Healthy Very Low Birth Weight Research Articles

The Thromboelastographic Profile at Birth in Very Preterm Newborns with Patent Ductus Arteriosus

Background: The role of hemostasis in the closure of patent ductus arteriosus (PDA) in preterm infants is controversial. Objective: To assess thromboelastography (TEG) at birth in very-low-birth-weight (VLBW) infants affected by PDA. Methods: This was an ancillary study of a prospective observational study aimed at defining the TEG profile in healthy VLBW infants in the first month of life. In this analysis, we included neonates of <33 weeks’ gestational age (GA) with PDA and compared TEG traces based on (1) spontaneous closure versus the need for pharmacological treatment and (2) treatment response. We collected blood samples in the 1st day of life to perform recalcified native-blood TEG (reaction time, maximum amplitude, and lysis at 30 min [Ly30)]), standard coagulation tests, and a full blood count. Results: We enrolled 151 infants with a PDA at the first echocardiogram; 111 experienced spontaneous PDA closure while 40 required treatment. Mean GA was 29.7 ± 1.7 and 27.6 ± 2.1 weeks, and birth weight was 1,158 ± 256 and 933 ± 263 g in the 2 groups, respectively (p < 0.001). The hemostatic profile was similar between groups. Median hematocrit (44.6 and 48.7%; p = 0.01) and platelet count (187 and 216 × 10³/μL; p = 0.04) were lower in the treated group, although differences lost significance after controlling for GA and illness severity in the multivariate analysis. Responders to PDA treatment (n = 20) had a significantly lower median Ly30 than nonresponders (0 and 0.7%; p = 0.02). Conclusion: TEG at birth does not predict spontaneous PDA closure in preterm newborns. Fibrinolysis is enhanced in nonresponders to PDA treatment; this observation warrants further investigation.

Brief Parenteral Nutrition Accelerates Weight Gain, Head Growth Even in Healthy VLBWs

IntroductionWhether parenteral nutrition benefits growth of very low birth weight (VLBW) preterm infants in the setting of rapid enteral feeding advancement is unclear. Our aim was to examine this issue using data from Japan, where enteral feeding typically advances at a rapid rate.MethodsWe studied 4005 hospitalized VLBW, very preterm (23–32 weeks' gestation) infants who reached full enteral feeding (100 ml/kg/day) by day 14, from 75 institutions in the Neonatal Research Network Japan (2003–2007). Main outcomes were weight gain, head growth, and extra-uterine growth restriction (EUGR, measurement <10th percentile for postmenstrual age) at discharge.Results40% of infants received parenteral nutrition. Adjusting for maternal, infant, and institutional characteristics, infants who received parenteral nutrition had greater weight gain [0.09 standard deviation (SD), 95% CI: 0.02, 0.16] and head growth (0.16 SD, 95% CI: 0.05, 0.28); lower odds of EUGR by head circumference (OR 0.66, 95% CI: 0.49, 0.88). No statistically significant difference was seen in the proportion of infants with EUGR at discharge. SGA infants and infants who took more than a week until full feeding had larger estimates.DiscussionEven in infants who are able to establish enteral nutrition within 2 weeks, deprivation of parenteral nutrition in the first weeks of life could lead to under nutrition, but infants who reached full feeding within one week benefit least. It is important to predict which infants are likely or not likely to advance on enteral feedings within a week and balance enteral and parenteral nutrition for these infants.

Urinary Neutrophil Gelatinase-Associated Lipocalin Is a Promising Biomarker for Late Onset Culture-Positive Sepsis in Very Low Birth Weight Infants

Need for the early identification of sepsis in very low birth weight (VLBW) infants has led to the search for reliable biomarkers. This study aims to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) rises in culture-positive sepsis and, if so, is elevated at the time sepsis is suspected. This is a prospective study of 91 VLBW infants whose urine was collected daily for uNGAL analysis. In 65 episodes of suspected sepsis, four groups were identified: a) culture-positive sepsis; b) single culture positive for Staphylococcus epidermidis; c) and d) negative culture with antibiotic treatment for >or=7 d and <7 d, respectively. Daily means of uNGAL of each group were estimated for comparison. Mean uNGAL in group A (179 ng/mL) was significantly elevated on the day blood culture was drawn (day 0) compared with the mean of healthy VLBW infants (6.5 ng/mL), and to the means in groups B, C, and D (p<0.05). In group A, mean uNGAL was significantly elevated on day 0 and daily for 5 days when compared with that of the day before culture (p<0.05 to <0.005). uNGAL shows promise as an early marker for culture-positive sepsis in VLBW infants.

