Showing papers on "Fetus published in 1987"

Effect of cocaine on uterine blood flow and fetal oxygenation.

Abstract: Five pregnant ewes and their singleton fetuses were instrumented at 115 to 120 days' gestation (term, 145 days) for heart rate, blood pressure, uterine blood flow, and arterial blood gas sampling. In separate studies, cocaine was given to the ewe or fetus as a 0.5-, 1.0-, or 2.0-mg/kg intravenous bolus, and cardiovascular and arterial blood gas values were obtained for 60 minutes after the injection. The results showed that maternal administration of cocaine produced dose-dependent increases in maternal blood pressure and decreases in uterine blood flow. Uterine vascular resistance increased by 52%, 96%, and 168%, respectively. These responses were accompanied by marked fetal hypoxemia, hypertension, and tachycardia. Direct cocaine administration to the fetus produced smaller increases in fetal heart rate and blood pressure than those observed following maternal cocaine injection, and no significant changes in fetal arterial blood gas values. The conclusions are (1) cocaine alters fetal oxygenation by reducing uterine blood flow and impairing oxygen transfer to the fetus; and (2) fetal cardiovascular changes to maternal administration of cocaine may reflect fetal hypoxemia, increased fetal levels of cocaine or fetal catecholamines, or a combination of these events. ( JAMA 1987;257:957-961)

Prenatal asphyxia, hyperlacticaemia, hypoglycaemia, and erythroblastosis in growth retarded fetuses.

Abstract: The umbilical venous oxygen and carbon dioxide tensions, pH, lactate and glucose concentrations, nucleated red cell (erythroblast) count, and haemoglobin concentration were measured in 38 cases of intrauterine growth retardation in which fetal blood sampling was performed by cordocentesis. The oxygen tension was below the normal mean for gestational age in 33 cases; in 14 it was below the lower limit of the 95% confidence interval for normal pregnancies. The severity of fetal hypoxia correlated significantly with fetal hypercapnia, acidosis, hyperlacticaemia, hypoglycaemia, and erythroblastosis. These findings indicate that "birth asphyxia" is not necessarily due to the process of birth.

The immunostimulatory effect of T cells and T cell lymphokines on murine fetally derived placental cells.

Abstract: Evidence for maternal immune recognition of the fetus can be found during pregnancy, yet the conceptus remains unharmed. Indeed, in some cases immunizing the mother with cells sharing histocompatibility antigens with the fetus is beneficial to fetal survival. This could be due to the effect of maternally derived lymphokines on placental growth and function, according to the immunostimulation hypothesis. We demonstrate here that placental cells in culture proliferate upon the addition of T cell-derived lymphokines. The lymphokine activity has been separated from IL 2 and B cell growth factor, and copurified with IL 3 and granulocyte-macrophage colony-stimulating factor (CSF-GM). Recombinant CSF-GM and recombinant IL 3 showed a similar effect. The placental cells that proliferate in culture are of fetal origin and are characterized by strong adherence, phagocytosis, nonspecific esterase staining, and response to the macrophage-specific colony-stimulating factor CSF-1. In addition, treatment of pregnant females with anti-thymocyte serum as well as anti-Ly-2.1 monoclonal antibody, at gestational times before Ly-2 antigen appearance in the fetus, leads to a reduction of the proliferative and phagocytic capacity of day 12 placentae. These results clearly demonstrate that maternal T cells act upon fetally derived placental cells to improve their proliferative and phagocytic potential, and thus provide evidence for the immunostimulatory role of these cells during pregnancy.

Doppler studies in the growth retarded fetus and prediction of neonatal necrotising enterocolitis, haemorrhage, and neonatal morbidity.

Abstract: In 82 consecutive cases of intrauterine growth retardation managed by established criteria fetal Doppler studies identified 29 fetuses with absence of end diastolic frequencies in the fetal aorta. These same fetuses were significantly more growth retarded (p less than 0.001) and had an earlier gestational age at delivery (p less than 0.001) than those with end diastolic frequencies present. A subgroup of these cases was analysed in more detail to examine the prognostic value of this phenomenon for the neonate. Two groups of neonates of equivalent gestational age and with a birth weight below 2000 g were compared. There were 26 neonates with absent end diastolic frequencies (group 1) and 20 with end diastolic frequencies (group 2) in the fetal aorta. Those in group 1 were more likely to suffer perinatal death (p less than 0.05), necrotising enterocolitis (p less than 0.01), and haemorrhage (p less than 0.05). Only 4 (15%) of the babies in group 1 had an uncomplicated neonatal period compared with 15 (75%) in group 2 (p less than 0.001). The circulatory changes identified in these cases may provide a more sensitive measure of critical fetal compromise than current techniques and thus allow the clinician to deliver the fetus before irreversible tissue damage has occurred.

