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Objective: The aim of the study was to review the outcome of fetuses with structural heart disease detected by echocardiography., Methods: A total of 99 fetuses with different types of cardiac defects, diagnosed at a median gestational age of 28.4 weeks (range 16-41 weeks), were included. The inclusion criteria were a structural heart defect confirmed postnatally or at post-mortem examination, and a complete, long-term follow-up in utero and after birth in the Hospital for Children and Adolescents, Helsinki, Finland from 1983 to 1999., Results: Of 99 fetuses with in utero diagnosed cardiac anomalies, 6 (6%) showed normal cardiac status postnatally. Thirty-five percent of fetuses (n = 10) with heart disease diagnosed before 24 weeks of gestation were terminated. Of 83 fetuses, 7 (8%) with a heart defect died in utero at a median gestational age of 33 weeks. Chromosomal abnormality was found in 28% of cases. Fetuses with normal chromosomes had extracardiac anomalies in 40% of cases. Mortality due to chromosomal abnormality was 73% and from extracardiac anomaly 48%. Intrauterine heart failure was detected in 27% of fetuses and was frequently associated with univentricular heart (UVH) and intracardiac tumors, in 36 and 67%, respectively; 12 fetuses (13%) were found to have associated arrhythmia; 4 of these died. Of 76 live births (median gestational age 38 weeks, birth weight 2878 g), a total of 37 (49%) neonates died. Twenty-four neonates (32%) underwent cardiac surgery or invasive procedure; six infants (25%) died after the procedure. Neonatal mortality was highest in fetuses with hypoplastic left heart syndrome (HLHS), ventricular septal defect (VSD), and UVH (87, 64, and 50%, respectively). In long-term follow-up (median 3.8 years), 34 children of 76 live births (45%) were alive, 59% of them were without symptoms., Conclusion: Our data indicate that despite elective, planned delivery the prognosis for fetuses with in utero diagnosed heart defect was poor. The outcome was largely attributable to associated extracardiac malformations and chromosomal abnormalities.

Objective: To study if later risk of violent offending and criminality among high-risk children can be estimated quantitatively on the basis of parental crimes., Method: The criminal and prison records of the offspring (N=11) of homicide recidivists (N=36) were compared with data from controls (N=220) who were matched for sex, domicile of birth and date of birth and death., Results: The risk (odds ratio) was increased up to 24-fold for violent crimes (P=0.01), and up to 17-fold for criminality (P=0.0008) among the offspring of homicide recidivists., Conclusion: The quantitative risk of a child for later violent offending and criminality can be estimated on the basis of parental homicide recidivism. This kind of method could be used to choose target groups for early preventive interventions, and to study the effectiveness of prevention.

Congenital heart block (CHB) can result in intrauterine cardiac failure leading to fetal or neonatal loss. To establish perinatal hemodynamic factors which might predict adverse outcome, six fetuses with CHB diagnosed between 20 and 30 gestational weeks were examined by echocardiography at 2-week intervals. Neonatal morbidity and outcome in infancy are detailed. The fetuses showed a significant decrease in ventricular rate (VR) with advancing gestation (60 +/- 7 vs 51 +/- 4 beats/min, p = 0.03). Cardiac decompensation defined as hydrops or pericardial effusion was associated with VR of lower than 55 beats/min in two fetuses. Three mothers had a therapeutic trial with a sympathomimetic and digoxin. Salbutamol increased VR 10% in one of three fetuses treated. Digoxin decreased pericardial effusion in one hydropic fetus with autoimmune myocarditis. In this fetus, poor left ventricular fractional shortening (LVFS) was accompanied with high umbilical artery resistance index (RI). High amniotic fluid erythropoietin indicated severe hypoxia preceding death. Pacemaker was indicated in all the newborns. At the age of 2 weeks all the surviving infants had tricuspid regurgitation and a shunt through foramen ovale due to asynchronized atrioventricular contraction. During the 12-month follow-up two of five surviving infants had no symptoms. One had symptomatic neonatal lupus. Two infants had patent ductus arteriosus, one with dilated cardiomyopathy. In conclusion, poor fetal outcome was associated with low VR, low LVFS, and high RI. Despite early pacing, morbidity was high in infancy due to cardiomyopathy and associated heart defects. Regular echocardiographic monitoring during pregnancy and after delivery is required in order to optimize care and timing of any interventions.

