First-trimester screening markers are altered in pregnancies conceived after IVF/ICSI.

OBJECTIVES: To determine the levels of first-trimester screening markers and to assess the false-positive rate for first-trimester combined screening for Down syndrome in a large national population of women pregnant after assisted reproductive technology (ART), in order to decide whether or not to correct risk calculation for mode of conception. METHODS: A national prospective cohort study of 1000 pregnancies achieved after ART was compared with a control group of 2543 pregnancies conceived spontaneously. All women completed a first-trimester combined screening program. Risk calculation was performed retrospectively based on the screening parameters to avoid bias due to the use of different algorithms of risk calculation. RESULTS: In chromosomally normal pregnancies conceived after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), the pregnancy-associated plasma protein-A multiples of the median value was significantly decreased when compared with that of pregnancies conceived spontaneously (0.78 and 0.79 vs. 0.98), while there was no difference in the group treated by frozen embryo replacement. There was no difference in the level of free beta-human chorionic gonadotropin between groups. The median nuchal translucency thickness was smaller in the overall ART group compared with controls. The false-positive rate of first-trimester combined screening in the overall ART group, adjusted for maternal age, was significantly higher when compared with controls (9.0% vs. 6.0%). CONCLUSIONS: It seems advisable to use a population of IVF/ICSI pregnancies to establish median curves for the first-trimester serum screening parameters and perhaps also for nuchal translucency thickness. However, care must be taken, as different ART treatment methods and aspects of medical history seem to alter the screening parameters in different ways.

The effect of a 'vanishing twin' on biochemical and ultrasound first trimester screening markers for Down's syndrome in pregnancies conceived by assisted reproductive technology.

BACKGROUND: Previous studies have found that 1 in 10 in vitro fertilization (IVF) singletons originates from a twin gestation. First trimester Down's syndrome screening markers are altered in assisted reproductive techniques (ART) pregnancies compared with spontaneously conceived pregnancies. The presence of a perished embryo may further complicate prenatal screening among women pregnant after ART. The aim of this study was to assess the impact of a 'vanishing twin' on first trimester combined biochemical and ultrasound screening in pregnancies conceived after IVF and intracytoplasmatic sperm injection. METHODS: From a national prospective cohort study concerning first trimester combined screening among women pregnant after ART, 56 cases of pregnancies with a vanishing twin were identified. As control group 897 cases of ART singleton pregnancies were used. All women completed a first trimester combined ultrasound and biochemical screening programme comprising serum PAPP-A and free beta-hCG together with nuchal translucency (NT) measurement. RESULTS: There were no significant differences in geometric mean MoM free beta-hCG and PAPP-A between pregnancies with an early (gestational week <9, EVT) or late vanishing twin (gestational week 9-13, LVT) or singleton pregnancies (0.98, 1.13 and 0.95 for free beta-hCG and 0.84, 0.80 and 0.74 for PAPP-A, respectively). Likewise, no difference was seen for NT measurements. The gestational age at the time of blood sampling and NT scan was similar for the three groups. The proportion of EVT pregnancies with a PAPP-A and free beta-hCG log(10)MoM value below the 5th%iles and above the 95th%iles of the value in the singleton pregnancies were 4.3%, 4.3%, 6.4% and 8.5%, respectively, which did not constitute a significant difference from singletons. The corresponding values for LVT pregnancies were 0%, 22.2%, 0% and 11.1%, respectively; however, these numbers were too small to allow for statistical calculations. CONCLUSIONS: First trimester biochemical screening markers in women pregnant after ART, and with a vanished twin diagnosed at early ultrasound, do not differ from those of other ART singleton pregnancies. In cases where the fetal demise was first diagnosed at the time of the NT scan, it is doubtful whether the serum risk assessment is as precise as it is in singleton ART pregnancies. No difference was seen for NT measurements.

First-trimester screening in pregnancies conceived by assisted reproductive technology: significance of gestational dating by oocyte retrieval or sonographic measurement of crown-rump length.

