Extremely Premature Newborns Research Articles

Pathomorphological Features of the Lesion of the Afterbirth in Extremely Premature Newborns with Intraventricular Hemorrhages

Objective. To evaluate morphological changes of placenta in 21 dead preterm babies with extremely low body weight. Materials and Methods. We evaluated the grade of immaturity of the placenta, inflammatory changes of placenta and extraplacental membranes in premature babies who died because of intraventricular hemorrhage (IVH) 2-3 grades and without sonographic and pathomorphological signs of IVH. Results. We identified the signs of ascending amniotic infections in 13 (100%) children with IVH and only in 4 (50%) babies without IVH. We also found that placenta damages in babies with IVH were associated with bacterial and mixed viral-bacterial infections, and the viral agent was represented mainly by the herpetic group. Only viral pathogens (mainly of the herpetic group) were identified as etiological factors of ascending infection in children without IVH. The role of compensatory changes of the placenta observed in children without signs of IVH in prolongation of pregnancy was noted. Conclusions. The presence of viral-bacterial lesions of placenta has a more pronounced impact on premature delivery, which increases the risk of complications in premature newborns in the form of damage to the central nervous system – intraventricular hemorrhages.

Prevention of Chronic Morbidities in Extremely Premature Newborns with LISA-nCPAP Respiratory Therapy and Adjuvant Perinatal Strategies.

Less invasive surfactant administration techniques, together with nasal continuous airway pressure (LISA-nCPAP) ventilation, an emerging noninvasive ventilation (NIV) technique in neonatology, are gaining more significance, even in extremely premature newborns (ELBW), under 27 weeks of gestational age. In this review, studies on LISA-nCPAP are compiled with an emphasis on short- and long-term morbidities associated with prematurity. Several perinatal preventative and therapeutic investigations are also discussed in order to start integrated therapies as numerous organ-saving techniques in addition to lung-protective ventilations. Two thirds of immature newborns can start their lives on NIV, and one third of them never need mechanical ventilation. With adjuvant intervention, these ratios are expected to be increased, resulting in better outcomes. Optimized cardiopulmonary transition, especially physiologic cord clamping, could have an additively beneficial effect on patient outcomes gained from NIV. Organ development and angiogenesis are strictly linked not only in the immature lung and retina, but also possibly in the kidney, and optimized interventions using angiogenic growth factors could lead to better morbidity-free survival. Corticosteroids, caffeine, insulin, thyroid hormones, antioxidants, N-acetylcysteine, and, moreover, the immunomodulatory components of mother's milk are also discussed as adjuvant treatments, since immature newborns deserve more complex neonatal interventions.

End-organ saturations correlate with aortic blood flow estimates by echocardiography in the extremely premature newborn \u2013 an observational cohort study

BackgroundNear-infrared spectroscopy (NIRS) measures of cerebral saturation (Csat) and renal saturation (Rsat) in extreme premature newborns may be affected by systemic blood flow fluctuations. Despite increasing clinical use of NIRS to monitor tissue saturation in the premature infant, validation of NIRS measures as a correlate of blood flow is still needed. We compared echocardiography (ECHO) derived markers of ascending aorta (AscAo) and descending aorta (DesAo) blood flow with NIRS measurements obtained during the ECHO.MethodsNewborns < 29 weeks’ gestation (2013–2017) underwent routine NIRS monitoring. Csat, Rsat and systemic saturation at the time of ECHO were retrospectively analyzed and compared with Doppler markers of aortic flow. Renal and cerebral fractional tissue oxygen extraction (rFTOE and cFTOE, respectively) were calculated. Mixed effects models evaluated the association between NIRS and Doppler markers.ResultsForty-nine neonates with 75 Csat-ECHO and 62 Rsat-ECHO observations were studied. Mean post-menstrual age was 28.3 ± 3.8 weeks during the ECHO. Preductal measures including AscAo velocity time integral (VTI) and AscAo output were correlated with Csat or cFTOE, while postductal measures including DesAo VTI, DesAo peak systolic velocity, and estimated DesAo output were more closely correlated with Rsat or rFTOE.ConclusionsNIRS measures are associated with aortic blood flow measurements by ECHO in the extremely premature population. NIRS is a tool to consider when following end organ perfusion in the preterm infant.

