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Role of endogenous atrial natriuretic peptide in chronic anemia in the ovine fetus: effects of a non-peptide antagonist for atrial natriuretic peptide receptor.

Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natriuresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 +/- 7 to 234 +/- 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 +/- 0.7 versus 34.6 +/- 2.3% and 0.7 +/- 0.1 versus 2.6 +/- 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 +/- 94 versus 497 +/- 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 +/- 0.03 to 0.70 +/- 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 +/- 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 +/- 0.13 to 0.25 +/- 0.06 and 1.30 +/- 0.66 +/- 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 +/- 5 to 9 +/- 2 and 83 +/- 16 to 39 +/- 5 mumol/min). GFR decreased after HS (3.0 +/- 0.8 to 2.4 +/- 0.5 and 3.6 +/- 0.3 to 2.6 +/- 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 +/- 2.7 to 2.7 +/- 0.5 and 16.1 +/- 2.4 to 11 +/- 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow was observed in the anemic fetuses (336 +/- 37 to 436 +/- 58 mL/min/100 g of kidney). Decreasing GFR and increasing renal blood flow suggests HS may alter the renal microcirculation by reversing ANP-induced constriction of the glomerular efferent arteriole. We conclude that sustained increases of the central venous pressure suggest that ANP inhibition results in decreased fluid movement into perivascular tissue. Endogenous ANP may help to maintain basal renal function in the normal fetal kidney and participates in the renal adaptation to chronic fetal anemia. ANP may promote urine flow and sodium excretion by its effects on both the renal microcirculation and the sodium reabsorptive capacity of the nephron.

Anemia↗

Heart rate patterns in trisomic fetuses.

A survey of the clinical records of fifteen fetuses with trisomy 21, six fetuses with trisomy 18, and two fetuses with trisomy 13 was made in order to find out typical patterns of fetal heart rate (FHR) possibly associated with these conditions. Antepartal FHR patterns of 55 normal pregnancies and intrapartal FHR patterns of 14 normal labors were used as a control material. Trisomic fetuses showed significantly fewer FHR accelerations than did the controls. Fetuses with trisomy 18 and 13 had more antepartal decelerations than fetuses with trisomy 21. Trisomic fetuses also showed more intrapartal late decelerations and epochs of silent FHR pattern than did the controls. The abnormal FHR patterns of the trisomic fetuses thus were similar to those in placental insufficiency. Cesarean section was performed for both fetuses with trisomy 13, for five of the six fetuses with trisomy 18 and for nine of fifteen fetuses with trisomy 21. In eleven of sixteen cesarean sections the main indication was abnormal cardiotocogram. Fetal karyotyping from an amniotic fluid sample should perhaps be considered when decelerations and silent patterns of FHR in a growth-retarded, late second or early third trimester fetus are seen. In most cases, however, the decision for optimal management o labor must be based on FHR patterns solely.

Chromosomes, Human, 13-15↗

In-vivo analysis of serum-borne growth factors in developing co-twinned fetuses.

Double-muscled fetuses develop more muscle fibers than normal-muscled fetuses. To examine whether serum growth factors modulate muscle development in cattle, twin pregnancies were induced in eight Holstein heifers using embryos from Belgian Blue and Holstein genetics representing heavy (HM) and light (LM) muscled cattle, respectively. Twin combinations were 1) two pairs of Belgian Blue fetuses that were designated as HM (HM), 2) two pairs of Holstein fetuses that were designated as LM (LM), and 3) four pairs of mixed fetuses; the four Holstein fetuses were designated as LM (HM) and the four Belgian Blue fetuses were designated as HM (LM). Pregnancies were terminated at 175 +/- 5 d after conception and fetuses, with evidence of vascular anastomosis, were dissected. Carcass weights were greatest (P < .05) for HM fetuses. Total bone and individual femur weights were greatest (P < .05) for LM (LM) fetuses. Total skeletal muscle mass and mass of semitendinosus, quadriceps femoris, infraspinatus, and longissimus muscles were in the order of HM (HM) > HM (LM) > LM (HM) = LM (LM) (P < .05). Estimated apparent muscle fiber number determined from a cross-section of semitendinosus muscle was in the order of HM (LM) > HM (HM) > LM (HM) = LM (LM) (P < .05). These data show that the presence of a co-twinned fetus with a lower genetic propensity for muscle development reduces the capacity of heavily muscled fetuses to develop muscle mass by 175 d after conception and strongly support the idea that blood-borne factors regulate muscle hypertrophy in fetal cattle.

