Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

OBJECTIVE To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. DESIGN Multicentre, randomised, double-blind, placebo-controlled trial. SETTING Twenty-nine centres in Switzerland and Argentina. POPULATION A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis. METHODS Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. MAIN OUTCOME MEASURES Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. RESULTS Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. CONCLUSION There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour.

Benign neonatal sleep myoclonus: a review of the literature

OBJECTIVE: Neurologically normal term infants sometimes present with repetitive, rhythmic myoclonic jerks that occur during sleep. The condition, which is traditionally resolved by 3 months of age with no sequelae, is termed benign neonatal sleep myoclonus. The goal of this review was to synthesize the published literature on benign neonatal sleep myoclonus. METHODS: The US National Library of Medicine database and the Web-based search engine Google, through June 2009, were used as data sources. All articles published after the seminal description in 1982 as full-length articles or letters were collected. Reports that were published in languages other than English, French, German, Italian, Portuguese, or Spanish were not considered. RESULTS: We included 24 reports in which 164 term-born (96%) or near-term-born (4%) infants were described. Neonatal sleep myoclonus occurred in all sleep stages, disappeared after arousal, and was induced by rocking the infant or repetitive sound stimuli. Furthermore, in affected infants, jerks stopped or even worsened by holding the limbs or on medication with antiepileptic drugs. Finally, benign neonatal sleep myoclonus did not resolve by 3 months of age in one-third of the infants. CONCLUSIONS: This review provides new insights into the clinical features and natural course of benign neonatal sleep myoclonus. The most significant limitation of the review comes from the small number of reported cases.

Air pollution during pregnancy and neonatal outcome: a review

There is increasing evidence of the adverse impact of prenatal exposure to air pollution. This is of particular interest, as exposure during pregnancy--a crucial time span of important biological development--may have long-term implications. The aims of this review are to show current epidemiological evidence of known effects of prenatal exposure to air pollution and present possible mechanisms behind this process. Harmful effects of exposure to air pollution during pregnancy have been shown for different birth outcomes: higher infant mortality, lower birth weight, impaired lung development, increased later respiratory morbidity, and early alterations in immune development. Although results on lower birth weight are somewhat controversial, evidence for higher infant mortality is consistent in studies published worldwide. Possible mechanisms include direct toxicity of particles due to particle translocation across tissue barriers or particle penetration across cellular membranes. The induction of specific processes or interaction with immune cells in either the pregnant mother or the fetus may be possible consequences. Indirect effects could be oxidative stress and inflammation with consequent hemodynamic alterations resulting in decreased placental blood flow and reduced transfer of nutrients to the fetus. The early developmental phase of pregnancy is thought to be very important in determining long-term growth and overall health. So-called "tracking" of somatic growth and lung function is believed to have a huge impact on long-term morbidity, especially from a public health perspective. This is particularly important in areas with high levels of outdoor pollution, where it is practically impossible for an individual to avoid exposure. Especially in these areas, good evidence for the association between prenatal exposure to air pollution and infant mortality exists, clearly indicating the need for more stringent measures to reduce exposure to air pollution.

A case report of Clarkson's disease: If you don't know it, you'll miss it

The systemic capillary leak syndrome (SCLS), also known as Clarkson's disease, is a rare disorder characterized by paroxysmal capillary hyperpermeability with a shift of plasma fluid from the intravascular to the interstitial space. A 35-year-old previously healthy woman was admitted with rapidly developing hypovolemic shock syndrome, rhabdomyolysis, and diffuse edema. Laboratory analysis revealed a severe hemoconcentration, renal insufficiency, and paraproteinemia. After exclusion of infection, allergy, burning or drug-induced conditions, the clinical presentation was consistent with the diagnosis of SCLS. Though this is a rare entity, the substantial morbidity and mortality associated with it necessitate the physician's awareness in order to provide timely therapy. This report is meant to enhance awareness of SCLS.

