Showing papers on "Fetus published in 1999"
TL;DR: The rapid turnover of circulating DNA suggests that plasma DNA analysis may be less susceptible to false-positive results, which result from carryover from previous pregnancies, than is the detection of fetal cells in maternal blood; also, rapid turnover may be useful for the monitoring of feto-maternal events with rapid dynamics.
Abstract: Summary Fetal DNA has been detected in maternal plasma during pregnancy. We investigated the clearance of circulating fetal DNA after delivery, using quantitative PCR analysis of the sex-determining region Y gene as a marker for male fetuses. We analyzed plasma samples from 12 women 1–42 d after delivery of male babies and found that circulating fetal DNA was undetectable by day 1 after delivery. To obtain a higher time-resolution picture of fetal DNA clearance, we performed serial sampling of eight women, which indicated that most women (seven) had undetectable levels of circulating fetal DNA by 2 h postpartum. The mean half-life for circulating fetal DNA was 16.3 min (range 4–30 min). Plasma nucleases were found to account for only part of the clearance of plasma fetal DNA. The rapid turnover of circulating DNA suggests that plasma DNA analysis may be less susceptible to false-positive results, which result from carryover from previous pregnancies, than is the detection of fetal cells in maternal blood; also, rapid turnover may be useful for the monitoring of feto-maternal events with rapid dynamics. These results also may have implications for the study of other types of nonhost DNA in plasma, such as circulating tumor-derived and graft-derived DNA in oncology and transplant patients, respectively.
1,110 citations
TL;DR: The data are consistent with the hypothesis that maternal undernutrition may programme the renal nephron number and hence impact upon adult blood pressure and the development of renal disease.
554 citations
TL;DR: The cardiopulmonary abnormalities observed in the calves and fetuses occurred in utero in conjunction with placental abnormalities, and it is likely that the cloning technique and/or in vitro embryo culture conditions contributed to these abnormalities, although the mechanism remains to be determined.
392 citations
TL;DR: The concept that the injury responsible for bronchopulmonary dysplasia in a subset of neonates may begin before birth and is associated with the development of a fetal systemic inflammatory response, as determined by plasma concentrations of interleukin 6 is supported.
334 citations
TL;DR: It is demonstrated that nicotine can alter fetal monkey lung development by crossing the placenta to interact directly with nicotinic receptors on non-neuronal cells in the developing lung, and that similar effects likely occur in human infants whose mothers smoke during pregnancy.
Abstract: It is well established that maternal smoking during pregnancy is a leading preventable cause of low birth weight and prematurity. Less appreciated is that maternal smoking during pregnancy is also associated with alterations in pulmonary function at birth and greater incidence of respiratory illnesses after birth. To determine if this is the direct result of nicotine interacting with nicotinic cholinergic receptors (nAChRs) during lung development, rhesus monkeys were treated with 1 mg/kg/day of nicotine from days 26 to 134 of pregnancy. Nicotine administration caused lung hypoplasia and reduced surface complexity of developing alveoli. Immunohistochemistry and in situ α-bungarotoxin (αBGT) binding showed that α7 nAChRs are present in the developing lung in airway epithelial cells, cells surrounding large airways and blood vessels, alveolar type II cells, free alveolar macrophages, and pulmonary neuroendocrine cells (PNEC). As detected both by immunohistochemistry and by αBGT binding, nicotine administration markedly increased α7 receptor subunit expression and binding in the fetal lung. Correlating with areas of increased α7 expression, collagen expression surrounding large airways and vessels was significantly increased. Nicotine also significantly increased numbers of type II cells and neuroendocrine cells in neuroepithelial bodies. These findings demonstrate that nicotine can alter fetal monkey lung development by crossing the placenta to interact directly with nicotinic receptors on non-neuronal cells in the developing lung, and that similar effects likely occur in human infants whose mothers smoke during pregnancy.
J. Clin. Invest. 103:637–647 (1999)
308 citations
TL;DR: The riddle of the high Pcr levels in term and particularly in preterm newborns seems to be solved, as the results in the newborn rabbits showed an unexpected underestimation of the Ccr vis-a-vis Cin, which means, as is explained at length in the “Discussion” of this article, that the pre term newborn infant reabsorbs creatinine along the renal tubule.
