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PubMed2000

Developmental toxicity of carbon black oil in mice.

BACKGROUND: Carbon black oil (CBO) is a refinery side-stream product used to produce asphalt and other commercial products. CBO contains several classes of hydrocarbons, several of which are known to exhibit systemic and gestational toxicities, making this mixture a candidate for causing reproductive toxicity. METHODS: Swiss-Webster mice were administered CBO (300, 350, 400 mg/kg/day) via oral gavage in a dosage volume of 10 microl/g body weight on gestation days (GD) 6-15. Uterine contents were evaluated on GD 18. RESULTS: Treatment with CBO at all dosage levels resulted in a high frequency of maternal clinical symptoms and a decrease in maternal weight gain. Decreased fetal viability was observed, manifested as a decrease in viable implants and, in a high percentage of treated dams, as early resorption of the entire litter. A significant reduction in fetal weight was also observed. However, neither structural malformations nor developmental delays in ossification were observed in any of the living offspring. To minimize maternal toxicity, the dosage range was lowered (100, 200, 300 mg/kg/day), and the concentration was adjusted such that the volume administered to each dam was decreased by 20%. In this trial, the only maternal effect observed was an increase in maternal liver weight at 200 and 300 mg/kg. The fetal lethality effects observed previously were reduced substantially. Nevertheless, the frequency of resorption among all treatment groups was higher statistically than in controls. CONCLUSIONS: These data support the hypothesis that CBO is reproductively toxic in Swiss-Webster mice at oral doses of >/=100 mg/kg/day.

Abnormalities, Drug-Induced↗
PubMed1996

Mummified fetus in a mare.

A 12-year-old Arabian mare with a history of repeated early embryonic losses gave birth to a mummified fetus. The fetus was not the result of a pregnancy with twins. The mare had been given a progestogen throughout gestation and expelled the mummified fetus at about 325 days of gestation, 2 weeks after progestogen treatment was discontinued. We estimate that the size of the fetus was consistent with a fetal age of 5 months. The mare and mummified fetus illustrated that progestogen administration after 100 days of gestation can promote retention of a nonviable fetus. When the fetoplacental unit is incapable of producing progestogens in adequate amounts for pregnancy maintenance at that stage of gestation, then it is also unlikely to provide sufficient oxygen and nutrients to meet the needs of the growing fetus. Monitoring fetal viability would enable practitioners to prevent prolonged retention of a nonviable fetus.

Animals↗
PubMed2003

Emergency delivery and perimortem C-section.

The emergency department is a suboptimal location for delivery, and the greater prevalence of complicated presentations and emergency deliveries results in higher morbidity and mortality. Any woman greater than 20 weeks' gestation in labor is considered medically unstable and should be triaged quickly. Fetal viability occurs after 24 to 26 weeks' gestation. Placenta previa and abruption should be considered in a woman in labor with ongoing bleeding, and ultrasound evaluation should be performed emergently. Continuous fetal monitoring is the best method to assess for heart rate variations, accelerations, or decelerations. After the fetus crowns, a finger sweep can exclude the presence of a cord prolapse or nuchal cord. Set up a safety net by notifying appropriate specialists when a complicated delivery is suspected. In shoulder dystocia, generous episiotomy, drainage of the bladder, McRobert's maneuver, and suprapubic pressure may all help disengage the anterior shoulder. With a cord prolapse, the mother is instructed not to push, and the presenting part is elevated off of the cord. Perimortum cesarean delivery is performed with gestational age greater than 24 to 26 weeks. The supine position can lead to aortocaval compression. Perimortum cesarean delivery should be performed within 4 minutes of maternal cardiopulmonary arrest.

Cesarean Section↗
PubMed2000

[Emergency cesarean section in a comatose parturient after head trauma].

Coma in pregnancy and labor is a rare and complicated situation. One of the causes is severe head trauma, which requires neurosurgical consultation and possibly urgent transfer to a neurosurgical unit. This should follow stabilization, confirmation of fetal viability, and cesarean section when indicated. A 38-year-old primigravida at term and in labor, with severe head injury from a vehicular accident is reported. Emergency cesarean section was performed for severe fetal distress during resuscitation. Fetal distress in a comatose parturient with severe head injury may require a short delay in referral to a tertiary trauma center to allow for an emergency cesarean section.

