This article was downloaded by: [Nanyang Technological University] On: 24 August 2015, At: 00:39 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: 5 Howick Place, London, SW1P 1WG

The Journal of Maternal-Fetal & Neonatal Medicine Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/ijmf20

Click for updates

Superior vena cava flow and intraventricular haemorrhage in extremely preterm infants a

ab

b

a

a

a

Sarah Bates , David Odd , Karen Luyt , Paul Mannix , Richard Wach , David Evans & Axel Heep

ab

a

Neonatal Intensive Care Unit, Southmead Hospital, North Bristol NHS Trust, Bristol, UK, and b

School of Clinical Science, University of Bristol, Bristol, UK Published online: 30 Jun 2015.

To cite this article: Sarah Bates, David Odd, Karen Luyt, Paul Mannix, Richard Wach, David Evans & Axel Heep (2015): Superior vena cava flow and intraventricular haemorrhage in extremely preterm infants, The Journal of Maternal-Fetal & Neonatal Medicine To link to this article: http://dx.doi.org/10.3109/14767058.2015.1054805

PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions

http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1–7 ! 2015 Informa UK Ltd. DOI: 10.3109/14767058.2015.1054805

ORIGINAL ARTICLE

Superior vena cava flow and intraventricular haemorrhage in extremely preterm infants Sarah Bates1, David Odd1,2, Karen Luyt2, Paul Mannix1, Richard Wach1, David Evans1, and Axel Heep1,2 Neonatal Intensive Care Unit, Southmead Hospital, North Bristol NHS Trust, Bristol, UK, and 2School of Clinical Science, University of Bristol, Bristol, UK

Downloaded by [Nanyang Technological University] at 00:39 24 August 2015

1

Abstract

Keywords

Objective: To evaluate the relationship between superior vena cava flow (SVCF) measurements within the first 24 h of life, and development of intraventricular haemorrhage (IVH) in extremely preterm infants. Study design: Single centre retrospective cohort study of 108 preterm infants born less than 28 weeks’ gestation. Main outcome measure was degree of IVH at day 7 postnatal age. Results: The mean GA of the study group was 25.4 weeks. Mean SVCF was lower (75 ml/kg/min) in infants later diagnosed with IVH (n ¼ 46) compared to infants, who did not develop IVH (87.7 ml/kg/min, p ¼ 0.055). PDA diameter was inversely associated with SVCF (p ¼ 0.024) and reversal of flow in the descending aorta (p ¼ 0.001). Sensitivity analysis did not confirm an independent association of SVCF with development of IVH [OR 0.990 (0.978–1.002), p ¼ 0.115]. Conclusion: Our study describes early SVCF in extremely preterm infants is associated with the extent of ductal shunting, but insensitive in predicting IVH.

Cardiac imaging techniques, colour Doppler echocardiography, extremely preterm infant, intraventricular haemorrhage, superior vena cava flow

Background The pathophysiology of intraventricular haemorrhage (IVH) in extremely preterm infants is complex. A major pathway in the pathogenesis of IVH is thought to be a hypoperfusion– reperfusion injury of the immature brain [1]. Functional echocardiography assessment of the heart has been established as a tool for use in management of extremely preterm infants during the first days of life. Assessment of Superior Vena Cava Flow (SVCF) as part of functional echocardiography has been previously described as a noninvasive measure of upper body (and therefore cerebral) blood flow return in preterm infants [2–4]. The occurrence and extension of IVH in extremely preterm infants has been correlated to low SVCF state on the first day of life [2,4–6]. However, only few centres perform routine echocardiography assessment of SVCF as it is a complex procedure. The National guidelines state that SVCF assessment requires further validation before being incorporated into standard practice [7]. In our unit, it is our chosen approach to measure SVCF as part of our routine functional echocardiographic assessment of extremely preterm babies, and to use this measurement to guide cardiovascular management through the early postnatal period. This has given us the opportunity

Address for correspondence: Dr Sarah Bates, Neonatal Intensive Care Unit, Southmead Hospital, North Bristol NHS Trust, University of Bristol, Southmead Road, Bristol BS10 NB5, UK. Tel: +44 117 323 3580. Fax: +44 117 323 5324. E-mail: [email protected]

History Received 7 December 2014 Revised 20 May 2015 Accepted 21 May 2015 Published online 26 June 2015

to present clinical data on SVCF and IVH in a large cohort of extremely preterm babies. The aim of the study was therefore to present a single centre long-term experience of SVCF evaluation on routine functional neonatal echocardiography of the heart within the first 24 h of life in extremely preterm born infants at highest risk of developing IVH. We hypothesised that low SVCF in the first 24 h of life, independent of the immaturity of the infant and other given perinatal risk factors, influences cerebral blood flow and predicts IVH risk at day 7 of life.

