A randomized trial of the effects of dietary counseling on gestational weight gain and glucose metabolism in obese pregnant women.

OBJECTIVE: Can gestational weight gain in obese women be restricted by 10-h dietary consultations and does this restriction impact the pregnancy-induced changes in glucose metabolism? DESIGN: A randomized controlled trial with or without restriction of gestational weight gain to 6-7 kg by ten 1-h dietary consultations. SUBJECTS: Fifty nondiabetic nonsmoking Caucasian obese pregnant women were randomized into intervention group (n=23, 28+/-4 years, prepregnant body mass index (BMI) 35+/-4 kg m(-2)) or control group (n=27, 30+/-5 years, prepregnant BMI 35+/-3 kg m(-2)). MEASUREMENTS: The weight development was measured at inclusion (15 weeks), at 27 weeks, and 36 weeks of gestation. The dietary intakes were reported in the respective weeks by three 7-day weighed food records and blood samples for analyses of fasting s-insulin, s-leptin, b-glucose, and 2-h b-glucose after an oral glucose tolerance test were collected. RESULTS: The women in the intervention group successfully limited their energy intake, and restricted the gestational weight gain to 6.6 kg vs a gain of 13.3 kg in the control group (P=0.002, 95% confidence interval (CI): 2.6-10.8 kg). Both s-insulin and s-leptin were reduced by 20% in the intervention group compared to the control group at week 27, mean difference: -16 pmol l(-1) (P=0.04, 95% CI: -32 to -1) for insulin and -23 ng ml(-1) (P=0.004, 95% CI: -39 to -8) for leptin. At 36 weeks of gestation, the s-insulin was further reduced by 23%, -25 pmol l(-1) (-47 to -4, P=0.022) and the fasting b-glucose were reduced by 8% compared with the control group (-0.3 mmol l(-1), -0.6 to -0.0, P=0.03). CONCLUSIONS: Restriction of gestational weight gain in obese women is achievable and reduces the deterioration in the glucose metabolism.

A longitudinal study of intrauterine growth and the placental growth hormone (GH)-insulin-like growth factor I axis in maternal circulation: association between placental GH and fetal growth.

The aim of the study was 1) to evaluate the association of maternal serum levels of placental GH and IGF-I with fetal growth, and 2) to establish reference data for placental GH, IGF-I, and IGF-binding protein-3 (IGFBP-3) in normal pregnancies based on longitudinal measurements. A prospective longitudinal study of 89 normal pregnant women was conducted. The women had, on the average, seven blood samples taken and three ultrasound examinations performed. All had normal umbilical artery pulsatility indexes during pregnancy and gave birth to singletons between 37 and 42 wk gestation with birth weights above -2 SD. Placental GH levels were detectable in all samples from as early as 5 wk gestation and increased significantly throughout pregnancy to approximately 37 wk when peak levels of 22 ng/ml (range, 4.64-69.22 ng/ml) were reached. Subsequently, placental GH levels decreased until birth. The change in placental GH during 24.5-37.5 wk gestation was positively associated with fetal growth rate (P = 0.027) and birth weight (P = 0.027). Gestational age at peak placental GH values (P = 0.007) was associated with pregnancy length. A positive association between the change in placental GH and the change in IGF-I levels throughout gestation was found in a multivariate analysis (r(2) = 0.42; P < 0.001). There was no association between placental GH and IGFBP-3 levels. The change in IGF-I throughout gestation (P = 0.039), but not placental GH, was significantly positively associated with placental weight at birth. We found a significant association between placental GH and fetal growth. In addition, we found a highly significant association between the increase in placental GH and the increase in IGF-I. The gestational age at peak placental GH levels was associated with pregnancy length.

Umbilical artery Doppler flow-velocity waveforms and fetal acid-base balance in Rhesus-isoimmunized pregnancies.