Adult↗
PubMed2003

Protective effect of N-acetylcysteine against fetal death and preterm labor induced by maternal inflammation.

OBJECTIVE: Intrauterine and maternal systemic infections are proposed causes of preterm labor. The resulting prematurity is associated with 75% of infant mortality and 50% of long-term neurologic handicaps. We hypothesize that free radicals generated in large quantities during an inflammatory response shift the fetomaternal redox balance to an oxidative state, compromising the fetus. Thus, if our working hypothesis is correct, selective inactivation of free radicals with N-acetylcysteine (NAC), an antioxidant and glutathione (GSH) precursor, would improve the outcome of preterm deliveries associated with inflammation. We tested aspects of this hypothesis in an animal model of preterm labor and fetal damage (death). STUDY DESIGN: NAC (1 g/kg) was administered orally to C57Bl/6 mice injected intraperitoneally with either 10 microg lipopolysaccharide (LPS) or saline solution (CRL) on day 16 of gestation. The latency period (time from injection to delivery of the first pup) and fetal viability were recorded. To discriminate between an effect of prematurity from an effect of inflammation, and to document any improvement in survival, mice were killed at 3, 6, and 16 hours after injection. Maternal and fetal redox states were approximated by measuring hepatic GSH. RESULTS: Each C57Bl/6 LPS-treated mouse delivered prematurely after a significantly shorter latency period (LPS: 16.8 hours [95% CI 15.9-17.6] vs CRL: 54.7 hours [95% CI 43.8-65.5]). NAC doubled the latency interval of LPS-treated animals to 35.2 hours (95% CI 21.0-49.2). LPS alone resulted in a 100% rate of stillbirth. Fifty-eight percent of fetuses were already dead 16 hours after LPS. In contrast, only 33% of fetuses were dead 16 hours after LPS (P =.001) when NAC was given. LPS was followed by a reduction in maternal (LPS: 26.3 nmol/mg [95% CI 19.9-32.8] vs CRL: 41.3 nmol/mg [95% CI 34.7-47.9, P <.01]) and fetal GSH (LPS: 19.7 nmol/mg [95% CI 11.7-27.8] vs CRL: 34.5 nmol/mg [95% CI 32.0-37.0, P <.001]). This decline was reversed by NAC (NAC/LPS maternal GSH: 37.0 nmol/mg [95% CI 22.5-51.5] and fetal GSH: 28.4 nmol/mg [95% CI 22.8-33.9]). Importantly, maternal liver GSH impacted on fetal survival. NAC/LPS mothers with living pups 16 hours after LPS had significantly higher liver GSH compared with NAC/LPS mothers whose pups died in utero. In fact, all NAC-treated mice whose hepatic GSH exceeded 20 nmol/mg had living fetuses at 16 hours. CONCLUSION: Maternal inflammation in C57Bl/6 mice results in oxidative stress associated with maternal and fetal GSH depletion. Oxidative stress damages the fetus independent of prematurity. Restoration of maternal and fetal oxidative balance by NAC protects the fetus and reduces the rate of preterm birth.

Acetylcysteine↗
PubMed1996

Developmental toxicity study of 60 Hz (power frequency) magnetic fields in rats.

Considerable public concern has developed regarding possible adverse reproductive outcomes resulting from exposure to power frequency magnetic fields (MF). To identify possible effects of MF exposure on fetal development, timed-pregnant female Sprague-Dawley rats (55/ group) received continuous exposure to linearly polarized, transient-free 60 Hz MF at field strengths of 0 Gauss (G; sham control), 0.02 G, 2 G, or 10 G, or intermittent (1 hr on/1 hr off) exposure to 10 G fields. Dams received MF or sham exposures for 18.5 hr/day on gestation days 6 through 19. A positive control group of 15 dams received daily oral doses of 85 mg ethylenethiourea (ETU)/kg body weight on gestation days 11, 12, and 13; positive control dams received no MF exposure. Ambient and experimentally generated MF were monitored continuously throughout the study. Experimentally generated MF were within 2% of the target field strengths at all times, and ambient MF to which sham controls were exposed did not exceed 0.7 mG at any point in the study. No evidence of maternal toxicity was identified in any MF-exposed dam; mean maternal body weight and organ weights in groups exposed to MF did not differ from those in sham controls. Comparisons of fetal viability and body weight demonstrated no biologically significant differences between MF-exposed groups and sham controls. Similarly, a battery of gross external, visceral, skeletal, and cephalic examinations demonstrated no significant differences in the incidence of fetal malformations or anomalies in MF-exposed groups vs. sham controls. By contrast, 100% of the fetuses in the positive control group treated with ETU demonstrated malformations and reduced body weight. Exposure of pregnant Sprague-Dawley rats to 60 Hz at field strengths up to 10 G during gestation days 6-19 did not produce biologically significant effects in either dams or fetuses. These results do not support the hypothesis that exposure to pure, linearly polarized 60 Hz MF is a significant risk factor for the developing fetus.