OBJECTIVES: To evaluate, in pregnancies conceived by assisted reproductive technology, whether determination of gestational age (GA) by date of oocyte aspiration (DOA) or crown-rump length (CRL) at first-trimester screening influences the distribution of serum and sonographic markers or the performance of first-trimester screening for chromosomal abnormalities. METHODS: GA was calculated using either DOA or CRL at blood sampling and nuchal translucency thickness (NT) measurement in 729 singleton pregnancies conceived by in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Weight-corrected log multiples of the median (MoM) marker distributions specific for IVF pregnancy were established using multiple log regression and compared for DOA- and CRL-based GA calculation. RESULTS: GA determined by CRL was significantly larger, albeit slightly, than was GA determined by DOA, with a mean difference of 1.50 (SD, 2.4) days (P < 0.001). Log MoM distributions of free beta-human chorionic gonadotropin and NT showed that GA dating by CRL resulted in significantly higher, albeit slightly, mean log MoM values compared with DOA dating. The reverse was the case for mean log MoM pregnancy-associated plasma protein-A. The SDs were similar for CRL and DOA dating. According to Monte Carlo simulation, the use of DOA or CRL for GA dating did not appreciably influence the performance of first-trimester screening. CONCLUSIONS: DOA and CRL are practically equivalent when calculating GA for first-trimester screening. The correct method of GA dating for other purposes (e.g. estimated time of delivery) in IVF/ICSI pregnancies is still unresolved.

Prenatal testing among women pregnant after assisted reproductive techniques in Denmark 1995-2000: a national cohort study.

BACKGROUND: Women pregnant after assisted reproductive techniques (ART) are generally older than women with spontaneously conceived pregnancies, and are consequently more likely to carry a child affected by a chromosomal disorder. Furthermore, a significantly increased rate of chromosomal abnormalities after intracytoplasmatic sperm injection (ICSI) has been reported. The aim of this study was to describe the use and results of prenatal invasive diagnostic testing in a national Danish cohort of in vitro fertilization (IVF)/ICSI pregnancies. Additionally, we examined to what extent second trimester serum screening was used. METHODS: We used a register-based cohort study including all ongoing clinical pregnancies achieved by IVF/ICSI in 1995-2000 in Denmark. Data on fertility treatment, pregnancy and pregnancy outcome together with data on cytogenic testing and the use of triple test were retrieved from national statutory registers. Data on the invasive testing rate among the general Danish population were retrieved from the same national registers. RESULTS: In this 6 year period, 8531 ART pregnancies were recorded representing an unselected national ART population (6122 IVF, 2087 ICSI and 322 'IVFICSI'). The number of prenatal invasive procedures was relatively low, 16.3%, and the uptake of second trimester serum screening was very low, 7.4%. The invasive testing rate, corrected for advanced maternal age distribution, was lower in the study population than in the general population. The rate of karyotype aberrations detected by prenatal testing was 2.7% (43/1586), whereas the overall rate of pre- and post-natally detected aberrations was 0.6% (62/9625). Chromosome aberrations were more common in the ICSI-treated group compared with the IVF-treated group [1.3% (30/2297) versus 0.5% (32/6957), P < 0.0001]. This was also the case if only prenatally diagnosed chromosome aberrations were compared [4.3% (24/556) versus 1.9% (19/975), respectively, P < 0.01]. CONCLUSIONS: ART pregnancies represent a group of high-risk pregnancies with regard to chromosomal aberrations, but nevertheless their uptake of prenatal testing was low. ICSI pregnancies compared with IVF pregnancies had a higher rate of chromosomal abnormalities, even though the average maternal age was lower.

Relationship between mood and TSH response to TRH stimulation in bipolar affective disorder.