Newborn Screening for Primary T- and B-Cell Immune Deficiencies—A Prospective Study in Andalucía

Background: Quantification of T-cell-receptor-excision circles (TRECs) and kappa-deleting-recombination-excision circles (KRECs) from dried blood spots (DBS) allows detection of neonates with severe T-cell and/or B-cell lymphopenia that are potentially affected by severe combined immunodeficiency (SCID), as well as X-linked agammaglobulinemia (XLA). Methods: Determination of TRECs and KRECs using a triplex RT-PCR (TRECS-KRECS-β-actin) assay from prospectively collected DBS between February 2014 and December 2016 in three hospitals in Seville, Spain. Cut-off levels were TRECs &lt; 6/punch, KRECs &lt; 4/punch and b-actin &gt; 700/punch. Internal (SCID, XLA, ataxia telangiectasia) and external controls (CDC) were included. Results: A total of 8943 DBS samples obtained from 8814 neonates were analysed. Re-punching was necessary in 124 samples (1.4%) due to insufficient β-actin values (&lt;700 copies/punch). Preterm neonates (GA &lt; 37 weeks) and neonates with a BW &lt; 2500 g showed significantly lower TRECs and KRECs levels (p &lt; 0.001). Due to repeated pathological results, ten neonates were re-sampled (0.11%), of which five neonates (0.055%) confirmed the pathological results: one case was a fatal chromosomopathy (TRECs 1/KRECs 4); two were extreme premature newborns (TRECs 0/KRECs 0 and TRECs 1/KRECs 20 copies/punch); and 2 neonates were born to mothers receiving azathioprine during pregnancy (TRECs 92/KRECs 1 and TRECs 154/KRECs 3 copies/punch). All controls were correctly identified. Conclusions: Severe T- and B-cell lymphopenias were correctly identified by the TRECS-KRECS-β-actin assay. Prematurity and low BW are associated with lower TREC and KREC levels. Extreme prematurity and maternal immune suppressive therapy can cause false positive results of TRECs and KRECs values.

Transcatheter Closure of PatentDuctusArteriosus in ExtremelyPrematureNewborns: Early Results and Midterm Follow-Up.

The goal of this study was to describe early and midterm outcomes of extremely premature newborns (EPNs) who underwent transcatheter echocardiographically guided patent ductus arteriosus (PDA) closure. Surgical ligation of PDA in EPNs confers significant risk for procedural morbidity and adverse long-termoutcomes. The Amplatzer Vascular Plug II was used in all cases. Post-ligation syndrome was defined using previously published parameters. Patients were followed at pre-specified intervals, and prospectively collected data were reviewed. Transcatheter closure was attempted in 24 EPNs (mean procedural age 30 days [range 5 to 80 days], mean procedural weight 1,249 g [range 755 to 2,380 g]) and was successful in 88%. The 3 procedural failures were related tothe development of left pulmonary artery (LPA) stenosis caused by the device, and all devices were removed uneventfully. Complications included 2 instances of device malposition, resolved with device repositioning, and 1 instance of LPA stenosis, requiring an LPA stent. There were no procedural deaths, cases of post-ligation syndrome, residual PDA, or device embolization. Survival to discharge was 96% (23 of 24), with a single late death unrelated to the procedure. After a median follow-up period of 11.1 months, all patients were alive and well, with no residual PDA or evidence of LPA or aortic coarctation. This newly described technique can be performed safely with a high success rate and minimal procedural morbidity in EPNs. Early and midterm follow-up is encouraging. Future efforts should be directed toward developing specific devices for this unique application.

33 The Black Box of Pain Assessment in Extremely Premature Newborns Remains Closed

Background and aimsIn our NICU nurses assess the neonates’ pain with the validated COMFORTneo scale three times per day and additionally if they suspect pain. We treat more and more...

1231 Pneumothorax and Air Leak Syndromes in the Newborn, a Cohort Study

Background: Pneumothorax is a common complication in the premature newborn with respiratory distress syndrome. Its incidence may have declined following the widespread use of antenatal steroids and surfactant. However clinicians are concerned that use of CPAP may be associated with increases risk of Pneumothorax.Aim: To describe the demographic profile of a cohort of premature infants with pneumothorax.Method: Regional tertiary neonatal centre in the north east of England. All newborns with pneumothorax or other air leak syndromes over 10 year period were included. Variables recorded; gestation, antenatal steroids, surfactant use and non-invasive respiratory support (CPAP).Results: 3804 admissions, 107 infants were diagnosed with pneumothorax or other air leak syndrome (overall incidence of 2.8%). This included 72 premature infants of whom 37 were under 28 weeks gestation. The incidence of pneumothorax and pulmonary interstitial emphysema (PIE) was 2.3% and 0.47% respectively. There was statistically significant association between the severity of pneumothorax and degree of prematurity, use of surfactant and CPAP. Severe pneumothorax requiring drainage was more in extremely premature infants who didn't received optimal dose of surfactant. No statistically significant effect was noted with variables such as lack of antenatal steroids, gender, mode of delivery, use of muscle relaxants and squad retrievals.Conclusion: Incidence of pneumothorax and other air leak syndromes was lower compared with other cohort studies. Risk of pneumothorax was increased with use of CPAP and suboptimal surfactant dose. Effect of CPAP in extreme premature newborns without antenatal steroids and postnatal surfactant exposure require further evaluation.

