Screening efficacy of the subcutaneous tissue width/femur length ratio for fetal macrosomia in the non-diabetic pregnancy.

BACKGROUND: Antenatal weight estimations have limited sensitivity and specificity for the detection of macrosomia. The objective of our study was to examine the screening efficacy of the subcutaneous tissue width/femur length ratio for the intrapartum detection of fetal macrosomia in a non-diabetic population at term. STUDY DESIGN: Intrapartum sonographic measurements were performed in 178 well-dated gravidas at 37-41 weeks' gestation with negative glucose tolerance screens. The biparietal diameter, femur length (FL), abdominal circumference and subcutaneous tissue width of the thigh (SCT) were determined. Subsequently, predictions for macrosomia (actual birth weights above the 90th centile) were made using varying cut-off points of the examined parameters or estimated fetal weights. RESULTS: Macrosomia occurred in 27 newborns (15.1%). The SCT/FL ratio was independent of gestational age (r = -0.017). Maternal age, gravidity, parity, gestational age and the ratio of male-to-female infants were similar in pregnancies resulting in appropriate-for-gestational-age and macrosomic infants (NS). There was no difference in the SCT/FL ratio between these groups (p = 0.067; 99% power to detect 2 standard deviation differences). Comparison of screening efficacy by the univariate z score for the area under receiver operating characteristic (ROC) curves (theta) revealed that the abdominal circumference had the best sensitivity-specificity trade-off (theta = 0.8843; p < 0.0001 for comparison with SCT/FL ROC curve), followed by weight estimations based on the Hadlock formula (theta = 0.8773; p < 0.0005), the Shepard formula (theta = 0.8606; p < 0.0001), subcutaneous tissue thickness alone (theta = 0.6872; p < 0.01) and the SCT/FL ratio (theta = 0.6303). CONCLUSIONS: We conclude that the SCT/FL ratio is a poor sonographic predictor of fetal macrosomia in the non-diabetic pregnancy and does not improve fetal weight estimations by conventional sonographic parameters.

The effect of betamethasone and dexamethasone on fetal heart rate patterns and biophysical activities. A prospective randomized trial.

UNLABELLED: BACKGROUND; Contradictory findings on the effect of betamethasone versus dexamethasone on antenatal tests of fetal well-being have been reported. The purpose of this study was to compare the effects of these steroid compounds on fetal heart rate patterns and biophysical activities in a prospective. randomized trial. STUDY DESIGN: Forty-six pregnant women (gestational age range 27-34 weeks) at risk for preterm delivery were randomized to receive betamethasone or dexamethasone for enhancement of fetal lung maturity. Fetal heart rate was recorded for 60 minutes and analyzed with the Sonicaid System 8000 before (0 hours), and 48 hours and 96 hours after steroid administration. Subsequently, fetal limb, body and breathing movements were sonographically observed and quantified for 30 minutes. To account for fetal circadian rhythms, all examinations were performed between 1 p.m. and 5 p.m., at least one hour after maternal meals. RESULTS: Fetal heart rate accelerations (p<0.001; p<0.01), short-term variation (p<0.0001; p<0.05), long-term variation (p<0.01; p=NS), duration of high episodes (p<0.001; p<0.05), total movement count (p<0.001; p<0.05), and duration of breathing time (p<0.0001; p<0.0001) were substantially reduced 48 h after betamethasone and dexamethasone administration, respectively, with percent reduction being larger for the betamethasone group, except for breathing movements (p<0.05; p<0.001; p<0.001; p<0.005; p<0.05; p=NS; respectively). In 68.2%( and 45.5% of fetuses, less than 30 seconds of continuous breathing movements were found in the betamethasone and dexamethasone groups, respectively. In 71.8% and 12.5%, of fetuses, respectively, less than 2 body/limb movements were observed. Therefore five and two fetuses in the betamethasone and dexamethasone study group, respectively, had both nonreactive fetal heart rate monitors for 60 minutes and biophysical profiles of < or =4/10. All parameters returned to baseline values at 96 h. Baseline fetal heart rate and numbers of decelerations remained unchanged (p=NS). CONCLUSIONS: Both betamethasone and dexamethasone induce a profound, albeit transient, suppression of fetal heart rate characteristics and biophysical activities in the preterm fetus. However, the effect of betamethasone is more pronounced. Awareness of these phenomena might prevent unwarranted iatrogenic delivery of preterm fetuses.

Teratological interaction between the bis-triazole antifungal agent fluconazole and the anticonvulsant drug phenytoin.

