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- Necrotizing Enterocolitis in Small-for-Gestational-Age Neonates: A Matched Case-Control Study. [JOURNAL ARTICLE]
- Neonatology 2013 Nov 26; 105(1):74-78.
Background: Small for gestational age (SGA) neonates are at increased risk of mortality and morbidity, including necrotizing enterocolitis (NEC), but detailed information on the incidence and risk factors of NEC in SGA neonates is lacking. Objective: This study aims to estimate the incidence of NEC in a large cohort of SGA neonates, compared to appropriate for gestational age (AGA) neonates. Methods: We included all SGA neonates without congenital malformations admitted to our neonatal nursery between 2004 and 2013. Neonates in the SGA group were matched for gestational age with a control group of AGA neonates admitted during the same study period. We recorded the occurrence of NEC and studied the association with SGA and other potential risk factors. Results: A total of 475 SGA neonates were matched for gestational age at birth to 475 control AGA neonates. The incidence of NEC in the SGA group was 3.2% (15/475) versus 1.3% (6/475) in the AGA group (OR 2.55, 95% CI 0.98-6.63, p = 0.047). The incidence of NEC in the subgroups with mild, moderate and severe SGA was 2.3% (5/215), 4.7% (5/1.07) and 3.2% (5/153), respectively (p = 0.531). Conclusions: The risk of development of NEC is more than twofold increased in SGA neonates compared to AGA neonates. We found no association between the severity of SGA and NEC. © 2013 S. Karger AG, Basel.
- Ventilator-Associated Pneumonia in Neonatal Patients: An Update. [JOURNAL ARTICLE]
- Neonatology 2013 Nov 29; 105(2):98-107.
Ventilator-associated pneumonia (VAP) is a serious complication related to mechanical ventilation in the neonatal period. However, lack of a specific definition and difficulties obtaining noncontaminated samples of the lower respiratory airway render microbiological diagnosis and etiological treatment extremely difficult. Thus far, only few studies have approached VAP using accepted Centers for Disease Control and Prevention criteria and reliable sampling techniques. In recent years, however, the blind-protected bronchoalveolar lavage technique with protected specimen brush and the development of validated biomarkers have attempted to overcome the diagnostic difficulties and assess the response to therapy. This updated review on neonatal VAP aims to stimulate neonatologists' interest in this subtle but serious complication of mechanical ventilation. © 2013 S. Karger AG, Basel.
- Prophylactic Systemic Antifungal Agents to Prevent Mortality and Morbidity in Very Low Birth Weight Infants. [JOURNAL ARTICLE]
- Neonatology 2013 Nov 28; 105(2):95-97.
Background: Invasive fungal infection is an important cause of mortality and morbidity in very low birth weight infants. Early diagnosis is difficult and treatment is often delayed. Systemic antifungal agents (usually azoles) are increasingly used as prophylaxis against invasive fungal infection. Objectives: To assess the effect of prophylactic systemic antifungal therapy on mortality and morbidity in very low birth weight infants. Search Methods: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 3), MEDLINE, EMBASE, and CINAHL (to August 2012), conference proceedings, and previous reviews. Selection Criteria: Randomized controlled trials or quasi-randomized controlled trials that compared the effect of prophylactic systemic antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very low birth weight infants. Data Collection and Analysis: We extracted data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two review authors. Main Results: We identified 11 eligible trials enrolling a total of 1,136 infants. Seven trials (involving 880 infants) compared systemic antifungal prophylaxis versus placebo or no drug. These trials were generally small but of good methodological quality. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection in infants who received systemic antifungal prophylaxis (typical risk ratio (RR) 0.41, 95% confidence interval (CI) 0.27-0.61; risk difference (RD) -0.09, 95% CI -0.14 to -0.05). The average incidence of invasive fungal infection in the control groups of the trials (16%) was much higher than that generally reported from large cohort studies (<5%). Meta-analysis did not find a statistically significant difference in the risk of death prior to hospital discharge (typical RR 0.74, 95% CI 0.52-1.05; RD -0.04, 95% CI -0.08 to 0.01). Very limited data on long-term neurodevelopmental outcomes were available. Two trials that compared systemic versus oral or topical non-absorbed antifungal prophylaxis did not detect any statistically significant effects on invasive fungal infection or mortality. Two trials that compared different dose regimens of prophylactic intravenous fluconazole did not detect any significant differences in infection rates or mortality. © 2013 S. Karger AG, Basel.
- High Latency of Tuberculosis Manifestation in a Premature Extremely Low Birth Weight Infant with Favorable Outcome. [JOURNAL ARTICLE]
- Neonatology 2013 Nov 28; 105(2):91-94.
