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[Evaluation of antimicrobial drugs and atmospheres for the isolation of Campylobacter fetus subspp. from the bovine genital tract].

Growth of 3 reference bovine C. fetus strains in media with and without antibiotics and bacteriostats active against the most common contaminant bacteria in the bovine genital tract was evaluated. In addition, 2 regional bovine C. fetus strains and 1 reference C. sputorum biovar bubulus strain were used in some experiments. Reference strain C. fetus subsp. venerealis was completely inhibited by polymyxin (> or = 0.25 IU/ml) whereas the other C. fetus strains were not inhibited. In Shepler's medium supplemented with rifampicin (10 micrograms/ml) subsp. fetus, was the only one to grow. When rifampicin was used at 5 micrograms/ml together with a reduced dose of the other Shepler's antibiotics, especially polymyxin B (0.85 IU/ml), subsp. venerealis was able to grow; nevertheless even at such a reduced dose, rifampicin was inhibitory for the biotype intermedius. It was demonstrated that triclosan (Irgasan) could be very useful at < or = 10 micrograms/ml in media with added blood, < or = 6 micrograms/ml in brucella broth and < or = 3 micrograms/ml in Mueller-Hinton broth for isolation of all subspecies of C. fetus. The sensitivity of C. fetus to 5-fluorouracil was variable: subsp. fetus was resistant (up to 800 micrograms/ml) whereas subspp. venerealis and biotype intermedius grew slowly or sometimes did not grow at all in concentrations of 6.25 micrograms/ml onwards. Fosfomycin was inhibitory to all C. fetus strains at > or = 50 micrograms/ml. C. sputorum biovar. bubulus was less inhibited than C. fetus with triclosan grew up to more than 100 micrograms/ml, with 5-fluorouracil up to 100 micrograms/ml and with fosfomycin up to 50 micrograms/ml. Growth of C. fetus subspp. was compared in different microaerophilic atmospheres contained in anaerobic jars (Oxoid HP 11) without palladium catalyzer. Growth with nitrogen or hydrogen was similar. When jars were replaced by 15 x 13 cm cylindrical cans without valves or gas measurement devices only pure hydrogen supported satisfactory growth of all C. fetus subspp. and C. sputorum biovar. bubulus strains. The candle system, a commercial nitrogen rich gas mixture and pure carbonic anhydride prepared in these cans failed to enable these strains to grow. C. fetus subsp. fetus was more aero-tolerant than subsp. venerealis and its biotype intermedius and was able to grow, although very weakly, with only carbonic anhydride added to an aerobic atmosphere. The growth obtained using a commercial gas generating microaerophilic kit (Oxoid BR-56) was comparable to the one achieved with the hydrogen rich atmosphere prepared in our laboratory.

Agar↗

First-trimester fetuses with increased nuchal translucency do not show altered intracardiac flow velocities.

OBJECTIVE: To study intracardiac flow velocities in first-trimester fetuses with normal nuchal translucency thickness (NT) and those with increased NT. METHODS: Ultrasound examinations were performed in 85 normal fetuses and 45 fetuses with NT > 95(th) percentile. Follow-up was complete and postmortem examination was performed on terminated pregnancies. Flow velocities during the early (e-wave) and late (a-wave) peaks across the tricuspid and mitral valves were measured and compared, using multilevel analysis, between the fetuses with normal and those with increased NT. In the group with increased NT, fetuses with and without a heart defect irrespective of the karyotype were compared, and in this group, euploid and aneuploid fetuses were compared, irrespective of the presence of a heart defect. RESULTS: No difference in intracardiac flow velocities was found between fetuses with normal and those with increased NT. Within the group of fetuses with increased NT, there was no difference between the fetuses with and without a cardiac defect. However, comparison of aneuploid with euploid fetuses within the group with increased NT showed that both the e-wave and a-wave peaks were decreased significantly by 3.03 cm/s and 5.95 cm/s, respectively, across the tricuspid valve, and by 3.47 cm/s and 5.92 cm/s, respectively, across the mitral valve (P < 0.05). The most common cardiac malformations were septal defects. CONCLUSION: There is no difference in intracardiac blood flow velocities between normal fetuses and those with increased NT. This contradicts the theory that NT is caused by impaired atrial contraction or cardiac failure. In fetuses with increased NT, those with aneuploidy show a decreased e-wave and a-wave compared with euploid fetuses. This cannot, however, be explained by the presence of cardiac defects, because there is no difference between fetuses with and without a cardiac defect. Therefore, we hypothesize that the relationship between enlarged NT and cardiac defects can only be explained by a developmental process that coexists at this period of gestation and is linked to cardiovascular development.