Abnormalities, Drug-Induced↗
PubMed2000

[Head injury and pregnancy].

Even mild, head injury during pregnancy can threaten either the maternal or the fetal life. Traffic accidents are the main causes so head injury is often associated with other lesions, frequently abdominal trauma. Among all these possible lesions, head injury and hemorrhagic shock are the main sources of fatality in pregnant women. All kinds of trauma and especially head injuries have a potentially deleterious effect on fetal viability. This risk is associated with systemic and cerebral consequences of post-traumatic arterial hypotension, anoxia or anemia. Moreover, diagnostic procedures and medications can add their noxious secondary effects, contributing more or less to poor fetal outcome. Decision making is necessarily dictated by the severity of the consciousness disorders and/or the encephalic lesions. A convergent discussion between the intensive care physician, the neurosurgeon, the obstetrician and the anesthesiologist is needed. Severe or prolonged traumatic coma is highly dramatic situation because the maternal outcome remains largely unknown for days or weeks. Technically, for these severe comas, there are no substantial differences with what is usually done in a similar case without pregnancy. Neurosurgical indications follow the usual rules, except that some non-urgent indications should be delayed for a while. Usually, this simple rule of independency in indications also applies to the obstetrician. Special care must be taken for fetal monitoring required throughout the initial critical phase.

Brain Injuries↗
PubMed1994

Gene complementation using myoblast transfer into fetal muscle.

Gene complementation by myoblast transfer into neonatal or adult muscle has been proposed as a therapy for primary myopathies as well as to augment non-muscle gene products that may be diminished in the adult circulation. This paper describes a technique whereby myoblasts have been injected into limb muscles of normal and dystrophin-deficient (mdx) fetal mice (during the period of active myotube formation and prior to the development of the host's immune competence) without significantly interfering with fetal viability or further maturation. More mosaic myofibers (myofibers containing both host- and donor-derived myonuclei) appear to result from these transfers than have been reported following myoblast transfer into neonatal muscle or adult muscle. The small size of the fetal hosts' muscles and the lack of well-defined connective tissue septa facilitate migration of donor myoblasts into muscle groups distal to the injection site. The use of donor myoblasts derived from a tetraploid variant of a mouse myogenic cell line (MM14) provides a convenient and permanent cytological marker for the recognition of donor myoblasts and donor-derived myonuclei. When MM14 myoblasts are injected into mdx fetuses, whose muscles lack dystrophin, mosaic myofibers contain sufficient dystrophin to be visualized with routine immunohistochemical techniques. The myoblast transfer system, using fetal hosts, described in this study will facilitate the evaluation of myoblasts as vectors to overcome genetic deficiencies that may be manifested during fetal development.

Animals↗
PubMed2000

Rectal cancer in pregnancy: a new management based on blended anesthesia and monitoring of fetal well being.

Colorectal carcinoma presenting during pregnancy is an extremely rare condition associated with a poor prognosis. In this report we studied a patient referred to our hospital at 26 weeks of gestation with the diagnosis of rectal adenocarcinoma. Tumor resection with a colostomy was planned in the attempt to preserve pregnancy until fetal viability could be reached. Blended anesthesia (general and epidural) was chosen to avoid surgical and anesthesiological risks; in fact this technique allows either an optimal block of neurohormonal response or a good control of surgical stress to be obtained. In order to monitor fetal well being during surgery, Doppler evaluations of fetal heart rate and umbilical artery flow velocity waveforms were performed. The patient was dismissed in good health and then rehospitalized at 32 weeks of gestation in order to perform an elective cesarean section. In conclusion we suggest that, with the choice of a good anesthesiological technique and monitoring of fetal well being, surgical treatment in case of rectal cancer could be performed without affecting the course of pregnancy.

