ABSTRACT
OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of 3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios 39 million and 1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between 2.4 million and 7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Subject(s)
Cervical Length Measurement/economics , Cervix Uteri/chemistry , Fibronectins/analysis , Obstetric Labor, Premature/economics , Cohort Studies , Cost-Benefit Analysis , Female , Gestational Age , Hospitalization/economics , Hospitalization/statistics & numerical data , Humans , Infant, Newborn , Netherlands , Obstetric Labor, Premature/diagnosis , Predictive Value of Tests , PregnancyABSTRACT
Climate change is expected to increase the frequency and intensity of droughts and heatwaves in Europe, leading to effects on forest growth and major forest dieback events due to hydraulic failure caused by xylem embolism. Inter-specific variability in embolism resistance has been studied in detail, but little is known about intra-specific variability, particularly in marginal populations. We evaluated 15 European beech populations, mostly from geographically marginal sites of the species distribution range, focusing particularly on populations from the dry southern margin. We found small, but significant differences in resistance to embolism between populations, with xylem pressures causing 50% loss of hydraulic conductivity ranging from -2.84 to -3.55 MPa. Significant phenotypic clines of increasing embolism resistance with increasing temperature and aridity were observed: the southernmost beech populations growing in a warmer drier climate and with lower habitat suitability have higher resistance to embolism than those from Northern Europe growing more favourable conditions. Previous studies have shown that there is little or no difference in embolism resistance between core populations, but our findings show that marginal populations have developed ways of protecting their xylem based on either evolution or plasticity.
Subject(s)
Droughts , Fagus/physiology , Plant Dispersal , Water/metabolism , Climate Change , Europe , Phenotype , Xylem/physiologyABSTRACT
OBJECTIVE: To describe the maternal and neonatal outcomes and prolongation of pregnancies with severe early onset pre-eclampsia before 26 weeks of gestation. DESIGN: Nationwide case series. SETTING: All Dutch tertiary perinatal care centres. POPULATION: All women diagnosed with severe pre-eclampsia who delivered between 22 and 26 weeks of gestation in a tertiary perinatal care centre in the Netherlands, between 2008 and 2014. METHODS: Women were identified through computerised hospital databases. Data were collected from medical records. MAIN OUTCOME MEASURES: Maternal complications [HELLP (haemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, eclampsia, pulmonary oedema, cerebrovascular incidents, hepatic capsular rupture, placenta abruption, renal failure, and maternal death], neonatal survival and complications (intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and sepsis), and outcome of subsequent pregnancies (recurrent pre-eclampsia, premature delivery, and neonatal survival). RESULTS: We studied 133 women, delivering 140 children. Maternal complications occurred frequently (54%). Deterioration of HELLP syndrome during expectant care occurred in 48%, after 4 days. Median prolongation was 5 days (range: 0-25 days). Neonatal survival was poor (19%), and was worse (6.6%) if the mother was admitted before 24 weeks of gestation. Complications occurred frequently among survivors (84%). After active support, neonatal survival was comparable with the survival of spontaneous premature neonates (54%). Pre-eclampsia recurred in 31%, at a mean gestational age of 32 weeks and 6 days. CONCLUSIONS: Considering the limits of prolongation, women need to be counselled carefully, weighing the high risk for maternal complications versus limited neonatal survival and/or extreme prematurity and its sequelae. The positive prospects regarding maternal and neonatal outcome in future pregnancies can supplement counselling. TWEETABLE ABSTRACT: Severe early onset pre-eclampsia comes with high maternal complication rates and poor neonatal survival.
Subject(s)
Infant, Newborn, Diseases/etiology , Pre-Eclampsia/diagnosis , Pregnancy Outcome , Adult , Female , Follow-Up Studies , Gestational Age , Humans , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/mortality , Male , Netherlands/epidemiology , Pre-Eclampsia/mortality , Pregnancy , Pregnancy Trimester, Second , Prognosis , Retrospective Studies , Severity of Illness IndexABSTRACT
OBJECTIVE: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. DESIGN: Post hoc analysis of frozen fFN samples of a nationwide cohort study. SETTING: Ten perinatal centres in the Netherlands. POPULATION: Symptomatic women between 24 and 34 weeks of gestation. METHODS: The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table. MAIN OUTCOME MEASURES: Spontaneous delivery within 7 days after study entry. RESULTS: We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. CONCLUSION: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. TWEETABLE ABSTRACT: Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD.