Patients/methods Design/patients The presented study design is a retrospective observational cohort study. All inborn and out born patients born at less than 28 completed weeks gestational age, who were admitted to the tertiary neonatal intensive care unit, at Southmead hospital, Bristol, UK, between March 2008 and January 2012, were eligible for this study. A total of 247 infants born at less than 27+6 weeks’ gestational age (GA) were admitted to our unit during this period. Twenty-two of these babies were admitted after the first day of life. Out of the remaining 225 eligible patients, 49 were excluded as they did not have an echo performed within the first 24 h of life. This left 176 infants who had early functional echocardiography. Fifty-seven of these patients did not have SVCF measurements recorded as part of their echo assessment (due to availability of one of the dedicated examiners to perform the study). A further 11

2

S. Bates et al.

patients were excluded as they died before 7 days’ postnatal age, leaving 108 infants for the analysis. Study infants were divided into groups according to the degree of IVH, diagnosed on cranial ultrasound (CrUS) at day 7 postnatal age. Clinical data and definitions Antenatal and perinatal characteristics of the study population were collected from patients’ electronic and written medical records. A full course of Antenatal Steroid Treatment was defined as administration of two doses of 12 mg betamethasone more than 24 h prior to delivery.

Downloaded by [Nanyang Technological University] at 00:39 24 August 2015

Laboratory data Blood samples were taken at two time points: (1) From umbilical catheter following admission to the neonatal unit and (2) at or near to 24 h postnatal age. Data collected included: haematocrit, total white cell count, total platelet count (Sysmex XE-2100 analyser, Milton Keynes, UK), serum C-reactive protein (CRP mg/l) (Roche COBAS analyser, Burgess Hill, UK), arterial blood gases (Premier Gem 4000, Instrumentation Laboratory, Roche, Burgess Hill, UK). Figure 1. SVCF assessment: (a) Low sub costal view of SVC/RA junction: Assessment of velocity time integral (VTI); (b) Parasagittal long axis: View of SVC diameter at entry to RA. Measurement of SVC diameter.

J Matern Fetal Neonatal Med, Early Online: 1–7

Echocardiographic studies and cardiovascular management All ultrasound studies were performed as part of the routine clinical assessment by two experienced examiners (DE, RW) using a Philips HD11XE USS machine (Guildford, UK) and 12 MHz sector probe. The Echocardiography followed the standardized protocol including assessment of left ventricular fractional shortening (FS; %), PDA diameter, descending aortic flow pattern and assessment of intra-atrial shunt measured on colour Doppler. The calculation of SVCF used a modified long axis view to assess SVC diameter and a subcostal view to assess shape of the SVC flow (Figure 1). Calculations followed those that have previously been described: [2] SVCflow ðml=kg=minÞ

 ! velocity time integral  ð  mean SVC2diameter =4

¼

 heart rate body weight

Low SVCF was defined as SVCF 41 ml/kg/min within first 24 h of life [2]. Arterial hypotension as well as the SVCF

Single centre retrospective observational cohort study

Downloaded by [Nanyang Technological University] at 00:39 24 August 2015

DOI: 10.3109/14767058.2015.1054805

findings were used to guide haemodynamic management as per our unit protocol. This protocol covers cardiovascular management in the first 24 h of life; arterial hypotension is defined as systemic blood pressure less than the 10th percentile for gestational age [8] and, in our unit, is managed initially with up to two 10 ml/kg crystalloid fluid boluses, followed by dobutamine 5–10 mg/kg/min, then dopamine at a similar dose, then 2.5 mg/kg hydrocortisone. Infants with Low SVCF assessment were commenced on dobutamine treatment, aiming for SVCF 450 ml/kg/min in the first 12 h of life. Based on cardio-circulatory stability (arterial BP, lactate), repeated echocardiographic assessment of SVCF was performed 12–24 hourly. Data on arterial ductal shunting were collected as measurements of arterial ductal diameter, pulsed or colour wave Doppler measurement of shunt direction and velocity and reversal of flow in the descending aorta. Arterial ductal significance was defined as 42.0 mm within first 6 h, 41.6 mm after 6 h of age with evidence of reversal of flow either in the descending aorta or anterior cerebral artery.

