1. health and fitness
2. disease

Neonatal Society Spring Meeting
19th March 2015
Institute of Child Health, London
Spring Meeting, 19th March 2015
Institute of Child Health, London
30 Guilford Street, London WC1N 1EH
09.15 Coffee
Session1: Chair – Dr James Boardman, Meetings Secretary
09.45 K Turner, University of Kent
Is preterm birth associated with accelerated telomere shortening?
10.00 R Kumar, Birmingham Women’s NHS Foundation Trust Hospital
Improving trends in the outcome of live inborn babies with congenital
diaphragmatic hernia following development of a centralised management protocol
10.15 P Seddon, Royal Alexandra Children’s Hospital, Brighton
Respiratory monitoring by pulse oximetry plethysmogram analysis in preterm
infants
10.30 P Shangaris, University College London
Correction of hemoglobin levels in a heterozygous humanized mouse model of
thalassemia after fetal gene therapy
10.45 N Aladangardy, Homerton University Hospital
Withdrawal of life sustaining treatment for newborn infants: the WiLST study
11.00 Tea / coffee
Session 2: Chair – Professor Howard Clark, President Elect
11.30 M Ezzati, University College London
Limb remote ischemic post-conditioning protects cerebral white matter in a piglet
model of perinatal asphyxia
11.45 R Lee-Kelland, University of Bristol
Excessive hypothermia during and temperature instability after completion of
therapeutic hypothermia are associated with a poorer neurodevelopmental
outcome
12.00 Keynote Lecture: Minimally invasive surfactant delivery in the preterm infant
Professor Peter Dargaville, University of Tasmania
13.00 Lunch break
Session 3: Chair – Dr David Carr, Committee member
14.00 A Walker, Birmingham Women’s NHS Foundation Trust
Outcome of antenatally detected encephalocele; tertiary centre experience over a
10 year period
14.15 B Ibrahim, Imperial College London
One-year mortality of very preterm infants admitted to neonatal units in England
14.30 E Moore, University of Edinburgh
Preterm birth is associated with atypical social cognition in infancy
14.45 S Mulla, Norfolk and Norwich University Hospitals NHS Foundation Trust
Severe biochemical disturbances after introduction of a new regional parenteral
nutrition formulation matching current ESPGHAN recommendations
15.00 N Przysiezna, Imperial College London
Postnatal age related metabolic changes in faecal water from premature babies
15.15 S Sparrow, University of Edinburgh
Preterm birth is associated with alterations in the methylome at sites that influence
neural development
15.30 Afternoon Tea / Coffee
Session 3: Chair – Dr Richard Thwaites, General Secretary
16.00 J Whistler, University of Nottingham
The impact of route of delivery on skeletal muscle metabolism in piglets
16.15 N Andreas, Imperial College London
The association between breast milk macronutrient content and maternal BMI
16.30 I Mawson, Guy’s and St Thomas’ NHS Foundation Trust
Does the sensitivity of pulse oximetry screening depend on the type of critical
congenital heart disease? An adjunct to the pulse oximetry screening debate
16.45 The McCance Lecture: Why preclinical trials fail to translate
Professor Malcolm Macleod, University of Edinburgh
Introduced by Professor Neena Modi, President of the Neonatal Society
17.45 Drinks and Close of Meeting
Title (Upper case)
IS PRETERM BIRTH ASSOCIATED WITH ACCELERATED TELOMERE SHORTENING?
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
1
2
2
1
Kara Turner , Shermi George , John Greenall , Darren Griffin and Vimal Vasu
Corresponding author e-mail address:
1,2
K.J.Turner-24@kent.ac.uk
Institution(s)
1. School of Biosciences, University of Kent
2. Department of Neonatal Medicine, William Harvey Hospital, Ashford, Kent, TN24 0LZ
Introduction (include hypothesis)
By term age preterm infants manifest an ‘aged’ phenotype characterised by altered body fat distribution, insulin
resistance and hypertension. Telomeres are nucleoprotein structures at the end of human chromosomes that
shorten with age and in association with the above morbidities. The aim of this study was to determine telomere
length in a cohort of preterm infants at term equivalent age and in comparison to a cohort of term born infants.
Our a priori hypothesis was that preterm at term infants would have shorter telomeres than term born controls.
ohypothesisthat telomere length is reduced in preterm infants by term equivalent age.
Methods (include source of funding and ethical approval if required)
With institutional research ethics approval and informed parental consent, blood samples were drawn from
preterm infants (<32 weeks completed gestation) within 48 hours after birth (n=18) and at term equivalent age
(n=18) alongside routine sampling. Blood samples were also drawn from term born controls (≥37 weeks
completed gestation) within 48 hours after birth (n=27) where sampling was deemed necessary for other clinical
purposes. DNA was extracted from blood and relative telomere length was assessed by qRT-PCR.
Results
Consistent with previously published data, telomere length appears to be highly variable among the newborn
population. Telomere length is negatively correlated with gestational age, however we could find no evidence to
indicate that overall telomere length was different between preterm infants sampled at birth compared to those
sampled at term equivalent age. Furthermore our results identify that relative telomere length is shortest in term
born controls. To the best of our knowledge this is the first study to measure telomere length in preterm infants
at term equivalent age.
Conclusions
Our results do not support the hypothesis that telomere length is reduced in the preterm infant by term
equivalent age. Given the high variability in telomere lengths among newborn infants, a longitudinal study in the
future may provide valuable detail on the rate of telomere attrition in relation to signs of an ‘aged phenotype’.
References (include acknowledgement here if appropriate)
Turner K et al. Telomere length analysis and preterm infant health. Biomark Med. 2014; 8(4): 485-498
Okuda K et al. Telomere length in the newborn. Pediatr Res. 2002;52(3):377–381.
Senior author supporting presentation on day of meeting: Vimal Vasu
Title (Upper case)
IMPROVING TRENDS IN THE OUTCOME OF LIVE INBORN BABIES WITH CONGENITAL DIAPHRAGMATIC
HERNIA FOLLOWING DEVELOPMENT OF A CENTRALISED MANAGEMENT PROTOCOL
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
1
2
1
1
R Kumar , A Shenvi , A Bedford Russell , AK Ewer and SV Rasiah
Corresponding author e-mail address:
1
Rohit.kumar@bwnft.nhs.uk
Institution(s)
1)
2)
Birmingham Women’s NHS Foundation Trust Hospital
University Hospital of North Midlands
Introduction (include hypothesis)
Background: The incidence of congenital diaphragmatic hernia (CDH) is 1:2500 live births. In accordance with findings from
1
the MBRRACE-UK CDH report , significant variations in practice were associated with high mortality. Since 2010, care has
been centralised within two West Midlands Newborn Networks. All antenatally detected cases of CDH are referred to the
regional perinatal centre for fetal medicine assessment, surgical and neonatal counselling. Babies are managed postnatally
using agreed guidelines developed by surgical, PICU and neonatal teams.
