Radiation and pregnancy

Irradiation during pregnancy may occur either as the result of radioactive pollution of the environment, or during a medical procedure using x-rays or radionuclides. While the former is usually unforeseeable, the latter is known and accepted by both physician and patient.Recent statistics estimate that about one quarter of pregnant women have had a radiographic experience during the pregnancy, either for obstetrical reasons or in the course of medical and dental examinations. The amount of radiation delivered to the fetus is in the range of one rad or less. Radionuclidic procedures may result in fetal radiocontamination, chiefly after placental transfer and fetal uptake. Radioiodine, radioactive calcium and selenomethionine are dangerous for the fetus, since they cross the placenta freely and are taken up by fetal tissues. The labelled proteins, radiocolloids and some mercury compounds remain in the maternal compartment and therefore can affect the fetus only through their gamma radiation at some distance from the fetus.The teratogenic effect, the leukemogenic threshold and the lowered resistance to neonatal infections have been demonstrated after irradiation with doses far higher than those encountered during diagnostic applications of ionizing radiation. Statistical data suggest an increase of susceptibility to leukemia in infancy after intra-uterine irradiation at a diagnostic level. Cytogenic analysis may.... offer valuable data for the establishment of the extent of radiation damage.     

Effects of alcohol on the fetus: impact and prevention.

In the spectrum of adverse effects on the fetus or infant associated with maternal drinking during pregnancy the most dramatic is the fetal alcohol syndrome, a pattern of malformation that has been associated with maternal alcohol abuse. Other undesirable outcomes of pregnancy linked to alcohol exposure in utero include growth deficiency, major and minor anomalies, decrements in mental and motor performance, and fetal and perinatal wastage. Alcohol, like other teratogens, does not uniformly affect all those exposed to it. Rather, there seems to be a continuum of effects of alcohol on the fetus with increasingly severe outcomes generally associated with higher intakes of alcohol by the mother. The cost of fetal damage associated with alcohol exposure is very high. A program to decrease the incidence of fetal alcohol effects is therefore imperative. The cornerstone of such a program must be not only education of the public but also careful training of all professionals who provide health care for pregnant women.     

彩色多普勒超声检查对胎儿颅内畸形筛查的应用价值及染色体异常分析

摘要 目的：探讨彩色多普勒超声检查对胎儿颅内畸形筛查的应用价值,并进行染色体异常分析。方法：选择2016年2月至2019年5月本院收治的进行胎儿颅内畸形筛查的高危孕妇120例,所有孕妇都给予彩色多普勒二维超声与三维超声筛查,对超声筛查异常者进行染色体异常分析,记录预后情况。结果：在120例孕妇中,二维超声诊断为胎儿颅内畸形12例,三维超声诊断为13例(预后都确诊为胎儿颅内畸形)。染色体核型筛查检出胎儿颅内畸形12例,其中21-三体综合征8例,18-三体综合征3例,13-三体综合征1例。确诊为胎儿颅内畸形的孕妇超声NT值都显著高于非胎儿颅内畸形孕妇,差异都有统计学意义(P<0.05)。孕妇选择终止妊娠10例,选择继续妊娠3例,继续妊娠3例胎儿都最终死亡。结论：产前彩色多普勒超声结合染色体核型在胎儿颅内畸形筛查中具有很高的价值,两者可互相补充,共同发挥诊断与预后评估价值。     

Rights of and duties to non-consenting patients--informed refusal in the developing world

The principle of informed refusal poses a specific problem when it is invoked by a pregnant woman who, in spite of having accepted her pregnancy, refuses the diagnostic and/or therapeutic measures that would ensure the well-being of her endangered fetus. Guidelines issued by professional bodies in the developed world are conflicting: either they allow autonomy and informed consent to be overruled to the benefit of the fetus, or they recommend the full respect of these principles. A number of medical ethicists advocate the overruling of alleged irrational or unreasonable refusal for the benefit of the fetus. The present essay supports the view of fetal rights to health and to life based on the principle that an 'accepted' fetus is a 'third person'. In developing countries, however, the implementation of the latter principle is likely to be in conflict with a 'communitarian' perception of the individual -- in this case, the pregnant woman. Within the scope of the limitations to the right to autonomy of J.S. Mill's 'harm principle', the South African Patients' Charter makes provision for informed refusal. The fact that, in practice, it is not implemented illustrates the well-known difficulty of applying Western bioethical principles in real life in the developing world.     

