrical care for mothers infected with HIV. ResultsWe found that six HIV-infected mothers suffered a major complication (two cases of pneumonia, one pleural effusion, two severe anaemia, and one sepsis) compared with only one HIV-negative woman who required blood transfusion after surgery. Minor complications like post-operative fever, endometritis, wound, and urinary tract infections were significantly more frequent in HIV-positive women than controls. Multivariate analysis revealed that in HIV-infected women the only factor associated with a significant increase in the rate of complications was a CD4 lymphocyte count <200±106/l. ConclusionsThe results of our study indicate that HIV-positive mothers are at an increased risk of post-operative complications when delivered by CS. The risk of post-operative complications is higher in HIV-infected women who are severely immunodepressed.

Fetal Plasma Leptin Concentrations: Relationship with Different Intrauterine Growth Patterns from 19 Weeks to Term

The relationship between in utero fetal growth and fetal leptin concentrations was investigated between 19 and 41 wk in 40 normal (appropriate for gestational age, AGA) fetuses, in 25 intrauterine growth-restricted (IUGR) fetuses, and in 18 fetuses from gestational diabetic mothers (GDM), representing different intrauterine growth patterns. Umbilical venous plasma leptin concentrations were determined at the time of either in utero fetal blood sampling or delivery. Plasma leptin was measurable as early as 19 wk of gestation. A significant difference was observed between umbilical venous and arterial plasma leptin concentrations (0.6 ± 0.6 ng/mL;p < 0.01). In AGA and in IUGR fetuses, significant positive relationships were found between fetal leptin concentrations and both gestational age (p < 0.001) and fetal weight (p < 0.001). Leptin concentrations were significantly higher in AGA than IUGR only after 34 wk (p < 0.05), but leptin per kilogram fetal weight (leptin/kg) was not significantly different. In IUGR with abnormal umbilical arterial Doppler velocimetry and fetal heart rate, leptin/kg significantly higher than in IUGR with normal biophysical and biochemical parameters was found (p < 0.05). Both circulating plasma leptin and leptin/kg were significantly higher in GDM than in normal fetuses (p < 0.001) and correlated with abdominal fat mass measured by ultrasound. No gender differences were observed in any group of fetuses. These findings indicate a clear relationship between fetal leptin concentrations and fetal fat mass. Data in severe IUGR suggest the presence of increased leptin concentrations associated with in utero signs of fetal distress.

Maternal concentrations and fetal-maternal concentration differences of plasma amino acids in normal and intrauterine growth-restricted pregnancies.

OBJECTIVES Our purpose was to determine whether maternal amino acid concentration changes during gestation in pregnancies with intrauterine growth restriction as in normal pregnancies and to verify whether these changes are related to changes in fetal-maternal differences. STUDY DESIGN Amino acid concentrations were measured in 5 nonpregnant women, in 11 second-trimester and 10 third-trimester pregnant women with appropriate-for-gestational-age fetuses, and in 23 pregnant women with intrauterine growth restriction. Umbilical venous amino acids were measured at the time of fetal blood sampling. The severity of intrauterine growth restriction was assessed by Doppler velocimetry and fetal heart rate and by evaluation of oxygenation and acid-base balance. RESULTS In normal pregnant women the maternal concentration of most amino acids was significantly lower in both the second and third trimesters compared with nonpregnant women. In intrauterine growth restriction the maternal concentrations of most essential amino acids were significantly higher than in appropriate-for-gestational-age pregnancies. This observation, coupled with lower fetal amino acid concentrations in intrauterine growth restriction, leads to significantly lower fetal-maternal differences. CONCLUSIONS Normal pregnant women have a significant decrease in amino acid concentrations compared with nonpregnant women, whereas in intrauterine growth restriction maternal amino acids are reduced less, Significantly lower fetal-maternal concentration differences are present in intrauterine growth restriction, independent of the degree of severity.

Intrauterine growth restriction is associated with changes in polyunsaturated fatty acid fetal-maternal relationships.