Development of [3H]nicotine binding sites in brain regions of rats exposed to nicotine prenatally via maternal injections or infusions.

Abstract: The fetal and postnatal development of binding sites for [3H]nicotine was examined in brain regions of normal rats and rats whose mothers received nicotine injections or infusions, starting before fetal implantation (gestational day 4) and continuing to gestational day 20. The normal ontogenetic pattern of binding indicated a small but detectable concentration of sites during late gestation, and a substantial increase after birth, primarily during the period in which the majority of cholinergic synapses is forming. The adult pattern of regional selectivity of binding capabilities, namely midbrain + brainstem greater than cerebral cortex much greater than cerebellum, was not present at birth, but rather developed over the ensuing 3 weeks postpartum. Fetal exposure to nicotine produced an elevation in binding detectable during the course of drug exposure (gestational day 18), a finding similar to nicotine's effects in mature brain. However, examination of the subsequent developmental pattern of [3H]nicotine binding indicated a generalized disruption of receptor acquisition, in that alterations persisted far beyond the period in which drug exposure was terminated. The greatest effect was seen in a region relatively poor in receptor sites (cerebellum), and a larger stimulation was obtained with injected vs. infused nicotine. Because the cerebellum is the primary target for disruption of cellular development by prenatal nicotine exposure, these results are consistent with a primary teratologic action of the drug rather than direct effects on development of [3H]nicotine receptors.

Effects of prenatal nicotine exposure on biochemical development of rat brain regions: maternal drug infusions via osmotic minipumps.

Abstract: The effects of a continuous 16-day gestational exposure to nicotine on brain development were examined in the offspring of dams who received a minipump implant on the 4th day of gestation. Maternal viability was unaffected and weight gain was only reduced slightly, but nearly half the dams failed to give birth; dams delivering pups had normal litter sizes. Examination of fetal macromolecules on the 18th day of gestation revealed specific deficits in cell number (DNA) in developing brain tissue as opposed to the rest of the fetus, accompanied by parallel shortfalls in other macromolecules (RNA, protein). After birth, brain development in the nicotine-exposed animals showed persistent abnormalities in the timing of maturational events, with elevated levels of ornithine decarboxylase (an enzymatic marker related to cellular maturation) detectable in all brain regions. Subsequent effects on macromolecules were highly selective regionally, with clear distinctions between areas in which neuronal replication occurs relatively late (cerebellum) compared to early-developing regions (midbrain plus brainstem). Differences apparent between the effects of infused maternal nicotine and those noted previously in studies with nicotine injections indicate that the drug does exert primary effects on developing neural tissues, but that other factors associated with the injection route (such as hypoxia and ischemia consequent to acute effects of nicotine) can interact with the drug to influence brain cell maturation.

Some aspects of placental function in chronically heat-stressed ewes.

Abstract: Pregnant ewes were exposed continuously to high ambient temperature (38-40 degrees C for 9 h, 30-32 degrees C for 15 h daily, relative humidity 40-50%) between about 45 days and 120 days of gestation and studied at 132-137 days. Results were compared with those of ewes of similar gestational age which were not exposed to heat at any stage of pregnancy. Heat exposure did not depress appetite but caused variable reductions in placental weight. Fetal weight was reduced to a lesser extent and correlated with placental weight. Uterine and umbilical blood flows and placental glucose transfer capacity were all significantly reduced and highly correlated with placental weight. These effects were accompanied by an enlargement of the PO2 difference between uterine and umbilical venous blood, a decrease in the PO2 and oxygen saturation of fetal arterial blood, and fetal hypoglycemia. Uteroplacental rates of oxygen and glucose utilization and the concentration of fructose in fetal blood were each significantly correlated with placental weight. It is suggested that reduced placental growth is a primary effect of chronic maternal heat stress and that the associated retardation of fetal growth represents a fetal adaptation to a decreased placental ability to supply oxygen and nutrients.

