Chorionic villus sampling significantly affects fetal cardiovascular function.

OBJECTIVE: To assess the effects of chorionic villus sampling (CVS) on fetal heart rate (FHR). METHODS: A prospective longitudinal study was conducted among 300 patients undergoing transabdominal CVS between 8 and 13 weeks of gestation. Duration of the procedure, number of needle passes, sample weight, maternal age, fetal gender, and FHR response to CVS were recorded. RESULTS: The FHR before but not after CVS was inversely correlated with gestational age (r = -0.406, p < 0.001). Conversely, following CVS, no correlation was observed between FHR and gestational age (r = -0.06, p = 0.27). The difference between FHR after CVS and that obtained before CVS (delta FHR) increased with increasing gestational age at sampling (r = 0.372, p < 0.0001), decreased with increasing specimen weight (r = -0.16, p = 0.01) and increased with increasing maternal age (r = 0.22, p < 0.0001). Duration of the procedure, fetal gender and number of needle passes did not affect delta FHR. Multiple logistic regression indicated that gestational age at CVS and maternal age but not the other variables significantly affected delta FHR and together they accounted for over 22% of the variance (R(2) = 0.224, p < 0.0001). CONCLUSIONS: In summary, our results suggest that acute fetal hemodynamic changes accompany CVS and that these changes vary with gestational age.     

Ontogeny of human fetal plasma progesterone, deoxycorticosterone, and deoxycorticosterone sulfate

The concentrations of progesterone, deoxycorticosterone (DOC), and deoxycorticosterone sulfate (DOC-SO4) were determined in mixed umbilical cord plasma of abortuses and newborn infants delivered between 18 and 42 weeks' gestation. A wide range of values among individual samples was found for progesterone (224 to 2,152 ng/ml), DOC (1.6 to 10.4 ng/ml), and DOC-SO4 (17 to 154 ng/ml). Levels of progesterone and DOC in mixed umbilical cord plasma were not correlated; those of DOC and DOC-SO4 were positively correlated significantly (r = 0.3945, P less than 0.001). Whereas the mean plasma levels of DOC were similar throughout gestation, significant variation, as a function of gestational age, was found for progesterone and DOC-SO4, with levels of these steroids generally being higher near term than earlier in gestation. The administration of glucocorticosteroids to the mother resulted in a significant decrease (p less than 0.001) in plasma concentrations of DOC and DOC-SO4 in the newborn infant; levels of progesterone in umbilical cord plasma were not affected by maternal glucocorticosteroid treatment. These results suggest that the fetal adrenal glands play a direct, or possibly an indirect, role in the production of the DOC and DOC-SO4 that is present in the fetal compartment. In addition, since fetal plasma levels of progesterone are quite high throughout gestation, the potential exists for circulating progesterone to serve as a precursor for adrenal and extra-adrenal production of DOC and DOC-SO4.     

Catecholamine physiology in the ovine fetus. III. Maternal and fetal response to acute maternal exercise

A study was made of the effects of maternal exercise on fetal plasma concentrations of catecholamines in nine ewes with chronically catheterized singleton fetuses at 125 to 137 days' gestation. The ewes were subjected to acute treadmill exercise of 2.5 mph for 45 minutes with continuous recording of maternal and fetal blood pressures. Samples of arterial blood were obtained for measurement of catecholamines, glucose, and blood gases. Changes in blood flow in fetal organs in response to maternal exercise were assessed by injection of radioactive microspheres. The maternal plasma catecholamine responses were related to the severity of the exercise stress as indicated by the index of cardiac effort. The fetal responses did not correlate with maternal cardiac effort. A significant decrease in fetal Po2 with a moderate alkalosis occurred, accompanied by a significant elevation in circulating levels of norepinephrine. At the peak of exercise, there was an increase in fetal renal, adrenal, and placental blood flows, as compared to the control period.     

