Maternal antenatal daytime sleepiness and child neuropsychiatric and neurocognitive development.

BACKGROUND: The prevalence of sleep problems among pregnant women is over 50%, and daytime sleepiness is among the most common sleep problems. Previous studies have associated antenatal sleep problems with adverse maternal health and neonatal outcomes, but the consequences of antenatal sleep problems and particularly daytime sleepiness on child psychological development have not been assessed prospectively. METHODS: In this prospective cohort study including 111 mother-child dyads, we examined the associations of maternal daytime sleepiness during pregnancy, assessed at 17 and 28 weeks of gestation using the Epworth Sleepiness Scale, with child neuropsychiatric problems and neuropsychological development, assessed with mother-rated questionnaires and individually administered neuropsychological tests, at child age 2.6-5.7 years (mean = 4.3 years). RESULTS: Independently of sociodemographic and perinatal covariates and maternal depressive and anxiety symptoms during and/or after pregnancy, maternal antenatal daytime sleepiness was associated with increased total [unstandardized regression coefficient (B) = 0.25 standard deviation (s.d.) units; 95% confidence interval (CI) 0.01-0.48] and internalizing (B = 0.25 s.d.s: 95% CI 0.01-0.49) psychiatric problems and ADHD symptoms (B = 0.27 s.d.s: 95% CI 0.04-0.50) in children, and with poorer executive function, particularly in the areas of attention, working memory and inhibitory control (B = -0.39 s.d.s: 95% CI -0.69 to -0.10). CONCLUSIONS: Maternal antenatal daytime sleepiness carries adverse consequences for offspring psychological development. The assessment of sleep problems may be an important addition to standard antenatal care.

Early life stress and frailty in old age: the Helsinki birth cohort study.

BACKGROUND: Evidence suggests that early life stress (ELS) may extend its effect into adulthood and predispose an individual to adverse health outcomes. We investigated whether wartime parental separation, an indicator of severe ELS, would be associated with frailty in old age. METHODS: Of the 972 participants belonging to the present sub-study of the Helsinki Birth Cohort Study, 117 (12.0%) had been evacuated abroad unaccompanied by their parents in childhood during World War II. Frailty was assessed at a mean age of 71 years according to Fried's criteria. RESULTS: Thirteen frail men (4 separated and 9 non-separated) and 20 frail women (2 separated and 18 non-separated) were identified. Compared to the non-separated men, men who had been separated had an increased relative risk ratio (RRR) of frailty (age-adjusted RRR 3.93, 95% CI 1.02, 15.11) that persisted after adjusting for several confounders. No associations were observed among women (RRR 0.62; 95% CI 0.13, 2.94). CONCLUSIONS: These preliminary results suggest that ELS might extend its effects not just into adulthood but also into old age, and secondly, that men may be more vulnerable to the long-term effects of ELS.

Common mental disorders in young adults born late-preterm.

BACKGROUND: Results of adulthood mental health of those born late-preterm (34 + 0-36 + 6 weeks + days of gestation) are mixed and based on national registers. We examined if late-preterm birth was associated with a higher risk for common mental disorders in young adulthood when using a diagnostic interview, and if this risk decreased as gestational age increased. METHOD: A total of 800 young adults (mean = 25.3, s.d. = 0.62 years), born 1985-1986, participated in a follow-up of the Arvo Ylppö Longitudinal Study. Common mental disorders (mood, anxiety and substance use disorders) during the past 12 months were defined using the Composite International Diagnostic Interview (Munich version). Gestational age was extracted from hospital birth records and categorized into early-preterm (<34 + 0, n = 37), late-preterm (34 + 0-36 + 6, n = 106), term (37 + 0-41 + 6, n = 617) and post-term (⩾42 + 0, n = 40). RESULTS: Those born late-preterm and at term were at a similar risk for any common mental disorder [odds ratio (OR) 1.11, 95% confidence interval (CI) 0.67-1.84], for mood (OR 1.11, 95% CI 0.54-2.25), anxiety (OR 1.00, 95% CI 0.40-2.50) and substance use (OR 1.31, 95% CI 0.74-2.32) disorders, and co-morbidity of these disorders (p = 0.38). While the mental disorder risk decreased significantly as gestational age increased, the trend was driven by a higher risk in those born early-preterm. CONCLUSIONS: Using a cohort born during the advanced neonatal and early childhood care, we found that not all individuals born preterm are at risk for common mental disorders in young adulthood - those born late-preterm are not, while those born early-preterm are at a higher risk. Available resources for prevention and intervention should be targeted towards the preterm group born the earliest.