Moderate to severe depression and mania are associated with a reduced thyroid stimulating hormone (TSH) response to TSH releasing hormone (TRH). Continued reduction of this response after clinical recovery seems indicative of early relapse. The aim of the present study was to test the relationship between mild changes in mood and the TSH response to TRH stimulation in patients with bipolar affective disorder. Nineteen outpatients with bipolar affective disorder were followed prospectively for three years. Every third month, mood symptoms were rated using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Bech-Rafaelsen Mania Scale (BRMS). A TRH test was performed in connection with each rating session (IV injection of 200 microg TRH), and serum TSH was measured at 0, 20, and 60 min. The maximum TSH response (D-max TSH) and the temporal change in D-max TSH between succeeding rating sessions (DD-max TSH) were determined. Psychometric rating and TRH data were obtained for a total of 198 examinations. The temporal change in mood symptom rating score was negatively correlated with the temporal change in D-max TSH, thus suggesting that increasing severity of mood symptoms was related to a reduced TSH response to TRH stimulation. The temporal change in TSH response to TRH stimulation correlated with the actual score on an overall index of symptom severity. In conclusion, milder fluctuations in mood in bipolar affective disorder seem to correlate with the TSH response to TRH stimulation: Increasing severity of mood symptoms seems to be associated with reduced TSH response.

Ward atmosphere in acute psychiatric in-patient care: patients' perceptions, ideals and satisfaction.

OBJECTIVE: To investigate the relationship between patients' perception of the real and ideal ward atmosphere and their satisfaction. METHOD: Patients filled in the Ward Atmosphere Scale (WAS, Real and Ideal Form) and a satisfaction questionnaire. Patient characteristics were derived from clinical assessments. RESULTS: WAS ratings were almost independent of patient characteristics. Patients in locked wards perceived more anger and aggression and patients subjected to coercive measures perceived less autonomy and practical orientation. Patient satisfaction was predicted by higher scores on the WAS Relationship- and System Maintenance dimensions, explaining 41% of the variance. In particular support, order and organization predicted satisfaction. Except from the areas of anger/aggression and staff control, patients gave the 'ideal' ward higher ratings on all subscales. The perceived gap between the 'ideal' and 'real' ward explained 45% of variance in satisfaction. CONCLUSION: Patients' perception of ward atmosphere is a clinically meaningful measure appearing to be a strong predictor of satisfaction.

Sharing the responsibilities: the roles of the government.

Developments in psychiatry have been steered by a number of factors influencing decisions taken by the politicians. Some of the more typical factors that could be mentioned are: political attitudes; trend phenomena in the population; economic aspects; and evidence-based knowledge. Bearing in mind the results of developments in psychiatry during the last decades, psychiatrists are encouraged to live up to their responsibility by focusing on scientific results, when giving their advice to politicians. Hopefully political initiatives will, in the future, primarily be based on evidence about psychiatric treatment.

[Bipolar affective disorder. A retrospective study of 158 patients in a well-defined geographical region]. / Bipolaer affektiv lidelse. En retrospektiv undersøgelse af 158 patienter i en geografisk velafgroenset region.

A cohort of 158 patients was identified from 723 patients admitted in 1990 or treated as outpatients in 1991 for affective disorders in three university hospitals in Copenhagen, covering a well-defined catchment area. The cohort was subclassified for seasonal pattern according to DSM-III-R. Meteorological data of temperature, hours of sunshine, rainfall and wind-velocity expressed as mean values/month were obtained from the Institute of Meteorology in Copenhagen. There was no relationship between the annual dis- tribution of affective episodes and meteorological data, neither in the total cohort nor in the subgroup of patients with seasonal patterns The present study does not support the hypothesis that a relation exists between start of a new episode and the season or climatic condition.

The Major Depression Rating Scale (MDS). Inter-rater reliability and validity across different settings in randomized moclobemide trials. Danish University Antidepressant Group.