Animals↗

Distribution of mucopolysaccharides and glycoproteins in the articular discs of temporomandibular joints in human fetuses.

AIMS: To evaluate the distribution of mucopolysaccharides and glycoproteins in the articular discs of temporomandibular joints (TMJs) in human fetuses at different stages of development in order to test the hypothesis that the development and histological maturation of the articular disc has already begun by the 12th week of gestation. METHODS: Eighteen human fetuses at gestational ages 12, 14, and 16 weeks were used (6 fetuses of each age). Sections (6 microm wide) of the articular discs were stained with trichromic stain for collagen fibers, Mayer's mucicarmine for mucopolysaccharides, and Schiff's periodic acid reaction for glycoproteins. The densities of the stained zones were measured by means of Image J software. The nonparametric Kruskal-Wallis test was used to evaluate the differences among stained zones in the 3 fetus groups. RESULTS: TMJ tissues of four of the six 12-week-old fetuses were stained positive for collagen fibers, mucopolysaccharides, and glycoproteins. In these fetuses the stain was localized to the articular posterior area and was denser in that area than in the middle and anterior areas. The stained areas in the 14-week-old fetuses were distributed throughout the articular discs, with isolated clear unstained areas. The stained areas of all the articular discs of the 16-week-old fetuses were more compact than those of the 12-and 14-week-old fetuses. In all the fetuses examined, the collagen fibers along the articular disc had a wavy appearance. The fossa of the temporal bone was observed in all the fetuses as a straight structure that was similar in the 3 fetus groups. The densities (mean +/- SD) of the stained zones were 38.36% +/- 3.39%, 59.5% +/- 1.56%, and 94.04% +/- 2.04% for 12, 14, and 16 weeks of gestation, respectively; these densities were significantly different (chi2 = 15.16; df = 2, P < .001). CONCLUSION: This study indicates that mucopolysaccharides and glycoproteins as well as collagen fibers are present at 12, 14, and 16 weeks of gestation. This suggests that the histological maturation of the articular disc has already begun at the 12th week and is complete by the 16th week of gestation.

Fetal Development↗

In utero infection of swine fetuses with infectious bovine rhinotracheitis virus (bovine herpesvirus-1).

The pathogenesis of infectious bovine rhinotracheitis (IBR) virus (bovine herpesvirus-1) was studied in porcine fetuses after in utero inoculation. Laparotomies were performed on 8 seronegative pregnant sows at 34 to 86 days of gestation, and all fetuses in 1 uterine horn of each sow were exposed to IBR virus via inoculation into the amniotic sacs. Fetuses in the other horn served as controls. Clinical signs of infection were not observed in the sows, except for 2 sows that aborted at postinoculation days (PID) 11 and 15. Fetuses of the remaining 6 sows were collected at slaughter on PID 15 to 28. Fetuses were examined for gross abnormalities, presence of IBR virus in tissues, and the formation of neutralizing antibodies to IBR virus. Of 33 inoculated fetuses from 6 sows, 10 were mummified, 11 were hemorrhagic and/or edematous, and 12 were alive. Necrotic lesions were observed on the skin and in the liver of dead and live fetuses. Virus was recovered from 29 of 33 inoculated fetuses. Infectious bovine rhinotracheitis virus was isolated from fetal skin, liver, lungs, kidney, spleen, stomach contents, brain, amniotic fluid, and placenta. Virus was isolated from 4 of 11 fetuses recovered from 1 aborting sow. Antibodies to IBR virus were not detected in sera from the sows. However, antibodies were detected in 6 of 15 fetuses inoculated at 63 to 86 days of gestation and collected at slaughter at 86 to 112 days of gestation. The youngest fetus with detectable IBR antibody was estimated to be 74 days of gestation by measuring crown-rump length of the fetus.

