Alanine production by the human fetus at term gestation

In a previous study, we demonstrated the complete dependence of the human fetus on the mother for its glucose needs. As alanine is considered the major glucogenic amino acid synthesized endogenously and an important source of urea nitrogen, in the present study we examined whether the human fetus at term gestation can produce alanine. 5 normal pregnant women, undergoing elective cesarean section, were given a constant infusion of [2,3-13C2]alanine in trace quantities for a period of 4 h prior to and during surgery. Isotopic steady state was achieved in the maternal blood by 1.5 h and maintained through anesthesia and surgery. The 13C enrichment (mol% excess) of alanine was measured in the peripheral blood of the mother and in the simultaneously obtained umbilical arterial and venous blood at delivery. Even though the umbilical venous and arterial concentrations of alanine were similar, a 42% decrease in 13C enrichment of alanine occurred between umbilical vein and artery, 1.00 +/- 0.23 and 0.58 +/- 0.15%, respectively (mean +/- SD). These data suggest that the human fetus at term gestation following an overnight maternal fast produces alanine endogenously. This may serve to transfer nitrogen from fetal muscle to the liver for urea synthesis.     

Standardized oculocardiac reflex in ex-premature near full term (93 cases)]

The aim of the study was to present data investigating vagal reactivity in a population of premature infants reaching term, using the oculo-cardiac reflex. PATIENTS AND METHODS: Ninety three premature infants, free of any disease, near full term at the moment of testing, were prospectively investigated at a time close to discharge from neonatal unit. After an all-night polygraphic recording, a standardized oculo-cardiac reflex test was performed during quiet sleep. Data were classified in relation to both chronological and postconceptional ages. Simple liner regression analyses were performed on the selected variables. RESULTS: The results showed heterogeneity of the vagal response in this population: longest asystole (1049 ms +/- 540; 95th percentile = 1894 ms); maximal percentage of deviation between two successive RR intervals (88% +/- 90; 95th percentile = 200%); and duration between the beginning of decrease in heart rate and return to mean heart rate (14 s +/- 10; 95th percentile = 30 s). CONCLUSION: Our healthy premature infants at time of discharge exhibited a wider range of vagal reactivity than previously reported for the full term newborns. Considering our findings, we recommend caution before proceeding with treatment of vagal bradycardia in a similar premature infant population.     

Characterization of anorectal pressure and the anorectal inhibitory reflex in healthy preterm and term infants

OBJECTIVES: To evaluate anorectal motor function in healthy premature and term infants with the use of micromanometric techniques. STUDY DESIGN: Anorectal manometry was performed in 22 healthy neonates (9 female) with a mean postmenstrual age of 32 weeks (range, 30 to 38 weeks) with a micromanometric anorectal assembly (od 2.0 mm). The assembly incorporated a 2-cm-long sleeve sensor for measurement of resting anal sphincter pressures and relaxation, and 4 sideholes recorded anal and rectal pressures. Rectal distension was performed with a latex balloon or direct air insufflation to elicit the anorectal inhibitory reflex (AR). RESULTS: The mean anal sphincter pressure, rectal pressure, and rhythmic wave frequency were 40 mm Hg (range, 7 to 65 mm Hg), 11 mm Hg (range, 1 to 27 mm Hg), and 10/min (range, 8 to 14/min), respectively. A normal AR could be elicited in 21 of the 22 infants studied. CONCLUSION: An anorectal micromanometric sleeve catheter is suitable for use in evaluating anorectal pressures in preterm and term neonates. Insufflation of air without the use of a balloon to elicit the AR is reliable and suitable for use in infants <34 weeks. Premature infants older than 30 weeks' postmenstrual age have normal anorectal pressures and a normal AR.     

Hourly fetal urine production rate in the near term fetus: is it really increased during fetal quiet sleep?

Fetal bladder volume and hourly fetal urine production (HFUPR) is calculated on the assumption that the fetal bladder is ellipsoid in shape. A recent validation study demonstrated a progressive overestimation at increasing bladder volumes. This may be due to changes in shape of the fetal bladder at increasing volumes. Two independent papers have shown increased HFUPR during fetal behavioural state 1F (S1F) when compared with S2F. The aim of the present study was to assess whether this increase of HFUPR during S1F, previously observed by others, could be the result of an error introduced by the method of volume calculation. A retrospective evaluation was performed in a series of 208 HFUPR measurements in 123 normal near term pregnant women attending a low-risk antenatal clinic. Adequate bladder filling in both states was identified in 43 recordings. Maximum fetal bladder volumes were greater (>10 ml) during S1F in comparison to S2F in 56% of these recordings and HFUPR was significantly greater during S1F only in these cases. Bladder volumes are usually lower during S2F as a result of fetal voiding, which occurred in association with 22 of 36 transitions from S1F to S2F, and only 1 of 13 transitions from S2F to S1F (P<0.001). When disregarding calculated bladder volumes in excess of 20 ml for the purpose of calculating HFUPR, eleven recordings remained. HFUPR calculated in this way was significantly lower in comparison to measurements where larger bladder volumes were included and no difference was observed between states.

