Nebulized pentoxifylline for prevention of bronchopulmonary dysplasia in very low birth weight infants: A pilot clinical study

Objective.?To evaluate the effectiveness of nebulized pentoxifylline (PTXF) compared to intravenous dexamethasone (DX) or placebo (nebulized distilled water) for the prevention of bronchopulmonary dysplasia (BPD).

Methods.?One hundred and fifty very low birth weight infants were randomly assigned to three groups. Entry criteria were the need for oxygen administration on the fourth day of life, irrespective of whether ventilatory support was required. PTXF was administered with a nebulizer every 6 hours on three consecutive days (a single course) in a dose of 20 mg/kg when infants were breathing spontaneously or 10 mg/kg when they needed ventilatory support. DX was given every 12 hours on three consecutive days in a dose of 0.25 mg/kg. Nebulized distilled water was administered with the schedule of inhalation as in the PTXF group. When the need for ventilatory support or oxygen dependency persisted, the course of both drugs and placebo administration was repeated every seven days until the diagnosis of BPD was established.

Results.?Both PTXF and DX reduced the incidence of disease when compared with placebo. The respective data obtained for the PTXF-group versus the placebo group were as follows: difference in risk, 27%; OR: 0.32; CI: 0.11–0.94; p = 0.039; whereas the results for the DX-group versus the placebo group were: difference in risk, ? 23%; OR: 0.39; CI: 0.14–1.14; p = 0.07.

Conclusion.?Our data show that nebulized PTXF reduces the risk of BPD and may be a potential alternative to steroids in the prevention of this disease.     

An epidemiologic study of very low and very very low birth weight infants

VVLBW infants constitute only 1 per cent of the total births, but account for 60 per cent of the NMR and 40 per cent of the IMR. While improved technology and refinements in care continue to improve survival for VVLBW infants, questions regarding the lower limits of viability must be considered. The medical community can rightly take credit for improvement in outcome of infants with weight and gestations so small that, just a decade ago, they were considered nonviable; however, an excruciatingly slow pace of decline in the prematurity rate is an agonizing fact. Can anything be done to prevent prematurity and avoid its devastating consequences on the family and society? The recent French experience suggests the answer could be "yes." A similar experience also has been reported in the United States. Although VLBW NMR is a major fraction of total IMR, nearly one quarter of first-year deaths occur in infants who are over 2500 gm at birth. That the postneonatal death of normal birth weight infants is only next in magnitude to the neonatal death of VLBW infants further points to the need for developing preventive child health programs encompassing periods before and during the pregnancy, through the immediate peripartum period, and well into infancy and childhood. Neither a woman's pregnancy experience nor the concerns of the health community end with her taking a baby home.     

Nutrition in very very low birth weight infants

The VVLBW infant's limited nutritional reserves, high requirements for normal growth and development, and gastrointestinal immaturity pose a particularly challenging nutritional problem. Given the potential consequences of inadequate or inappropriate nutritional management, we are obligated to make nutrition a high priority in the overall care of VVLBW infants.     

Outcome of very very low birth weight infants

This review of the literature and selected unpublished data documents normal early outcome in 50 to 81 per cent of tiny infants. Educational outcome described by a few studies is less encouraging, with only 32 to 36 per cent considered normal. Each study investigated the contribution of different perinatal, environmental, or social variables, therefore it is difficult to determine which has most impact on neurodevelopmental outcome.     

Unconjugated hyperbilirubinemia in very low birth weight infants.

In very low birth weight infants, the occurrence of bilirubin-related brain damage has been repeatedly observed at low serum bilirubin concentrations in close association with altered pathophysiologic status (hypoxia, acidosis, hypothermia, and so on). This increased susceptibility is accompanied by increased severity and duration of unconjugated hyperbilirubinemia as compared with more mature infants. Clinical manifestations of kernicterus in very low birth weight infants are almost always nonspecific. No single biochemical or physiologic measurement is sufficient to predict the risk for development of the bilirubin-related brain damage in this group. Prevention of bilirubin-related brain damage in very low birth weight infants requires not only the maintenance of physiologic and biochemical milieu within normal limits, but also specific therapy to alleviate unconjugated hyperbilirubinemia. Although exchange transfusion has been the mainstay of therapy for unconjugated hyperbilirubinemia, the increased morbidity and mortality associated with exchange transfusion in these immature infants and the need to maintain very low serum bilirubin concentrations suggest that prophylactic phototherapy may be more beneficial for this group.     

