Through exploring the role of placental endocrine,the relationship between placental endocrine changes and certain disease states,and the relationship between placental endocrine and rational use of drugs commonly used in pregnancy were summarized.Placental hormones play an important role during pregnancy.Placental endocrine abnormality can cause some diseases that may need drug treatment.Besides,some drugs also can affect the placenta endocrine,resulting in adverse pregnancy outcomes.Drug safety during pregnancy requires the consideration of the interaction between medicine and placenta endocrine.
妊娠早期恶心呕吐(nausea and vomiting of pregnancy,NVP)是影响女性平稳妊娠及生活、工作的重要原因。据国外文献报道,70%~80%孕妇在妊娠期间出现恶心,50%出现呕吐,0.1%~2%为妊娠剧吐[6]。NVP可能与多种因素有关,包括免疫功能的改变、母体遗传、既往妊娠及内分泌变化等。目前普遍认为,NVP主要与妊娠早期母体血浆中HCG水平升高相关,HCG达高峰时,恶心呕吐症状往往最重,在HCG较高的情况下,如多胎妊娠、葡萄胎等,恶心呕吐的症状常常更重。妊娠期恶心呕吐特别是妊娠剧吐可增加出生低体质量儿、早产儿及小于胎龄儿的风险,影响新生儿Apgar评分。
Fetal growth is largely determined by the availability of nutrients to the fetus. The fetus is at the end of a supply line that ensures delivery of nutrients from the maternal/uterine circulation to the fetus via the placenta. However, this supply line can not be regarded as a linear relationship. Maternal undernutrition will not only reduce global nutrient availability but will also influence the maternal and fetal somatotrophic axis. Both endocrine systems react in a very similar way to limited substrate supply. The hormones of the fetal somatotrophic axis, and in particular insulin-like growth factor (IGF)-1, are important regulators of fetal growth. Placental function is pivotal to materno-fetal nutrient and metabolite transfer. Placental function in turn, is heavily influenced by the maternal and fetal growth hormone (GH)-IGF-1 system. The placenta itself is also an active endocrine organ and it produces a large number of hormones including GH and IGF-1 as well their corresponding receptors. Thus the placenta can no longer be considered merely a passive conduit for fetal nutrition. Rather, it is actively involved in the integration of nutritional and endocrine signals from the maternal and fetal somatotrophic axes.
RILEY EH,FUENTES-AFFLICKE,JACKSON RA,et al.Correlates of prescription drug use during pregnancy[J].J Womens Health,2005,14(5):401-409.
Purpose: To evaluate the extent of prescription drug use and the use of category D or X drugs during pregnancy and examine the maternal characteristics associated with use. Methods: Medical record and survey data from an observational cohort of pregnant women from 2001 to 2003 ( n = 1626) were analyzed to examine the use of prescription drugs and the use of category D or X drugs. Results: A majority of these pregnant women were prescribed a prescription drug (56%), and 4% of women were prescribed a category D or X drug. The most common classes of medications prescribed were antibiotics (62%), analgesics (18%), asthma medications (18%), and antiemetics (17%). After adjustment for sociodemographic and clinical characteristics, African American women were more likely to use a prescription drug than white women. Lower levels of educational attainment were also associated with greater use of prescription drugs compared with women who had graduated from college. Women with a chronic health condition, gestational diabetes, a prenatal hospitalization, a history of infertility, or symptoms of acid reflux were also more likely to use a prescription drug than women without these conditions. Nulliparous women and women who were married or living with a partner were less likely to use category D or X drugs during pregnancy than women without these characteristics. Women with a history of infertility and those with a chronic health condition were more likely to use a category D or X drugs during pregnancy than those without these conditions. Conclusions: The common use of prescription drugs during pregnancy supports the importance of expanding the evidence about the risks and benefits of prescription drug use during pregnancy and suggests the need for systems to safeguard prescribing practices for women of reproductive age.
ROTIE,GNUDIA,BRAVERMAN LE.The placental transport,synthesis and metabolism of hormones and drugs which affect thyroid function[J].Endocr Rev,1983,4(2):131-149.
