S. Nadya J. Kazzi

A Cluster-Randomized Trial of Benchmarking and Multimodal Quality Improvement to Improve Rates of Survival Free of Bronchopulmonary Dysplasia for Infants With Birth Weights of Less Than 1250 Grams

OBJECTIVE. We tested whether NICU teams trained in benchmarking and quality improvement would change practices and improve rates of survival without bronchopulmonary dysplasia in inborn neonates with birth weights of <1250 g. METHODS. A cluster-randomized trial enrolled 4093 inborn neonates with birth weights of <1250 g at 17 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Three centers were selected as best performers, and the remaining 14 centers were randomized to intervention or control. Changes in rates of survival free of bronchopulmonary dysplasia were compared between study year 1 and year 3. RESULTS. Intervention centers implemented potentially better practices successfully; changes included reduced oxygen saturation targets and reduced exposure to mechanical ventilation. Five of 7 intervention centers and 2 of 7 control centers implemented use of high-saturation alarms to reduce oxygen exposure. Lower oxygen saturation targets reduced oxygen levels in the first week of life. Despite these changes, rates of survival free of bronchopulmonary dysplasia were all similar between intervention and control groups and remained significantly less than the rate achieved in the best-performing centers (73.3%). CONCLUSIONS. In this cluster-randomized trial, benchmarking and multimodal quality improvement changed practices but did not reduce bronchopulmonary dysplasia rates.

Cumulative Index of Exposure to Hypocarbia and Hyperoxia as Risk Factors for Periventricular Leukomalacia in Low Birth Weight Infants

BACKGROUND. Hypocarbia and hyperoxia are risk factors for periventricular leukomalacia in low birth weight infants. The association of a cumulative index of exposure to hypocarbia and hyperoxia and periventricular leukomalacia has not been evaluated. OBJECTIVE. Our goal was to examine the relationship between cumulative index of exposure to hypocarbia and hyperoxia and periventricular leukomalacia during the first 7 days of life in low birth weight infants. METHODS. Blood gas results were recorded in 6-hour intervals among low birth weight infants in a prospective data registry. Cumulative index of exposure to hypocarbia was calculated as the difference between arterial carbon dioxide level and 35 mmHg multiplied by the time interval in hours for each 6-hour block in a 24-hour day for the first 7 days of life. Cumulative index of exposure to hyperoxia was calculated in the same manner for arterial oxygen level >80 mm Hg. The relationship between exposure to hypocarbia, hyperoxia, and periventricular leukomalacia was examined in 778 infants with blood gas and cranial sonography data. RESULTS. Twenty-one infants had periventricular leukomalacia. Hypocarbia occurred in 489 infants and hyperoxia in 502 infants. Infants with periventricular leukomalacia were more likely to have a lower gestational age and to require delivery room resuscitation than those without periventricular leukomalacia. More infants in the highest quartile of exposure to hypocarbia had periventricular leukomalacia compared to those with no hypocarbia. Risk of periventricular leukomalacia was increased in infants with the highest quartile of exposure to hypocarbia after adjusting for maternal and neonatal variables, none to be associated with periventricular leukomalacia. Cumulative index exposure to hyperoxia was not related to periventricular leukomalacia. CONCLUSIONS. Cumulative exposure to hypocarbia and not hyperoxia was independently related to risk of periventricular leukomalacia in low birth weight infants.

Oxygen Delivery Through Nasal Cannulae to Preterm Infants: Can Practice Be Improved?