3

Data analysis Initially patient characteristics were derived and then comparison of demographics between those infants with an IVH and those without was investigated. Two sensitivity analyses were performed. In the first, the association between SVCF and IVH was adjusted for gestational age using a logistic regression model. In the second, the associations between PDA size (as measured on echo) and SVCF flow were investigated. Data were compared using t-test, Chi-square or Mann–Whitney U tests as appropriate. All analyses were conducted with Stata 10 software (Stata Corp, College Station, TX), and results are presented as number (percent), mean (SD) or median (range) as appropriate. Ethics Ethical approval was obtained from the North West NRES committee, UK (Reference: 12/NW/0903). According to the retrospective design of the study and given anonymised data, the committee did not require parental informed consent.

Cranial ultrasound imaging All studies were performed with a Philips HD11XE USS machine using a 8.5 MHz sector transducer. The presence of IVH was noted and classified according to Volpe [1]. Cranial Ultrasound findings and peak systolic and end diastolic velocities of blood flow measured by pulsed wave Doppler in the anterior cerebral artery proximal to the pericallosal branches were recorded at 12 h, 24 h and 7 days of postnatal age. Table 1. Demographics of the study population (n ¼ 108). Male

60 (55.6%)

Birth weight (g) Gestational age (weeks) IVH, n (%) Birth weight 59th centile, n (%) Mode of delivery *, n; (SVD/CS/IVD) Apgar score at 5 min Arterial cord Ph Antenatal Steroids* n (%)

746 (SD 172) 25.4 (SD 1.2) 46 (43%) 15 (14%) 59/44/3 8 (6–8) 7.3 (7.2–7.3) 67 (63%)

SVD: spontaneous vaginal delivery, CS: caesarean section, IVD: instrumental vaginal delivery, Antenatal steroids: defined as complete course of antenatal steroids (2  12 mg betamethasone), *(n ¼ 106).

Results Demographic information of the study population is given in Table 1. Table 2 summarises the perinatal data of the study population divided into groups according to development of IVH. Initiation of treatment with inotropes (following the protocol as given in Methods) was similar in both groups. 89% of our study cohort survived to 28 days. 12 babies died within the neonatal period. In 74/108 of study patients, early cranial US (512 h of life) was performed. IVH was diagnosed in 8/74 (11%) of the early US. Table 3 provides the initial and 24 h blood testing for WBC, CRP, Hct and platelets in both patient subgroups. Table 4 summarises the echocardiography study results including Doppler measurements on the anterior cerebral artery during subsequent cranial ultrasound examinations. The age for initial cranial ultrasound/echocardiography assessment including SVCF within the study group was 7 h postnatal age (range 4–24 h). According to the definition of low SVCF, patients were stratified according to SVCF 41 ml/kg/min. The two sensitivity analyses were then performed.

Table 2. Patient characteristics. IVH (n ¼ 46) Male Birth weight (g) Gestational age (weeks) Birth weight 59th centile Mode of delivery (SVD/CS/IVD) Apgar score at 5 min Arterial cord pH Antenatal steroids (0/1/2) Inotropes*

25 761 25.1 2 33/11/1 8 7.3 7/15/22 27

(54%) (SD 212) (SD 1.3) (6.5%) (73.3%/24.5%/2.2%) (6–8) (6.8–7.3) (16%/34%/50%) (61.4%)

No IVH (n ¼ 62) 35 734 25.7 12 26/33/2 8 7.3 3/13/45 23

(56%) (SD 135) (SD 1.0) (19.4%) (43%/54%/3%) (7–9) (7.2–7.3) (5%/21%/74%) (41.8%)

p value 0.828 0.436 0.019 0.09 0.007 0.0527 0.9365 0.038 0.053

Study group (n ¼ 108) divided according to the diagnosis of IVH (IVH grades I–IV) on cranial ultrasound examination at day 7 of postnatal age. Mode of delivery (n ¼ 106): SVD: spontaneous vaginal delivery, CS: caesarean section, IVD: instrumental vaginal delivery, Antenatal steroids (n ¼ 105): 0 none, 1 incomplete course, 2 complete course, Inotropes: start of inotropic support to maintain arterial blood pressure in the normal range [8],*(n ¼ 99). IVH grades: (I) n ¼ 11; (II) n ¼ 13; (III) n ¼ 6; (IV) n ¼ 16.