Abortion, Veterinary↗

Erythropoietin in human fetuses with immune hemolytic anemia and hydrops fetalis.

OBJECTIVE: To determine whether plasma erythropoietin is increased in fetuses with anemia due to Rh isoimmunization. METHODS: Hemoglobin and erythropoietin were measured in samples obtained by funipuncture from 15 fetuses with Rh isoimmunization (gestational age 26.2 +/- 5.0 weeks, mean +/- standard deviation) and from 13 control fetuses (23.1 +/- 6.7 weeks). Hemoglobin and erythropoietin also were determined in umbilical cord blood collected at birth from 20 term fetuses delivered by elective cesarean. RESULTS: Fetuses with Rh isoimmunization had lower hemoglobin and higher plasma erythropoietin measurements than mid-gestation controls (6.1 +/- 3.9 versus 10.7 +/- 1.5 g/dL and 105.5 +/- 168.1 versus 12.5 +/- 3.1 mU/mL, P < .05, respectively). Hemoglobin and plasma erythropoietin increased with gestational age in control fetuses. There was an inverse association between hemoglobin and plasma erythropoietin in control and Rh-isoimmunized fetuses (r = -0.56, P < .005). Using multiple linear regression, hemoglobin and gestational age were associated independently with plasma erythropoietin (overall F2,25 = 12.3, multiple r2 = 0.49, P < .001). Despite marked decreases in hemoglobin, fetuses below 24 weeks' gestation had minimal increases in plasma erythropoietin compared to fetuses above that gestational age. Mildly anemic Rh-isoimmunized fetuses (hemoglobin 11.6 +/- 2.0 g/dL) delivered vaginally had significantly higher erythropoietin levels in umbilical cord plasma than Rh-isoimmunized fetuses with comparable hemoglobin (10.9 +/- 3.5 g/dL) delivered by elective cesarean without labor (1246 +/- 856 versus 106 +/- 66 mU/mL, respectively, P < .05). CONCLUSION: Fetuses with anemia at mid to late gestation respond with increases in plasma erythropoietin, but these changes are substantially attenuated before 24 weeks' gestation.

Anemia, Hemolytic, Autoimmune↗

Weights of fetuses with autosomal trisomies at termination of pregnancy: an investigation of the etiologic factors of low serum alpha-fetoprotein values.

In order to determine whether the low values of maternal serum alpha-fetoprotein observed with autosomal trisomies are associated with smaller fetal weights, 50 fetuses with Down syndrome (trisomy 21), 10 with trisomy 18, and 65 normal control fetuses, all aborted in the second trimester of pregnancy, were compared. The mean multiple of the median maternal serum alpha-fetoprotein was found to be 0.79 +/- 0.61 for fetuses with Down syndrome and 0.50 +/- 0.26 for those with trisomy 18, both results being significantly lower than results from the control fetuses (0.97 +/- 0.86). No significant difference in the weight distribution between fetuses with Down syndrome and control fetuses, corrected for gestational age, was found. By contrast, fetuses with trisomy 18 had a significantly lower weight distribution compared with that of the control fetuses (p less than 0.001). A linear relationship was found in normal fetuses between maternal serum alpha-fetoprotein values and fetal weight at a given gestational age. Fetal weight does not seem to account for the lower maternal serum alpha-fetoprotein levels seen in fetuses with Down syndrome but may partially account for the lower levels seen in fetuses with trisomy 18.

Abortion, Induced↗

Change in fetal urine production rate in growth-restricted fetuses after maternal meal ingestion.