Non-sinus bradyarrhythmias in very low birth weight infants.

Transient bradycardias occur frequently in preterm infants with apnea of prematurity. However, occurrence of non-sinus bradyarrhythmias in very low birth weight (VLBW) infants has received very little attention. This case series documents transient bradyarrhythmias in VLBW infants. Most frequently observed arrhythmia was a non-sinus atrial rhythm followed by junctional escape rhythm. Ventricular rhythm with wide QRS complexes occurred rarely. The majority of these episodes occurred in the absence of oxygen desaturation. Increase in vagal tone is presumed to mediate this response.     

Bronchopulmonary dysplasia in very low birth weight infants is associated with prolonged hospital stay.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is associated with prolonged hospital length of stay (LOS) and delayed discharge home. OBJECTIVES: To evaluate the association between BPD and LOS and to assess the contribution of concomitant major morbidities on LOS among infants with BPD. STUDY DESIGN: A population-based observational study of very low birth weight (VLBW) infants born from 1995 through 2003. Multivariate analyses, adjusted for perinatal variables, assessed the association between BPD and concomitant morbidities on LOS. RESULTS: Of 10 134 survivors, 1926 (19.0%) had BPD. The adjusted LOS for infants with and without BPD was 84.1 days (95% CI, 82.8, 85.6) and 58.1 days (95% CI, 57.2, 59.0), respectively. Addition of a single concomitant morbidity increased mean LOS by 4 to 13 days. CONCLUSIONS: BPD is a major cause of increased length of hospitalization among VLBW infants. Preventive or therapeutic modalities are required to reduce the significant burden of this condition.     

Neurodevelopmental status of low birth weight infants with bronchopulmonary dysplasia requiring prolonged oxygen supplementation

Fifty infants weighing 1,500 g or less at birth with a diagnosis of bronchopulmonary dysplasia (BPD) were followed to a mean age of 25 months to determine their clinical course and short-term neurodevelopmental outcome after discharge from the Neonatal Intensive Care Unit, and to identify possible predictive factors for outcome. Because study participation was voluntary, the subjects may not have represented the total population of BPD survivors. Occurrences of abnormalities were high: 11 hearing impaired, 10 legally blind, 14 cerebral palsy, and 23 abnormal development scores. Twenty-one subjects had feeding problems and weight was below the fifth percentile in 26. Home-oxygen therapy was required by 50 per cent of the subjects. Although severity of illness, duration of oxygen therapy and feeding problems were greater among those sent home on oxygen, their neurodevelopmental status did not differ from that of infants breathing room air by discharge. Factors associated with neurodevelopmental outcome were intracranial hemorrhage, pulmonary air leak, and length of hospital stay.     

Enriched post-discharge formula versus term formula for bone strength in very low birth weight infants: a longitudinal pilot study

AIM: To initiate a longitudinal pilot study comparing the effect of nutrient-enriched post-discharge formula (PDF) with standard term formula (TF) on bone strength of very low birth weight (VLBW) infants in the first six months post-term. METHODS: Two matched groups of VLBW infants were randomly assigned to enriched PDF (n=10) or TF (n=10) at corrected age of 40 weeks. Anthropometric measurements of growth and measurements of bone speed of sound (SOS) indicating bone strength and bone turnover markers (bone-specific alkaline phosphatase and cross-linked carboxy terminal telopeptide of type I collagen) were taken at term and at three and six months corrected age. RESULTS: The anthropometric measurements of infants fed PDF and TF were comparable at three and six months corrected age. Bone SOS of the PDF group increased from 2760+/-113 m/s at term to 2877+/-90 m/s and 3032+/-60 m/s at three and six months corrected age, respectively (P<0.001). Likewise, bone SOS of the TF group increased from 2695+/-116 m/s at term to 2846+/-72 and 2978+/-83 m/s at three and six months, respectively (P<0.001). No statistically significant difference was found between the groups in terms of growth and bone SOS measurements. The levels of both bone turnover markers decreased significantly during the study period (P<0.001 for both groups). CONCLUSION: Feeding with PDF after term had no short-term beneficial effect on bone strength and bone turn-over of VLBW infants.     