4

S. Bates et al.

J Matern Fetal Neonatal Med, Early Online: 1–7

(1) There remained weak evidence that SVCF flow as associated with IVH risk in the univariable model (OR 0.988 (0.976–1.000), p ¼ 0.059); however, after correction for gestational age at birth this association weakened further (OR 0.990 (0.97781.002), p ¼ 0.115) (Figure 2). (2) PDA diameter was inversely associated with SVCF flow (p ¼ 0.024) and reversal of flow in the descending aorta (DAO) (p50.001). However, reversed flow in DAO was not correlated with SVCF (p ¼ 0.182) (Figure 3a and b).

Downloaded by [Nanyang Technological University] at 00:39 24 August 2015

Discussion We present a retrospective observational study examining the value of SVCF measurement on the first day of life in predicting risk of developing IVH in preterm infants born528 weeks’ GA, thereby focusing on infants at highest risk of developing IVH. Eight of the 46 study infants diagnosed with IVH were found to have early IVH on initial CrUS diagnosed at 12 h of age. There was a trend towards a lower GA in patients with early diagnosis of IVH; however, none of the analysed perinatal or echocardiography variables were different in those patients compared to those with IVH diagnosed later than 12 h of life. This finding is in contrast to Osborn et al. [4], who were able to describe distinct and different risk factors for early versus late IVH, in particular, late IVH to be associated with low SVCF on the first day of life. Other studies have speculated SVCF to be a surrogate marker for cerebral perfusion [9,10]. The regulation of cardiac output distribution in the preterm and term neonate is complex [11], and although the cardiac output is approximately equally Table 3. Laboratory findings at delivery (initial) and at 24 h postnatal age. IVH (n ¼ 46) Initial CRP (mg/dl) Hct (%) Platelets WBC (n) At 24 h CRP (mg/dl) Hct (%) Platelets WBC (n)

No IVH (n ¼ 62)

p value

1 42 176 7.6

(0.6–4.3) (37–45) (145–224) (4.6–13.9)

1 41 182 8.0

(0.6–1.00) (39–48) (154–229) (4.4–14.2)

0.4963 0.2881 0.3841 0.9925

3.4 40 147 7.7

(1.0–14.5) (36–45) (105–182) (5.3–14.8)

1.6 41 182 10.2

(1.0–4.0) (37–46) (150–247) (7.3–19.1)

0.1622 0.6010 0.0014 0.1113

Study group divided according diagnosis of IVH on cranial ultrasound examination at day 7 of postnatal age.

distributed to the upper and lower body, only 25–30% of the blood flow to the upper body reaches the brain [12,13]. It has been advocated to use near infrared spectroscopy [14], as well as MRI techniques to study systemic and organ-specific blood flow in newborn infants [15,16]. SVCF measurements and analysis followed a standardised protocol for SVCF assessment in echocardiography [2]. However, MRI studies [15,16] illustrate a non-laminar SVC profile, which might account for differences in ultrasound versus MRI SVCF assessments and might indicate a need to reassess the calculation of SVCF. We compared our measurements to normal SVCF values for preterm born infants [2]. Those normal values are based on assessment of otherwise stable preterm infants not requiring mechanical ventilation. Previous studies describe an increase of SVCF over time within the first 24 h of life [2,10]. In our study, first SVCF measurement was performed at a mean of 7 h, giving a mean SVCF of 80 ml/kg/min, which is in a similar range compared to recently published studies [6]. Kluckow and Evans [2–4] define low SVCF values as repetitive measurements of persistent SVCF 41 ml/kg/min, which, in their cohort, is strongly predictive of development of IVH. However, six of the 11 infants in their cohort who developed grade 3 or 4 IVH had co-incident acute pulmonary haemorrhage and air leak syndrome as confounding factors [2]. The incidence of IVH or separately severe IVH (grade 3 or 4) in our study did not correlate with this low SVCF state. Statistical analysis demonstrated a weak correlation of decreased SVCF with the development of IVH in our study, but the strength of this correlation was not predictive of IVH. This finding might be explained by the difference in timing of the SVCF measurement and the perinatal management within the studies. Compared to Holberton et al.’s [6] study, SVCF measurements in our study were performed earlier (7 h versus 12 h). Our study is the first to describe a cohort of ELBW babies, where low SVCF was being actively managed with cardiovascular support. In clinical practice, infants were managed following a standardised protocol for cardiovascular management. Cardiovascular intervention, as described in ‘‘Methods’’, was initiated in infants with diagnosed low arterial BP or Low SVCF. According to Kluckow and Evans [17], we chose SVCF as surrogate for systemic blood flow. The limit for cardiovascular intervention in SVCF was less than 50 ml/kg/min within the first 24 h of life, slightly higher than the cut-off of for healthy preterm infants (45 ml/kg/min) as presented in a previous study.

