Lipid droplets in human milk have a mode diameter of ∼4 μm and are surrounded by a native phospholipid-rich membrane. Current infant milk formulas (IMFs) contain small lipid droplets (mode diameter ...∼0.5 μm) primarily coated by proteins. A concept IMF was developed mimicking more closely the structure and composition of human milk lipid droplets.
This randomized, controlled, double-blind equivalence trial evaluates the safety and tolerance of a concept IMF with large, milk phospholipid–coated lipid droplets (mode diameter 3–5 μm) containing vegetable and dairy lipids in healthy, term infants.
Fully formula-fed infants were enrolled up to 35 d of age and randomly assigned to 1 of 2 formulas until 17 wk of age: 1) Control IMF with small lipid droplets containing vegetable oils (n = 108); or 2) Concept IMF with large, milk phospholipid–coated lipid droplets comprised of 48% dairy lipids (n = 115). A group of 88 breastfed infants served as reference. Primary outcome was daily weight gain during intervention. Additionally, number and type of adverse events, growth, and tolerance parameters were monitored.
Equivalence of daily weight gain was demonstrated (Concept compared with Control IMF: −1.37 g/d; 90% CI: −2.71, −0.02; equivalence margin ± 3 g/d). No relevant group differences were observed in growth, tolerance and number, severity, or relatedness of adverse events. We did observe a higher prevalence of watery stools in the Concept than in the Control IMF group between 5 and 12 wk of age (P < 0.001), closer to the stool characteristics observed in the breastfed group.
An infant formula with large, milk phospholipid–coated lipid droplets containing dairy lipids is safe, well tolerated, and supports an adequate growth in healthy infants. This trial was registered in the Dutch Trial Register (www.trialregister.nl) as NTR3683.
Abstract
Background
Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics ...may be harmful.
Methods
We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis).
Results
We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis.
Conclusions
Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.
Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is ...no consensus on a treatment threshold that is safe but also avoids overtreatment.
In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg per deciliter 2.0 mmol per liter) would be noninferior to a traditional threshold (treatment at a glucose concentration of <47 mg per deciliter 2.6 mmol per liter) with respect to psychomotor development at 18 months, assessed with the Bayley Scales of Infant and Toddler Development, third edition, Dutch version (Bayley-III-NL; scores range from 50 to 150 mean {±SD}, 100±15), with higher scores indicating more advanced development and 7.5 points (one half the SD) representing a clinically important difference). The lower threshold would be considered noninferior if scores were less than 7.5 points lower than scores in the traditional-threshold group.
Bayley-III-NL scores were assessed in 287 of the 348 children (82.5%) in the lower-threshold group and in 295 of the 341 children (86.5%) in the traditional-threshold group. Cognitive and motor outcome scores were similar in the two groups (mean scores ±SE, 102.9±0.7 cognitive and 104.6±0.7 motor in the lower-threshold group and 102.2±0.7 cognitive and 104.9±0.7 motor in the traditional-threshold group). The prespecified inferiority limit was not crossed. The mean glucose concentration was 57±0.4 mg per deciliter (3.2±0.02 mmol per liter) in the lower-threshold group and 61±0.5 mg per deciliter (3.4±0.03 mmol per liter) in the traditional-threshold group. Fewer and less severe hypoglycemic episodes occurred in the traditional-threshold group, but that group had more invasive diagnostic and treatment interventions. Serious adverse events in the lower-threshold group included convulsions (during normoglycemia) in one newborn and one death.
In otherwise healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold (36 mg per deciliter) was noninferior to a traditional threshold (47 mg per deciliter) with regard to psychomotor development at 18 months. (Funded by the Netherlands Organization for Health Research and Development; HypoEXIT Current Controlled Trials number, ISRCTN79705768.).
ECMO in neonates: Neuroimaging findings and outcome van Heijst, Arno F.J., MD, PhD; de Mol, Amerik C., MD, PhD; IJsselstijn, Hanneke, MD, PhD
Seminars in perinatology,
03/2014, Letnik:
38, Številka:
2
Journal Article
Recenzirano
Abstract Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for newborns with severe but reversible respiratory failure. Although ECMO has significantly improved survival, it is ...associated with substantial complications, of which intracranial injuries are the most important. These injuries consist of hemorrhagic and non-hemorrhagic, ischemic lesions. Different from the classical presentation of hemorrhages in preterm infants, hemorrhages in ECMO-treated newborns are mainly parenchymal and with a high percentage in the posterior fossa area. There are conflicting data on the predominant occurrence of cerebral lesions in the right hemisphere. The existence of intracerebral injuries and the classification of its severity are the major predictors of neurodevelopmental outcome. This section will discuss the known data on intracranial injury in the ECMO population and the effect of ECMO on the brain.
