Does dehydration contribute to retarded fetal growth in rats exposed to alcohol during gestation?

An earlier study showed that pregnant rats given ethanol in drinking water exhibited a significant degree of dehydration. The objective of the present study was to determine whether dehydration alone contributes to fetal growth retardation in alcohol treated rats. Female Sprague-Dawley rats were divided into 4 dietary groups. Group 1 (alcohol) received 20% ethanol in drinking water for four weeks prior to mating and 30% alcohol in drinking water throughout pregnancy and a stock diet $\text{ad libitum}$. Group 2 (pair-fed) was given an amount of food equal to that consumed by the alcohol group with the alcohol isocalorically substituted by corn starch. Water was available $\text{ad libitum}$. Group 3 (pair-water) was given an amount of food and water equal to that consumed by the alcohol animals. Group 4 ($\text{ad libitum}$) was given food and water $\text{ad libitum}$. On day 21 of gestation body weights of the alcohol exposed fetuses were significantly lower than those of the other three treatment groups. The difference in fetal body weights between the pair-fed and pair-water groups was not significant. Placentas were significantly heavier in the alcohol group than in the pair-fed and pair-water groups. Maternal plasma osmolality was significantly higher in the alcohol treated rats when compared to the pair-fed and $\text{ad libitum}$ controls but not the pair-water group. No significant differences were seen in fetal plasma osmolality among the four treatment groups. It is concluded that dehydration does not contribute significantly to retarded fetal growth in rats given alcohol in drinking water as the sole source of fluid prior to and during gestation.     

Vasoactive intestinal peptide mRNA and immunoreactivity are decreased in fetal alcohol syndrome model

Vasoactive intestinal peptide (VIP) regulates growth in the early post-implantation embryo. Previous work has demonstrated that peptide agonists (SALLRSIPA and NAPVSIPQ) from downstream mediators that are regulated by VIP were able to prevent the alcohol-induced fetal death, growth restriction and microcephaly associated with fetal alcohol syndrome. Here we evaluated the role of VIP in this mouse model of fetal alcohol syndrome, to determine if fetal or maternal levels of VIP are altered. In addition, we evaluated whether peptide treatment would alter the effects of alcohol on VIP levels. Treatment groups included control, alcohol, and alcohol+peptides. VIP levels were measured with enzyme immunoassay [EIA] (Peninsula Laboratories, Belmont, CA). Quantitation of VIP expression was measured with rt-PCR using mimic cDNA primers. Embryo/decidual VIP levels were similar in control and alcohol-treated groups 6 h after treatment. However, in the embryo/deciduas at 12 and 24 h, VIP levels were below the EIA's detection limit in the alcohol-treated groups, and significantly lower than the control or peptide-pretreated groups (p<0.05). Maternal cortex VIP levels were undetectable and significantly lower in the alcohol-treated group than control or peptide+alcohol group at 6 and 12 h (p<0.001). VIP mRNA expression was quantitated in the embryo and deciduas, with a significant decline noted at 6 h to 58% of control levels (p=0.02). Pretreatment with the peptides attenuated the alcohol-induced decrease in VIP mRNA. These studies demonstrate that treatment with alcohol can decrease the expression and immunoreactivity of VIP in both maternal and fetal tissues. This alcohol-induced loss of a recognized regulator of embryonic growth and differentiation may contribute to the sequelae of toxicity observed in fetal alcohol syndrome.     

Zinc,ethanol, and lipid peroxidation in adult and fetal rats

Studies were performed on adult and fetal rats receiving either a zinc-deficient (<0.5 ppm) diet and/or ethanol (20%) throughout pregnancy. Liver zinc levels were depressed in fetuses exposed toin utero zinc deficiency, but brain zinc levels were unchanged. Ethanol had no effect on the concentration of zinc in the several fetal and adult tissues studies. Lipid peroxidation, as measured by endogenous levels of malondialdehyde (MDA) increased following food restriction, zinc improverishment, and alcoholism in adult and fetal livers, but not in fetal brains. Generally, levels of MDA were highest when both zinc deficiency and the ingestion of alcohol occurred concurrently. Glutathione (GSH) was depressed by zinc restriction in several adult and fetal tissues, but not in the fetal brain. Ethanol alone had no effect on GSH levels. The activity of the enzyme glutathione peroxidase (GSH-Px) was not changed in either organism by alcohol or zinc deficiency. Overall, the data point to increased lipid peroxidation in maternal and fetal rat tissues following zinc depletion and/or treatment with alcohol and draw attention to the apparent vulnerability of the fetal liver toin utero alcoholism. By contrast, the fetal brain seems to be especially resistant to alcohol and zinc-related lipoperoxidation. An association is suggested between the increased lipoperoxidation accompanying zinc deficiency and reduced levels of GSH, but this does not appear to relate to changes in the activity of GSH-Px. A similar relationship is not evident with respect to the increased levels of MDA in fetal and adult livers following chronic alcohol intoxication. A possible basis for the zinc-GSH interaction is discussed.     