Table 4. Cerebral (ACA) and superior vena cava flow (SCVF) Doppler studies at 24 h of age. Patients (n) % Age at SVCF assessment (h) SVC flow (ml/kg/min) SVC flow 41 ml/kg/min (%) Vmax ACA syst (m/s) Vmax ACA diast PDA (mm) FS (%) Inotropes 524 h#

IVH (46) 43% 7 75.0 4 0.18 0.04 1.8 31.1 27

(4–14) (SD 24.7) (8.7%) (0.12–0.4) (0.01–0.09) (SD 0.6)) (SD 7.8) (61.4%)

No IVH (62) 57% 8 87.7 6 0.17 0.04 1.7 32.1 23

(4–15) (SD 38.9) (9.7%) (0.10–0.38) (0–0.12) (SD 0.6) (SD 6.7) (41.8%)

PDA diameter measured during Colour Doppler assessment at 24 h of age.

p value 0.8905 0.055 0.862 0.41 0.65 0.414 0.537 0.053

DOI: 10.3109/14767058.2015.1054805

Downloaded by [Nanyang Technological University] at 00:39 24 August 2015

Infants also received a top up blood transfusion if their total estimated blood loss exceeded 10 ml/kg. We speculate that the cardiovascular management might have influenced on low SVCF in our study population and potentially thereby may have influenced the incidence of IVH. Our study results demonstrate SVCF to be significantly related to PDA diameter and therefore, potentially, to PDA shunt volume. This finding is in accordance with the published MRI study results [16]. However, our results did not demonstrate an association between reversed flow in the DOA with reduced SVCF in the cohort. In contrast to Broadhouse et al. [16], all PDA studies were performed during first 24 h of life, unsurprisingly giving an increased PDA diameter compared to their findings. None of our

Single centre retrospective observational cohort study

5

patients had been treated with indomethacin or ibuprofen prior to their first SVCF measurement: it is our practice to use this first functional echocardiographic assessment to guide initiation of treatment for ductal closure. The echocardiography assessment of the patients followed a standardised protocol and was performed by two examiners (RW, DE) experienced in assessing the SVCF parameters as described. We acknowledge that our study suffers from a possible confounding factor of inter-observer variability, which potentially could have influenced the results. Groves et al. [18] pointed out the difficulty to assess repeatability of measurement of SVCF and descending aortic flow in preterm infants, reflecting the difficulty to standardise the Doppler technique. Ficial et al. [15] described a strong correlation of

Figure 2. SVCF (ml/kg/min) estimated from echocardiography. Study group divided according to the diagnosis of IVH (any grade) on day 7 CrUS. Data given as box plots: Box giving median and 25th to 75th percentile and whiskers indicating 5th and 95th percentile.

Figure 3. SVCF (a) and PDA size (b) estimated on echocardiography. Study group divided according to the diagnosis of reverse flow in the descending aorta (DAO). Data given as box plots: Box giving median and 25th to 75th percentile and whiskers indicating 5th and 95th percentile.