We report a case of possible congenital tuberculosis in a 22+2 weeks, 460 g, vaginally delivered female infant born to a mother suffering from tuberculous endometritis, diagnosed soon after delivery. At 156 days of age, Mycobacterium tuberculosis was detected via PCR from the infant's gastric juice and was subsequently isolated. There was no evidence for horizontal transmission. Mother and child were treated successfully. This case illustrates the possibility of significant latency between infection and clinical manifestation in preterm infants and also emphasizes the need for urgent treatment of neonates in such situations. © 2013 S. Karger AG, Basel.
- Clinical Characteristics and Outcome of Incidental Atrial Septal Openings in Very Low Birth Weight Infants. [JOURNAL ARTICLE]
- Neonatology 2013 Nov 28; 105(2):85-90.
Background: Atrial septal openings (ASOs) are very common in premature infants. Objective: The study aimed to evaluate the prevalence and natural course of ASOs in very low birth weight (VLBW) infants diagnosed in the first week of life and the association of ASOs with various clinical factors. Methods: We retrospectively reviewed the medical records of 217 infants born with a weight of <1,500 g between January 2007 and December 2011. Echocardiography was conducted within the first week of life in all infants. Clinical factors were compared between infants with ASO and those with an intact atrial septum. ASO closure was confirmed by echocardiography at the 3-month follow-up and subsequently every 6 months. Results: The incidence of ASOs was 40.3% in VLBW infants. Patent ductus arteriosus (PDA) was associated with a higher incidence of ASO in a multivariate analysis (OR 4.005, 95% CI 2.015-7.960, p < 0.001), and PDA was a predictor of early ASO closure. The rate of oxygen requirement for at least 28 days was higher in infants with ASO, whereas oxygen dependency at 36 weeks' postmenstrual age did not differ between the infant groups. The mean time of closure was 5.8 ± 7.1 months of age (range 0-36). All followed infants showed spontaneous closure within 3 years. Conclusions: ASOs occur at a relatively high incidence in VLBW infants, but most of these close spontaneously within 3 years. PDA was predictive of ASO at the first echocardiography but did not delay ASO closure. The ASOs in VLBW infants were not a significant cause of concern. © 2013 S. Karger AG, Basel.
- Survival and Neurodevelopmental Outcome of Preterm Infants Born at 22-24 Weeks of Gestational Age. [JOURNAL ARTICLE]
- Neonatology 2013 Nov 28; 105(2):79-84.
Background: The limits of viability in extremely premature infants are challenging for any neonatologists in developed countries. The neurological development and growth of extremely preterm infants have come to be the emerging issue following the management in the neonatal intensive care unit. Objective: To assess potential associations between changes in practice and survival/neurodevelopmental outcome, and clinical outcomes of extremely preterm infants born at the limit of viability studied in a tertiary center. Study Design: A retrospective study enrolled 51 infants who had no congenital disorders, and were born at 22-24 weeks of gestational age (GA) in 2000-2009 in our institution. Clinical variables and interventions were studied with regard to one-year survival and developmental quotient (DQ) at 3 years of age. Results: The one-year survival rate of 24 preterm infants born in 2005-2009 (79%) was higher than that of the 27 infants born in 2000-2004 (52%, p = 0.04). Infants born after 2005 underwent less tocolysis (54 vs. 94%, p < 0.01) and more frequently antenatal steroid therapy (32 vs. 6%, p = 0.01) than those born before 2004. The post-2005 survivors (n = 19) received more frequently indomethacin therapy (89 vs. 50%, p = 0.03) and early parenteral nutrition (95 vs. 36%, p < 0.01) than the pre-2004 survivors (n = 14). There were no differences in the proportion of infants who attained a DQ of >50 at 3 years of age between pre-2004 (9/13, 69%) and post-2005 groups (10/17, 59%). Multivariate analysis indicated that extremely premature birth at GA <24 weeks was the sole critical factor for a DQ of >50 in survivors. Conclusions: The perinatal care after 2005 improved the overall survival rate, but not the neurological outcome of preterm survivors at the limit of viability. Neurodevelopmental impairments were associated with extremely premature birth at GA <24 weeks. © 2013 S. Karger AG, Basel.
- Probiotics for Preterm Neonates: What Will It Take to Change Clinical Practice? [JOURNAL ARTICLE]
- Neonatology 2013 Nov 23; 105(1):64-70.