ILIODROMITIZ,ANTONAKOPOULOSN,SIFAKISS,et al.Endocrine,paracrine,and autocrine placental mediators in labor[J].Hormones,2012,11(4):397-409.
Abstract Considering that preterm birth accounts for about 6-10% of all births in Western countries and of more than 65% of all perinatal deaths, elucidation of the particularly complicated mechanisms of labor is essential for determination of appropriate and effective therapeutic interventions. Labor in humans results from a complex interplay of fetal and maternal factors, which act upon the uterus to trigger pathways leading gradually to a coordinated cervical ripening and myometrial contractility. Although the exact mechanism of labor still remains uncertain, several components have been identified and described in detail. Based on the major role played by the human placenta in pregnancy and the cascade of labor processes activated via placental mediators exerting endocrine, paracrine, and autocrine actions, this review article has aimed at presenting the role of these mediators in term and preterm labor and the molecular pathways of their actions. Some of the aforementioned mediators are involved in myometrial activation and preparation and others in myometrial stimulation leading to delivery. In the early stages of pregnancy, myometrial molecules, like progesterone, nitric oxide, and relaxin, contribute to the retention of pregnancy. At late stages of gestation, fetal hypothalamus maturation signals act on the placenta causing the production of hormones, including CRH, in an endocrine manner; the signals then enhance paracrinically the production of more hormones, such as estrogens and neuropeptides, that contribute to cervical ripening and uterine contractility. These molecules act directly on the myometrium through specific receptors, while cytokines and multiple growth factors are also produced, additionally contributing to labor. In situations leading to preterm labor, as in maternal stress and fetal infection, cytokines trigger placental signaling sooner, thus leading to preterm birth.
KALANTARIDOU SN,ZOUMAKISE,MAKRIGIANNA-KISA,et al.Corticotropin-releasing hormone,stress and human reproduction:an update[J].J Reprod Immunol,2010,85(1):33-39.
Abstract The stress system has suppressive effects on female and male reproductive function. Corticotrophin-releasing hormone (CRH), the principal regulator of stress, has been identified in the female and male reproductive system. Reproductive CRH participates in various reproductive functions that have an inflammatory component, where it serves as an autocrine and paracrine modulator. These include ovarian and endometrial CRH, which may participate in the regulation of steroidogenesis and the inflammatory processes of the ovary (ovulation and luteolysis) and the endometrium (decidualization and blastocyst implantation) and placental CRH, which is secreted mostly during the latter half of pregnancy and is responsible for the onset of labor. It has been suggested that there is a "CRH placental clock" which determines the length of gestation and the timing of parturition and delivery. The potential use of CRH-antagonists is presently under intense investigation. CRH-R1 antagonists have been used in animal studies to elucidate the role of CRH in blastocyst implantation and invasion, early fetal immunotolerance and premature labor. The present review article focuses on the potential roles of CRH on the physiology and pathophysiology of reproduction and highlights its participation in crucial steps of pregnancy, such as implantation, fetal immune tolerance, parturition and fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
EINARSON TR,PIWKOC,KORENG.Quantifying the global rates of nausea and vomiting of pregnancy:a meta analysis[J].J Popul Clin Pharmacol,2013,20(2):171-183.
Abstract BACKGROUND: Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, affecting women worldwide. It is unclear whether its prevalence and severity NVP are variable across different nations and races. PURPOSE: To summarize global rates of NVP as reported in the literature using meta-analysis. METHODS: We searched Medline, Embase and Cochrane databases for all peer-reviewed articles reporting rates of NVP and/or hyperemesis gravidarum (HG). No restrictions were imposed on publication year or language. Numbers of women, studies and NVP rates were extracted and aggregated using a random effects model. Outcomes included: overall rates (i.e., women suffering any nausea or vomiting or both) in early and in late pregnancy, rates of nausea only, symptom severity, and HG rates. RESULTS: We identified 116 studies, rejecting 37 and accepting 79, of which 59 provided data for NVP (N=93,753 in 13 countries) and 26 for HG (N= 6,155,578). All developed regions of the world were represented (2 studies from Africa, 1 India; none from Latin America). Reported NVP rates varied from 35%-91% (median 69%); the meta-analytic average rate was 69.4% (CI95%:66.5%-72.3%). Among pregnant women, 32.7% had nausea without vomiting and 23.5% overall had NVP continuing into the third trimester. NVP was rated as mild in 40%, moderate in 46% and severe in 14% of cases. The prevalence of HG was 1.1% (CI95%:0.8%-1.3%), with a range of 0.3%-3.6%. CONCLUSIONS: Almost 70% of women worldwide experience NVP, but reported rates vary widely. HG, the most severe form, affects 1.1%.