Maternal depressive symptoms throughout pregnancy are associated with increased placental glucocorticoid sensitivity.

BACKGROUND: Maternal prenatal depression predicts post-partum depression and increases risk of prematurity and low birth weight. These effects may be mediated by altered placental function. We hypothesized that placental function would be influenced by the gestational week of experiencing depressive symptoms and aimed to examine associations between maternal depressive symptoms during pregnancy and placental expression of genes involved in glucocorticoid and serotonin transfer between mother and fetus. METHOD: We studied women participating in a prospective pregnancy cohort: the Prediction and Prevention of Preeclampsia (PREDO) Study, Helsinki, Finland. Maternal depressive symptoms were assessed at 2-week intervals throughout pregnancy in 56 healthy women with singleton, term pregnancies. Messenger ribonucleic acid (mRNA) levels of glucocorticoid (GR) and mineralocorticoid (MR) receptors and serotonin transporter (SLC6A4), 11ß-hydroxysteroid dehydrogenase type 1 (HSD1) and 2 (HSD2) were quantified in placental biopsies. RESULTS: In adjusted analyses women who reported higher depressive symptoms across the whole pregnancy had higher mRNA levels of GR [effect size 0.31 s.d. units, 95% confidence interval (CI) 0.01-0.60, p = 0.042] and MR (effect size 0.34 s.d. units, 95% CI 0.01-0.68, p = 0.047). These effects were significant for symptoms experienced in the third trimester of pregnancy for GR; findings for MR were also significant for symptoms experienced in the second trimester. GR and MR mRNA levels increased linearly by having the trimester-specific depressive symptoms scores 0, 1 or 2-3 times above the clinical cut-off for depression (p = 0.003, p = 0.049, respectively, and p = 0.004, p = 0.15 in adjusted analyses). CONCLUSIONS: Our findings offer potential gestational-age-specific mechanisms linking maternal depressive symptoms during pregnancy via placental biology. Future studies will test whether these also link with adverse offspring outcomes.

Maternal depressive symptoms during pregnancy, placental expression of genes regulating glucocorticoid and serotonin function and infant regulatory behaviors.

BACKGROUND: Glucocorticoids and serotonin may mediate the link between maternal environment, fetal brain development and 'programming' of offspring behaviors. The placenta regulates fetal exposure to maternal hormonal signals in animal studies, but few data address this in humans. We measured prospectively maternal depressive symptoms during pregnancy and mRNAs encoding key gene products determining glucocorticoid and serotonin function in term human placenta and explored associations with infant regulatory behaviors. METHOD: Bi-weekly self-ratings of the Center for Epidemiologic Studies Depression Scale from 12th to 13th gestational week onwards and term placental mRNAs of 11beta-hydroxysteroid dehydrogenase type 2 (HSD2B11), type 1 (HSD1B11), glucocorticoid (NR3C1), mineralocorticoid receptors (NR3C2) and serotonin transporter (SLC6A4) were obtained from 54 healthy mothers aged 32.2 ± 5.3 years with singleton pregnancies and without pregnancy complications. Infant regulatory behaviors (crying, feeding, spitting, elimination, sleeping and predictability) were mother-rated at 15.6 ± 4.2 days. RESULTS: Higher placental mRNA levels of HSD2B11 [0.41 standard deviation (s.d.) unit increase per s.d. unit increase; 95% confidence interval (CI) 0.13-0.69, p = 0.005], HSD1B11 (0.30, 0.03-0.57, p = 0.03), NR3C1 (0.44, 0.19-0.68, p = 0.001) and SLC6A4 (0.26, 0.00-0.53, p = 0.05) were associated with more regulatory behavioral challenges of the infant. Higher placental NR3C1 mRNA partly mediated the association between maternal depressive symptoms during pregnancy and infant regulatory behaviors (p < 0.05). CONCLUSIONS: Higher placental expression of genes regulating feto-placental glucocorticoid and serotonin exposure is characteristic of infants with more regulatory behavioral challenges. Maternal depression acts, at least partly, via altering glucocorticoid action in the placenta to impact on offspring regulatory behaviors.