Acid-Base Equilibrium↗
PubMed2001

Targeted genomic disruption of H-ras and N-ras, individually or in combination, reveals the dispensability of both loci for mouse growth and development.

Mammalian cells harbor three highly homologous and widely expressed members of the ras family (H-ras, N-ras, and K-ras), but it remains unclear whether they play specific or overlapping cellular roles. To gain insight into such functional roles, here we generated and analyzed H-ras null mutant mice, which were then also bred with N-ras knockout animals to ascertain the viability and properties of potential double null mutations in both loci. Mating among heterozygous H-ras(+/-) mice produced H-ras(-/-) offspring with a normal Mendelian pattern of inheritance, indicating that the loss of H-ras did not interfere with embryonic and fetal viability in the uterus. Homozygous mutant H-ras(-/-) mice reached sexual maturity at the same age as their littermates, and both males and females were fertile. Characterization of lymphocyte subsets in the spleen and thymus showed no significant differences between wild-type and H-ras(-/-) mice. Analysis of neuronal markers in the brains of knockout and wild-type H-ras mice showed that disruption of this locus did not impair or alter neuronal development. Breeding between our H-ras mutant animals and previously available N-ras null mutants gave rise to viable double knockout (H-ras(-/-)/N-ras(-/-)) offspring expressing only K-ras genes which grew normally, were fertile, and did not show any obvious phenotype. Interestingly, however, lower-than-expected numbers of adult, double knockout animals were consistently obtained in Mendelian crosses between heterozygous N-ras/H-ras mice. Our results indicate that, as for N-ras, H-ras gene function is dispensable for normal mouse development, growth, fertility, and neuronal development. Additionally, of the three ras genes, K-ras appears to be not only essential but also sufficient for normal mouse development.

Animals↗
PubMed1990

Assessment of the viability and pregnancy potential of mouse embryos biopsied at different preimplantation stages of development.

The developmental potential in vitro and in vivo of preimplantation mouse embryos biopsied at the 4-cell, 8-cell and morula stages were investigated. Biopsy had the least impact when performed at the 8-cell stage. There was no effect of biopsy on the development of 8-cells of blastocysts in vitro (95% compared with 99% of controls) or the implantation rate after transfers (82 versus 87%, P greater than 0.05); however, fewer embryos (52 versus 71%, P less than 0.05) resulted in viable fetuses. There was no effect of biopsy at the 8-cell stage on fetal weight on day 17. Blastocyst formation in vitro was significantly less for 4-cell biopsies compared with their controls (76 versus 90%, P less than 0.001) and biopsy also affected the implantation rate (44 versus 59%, P less than 0.01). Biopsy was most detrimental when performed on morulae, reducing the implantation rate from 65% for controls to 21% for biopsies (P less than 0.001). Fetal viability was also markedly affected with a reduction on day 17 from 42 to 26% accompanied by a significant reduction (24%, P = 0.02) of the mean fetal weight. Handling of embryos for biopsy at the morula stage, which involved removal of the zona pellucida, was a significant but not complete cause of the reduced implantation potential observed (sham-controls and intact-controls: 34 and 65%, P less than 0.001), while puncture of the zona during the biopsy of 4-cell and 8-cell embryos had no effect. Therefore, the 8-cell mouse embryo is the most suitable state for embryo biopsy.

Animals↗
PubMed1994

Ultrasonography of the uterus of the goat.

The use of a transabdominal or a transrectal scanning technique to visualize the uterus in goats is discussed. The results of sonographic imaging of normal (non-pregnant, pregnant, postpartum) and abnormal (endometritis, hydrometra, fetal death) uterine structures are reviewed. In the goat, special attention must be paid to distinguishing between the sonographic image of hydrometra and early pregnancy. A case of hydrometra that developed in the presence of three dead fetuses is reported. It is concluded that, under field conditions, transabdominal scanning of goats, performed between days 40 and 70 after mating, yields information about pregnancy, fetal viability, and single or multiple pregnancy, while at the same time making possible a reliable differential diagnosis of pregnancy and hydrometra.