FOWDEN AL,SFERRUZZI-PERRI A N,COAN P M,et al.Placental efficiency and adaptation:endocrine regulation[J].J Physiol,2009,587(Pt 14):3459-3472.
Abstract Size at birth is critical in determining life expectancy and is dependent primarily on the placental supply of nutrients. However, the fetus is not just a passive recipient of nutrients from the placenta. It exerts a significant acquisitive drive for nutrients, which acts through morphological and functional adaptations in the placenta, particularly when the genetically determined drive for fetal growth is compromised by adverse intrauterine conditions. These adaptations alter the efficiency with which the placenta supports fetal growth, which results in optimal growth for prevailing conditions in utero . This review examines placental efficiency as a means of altering fetal growth, the morphological and functional adaptations that influence placental efficiency and the endocrine regulation of these processes.
YOKOYAMAU,MINAMISAWAS,QUANH,et al.Chronic activation of the prostaglandin receptor EP4 promotes hyaluronan-mediated neointimal formation in the ductus arteriosus[J].J Clin Investig,2006,116(11):3026-3034.
PGE, a potent vasodilator, plays a primary role in maintaining the patency of the ductus arteriosus (DA). Genetic disruption of the PGE-specific receptor EP4, however, paradoxically results in fatal patent DA (PDA) in mice. Here we demonstrate that EP4-mediated signals promote DA closure by hyaluronic acid-mediated (HA-mediated) intimal cushion formation (ICF). Chronic EP4 stimulation by ONO-AE1-329, a selective EP4 agonist, significantly enhanced migration and HA production in rat DA smooth muscle cells. When HA production was inhibited, EP4-mediated migration was negated. Activation of EP4, adenylyl cyclase, and PKA all increased HA production and the level of HA synthase 2 (HAS2) transcripts. In immature rat DA explants, ICF was promoted by EP4/PKA stimuli. Furthermore, adenovirus-mediated Has2 gene transfer was sufficient to induce ICF in EP4-disrupted DA explants in which the intimal cushion had not formed. Accordingly, signals through EP4 have 2 essential roles in DA development, namely, vascular dilation and ICF. The latter would lead to luminal narrowing, helping adhesive occlusion and permanent closure of the vascular lumen. Our results imply that HA induction serves as an alternative therapeutic strategy for the treatment of PDA to the current one, i.e., inhibition of PGE signaling by cyclooxygenase inhibitors, which might delay PGE-mediated ICF in immature infants.
HAMRICK SE,HANSMANNG.Patent ductus arteriosus of the preterm infant[J].Pediatrics,2010,125(5):1020-1030.
Abstract A persistently patent ductus arteriosus (PDA) in preterm infants can have significant clinical consequences, particularly during the recovery period from respiratory distress syndrome. With improvement of ventilation and oxygenation, the pulmonary vascular resistance decreases early and rapidly, especially in very immature infants with extremely low birth weight (<1000 g). Subsequently, the left-to-right shunt through the ductus arteriosus (DA) is augmented, thereby increasing pulmonary blood flow, which leads to pulmonary edema and overall worsening of cardiopulmonary status. Prolonged ventilation, with the potential risks of volutrauma, barotrauma, and hyperoxygenation, is strongly associated with the development and severity of bronchopulmonary dysplasia/chronic lung disease. Substantial left-to-right shunting through the ductus may also increase the risk of intraventricular hemorrhage, necrotizing enterocolitis, and death. Postnatal ductal closure is regulated by exposure to oxygen and vasodilators; the ensuing vascular responses, mediated by potassium channels, voltage-gated calcium channels, mitochondrial-derived reactive oxygen species, and endothelin 1, depend on gestational age. Platelets are recruited to the luminal aspect of the DA during closure and probably promote thrombotic sealing of the constricted DA. Currently, it is unclear whether and when a conservative, pharmacologic, or surgical approach for PDA closure may be advantageous. Furthermore, it is unknown if prophylactic and/or symptomatic PDA therapy will cause substantive improvements in outcome. In this article we review the mechanisms underlying DA closure, risk factors and comorbidities of significant DA shunting, and current clinical evidence and areas of uncertainty in the diagnosis and treatment of PDA of the preterm infant.