Downloaded by [Nanyang Technological University] at 00:39 24 August 2015

6

S. Bates et al.

echocardiographic assessment of left ventricular output with MRI. However, estimation of SVCF on echocardiography following standard SVCF assessment [2] showed a poor correlation to MRI assessment. SVC diameter from sagittal diameter measurement in the study systematically underestimated SVC area compared to MRI. Ficial et al. [15] also suggest an adaptation of the commonly used algorithm for SVCF measurement on echocardiography taking SVC area measurement directly from an axial view and applying a 50% reduction of VTI. Fluctuations in systolic and diastolic cerebral blood flow have been shown to be associated with the development of IVH [19]. Assessment of cerebral Doppler flow velocities prior to the development of IVH seems insensitive for prediction of IVH [20]. Our study results confirm that systolic and diastolic flow velocities of the anterior cerebral artery do not correlate with either PDA size or later development of IVH. Studies assessing the relationship between brain oxygenation measured via near infrared spectroscopy cerebral tissue oxygenation index (cTOI) and SVCF in preterm infants on day 1 are inconsistent. Moran et al. [21] described a positive relationship within the first 24 h of life in preterm infants 51500 g were as Sirc et al. [10] confirmed an increase of SVCF during first 48 h of life, however, did not reveal a correlation with cTOI. Given a continuous registration of cerebral oxygenation, blood flow velocities would be helpful to quantify hypoperfusion and reperfusion states predisposing to the development of IVH [14]. In our study cohort, infants who developed IVH were significantly more likely to have been born via spontaneous vaginal delivery (SVD). Several studies of preterm deliveries have demonstrated an increased risk of development of IVH according to duration of labour and following SVD [22]. In our institution, SVD is generally attempted in early induction due to suspected amniotic infection before 26 weeks’ post-conceptual age as well as in acute onset of labour. However, following inclusion of confounding factors and after adjustment for gestational age at delivery, SVD was not associated with the risk of IVH. Lack or incomplete antenatal steroid medication is known to be associated with the development of IVH. In our study, presence of IVH on day 7 was associated with a lower platelet count within the first 24 h of life. This finding of an association between relative thrombocytopenia and IVH is in line with other published data [23,24]. The study suffers from limitations. Firstly, assessment of SVCF on echocardiography is dependent on clinical circumstances. Clinical factors like mechanical ventilation, positioning of the patient, fluid and cardiovascular management may well affect SVCF measurements. This may well have influenced our results, and to some degree might explain differences within the published literature on SVCF and development of IVH. Due to the sample size we might have underestimated these factors. Secondly, SVCF might be used as a surrogate marker for upper body blood flow return to the heart, however, brain circulation only contributes 25–30% to SVCF [12,13]. Further studies are needed to quantify the contribution of alterations in systemic blood flow, intra-extra cardiac shunts and vascular autoregulation on cerebral perfusion.

J Matern Fetal Neonatal Med, Early Online: 1–7

We speculate that the standardised treatment of low SVCF focusing on optimising circulating blood volume, haemodynamic significant PDA shunt and inotropic support irrespective of ‘‘normal blood pressure’’ in our study could have positively impacted on the development of severe IVH. This might explain the weak association of SVCF and IVH risk in our study in comparison to published initial studies on SVCF in preterm infants.

Conclusion Monitoring SVCF during routine echocardiography on first day of life is a weak predictor of IVH in extremely preterm infants. This study describes SVCF to be mainly affected by the size and flow pattern of a PDA. Future studies should focus on defining which ELBW subgroups would benefit from cardiovascular interventions informed by early echocardiography and SVCF assessment to prevent IVH. What is already known on this topic The assessment of SVCF on routine echocardiography in preterm neonates describes a physiological increase of SVC flow during the first 48 h of life. The occurrence and extension of IVH has been correlated to persistent low SVCF in extremely preterm infants on the first day of life. It is controversial whether echocardiographic measurement of low SVCF is adequately reflective of reduced upper body, and therefore cerebral, blood flow, which could contribute to the pathophysiology of IVH. What this study adds Clinical observational data on SVCF and IVH in a large cohort of extremely preterm infants. Monitoring SVCF during routine clinical practice on the first day of life was found to be a weak predictor of IVH in extremely preterm infants. SVCF on first day of life is mainly affected by the size and flow pattern of a Patent Ductus Arteriosus.

Declaration of interest No financial assistance was received in support of the study.

References 1. Volpe JJ. Intracranial haemorrhage: germinal matrix-intraventricular haemorrhage of the premature infant. In: Volpe JJ, ed. Neurology of the newborn. Philadelphia: WB Saunders; 2001:428–93. 2. Kluckow M, Evans N. Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child Fetal Neonatal Ed 2000;82:F188–94. 3. Evans N, Kluckow M, Simmons M, Osborn D. Which to measure, systemic or organ blood flow? Middle cerebral artery and superior vena cava flow in very preterm infants. Arch Dis Child Fetal Neonatal Ed 2002;87:F181–4. 4. Osborn DA, Evans N, Kluckow M. Hemodynamic and antecedent risk factors of early and late periventricular/intraventricular haemorrhage in premature infants. Pediatrics 2003;112:33–9. 5. Miletin J, Dempsey EM. Low superior vena cavaflow on day 1 and adverse outcome in the very low birthweight infant. Arch Dis Child Fet Neonat Ed 2008;93:368–71.

