BNP, troponin I, and YKL-40 as screening markers in extremely preterm infants at risk for pulmonary hypertension associated with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is often complicated by pulmonary hypertension (PH). We investigated three biomarkers potentially suitable as screening markers for extremely preterm infants at risk of BPD-associated PH. In this prospective observational cohort study conducted in a tertiary neonatal intensive care unit, 83 preterm infants with BPD born <28-wk gestation and still inpatients at 36-wk corrected age received an echocardiogram and blood tests of B-type natriuretic peptide (BNP), troponin I, and YKL-40. Infants were analyzed according to echocardiographic evidence of tricuspid regurgitation (TR). Thirty infants had evidence of TR on echocardiogram at 36-wk corrected age. Infants with or without TR had similar baseline demographics: mean ± SD gestational age 261 ± 12 vs. 261 ± 11 wk and birth weight 830 ± 206 vs. 815 ± 187 g, respectively. There was no difference in duration of respiratory support. The right ventricular systolic pressure of infants with evidence of TR was 40 ± 16 mmHg. BNP was the only biomarker that proved to be significantly higher in infants with evidence of TR: median (interquartile range) serum level 54.5 (35-105) vs. 41.5 (30-59) pg/ml, P = 0.043. Subgroup analysis of infants with severe BPD requiring discharge on home oxygen or BPD-related mortality revealed similar results. There was no difference between groups for troponin I and YKL-40. In conclusion, increased serum levels of BNP were associated with evidence of TR at 36-wk corrected gestational age in extremely preterm infants, suggesting a potential role as a screening biomarker for BPD-associated PH.

Gentamicin trough levels using a simplified extended-interval dosing regimen in preterm and term newborns.

UNLABELLED: To evaluate a simplified gentamicin extended-interval dosing regimen in a large cohort of preterm and term newborns, we conducted a retrospective cohort study over a 4-year period. All inborn newborns who received gentamicin for the first episode of suspected or proven sepsis were eligible. Newborns received 4 mg/kg gentamicin intravenously 24-hourly, except for those at <28 weeks of gestation who received gentamicin 36-hourly. Trough levels were taken before the third dose and considered non-toxic if ≤2 µg/mL. Infants were analysed in gestational age subgroups: <28 weeks, 28-31 weeks, 32-35 weeks, 36-39 weeks and ≥40 weeks. Newborns who received indomethacin co-medication were analysed separately. Nine hundred ninety-three newborns, gestational age range 23(+2)-42(+1) weeks, birth weight range 397-5936 g, were included. The median (interquartile range (IQR)) gentamicin trough level for all newborns was 1.3 µg/mL (0.8-1.7). Ninety per cent of newborns had non-toxic trough levels. The incidence of trough levels >2 µg/mL was between 2.2 and 9.7 % in all subgroups except for infants born at 28-31 weeks of gestation, where 21.7 % of trough levels were >2 µg/mL. Indomethacin co-medication significantly increased the median gentamicin trough level in preterm infants at <32 weeks of gestation. CONCLUSION: This study demonstrates that simplified gentamicin dosage regimens are feasible. Prospective evaluations are required to establish safety profiles.

B-type and N-terminal pro-B-type natriuretic peptides are equally useful in assessing patent ductus arteriosus in very preterm infants.

AIM: B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NTproBNP) have been shown to correlate with the size of the patent ductus arteriosus (PDA) in preterm infants. We investigated whether BNP or NTproBNP was more closely correlated with PDA size. METHODS: This prospective observational study included preterm infants born <32 weeks' gestation who had an echocardiogram performed within the first four days of life. Blood samples were taken simultaneously for BNP and NTproBNP measurements prior to echocardiographic examination. RESULTS: Of the 60 infants recruited, 58 had complete data sets. The cohort's mean and standard deviation (SD) gestational age was 27(+3) (2(+2)) weeks, the mean (SD) birthweight was 1032 (315) grams, and 46 (79.3%) infants had a PDA with a mean (SD) diameter of 3.2 (0.9) mm. Median and interquartile range (IQR) BNP levels were 486.5 (219-1316) pg/mL for infants with a PDA and 190 (95.5-514.5) pg/mL for infants without a PDA. Median (IQR) NTproBNP levels were 10 858.5 (6319-42 108) pg/mL for infants with a PDA and 7488 (3363-14 227.5) pg/mL for infants without a PDA. Both BNP (R = 0.35, p = 0.0066) and NTproBNP (R = 0.31, p = 0.018) were significantly correlated with PDA size. CONCLUSION: BNP and NTproBNP are similarly useful for assessing PDA size in preterm infants.

