Client-rated facilitators and barriers to long-term youth anxiety disorder recovery.

OBJECTIVE: This study examined client ratings of 26 facilitators and barriers to anxiety improvement approximately 6 years after randomization to treatment for anxiety. METHOD: 319 youth (average 17.12 years old; 82.1% Caucasian; 58.6% female) participated in the longitudinal follow-up study to child and adolescent anxiety multimodal study (CAMS), a randomized controlled trial of medication, cognitive-behavioral therapy (CBT), combination, and placebo. RESULTS: Correcting for multiple comparisons, CBT components (i.e., problem solving, changing unhelpful thoughts, relaxation skills) were rated significantly more helpful among youth without, versus with, an anxiety disorder at follow-up. Barriers that differentiated youth with and without an anxiety disorder included being bullied and difficulty applying therapy content to new situations. Comparisons between youth with different anxiety disorder trajectories (e.g., stable remission, relapsed, or chronically ill) also revealed several differences. CONCLUSION: Findings suggest that client-rated facilitators and barriers covary with anxiety disorder recovery and may serve as useful tools when evaluating long-term treatment efficacy.

Common Elements of Childhood Universal Mental Health Programming.

Despite the availability of multiple mental health prevention and promotion programs for children, challenges related to their dissemination limit their reach and impact. This review identifies the most common practice elements of effective childhood universal mental health programming for children ages 3-11, based on a structured interpretation and coding of program manuals and descriptions in peer-reviewed articles. Across a range of program goals and targeted outcomes, psychoeducation and problem solving emerged as the most common practice elements, followed by social skills training, insight building, and communication skills. These skills were largely taught via role-plays and modeling. Synthesizing what we know from the universal mental health programming literature has potential to facilitate dissemination of information to inform the development, adaptation or adoption of programs for children.

Does Poverty Moderate Psychosocial Treatment Efficacy for ADHD? A Systematic Review.

Objective: To determine the extent to which children in poverty show differential benefit versus non-impoverished peers when undergoing behavioral treatment for ADHD. Method: Multiple readers conducted a systematic review using four research databases, one national treatment database, and multiple recent reviews and meta-analyses to identify appropriate studies. Results: Of 1192 initial search results, only five studies met inclusion criteria and were fully abstracted. Conclusion: Results suggest mixed evidence that low-income children may benefit less, compared with peers from higher income families, from psychosocial treatment for ADHD. Findings point to the need for more consistent, more precise, and higher quality reporting of income information.

RNAi modulation of placental sFLT1 for the treatment of preeclampsia.

Preeclampsia is a placentally induced hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality to mothers and fetuses. Clinical manifestations of preterm preeclampsia result from excess circulating soluble vascular endothelial growth factor receptor FLT1 (sFLT1 or sVEGFR1) of placental origin. Here we identify short interfering RNAs (siRNAs) that selectively silence the three sFLT1 mRNA isoforms primarily responsible for placental overexpression of sFLT1 without reducing levels of full-length FLT1 mRNA. Full chemical stabilization in the context of hydrophobic modifications enabled productive siRNA accumulation in the placenta (up to 7% of injected dose) and reduced circulating sFLT1 in pregnant mice (up to 50%). In a baboon preeclampsia model, a single dose of siRNAs suppressed sFLT1 overexpression and clinical signs of preeclampsia. Our results demonstrate RNAi-based extrahepatic modulation of gene expression with nonformulated siRNAs in nonhuman primates and establish a path toward a new treatment paradigm for patients with preterm preeclampsia.

Population attributable fractions of perinatal outcomes for nulliparous women associated with overweight and obesity, 1990-2014.