Oxidative Stress Markers and Antioxidant Status after Oral Iron Supplementation to Very Low Birth Weight Infants

To evaluate whether our current practice of giving iron 18 mg daily to 6-week-old infants with very low birth weight (VLBW) was associated with increased oxidative stress markers or decreased antioxidant status. The study was a prospective observational study of 21 healthy VLBW infants (born at gestational age <32 weeks, birth weight <1500 g). Blood and urine were sampled twice before starting iron supplementation at 6 weeks postnatal age and after 1 week of iron supplementation at age 7 weeks. Urine 8-isoprostane was analyzed by gas chromatography-mass spectrometry and plasma total hydroperoxides were measured. Antioxidant status was assessed by ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), ferric-reducing ability of plasma, and plasma glutathione. After 1 week of iron supplementation, no significant changes in urine 8-isoprostane or plasma total hydroperoxides were seen, and plasma antioxidants were largely unchanged. Markers of oxidative stress in urine and plasma antioxidant status in healthy VLBW infants fed human milk remained unchanged after high-dose oral iron supplementation.

Brainstem auditory evoked responses in very low birthweight infants with chronic lung disease

Very low birthweight (VLBW) infants who had prolonged oxygen dependence due to chronic respiratory problems, typically neonatal chronic lung disease (CLD), are at high risk of neurodevelopmental impairment. To assess the effect of CLD on neonatal auditory function we studied brainstem auditory evoked response (BAER) in VLBW infants who suffered CLD but no other major perinatal complications or problems. At 37–42 week postconceptional age, the latencies of waves I, III and V in CLD infants were all significantly longer than in normal term infants (all p < 0.001 ). The differences between CLD infants and the term controls were greater for the later waves than for the earlier waves. Abnormally prolonged wave latency (>2.5 SD of the mean measurement) was seen in 7 (21.2%) CLD infants for wave I, suggesting peripheral auditory impairment, 8 (24.2%) for wave III and 14 (42.4%) for wave V. I–V interval in CLD infants was significantly longer than in the term controls ( p < 0.001 ) . Seven (21.2%) infants had abnormally prolonged I–V interval, suggesting brainstem or central auditory impairment. Of these infants, 2 had both prolonged wave latencies and prolonged I–V interval, suggesting both peripheral and central auditory impairment. Similar abnormalities were found in CLD infants when compared with the BAER in birthweight- and age-matched healthy VLBW infants without CLD. Conclusion Neonatal auditory function is impaired, both peripherally and centrally, at term age in VLBW infants who suffer neonatal CLD.

Does the choice of bottle nipple affect the oral feeding performance of very-low-birthweight (VLBW) infants?

Background: There is a continuous debate regarding the best bottle nipple to be used to enhance the bottle-feeding performance of a preterm infant. Aim: To verify that feeding performance can be improved by using the bottle nipple with the physical characteristics that enhance infants’ sucking skills. Methods: Ten “healthy” VLBW infants (941±273 g) were recruited. Feeding performance was monitored at two time periods, when taking 1–2 and 6–8 oral feedings/d. At each time and within 24 h, performance was monitored using three different bottle nipples offered in a randomized order. Rate of milk transfer (ml/min) was the primary outcome measure. The sucking skills monitored comprised stage of sucking, suction amplitude, and duration of the generated negative intraoral suction pressure. Results: At both times, infants demonstrated a similar rate of milk transfer among all three nipples. However, the stage of sucking, suction amplitude, and duration of the generated suction were significantly different between nipples at 1–2, but not 6–8 oral feedings/d. Conclusion: We did not identify a particular bottle nipple that enhanced bottle feeding in healthy VLBW infants. Based on the notion that afferent sensory feedback may allow infants to adapt to changing conditions, we speculate that infants can modify their sucking skills in order to maintain a rate of milk transfer that is appropriate with the level of suck-swallow-breathe coordination achieved at a particular time. Therefore, it is proposed that caretakers should be more concerned over monitoring the coordination of suck-swallow-breathe than over the selection of bottle nipples.

