Changes in interleukin-6 levels during electroconvulsive therapy may reflect the therapeutic response in major depression.

OBJECTIVE: Interleukin-6 (IL-6) has been reported to be elevated in major depressive disorder (MDD) but decreased by antidepressive medication. IL-6 levels are markedly elevated both after epileptic seizures and single electroconvulsive therapy (ECT) session, but long-term changes in IL-6 levels after ECT have not been studied. The correlation between immediate and long-term changes in proinflammatory cytokines and outcome after ECT was investigated. METHOD: Thirty patients suffering from MDD participated in the study. IL-6, interleukin-1ß (IL-1ß) and interleukin-1 receptor antagonist (IL-1RA) levels were examined at baseline and at 2 and 4 h after the first, fifth and the last ECT sessions. The response to ECT was measured with Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: ECT repeatedly caused an increase in IL-6 levels at the 4-h time point. However, the baseline IL-6 levels decreased among remitters, but not among non-remitters, towards the end of ECT. IL-1ß levels were mostly below detectable level, and IL-1Ra levels did not change during and after ECT. CONCLUSION: ECT has distinct acute and long-term effects on IL-6 levels. Interestingly, the long-term effect of ECT on IL-6 seems to correlate with outcome, providing further evidence of the mechanism of action of ECT and supporting the inflammation theory in MDD.

Long-term stability of communication deviance.

Communication deviance (CD), forms of communication that are not bizarrely thought disordered but are hard to follow and that make difficult the consensual sharing of attention and meaning, has been hypothesized as a nonspecific contributor of rearing parents to psychopathology of offspring, including schizophrenia. This hypothesis, or an alternative of genetic transmission, would gain plausibility if CD has long-term stability. CD was evaluated, using tape-recorded and reliably scored Rorschachs in 158 Finnish adoptees, and retested after a median interval of 11 years. Adolescent CD was not stably correlated with follow-up CD. However, initial CD at a mean age of 32 and follow-up CD were significantly correlated. Gender, genetic risk for schizophrenia, and DSM-III-R (American Psychiatric Association, 1987) psychiatric diagnoses had no effect on adult CD stability. CD appears to be a stable, traitlike feature of adult but not adolescent functioning.

Finnish adoptive family study: sample selection and adoptee DSM-III-R diagnoses.

OBJECTIVE: To evaluate the genetic contribution to schizophrenia using an adoption design that disentangles genetic and environmental factors. METHOD: Finnish hospital diagnoses of schizophrenic/paranoid psychosis in a nationwide sample of adopting-away women are compared with DSM-III-R research diagnoses for these mothers. DSM-III-R diagnoses of their index offspring are blindly compared with adopted-away offspring of epidemiologically unscreened control mothers. RESULTS: Primary sampling diagnoses of index mothers were confirmed using DSM-III-R criteria. Lifetime prevalence of typical schizophrenia in 164 index adoptees was 6.7% (age-corrected morbid risk 8.1%), significantly different from 2.0% prevalence (2.3% age-corrected morbid risk) in 197 control adoptees. When adoptees with diagnoses of schizoaffective disorder, schizophreniform disorder, schizotypal disorder and affective psychoses were added, the contrast between the index and control adoptees increased. CONCLUSION: The genetic liability to 'typical' DSM-III-R schizophrenia is decisively confirmed. Additionally, the liability also extends to a broad spectrum of other psychotic and non-psychotic disorders.

Thought disorder index of Finnish adoptees and communication deviance of their adoptive parents.

BACKGROUND: Diverse forms of thought disorder, as measured by the Thought Disorder Index (TDI), are found in many conditions other than schizophrenia. Certain thought disorder categories are primarily manifest during psychotic schizophrenic episodes. The present study examined whether forms of thought disorder qualify as trait indicators of vulnerability to schizophrenia in persons who are not clinically ill, and whether these features could be linked to genetic or environmental risk or to genotype-environment interactions. The Finnish Adoptive Study of Schizophrenia provided an opportunity to disentangle these issues. METHODS: Rorschach records of Finnish adoptees at genetic high risk but without schizophrenia-related clinical diagnoses (N = 56) and control adoptees at low genetic risk (N = 95) were blindly and reliably scored for the Thought Disorder Index (TDI). Communication deviance (CD), a measure of the rearing environment, was independently obtained from the adoptive parents. RESULTS: The differences in total TDI between high-risk and control adoptees were not statistically significant. However, TDI subscales for Fluid Thinking and Idiosyncratic Verbalization were more frequent in high-risk adoptees. When Rorschach CD of the adoptive rearing parents was introduced as a continuous predictor variable, the odds ratio for the Idiosyncratic Verbalization component of the TDI of the high-risk adoptees was significantly higher than for the control adoptees. CONCLUSIONS: Specific categories of subsyndromal thought disorder appear to qualify as vulnerability indicators for schizophrenia. Genetic risk and rearing-parent communication patterns significantly interact as a joint effect that differentiates adopted-away offspring of schizophrenic mothers from control adopted-away offspring.

