The association of early postnatal weight loss with outcome in extremely low birth weight infants.

BACKGROUND: To compare outcomes of extremely low birth weight (ELBW) infants having different weight losses in the first 3 days of life. METHODS: One hundred and twenty six ELBW infants were evaluated retrospectively for weight loss percentages on the third day of life compared to their birth weight. We examined the weight loss on the third day of life compared to the birth weight for the ELBW infants and tested its association with mortality and morbidities. The mortality was subgrouped as overall mortality and mortality in the first 7 days of life. The morbidities were patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH) and bronchopulmonary dysplasia (BPD). BPD was defined as need for supplemental oxygen at 36 weeks' postconceptional age. We grouped the infants into four quartiles according to weight loss percentage on the third day of life: Group 1 (Quartile 1), infants with weight loss of 0-3% of birth weight; Group 2 (Quartile 2); infants with weight loss of 3.1-7.5%, Group 3 (Quartile 3), infants with weight loss of 7.51-12%; and Group 4 (Quartile 4), infants with weight loss of more than 12%. The mortality and morbidities were analyzed according to these groups and other risk factors. RESULTS: Overall mortality and mortality in the first 7 days of life were significantly higher in Groups 1 (36% and 27%) and 4 (43% and 24%), compared to Groups 2 (10% and 10%) and 3 (18% and 9%), respectively. CONCLUSION: Weight loss less than 3% and more than 12% was significantly associated with an increase in mortality. There was a positive correlation between weight loss on the third day of life and IVH. CONCLUSION: Inappropriate weight loss in ELBW infants is associated with increased mortality and IVH. Appropriate weight loss can improve outcomes in this population.

Early regular versus late selective poractant treatment in preterm infants born between 25 and 30 gestational weeks: a prospective randomized multicenter study.

OBJECTIVE: Surfactant treatment in the early hours of life significantly decreases the rates of death and air leak, and increases survival without bronchopulmonary dysplasia (BPD) in preterm infants. We aimed to compare the impact of early surfactant (ES) administration to late selective (LS) treatment on neonatal outcomes in preterm infants. METHODS: All preterm infants between 25 and 30 wks gestational age and who were not entubated in the delivery room and did not have any major congenital malformation or perinatal asphyxia were randomized to ES treatment (200 mg/kg Curosurf® administration in 1 hour after birth) or LS treatment (200 mg/kg Curosurf®administration in the first 6 h of life if needed). The patients were treated by nasal continuous positive airway pressure (nCPAP) treatment regardless of the surfactant requirement. Outcomes were the necessity of mechanical ventilation, nCPAP duration, the oxygen requirement duration, the rates of BPD, retinopathy of prematurity (ROP) and mortality, and the assessment of the following situations; (pneumothorax, patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH) ≥ grade III). RESULTS: Among 159 infants enrolled in the study, 79 were randomized to ES and 80 to LS treatment groups. Thirty-five patients (44%) in the LS treatment group needed surfactant administration. Necessity of second dose surfactant administration was 8.9% in the ES treatment group. Although necessity of mechanical ventilation, nCPAP duration, oxygen need duration, rates of PDA, NEC, BPD, ROP stage >3 and mortality did not show a significant difference between groups, the ES treatment group had lower rates of pneumothorax and IVH ≥ grade III when compared to the LS treatment group. CONCLUSIONS: ES treatment decreases IVH (≥ grade III) and pneumothorax rates but does not have any effect on BPD when compared to LS.

Preeclampsia is an independent risk factor for spontaneous intestinal perforation in very preterm infants.

BACKGROUND: Spontaneous intestinal perforation (SIP) is an important surgical emergency in preterm infants. AIMS: To evaluate the effect of maternal preeclampsia on development of SIP in premature infants. STUDY DESIGN: Retrospective observational study in a large tertiary neonatal intensive care unit. SUBJECTS: The preterm infants of ≤32 weeks of gestational age and birthweight ≤1500 g who were hospitalized were enrolled. OUTCOME MEASURES: The primary outcome was to determine the association between preeclampsia and SIP. RESULTS: A total of 22 infants had SIP diagnosis. The incidence of SIP in infants born to preeclamptic mothers (6.2%) was significantly higher compared with those born to normotensive mothers (0.2%). In multinominal logistic regression model, preeclampsia was found to be an independent risk factor of SIP with an odds ratio of 13.5 (95% confidence interval 2.82-65.1). CONCLUSIONS: Maternal preeclampsia seemed to be an independent risk factor for development of SIP in premature infants.

Effects of red cell transfusion on cardiac output and perfusion index in preterm infants.