Objective: To assess the impact of increased nuchal translucency observed during early pregnancy on the subsequent health of children with normal chromosomes, with special attention to cardiac anatomy and function., Methods: Clinical examination and detailed cardiac evaluation were carried out in 50 chromosomally normal children at the age of 2.4-7.1 years who had had a nuchal translucency measurement of > or = 3 mm at 13-15 weeks' gestation. The data of two babies who died of heart defects were also included., Results: Major cardiac defects were identified in four (8%) of the children. The growth of all children was within normal limits. One child had Noonan syndrome, one had a cleidocranial dysplasia and a third had a developmental delay together with an unrecognized syndrome. Webs in the neck region were noticed in two children, with no associated pathology., Conclusions: In chromosomally normal fetuses with increased nuchal translucency, fetal echocardiography is necessary to identify major cardiac defects. In general, the parents can be reassured that, in the great majority, postnatal development is normal.

The aims of this study were to assess morbidity, mortality, and long-term cardiac outcome of children with congenital complete heart block (CHB) diagnosed between the ages of 3 months and 15 years. The study population consists of 61 children with CHB diagnosed in five tertiary referral centers in Finland. There were two study groups: CHB diagnosed 3 months to 2 years of age (group 1; n = 29) and CHB diagnosed between the age of 2 and 15 years (group 2; n = 32). Neonatal morbidity was significantly higher in group 1 than in group 2 (p = 0.047). In the whole study population, permanent pacemaker implantation with the main indications of low ventricular rate and syncope (52%) was performed in 80% of cases, with a median age of 11.2 years. Structural heart defect not causally associated with CHB was evident in 9 of 61 patients (15%). Of 8 patients with atrial septal defect (ASD) secundum, 6 (75%) were operated on and 7 (88%) were paced. One patient had small ventricular septal defect. The incidence of dilated cardiomyopathy was 7%. The mortality with cardiomyopathy was very high (75%). Of the 61 children, 3 (5%) died due to cardiomyopathy at the ages of 2, 26, and 31 years. In the long-term follow-up of 17 years (median, range 2.9-46 years) 17% of patients who survived had cardiac problems: arrhythmias in 5, mitral valve insufficiency in 3, ASD secundum in 1, and cardiomyopathy in 1. The long-term outcome did not depend on the age at which CHB was diagnosed. In conclusion, CHB diagnosed after the newborn period carries relatively low mortality and morbidity. Pacemaker application was indicated in most children. The possibility of an associated heart defect or dilated cardiomyopathy indicates regular echocardiographic monitoring in all children and young adults with CHB.

Idiopathic arterial calcification of infancy (IACI) is a rare condition characterized by extensive arterial calcification and stenoses of large and medium-sized arteries. Its complications include severe cardiac failure diagnosed in utero as hydrops fetalis or postnatally as respiratory failure combined with cardiomegaly. Two newborn male siblings with IACI are described. In utero, echocardiography revealed poor ventricular function and hyperechogenic foci in arterial walls. Both had fatal outcome during the newborn period. At autopsy, medial calcifications in the walls of great arteries, in coronary arteries, in glomeruli, and in subendocardium were detected. In addition, an inflammatory process in the shoulder joint was determined to be large periarticular tissue calcifications. Because of an autosomal recessive inheritance pattern of IACI, fetal echocardiography is recommended in future pregnancies of all affected families.

Objective: To study the long-term outcome of mothers of children with isolated heart block in a defined population., Methods: We reviewed the Finnish hospital registries for patients born between 1950 and 1999 who had been diagnosed as having isolated heart block before the age of 15 years. We identified 101 children with isolated congenital heart block (CHB) and 55 with isolated heart block detected after the newborn period. Eighty-three (91%) of the 91 mothers of children with CHB and 48 (87%) of the 55 mothers of children with heart block detected after the newborn period were studied according to a protocol defining clinical characteristics (mean 9.9 years, range 0-49 years, and mean 22.9 years, range 4-47 years after the index delivery, respectively). Maternal survival was compared with survival in an age-matched population of normal Finnish women., Results: Before the index delivery, 29 (37%) of the 78 surviving mothers of children with CHB had a self-reported clinical diagnosis of a chronic autoimmune disease, and 55 (71%) had had symptoms, signs, or abnormal laboratory findings suggesting an underlying subclinical disease. Of the 23 mothers who were completely asymptomatic before the index delivery, 10 (13% of the surviving mothers) remained so after a mean followup of 9.6 years (range 0-21 years). In mothers of children with CHB, clinical characteristics different from those of healthy mothers were photosensitivity, fatigue, dry eyes, and dry mouth. Forty-eight (58%) of these 83 mothers developed an autoimmune disease during followup. The most common diagnosis was primary Sjögren's syndrome (22 definite, 11 probable), followed by systemic lupus erythematosus (SLE). The standardized mortality ratio of mothers of children with CHB was 5.1, and 3 of the 5 deaths were associated with SLE. Mothers of children with heart block detected after the newborn period had similar symptoms and signs of autoimmune diseases as the healthy controls, and their standardized mortality ratio was 1.9., Conclusion: Primary Sjögren's syndrome, either definite or subclinical, is the predominant autoimmune disorder in mothers of children with CHB. Mothers of children with isolated heart block detected after the newborn period do not, as a group, have clinical features suggestive of autoimmune diseases.