Atrial natriuretic factor, digoxin-like immunoreactive substance, norepinephrine, epinephrine, and plasma renin activity in human fetuses and their alteration by fetal disease

We measured five hormones presumably involved in fetal homeostasis in specimens obtained by cordocentesis for clinical indications from 106 fetuses. Norms for atrial natriuretic factor, digoxin-like immunoreactive substance, plasma renin activity, norepinephrine, and epinephrine were derived from fetuses ultimately shown to be free of detectable abnormality. Atrial natriuretic factor, digoxin-like immunoreactive substance, and plasma renin activity were unrelated to umbilical vessel source or gestational age. Digoxin-like immunoreactive substance was directly related to PCO2 (r = 0.63, p = 0.02). Digoxin-like immunoreactive substance level was elevated in all fetal disease states studied except isoimmunization. The level of atrial natriuretic factor was elevated in fetuses with immune hydrops (NS). Norepinephrine and epinephrine levels were higher in the umbilical artery than in the vein (p = 0.05 and 0.006, respectively). There was a significant correlation between norepinephrine and gestational age in normal fetuses (r = 0.7637, p less than 0.025) and between both catecholamines and many of the respiratory blood gas measurements, with pH and PCO2 being the major determinants. Most disease states were associated with an elevated norepinephrine concentration. There was a negative correlation between plasma renin activity and base deficit (p less than 0.0001). Plasma renin activity was elevated in fetuses with idiopathic growth retardation and nonimmune hydrops (p less than 0.05 for each). In summary, fetal homeostasis as reflected by these five hormones was altered by a variety of disorders. With these baseline values the effects of direct or indirect fetal therapy can begin to be studied.     

Plasma immunoreactive erythropoietin in normal women studied sequentially during and after pregnancy

Six healthy, nonanemic women with uncomplicated singleton pregnancies were sequentially studied for plasma immunoreactive erythropoietin levels, hematologic indices, and human placental lactogen. Mean group levels of erythropoietin as well as human placental lactogen were significantly increased (p less than 0.01) after 18 weeks' gestation compared to nonpregnant values (20 to 30 weeks post partum). However, individual responses of erythropoietin during pregnancy were found to be highly variable. There was a direct correlation of both maternal plasma erythropoietin and human placental lactogen with gestational age (p less than 0.001) but no detectable relation of erythropoietin with human placental lactogen levels. We speculate that the increase in erythropoietin levels during pregnancy acts as a trophic stimulus for effecting an increase in maternal red blood cell mass presumably to meet the increased metabolic (oxygen) demands of pregnancy.     

Increased immunoreactive erythropoietin in cord serum after labor

Since several hours of hypoxemia in fetal animals is sufficient to cause an increase in the plasma erythropoietin level and since labor may be associated with fetal hypoxemia, this study was undertaken to determine if erythropoietin levels in cord blood were higher in fetuses subjected to labor. Two groups of term (37 to 41 weeks) singleton pregnancies were compared: (1) those delivered by elective repeat cesarean section without prior labor (n = 18) and (2) those delivered vaginally (n = 23). Erythropoietin was measured by a radioimmunoassay in which a highly purified human erythropoietin (70,000 U/mg of protein) was used and which has a sensitivity limit of 4 to 5 mU/ml. The mean cord serum erythropoietin level was higher in pregnancies with labor (46 +/- 34 mU/ml, mean +/- SD) compared to those without (26 +/- 10, p less than 0.02). There were no differences between the two groups for maternal age, gestational age, birth weight, infant sex, or Apgar scores. No association of erythropoietin with either gestational age or sex was found. In 11 pregnancies without labor, comparisons were made among simultaneously obtained samples of umbilical arterial plasma, umbilical venous plasma, and mixed cord serum. Although there were no differences between umbilical arterial and umbilical venous plasma erythropoietin levels (21.3 +/- 9.3 versus 19.0 +/- 7.8 mU/ml), mixed cord serum was inexplicably higher (24.4 +/- 9.5 mU/ml, p less than 0.01). We concluded that in uncomplicated pregnancies the duration and intensity of labor are sufficient to cause an increase in the fetal erythropoietin level at delivery.     