Validation of cerebral venous oxygenation measured using near-infrared spectroscopy and partial jugular venous occlusion in the newborn lamb.

Near-infrared spectroscopy combined with partial jugular venous occlusion (JVO) offers promise for determining cerebral venous saturation (CSvO(2)) in sick preterm infants, but has not been validated in the newborn brain or under conditions of hypoxaemia. We assessed the accuracy of the CSvO(2) estimate using cerebral venous oxygen saturation in superior sagittal sinus blood (SSSO(2)) as the 'gold standard'. Comparisons were made in seven newborn lambs over a wide range of arterial oxygen saturations (SaO(2)) of 20% to 100%. Overall, median (range) CSvO(2) was 49.8% (10.6% to 88.5%), whereas SSSO(2) was 45.5% (4.3% to 76.6%); Bland-Altman analysis revealed a mean difference (CSvO(2)-SSSO(2)) of 5.1% and limits of agreement of +/-27.4%. The change in cerebral blood volume (DeltaCBV) induced by JVO increased with SaO(2) (P<0.05). In addition, the strength of the correlation of CSvO(2) with SSSO(2) progressively improved with increasing change in total haemoglobin concentration (DeltaHbT) induced by JVO. With Bland-Altman analysis repeated for data with DeltaHbT >30 micromol cm, the mean difference (CSvO(2)-SSSO(2)) decreased to 2.4% with limits of agreement of +/-18.8%. We conclude that the accuracy of estimating CSvO(2) varies with the DeltaCBV induced by JVO. Potential differences of optical properties between the head of the lamb and the human infant suggest that caution be exercised in directly applying these data to the human newborn. Nevertheless, this critical aspect of the JVO technique needs to be taken into consideration in developing an accurate measurement for sick preterm human infants.

Power spectral analysis of two-channel EEG in hypoxic-ischaemic encephalopathy.

AIMS: Power spectral analysis combined with a two-channel EEG system may be useful in management of newborn term infants at risk of hypoxic-ischaemic encephalopathy (HIE). This pilot study aimed to determine differences in the EEG power spectrum between normal term infants, infants who were at risk of but had not developed HIE, and infants who had developed HIE. DESIGN: Observational. METHODS: EEG recordings from normal term newborn infants and term infants at risk of HIE were analyzed using fast Fourier transforms. EEG total power (TP), TP variance, TP coefficient of variation (TP CV) and spectral edge frequency (SEF) were compared between three groups: control infants (n=15); at-risk infants who had not developed clinically diagnosed HIE (n=4); and at-risk infants who had developed HIE (n=7). RESULTS: Total power was similar in all groups. Variation of TP (variance and CV) was higher (p<0.05) in control infants than in infants at risk of HIE, regardless of whether they had developed HIE. SEF values were similar across all three groups. CONCLUSION: Reduced variation of EEG power is a feature of infants at risk of HIE.

Association of BNP, NTproBNP, and early postnatal pulmonary hypertension in very preterm infants.