Blood Flow Velocity↗

Simultaneous measurements of umbilical venous, fetal hepatic, and ductus venosus blood flow in growth-restricted human fetuses.

OBJECTIVE: The purpose of this study was to evaluate the changes in the distribution of the umbilical venous blood flow to the liver and to the ductus venosus in intrauterine growth-restricted human fetuses in relationship with dilation of the ductal isthmic diameter. STUDY DESIGN: Umbilical venous flow, ductus venosus blood flow, and blood flow to the fetal liver were measured in 56 severely intrauterine growth-restricted fetuses with an abnormal pulsatility index of the umbilical artery and were compared with 137 normal control fetuses. Percentages of umbilical venous blood flow through the ductus venosus and to the fetal hepatic lobes were calculated. Z-scores for control fetuses and intrauterine growth-restricted fetuses were constructed by the evaluation of the inverted smoothed percentiles. The distributions of the Z-scores was compared with a 1-sample t-test. RESULTS: The ductus venosus blood flow that was corrected for fetal weight was increased significantly in intrauterine growth-restricted fetuses compared with control fetuses (P=0); the median values (interquartile range) for comparable ages of gestation was 41.3 mL/min/kg (range, 26.2-64.0 mL/min/kg) and 30.8 mL/min/kg (range, 19.9-42.8 mL/min/kg), respectively. As a consequence, ductus venosus shunting was increased in intrauterine growth-restricted fetuses compared with control fetuses (P =0). In 23 of 30 intrauterine growth-restricted fetuses, the percentage of umbilical blood flow that was shunted through the ductus was>90th percentile of control fetuses. Ductal diameters were significantly greater in growth-restricted fetuses than in control fetuses (P =.0001). The percentage of blood flow to the right lobe showed a significant reduction (P =.0223), with evidence of reversed blood flow from the right lobe and portal system into the ductus venosus that was provided both by volume blood flow calculations and by direct pulsed Doppler waveform direction. CONCLUSION: In severe intrauterine growth-restricted fetuses, Doppler examination of blood flow volume proved a significant increase in the shunting of umbilical vein blood flow through the ductus venosus that was associated with the dilation of the ductal isthmic diameter. These changes provide a relatively constant blood flow to the heart and brain at the expense of fetal hepatic perfusion.

Adult↗

Autoregulation of cerebral blood flow in fetuses with congenital heart disease: the brain sparing effect.

Fetuses with congenital heart disease (CHD) have circulatory abnormalities that may compromise cerebral oxygen delivery. We believe that some CHD fetuses with decreased cerebral oxygen supply have autoregulation of blood flow that enhances cerebral perfusion (brain sparing). We hypothesize that cerebral autoregulation occurs in CHD fetuses, and the degree of autoregulation is dependent on the specific CHD and correlates with intrauterine head circumferences. CHD fetuses were compared to normal fetuses. Data included cardiac diagnosis, cerebral and umbilical artery Doppler, head circumference, weight, and gestational age. The cerebral-to-placental resistance ratio (CPR) was assessed as a measure of cerebral autoregulation. CPR = cerebral/umbilical resistance index (RI) and RI = systolic-diastolic/systolic velocity (normal CPR > 1). CPR > 1 was found in 95% of normal vs 44% of CHD fetuses. The incidence of CPR < 1 was greatest in hypoplastic left or right heart fetuses. Compared to normal, cerebral RI was decreased in CHD fetuses. The CPR vs gestational age relationship, and the relationship among weight, head circumference, and CPR differed across normal and CHD fetuses. Fetuses > 2 kg with CHD and a CPR < 1 had smaller head circumferences than normal. Brain sparing occurs in CHD fetuses. Fetuses with single ventricular physiology are most affected. Inadequate cerebral flow in CHD fetuses, despite autoregulation, may alter brain growth.

Blood Flow Velocity↗

Cardiac and venous blood flow in fetuses of insulin-dependent diabetic mothers: evidence of abnormal hemodynamics in early gestation.