Previous studies implicated the cytochrome P450 (CYP) system as critical in the teratogenic bioactivation of phenytoin (PHT). Fluconazole (FCZ) is an antifungal bis-triazole with potent inhibitory effect on the principal CYP-dependent metabolic pathway of PHT. In this study an in vivo experimental model was used to evaluate the potential ability of FCZ (2, 10, or 50 mg/kg intraperitoneally) to modulate PHT (65 mg/kg intraperitoneally) teratogenesis on day 12 (plug day = day 1) Swiss mice. PHT alone elicited embryocidal and malformative effects, with cleft palate as the major malformation. Pretreatment with the nonembryotoxic dosage of 10 mg FCZ/kg potentiated PHT-induced teratogenesis, as indicated by a twofold (from 6.2% to 13.3%) increment of cleft palate incidence (P < 0.05). Combined treatment with 50 mg FCZ/kg plus PHT resulted in a statistically significant (P < 0.05) increment of the resorption incidence recorded after PHT-alone exposure, but possibly as a consequence of the increased embryolethality, in the loss of the potentiative effect on PHT teratogenesis. Although the mechanistic nature of teratological interaction between FCZ and PHT remains to be established, these results may not support CYP system-mediated metabolic conversion as the mechanistic component of PHT teratogenesis.

Aspirin pretreatment potentiates hyperthermia-induced teratogenesis in the mouse.

OBJECTIVE: Our purpose was to investigate the effect of aspirin pretreatment on hyperthermia-induced teratogenesis. The rationale for the study was based on the growing evidence that prostaglandin pathway may be involved in the cellular response to the thermic injury. STUDY DESIGN: On gestation day 8.5 Swiss mice were treated with 0 or 200 mg/kg of aspirin and 1 hour later exposed to a single 10-minute thermostatic bath treatment at 38 degrees C, 41 degrees C, 42 degrees C, or 43 degrees C. On gestation day 18 uterine contents were evaluated for developmental disorders, including prenatal mortality, intrauterine growth restriction, and external, visceral, and skeletal abnormalities. RESULTS: Consistent with expectations, hyperthermia impaired morphogenesis in a dose-related manner. Although aspirin alone did not reveal embryotoxicity, its administration potentiated hyperthermia-induced teratogenesis. A statistically significant interaction (p < 0.05) was observed at 42 degrees C, where the incidence of fetuses per litter with axial skeletal malformations increased from 20.3% to 55.7%. CONCLUSION: A nonteratogenic dose of aspirin enhanced the teratogenic response to hyperthermia. This result fits the hypothesis that prostaglandins may play a protective role in hyperthermia-induced teratogenesis.

The effect of follicle-stimulating hormone therapy on sperm quality: an ultrastructural mathematical evaluation.

We investigated the effect of follicle-stimulating hormone (FSH) administration on the ultrastructure of spermatozoa in order to evaluate the potential of FSH therapy for improving sperm quality. Forty-six patients exhibiting idiopathic oligoasthenoterato-zoospermia who attended the intrauterine insemination (IU), in vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI) program at our clinic received FSH in daily dosages of 150 IU over a period of 12 weeks. Using transmission electron microscopy, the ultrastructural analysis of spermatozoa was performed prior to the start of FSH therapy, after the treatment had been finished, and 6 weeks posttherapy. Applying a mathematical formula based on submicroscopic characteristics, we calculated the number of morphologically normal spermatozoa. After the FSH treatment, the examined subcellular organelles achieved a higher percentage of integrity. Follicle-stimulating hormone treatment leads to a higher number of morphologically normal spermatozoa. The electron microscopic findings indicate that treatment with pure FSH may be an effective way to improve sperm quality in cases with oligoasthenoterato-zoospermia. Applying the mathematical analysis based on the whole complex of the selected sperm characteristics, we obtained a way to evaluate the success of therapy for the first time.

Uterine artery Doppler velocimetry in pregnant women with lateral placentas.