Pulsed Doppler blood-flow velocity waveforms in the umbilical arteries, as well as blood gases, hematocrit, and lactate concentration in umbilical venous blood, were examined in 21 patients undergoing 49 cordocentesis, 34 of which were followed by fetal blood transfusion into the umbilical vein. The aim of the study was to evaluate the correlations, if any, between the Doppler indices from the umbilical artery (pulsatility index, resistance index, systolic/diastolic ratio) and the blood gas values (pO2, pCO2, O2 content, pH) and lactate content in the umbilical vein. The only correlation confirmed in this study was in the subgroup of anemic fetuses undergoing fetal blood transfusion, where correlation existed between A/B and the initial O2 content (r = -0.41, p < 0.02). We conclude that, in Rhesus-isoimmunized pregnancies, in contrast to other pregnancies, a close correlation does not exist between the Doppler indices in the umbilical artery and the fetal blood gas values.

Umbilical artery Doppler flow-velocity waveforms in Rhesus-isoimmunized fetuses before and after fetal blood sampling or transfusion.

Pulsed-Doppler examinations of blood-flow velocities in the umbilical artery were carried out before and after 15 diagnostic cordocenteses and 34 fetal blood transfusions into the umbilical vein. There were decreases in the systolic/diastolic ratio (A/B) (p < 0.01), the pulsatility index (PI) (p < 0.05), and the resistance index (RI) (p < 0.01) after cordocentesis but not after fetal blood transfusion. There were no correlations between the initial hematocrit and the umbilical artery Doppler indices in the sample nor in the fetal blood sampling group. In the fetal blood transfusion group, on the other hand, there was a negative correlation between the initial hematocrit and A/B (r = -0.44; p < 0.01) and the RI (r = -0.35; p < 0.05). The umbilical artery Doppler flow-velocity indices did not predict the fetal hematocrit.

Prediction of mode of delivery and 'DisFIL score' following induction of labor by local PGE2.

The objective of the study was to evaluate pre-induction risk factors for (i) assisted vaginal delivery (forceps or vacuum extraction), (ii) caesarean section, (iii) failed induction followed by caesarean section, and from these to evaluate a score of the 'Disadvantages Following Induction of Labour' (the DisFIL score). The study was a case-control study applied on a prospective cohort of 336 pregnant women induced by local PGE2. Assisted vaginal delivery was associated with primiparity (OR (odds ratio) = 10.7; CI, 3.6-32.0) and higher pelvic scores (Bishop score: OR = 1.9; CI, 1.4-2.6). Caesarean section was related to higher maternal age (P < 0.001) and lower pelvic scores (Bishop score: OR = 0.7; CI, 0.5-1.0, P < 0.05). When performed because of fetal distress, assisted vaginal delivery and caesarean section were both associated with lower fetal weights (P < 0.05). Failed induction followed by caesarean section was related to primiparity (P < 0.0001, Fisher's test) and lower pelvic scores (Bishop score: OR = 0.6; CI, 0.4-0.9). A higher 'DisFIL score' was associated with primiparity (OR = 4.7; CI, 2.8-8.0), higher maternal age (P < 0.01), lower pelvic scores (P < 0.01, chi 2 test) and PGE2 in intracervical gel rather than in vaginal pessaries (OR = 2.1; CI, 1.4-3.2). It is concluded that the major predictors of 'Disadvantages Following Induction of Labor' by local PGE2 are primiparity, high maternal age, low pelvic scores and the method of.

[The antiprogesterone preparation mifepristone (RU 486). Should this "abortion pill" be introduced in Denmark?]. / Antiprogesteronpraeparatet mifepriston (RU 486). Bør man indføre denne "abortpille" i Danmark?

The antiprogesterone mifepristone (RU 486) was synthesized in 1980 by Roussel-Uclaf (Paris). Since 1982 several studies have examined the ability of the drug to interrupt early pregnancies. 600 mg of mifepristone given by mouth to pregnant women with an amenorrhea of less than 50 days will lead to vaginal bleeding in more than 97% of the cases. The bleeding will be followed by moderate (menstruation-like) pain, and complete abortion will occur in 75% of the cases. A success rate of 75% is not sufficient for clinical use. The treatment should therefore consist of a combination of mifepristone and prostaglandin. The prostaglandin can be administered either by i.m. injections or as a vaginal suppository given 38-48 hours after the patient has received 600 mg of mifepristone by mouth. Such a combination of mifepristone and prostaglandin results in a complete abortion rate of more than 95%. Pelvic inflammatory disease (P.I.D.) after these abortions is extremely rare (below 0.5%), and other serious side effects are also uncommon. We find that mifepristone in combination with prostaglandin should be offered to Danish women seeking abortion as an alternative to the traditional method of vacuum aspiration.