Effects of l-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and l-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75–2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal l-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. l-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid–base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, l-glutamine supplementation mitigates alcohol-induced acid–base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy.     

Effect of maternal alcohol consumption on the fetal thyroid in the rat

To investigate the effect of maternal alcohol consumption on the development of the fetal thyroid gland, Sprague-Dawley rats were given 20% ethanol for 4 weeks prior to mating and 30% ethanol throughout gestation. Pair-fed controls received an isocaloric amount of corn starch and chow, with water ad libitum, and ad libitum controls received rat chow and water. On Days 17, 18, 19, and 20 of gestation, the fetuses were weighed and the fetal thyroids were removed for histometric observation. On Days 19 and 20, the fetal thyroids of alcohol-exposed fetuses weighed significantly less than those of the two control groups, but more than the control thyroids 1 day earlier. Maternal alcohol consumption caused a significant decrease in both the follicular cell height and the follicle diameter of the fetal thyroid on all days examined. In the alcohol group on Days 19 and 20 of gestation, the cell height was less than, and the follicle diameter was approximately equal to those in the two controls 2 days earlier. These results indicate that, as a consequence of maternal alcohol consumption, growth of the fetal thyroid gland is retarded, and there are indications of fetal hypothyroidism, as seen from the histometric data. This latter is suggestive of a retarded thyrotropic activity of the fetal pituitary gland.     

Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms

Recent evidence indicated that alcohol exposure during the fetal period increases the susceptibility to tumor development in mammary and prostate tissues. Whether fetal alcohol exposure increases the susceptibility to prolactin-producing tumor (prolactinoma) development in the pituitary was studied by employing the animal model of estradiol-induced prolactinomas in Fischer 344 female rats. We employed an animal model of fetal alcohol exposure that simulates binge alcohol drinking during the first two trimesters of human pregnancy and involves feeding pregnant rats with a liquid diet containing 6.7% alcohol during gestational day 7 to day 21. Control rats were pair-fed with isocaloric liquid diet or fed ad libitum with rat chow diet. Adult alcohol exposed and control female offspring rats were used in this study on the day of estrus or after estrogen treatment. Results show that fetal alcohol-exposed rats had increased levels of pituitary weight, pituitary prolactin (PRL) protein and mRNA, and plasma PRL. However, these rats show decreased pituitary levels of dopamine D2 receptor (D2R) mRNA and protein and increased pituitary levels of D2R promoter methylation. Also, they show elevated pituitary mRNA levels of DNA methylating genes (DNMT1, DNMT3b, MeCP2) and histone modifying genes (HDAC2, HDAC4, G9a). When fetal alcohol exposed rats were treated neonatally with a DNA methylation inhibitor 5-Aza deoxycytidine and/or a HDAC inhibitor trichostatin-A their pituitary D2R mRNA, pituitary weights and plasma PRL levels were normalized. These data suggest that fetal alcohol exposure programs the pituitary to increase the susceptibility to the development of prolactinomas possibly by enhancing the methylation of the D2R gene promoter and repressing the synthesis and control of D2R on PRL-producing cells.     

妊娠期糖尿病与妊娠结局的临床分析

目的:探讨妊娠期糖尿病(GDM)对孕妇妊娠结局和胎儿健康的影响。方法:回顾性分析2009年8月~2012年12月在我院分娩的184例GDM患者及200例健康孕妇的临床资料,并对两组孕妇的妊娠结局进行比较。结果:GDM组妊高症35例(19.0%)、羊水过多17例(9.2%)、早产21例(11.4%)、产后出血14例(7.6%)、产褥感染12例(6.5%),发生率均显著高于对照组(P0.05);GDM组中发生巨大儿48例(26.1%)、新生儿低血糖31例(16.8%),与对照组比较均显著增高(P0.05),而胎儿宫内窘迫的发生率(3.3%)也较对照组升高,但差异无统计学意义(P0.05);GDM组剖宫产141例(76.6%),阴道产43例(23.4%),剖宫产比例较对照组显著升高(P0.05)。结论:GDM对孕妇的妊娠结局有不利影响,孕妇应加强孕期保健,规范治疗妊娠期糖尿病,减少各种并发症的发生。     