Constriction of fetal ductus arteriosus by non-steroidal anti-inflammatory drugs

Transplacental effects of 24 non-steroidal anti-inflammatory drugs (NSAIDs) on the fetal ductus arteriosus were studied in full-term pregnant rats using the whole-body freezing technique. All sixteen acidic NSAIDs constricted the fetal ductus in a dose-dependent relationship, but considerable differences in the intensity of effect was noticed with the clinical dose of each drug. Six of the eight basic NSAIDs did not constrict the fetal ductus at 50 to 100 times the usual clinical dose. It is concluded that acidic NSAIDs probably should not be administered to pregnant women. However, it may be established in the future that some basic NSAIDs can be administered safely to pregnant women without hazardous effect on the fetus.     

Timed maternal melatonin treatment reverses circadian disruption of the fetal adrenal clock imposed by exposure to constant light

Surprisingly, in our modern 24/7 society, there is scant information on the impact of developmental chronodisruption like the one experienced by shift worker pregnant women on fetal and postnatal physiology. There are important differences between the maternal and fetal circadian systems; for instance, the suprachiasmatic nucleus is the master clock in the mother but not in the fetus. Despite this, several tissues/organs display circadian oscillations in the fetus. Our hypothesis is that the maternal plasma melatonin rhythm drives the fetal circadian system, which in turn relies this information to other fetal tissues through corticosterone rhythmic signaling. The present data show that suppression of the maternal plasma melatonin circadian rhythm, secondary to exposure of pregnant rats to constant light along the second half of gestation, had several effects on fetal development. First, it induced intrauterine growth retardation. Second, in the fetal adrenal in vivo it markedly affected the mRNA expression level of clock genes and clock-controlled genes as well as it lowered the content and precluded the rhythm of corticosterone. Third, an altered in vitro fetal adrenal response to ACTH of both, corticosterone production and relative expression of clock genes and steroidogenic genes was observed. All these changes were reversed when the mother received a daily dose of melatonin during the subjective night; supporting a role of melatonin on overall fetal development and pointing to it as a 'time giver' for the fetal adrenal gland. Thus, the present results collectively support that the maternal circadian rhythm of melatonin is a key signal for the generation and/or synchronization of the circadian rhythms in the fetal adrenal gland. In turn, low levels and lack of a circadian rhythm of fetal corticosterone may be responsible of fetal growth restriction; potentially inducing long term effects in the offspring, possibility that warrants further research.     

Blunt abdominal trauma in pregnancy.

Two cases are presented in which the effects of blunt trauma to a pregnant woman''s abdomen were apparently minor but resulted in fetal death. Blunt trauma may result in serious injury to the fetus or the placenta. Three-point restraint systems should be worn by pregnant women travelling in automobiles to minimize the risks to mother and fetus. Awareness of the potential for injury in these circumstances is essential to reduce the risks to the fetus.     

Fetal and maternal body temperatures measured by radiotelemetry in near-term sheep during thermal stress.

Using implanted radiotelemeters, we have measured amniotic temperature and fetal lamb and pregnant ewe body temperatures continuously over the last 34 days of gestation and during conditions of thermal stress. Body temperature of the fetus was approximately 0.6 degrees C higher than that of the mother, and the fetomaternal temperature difference remained constant over the last 25 days of gestation, until the immediate prepartum period, when it rose. During exposure to mild heat stress (35 degrees C dry-bulb temperature, 24 degrees C wet-bulb temperature), ewe and fetal body temperatures rose, but fetal temperature rose at a slower rate. Thus the fetomaternal temperature gradient fell significantly in the initial exposure period. In an environment of 4 degrees C, body temperature of the pregnant ewes fell, but the fetomaternal gradient did not change significantly. During maternal fever, heat loss from the fetus was compromised; body temperature of the fetus rose more than that of the mother, and the fetomaternal temperature gradient rose significantly. We suggest that mild heat or cold exposure in pregnant animals constitutes little risk of fetal thermal stress. During maternal fever, however, the fetus may be at risk of thermal injury.     