Hypoxanthine in fetal umbilical venous blood and amniotic fluid from pregnancies complicated by rhesus isoimmunization.

Concentrations of hypoxanthine (HX) was determined in umbilical venous blood and amniotic fluid obtained at 74 instances in 36 rhesus immunized patients before the onset of labor. HX concentrations were related to gestational age, concentrations of hemoglobin and lactate, pH, and partial oxygen pressure in umbilical venous blood. Multiple regression analysis revealed hemoglobin concentration to be the only variable that had any explanatory power to HX in amniotic fluid. No one of the studied variables gave any significant contribution to a regression model to explain HX in umbilical venous blood. We conclude that HX levels in umbilical venous blood and in amniotic fluid from rhesus immunized patients were not associated with fetal blood gases before the onset of labor.

Placenta previa-percreta: magnetic resonance imaging findings and methotrexate therapy after hysterectomy.

A case is reported of a 42-year-old woman with placenta previa-percreta and multiple previous cesarean sections. Preoperative magnetic resonance imaging findings are described. Management included a cesarean supracervical hysterectomy, bilateral hypogastric arterial ligation, and intraoperative methotrexate administration. The placental portion that invaded the urinary bladder wall was left in place, without attempt to remove it surgically.

Erythropoietin concentrations in amniotic fluid and umbilical venous blood from Rh-immunized pregnancies.

We set out to investigate prospectively the levels of erythropoietin in amniotic fluid and umbilical venous blood, and to attempt to relate these to fetal haemoglobin and lactate concentrations and to pCO2 and PO2 in Rh immunised patients studied before the onset of labor. Fetal blood was obtained by cordocentesis, and amniotic fluid by amniocentesis from a consecutive series of 36 Rh immunized patients at the time of fetal blood sampling. There was a close correlation (tau = 0.357, P = 0.0001) between the concentrations of erythropoietin in umbilical venous blood and those in amniotic fluid. Erythropoietin in umbilical venous blood correlated inversely with hemoglobin (tau = 0.453, P = 0.0001), and directly with lactate concentrations (tau = 0.450, P = 0.0005). When all other variables were considered, multiple regression analysis demonstrated hemoglobin concentration to be the only variable to be related to the level of erythropoietin in umbilical venous blood taken before transfusion. When the same analysis was performed on the same variables, adding erythropoietin concentration in amniotic fluid as the dependent variable, only erythropoietin in umbilical venous blood was found to be related to the level of erythropoietin in amniotic fluid. We conclude that the erythropoietin concentration in umbilical venous blood from Rh-immunized patients before the onset of labor, is related to fetal anemia. We also conclude that erythropoietin concentration in amniotic fluid is related to that in fetal blood, thereby indicating that the fetus is an important source of amniotic fluid erythropoietin in non laboring patients.

Lack of relation between fetal blood gases and fetal blood flow velocity waveform indices found in rhesus isoimmunised pregnancies.

OBJECTIVE: To investigate the relation between umbilical vein blood gas components and the vascular resistance in four fetal arteries in Rh-immunised pregnancies. DESIGN: A prospective observational study over a 4-month period. SETTING: King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. SUBJECTS: Fifteen Rh-isoimmunised pregnant women. INTERVENTIONS: Pulsed Doppler examinations of the umbilical artery, fetal internal carotid artery, thoracic aorta and abdominal aorta before transabdominal fetal blood sampling from the umbilical vein on 38 occasions. MAIN OUTCOME MEASURES: Doppler flow velocity pulsatility index (PI), systolic/diastolic ratio (A/B) and resistance index (RI) in the four fetal arteries investigated were related to the umbilical vein blood gases and acid-base status (PO2, PCO2, O2-content, CO2-content, HCO3, base excess and lactate concentration). RESULTS: There were no correlations between the Doppler indices in any of the vessels studied and the blood gases components in the umbilical vein. The ratios between the corresponding Doppler indices in the different vessels were also independent of the blood gases and acid-base status and there were no significant differences in the Doppler indices in the same vessel between fetuses with blood gas values over the 75th centile and those with values below the 25th centile. CONCLUSION: This study does not support a reduction in peripheral vascular resistance in the fetal cerebrum in relation to fetal hypoxia in Rh-immunized pregnancies.