Alcohol,tobacco and cannabis use among Nova Scotia adolescents: implications for prevention and harm reduction

OBJECTIVE: To characterize adolescent drug use in terms of a risk continuum and to explore the rationale for harm reduction as a potential approach for school-based drug prevention. DESIGN: Self-reported surveys, in 1991 and 1996, of adolescent students concerning their use of drugs, especially alcohol, tobacco and cannabis, and the harmful consequences of such use. SETTING: Nova Scotia. PARTICIPANTS: A total of 3452 (in 1991) and 3790 (in 1996) junior and high school students in randomly selected classes in the public school system. OUTCOME MEASURES: Prevalence of drug use and patterns of multiple drug use and of alcohol- and drug-related problems; independent risk factors for multiple drug use. The risk continuum for the response to alcohol problems was used as a policy framework. RESULTS: The prevalence of cigarette smoking and the use of hallucinogens and stimulants was markedly higher in 1996 than in 1991. Over one-fifth (21.9%) of the students reported multiple drug use of alcohol and tobacco and cannabis in the 12 months before the 1996 survey. The 3 main subgroups--nonusers, users of alcohol only and users of multiple drugs--had distinct patterns of use, numbers of problems and risk factors. In all, 27.1% of the students had experienced at least 1 alcohol-related problem and 6% had experienced at least 1 drug-related problem in the 12 months before the 1996 survey. CONCLUSION: There is a need for integrated school- and community-based drug prevention programs, with goals, strategies and outcome measures capturing the full spectrum of patterns of use and levels of risk among subgroups of the adolescent student population.     

Determinants of recall and recall bias in studying drug and chemical exposure in pregnancy

Case-control studies on effects of drugs in pregnancy rely heavily on maternal recall. At the Motherisk Program in Toronto we counsel women during early pregnancy on the risk of drug and chemical exposure; subsequently, we follow up the outcome of pregnancy after birth. This cohort has given us an opportunity to assess the magnitude of recall of early pregnancy exposure and determinants likely to affect it in 145 consecutive cases. The mean recall of exposure identity was 62%, while accurate recall of timing of exposure was 37% and of dosage 24%. Exposures that prompted the clinic visit, chronic therapeutic exposures, environmental agents, and known teratogens were recalled significantly better than were other exposures. Accurate report of smoking was significantly higher than of alcohol use (79.4% vs. 59%, respectively, P = .0002). The number of agents consumed by the pregnant woman negatively correlated with her recall; mean recall of 1 agent was 85% vs. only 40% recall of 4 agents. Women greater than or equal to 30 years of age recalled significantly worse (mean +/- SEM, 52 +/- 4%) than women younger than 30 (70 +/- 4%), P = .002) despite a similar mean number of exposures. No difference in mean recall was found between women having normal (n = 112) or adverse pregnancy outcome (n = 33). There was a recall bias in reporting alcohol consumption; postnatally, women with adverse outcome tended to report significantly less than the amount initially reported by them.     

Placental blood flow in rats fed alcohol before and during gestation

Female Sprague-Dawley rats were either given 20% alcohol in drinking water and solid diet $\text{ad libitum}$ (alcohol group) or were pair-fed to the alcohol group (pair-fed group) or were given water and solid diet $\text{ad libitum (ad libitum}$ group) for four weeks. They were then mated and the alcohol group was changed to 30% alcohol in water. On day 20 of gestation each rat was injected with ⁵⁷Co-labeled microspheres into the left ventricle and radioactivity was determined in the placentas and kidneys. Cardiac output and blood flow to the placentas and kidneys was calculated. Fetuses and placentas were weighed, and the osmolality of the maternal plasma and water content of the muscle was determined. Cardiac output and blood flow to the kidneys did not differ among the three groups. Blood flow to the placenta, whether expressed as m1/min/g placenta or m1/min/placenta, or as % of cardiac output was significantly reduced in the alcohol group compared with the pair-fed and $\text{ad libitum}$ groups, which did not differ from one another. Fetuses were significantly lighter and placentas were significantly heavier in the alcohol group than in the other two groups. Plasma osmolality was increased and muscle water was decreased about 7% in the alcohol group, indicating a moderate degree of dehydration. It is concluded that chronic alcohol consumption leads to a redistribution of blood, with less blood supplying the placentas. This may contribute to the growth retardation seen in fetal alcohol syndrome.     