Methods (include source of funding and ethical approval if required)
Aim: To review the outcomes of all inborn and live-born babies with CDH, in a regional neonatal intensive care unit (NICU)
between January 2000 and December 2014 (15 years), following the implementation of a regional care pathway.
Methods: All live-born babies with CDH were identified using the clinical diagnosis code and Badger electronic records. A
retrospective review of the patient’s clincal case notes was then done.
Results
Year
2000-2004
2005-2009
2010-2014
N (Live Inborn Babies)
17
43
68
Transferred to PICU
9 (53%)
20 (47%)
36 (53%)
PICU Surgical Survival
8 (88%)
19 (95%)
34 (95%)
Transferred for ECMO
0
6 (14%)
14 (21%)
ECMO Survival
0
4 (67%)
8 (57%)
Overall Survival
8(47%)
23 (53%)
42(62%)
The table above summarises the outcomes over five year epochs, the centralised management protocol was implemented in
2010 and the overall survival for 2014 was 73%.
Conclusions
Centralised management of CDH resulted in all antenatally diagnosed babies being delivered in the regional NICU and reduced variation in
postnatal management. There is an improving trend in survival; however benefits have taken 4 years to be realised. ECMO referral has
increased. Postsurgical survival without ECMO is excellent. These figures provide important information when counselling parents
antenatally.
References (include acknowledgement here if appropriate)
1)
MBRRACE-UK Perinatal Confidential Enquiry Congenital Diaphragmatic Hernia Report 2014
Senior author supporting presentation on day of meeting: Dr Alison Bedford Russell
Title (Upper case)
RESPIRATORY MONITORING BY PULSE OXIMETRY PLETHYSMOGRAM ANALYSIS IN PRETERM
INFANTS
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
1
1
1
2
3
Paul Seddon , Sonia Sobowiec-Kouman , Grace Castronovo , Heike Rabe and David Wertheim .
Corresponding author e-mail address:
seddop@gmail.com
Institution(s)
1
Respiratory Unit, Royal Alexandra Children’s Hospital, Brighton, UK.
Trevor Mann Baby Unit, Royal Sussex County Hospital, Brighton, UK.
3
Faculty of Science, Engineering and Computing, Kingston University, UK
2
Introduction (include hypothesis)
We have previously shown that respiratory data can be derived from pulse oximetry plethysmogram (pleth)
recordings in newborn term babies and older infants (Wertheim et al., 2009, Wertheim et al., 2014). The aim of
this study was to examine if respiratory rate can be derived from pleth traces in preterm infants.
Methods (include source of funding and ethical approval if required)
Pulse oximeter pleth, saturation (SpO2) and thoracic/abdominal respiratory inductance plethysmography (RIP)
bands were recorded for five minutes from 15 spontaneously breathing infants using a SOMNOscreen Plus
system (Somnomedics GmbH, Germany). The pleth data were low pass filtered (LPF) to derive respiratory data
using software that we developed using MATLAB (The MathWorks, Inc., USA). Further software was developed
in order to display the LPF pleth data together with the thoracic and abdominal band traces as well as SpO2 and
pulse rate. Funding was from the NIHR, RfPB scheme; approval was from NRES West Midlands Committee.
Results
Median (range) gestation at birth was 33 (25-36) weeks and median (range) post-conceptional age at time of
recording was 35 (32-37) weeks. Periods of the recordings were analysed, excluding segments with clear
artefact and / or low amplitude. Visual assessment of the recordings showed good agreement between the LPF
pleth and RIP band data in traces. The median pulse rate in the analysed sections was 145 / minute.
Respiratory rate calculated from the LPF pleth data (median 57, range 32 to 66 breaths/ minute) was compared
with that computed from the bands (median 62, range 32 to 72 breaths/ minute); the median difference (LPF –
band) was -4 and the maximum difference was -9 breaths / minute.
Conclusions
Our results indicated good agreement between respiratory rate from LPF pleth traces and RIP bands. This study
suggests that respiratory rate can be derived from good quality pleth recordings in spontaneously breathing
preterm infants in the first few weeks after birth.
References (include acknowledgement here if appropriate)
Wertheim D, Olden C, Savage E and Seddon P. Arch Dis Child Fetal Neonatal Ed., 2009; 94: F301-3.
Wertheim D, Parsley C, Burgess S, Dakin C and Seddon P. Acta Paediatr., 2014; 103: e222-4.
Senior author supporting presentation on day of meeting: Dr Paul Seddon
Title (Upper case)
CORRECTION OF HEMOGLOBIN LEVELS IN A HETEROZYGOUS HUMANIZED MOUSE MODEL OF
THALASSEMIA AFTER FETAL GENE THERAPY
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
Panicos Shangaris1,2, Stavros P Loukogeorgakis1,3, Sindhu Subramaniam1, Mike Blundell7, Nahla Bakhamis2,
Shanrun Liu4, Simon Eaton1, Durrgah Ramachandra1, Panayiotis Maghsoudlou1, Luca Urbani1, Simon Waddington2, Joy
Archer5, Mike Antoniou6, Adrian J Thrasher7, Thomas Ryan5, Paolo De Coppi1 and Anna David2
Corresponding author e-mail address:
p.shangaris@ucl.ac.uk
Institution(s)
1Surgery Unit, Institute of Child Health, University College London; 2Institute for Women's Health, Maternal & Fetal
Medicine, University College London; 3Center for Fetal Research, The Children's Hospital of Philadelphia, Philadelphia, PA;
4University of Alabama at Birmingham, Birmingham, AL; 5Central Diagnostic Services, Queen's Vet School Hospital,
University of Cambridge ; 6Department of Medical and Molecular Genetics, King’s College London; 7Molecular
Immunology Unit, Institute of Child Health
Introduction (include hypothesis)
Beta thalassaemia is a genetic blood disease that causes life-threatening anemia. Hematopoietic stem cell
(HSC) transplantation successfully cures the disease but in only 30% of patients. We hypothesized that in
utero gene therapy (IUGT) to the fetal HSC compartment with the corrected beta globin gene might cure the
disease before birth.