Abstract: Background. Plasma creatinine (Pcr) levels at birth are greatly elevated in relation to the size (and the muscle mass) of the newborn infant and remain so for 1 to 2 weeks. Particularly intriguing is the fact that Pcr levels are higher in preterm than in term infants and for a longer postnatal period. The smaller the birth weight, the higher the Pcr. This cannot be explained by maternal transfer of Pcr or by the absolute and relative (to adult body surface area) reduced glomerular filtration rate of the newborn. Perhaps the renal handling of creatinine is involved. Design. In 522 pairs of mothers and fetuses, maternal and fetal Pcr were compared from 16 weeks of gestation until term. Pcr was measured in 66 newborns of various birth weights and followed for 1 month. Creatinine clearance (Ccr) and inulin clearance (Cin) were measured simultaneously in adult ( n = 8) and newborn ( n = 20) New Zealand White rabbits. In the latter, nephrogenesis continues after birth and they are therefore a good animal model for the study of the renal function in premature infants. Patient. A case of a premature male infant is presented (gestation: 29 weeks; birth weight: 1410 g) suspected of having sepsis because of premature rupture of membranes and postpartum maternal fever. This suspicion was not confirmed. Blood chemistry evaluation showed a high Pcr at birth (0.85 mg/dL, 75 μmol/L), even higher than that of the mother (0.77 mg/dL, 68 μmol/L). The Pcr started to decrease after ∼1 week but remained elevated throughout 1 month of follow-up. Results. From the maternal-fetal Pcr measurements it was quite evident that during the second half of gestation the small molecular weight creatinine (113 dalton, 0.3 nm radius) of the mother and fetus equilibrates at all maternal Pcr levels. The newborn Pcr levels were not only high at the time of birth but remained so for more than 3 weeks. It was also shown that the smaller the infant the higher the Pcr levels. The results of the animal experimental data showed that adult rabbits had the normal physiologic pattern in which Ccr overestimates Cin (Ccr/Cin ratio >1.0). In contrast, the results in the newborn rabbits showed an unexpected underestimation of the Ccr vis-a-vis Cin (Ccr/Cin ratio Conclusion. The riddle of the high Pcr levels in term and particularly in preterm newborns seems to be solved. Once the umbilical cord is severed, the perfect intrauterine maternal-fetal biochemical balance is disturbed. Thereafter, the already transferred exogenous, adult-level creatinine will rapidly disappear in the first urine specimens passed by the now autonomous newborn infant. A new steady state is achieved in due time, based on independent neonatal factors. One of these factors is the unusual occurrence of tubular creatinine reabsorption. We hypothesize that this latter temporary phenomenon is attributable to back-flow of creatinine across leaky immature tubular and vascular structures. With time, maturational renal changes will impose a barrier to creatinine. From that point onwards, total body muscle mass, glomerular filtration rate, and tubular secretion will in health determine the Pcr level of the individual. plasma creatinine, tubular handling of creatinine, newborn, premature infants.
279 citations
TL;DR: Over the past decade, increased attention has been paid to noninvasive techniques of screening for fetal trisomy 21 that can be offered to all pregnant women.
Abstract: Over the past 25 years the utilization of prenatal diagnosis by expectant couples and their physicians has expanded due primarily to two trends: smaller family size, with an increased emphasis on assurance of the ‘normalcy’ of each child, and advancing parental age. In the United States it is currently considered ‘standard of care’ to offer prenatal cytogenetic diagnosis to pregnant women who will be 35 years or older at the time of delivery (American College of Obstetricians and Gynecologists, 1996). Such cytogenetic diagnoses are facilitated by obtaining fetal nucleated cells via an invasive technique such as chorionic villus sampling (CVS) or amniocentesis. 35 years of age was established as the threshold for these procedures because the liveborn incidence of an infant with the most common autosomal aneuploidy, trisomy 21, is roughly equal to the chance of a miscarriage secondary to these procedures (approximately 1 in 250). Despite the safety and accuracy of these techniques, to date there has been little impact upon the incidence of trisomy 21, which is still close to 1 per 1000 live births. A major reason for this is that prenatal diagnostic techniques are directed towards a minority of pregnant women. Although, individually, older pregnant women are at increased risk for having a baby with trisomy 21, as a group they are having a relatively small fraction of the total births. 