极低和超低出生体重儿败血症临床分析

目的 了解极低和超低出生体重儿败血症临床特点、病原菌分布及药物敏感情况,以指导临床合理用药.方法 对1999年1月1日至2008年12月31日温州医学院附属育英儿童医院新生儿重症监护病房收治的56例极低和超低出生体重儿败血症(早发型败血症3例,晚发型败血症53例)临床特点、血培养结果及药物敏感情况进行回顾性分析.结果 极低和超低出生体重儿败血症临床表现无特征性.血培养结果阳性43例,以条件致病菌为主,其中新生儿早发型败血症血培养阳性1例.为脑膜炎败血黄杆菌;新生儿晚发型败血症血培养病原菌中,革兰阴性细菌主要是肺炎克雷伯菌(33.3%,14/42);革兰阳性细菌以凝固酶阴性葡萄球菌为首(26.2%,11/42),其次是肠球菌(11.9%,5/42);另有真菌感染2例,为白念珠菌败血症(4.8%,2/42).药物敏感试验方面,所有凝固酶阴性葡萄球菌均为耐苯唑西林凝同酶阴性葡萄球菌,对大部分β-内酰胺类抗生素耐药,对林可霉素、氨基糖苷类、大环内酯类及喹诺酮类抗生素亦不敏感,但对万古霉素未发现耐药,对利福平均敏感;所有肺炎克雷伯菌均产超广谱β-内酰胺酶,仅对碳青霉烯类、氨基糖苷类以及喹诺酮类等少数抗生素敏感.56例败血症患儿治愈43例,死亡13例(包括6例病情恶化放弃治疗),病死率为23.2%.结论极低和超低出生体重儿败血症临床表现缺乏特异性,病原菌主要为条件致病菌,并存在多重耐药,对可疑败血症患儿应及时行病原学检查及药物敏感试验,合理选择抗生素.为减少多重耐药菌感染的发生,应正确合理使用第三代头孢菌素.     

极低出生体重儿脑室周围-脑室内 出血高危因素分析

目的　探讨极低出生体重儿（VLBWI）脑室周围-脑室内出血（PVH-IVH）的高危因素。方法　回顾性对照分析2009年10月至2010年11月青岛大学医学院附属医院VLBWI 117例病例,PVH-IVH 39例为PVH-IVH组,按胎龄、出生体重1 ∶ 2配对的无PVH-IVH 78例为对照组,对其相关因素采用SAS 9.0软件进行配对条件Logistic 回归分析。结果　130例VLBWI中发生PVH-IVH 39例,发生率为30.00%。应用1 ∶ 2配对的条件Logistic回归分析示经阴分娩（OR = 1461.699,CI 7.216～296094.700,P < 0.0001）、胎儿宫内窘迫（OR = 95.172,CI 2.213～4093.612,P = 0.0006）、机械通气（OR = 65.124,CI 2.258～1878.432,P = 0.0228）、动脉导管未闭（PDA）（OR = 42.051,CI 1.935～913.839,P = 0.0283）、低钠血症（OR = 33.415,CI 0.936～1192.593,P = 0.0475）、低钙血症（OR = 25.175,CI 1.328～477.243,P = 0.0325）是VLBWI发生PVH-IVH的高危因素;产前使用激素（OR = 0.061,CI 0.004～0.884,P = 0.0017）是避免患儿发生PVH-IVH的保护因素。结论　经阴分娩、胎儿宫内窘迫、机械通气、PDA及电解质紊乱是VLBWI发生PVH-IVH 的高危因素,而产前使用激素可预防PVH-IVH的发生,因此PVH-IVH的发生是多种因素相互作用的复杂结果。在围生期工作中应当高度重视这些因素,以提高早产儿的生存质量。     

Below median birth weight in appropriate-for-gestational-age preterm infants as a risk factor for bronchopulmonary dysplasia

AIMS: To assess the presence of chorioamnionitis and intrauterine growth as prenatal risk factors for broncho pulmonary dysplasia (BPD) in appropriate-for-gestational-age (AGA) infants of <28 weeks' gestation. METHODS: Gender, race, birth weight, gestational age, histology of the placenta, diagnosis of BPD at 36 weeks' gestation, postnatal dexamethasone treatment, and death were recorded in 150 preterm infants born at <28 weeks' gestation, and admitted between 1996 and 2001. RESULTS: In 122 AGA infants (mean gestational age: 26.18 weeks, mean birth weight: 837 g), BPD was associated with gestational age-related birth weights below the 50(th) centile. Intrauterine growth deceleration started between 25 and 26 weeks' gestation. Chorioamnionitis was not related to BPD. CONCLUSIONS: AGA infants of 26-28 weeks' gestation with birth weights below the median showed an increased risk of developing BPD.     