Gene-environment interaction in vulnerability to schizophrenia: findings from the Finnish Adoptive Family Study of Schizophrenia.

OBJECTIVE: This study assessed the interaction of genetic risk and rearing-family risk as a subsyndromal test measure of schizophrenic thought disorder in adoptees. METHOD: A group of 58 adoptees with schizophrenic biological mothers was compared with 96 comparison adoptees at ordinary genetic risk; putative adoptee vulnerability was assessed blindly and reliably by using the Rorschach Index of Primitive Thought. Environmental risk was measured by using frequency of communication deviance as a continuous variable, scored independently from Rorschach assessments of the adoptive parents. RESULTS: High genetic risk in itself was not associated with greater vulnerability to schizophrenic thought disorder in the adoptees, as indicated by the Index of Primitive Thought. Also, greater communication deviance in the adoptive parents was not associated with greater thought disorder in the comparison adoptees. However, there was a highly significant gene-environment interaction. Among the offspring of the adoptive parents with high levels of communication deviance, a higher proportion of high-risk than comparison adoptees showed evidence of thought disorder. In contrast, among the offspring of adoptive parents with low communication deviance, a lower proportion of high-risk than comparison adoptees showed evidence of thought disorder. The distribution of communication deviance scores did not differ significantly between the adoptive parents of high-risk offspring and the adoptive parents of comparison offspring. CONCLUSIONS: The findings are consistent with genetic control of sensitivity to the environment. There is no evidence that high genetic risk of schizophrenia among offspring is associated with high levels of communication problems in rearing parents.

The Finnish adoptive family study of schizophrenia. Implications for family research.

A nationwide Finnish sample of schizophrenics' offspring given up for adoption was compared blindly with matched controls, who were adopted offspring of non-schizophrenic biological parents. The adoptive families were investigated thoroughly using joint and individual interviews and psychological tests. The biological parents were also interviewed and tested. Among the 155 index offspring, the percentage of both psychoses and other severe diagnoses (borderline syndrome and severe personality disorders) was significantly higher than in the 186 matched control adoptees. This supports a genetic hypothesis. However, notable differences between these two groups only emerged in the families which were rated as disturbed. Thus the genetic effect (i.e. the differences between high and low genetic propensity) was only manifested as a psychiatric disorder in the presence of a disturbed family environment. The impact of disturbed family relations was strongest in the presence of the appropriate genotype.

Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin-thromboxane balance in mother and newborn.

OBJECTIVE: To study the effect of daily treatment with 50 mg of aspirin (ASA) on the hypertensive pregnancy complications and on the production prostacyclin (PGI2) and thromboxane A2 (TxA2) in high risk pregnant women and their infants. DESIGN: Placebo controlled prospective study. SETTING: Departments of Obstetrics and Gynaecology, University of Helsinki, University of Oulu and Central Hospital of Middle Finland, Finland. SUBJECTS: Two hundred and eight pregnant women with pre-existing hypertension or a history of severe preeclampsia in their previous pregnancy. Prostanoids were studied in a subgroup of 18 women. INTERVENTIONS: The women were randomised to receive ASA (50 mg/day, n = 103) or placebo (n = 105) from the mean of 15 weeks gestational age to delivery. The exacerbation of pre-existing hypertension or the appearance of hypertension in previously normotensive women, the appearance of proteinuria and fetal growth were the main end points, but some other clinical characteristics were also recorded. Urinary excretion of PGI2 and TxA2 metabolites by mothers and infants and their production in umbilical arteries in vitro were also studied. RESULTS: Two women (one in both groups) had miscarriages, and one pregnancy was terminated for fetal anencephaly (ASA group). In addition, seven women discontinued the treatment due to urticaria (two women in ASA group), increased activity of aspartate amino transferase in serum (one woman in both groups), or increased bleeding time (one woman in ASA group, two women in placebo group), and one woman in the placebo group was lost from follow-up. Thus the end points could be assessed in 97 women taking ASA and 100 women taking placebo. ASA did not diminish the rate of the rise of blood pressure without (12 vs 14, respectively) or with proteinuria (9 vs 11), but fetal haemodynamic disturbances as assessed by Doppler equipment (1/44 vs 6/45 women studied, P = 0.05) and need for treatment in neonatal intensive care unit (10 vs 21, P = 0.04) were more rare in ASA group. ASA tended to increase the birthweight of the newborn (3348 +/- 707 g vs 3170 +/- 665 g, mean +/- SD, P = 0.07), but two perinatal deaths occurred in ASA group. ASA prolonged the bleeding time of the mother (435 s, 210-998 s (geometric mean, range) vs 349 s, 210-690 s, P = 0.02), but caused no extra blood loss during delivery, nor affected neonatal hemostasis. In a subgroup of mothers (ASA, n = 10; placebo, n = 8), ASA inhibited more than 90% of platelet TxA2-production, and caused a 65 to 80% decrease in the urinary excretion of TxA2 metabolites, but no decrease in the urinary excretion of PGI2 metabolites. CONCLUSIONS: ASA did not prevent the rise of maternal hypertension, but improved fetal haemodynamic performance and reduced the need of intensive neonatal care. It inhibited strongly maternal thromboxane A2 but not PGI2 production and thus shifted the balance between PGI2/TxA2 to the dominance of the vasodilatory, anti-aggregatory side.