Intrauterine therapy for presumptive fetal myocarditis with acquired heart block due to systemic lupus erythematosus. Experience in a mother with a predominance of SS-B (La) antibodies.

Abstract: An experimental therapeutic regimen for congenital lupus erythematosus, which consists of treating the mother with high doses of dexamethasone and performing plasmapheresis (3 times per week), was developed. This regimen was administered to a woman whose pregnancy was complicated by the abrupt onset of fetal pericarditis, myocarditis, and complete heart block in the twenty-fourth week of gestation. The effectiveness of plasmapheresis was evidenced by a decrease in the very high titer of SS-B (La) antibodies in the mother. After 5 weeks of therapy, the cardiac disease was ameliorated. The infant tolerated delivery at week 31, and the heart block has persisted. The rationale for this therapy for fetal disease is discussed, with emphasis on 2 goals: to diminish the quantity of maternal antibody that is transmitted to the fetus, and to suppress the manifestations of fetal carditis with the use of glucocorticoids that are not inactivated by the placenta. Tentative recommendations for more intensive prenatal monitoring of maternal and fetal status for those at risk are outlined.

Developmental changes in the rat atriopeptin hormonal system.

Abstract: We undertook a study of fetal synthesis, storage, and release of atriopeptin (AP). Plasma levels of both atriopeptin immunoreactivity (APir) and the NH2-terminal fragment of the prohormone immunoreactivity (NTFir) were very high in the fetus (4 and 20 times the maternal plasma, respectively). However, the atrial content of the AP was low, but surprisingly, ventricular content of AP was quite high (relative to the adult) in the fetus and fell postnatally. Atrial AP messenger RNA (mRNA) increased with postnatal age, whereas ventricular mRNA was extremely high in the fetus and fell rapidly after birth. High fetal plasma peptide levels may derive from the mother since infusion of exogenous atriopeptin 24 into the mother resulted in parallel increases in fetal and maternal peptide levels. Fetal plasma APir and NTFir levels partially reflect the markedly reduced total renal metabolic capacity compared with that of the adult. Plasma levels fell progressively after birth; whereas neonatal atrial content rose substantially. Plasma AP and NTF were simultaneously elevated in both the maternal and fetal circulation after vasopressin injection of the mother. The fetus can also respond to exogenous stimuli (vasopressin or indomethacin--presumably via ductal closure) and promptly release substantial amounts of peptide into its circulation. Thus, it appears that the AP hormonal system is functional during fetal life and responds avidly to increases in intracardiac pressure as does the mature animal.

Screening for fetal Down's syndrome in pregnancy by measuring maternal serum alpha-fetoprotein levels.

Abstract: Although the risk of Down's syndrome increases with maternal age, women under 35 bear about 80 percent of the infants born with this condition. We prospectively investigated the utility of measuring maternal serum alpha-fetoprotein during the second trimester in women under 35 in order to identify pregnancies in which the fetus was affected with Down's syndrome. Over a two-year period, 34,354 women in this age group were screened. Amniocentesis was offered when the risk of Down's syndrome, calculated as a function of maternal age and maternal serum alpha-fetoprotein concentration adjusted for maternal weight and race, was 1:270 or higher, the risk for a 35-year-old woman. This threshold was exceeded in 1451 women in whom gestational age was confirmed by ultrasound; 9 women in this group had a fetus with the syndrome. In three women whose fetuses had trisomy 18 and one whose fetus had trisomy 13, the calculated risk of Down's syndrome was 1:270 or higher. Thus, among women in whom the risk exceede...

Melatonin rhythms in fetal and maternal circulation during pregnancy in sheep.