Predictive value of pelvic scores for induction of labor by local PGE2.

The predictive value of pelvic scores, parity, age and gestational age for induction of labor by local prostaglandin-E2 (PGE2) was examined in 336 women attempting induction of labor by intracervical or vaginal PGE2. The patient characteristics were correlated to: (1) vaginal delivery within 48 h, (2) the period from induction to onset of labor (latency period), and (3) the duration of labor. The Bishop score (P < 0.01) and even more the Lange score (P < 0.0001) were significantly inversely correlated to both latency period and induction-delivery period. This was caused by cervical dilatation (P < 0.001), fetal station (P < 0.05) and cervical length (P < 0.05), whereas position and consistency of the cervix were of no importance. All three periods studied were significantly (P < 0.0001) shorter in parous women. In primiparous women, gestational age was of no importance for the latency period; however, higher gestational age was associated with longer labor (P < 0.001). We conclude that the predictive value of pelvic scores on induction hardly differs using local PGE2 compared to conventional methods; furthermore, the Bishop score should be substituted, disregarding position and consistency of the cervix, but putting more weight to cervical dilatation. A new pelvic score is proposed.

Inhomogeneous broadening and kinetic carbon monoxide isotope effects in low-temperature carbon monoxide recombination with myoglobin and hemoglobin.

We have analyzed the non-exponential kinetics, the temperature variation, and the CO isotope effects of the CO recombination reactions with myoglobin and single-chain hemoglobin. The analysis rests on multiphonon quantum-mechanical chemical-rate theory combined with static inhomogeneous broadening of either the reorganization free energy or the reaction Gibbs free energy. The simplest specific model which can account for all the data contains an inhomogeneous distribution function of width 0.2-0.3 eV, independent of temperature down to the tunnel transition at about 20 K, two discrete nuclear coordinates of low vibrational frequency (60-150 cm-1) representing iron-heme and CO bending motion, the CO stretching motion of frequency about 2000 cm-1, and additional inhomogeneous broadening of the protein and CO bending configuration below the tunnel transition temperature. The model appears somewhat involved but in return provides corresponding insight in the dynamics of this important class of processes.

Intramural pregnancy after in vitro fertilization and embryo transfer.

A case of intramural but not interstitial pregnancy, established after IVF/ET, is described. The etiologic, diagnostic, and therapeutic aspects of this clinical dilemma are discussed.

Mifepristone or vacuum aspiration in termination of early pregnancy.

This trial compared the termination of early pregnancy (amenorrhoea less than 43 days) by 600 mg orally of the antiprogesteron Mifepristone to the traditional method of vacuum aspiration. Fifty women were randomly assigned to either of the treatments. All the patients treated with vacuum aspiration had a complete abortion. Three of these patients developed pelvic inflammatory diseasae (PID) after the aspiration. Another patient had the uterus perforated during the procedure, and an emergency laparotomy had to be performed. The patients in the evacuation group spent more days in bed and needed longer sick leave after the treatment than the patients in the Mifepristone group. In the Mifepristone group, six patients had incomplete abortions and all were treated by evacuation. Three of the patients developed PID after the evacuation. A decrease of 40% or more in beta hCG from the initial value to the value 1 week later were invariably associated with complete abortion. In both groups the changes in hemoglobin were insignificant and no patients needed blood transfusion or emergency evacuation. The Mifepristone treatment is a simple and safe alternative to vacuum aspiration for termination of early pregnancies.

PIP: This trial compared the termination of early pregnancy (amenorrhea less than 43 days) by 600 mg mifepristone, an antiprogesterone, to traditional method of vacuum aspiration. 50 women were randomly assigned to either of the treatments. All patients who underwent vacuum aspiration had a complete abortion. 3 of these patients developed pelvic inflammatory disease (PID) following aspiration. Another patient experienced a uterine perforation during the procedure, and an emergency laparotomy was performed. The patients in the evacuation group spent more days in bed and needed more sick leave after the treatment than the patients in the mifepristone group. In that group, 6 patients had incomplete abortions and all were treated with evacuation. 3 developed PID after the procedure. A decrease of 40% or more ion the beta-hCG from the initial value to the value 1 week later wee invariably associated with complete abortion. In both groups, the changes in hemoglobin were insignificant and no patients needed blood transfusions or emergency evacuations. The mifepristone treatment is simple and a safe alternative to vacuum aspiration for termination of early pregnancies.