Current strategies for risk stratification and prediction of neonatal early-onset sepsis (EOS) are inefficient and lack diagnostic performance. The aim of this study was to use machine learning to ...analyze the diagnostic accuracy of risk factors (RFs), clinical signs and biomarkers and to develop a prediction model for culture-proven EOS. We hypothesized that the contribution to diagnostic accuracy of biomarkers is higher than of RFs or clinical signs.
Secondary analysis of the prospective international multicenter NeoPInS study. Neonates born after completed 34 weeks of gestation with antibiotic therapy due to suspected EOS within the first 72 hours of life participated. Primary outcome was defined as predictive performance for culture-proven EOS with variables known at the start of antibiotic therapy. Machine learning was used in form of a random forest classifier.
One thousand six hundred eighty-five neonates treated for suspected infection were analyzed. Biomarkers were superior to clinical signs and RFs for prediction of culture-proven EOS. C-reactive protein and white blood cells were most important for the prediction of the culture result. Our full model achieved an area-under-the-receiver-operating-characteristic-curve of 83.41% (±8.8%) and an area-under-the-precision-recall-curve of 28.42% (±11.5%). The predictive performance of the model with RFs alone was comparable with random.
Biomarkers have to be considered in algorithms for the management of neonates suspected of EOS. A 2-step approach with a screening tool for all neonates in combination with our model in the preselected population with an increased risk for EOS may have the potential to reduce the start of unnecessary antibiotics.
Background: Antenatal hydronephrosis (ANH) is characteristic for congenital obstructive abnormalities of the urinary tract (COAUT). COAUT is the most common cause of urinary tract infections (UTI's) ...in newborns. The prognosis of mild to moderate ANH is unclear. The aim of this study was to determine the diagnostic value of antenatal ultrasound screening for ANH in order to inform patients correctly.
Methods: A retrospective cohort study over the period 2009-2011, evaluating all structural ultrasounds and proven cases of ANH. Also, evaluation of all patients diagnosed with UTIs caused by COAUT in the same period.
Results: About 7003 children underwent antenatal screening. Of them, 0.7% (n = 47) were diagnosed with ANH. In the same period, 257 children without ANH had a proven UTI. Of them, 4.3% (n = 11) were diagnosed with COAUT, which was not found during antenatal screening. The predictive value of the antenatal ultrasound was higher in the third trimester than the second trimester (sensitivity 0.97 versus 0.62, respectively).
Conclusion: Antenatal ultrasound screening is a reliable method in diagnosing ANH. Third trimester scanning is more specific for diagnosing ANH than second trimester scanning. Our findings allow collaborating gynecologists and pediatricians to inform patients more accurately in the future after the antenatal detection of COAUT.
Abstract Background There is a gap in the knowledge of longterm outcome of mild to moderate prematures compared to the extreme prematures or very low birth weight infants. Aim Determine ...health-related quality of life (HRQoL) and prevalence of emotional and behavioral problems in (pre-)school age children born at 32 to 36 weeks' gestation. Study design A descriptive cohort study in a non-Neonatal Intensive Care Unit. Patient characteristics, diagnoses, treatment and social economic status (SES) were analyzed. Study tools were the TNO-AZL Preschool Quality of Life (TAPQoL) and Child Behavior Checklist (CBCL). Subjects 362 children born between 32 and 36 weeks' gestation who had a follow-up evaluation at 2–5 years of age. Outcome measure Health-related quality of life and the occurrence of emotional and behavioral problems. Results Main characteristics (mean ± SD) were: gestation 34.7 ± 1 weeks and birth weight 2360 ± 444 g. Most families were two-parent middle-class households with parents employed at their educational level. Questionnaire response rate was 62.7%. The 12-item TAPQoL showed significantly lower scores for stomach and liveliness, while scores for behavior, communication and sleep were significantly higher compared to the general population. The TAPQoL subscale score for lung problems was significantly lower for children who had received continuous positive airway pressure (CPAP). CBCL scores were within the validated normal range although the study-population scored higher on emotionally reactive, somatic complaints and attention problems compared to their full-term peers. Conclusion Children born at 32 to 36 weeks' gestational age do not experience an overall lower HR-QoL at 2 to 5 years of age. CPAP results in lower HRQoL scores for lung problems. The overall occurrence of behavioral and emotional problems does not differ from the general term-born pediatric population. Several subitems need further attention.