Subject(s)
Cervical Length Measurement , Fibronectins , Cervix Uteri/chemistry , Cohort Studies , Female , Humans , Infant, Newborn , Obstetric Labor, Premature , Predictive Value of Tests , Premature BirthABSTRACT
OBJECTIVES: Clinical data of pregnant women with heart disease were obtained with the intention to provide input for local counseling and management guidelines. STUDY DESIGN: Retrospective data from all pregnant women with congenital or acquired heart disease between 2000 and 2011 in the VU University Medical Centre Amsterdam. MAIN OUTCOME MEASURES: Maternal and neonatal outcomes were evaluated. RESULTS: Data of 122 women with 160 pregnancies were obtained. The most common heart diseases were congenital heart disease (n=65, 53.3%) and arrhythmia (n = 20, 16.4%). Based on the functional criteria of the New York Heart Association (NYHA), 114/122 patients (93.4%) were classified NYHA class I-II. Patients in NYHA class III-IV (n = 8/122, 6.6%), mainly had a history of myocardial infarction or pulmonary hypertension. There were 156 singleton and 4 twin pregnancies. 22 (13.5%) pregnancies were complicated by hypertensive disorders. Heart failure developed in 11 women (9.0%), 37.5% in NYHA class III-IV and 6.5% in NYHA class I-II. Mean gestational age and birth weight were 270 days and 3196 g in NYHA class I-II compared to 237 days and 1972 g for NHYA class III-IV. There were two maternal deaths (1.6%) and 5 fetal deaths (3.1%). There were 29 (12.8%) preterm births, 20 (12.8%) neonates small for gestational age and 34 (21.8%) admittances on the Neonatal Intensive Care Unit (NICU). CONCLUSIONS: Pregnancy in women with pre-existing heart disease in all NYHA classes is associated with increased maternal morbidity and perinatal morbidity. Risk of structural fetal anomalies is especially high in women with congenital heart disease.
Subject(s)
Heart Diseases/epidemiology , Pregnancy Complications, Cardiovascular/epidemiology , Abortion, Induced/statistics & numerical data , Adult , Birth Weight , Delivery, Obstetric/statistics & numerical data , Female , Humans , Netherlands/epidemiology , Pregnancy , Pregnancy Outcome/epidemiology , Premature Birth/epidemiology , Retrospective Studies , Young AdultABSTRACT
OBJECTIVE: Maternal morbidity, either pregnancy related or pre-existent, can become life threatening and of such severity as to warrant termination of pregnancy (TOP). In this situation, chances of fetal survival are usually poor, either because of low gestational age and/or because of the fetal effects of the maternal condition. Examples include severe growth restriction in pre-eclampsia and intrauterine infection due to the very early preterm prelabour rupture of membranes. There are very few reports on the prevalence of TOP for maternal indication at the limits of fetal viability. We investigated the prevalence of and indications for TOP on maternal indication in the 10 tertiary care centres in the Netherlands during the past decade. STUDY DESIGN: We conducted a retrospective review of the medical records of all women who underwent TOP for maternal indications between 22 and 27 completed weeks of gestation in all 10 tertiary care centres from 2000 to 2009. RESULTS: During the study period, there were 1â 929â 470 deliveries; 163â 052 (8.4%) of these took place in one of the 10 tertiary care centres and 177 pregnancies were terminated for severe maternal disease, 131 for hypertensive disorders, 29 for intrauterine infection and 17 for other reasons. The mean gestational age at TOP was 171â days (24(3/7))±10â days. No maternal deaths were recorded. The overall perinatal mortality was 99.4%. CONCLUSIONS: Over a 10-year period, TOP for maternal indications was performed in 1 in 1000 deliveries in the 10 Dutch tertiary care centres. Hypertensive disorders comprised three-quarters of the cases.