Assessment of motor development in very low birth weight infants.

OBJECTIVE: The purpose of the current investigation was to describe the fine- and gross-motor acquisitions of very low birth weight (VLBW) infants during their first 12 months without imposing traditional assessment assumptions. STUDY DESIGN: A nonrandomized, prospective study was used for a sample consisting of 89 VLBW infants whose motor development was assessed neonatally and at 4, 8, and 12 months chronological age. Fine- and gross-motor assessment items were selected and adapted from three standardized assessment instruments. RESULTS: The fine- and gross-motor systems of development appeared to be relatively independent of one another before the 8-month assessment. Thus, early fine-motor control appeared to develop almost to the exclusion of gross-motor progress. Once fine-motor control was established by 8 months, numerous gross-motor milestones followed and were present at 12 months chronological age. CONCLUSION: Current and previous data continue to define a developmental picture in which VLBW and fullterm infants achieve the same fine- and gross-motor milestones; however, the developmental pathways whereby milestones are achieved, during at least the first 12 months, appear to be different. Accordingly, applying instruments standardized on fullterm infants to the assessment of VLBW babies may not be serving us well on a number of different issues.     

Fluid and electrolyte balance in very low birth weight infants.

Correct fluid and electrolyte concentrations are essential to reduce mortality in critically ill infants. The authors list considerations in calculating the necessary maintenance volumes and emphasize the importance of continuous monitoring of data and a review and retabulation every eight hours, because requirements vary from one infant to the other, and in the same infant under different circumstances.     

147例极低和超低出生体重儿胃肠道内喂养的影响因素

目的 分析影响极低出生体重儿(very low birth weight infant,VLBWI)和超低出生体重儿(extremely low birth weight infant,ELBWI)胃肠道内喂养的相关因素.方法 对147例出院前达到足量胃肠道内喂养,即奶量达到120 ml/(kg·d)的VLBWI和ELBWI的临床资料进行回顾性研究,分析影响胃肠道内喂养的相关因素.对服从双变量正态分布的资料,采用Pearson法进行相关性分析,否则采用Spearman法进行相关性分析;应用t检验进行单因素分析;应用多元线性回归探讨达足量胃肠道内喂养时间的影响因素.结果 147例研究对象的平均胎龄(31.0±2.0)周;平均出生体重(1246±185)g;达到足量胃肠道内喂养的时间为(24.4±10.5)d.单因素分析显示出生体重(r=-0.477,P=0.000)、胎龄(r=-0.405,P=0.000)、机械通气时间(r=0.393,P=0.000)、开奶日龄(r=0.318,P=0.000)、开奶量(r=-0.263,P=0.001)、第3天奶量(r=-0.412,P=0.000)及第7天奶量(r=-0.592,P=0.000)、新生儿呼吸窘迫综合征(t=3.368,P=0.001)、血糖异常(t=3.285,P=0.001)、败血症(t=3.244,P=0.001)、脐静脉置管(t=3.571,P=0.000)、应用氨茶碱(t=4.341,P=0.000)、光疗(t=3.054,P=0.003)与达到足量喂养时间相关.多元线性回归分析显示出生体重(t=4.175,P=0.000)、开奶日龄(t=2.851,P=0.005)、应用氨茶碱(t=2.231,P=0.027)、光疗(t=2.852,P=0.005)、败血症(t=3.895,P=0.000和第7天奶量(t=7.332,P=0.000)与达到足量喂养时间相关.结论 VLBWI和ELBWI的喂养不但受消化道成熟程度影响,还受其他胃肠道外相关因素的影响,因此应综合考虑临床各方面的具体情况,正确实施胃肠道内喂养.