OBJECTIVE: To examine the prevalence across 25 years of overweight and obesity among nulliparous Australian women during early pregnancy; to estimate the proportions of adverse perinatal outcomes attributable to overweight and obesity in this population. DESIGN: Cohort study; retrospective analysis of electronic maternity data. Setting, participants: 42 582 nulliparous women with singleton pregnancies giving birth at the Royal Prince Alfred Hospital, an urban teaching hospital in Sydney, January 1990 - December 2014. MAIN OUTCOME MEASURES: Maternal body mass index (BMI), socio-demographic characteristics, and selected maternal, birth and neonatal outcomes; the proportion of adverse perinatal outcomes that could be averted by reducing the prevalence of overweight and obesity in women prior to first pregnancies (population attributable fraction, PAF). RESULTS: The prevalence of overweight among nulliparous pregnant women increased from 12.7% (1990-1994) to 16.4% (2010-2014); the prevalence of obesity rose from 4.8% to 7.3% in the same period, while the proportion with normal range BMIs fell from 73.5% to 68.2%. The PAFs for key adverse maternal and neonatal outcomes increased across the study period; during 2010-2014, 23.8% of pre-eclampsia, 23.4% of fetal macrosomia, and 17.0% of gestational diabetes were attributable to overweight and obesity. Were overweight and obese women to have moved down one BMI category during 2010-2014, 19% of pre-eclampsia, 15.9% of macrosomia, 14.2% of gestational diabetes, 8.5% of caesarean deliveries, 7.1% of low for gestational age birthweight, 6.8% of post partum haemorrhage, 6.5% of admissions to special care nursery, 5.8% of prematurity, and 3.8% of fetal abnormality could have been averted. CONCLUSIONS: Over the past 25 years, the proportions of adverse perinatal outcomes attributable to overweight and obesity have risen with the increasing prevalence of maternal overweight and obesity. A substantial proportion of these outcomes might be averted with obesity prevention strategies that reduce pre-pregnancy maternal weight.

All Hypertensive Disorders of Pregnancy Increase the Risk of Future Cardiovascular Disease.

Hypertensive disorders of pregnancy are associated with vascular dysfunction in the pregnancy and an increased risk of long-term cardiovascular disease (CVD) in the mother. What remains to be understood is whether the length, severity of the disease, the treatment of hypertension in pregnancy, or the subtype of hypertensive disorders of pregnancy are significant predictors of future CVD. We undertook a retrospective cohort study to review all women who gave birth at a tertiary hospital in Sydney between the years 1980 and 1989 (n=31 656). A cohort of women was further defined by having hypertension during the antenatal, intrapartum, or postnatal periods (n=4387). Randomly selected records of women (n=1158) with a hypertensive disorder of pregnancy were individually reviewed to collect data on their pregnancy and pregnancy outcomes. The entire cohort then underwent linkage analysis to future CVDs. Women who presented with gestational hypertension were at greater risk of future hypertension and ischemic heart disease compared with the women who were diagnosed with preeclampsia. There was no significant difference between the women who were treated with antihypertensive medication and the women who did not receive antihypertensive medication or the duration of hypertensive disorders of pregnancy and future admission for CVD, although severity of hypertension tracked with increased risk of future hypertension in all groups. This study demonstrated that all women who present with any of the subtypes of hypertensive disorders in pregnancy are at significant risk of future CVD compared with women who remain normotensive during their pregnancy.

Benchmarking the Hypertensive Disorders of Pregnancy.

INTRODUCTION: The Hypertensive Disorders of Pregnancy (HDP) affect 7-10% of pregnancies worldwide and are one of the leading causes of mortality and morbidity in the perinatal period. An accurate assessment of mortality and morbidity is essential to provide effective care and treatment and benchmarking of these issues is required to enhance outcomes and define standards. AIM: To benchmark outcomes for women and babies following a diagnosis of hypertension between obstetric units in similar settings. METHODS: Utilising a set of pre-defined clinical indicators, Individual Patient Data analysis techniques applied to the medical records of all women diagnosed with a HDP over a 12month period at six obstetric units within Australia and Canada. Statistical analysis included contingency table sand means testing oas appropriate utilising IBM SPSS V.18. RESULTS: Overall HDP rate of 7.6% of all deliveries, with a 3.0% preeclampsia rate. Outcomes differed significantly between units and did not cluster within any individual unit.