OBJECTIVE: To determine if fetal urine production is affected by maternal meal ingestion in growth-restricted fetuses. METHODS: We studied 25 normal-growth fetuses in uncomplicated pregnancies and 15 growth-restricted fetuses, all after 30 weeks' gestation. Serial fetal bladder volume measurements were obtained at 2-3 minute intervals with ultrasonography 2 hours before and 2 hours after maternal breakfast. The hourly fetal urine production rate in each maternal state was calculated from the bladder volume measurements. The amniotic fluid index (AFI) and the pulsatility index of both umbilical and fetal middle cerebral arteries were also measured. RESULTS: Two of the 15 growth-restricted fetuses were excluded from analysis, one because it was anomalous and the other because it was not small for gestational age at birth. In the normal-growth fetuses, the hourly fetal urine production rate increased significantly after maternal breakfast (mean +/- standard deviation 30.2 +/- 11.7 versus 41.1 +/- 14.6 mL/hour, P < .001). In contrast, in the growth-restricted fetuses, the rate did not change after maternal breakfast (24.6 +/- 6.2 versus 24.9 +/- 5.7 mL/hour). Although the urine production rate before breakfast did not differ between groups, 2 hours after maternal breakfast it was significantly lower in the growth-restricted fetuses than in the control group (normal-growth) (P < .001). The AFI also was significantly lower in the growth-restricted fetuses than in the control group (15.0 +/- 3.5 versus 18.6 +/- 5.0 cm, P < .04). There were no significant differences in the pulsed Doppler studies. CONCLUSION: In contrast to normal-growth fetuses, maternal meal ingestion for growth-restricted fetuses does not increase fetal urine production. Decreased fetal urine production in the maternal fed state may lead to decreased amniotic fluid volume in growth-restricted fetuses without obvious hypoxia.

Amniotic Fluid↗

Cardiac compliance in fetuses of diabetic women.

OBJECTIVE: To examine possible changes in cardiac function in fetuses of pregestational diabetic mothers. METHODS: We conducted a prospective longitudinal study of 31 women whose pregnancies were between 22 weeks' gestation and term, and who had pregestational diabetes. All diabetic women included in the study had glycosylated hemoglobin lower than 6.5%. All patients included in the study had an early ultrasound confirming gestational age. Doppler studies of the blood flow through the mitral and tricuspid valves were done every 4 weeks using a pulsed-wave Doppler ultrasound device with a 3.5- or 5-MHz transducer. The following indices were calculated from the flow velocity waveforms: the peak velocity during the rapid ventricular filling (E wave) and during the atrial systole (A wave), and the ratio between these velocities (E/A ratio); and the velocity time integral of the atrioventricular blood flow (this integral correlates with volume flow). A comparison between the Doppler indices obtained in fetuses of diabetic women and of normal women was made by using the Mann-Whitney test. RESULTS: Each patient had four to five fetal echocardiographic examinations at 22, 26, 30, 34, and 38 weeks' gestation. The E/A ratio of the mitral and tricuspid valves did not increase in fetuses of diabetic women during the third trimester and was significantly higher in fetuses of nondiabetic women compared with fetuses of diabetic women at 34 and 38 weeks' gestation. The velocity time integral of the mitral and tricuspid valves multiplied by heart rate was higher, but not significantly, in fetuses of nondiabetic women compared with fetuses of diabetic women at 34 and 38 weeks' gestation. The E-wave of the mitral and tricuspid valves increased in both groups throughout gestation. The A-wave of the mitral and tricuspid valves increased only in fetuses of diabetic women throughout the third trimester and was significantly higher at 34 and 38 weeks' gestation compared with fetuses of nondiabetic women. CONCLUSION: Differences in atrioventricular blood flow patterns between fetuses of diabetic women and normal fetuses do not necessarily result from differences in cardiac compliance.

Diabetes, Gestational↗

PrPSc accumulation in fetal cotyledons of scrapie-resistant lambs is influenced by fetus location in the uterus.