The Major Depression Rating Scale (MDS) has been derived from the Hamilton Depression Scale and the Melancholia Scale. The MDS contains the nine DSM-IV items for major depression which all have anchoring scores from 0 to 4; hence, the theoretical score range is up to 36. The Major Depression Rating Scale has in this study been psychometrically analysed in randomized moclobemide trials. The results showed that the MDS had higher internal validity than the Hamilton Depression Scale. Thus, the homogeneity of the items was higher; factor analysis identified only one general depression factor (after 4 weeks of treatment explaining more than 50% of the variance). The inter-rater reliability of the two scales was of the same high level. The ability to measure changes (external validity) was tested in randomized clinical trials with moclobemide versus tricyclics (clomipramine and notriptyline) performed in Denmark in the psychiatric setting as well as in the general practice. The results showed that in the psychiatric setting tricyclics were superior to moclobemide with effect sizes ranging between 0.43 and 0.53. The highest effect size was obtained with the Melancholia Scale and the Major Depression Rating Scale, while the Hamilton Depression Scale was below 0.50. In the general practice setting no difference was found between moclobemide and clomipramine. In conclusion, the Major Depression Rating Scale has been found to have a more homogeneous factor structure than the Hamilton Depression Scale, but still with the same level of reliability and external validity. However, studies are needed to standardize the scale, especially in the general practice setting.

[Child psychiatric intervention in connection with district psychiatry. A 2-year experimental project with child psychiatric consultation]. / Børnepsykiatrisk intervention i forbindelse med distriktspsykiatri. Et toårigt forsøgsprojekt med børnepsykiatrisk konsulentfunktion.

The aim of the study was to describe the requirement for child psychiatric intervention in children of psychiatric patients treated within community psychiatry and to test the possibilities for intervention in practice. The study was carried out in a community psychiatric centre in Copenhagen, to which a child psychiatrist was associated as a consultant for two years. Assessment of known risk factors for child psychiatric illness was carried out in the families of all patients admitted to the centre who had children aged 0-14 years. Intervention was systematically carried out and described. The project was evaluated in a survey among the staff of the centre. Sixty-five patients, of which the majority were women, and 86 children were evaluated. The most frequent diagnoses were psychosis and personality disorder. More than half of the children were less than three years old. Fourteen children had no contact with their ill parent and 13 were placed in care. Ten families were referred to child psychiatric treatment. Primary intervention was carried out in six cases. A questionnaire among the members of the psychiatric staff showed that the project was well accepted and considered to be of great profit to the patients and their children. We conclude that a high frequency of risk factors for child psychiatric illness were identified in families of patients in community psychiatry. The community psychiatric setting made preventive intervention possible at a time where no such measures otherwise would have been taken. It is therefore recommended that child psychiatrists are integrated in community psychiatry as consultants.

[The adolescent psychiatric clientele in a district psychiatric center]. / Det ungdomspsykiatriske klientel i et distriktspsykiatrisk center.

This study is retrospective and based on the charts of 44 adolescents (age 17-22) admitted to a Danish community psychiatric centre during the first 32 months after the opening of the centre. The social status of the adolescents, reasons for admission, previous treatment and need for psychiatric treatment are presented. The adolescents were generally a little older than a typical adolescent psychiatric clientele, and comparatively many of them had rather mild psychiatric conditions. A characteristic feature of these patients was a certain instability in their contact to the centre. Although many of them had long-lasting basic disabilities (e.g. personality disorders), only a few of them achieved a stable treatment alliance with the ward. This indicates difficulties of integrating an adolescent clientele in a community psychiatric centre that primarily takes care of adult patients.

[Seasonal affective disorders]. / Saesonrelaterede affektive lidelser.

In 1984 Rosenthal described for the first time the syndrome "Seasonal Affective Disorder", SAD, characterized by annual recurrent depressive episodes in the autumn and winter months possibly followed by mania/hypomania in the summer months. The depressive phases showed atypical symptoms such as hypersomnia, carbohydrate-craving, and weight gain. Melatonin seems to be an indicator of disturbed circadian rhythm rather than the cause of SAD. The importance of other circadian and annual biological rhythm in relation to SAD and other depressive syndromes is quite unknown. SAD differs from classical manic-depressive disorders by frequency, severity, symptomatology, and the typical seasonal variations, and is probably not a subgroup of the classical affective disorders, but an extreme variation of the normal seasonal affective variations seen in the general population. Light therapy can be used successfully in depressive states in SAD.