Methods (include source of funding and ethical approval if required)
A humanized mouse model of thalassemia (Cooley’s anemia;CA) was used in which heterozygous animals
are affected by anemia, splenomegaly and extra-medullary hematopoiesis. At E13.5 a “GLOBE” vector
(HIV-2 based lentiviral vector that incorporates a mini hemoglobin beta gene, the beta-globin promoter and
HS2/3β-LCR element) was injected into the liver of each fetus (n=12). At 12 weeks of age, recipient blood,
liver, spleen and bone marrow were collected for complete blood count, blood film, as well as RNA and DNA
isolation. Extra-medullary hematopoiesis was examined in the spleen and liver using flow cytometry
(CD71+/Ter119+cells) and histo-pathological analysis.
Results
Compared to non-injected heterozygous pups (control), IUGT increased hemoglobin levels [11.3±0.4g/dl (n=6)
vs. 7.6±0.6g/dl (n=8); p<0.01], red blood cell count [9.3±0.3*1012/L vs. 6.2±0.5*1012/L; p<0.01), and hematocrit
[41.2±2.2% vs. 27.2±2.0; p<0.01]. Moreover, treated CA animals had reduced spleen weight [130±5mg
vs.310±21mg; p <0.01], as well as reduced extra-medullary hematopoiesis in the liver [0.7±0.1% (n=4) vs.
6.0±0.9% (n=5); p<0.01] and spleen [6.6±1.8 (n=4) vs. 23.1±1.4 (n=3); p<0.05]. qPCR analysis demonstrated
increased gene expression of human beta globin and reduced expression of human gamma globin in blood and
bone marrow of IUGT offspring. HPLC analysis confirmed these findings at protein level. The average vector
copy number in the liver was 0.1.
Conclusions
IUGT resulted in phenotypic normalization in a heterozygous humanized mouse model of CA. Increased levels of
beta globin and associated down-regulation of gamma globin is consistent with a switch from fetal to adult human
hemoglobin, confirming successful prenatal correction of the genetic defect.
References (include acknowledgement here if appropriate)n/a
Check box if presenting author is a trainee:
basic science trainee
clinical trainee
All authors have approved the abstract, actual or potential conflicts of interest have been declared to the
meetings secretary, and the abstract has not been presented previously:
Presented at ASH & ESGCT
Senior author supporting presentation on day of meeting: Dr Anna David
Title (Upper case)
WITHDRAWAL OF LIFE SUSTAINING TREATMENT FOR NEWBORN INFANTS: The WiLST Study
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
1,2
1,3
3
3
Narendra Aladangady , Chloe Shaw , Katie Gallagher and Neil Marlow for Collaborator Group
Corresponding author e-mail address:
Narendra.aladangady@homerton.nhs.uk
Institution(s)
1.Neonatal Unit, Homerton University Hospital, London; 2,Centre for Paediatrics, Barts and the London School
of Medicine and Dentistry, QMUL, London; 3.Institute for Women’s Health, University College London, London.
Introduction (include hypothesis)
1
Withdrawal of Life Sustaining Treatment (LST) for newborn infants was first described in 1973 . There are no
prospective multicentre studies of the outcomes for babies for whom redirecting Life Sustaining Treatment has
2,3
been considered .
Aim: To determine the short-term outcomes of infants for whom clinicians or parents have started discussions
about the withholding or withdrawal of LST and/or institution of “do not resuscitate” (DNR) orders.
Methods (include source of funding and ethical approval if required)
Utilising a secure on-line database (RedCap), we prospectively collected neonatal unit outcomes (death or
discharge home) and care practices for babies for whom limiting LST was considered over one year in 9
hospitals in the NEL Neonatal Network.
The study was funded by a Programme Development Grant (NIHR) and approved by the East London REC.
Results
Data from 88 infants (58 males) were studied; mean gestational age 30.1 (SD: 6.8) weeks, birthweight 1592g
(SD: 1165). Limiting LST was discussed with parents of 67 infants and in 2 cases discussions were only among
the clinical team. Limiting LST was first raised by clinicians in 64 cases and by parents in 3 cases; 23
discussions concerned withholding LST, and 47 withdrawing LST.
Following initial discussions, 33 parents (49%) were not in agreement with the clinical team. The parents of 13
infants (27.7%) did not agree for withdrawal of LST. In contrast, of 24 parents specifically asked, all agreed to
make a DNR Order.
Fifty infants (56.8%) died following limitation of LST, 25 (28.3%) died receiving full intensive care support, 5
(5.7%) survived despite parents agreeing to limit LST and 8 (9.1%) infants survived as result of non-agreement
to limit LST. Following limitation of LST, a significantly lower proportion of parents were offered an autopsy (n=
25) or agreed to one (n=6) compared to infants died receiving full intensive care support (17 parents offered and
10 agreed; p=0.018).
Conclusions
A significant number of parents do not agree with professional opinion to limit LST for their infants and a
significant proportion of these infants survive. Reasons for non-agreement are being sought as part of our
continuing study.
References (include acknowledgement here if appropriate)
1.Duff and Campbell. N Engl J Med 1973; 2.Nuffield Council on Bioethics 2006 and 3.N Aladangady. Early
Human Development 2012.
Senior author supporting presentation on day of meeting: Narendra Aladangady
Title (Upper case)
LIMB REMOTE ISCHEMIC POST-CONDITIONING PROTECTS CEREBRAL WHITE MATTER IN A PIGLET
MODEL OF PERINATAL ASPHYXIA
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
1
1
1
1
1
1
1
1
M Ezzati , K D Broad , G Kawano , E Rocha Ferreira , D Alonso Alconada , I Fierens , J Rostami , J Hassell , I
2
3-4
3-4
5
5
6
1
Tachtsidis , P Gressens , B Fleiss , D Yellon , D J Hausenloy , X Golay , N J Robertson
Corresponding author e-mail address:
n.robertson@ucl.ac.uk
Institution(s)
1 Institute for Women’s Health, University College London, 2 Medical Physics and Biomedical Engineering, UCL,
3 Department of Perinatal Imaging and Health, King’s College London, 4 Inserm, U1141, Paris, 5 The Hatter
Cardiovascular Institute, UCL, 6 Institute of Neurology, UCL
Introduction (include hypothesis)
Despite therapeutic hypothermia, ~ 50% treated babies have adverse outcomes; additional simple, safe,
effective treatments are needed. Ischaemic postconditioning is a powerful innate protective mechanism against
ischaemic-reperfusion injury (1). We aimed to determine if remote ischaemic postconditioning (RIPostC) after
cerebral hypoxia-ischaemia (HI) is neuroprotective in a piglet model.