Necrotizing enterocolitis (NEC) is a major cause of mortality (25%) and morbidity including recurrent sepsis, dependence on parenteral nutrition, need for surgery, and survival with short bowel syndrome in preterm very low birth weight infants. Mortality (45-100%) and morbidity including the risk of long-term neurodevelopmental impairment are higher in extremely preterm infants needing surgery for NEC. Systematic reviews of randomized controlled trials (RCT) indicate that probiotics significantly reduce the risk of NEC (RR 0.39; 95% CI 0.29-0.52; p < 0.00001) and all-cause mortality (RR 0.52; 95% CI 0.40-0.69; p < 0.00001) while facilitating enteral feeds in preterm infants. At present, data from 25 RCT (∼5,000 neonates) and reports on routine use (∼3,000 neonates) indicates that significant adverse effects of probiotics are rare. Despite the robust evidence, there is still reluctance in incorporating routine probiotic prophylaxis in clinical practice. If the goal is to have zero tolerance for NEC, then probiotic prophylaxis must be adopted as soon as possible. Current gaps in knowledge can be addressed by continued research while providing routine probiotic supplementation. We believe that the concept of evidence-based practice of medicine has been stretched too far in this case. Trial sequential analysis has already shown that the evidence for probiotic supplementation was conclusive after 10 trials. Results of the ongoing trials are unlikely to change the conclusions of the systematic reviews significantly. Currently we are at trial number 25; how many more trials do we need? What will it take to change clinical practice? © 2013 S. Karger AG, Basel.
- Continuous Infusion of Ibuprofen for Treatment of Patent Ductus Arteriosus in Very Low Birth Weight Infants. [JOURNAL ARTICLE]
- Neonatology 2013 Nov 19; 105(1):46-54.
Background: Ibuprofen (IBU) has proved as effective as indomethacin in the pharmacological closure of hemodynamically significant patent ductus arteriosus (HsPDA), with an efficacy inversely related to gestational age (57-89%). Objective: This study aimed to establish whether continuous infusions of IBU could be more effective in very low birth weight infants with no additional adverse effects and reduce the need for surgical ligation. Methods: A prospective, randomized, double-dummy study was conducted on 112 very low birth weight infants (mean gestational age 27.2 weeks, SD 2; birth weight 1,019 g, SD 330) with HsPDA, 56 of whom were given IBU in conventional 15-min intermittent boluses, while the other 56 were administered IBU as a 24-hour continuous infusion, both at standard doses (10/5/5 mg/kg). Extensive echocardiography was performed before and after treatment, and adverse effects were monitored. Results: Pharmacological PDA closure was achieved after 1 or 2 IBU courses in 36 of 56 infants (64.3%) after bolus administration and in 46 of 55 (83.6%) after continuous infusion (p = 0.020), and in 9 of 26 (34.6%) and 24 of 30 (80.0%), respectively, in the infants with a gestational age of 23-27 weeks (p = 0.006). Sustained pharmacological closure was observed in 38 of 56 infants (67.9%) after bolus IBU and in 47 of 55 (85.5%) after continuous infusion (p = 0.029). Surgical ligation was used less after continuous infusion than after bolus IBU (5.5 vs. 19.6%; p = 0.024). The continuous infusion group had fewer symptoms of necrotizing enterocolitis (NEC), especially in the more preterm infants, while other neonatal morbidity and mortality rates were similar. Conclusion: Continuous IBU infusion is more effective than standard boluses for sustained closure of HsPDA, with fewer NEC symptoms and less need for surgical ligation in very low birth weight infants. © 2013 S. Karger AG, Basel.
- Altered Small Airways in Aged Mice following Neonatal Exposure to Hyperoxic Gas. [JOURNAL ARTICLE]
- Neonatology 2013 Nov 19; 105(1):39-45.
Background: Supplemental oxygen is necessary in the respiratory support of very preterm infants, but it may contribute to bronchopulmonary dysplasia and an increased risk of poor lung function in later life. It is well established that hyperoxia can inhibit alveolarization, but effects on the developing conducting airways, which are important determinants of lung function, are poorly understood. It is possible that prolonged exposure of the immature lung to hyperoxic gas alters the development of small conducting airways (bronchioles), and that these effects may persist throughout life. Objectives: To examine the effects of neonatal inhalation of hyperoxic gas on the bronchiolar walls in adulthood. Methods: Neonatal mice (C57BL/6J) born at term inhaled 65% O2 from birth until postnatal day 7; thereafter, they were raised in room air until 10 months postnatal age (P10mo), which is advanced adulthood. Age-matched controls inhaled room air from birth. We investigated small conducting airways with a diameter between 105-310 µm. Results: At P10mo, bronchiolar walls of hyperoxia-exposed mice contained ∼18% more smooth muscle than controls (p < 0.05), although there was no effect on bronchiolar epithelium or collagen. Neonatal hyperoxia resulted in significantly fewer bronchiolar-alveolar attachments at P10mo (p < 0.05); this was accompanied by persistent simplification of the lung parenchyma, as indicated by greater mean linear intercept and less parenchymal tissue (p < 0.05). Conclusions: Neonatal exposure to hyperoxia induces remodeling of the bronchiolar walls and loss of bronchiolar-alveolar attachments in adulthood, both of which could contribute to impaired lung function and airway hyper-reactivity. © 2013 S. Karger AG, Basel.