80% of the newborn infants with Down syndrome are born to women under age 35, who are not offered the invasive prenatal diagnostic techniques because the risk of a procedural complication is greater than the incidence of Down syndrome in a given fetus. Therefore, over the past decade, increased attention has been paid to noninvasive techniques of screening for fetal trisomy 21 that can be offered to all pregnant women. Trisomy 21 is used as a benchmark because it is the most common liveborn aneuploidy associated with mental retardation and serious congenital anomalies. At present, screening for trisomy 21 consists initially of assessing the maternal age, because the risk of fetal chromosomal abnormalities due to nondisjunction increases as maternal age advances. In addition, second-trimester maternal serum screening for proteins such as human chorionic gonadotropin (hCG), oestriol, and alphafetoprotein (AFP) has been incorporated into routine obstetric care. Results are measured in absolute values, expressed in terms of multiples of the median, and interpreted as a mathematical risk for fetal trisomy 21. Women who have a test result that indicates a fetal Down syndrome risk of greater than 1 in 270 are offered amniocentesis. Because of the large-scale success of the serum-screening programmes which have been employed in the United States, Europe and Asia, research has been directed towards improving both their sensitivity and specificity. Current tests detect 60–70% of the cases of trisomy 21 with a calculated false positive rate of 5% (Wald et al, 1988). Addition of another marker such as dimeric inhibin A raises the sensitivity to 75% (Wald et al, 1996). More recently, a study measuring serum markers expressed during the first trimester, b-hCG and pregnancy-associated plasma protein A (PAPP-A), concluded that the sensitivity of screening at 10– 13 weeks of gestation is nearly as good as the secondtrimester test (Haddow et al, 1998). An independent and newer method to screen for fetal trisomy 21 is the sonographic assessment of a fluid-filled space at the back of the fetal neck known as the nuchal translucency (NT) measurement. An increased NT measurement over that expected for gestational age is associated with an increased risk of fetal chromosome and cardiac abnormalities (Nicolaides et al, 1992; Hyett et al, 1997). In a study of 96 127 singleton pregnancies, the combination of maternal age and NT measurement enabled detection of 77% of the fetuses with trisomy 21 in the 5% of patients with the largest NTs (Snijders et al, 1998). However, by recommending amniocentesis or CVS following a positive screening test, 30 invasive tests are required to find one affected fetus. According to an editorial that accompanied the above study, antenatal screening research for Down syndrome is likely to place more emphasis on lowering the false-positive rate to 1% or less by discovering new markers and reconfiguring existing screening techniques (Haddow, 1998). It is into the existing context of noninvasive screening for Down syndrome that fetal cells in maternal blood must be placed. Successful isolation of fetal cells from maternal blood represents a source of fetal chromosomes or DNA obtained non-invasively by maternal venepuncture. This test could be used as a primary screen, a secondary screen designed to be used in concert with the aforementioned screening tests (to reduce the 5% false-positive rate) (Farina & Bianchi, 1998), or, ultimately, as a diagnostic test. This review will summarize the key areas related to this field: the clinical implications of this test for the clinical practice of obstetrics and gynaecology, the surprising insights into the biology of pregnancy that have come from the study of fetal cells in maternal blood, and the technical challenges associated with rare event cell separation. British Journal of Haematology, 1999, 105, 574–583
208 citations
TL;DR: Effective evaluation of fetal-maternal transfer of drugs must consider not only the components of the interhemal barrier of the fully developed placenta characteristic for each species, but also the placental structures functioning at each gestational stage of the fetus.
206 citations
TL;DR: It is demonstrated that active fetal immunization can serve as a safe and efficient vaccination strategy for the fetus and neonate and to characterize the ability of the fetal immune system to respond to in utero vaccination.
Abstract: Neonates face a high risk of infection because of the immaturity of their immune systems. Although the transplacental transfer of maternal antibodies to the fetus may convey improved postnatal immunity, this transfer occurs late in gestation and may fail to prevent in utero infection. Both fetal immunization and in utero exposure to antigen can result in a state of immunologic tolerance in the neonate. Tolerance induction of fetal and premature infant lymphocytes has become a paradigm for neonatal responsiveness. However, fetal IgM responses have been demonstrated to maternal immunization with tetanus toxoid and to congenital infections such as rubella, toxoplasma, cytomegalovirus and human immunodeficiency virus. Moreover, 1-week-old infants can respond to standard pediatric vaccination, and neonates immunized with polysaccharide antigens do not develop immunologic tolerance. Here, direct immunization of the baboon fetus with recombinant hepatitis B surface antigen produced a specific fetal IgG antibody response. No specific maternal antibody response was detected, eliminating the possibility of vertical antibody transmission to the fetus. Some infants also responded to later vaccinations with hepatitis B surface antigen, indicating that no immunological tolerance was induced by prior fetal immunization. These results characterize the ability of the fetal immune system to respond to in utero vaccination. We demonstrate that active fetal immunization can serve as a safe and efficient vaccination strategy for the fetus and neonate.