Catecholamines in arterial and venous umbilical blood: placental extraction, correlation with fetal hypoxia, and transcutaneous partial oxygen tension

In 34 parturient women the levels of free epinephrine (E), norepinephrine (NE), and dopamine (D) were determined by a radioenzymatic method using maternal venous and umbilical arterial and venous blood. The study was conducted to investigate the relationship between fetal catecholamines and hypoxia, fetal heart rate (FHR), and transcutaneous pO2 (tcpO2). The placental catecholamine extraction rates were also calculated. Results The NE concentrations (10,200 pg/ml) and the E concentrations (1,120 pg/ml) in the fetal arterial blood were highly elevated with mean values increased 4-fold over umbilical vein values. Compared with the maternal venous blood, NE values were increased 20-fold, and E values 10-fold. Free D concentrations in fetal arterial blood (130 pg/ml) had risen 2.5-fold over maternal levels. These results suggest that the catecholamines measured in cord blood are of fetal origin and that the placenta has a high capacity for inactivation of free catecholamines. The placental extraction rate is 77 +/- 14% for NE, 76 +/- 16% for E, and 33 +/- 25% for D. The placental extraction rates for E and NE were virtually identical; in agreement with morphological studies they demonstrated absence of sympathetic innervation on the fetal side of the placenta. Highly significant correlations were found between fetal arterial NE concentrations and the 1-minute APGAR score, pH and base deficit in the umbilical artery and alterations of the FHR (deceleration area, baseline FHR). Further analysis of FHR alterations reveals that an increase in deceleration area without tachycardia is not correlated with an increase of fetal arterial NE concentration. A significant rise in NE was only found with additional tachycardia which is often associated with a loss of oscillation amplitude. Fetal arterial E concentrations were found to correlate with the fetal parameters indicating increased adrenal secretion of the hormone during fetal stress. However, correlation coefficients were lower than those obtained for NE. A significant effect of fetal hypoxia on arterial and venous D levels could not be demonstrated. Fetal tcpO2 varies between 0-25 mm Hg during the last two hours before delivery. In most cases tcpO2 was lower than the arterial pO2. Besides epidermal thickness and artifacts, skin perfusion is a major factor influencing the tcpO2 (transcutaneous arterial pO2 difference). Vasoconstriction of the cutaneous vessels induced by increased NE secretion during hypoxia may obviously produce a fall in tcpO2.(ABSTRACT TRUNCATED AT 400 WORDS)     

A comparison of intravenous and intramuscular magnesium sulfate regimens in preeclampsia

A prospective study comparing continuous intravenous magnesium sulfate to intramuscular magnesium sulfate was performed in 32 preeclamptic patients. Eighteen patients received the intramuscular regimen for mild and severe preeclampsia as recommended by Pritchard. The remaining 14 patients received an intravenous regimen consisting of a 4 gm loading dose administered over 15 minutes followed by a maintenance dose of either 1 gm/hr (n = 7) or 2 gm/hr (n = 7). All groups were similar regarding maternal age, height, weight, fetal gestational age, and laboratory findings. The intravenous regimen with a maintenance dose of 1 gm/hr produced serum magnesium levels that were much lower than those achieved with the intramuscular regimen. There was no significant difference after 3 hours of therapy between the mean magnesium levels achieved with the intramuscular regimen and the levels achieved with the intravenous regimen with a maintenance dose of 2 gm/hr. However, during the first 3 hours of therapy the intramuscular regimen for severe preeclampsia produced mean magnesium levels that were significantly higher than those levels obtained with the intravenous regimen with a maintenance dose of 2 gm/hr (p less than 0.001). Both methods were safe. However, the intravenous regimen with a maintenance dose of 1 gm/hr is inadequate in management of preeclamptic patients.     

Comparison of fetal and maternal hind limb metabolic quotients in sheep

This study compared substrate utilization by the fetal hind limb and the maternal hind limb in 26 sheep at 120 to 135 days of gestation. Catheters were placed in the mother and the fetus to sample femoral arterial and venous blood by use of a nonocclusive technique. Arterial and venous concentrations of oxygen content, glucose, lactate, acetate, and ketoacids were measured simultaneously and were used to calculate metabolic quotients. The fetal hind limb was perfused with arterial blood having a lower oxygen content than the maternal hind limb (3.03 +/- 0.17 versus 4.94 +/- 0.24 mmol/L, p less than 0.001) and had a smaller arteriovenous difference of oxygen content (0.97 +/- 0.05 versus 2.68 +/- 0.104 mmol/L, p less than 0.001). Despite a lower fetal arterial glucose concentration (0.81 +/- 0.05 versus 2.58 +/- 0.13 mmol/L, p less than 0.001), the glucose/oxygen quotient (0.82 +/- 0.05 versus 0.20 +/- 0.02, p less than 0.001) and the arteriovenous difference of glucose (0.13 +/- 0.01 versus 0.08 +/- 0.01 mmol/L, p less than 0.001) were higher in the fetal hind limb than in the maternal hind limb. Both limbs were net producers of lactate. The (glucose + lactate)/oxygen quotient was also higher in the fetal hind limb than in the maternal hind limb (0.68 +/- 0.05 versus 0.12 +/- 0.04, p less than 0.001). In the maternal hind limb, acetate and ketoacids uptake could account for 48% +/- 6% of total oxygen consumption whereas in the fetal hind limb it accounted for only 12% +/- 4% (p less than 0.001). The data demonstrate that, in relation to oxygen uptake, fetal hind limbs have approximately a 2.8% higher rate of perfusion and take up approximately four times as much glucose as the hind limbs of the mother in the resting state.     