OBJECTIVE: Our purpose was to determine whether in early gestation cardiac and venous blood flow patterns of fetuses of insulin-dependent diabetic mothers differ from those of normal fetuses. STUDY DESIGN: Serial recordings were obtained at 12, 16, and 20 weeks of gestation in 11 normal fetuses, 16 fetuses of insulin-dependent diabetic mothers with first-trimester glycosylated hemoglobin levels < or = 8.5% (group 1), and 11 fetuses of insulin-dependent diabetic mothers with first-trimester glycosylated hemoglobin levels > 8.5% (group 2). Velocity waveforms at the level of atrioventricular valves, inferior vena cava, and umbilical vein were recorded by means of color and pulsed Doppler equipment by either transvaginal or transabdominal approaches. The following variables were measured: ratio between the peak velocities during early passive ventricular filling and active atrial filling at the level of atrioventricular valves, percent reverse flow during atrial contraction in inferior vena cava, and pulsations in umbilical vein. RESULTS: In all the fetuses the ratios between early and active ventricular filling increased linearly with advancing gestation, whereas the percent reverse flow in the inferior vena cava decreased linearly. However, fetuses of diabetic mothers showed significant differences in the slope of the functions describing the development with gestation of these index values, resulting in lower values of the ratios between early and active ventricular filling at the level of both ventricular valves and higher values of percent reverse flow in inferior vena cava. These differences were more evident in group 2 fetuses of diabetic mothers, and statistically significant differences were found in the slope values compared with group 1 fetuses. In normal fetuses umbilical vein pulsations were present only in two fetuses at 12 weeks of gestation (18.18%) and were never evidenced later in gestation. A significantly higher incidence of pulsations was found at 12 weeks in fetuses of diabetic mothers (group 1, 56.25%; group 2, 81.81%) and pulsations were present until 16 weeks (group 1, 37.5%; group 2, 45.47%). CONCLUSIONS: An impaired development of cardiac and venous blood flow patterns occurs in fetuses in insulin-dependent diabetic mothers. These abnormalities are more evident in pregnancies with poorer glycemic control but still occur in the presence of stricter metabolic control.

Adult↗

Ductus venosus velocity waveforms in appropriate and small for gestational age fetuses.

The objective of this study was to evaluate differences in ductus venosus velocity waveforms between appropriate and small for gestational age fetuses by using a new index based on the ratio between systolic and atrial peak velocities. Ductus venosus velocity waveforms were cross-sectionally recorded in 164 appropriate for gestational age fetuses at 16-42 weeks of gestation and in 97 small for gestational age fetuses free from structural and chromosomal abnormalities between 24-36 weeks of gestation. Small for gestational age fetuses were divided according to the Doppler findings in arterial peripheral vessels: group A (n = 33), normal ratio between umbilical artery and middle cerebral artery Pulsatility Indices; group B (n = 41), umbilical artery/middle cerebral artery ratio > 95th centile but presence of end diastolic flow in umbilical artery; group C (n = 23), umbilical artery/middle cerebral artery ratio > 95th centile and absence of end diastolic flow in umbilical artery. Eighteen small for gestational age fetuses (10 from group B and 8 from group C) were also serially studied until delivery due to fetal distress. Ductus venosus velocity waveforms were recorded at the level of its origin from umbilical vein and the ratio between systolic and atrial peak velocities (systolic/atrial ratio) calculated. In appropriate for gestational age fetuses, systolic/atrial ratio values significantly decrease with gestation. No significant differences were found in systolic/atrial ratio between appropriate for gestational age fetuses and group A small for gestational age fetuses while, after correction for gestational age, significantly higher values were found in group B (P < or = 0.01) and group C (P < or = 0.001) fetuses. Among these fetuses, those with systolic/atrial ratio above the 95th confidence interval showed a poorer perinatal outcome. No relationships were found between systolic/atrial ratio and Pulsatility Index values from fetal arterial peripheral vessels, while a positive relationship was found with the percentage reverse flow in inferior vena cava. In fetuses serially followed, the systolic/atrial ratio progressively increased approaching the onset of abnormal fetal heart rate patterns. The systolic/atrial ratio allows the evaluation of ductus venosus hemodynamics in small for gestational age fetuses and this index may be useful in the monitoring of such fetuses.

Aorta, Thoracic↗

Middle cerebral artery flow velocity waveforms in normal and small-for-gestational-age fetuses.