SHAH MS,DAVIES TF,STAGNAROGREENA.The thyroid during pregnancy:a physiological and pathological stress test[J].Minerva Endocrinol,2003,28(3):233-245.
Pregnancy and the postpartum are times of marked and rapid change in the thyroid gland. Normal physiological changes include enhanced thyroid hormone production, modulation of thyroid hormone metabolism by placental deiodinases, and decreasing titers of thyroid antibodies in thyroid antibody positive women. Hyperemesis gravidarum is associated with suppressed thyroid stimulating hormone levels and free T4 elevations. Graves' disease typically becomes quiescent during pregnancy, followed by a postpartum flare. Women with pre-existing hypothyroidism frequently require an increase in their levothryoxine requirement in the 1(st) trimester, and subclinical hypothyroidism early in pregnancy is linked to both miscarriage and impaired neurological development in the unborn child. Postpartum thyroiditis occurs in 7.2% of women, and euthyroid women who are thyroid antibody positive in the 1(st) trimester of pregnancy have a doubling of the miscarriage rate.
ALEXANDER EK,PEARCE EN,BRENT GA,et al.2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum[J].Thyroid,2017,27(3):315-389.
Abstract BACKGROUND: Thyroid disease in pregnancy is a common clinical problem. Since the guidelines for the management of these disorders by the American Thyroid Association (ATA) were first published in 2011, significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid disease in women during pregnancy, preconception, and the postpartum period. METHODS: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations. The guideline task force had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. RESULTS: The revised guidelines for the management of thyroid disease in pregnancy include recommendations regarding the interpretation of thyroid function tests in pregnancy, iodine nutrition, thyroid autoantibodies and pregnancy complications, thyroid considerations in infertile women, hypothyroidism in pregnancy, thyrotoxicosis in pregnancy, thyroid nodules and cancer in pregnant women, fetal and neonatal considerations, thyroid disease and lactation, screening for thyroid dysfunction in pregnancy, and directions for future research. CONCLUSIONS: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid disease in pregnant and postpartum women. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with these disorders.
BAHN RS,BURCH HS,COOPER DS,et al.The role of propylthiouracil in the management of Graves' disease in adults:report of a meeting jointly sponsored by the American Thyroid Association and the food and drug administration[J].Thyroid,2009,19(7):673-674.
MA XH,WU WX,NATHANIELSZ PW.Gestation-related and betamethasone-induced changes in 11beta-hydroxysteroid dehydrogenase types 1 and 2 in the baboon placenta[J].Am J Obstet Gynecol,2003,188(1):13-21.
Objective: We determined developmental and labor-related changes in 11β-hydroxysteroid (HSD) 1 and 2 expression in baboon placentas during the final third of gestation and labor. We examined whether maternal glucocorticoid administration alters placental 11β-HSD 2 expression. Study Design: Maternal and fetal plasma cortisol concentrations were measured in five animals. Types 1 and 2 11β-HSD messenger RNA (mRNA) and protein in placentas obtained at 121 to 185 days' gestation (dGA, term approximately 185 dGA, n = 16), during labor between 141 and 193 dGA (n = 8), and after maternal administration of four doses of 87.5 μg/kg betamethasone (n = 5) at 12-hour intervals at 121 to 135 dGA were analyzed by Northern and Western blot. Results: Cortisol levels were higher in maternal plasma than fetal (4-fold, P < .mob031). Placental 11β-HSD 2 mRNA and protein decreased after 0.9 gestation ( P < .001). 11β-HSD 1 mRNA remained unchanged. There was no effect of labor on placental 11β-HSD 1 and 2 mRNA and protein levels. Maternal betamethasone administration dramatically increased ( P < .05) 11β-HSD 2 mRNA as well as protein without effect on 11β-HSD 1 mRNA and protein expression. Conclusions: The late-gestation baboon maternal plasma cortisol concentration is four times the fetal plasma concentration. Decreased placental 11β-HSD 2 may enhance maternal cortisol passage to the fetus at the end of gestation, thereby contributing to cortisol-mediated changes within the placenta and cortisol in fetal plasma at this stage of fetal development. The positive effect of betamethasone on placental 11β-HSD 2 induction further suggests an ability of the placenta to regulate glucocorticoid transfer in the presence of elevated maternal glucocorticoid. (Am J Obstet Gynecol 2003;188:13-21.)
