Long-term effects of prenatal progesterone exposure: neurophysiological development and hospital admissions in twins up to 8 years of age.

OBJECTIVES: To perform a neurophysiological follow-up at 48 or 60 months of age in children exposed prenatally to progesterone compared with a placebo and evaluate their medical histories up to 8 years of age. METHODS: In this study, Danish participants of the PREDICT study, including 989 surviving children from 498 twin pregnancies, were followed-up. PREDICT was a placebo-controlled randomized clinical trial examining the effect of progesterone for prevention of preterm delivery in unselected twin pregnancies. Medical histories of the children were reviewed and neurophysiological development was evaluated by the parent-completed Ages and Stages Questionnaire (ASQ) at either 48 or 60 months after the estimated date of delivery. We used the method of generalized estimating equation to account for the correlation within twins. RESULTS: A total of 492 children had been exposed prenatally to progesterone and 497 to placebo. There was no difference in the number of admissions to or length of stay in hospital between the treatment groups, and we found no overall difference in the rates of diagnoses made. However, the odds ratios (ORs) for a diagnosis concerning the heart was 1.66 (95% CI, 0.81-3.37), favoring placebo, among all children, 2.38 (95% CI, 1.07-5.30) in dichorionic twins and 8.19 (95% CI, 1.02-65.6) in all children when excluding diagnoses made at outpatient clinic visits. ASQ scores were available for 437 children (progesterone, n = 225; placebo, n = 212). Mean ASQ score was slightly higher in the progesterone group compared with the placebo group (P = 0.03). In dichorionic twins, the risk of having a low ASQ score (< 10(th) centile) was decreased in the progesterone group (OR, 0.34 (95% CI, 0.14-0.86)). CONCLUSION: Second- and third-trimester exposure of the fetus to progesterone does not seem to have long-term harmful effects during childhood, but future studies should focus on cardiac disease in the child. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.

BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

Influence of chorionicity on perinatal outcome in a large cohort of Danish twin pregnancies.

OBJECTIVE: To assess outcome in twin pregnancies according to chorionicity. METHODS: A cohort was retrieved from local ultrasound databases at 14 obstetric departments in Denmark, comprising all twin pregnancies with two live fetuses scanned between weeks 11 and 14 in the period 1 January 2004 to 31 December 2006. Outcome data were retrieved from the National Board of Health. RESULTS: Among 2038 twin pregnancies, 1757 (86.2%) were dichorionic (DC) and 281 (13.8%) were monochorionic diamniotic (MC). In MC pregnancies, the rate of spontaneous fetal loss in both second and third trimesters was more than threefold higher than the comparable rate in DC pregnancies: 6.0% vs. 1.9% for at least one fetus in the second trimester (P < 0.001) and 2.1% vs. 0.7% in the third trimester (P = 0.03). In 98.4% of DC pregnancies and in 91.1% of MC pregnancies, at least one infant was liveborn. Amongst pregnancies with two live fetuses at 24 weeks, the proportion with two live infants at 28 days after delivery was 97.5% and 95.1%, respectively. CONCLUSIONS: The increased incidence of fetal loss in MC pregnancies compared with DC pregnancies predominantly occurs before 24 weeks' gestation. After this stage, although the risk of intrauterine fetal death is still higher in MC than in DC pregnancies, if both fetuses are alive at 24 weeks, the chance of a woman having two live infants 1 month after delivery is similar in MC and DC pregnancies.

Postoperative urinary retention in gynecologic patients.

The aim of this study was to determine the prevalence of postoperative urinary retention (PU) based on preoperative estimation of bladder capacity in gynecologic patients and to evaluate the reliability of clinical examination in diagnosing PU. Over a 3-year period 284 consecutive patients undergoing surgical intervention were included in the study. Bladder capacity was assessed preoperatively. If PU was suspected a clinical examination, bladder scan and catheterization were performed. The prevalence of postoperative urinary retention was 9.2%. There was a significant association between PU and the type of operation, but not with the type or the duration of anesthesia or total blood loss. Clinical examination was reliable, with a positive and negative predictive value of 76.2% and 100%, respectively. In conclusion, PU is a substantial problem after gynecologic surgery. Patients at risk are difficult to predict. The risk is higher after laparotomy than after laparoscopy. The clinical diagnosis is fairly accurate.

[An outpatient unit for early pregnancy. Establishment and effects on the pattern of hospital admissions]. / Ambulatorium for tidlig graviditet. Etablering og indflydelse på indlaeggelsesmønster.