The middle cerebral artery flow velocity waveforms were obtained in 16 normal fetuses in a longitudinal study and in 128 normal fetuses in a cross-sectional study with pulsed Doppler ultrasonography. The pulsatility index values of the middle cerebral artery were higher at 25 to 30 weeks' gestation than those observed during the two periods of major cerebral cellular multiplication in the human fetus. In 9 of the 16 fetuses studied longitudinally we compared the pulsatility index values obtained at the end of gestation with those obtained at 1 month after delivery; no significant difference was observed. The pulsatility index of the middle cerebral artery was also determined in 33 small-for-gestational-age fetuses. A middle cerebral artery pulsatility index value below our normal range was recorded in 9 of the 33 small-for-gestational-age fetuses (27.3%). These small-for-gestational-age fetuses with abnormal pulsatility index values had a significantly higher incidence of abnormal fetal heart rate and admission into the neonatal intensive care unit. There were three deaths in the nine small-for-gestational-age fetuses with abnormal pulsatility index values (33.3%) and three deaths in the 24 small-for-gestational-age fetuses with normal pulsatility index values (12.5%). Our data indicate that the pulsatility index of the middle cerebral artery in the normal human fetus has a parabolic pattern during pregnancy and does not change significantly after delivery. The results suggest that the small-for-gestational-age fetus with a normal middle cerebral artery pulsatility index is at lower risk than the fetus with abnormal pulsatility index values; moreover, management of the small-for-gestational-age fetus may be aided by the study of the middle cerebral artery waveforms.

Blood Flow Velocity↗

Lipopolysaccharide structures of Campylobacter fetus are related to heat-stable serogroups.

To determine whether lipopolysaccharide (LPS) structures of Campylobacter fetus are related to the three known heat-stable serogroups, proteinase K-treated whole cell lysates obtained from strains of each serogroup were electrophoresed in polyacrylamide gels. All strains had smooth-type LPS with multiple high-molecular-weight repeating units. The profiles of serogroup A from C. fetus subsp. fetus and from C. fetus subsp. venerealis were identical, but they were different from those of C. fetus subsp. fetus serogroups B and AB. When we immunoblotted the LPS of these serogroups with normal or immune rabbit serum we found homologous recognition between serogroups A from C. fetus subsp. fetus and C. fetus subsp. venerealis. Similarly, serogroups AB and B from C. fetus subsp. fetus showed homologous recognition. However, antiserum against serogroup A did not recognize serogroups B and AB and vice versa. Absorption studies confirmed the identity of LPS from all serogroup A C. fetus strains and cross-reactivity of the serogroup B and AB strains with one another. Serogroup A strains were resistant to the bactericidal activity in normal human serum, whereas serogroup B and AB strains generally were susceptible; isolates from humans predominantly belonged to serogroup A. Results of these studies suggest that the LPS composition forms the basis for the heat-stable serotyping system for C. fetus and that the structural and antigenic variants are associated with differential serum susceptibility.

Animals↗

Hormone ontogeny in the ovine fetus. XV. Studies of adenohypophysial hormones after fetal pituitary stalk section: evidence for an extrahypothalamic dopaminergic influence on fetal prolactin secretion.

The administration of a dopamine antagonist, haloperidol, to the ovine fetus in late gestation elevates plasma concentrations of PRL, suggesting tonic dopaminergic inhibition of fetal PRL secretion. The source of this dopaminergic inhibition was investigated in chronically catheterized ovine fetuses (104-135 days of gestation) after hypophysial stalk section (SS; n = 4) and in sham-operated controls (CON; n = 7). Basal PRL levels were similar in the two groups of fetuses. After the administration of TRF (250 micrograms, iv), PRL levels rose comparably in both the SS and CON fetuses. The only difference was a higher mean incremental response (P less than 0.02) in the SS fetuses. The dopamine agonist apomorphine (100 micrograms/kg, iv) induced a similar suppression of fetal PRL concentrations in CON (n = 4) and SS (n = 2) fetuses. After the administration of haloperidol (1 mg, iv) to the CON fetuses (n = 7), the concentration of fetal PRL rose (P less than 0.01). In the SS fetus (n = 4), haloperidol induced a rise in PRL concentrations (P less than 0.01); however, the response to haloperidol was less (P less than 0.01) in SS than in CON fetuses. These data suggest that there is persistent dopaminergic inhibition of PRL secretion in the fetus after complete stalk section, and that the source of this dopamine is extrahypothalamic. The greater incremental PRL response to TRH and the lesser response to haloperidol in the SS fetus than in CON are evidence for a hypothalamic component to the dopaminergic inhibition in the intact fetus. Basal FSH concentrations and the gonadotropin response to LRF were not affected by stalk section in fetuses studied 5-8 days after surgery. Both the PRL and the GH responses to 5-hydroxytryptophan were abolished by stalk section. After stalk section GH levels fell, however, significant concentrations of GH were measurable in fetal plasma in late gestation, which suggests that the fetal pituitary can secrete GH in the absence of hypothalamic stimulation at this stage in gestation.