Objectives: Few data are available in the literature regarding the long-term outcome of newborns with congenital complete heart block (CHB). The aims of this retrospective study were to assess neonatal morbidity and mortality, incidences of dilated cardiomyopathy (DCM), and associated heart defects, and to establish prenatal and postnatal factors that might predict adverse outcome in children with CHB., Design and Setting: The cohort includes 91 infants with CHB diagnosed in 5 tertiary centers in Finland between 1950 and 1998., Patients: Maternal connective tissue disease was evident in 89% of the patients. At birth, the median gestational age was 37.1 weeks, and the median weight was 2969 g. Of the 91 infants, 60 (66%) were girls and 7 (8%) were twins., Results: Incidences of perinatal morbidity and mortality were 58% and 7%, respectively. The total mortality of CHB was 16%; 11 of 15 (73%) died during the first 12 months. Cumulative probability of survival at 10 years old was 82%. Pacing as a newborn was indicated in 48 of 90 cases (53%), and 36 received pacemakers at older ages. Cardiac defects not causally related to CHB were found in 38 of 90 patients (42%), of whom 22 were operated on. DCM was found in 21 (23%), of whom 13 died. During the follow-up, among 75 survivors with a median age of 9 years, 54 (72%) are free from symptoms. Poor outcome defined as clinically or pathologically evident congestive DCM was associated with intrauterine hydrops, low fetal and neonatal heart rate, low birth weight, male sex, and neonatal problems attributable to prematurity or neonatal lupus., Conclusions: Despite early pacing, CHB carries high mortality during the first 12 months of life. High incidences of DCM and associated heart defects indicate close echocardiographic monitoring of all children with CHB.

Cohen syndrome (MIM no. 216550) is an autosomal recessive disorder with a typical clinical picture. Since the first report, most publications have represented single case reports. In this study, our aim was to describe cardiac, endocrine and radiological abnormalities in 22 Cohen patients of Finnish descent. Detailed investigations of the heart revealed the anatomy of the heart to be normal with no evidence for clinically significant mitral prolapse. However, a decreased left ventricular function with advancing age was identified. No significant endocrine abnormalities were found at the examination of pituitary, adrenal and thyroid function. The height was either normal or patients were moderately short (mean height standard deviation score (SDS) - 2) at all ages, associated, however, often with the marked kyphosis. Truncal obesity was seen in 4/22 patients. X-rays of the chest, lumbar and thoracic spine, long bones, ankles and metacarpophalangeal pattern profiles revealed kyphosis, scoliosis and calcaneo planovalgus as common features. Fingers of these patients were slender but short with a characteristic metacarpophalangeal pattern profile.

This paper reviews the current state of the debate on the relationship between mental disorder and violent behaviour. Starting from the discussion of methodological approaches to assessing a possible association, the most important studies carried out on the issue in recent years are discussed. Their results concur in supporting the assumption that there is a moderate but reliable association between mental disorder and violence. However, this does not imply that people with mental illness are generally more likely to commit violent acts than members of the general population. An elevated risk of violent behaviour is only evident for specific psychiatric diagnoses and symptom constellations. For schizophrenia and other psychotic disorders, a significant increase in the likelihood to commit violent acts is reported. Substance use disorders and antisocial personality disorder, however, represent a markedly higher risk for violent behaviour. The article further discusses possible determinants of violent behaviour such as psychotic symptoms and comorbidity with substance abuse and considers who is at particular risk of becoming a target of violent acts.