Late preterm birth, post-term birth, and abnormal fetal growth as risk factors for severe mental disorders from early to late adulthood.

BACKGROUND: Late preterm births constitute the majority of preterm births. However, most evidence suggesting that preterm birth predicts the risk of mental disorders comes from studies on earlier preterm births. We examined if late preterm birth predicts the risks of severe mental disorders from early to late adulthood. We also studied whether adulthood mental disorders are associated with post-term birth or with being born small (SGA) or large (LGA) for gestational age, which have been previously associated with psychopathology risk in younger ages. METHOD: Of 12 597 Helsinki Birth Cohort Study participants, born 1934-1944, 664 were born late preterm, 1221 post-term, 287 SGA, and 301 LGA. The diagnoses of mental disorders were identified from national hospital discharge and cause of death registers from 1969 to 2010. In total, 1660 (13.2%) participants had severe mental disorders. RESULTS: Individuals born late preterm did not differ from term-born individuals in their risk of any severe mental disorder. However, men born late preterm had a significantly increased risk of suicide. Post-term birth predicted significantly increased risks of any mental disorder in general and particularly of substance use and anxiety disorders. Individuals born SGA had significantly increased risks of any mental and substance use disorders. Women born LGA had an increased risk of psychotic disorders. CONCLUSIONS: Although men born late preterm had an increased suicide risk, late preterm birth did not exert widespread effects on adult psychopathology. In contrast, the risks of severe mental disorders across adulthood were increased among individuals born SGA and individuals born post-term.

Maternal hypertensive disorders during pregnancy: adaptive functioning and psychiatric and psychological problems of the older offspring.

OBJECTIVE: To study whether pre-eclampsia and hypertension without proteinuria during pregnancy are associated with adaptive functioning, and psychiatric and psychological problems, of older offspring. DESIGN: Retrospective longitudinal cohort study. SETTING: Participants in the Helsinki Birth Cohort 1934-44 Study. POPULATION: A cohort of 778 participants born after normotensive, pre-eclamptic, or hypertensive pregnancies, defined based on the mother's blood pressure and urinary protein measurements at maternity clinics and birth hospitals. METHODS: Pearson's chi-squared tests and multivariable logistic regression. MAIN OUTCOME MEASURES: Achenbach System of Empirically Based Assessment Older Adult Self-Report scores, completed at age 69.3 years (SD 3.1 years). RESULTS: Compared with offspring born after normotensive pregnancies, offspring born after pre-eclamptic pregnancies had increased odds of reporting total problems (aOR 4.00, 95%CI 1.64-9.77) and problems of particular concern to clinicians (critical items; aOR 5.28, 95%CI 1.87-14.96), as well as: anxious/depressed, functional impairment, memory, thought, and irritable/disinhibited problems on syndrome scales; depressive, somatic, and psychotic problems on Diagnostic and Statistical Manual of Mental Disorders scales; and adjustment problems in relationship satisfaction with spouse/partner. Maternal hypertension without proteinuria was not consistently associated with adjustment and problems (total problems, aOR 1.08, 95%CI 0.75-1.57; critical items, aOR 1.58, 95%CI 0.91-2.72). CONCLUSIONS: Maternal hypertensive disorders in pregnancy, during a period of expectant treatment, carry an increased risk of problems in adaptive functioning and mental wellbeing in the offspring seven decades later. Being the longest follow-up on transgenerational consequences of maternal hypertensive disorders reported thus far, our study points to the life-time increased risk of an adverse intrauterine environment.

Aspirin in the prevention of pre-eclampsia in high-risk women: a randomised placebo-controlled PREDO Trial and a meta-analysis of randomised trials.

