Neurodevelopmental outcomes in children with isolated congenital diaphragmatic hernia: A systematic review and meta-analysis

Background: Congenital diaphragmatic hernia (CDH) reportedly has neurologic consequences in childhood however little is known about the impact in isolated CDH. / Aims: Herein we aimed to describe the risk of neurodevelopmental complications in children born with isolated CDH. / Materials & Methods: We systematically reviewed literature for reports on the neurological outcome of infants born with isolated CDH. The primary outcome was neurodevelopmental delay. Secondary outcomes included, motor skills, intelligence, vision, hearing, language and behavior abnormalities. / Results: Thirteen out of 87 (15%) studies reported on isolated CDH, including 2624 out of 24,146 children. Neurodevelopmental delay was investigated in four studies and found to be present in 16% (3‐34%) of children. This was mainly attributed to motor problems in 13% (2‐30%), whereas cognitive dysfunction only in 5% (0‐20%) and hearing in 3% (1‐7%). One study assessed the effect of fetal surgery. When both isolated and non‐isolated children were included, these numbers were higher. / Discussion: This systematic review demonstrates that only a minority of studies focused on isolated CDH, with neurodevelopmental delay present in 16% of children born with CDH. / Conclusion: To accurately counsel patients, more research should focus on isolated CDH cases and examine children that underwent fetal surgery

Sustained versus standard inflations during neonatal resuscitation to prevent mortality and improve respiratory outcomes

Background: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable effective breathing. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs. Objectives: To assess the efficacy of an initial sustained (> 1 second duration) lung inflation versus standard inflations (\ue2\u89\ua4 1 second) in newly born infants receiving resuscitation with intermittent PPV. Search methods: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1), MEDLINE via PubMed (1966 to 17 February 2017), Embase (1980 to 17 February 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 17 February 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials. Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth. Data collection and analysis: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and weighted mean difference (WMD) for continuous data. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Main results: Eight trials enrolling 941 infants met our inclusion criteria. Investigators in seven trials (932 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review - mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40; participants = 479; studies = 5; I2 not applicable) and mortality during hospitalisation (typical RR 1.01, 95% CI 0.67 to 1.51; participants = 932; studies = 7; I2 = 19%); the quality of the evidence was low for death in the delivery room (limitations in study design and imprecision of estimates) and was moderate for death before discharge (limitations in study design of most included trials). Amongst secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; participants = 524; studies = 5; I2 = 95%; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study: When this study was removed from the analysis, the effect was largely reduced (MD -1.71 days, 95% CI -3.04 to -0.39, I2 = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. rate of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.93, 95% CI 0.79 to 1.09; participants = 811; studies = 5; I2 = 0%); need for surfactant administration during hospital admission (typical RR 0.97, 95% CI 0.86 to 1.10; participants = 932; studies = 7; I2 = 0%); rate of chronic lung disease (typical RR 0.95, 95% CI 0.74 to 1.22; participants = 683; studies = 5; I2 = 47%); pneumothorax (typical RR 1.44, 95% CI 0.76 to 2.72; studies = 6, 851 infants; I2 = 26%); or rate of patent ductus arteriosus requiring pharmacological treatment (typical RR 1.08, 95% CI 0.90 to 1.30; studies = 6, 745 infants; I2 = 36%). The quality of evidence for these secondary outcomes was moderate (limitations in study design of most included trials - GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates - GRADE). Authors' conclusions: Sustained inflation was not better than intermittent ventilation for reducing mortality in the delivery room and during hospitalisation. The number of events across trials was limited, so differences cannot be excluded. When considering secondary outcomes, such as need for intubation, need for or duration of respiratory support, or bronchopulmonary dysplasia, we found no evidence of relevant benefit for sustained inflation over intermittent ventilation. The duration of mechanical ventilation was shortened in the SLI group. This result should be interpreted cautiously, as it can be influenced by study characteristics other than the intervention. Future RCTs should aim to enrol infants who are at higher risk of morbidity and mortality, should stratify participants by gestational age, and should provide more detailed monitoring of the procedure, including measurements of lung volume and presence of apnoea before or during the SLI

As it increases the risk of developing cancer in children exposed to CT?

What is the excess risk of cancer after CT scan in children? Recently The Lancet published a study in which a positive association between radiation dose from CT scan and leukemia and brain tumor was found. Data came from this retrospective cohort study in UK of almost 180,000 patients younger than 22 years of age without previous cancer diagnoses who were first examined with CT in some National Health Service (NHS) centres. Follow-up for leukemia began 2 years after the first CT and for brain cancer 5 years after the first CT in order to avoid inclusion of CT scans related to cancer diagnosis. A positive association between radiation dose from CT scans and leukemia and brain cancer was found. Compared with patients who received a dose of less than 5 mGy, leukemia incidence was about three times higher in patients who received a cumulative dose of at least 30 mGy and for brain cancer in patients who received a dose of 50-74 mGy. Since these cancers are relatively rare, the cumulative absolute risks are small. Nevertheless, although clinical benefits should outweigh the small absolute risks, radiation doses from CT scans ought to be kept as low as possible and alternative procedures, which do not involve ionizing radiation, should be taken in consideration if appropriate

Amniotic fluid S100B protein in mid-gestation and intrauterine fetal death.

Fetal death in the mid-trimester of pregnancy is unexplained and no reliable markers are available to identify at-risk women. We aimed to assess use of alpha fetoprotein and S100B concentrations in amniotic fluid as markers. We did a case-control study in 758 healthy women undergoing amniocentesis at mid-gestation, of whom 12 had a spontaneous intrauterine fetal death before 28 weeks, and 746 matched controls. Concentrations were corrected for gestational age by conversion to multiples of median (MoM) of healthy controls of the same gestational age. Concentrations of S100B, but not alpha fetoprotein, were significantly higher (p<0.0001) in women who later had spontaneous fetal death (median 4.431 MoM [95%CI 3.605-6.197]) than in controls (1.000 MoM [1.062-1.121]). Sensitivity, specificity, and positive and negative predictive values of S100B as a diagnostic test were 100%, suggesting that measurement of this protein at amniocentesis could be useful to identify at-risk wome

SPSS Data for: Behavioral testing and litter effects in the rabbit

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Amniotic fluid levels of S100B protein in normal and trisomy-21 foetuses.

BACKGROUND: The human chromosome 21 has been shown to contain the gene for the beta subunit of the S100B protein. The present case-control study was aimed at investigating whether overproduction of S100B protein is detectable in the amniotic fluid of foetuses with trisomy-21. METHODS: Measurements of S100B in amniotic fluid samples from 14 pregnant women with trisomy-21 foetuses were compared with those obtained from 182 physiological pregnancies. S100B was measured in the samples using an immunoluminometric assay (LIA-mat Sangtec 100). RESULTS: Our results showed that S100B protein amniotic fluid levels were significantly higher in trisomy-21 foetuses (0.83+/-0.21 microg/l) than in controls (0.51+/-0.22 microg/l) (p<0.05). CONCLUSION: The present finding supports the notion that the expression of S100B is increased in trisomy-21 foetuses; it also constitutes a prerequisite basis for a possible involvement of the protein in pathogenic processes associated with trisomy-21, and/or for its potential employment as a diagnostic tool