190 citations
TL;DR: This review will focus on the dynamic changes of the fetal circulation, the distribution of organ blood flow during normoxemia, and that during hypoxia and asphyxia caused by various experimental perturbations.
180 citations
TL;DR: The results indicate that the fetus is capable of mounting an independent noradrenaline stress response to a needle transgressing its trunk from 18 wk gestation and that the observed fetal responses are not due to direct transport from the mother.
Abstract: Fetal and maternal plasma noradrenaline responses to invasive procedures were determined in pregnancies of 18 to 37 wk gestation. Fetal umbilical venous blood sampling was performed either from the placental cord insertion, which is not innervated, or the intrahepatic vein, which is innervated, and thus may be more stressful for the fetus. Samples from diagnostic procedures, as well as from transfusion procedures, were compared between the two sites. Fetal plasma levels were significantly elevated in blood samples obtained from the intrahepatic vein compared with those from the placental cord insertion during diagnostic procedures [p < 0.05, geometric means and 95% confidence intervals (CI) were 0.67 nmol/L (0.43-1.04) and 0.36 nmol/L (0.25-0.54), respectively]. Plasma levels in samples taken before transfusion from the intrahepatic vein were also significantly higher than those from the placental cord insertion. After transfusion, there was a significant rise in fetal plasma noradrenaline levels at both sites; however, after transfusion through the intrahepatic vein, the rise was substantially greater than after transfusion through the placental cord insertion (p < 0.05, change, mean deltaNA, and 95% CI were 0.67 (0.37-1.22), and 0.20 (0.12-0.33), respectively). The deltaNA was significantly associated with the duration of the stimulus (the time the needle remained in situ) (p = 0.05, adjusted R2 = 0.48) and with gestational age. Maternal levels rose substantially and equally after transfusions at either site (mean deltaNA and 95% CI, 6.46 nmol/L, 1.74 to 11.18 and 9.49 nmol/L, 6.24 to 12.75 for the intrahepatic vein and placental cord insertion groups, respectively). There was no significant correlation between baseline fetal and maternal levels (r = 0.08, n = 41) or between deltaNA pre- and posttransfusion maternal and fetal values in either group. These results indicate that the fetus is capable of mounting an independent noradrenaline stress response to a needle transgressing its trunk from 18 wk gestation. The effect was observable in samples taken at a mean of 5.6 min after needling. The lack of correlation between maternal and fetal levels suggests that virtually no noradrenaline crosses the placenta directly, and that the observed fetal responses are not due to direct transport from the mother.
TL;DR: It is concluded that GH resistance and consequent reduction in peripheral IGF-I levels is associated with delay of female puberty, alterations in fetal and placental growth, delay of parturition, and reduced litter size.
Abstract: Mice homozygous for targeted disruption of the GH receptor/GH binding protein gene (GH-R-KO mice; −/−) exhibit reduced plasma IGF-I levels, elevated plasma GH levels, and dwarf phenotype. Although most GH-R-KO mice are fertile, age at first conception is greatly delayed in −/− x− /− matings. Here we report that the age of vaginal opening is significantly delayed in GH-R-KO vs. normal mice, but it can be advanced by treatment with recombinant human (rh)IGF-I. In pregnant GH-R-KO females, fetal size is reduced and pregnancy is prolonged while placental weight is, unexpectedly, increased. Alterations in fetal and placental weight are related to maternal rather than fetal genotype. Moreover, litter size and body weight of newborn pups are significantly reduced in GH-R-KO vs. normal females. Reduction in litter size reflects both dam and sire effects. We conclude that GH resistance and consequent reduction in peripheral IGF-I levels is associated with delay of female puberty, alterations in fetal and placental...
TL;DR: The focus of this review is on the biology of the 11beta-HSD enzymes in the placenta, where they also regulate passage of maternal glucocorticoids to the fetus, and because some progesterone effects are exerted via the GR, placental 11 beta- HSD may regulate progester one-glucocortioid competition for access to this receptor and thereby affect the biological actions of both steroids in the Placenta.