The aim of this study was to compare the efficacy of placental, non-placental, mean of both uterine arteries Doppler velocimetry at 22-24 weeks gestation in the prediction of pregnancy induced hypertension (PIH) and intrauterine growth retardation (IUGR). Flow velocity waveforms were obtained by means of color and pulsed Doppler in 481 patients with lateral placentas at 22-24 weeks gestation. Placental location was determined by real time ultrasonography. Comparisons were performed between controls and pregnancies complicated by PIH and IUGR. Sensitivities, false positive rates and positive predictive values for PIH and IUGR of resistance indices (RI) above the 90th percentile, and diastolic notches in placental, non-placental or both uterine arteries were calculated. A mean uterine artery RI > or = 0.66 (90th centile) had better sensitivity than the placental (26.8% vs 17.1% for IUGR and 41.7% vs 33.3% for PIH) and the non-placental uterine artery (26.8% vs 21.9% for IUGR and 41.7% vs 33.3% for PIH). The presence of a diastolic notch in the placental uterine artery increased sensitivity (31.7% for IUGR and 50.0% for PIH) and positive predictive value of the test. In patients with laterally implanted placentas a mean of both uterine arteries RI above the 90th centile and the presence of a diastolic notch in the placental uterine artery at 22-24 weeks have a higher predictive value for the subsequent development of PIH and IUGR than the separate evaluation of the 2 uterine arteries.

Cardiotocographic and Doppler velocimetric patterns, pre- and post-thoracentesis, in a case of fetal hydrothorax.

Fetal hydrothorax is associated with elevated perinatal mortality. Management of this condition is controversial given that in utero spontaneous resolution has been described. A case of fetal hydrothorax associated with an extralobar lung sequestration that showed pathologic cardiotocographic patterns and abnormal Doppler velocimetry indices in several fetal vascular beds in reported. All pathologic patterns improved after fetal thoracentesis. It can be concluded that monitoring fetal well-being by means of cardiotocography and Doppler velocimetry may help in timing thoracentesis in cases of fetal hydrothorax.

Spatial distribution of glutathione, glutathione-related and antioxidant enzymes in cultured mouse embryos.

The present study was undertaken to evaluate the detoxifying capacity of organogenesis-stage murine concepti cultured in vitro. Investigative attention was particularly focused on the embryonic tissue distribution of cytoprotective pathways. Glutathione (GSH) status, GSH-related and antioxidant enzymes were assayed in the embryo proper (EP), visceral yolk sac (VYS) and ectoplacental cone (EC) of 29.44 +/- 1.56 (mean +/- SD) somite pairs concepti. All the tissues displayed significant and comparable concentrations of GSH, further supporting this tripeptide as critical in protection against embryotoxicants. The totality of enzymatic activities was detectable in the selected embryonic compartments. In terms of spatial distribution analysis, maximal activities were found in EC (glutathione peroxidase, glutathione reductase, superoxide dismutase and glyoxalase I and II), and VYS (glutathione transferase and catalase). These results indicate: (1) the organogenesis-stage conceptus, in addition to significant amounts of GSH, expresses constitutive activities of GSH-related and antioxidant enzymes; (2) maximal activity levels are detectable in the embryonic sites which, at the developmental stage selected for assay, serve (VYS) or are evolving to serve (EC) embryo/maternal exchange, and thus represent the primary sites of interaction with foreign compounds.

Doppler velocimetry of the uterine and fetal circulations during prostaglandin E2 cervical ripening.

The objective of the study was to investigate flow characteristics of the maternal uterine and fetal umbilical and middle cerebral arteries following intracervical administration of prostaglandin E2 (PGE2). Doppler velocimetry of uterine, umbilical and middle cerebral arteries was performed immediately before and 2 h after PGE2 administration in 28 women with uncomplicated post-term pregnancy and an unfavorable cervix. Placental position was determined in all cases. When all patients were considered jointly, regardless of placental position, the mean uterine artery resistance index (RI) values were 0.41 +/- 0.07 before and 0.48 +/- 0.13 2 h after PGE2 administration (p < 0.05). When patients with lateral placentas (n = 20) were analyzed separately, only the non-placental uterine artery showed a significant increase 2 h after PGE2 administration, whereas no significant differences were found in the placental uterine artery. No changes were observed in uterine RI values of patients with central placentas. No significant differences were observed for umbilical artery and middle cerebral artery before and after PGE2 administration. It is concluded that intracervical PGE2 administration increases uteroplacental resistance but probably does not substantially affect placental perfusion; that the umbilical circulation is not affected; and that there were no signs of redistribution of fetal blood flow.

[Efficacy of estrogen-progestin replacement therapy after bone marrow transplantation]. / Efficacia del trattamento sostitutivo con estro-progestinici in pazienti sottoposte a trapianto di midollo osseo.

Ovarian failure is a common consequence of chemotherapy and radiotherapy in women undergoing bone marrow transplantation. The longer survival in these women has raised, during the past years, the need for a better quality of life. The objective of the present study has been to evaluate perspectively the potential benefit of hormonal replacement therapy in 24 women who underwent bone marrow transplantation. The data obtained indicated that hormonal replacement therapy results effective in preventing and/or relieving the multiple manifestations of gonadal failure, including amenorrhea, hot flashes, atrophy of genital apparatus, osteoporosis and cardiovascular disease.