Plasma S-nitrosothiol status in neonatal calves: ontogenetic associations with tissue-specific S-nitrosylation and nitric oxide synthase

Neonatal cattle and in part neonates of other species have manyfold higher plasma concentrations of nitrite plus nitrate than mature cows and subjects of other species, suggesting an enhanced and needed activation of the nitric oxide (NO) axis at birth. While the biological half-life of NO is short (<1 sec), its functionality can be prolonged, and in many regards more discretely modulated, when it reacts with low-molecular-weight and protein-bound thiols to form S-nitrosothiols (RSNO), from which NO subsequently can be rereleased. We used the calf as a model to test the hypothesis that plasma concentrations of RSNO are elevated at birth in mammals, correlate with ascorbate and urate levels, are selectively generated in critical tissue beds, and are generated in a manner temporally coincident with changes in tissue levels of active NO synthases (NOS). Plasma concentrations of RSNO, ascorbate, and urate were highest immediately after birth (Day 0), dropped >50% on Day 1, and gradually decreased over time, reaching a nadir in mature cattle. Albumin and immunoglobulin G were identified as major plasma RSNO. The presence of S-nitrosocysteine (SNC, a validated marker for S-nitrosylated proteins), inducible NOS (iNOS), and activated endothelial NOS (eNOS phosphorylated at Ser1177) in different tissues was analyzed by immunohistochemistry in another group of similar-aged calves. SNC, iNOS, and phosphorylated eNOS were detected in liver and ileum at the earliest timepoint of sampling (4 hrs after birth), increased between 4 and 24 hrs, and then declined to near-nondetectable levels by 2 weeks of life. Our data show that the neonatal period in the bovine species is characterized by highly elevated and coordinated NO-generating and nitrosylation events, with the ontogenetic changes occurring in iNOS and eNOS contents in key tissues as well as RSNO products and associated antioxidant markers.

Pneumococcal meningitis induces apoptosis in recently postmitotic immature neurons in the dentate gyrus of neonatal rats

Bacterial meningitis is associated with high rates of morbidity and mortality, despite advances in antibiotic therapy. Meningitis caused by Streptococcus pneumoniae is associated with a particularly high incidence of neurological sequelae including deficits resulting from damage to the hippocampus. Previous studies have documented that in neonatal rats with experimental pneumococcal meningitis, cells in the subgranular layer of the dentate gyrus undergo apoptosis. The aim of the present study was to define in more detail the nature of the dying cells in the dentate gyrus. Using bromodeoxyuridine labeling at different times before infection combined with immunocytochemistry, we identified the vulnerable cells as those which underwent mitosis 6-10 days before infection. A majority of these cells are of neuronal lineage. Thus, immature neuronal cells several days after the last cell division are preferentially triggered into apoptosis during pneumococcal meningitis. The loss of these cells may contribute to the long-lasting impairment of hippocampal function identified in animal models and in humans after bacterial meningitis.

Minimally invasive strabismus surgery (MISS) for inferior obliquus recession

PURPOSE: To present a novel, minimally invasive strabismus surgery (MISS) technique for inferior obliquus recessions. METHODS: Graded MISS inferior obliquus recessions were performed in 20 eyes of 15 patients by applying two small conjunctival cuts, one at the insertion of inferior obliquus and another where the scleral anchoring of the muscle occurred. RESULTS: The amount of recession was 12.2 +/- 2.3 mm (range 6 to 14 mm). The vertical deviation, which was measured in 25 degrees of adduction, decreased from preoperatively 12.8 degrees +/- 5.6 degrees to 2.7 degrees +/- 2.2 degrees (p < 0.0001) at 6 months. LogMAR visual acuity was preoperatively -0.10 +/- 0.17 and at 6 months -0.14 +/- 0.22 (p > 0.1). In one eye (2.5%) the two cuts had to be joined because of excessive bleeding. Binocular vision improved in eight patients, remained unchanged in six patients, and decreased from 30 to 60 arcsec in one patient (p > 0.1). Conjunctival and lid swelling were hardly visible on the first postoperative day in primary gaze position in 10/20 (50%) of eyes. Five of the eyes (25%) had mild and five (25%) moderate visibility of surgery. One patient out of 15 (7%) needed repeat surgery because of insufficient reduction of the sursoadduction within the first 6 months. The dose-effect relationship 6 months postoperatively for an accommodative near target at 25 degrees adduction was 0.83 degrees +/- 0.43 degrees per mm of recession. CONCLUSIONS: This study demonstrates that small-incision, minimal dissection inferior obliquus graded recessions are feasible and effective to improve ocular alignment in patients with strabismus sursoadductorius.