This implies that the differences observed are the result of the greater error in calculating bladder volumes and HFUPR during S1F, where volumes are usually greater and that calculation of fetal bladder volume should not be performed on the assumption that the bladder is ellipsoid in shape. Alternative techniques include limiting measurements to a maximum volume of approximately 20 ml, when the bladder is usually ellipsoid in shape or basing volume calculation on the surface area of a series of sagittal views as suggested by Hedriana and Moore [Hedriana HL, Moore TR. Ultrasonographic evaluation of human fetal urinary flow rate: accuracy of bladder volume estimations. Am J Obstet Gynecol 1994;170:1250–1254; Hedriana HL, Moore TR. Accuracy limits of ultrasonographic estimation of fetal urinary flow rate. Am J Obstet Gynecol 1994;171:989–992.]     

Diurnal variation of eye movement and heart rate variability in the human fetus at term.

To elucidate diurnal variations in eye movement and fetal heart rate (FHR) variability in the term fetus, we observed these two parameters continuously for 24 h, using real-time ultrasound and Doppler cardiotocograph, respectively. Studied were five uncomplicated fetuses at term. The time series data of the presence and absence of eye movement and mean FHR value for each 1 min were analyzed using the maximum entropy method (MEM) and subsequent nonlinear least squares fitting. According to the power value of eye movement, all five cases were classified into two groups: three cases in the large power group and two cases in the small power group. The acrophases of eye movement and FHR variability in the large power group were close, thereby implying the existence of a diurnal rhythm in both these parameters and also that they are synchronized. In the small power group, the acrophases were separated. The synchronization of eye movement and FHR variability in the large power group suggests that these phenomena are governed by a common central mechanism related to diurnal rhythm generation.     

Effect of premature delivery on the maturation of the Hering-Breuer inspiratory inhibitory reflex in human infants.

The Hering-Breuer inspiratory inhibitory reflex was studied serially in a group of premature infants and in a group of term infants in the immediate postnatal period. The premature infants had a stronger inspiratory inhibitory reflex than did the term infants at birth; this reflex decreased with maturation of the premature. Development in the extrauterine environment significantly delayed the rate of disappearance of this reflex. This may indicate that premature delivery retards the neurologic maturation of the human infant. The term infant showed no change in the activity of the inspiratory inhibitory reflex in the first five days of life.     

Maturation of the rectoanal inhibitory reflex in very premature infants

OBJECTIVE: To characterize anal sphincter function in very premature infants < or =30 weeks' postmenstrual age (PMA) and to evaluate the time of maturation of the rectoanal inhibitory reflex (RAIR) by using a sleeve catheter. STUDY DESIGN: Anorectal manometry was performed in 16 healthy neonates (nine girls) with a mean PMA of 29 weeks (range, 27-30 weeks) and a birth weight of 640 to 1590 g (median, 1220 g) with a micromanometric assembly (outer diameter, 2.0 mm). The assembly incorporated a 1.5-cm-long sleeve sensor for measurement of resting anal sphincter pressures and relaxation, and four side holes recorded anal and rectal pressures. Rectal distention was performed with direct air insufflation to elicit the RAIR. RESULTS: The mean anal sphincter pressure, rectal pressure, and anal sphincter oscillation frequency were 24.5+/-11.4 mm Hg, 6.5+/-4.8 mm Hg, and 11.1+/-2.3/min, respectively. A normal RAIR could be elicited in 13 (81%) infants studied. In two infants, the RAIR could not be elicited because of a low anal sphincter pressure of only 5 mm Hg. In the other child, no RAIR was seen despite the repeated insufflation of at least 5 mL of air. CONCLUSION: The majority (81%) of premature infants older than 26 weeks' PMA have normal anorectal pressures and a normal RAIR.     