Objective: To study 10-year changes in selected quality of life dimensions in a cohort of aging Eastern Finnish women., Design: Ten-year follow-up of a representative population sample., Setting: The county of Kuopio in Eastern Finland., Participants: In 1982, a representative sample (n = 296) of 50 to 60-year-old women was examined in the FIN-MONICA study. Ten years later, 241 of the participants were re-examined., Measurements: Self-administered questionnaires were used to collect the data. Self-rated health, self-rated physical fitness, frequency of leisure time physical activity, functional capacity, reported symptoms, occurrence of diseases, and satisfaction with family life and economic situation were measured. In 1992, total life satisfaction at that moment and 5 years earlier were also assessed., Results: The self-rated health assessment remained unchanged. During the 10 years from 1982 to 1992, the proportion of women who reported diagnosed cardiopulmonary diseases increased; angina pectoris, in particular, increased from 6% to 20%. However, even though their running ability had decreased, the number of women rating their physical fitness as good or fairly good increased from 23% to 32%. The participants reported significantly less headache and feelings of exhaustion than they had 10 years earlier. Average satisfaction with their economic situation increased, and satisfaction with family life remained the same. Thirty-seven percent of the women rated their current life situation as better than 5 years previously, 29% felt that it had remained the same, and 34% indicated that it had become worse during the past 5 years., Conclusion: These data suggest that some quality of life dimensions may improve during aging in postmenopausal women.

To study the effect of prostacyclin treatment on pulmonary arterial pressure (PAP), systolic pressure (BP), and systemic oxygenation, eight infants with persistent pulmonary hypertension of the newborn (PPHN) born between 34 and 42 weeks' gestation and having a birth weight of 2540-4130 g were studied using Doppler echocardiography. At a mean age of 19 hours (range 3-32 hours), despite maximal ventilator therapy and an FIO2 of 1.0, the mean PaO2/PAO2 was 0.07 (range 0.04-0.09) and the AaDO2 was 616 mmHg (range 521-654 mmHg). After volume correction and during inotropic medication with dopamine and dobutamine, the mean PAP by echocardiography was 68.6 +/- 6.5 mmHg and the mean BP 59.8 +/- 4.8 mmHg. Prostacyclin infusion was then started at a dose of 20 ng/kg/min and increased stepwise to a mean dose of 60 ng/kg/min (range 30-120 ng/kg/min) over 4-12 hours, at which time PAP decreased to 49.2 +/- 3.5 mmHg (p = 0.0005) and BP to 53.2 +/- 9.1 mmHg (p = 0.17); the PAP thereafter remained below the BP. After 72 hours of prostacyclin infusion, PAP was 49.6 +/- 18 mmHg, BP 66.1 +/- 5.4 mmHg, PaO2/PAO2 0.14 +/- 0.12, and AaDO2 428 +/- 189 mmHg at FIO2 0.65. The median duration of prostacyclin infusion was 3.6 days and of respirator treatment 7.0 days. All patients survived without extracorporeal membrane oxygenation. At 6-12 months, none of the patients had severe central nervous system complications, but two had bronchopulmonary dysplasia. These findings indicate that prostacyclin is able to reverse the right-to-left shunt in PPHN by decreasing PAP, and that systemic hypotension can be prevented with adequate volume correction and inotropic medication.

Until recently, many researchers have been sceptical about any relationship between psychiatric disorders and violence. Since public opinion has always been prejudiced against the mentally ill, professionals in the field of psychiatry have been very cautious about further stigmatizing individuals with psychiatric illnesses. The authors have reviewed studies of mental disorders and violence, particularly the most recent, and find that there is increasing evidence for an association between psychiatric disorders and violence. Recent data suggest that the combination of previous violent behavior, alcoholism and antisocial personality disorder markedly increases the risk of future violent behavior. Schizophrenia, personality disorders and alcoholism per se do not increase the risk of violent behavior as much as do the above factors, but the risk among these diagnostic groups is, however, notably higher than that in the general population. The authors emphasize that only a minority of patients with mental disorders are violent. Future research is needed to better identify and treat these potentially violent patients.