Abstract: In many seasonally breeding species, the nocturnal melatonin rhythm is part of an endogenous biological clock mediating information about day length to time the onset of puberty and the annual adult reproductive cycle. To determine whether timekeeping persists during pregnancy, we studied the pattern of melatonin in circulation in sheep during the last trimester of gestation. We measured plasma melatonin concentrations in the chronically catheterized ewe and fetus (n = 6) over a 48-h period (every 1-4 h) at approximately 120 days gestation. A typical rhythm was present in the pregnant ewes; plasma melatonin was low during the day and remained increased throughout the night. In the fetus, a modest 24-h pattern was detected, which lagged 0.5-1.5 h behind that of the maternal circulation. In combination with findings later in gestation (126 and 135 days) or even during parturition, it is clear that melatonin rhythms were sustained in all pregnant ewes and a 24-h pattern was present in the fetus. In those sheep that went to full term, births occurred during the night at 0130 +/- 2.6 h (mean +/- SE, n = 3). These findings suggest that measurement of day length is maintained in female sheep during the last trimester of pregnancy. Moreover, information about day length and/or time of day may be transferred across the placenta, because the pattern of melatonin in fetal circulation follows the maternal circadian melatonin rhythm.

Low Fetal Loss Rates After Ultrasound-Proved Viability in Early Pregnancy

Abstract: Once pregnancy is recognized clinically, it is accepted that 12% to 15% undergo spontaneous abortion. However, the actual time of fetal demise has not yet been determined. To address this question, the outcomes of pregnancies identified before 21 days of conception by serum β-human chorionic gonadotropin assays were studied. All subjects underwent ultrasound examinations at eight and 12 weeks' gestation. Among 220 women who had a viable pregnancy at eight weeks, only seven (3.2%) experienced a fetal loss thereafter. The results of this study suggest that most clinically recognized spontaneous abortions manifested after eight weeks actually represent pregnancies in which fetal demise occurred before eight weeks. These findings have important implications with respect to the safety of chorionic villi sampling and to the identification of exogenous agents that cause fetal wastage. ( JAMA 1987;258:2555-2557)

Fetal and maternal thyroid hormones.

Abstract: It is well known that insufficient production of thyroid hormones during the fetal and neonatal period of development may result in permanent brain damage unless treatment with thyroid hormone is instituted very soon after birth. But congenital hypothyroidism is not the only situation in which brain damage may be related to insufficient thyroid function. Cretinism is the most severe manifestation of iodine deficiency disorders found in areas where iodine intake is greatly reduced. Some of the manifestations of cretinism suggest that the insult to the developing brain starts earlier than in the case of congenital hypothyroidism. Hypothyroxinemia of mothers with adequate iodine intake may also leave permanent, though less severe, mental retardation. For these reasons the possible role of maternal transfer of thyroid hormones during early fetal development have been reinvestigated, using the rat to obtain various experimental models. It has been shown that thyroid hormones are found in embryonic tissues before onset of fetal thyroid function and that thyroidectomy of the mother results in delayed development of the concepta. The concentrations of T4 and T3 in embryonic tissues from thyroidectomized dams were undetectable before the onset of fetal thyroid function, and still reduced in some tissues near term, despite the onset of fetal thyroid function. Treatment of control and thyroidectomized dams with methyl-mercaptoimidazole to block fetal thyroid function reduced thyroid hormone concentrations in fetal tissues near term, but this decrease could be partially avoided by infusion of physiological doses of thyroxine to the mothers. Iodine deficiency of the mothers resulted in thyroid hormone deficiency of the developing embryo, which was very marked until term in all tissues including the brain. The results strongly support a role of maternal thyroid hormones in fetal thyroid hormone economy both before and after the onset of the fetal thyroid function, at least in the rat. They also support a role of the hypothyroxinemia of iodine-deficient mothers in initiating the brain damage of the endemic cretin, a damage which would not be corrected once the fetal thyroid becomes active, as iodine-deficiency of the fetus would impair adequate production of hormones by its own thyroid, and maternal transfer would continue to be low.

Marker chromosomes in A series of 10000 prenatal diagnoses. Cytogenetic and follow-up studies

Abstract: In a series of 10 000 prenatal diagnoses 15 marker chromosomes were detected in our centre. Six of these were familial whilst nine had originated de novo. They were analysed with various staining methods. DA-DAPI staining was positive in nine out of 12 pregnancies. Six pregnancies were continued. Five normal children were born, one ended in intrauterine fetal death of a normal fetus at 37 weeks. Nine pregnancies were terminated, showing six normal fetuses, one familial cat-eye syndrome, one fetus with Down syndrome caused by additional trisomy 21 and one fetus with cystic kidneys resp. It is concluded that it seems safe to continue the pregnancy in cases of a familial marker, identical to that of one parent, whilst a de novo DA-DAPI positive marker seems to present a low risk for fetal anomalies.