Abstract: Target cell metabolism of glucocorticoids is now recognized as an important modulator of ligand access to the glucocorticoid receptor (GR). This metabolism occurs via two distinct 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes (types 1 and 2) that catalyze interconversion of active glucocorticoids (cortisol and corticosterone) and their inactive 11-keto products (cortisone and 11-dehydrocorticosterone, respectively). The focus of this review is on the biology of the 11beta-HSD enzymes in the placenta, where they also regulate passage of maternal glucocorticoids to the fetus. The presence of this metabolic barrier at the maternal-fetal interface is potentially crucial to fetal growth and development, since maternal glucocorticoid levels are elevated in pregnancy and since excess glucocorticoid exposure in fetal life has detrimental effects on prenatal growth and increases susceptibility to disease in subsequent adult life. In primates, transplacental glucocorticoid passage also appears to play an important role in the induction of an autonomous fetal hypothalamic-pituitary-adrenal axis near term. Placental 11beta-HSD is also likely to modulate glucocorticoid actions within the placenta, per se, by regulating their access to placental GR. Moreover, because some progesterone effects are exerted via the GR, placental 11beta-HSD may regulate progesterone-glucocorticoid competition for access to this receptor and thereby affect the biological actions of both steroids in the placenta.
TL;DR: Collectively, these studies show that fetal growth and viability are jeopardized in the absence of maternal GM-CSF, suggesting that GM- CSF of either maternal or fetal origin is required for optimal growth and survival of the fetus in mice.
Abstract: Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been identified as a potentially important mediator of intercellular communication in the female reproductive tract, with principal target cells being the large populations of myeloid leukocytes in the cycling and pregnant uterus, the preimplantation embryo, and trophoblast cells of the developing placenta To determine the physiological significance of this cytokine in reproduction, the fertility of genetically GM-CSF-deficient (GM-/-) mice was examined Implantation rates were normal in GM-/- mice, and viable pups were produced However, the mean litter sizes of GM-/- x GM-/- breeding pairs were 25% smaller at weaning than those of GM+/- x GM+/- pairs, due to fetal death late in gestation and early in postnatal life, with a disproportionate loss of male pups On Day 17 of pregnancy, the mean number of resorbing and malformed fetuses was twice as high in pregnant GM-/- females (21%, vs 11% in GM+/- females); the mean fetal weight and the mean fetal:placental ratio in surviving conceptuses were diminished by 7% and 6%, respectively; and the number of very small fetuses (< 500 mg) was 9-times as high (23% vs 25%) Mortality during the first 3 wk of life was 45-times as high in pups born to GM-/- mothers (9%, vs 2% in GM+/- females), and diminished size persisted in GM-/- pups, particularly males, into adulthood The detrimental effect of maternal GM-CSF deficiency was less apparent when GM-/- females were mated with GM+/+ males; litter sizes at birth and at weaning were not significantly smaller than in GM+/- matings, and fetal weights and fetal:placental ratios were also comparable When polymerase chain reaction was used to genotype embryonic tissue in heterozygote matings, GM-/- fetuses from GM-/- females were found to be smaller than their GM+/- littermates and smaller than GM-/- fetuses gestated in GM+/- females The size and distribution of uterine granulocyte and macrophage populations were normal during the estrous cycle, during early pregnancy, and in midgestation Analysis of placental structure revealed that the ratio of labyrinthine to spongiotrophoblast areas was reduced by approximately 28% in GM-/- placentae, and the proportion of vacuolated trophoblast "glycogen cells" in the spongiotrophoblast layer was diminished Compromised placental function as a result of subtle developmental aberrations may therefore partially account for embryonic growth retardation in GM-CSF-deficient mice Collectively, these studies show that fetal growth and viability are jeopardized in the absence of maternal GM-CSF The detrimental effects are most clearly evident when the conceptus is also GM-CSF deficient, suggesting that GM-CSF of either maternal or fetal origin is required for optimal growth and survival of the fetus in mice
TL;DR: It is reported that the pregnant rat uterus expresses extremely high levels of the type 3 iodothyronine deiodinase (D3), which inactivates thyroxine and 3,3', 5-triiodothyronines by 5-deiodination, and these findings strongly suggest that the pregnancy plays a critical role in determining the level of exposure of the fetus to maternal thyroid hormones.
Abstract: Although thyroid hormones are critically important for the coordination of morphogenic processes in the fetus and neonate, premature exposure of the embryo to levels of the hormones present in the adult is detrimental and can result in growth retardation, malformations, and even death. We report here that the pregnant rat uterus expresses extremely high levels of the type 3 iodothyronine deiodinase (D3), which inactivates thyroxine and 3,3', 5-triiodothyronine by 5-deiodination. Both D3 mRNA and activity were present at the implantation site as early as gestational day 9 (E9), when expression was localized using in situ hybridization to uterine mesometrial and antimesometrial decidual tissue. At later stages of gestation, uterine D3 activity remained very high, and the levels exceeded those observed in the placenta and in fetal tissues. After days E12 and E13, as decidual tissues regressed, D3 expression became localized to the epithelial cells lining the recanalized uterine lumen that surrounds the fetal cavity. These findings strongly suggest that the pregnant uterus, in addition to the placenta, plays a critical role in determining the level of exposure of the fetus to maternal thyroid hormones.