Animals↗

Growth hormone in encephalectomized rat fetuses, with comments on the effects of anesthetics.

Plasma and pituitary immunoreactive growth hormone (GH) was measured in 21.5-day-old rat fetuses under various experimental conditions. Encephalectomy on day 19.5 was used as a method for depriving the fetus of its hypothalamus. The fetuses were recovered on day 21.5 under maternal pentobarbital anesthesia. Total encephalectomy or partial encephalectomy (ablation of superficial brain structures) similarly affected fetal growth. The mean GH contents of the pituitaries were not significantly different in the four groups of fetuses studied: controls from intact females (1.38 +/- 0.19 mug/gland), controls from females submitted to surgery on day 19 (1.47 +/- 0.13 mug/gland), surgically encephalectomized fetuses (1.13 +/- 0.12 mug/gland), sham-operated fetuses (1.19 +/- 0.10 mug/gland). The mean plasma GH levels were the same in control fetuses of intact females (147 +/- 8 ng/ml) and in control fetuses of females submitted to surgery (168 +/- 9 ng/ml). The values were lower in sham-operated fetuses (118 +/- 11 ng/ml) and considerably reduced (P less than 0.001) in encephalectomized fetuses (60 +/- 8 ng/ml). Plasma GH was higher in the fetuses of females killed less than 2 min earlier, than in the fetuses of anesthetized females. In dams anesthetized with pentobarbital or ether, the fetal plasma levels of GH were not different after 15 or 45 min of maternal anesthesia. Under maternal urethane anesthesia, the fetal plasma GH was at 15 min significantly lower than it was under (P less than 0.01) or pentobarbital (P less than 0.05); 30 min later, it had increased by 40% (P less than 0.025). It appears that the release of GH in the fetus can be modified by anesthetics, and that some GH still is released by the pituitary gland in the absence of the hypothalamus.

Anesthetics↗

Significance of an echogenic intracardiac focus in fetuses at high and low risk for aneuploidy.

Our objective was to evaluate the significance of an echogenic intracardiac focus in a mixed population of fetuses at high and low risk for aneuploidy. Over a 1 year period, we prospectively identified all fetuses with an echogenic intracardiac focus seen during prenatal sonography. A detailed structural evaluation was performed on each fetus as permitted by gestational age. The location and number of foci were tabulated prospectively, as were associated abnormalities. Follow-up was obtained by review of the medical record. Of the 290 fetuses who had an echogenic intracardiac focus, 14 of them were aneuploid (4.8%). Of the 290 mothers, 125 women were aged 35 years or older and 165 women were younger than 35 years old. Among the 125 fetuses born to women 35 years or older, eight were aneuploid fetuses (6.4%), while among the 165 fetuses of younger mothers, six were aneuploid fetuses (3.6%) (rate ratio = 1.8; 95% confidence interval [extremes] = 0.6, 4.9). Only one of the 14 aneuploid fetuses had an echogenic intracardiac focus as the only sonographic finding, and this occurred in a woman aged 41 years. The majority of the echogenic intracardiac foci (87.6%) were located in the left ventricle, while 4.8% of the foci were right-sided and 7.6% were bilateral. Among the 14 aneuploid fetuses, 14% had bilateral echogenic intracardiac foci and 7% had right-sided foci. Among the euploid fetuses, 7.3% had bilateral echogenic intracardiac foci and 4.7% had right-sided foci. In conclusion, we have shown that the presence of an echogenic intracardiac focus does raise the risk that the fetus has a chromosomal abnormality, most commonly Down syndrome, although all but one aneuploid fetus in our study had other sonographic findings.

Adult↗

[Identification and differentiation of Campylobacter fetus subspecies by PCR].