Amino acid metabolism in the human fetus at term: leucine, valine, and methionine kinetics

Human fetal metabolism is largely unexplored. Understanding how a healthy fetus achieves its fast growth rates could eventually play a pivotal role in improving future nutritional strategies for premature infants. To quantify specific fetal amino acid kinetics, eight healthy pregnant women received before elective cesarean section at term, continuous stable isotope infusions of the essential amino acids [1-13C,15N]leucine, [U-13C5]valine, and [1-13C]methionine. Umbilical blood was collected after birth and analyzed for enrichments and concentrations using mass spectrometry techniques. Fetuses showed considerable leucine, valine, and methionine uptake and high turnover rates. α-Ketoisocaproate, but not α-ketoisovalerate (the leucine and valine ketoacids, respectively), was transported at net rate from the fetus to the placenta. Especially, leucine and valine data suggested high oxidation rates, up to half of net uptake. This was supported by relatively low α-ketoisocaproate reamination rates to leucine. Our data suggest high protein breakdown and synthesis rates, comparable with, or even slightly higher than in premature infants. The relatively large uptakes of total leucine and valine carbon also suggest high fetal oxidation rates of these essential branched chain amino acids.     

Benzodiazepine receptors in the human fetus

The existence of benzodiazepine receptors in the human fetal brain, liver and placenta has been studied. At 12-15 weeks of gestation specific binding to fetal brain occurs. The dissociation constant of [3H]-flunitrazepam-specific binding was 1.5-2 nM and the maximum number of binding sites was 2.3-3.8 fmol/mg of total brain tissue. In the fetal liver and placenta some specific binding exists, yet the nonspecific binding is more extensive.     

Phosphofructokinase in human fetus

The isozymic composition of phosphofructokinase (EC.2.7.1.11) from human fetal tissues has been investigated by immunological characterization, electrophoresis, purification, and SDS-polyacrylamide gel electrophoresis of the dissociated subunits. One of the characteristics of fetal tissues is the indiscriminate expression by all the cells of two or three of the basic forms of phosphofructokinase without any isozyme really corresponding to a specifically fetal form. In particular, L-type enzyme, identical to the highly regulatory enzyme synthesized by the adult hepatocytes, is found in most fetal tissues, especially in muscle and brain. M-type subunits are also detected in most of the organs and constitute the major form in fetal muscle and adrenals. F-type subunits are predominant in fetal stomach and yolk sac and are practically the only form in fetal heart. Some electrophoretic and chromatographic differences between fetal and adult M-type phosphofructokinase exist; whether their nature is genetic or posttraductional is so far unknown. Some differences (of molecular weight and chromatographic properties) are also detected between the fetal L-type subunits and enzyme from adult granulocytes. A mild proteolytic attack of the former by subtilisin transforms it into an enzyme form indistinguishable from granulocyte phosphofructokinase.     

Erythrocyte deformability in the fetus, preterm, and term neonate

Deformability of red blood cells (RBC) is an important determinant of microcirculation, of oxygen transport and release to the tissues, and of RBC life span. Deformability of RBC from five fetuses, 20 preterm infants, 20 term neonates, and 20 adults was determined by direct microscopic observation of RBC subjected to shear stresses of 6 to 85 dyn/cm2 using a counter-rotating rheoscope. There was no significant difference in deformability among RBC from the fetuses, the preterm and term neonates, and the adults at any shear stress. More than 95% of fetal, neonatal, and adult RBC were capable of tank-tread motion. Compared to adults, the frequency distribution of RBC deformability was slightly broader in the fetuses and neonates because of the presence of more highly and poorly deformable RBC. The increased number of rigid RBC may contribute to the shortened life span of fetal RBC.     

Mineral accretion in the human fetus.

Bone mineral content of the mid forearm was measured by photon absorptiometry in 73 white singletons (36 boys, 37 girls) born between 18 and 43 weeks'' gestation. Results obtained within two weeks of birth for liveborn infants were used to establish bone mineral deposition curves approximating normal in utero development. Results for stillborn infants indicated a retardation of bone mineralisation relative to liveborn infants. This has important implications concerning previous estimates of daily calcium needs for preterm infants. Eleven liveborn Asian singletons and nine pairs of white twins were examined similarly. With respect to bone mineral content, weight, and crown-heel length, Asians with gestational ages over 35 weeks and twins were closely comparable with their white singleton peers. Asians under 35 weeks tended to be smaller than white singletons of comparable age.     

Hyaloid vascular pattern in the human fetus

The hyaloid vascular system of developing human eyeballs is studied to elucidate the relationship to the retinal vascular patterns. The process of the regression of the hyaloid vascular system in fetuses consisted of gradual shrinkage of the wall of the vessels with lessening of the lumen and eventually, thread-like acellular strands that remained as a consequence. The intercapillary bridge in the retinal vessel appeared to be a remnant of the degenerated vessel as in the hyaloid vascular system. At the ninth month of intra-uterine life, the regression of the hyaloid vascular system was almost complete.