The aim of the study was to evaluate the effect of an assessment of complications in early pregnancy in an "early pregnancy unit" opened in May 1993. The purpose of the "early pregnancy unit" was to avoid routine admission of women with pain/bleeding in early pregnancy. All general practitioners were informed of the possibility of referring patients to examination and ultrasonography in the "early pregnancy unit" during daytime, instead of acute admission to the ward. Data was compiled from the hospital admission and the emergency unit register for the years 1992-1996. These showed that admissions for early pregnancy complications decreased from 714 (1992) to 315 (1996) accounting for 41% (1992) and 16% (1996) of total admissions to the department, and 23% (1992) and 10% (1996) of the numbers of deliveries, respectively. Women referred between 00:00 hours and 7 a.m. accounted for 23% (1992) and 9% of admissions of total admissions or of deliveries (1996). It is concluded that initiation of the early pregnancy assessment unit resulted in a reduction in the number of admissions. The hospital staff experienced a reduced workload during the night.

Pyloric size in normal infants and in infants suspected of having hypertrophic pyloric stenosis.

Pyloric muscle thickness (PMT) and pyloric diameter (PD) were determined by sonography in 92 healthy infants aged 8 to 70 days. PMT and PD measured median 2.0 mm and 10.0 mm. There was a significant correlation between the pyloric dimensions and the infant's age, p < 0.02 and p < 0.00001 for PMT and PD, respectively. In 26 infants with an initial diagnosis of hypertrophic pyloric stenosis (HPS), but with a final diagnosis of no HPS the mean figures were 2.4 and 11.0 mm, and in 21 infants with HPS, confirmed at surgery, the figures were 4.0 and 14.0. The pyloric dimensions in the 3 groups differed significantly. The larger-than-normal pyloric dimensions in the "no HPS" group suggest that some of these patients suffered from milder degrees of HPS.

Personality and drug preferences in normal volunteers.

This study examined the relationship between drug preferences as measured in a laboratory-based choice procedure and measures of personality and attitudes toward drugs. Healthy volunteers participated in laboratory-based double-blind studies measuring preference for ethanol or diazepam vs placebo. Frequency of drug choice was examined in relation to subjects' scores on personality questionnaires. Drug choice was not related to any of the personality measures examined. Personality scores were, however, related to both gender and habitual drug use. These data suggest that personality does not strongly influence responses to single doses of drugs as assessed under controlled conditions. Personality may, nevertheless, affect drug use in natural settings via other mechanisms (e.g., interacting with psychosocial variables).

Rate of increase of plasma drug level influences subjective response in humans.

This study addressed the commonly held, but seldom tested, notion that faster rates of increase of drug effects are associated with more positive subjective effects. Sodium pentobarbital was administered to normal healthy volunteers in either a single oral dose or in a series of divided, cumulating doses, and subjective responses were monitored. Twelve subjects participated in three weekly sessions, during which they received capsules containing placebo, 150 mg pentobarbital in a single dose (SIN) or 180 mg pentobarbital administered in six divided doses (DIV) of 30 mg every 30 min. Doses of pentobarbital in the SIN and DIV were selected to produce similar peak plasma levels. Blood samples were obtained at regular intervals for plasma drug level determinations, and throughout the session subjects completed self-report mood questionnaires (e.g., Profile of Mood States, visual analog ratings of drug liking and drug "high") and psychomotor performance tests (e.g., Digit Symbol Substitution Test). As expected, the SIN and DIV conditions yielded similar peak levels of pentobarbital, but the peak was attained more rapidly in the SIN condition. Despite the similarity in peak plasma levels, subjects reached greater peaks in ratings of "high" and wanted more of the drug when they were in the SIN condition. On an end-of-session liking questionnaire they also reported significantly greater liking of the drug in the SIN condition. On other measures of drug effects (e.g., sedation and psychomotor impairment) no significant differences were observed between the conditions. Thus, the rate of increase of the drug's effects specifically influenced subjects' ratings on subjective measures (e.g., "high" and liking) that may be associated with risk for abuse.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of setting on the subjective and behavioral effects of d-amphetamine in humans.

The effects of setting on the subjective and behavioral effects of 20 mg oral d-amphetamine were studied in eight healthy volunteers. A within-subjects design was used in which subjects ingested either amphetamine or placebo capsules in either an inpatient (isolated laboratory room) or an outpatient (normal daily environment) setting. The order of the four experimental conditions was randomized across subjects. Subjective drug effects were assessed using the Profile of Mood States, the Addiction Research Center Inventory, a Visual Analogue Scale, and a Drug Effects/Liking questionnaire, completed prior to and 1, 3, and 6 h after capsule ingestion. In addition, an End-of-Session questionnaire measuring overall drug liking and drug identification was completed at the 6-h timepoint. Subjects wore wrist monitors to record their physical activity levels during the 6-h postingestion period. Amphetamine produced typical stimulant-like subjective effects such as elation, euphoria, and friendliness, but the setting neither quantitatively nor qualitatively altered the drug response.

