Clinical characteristics of premature infants who orally feed on continuous positive airway pressure.

BACKGROUND: Between 32 and 34 weeks postconceptional age (PCA), premature infants typically achieve neuromuscular maturation to initiate the coordination of a nutritive suck triad. Many premature infants also require intubation, which has been associated with dysphagia in adults and infants. At our institution, despite these factors, some infants have been noted to tolerate oral feeds while on continuous positive airway pressure (CPAP). AIMS: Compare the clinical characteristics and duration of intubation in infants that initiate oral feedings on CPAP to infants that did not begin oral feeding on CPAP. STUDY DESIGN: Retrospective case control study. SUBJECTS: Infants with gestational age < 32 weeks who required CPAP at 32 weeks PCA. OUTCOME MEASURES: Oral feeding was defined as any oral feed ≥5 ml. Duration of intubation was defined as the number of intubated days prior to 32 weeks PCA. RESULTS: Of the 243 infants on CPAP at 32 weeks PCA, 31% (n = 76) began oral feeding on CPAP. Infants who initiated oral feeding on CPAP were of younger gestational age at birth (median 26 versus 27 weeks, p < 0.001) and remained intubated for longer (median 10.5 versus 2 days, p < 0.001). CONCLUSIONS: Infants who began oral feeding on CPAP had lower gestational age and longer duration of intubation than infants who started oral feeding off CPAP.

Neonatal Hypoglycemia.

Lower blood glucose values are common in the healthy neonate immediately after birth as compared to older infants, children, and adults. These transiently lower glucose values improve and reach normal ranges within hours after birth. Such transitional hypoglycemia is common in the healthy newborn. A minority of neonates experience a more prolonged and severe hypoglycemia, usually associated with specific risk factors and possibly a congenital hypoglycemia syndrome. Despite the lack of a specific blood glucose value that defines hypoglycemia, concern for substantial neurologic morbidity in the neonatal population has led to the generation of guidelines by both the American Academy of Pediatrics (AAP) and the Pediatric Endocrine Society (PES). Similarities between the 2 guidelines include recognition that the transitional form of neonatal hypoglycemia likely resolves within 48 hours after birth and that hypoglycemia that persists beyond that duration may be pathologic. One major difference between the 2 sets of guidelines is the goal blood glucose value in the neonate. This article reviews transitional and pathologic hypoglycemia in the neonate and presents a framework for understanding the nuances of the AAP and PES guidelines for neonatal hypoglycemia.

Low-Dose Parenteral Soybean Oil for the Prevention of Parenteral Nutrition-Associated Liver Disease in Neonates With Gastrointestinal Disorders.

BACKGROUND: Neonates with gastrointestinal disorders (GDs) are at high risk for parenteral nutrition-associated liver disease (PNALD). Soybean-based intravenous lipid emulsions (S-ILE) have been associated with PNALD. This study's objective was to determine if a lower dose compared with a higher dose of S-ILE prevents cholestasis without compromising growth. MATERIALS AND METHODS: This multicenter randomized controlled pilot study enrolled patients with GDs who were ≤5 days of age to a low dose (~1 g/kg/d) (LOW) or control dose of S-ILE (~3 g/kg/d) (CON). The primary outcome was cholestasis (direct bilirubin [DB] >2 mg/dL) after the first 7 days of age. Secondary outcomes included growth, PN duration, and late-onset sepsis. RESULTS: Baseline characteristics were similar between the LOW (n = 20) and CON groups (n = 16). When the LOW group was compared with the CON group, there was no difference in cholestasis (30% vs 38%, P = .7) or secondary outcomes. However, mean ± SE DB rate of change over the first 8 weeks (0.07 ± 0.04 vs 0.3 ± 0.09 mg/dL/wk, P = .01) and entire study (0.008 ± 0.03 vs 0.2 ± 0.07 mg/dL/wk, P = .02) was lower in the LOW group compared with the CON group. CONCLUSION: In neonates with GDs who received a lower dose of S-ILE, DB increased at a slower rate in comparison to neonates who received a higher dose of S-ILE. Growth was comparable between the groups. This study demonstrates a need for a larger, randomized controlled trial comparing 2 different S-ILE doses for cholestasis prevention in neonates at risk for PNALD.

Neonate with VACTERL Association and a Branchial Arch Anomaly without Hydrocephalus.