TL;DR: Most nonobstetric procedures result from circumstances common for the maternal age group, such as appendicitis, cholelithiasis, ovarian cysts or ovarian torsion, breast tumors, trauma, and more rarely for life-threatening cardiac or neurosurgical conditions or organ transplantation.
Abstract: ESTIMATES suggest that 1% or 2% of pregnant women undergo anesthesia for surgical procedures unrelated to delivery in the United States, but pregnancy may be unrecognized at the time of surgery, and there are no formal reporting mechanisms for data collection. Cerclage procedures for cervical incompetence typically are performed at the end of the first trimester. Most nonobstetric procedures result from circumstances common for the maternal age group, such as appendicitis, cholelithiasis, ovarian cysts or ovarian torsion, breast tumors, trauma, and more rarely for life-threatening cardiac or neurosurgical conditions or organ transplantation. Anesthetic considerations for surgery during pregnancy include concern for the safety of two patients, the mother and fetus. Alterations in maternal anatomy and physiology induced by pregnancy have clinical anesthetic implications and present potential hazards for the mother and fetus undergoing anesthesia. The fetus may be subjected to hazard by (1) the risk of intraoperative hypoxemia or asphyxia caused by reduced uterine blood flow, maternal hypotension, excessive maternal mechanical ventilation or maternal hypoxia, depression of the fetal cardiovascular system or central nervous system from placental passage of anesthetic agents; (2) exposure to teratogenic drugs; and (3) the risk for preterm delivery as a consequence of the surgical procedure or drugs administered. In most circumstances, the fetus is a passive recipient of anesthesia administered to the mother, suffers no blood loss, and undergoes passive changes rather than direct stress or hemodynamic alterations caused by surgery (fig. 1).
TL;DR: Administration of repeated doses of betamethasone directly to the sheep fetus does not produce the growth-restricting effects induced by maternal administration and does not affect the placental/birthweight ratio.
Abstract: Objective: Previous studies have shown that repeated doses of corticosteroids given to pregnant sheep improve postnatal lung function, but restrict fetal growth. Repeated administration of corticosteroids directly to the fetus also enhances postnatal lung function. The purpose of the present study was to investigate and characterize the relative effects on growth of repeated maternal and fetal treatments by study of body, organ, and placental weights.Methods: Date-bred pregnant sheep were given intramuscular betamethasone or saline to either the mother or fetus on three occasions at weekly intervals commencing at 104 days gestation, followed by cesarean section at 125 days. Twenty-two animals which had received three doses of betamethasone were compared with 21 which had received a single dose at 104 days and with 12 saline-treated controls.Results: Repeated maternal doses of betamethasone resulted in reductions in birthweight and weights of the placenta and major organs. Direct fetal injection did not af...
TL;DR: Investigation of clinical and sonographic parameters, in particular Doppler blood flow measurements, in severe second‐trimester twin–twin transfusion syndrome before and after endoscopic laser coagulation of the placental vascular anastomoses determines whether fetal blood flow measured could help to estimate the probability of fetal survival.
Abstract: Objective
The aim of this study was to investigate clinical and sonographic parameters, in particular Doppler blood flow measurements, in severe second-trimester twin–twin transfusion syndrome before and after endoscopic laser coagulation of the placental vascular anastomoses, to correlate these data with fetal outcome and to determine whether fetal blood flow measurements could help to estimate the probability of fetal survival.
Methods
In 121 cases of severe twin–twin transfusion syndrome examined between 17 and 26 weeks of gestation, the following investigations were performed: fetal biometry, placental location, deepest pool of amniotic fluid, echocardiography and Doppler sonography of the umbilical arteries and the ductus venosus of both twins before and after fetoscopic laser ablation of the placental anastomoses.