OBJECTIVE: B-type natriuretic peptide (BNP) has been shown to correlate with pulmonary hypertension (PH) in term neonates with persistent pulmonary hypertension of the newborn or congenital diaphragmatic hernia, and in very preterm infants with bronchopulmonary dysplasia. This study investigated the potential association of BNP and N-terminal-pro-BNP (NTproBNP) and PH within the first 72 hr of life in very preterm infants. METHODS: Preterm infants <32 weeks gestational age who received an echocardiogram within the first 72 hr of life were eligible. BNP and NTproBNP were sampled at the time of the echocardiogram. Right ventricular systolic pressure (RVSP) was calculated as a surrogate marker of PH. Simple and multiple linear regression analysis was performed to examine associations and potential confounding factors. RESULTS: Sixty-one infants were included with a median (IQR) birth weight of 983 g (826-1,167) and a median (IQR) gestational age of 27(2) weeks (26(2) -28(6) ). There was no difference between BNP or NTproBNP levels for infants with or without measurable RVSP. There was no significant correlation of BNP and RVSP in multiple linear regression analysis (regression coefficient -0.0035 (95%CI: -0.020 to 0.013), P = 0.67). Also, NTproBNP and RVSP were not significantly correlated in multiple linear regression analysis (regression coefficient 0.0071 (95%CI: -0.019 to 0.033), P = 0.58). CONCLUSION: B-type natriuretic peptides did not correlate with RVSP in the early postnatal period of very preterm infants. Pediatr Pulmonol. 2016;51:820-824. © 2016 Wiley Periodicals, Inc.

Point-of-care testing of blood glucose in the neonatal unit using the AVL Omni 9 analyser.

BACKGROUND: Blood glucose measurements in newborns at risk of hypoglycaemia are an essential part of their medical management. Blood glucose measurements obtained by point-of-care testing using an AVL Omni 9 blood gas and metabolite analyser were compared with those obtained in the central laboratory using a Dade Dimension RXL analyser. METHODS: Blood glucose was measured at the point of care by nursing staff using an AVL Omni 9 blood gas and metabolite analyser and compared to results obtained in the central laboratory using a DADE Dimension RXL analyser. In total, 123 samples were taken from 114 babies admitted to the neonatal unit. RESULTS: The limits of agreement between the AVL Omni 9 and the central laboratory were 0.0 +/- 0.6 mmol/L for glucose values between 0.5 and 13 mmol/L. Regression analysis showed: AVL Omni 9 glucose = 0.977 x plasma glucose+0.14. There was also a good correlation (r = 0.92) between the AVL Omni 9 and the DADE Dimension RXL analyser for glucose values < 3 mmol/L. The limits of agreement for the AVL Omni 9 when compared with the DADE Dimension RXL analyser were -0.1 +/- 0.5 mmol/L. DISCUSSION: Point-of-care testing of blood glucose using the AVL Omni 9 blood gas and metabolite analyser is a reliable means of measuring blood glucose and has the advantage of providing a fast result using small volumes of blood.

The effect of sildenafil on evolving bronchopulmonary dysplasia in extremely preterm infants: a randomised controlled pilot study.

OBJECTIVE: Sildenafil has been shown to preserve alveolar growth and lung angiogenesis in a rat model of bronchopulmonary dysplasia. We conducted a proof-of-concept randomised controlled pilot study to assess the feasibility of oral sildenafil treatment in extremely preterm infants with evolving bronchopulmonary dysplasia. METHODS: Preterm infants <28 weeks gestational age were eligible if they were mechanically ventilated on day 7 of life. Infants were randomised to a 4-weeks course of either oral sildenafil (3 mg/kg/day) or placebo solution. Pre-discharge cardiorespiratory outcomes and medication side effects were collected. RESULTS: Twenty infants were randomised, 10 received sildenafil (mean gestational age 24 + 5 weeks (SD 4.9 days), mean weight 692 g (SD 98)) and 10 received placebo (mean gestational age 24 + 5 weeks (SD 6.5 days), mean weight 668 g (SD 147)). One infant in the sildenafil group did not receive treatment because of an early pneumoperitoneum. Two infants did not complete the study (transferred out). Of the remaining seven treated infants, three died (two from respiratory-related causes). One infant in the control group died from a non-respiratory cause. Sildenafil did not reduce length of invasive (median 688 versus 227 h) or non-invasive ventilation (median 1609 versus 1416 h). More infants in the sildenafil group required postnatal steroid treatment. One infant developed hypotension following sildenafil administration and was excluded after three doses. CONCLUSIONS: In this pilot study, oral sildenafil treatment did not improve any short-term respiratory outcomes in extremely preterm infants.