Neonatal extracorporeal membrane oxygenation (ECMO) is a lifesaving therapeutic approach in newborns suffering from severe, but potentially reversible, respiratory insufficiency, mostly complicated ...by neonatal persistent pulmonary hypertension. However, cerebral damage, intracerebral hemorrhage as well as ischemia belong to the most devastating complications of ECMO.
The objectives are to give insights into what is known from the literature concerning cerebral damage related to neonatal ECMO treatment for pulmonary reasons.
A short introduction to ECMO indications and technical aspects of ECMO are provided for a better understanding of the process. The remainder of this review focuses on outcome and especially on (potential) risk factors for cerebral hemorrhage and ischemia during ECMO treatment.
Although neonatal ECMO treatment shows improved outcome compared to conservative treatment in cases of severe respiratory insufficiency, it is related to disturbances in various aspects of neurodevelopmental outcome. Risk factors for cerebral damage are either related to the patient's disease, EMCO treatment itself, or a combination of both.
It is of ongoing importance to further understand pathophysiological mechanisms resulting in cerebral hemorrhage and ischemia due to ECMO and to develop neuroprotective strategies and approaches.
β-Trace protein (BTP) has been proposed as an alternative endogenous marker of glomerular filtration rate. Data on BTP reference ranges in young children are scarce. We therefore aim to establish ...reference ranges and examine the developmental course of serum BTP in basically healthy children younger than 1 year of age.
Single blood samples were taken from healthy children (born at gestational age ≥37 weeks) <12 months of age. Serum BTP was measured using the N latex B-trace protein assay (Siemens Diagnostics, Deerfield, IL, USA) on an Immage
800 Rate Nephelometer (Beckman Coulter Inc. Brea, CA, USA). Serum creatinine and cystatin C were additionally determined and compared to reference values to confirm a normal renal function.
From June 2010 to January 2014, 95 blood samples were collected from 95 children {67.4% male; median age 120 days inter quartile range 57–166}. BTP was normally distributed (mean concentration 0.84±standard deviation 0.35 mg/L). Considering all children, the 50th centile BTP reference concentration was 0.82 mg/L (5th–95th centiles; 0.27–1.38). BTP concentrations were the highest in neonates and steadily declined with increasing age (Spearman’s rank correlation was –0.415, p=0.002). No gender differences were found.
Our data provide a BTP reference range for the first year of life. Seeing the biological pattern of BTP, with only a limited postnatal decline, this marker might offer a promising alternative to serum creatinine-based methods for estimating glomerular filtration rate in newborns.
Specific immunoglobulin E to Ara h 2 (sIgE to Ara h 2) is described as an upcoming predicting factor for diagnosing peanut allergy in children. The gold standard for diagnosing peanut allergy is a ...double blind placebo controlled food challenge, however this is time consuming and potentially harmful. We investigate Ara h 2 as a preliminary less invasive diagnostic tool for diagnosing peanut allergy in a general population of peanut sensitized children.
Children (n=52) with peanut sensitization were retrospectively included. An oral food challenge (OFC) confirmed peanut allergy or tolerance, as primary outcome. Individual candidate predictors were identified by univariate regression analysis and used in a prediction model. Different cut-off values were obtained and receiver operating characteristic curves were plotted.
Multivariate analyses resulted in Ara h 2 as best predictor, with a discriminative ability of 0.87 (95% confidence interval, 0.77–0.97). Sensitivity and specificity of 55% and 95%, respectively, were found for a sIgE to Ara h 2 cut-off value of 4.25 kU/L. The highest positive predictive value of 100% was reached at 5.61 kU/L. No absolute relation was found between the value of Ara h 2 and the severity of the reaction during OFC.
This study developed a prediction model in which sIgE to Ara h 2 was the best predictor for peanut allergy in sensitized children in a general hospital. Therefore depending on the history and the Ara h 2 results, an OFC is not always needed to confirm the diagnosis.
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