Effect of restriction of placental growth on fetal and utero-placental metabolism

Abstract: The effect of restriction of placental growth on the supply of glucose to the gravid uterus and fetus and on fetal and utero-placental metabolism of glucose and lactate was examined in this study. Endometrial caruncles were removed from 13 sheep (caruncle sheep) prior to mating, which restricted placental growth in the subsequent pregnancy. Half the fetuses of caruncle sheep were small or growth retarded, with the remainder normal in size. After insertion of vascular catheters at 110 days gestation, the caruncle sheep, together with 16 control sheep, were studied between 121 and 130 days of gestation. Glucose delivery to and consumption by the gravid uterus and its contents, both as a total and per kg of tissue mass, was significantly lower in caruncle ewes with small fetuses, although glucose extraction was similar to that in controls. Utero-placental glucose consumption was significantly lower in caruncle ewes carrying small fetuses compared to that in control ewes, both as a total and per kg of placenta. Small caruncle fetuses were hypoxaemic and hypoglycaemic and the lactate concentration in the common umbilical vein was significantly higher than in control sheep. Glucose delivery to and consumption by the fetus was significantly lower in normal-sized and in small caruncle fetuses compared to controls. Fetal glucose consumption per kg of fetus was similar in control and caruncle sheep. Fetal glucose extraction increased as fetal weight decreased. Utero-placental production of lactate was similar in control and caruncle ewes. However, uterine output of lactate decreased as placental weight fell. Utero-placental production of lactate per kg of placenta was significantly higher in caruncle ewes compared to controls and increased as oxygen content in blood from the fetal femoral artery decreased. Fetal lactate consumption per kg of fetus increased as the concentration of lactate in blood from the common umbilical vein increased. It is concluded that intrauterine growth retardation due to restriction of placental growth is associated with a reduced supply of glucose to both the pregnant uterus and fetus and a redistribution of glucose therein to the fetus, both directly as glucose and indirectly as lactate. This reflects the disproportionate maintenance of fetal weight relative to that of the placenta, reduced utero-placental consumption of glucose per kg of placenta, conversion of a greater proportion of that glucose or other substrate(s) to lactate by the placenta and an increase in the fraction of the lactate produced by utero-placental tissues that is secreted into the fetal circulation.

Pathogenesis of Campylobacter fetus Infections: Serum Resistance Associated with High-Molecular-Weight Surface Proteins

Abstract: Campylobacter fetus subspecies fetus causes both systemic and diarrheal illnesses. We studied 38 strains of C. fetus isolated from 34 patients; underlying illness was present in eight (89%) of nine patients with only systemic isolates compared with three (20%) of 15 patients with only fecal isolates (P = .002). In a standardized assay of susceptibility to normal human serum, 27 (71%) strains were resistant, six (16%) had intermediate susceptibility, and five (13%) were serum sensitive. Major protein bands migrating at 100 kDa or 125 kDa on polyacrylamide gels were present in all of the 25 serum-resistant strains tested but in only four of seven serum-sensitive isolates of C. fetus from humans and animals (P = .007). The presence of these bands was associated with type A lipopolysaccharide. A low-passaged strain, 82-40, was serum resistant and contained the 100-kDa protein; however, a spontaneous mutant of this strain lacked this band and was serum sensitive. The 100-kDa and 125-kDa proteins of three strains of C. fetus were antigenically cross reactive or identical and were exposed on the surface of the C. fetus cell. Serum resistance is inherent to most C. fetus isolates from humans and is associated with the presence of cross-reactive surface proteins.

Human Parvovirus B19 Infection During Pregnancy

Abstract: Human parvovirus B19 (B19) has been implicated as the cause of fifth disease and has been associated with fetal death. We identified pregnant women who were at risk of contracting B19 infection during an outbreak of fifth disease. The sera of 12 women classified at high risk of exposure and 19 classified at low risk were tested during prenatal care, at delivery, or at both times for IgG and IgM antibodies to B19. Four women at high risk but none at low risk were considered infected because they were IgM positive. One IgM-positive woman gave birth to a stillborn hydropic fetus whose tissues were positive for B19 DNA by a nucleic acid hybridization assay. The other three IgM-positive women gave birth to normal offspring, of whom one had IgM-positive cord serum. We conclude that B19 infection during pregnancy can lead to fetal infection with at least two associated outcomes--no adverse effect on the fetus or fetal death.