Beta-endorphin concentrations in fetal blood during the second half of pregnancy.

OBJECTIVE: Endogenous opiates may play a role in both fetal physiologic functions and the adaptation to intrauterine stress. However, our understanding of this role is hampered by an absence of data on circulating levels of these substances during fetal life. STUDY DESIGN: We measured serum beta-endorphin values with a radioimmunoassay in 81 paired fetal and maternal blood samples and 24 neonatal cord specimens. The former samples were uneventfully obtained from uncomplicated pregnancies between 18 and 39 weeks of gestation at the time of cordocentesis for prenatal diagnosis. RESULTS: Mean fetal beta-endorphin concentrations were significantly lower than beta-endorphin values from neonates (90.5 pg/ml [+/- 59.4] vs 228.4 pg/ml [+/- 166.2]; p less than 0.001), but significantly higher than mean maternal values (70.5 pg/ml [+/- 48.8]; p less than 0.02). Although fetal beta-endorphin levels decreased between 18 and 28 weeks' gestation, the correlation between fetal beta-endorphin values and gestational age was not significant (r = -0.193; p = 0.07). However, fetal beta-endorphin concentrations were significantly correlated with maternal values (Spearman's rank r = 0.47; p less than 0.001). CONCLUSION: These findings suggest that delivery or fetal adaptation to an extrauterine environment is associated with significant increases in beta-endorphin release. Moreover, although the fetal pituitary may be the primary source of circulating fetal beta-endorphin, a maternal or placental contribution cannot be excluded. Our data identify a physiologic range for fetal beta-endorphin concentrations.     

Unexplained fetal death: another anti-angiogenic state.

BACKGROUND: Pregnancy creates a unique situation in which both vasculogenesis and extensive angiogenesis are required for successful fetal and placental development. Recently, the soluble form of vascular endothelial growth factor (VEGF) receptor-1 (sVEGFR-1), an antagonist to VEGF and placental growth factor (PlGF) (two important angiogenic factors), has been implicated in the pathophysiology of preeclampsia and small for gestational age (SGA) without preeclampsia. There is, however, a paucity of information concerning plasma sVEGFR-1 concentrations in other obstetrical disorders. The purpose of this study was to determine plasma sVEGFR-1 concentrations in normal pregnancy, term gestation in labor, and in patients with pregnancy complications including spontaneous preterm labor, preterm premature rupture of the membranes (PROM), fetal death, and acute pyelonephritis. METHODS: A cross-sectional study was conducted to determine the concentrations of sVEGFR-1 in plasma obtained from 499 women in the following groups: (1) non-pregnant women (n = 40); (2) pregnant women (n = 135); (3) normal pregnant women at term in labor (n = 60); (4) fetal death (n = 60); (5) spontaneous preterm labor with intact membranes (n = 102); (6) preterm PROM (n = 64); and (7) pregnancy with acute pyelonephritis (n = 38). Since plasma sVEGFR-1 concentration changes with gestational age, the difference between the actual and the expected plasma sVEGFR-1 concentration (derived from regression equation of normal pregnancy) for each patient (delta value) was calculated and used to examine the differences of plasma sVEGFR-1 concentrations among various groups. Plasma concentrations of sVEGFR-1 were determined by enzyme-linked immunoassay. Regression analysis and non-parametric statistics were used for analysis. RESULTS: (1) Normal pregnant women before term had a median plasma sVEGFR-1 concentration significantly higher than non-pregnant women (p < 0.001); (2) plasma sVEGFR-1 concentration increased with advancing gestational age in normal pregnancy (r = 0.5; p < 0.001); (3) there was no significant difference in the median delta plasma concentration of sVEGFR-1 between normal pregnant women at term with and without labor (p = 0.09); (4) patients with fetal death had a median delta plasma concentration of sVEGFR-1 significantly higher than normal pregnant women (p = 0.001). Among patients with fetal death, those with unexplained causes (p = 0.04) and those with preeclampsia (p < 0.001) had a significantly higher delta plasma sVEGFR-1 concentration than normal pregnant women; and (5) there was no significant difference in the median delta plasma sVEGFR-1 concentration between normal pregnancy and preterm labor with intact membranes, preterm PROM (regardless of the presence or absence of microbial invasion of the amniotic cavity), or acute pyelonephritis (all p > 0.05). CONCLUSIONS: Plasma sVEGFR-1 concentration is increased in a subset of patients with fetal death, but does not change in term and preterm parturition, rupture of fetal membranes, or acute pyelonephritis.     