Results
The overall survival rate was 64% (156/242). Both fetuses survived in 48% (58/121) and one fetus survived in 33% (40/121), resulting in 81% (98/121) of pregnancies with at least one survivor. Gestational age at the time of the procedure and placental location had no significant influence on fetal survival. The amniotic fluid volume drained after laser coagulation correlated significantly (p = 0.038) with the risk of miscarriage or extremely premature delivery within 4 weeks of the procedure. Intertwin discrepancy in abdominal circumference showed a significant negative correlation (p = 0.004) with the probability for survival of donor fetuses. Before the procedure, 19% (23/121) of donor twins and 5% (6/121) of recipient twins showed absent or reversed end-diastolic flow in the umbilical artery (p = 0.001). This finding had no significant influence on the survival rate of donors. An increase of waveform indices in the umbilical artery 1 day after the procedure compared to immediately after the procedure correlated significantly with a lower probability for survival of donors (p = 0.042) and recipients (p = 0.018). Before the procedure, 37% (45/121) of recipient twins and 9% (10/113) of donor twins showed absent or reversed flow during atrial contraction in the ductus venosus (p < 0.0001). This finding had a significant negative influence on the survival rate of recipient fetuses (p = 0.02). Furthermore, an increase of waveform indices in the ductus venosus 1 day after the procedure compared to immediately after the procedure correlated significantly with a lower probability of survival in recipients (p = 0.005).
Conclusions
Fetoscopic laser coagulation of the placental vascular anastomoses in severe mid-trimester twin–twin transfusion is a potentially corrective and effective, minimally invasive procedure. Doppler investigation of the umbilical and fetal circulations provides important information on the fetal condition, prognosis and therapeutic effects of the intervention. Signs of congestive heart failure in the recipient may reduce the probability of survival, whereas increased placental resistance in the donor before the procedure is not necessarily associated with a reduction in the probability of survival after laser coagulation. Copyright © 1999 International Society of Ultrasound in Obstetrics and Gynecology
TL;DR: The duration-dependent effects of prenatal stress on the development of fetal hypothalamic paraventricular nucleus neurons, including corticotropin-releasing factor-containing neurons, are suggested, which may contribute to behavioral changes of the offspring after birth.
TL;DR: The data suggest that "pathologic" fetal acidemia is indicated by an umbilical artery pH <7.00 with a metabolic component, which is the most important variable in subsequent neonatal morbidity.
TL;DR: Abnormal elevations in corticotropin-releasing hormone, which may be a hormonal response to stressors arising in either the mother, placenta, or fetus, may prove to participate in the premature onset of parturition.
TL;DR: Analysis of the expression of the two isoforms of the central prostaglandin synthetic enzyme, cyclo-oxygenase (COX-1 and COX-2), in human fetal membranes throughout pregnancy, at mRNA, protein and activity levels suggests that it is up-regulation of COx-2, rather than of COZ-1, which mediates increased prostaglandsin synthesis within the fetal membranes at term.
Abstract: Human labour is associated with increased prostaglandin synthesis within the fetal membranes. We have studied the expression of the two isoforms of the central prostaglandin synthetic enzyme, cyclo-oxygenase (COX-1 and COX-2), in human fetal membranes throughout pregnancy, at mRNA, protein and activity levels. COX-1 mRNA expression was low in human amnion and chorion-decidua and did not change with gestational age. COX-2 mRNA expression in fetal membranes increased with gestational age, with significant up-regulation prior to the onset of labour and in association with labour. Protein concentrations of COX-1 did not change, whilst concentrations of COX-2 increased from the first to the third trimester. COX activity increased with gestational age and in association with labour, although prostaglandin production in fetal membranes collected after labour was reduced, suggesting reduced substrate supply. These data suggest that it is up-regulation of COX-2, rather than of COX-1, which mediates increased prostaglandin synthesis within the fetal membranes at term. Much of the increase in COX-2 expression precedes the onset of labour, suggesting that it is a cause, rather than a consequence, of labour.
TL;DR: The effect of synthetic glucocorticoid on the developing brain GR and MR systems is sex-specific and is confined to very specific regions of the hippocampus.
TL;DR: The authors' understanding of fetal hepatic elimination processes has advanced steadily over the years, but future developments, however, should consider more fully the influence of the unique physiological milieu of the fetal liver, in addition to the expression and activity of drug metabolizing enzymes.
TL;DR: Growth of the human fetal adrenal cortex involves cellular hyperplasia, mainly in the DZ and to a lesser extent in the FZ, which is probably dependent on ACTH; and apoptosis occurs predominantly in the inner cortical compartment and may be responsible for the rapid regression of theFZ after birth, a process that may be regulated by activin A and/or TGFbeta.