The Pharmacokinetics of Antiarrhythmic Agents in Pregnancy and Lactation

Abstract: The pharmacokinetics of various drugs may be profoundly altered during different stages of pregnancy, parturition, and lactation. Gastrointestinal absorption or bioavailability of drugs may vary due to changes in gastric secretion and motility. Various haemodynamic changes such as an increase in cardiac output, blood volume, and renal plasma flow may affect drug disposition and elimination. The increase in blood volume and total body water which occurs during pregnancy can alter the volume of distribution for various drugs. Although exact quantifications are not easy, these changes in pharmacokinetic parameters should be considered when dosing antiarrhythmic agents in pregnant women. Plasma protein concentrations and drug binding capacity are altered in the mother and fetus as pregnancy advances. With highly protein bound drugs, these changes may be clinically significant, as the pharmacological efficacy and toxicity are presumed to be related to the concentration of free drug in both the mother and fetus. In some instances, the fetus may be susceptible to greater drug toxicity as free drug concentrations may be underestimated by measurement of total drug concentrations. Changes in maternal drug metabolism and metabolism by the fetoplacental unit also contribute to alterations in the pharmacokinetics of drugs. As the placenta contains many metabolising enzymes, biotransformation of drugs at this site could potentially convert a drug into an active metabolite, or prevent fetal exposure to a toxic drug. Placental transfer of drugs, leading to toxicity in the fetus, is a major concern in the pharmacological management of the pregnant patient. The passage of individual drugs will vary depending on their apparent volumes of distribution, degree of protein binding, the rates of metabolic conversion and excretion within the placenta and fetus, the pH difference between the maternal and fetal fluids, and maternal haemodynamic changes. Drug properties such as lipid solubility, protein binding characteristics, and ionisation constant (pKa) also influence the placental passage of drugs. For weakly basic antiarrhythmic agents, the fetal drug concentration may potentially exceed the maternal plasma concentration when the fetal pH is lowered as in the case of fetal acidosis; this is due to ‘ion trapping’. Additionally, higher free drug concentrations of these basic drugs may exist, due to decreased α1acid glycoprotein concentration and binding affinity in the fetus. Lignocaine(lidocaine) has been shown to enter fetal plasma rapidly with fetal-maternal concentration ratios in the range of 0.52 to 0.66. The metabolites, monoethylglycinexylidide and glycinexylidide have been detected in the maternal plasma within 10 minutes and 40 minutes, respectively, after epidural administration. Fetal-maternal concentration ratios for these metabolites range between 0.55 to 1.0. Alterations in protein binding and pH differences between the mother and fetus may thus be clinically important considerations with lignocaine. Increased dose requirements and reduced plasma phenytoin (diphenylhydantoin) concentrations have been reported during the administration of phenytoin. Impaired drug absorption has also been reported, although the data are conflicting. Phenytoin appears to readily cross the placenta, with fetal cord concentrations ranging from 65 to 100% of the maternal concentrations. Decreases in the maternal albumin concentration with advancing pregnancy have been correlated with a progressive increase in the phenytoin free fraction. However, both total and free drug concentrations were found to be lower during late pregnancy than in the non-pregnant state. Increases in phenytoin plasma clearance have also been reported. Quinidine appears to readily cross the placenta with fetal cord-maternal concentration ratios ranging from 0.24 to 1.4. High concentrations of quinidine have also been detected in the amniotic fluid. Procainamide appears to be transferred across the placenta with fetal-maternal concentration ratios reported as high as 1.32. The N-acetyl procainamide metabolite has been detected in the fetal cord with fetal-maternal concentration ratio of 123. Reports of isolated experiences with disopyramide and mexiletine reveal fetal-maternal concentration ratios of 0.39 and 1.0, respectively. Both digitoxin and digoxin appear to be rapidly transferred into the fetus after maternal administration, with fetal-maternal concentration ratios ranging from 0.38 to 1.0. Both amiodarone and desethylamiodarone have been detected in fetal cord blood. Fetal-maternal drug concentration ratios for amiodarone range from 0.095 to 0.145, while one neonatal-maternal concentration ratio was 0.26. The fetal-maternal concentration ratios for desethylamiodarone ranged from 0.17 to 0.285. Both amiodarone and desethylamiodarone were detected in the amniotic fluid, and high concentrations of desethylamiodarone were detected in the amniotic fluid, and high concentrations of desethylamiodarone were found in the placental tissue. Experience with verapamil in pregnancy is quite limited, but the drug appears to cross the placental membrane with fetal-maternal concentration ratios of 0.17 and 0.26 at 49 minutes and 109 minutes, respectively, after a single oral dose. The β-adrenoceptor blockers reviewed, propranolol, metoprolol, atenolol, and acebutolol all appear to transfer across the placenta, showing fetal-maternal concentration ratios in the range of 0.88 to 1.27. The protein binding of propranolol and alprenolol, but not metoprolol, were reduced during pregnancy. Increased plasma clearance, decreased bioavailability, and an increase in total urinary metabolites are reported with metoprolol during pregnancy. Protein binding, lipid solubility, and ionisation characteristics of the antiarrhythmic agents similarly influence partitioning of these drugs into breast milk during lactation. The pH difference between the maternal plasma and milk may also allow for accumulation of weakly basic agents into breast milk. Although data are limited, attempts have been made to estimate breast milk-maternal plasma concentration ratios with equations that include these physiochemical properties. However, better clinical data supporting the use of the equations to predict milk-maternal concentration ratios are still needed. Several of the antiarrhythmic agents reviewed show that many of these agents show wide variation in the milk-plasma concentration ratios. The clinical impact of antiarrhythmic drug partitioning to the fetus and into breast milk remains to be established. More rigorous studies with appropriate body fluid sampling and pharmacokinetic modelling would provide necessary data to help clinicians establish safe and effective antiarrhythmic dosage regimens in the pregnant and lactating patient.