Placental Growth Factor Reduces Blood Pressure in a Uteroplacental Ischemia Model of Preeclampsia in Nonhuman Primates.

An imbalance in the angiogenesis axis during pregnancy manifests as clinical preeclampsia because of endothelial dysfunction. Circulating soluble fms-like tyrosine kinase 1 (sFLT-1) increases and placental growth factor (PlGF) reduces before and during disease. We investigated the clinical and biochemical effects of replenishing the reduced circulating PlGF with recombinant human PlGF (rhPlGF) and thus restoring the angiogenic balance. Hypertensive proteinuria was induced in a nonhuman primate (Papio hamadryas) by uterine artery ligation at 136 days gestation (of a 182-day pregnancy). Two weeks after uteroplacental ischemia, rhPlGF (rhPlGF, n=3) or normal saline (control, n=4) was administered by subcutaneous injection (100 µg/kg per day) for 5 days. Blood pressure was monitored by intra-arterial radiotelemetry and sFLT-1 and PlGF by ELISA. Uteroplacental ischemia resulted in experimental preeclampsia evidenced by increased blood pressure, proteinuria, and endotheliosis on renal biopsy and elevated sFLT-1. PlGF significantly reduced after uteroplacental ischemia. rhPlGF reduced systolic blood pressure in the treated group (-5.2±0.8 mm Hg; from 132.6±6.6 mm Hg to 124.1±7.6 mm Hg) compared with an increase in systolic blood pressure in controls (6.5±3 mm Hg; from 131.3±1.5 mm Hg to 138.6±1.5 mm Hg). Proteinuria reduced in the treated group (-72.7±55.7 mg/mmol) but increased in the control group. Circulating levels of total sFLT-1 were not affected by the administration of PlGF; however, a reduction in placental sFLT-1 mRNA expression was demonstrated. There was no significant difference between the weights or lengths of the neonates in the rhPlGF or control group; however, this study was not designed to assess fetal safety or outcomes. Increasing circulating PlGF by the administration of rhPlGF improves clinical parameters in a primate animal model of experimental preeclampsia.

Hypertension in pregnancy and long-term cardiovascular mortality: a retrospective cohort study.

BACKGROUND: There is growing evidence that hypertensive disorders of pregnancy are associated with increased long-term cardiovascular mortality in the mother. Hypertension in pregnancy, until recently, however, has been ignored largely as a risk factor for future cardiovascular disease and mortality because the link between the 2 is not fully understood. OBJECTIVE: To determine the association between women with hypertension in pregnancy and long-term cardiovascular disease mortality. STUDY DESIGN: All women who delivered at a metropolitan hospital between the periods of January 1, 1980, and December 31, 1989, were identified by use of the International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification. RESULTS: The total number of deliveries in the given time period was 31,656, with 4387 (14%) of the women identified as having had hypertension in their pregnancy. Using information from the New South Wales Births, Deaths and Marriages Registry and the Australian Bureau of Statistics Death Registry, we identified a total of 651 deaths from this cohort (n = 31,656). There were 521 deaths among the women who remained normotensive in their pregnancy and 129 deaths for women who had hypertension during their pregnancy. Overall, the women with hypertensive disorders of pregnancy were at greater risk of death than the women who remained normotensive in their pregnancy (odds ratio 1.56; 95% confidence interval 1.28-1.89; P < .001). CONCLUSION: Women with a history of hypertension in their pregnancy are at an increased risk of future cardiovascular mortality, and this work identifies a group of women who may benefit from early screening and intervention strategies to help decrease their risk of future cardiovascular disease.

Treatment of Primary Fetal Hydrothorax with OK-432 (Picibanil): Outcome in 14 Fetuses and a Review of the Literature.