Subject(s)
Abortion, Induced/statistics & numerical data , Fetal Viability , Pregnancy Complications/surgery , Cohort Studies , Female , Gestational Age , Humans , Netherlands , Pregnancy , Retrospective Studies , Tertiary Care CentersABSTRACT
BACKGROUND: Post-partum haemorrhage (PPH) causes rapidly developing deficiencies in clotting factors and contributes to substantial maternal morbidity and mortality. Rotational thromboelastometry (ROTEM(®)) is increasingly used as a point of care coagulation monitoring device in patients with massive haemorrhage; however, there are limited data on reference ranges in the peri-partum period. These are required due to the haemostatic changes in pregnancy. METHODS: In a Dutch multi-centre trial, 161 subjects were included; blood samples were obtained during labour (T1) and within 1 h of delivery (T2). Reference ranges of ROTEM(®) INTEM, EXTEM, FIBTEM, and APTEM were set and correlation with laboratory results was investigated using the guidelines of the International Federation of Clinical Chemistry. RESULTS: Reference ranges were obtained for clotting time (CT), clot formation time (CFT), α-angle, clot firmness at 10 and 20 min (A10, A20), maximum clot firmness (MCF), and maximum lysis (ML). These were comparable from centre to centre, and between T1 and T2. Reference ranges T1: EXTEM: CT 31-63 s, CFT 41-120 s, and MCF 42-78 mm. INTEM: CT 109-225 s, CFT 40-103, and MCF 63-78 mm. FIBTEM: CT 31-79 s and MCF 13-45 mm. APTEM: CT 33-62 s, CFT 42-118, and MCF 61-79 mm. CONCLUSIONS: Reference values for ROTEM(®) parameters are reported. The previously published correlation between FIBTEM parameters and plasma fibrinogen levels by the Clauss method is confirmed. Further research is needed to define threshold values for haemostatic therapy in the course of PPH. Clinical trial registration NTR 2515 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2515).
Subject(s)
Blood Coagulation/physiology , Monitoring, Physiologic/methods , Postpartum Hemorrhage/diagnosis , Thrombelastography/methods , Adult , Blood Coagulation Tests/methods , Blood Coagulation Tests/statistics & numerical data , Female , Humans , Monitoring, Physiologic/statistics & numerical data , Netherlands , Peripartum Period , Pregnancy , Reference Values , Thrombelastography/statistics & numerical dataABSTRACT
OBJECTIVE: To investigate the association between maternal intrapartum fever and ST-waveform changes of the fetal electrocardiogram. DESIGN: Retrospective cohort study. SETTING: Three academic and six non-academic teaching hospitals in the Netherlands. POPULATION: Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation. METHODS: We studied 142 women with fever (≥38.0°C) during labour and 141 women with normal temperature who had been included in two previous studies. In both groups, we counted the number and type of ST-events and classified them as significant (intervention needed) or not significant, based on STAN(®) clinical guidelines. MAIN OUTCOME MEASURES: Number and type of ST-events. RESULTS: Both univariable and multivariable regression analysis showed no association between the presence of maternal intrapartum fever and the number or type of ST-events. CONCLUSIONS: Maternal intrapartum fever is not associated with ST-segment changes of the fetal electrocardiogram. Interpretation of ST-changes in labouring women with fever should therefore not differ from other situations.
Subject(s)
Arrhythmias, Cardiac/etiology , Electrocardiography/methods , Fetal Diseases/etiology , Fetal Monitoring/methods , Fever/complications , Pregnancy Complications , Arrhythmias, Cardiac/diagnosis , Cohort Studies , Female , Fetal Diseases/physiopathology , Heart Rate, Fetal , Humans , Labor, Obstetric , Logistic Models , Netherlands , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy, High-Risk , Retrospective Studies , Risk FactorsABSTRACT
INTRODUCTION: Hypertensive disorders in pregnancy are one of the main causes of maternal morbidity and mortality. Internationally, several organizations have developed clinical guidelines to assist professionals and to supply patients with the best possible care. To improve the care for this group of patients, insight into the application of clinical guidelines in daily practice is needed. Valid quality indicators are necessary to estimate actual guideline adherence. In this study, we developed a set of valid guidelines based quality indicators for hypertensive diseases in pregnancy. OBJECTIVES: None. METHODS: A systematic RAND-modified Delphi method was used to develop a set of quality indicators based on evidence-based guidelines and the literature, about hypertension and pregnancy. Experts' opinions were used to select the indicators regarding specific criteria such as efficacy, level of health gain and potential for care improvement. RESULTS: A representative set of 14 quality indicators was selected from 48 initial guideline recommendations. Indicators concerned both professional performance and organisation of care for patients with hypertension in pregnancy. CONCLUSION: This study describes the systematic, stepwise method used to develop quality indicators that can be used to monitor care for hypertensive diseases in pregnancy.