Does the choice of bottle nipple affect the oral feeding performance of very‐low‐birthweight (VLBW) infants?

There is a continuous debate regarding the best bottle nipple to be used to enhance the bottle-feeding performance of a preterm infant. To verify that feeding performance can be improved by using the bottle nipple with the physical characteristics that enhance infants' sucking skills. Ten "healthy" VLBW infants (941+/-273 g) were recruited. Feeding performance was monitored at two time periods, when taking 1-2 and 6-8 oral feedings/d. At each time and within 24 h, performance was monitored using three different bottle nipples offered in a randomized order. Rate of milk transfer (ml/min) was the primary outcome measure. The sucking skills monitored comprised stage of sucking, suction amplitude, and duration of the generated negative intraoral suction pressure. At both times, infants demonstrated a similar rate of milk transfer among all three nipples. However, the stage of sucking, suction amplitude, and duration of the generated suction were significantly different between nipples at 1-2, but not 6-8 oral feedings/d. We did not identify a particular bottle nipple that enhanced bottle feeding in healthy VLBW infants. Based on the notion that afferent sensory feedback may allow infants to adapt to changing conditions, we speculate that infants can modify their sucking skills in order to maintain a rate of milk transfer that is appropriate with the level of suck-swallow-breathe coordination achieved at a particular time. Therefore, it is proposed that caretakers should be more concerned over monitoring the coordination of suck-swallow-breathe than over the selection of bottle nipples.

Genetic Variants of TNF-α, IL-1β, IL-4 Receptor α-Chain, IL-6 and IL-10 Genes Are Not Risk Factors for Sepsis in Low-Birth-Weight Infants

The amount of inflammatory cytokines is a major determinant for the development of sepsis in very-low-birth-weight (VLBW) neonates. We investigated whether variants of tumor necrosis factor-α, interleukin (IL)-1β, IL-4 receptor α-chain, IL-6 and IL-10 genes, associated with altered cytokine production, might influence the risk and complications of sepsis in VLBW infants. We determined the presence of these genetic variants in dried blood samples of 33 septic, 35 infected and 35 healthy VLBW neonates by PCR and RFLP methods and analyzed their association with the risk and complications of sepsis. The frequencies of genetic variants did not differ in uninfected and in infected infants with or without sepsis. Moreover, none of the studied complications was associated with carrier state of any of genetic variants. Four of the 5 septic neonates with disseminated intravascular coagulation, however, carried simultaneously the variants of IL-1β and IL-10 genes. We concluded that these genetic polymorphisms do not influence the risk and course of sepsis in VLBW neonates.

Bronchopulmonary dysplasia: an enduring challenge.

1. Yvonne E. Vaucher, MD, MPH* 1. *Clinical Professor of Pediatrics, Division of Neonatology, University of California, San Diego, Calif. After completing this article, readers should be able to: 1. Describe the most common cause of chronic lung disease during infancy. 2. Explain the importance of a history of bronchopulmonary dysplasia throughout childhood. 3. Identify infants at high risk for developing bronchopulmonary dysplasia. 4. List the adverse effects associated with postnatal corticosteroids. Despite clinical advances in antepartum, intrapartum, and neonatal care, bronchopulmonary dysplasia (BPD) continues to challenge infants who have been in neonatal intensive care units and their caretakers. BPD is the most common cause of chronic respiratory disease during infancy and remains a major cause of long-term medical, pulmonary, and neurodevelopmental morbidity, increasing the cost of health care and the utilization of medical and educational resources throughout childhood. BPD is a clinical diagnosis, defined by oxygen dependence for a specific period of time after birth and accompanied by characteristic radiographic findings that correspond to anatomic abnormalities. Thus far, a precise physiologic definition of BPD is lacking. As the clinical presentation has evolved over the past 30 years, so has the definition. As originally described by Northway in the 1960s, the diagnosis of classic BPD was based on progressive radiographic changes in preterm infants who were treated for severe respiratory distress syndrome (RDS) immediately after birth and had prolonged ventilator and oxygen dependence. This form of BPD occurred in larger, relatively mature preterm infants, who required treatment with high-pressure mechanical ventilation and high concentrations of oxygen. Although the acute respiratory disease initially improved in these infants, oxygen requirements increased 7 to 10 days after birth and persisted for at least 28 days. The definition of BPD subsequently was modified by Bancalari to include preterm infants who had less severe RDS that initially required short-term mechanical ventilation, but who also developed persistent respiratory symptoms and an oxygen requirement for at least 28 days after birth …

Stool water loss in very-low-birth-weight neonates.