Objective. Oxygen delivery through nasal cannulae to convalescent preterm infants is a common but largely unstudied practice. To learn more about current nasal cannula oxygen delivery practices, we examined the variations in oxygen delivery through nasal cannulae among the centers of the Neonatal Research Network, the frequency of prescription of low levels of oxygen, and the success of weaning to room air. We hypothesized that some infants treated with oxygen through nasal cannulae were receiving oxygen levels equivalent to those of room air. Methods. This was a descriptive, nested, cohort study of nasal cannula oxygen prescription among 187 infants with birth weights of <1250 g. All infants were studied at a postmenstrual age of 36 weeks, with a timed oxygen reduction challenge to establish their ability to be weaned to room air. The results of this challenge were compared with the fraction of inspired oxygen (Fio2) delivered, calculated as effective Fio2. Infants who maintained oxygen saturation values of ≥90% during oxygen weaning and during a 30-minute period in room air were defined as passing the challenge. Results. Fifty-two infants (27.8%) were receiving oxygen concentrations and flow rates through nasal cannulae that delivered an effective Fio2 of <0.23, of whom 16 were receiving oxygen concentrations and flow rates that delivered an effective Fio2 of 0.21. In addition, 22 infants (11.8%) were prescribed room air through nasal cannulae intentionally. Seventy-two percent of those prescribed an effective Fio2 of <0.23 passed the room air challenge. Conclusions. Prescription of oxygen with combinations of flow rates and oxygen concentrations that delivered a low effective Fio2 was common. We speculate that some of this, including the inadvertent prescription of an effective Fio2 equivalent to that of room air, is related to lack of knowledge of the effective Fio2. Routine calculation of effective Fio2 values may prompt earlier trials of room air and thus reduce unnecessary days of oxygen therapy.

Auditory Brainstem Response Abnormalities and Hearing Loss in Children With Craniosynostosis

OBJECTIVES. Craniosynostosis is a devastating disorder characterized by premature closure of the cranial plates before or shortly after birth. This results in an abnormally shaped skull, face, and brain. Little is known about hearing disorders in such patients, and nothing has been published about their auditory brainstem responses. Our objective was to evaluate such patients for auditory brainstem response and hearing disorders with the long-term goal of improving patient evaluation and management. PATIENTS AND METHODS. We evaluated the auditory brainstem responses, hearing, and brain images of children with fibroblast growth factor receptor 2 craniosynostosis (n = 11). RESULTS. Prolongation of the auditory brainstem response I-to-III interpeak latency was a frequent characteristic of fibroblast growth factor receptor 2 craniosynostosis, occurring in 91% of our patients. Prolongation of the III-to-V interpeak latency was an occasional characteristic, occurring in 27% of our patients. Whenever the I-to-III interpeak latency was prolonged, wave II was always abnormal. Associated morbidities included sensorineural hearing loss (27%), recurrent otitis media (100%), and Arnold-Chiari malformation (27%). Cranial decompression improved the interpeak latencies of 2 children. CONCLUSIONS. These previously undocumented auditory brainstem response abnormalities reflect abnormal neural transmission, which could cause peripheral and central auditory processing disorders. We speculate that the major pathogenic basis of the I-to-III interpeak latency and wave II abnormalities is compression of the auditory nerve as it passes through the internal auditory meatus and posterior fossa, which would explain the auditory nerve hearing loss, tinnitus, and vertigo that affect these children. Awareness of these abnormalities could lead to important advancements in the auditory and neurosurgical assessment and management of this overlooked patient group. We provide recommendations for the improved assessment and management of these patients. In particular, we recommend that auditory brainstem response diagnostics become standard clinical care for this patient group as the best way to detect auditory nerve compression.

Role of spontaneous breathing trial in predicting successful extubation in premature infants

The ability of clinicians to predict successful extubation in mechanically ventilated premature neonates is limited. Identifying objective criteria for predicting successful extubation may reduce the incidence of failed extubation and the duration of mechanical ventilation.

Role of angiotensin-converting enzyme gene polymorphism in persistent pulmonary hypertension of the newborn.

Aim:  To evaluate the association of angiotensin‐converting enzyme (ACE) gene polymorphism with risk/severity of persistent pulmonary hypertension of the newborn (PPHN) among at risk infants.

Does vitamin D deficiency affect placental inflammation or infections among very low birth weight infants

Abstract Objective: Examine the association between placental inflammation and neonatal infections, and 25OH vitamin D (25OH D) levels at birth among very low birth weight infants (VLBWI). Study design: Serum 25OH D levels were measured in 89 VLBWI (≤1250 g) and 47 mothers on day one, and in 78 infants on day 21. Placentas were examined for maternal and fetal inflammation. Infants were divided into deficient (≤10 ng/ml) and adequate (>10 ng/ml) groups based on 25OH D levels on day 1. Results: Mean ± SD maternal levels of 25OH D (21 ± 9 ng/ml) correlated with infants’ levels (15 ± 8 ng/ml), (p < .001). 25OH D levels were lower in deficient (32/89) than in adequate group (8 ± 2 versus 20 ± 7 ng/ml, p = .011). Infants’ 25OH D levels rose significantly by day 21 (p < .001). Univariate analyses showed no differences between infant groups in maternal or fetal inflammation, or neonatal infections (p > .05). Logistic regression analyses revealed no association between deficient 25OH D levels and the odds of maternal or fetal inflammation or other infections. Levels of 25OH D did not correlate with severity of placental inflammation. Conclusions: Deficient levels of 25OH D at birth are not associated with the occurrence of placental inflammation or neonatal infections among VLBWI.