Predominance of L-dopa in fetal plasma and the amniotic fluid during late gestation in the rat

The purpose of this study was to reevaluate catecholamine distribution in fetal and maternal compartments during late gestation in the rat. Fetal and maternal plasma and amniotic fluid were collected from anesthetized rats on consecutive days from day 17 to day 22, the day of parturition. The fluid was analyzed for dihydroxyphenylalanine (L-dopa), dopamine, norepinephrine, and epinephrine by radioenzymatic assays. Amniotic fluid volume was determined by a direct weighing method. L-Dopa concentrations constituted approximately 50% of total fetal plasma catecholamines and were significantly higher in fetal than in maternal circulation. Dopamine concentrations in fetal plasma were tenfold lower than those of L-dopa but were also significantly higher in fetal than in maternal plasma; norepinephrine levels were similar in both. Maternal plasma epinephrine levels remained relatively constant, whereas fetal epinephrine levels increased fiftyfold from day 17 to day 22. L-Dopa concentrations in the amniotic fluid were tenfold higher than those of dopamine, and the concentrations of both increased markedly during the last 2 days of gestation. However, this apparent rise could be attributed to the concomitant fivefold reduction in the amniotic fluid volume observed at this time. It is concluded that L-dopa is the predominant catecholamine in both the fetal plasma and the amniotic fluid during late gestation in the rat. At the present time, neither the source nor the possible physiologic functions of L-dopa during fetal life are known.     

Correlation of the interpretation of fetal heart rate records with cord plasma erythropoietin levels

Summary. On the basis that fetal levels of plasma erythropoietin (Ep) may reflect fetal oxygenation the primary purpose of the present study was to assess the relation between Ep measured in cord plasma at delivery and the intrapartum fetal heart rate (FHR) record. A scoring system for interpreting FHR recordings blindly was prospectively utilized in 41 selected human pregnancies during the 4 h immediately preceding birth. The correlation of the overall mean FHR score for each individual patient with cord plasma Ep was significant such that the highest Ep levels were observed in those infants with the most abnormal FHR scores. Furthermore, when the birthweights of the infants were adjusted for gestational age, sex, and birth order, birthweight centile was negatively correlated with cord plasma Ep. When both FHR score and birthweight were simultaneously correlated with cord plasma Ep using multiple regression, the combined effect of these two factors improved the association of either alone with both contributing approximately equally.     

Fetal maturation and amniotic fluid levels of catecholamines and their metabolites

Phosphatidylglycerol (PG), a phospholipid closely associated with fetal lung maturity, appears in the amniotic fluid (AF) of complicated pregnant women much earlier than it usually increases during uneventful pregnancy. In this study, AF PG levels, measured by an enzymatic method, were correlated with AF concentrations of catecholamines (CAT) and the deaminated metabolites of dopamine (3,4-dihydroxyphenylacetic acid; DOPAC) and norepinephrine (3,4-dihydroxyphenylglycol; DOPEG), all of which were determined by radioenzymatic assay. AF concentrations of CAT increased with the advance of gestation especially after 36 weeks of gestation, when clinically apparent fetal distress was not present. Three to four fold higher levels of DOPAC and DOPEG over their parent CAT were found in AF. Even prior to 37 weeks of gestation, high concentrations of CAT were found in the pregnancies complicated with fetal distress, and significant correlation was noted for PG versus dopamine (p less than 0.005), norepinephrine (p less than 0.05) epinephrine (p less than 0.02) and DOPEG (p less than 0.05), but not DOPAC. Such a correlation was not observed after 37 weeks of gestation. These findings suggest that fetal CAT plays a primary role in developing fetal lung maturation and that AF PG and CAT increase as a response to chronic distress, only before 37 weeks of gestation.     