Bioethics for clinicians: 12. Ethical dilemmas that arise in the care of pregnant women: rethinking "maternal-fetal conflicts".

When a pregnant woman makes a decision or acts in a manner that may be detrimental to the health and well-being of her fetus, her physician may be faced with an ethical dilemma. Is the physician''s primary duty to respect the woman''s autonomy, or to promote behaviour that may be in the best interest of the fetus? The controversial concept of "fetal rights" or the "fetus as a patient" contributes to the notion that the pregnant woman and her fetus are potential adversaries. However, Canadian law has upheld women''s right to life, liberty and security of the person and has not recognized fetal rights. If a woman is competent and refuses medical advice, her decision must be respected even if the physician believes that her fetus will suffer as a result. Coercion of the woman is not permissible no matter what appears to be in the best interest of the fetus.     

Protecting Future Children from In‐Utero Harm

The actions of pregnant women can cause harm to their future children. However, even if the possible harm is serious and likely to occur, the law will generally not intervene. A pregnant woman is an autonomous person who is entitled to make her own decisions. A fetus in‐utero has no legal right to protection. In striking contrast, the child, if born alive, may sue for injury in‐utero; and the child is entitled to be protected by being removed from her parents if necessary for her protection. Indeed, there is a legal obligation for health professionals to report suspected harm, and for authorities to protect the child's wellbeing. We ask whether such contradictory responses are justified. Should the law intervene where a pregnant woman's actions risk serious and preventable fetal injury? The argument for legal intervention to protect a fetus is sometimes linked to the concept of ‘fetal personhood’ and the moral status of the fetus. In this article we will suggest that even if the fetus is not regarded as a separate person, and does not have the legal or moral status of a child, indeed, even if the fetus is regarded as having no legal or moral status, there is an ethical and legal case for intervening to prevent serious harm to a future child. We examine the arguments for and against intervention on behalf of the future child, drawing on the example of excessive maternal alcohol intake.     

西藏小型猪胚胎成纤维细胞的分离培养及性别鉴定

目的探索和建立西藏小型猪胚胎成纤维细胞体外分离培养及性别鉴定的技术方法。方法取35d的西藏小型猪胚胎分离胚胎成纤维细胞,进行体外原代培养及传代培养,观察细胞成纤维细胞的形态和生长状况。根据猪Y染色体上性别决定基因SRY设计引物进行性别鉴定,同时以β珠蛋白作为内参基因,建立PCR反应体系鉴别胚胎的性别。结果西藏小型猪胚胎成纤维体外分离后,呈贴壁生长,快速增殖。PCR性别鉴定结果表明雄性胚胎细胞可扩增出一特异性SRY基因条带,而雌性则没有。该法可快速鉴定胚胎的性别,可用于体细胞克隆动物早期性别鉴定。结论研究结果表明利用胶原酶消化法所获得的西藏小型猪胚胎成纤维细胞可在体外稳定培养并传代,利用PCR鉴定猪胎儿性别具有简单、快速、准确的特点,可应用于克隆猪研究中体细胞系的早期性别鉴定。     

Prostaglandin F and E levels in the conceptus, uterus and plasma during early pregnancy in the ewe

Concentrations of prostaglandins E and F (PGE and PGF) were measured in the embryo or fetus, extra embryonic or fetal membranes (membranes), intercaruncular and caruncular endometrium and plasma collected from uterine and ovarian arterial and venous vessels from separate groups of ewes laparotomized at 5 day intervals from day 10 to day 55 of pregnancy. Our purpose was to investigate the role of prostaglandins E and F in the maternal recognition of pregnancy, implantation and early placental function. Our data suggest that the initial maintenance of the corpus luteum in the pregnant ewe does not involve a reduction in PGF production, compared to pregnant ewes; but a change in the pattern of PGF secretion. This is accompanied by an elevation in PGE production of similar magnitude to that observed in non pregnant ewes. The extra embryonic/fetal membranes appear to be the major source of elevated PGF levels in the maternal circulation prior to day 30 of pregnancy. Between days 35 and 55 of gestation the rising PGF levels in maternal serum probably come from the fetus. Over the same period PGE levels rise in the fetus and intercaruncular endometrium, but PGE secretion into the maternal circulation is not enhanced. A role for PGF and PGE in fetal, placental and uterine growth is suggested; placental and uterine endocrine function may also be targets.     