Placentae from scrapie-infected ewes have been shown to accumulate PrPSc when the genotype of the fetus is of a susceptible genotype (VRQ/VRQ, ARQ/VRQ or ARQ/ARQ). Cotyledons from fetuses of genotypes ARR/ARR, ARQ/ARR and ARQ/VRR have previously been shown to be resistant to PrPSc accumulation. By using ewes from a naturally infected scrapie flock, cotyledons from fetuses of multiple births of different genotypes were examined. PrPSc was detected in fetal cotyledons of genotype ARQ/ARQ, but not in cotyledons from their dizygotic twin of genotype ARQ/ARR. This confirms earlier reports of single fetuses of these genotypes, but is the first description of such a finding in twin fetuses, one of each genotype. It is also demonstrated that cotyledons from sibling fetuses of genotypes ARQ/VRQ and ARQ/ARQ have different patterns of PrPSc accumulation depending on whether the dam is of genotype ARQ/ARQ or ARQ/VRQ. Lastly, it is shown that cotyledons from fetuses with resistant genotypes are weakly positive for PrPSc when they have shared the same pregnant uterine horn with a fetus of a susceptible genotype with cotyledons positive for the detection of PrPSc. Additionally, a PCR product for the Sry gene, a product specific to males, was found in cotyledons from female fetuses that had shared a uterine horn with a male fetus. This indicates that some sharing of fetal blood occurs between placentomes and fetuses residing in the same uterine horn, which can result in PrPSc accumulation in cotyledons with resistant genotypes.

Animals↗

The effects of pancreatectomy on the rates of glucose utilization, oxidation and production in the sheep fetus.

The effects of fetal pancreatectomy on the uptake and metabolism of glucose were investigated in chronically catheterized sheep fetuses during late gestation by using tracer methodology. Rates of glucose uptake and metabolism were also measured in pancreatectomized fetuses during the infusion of insulin. Pancreatectomy produced hypoinsulinaemia and significantly reduced the rates of fetal glucose utilization and umbilical glucose uptake in comparison to intact fetuses of a similar gestational age. There was no significant alteration in the glucose oxidation fraction after pancreatectomy but because glucose utilization was low in the pancreatectomized fetuses, the rate of fetal glucose oxidation was significantly less after pancreatectomy than in intact animals. No apparent endogenous production of glucose was observed in the pancreatectomized fetuses. Insulin infusion into the pancreatectomized fetuses raised the rates of umbilical glucose uptake and of fetal glucose utilization and oxidation by 40-50% to values similar to those observed in intact animals. The endogenous production of glucose remained negligible during the infusion of insulin into the pancreatectomized fetuses. There was a net flux of radioactive glucose from the pancreatectomized fetus to the uteroplacental tissues and from the uteroplacental tissues into the uterine circulation. These net fluxes and the rate of placental metabolism of tracer glucose decreased significantly during the infusion of insulin into the pancreatectomized fetus. When all the data were combined, partial correlation analyses of the net uteroplacental uptake of tracer glucose and the fetal concentrations of plasma insulin and blood glucose showed that the fetal arterial glucose concentration was the major influence on the net flux of tracer from the fetus to the uteroplacental tissues. These observations demonstrate that the endogenous concentration of insulin has an important role in regulating glucose metabolism in sheep fetus during late gestation.

Animals↗

Adrenocortical responsiveness is blunted in twin relative to singleton ovine fetuses.