Determination of endogenous testosterone in rat tissues following fetal alcohol exposure using HPLC with UV detection

A novel method for quantitation of brain neurosteroid levels using HPLC with UV detection is described. In this simple and reliable method, testosterone from the brain and whole blood, and the internal standard, 17alpha-methyl testosterone, were extracted in 20% acetonitrile-phosphate buffer (pH 2.8), followed by solid phase extraction (SPE). The calibration curve was linear in concentration ranges from 0.1 to 10 ng from 0.2 g of tissue. We successfully applied this method to the analysis of endogenous testosterone in the male offspring of rats exposed to alcohol in utero. The concentration of testosterone at 21 post delivery in fetal alcohol exposure (FAE) group was significantly greater than the concentrations in either pair-fed or the ad libitum controls. These results support the usefulness of this method as a means of quantitating neurosteroids, and illustrate its applicability to fetal alcohol exposure.     

Prenatal Alcohol Exposure Increases Postnatal Acceptability of Nicotine Odor and Taste in Adolescent Rats

Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol''s bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine''s odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams'' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our results suggest broader implications related to the consequence of fetal exposure with one substance of abuse and initial acceptability of others.     

Some teratogenic properties of ethanol and acetaldehyde in C57BL/6J mice: implications for the study of the fetal alcohol syndrome

To investigate the teratogenic effect of acute alcohol exposure, pregnant C57BL/6J mice were exposed to 25% ethanol (either two doses of 2.9g/kg or one dose 5.8g/kg) during the organogenic period either by intraperitoneal injections or by intubation. The incidence of malformations varied according to (1) the stage of embryonic development at the time of exposure, (2) the route of administration of the alcohol, and (3) the amount of alcohol given and the time period over which it was administered. Oral doses of alcohol were teratogenic although less so than the same dose given intraperitoneally, and two intraperitoneal doses four hours apart produced significantly more malformation than the same two doses six hours apart. The primary metabolite of alcohol, acetaldehyde, was also investigated for its teratogenicity. It was found that one or two doses of four percent acetaldehyde (0.32g/kg), administered intraperitoneally were teratogenic. A further attempt was made to raise blood acetaldehyde levels by exposing mice to disulfiram, an inhibitor of acetaldehyde dehydrogenase, prior to administration of alcohol. The disulfiram pretreatment did not increase the malformation rate. Treatment with alcohol on day 7 or 8 caused a variety of facial abnormalities, some of which were comparable to those seen in children with fetal alcohol syndrome. Exposure on day 9 or 10 resulted in limb defects. The results suggest that one or more episodes of heavy maternal drinking at critical periods in pregnancy may severely damage the embryo and may produce many features of the fetal alcohol syndrome.     

Long-term alcohol exposure prior to conception results in lower fetal body weights

BACKGROUND: It is well known that alcohol consumption during pregnancy can result in lower birth weight babies but many women stop consuming alcohol prior to conception as a part of pregnancy planning. The purpose of this study was to determine whether alcohol consumption prior to conception may also have an effect on fetal development. METHODS: Male and female C57BL/6J mice at 4, 6, or 8 weeks of age received either a single administration of alcohol (3.0 g/kg) via intragastric gavage (IG) each day for at least 60 days, or an isovolumetric IG administration of sterile water. After 60 treatment days, males and females within each age and treatment group were mated overnight. Females continued to receive daily alcohol treatments until conception. Males continued to receive treatments until all females were successfully mated. At conception, females were isolated and left undisturbed. On embryonic day 14, fetus number, size, and weight was determined. RESULTS: Maternal food consumption, body weight at conception, and delay to conception onset did not differ between the two treatment groups or among the three age groups. Fetal body weights did not differ among the three age groups. Fetuses from females treated with alcohol had lower body weights compared to those treated with water. Male treatments did not seem to affect fetal body weight. CONCLUSIONS: Fetal growth and development can be affected by alcohol consumption prior to the time of conception. Alcohol consumption prior to conception is a potential risk factor to fetal outcome and an important consideration for those females planning to have children.     