Abstract OBJECTIVE: Placental 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which converts active cortisol to inactive cortisone, has been proposed to be the mechanism guarding the fetus from the growth retarding effects of maternal glucocorticoids; however, other placental enzymes have also been implicated. Placental 11 beta-HSD is unstable in vitro, and enzyme activity thus detected may not be relevant to the proposed barrier role. We have therefore examined placental glucocorticoid metabolism in dually perfused freshly isolated intact human placentas. DESIGN: Placentas were obtained from randomly selected normal term deliveries. The maternal circuit was perfused with physiological concentration of cortisol, the fetal effluent collected and steroid metabolites separated and quantified using silica columns (Sep-pak Plus) and HPLC. RESULTS: Most of the maternally administered cortisol was metabolized to cortisone, and no conversion of cortisone to cortisol was detected. Cortisone was the only product of cortisol metabolism. Inhibition of 11 beta-HSD with glycyrrhetinic acid allowed cortisol to gain direct access to the fetal circulation. CONCLUSION: We conclude that human placental 11 beta-HSD plays a crucial role in controlling glucocorticoid access to the fetus. Other enzymes are not significant contributors at physiologically relevant cortisol concentrations.
BAKHIREVA LN,SCHATZM,CHAMBERS CD.Effect of maternal asthma and gestational asthma therapy on fetal growth[J].J Asthma,2007,44(2):71-76.
Abstract Asthma is a common chronic condition that might seriously complicate pregnancy and fetal development. This article provides a comprehensive review of the existing literature regarding the effect on fetal growth of maternal asthma and common asthma medications used during pregnancy, including short-and long-acting beta (2)-agonists, inhaled and oral corticosteroids, chromones, leukotriene receptor agonists, and theophylline. Evaluated outcomes of fetal growth include low birth weight, mean birth weight, small for gestational age, birth length and head circumference, and measures of asymmetrical growth retardation. Methodological and practical considerations related to safety of asthma medications in pregnancy and management of gestational asthma are discussed.
SHAPIRO-MENDOZA CK,TOMASHEK KM,KOTEL-CHUCKM,et al.Effect of late-preterm birth and maternal medical conditions on newborn morbidity risk[J].Pediatrics,2008,121(2):223-232.
Late-preterm infants (34-36 weeks' gestation) account for nearly three quarters of all preterm births in the United States, yet little is known about their morbidity risk. We compared late-preterm and term (37-41 weeks' gestation) infants with and without selected maternal medical conditions and assessed the independent and joint effects of these exposures on newborn morbidity risk.We used 1998-2003, population-based, Massachusetts birth and death certificates data linked to infant and maternal hospital discharge records from the Massachusetts Pregnancy to Early Life Longitudinal data system. Newborn morbidity risks that were associated with gestational age and selected maternal medical conditions, both independently and as joint exposures, were estimated by calculating adjusted risk ratios. A new measure of newborn morbidity that was based on hospital discharge diagnostic codes, hospitalization duration, and transfer status was created to define newborns with and without life-threatening conditions. Eight selected maternal medical conditions were assessed (hypertensive disorders of pregnancy, diabetes, antepartum hemorrhage, lung disease, infection, cardiac disease, renal disease, and genital herpes) in relation to newborn morbidity.Our final study population included 26,170 infants born late preterm and 377,638 born at term. Late-preterm infants were 7 times more likely to have newborn morbidity than term infants (22% vs 3%). The newborn morbidity rate doubled in infants for each gestational week earlier than 38 weeks. Late-preterm infants who were born to mothers with any of the maternal conditions assessed were at higher risk for newborn morbidity compared with similarly exposed term infants. Late-preterm infants who were exposed to antepartum hemorrhage and hypertensive disorders of pregnancy were especially vulnerable.Late-preterm birth and, to a lesser extent, maternal medical conditions are each independent risk factors for newborn morbidity. Combined, these 2 factors greatly increased the risk for newborn morbidity compared with term infants who were born without exposure to these risks.