Obstetric shoulder injury. Associated risk factors, prediction and prognosis.

A prospective case-control study was made to estimate the incidence of clavicular fracture and brachial plexus palsy, to find out possible risk factors during pregnancy and labor associated with these injuries, and to ascertain the prognosis of injured infants. Clavicular fracture occurred in 165 (3.2%) and brachial plexus palsy in 10 (0.2%) of the 5082 infants born during the study period. From maternal characteristics the Body Mass Index (kg/m2) and pregnancy weight gain were significantly greater in the cases than in the controls. Symphysis-to-fundus height was, on average, higher in the case group. There were no more instrumental vaginal deliveries in cases than in controls. The shoulder injured infants were in every way bigger, but only in 30% of the cases macrosomic (birthweight over the 90th percentile), and they were more often males than in the controls. The prediction of shoulder injury by ultrasound was not successful in our study. The prognosis of injured infants was good, all children except one recovered soon after birth.

Labour induction policy in hospitals of different levels of specialisation.

OBJECTIVE: To examine indications for the induction of labour and variations in the current policy of induction at different levels of obstetric specialisation and to compare the outcome of induced and spontaneous labour. DESIGN: A prospective 1 year birth cohort. SETTING: Maternity hospitals in the two northernmost administrative provinces of Finland, including one university hospital and three central hospitals, three local hospitals and five health centres. SUBJECTS: Eight thousand six hundred and six singleton pregnancies, including 1679 with induced labour. MAIN OUTCOME MEASURE: Data collection on age, parity, social factors and education at antenatal clinic. Data on labour collected from the hospital records after delivery. RESULTS: Labour was induced significantly more often at units of the lowest level of specialisation, the health centres (29.4%) than at the local hospitals (23.6%, P < 0.003) or in the most specialised central hospitals (17.7%, P < 0.0001). Cases of induced labour accumulated on working days. Indicative reasons, such as maternal or fetal conditions, comprised 45.0% of the indications for induction, the most common causes being elective reasons, e.g. timing of labour (51.3%). The risk of elective induction was 2.6 times greater at the primary care level than at the central hospitals (95% confidence limit, CL 2.0-3.2). The corresponding risk ratio for local hospitals was 1.8 (CL 1.5-2.1). The risk of caesarean section was 1.5 times greater in the elective induction group than in the spontaneous group (CL 1.1-1.9) and 2.9 times greater in the indicative induction group. The most common indication for caesarean section was dysfunctional, arrested labour, causes such as fetal asphyxia or antenatal haemorrhage were not seen in excess. CONCLUSION: The practice of induction of labour are not consistent in different hospitals. The opinions of individual practitioners and staff routines influence the induction policy nearly as much as do medical reasons. Despite the safety of induction, a liberal induction policy leads to an increase in operative deliveries creating potential risks for the mother and child and greater expense.

Perinatal outcome of pregnancies complicated by vaginal bleeding.