Immediate fatal outcome vs. fatal outcome within the first 48 hours following a severe traffic trauma--analysis of the possible effect of alcohol intoxication on the outcome

This paper is a retrospective analysis of data on 278 persons with fatal outcomes in traffic accidents in Osjecko--baranjska County, Croatia, during a five-year period. The observed sample of casualties was divided according to the time of fatal outcome into three groups: immediately deceased (139 or 50.0%), deceased within the first 48 hours (84 or 30.2%) and deceased after 48 hours (55 or 19.8%). A comparison of data was made for the first two groups of casualties, based on the level of alcohol intoxication, and an analysis of the possible influence of alcohol intoxication on an early outcome of severe trauma, which was defined as immediate fatal outcome and fatal outcome within the first 48 hours following the trauma. Casualties from the group of immediately deceased had a significantly higher average blood alcohol level than casualties from the group of persons deceased within the first 48 hours (shown through arithmetic mean of 0.81 g/kg vs. 0.33 g/kg, p =0.000). A binary logistic regression analysis showed that every increase in blood alcohol level by 1 g/kg also increased the odds of an immediate fatal outcome by 1.92 times (p=0.004). CONCLUSION: Beside increased risks of traffic accidents, the collected data showed that alcohol intoxication of accident participants also increases their chances of an immediate fatal outcome.     

Method of ethanol administration as a confounding factor in studies of fetal alcohol syndrome

Female Sprague-Dawley rats were fed a complete liquid diet containing either 5.5% ethanol (mean daily intake of about 9g of ethanol per kg body weight) or an isocaloric amount of dextrose (control group), with additional water available $\text{ad}$$\text{libitum}$. The diets were fed for four weeks prior to and throughout pregnancy. On day 20 of gestation cardiac output and blood flow to the placeta, heart, kidneys and uterus were measured and plasma osmolality and muscle dry weight were determined. No significant differences were seen between alcohol and control groups with respect to litter size, fetal weight, maternal cardiac output, blood flow to the placenta or other organs, plasma osmolality, or muscle dry weight. This contrasts with previous experiments in which a similar quantity of alcohol (as % calories) was offered in drinking water (equivalent to a mean daily ethanol intake of 10g/kg body weight). Under those conditions fetal weight was reduced, blood flow to the plascenta was reduced, and plasma osmolality and muscle dry weight were increased, indicating a moderate degree of dehydration. It is concluded that the effect of ethanol ingestion is influenced by the mode of administration of the ethanol. Dehydration may be a confounding factor in studies of animal models of fetal alcohol syndrome, although it is not possible to rule out a differential metabolic response to alcohol, depending on the mode of administration.     

Morphometric analysis of the craniofacial development of the CD-1 mouse fetus exposed to alcohol on gestational day eight

Fetal alcohol syndrome (FAS) describes a pattern of dysmorphogenesis observed in some offspring of women who consumed alcohol during pregnancy; partial expression of this pattern are fetal alcohol effects (FAE). The purpose of this investigation was to measure selected craniofacial parameters in the CD-1 mouse fetus following exposure to alcohol on gestational day (D) 8. CD-1 mice were mated for 1 hr; D0.0 designated by the presence of a vaginal plug. On D8, 0 hr, and D8, 4 hr, 33 dams were injected intraperitoneally (IP) with 25% (v/v) alcohol in physiological saline solution (0.015 ml/gm maternal body weight). Appropriate controls were maintained. The animals were sacrificed every 12 hr from D12.0 through D17.0. Implantation sites were examined and recorded as live, dead, or resorbed fetuses. All live fetuses were weighed, examined for gross defects, and fixed in Bouin's solution. Twenty-three bilateral parameters were recorded for linear dimensions defining face and cranium. The fetal weights were statistically lower in treated as compared to control fetuses only on D16.0 through D17.0. Statistical analysis of the morphometrics identified five distinct growth patterns in treated mice as compared to controls. The anomalies induced in the CD-1 mouse fetus following exposure to alcohol on D8.0 resembled FAE rather than FAS. Morphometric analysis of the craniofacial region may be an important clinical tool for the quantitative identification of alcohol-related effects in the offspring of women who consumed alcohol while pregnant.     

Randomised controlled trial of intrapartum fetal heart rate monitoring.