VACTERL (vertebral anomalies, anal atresia, cardiac defect, tracheoesophageal fistula, renal anomaly, limb anomalies) is an association of anomalies with a wide spectrum of phenotypic expression. While the majority of cases are sporadic, there is evidence of an inherited component in a small number of patients as well as the potential influence of nongenetic risk factors (maternal diabetes mellitus). Presence of hydrocephalus has been reported in VACTERL patients (VACTERL-H) in the past, with some displaying branchial arch anomalies. We report the unique case of an infant of diabetic mother with VACTERL association and a branchial arch anomaly-in the absence of hydrocephalus.

Screening for Critical Congenital Heart Disease in Newborns.

CCHD affects more than 25% of neonates born with congenital heart disease. Patients with CCHD require timely intervention in the form of surgery or cardiac catheterization to survive. These interventions may improve survival and outcomes for these patients. There is strong evidence that performing newborn pulse oximetry screening after the first 24 hours of life may help to detect more than 1200 neonates in the United States each year with CCHD. Pulse oximetry screening for CCHD has been demonstrated to be reasonable to implement and seems to be cost-effective. There is evidence that asymptomatic patients with CCHD can be diagnosed before clinical presentation or cardiovascular collapse with this screening. Pulse oximeter screening has been endorsed by several national organizations as a valuable newborn screening tool. Implementation of pulse oximetry screening programs in a standardized manner with strong communication among all involved parties will likely improve outcomes as well. As we move forward, we as clinicians should work to have a centralized system of reporting positive CCHD results, prompt patient evaluation, and good follow-up for the families of those neonates with positive screening results. Achieving these objectives will likely help us to achieve the goal of improving outcomes of the most critical neonates with CCHD.

Packed red blood cell transfusion (PRBC) attenuates intestinal blood flow responses to feedings in pre-term neonates with normalization at 24 hours.

OBJECTIVE: To determine whether packed red blood cell (PRBC) transfusion affects post-prandial superior mesenteric artery blood flow velocities (SMA BFVs) in very-low birth weight (VLBW) neonates and if so, at what time point after transfusion restoration of previous SMA BFV patterns occurs. DESIGN/METHODS: VLBW pre-term neonates, older than 14 days and tolerating bolus enteral feedings administered every 3 h were enrolled in this prospective observational study. Pulsed Doppler ultrasound was used to measure pre- and post-prandial (at 45 min) time-averaged mean, peak and end diastolic velocities (TAMV, PSV, EDV) immediately before and after 15 ml/kg of PRBC transfusion was given over 3 h; patent ductus arteriosus (PDA) status was also evaluated. Subsequent pre- and post-prandial SMA BFVs were recorded 24 and 48 h after the transfusion. RESULTS: Pre- and post-prandial measurements were obtained for 21 out of 25 enrolled infants. Post-prandial SMA BFVs were attenuated during the feedings immediately after transfusion; at 24 and 48 h after transfusion, changes in post-prandial SMA BFVs were similar to those measured prior to transfusion; the presence of the PDA did not affect results. CONCLUSIONS: PRBC transfusion blunted SMA BFV responses to feedings immediately after the transfusion with normalization observed 24 h post-transfusion.

Feeding preterm neonates with patent ductus arteriosus (PDA): intestinal blood flow characteristics and clinical outcomes.

OBJECTIVE: To evaluate the effects of patent ductus arteriosus (PDA) on postprandial superior mesenteric artery blood flow velocities (SMA BFV)s and feeding tolerance in extremely low birth weight (ELBW) neonates. METHODS: Appropriate for gestational age, ELBW preterm neonates, tolerating bolus enteral feedings were eligible to participate in this prospective observational study. Pulsed Doppler was used to measure preprandial and postprandial (at 30 and 60 min) time-averaged mean velocity (TAMV), peak systolic velocity (PSV) and end diastolic velocity (EDV) once during the day of life 5-7; at the same time, PDA size was estimated using the PDA: left pulmonary artery (LPA) ratio. RESULTS: A total of 38 infants were studied, 16 in small, 13 in moderate and 9 in large PDA groups. The postprandial SMA BFVs were lower in the large PDA group, although not reaching statistical significance. Importantly, infants in the large PDA group reached full enteral intake later (p = 0.02) and had higher incidence of death secondary of necrotizing enterocolitis (NEC; p = 0.04). CONCLUSIONS: ELBW preterm neonates with large PDA may have attenuated intestinal blood flow responses to feedings. There was also an association with higher rates of necrotizing enterocolitis and feeding intolerance in the large PDA group.

Neonatal pancytopenia associated with de novo 1q43-44 deletion and 10p15 duplication.