Background: Owing to the fact that Finnish police have been able to solve about 95% of all homicides during recent decades and because most homicide offenders are subjected to an intensive psychiatric evaluation, it was possible to examine data on 693 of 994 homicide offenders during an 8-year period., Methods: The prevalences of mental disorders of the homicide offenders were used to calculate odds ratios (ORs) for the statistical increase in risk associated with specific mental disorders., Results: The results indicate that schizophrenia increases the OR of homicidal violence by about 8-fold in men and 6.5-fold in women. Antisocial personality disorder increases the OR over 10-fold in men and over 50-fold in women. Affective disorders, anxiety disorders, dysthymia, and mental retardation did not elevate the OR to any significant extent (OR < 5.0)., Conclusion: Homicidal behavior in a country with a relatively low crime rate appears to have a statistical association with some specific mental disorders classified according to DSM-III-R classifications.

We studied the risk of homicidal behavior among 281 released male forensic psychiatric patients during the 14-year period 1978-1991. Released patients were about 300 times more likely to commit a homicide than the general male population during the first year outside hospital, and the corresponding risk was 53-fold during a mean follow-up period of 7.8 years. The odds ratio for committing a homicide among all Finnish schizophrenics during the 12-year period 1980-1991 was 9.7, which indicates that previous criminality associated with schizophrenia also increases the risk of homicidal behavior remarkably when compared with schizophrenia per se. We believe that this kind of epidemiological approach is a useful method of identifying and classifying factors associated with very high risk of homicidal behavior and preventing homicidal behavior among high-risk populations.

Objective: Data on persons known to have committed homicide during a 13-year period were studied to determine factors associated with increased risk of repeating homicide., Methods: Between 1981 and 1993, a total of 1,649 homicides were committed in Finland. In 1,089 cases (66 percent), the offenders received an exhaustive forensic psychiatric examination. Data from reports of these examinations were analyzed to determine whether mental disorder and other factors were associated with homicide recidivism., Results: Thirty-six homicide recidivists were identified. Twenty-four were alcoholics, 23 had a personality disorder, in most cases combined with alcoholism, four had schizophrenia, and two had major depression. Homicidal behavior was ten times more likely in men who had committed a previous homicide than in the general male population. Alcoholism increased the odds ratio of additional homicidal behavior in male homicide offenders about 13 times, and schizophrenia increased the odds ratio more than 25 times. During their first year after release from prison, male homicide offenders were about 250 times more likely to commit homicide than members of the general male population., Conclusions: The data suggest that mentally abnormal offenders are overrepresented among homicide recidivists in Finland. The risk of repeat homicide appears to be very high during the first year after release from prison.

Objective: Although violent behavior is one of the most important factors that have a detrimental effect on quality of life, there are very few quantitative epidemiological studies published on this issue. In particular, female homicidal behavior has remained poorly studied. This study reveals the association between some specific DSM-III-R disorders and female homicidal behavior., Method: The author reviewed forensic psychiatric examination of 127 female homicide offenders in Finland over a 13-year period., Results: Female homicide offenders had about a 10-fold higher odds ratio than the general female population for having schizophrenia or a personality disorder. The disorders with the most substantially higher odds ratios were alcohol abuse/dependence and antisocial personality disorder., Conclusions: Mental disorders appear to have a statistical relationship with homicidal behavior in countries with relatively low crime rates. On the basis of the data, there may be special subgroups of women among whom the risk of homicidal behavior is very high.

Using high-resolution single photon emission computed tomography, the authors studied changes in cerebral blood flow (CBF) in six healthy men after the men rapidly consumed intoxicating amounts of ethanol. When the subjects were given intravenous placebo before ethanol intake, regional CBF was significantly increased over baseline in the right prefrontal cortex, but no significant change in CBF was observed when the subjects received intravenous naloxone before ethanol intake. The results indicate that euphoria occurring during acute ethanol intake is associated with activation of the right prefrontal cortex and mediated through the endogenous opioid system.