Group B Streptococcus colonization in pregnancy: prevalence and prevention strategies of neonatal sepsis

Early onset neonatal sepsis due to Group B streptococci (GBS) is responsible for severe morbidity and mortality of newborns. While different preventive strategies to identify women at risk are being recommended, the optimal strategy depends on the incidence of GBS-sepsis and on the prevalence of anogenital GBS colonization. We therefore aimed to assess the Group B streptococci prevalence and its consequences on different prevention strategies. We analyzed 1316 pregnant women between March 2005 and September 2006 at our institution. The prevalence of GBS colonization was determined by selective cultures of anogenital smears. The presence of risk factors was analyzed. In addition, the direct costs of screening and intrapartum antibiotic prophylaxis were estimated for different preventive strategies. The prevalence of GBS colonization was 21%. Any maternal intrapartum risk factor was present in 37%. The direct costs of different prevention strategies have been estimated as follows: risk-based: 18,500 CHF/1000 live births, screening-based: 50,110 CHF/1000 live births, combined screening- and risk-based: 43,495/1000 live births. Strategies to prevent GBS-sepsis in newborn are necessary. With our colonization prevalence of 21%, and the intrapartum risk profile of women, the screening-based approach seems to be superior as compared to a risk-based approach.

The Swiss Neonatal Quality Cycle, a monitor for clinical performance and tool for quality improvement

BACKGROUND We describe the setup of a neonatal quality improvement tool and list which peer-reviewed requirements it fulfils and which it does not. We report on the so-far observed effects, how the units can identify quality improvement potential, and how they can measure the effect of changes made to improve quality. METHODS Application of a prospective longitudinal national cohort data collection that uses algorithms to ensure high data quality (i.e. checks for completeness, plausibility and reliability), and to perform data imaging (Plsek's p-charts and standardized mortality or morbidity ratio SMR charts). The collected data allows monitoring a study collective of very low birth-weight infants born from 2009 to 2011 by applying a quality cycle following the steps 'guideline - perform - falsify - reform'. RESULTS 2025 VLBW live-births from 2009 to 2011 representing 96.1% of all VLBW live-births in Switzerland display a similar mortality rate but better morbidity rates when compared to other networks. Data quality in general is high but subject to improvement in some units. Seven measurements display quality improvement potential in individual units. The methods used fulfil several international recommendations. CONCLUSIONS The Quality Cycle of the Swiss Neonatal Network is a helpful instrument to monitor and gradually help improve the quality of care in a region with high quality standards and low statistical discrimination capacity.

Can infant lung function predict respiratory morbidity during the first year of life in preterm infants?

Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms.The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data.In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child.Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm.

Microglial Cells Prevent Hemorrhage in Neonatal Focal Arterial Stroke

Perinatal stroke leads to significant morbidity and long-term neurological and cognitive deficits. The pathophysiological mechanisms of brain damage depend on brain maturation at the time of stroke. To understand whether microglial cells limit injury after neonatal stroke by preserving neurovascular integrity, we subjected postnatal day 7 (P7) rats depleted of microglial cells, rats with inhibited microglial TGFbr2/ALK5 signaling, and corresponding controls, to transient middle cerebral artery occlusion (tMCAO). Microglial depletion by intracerebral injection of liposome-encapsulated clodronate at P5 significantly reduced vessel coverage and triggered hemorrhages in injured regions 24 h after tMCAO. Lack of microglia did not alter expression or intracellular redistribution of several tight junction proteins, did not affect degradation of collagen IV induced by the tMCAO, but altered cell types producing TGFβ1 and the phosphorylation and intracellular distribution of SMAD2/3. Selective inhibition of TGFbr2/ALK5 signaling in microglia via intracerebral liposome-encapsulated SB-431542 delivery triggered hemorrhages after tMCAO, demonstrating that TGFβ1/TGFbr2/ALK5 signaling in microglia protects from hemorrhages. Consistent with observations in neonatal rats, depletion of microglia before tMCAO in P9 Cx3cr1(GFP/+)/Ccr2(RFP/+) mice exacerbated injury and induced hemorrhages at 24 h. The effects were independent of infiltration of Ccr2(RFP/+) monocytes into injured regions. Cumulatively, in two species, we show that microglial cells protect neonatal brain from hemorrhage after acute ischemic stroke. SIGNIFICANCE STATEMENT The pathophysiological mechanisms of brain damage depend on brain maturation at the time of stroke. We assessed whether microglial cells preserve neurovascular integrity after neonatal stroke. In neonatal rats, microglial depletion or pharmacological inhibition of TGFbr2/ALK5 signaling in microglia triggered hemorrhages in injured regions. The effect was not associated with additional changes in expression or intracellular redistribution of several tight junction proteins or collagen IV degradation induced by stroke. Consistent with observations in neonatal rats, microglial depletion in neonatal mice exacerbated stroke injury and induced hemorrhages. The effects were independent of infiltration of monocytes into injured regions. Thus, microglia protect neonatal brain from ischemia-induced hemorrhages, and this effect is consistent across two species.