Elevated amniotic fluid leptin levels in pregnant women who are destined to develop preeclampsia

OBJECTIVE: To analyze whether leptin levels of the amniotic fluid elevate during early pregnancy in women destined to develop preeclampsia and to evaluate the relationship between amniotic fluid leptin levels and gestational age, maternal body mass index, and fetal sex. STUDY DESIGN: Leptin levels of the amniotic fluid were compared in two groups of women, preeclamptic (n = 20) and normotensive pregnant (n = 40), matched for fetal sex, maternal body mass index at sampling, gravidity and fetal gestational age at sampling. Furthermore, amniotic leptin levels in 400 normotensive pregnant women were analyzed for their correlation with gestational age, maternal body mass index, and fetal sex. RESULTS: Median leptin concentrations were significantly higher (p < 0.001) in the women with preeclampsia (7.3+/-0.7 ng/ml) than in the normotensive pregnant women (4.1 +/- 0.3 ng/ml), independent of fetal sex. The leptin levels in the amniotic fluid decreased with advanced gestational age (r = 0.24, p < 0.001). Amniotic fluid leptin levels in the pregnant women carrying a female fetus (5.6+/-0.3ng/ml) were significantly higher than those carrying a male fetus (4.7+/-0.2 ng/ml) (p = 0.004). CONCLUSION: Higher amniotic fluid leptin levels were observed in the preeclamptic pregnant women, and they decreased as gestational age advanced. Furthermore, the women with a female fetus were noted to have higher amniotic fluid leptin levels.     

Gender-related differences in fetal heart rate during first trimester

OBJECTIVE: Many expecting parents wish to ascertain fetal gender early in pregnancy. Our goal was to determine whether fetal heart rate (FHR) of males and females during the first trimester is significantly different. MATERIALS AND METHODS: From November 1997 to February 2003 we enrolled pregnant women with singleton gestations who underwent obstetric sonography at less than 14 weeks of gestational age. Indications for the sonographic study included first-trimester bleeding, uncertain gestational dating, poor obstetrical history, and aneuploidy screening by nuchal translucency. The sonographic studies were performed by a single sonographer and reviewed by the first author. The FHR was determined by m-mode. All subjects underwent second-trimester sonography at 18.0-24.0 weeks' gestation by the same team, and fetal gender was recorded. Multiple gestations, miscarriages and pregnancies with uncertain fetal gender were excluded. Sonographically assigned fetal gender was confirmed at delivery. RESULTS: Of the 966 first-trimester studies performed, 477 met the inclusion criteria. Of these, 244 (51%) were female and 233 (49%) were males. There were no statistical differences in mean maternal age, gravidity, parity, and mean gestational age at the time of the first study (9.0 +/- 2.3 weeks for female fetuses and 9.0 +/- 2.3 weeks for males, p = 0.7). The average female FHR was 151.7 +/- 22.7 bpm and male FHR was154.9 +/- 22.8 bpm (p = 0.13). DISCUSSION: Contrary to beliefs commonly held by many pregnant women and their families, there are no significant differences between male and female FHR during the first trimester.     

Antenatal fetal heart rate variation in relation to the respiratory and metabolic status of the compromised human fetus

Three groups of women were delivered by caesarean section before labour: for an abnormal fetal heart rate (FHR) trace (21 cases, group 1), or for maternal deterioration in severe pre-eclampsia without gross fetal heart rate abnormalities (20 cases, group 2), or to avoid mechanical difficulties in labour at term (30 cases, group 3). The mean gestational ages of the first two groups were 32 weeks with a high proportion of infants small-for-gestational-age. In group 1, FHR variation (mean range of pulse intervals) was less than half (20.6 SE 1.2 ms) of the normal value at the same age (44.4 SE 1.5 ms). This was associated with hypoxaemia (mean umbilical artery PO2 of 6 mmHg at delivery), with evidence of compensation shown by an elevated amniotic fluid erythropoietin. The fetuses were hypoglycaemic and had greater umbilical artery blood alanine concentrations, but no large changes in adenine nucleotide or endorphin plasma concentrations. Although there was a minor degree of respiratory acidaemia at birth, there was not significant metabolic acidaemia. The results demonstrate that the reduced variation of 'suboptimal' and 'decelerative' fetal heart rate records is associated with fetal hypoxaemia and evidence of nutritional deprivation, but not with asphyxia.     