Deletion of 1q43-44 has been reported in >50 cases. Phenotype-genotype correlation of this deletion has recently been described based on 20 pure cases. This led to the definition of critical regions and candidate genes for microcephaly, corpus callosum abnormalities, and seizure disorders. Variable penetrance and expressivity are associated with 1q43-44 microdeletion syndrome, explaining the lack of correlation in rare cases. Despite variation in size of the deletion, most cases are characterized by typical dysmorphic features, but none have demonstrated neonatal pancytopenia. We report on a newborn with partial monosomy 1q43-44 and partial trisomy 10p15.1→10pter born with dysmorphic features and neonatal pancytopenia. Array-CGH analysis characterizes the deletion and the duplication as terminal with estimated sizes of 8 to 9 and 5 to 6 Mb, respectively. Conventional cytogenetic analysis showed the 10p duplication as unbalanced and translocated onto 1q. The deletion in the 1q43-44 region is the largest among the 20 cases reported most recently. The 10p partnership with the derivative 1q43-44 region is unique. We discuss the association of neonatal pancytopenia with 1q deletion and 10p duplication, in light of a recent published case of acute lymphoblastic leukemia in a constitutional case of 1q deletion and 1p duplication.

Plasma fatty acids in premature infants with hyperbilirubinemia: before-and-after nutrition support with fish oil emulsion.

Infants who are dependent on parenteral nutrition (PN) sometimes develop PN-associated cholestasis (PNAC). A compassionate use protocol, approved by the U.S. Food and Drug Administration and the institutional review board, guided enrollment of hospitalized infants with PNAC (<1 year of age, PN dependence for >3 weeks). Plasma concentrations of essential fatty acids were monitored before and after a soybean-based PN lipid, infused at 3 g/kg body weight/d, was replaced by an experimental fish oil-based intravenous fat emulsion (FO-IVFE) at 1.0 g/kg/d. All participants were born premature (n = 10; 20% male). At enrollment, infants were (mean ± SD) 86.5 ± 53.5 days of life and weighed 2.24 ± 0.87 kg; direct bilirubin was 5.5 ± 1.3 mg/dL. After treatment, blood concentrations significantly increased from baseline (P < .017) for circulating eicosapentaenoic acid (6.3 ± 3.0 to 147.8 ± 53.1 µg/mL), docosahexaenoic acid (20.7 ± 6.5 to 163.7 ± 43.4 µg/mL), pristanic acid (0.01 ± 0.01 to 0.17 ± 0.03 µg/mL), and phytanic acid (0.06 ± 0.03 to 0.64 ± 0.15 µg/mL). In contrast, total plasma ω-6 fatty acids (including linoleic acid) decreased (P < .017). The triene/tetraene ratio remained below the threshold value of 0.2 that defines ω-6 deficiency. No adverse effects were observed attributable to FO-IVFE. Discontinuation of FO-IVFE was typically due to infants (body weight 3.76 ± 1.68 kg) transitioning to enteral feeding rather than for resolution of hyperbilirubinemia (direct bilirubin 7.9 ± 4.8 mg/dL). These exploratory results suggest that FO-IVFE raises circulating ω-3 fatty acids in premature infants without development of ω-6 deficiency in the 8.3 ± 5.8-week time frame of this study.

Factors that affect the postnatal increase in superior mesenteric artery blood flow velocity in very low birth weight preterm infants.

OBJECTIVE: To identify factors related to the postnatal increase in superior mesenteric artery blood flow velocity (SMA BFV). STUDY DESIGN: SMA BFV was measured in 35 infants (birth weight 1047±246 g) on day of life (DOL) 1, 3, 5, 7 10 and 14. Latent curve modeling (LCM) was used to measure the longitudinal change in BFV for each subject, and the correlation between changes in BFV and baseline values. Non-parametric correlations were calculated between BFV and variables previously reported to be related to SMA BFV. RESULTS: There was significant variability in SMA BFV on DOL 1, a significant increase from DOL 1-14, and significant variability in the postnatal increase. Infants with higher enteral feeding volumes had greater increases, while infants receiving positive pressure ventilation or hyperalimentation had lower increases. CONCLUSIONS: Several clinical factors affect the postnatal increase in SMA BFV. The use of LCM is useful in longitudinal studies of very low birth weight (VLBW) infants, who are clinically and demographically heterogeneous.

Effects of maternal magnesium sulfate administration on intestinal blood flow velocity in preterm neonates.