Objectives: A placebo-controlled, randomized, double-blind study was performed to determine whether prenatal dexamethasone (DEX) treatment improves the outcome of the preterm infant when exogenous surfactant is available., Methods: 157 pregnant women at five hospitals with threatened preterm delivery and with lengths of gestation < 32 weeks received either DEX (dose 6 mg four times at 12-hour intervals) or placebo (PL). Prenatal treatment was not repeated. Preterm infants received rescue therapy of human surfactant (maximum four doses) if they required ventilatory support and at least 40% oxygen for the treatment of respiratory distress syndrome (RDS)., Results: Enrolled pregnant women delivered 188 live-born neonates, of whom 79 (DEX 41 and PL 38 neonates) were born 1 to 14 days after the prenatal treatment. Neonates born within 1 to 14 days after the initial DEX treatment had a lower incidence of RDS (DEX, 44%; PL, 79%; P < .01), lower requirements of surfactant (DEX, 22%; PL, 53%; P < .01), shorter duration of ventilatory support (DEX, 2.0 days; PL, 5.3 days; P < .05) and oxygen therapy (DEX, 2.0 days; PL, 7.0 days; P < .01), and a higher neonatal survival without ventilatory support (P < .05) than PL-treated neonates. DEX-treated neonates had higher mean blood pressure than PL-treated neonates during the first 3 days after birth. Among all neonates treated with DEX, there was a lower incidence of intraventricular hemorrhage or periventricular leucomalacia (DEX, 13%; PL, 33%; P < .01). Reduction in the incidence of intraventricular hemorrhage or periventricular leucomalacia in DEX-treated neonates was particularly associated with exogenous human surfactant therapy (DEX+surfactant 10%; PL+surfactant 48%; P < .01)., Conclusions: Prenatal DEX treatment combined with exogenous human surfactant therapy in preterm infants decreases pulmonary morbidity and cerebral complications, and increases survival without severe morbidity.

The functional anatomy of human emotional responses has remained poorly understood, mainly because invasive experiments in humans are unacceptable due to ethical reasons. The new functional imaging techniques such as positron emission tomography and single photon emission computed tomography have made it possible to study the neurophysiology of living humans noninvasively. We studied the regional cerebral blood flow with semi-quantitative 99mTc-HMPAO single photon emission computed tomography in eight healthy right-handed heterosexual males during organism. The results showed decrease of cerebral blood flow during orgasm in all other cortical areas except in right prefrontal cortex, where the cerebral blood flow increased significantly (P < 0.005).

To study the effect of antenatal indomethacin or nylidrin hydrochloride treatment on the fetal and neonatal ductus arteriosus and tricuspid valve function, 84 pregnant women with threatened premature birth between 22.9 and 34.0 wk gestation and 94 of their offspring born at 24.7 to 41.6 wk of gestation were studied by Doppler echocardiography. Forty-six women were treated with indomethacin and 38 with nylidrin. Both peak systolic and peak diastolic velocities in the ductus increased after administration of indomethacin and exceeded the corresponding velocities in the fetuses of the nylidrin group (p = 0.0001). Ductal constriction occurred in 42 of 49 fetuses treated with indomethacin (86%). Tricuspid valve regurgitation (TR) was evident in 11 of 49 fetuses treated with indomethacin (22%). The mean gestational age of the fetuses with TR (30.0 wk) tended to be higher than those without TR (28.3 wk, p = 0.056). In the nylidrin group, no fetus had ductal constriction or TR. A significant increase in peak systolic velocity (r = 0.54, p = 0.0001) and in peak diastolic velocity (r = 0.46, p = 0.0001) in the ductus with advancing gestational age was demonstrated in the indomethacin group; however, in the nylidrin group, there was a less remarkable increase in peak systolic velocity (r = 0.35, p = 0.04) and no increase in peak diastolic velocity (r = 0.02, p = 0.93). In infants born at or before 35 wk gestation, incidences of both spontaneous closure and indomethacin-induced closure of ductus were similar in both study groups (p > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To determine whether antenatal dexamethasone sodium phosphate administration constricts the fetal ductus arteriosus or improves spontaneous closure of the ductus in premature infants., Design: A randomized double-blind study., Setting: University hospital of Helsinki, Finland., Participants: Sixty-one pregnant women with threatened preterm delivery between 24 and 31.9 weeks' gestation and 57 of their offspring (28 in the dexamethasone and 29 in the placebo group), born at 24 to 34.9 weeks' gestation, were studied using Doppler echocardiography., Interventions: None., Measurements and Main Results: Between the dexamethasone and placebo groups, there were no significant differences in systolic or diastolic flow velocity values in the fetal ductus arteriosus. Of the 29 infants with respiratory distress syndrome, 26 (90%) had hemodynamically significant patent ductus arteriosus and received indomethacin sodium: 12 (92%) of 13 dexamethasone-treated infants and 14 (88%) of 16 placebo-treated infants. One placebo-treated infant was ligated. Of the 28 infants without respiratory distress syndrome, only four (14%) had hemodynamically significant patent ductus arteriosus. In infants born at or before 30 weeks' gestation, spontaneous closure of the ductus occurred more frequently after administration of prenatal dexamethasone (in six of 17 infants; 35%) than placebo (in none of 10 infants; P < .05)., Conclusions: Our data indicate that antenatal dexamethasone administration had no constrictive effect on the ductus arteriosus of the fetus between 24 and 31 weeks' gestation. However, antenatal dexamethasone had a beneficial effect on ductal closure in very premature infants.