Methods (include source of funding and ethical approval if required)
*UK Home Office Guidelines [Animals (Scientific procedures) Act, 1986]. After HI, randomisation to: (i) No
intervention (n=8); or (ii) RIPostC - four 10 minute cycles of bilateral lower limb ischaemia /reperfusion
immediately after HI (n=8). Magnetic resonance spectroscopy was acquired at 24 & 48 h; assessment of
regional cell death by immunohistochemistry and gene expression by microarray and qPCR.
Results
Cerebral white matter protection was seen with four 10 minute cycles of hind-limb ischaemia /reperfusion,
evidenced by improved brain energy metabolism at 48h with reduced lactate/N-acetyl aspartate in white matter
(p=0.005) and increased NTP/exchangeable phosphate pool (p=0.039). On immunohistochemistry, cell death
was reduced in periventricular white matter (PvWM) (p=0.03), internal capsule (p=0.002) and corpus callosum
(CC) (p=0.021); there was reduced microglial activation in the CC (p=0.001) and higher numbers of surviving
oligodendrocytes in the CC (0.029) and PvWM (p=0.001). Changes in gene expression included the ATPsensitive potassium channel and endothelin A receptor, changes previously seen with RIPostC protection.
Phosphorylated ERK activity was increased in the white matter, indicating activation of pro-survival cell
pathways.
Conclusions
Four cycles of 10 minute hind limb ischaemia /reperfusion immediately after cerebral hypoxia-ischaemia
protected cerebral white matter. RIPostC was well tolerated and simple to perform. Such a degree of protection
is likely to translate into a meaningful clinical effect; further studies are needed.
References (include acknowledgement here if appropriate)
(1). Pignataro et al., In vivo and in vitro characterization of a novel neuroprotective strategy for stroke: ischaemic
post conditioning. J Cereb Blood Flow Metab 2008:28(2):232-41.
* MRC grant (MR/J00457X/1)
Senior author supporting presentation on day of meeting: Professor NJ Robertson
Title (Upper case)
Excessive Hypothermia During And Temperature Instability After Completion Of Therapeutic Hypothermia Are
Associated With A Poorer Neurodevelopmental Outcome.
Authors
1,2
1,2
1
1
Richard Lee-Kelland, MRCPCH , Ela Chakkarapani, MD , Sally Jarry, PHD , Xun Liu, PHD , Emma Scull1
1,2
Brown and Marianne Thoresen, PHD .
Corresponding author e-mail address:
Richardleekelland@gmail.com
Institution(s)
1.) University of Bristol. 2.) St Michael’s Hospital, University Hospitals Bristol.
Introduction (include hypothesis)
o
Therapeutic hypothermia at rectal temperature 33.5 C is now standard of care for babies with neonatal
encephalopathy (NE). Infants receiving hypothermia have been noted to overshoot the target temperature during
1
2
both passive and active cooling, even with a servo controlled device . This may reflect a dysfunction in
autonomic regulation secondary to cerebral damage. Our hypothesis is that excessive hypothermia during
cooling and temperature instability post therapeutic hypothermia are associated with a poorer
neurodevelopmental outcome.
Methods (include source of funding and ethical approval if required)
A case note review of 145 neonates treated with therapeutic hypothermia under the CoolCap/TOBY protocol
was undertaken. We recorded hourly rectal temperature measurements during passive cooling, active (servo
o
controlled) cooling, rewarming and for 24h post rewarming. The target temperature during cooling was 33.5 C.
o
Excessive hypothermia during passive/active cooling was defined as a temperature <33.0 C. After rewarming,
o
o
Temperature instability was defined as hypothermia <36.0 C and hyperthermia ≥38 C. Temperature was
o
maintained by using a heated bed, overhead heating or the servo controlled device set at 36.5 C. Outcomes
were assessed by neurodevelopmental assessment at 18 months using converted Bayley II mental development
3
index (MDI). Poorer neurodevelopmental outcome was defined as Bayley II MDI <85 (<1SD from the mean).
Significance was assessed via chi squared test (p<0.05 two-sided).
Results
Excessive hypothermia occurred in 31% of infants during the passive or active cooling phase. The excessive
hypothermia group had a significantly higher proportion of infants with a poorer neurodevelopmental outcome
compared with the rest of the cohort (57% vs 37% P=0.03). Following rewarming 56% of infants became
hypothermic, despite being cared for in an incubator or with other external heating. Only one infant at one time
point became hyperthermic. The proportion of children with a poorer neurodevelopmental outcome was
significantly higher in the group that became hypothermic following rewarming compared to the rest of the cohort
(44% vs 19% respectfully P = 0.018).
Conclusions
Excessive hypothermia during active cooling and temperature instability leading to hypothermia after rewarming
are associated with a poorer neurodevelopmental outcome. We do not know whether optimising therapeutic
hypothermia to prevent excessive hypothermia will improve neurodevelopmental outcome. Hyperthermia is
negligible following therapeutic hypothermia using current practise.
References (include acknowledgement here if appropriate)
1.)
2.)
3.)
Fairchild, K., Sokora, D., Scott, J., & Zanelli, S. (2010). Therapeutic hypothermia on neonatal transport: 4-year experience in a
single NICU. Journal of Perinatology, 30(5), 324–329.
Massaro AN et al. Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children's Hospitals
Neonatal Consortium HIE focus group. (2014) Journal of Perinatology 13, 1-7
Jary, S., Whitelaw, A., Walløe, L., & Thoresen, M. (2013). Comparison of Bayley-2 and Bayley-3 scores at 18 months in term
infants following neonatal encephalopathy and therapeutic hypothermia. Developmental Medicine and Child Neurology, 55(11),
Senior author supporting presentation on day of meeting: Dr Ela Chakkarapani
Title (Upper case)
OUTCOME OF ANTENATALLY DETECTED ENCEPHALOCELE; TERTIARY CENTRE EXPERIENCE OVER A
10 YEAR PERIOD.
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
1
2
1,3
Amy Walker, , Desidero Rodrigues, Denise Williams,
Corresponding author e-mail address:
1
4
Tamas Marton, Ann Tonks, Andrew K Ewer.