Abstract：

Objective To summarize and analyze the impact factors on enteral feeding in very low birth weight infants (VLBWI) and extremely low birth weight infants (ELBWI). Methods A retrospective study was carried out in VLBWI and ELBWI who had achieved full enteral feeding prior to discharge. The impact factors correlated to the time of achieving full enteral feeding were analyzed. If the data underwent bi-variable normal distribution, they were analyzed with Pearson correlation test; otherwise they would be analyzed with Spearman correlation test. T test was used for single factor analysis and multiple linear regression analysis was carried out to determine the significant risk factors associated with the time of achieving full enteral feeding. Results One hundred and forty-seven infants with mean gestational age of (31.0±2.0) weeks, mean birth weight of (1246±185) g and mean time of achieving full enteral feeding of (24. 4± 10. 5) days were admitted. With the single factor analysis, it was found that birth weight (r=- 0. 477, P = 0. 000), gestational age (r = - 0. 405, P= 0. 000), mechanical ventilation duration (r= 0. 393, P = 0. 000), the time began to enteral feeding (r = 0. 318, P = 0. 000), initial milk volume (r = - 0. 263, P = 0. 001 ), the milk volume on the third day (r= -0. 412, P=0. 000) and the seventh day (r= -0. 592, P=0. 000),neonatal respiratory distress syndrome (t = 3. 368, P = 0. 001), umbilical catheterization (t = 3. 571,P=0. 000), abnormal blood glucose level (t=3. 285, P=0. 001), aminophylline using (t=4. 341,P=0. 000), phototherapy (t=3. 054, P=0. 003) and sepsis (t=3. 244, P=0. 001) were correlated to the time of achieving full enteral feeding. Multiple linear regression showed that the birth weight (t=4. 175, P= 0. 000), the time began to enteral feeding (t= 2. 851, P = 0. 005), aminophylline using (t=2. 231, P=0. 027), sepsis (t=3. 895, P=0. 000), phototherapy (t=2. 852, P=0. 005)and the milk volume on the seventh day (t= 7. 332, P=0. 000) were significantly correlated with the time of achieving full enteral feeding. Conclusions The enteral feeding of VLBWI and ELBWI was not only influenced by maturity of gastrointestinal tract, but also by other parenteral correlation factors. Multiple factors associated with all around clinical conditions should be considered when providing enteral feeding for VLBWI and ELBWI.     

Nephrotoxic medication exposure in very low birth weight infants

Abstract

Objective: To quantify exposure to potentially nephrotoxic medications among very low birth weight (VLBW) infants and determine the relationship of nephrotoxic medication exposure to acute kidney injury (AKI) in this vulnerable population.

Methods: We reviewed 107 VLBW infants who survived to discharge from April 2011 to March 2012 and measured exposure to the following nephrotoxic medications: acyclovir, amikacin, amphotericin B, gentamicin, ibuprofen, indomethacin, iohexol, tobramycin and vancomycin. Acute kidney injury was determined by the KDIGO guidelines.

Results: Exposure to ≥1 nephrotoxic medication occurred in 87% of infants. The most common exposures were gentamicin (86%), indomethacin (43%) and vancomycin (25%). There was an inverse linear relationship between birth weight and nephrotoxic medications received per day (R^2?=?0.169, p?<?0.001). Infants with AKI received more nephrotoxic medications per day than those who did not (0.24 versus 0.15; p?=?0.003).

Conclusions: VLBW infants are frequently exposed to nephrotoxic medications, receiving approximately two weeks of nephrotoxic medications before discharge or 1 for every 6?d of hospitalization. The greatest exposure occurred among the smallest, most immature infants and those who experienced AKI.     

Hematological profile of Korean very low birth weight infants

For very low birth weight (VLBW) infants, diagnostic and therapeutic decisions widely depend on hematological values. Although ethnic differences for hematologic parameters have been reported, few studies have been reported for Korean VLBW infants. This study aimed at defining the hematological reference values for medical research and clinical practice. Retrospectively we selected 149 infants confirmed as healthy at birth and had no medical conditions that may have affected the hematological profile. Hematological values obtained within the first 4 h after birth were classified into gestational age and we determined the influence of gender, mode of delivery, sampling site, 1-min and 5-min Apgar scores on these values. Red blood cell (RBC), hemoglobin (Hb) and hematocrit (Hct) values increased, whereas the white blood cell (WBC) and platelets decreased as the gestational age increased. In relation to the mode of delivery and the 5-min Apgar score, WBC, neutrophil, mean corpuscular volume (MCV), RBC, Hb, Hct and the platelets differed selectively. No differences in any hematological values were observed in relation to gender, sampling site, and the 1-min Apgar score. This study should be useful as a guide to the reference range of these hematological values for Korean VLBW infants.