GUARINON,OUET,SHIMAH,et al.Antenatal dexame-thasone enhances surfactant protein synthesis in the hypoplastic lung of nitrofen-induced diaphragmatic hernia in rats[J].J Pediatr Surg,2000,35(10):1468-1473.
Background/Purpose: Pulmonary hypoplasia is one of the main causes for the high mortality rate in patients with congenital diaphragmatic hernia (CDH). The expression of surfactant protein A in the hypoplastic CDH lung is reduced, and its concentration is decreased in the amniotic fluid of pregnancies complicated by CDH. In a CDH experimental model, prenatal glucocorticoid treatment has proved its efficacy in correcting the parameters of pulmonary biochemical and morphologic immaturity. The aim of this study was to investigate whether maternal administration of dexamethasone has any effect on the expression of surfactant protein A and surfactant protein B in nitrofen-induced experimental CDH rat model. Methods: CDH was induced in pregnant rats after administration of 100 mg of nitrofen on day 9.5 of gestation (term, 22 days). Dexamethasone (Dex, 0.25 mg/kg) was given by intraperitoneal injection on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21 of gestation. The fetuses were divided into 3 groups: group I, control (n = 16); group II, nitrofen-induced CDH (n = 16); group III, nitrofen-induced CDH with antenatal Dex treatment (n = 16). Indirect immunohistochemistry was performed using alkaline-phosphatase-coagulated streptavidin using anti-SP-A and anti-SP-B polyclonal antibodies. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate relative amount of SP-A and SP-B mRNA expression. Results: In the CDH lung (group II) we observed a markedly reduced number of type II pneumocytes positive for SP-A, and SP-B was increased to a level close to that of the control group. The relative amount of SP-A and SP-B was reduced significantly in group II compared with controls (P <.05) and significantly increased in group III compared with group II animals (P <.01). Conclusion: These results suggest that antenatal glucocorticoid treatment increases the production of surfactant proteins in the CDH hypoplastic lung. J Pediatr Surg 35:1468-1473. Copyright 漏 2000 by W.B. Saunders Company.
BENNETTP,SLATERD.COX-2 expression in labour[M].Springer Netherlands,1996:167-188.
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[21]
OLSON DM,AMMANNC.Role of the prostaglandins in labour and prostaglandin receptor inhibitors in the prevention of preterm labour[J].Front Biosci,2007,12(4):1329-1343.
Abstract Parturition is composed of five separate but integrated physiological events: fetal membrane rupture, cervical dilatation, myometrial contractility, placental separation, and uterine involution. Prostaglandins (PGs) have central roles in each of these events, but the most studied is myometrial contraction. Elevated uterine PGs or the enhanced sensitivity of the myometrium to PGs leads to contractions and labour. The primary regulator of PG synthesis is the mRNA expression of PG H Synthase (PGHS-2 or COX-2). Given the central role of PGs in labour, this enzyme becomes an obvious therapeutic target for the prevention of preterm labour, the major cause of perinatal mortality and morbidity. Unfortunately, even though the non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit PGHS, are usually successful in suppressing preterm labour or prolonging pregnancy in animal and human studies, the NSAIDS have had adverse effects on fetal physiology and development. Therefore, other means to suppress PG synthesis or action to arrest preterm labour need to be investigated. The PGF2alpha receptor, FP, may prove to be a reasonable target for tocolysis. FP mRNA increases in the mouse uterus at preterm birth, whereas PGF2alpha concentrations do not increase, suggesting elevated uterine sensitivity to contractile agonists is one mechanism for preterm labour initiation. New data shows that administration of a specific FP antagonist, Theratechnologies (THG) 113.31, delays preterm birth in mice and sheep with no observable maternal or fetal side effects. Hence antagonizing PG action offers new hope for delaying preterm birth.