1,5
amy@thewalkers.me.uk
Institution(s)
1
3
2
Birmingham Women’s NHS Foundation Trust, Birmingham Children’s Hospital
4
5
West Midlands Regional Genetics Service, West Midlands Perinatal Institute, University of Birmingham.
Introduction (include hypothesis)
Encephalocele is a rare congenital abnormality of the central nervous system (CNS) with protrusion of the
meninges and brain through a defect in the skull. There is a lack of information about the outcome of these
1
pregnancies. The aim of this study was to collate outcome data on all cases of encephalocoele so that
antenatal counselling may be more informative.
Methods (include source of funding and ethical approval if required)
Cases of antenatally diagnosed encephalocele between 01/01/00 and 31/12/09, were identified from fetal
medicine, regional anomaly, genetics and pathology databases. Notes were reviewed to collate pregnancy and
neurodevelopmental outcomes. Ethical approval was obtained.
Results
53 cases were identified. 40 posterior, 4 anterior and 1 interparietal. In 8, site was not classified. 43% had other
CNS abnormalities; (ventriculomegaly - 9, microcephaly - 5 , spinal bifida – 5, holoprosencephaly - 2 other CNS
abnormalities – 2). Non-CNS abnormalities occurred in 18 cases (15 renal, 3 cardiac). 40 pregnancies were
terminated, 6 resulted in live births and 7 were lost to follow up. 58% of cases had chromosomal testing - 4 were
abnormal. Post-mortem was performed in 53% of cases identifying 7 additional CNS defects and 11 non-CNS
abnormalities.14 cases had a diagnosis of Meckel Gruber syndrome (MG). Of the live births, 3 died within 2
months of age and 3 were still alive. Two long-term survivors have learning difficulties, the other had reported
normal development at 21 months.
Conclusions
This is the largest cohort of antenatally diagnosed encephalocele. As with other reported data we have a high
termination rate. With only 3 long-term survivors the outcome remains guarded for this condition.
References (include acknowledgement here if appropriate)
1. Ultrasound Obstet Gynecol. 2014 Sep 5. doi: 10.1002/uog.14661. [Epub ahead of print]Fetal Cephalocele: First-Trimester Sonographic
Spectrum In A Review Of 35 Cases.Sepulveda W1, Wong AE, Andreeva E, Odegova N, Martinez-Ten P, Meagher S.
Senior author supporting presentation on day of meeting: Dr Andrew K Ewer
Title (Upper case)
ONE-YEAR MORTALITY OF VERY PRETERM INFANTS ADMITTED TO NEONATAL UNITS IN ENGLAND
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
Buthaina Ibrahim, Yevgeniy Statnikov, Daniel Gray, Neena Modi, Sonia Saxena and the Medicines for Neonates
Investigator Group*
Corresponding author e-mail address:
b.ibrahim@imperial.ac.uk
* Neena Modi, Peter Brocklehurst, Jane Abbott, Kate Costeloe, Elizabeth Draper, Azeem Majeed, Jacquie
Kemp, Deborah Ashby, Alys Young, Stavros Petrou
Institution(s)
Department of Primary Care and Public Health, Charing Cross campus; Section of Neonatal Medicine,
Department of Medicine, Chelsea and Westminster Hospital campus, Imperial College London, SW10 9NH, UK
Introduction (include hypothesis)
Globally 130 million babies are born every year and nearly 4 million die in the first 28 postnatal days [1]. Infants born very
preterm constitute approximately one third of these deaths [2]. The survival to discharge of preterm infants has been the
focus of many studies however, there are few objective estimates of later survival. The purpose of this study was to describe
mortality over the first year among very preterm infants by gestational age and differences in maternal characteristics by
gestational age band.
Methods (include source of funding and ethical approval if required)
We analysed data on infants, with a completed gestational age between 23+0 and 32+6 weeks, born in England between 1
January 2010 and 31 December 2010 and admitted to a neonatal unit (NNU). Data were extracted from a birth cohort
created by linking the National Neonatal Research Database (NNRD) and the Hospital Episode Statistics (HES). We
assessed differences in the frequency distributions of maternal characteristics by gestational weeks: maternal age (<20
years, 20-24 years, 25-29 years, 30-34 years and ≥35), ethnicity (White, Asian or Asian British, Black or Black British, Mixed
and other Ethnic Groups) and social deprivation (defined using the Index of Multiple Deprivation quintile categories). We
used chi-squared test to compare categorical variables by gestational age band. We determined mortality in the early
neonatal (0-6 days), late neonatal (7-27 days) and postneonatal (28-365 days) periods by gestational age. This abstract
presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for
Applied Research Programme (RP-PG-0707-10010). The views expressed are those of the author(s) and not necessarily
those of the NHS, the NIHR or the Department of Health.
Results
We identified 7,463 live-born infants; 1.7% (n=129) were births at 23 weeks, 3.7% (n=273) at 24 weeks, 4.1 (n=307) at 25
weeks, 6.3% (n=468) at 26 weeks, 7.2% (n=535) at 27 weeks, 9.8 (n=733) at 28 weeks, 10.7% (n=801) at 29 weeks, 13.1%
(n=977) at 30 weeks, 17.8 (n=1329) at 31 weeks and 25.6% (n=1911) at 32 weeks. There were significant differences in
maternal age, ethnicity and social deprivation by gestational age. The frequency of mothers younger than 20 years of age, of
black ethnicity and from the most deprived areas was higher in infants born at 23 weeks than those born at 32 weeks (23
weeks: 23.4%, 13.3% and 46.6%, respectively; 32 weeks:7.8%, 6.4% and 32.2%, respectively; p-values .0001, <.0001
and .009, respectively).
Of all infants, 228 (3.1%) died during the early neonatal period, with mortality ranging from 35.7% at 23 weeks to 0.5% at 32
weeks, and 122 (1.7%) died during the late neonatal period, with mortality ranging from 18.1% at 23 weeks to 0.3% at 32
weeks. 178 infants (2.4%) died before in the postneonatal period and mortality ranged from 14.7% at 23 weeks to 0.7% at 32
weeks.
Conclusions
We found that among very preterm infants there were significant differences in maternal age, ethnicity and social deprivation.