The species Campylobacter (C.) fetus is divided into the subspecies venerealis and fetus, which differ in epidemiology and clinical importance. The differences between these subspecies make an accurate distinction essential. Differentiation of C. fetus by traditional microbiological methods is only based on two reactions (tolerance to glycin, Na selenite reduction), in which C. fetus ssp. venerealis reacts negatively. However, the value of both reactions is limited. We used a specific PCR-based assay for identifying and differentiating the two C. fetus subspecies, which was recently developed by HUM et al. (1997). In this assay, a 764 bp amplicon is produced using primers MG3F and MG4R for both subspecies of C. fetus. In contrast to HUM et al. (1997), this amplicon was approximately 200 bp smaller. This discrepancy can't be explained. Afterwards, the primers VenSF and VenSR are used for differentiation. The identification of the sub-species venerealis is based on the presence of a 142 bp amplicon, which is not formed with subspecies fetus. The type strains of both C. fetus subspecies were used as positive controls. Non-specific reactions were not observed. In this PCR assay, 73 field strains were investigated (among them 24 C. fetus ssp. veneralis, 26 C. fetus ssp. fetus). In these investigations, the method has proved its diagnostic suitability. The results of the traditional microbiological differentiation of the C. fetus field strains could be confirmed by the PCR assay. In future, the traditional phenotypic characterization of C. fetus subspecies remains indispensable, but this PCR assay constitutes a valuable method for the confirmation of these results.

Animals↗

Effect of restriction of placental growth on oxygen delivery to and consumption by the pregnant uterus and fetus.

Endometrial caruncles were excised from 13 sheep (caruncle sheep) before pregnancy to restrict placental growth. In subsequent pregnancies, half the caruncle fetuses were growth retarded or small (weight more than 2 SD below mean weight for control fetuses) with the remainder, normal-sized (weight within 2 SD of mean weight for control fetuses). The caruncle and 16 control sheep, each with indwelling vascular catheters, were studied between 121 and 130 days of pregnancy. Oxygen delivery to and consumption by the pregnant uterus in caruncle sheep with small fetuses was significantly reduced compared to controls while oxygen extraction was significantly increased. Oxygen tension (P02) and content in the common umbilical vein and in the descending aorta were significantly lower in small caruncle fetuses compared to controls but only P02 was lower in normal-sized caruncle fetuses. Oxygen delivery to, and consumption by, the fetus was significantly reduced in normal-sized and in small caruncle sheep compared to controls while oxygen extraction was increased in small caruncle sheep. Utero-placental oxygen consumption was significantly lower in caruncle sheep with small fetuses compared to that in controls. Despite these changes, oxygen consumption by the gravid uterus and fetus, per kg of tissue mass, was similar in both groups of caruncle and in control sheep. Utero-placental oxygen consumption per kg of utero-placental mass in caruncle sheep with small fetuses was not significantly different to that in sheep with normal-sized caruncle or control fetuses, although it averaged only 25% of that in controls. It is concluded that intrauterine growth retardation following restriction of placental growth is associated with a reduced supply of oxygen to both the pregnant uterus and fetus and a redistribution of oxygen to the fetus. This is due to the disproportionate maintenance of fetal growth relative to that of the placenta, since oxygen consumption by either, in terms of tissue mass, was not altered. Further, the greater uterine and fetal extraction of oxygen suggests that a smaller margin of safety may exist between supply and demand in intrauterine growth retardation.

Animals↗

Metabolism of glucose by fetus and placenta of sheep. The effects of normal fluctuations in uterine blood flow.