Twin fetuses experience much higher rates of perinatal mortality/morbidity than age- and weight-matched singletons. Across species, the prepartum increase in fetal plasma cortisol is responsible for maturing a number of systems in preparation for birth and the immediate postnatal period. In sheep, it is known that basal adrenocortical function is delayed in twins relative to singletons. Thus, it could be argued that relative immaturity in twins may explain their increased susceptibility to stress in the perinatal period and their relatively poor perinatal outcome. However, whether adrenocortical responsiveness to stress is also diminished in the twin fetus and whether the fetal cardiovascular, metabolic and endocrine defences to acute stress are comparatively weak in the twin fetus is unknown. This study investigated the effect of twinning on adrenocortical responsiveness to either the physiological stress of acute hypoxaemia or to an exogenous ACTH test, and on the fetal cardiovascular, metabolic and endocrine responses to acute hypoxaemic stress. Twenty Welsh Mountain sheep fetuses were chronically instrumented (1-2% halothane) at 121 +/- 3 days of gestation (term is ca 145 days) with amniotic and vascular catheters and with a transit-time flow probe around a femoral artery. The animals were divided into two groups based upon fetal number (singletons, n= 10; twins, n= 10), as determined at surgery. At 130 +/- 2 days, a 1 h episode of acute, isocapnic hypoxaemia (to reduce carotid P(O(2)) to 12 +/- 1 mmHg) was induced in all fetuses by reducing the maternal inspired O(2) fraction (F(IO(2)); 9% O(2) in N(2)). Fetal cardiovascular variables were recorded at 1 s intervals throughout the experimental protocol and arterial blood samples taken at appropriate intervals for biophysical (blood gases, glucose, lactate) and endocrine (catecholamines, vasopressin, cortisol, ACTH) measures. At 133 +/- 2 days a 2.5 microg bolus dose of synthetic ACTH (Synacthen; Ciba Pharmaceuticals, UK) was injected i.v. into eight of the singleton and six of the twin fetuses to determine adrenocortical steroidogenic sensitivity to exogenous ACTH. Under basal conditions, twins had lower plasma cortisol concentration, arterial blood pressure and femoral blood flow relative to singleton fetuses. Twins responded to acute hypoxaemia with similar pressor and vasopressor responses compared to singleton fetuses. However, the rate pressure product, an index of myocardial work, tended to decrease during hypoxaemia in twins, in contrast to the increase observed in singletons. Similar increases in the fetal plasma concentrations of ACTH, AVP, noradrenaline and adrenaline were observed during hypoxaemia in both groups; however, both the increments in fetal plasma concentration of cortisol in response to acute hypoxaemia and to exogenous ACTH were blunted in twins relative to singletons. This study shows that basal adrenocortical function as well as adrenocortical responsiveness is blunted in the twin relative to the singleton fetus. Further, the mechanism for adrenocortical blunting resides at the level of the adrenal cortex rather than higher up the axis. Relative adrenocortical immaturity in the twin fetus may reflect a specific endocrine adaptation to prolong gestation in multiple ovine pregnancies; however, such an adaptation does not affect the cardiovascular, metabolic or endocrine defence responses to acute hypoxaemia in the twin fetus.

Acid-Base Equilibrium↗

Effects of maternal hyperoxygenation on atrioventricular velocity waveforms in healthy and growth-retarded fetuses.

In order to assess whether maternal hyperoxygenation induces modifications of Doppler-measured velocity waveforms across atrioventricular valves, 15 healthy and 15 growth-retarded fetuses were studied in basal conditions and during the maternal administration of 60% humidified oxygen. Recordings were performed at 5-min intervals before, during and after maternal oxygen administration. In basal conditions, growth-retarded fetuses exhibited significantly lower ratios between the velocities during early passive ventricular filling and active ventricular filling (E/A ratio) at the level of both mitral and tricuspid valves when compared to healthy fetuses. Furthermore in healthy fetuses the velocity time integral across the tricuspid valve always slightly exceeded that across the mitral valve, whilst growth-retarded fetuses showed an inversed ratio between these velocities. During oxygen administration no changes were found between the two groups of fetuses with regard to the E/A ratios. Similarly the velocity time integrals were unaffected by oxygen administration in the healthy fetuses. Besides growth-retarded fetuses exhibited significant temporary modifications during oxygen administration as expressed by an increase in the velocity time integral across the mitral valve associated with a decrease of that across the tricuspid. These changes result in an inversion of the ratio between transtricuspid and transmitral velocity time integrals reaching values similar to those of healthy fetuses. Short-term oxygen administration affects the intracardiac flow redistribution present in growth-retarded fetuses bringing it to a pattern similar to that of healthy fetuses whereas the E/A ratios were not affected by the treatment.

