The role of 22q11.2 deletion syndrome in the relationship between congenital heart disease and scoliosis.

BACKGROUND CONTEXT: For over four decades, clinicians and researchers have suggested a relationship between congenital heart disease (CHD) and scoliosis, attributed to either the disease itself or to the long-term effects of cardiac surgery on the immature thoracic cage. However, no study has yet accounted for 22q11.2 deletion syndrome (22q11.2DS), the second most common cause of CHD after Down syndrome. 22q11.2DS has a scoliosis risk of 50%, but within 22q11.2DS a previous report found no significant association between scoliosis and CHD. We, therefore, hypothesized that scoliosis within a CHD cohort would be related to an underlying 22q11.2 deletion. PURPOSE: To determine the prevalence of scoliosis in CHD patients with and without 22q11.2DS. STUDY DESIGN/SETTING: Cross-sectional. PATIENT SAMPLE: A well-characterized existing database of 315 adults with CHD (primarily tetralogy of Fallot), with (n=86) and without (n=229) 22q11.2DS, matched by sex and CHD severity, and excluding other known syndromic diagnoses. We compared the scoliosis prevalence of patients with 22q11.2DS and CHD patients to the prevalence of scoliosis in a cohort of adults with 22q11.2DS without CHD based on medical records. OUTCOME MEASURES: Presence of scoliosis (Cobb angle ≥10°). METHODS: We systematically determined the presence of scoliosis in all included patients using chest radiographs, blind to genetic diagnosis. Besides 22q11.2DS, we analyzed other suspected risk factors for scoliosis using a regression model: thoracotomy before the age of 12 years, severe CHD type and sex. RESULTS: The prevalence of scoliosis in adults with CHD and 22q11.2DS (n=46, 53.5%) was significantly greater than in those without 22q11.2DS (n=18, 7.9%, p<.0001). The presence of a 22q11.2 deletion (odds ratio [OR] 25.4, 95% confidence interval [95% CI] 11.2-57.4, p<.0001), a history of thoracotomy before the age of 12 years (OR 3.5, 95% CI 1.6-8.1, p=.0027) and most complex CHD class (OR 2.3, 95% CI 1.1-4.7, p=.0196), but not sex, were significant independent predictors of scoliosis. In the 22q11.2DS group, a right-sided aortic arch was associated with a left thoracic scoliotic curve (p=.036). CONCLUSIONS: The prevalence of scoliosis in those with CHD but without a 22q11.2 deletion approximates that of the general population. However, in the CHD population with a 22q11.2 deletion, the prevalence of scoliosis approximates that of others with 22q11.2DS. The pediatric surgical approach and severity of CHD were weaker independent contributors as compared to the 22q11.2 deletion. The results support the importance of a genetic diagnosis of 22q11.2DS to the risk of developing scoliosis in individuals with CHD. The 22q11.2 deletion may represent a common etiopathogenetic pathway for both CHD and scoliosis, possibly involving early laterality mechanisms.

The Value of a Checklist for Child Abuse in Out-of-Hours Primary Care: To Screen or Not to Screen.

OBJECTIVES: To assess the diagnostic value of the screening instrument SPUTOVAMO-R2 (checklist, 5 questions) for child abuse at Out-of-hours Primary Care locations (OPC), by comparing the test outcome with information from Child Protection Services (CPS). Secondary, to determine whether reducing the length of the checklist compromises diagnostic value. METHODS: All children (<18 years) attending one of the participating OPCs in the region of Utrecht, the Netherlands, in a year time, were included. The checklist is an obligatory field in the electronic patient file. CPS provided data on all checklist positives and a sample of 5500 checklist negatives (dataset). The checklist outcome was compared with a report to CPS in 10 months follow up after the OPC visit. RESULTS: The checklist was filled in for 50671 children; 108 (0.2%) checklists were positive. Within the dataset, 61 children were reported to CPS, with emotional neglect as the most frequent type of abuse (32.8%). The positive predictive value (PPV) of the checklist for child abuse was 8.3 (95% CI 3.9-15.2). The negative predictive value (NPV) was 99.1 (98.8-99.3), with 52 false negatives. When the length of the checklist was reduced to two questions closely related to the medical process (SPUTOVAMO-R3), the PPV was 9.1 (3.7-17.8) and the NPV 99.1 (98.7-99.3). These two questions are on the injury in relation to the history, and the interaction between child and parents. CONCLUSIONS: The checklist SPUTOVAMO-R2 has a low detection rate of child abuse within the OPC setting, and a high false positive rate. Therefore, we recommend to use the shortened checklist only as a tool to increase the awareness of child abuse and not as a diagnostic instrument.

Placental characteristics in women with polycystic ovary syndrome.