BACKGROUND: Antenatal MgSO4 administration is used extensively as a tocolytic agent and to treat preeclampsia. Various effects on the fetus and newborn have been reported, and MgSO4 has well-documented vasoactive effects. OBJECTIVE: To determine if antenatal MgSO4 administration affects intestinal blood flow velocity in newborn preterm infants. METHODS: Peak, mean and end-diastolic velocities in the superior mesenteric artery were measured on day 1 of life. Maternal medical records were reviewed to identify infants whose mothers had been administered MgSO4 for preterm labor or preeclampsia within 24 h of delivery. RESULT: Fifty-six infants were studied: 27 were exposed and 29 were not exposed to antenatal MgSO4. Mean birth weight (1,371 ± 349 and 1,401 ± 469 g, respectively), gestational age (29.7 ± 2.0 and 30.0 ± 2.9 weeks, respectively) and infant hemodynamic and clinical variables (other than clinical indication for antenatal MgSO4 administration) were similar between groups. There were no significant differences between the exposed and unexposed groups in intestinal blood flow velocities. For the exposed group, however, there was a significant negative correlation between mean velocity and the number of hours from birth to the time superior mesenteric artery blood flow velocity measurements were made (p = 0.002); there was no correlation for the unexposed group (p = 0.852). CONCLUSION: Group mean values indicate that antenatal exposure to MgSO4 does not significantly affect intestinal blood flow velocity in newborn preterm infants. However, the significant negative relationship between mean blood flow velocity and time from birth to blood flow velocity measurement in exposed infants suggests that there may be measurable effects of MgSO4 exposure within the hours immediately after birth. Trials that prospectively evaluate the development of intestinal blood flow velocities are needed to further clarify potential effects of antenatal MgSO4 on the gastrointestinal tract of preterm infants.

Increased poly(ADP-ribose) polymerase (PARP)-1 expression and activity are associated with inflammation but not goblet cell metaplasia in murine models of allergen-induced airway inflammation.

Inflammation plays a key role in lung injury and in the pathogenesis of asthma. Two murine models of allergic airway inflammation-sensitization and challenge to ovalbumin (OVA) and intratracheal exposure to interleukin-13 (IL13)-were used to evaluate the expression of poly(ADP-ribose) polymerase-1 (PARP-1) in allergic airway inflammation. Inflammation is prominent in OVA-induced allergic asthma, but this inflammation is greatly reduced by a PARP-1 inhibitor and almost eliminated when PARP-1 knockout mice are subjected to the OVA model. The present study temporally evaluated PARP-1 protein expression, localization, and activity, as well as inflammation and goblet cell metaplasia (GCM), in murine lungs following a single OVA challenge or IL13 exposure. Following OVA challenge PARP-1 protein expression and activity were greatly increased, being maximal at 3 to 5 days following OVA exposure and beginning to decrease by day 8. These changes correlated with the timing and degree of inflammation and GCM. In contrast, PARP-1 protein or activity did not change following single IL13 exposure, though GCM was manifested without inflammation. This study demonstrates that both PARP-1 protein and activity are increased by allergen-activated inflammatory mediators, excluding IL13, and that PARP-1 increase does not appear necessary for GCM, one of the characteristic markers of allergic airway inflammation in murine models.

Enteral administration of a simulated amniotic fluid to very low birth weight neonates.

OBJECTIVE: To reduce feeding intolerance among very low birth weight neonates. STUDY DESIGN: A total of 10 neonates with birth weights of 750 to 1250 g were given oral-gastric boluses (2.5 ml/kg every 3 hours) of a solution patterned after amniotic fluid. When milk feedings were begun the milk was mixed with the test solution. The solution was given at a constant daily dose of 20 ml/kg/day while the volumes of milk feedings were gradually increased. When milk feedings reached 80 ml/kg/day the test solution was discontinued. A comparison group consisted of neonates who met study criteria but were cared for during the period immediately preceding the study. The outcome was the number of calories taken enterally over the first 21 days of life. RESULTS: The test solution was begun an average of 27 hours after birth (range, 4 to 45). In the test group the first milk feedings were introduced 74 hours after birth (range, 18 to 144), which was similar to the time milk was introduced in the comparison subjects (79 hours; range, 18 to 168). After milk feedings were started, the test patients had a total of four NPO days (0.4 NPO days per patient) during their first 21 days, while the comparison group had 34 NPO days (3.4 NPO days per patient). During the first 14 days of life the test solution recipients had a median of 26.5 enteral cal/kg/day (range, 4.3 to 68.9), while the comparison neonates had 8.5 (range, 0.2 to 25; p < 0.05). During the first 21 days of life the test solution recipients had a median of 56.9 enteral cal/kg/day (range, 11.5 to 89.4), while the comparison neonates had 19.2 (range, 0.9 to 52.8; p < 0.05). CONCLUSION: In all, 10 VLBW infants tolerated the test solution for periods up to 14 days with no significant adverse effects. A randomized trial to determine whether this solution reduces feeding intolerance among VLBW neonates should be conducted.