Vitamin D deficiency and respiratory morbidity among African American very low birth weight infants

BACKGROUND Very low birth weight infants (VLBWI) have unexplained variation in respiratory morbidity, including respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). We examined a potential association to serum 25-hydroxyvitamin D (s-25OHD) on day one. STUDY DESIGN Prospective, observational study on 89 VLBWI (≤1250 g). S-25OHD (day one and 21) and respiratory severity score (RSS) (day one) were examined. Other respiratory morbidities including BPD were compared between infants with s-25OHD ≤ 10 ng/ml (deficient) versus >10 ng/ml (adequate). RESULTS Eighty one neonates (91%) were African Americans. The mean (SD) birthweight was 868 (229) g, gestational age 27 (2) weeks. On day one, mean (SD) s-25OHD was 15.48 (8.31) ng/ml, with 32 (37%) being vitamin D deficient. The deficiency and adequate VLBWI groups had similar birthweight; 860 (262) vs 873 (210) g, and gestational age; 27 (2) vs 27 (2) weeks. In 78 survivors, s-25OHD rose from 15.48 (8.31) ng/ml day one to 52.36 (22.49) ng/ml day 21 after supplementation, p < 0.001. On day one, increasing RSS was inversely related to s-25OHD, trend p = 0.054. Compared to the adequate group, the deficiency group had higher RSS (5.0 ± 2.7 vs 3.6 ± 1.9), required surfactant therapy more frequently (91% vs 72%), and needed home oxygen therapy more often (48% vs 26%), p ≤ 0.05 for all. Among infants with BPD, the severity of disease was inversely related to s-25OHD, trend p < 0.09. CONCLUSION Lower levels of s-25OHD were associated with increased severity of RDS and BPD among a cohort of mostly African American VLBWI.

Does Antenatal Indomethacin Decrease the Incidence of Severe Intraventricular Hemorrhage? 1173

Postnatal administration of indomethacin to preterm infants has been associated with a decreased incidence of severe intraventricular hemorrhage(IVH). However, maternal administration of indomethacin for preterm labor has been associated with increased neonatal complications, including severe IVH. Hypothesis: Antenatal indomethacin decreases the incidence of IVH in extremely premature infants. Method: Records of neonates between 24-28 wks of gestation, born from 1995-1997 to mothers in preterm labor were obtained from the hospital data base. Infants with prolonged premature rupture of membranes (> 18 hrs), no head ultrasound performed or incomplete records were excluded. Demographic variables were evaluated using T-test or Chi-square, as appropriate. Results: 109 infant met inclusion criteria, 26 infants were exposed to indomethacin and 83 were not. There were no difference between the two groups with respect to gestational age, birth weight, route of delivery, Apgar scores and maternal complications. Although the incidence of grades III-IV IVH was lower in the infants exposed to indomethacin (7% vs. 18%), this was not statistically different. There were no difference between the indomethacin-exposed and control groups with regard to incidence of NEC (15% vs. 13%), BPD (56% vs. 60%), PDA (50% vs. 66%), air leak(12% vs 24%), pulmonary hemorrhage (19% vs. 15%) and number of doses of surfactant (2.4% vs. 1.8%). Further analysis revealed that more mothers of indomethacin-exposed infants were given steroids prior to delivery (96% vs 61%, p < 0.001). Antenatal steroid administration was associated with a lower incidence of severe IVH (14% vs 45%, p < 0.001). Conclusion: Antenatal exposure to indomethacin among preterm infants is not associated with lower incidence of severe IVH nor increased occurrence of neonatal complications. Antenatal steroid administration significantly lowers the incidence of severe IVH in these infants.