OBJECTIVE--To compare effectiveness of different methods of monitoring intrapartum fetal heart rate. DESIGN--Prospective randomised controlled trial. SETTING--Referral maternity hospital, Harare, Zimbabwe. SUBJECTS--1255 women who were 37 weeks or more pregnant with singleton cephalic presentation and normal fetal heart rate before entry into study. INTERVENTIONS--Intermittent monitoring of fetal heart rate by electronic monitoring, Doppler ultrasound, use of Pinard stethoscope by a research midwife, or routine use of Pinard stethoscope by attending midwife. MAIN OUTCOME MEASURES--Abnormal fetal heart rate patterns, need for operative delivery for fetal distress, neonatal mortality, Apgar scores, admission to neonatal unit, neonatal seizures, and hypoxic ischaemic encephalopathy. RESULTS--Abnormalities in fetal heart rate were detected in 54% (172/318) of the electronic monitoring group, 32% (100/312) of the ultrasonography group, 15% (47/310) of the Pinard stethoscope group, and 9% (28/315) of the routine monitoring group. Caesarean sections were performed for 28% (89%), 24% (76), 10% (32), and 15% (46) of the four groups respectively. Neonatal outcome was best in the ultrasonography group: hypoxic ischaemic encephalopathy occurred in two, one, seven, and 10 cases in the four groups respectively; neonatal seizures occurred only in the last two groups (six and nine cases respectively); and deaths occurred in eight, two, five, and nine cases respectively. CONCLUSIONS--Abnormalities in fetal heart rate were more reliably detected by Doppler ultrasonography than with Pinard stethoscope, and its use resulted in good perinatal outcome. The use of relatively cheap ultrasound monitors should be further evaluated and promoted in obstetric units caring for high risk pregnancies in developing countries with scarce resources.     

Acute alcohol exposure, acidemia or glutamine administration impacts amino acid homeostasis in ovine maternal and fetal plasma

Fetal alcohol syndrome (FAS) is a significant problem in human reproductive medicine. Maternal alcohol administration alters maternal amino acid homeostasis and results in acidemia in both mother and fetus, causing fetal growth restriction. We hypothesized that administration of glutamine, which increases renal ammoniagenesis to regulate acid–base balance, may provide an intervention strategy. This hypothesis was tested using sheep as an animal model. On day 115 of gestation, ewes were anesthetized and aseptic surgery was performed to insert catheters into the fetal abdominal aorta as well as the maternal abdominal aorta and vena cava. On day 128 of gestation, ewes received intravenous administration of saline, alcohol [1.75 g/kg body weight (BW)/h], a bolus of 30 mg glutamine/kg BW, alcohol + a bolus of 30 mg glutamine/kg BW, a bolus of 100 mg glutamine/kg BW, alcohol + a bolus of 100 mg glutamine/kg BW, or received CO₂ administration to induce acidemia independent of alcohol. Blood samples were obtained simultaneously from the mother and the fetus at times 0 and 60 min (the time of peak blood alcohol concentration) of the study. Administration of alcohol to pregnant ewes led to a reduction in concentrations of glutamine and related amino acids in plasma by 21–30 %. An acute administration of glutamine to ewes, concurrent with alcohol administration, improved the profile of most amino acids (including citrulline and arginine) in maternal and fetal plasma. We suggest that glutamine may have a protective effect against alcohol-induced metabolic disorders and FAS in the ovine model.     

怀孕前后酒精摄入对雌鼠植入前胚胎DNA甲基化模式建立的影响

女性怀孕前后饮酒会对胎儿的发育及神经系统造成不利影响,称为“胎儿酒精综合征”（fetal alcohol spectrum disorders,FASD）。小鼠通常作为研究该病的动物模型。该实验采用体外培养技术及体内冲胚法研究雌鼠怀孕前后酒精摄入对各期植入前胚胎全基因组DNAT基化模式建立的影响。小鼠植入前胚胎体外培养实验发现,体外实验组I（怀孕前酒精处理组1,除8-cell外,其他各期胚胎的DNA甲基化水平明显低于体外对照组;体外实验组II（正常胚胎在含乙醇的培养基中培养）,各期植入前胚胎DNA甲基化水平均明显低于体外对照组。体内实验发现,体内实验组I（怀孕前酒精处理组）与体内的实验组II（怀孕后酒精处理组）,各期植入前胚胎DNA甲基化水平明显低于体内对照组。体内、外实验结果表明：受精前后酒精对各期植入前胚胎DNA甲基化模式的正确建立造成紊乱,该结果可为进一步揭示FSAD发病机制提供一定的实验基础。