Fetuses with intrauterine growth restriction (IUGR) are at increased risk of death and disease during neonatal, pediatric, and adult life. Postnatal deficits in essential fatty acids have been associated with the neural and vascular complications of premature neonates. We studied whether fetal-maternal fatty acid relationships are already impaired in utero in IUGR fetuses. Fetal (F) and maternal (M) fatty acid profiles were determined in utero in 11 normal [appropriate for gestational age (AGA)] and in 10 IUGR fetuses by fetal blood sampling (FBS) between 19 and 39 wk. Total plasma fatty acid concentrations were significantly higher in M than in F of both AGA (M: 2.03 ± 0.53 mg/mL; F: 0.64 ± 0.29 mg/mL;p < 0.001) and IUGR (M: 2.16 ± 0.59 mg/mL; F: 0.73 ± 0.17 mg/mL;p < 0.001). The F/M ratio was significantly higher for linoleic acid (AGA: 0.36 ± 0.09; IUGR: 0.52 ± 0.12;p < 0.01) and significantly lower for the long-chain polyunsaturated fatty acid docosahexaenoic acid (AGA: 1.94 ± 0.32; IUGR: 1.25 ± 0.19;p < 0.05) and arachidonic acid (AGA: 2.35 ± 0.35%; IUGR: 2.04 ± 0.3%;p < 0.05) in IUGR compared with AGA pregnancies. The differences observed in the relative amounts but not in total plasma concentrations of fatty acid fetal-maternal relationships in pregnancies associated with IUGR could be related to inadequate transplacental supply as well as to a fetal lack of the enzymes necessary for elaboration of these metabolically relevant conditionally essential fatty acids. These differences might have a role in determining the biochemical environment leading to the neural and vascular complications associated with IUGR.

Absence of Hepatitis C Virus and Detection of Hepatitis G Virus/GB Virus C RNA Sequences in the Semen of Infected Men

The identification of hepatitis C virus (HCV) in semen remains controversial and that of hepatitis G virus (HGV) or GB virus C (GBV-C) has never been investigated. Serum and semen from 90 anti-HCV-positive drug users were tested (27 infected with HIV) for HCV and HGV/GBV-C RNAs by polymerase chain reaction (PCR) assay, hybridization, and sequence analysis. Semen was processed into round cells, seminal plasma, and spermatozoa. Fifty-six patients were HCV-viremic, but HCV-RNA was not identified in their seminal fractions. However, PCR inhibitors were found in the semen of 34 of these men. Twenty-eight patients had HGV/GBV-C RNA in their blood and for 24 of them, ejaculates were available for analysis. HGV/GBV-C RNA was found in the seminal plasma of 6 of 12 samples free from PCR inhibitors. These results agree with the low risk of sexual transfer of HCV and provide preliminary evidence for the presence of HGV/GBV-C in semen.

Steady state maternal-fetal leucine enrichments in normal and intrauterine growth-restricted pregnancies.

The aim of this study was to compare the fetal/maternal (F/M) leucine-enrichment ratio in normal (AGA) and intrauterine growth-restricted (IUGR) pregnancies at the time of fetal blood sampling (FBS). A maternal primed-constant infusion of L-[1-13C]-leucine was given in six AGA and 14 IUGR pregnancies, divided into three groups according to the pulsatility index (PI) of the umbilical artery and to fetal heart rate (FHR): group 1 (normal FHR and PI, four cases); group 2 (normal FHR and abnormal PI, five cases); and group 3 (abnormal FHR and PI, five cases). Maternal arterialized samples were taken at time zero and every 20 min for 125 ± 7 min. Umbilical venous samples were obtained after 114 ± 42 min of infusion. Under steady state conditions, there was a significant linear relationship between maternal leucine disposal rate and maternal leucine concentration. The comparison of fetal to maternal leucine enrichment showed a progressive dilution of the fetal enrichment relative to the mother between AGA and IUGR of group 1 (0.89 versus 0.78, p < 0.02), group 2 (0.71, p < 0.001), and group 3 (0.62, p < 0.001), and also among the three IUGR groups. The F/M leucine molar percent enrichment (MPE) ratio showed a positive correlation with the umbilical venous oxygen content and an inverse correlation with fetal lactate concentration. We conclude that the dilution in the fetal/maternal leucine-enrichment ratio correlates with the severity of growth restriction and reflects decreased transplacental leucine flux and/or increased protein breakdown within the fetoplacental compartments.

Venous drainage of the human uterus: Respiratory gas studiesin normal and fetal growth-retarded pregnancies

OBJECTIVE To determine respiratory gas relationships between the uterine veins and umbilical vein in normal and pregnancies complicated by intrauterine growth retardation. STUDY DESIGN Respiratory gases were measured in both uterine veins and the umbilical vein in eight normal and 13 pregnancies with intrauterine growth retardation. RESULTS No significant differences were found in the placental versus nonplacental uterine veins. There was a significant correlation for umbilical and uterine venous values of PO2 (p less than 0.002) and PCO2 (p less than 0.004) in appropriate-for-gestational-age pregnancies, umbilical venous PO2 was always less than uterine venous PO2, and PCO2 always greater than uterine. The transplacental gradient was significantly higher in intrauterine growth retarded than appropriate-for-gestational-age pregnancies for both POC2 and PCO2. There was a lower uterine oxygen extraction in intrauterine growth retarded pregnancies (p less than 0.05). CONCLUSION There is no consistent relationship between placental venous drainage in each uterine vein and placental location. The human placenta simulates a relatively inefficient venous equilibrator and the larger transplacental gradients in intrauterine growth retarded pregnancies may reflect differences in both perfusion pattern and placental structure.