OBJECTIVE: To study the effect of aspirin in the prevention of pre-eclampsia in high-risk women. DESIGN: Randomised, double-blinded, placebo-controlled trial. SETTING: Maternity clinics in ten Finnish hospitals participating in the PREDO Project. SAMPLE: A total of 152 women with risk factors for pre-eclampsia and abnormal uterine artery Doppler velocimetry. METHODS: Participants were randomised to start either aspirin 100 mg/day or placebo at 12 + 0 to 13 + 6 weeks + days of gestation. Because of the limited power of this trial, we also conducted a meta-analysis of randomised controlled trials that included data on 346 women with abnormal uterine artery Doppler flow velocimetry, and aspirin 50-150 mg/day started at or before 16( ) weeks of gestation. MAIN OUTCOME MEASURE: Pre-eclampsia, gestational hypertension and birthweight standard deviation (SD) score. Outcome measures for the meta-analysis were pre-eclampsia, severe pre-eclampsia, preterm (diagnosed <37 + 0 weeks of gestation) and term pre-eclampsia. RESULTS: From the 152 randomised women, 121 were included in the final analysis. Low-dose aspirin did not reduce the rate of pre-eclampsia (relative risk [RR] 0.7, 95% CI 0.3-1.7); gestational hypertension (RR 1.6, 95% CI 0.6-4.2); early-onset pre-eclampsia (diagnosed <34 + 0 weeks of gestation) (RR 0.2, 95% CI 0.03-2.1); or severe pre-eclampsia (RR 0.4, 95% CI 0.1-1.3); and the results were not statistically significant in an intention-to-treat analysis. However, our meta-analysis, including the current data, suggested that low-dose aspirin initiated before 16 weeks of gestation reduces the risk of pre-eclampsia (RR 0.6, 95% CI 0.4-0.8) and severe pre-eclampsia (RR 0.3, 95% CI 0.1-0.7). CONCLUSIONS: Our trial showed no statistically significant effect of aspirin in preventing pre-eclampsia in high-risk women. However, our meta-analysis suggested that aspirin may reduce the incidence of pre-eclampsia.

Stress, glucocorticoids and liquorice in human pregnancy: programmers of the offspring brain.

A suboptimal prenatal environment may induce permanent changes in cells, organs and physiology that alter social, emotional and cognitive functioning, and increase the risk of cardiometabolic and mental disorders in subsequent life ("developmental programming"). Although animal studies have provided a wealth of data on programming and its mechanisms, including on the role of stress and its glucocorticoid mediators, empirical evidence of these mechanisms in humans is still scanty. We review the existing human evidence on the effects of prenatal maternal stress, anxiety and depression, glucocorticoids and intake of liquorice (which inhibits the placental barrier to maternal glucocorticoids) on offspring developmental outcomes including, for instance, alterations in psychophysiological and neurocognitive functioning and mental health. This work lays the foundations for biomarker discovery and affords opportunities for prevention and interventions to ameliorate adverse outcomes in humans.

Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial.

BACKGROUND: In this prospective, randomized, double-blind, placebo-controlled study, we investigated the effect of pregabalin on oxycodone consumption, postoperative confusion, and pain in elderly cardiac surgery patients. METHODS: Seventy patients, aged ≥75 yr, were randomized to receive either 150 mg of pregabalin before operation and 75 mg of pregabalin twice daily for 5 postoperative days or placebo. Pain intensity was measured with the Verbal Rating Scale (VRS). When pain intensity was ≥2 on the VRS, patients received oxycodone either i.v. (0.05 mg kg(-1)) or orally (0.10-0.15 mg kg(-1)). Postoperative confusion was measured with the Confusion Assessment Method for the intensive care unit (CAM-ICU). Postoperative pain was assessed by a telephone interview 1 and 3 months after operation. RESULTS: Cumulative consumption of parenteral oxycodone during 16 h after extubation was reduced by 44% and total oxycodone consumption from extubation to the end of the fifth postoperative day was reduced by 48% in the pregabalin group. Time to extubation was 138 min shorter and CAM-ICU scores were significantly lower on the first postoperative day in the placebo group, although there was no significant difference with respect to the Mini-Mental State Examination or the Richmond Agitation Sedation Score. The incidence of pain during movement was significantly lower in the pregabalin group at 3 months postoperative. CONCLUSIONS: The administration of pregabalin reduced postoperative opioid consumption after cardiac surgery reduced the incidence of confusion on the first postoperative day and increased time to extubation when compared with placebo. Three months after operation, patients in the pregabalin group experienced less pain during movement.

Prenatal growth, postnatal growth and trait anxiety in late adulthood - the Helsinki Birth Cohort Study.