SCHOENFELDA,BARY,MERLOBP,et al.NSAIDs:maternal and fetal considerations[J].Am J Reprod Immunol,2013,28(3/4):141-147.
ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) gained popularity in the late 1970s. Inhibition of prostaglandin synthesis with indomethacin has been reported to be effective for prevention of labor and for treatment for symptomatic polyhydramnios. Concern about its possible constrictive effect on the fetal ductus arteriosus has limited its use in pregnancy. Maternal indomethacin therapy has also been associated with reduction in urine production in the fetus and with oligohydramnios.Obstetricians have discouraged pregnant women from taking analgesic doses of aspirin, mainly because of the availability of paracetamol (acetaminophen), which causes less gastric irritation, but also because of fear of maternal and fetal hemorrhage and of possible premature closure of the ductus. These fears largely derive from studies on patients taking large doses and from extrapolation from other NSAIDs. The likelihood that treatment with 60芒聙聯75 mg/day of aspirin markedly reduces the incidence of preeclampsia and fetal intrauterine growth retardation makes it important to reexamine its use.This review describes the pharmacology and pharmacokinetics of aspirin with particular reference to pregnancy and considers teratogenesis, prolongation of pregnancy and labor, maternal bleeding, fetal and neonatal bleeding, possible effects on the ductus arteriosus and pulmonary circulation, and possible nonspecific effects on intelligence and breast feeding and acute toxicity in the neonate.
DANIELS,MATOKI,GORODISCHERR,et al.Major malformations following exposure to nonsteroidal antiinflammatory drugs during the first trimester of pregnancy[J].J Rheumatol,2012,39(11):2163-2169.
Quantifying the global rates of nausea and vomiting of pregnancy:a meta analysis
1
2013
... 妊娠早期恶心呕吐(nausea and vomiting of pregnancy,NVP)是影响女性平稳妊娠及生活、工作的重要原因.据国外文献报道,70%~80%孕妇在妊娠期间出现恶心,50%出现呕吐,0.1%~2%为妊娠剧吐[6].NVP可能与多种因素有关,包括免疫功能的改变、母体遗传、既往妊娠及内分泌变化等.目前普遍认为,NVP主要与妊娠早期母体血浆中HCG水平升高相关,HCG达高峰时,恶心呕吐症状往往最重,在HCG较高的情况下,如多胎妊娠、葡萄胎等,恶心呕吐的症状常常更重.妊娠期恶心呕吐特别是妊娠剧吐可增加出生低体质量儿、早产儿及小于胎龄儿的风险,影响新生儿Apgar评分. ...
SFERRUZZI-PERRI A N,COAN P M,et al.Placental efficiency and adaptation:endocrine regulation
The role of propylthiouracil in the management of Graves' disease in adults:report of a meeting jointly sponsored by the American Thyroid Association and the food and drug administration
Major malformations following exposure to nonsteroidal antiinflammatory drugs during the first trimester of pregnancy
1
2012
... 在动物实验中,大剂量的NSAIDs具有致畸性.人类研究中并未发现妊娠早期使用NSAIDs明显增加后代先天性异常的风险.研究发现,尽管NSAIDs在妊娠早期及妊娠中期耐受良好,但在受孕期间应避免使用,以免影响胚泡的植入.并且在妊娠30周后使用NSAIDs时,可能会因动脉导管提前关闭引起PPHN,以及羊水过少[23].故妊娠30周后以及分娩过程中,应停止使用NSAIDs.关于在妊娠期间使用COX-2抑制药的数据有限,已有研究发现COX-2抑制药可干扰胚泡植入.最近一项研究显示,宫内接触COX-2抑制药可能会增加先天性异常的风险.因此,妊娠期间应避免使用COX-2抑制药.妊娠期间确需使用NSAIDs时,尤其是在妊娠30周后,推荐使用对乙酰氨基酚,其对COX-1和COX-2抑制作用较弱,但使用时间不宜超过72 h. ...
, 黄银