Myocardial contractility in the anemic human fetus.

Severely anemic fetuses in Rh-isoimmunized pregnancies are often found to have hydrops and the etiology is debated. Fifteen fetal blood samplings were performed in nine fetuses for determination of the degree of anemia and of the acid-base balance. Waveform analysis was performed on the maximum blood velocity curve in the umbilical arteries and the ascending fetal aorta, obtained by means of a pulsed Doppler technique. The blood acceleration in the ascending aorta increased down to a hematocrit of 0.18 and a hemoglobin concentration of 65 g/l, which might constitute a cardiac response to the anemia aimed at maintaining the peripheral blood circulation. Below these levels there was a decrease in blood acceleration, which could be caused by impaired cardiac oxygenation. This relationship could be described as a six-power function (r = 0.87; p = 0.032). A second-power relationship was found between the umbilical artery pulsatility index and the blood acceleration in the fetal ascending aorta (r = 0.64; p = 0.0418), which suggests that the cardiac pump function can alter the blood velocity waveform in the umbilical arteries.

Induction of labour: the effect of vaginal prostaglandin or i.v. oxytocin--a matter of time only?

Ninety-one pregnant women with unfavourable cervix (Bishop score no higher than 6) were randomly allocated to induction of labour with either prostaglandin E2 suppositories 2.5 mg 1-2 a day or i.v. oxytocin 4-32 mU/min. The induction procedure was carried on for 2 days. For statistical comparison of efficacy, life table analysis and the logrank test were used with vaginal delivery as the aimed 'event'. Prostaglandin suppositories were more efficient after 12 h (p less than 0.025) and 24 h (p less than 0.005), whereas no difference in efficacy was observed after 48 h. Vaginal delivery was obtained within 48 h in 74% of the women in the prostaglandin group and in 70% in the oxytocin group. No difference was observed in methods of delivery or neonatal Apgar scores, though, in neonates delivered vaginally within 2 days, lowered umbilical artery blood pH values were found after prostaglandin E2 suppositories (p less than 0.05). The patients attitude toward the method of induction was highly in favour of the prostaglandin suppositories. Prostaglandin E2 suppositories are considered excellent for induction of labour if delivery has to be within 24 h, whereas the two methods are equally effective after 48 h.

Doppler blood velocity waveforms and the relation to peripheral resistance in the brachial artery.

The relationship between peripheral resistance and the Doppler blood velocity indices--pulsatility index (PI), A/B ratio, resistance index (RI), and the minimum velocity (Vmin)--was evaluated in the brachial arteries of five young women. All the indices showed a very good correlation with resistance (r greater than 94%); the regression line for both PI and A/B were linear, whereas the relationships between resistance and RI, and resistance and Vmin, were best described by a logarithmic and by power function, respectively. Although the women were carefully selected to be as alike as possible, there were significant differences in the individual slopes of the regression lines.

Characteristics of Doppler blood-velocity waveforms in a cardiovascular in vitro model. I. The model and the influence of pulse rate.

In order to study the indices describing the flow-velocity curves a cardiovascular in vitro model has been constructed. The model consists of two parts: (i) A heart simulator producing controllable cardiac output, pulse rate and pressure variations, (ii) a circulatory system made of elastic butyl rubber tubes with adjustable peripheral resistance bed. The flow-velocity curves were obtained by a Doppler velocity meter as a function of the pulse rate (PR) when pressure, volumetric flow, and peripheral resistances were constant. The four evaluated indices, pulsatility index (PI), peak velocity (Vpeak), rising slope (RS) and A/B ratio (A/B i.e. maximum/minimum velocity ratio) all showed significant correlation with pulse rate. PI, A/B and Vpeak showed a marked increased at low pulse rate and the inverse relation between these indices and pulse rate were best described by power functions, whereas RS was found to be inversely proportional to pulse rate. The results are in good agreement with the few existing clinical observations, and we suggest that the relations described are taken into consideration in the clinical interpretation of blood velocity indices.