Animals↗
PubMedDate not supplied

Antenatal steroid treatment and adverse fetal effects: what is the evidence?

This article reviews current animal and human data regarding possible adverse fetal effects from antenatal steroid treatment. Although it is now well accepted that such treatment is of benefit to fetal lung development, the potential for adverse fetal outcomes as a result of single or multiple glucocorticoid dosing has not been widely recognized. There are now growing concerns, based on animal and some human data, that repeated antenatal doses could lead to a decrease in birth weight, a decrease in fetal brain and other organ size, and abnormal neuronal development. Previous investigations have been hampered by nonstandardization in the type of glucocorticoid, route of delivery, timing of administration, and number of treatment courses. It is recommended that these concerns be addressed through large randomized, controlled clinical trials. In the meantime, it would be prudent to minimize antenatal steroid treatments to a single course with repeated dosing only if there is a persistent threat of preterm delivery. The practice of giving weekly injections of steroids starting at fetal viability and continuing into the third trimester is not supported.

Adrenal Cortex Hormones↗
PubMed2004

Embryo/fetal toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in rats and rabbits.

BACKGROUND: The purpose of this study was to evaluate the effects of lasofoxifene, a selective estrogen receptor modulator (SERM), on rat and rabbit fetal development. METHODS: Lasofoxifene was administered orally to rats (1, 10, 100 mg/kg) between gestation days (GD) 6-17, and in rabbits (0.1, 1, 3 mg/kg) between GD 6-18. Maternal body weight and food consumption were monitored throughout pregnancy. Fetuses were delivered by Cesarean section on GD 21 in rats, and GD 28 in rabbits, to evaluate fetal viability, weight, and morphology. Drug concentrations in maternal plasma were measured in a separate cohort of animals at several time points commencing on GD 17 (rats) and 18 (rabbits). On GD 18 (rat) and GD 19 (rabbit) drug concentrations were measured in maternal plasma and in fetal tissue 2 hr post dosing to determine the fetal to maternal drug ratio. RESULTS: In rats, there were dose-related declines in maternal weight gain and food consumption. Post implantation loss was significantly increased at dosages of 10 and 100 mg/kg, and the number of viable fetuses was decreased at 100 mg/kg. The placental weights increased, whereas fetal weights decreased in a dose-dependent manner. Lasofoxifene-related teratologic findings were noted at 10 and 100 mg/kg and included imperforate anus with hypoplastic tails, dilatation of the ureters and renal pelvis, misaligned sternebrae, hypoflexion of hindpaw, wavy ribs, and absent ossification of sternebrae. In rabbits, neither maternal weight gain nor food consumption were affected during treatment. Between GD 26-28, there was a dose-dependent increased incidence of red discharge beneath the cages. At 1 and 3 mg/kg, resorptions and post-implantation loss increased. There were no significant external or visceral effects, but 3 mg/kg there was an increased incidence of supernumerary ribs. Although the maternal plasma Cmax and AUC(0-24) were dose-dependent, the exposures in the rat were many orders of magnitude greater than in the rabbit even for the same 1 mg/kg dose. The single time point fetal/maternal drug ratio was higher in the rat (1.3-0.78) than in the rabbit (0.21-0.16). CONCLUSION: In general, both maternal and fetal effects of lasofoxifene were similar to those reported with other SERMs. Although the incidence or severity of these effects was, in some instances, greater in the rat than in the rabbit, the doses and the resultant maternal and fetal exposures were many orders of magnitude higher in the rat, suggesting the rabbit to be more sensitive to the toxicological effects of lasofoxifene.

Animals↗
PubMed1999

A longitudinal study of pregnancy outcome following idiopathic recurrent miscarriage.