BACKGROUND: Primary fetal hydrothorax (PFHT) is an uncommon condition with an estimated prevalence of 1 in 10,000/15,000 pregnancies. Therapeutic interventions include thoracocentesis, thoraco-amniotic shunting (TAS), and pleurodesis using OK-432. METHODS: A review of the literature was performed to identify all cases of PFHT treated with TAS and OK-432. All cases of PFHT referred to the Fetal Maternal Unit at Royal Prince Alfred Hospital between 2002 and 2012 were retrospectively reviewed. In the cohort of fetuses treated with OK-432, the main perinatal outcomes evaluated were termination of pregnancy, live birth, neonatal death, and fetal death in utero. Secondary outcomes included gestational age (GA) at diagnosis, GA at treatment, GA at resolution, birth weight, and GA at birth. The development of the children was screened using the Ages and Stages Questionnaires, Version 3 (ASQ-3, 2009). RESULTS: Primary hydrothorax was diagnosed in 31 fetuses, of which 14 had treatment with OK-432. One pregnancy terminated after treatment with OK-432. Survival was 85% (11/13): 100% in fetuses treated with OK-432 without hydrops, and 78% in those treated with hydrops. This compares well to the cases of TAS in the literature with an average survival of 63%: 85% in fetuses without hydrops and 55% with hydrops. The mean GA at birth was 36(+4) weeks and mean birth weight 3,007 g. Eight of the 9 children screened with ASQ-3 scored well within the normal range. CONCLUSION: OK-432 appears to be a valid treatment option in fetuses with PFHT, particularly in those diagnosed at early GAs.

Common elements of adolescent prevention programs: minimizing burden while maximizing reach.

A growing number of evidence-based youth prevention programs are available, but challenges related to dissemination and implementation limit their reach and impact. The current review identifies common elements across evidence-based prevention programs focused on the promotion of health-related outcomes in adolescents. We reviewed and coded descriptions of the programs for common practice and instructional elements. Problem-solving emerged as the most common practice element, followed by communication skills, and insight building. Psychoeducation, modeling, and role play emerged as the most common instructional elements. In light of significant comorbidity in poor outcomes for youth, and corresponding overlap in their underlying skills deficits, we propose that synthesizing the prevention literature using a common elements approach has the potential to yield novel information and inform prevention programming to minimize burden and maximize reach and impact for youth.

Ultrasound assessment of cervical length at 18-21 weeks' gestation in an Australian obstetric population: comparison of transabdominal and transvaginal approaches.

BACKGROUND: Using a fixed cut-off of ≤25 mm, ultrasound assessment of cervical length during the 18-23 week anomaly scan has been shown to identify approximately 50% of pregnancies that would deliver prior to 34 weeks. AIM: To determine whether a policy of reverting to transvaginal cervical assessment only if the cervix appears short (≤25 mm) on transabdominal assessment affects the efficiency of screening. METHODS: Women with a singleton pregnancy that presented for a routine anomaly scan had their cervical length assessed transabdominally, initially with the maternal bladder full (TABF) and then empty (TABE). Cervical length was then assessed transvaginally (TV). RESULTS: One hundred and ninety-eight women agreed to participate in the study. Identification of the internal and external cervical os was possible during TABF, TABE and TV sonography in 97.0, 82.8 and 100%, respectively. Compared with TV sonography, TABF overestimates cervical length (6.1 mm difference in median values; P < 0.01). There was no significant difference between TV and TABE. However, TABE assessment was not possible in one in six women. If TABF sonography was to be used as a screening tool and using ≤25 mm as the critical cut-off, the sensitivity and specificity was 15.4 and 93.2%, respectively. CONCLUSION: This study has shown that assessment of cervical length using a TA approach is only routinely possible when the bladder is full. However, measurements are significantly overestimated. Therefore, we feel that TV assessment of cervical length is the preferred method of reliable cervical assessment. As such, all women should be offered a TV assessment of cervical length at the time of the fetal anomaly ultrasound as a screening test for preterm birth.

Maternal outcome after conservative management of placenta percreta at caesarean section: a report of three cases and a review of the literature.

Retaining the placenta in situ at caesarean section for placenta percreta and awaiting placental reabsorption is widely practiced; however, there is limited evidence on the efficacy and complications of this strategy. We present three cases of placenta percreta managed conservatively and note that all three women experienced significant complications. A review of the literature showed that despite initial conservative management, 40% of women subsequently require emergency hysterectomy and 42% will experience major morbidity.