Prostaglandin F and E levels in the conceptus, uterus and plasma during early pregnancy in the ewe

Concentrations of prostaglandins E and F (PGE and PGF) were measured in the embryo or fetus, extra embryonic or fetal membranes (membranes), intercaruncular and caruncular endometrium and plasma collected from uterine and ovarian arterial and venous vessels from separate groups of ewes laparotomized at 5 day intervals from day 10 to day 55 of pregnancy. Our purpose was to investigate the role of prostaglandins E and F in the maternal recognition of pregnancy, implantation and early placental function. Our data suggest that the initial maintenance of the corpus luteum in the pregnant ewe does not involve a reduction in PGF production, compared to pregnant ewes; but a change in the pattern of PGF secretion. This is accompanied by an elevation in PGE production of similar magnitude to that observed in non pregnant ewes. The extra embryonic/fetal membranes appear to be the major source of elevated PGF levels in the maternal circulation prior to day 30 of pregnancy. Between days 35 and 55 of gestation the rising PGF levels in maternal serum probably come from the fetus. Over the same period PGE levels rise in the fetus and intercaruncular endometrium, but PGE secretion into the maternal circulation is not enhanced. A role for PGF and PGE in fetal, placental and uterine growth is suggested; placental and uterine endocrine function may also be targets.     

Analysis of cell-free fetal DNA in plasma and serum of pregnant women.

Sixty blood samples from pregnant women during gestational weeks 9-28 were investigated. Cell-free fetal DNA was extracted from maternal plasma or serum to be detected by nested PCR for determination of fetal gender. The SRY gene as a marker for fetal Y chromosome was detected in 34/36 women carrying a male fetus. In 3/24 women carrying female fetuses, the SRY sequence was also detected. Overall, fetal sex was correctly predicted in 91.7% of the cases. Therefore, the new, non-invasive method of prenatal diagnosis of fetal gender for women at risk of producing children with X-linked disorders is reliable, secure, and can substantially reduce invasive prenatal tests.     

Tissue distribution of cocaine in the pregnant rat

Cocaine hydrochloride was administered by single intraperitoneal (IP) doses to pregnant rats at day 18 or 19 of gestation. Plasma and tissue cocaine and norcocaine concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic analysis of concentration versus time data showed rapid distribution of cocaine and its metabolite to maternal and fetal tissues. The area under the cocaine concentration versus time curve (AUC) in fetus compared to maternal plasma was 3.33. The half-life of cocaine in the maternal plasma and fetus was 46 and 55 minutes, respectively, similar to values reported for cocaine elimination half-life in human plasma. The order of cocaine concentrations was placenta greater than fetal liver greater than maternal heart greater than whole fetus greater than fetal brain greater than maternal brain = maternal plasma. Norcocaine concentrations were usually less than 20% of cocaine concentrations in plasma and tissues. These results support extensive fetal exposure to cocaine following administration to pregnant rodents. Pharmacodynamic studies of cocaine in pregnancy should consider the effects of the drug on the developing fetus.     

Transfer of antibodies directed to paternal major histocompatibility class I antigens from pregnant mice to the developing fetus

The placental transmission of antibodies directed toward paternal MHC Class I antigens to the developing fetus was studied to assess their effect on the expression of MHC antigens during fetal development and on the development of immune function. 125I-monoclonal anti-paternal MHC antibodies injected i.v. into pregnant mice on day 15 of gestation were efficiently transferred to the fetus within 24 hr in a dose-dependent manner. Biochemical studies on the transferred radioactivity showed that intact antibodies accumulated in the fetus for up to 3 days after antibody injection. During the same period, antibodies were eliminated from the maternal system. The transfer and accumulation of anti-MHC antibodies were independent of the MHC haplotype of the fetus. The pathway of antibody transfer and the localization of transmitted antibodies in the fetus were studied by autoradiographic analysis of the entire fetoplacental unit 24 hr after the injection of anti-paternal MHC antibodies. Our results indicate that antibodies are transferred by way of the placenta and yolk sac, and reach the fetus predominantly via the circulation. Within the embryo proper, the highest levels of antibody were found in the order of blood greater than thymus greater than fetal liver. Most other fetal organs, with the exception of brain and cartilage, showed antibody accumulation, but to a lesser extent. This pattern of antibody distribution over different tissues was similar for allogeneic and syngeneic fetuses. These findings demonstrate that various fetal tissues, including developing lymphoid cells can be directly exposed to the maternally transmitted anti-MHC antibodies, with possible functional consequences on the development of the fetal immune system.     