Downloaded by [Nanyang Technological University] at 00:39 24 August 2015

DOI: 10.3109/14767058.2015.1054805

6. Holberton JR, Drew SM, Mori R, Konig K. The diagnostic value of a single measurement of superior vena cava flow in the first 24 h of life in very preterm infants. Eur J Pediatr 2012;171:1489–95. 7. Mertens L, Seri I, Marek J, et al. Targeted neonatal echocardiography in the neonatal intensive care unit: practice guidelines and recommendations for training. J Am Soc Echocardiogr 2011;24: 1057–78. 8. Watkins AM, West CR, Cooke RW. Blood pressure and cerebral haemorrhage and ischaemia in very low birthweight infants. Early Hum Dev 1989;19:103–10. 9. Drayton MR, Skidmore R. Vasoactivity of the major intracranial arteries in newborn infants. Arch Dis Child 1987;62: 236–40. 10. Sirc J, Dempsey EM, Miletin J. Cerebral tissue oxygenation index, cardiac output and superior vena cava flow in infants with birth weight less than 1250 grams in the first 48 hours of life. Early Hum Dev 2013;89:449–52. 11. Greisen G. Autoregulation of vital and non-vital organ blood flow in the preterm and term neonate. In: Kleinman CS, Seri I, eds. Hemodynamics and cardiology: neonatology questions and controversies. Philadelphia: Saunders; 2007:19–38. 12. Kehrer M, Kraegeloh-Mann L, Goelz R, Schoening M. The development of cerebral perfusion in healthy preterm and term neonates. Neuropediatrics 2003;34:281–6. 13. Sinha AK, Cane C, Kempley ST. Blood flow in the common carotic artery in term and preterm infants: reproducibility and relation to cardiac output. Arch Dis Child 2006;91:31–5. 14. Alderliesten T, Lemmers PMA, Smarius JJM, et al. Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage. J Pediatr 2013;162: 698–704.

Single centre retrospective observational cohort study

7

15. Ficial B, Finnemore AE, Cox DJ, et al. Validation study of the accuracy of echocardiographic measurements of systemic blood flow volume in newborn infants. J Am Soc Echocardiogr 2013;26: 1365–71. 16. Broadhouse KM, Price AN, Durighel G, et al. Assessment of PDA shunt and systemic blood flow in newborns using cardiac MRI. NMR Biomed 2013;26:1135–41. 17. Kluckow M, Evans N. Superior vena cava flow in preterm infants: a novel marker of systemic blood flow. Arch Dis Child Fetal Neonatal Ed 2000;82:182–7. 18. Groves AM, Kuschel CA, Knight DB, Skinner JR. Echocardiographic assessment of blood flow volume in the superior vena cava and descending aorta in the newborn infant. Arch Dis Child Fetal Neonatal Ed 2008;93:F24–8. 19. Perlman JM, McMenamin JB, Volpe JJ. Fluctuating cerebral blood flow velocity in respiratory-distress syndrome: relation to the development of intraventricular hemorrhage. N Engl J Med 1983; 309:204–9. 20. Pellicer A, Valverde E, Gaya F, et al. Postnatal adaptation of brain circulation in preterm infants. Pediatr Neurol 2001;24:103–9. 21. Moran M, Miletin J, Pichova K, Dempsey EM. Cerebral tissue oxygenation index and superior vena cava blood flow in the very low birth weight infant. Acta Paediatr 2009;98:43–6. 22. Shankaran S, Bauer CR, Bain R. Prenatal and perinatal risk and protective factors for neonatal intracranial hemorrhage. Arch Pediatr Adolesc Med 1996;150:491–7. 23. Setzer E, Webb I, Wassenaar J, et al. Platelet dysfunction and coagulopathy in intraventricular haemorrhage in the premature infant. J Pediatrics 1982;100:599–605. 24. Andrew M, Castle V, Saigal S, et al. Clinical impact of neonatal thrombocytopenia. J Pediatrics 1987;110:457–64.

Superior vena cava flow and intraventricular haemorrhage in extremely preterm infants.

To evaluate the relationship between superior vena cava flow (SVCF) measurements within the first 24 h of life, and development of intraventricular ha...
382KB Sizes 0 Downloads 5 Views