[Electron microscopic analysis of possible ultrastructural damage to spermatozoa after preparation by various methods]. / Analisi al microscopio elettronico di eventuali danni ultrastrutturali agli spermatozoi dopo preparazione con tecniche diverse.

We investigated the possibility of ultrastructural damage to human spermatozoa induced by different sperm preparation techniques. Ejaculates from 20 normozoospermic men were divided into equal aliquots and processed by glass wool filtration, Percoll density gradient centrifugation, and a simple two step centrifugation procedure which served as a control. Ultrastructural damage was assessed by scanning electron microscopy. Compared with Percoll density gradient centrifugation, glass wool filtration yielded a significantly increased proportion of intact acrosomes (p < 0.05). However, both preparations gave significantly better results than control (p < 0.001 and p < 0.01 for glass wool filtration and Percoll centrifugation, respectively). The conspicuous bending of sperm tails after Percoll centrifugation has a yet unknown importance. In conclusion, both glass wool filtration and Percoll centrifugation are efficient techniques for the accumulation of spermatozoa with intact acrosomes. Because of the higher sperm recovery rate, glass wool filtration appears to be the more appropriate method.

[Evaluation of the effect of a "Mediterranean diet" and pre-pregnancy body mass on fetal growth]. / Valutazione dell'influenza di una dieta "mediterranea" e della massa corporea pregravidica sull'accrescimento intrauterino.

In this study we compared the pregravidic body mass index (Quetelet index) with some variables recorded during pregnancy (caloric intake; weight increase, neonatal birth weight) in a group of patients consumers of a typical mediterranean diet. We studied the dietary habits of 100 pregnant women with gestational ages between 13 and 38 weeks. Each woman has been provided with daily, for seven consecutive days. The data have been analyzed evaluating, for each dietary componene, the caloric, proteic, glucidic, lipidic and microelements share. Our results showed degree of pregravidic obesity. However also in overweight patients that used diets with caloric intake as low as about 1600 Kcal/day, the neonatal weights were always within the normal range, confirming the adequacy of the "mediterranean diet" to the specific nutritional needs in pregnancy. Neonatal weight was better correlated to the pregravidic IQ than to the caloric intake.

Time-dependent and tissue-specific variations of glutathione transferase activity during gestation in the mouse.

Glutathione transferases (GSTs; EC. 2.1.5.18) activity was measured in maternal liver and conceptal tissues during gestation. In maternal liver, maximum activity was found at gestational day (GD) 9 after which it slowly decreased up to the end of gestation. The placental GSTs activity at GD18 was three times lower than that found at GD14. Conversely, fetal liver GSTs at GD14 was about 75% that at GD18. It was also observed that GSTs activity at GD9 and GD10 was higher in visceral yolk sac than in embryo proper. Substrate specificity measurements, SDS PAGE analysis and HPLC runs, carried out on GSH-affinity purified fractions, revealed that with the progress of gestation in maternal liver an increase in pi class GSTs subunit occurs, with a concomitant decrease in alpha class GSTs. With respect to the time of gestation, a significant change in alpha, mu and pi class GSTs expression also occurred in fetal liver and in chorioallantoic placenta. It was concluded that during gestation the GSTs system is subjected to a time-dependent and tissue-specific modulation which may play a protective role against developmental toxicants.

Color Doppler flow patterns and flow velocity waveforms of the intraplacental fetal circulation in growth-retarded fetuses.

OBJECTIVE: We examined intraplacental color Doppler flow patterns and spectral Doppler flow velocity waveforms of villous arteries in pregnancies with intrauterine growth retardation. STUDY DESIGN: A total of 192 uncomplicated pregnancies and 29 pregnancies with intrauterine growth retardation between 26 and 41 weeks' gestation were examined in this cross-sectional study. Intraplacental color Doppler flow findings and pulsatility indexes of umbilical and villous arteries were correlated with the presence of intrauterine growth retardation and multiple outcome variables. Villous arteries were identified by their intraplacental color Doppler flow image, and flow velocity waveforms were obtained by superimposition of pulse-wave Doppler. RESULTS: (1) Intraplacental color Doppler flow signals from two or more villous arteries were detected in all 192 normal pregnancies but were undetectable in 8 of 29 fetuses with intrauterine growth retardation (27.6%, p < 0.0001). Absence of intraplacental color Doppler flow signals was associated with fetal distress in 6 of 8 cases (87.5%) and perinatal death in two cases (25.0%), compared with 3 of 21 (14.2%, p < 0.005) and 0 of 21 (not significant) cases of intrauterine growth retardation with detectable intraplacental color Doppler flow. Median Apgar scores at 1 minute were 5 and 8 (p < 0.05), respectively, and at 5 minutes were 8 and 8 (not significant), respectively. (2) Umbilical artery flow velocity waveforms were abnormal (> 95th percentile) in 8 of 21 cases of intrauterine growth retardation (38.0%) with detectable intraplacental color Doppler flow, including two cases with reversed end-diastolic flow. In contrast, the corresponding villous artery flow velocity waveforms were abnormal in only 1 of 21 cases (p < 0.04). CONCLUSION: (1) Failure to detect intraplacental color Doppler flow signals is associated with intrauterine growth retardation and fetal distress. (2) Flow velocity waveforms of detectable villous arteries are usually normal in intrauterine growth retardation, even in the presence of extremely abnormal umbilical artery flow velocity waveforms.