The metabolism by the fetus and placenta of [2-3H, U-14C]glucose infused into fetal sheep has been studied. Uptake of glucose from the fetus by the placenta and transfer to the ewe, as well as placental metabolism of glucose to fructose and lactate have been quantified. About two-thirds of the glucose removed from the fetal circulation was taken up by placenta. Less than 15% of this passed back into the maternal circulation, the remainder was converted, at roughly equivalent rates, into lactate and fructose, most of which was transferred back to the fetus. It seems likely that little of this glucose is oxidised by the placenta. This data indicates that there are substrate cycles between the placenta and fetus, one possible function of which is to limit fetal glucose loss back to the mother; lactate and fructose have limited placental permeability. At uterine blood flow rates in the middle of the normal range net glucose uptake by the placenta from the maternal circulation was about 7-fold higher than that from the fetus. About 20% of this was transported to the fetus, 50% was oxidised and much of the remainder converted to lactate and transferred back to the ewe. Labelling patterns in fructose and lactate make it unlikely that this placental pool of glucose mixes freely with that derived from uptake from the fetus. Net movement of glucose across the placenta is markedly influenced by fluctuations in uterine blood flow over the normal range of 500-3000 ml/min. At low flow rates there is net output of glucose from the fetus to the placenta, and in some instances from the placenta to the ewe, i.e. there is evidence of net utero-placental production of glucose to the ewe separate from output by the fetus. There is a close linear relationship between uterine glucose supply (maternal arterial concentration x uterine blood flow) and net balance across the placenta. As uterine supply of glucose falls there is increased uptake by the placenta of glucose from the fetal circulation and corresponding enhanced recycling of fructose and lactate to the fetus. This production of fructose and lactate by the placenta may function to reduce glucose loss from the fetus to the ewe. Hence at high rates of placental uptake of glucose from the fetus placental production of lactate and particularly fructose may approach saturation and allow significant backflow of glucose from the fetus to the ewe. Under these conditions glucose uptake may in part sustain placental oxygen consumption.

Animals↗

Pulmonary maturation in the hypophysectomised ovine fetus. Differential responses to adrenocorticotrophin and cortisol.

Pulmonary maturation in six ovine fetuses hypophysectomised by a cryosurgical method at 0.7-0.8 of pregnancy and delivered by hysterotomy at 152.2 +/- 2.9 (SD) days was compared with that in seven control fetuses delivered at 144.5 +/- 3.5 days. Both the wet and the dry weight of the lungs was less in the hypophysectomised fetuses but total DNA did not differ. Lung volumes at 40 cm of H2O and at 5 cm of H2O on deflation in hypophysectomised fetuses were less than one-third that of controls. Saturated phosphatidylcholine, as an estimate of surfactant, was lower in both lung tissue and lavage fluid. A further group of hypophysectomised fetuses was infused intravenously either with cortisol at 1 mg/h for 72 h (n = 6), or with ACTH1-24 at 5 microgram/h for 84 h (n = 6) before delivery at 155.0 +/- 2.1 days and 154.2 +/- 3.9 days respectively. None of the indices of pulmonary maturation in the cortisol-treated fetuses differed from those in untreated hypophysectomised fetuses whereas values for lung volumes at 40 and 5 cm of H2O in ACTH-treated fetuses were more than twice those of untreated hypophysectomised fetuses and did not differ significantly from controls. In addition, the amount of saturated phosphatidylcholine in lavage fluid was greater in ACTH-treated fetuses (0.13 +/- 0.10 mg/g) than in untreated hypophysectomised fetuses (0.04 +/- 0.48 mg/g). Lung volume at 40 cm of H2O in four fetuses that were thyroidectomised at the time of hypophysectomy responded to ACTH as in hypophysectomised fetuses with intact thyroids but other indices were unaffected. We conclude that hypophysectomy retards pulmonary maturation in fetal sheep. Since ACTH restores distensibility and increases alveolar surfactant in the absence of other pituitary hormones it is likely that ACTH has a major role in lung maturation. The lack of response to cortisol suggests that the effect of ACTH is not mediated only by circulating cortisol.

Adrenocorticotropic Hormone↗

The Tei index for evaluation of fetal myocardial performance in sick fetuses.

OBJECTIVE: The Tei index is a useful, new, noninvasive Doppler index of combined systolic and diastolic function calculated by isovolumic relaxation time plus isovolumic contraction time divided by ejection time. Sick fetuses were evaluated with the Tei index. METHODS: The study group underwent two-dimensional/Doppler echocardiographic measurement of their Tei index and included 10 monochorionic diamniotic (MD) twin pairs with non-twin to twin transfusion syndrome (TTTS), 4 twin pairs with TTTS, 12 fetuses with intrauterine growth retardation (IUGR), 14 fetuses of diabetic mothers, 3 hydrops fetalis fetuses, 8 fetuses of mothers treated with a tocolytic agent, and 40 normal fetuses (control group). RESULTS: The Tei indices in the following groups were significantly higher than the control: recipient fetuses in TTTS, large for gestational age (LGA) fetuses of diabetic mothers, and fetuses with hydrops fetalis. CONCLUSION: The Tei index may be a useful tool for the assessment of fetal cardiac status in a variety of sick fetuses. Recipient fetuses in TTTS, LGA fetuses of diabetic mothers, and hydrops fetalis fetuses may have abnormal myocardial performance. The Tei index readily provides early detection of diminished myocardial function, particularly ventricular dysfunction.