Fluid requirements in very-low-birth-weight (VLBW) infants include compensation for renal, insensible (skin and lung), and stool losses and provision for fluid retained for growth. Current estimates of stool water losses in VLBW infants are based on measurements established in term neonates. Therefore, the water content of 24-hour stool collections were determined in 11 healthy VLBW male infants on full enteral feeds and compared to the working norms. The neonates in this study were less than 2 weeks old with a mean +/- SD birth weight and gestational age of 1,311 +/- 112 g and 30.8 +/- 1.5 weeks, respectively. They were receiving only enteral formula feedings of 100 ml/kg/day or more with no parenteral fluid supplementation. The mean +/- SD number of stools and water content of the stools was 2.7 +/- 2.0/day and 7.2 +/- 4.0 ml/kg/day, respectively. There was a significant correlation (r = 0.696, p less than 0.02) between gestational age at birth and number of stools per day, but the correlation between stool water loss per day, gestational age, volume of feedings per day, and birthweight was not significant. Based on this study, 7 ml/kg/day is a reasonable estimate of daily stool water loss in VLBW babies.

Fortified mothers' milk for very low birth weight infants: Results of growth and nutrient balance studies

Mothers' milk, fortified daily with skim and cream components derived from mature donor human milk, was fed fresh during the first 2 postnatal months to 18 (group FMM) healthy, very low birth weight (VLBW) infants. Following the same feeding protocol, 16 additional VLBW infants were fed commercial formula that had a similar range of energy and nitrogen. Infants were evaluated for growth, metabolizable energy, balances of nitrogen and fat, and biochemical markers of nutritional status. Growth measurements from birth to 1800 gm were similar in the two groups. Nutritional balance was performed at approximately 2.5 (first study period) and 6 (second study period) weeks. Metabolizable energy (average 109 kcal/kg/day) was similar in both groups and met theoretical needs of the growing VLBW infant. Apparent nitrogen retention was similar and equivalent to estimates of intrauterine nitrogen accretion (approximately 325 mg/kg/day). Fat absorption increased from the first (70% of intake) to the second study (80% of intake) and was similar in both groups. Serum values for albumin, total protein, prealbumin, hemoglobin, and creatinine were also similar, and declined with increases in postnatal age. Significant differences were observed between feeding groups for serum phosphorus and calcium. These results indicate that healthy VLBW infants maintain adequate growth and macronutrient balance for the first 2 months postnatally when fed mothers' milk fortified with additional skim and cream components.

52 WHO IS REALLY DEVELOPMENTALLY AT RISK AMONG VERY LOW BIRTHWEIGHT INFANTS?

We studied the neurobehavioral development of 78 very low birthweight (VLBW) infants (< 1500 gms), beginning with the 1st week of life and continuing to 3 years of age. From birth through 40 weeks post-conceptional age (PCA) we used the Einstein Neonatal Neurobehavioral Exam (ENNBAS); from 40 weeks PCA to 2 years of age we used the Bayley Scales; in the third year we used the Stanford-Binet. The VLBW infants were divided into three age and weight-matched groups: 1) 12 infants with perinatal asphyxia (PNA) determined by an Apgar score of ≤ 4 at 5 minutes; 2) 14 infants with severe respiratory distress (RDS), requiring assisted ventilation for > 3 days (x=10 days), and 3) 52 healthy preterm infants without PNA, RDS, biochemical abnormalities, CNS infections or seizures. We found that: 1) during the preterm period, healthy VLBW infants and those with PNA develop equally well, and both do significantly better than RDS babies on all measures of visual, auditory and motor development; 2) from 40 weeks PCA to 3 years of age, healthy VLBW infants and those who had PNA consistently perform within normal standards on all tests of neurobehavioral development. VLBW infants who had RDS do significantly worse. We conclude that; 1) a short term respiratory insult (PNA) has very different developmental effects than a longer duration insult (RDS); 2) disturbances in neurobehavioral development which persist for up to 3 years may be detectable as early as the preterm period in certain groups of VLBW infants; 3) the “healthy” VLBW infant in our cohort develop normally through the third year of age.