We compared the tocolytic effect of indomethacin and nylidrin in a prospective double-blind trial in which the appearance of the tocolytic treatment (always intravenous infusion and rectal suppositories/oral capsules) was identical to the subjects. Sixty healthy women in imminent preterm labor between 25-34 weeks of singleton gestation were included. Thirty of these women received indomethacin (concomitantly with placebo infusion), with doses as follows: day 1, 100-mg rectal suppository followed by two oral capsules (50 mg) at 8-hour intervals; days 2 and 3, three 50-mg oral capsules each day. Thirty women received intravenous nylidrin (concomitantly with rectal/oral placebo), initiated with the dose of 50 micrograms/minute and continued at the dose of 100-150 micrograms/minute for a maximum of 3 days. Preterm labor was arrested for 24, 48, and 72 hours in 100, 96, and 90%, respectively, of subjects in the indomethacin group, compared with 100, 76, and 73% of women in the nylidrin group; the difference was significant (P less than .05) at 48 hours. Women progressed beyond 37 gestational weeks more commonly (P less than .05) with indomethacin (21 of 30, 70%) than with nylidrin (13 of 30, 43%). Indomethacin treatment was accompanied by maternal side effects 20% of the time, significantly less commonly (P less than .001) than with nylidrin (83%). The neonatal outcome was similar in the two study groups. We conclude from this double-dummy technique trial that indomethacin is more effective and better tolerated than nylidrin in arresting imminent preterm labor.

To study the effect of maternal indomethacin or nylidrine hydrochloride treatment on the fetus ductus arteriosus and the pulmonary artery, 27 women with threatened preterm labor between 24 and 34 weeks' gestation were studied by echocardiography. Fourteen women were treated with indomethacin and 13 with nylidrin. Both systolic and diastolic velocities in the ductus increased after administration of indomethacin indicating constriction in nine fetuses, and exceeded the corresponding velocities in the fetuses of the nylidrin group (p = 0.001). However, there were no changes in pulmonary artery flow velocities (p greater than 0.5). In the indomethacin group, there was a significant linear positive relationship between the gestational age and the change in ductal flow velocity. Three of the nine patients with ductal constriction also had tricuspid regurgitation. These findings indicate that indomethacin, not nylidrin, causes transient constriction of the ductus arteriosus and the constrictive response increases with the gestational age. We recommend echocardiographic surveillance of fetal hemodynamics when prostaglandin synthesis inhibitors are used in the treatment of spontaneous preterm labor.

Six women, 13 to 16 weeks pregnant, and 12 women at 38 to 40 weeks gestation, received oral oxazepam about 12 h before legal abortion, by hysterotomy in the former and before elective caesarean section in the latter group. The concentrations of free and conjugated oxazepam in maternal and fetal plasma were determined by gas-liquid chromatography. In early pregnancy the mean ratio between the plasma concentration of total (free + conjugated) drug in the umbilical cord and a maternal vein was 0.6 whereas in late preganancy the ratio vein was 1.1. Both in early and late pregnancy, the free and glucuronide conjugate of oxazepam were found in the fetus at concentrations which indicated transplacental passage of the parent drug and its metabolite. There was great interindividual variation in the plasma levels both of free and conjugated oxazepam.

Plasma renin activity and urinary excretions of aldosterone, sodium and potassium were studied before and during one week's chlorthiazide treatment in eight women with a slight peripheral oedema in the 31st week of pregnancy. Plasma renin activity and excretion of aldosterone increased clearly on the first day of treatment, but on the 7th day it was more than doubled in comparison with the level before the treatment. Diuresis and excretion of sodium increased promptly on the 1st day, but did not differ from the level found before the treatment on the 7th day. The high reserves of renin and aldosterone secretion found in this study may be regarded important in ensuring blood pressure, plasma volume and placental flow during pregnancy.