OBJECTIVE: Trait anxiety may predispose to anxiety disorders and cardiovascular events. We tested whether prenatal growth or postnatal growth from birth to 11 years of age and in adulthood predict trait anxiety in late adulthood. METHOD: Women (n = 951) and men (n = 753) reported trait anxiety using the Spielberger Trait Anxiety Scale at an average age of 63.4 years and growth was estimated from records. RESULTS: Higher trait anxiety was predicted by smaller body size at birth, in infancy and in adulthood. Moreover, faster growth particularly from seven to 11 years of age and slower growth between 11 and 63 years predicted higher trait anxiety. CONCLUSION: We found a pattern of pre- and postnatal growth that predisposed to higher trait anxiety in late adulthood. This pattern resembles that found to increase the risk of cardiovascular events and, thus, points to a shared common origin in a suboptimal prenatal and childhood developmental milieu.

Depressive symptoms in adulthood and intrauterine exposure to pre-eclampsia: the Helsinki Birth Cohort Study.

OBJECTIVE: We studied whether pre-eclampsia predicts depressive symptoms in offspring. DESIGN: Retrospective longitudinal cohort study. SETTING: Participants in the Helsinki Birth Cohort 1934-44 Study. POPULATION: We classed 788 women and men born at term after a normotensive, hypertensive or pre-eclamptic pregnancy, by using the mother's blood pressure and urinary protein measurements, at maternity clinics and birth hospitals. METHODS: Linear and logistic regression analyses. We made adjustments for the mother's age and body mass index (BMI) at delivery, the participant's body size at birth/length of gestation, sex and childhood socio-economic status, age and educational attainment at testing. MAIN OUTCOME MEASURES: Beck depression inventory (BDI) scores completed twice, at the ages of 60 and 63 years. RESULT: Participants born after a primiparous pregnancy complicated by pre-eclampsia had over 30% (P < 0.04) higher depressive symptom scores in adulthood compared with those born after a primiparous normotensive pregnancy. We found no evidence of the association between pre-eclampsia and depression among participants born after multiparous pregnancies. Gestational hypertension and depressive symptoms were not significantly associated. The models adjusting for mother's age and BMI at delivery, the participant's body size at birth/length of gestation, sex, childhood socio-economic status, age and educational attainment at testing did not change the results. CONCLUSION: Pre-eclampsia is associated with later depressive symptoms in individuals born at term and after a primiparous pregnancy. These findings are compatible with the adverse fetal 'programming' by a suboptimal prenatal environment.

Evaluation of easily applicable pain measurement tools for the assessment of pain in demented patients.

BACKGROUND AND OBJECTIVES: Difficulties in communication and lack of suitable pain scales may lead to undertreatment of pain in cognitively impaired patients. We performed a study in this type of patients and evaluated the usefulness of four simple pain scales. PATIENTS AND METHODS: We studied 41 hospitalized elderly (76-95 years) who suffered from pain with an acute component. Cognitive function was assessed with the mini-mental state examination (MMSE) and the degree of depression was assessed on the geriatric depression scale (GDS). Pain intensity was assessed at rest and after a pain-provoking movement three times at 2-week intervals by repeating the test at a 10-min interval at each test session. The pain scales were the 50 cm red wedge scale (RWS), the seven-point faces pain scale (FPS), the 10 cm visual analogue scale (VAS) and the five-point verbal rating scale (VRS). RESULTS: In group MMSE> or =24, patients were able to use all four scales rather successfully. In the other groups (MMSE 17-23, 11-16 and < or =10), only the use of VRS was successful to a reasonable degree (64-85% on average). GDS scores did not correlate with the pain scores, with the exception of pain scores on FPS during movement (P<0.01). The estimations of intensity and frequency of pain performed by nurses failed to correlate with the patient's own pain intensity estimations. CONCLUSION: Scoring of pain with RWS, FPS and VAS seems to be feasible in elderly patients with a normal cognitive dysfunction. In our study VRS appeared to be applicable in the elderly with a clear cognitive dysfunction, i.e., with MMSE<17.

Comparison of effects and plasma concentrations of opioids between elderly and middle-aged patients after cardiac surgery.