Early neonatal, late neonatal and postneonatal mortality was 3.1%, 1.7% and 2.4%, respectively.Our results for postneonatal
mortality were similar to those reported by ONS for live-births in 2010 although we found higher mortality for infant born at 23
and 24 gestational weeks (14.7% and 11,7%; 7.6% and 9.9%). This may be explained by live born babies that die before
admission to a NNU that are not therefore included in the NNRD, and to the fact that in the ONS reports there were high
proportions of ‘Not Stated’ gestational ages concentrated in the North East Region. Our study reinforces the relevance of
socio-economic circumstances in relation to preterm birth, and the importance of complete, accurate data recording.
References (include acknowledgement here if appropriate)
[1] Zupan, J. Perinatal mortality in developing countries. N Engl J Med 2005; 352: 2047-8
[2] Zeitlin, J et al. Differences in rates and short-term outcome of live births before 32 weeks of gestation in
Europe in 2003: results from the MOSAIC cohort. Pediatrics 2008; 121: e936-44
Senior author supporting presentation on day of meeting: Professor Neena Modi
Title (Upper case)
PRETERM BIRTH IS ASSOCIATED WITH ATYPICAL SOCIAL COGNITION IN INFANCY
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
1. Dr Emma J Moore, 2. Dr Karri Gillespie-Smith 3. Dr Sue Fletcher-Watson, 1,3. Dr James P Boardman
Corresponding author e-mail address:
emma.moore@ed.ac.uk
Institution(s)
1.MRC Centre for Reproductive Health, University of Edinburgh; 2. Psychology, University of West of Scotland
3. Centre for Clinical Brain Sciences, University of Edinburgh
Introduction (include hypothesis)
1,2
Preterm infants are at increased risk of developing neurocognitive and psychiatric impairment in childhood .
Early identification of children at risk could facilitate early interventions designed to improve outcome. Eyetracking is a technique that can objectively and quantifiably assess eye-gaze behaviour in response to stimuli in
3
non-verbal populations and allows inferences to be made about underlying cognitive function. Here we test the
hypothesis that social cognition in infancy is altered by preterm birth.
Methods (include source of funding and ethical approval if required)
+3,
+2
+6
43 preterm infants (mean postmenstrual age [PMA] birth,29 range 23 -34 ; 17 males) and 42 term infants (≥
37 weeks PMA, 21 males) were assessed between 6 and 18 months corrected PMA using the Tobii x60 eyetracker. Infants were presented with stimuli of increasing complexity: static face, face with objects within a gridlike array and pairs of naturalistic scenes with and without social content. Time to first fixation, fixation duration
and location of fixation were recorded and analysed using Student’s t-tests, repeated measures ANOVA, and
non-parametric tests as required. Informed parental consent and ethical approval were obtained.
Results
There was no significant difference in age at testing between
groups; 8.77 months (preterm) and 8.48 months (term), p= 0.581.
Preterm infants demonstrated a reduced preference to social
information when compared to term infants as demonstrated by a
difference score of fixation duration (eyes- mouth) within the face,
p= 0.045 (figure 1). This pattern was repeated in more complex
tasks in fixation duration; grid-like array (median fixation duration to
face 1.16 vs. 1.3s, p=0.023); naturalistic scene (mean fixation of
social content 1.1 vs. 1.4s and non-social content 0.79 vs. 0.72s,
p=0.026).
Conclusions
Eye-gaze behaviours in response to stimuli depicting social content of varying complexity differ between preterm
infants and term controls, when assessed in late infancy. These data suggest that the development of social
cognition is altered by preterm birth.
References (include acknowledgement here if appropriate)
1. Bhutta AT et al JAMA 2002 2. Johnson S et al JAACAP 2010 3. Jones W, Klin A. Nature. 2013 Funding:
Theirworld.
Senior author supporting presentation on day of meeting: Dr James Boardman
Title
SEVERE BIOCHEMICAL DISTURBANCES AFTER INTRODUCTION OF A NEW REGIONAL PARENTERAL
NUTRITION FORMULATION MATCHING CURRENT ESPGHAN RECOMMENDATIONS
Authors
1
1
1
1
1
2
1
Shaveta Mulla , Sarah Cowey , Rosie Close , Sara Pullan , Rosalind Howe , Lynne Radbone , Paul Clarke .
Corresponding author e-mail address:
shavetamulla@gmail.com
Institutions
1 Neonatal Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK.
2 East of England Neonatal Operational Delivery Network, UK.
Introduction
Enhanced early postnatal nutrient supply to very low birth weight infants is associated with improved growth
[1]
velocity, white matter maturation and head growth. Current ESPGHAN guidelines recommend a maximum amino
2+
acid content of 4.0 g/kg/day and a Ca :PO4 ratio within the range 1.3-1.7:1 for preterm parenteral nutrition (PN). In
January 2013 East of England regional NICUs introduced a new PN formulation that essentially accorded with
2+
these latest ESPGHAN recommendations. Our aqueous bag contained 3.3 g amino acids, 1.7 mmol Ca , and 1.1
2+
mmol PO4 per 100 mL and, including lipid, achieved a first-week Ca :PO4 ratio in the range 1.4-1.3:1. During 2013
several regional NICUs, including our own, reported cases of severe hypercalcaemia and/or hyposphataemia in
preterm infants during the first postnatal week. Our hypotheses were that these electrolyte disturbances were due
[2, 3]
2+
to the ‘refeeding syndrome’,
and that increasing the PO4 content to match Ca in an equimolar ratio would
prevent these abnormalities. We report our audit of first-week biochemistry in preterm babies who received the new
PN formulation in epochs before and after provision of increased phosphate supplementation.
Methods
We retrospectively reviewed casenotes, PN charts, and serum biochemistry of all preterm infants in our NICU, who
received the new regional PN formulation in two discrete ~6-month epochs before (Phase 1) and after (Phase 2)
the date of ad hoc-increased PO4 supplementation (December 2nd 2013). The PN recipe was otherwise unchanged
across epochs. We assessed the incidence and severity of biochemical derangements occurring with PN delivery in
2+
the first postnatal week. We pre-defined severe hypercalcaemia as serum Ca >3.0 mmol/L, hypophosphataemia
as PO4 <1.5 mmol/L, and severe hypophosphataemia as PO4 <1.0 mmol/L. We analysed by intention to treat.