[User evaluation of a psychiatric day center]. / Brugerevaluering af psykiatrisk dagcenter.

When community mental health centres were introduced in Copenhagen, day centres were attached to them. With the purpose of highlighting users' perspective in psychiatry, 48 patients in a psychiatric day centre were included in the study one year after the opening of the day centre. User satisfaction was investigated by means of a questionnaire, which was completed by the patient, while information on other aspects of the patients' lives was gathered from interviews with the patients and from case-records. The users of psychiatric day centres were mostly schizophrenic patients. The average number of years since first contact with psychiatric services was 12. In comparison with an age and sex-matched population in Copenhagen, patients were more isolated. There was a insignificant tendency towards use of psychiatric bed capacity decreasing from the one year period before the opening of the day centre to the one year period after. The users were very satisfied with the treatment in the day centre. The majority expressed that they trusted the staff, and that they believed that the treatment in the centre had affected their situation in a positive way. It is concluded that psychiatric day centres are useful and should form a part of psychiatric services.

The influence of community-based psychiatry in Copenhagen on the treatment of chronic psychoses.

Several factors influence the outcome of prevention of relapse in patients with chronic psychoses--mainly schizophrenia. A key word in the prophylactic treatment is compliance. Compliance is primarily related to drug treatment, but seen in a broader perspective it depends on the circumstances under which the treatment is offered. From 3 cohort investigations in Copenhagen mainly including patients with chronic psychoses, it seems as if community-based psychiatry in Copenhagen possesses some of the ingredients--high professional standard, continuity, care and support--that are considered to improve the outcome of treatment. However, suicidality and social isolation are some of the important areas that need further attention.

Cerebrospinal fluid concentrations of neuropeptide Y in depressed patients and in controls.

Concentrations of Neuropeptide Y-like (NPY-LI) immunoreactivity in cerebrospinal fluid (CSF) were measured in a group of depressed patients (n = 24) and compared with that of control subjects (n = 12). CSF-NPY-LI was significantly reduced in the group of non-endogenously depressed patients when classified according to Newcastle Rating Scale for Depression--1971 (N-II). No significant correlation was found in the control or depressed groups between lumbar concentrations of NPY-LI and a number of other neurotransmitters.

Moclobemide in depression: a randomized, multicentre trial against isocarboxazide and clomipramine emphasizing atypical depression.

Moclobemide was compared with isocarboxazide and clomipramine in patients with depression. A total of 167 outpatients were allocated to daily treatment with 300 mg moclobemide, 30 mg isocarboxazide or 150 mg clomipramine for 6 weeks. Moclobemide was slightly inferior to clomipramine, whereas isocarboxazide had an intermediate position. There was no interaction between treatment and atypical or nonatypical depression. Anticholinergic symptoms and orthostatic hypotension were most pronounced in the clomipramine group.

Cerebral Edema and Vascular Permeability to Serum Proteins Following Electroconvulsive Shock in Rats.

The regional brain specific gravity and the cerebrovascular permeability to serum proteins were investigated in rats subjected to electroconvulsive shock (ECS) with different stimulus intensity and different stimulus periods. The following experimental situations were studied: one ECS daily for 9 days (50 mA in 0.3 s), one ECS daily for 9 days (50 mA in 0.9 s), and one ECS three times weekly for 4 weeks (50 mA in 0.3 s). Age-matched animals receiving sham ECS served as controls. In the group having stronger stimulus intensity and in the one treated for 4 weeks, there was an increase in tissue water content in the hypothalamus and in both hypothalamus and hippocampus, respectively. In none of the experimental groups could cerebral edema be demonstrated in parietal cortex or in white matter. The findings point to an increased blood-to-brain transfer of water with increasing stimulus intensity and with the length of the ECS series. The study showed no increased cerebrovascular permeability to serum proteins and no signs of neuronal damage in any of the experimental groups.