Clinical significance of fetal heart rate patterns during labor: IV. Agonal patterns

The characteristics of fetal heart rate (FHR) patterns were reviewed in 11 cases where the infants died either intrapartum or within eight hours of birth as a consequence of distress during labor without prior recovery. The neonatal charts and the autopsy reports were also reviewed. The infants were grouped according to gestational age as premature (four), term (four), and postmature (three). Similarities and differences were studied in an attempt to delineate some common underlying factors. The premature fetuses have an extraordinary capacity to withstand clinical signs of severe distress (late deceleration and fixed and tachycardic base line) for many hours until the very moment of death and rarely pass meconium. The term fetuses can withstand less prolonged periods of severe distress, the fixed FHR base line and impressive decelerations preceding immediate death; they consistently passed meconium, three of four had aspirated meconium. All of the postterm fetuses had massive meconium aspiration, but the FHR patterns had a bizarre appearance; several hours before death some late decelerations were followed by tachycardia and fixed base lines but no decelerations. Subsequent occurrence of erratic severe decelerations immediately preceded sudden death. Possible reasons for these different pathophysiologic responses are discussed. In the study of FHR tracings, a variable of utmost importance is chronologic age of gestation. Its value cannot be overemphasized for an accurate interpretation of the fetal condition and good decisions for management.     

Sex differences in lung and adrenal neurosympathetic development in rabbits

To assess the possible mechanism for the increased incidence and severity of the respiratory distress syndrome (RDS) in male versus female infants, we studied neurosympathetic development in the lung and adrenal glands in male and female fetal and newborn rabbits. Tissue levels of catecholamines, norepinephrine (NE), epinephrine (E), and dopamine (DA) were measured using a sensitive radioenzymatic assay. Beta adrenergic receptor development in the lung was studied using the tritiated radioligand dihydroalprenolol. Neurosympathetic innervation of the lung was assessed by measuring tissue NE levels, which increased gradually from 27-day fetuses to 8-day-old newborns. Sex differences were not significant. Lung beta-receptor number was significantly elevated in females as compared with males at each gestational age and throughout the neonatal period (p less than 0.005). Adrenal gland content of E, NE, and DA increased exponentially with advancing developmental age (each p less than 0.005). Adrenal E was significantly (p less than 0.01 elevated in female as compared with male fetuses, as was the proportion of E. Adrenal NE and DA were similar in male and female fetuses. Sex differences were not significant in the newborn animals. The significant relative delay in adrenal medullary and lung beta-receptor matration may relate to the male susceptibility to neonatal morbidity and neonatal RDS.     

Autonomic nervous system regulation of baseline heart rate in the fetal lamb.

OBJECTIVE: We examined 29 chronically instrumented fetal lambs from 125 to 143 days' gestation to investigate the effects of fetal behavioral states and autonomic nervous system maturation on baseline fetal heart rate. STUDY DESIGN: Behavioral states were defined from electrocorticographic analysis as low-voltage fast activity or high-voltage slow activity. Decrease and increase in baseline fetal heart rate subsequent to administration of propranolol and methylatropine represented beta-sympathetic and parasympathetic activity. RESULTS: Baseline fetal heart rate decreased with gestation in both states, with steeper regression in low-voltage fast activity (p less than 0.001). Positive correlation was noted between gestational age and percent decrease baseline fetal heart rate in both states with steeper regression in high-voltage slow activity (p less than 0.001), and between gestational age and percent increase baseline fetal heart rate with steeper regression in low-voltage fast activity (p less than 0.001). Fetal heart rate beta-sympathetic and parasympathetic tones increased with age in both states, with elevation of beta-sympathetic tone in high-voltage slow activity and parasympathetic tone in low-voltage fast activity. CONCLUSION: Sympathetic and parasympathetic systems influence baseline fetal heart rate in these behavioral states and with age.