Changes in retinal microvascular caliber precede the clinical onset of preeclampsia.

Preeclampsia is a leading cause of maternal morbidity and mortality. The degree of maternal cardiovascular dysfunction that precedes the onset of preeclampsia is largely unknown. This prospective cohort study aimed to characterize differences in vivo in retinal microvascular caliber and blood pressure throughout pregnancy in relation to preeclampsia development. Women were recruited from Royal Prince Alfred Hospital, Sydney, Australia, of which 92 women were included in the study. Retinal images and blood pressures were collected at 13, 19, 29, and 38 weeks of gestation. Retinal vessels were analyzed as the central retinal arteriolar equivalent corrected for mean arterial blood pressure and the central retinal venular equivalent corrected for mean arterial blood pressure, using generalized linear models adjusted for age and body mass index. The preeclampsia group were significantly older (P=0.002) and had a significantly higher mean body mass index (P=0.005). The central retinal arteriolar equivalent corrected for mean arterial blood pressure was significantly reduced at 13 (P=0.03), 19 (P=0.007), and 38 (P=0.03) weeks of gestation in the preeclampsia group. The central retinal venular equivalent corrected for mean arterial blood pressure was also significantly lower at 13 (P=0.04) and 19 (P=0.001) weeks of gestation in the women who progressed to preeclampsia. This study directly documents increased peripheral resistance in vivo, observed as the combination of constricted retinal arterioles or venules and elevated blood pressure, in women who later developed preeclampsia. This difference preceded the clinical signs of preeclampsia.

Temporal changes in retinal microvascular caliber and blood pressure during pregnancy.

The microvasculature plays an important role in regulating cardiovascular changes in pregnancy, but changes in microvasculature have been difficult to document in vivo. This study objectively quantifies changes in the maternal retinal arteriolar and venular caliber over the course of healthy pregnancy. Healthy pregnant women (n=53) were recruited from Royal Prince Alfred Hospital, Sydney, Australia. Retinal images and mean arterial blood pressures (MAP) were collected at 13, 19, 29, and 38 weeks of gestation and at 6-month postpartum. Retinal vessels were analyzed and summarized as the central retinal arteriolar equivalent and central retinal venular equivalent. Central retinal arteriolar equivalent and central retinal venular equivalent were corrected for MAP. Paired t tests were performed comparing consecutive time points, with a significance level of P<0.01. There was a decrease in MAP between 13- and 19-week gestation (P=0.001) followed by a return to baseline from 19 weeks to delivery. This was correlated by an increase in vessel caliber between 13- and 19-week gestation (central retinal arteriolar equivalent: P<0.001, central retinal venular equivalent: P=0.007) and a return to baseline from 19 weeks to delivery. There were no differences in the central retinal arteriolar equivalent or central retinal venular equivalent (both uncorrected and corrected for MAP) between nulliparous and parous women. The pattern of dilatation and constriction in the microvasculature mirrored the changes in MAP throughout pregnancy, reflecting changes in peripheral resistance. This study provides insights into physiological changes in the microvasculature throughout a healthy pregnancy. These results can be used as a baseline with which to compare the changes observed in pathological conditions of pregnancy.

Urinary placental growth factor differentiates the hypertensive disorders of pregnancy.