BACKGROUND: In elderly patients, opioids may cause prominent postoperative sedation and respiratory depression. We evaluated the influence of age on the effects of opioids and plasma concentrations of fentanyl and oxycodone in cardiac surgery patients. METHODS: Thirty (>or=75 years, gender M9/F21) and 20 (

Using big data to explore worldwide trends in objective sleep in the transition to adulthood.

BACKGROUND: Development induces changes in sleep, and its duration has been reported to change as a function of aging. Additionally, sleep timing is a marker of pubertal maturation, where during adolescence, the circadian rhythm shifts later. Typically, this is manifested in a later sleep onset in the evening and later awakening in the morning. These changes across development seem to be universal around the world but are unlikely to persist into adulthood. METHODS: This study utilized accelerometer data from 17,355 participants aged 16-30 years (56% female) measured by validated Polar wearables over a 14-day period. We compared sleep duration, chronotype (sleep midpoint) and weekend catch-up (ie, social jetlag) sleep across ages and regions over 242,948 nights. RESULTS: The data indicate a decline in sleep duration as well as a dramatic shift in sleep onset times throughout adolescence. This continues well into early adulthood and stabilizes nearer age 30. Differences in sleep duration across ages were significant, and ranged from 7:53 h at age 16 to 7:29 h at age 30 in the sample. Additionally, there was a clear difference between females and males throughout adolescence and young adulthood: girls had longer sleep duration and earlier timed sleep in the current study. Differences in sleep were found between regions across the world, and across European areas. CONCLUSIONS: Both sleep duration and sleep timing go through a clear developmental pattern, particularly in early adulthood. Females had an earlier sleep midpoint and obtained more sleep. Regional differences in sleep occurred across the world.

Applicability of tools to assess pain in elderly patients after cardiac surgery.

BACKGROUND: Post-operatively, elderly patients with impaired vision and cognitive dysfunction may experience difficulties understanding standard pain assessment tools such as the 10-cm Visual Analogue Scale (VAS) and the Verbal Rating Scale (VRS). Thus, there is a need to identify more feasible post-operative pain assessments for elderly patients. With this goal in mind, we compared the VAS and VRS with two more expressive tools: the 50-cm Red Wedge Scale (RWS) and the Facial Pain Scale (FPS). METHODS: Cardiac surgery patients (73 +/- 5 years, mean +/- SD) were allocated to an RWS (n=80) or an FPS (n=80) group. Pain was assessed at rest and after movement during the first 4 days after tracheal extubation. The RWS or FPS assessments were repeated after 10 min. All patients completed the VRS and VAS. RESULTS: The rates of successful pain measurement on study day 1 were: VRS 86%, VAS 62%, RWS 78%, and FPS 60%. Pain measurements with the RWS correlated with the VAS (r=0.758, P<0.001) and weaker with the VRS (r=0.666, P<0.001) measurements. Pain measurements with the FPS correlated well with the VAS (r=0.873, P<0.001) and weaker with the VRS (r=0.583, P<0.001) measurements. With all scales, success rates improved during the study period. CONCLUSION: In elderly patients, immediately after cardiac surgery, the VRS is the most feasible pain scale, followed by the RWS. The traditional 10-cm VAS is unsuitable for pain measurement in this population.

The effect of low-dose aspirin on serum placental growth factor levels in a high-risk PREDO cohort.

OBJECTIVES: Our first aim was to study the longitudinal changes of serum placental growth factor (PlGF) concentration between 12+0 and 28+0 weeks of gestation in the prospective PREDO cohort. Our second aim was to study the effect of low-dose acetylsalicylic acid (LDA; 100 mg/day), started before the 14th week of gestation, on PlGF concentration. STUDY DESIGN: Blood samples were collected at 12+0-14+0, 18+0-20+0 and 26+0-28+0 weeks of gestation in 101 women without and 309 with clinical risk factors for pre-eclampsia. Risk-women were divided into two groups: to those who had medium risk for pre-eclampsia and to those who had high risk for pre-eclampsia. Finally there were seven groups according to risk, treatment (no prevention/placebo/LDA) and outcome measure pre-eclampsia. Longitudinal changes in the PlGF concentration between groups were compared. To investigate the effect of LDA on serum PlGF concentration, placebo (N = 62) and LDA (N = 61) groups were compared. A repeated measures ANOVA was used to analyze differences in PlGF levels between the groups. RESULTS: The increase in serum PlGF concentration was higher in LDA than in placebo group (time × group effect, p = 0.046). The increase in serum PlGF concentration during pregnancy was lower in high-risk women who had placebo and developed pre-eclampsia and in medium-risk women who developed pre-eclampsia compared to the other women (time × group effect, p < 0.001). There were no differences in PlGF change between low-risk women, medium-risk women who did not develop pre-eclampsia, high-risk women in the placebo group without pre-eclampsia and high-risk women in the LDA group with and without pre-eclampsia (p = 0.15). CONCLUSIONS: Our finding suggests an association between LDA started before 14 weeks of gestation and higher increase in serum PlGF concentration.