Blood Circulation↗

The fetus as patient: implications for directive versus nondirective counseling for fetal benefit.

The authors provide an ethical account of the fetus as patient and identify the implications of that account for directive versus nondirective counseling for fetal benefit. They argue that such an account cannot be grounded in the independent moral status of the fetus. Instead, the concept of the fetus as patient is best understood in terms of the principle of beneficence. On the basis of this principle, the fetus is a patient depending on whether links can be established between the fetus and the child it can become. The viable fetus is a patient. Directive counseling for fetal benefit of the viable fetus is appropriate, provided that it takes account of the presence and severity of fetal anomalies, extreme prematurity, and obligations to the pregnant woman. The previable fetus, including the in vitro embryo and the near-viable fetus, is a patient solely as a function of the pregnant woman's autonomous decision to confer such status. If she confers such status, the fetus is a patient and directive counseling is appropriate, provided that it takes account of the factors noted above. If she denies such status, the fetus is not a patient and nondirective counseling is appropriate.

Beneficence↗

[The relationship between weights of fetuses with autosomal trisomies and low maternal serum alpha-fetoprotein].

An association between low maternal serum alpha-fetoprotein (MSAFP) and fetal trisomy has now been thoroughly documented. The mechanisms resulting in low MSAFP are still unclear. In order to determine whether the low values of MSAFP in autosomal trisomies are associated with smaller fetal weights, we compared 11 fetuses with Down syndrome (trisomy 21), 4 with trisomy 18, with 45 normal fetuses. All of them are aborted in the second trimester of pregnancy. No significant difference in the weight distribution between fetuses with Down syndrome and control fetuses was found. In contrast, as compared with the control fetuses, fetuses with trisomy 18 had a significant lower weight distribution. The mean value of MSAFP was 0.72 +/- 0.26 MoM for those with Down syndrome and 0.51 +/- 0.33 MoM for fetuses with trisomy 18; both results being significantly lower than that of normal control (1.01 +/- 0.28). The mean value of amniotic fluid AFP was 0.63 +/- 0.23 MoM for fetuses with Down syndrome. This value was significantly lower than those of the fetuses with trisomy 18 and normal controls (1.02 +/- 0.09 and 1.02 +/- 0.30). A linear relationship between MSAFP and fetal weight was found in normal fetuses at a given gestational age but was not found in trisomy pregnancy. Fetal weight cannot be used to explain the reason for low MSAFP in Down syndrome pregnancy but may partially account for the lower levels noted in fetuses with trisomy 18.

Body Weight↗

Doppler assessment of cardiac function at 11-14 weeks' gestation in fetuses with normal and increased nuchal translucency.

OBJECTIVE: To investigate cardiac dysfunction as a potential underlying mechanism for increased nuchal translucency (NT) in fetuses with chromosomal abnormality or heart defects. METHODS: Myocardial performance index (MPI) and atrioventricular valve E/A ratios for both sides of the heart were measured by Doppler echocardiography in fetuses at 11-14 weeks' gestation. The study groups consisted of 159 normal control fetuses, 199 otherwise normal fetuses but with increased NT > or = 4 mm, 142 fetuses with trisomy 21, 58 with trisomy 18, 19 with trisomy 13, 37 with Turner's syndrome and 24 with isolated heart defects. Groups were compared using Student's t-test and confidence intervals for differences between groups were calculated. RESULTS: Otherwise normal fetuses with increased NT showed no difference in any of the cardiac Doppler parameters from normal controls. Mean E/A ratio was slightly but significantly increased in trisomy 21 fetuses compared with normal controls (0.604 vs. 0.578 on the right, P = 0.011; 0.581 vs. 0.542 on the left, P = 0.0001). E/A ratio was not significantly different between any of the other groups and the normals but there was a small increase in absolute E-wave velocity in trisomy 18 fetuses. MPI was significantly decreased in trisomy 21 fetuses, (0.330 vs. 0.378, P = 0.002 on the left) and also in Turner's syndrome fetuses (0.301 vs. 0.352 on the right, P = 0.04; 0.320 vs. 0.378 on the left, P = 0.034) implying better performance, but not in the other groups. CONCLUSIONS: The magnitude and/or direction of the differences shown do not support a major role for cardiac functional abnormality in the development of NT. Important cardiac dysfunction could not be demonstrated in association with increased NT in normal or abnormal fetuses.