OBJECTIVE: To examine the effect of first and/or second trimester vaginal bleeding on pregnancy outcome. DESIGN: A prospective one-year birth cohort. SETTING: Two northernmost administrative districts of Finland. PATIENTS: 8718 singleton pregnancies, of whom 807 (9.3%) reported bleeding during the first (601) and/or second trimester (206); light bleeding in 595 cases and heavy bleeding in 212. The remaining 7911 women served as a reference group. MAIN OUTCOME MEASURES: Low birth weight rate (LBW), preterm birth rate, congenital malformations and perinatal mortality rate. RESULTS: Bleeding was most frequent in women of more advanced age (> or = 35 years old), with previous miscarriages, with infertility problems or using an IUCD prior to the pregnancy. Parity, smoking and social status were not associated with bleeding. Caesarean section rate and placental complications during the third trimester and at delivery were more common among the bleeders than in the reference group. The LBW rate was three-fold among the bleeders and the preterm birth rate two-fold. The risk (OR) of a LBW infant among second trimester bleeders was 4.1 (95% CI 2.6-6.4), that of preterm birth 2.9 (95% CI 1.9-4.6), and that of congenital malformations 2.9 (95% CI 1.7-4.7). No association existed between bleeding and perinatal mortality. CONCLUSIONS: Bleeding during the second trimester indicates a poor pregnancy outcome and an increased risk of LBW, and preterm birth and/or congenital malformation.

Occurrence of antinuclear antibodies in an unselected pregnancy population.

The occurrence of antinuclear antibodies (ANA) in an unselected population of pregnant women was studied by an indirect immunofluorescence method. Six women out of 116 were ANA-positive (5.2%), 2 of them having a moderately high titre (1:160 and 1:320) and 1 complement-fixing ANA. The antigenic specificity of ANA was anti-single-stranded DNA in 2 cases and RNAase-sensitive anti-extractable nuclear antigen in 1 case. Two of the ANA-positive women had pre-eclampsia laevis and 1 had a premature delivery. None of the infants of the ANA-positive women had symptoms of connective tissue disease. The occurrence of ANA among pregnant women was not significantly higher than among 70 non-pregnant female control subjects (7.1%).

Monitoring of smooth muscle antibodies in hypertensive complications during pregnancy.

Smooth muscle antibodies (SMA) were monitored in terms of titer, immunoglobulin class and staining pattern by indirect immunofluorescence assay during the pregnancies of 32 women with pregnancy induced hypertension (PIH), 21 with essential hypertension (EH), and 43 with a normal pregnancy. The mean SMA titer was higher both in PIH and EH than in normal pregnancy. SMA were mainly of the IgG class and gave a "vessel wall" staining pattern in immunofluorescence. The tendency for the mean SMA titer to increase was observed in PIH, whereas a falling tendency was found in EH and normal pregnancy. These tendencies suggest that hypertension, the duration of which has been shorter in PIH, induces SMA production. The observed staining pattern suggests the same kind of non-actin specificity for SMA as in our previous study of complications in early pregnancy.

No effect of experimental noise exposure on human pregnancy.

The effect of experimental noise exposure (15 minutes of 90-dB white noise via headphones) was examined on systolic, diastolic, and mean arterial pressures; heart rate; and stress hormones (ACTH, cortisol, prolactin, epinephrine, and norepinephrine) in normotensive and hypertensive pregnant women. No significant effects induced by noise exposure could be registered in these variables. Fetal and uterine blood circulation was also examined with a duplex pulsed Doppler system. No changes were seen on the fetal side as measured from the descending aorta in blood flow velocity (cm/second) or pulsatility or resistance indexes in either normotensive or hypertensive pregnancy. The only change observed was an increase in fetal heart rate in normotensive pregnancy. However, this increase could not be confirmed by cardiotocographic registration and is not clinically important. Uterine blood circulation was recorded from the proximal uterine artery on the placental side, and no effect of exposure was seen on pulsatility or resistance indexes.

Immediate correction of congenital nasal deformities; follow-up of 8 years.