ABSTRACT
INTRODUCTION: The number of women presenting with cardiac disease during pregnancy is increasing because more women with repaired congenital heart disease are reaching childbearing age and because of more pregnancies occurring in women with ischemic heart disease. Cardiac disease is the leading cause of indirect maternal mortality in the Netherlands. OBJECTIVES: Clinical data of pregnant women with heart disease that received obstetric care and delivered in our center have been obtained with the intention to evaluate the cardiac and obstetric pregnancy outcomes and to provide data for local counseling and management guidelines. METHODS: Data were collected from all pregnant women with congenital or acquired heart disease who delivered between 2000 and 2010 in the VU University Medical Center Amsterdam. At least one consultation of a cardiologist during pregnancy was advised. The maternal outcomes of these pregnancies were evaluated. RESULTS: Data of 122 women with 160 pregnancies were obtained. In this study the main heart diseases in pregnancy were congenital heart disease (n=75.61%) and arrhythmia (n=22.18%). Rheumatic heart disease was accountable for 6% (n=7) and ischemic heart disease for 4% (n=5) of inclusions. Based on the functional criteria of the New York Heart Association (NYHA), 114/122 patients (93.4%) were classified NYHA Class I-II. Patients in NYHA Class III-IV (n=8/122, 6.6%), mainly had a history of myocardial infarction or pulmonary hypertension. Of all the women, 35 had cardiac surgery before pregnancy, mainly repair of congenital heart disease. In women with acquired heart disease the interventions before pregnancy included permanent cardiac pace-maker implantation (n=2), radiofrequency catheter ablation (RFCA) (n=4) and percutaneous transluminal coronary angioplasty or coronary artery bypass graft (n=4). There were 156 singleton and 4 twin pregnancies. Termination of pregnancy was performed in 3 cases; 1 for maternal cardiac and 2 for obstetric indications. There were 156 life-births of which 100 (64.1%) were spontaneous vaginal deliveries, 17 (10.9%) operative vaginal deliveries and 39 (25%) cesarean sections: 9 for maternal cardiac indication and 30 for obstetric reasons. 36 (36%) women received epidural analgesia during labor and delivery. Cesarean section under general anesthesia was performed in 14 cases (7 for maternal cardiac indication); 25 were performed under spinal/epidural anesthesia. Induction of labour occurred in 48 pregnancies: 10 for maternal cardiac indications and 38 for other maternal and fetal indications. 28 (17.5%) pregnancies were complicated by hypertensive disorders. Cardiac complications such as heart failure developed in 15 (9.4%) pregnancies. There were two maternal deaths (1.6%). CONCLUSION: Congenital heart disease is the type of heart disease that has the highest incidence in pregnancy, while main types of heart disease that lead to impaired cardiac function during pregnancy are ischemic disease and pulmonary hypertension. Incidence of pregnancy induced hypertensive disorders is increased in women with preexistent cardiac disorders. Maternal outcome is generally favourable for women with cardiac heart in NYHA class I/II.
ABSTRACT
OBJECTIVES: To evaluate the recommendations for additional fetal blood sampling (FBS) when using ST-analysis of the fetal electrocardiogram. DESIGN: Prospective cohort study. SETTING: Three academic and six non-academic teaching hospitals in the Netherlands. POPULATION: Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation. METHODS: In labouring women allocated to the STAN® arm of a previously published randomised controlled trial who underwent one or more FBS during delivery, we assessed whether FBS was performed according to the trial protocol and how fetal acidosis, defined as an FBS pH < 7.20, was related to ST-waveform analysis. MAIN OUTCOME MEASURES: The number of FBS showing fetal acidosis, related to the different STAN® criteria where additional FBS is recommended. RESULTS: Among 2827 women monitored with STAN®, 297 underwent FBS, of whom 171 (57.6%) were performed according to the predefined criteria and 126 were performed in absence of these criteria. In the first group, rates of fetal acidosis (pH < 7.20) were two of 18, none of nine, 12 of 111 and three of 33 when FBS was taken for abnormal cardiotocogram (CTG) at the start, intermediary CTG at the start, abnormal CTG >60 minutes, and poor electrocardiogram quality, respectively. When the predefined criteria were not met and ST-analysis showed no ST-events, only two incidents of fetal acidosis were seen. CONCLUSIONS: The performance of FBS is valuable in the advised STAN® criteria. When these criteria are not met, performance of FBS does not seem helpful in the detection of fetal acidosis.