AIMS: To evaluate the discriminating capacity of urinary placental growth factor (uPlGF) for different hypertensive diseases of pregnancy during the third trimester. METHODS: A prospective descriptive case-control study conducted in an urban tertiary referral hospital and district general hospital, Sydney South West Area Health Service, Australia. Inpatients and outpatients with and without hypertension in the third trimester were recruited. Eligible patients provided a urine sample for protein, creatinine and a uPlGF level by ELISA. Patients were categorised into clinical hypertensive groups based on the diagnostic criteria of SOMANZ. RESULTS: Eighty-eight women were evaluated; 41 had hypertension (15 pre-eclampsia; 13 gestational hypertension; eight chronic hypertension; five pre-eclampsia superimposed on chronic hypertension) and 47 women without hypertension as the control group. There was a significant difference in uPlGF levels between the pre-eclamptic group (median 2.56 IQR 1.12-4.51) and the normotensive controls (median 13.18 IQR 5.95-31.39) (P < 0.0001); the gestational hypertensive group (median 3.74 IQR 2.49-4.91) and the normotensive group (median 13.18 IQR 5.95-31.39) (P=0.002) and for a subgroup comparison of placental-mediated hypertension (median 2.75 IQR 1.38-4.82) versus non-placental-mediated hypertensives (median 6.96 IQR 3.87-12.54) (P=0.007). CONCLUSIONS: Urinary placental growth factor is a simple non-invasive test, which is discriminatory for pre-eclampsia in the third trimester of pregnancy. Results from this study indicate that it may be discriminatory for hypertension related to placental dysfunction (pre-eclampsia and gestational hypertension) when compared with hypertension unrelated to placental function. Further work is required to assess the ability to detect hypertensive diseases before they are clinically apparent.

Normal ranges for fetal nasal bone length determined by ultrasound at 18-20 weeks of gestation in a multiethnic Australian population.

OBJECTIVE: Absence or hypoplasia of the nasal bone is commonly reported in Down syndrome fetuses. We define normal ranges and the 2.5th centile for fetal nasal bone length (NBL) in a multiethnic Australian population at 18-20 weeks of gestation. METHODS: A prospective cohort study of women attending for a routine anomaly scan. Ethnicity of the patient and their partner was recorded, and the nasal bone was measured three times. Two methods of nasal bone assessment were used to define normal ranges: a single (first) measurement and the mean value of three measurements. Mixed-effects regression models were employed to account for interoperator differences treating sonographers as random effects. Nonparametric methods were used to define the 2.5th centile for gestational age. RESULTS: A total of 1199 women were included with a mean gestational age 19.1 (SD 0.4; range 18-20) weeks. There is significant linear relationship between NBL and gestational age (P<0.001). The mean of three nasal bone measurements had a smaller standard deviation than single nasal bone measurements. Nonparametric assessment was used to define the 2.5th centile, which is 4.4 mm at 18 weeks and 5.0 mm at 20 weeks of gestation. CONCLUSIONS: This study provides a reference range for fetal NBL at 18-20 weeks of gestation in an unselected multiethnic Australian population. Whilst NBL increases linearly from 18 to 20 weeks, the data are not normally distributed and nonparametric techniques are required to define the 2.5th centile. The mixed-effects model also accounts for variation in sonographer measurements.

Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas).

Preeclampsia is a common disease of pregnancy characterised by maternal hypertension and proteinuria. Abnormal placentation in early pregnancy and abnormal cytokine and anti-angiogenic factor expression are thought to contribute to the clinical syndrome of endothelial dysfunction evident in the second half of gestation. The mechanisms underlying both the placental pathology and its translation to the maternal clinical syndrome are not fully understood. A model of preeclampsia manifest by clinically evident endothelial dysfunction (increased blood pressure and proteinuria) was induced by administration of low-dose TNF-α for 2weeks at mid-gestation in pregnant baboons (Papio hamadryas). Blood pressure was monitored continuously and remotely by intra-arterial radiotelemetry. Following TNF-α infusion, there was an increase in systolic and diastolic blood pressure and development of proteinuria in pregnant treated animals, but not in pregnant saline controls nor in non-pregnant TNF-α treated animals. The treated pregnant animals also developed elevated plasma soluble FMS-like tyrosine kinase-1 (sFLT-1) and increased placental mRNA expression of sFLT-1 and soluble endoglin (sEng). These results clearly demonstrate that the cytokine TNF-α can induce the clinical and biochemical features of human preeclampsia. The results identify a link between cytokines, placental dysfunction and endothelial dysfunction resulting in a loss of maternal blood pressure control.