Abstract: After 10–15 weeks of gestation, the human fetal adrenal cortex undergoes rapid growth due to enlargement of a specialized cortical compartment known as the fetal zone (FZ). Soon after birth, the FZ regresses and the adult zonation pattern develops at least in part from cells derived from the persistent definitive zone (DZ), a thin layer of tightly packed cells surrounding the FZ. We postulated that growth of the fetal adrenal cortex involves zone-specific cellular hyperplasia, whereas the postnatal involution of the FZ is due to apoptosis. Therefore, we investigated the pattern of cellular proliferation and death in the FZ and DZ of the human fetal and postnatal adrenal cortex using immunohistochemical staining for proliferating cell nuclear antigen as a marker of mitosis and in situ detection of DNA fragmentation as a marker of apoptosis. Between 10–14 weeks’ gestation, the mitotic indexes (percentage of proliferating cell nuclear antigen-positive cells) in the DZ (26.46 ± 2.95%) and in the FZ (21.26 ± 2...
TL;DR: Although the levels of thyroid hormones in the maternal and fetal plasma were not affected by MeHg, 5-DI decreased and 5'-DI increased in the fetal brain, as if they had responded to hypothyroidism, these changes in enzymatic activities may result in a harmful excess of T3 in the prenatal brain.
TL;DR: Compared with adults, plasma T3 concentrations in the human fetus are decreased, whereas levels of rT3 and the different iodothyronine sulfates, T4S, T3S, rT 3S and 3,3'-T2S, are increased.
TL;DR: There was a strong correlation between absolute umbilical vein flow and the fetal head and abdominal circumferences and the triplex mode ultrasonographic technique can play an innovative role in obtaining quick and reproducible measurements of umbilicals vein blood flow.
TL;DR: The placenta is a rather unique endocrine organ, growing and developing during pregnancy but disappearing at parturition, suggesting that a distinct set of hormones are required to bring about the physiological changes of pregnancy rather than simply producing more of certain hormones.
Abstract: After fertilization, the next major hurdle for reproduction in eutherian mammals is trophoblast differentiation, which is required for implantation. This in turn is followed lock step by the rapid assembly of these cells into a functional placenta. Although there is a great deal of species-to-species variation in the assemblage process per se, the functional results are always the same. For the remainder of gestation, whether an additional 16 days in a mouse or 9 months in a human, the development of the embryo/fetus and the health of the mother critically depend on the placenta. In humans, this fact is graphically illustrated by the spectrum of pregnancy complications that are associated with just one type of pathology, superficial attachment of the placenta to the uterus. In some cases fetal growth stalls, leading to intrauterine growth retardation. In other instances the effects extend to the mother, who may suddenly show signs of widespread vascular damage so severe that death may quickly ensue, hence the name eclampsia (Gk. eklampsis, sudden flash or development). Although the placenta is a transient organ, it has evolved to meet the significant challenge of accommodating the nutritional and growth-regulatory needs of the developing fetus within the overall physiological environment of the mother. Not only must maternal physiology change to meet these needs of the fetus, but changes must also occur to prepare the mother for the distinct needs of the newborn after parturition. For successful reproduction, the physiology of pregnancy in the mother must therefore be significantly different from the physiology of the nonpregnant adult female, with differences in numerous systems, including blood vessel growth, hematopoiesis, immune response, metabolism, steroid hormone production, behavior, and mammary development. The widespread physiological changes that occur during pregnancy must be temporally coordinated among many organs and tissues, an organizational task that typically falls to circulating hormones, and a strong case can be made for the placenta as the most important source of these hormones that reprogram maternal physiology during pregnancy. The placenta is a rather unique endocrine organ. First, since the hormone-producing placental trophoblast cells are derived from the fertilized egg, the placenta is genetically distinct from the maternal targets of the placental hormones (except, of course, in matings of highly inbred parents, such as inbred strains of mice). Second, the organ is transient, growing and developing during pregnancy but disappearing at parturition. Third, placental hormones are often present in the circulation at concentrations far in excess of what is found for similar hormones in the nonpregnant adult. And fourth, the placenta produces a number of hormones that are not otherwise synthesized in the organism, suggesting that a distinct set of hormones are required to bring about the physiological changes of pregnancy rather than simply producing more of certain hormones. In these properties, the placenta can be seen to resemble a “pharmacological” organ, dispensing high levels of foreign compounds over a restricted time period. The placental hormones almost certainly target receptors and signaling pathways in the mother that exist in the nonpregnant state, again much like pharmaceuticals, and therefore the novel and highly expressed placental hormones may provide valuable probes to identify receptors and signaling pathways that have otherwise remained obscure. In rodents, ruminants, and primates (including humans), prominent among these placental-specific hor0888-8809/99/$3.00/0 Molecular Endocrinology Copyright © 1999 by The Endocrine Society