Subject(s)
Acidosis/diagnosis , Electrocardiography , Fetal Blood/chemistry , Fetal Diseases/diagnosis , Fetal Heart/physiology , Fetal Monitoring/methods , Cohort Studies , Female , Humans , Labor, Obstetric , Pregnancy , Prospective StudiesABSTRACT
Two pregnant patients with a sustained symptomatic maternal supraventricular arrhythmia are presented. Both patients were treated with direct-current cardioversion. Electrical cardioversion during pregnancy is a rarely applied but highly effective procedure in the treatment of maternal cardiac arrhythmias and is assumed safe for both mother and child. However, once foetal viability is reached, monitoring of the foetal heart rate is advised and facilities for immediate caesarean section should be available.
ABSTRACT
OBJECTIVE: To compare the actual situation in tertiary perinatal care in the Netherlands with the objectives laid down in the 2001 decree on perinatal care by the Dutch Ministry of Health, Welfare and Sport. DESIGN: Descriptive, retrospective. METHOD: Data on tertiary perinatal care, the transfer or refusal of women with very endangered pregnancies and the personnel of obstetric high care (OHC) units in 2006 were compared with the targets laid down in the planning decree on perinatal care and in a report by the Dutch Health Council from 2000. Parameters of tertiary perinatal care output were the number of admissions, and the number of beds in OHC units and neonatal intensive care units (NICU). RESULTS: In 2006, 128 of the 250 beds intended for OHC had been obtained. The degree of capacity utilisation was 94%, while the norm is 80%. 312 women were transferred due to lack of capacity of OHC units and NICU. The number of staff, specialised physicians as well as nurses, was considerably lower than the planned capacity. But training for obstetric perinatologists and OHC nurses was given. CONCLUSION: The targets for the number of beds for tertiary obstetric care and associated medical personnel have not been achieved as yet. As a consequence, the number of transfers is still too high. The funding of OHC units is not attuned to the complexity of tertiary perinatal care. Closer supervision of the execution of the planning decree and an adequate financing system are needed to achieve the objectives of the planning decree in the next 3 years.
Subject(s)
Intensive Care Units, Neonatal , Maternal-Child Health Centers/standards , Patient Transfer/statistics & numerical data , Perinatal Care/standards , Quality of Health Care , Bed Occupancy/statistics & numerical data , Female , Health Services Accessibility/statistics & numerical data , Health Services Needs and Demand , Hospital Bed Capacity , Humans , Intensive Care Units, Neonatal/standards , Intensive Care Units, Neonatal/statistics & numerical data , Midwifery , Netherlands , Pregnancy , Retrospective StudiesABSTRACT
OBJECTIVE: To construct reference ranges for spiral artery (SA) flow velocities and examine the possibility to predict intra uterine growth restricted (IUGR) fetuses, pregnancy-induced hypertension (PIH) and/or preeclampsia. METHODS: Spiral artery flow velocity measurements were performed using Color Doppler between 11 to 13 + 6, between 14 to 17 + 6 and between 18 to 24 weeks of gestation, each measurement was performed twice. Spiral artery flow velocities were analyzed with multilevel modeling: individual regression curves were estimated and combined to obtain the reference intervals for SA flow velocities in normal pregnancies. Mann-Whitney U tests was used to compare the deviation from expected flow velocity between normal and complicated pregnancies. RESULTS: One hundred and eight pregnancies were included; 4 pregnancies were complicated with preeclampsia, 10 pregnancies with IUGR fetuses (Subject(s)
Fetal Growth Retardation/diagnosis
, Hypertension, Pregnancy-Induced/diagnosis
, Placenta/blood supply
, Ultrasonography, Doppler, Color
, Adult
, Female
, Gestational Age
, Humans
, Longitudinal Studies
, Placenta/diagnostic imaging
, Pregnancy
, Pregnancy Outcome
, Prognosis
, Regional Blood Flow
, Ultrasonography, Prenatal
ABSTRACT
In 7 women with premature labour pains, severe dyspnoea developed that was possibly related to the use of nifedipine as an 'off-label' tocolytic. 6 of these women had a twin pregnancy. Diuretics and oxygen therapy had little effect, but the patients recovered after the administration of nifedipine was stopped. The efficacy and safety of nifedipine as a tocolytic agent has been investigated in a number of well-designed randomised studies. However, these studies were performed in a selected group of pregnant women and women with multiple pregnancies or prematurely ruptured membranes were mostly excluded. It can be hypothesised that the respiratory complications in these cases are due to unequal ventilation/perfusion of the lungs in the presence of a physiologically elevated diaphragm due to the pregnancy. These changes are more pronounced in multiple pregnancies. After administration ofnifedipine, there is perfusion of atelectatic areas of the lung that are not or not well ventilated, resulting in ventilation-perfusion discrepancy and hence dyspnoea. Although case reports permit only limited extrapolation, these observations warrant caution with regard to the safety ofnifedipine as a tocolytic agent in patients with multiple pregnancies. The use of medication in groups of patients for which the agent has not been investigated, or which were explicitly excluded from the study, should be done with extreme caution. One should in any case be aware of the possible risks.