A total of 4724 newborns was screened for congenital nasal deformities. Altogether 91 (1.9%) pathological, screening-positive cases were found. Because of refusal to participate, 3 pathological cases were lost leaving 88 cases. The first 55 screening positive newborns were left without treatment while an attempt was made by an otolaryngologist to correct the remaining 33 cases within a week from delivery. Eighty-two newborns of those who passed the screening tests were analyzed as a control group. In 1987, at the age of 8 years the case and control children were interviewed by mailed questionnaire and invited to be re-examined by an ENT-surgeon. Forty-seven of the not corrected, 21 of the corrected cases and 61 controls came to the re-examination. The luxated septal cauda tended to be straight both spontaneously as well as after active treatment. The few mid-septal pathologies (vomerine junction) in the corrected group were resistant to the treatment attempted. The mid-septal deformities found in the follow-up were connected with frequent antibiotic prescriptions but not respiratory infections. No increase in frequency of otitis media or sinusitis was noticed. The immediate treatment of nasal deformities did not significantly affect the clinical status of the nose at the follow-up. Thus the benefit of immediate treatment on nasal deformities in newborns and screening to find them remains questionable.

Is a child's history of acute otitis media and respiratory infection already determined in the antenatal and perinatal period?

A random sample of 2512 children were followed up from fetal period to the age of two years and the relation of various antenatal and perinatal factors to acute respiratory infection, wheezy bronchitis and otitis media was studied. A model containing the relationships between the variables was used as a basis for the analysis and the powerful confounding effects of postnatal factors were standardized. Acute otitis media with effusion (AOME) demonstrated by myringotomy was analyzed as a specific subgroup of acute otitis media (AOM). Low birth weight (less than or equal to 2500 g) and prematurity (birth before the 37th gestational week) did not influence either AOM or AOME. The odds ratio for low birth weight infants becoming 'otitis-prone' (greater than or equal to 3 episodes of AOME) was 1.5 (0.9-2.1, P greater than 0.1). The various neonatal ventilation therapies were not associated with either AOM or AOME, but intermittent positive pressure ventilation, low birth weight and prematurity were distinctly related to wheezy bronchitis. The odds ratio regarding intermittent positive pressure ventilation was 2.0 (1.0-3.0, P less than 0.05) and that regarding low birth weight 1.7 (1.0-2.3, P less than 0.05). Boys had a slightly increased risk with respect to all the infective parameters. Birth order was closely correlated with the infective parameters, but much of this correlation was due to the postnatal effect of siblings. Altogether the antenatal and perinatal factors had only a slight effect on the infective parameters studied.

Changes in prognosis of twin births over 20 years.

The study is based on two birth cohorts from the years 1966 and 1985-1986. Perinatal mortality of twins has fallen over 20 years from 9.2% to 3.1%. Improvement is particularly remarkable in neonatal mortality (less than 28 days) of preterm (less than 34 gestational weeks) twins, from 47.4% to 8.6%, whereas the incidence of stillbirths has not fallen greatly. The proportion of preterm births has not fallen significantly, 48.4% vs. 38.1%. Many factors, considered favourable to the course and outcome of pregnancy have improved simultaneously: women are taller, less overweight, and more educated; pregnancies are wanted and sick and maternity leave provisions have improved. The follow-up of twin pregnancies and deliveries has been centralized and is more effective. In particular, neonatal care is also better than 20 years ago. The prognosis of twins has improved in parallel with the singletons, but the perinatal mortality is still approximately four time and the incidence of prematurity ten times more than in singletons.

The grand multipara--still an obstetrical challenge?

To study whether grand multiparity (parity of 6 or more) still carries risk, we studied two birth cohorts in northern Finland: the first comprised 12,231 births to 12,068 mothers in 1966 and the second comprised 9478 births to 9362 mothers in 1985/86. The percentage of grand multipara decreased from 7.7 to 4.0. The grand multipara made fewer antenatal visits than the others. The proportion of grand multipara referred to maternity outpatient clinics of hospitals was smaller, but the mean number of visits was higher than of lower parity women. The mean number of admissions to hospital was similar in both groups but grand multipara stayed longer in hospital, smoked less (4.3% vs. 22.7%) and had a higher incidence of essential hypertension than women of lower parity. The grand multipara had fewer caesarean sections (7.5% vs. 14.1%) and vacuum extractions (0.5% vs. 5.1%) but more inductions of labour (33.1% vs. 23.5%) than mothers of lower parity. The number of low birth weight (LBW) infants (less than 2500 grams), stillbirths and neonatal deaths (before 28 days) was significantly lower in 1985/86 than in 1966 in women of lower parity but there was no such change in grand multipara. However, the percentage of LBW infants was smaller among grand multipara than among women of lower parity in both cohorts (2.7% vs. 4.1%, NS). The stillbirth plus neonatal death rate in grand multipara was higher than in women of lower parity (1.9% vs. 0.9%, P less than 0.05) partly because of a higher incidence of major congenital anomalies.