OBJECTIVE/AIM: The present investigation was designed to study the effect of blood transfusion on cardiac output and perfusion index. The aim was to demonstrate a relationship between hematocrit, lactate, cardiac output and perfusion index in anemic preterm infants and to investigate significant changes in these parameters induced by RBC transfusion. METHODS: Anemic infants who were under 35 weeks of gestational age (GA) and were in a stable clinical condition without respiratory or cardiac problems, signs of sepsis, or renal disease at the time of investigation were enrolled in the study. Enrolled infants received 15 ml/kg pure red blood cells over 4 h. Hematocrit and lactate levels were studied before and after transfusion. Cardiac output was measured by an ultrasound device (USCOM 1A) and perfusion index was monitored by pulse oximeter (MasimoRad7). RESULTS: Cardiac output decreased by 9% (p < 0.05), due to decrease in heart rate by 10% (p < 0.05) and stroke volume significantly by 5% (p < 0.05) both in left and right sided cardiac measurements. Perfusion index significantly increased and lactate levels significantly decreased after transfusion (p < 0.05). Htc was inversely correlated with lactate levels, HR, CI and CO (r = -0.33, p = 0.01; r = -0.53, p = 0; r = -0.37, p = 0.004, r = -0.28, p = 0.03). PI was not significantly correlated with Htc levels before and after transfusion (r = 0.07, p = 0.7 and r = 0.007, p =0.97). CONCLUSION: Our data support that heart rate, CO and CI and lactate levels increased as a response to anemia in preterm infants and RBC transfusion improved perfusion index suggesting better tissue oxygenation.

Hypercalcemia due to subcutaneous fat necrosis in a newborn after total body cooling.

Subcutaneous fat necrosis is an inflammatory disorder of adipose tissue. Although patients need long-term follow-up to prevent hypercalcemia, the prognosis is generally favorable. We herein present a case of a newborn who developed subcutaneous fat necrosis-related hypercalcemia after hypothermia treatment for hypoxic ischemic encephalopathy. Widespread use of hypothermia treatment for hypoxic ischemic encephalopathy in the neonatal intensive care unit may increase the risk of developing subcutaneous fat necrosis and subsequently hypercalcemia. Great care should be taken to recognize skin findings early in newborns receiving hypothermia treatment, and those diagnosed with subcutaneous fat necrosis require close follow-up because they are at risk for developing hypercalcemia.

The acute-phase response in differentiating sepsis from inflammation in neonates who require abdominal surgery.

INTRODUCTION: In neonates, the influence of surgery on the inflammatory response has not been fully characterized and it remains difficult to differentiate an inflammatory response from sepsis. In this study, we evaluated changes in interleukin-6 (IL-6) and C-reactive protein (CRP) in neonates undergoing different major abdominal surgeries who had a normal postoperative course without infection. MATERIAL AND METHODS: In total, 43 neonates undergoing major abdominal surgery owing to congenital malformations involving the gastrointestinal tract, and who did not show blood culture positivity were enrolled in the study. As a control group, 40 neonates with proven sepsis were enrolled in the study over the same period. Blood samples for IL-6, CRP, and white blood cell count (WBC) determination were drawn before surgery and 48, 96, and 144 h [postoperative days (POD) 2,4, and 6] after surgery. RESULTS: There was a statistically significant increase in IL-6 concentrations on POD 2 compared with preoperative levels (p < 0.05). After POD 2, IL-6 levels decreased to preoperative levels. There was a statistically significant increase in CRP concentrations on POD 2, 4, and 6 (p < 0.05). Levels of CRP tended to be higher after surgery, and began to fall by the 6th day, but were still statistically higher than preoperative levels. In the sepsis group, CRP concentrations on day 6 were lower than in the surgery group (p < 0.05). White blood cell counts did not show statistically significant differences preoperatively versus postoperatively. CONCLUSIONS: In contrast to previous studies, our results show high levels of IL-6 on POD 2 and CRP on POD 6. It is important to differentiate between the diagnoses of sepsis and postoperative inflammation, because of the need to treat the infection. High levels of IL-6 and CRP are not always associated with sepsis after major abdominal surgeries, but may instead be associated with the inflammatory response and multiorgan dysfunction. Further studies are needed to better differentiate sepsis from inflammatory responses in patients undergoing other surgeries.

Off-label and unlicensed drug use in neonatal intensive care units in Turkey: the old-inn study.