Subject(s)
Dyspnea/chemically induced , Nifedipine/adverse effects , Obstetric Labor, Premature/drug therapy , Tocolysis/methods , Tocolytic Agents/adverse effects , Adult , Female , Humans , Nifedipine/therapeutic use , Pregnancy , Pregnancy Outcome , Pregnancy, Multiple , Risk Factors , Safety , Tocolytic Agents/therapeutic use , Treatment OutcomeABSTRACT
Electrostatic amino acid interactions between receptor subunits within the T-cell antigen receptor (TCR) transmembrane domain are critical for the formation of the TCR-CD3 complex. Core peptide, a short peptide corresponding to the TCR-alpha transmembrane region, containing two positively charged amino acids, is known to inhibit T-cell function in vitro and in vivo. The aim of this study was to examine peptides corresponding to the syntactic transmembrane CD3 region binding to TCR-alpha for their ability to inhibit T-cell activation in vitro and in vivo. Three peptides matching the transmembrane sequence of CD3-delta, -epsilon and -gamma were synthesized and tested in different biological in vitro and in vivo systems for their effect on T-cell activity. The CD3-peptides had no impact on T-cell function in vitro, but surprisingly, decreased signs of inflammation in the adjuvant arthritis rat model in vivo. Preliminary evidence suggests that peptides with CD3 transmembrane-derived sequences can inhibit an immune response as assessed by adjuvant-induced arthritis. The lack of in vitro activity may lead to a wasteful disregard of active compounds in the process of drug discovery and development.
Subject(s)
Immunosuppressive Agents , Lymphocyte Activation/immunology , Peptide Fragments/physiology , Receptor-CD3 Complex, Antigen, T-Cell/physiology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Animals , Cell Line, Tumor , Hybridomas , Immunosuppressive Agents/metabolism , Interleukin-2/antagonists & inhibitors , Interleukin-2/biosynthesis , Lymph Nodes/cytology , Lymph Nodes/immunology , Lymph Nodes/metabolism , Male , Mice , Peptide Fragments/metabolism , Protein Structure, Tertiary/physiology , Rats , Rats, Wistar , Receptor-CD3 Complex, Antigen, T-Cell/metabolismABSTRACT
Early postpartum hemorrhage remains a significant cause of maternal morbidity and mortality. Postpartum hemorrhage is most commonly due to uterine atony and often responds to medical treatments such as administration of uterotonic drugs, alone or in combination with uterine massage or bimanual compression. As the incidence of cesarean section continues to rise, the problem of placenta previa and accreta is likely to become more common. For first-line management of postpartum hemorrhage adequate blood and fluid replacement is mandatory. In recent years new therapeutic measures to control the bleeding have gained attention. Although, these newer therapies focus on avoiding the need for emergency hysterectomy and preservation of reproductive function, reports of subsequent pregnancies are still scarce. Established management options are shortly reviewed and novel medical and surgical treatments are more extensively discussed.