Relationships between uterine length and number of fetuses and prenatal mortality in pigs.

Abstract: Relationships between the length of uterine horn and number of fetuses and prenatal mortality were characterized in 320 pregnant pigs at 3, 5, 7, 9, 11, 13 and 15 wk of gestation in a cross-sectional design. Genital tracts of all pregnant animals available on the days of collection were measured. Length of each uterine horn, numbers of fetuses and corpora lutea (CL) were recorded and prenatal mortality was calculated. With each additional fetus, length of the uterus increased 10 cm regardless of stage of gestation (P less than .001). The association of number of fetuses and uterine length was local and confined to that horn in which the fetus resided and did not extend to the opposite horn. As number of CL increased, number of fetuses also increased as did prenatal mortality. There was a significantly negative correlation between uterine length and prenatal mortality when animals were classified into four groups on the basis of number of CL; less than 10, 10 to 14, 15 to 18 and greater than 18. Results indicated that the number of fetuses and prenatal mortality were closely correlated with length of the uterus. Length of the uterus appeared to be an important limiting factor to litter size as number of CL increased.

Blood Chemistry of Normal Human Fetuses at Midtrimester of Pregnancy

Abstract: Thirteen biochemical parameters and five enzymatic activities were determined on sera of 63 normal human fetuses sampled by direct puncture under ultrasound guidance, between the 20th and the 26th wk of gestation, and on their mothers. They were referred to us for various prenatal diagnoses but were well and confirmed healthy at birth. Some parameters were found to be very similar in both groups, mainly creatinine, calcium, creatine kinase, aspartate aminotransferase, and gamma-glutamyl transferase. Some values were significantly higher in the fetuses, such as total bilirubin, direct bilirubin, phosphorus, lactic dehydrogenase and alkaline phosphatase activities, and alpha-fetoprotein. Urea, uric acid, glucose, triglycerides, cholesterol, total protein, and albumin levels were found to be lower in fetuses. These data indicate a slower metabolism in fetuses compared to their mothers, a lower level of energy requirement, and a relative liver immaturity. These normal values of fetal biochemistry will improve our knowledge of physiology and help to determine the specific values of a test in fetal pathology.