BACKGROUND: Recently several developed countries have improved the safety and efficacy of drugs used in infants and pediatric patients. Most drugs administered to adults have licensed approvals outlining indications, doses, and the recommended route of administration. However, many drugs that are given to children are unlicensed or used off-label. OBJECTIVES: To assess the extent and nature of unregistered and off-label drug use in neonatal intensive care units (NICUs) in Turkey, and to explore awareness and views of the general public on the unlicensed use of medicine in preterm and term infants in developing countries. STUDY DESIGN: A prospective observational study of a dynamic cohort of 464 neonates from 17 NICUs in Turkey. All medications administered to neonates who were hospitalized and admitted to the NICU over a 24-h period were recorded. The prescriptions were analyzed to determine whether the medicines were used in a licensed or unlicensed manner. RESULTS: In total, 1,315 prescriptions comprising 93 different medicines were written. We found that 62.3% of the drugs prescribed to the neonates over the 24-h period were unlicensed or off-labeled. CONCLUSIONS: The present study indicates that unlicensed and off-label medicines are frequently used in preterm and term infants in Turkish NICUs. This finding is consistent and reported in other countries. We believe that the needs of the neonatal population must be a priority and access to safe and appropriate medicines requires urgent attention.

Serum thyroid hormone levels in preterm infants born before 33 weeks of gestation and association of transient hypothyroxinemia with postnatal characteristics.

BACKGROUND: Fetal thyroid function and the hypothalamopituitary-thyroid axis continue to mature throughout pregnancy. Therefore, thyroid hormone levels of premature infants differ from those of mature ones. Our primary objective was to evaluate the reference values of serum thyroid hormones in preterm infants born before 33 wk gestation. The second objective was to define a cut-off value for transient hypothyroxinemia of prematurity (THOP) according to gestational age and association of THOP with postnatal characteristics in these infants. SUBJECTS AND METHODS: We recruited a cohort of 200 infants (26-32 wk gestation) admitted to neonatal intensive care units (NICU) between March 2008 and February 2009. We assessed serum levels of thyroid hormones and thyrotropin (TSH), at 1st, 2nd, and 3rd-4th wk of life. Thyroid-binding globulin (TBG), thyroglobulin (Tg), and urinary iodine values were also measured at the 1st wk of life. The infants were divided into two groups according to gestational ages; group 1: 26-29 wk and group 2: 30-32 wk. Association of THOP with postnatal characteristics of these infants were evaluated. RESULTS: TT4 and TT3 values steadily increased from 1st wk to 3rd-4th wk while FT4 value did not significantly changed. FT3 value slightly decreased from 1st wk to 2nd wk and not significantly changed after this period. TSH value steadily decreased from 1st wk to 3rd-4th wk. For all postnatal ages, TT4, TT3, and FT3 values were lower in the lower gestational age group, while there was no significant difference for FT4 and TSH values between two gestational age groups. THOP rate decreased from first wk (24.0%, n=47) to 3rd-4th (14.0%, n=24) in all infants. When adjusted for age, THOP was associated with need for mechanical ventilation (P=0.03, OR:0.65, CI 95% 0.4-0.9) and for having respiratory distress syndrome (RDS) (P=0.02, OR:0.61 CI95%: 0.4-0.9). Longer hospital stay (P=0.006, OR:0.96, CI 95% 0.94-0.99) was also found to be associated with THOP. CONCLUSIONS: In preterm infants below 30 wk, thyroid hormones were lower and urinary iodine values were higher compared to infants with older gestational age. THOP at the first wk of life may convey important prognostic information about neonatal morbidity and length of hospitalization stay.

Predictive values of neutrophil CD64 expression compared with interleukin-6 and C-reactive protein in early diagnosis of neonatal sepsis.

BACKGROUND: Despite major advances in the management of newborn infants, neonatal sepsis (NS) remain important causes of neonatal morbidity and mortality in the newborn, mainly among preterm and low birth weight infants. OBJECTIVE: The aim of this study was to investigate the usefulness of neutrophil CD64 expression alone and together with other infection markers in NS. METHODS: Peripheral blood samples were taken from 109 neonates, who were categorized into three groups: proven or clinical sepsis (n=35); disease without infection (n=42); and healthy controls (n=32). Complete blood count with differential, interleukin-6 (IL-6), C-reactive protein (CRP), and cell surface expression of CD64 on neutrophils have been evaluated in a prospective manner as a diagnostic aid for NS. RESULTS: Expression of CD64 was significantly enhanced in neonates with sepsis compared with newborns with disease without infection and healthy controls (P=0.001 and P=0.001, respectively). Cutoff values of IL-6, CRP, CD64(MFI), and CD64(i) were 24.9 pg/ml, 4.05 mg/l, 87.7, and 4.39, respectively. Sensitivity-negative predictive values of IL-6, CRP, and CD64(MFI)/CD64(i) were 80.0-90.6%, 80.0-88.8%, and 88.6-94.0%, respectively. Combining all three tests increased the sensitivity to 100%; however, specificity and positive predictive value decreased to 62.1 and 55.5%, respectively. CONCLUSIONS: CD64 might be used either alone or combined with IL-6 and CRP for early diagnosis of NS. The advantages of CD64 when compared with IL-6 and CRP are rapid quantitation, very small blood volume required, and easy handling.