Results
Data for 102 infants were reviewed. There were no significant differences in baseline characteristics or amino acid
2+
intakes between the two epochs. The table shows median (range) first-week serum Ca and PO4 concentrations in
the phases and numbers of infants with deranged biochemistry:
Phase 1, N = 51
Phase 2, N = 51
P value
Calcium
2+
Peak Ca concentration, mmol/L
3.05 (2.67─3.73)
2.84 (2.20─3.15)
<0.0001
2+
Ca
>3.0 mmol/L, n (%)
31 (61)
11 (22)
0.0001
Phosphate
Nadir PO4 concentration, mmol/L
1.37 (0.43─1.98)
1.59 (0.59─2.62)
0.004
PO4 <1.5 mmol/L, n (%)
31 (6 )
11 (22)
0 0001
PO4 <1.0 mmol/L, n (%)
17 (33)
7 (14)
0.04
Conclusions
2+
Introduction of the latest ESPGHAN-recommended intakes for amino acids with the recommended Ca :PO4 ratio
for preterm PN led to severe hypercalcaemia and hypophosphataemia in most preterm babies in our NICU. Extra
2+
phosphate supplementation to achieve an equimolar Ca :PO4 ratio significantly reduced the incidence and severity
2+
of these biochemical disturbances, while maintaining the recommended amino acid, Ca and PO4 intakes. Our
audit findings have assisted a revised regional PN formulation and may inform future ESPGHAN recommendations.
References
1. Strømmen K, et al. Neonatology. 2015; 107: 68-75.
3. Bonsante F, et al. PLoS One. 2013; 8: e72880.
2. Moltu SJ, et al. Clin Nutr. 2013; 32: 207-12.
Senior author supporting: Dr Paul Clarke
Title (Upper case)
POSTNATAL AGE RELATED METABOLIC CHANGES IN FAECAL WATER FROM PREMATURE BABIES
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
Przysiezna N1, Wijeyesakera AD2, Parkinson JR1, Hyde MJ1, Uthaya S1, Holmes E2, Modi N1
Corresponding author e-mail address:
n.przysiezna12@imperial.ac.uk
Institution(s)
1
Section of Neonatal Medicine, Department of Medicine, Imperial College London, Chelsea & Westminster campus, 369 Fulham Road,
London, UK; 2 Computation Systems Medicine, Sir Alexander Fleming Building, Imperial College London, South Kensington, SW7 2AZ
Introduction (include hypothesis)
The composition of biofluids can provide useful information regarding health, physiology and may identify biomarkers of
disease risk. Microbiota colonising the gut in early life may be a causal factor in long term health outcomes. Given their
hospital environment it is to be expected that preterm babies will have a considerably different pattern of colonisation
compared to term born infants. Here we used stool water metabonomics as a surrogate for gut microbiota activity, to answer
the research question: Is there a time (post-natal age) dependant trend in the composition of stool water.
Methods (include source of funding and ethical approval if required)
The study was conducted with Research Ethics Committee (09/H0707/88) approval as part of the NIHIR funded doubleblind 2x2 factorial randomised trial of early nutrition (NEON). Weekly stool samples were collected from 160 infants and
stored at -80°C until analysis (total number of samples = 1187). Stool water was extracted and analysed using onedimensional 1H NMR spectroscopy at 300K on a Bruker LC-NMR 600 MHz spectrometer, using standard parameters and
Bruker pre-processing algorithms. The spectra were phased, baseline corrected and referenced using an in-house script
(MATLAB). We used probabilistic normalisation and analysed the spectra using Principal Component Analysis (PCA) and
Orthogonal Partial Least Squares analysis (O-PLS).
Results
Analysing data from all babies (time points from 1 to 21 weeks
postnatal age), we showed that the metabolic profile of stool samples
from preterm infants altered over time (Fig 1). The PCA plot indicates
that the variation in the metabolic profile of the faecal water decreases
with increasing postnatal age. The greatest variation is seen during the
first four weeks of postnatal life. The following metabolites increased
with postnatal age: alanine, acetate, trimethylamine and tyramine. The
source of acetate and trimethylamine is likely to be bacterial
metabolism.
Figure 1: PCA scores scatter plot from NMR spectra of stool samples
representing multiple time points for 160 premature infant. Samples
coloured according to postnatal age (in weeks).
Conclusions
Indirect assessment of gut microbiota activity in preterm infants indicates that the variation observed in the first few weeks
of life is reduced after a month. This overlaps with increasing amounts of enteral feeding and decreasing reliance on
parenteral nutrition. Given the high exposure to breast milk in this cohort and that breast fed infants have lower microbial
variability this may explain our findings. Infants are also likely to be commonly exposed to hospital specific bacteria.
References (include acknowledgement here if appropriate)
1. Parkinson JRC et al (2013) Pediatrics. 131:E1240
Senior author supporting presentation on day of meeting: n.modi@imperial.ac.uk
Title (Upper case)
PRETERM BIRTH IS ASSOCIATED WITH ALTERATIONS IN THE METHYLOME AT SITES THAT INFLUENCE NEURAL
DEVELOPMENT.
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
1
2
3
1
1
3
Sarah A Sparrow , Jonathan Manning , Chinthika Piyasena , Rozi Pataky , Emma Moore Amanda J Drake , and James P
1,4
Boardman
Corresponding author e-mail address:
sarahannemitchell@hotmail.co.uk
Institution(s)
1
2
MRC Centre for Reproductive Health, University of Edinburgh; Centre for Regenerative Medicine, University of Edinburgh
4
University/BHF Centre for Cardiovascular Sciences, University of Edinburgh; and Centre for Clinical Brain Sciences,
University of Edinburgh.
3
Introduction (include hypothesis)
Early exposure to the extra-uterine environment is closely associated with altered brain development and long term
neurodevelopmental impairment. DNA methylation, involving the addition of a methyl group to cytosine nucleotides,
influences gene expression and is fundamental to normal neural development. DNA methylation is dynamic and can be
influenced by stressful early life environmental exposures. We test the hypothesis that preterm birth affects the methylome,
leading to differences between preterm infants at term equivalent age and term controls.
Methods (include source of funding and ethical approval if required)
Subjects included 36 preterm infants (mean postmenstrual age [PMA] at birth 28+3 weeks, range 23+2 to 32+5) at term
equivalent age (mean 39+5 weeks' PMA, range 38+0 to 42+4) and 36 term controls (mean 41+2 weeks' PMA, range 38+3 to
47+1), matched for sex. Ethical approval and informed parental consent were obtained. DNA was extracted from buccal
cells. DNA methylation was measured at over 485,000 sites throughout the methylome using Illumina HM450 BeadChip
array. Differential Methylation was assessed using RnBeads v 0.99.13.