Dopamine therapy promotes cerebral flow-metabolism coupling in preterm infants.

OBJECTIVE: Dopamine is widely used to maintain blood pressure in very preterm infants, but it may affect neurovascular regulation as it crosses the immature blood-brain barrier. We contrasted the relationship between cerebral perfusion and oxygen metabolism in preterm infants treated with dopamine because of hypotension with normotensive controls. DESIGN: Prospective observational study in a neonatal intensive care unit. METHODS: Cerebral metabolic rate of oxygen consumption (CMRO2) was determined via measurements of cerebral blood flow (CBF) and cerebral venous saturation (CSvO2) using near infrared spectroscopy. Twenty-six infants (median gestation 26 weeks) were studied at a median postnatal age of 17 h. Infants were categorised as control (n = 16) or dopamine-treated (DOPA, n = 10). RESULTS: No relationship was found between CBF and CMRO2 in the control group, while a strong positive correlation was found in the DOPA group (R (2) = 0.62, P = 0.01). Cerebral fractional oxygen extraction (CFOE) and CBF showed strong negative correlation in the control infants (R2 = 0.65, P < 0.001), but not in the DOPA group. CSvO2 was lower at decreased CBF (R2 = 0.56, P < 0.001) in the control infants, but not in the DOPA group. CONCLUSIONS: Cerebral blood flow-metabolism coupling in the very preterm brain differs strikingly from that in the mature brain, where CBF is coupled to CMRO2. In the very preterm brain, variations of cerebral oxygen extraction, not CBF, sustain CMRO2. In contrast, preterm infants receiving dopamine exhibit flow-metabolism coupling similar to the mature brain. These findings suggest a previously unrecognised role for dopamine in the preterm brain in promoting flow-metabolism coupling.

Hypotensive extremely low birth weight infants have reduced cerebral blood flow.

OBJECTIVES: Whether extremely low birth weight (ELBW) infants are at risk of cerebral hypoperfusion is uncertain because key issues concerning their cerebral blood flow (CBF) and mean arterial pressure (MAP) are unresolved: (1) whether CBF is pressure-passive or autoregulated; (2) the normal level of MAP; and (3) whether inotropic drugs used to increase MAP might inadvertently impair CBF. We addressed these issues in ELBW infants undergoing intensive care. METHODS: CBF (measured by near-infrared spectroscopy) and MAP were measured in 17 infants aged 1.5 to 40.5 hours. RESULTS: Five infants remained normotensive (MAP 37 +/- 2 mm Hg, [mean +/- SEM]); twelve became hypotensive (MAP 25 +/- 1 mm Hg) and were treated with dopamine (10-30 mug x kg(-1) per min). CBF of hypotensive infants (14 +/- 1 mL x 100 g(-1) per min) was lower than the CBF of normotensive infants (19 +/- mL x 100 g(-1) per min). After commencement of dopamine in hypotensive infants, MAP increased (29 +/- 1 mm Hg) and CBF also increased (18 +/- 1 mL x 100g(-1) per min). CBF was correlated with MAP in hypotensive infants before (R = 0.62) and during (R = 0.67) dopamine, but not in normotensive infants. A breakpoint was identified in the CBF versus MAP autoregulation curve of untreated infants at MAP = 29 mm Hg; no breakpoint was evident in dopamine-treated infants. CONCLUSIONS: In ELBW infants (1) cerebral autoregulation is functional in normotensive but not hypotensive infants; (2) a breakpoint exists at approximately 30 mm Hg in the CBF-MAP autoregulation curve; and (3) dopamine improves both MAP and CBF.