Combined Treatment With a Nonselective Nitric Oxide Synthase Inhibitor (L-NMMA) and Indomethacin Increases Ductus Constriction in Extremely Premature Newborns

Combined Treatment With a Nonselective Nitric Oxide Synthase Inhibitor (L-NMMA) and Indomethacin Increases Ductus Constriction in Extremely Premature Newborns

Combined Treatment With a Nonselective Nitric Oxide Synthase Inhibitor (L-NMMA) and Indomethacin Increases Ductus Constriction in Extremely Premature Newborns

Studies in premature animals suggest that 1) prolonged tight constriction of the ductus arteriosus is necessary for permanent anatomic closure and 2) endogenous nitric oxide (NO) and prostaglandins both play a role in ductus patency. We hypothesized that combination therapy with an NO synthase (NOS) inhibitor [N(G)-monomethyl-L-arginine (L-NMMA)] and indomethacin would produce tighter ductus constriction than indomethacin alone. Therefore, we conducted a phase I and II study of combined treatment with indomethacin and L-NMMA in newborns born at <28 weeks' gestation who had persistent ductus flow by Doppler after an initial three-dose prophylactic indomethacin course (0.2, 0.1, 0.1 mg/kg/24 h). Twelve infants were treated with the combined treatment protocol [three additional indomethacin doses (0.1 mg/kg/24 h) plus a 72-hour L-NMMA infusion]. Thirty-eight newborns received three additional indomethacin doses (without L-NMMA) and served as a comparison group. Ninety-two percent (11/12) of the combined treatment group had tight ductus constriction with elimination of Doppler flow. In contrast, only 42% (16/38) of the comparison group had a similar degree of constriction. L-NMMA infusions were limited in dose and duration by acute side effects. Doses of 10-20 mg/kg/h increased serum creatinine and systemic blood pressure. At 5 mg/kg/h, serum creatinine was stable but systemic hypertension still limited L-NMMA dose. We conclude that combined inhibition of NO and prostaglandin synthesis increased the degree of ductus constriction in newborns born at <28 weeks' gestation. However, the combined administration of L-NMMA and indomethacin was limited by acute side effects in this treatment protocol.

A quantitative review of mortality and developmental disability in extremely premature newborns.

To summarize the literature on mortality rates and prevalences of major neurodevelopmental disabilities and to examine trends of these outcomes over time in extremely premature neonates. MEDLINE was used to search the English literature for studies published since 1970 reporting on both mortality and disability in infants born at or before 26 weeks' gestation (extremely immature [EI] cohort), with a birth weight of 800 g or less (extremely small [ES] cohort), or subgroups of these. Studies were included in the analysis if all of the following were reported: mortality; direct examination of 75% or more of the survivors; and the proportion of patients with at least 1 of the following disabilities: cerebral palsy, mental retardation, blindness, and deafness. Studies reporting cohorts included as a subset of cohorts in another study were excluded. Forty-two studies providing mortality and disability data for 20 cohorts of 4116 EI infants and 38 cohorts of 4345 ES infants born after 1972 met the inclusion criteria. Data were abstracted from all studies that met these criteria by two of us (J.M.L. and D.E.W.), independently; the data were then cross-checked to ensure accuracy. Survival averaged 41% for EI infants and 30% for ES infants, and it increased significantly with time. In contrast to mortality, the prevalences of major neurodevelopmental disabilities among survivors have not changed over time. The most common major disability was mental retardation, found in 14% of EI and ES survivors. Cerebral palsy was found in 12% of EI survivors and 8% of ES survivors, blindness was found in 8% of EI and ES survivors, and deafness was found in 3% of EI and ES survivors. Overall, 22% of EI survivors and 24% of ES survivors were classified as having at least 1 major disability. Each 100 EI or ES livebirths yielded 7 children with major disabilities; this prevalence was correlated with survival across cohorts. The prevalence of disabilities had not changed among EI or ES survivors with increasing survival. However, increasing survival of these infants has resulted in a steadily increasing prevalence of children with disabilities.