[Alcoholism and pregnancy]. / Alcolismo e gravidanza.

The T-ACE test, introduced by Sokol, is currently used in the screening of the pregnant women at risk for alcohol abuse. In this study, this test has been applied to a group of 150 pregnant women to verify the congruity of the methodology used, sensitivity and specificity of the test. According to the answers given by the patients in the preliminary interview, 9 patients (6%) proved at risk for alcohol abuse. At the subsequent, control, interview, the answers given were all in agreement with the data obtained with the T-ACE test. The results obtained confirmed the high sensitivity and specificity of this method. Even though the comprehension of the utilized verbalization was excellent, nevertheless the test, applied to patients of a different culture in comparison with that studied by Sokol, cannot be applied in its original form, but must be diluted within a group of questions.

[Experience regarding the use of arginine-lysine-lactose treatment in menopausal osteoporosis]. / Esperienza sull' utilizzo di arginina-lisina-lattosio nella terapia dell' osteoporosi menopausale.

Two matched groups of postmenopausal patients were treated respectively with calcitonin or calcitonin and an arginine-lysine-glycerophosphoric acid-lactose association. The rationale underlying this therapy took the form of data in the literature which indicated an action of these amino acids and lactose on calcium absorption and on the metabolism of protein components in the skeletal structure. The following tests were performed: mineralometric evaluation, evaluation of painful symptoms and intake of pain-relieving drugs, serum levels of calcium, phosphorus, alkaline phosphatase, osteocalcin, parathormone, and calciuria and hydroxyproline. These parameters were assayed at the beginning and end of treatment which lasted six months. The results, or in other words the comparison between the two groups, basal or after treatment, and the values recorded before and after treatment in each group, enable the authors to affirm that the administration of the arginine-lysine-glycerophosphoric acid-lactose association leads to an increase in bone density and plasma osteocalcin, a reduction in painful symptoms and analgesic intake, and a reduction in the serum levels of parathromone and hydroxyproline. Data reported in the literature support the conclusion that the results obtained are the consequence of an improved intestinal absorption calcium. It is highly probable that the protein components of the association administered, arginine-lysine-glycerophosphoric acid-lactose, also exercise a direct action on osteoblasts and on the metabolism of bone matrix protein components.

[Analytic evaluation of a "Mediterranean" diet in pregnancy]. / Valutazione analitica di una dieta "mediterranea" in gravidanza.

OBJECTIVE: To evaluate the effectiveness of the Mediterranean diet in pregnancy in relation to the increased maternal nutritional needs and to fetal outcome. SUBJECTS AND METHODS: We studied dietary habits of 100 pregnant women with gestational ages between 13 and 38 weeks. Each woman has been provided with a questionnaire to explore types and amount of food taken daily, for 7 consecutive days. The data have been analyzed evaluating, for each dietary component, the caloric, proteic, glucidic, lipidic and microelement share. The results obtained have been compared with the "recommended levels of daily intake of calories and nutrients for the Italian population" (LARN), and with the American "Recommended Daily Dietary Allowances" (RDA). RESULTS AND CONCLUSION: The Mediterranean diet proved able to completely satisfy pregnancy's increased biological needs except for iron. In fact the daily mean iron intake of the examined population was about 13 mg/day, while the recommended intake is about 36 mg/day. The dietary caloric intake was represented by proteins (16%), glucides (47.5%) and lipids (36.5%), with bread and cereals giving the higher energetic share (38%) in the examined diets. The mean caloric intake resulted lower than the one recommended by LARN and RDA, however neonatal birth weights were always within the normal range.