Autism spectrum traits and visual processing in young adults with very low birth weight: the Helsinki Study of Very Low Birth Weight adults.

Visual processing problems may be one underlying factor for cognitive impairments related to autism spectrum disorders (ASDs). We examined associations between ASD-traits (Autism-Spectrum Quotient) and visual processing performance (Rey-Osterrieth Complex Figure Test; Block Design task of the Wechsler Adult Intelligence Scale-III) in young adults (mean age=25.0, s.d.=2.1 years) born preterm at very low birth weight (VLBW; <1500 g) (n=101) or at term (n=104). A higher level of ASD-traits was associated with slower global visual processing speed among the preterm VLBW, but not among the term-born group (P<0.04 for interaction). Our findings suggest that the associations between ASD-traits and visual processing may be restricted to individuals born preterm, and related specifically to global, not local visual processing. Our findings point to cumulative social and neurocognitive problems in those born preterm at VLBW.

Atrial natriuretic peptide in plasma, atria, ventricles, and hypothalamus of Long-Evans and vasopressin-deficient Brattleboro rats.

To evaluate the role of vasopressin in the regulation of atrial natriuretic peptide (ANP) secretion, the plasma, atrial, ventricular, and hypothalamic levels of ANP were measured in Long-Evans (LE) and vasopressin-deficient Brattleboro (DI) rats. Total atrial immunoreactive ANP (IR-ANP) as well as right auricular IR-ANP concentration were higher in the DI than in the LE rats, whereas no significant difference was noted in left auricular IR-ANP concentration. In the left ventricle of DI rats, the IR-ANP concentration was 82% greater than that in the LE rats, while no substantial difference was found in the right ventricular IR-ANP concentration between the strains. Normal LE rats had low levels of left ventricular ANP mRNA and barely detectable ANP mRNA in the right ventricle, DI rats showed a 3-fold greater ANP mRNA concentration in the left ventricle than age-matched LE controls, and ANP mRNA levels were also increased in the left auricle of DI rats. The hypothalamic IR-ANP content, but not the concentration, was significantly increased in the DI compared to the LE rats. Despite increased cardiac IR-ANP and ANP mRNA levels, plasma IR-ANP concentrations were similar in the conscious DI rats (97 +/- 9 pg/ml; n = 13) and the LE rats (95 +/- 8 pg/ml; n = 15). Volume expansion (1.1 ml/100 g BW of 0.9% saline, iv) increased right atrial pressure and caused a significant rise in plasma IR-ANP in both strains (P less than 0.01). Elevations of plasma IR-ANP concentrations caused by volume loading were comparable in LE and DI rats in either the absence or presence of exogenous vasopressin (5 ng/kg.min, iv), which, when infused alone, did not significantly influence the plasma IR-ANP concentration. However, the relation between the change in IR-ANP concentration and the change in right atrial pressure shifted to the left, and thus, for a given increase in right atrial pressure, a greater amount of IR-ANP was released in the vasopressin-treated rats than in the control animals. These results demonstrate that although acute volume expansion does not necessarily require endogenous vasopressin for the ANP secretory response, vasopressin increased the ability of volume expansion to induce ANP release, thus modulating the direct mechanical stimulus-induced ANP secretion. The increased left ventricular levels of immunoreactive ANP and augmentation of ANP mRNA levels in Brattleboro rats despite normal left ventricular weight to body weight ratio show that increased ANP gene expression may occur in the ventricles independently of hypertrophy.