Subject(s)
Postpartum Hemorrhage/therapy , Adult , Embolization, Therapeutic , Female , Humans , Postpartum Hemorrhage/drug therapy , Postpartum Hemorrhage/etiology , Postpartum Hemorrhage/prevention & control , Postpartum Hemorrhage/surgery , PregnancyABSTRACT
A total of 54 domestic white meat-type geese were included in vaccination/challenge trials to evaluate susceptibility to disease and humoral immune responses using the haemagglutination inhibition (HI) and virus neutralization (VN) tests against Newcastle disease (ND). Two groups of twenty geese, five weeks of age, were conjunctivally vaccinated with either 100 x 10(6) or 2.5 x 10(6) EID50 (egg infectious dose 50 per cent) per bird of live La Sota virus, respectively, and 14 geese remained unvaccinated. At 15 weeks of age all vaccinated geese and seven unvaccinated geese were subcutaneously injected with 0.5 ml of inactivated oil emulsion ND vaccine, whereas seven geese remained as negative controls. At an age of 20 weeks, all 54 geese were challenged with 10(8.0) EID50 per bird of the viscerotropic velogenic NDV strain Herts 33/56. Live virus application as well as the oil emulsion vaccine did not induce discernible clinical signs and have no detrimental effect on body weight gains. At days 1, 3, 5, 8, 13, 16, 20, 23 and 27 after the application of lentogenic vaccine pharyngeal and cloacal swabs were taken, after challenge samples were taken at days 2, 5 and 8. Lentogenic as well as velogenic virus were never reisolated. Low and shortlived antibody responses post vaccination were equally well measured in HI and VN tests. Only two out of seven unvaccinated but challenged geese developed signs of ND whereas all vaccinated/challenged geese remained normal but developed high to moderate levels of HI and VN antibodies. Since domestic geese do not readily excrete NDV's in detectable amounts and since they do not contain detectable amounts of the challenge virus fourteen days post challenge in their tissues the assumption is promoted that geese do not play a major role in the epidemiology of Newcastle disease.
Subject(s)
Geese/immunology , Newcastle Disease/prevention & control , Newcastle disease virus/immunology , Poultry Diseases/prevention & control , Viral Vaccines , Animals , Antibodies, Viral/blood , Vaccination/veterinary , Vaccines, Inactivated/immunology , Viral Vaccines/immunologyABSTRACT
OBJECTIVE: In the presented paper, obstetrical management after previous caesarian section was studied in a large patient collective at the University Department of Gynaecology and Obstetrics in Cologne from 1979 to 1995. Particular attention was given to the feared complication of rupture of the uterus. PATIENTS: From a total of 15,166 deliveries, 1,086 of the births had been preceded by one or more caesarian section. These 1,086 births formed the patient collective for the present study. RESULTS: Vaginal delivery was attempted in 44.5% of patients and was successful in 86% of those cases. If there had been a previous caesarian section, the percentage shifted in favour of vaginal delivery. All patients with more than two previous caesarian sections were delivered by a primary caesarian section. The feared complication of rupture of the uterus occurred in four cases, for which case reports are presented. In view of such cases, signs of imminent uterus rupture often constitute an indication for primary (11.5%) or secondary resectioning (31.9%). No relationship was found between fetal outcome and mode of delivery. CONCLUSION: This retrospective study confirms the general recommendation of vaginal delivery following previous caesarian section as long as risks are minimized by a readiness to proceed with resectioning when signs of imminent rupture of the uterus arise.
Subject(s)
Cesarean Section/adverse effects , Uterine Rupture/epidemiology , Vaginal Birth after Cesarean/adverse effects , Adult , Cesarean Section/statistics & numerical data , Contraindications , Female , Germany/epidemiology , Humans , Incidence , Infant, Newborn , Pregnancy , Pregnancy Outcome , Reoperation/statistics & numerical data , Retrospective Studies , Uterine Rupture/diagnosis , Vaginal Birth after Cesarean/statistics & numerical dataABSTRACT
Preeclampsia is associated with increased maternal and perinatal morbidity and mortality. Preeclampsia is more than pregnancy-induced hypertension. The hypertension is only one manifestation of an underlying multifactorial, multisystem disorder, initiated early in pregnancy. In established severe disease there is volume contraction, reduced cardiac output, enhanced vascular reactivity, increased vascular permeability and platelet consumption. Medical treatment of severe hypertension in pregnancy is required. The more controversial issues are the role of pharmacological treatment in conservative management of severe preeclampsia aiming at prolongation of pregnancy, the ability of such therapy to modify the course of the underlying systemic disorder and the effects on fetal and maternal outcome. This paper presents an overview concerning the current developments in management and monitoring of severe preeclampsia. Controversial topics such as the role of plasma volume expansion in preeclampsia, expectant versus aggressive management of severe preeclampsia remote from term, and pharmacological interventions in the management of eclampsia and the HELLP syndrome are addressed.