Drugs of abuse and human placenta

Drugs of abuse such as cocaine and amphetamines, when used by pregnant women, exert deleterious effects on the fetus. These drugs produce their effects through inhibition of the serotonin transporter, norepinephrine transporter, and dopamine transporter. The inhibition can occur in the pregnant mother as well as in the fetus. These events contribute to the detrimental effects of these drugs on the fetus. However, the role of placenta, which serves as the link between the pregnant mother and the fetus, in the process remains understudied. It has been assumed that the placenta did not play any direct role in the process except that it allowed the passage of these drugs from maternal circulation into fetal circulation. This was before the discovery that the placenta expresses two of the three monoamine transporters. The serotonin transporter and the norepinephrine transporter are expressed on the maternal-facing side of the syncytiotrophoblast, thus exposed to the inhibitory actions of cocaine and amphetamines if present in maternal blood. Inhibition of these transporters in the placenta could lead to elevation of serotonin and norepinephrine in the intervillous space that may cause uterine contraction and vasoconstriction, resulting in premature delivery, decreased placental blood flow, and intrauterine growth retardation. Thus, the placenta is actually a direct target for these abusable drugs. Since the placental serotonin transporter and norepinephrine transporter are also inhibited by many antidepressants, therapeutic use of these drugs in pregnant women may have similar detrimental effects on placental function and fetal growth and development.     

Acute effects of ethanol on brain,plasma and adrenal monoamine concentrations in virgin and pregnant rats and their fetuses

The dose-response relationship in brain, plasma, and adrenal monoamine changes after acute oral ethanol administration (1, 2, 4 g/kg body wt) was studied in virgin rats to determine whether the response to the highest dose differed in 21-day pregnant animals, and to assess the potential consequences of ethanol on the neurotransmitter systems of their fetuses. Blood ethanol and acetaldehyde concentrations in blood increased progressively with the ethanol dose in virgin rats, and values in pregnant animals were very similar. Ethanol concentration in fetal blood and amniotic fluid did not differ from that in mother's blood whereas fetal acetaldehyde concentrations were negligible. In a dose-related manner, ethanol decreased brain DA, DOPAC and 5HT concentrations did not affect those of NA and 5HIAA, or adrenal A and NA concentrations, whereas it enhanced plasma NA levels. Basal levels of monoamines and their changes after ethanol intake did not differ in pregnant and virgin rats. Monoamine and metabolite concentrations were much lower in fetal than in maternal brains whereas plasma and adrenal catecholamine concentrations were very similar and maternal ethanol intake did not modify these fetal parameters in the fetus. Results are in agreement with the known similar metabolic response to ethanol in fed pregnant and virgin rats. The lack of fetal monoamine response to maternal ethanol intake may be a consequence of the incapacity of fetal liver to form acetaldehyde and the ability of the placenta to oxidize maternal acetaldehyde which protects the fetus from maternal alcohol intake at late gestation.     

Rat acetoacetate decarboxylase: its role in the disposal of 4C-ketone bodies by the fetus

21-day pregnant rats show high tissular and plasmatic acetone concentrations when submitted to a 48-hr fast. This rise is, in fact, associated with an enhanced placental and fetal acetoacetate decarboxylase activity. We propose that acetone formation by the fetus could be a mechanism for pH maintenance and that acetoacetate decarboxylase can play a significant role in the handling of 4C-ketone bodies under conditions in which the substrate concentration cannot easily be controlled by other physiological mechanisms.