Chromosome Aberrations↗

Influence of sire, sex of fetus and type of pregnancy on conceptus development.

Estrus was synchronized in 93 crossbred cows 3 to 7 yr old which were then superovulated with 10 mg FSH-P and bred artificially to either a Jersey or Charolais bull. Females pregnant to the Jersey sire were slaughtered at 95, 180 or 250 d of gestation; low pregnancy rate from the Charolais sire resulted in enough dams for slaughter and valid comparisons at 95 d only. Conceptus tissue and organ weights and dam carcass weights and measurements were collected at slaughter. At 95 d of gestation, sire differences were not significant; type of pregnancy (single vs multiple) had significant effects on placentome and membrane weight; fetus sex had highly significant effects on fetus weight and crown-rump length. Fetal brain and heart weights showed little effect of sire, fetus sex or type of pregnancy, indicating these early differentiating tissues are highly competitive for available nutrients for growth. Fetal data at 180 and 250 d of gestation showed highly significant effects of gestation stage on placentome, membrane and fetus weights, crown-rump and metatarsal lengths, and liver, kidney, heart and total brain weights. Type of pregnancy had greater effects on the conceptus traits than did fetus sex at these stages. Nonorthogonal analyses of data from the Jersey-sired pregnancies indicated growth of fetuses in multiple pregnancies was suppressed, and the reduction in fetus weight became more pronounced as gestation progressed. Correlations among conceptus traits and dam carcass data showed different relationships within single and multiple pregnancies. We suggest that the genetic contribution for fetal growth has a positive effect on fetal size throughout gestation while the importance of metabolite availability may change during gestation depending on the genetic growth potential of the fetus and on whether the pregnancy is single or multiple. We speculate that these fetus-dam relationships involve systems controlling fetus growth that arise from the fetus genetic growth potential interacting with positive and negative dam effects that are linked or related to the carcass skeletal-fat-muscle endpoints studied.

Journal Article↗

Behavioural states in growth-retarded human fetuses.

Behavioural state observations were carried out on 12 fetuses which subsequently had birthweights below the 10th percentile. Their gestational ages at the time of study ranged from 32 to 40 weeks. Real-time ultrasound scanning was used to detect fetal body and eye movements, and the fetal heart rate was continuously recorded using a clinical fetal monitor. None of these fetuses was severely acidemic or depressed at birth. Findings in the growth-retarded fetuses were compared with those obtained in the fetuses of 14 low risk nulliparae and 14 low risk multiparae by means of the same techniques (van Vliet et al. (1985) Early Hum. Dev., 12, 121-135.; Nijhuis et al. (1982) Early Hum. Dev., 6, 177-195). The appearance of states seemed to be delayed in the growth-retarded fetuses. States were present in only three of eight growth-retarded fetuses studied at 40 weeks, whereas only one of 16 low risk fetuses did not show states at this age. Also at 40 weeks, the proportion of discordant association of the state variables was increased in the growth-retarded fetuses in comparison to the low risk group. There were no consistent differences between the two groups in the occurrence of defined combinations of parameters of the state variables at earlier ages. The growth-retarded fetuses showed differences in the quality and quantity of somatic motility in comparison to low risk fetuses of equivalent gestational age. These observations suggest that some aspects of central nervous system function are disturbed in growth-retarded fetuses, even in the absence of fetal distress.

Birth Weight↗