STUDY QUESTION: Are macroscopic and microscopic placental characteristics in a heterogeneous group of women diagnosed with polycystic ovary syndrome (PCOS) different from those of a low-risk general population? SUMMARY ANSWER: Women with PCOS have significantly different microscopic placental characteristics compared with control women, independently from pregnancy complications. WHAT IS KNOWN ALREADY: Non-obese women with PCOS who conceived spontaneously have a significantly reduced placental volume and weight, with more chronic villitis and intervillositis compared with healthy controls. STUDY DESIGN, SIZE, DURATION: A subset of a large prospective cohort study of pregnant women with PCOS was used. Healthy (low-risk) women who delivered at term after an uncomplicated pregnancy were used as the reference population. The placentas of 73 women with PCOS were analysed and compared with 209 placentas of healthy women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Placentas were collected after delivery from women with PCOS who were followed from prior to conception until delivery. The placentas were macroscopically and microscopically analysed and compared with placentas of healthy women with either a spontaneous start of labour who delivered at term or who had an elective Caesarean section. MAIN RESULTS AND THE ROLE OF CHANCE: After adjusting for potential confounders, placentas from women with PCOS showed more chorioamnionitis (P < 0.001), funisitis (P = 0.019), villitis (P = 0.045), thrombosis (P = 0.018), infarction (P = 0.010), villous immaturity (P = 0.009) and nucleated fetal red blood cells (P < 0.001). In a subgroup analysis, among women with and without pregnancy complications within the PCOS group, only the occurrence of thrombosis was increased in pregnancies complicated by pregnancy-induced hypertension or pre-eclampsia (30%, versus 0% in gestational diabetes pregnancies and 13% in uncomplicated pregnancies; P = 0.008). LIMITATIONS, REASONS FOR CAUTION: There might be a small proportion of women with PCOS in the reference group, since this group was not screened for PCOS. As a result, the observed difference may be an underestimation of the true difference. Placentas were stored for up to 72 h at 4°C, this is common practice but some degenerative changes cannot be ruled out absolutely. Also, there is possibility that baseline differences between the groups may in part explain some of the differences in placental pathology. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that, in general, women with PCOS can have placental alterations associated with an increased hypoxic state, which seems not to be caused by the increased incidence of pregnancy complications.

High concentrations of amniotic fluid proinflammatory cytokines in healthy neonates are associated with low risk of respiratory syncytial virus bronchiolitis.

BACKGROUND: The burden of respiratory syncytial virus (RSV) bronchiolitis in individual children and their families, the medical system and society is considerable. Mechanisms underlying RSV bronchiolitis in healthy term infants are largely unknown. Sterile intraamniotic inflammation and chorioamnionitis have been associated with increased lung volume and compliance. OBJECTIVE: The aim of this study was to determine whether high amniotic fluid interleukin-8 (IL-8), and tumor necrosis factor-α protect against RSV bronchiolitis in healthy term infants. METHODS: We conducted a prospective birth cohort study of healthy term newborns, born after uncomplicated pregnancy. Amniotic fluid was collected during labor. In case of medical attention for respiratory symptoms during the first year of life, a nose-throat swab was taken to establish the presence of respiratory viruses by polymerase chain reaction. RESULTS: Physician-attended RSV infection was observed in 27 (9.3%) of 292 children at median age 6 months. Amniotic fluid concentrations of IL-8 were higher in children without physician-attended RSV infection than in children with physician-attended RSV infection (11.1 versus 5.5 ng/mL; P = 0.002). Similarly, in children without physician-attended RSV, the proportion of detectable amniotic fluid tumor necrosis factor-α was higher (159/265 [60%] versus 8/27 [30%]; P = 0.002). Among children with physician-attended RSV infection, amniotic fluid IL-8 was inversely correlated to the number of wheezing days during the first year of life (ρ = -0.38; P = 0.048). CONCLUSIONS: High concentrations of amniotic fluid IL-8 and tumor necrosis factor-α are associated with low risk of RSV bronchiolitis in healthy term infants. We hypothesize that direct exposure of fetal lungs to proinflammatory signals induces local protection against viral infection during infancy.

Bedside prediction rule for infections after pediatric cardiac surgery.

PURPOSE: Infections after pediatric cardiac surgery are a common complication, occurring in up to 30% of cases. The purpose of this study was to develop a bedside prediction rule to estimate the risk of a postoperative infection. METHODS: All consecutive pediatric cardiac surgery procedures between April 2006 and May 2009 were retrospectively analyzed. The primary outcome variable was any postoperative infection, as defined by the Center of Disease Control (2008). All variables known to the clinician at the bedside at 48 h post cardiac surgery were included in the primary analysis, and multivariable logistic regression was used to construct a prediction rule. RESULTS: A total of 412 procedures were included, of which 102 (25%) were followed by an infection. Most infections were surgical site infections (26% of all infections) and bloodstream infections (25%). Three variables proved to be most predictive of an infection: age less than 6 months, postoperative pediatric intensive care unit (PICU) stay longer than 48 h, and open sternum for longer than 48 h. Translation into prediction rule points yielded 1, 4, and 1 point for each variable, respectively. Patients with a score of 0 had 6.6% risk of an infection, whereas those with a maximal score of 6 had a risk of 57%. The area under the receiver operating characteristic curve was 0.78 (95% confidence interval 0.72-0.83). CONCLUSIONS: A simple bedside prediction rule designed for use at 48 h post cardiac surgery can discriminate between children at high and low risk for a subsequent infection.

Pancreatitis, complicated by a pancreatic pseudocyst associated with the use of valproic acid.

A 12-year-old boy developed pancreatitis, complicated by a pancreatic pseudocyst, as an adverse reaction to valproic acid (VPA) treatment for epilepsy. Pancreatitis subsided within three weeks after discontinuation of VPA. The pancreatic pseudocyst was managed without surgery and resolved spontaneously in four weeks. Valproic acid was concluded to be the most probable cause, since no other explanation was found. According to the literature VPA is a rare but known cause of pancreatitis. A computer-assisted literature search revealed seven previously reported cases of VPA-induced pancreatitis complicated by a pancreatic pseudocyst. Six of these patients were under 20 years of age. Four patients were treated conservatively; three needed cystostomy or external drainage. All patients recovered. Patients using VPA, especially children, presenting with acute abdominal pain should be suspected of valproic acid-induced pancreatitis. If VPA induced pancreatitis is complicated by a pseudocyst, conservative treatment should be the first line of treatment.