Recurrent miscarriage is a difficult clinical problem occurring in approximately 1-2% of fertile women. Following investigation, most cases fail to reveal an identifiable cause and are therefore classified as idiopathic. The aim of this study was to identify important gestational milestones for pregnancy success prediction in women following idiopathic recurrent miscarriage. A total of 325 consecutive patients with idiopathic recurrent miscarriage was involved in a prospective longitudinal observational study. Patients were identified from a miscarriage database of 716 patients. Preconceptual presentation and investigation excluded patients from the study sample with known associations of recurrent pregnancy loss, such as antiphosholipid syndrome, oligomenorrhoea, mid-trimester loss and other rare causes, e.g. abnormal parental karyotype. Following early presentation in a subsequent pregnancy, all patients followed a standard clinic protocol including fetal viability ultrasonography on a fortnightly basis throughout the first trimester. Kaplan-Meier curves were constructed for pregnancy outcome. Out of 325 idiopathic cases, 70% (n = 226) conceived, with a 75% success rate. Of 55 miscarriages, longitudinal assessment showed that six losses occurred following detection of fetal cardiac activity (3%). Data from this large study group have enabled accurate prediction of future pregnancy success and have established important gestational milestones for women with idiopathic recurrent miscarriage.

Abortion, Habitual↗
PubMed1993

Homozygous nonsense mutation in the insulin receptor gene in infant with leprechaunism.

Mutations in the insulin receptor gene have been detected in patients with severe insulin resistance, but the absence of insulin receptors has not been recorded. We report a severely insulin resistant newborn baby, the offspring of consainguineous parents, who was homozygous for a nonsense mutation (Lys 121-Amber) in this gene. Translation of this very truncated N-terminal fragment would not be expected to result in a functional insulin receptor. The infant had all the typical features of the syndrome of leprechaunism. The baby probably represents the null phenotype with respect to the insulin receptor. Because insulin receptors are expressed very early in the developing embryo, the absence of functional insulin receptors is thought to be incompatible with fetal viability: the normal organogenesis in this infant who survived beyond term implies that this assumption is probably incorrect.

Base Sequence↗
PubMed1999

Developmental toxicity studies of four fragrances in rats.

Four fragrances, 6-acetyl-1,1,2,4,4,7-hexamethyltetraline (AHTN), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-ben zopyran (HHCB), musk ketone and musk xylene were tested for developmental toxicity in Sprague-Dawley rats (25/group, 3 groups/fragrance, 2 fragrances/corn oil control). Dosages tested were HHCB: 50, 150, 500 mg/kg per day; AHTN: 5, 15, 50 mg/kg per day; musk ketone: 15, 45, 150 mg/kg per day; musk xylene: 20, 60, 200 mg/kg per day. All dosages tested exceeded multiples of the estimated maximal daily human dermal exposure. Treatment (gavage, 5 ml/kg) occurred on GDs 7-17 and Caesarean-sectioning on GD 20. Based on the results of these studies, none of the four fragrances tested were more toxic in the conceptuses than in the dams. Maternal NOAELs were 50, 5, 15 and 20 mg/kg per day for HHCB, AHTN, musk ketone and musk xylene, respectively (150, 50, 45 and 60 mg/kg per day caused clinical signs and reduced weight gain and feed consumption). Developmental NOAELs were 150, 50, 45 and 200 mg/kg per day for HHCB, AHTN, musk ketone and musk xylene, respectively. No adverse effects on embryo-fetal viability, growth or morphology occurred at the highest dosages of AHTN (50 mg/kg per day) or musk xylene (200 mg/kg per day). Developmental toxicity occurred at the high-dosages of HHCB (axial skeletal malformations at 500 mg/kg per day) and musk ketone (increased postimplantation loss and reduced fetal body weight at 150 mg/kg per day). The results of this study indicate that under conditions of normal use, the tested fragrances do not pose a risk to human conceptuses.

Animals↗
PubMed1989

Diagnosis of early pregnancy by ultrasound in Macaca fascicularis.

Real-time ultrasonography was used to detect early pregnancy in 32 longtailed macaques (Macaca fascicularis). In 92% of the successful conceptions, a correct diagnosis was made. The earliest sign of pregnancy was an intrauterine ringlike structure (11 days). A "line swelling" (14 days) preceded definite fetal echoes (21 days), and fetal heart motion (30 days) proved fetal viability. Ultrasound is a rapid, noninvasive, and relatively cost-effective method of diagnosing and monitoring early pregnancy in M. fascicularis.

Animals↗