[Qualitative determination of U-pregnanediol-3 alpha-glucuronide in 5 minutes. A clinical trial of a new matrix cushion test]. / Kvalitativ bestemmelse af U-pregnandiol-3 alpha-glukuronid på 5 minutter. Afprøvning af en ny "matrixpudetest".

We have tested an easy and rapid "matrix cushion test" for qualitative determination of U-pregnandiol-3 alpha-glucuronide (U-PGD). The specificity of the test is high, the sensitivity is 4.0 microM, the inter-analysis variation is low as in 96% of the double determinations, agreement was present between the first and second analyses. A positive result on the 21st of the menstrual cycle indicates that ovulation has occurred while this cannot be exluded by a negative or doubtful result. If demonstration of a functioning corpus luteum is also required, the urine should be diluted 1:2 with tap water.

Increased concentration of circulating atrial natriuretic peptide during normal pregnancy.

Atrial natriuretic peptide (ANP) is a recently discovered cardiac hormone involved in blood-volume homeostasis. Known stimulating factors for ANP release are rise in atrial pressures or atrial distension, suggesting that blood volume regulates ANP release. This study was undertaken to test the hypothesis that plasma levels of ANP are high and increase during normal pregnancy secondary to the expanding plasma volume. In a cross-sectional study plasma concentrations of ANP were measured in 99 normal pregnant women at different gestational ages and compared with the values found in an age-matched non-pregnant control group. Mean plasma ANP was already significantly increased in the first trimester as opposed to the non-pregnant women, but despite a continuously expanded plasma volume there was no further increase during pregnancy. Our findings suggest that other factors must interact with plasma volume in regulating plasma ANP during pregnancy.

Chemotherapy for adenocarcinoma of the lung (WHO III): A randomized study of vindesine versus lomustine, cyclophosphamide, and methotrexate versus all four drugs.

Two hundred seventy-nine patients with previously untreated nonresectable adenocarcinoma of the lung (ACL) entered a prospective randomized trial, comparing vindesine (VDS) to a combination of lomustine (CCNU), cyclophosphamide (CTX), and methotrexate (MTX), and to a regimen including all four drugs. Response assessment was possible in 218 patients, while 259 were evaluable for survival. Response rates were similar (22%, 23%, and 27%, respectively) as were median durations of response (15 weeks overall) and survival (29 weeks overall). Patients with dose-limiting toxicity had significantly higher response rate and longer survival than patients without toxicity. The major toxicity was peripheral neuropathy with VDS treatment and myelosuppression with the other two regimens. The VDS single-agent activity in ACL was confirmed, but addition of VDS to the three-drug regimen did not increase activity. Future studies of VDS in combination with other active agents, and comparison to a matched control group on supportive care, are indicated.

Atrial natriuretic peptide concentrations in pre-eclampsia.

The concentration of plasma immunoreactive atrial natriuretic peptide is positively associated with right atrial and pulmonary capillary wedge pressure, suggesting that blood volume and hence atrial pressure govern its release. Expansion of plasma volume is a central physiological adjustment in normal pregnancy. Conversely, pregnancies complicated by pre-eclampsia are associated with a reduction in plasma volume and central venous pressure. A study was therefore undertaken to test the hypothesis that plasma atrial natriuretic peptide concentrations are low in pre-eclampsia owing to deficient secretion. Concentrations of the peptide were measured by a specific radioimmunoassay. The mean plasma immunoreactive atrial natriuretic peptide concentration in healthy pregnant women (n = 22; third trimester) was higher (56 (1 SD 29) ng/l) than in 25 young, non-pregnant controls (37 (19) ng/l). Concentrations in patients suffering from mild pre-eclampsia (n = 9) were higher (127 (60) ng/l) than in normal pregnant women, and in patients with severe pre-eclampsia (n = 6) concentrations were higher still (392 (225) ng/l). Despite failure of plasma volume expansion and low central venous and pulmonary capillary wedge pressures in pre-eclampsia this condition is associated with greatly increased plasma concentrations of plasma immunoreactive atrial natriuretic peptide, which increase still further with the severity of the disease. These findings are clear evidence that atrial pressure may not be the principal determinant of the release of the natriuretic peptide in pre-eclampsia.