Cardiomyopathies↗

Cardiac malformations in first-trimester fetuses with increased nuchal translucency: ultrasound diagnosis and postmortem morphology.

OBJECTIVE: The aim of this study was to explore the diagnostic accuracy of first-trimester transvaginal echocardiography in fetuses with increased nuchal translucency (NT) thickness, by comparing the ultrasound diagnosis with the findings on postmortem examination or mid-gestational ultrasound and neonatal outcome. METHODS: Transvaginal echocardiography was performed in 45 fetuses with a NT > 95th centile. Karyotyping was performed in 43. In 20 of the 23 pregnancies in which termination of pregnancy was carried out, postmortem examination was performed to determine the presence and type of heart defect. Mid-gestational echocardiography was performed in ongoing pregnancies and neonatal follow-up information was obtained. Findings on first-trimester transvaginal echocardiography were compared to those of second-trimester echocardiography or the results of postmortem examination. The mean NT in the fetuses with and without heart defects was calculated. RESULTS: Of the 45 fetuses, heart malformations were suspected on first-trimester ultrasound in 10 (22%), of which eight (80%) were found to have a chromosomal abnormality. Postmortem examination showed minor additional findings in some cases and major discrepancies occurred in none. Septal defects were the most common defects in trisomic fetuses. In three fetuses with a 45 X karyotype, hypoplastic left heart syndrome was diagnosed. Heart defects were diagnosed in three euploid fetuses in which fetal demise occurred. The sensitivity and specificity for the detection of heart defects of transvaginal echocardiography were 88% and 97%, respectively. The mean NT in fetuses with a normal heart (4.3 mm) was significantly smaller than that of fetuses with heart defects (7.4 mm). CONCLUSION: Transvaginal echocardiography can be performed reliably in first-trimester fetuses with an increased NT. In this study, the proportion of chromosomally abnormal fetuses with a heart defect was not different from that found in newborns, except for cases of Turner syndrome. Fetal demise occurred in all three euploid fetuses with a heart malformation. The fetuses with a heart defect had a larger NT than did those without.

Chromosomes, Human, Pair 18↗

Central and peripheral haemodynamic changes in post-term fetuses: correlation with oligohydramnios and abnormal fetal heart rate pattern.

OBJECTIVE: To assess the hypothesis that the occurrence of oligohydramnios and abnormal fetal heart rate (FHR) pattern in post-term fetuses is associated with impaired fetal cardiac function. DESIGN: A cross sectional study was performed on post-term and term fetuses. Fetal tests included a computerised analysis of the FHR, a biophysical profile and Doppler studies of the abdominal aorta, umbilical artery, middle cerebral artery and the fetal heart. Pulsatility index (PI) was calculated from the abdominal aorta, umbilical and middle cerebral artery flow velocity waveforms. Peak velocity, velocity time integral (VTI), E:A ratio, and heart rate (HR) were calculated from the flow velocity waveforms obtained from the aortic and pulmonic outflow, and from the mitral and tricuspid valves. SETTING: Maternal fetal laboratory, Department of Obstetrics. SAMPLE: One hundred and twenty post-term and 42 term fetuses. RESULTS: Only the tricuspid E:A ratio was significantly higher (P < 0.05) in post-term fetuses with a normal amniotic fluid index compared with term fetuses. Post-term fetuses with an abnormal amniotic fluid index had a significantly lower aortic peak velocity (P < 0.01), aortic VTI x HR (P < 0.01), and mitral VTI x HR (P < 0.05) compared with post-term fetuses with a normal amniotic fluid index or compared with term fetuses. Post-term fetuses with reduced FHR variation had a significantly lower aortic peak velocity (P < 0.01), pulmonic peak velocity (P < 0.05), aortic VTI x HR (P < 0.01), pulmonic VTI x HR (P < 0.05) and a significantly lower mitral VTI x HR (P < 0.05) when compared with post-term fetuses with normal FHR variation. Similar results were obtained in comparing fetuses with normal and adverse perinatal outcome. CONCLUSION: The occurrence of oligohydramnios and abnormal FHR pattern in post-term fetuses appears to be associated with impaired fetal cardiac function. This finding should allow further investigations of post-term fetuses.

Adult↗