Results
18 protein coding genes and 33 protein coding associated promoters showed significantly different methylation between
preterm and term infants (FDR-corrected combined p value <= 0.05). Genes of interest with regards to CNS development
and signalling included:
Gene
% diff.
p-value
Description
SLC2A1
2.2
.04
Solute carrier family 2 (facilitated glucose transporter), member 1
APOL1
2.7%
.043
apolipoprotein L, 1
QPRT
3.7%
.0077
quinolinate phosphoribosyltransferase
NPBWR1 9.7%
.021
neuropeptides B/W receptor 1
RTP4
11.1%
.00086
receptor (chemosensory) transporter protein 4
GPR21
4.1%
.0086
G protein-coupled receptor 21
Conclusions
Preterm birth is associated with alterations in the methylome at sites that influence neural function. DNA methylation may
provide a molecular link between the stress of preterm birth and accompanying alterations in brain development.
References (include acknowledgement here if appropriate)
1.
2.
3.
Murphy S et al PloS ONE 2012
Klengel et al. Nature Neuroscience 2013
Khulan B et al. Translational Psychiatry 2014
Senior author supporting presentation on day of meeting: James P Boardman
Title (Upper case)
THE IMPACT OF ROUTE OF DELIVERY ON SKELETAL MUSCLE METABOLISM IN PIGLETS
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
James Whistler, Alison Mostyn, Matthew J. Hyde
Corresponding author e-mail address:
alison.mostyn@nottingham.ac.uk
Institution(s)
School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, Leicestershire,
LE12 5RD and Neonatal Medicine, Imperial College London, Chelsea and Westminster Campus, 369 Fulham
Road, London, SW10 9NH.
Introduction (include hypothesis)
The occurrence of pre-labour Caesarean section (CS) delivery is increasing, despite limited research on the
effects on neonatal metabolism. We have previously described differences in adipose tissue in offspring
(1)
delivered by CS delivery; and attributed these to the loss of the intrapartum cortisol surge . We now explore the
impact of route of delivery on skeletal muscle (SM) metabolic pathways in porcine neonates. We hypothesise
that CS delivery will reduce SM metabolic processes which are essential for neonatal survival.
pathways in porcine neonates
Methods (include source of funding and ethical approval if required)
Four pregnant sows were randomly allocated to CS at 112 days gestation (~115 days is full term) or
spontaneous vaginal delivery (VD). Both CS (n=4) and VD (n=5) offspring were fed a sow milk replacer. At 7
days of age piglets were humanely euthanased and SM sampled. Gene expression was assessed using real
time PCR, tissue glycogen, lipid and protein were measured by biochemical assay. All animal work had full local
(2)
ethical and national Home Office approval; further information on the methods are described by Hyde et al .
Data was analysed using SPSS and Arraymining.net.
Results
11β-Hydroxysteroid dehydrogenase type 2 (CS=0.89±0.02, VD=1±0.02; p=0.03) and insulin-like growth factor 1
(CS=0.95±0.02, VD=1±0.01; p=0.03) expression was reduced in the CS group while pyruvate dehydrogenase
kinase 4 was increased (CS=1.19±0.06, VD=1±0.02; p=0.03). A significant reduction in glycogen was observed
in the VD group (CS=67.8±0.2, VD=32.4±0.3; p=0.03), however, tissue lipid and protein concentrations were
similar. Serum hormone and metabolite concentrations were made available via MJH and significant reductions
in glucose, lactate and triglyceride were identified. A significant negative relationship between IGF1 expression
2
and fractional growth rate was observed in the CS group only (R =0.91, P=0.05). Cluster analysis segregated
the data into two independent clusters: one single cluster included all VD offspring and all the CS offspring in the
second cluster.
Conclusions
Despite the small animal numbers, this study demonstrates striking differences in crucial metabolic pathways,
particularly glycogenolysis, between Caesarean section and vaginally delivered neonatal offspring. The longterm impacts of these changes remain to be elucidated.
References (include acknowledgement here if appropriate)
1. Thickett A, et al.Proc Nutr Soc. 2011;70:E28.
2. Hyde MJ, et al.Clin Sci. 2009;118:47.
UG research project funded by The School of Veterinary Medicine and Science, University of Nottingham
Senior author supporting presentation on day of meeting: Matthew Hyde
Title (Upper case)
THE ASSOCIATION BETWEEN BREAST MILK MACRONUTRIENT CONTENT AND MATERNAL BMI
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
1
1
1
2
Nicholas J. Andreas , Matthew J. Hyde , Suzan Jeffries , Elaine Holmes & Neena Modi
Corresponding author e-mail address:
1
n.andreas11@imperial.ac.uk
Institution(s)
1
2
Section of Neonatal Medicine, Department of Medicine, Imperial College London, UK
Section of Computational and Systems Medicine, Faculty of Medicine, Imperial College London, UK
Introduction (include hypothesis)
Previous research on donor breast milk has suggested a positive correlation between maternal Body Mass Index
1
(BMI) and breast milk concentration of protein, carbohydrate and fat . We sought to further study the relationship
between maternal BMI and fore and hind milk composition, over the first three months of lactation. We tested the
hypothesis that we would observe differences in breast milk composition between high and normal BMI mothers.
Methods (include source of funding and ethical approval if required)
We obtained fore and hind milk samples from 95 mothers delivering at full-term, at seven days and three months
post-partum. 52 mothers had a BMI <25, 43 a BMI >25. Samples were frozen at -80°C until analysis, when they
were thawed and homogenised using sonication prior to analysis. Macronutrient content was determined using
mid-infrared spectroscopy (Miris Human Milk Analyser loaned by MIRIS AB, Sweden), in accordance with
manufacturer instructions. We used ANOVA (SPSS) to assess the relationship of breast milk macronutrient
content in relation to maternal BMI. The study received Research Ethics approval (12/LO/0203) and was funded
by Westminster Medical School Research Trust.
Results
We obtained a total of 284 samples (1 week, fore milk=95, hind milk=40; 3 months, fore milk=90, hind milk=59).
We found no statistically significant or clinically relevant correlations between maternal BMI and breast milk
protein, carbohydrate or fat content at either of the time points, nor did maternal pregnancy weight gain influence
the concentration of macronutrients. In agreement with previous reports at three months only 24% of women
with a BMI >25 were still breast feeding compared to 75% of mothers with a BMI <25. Also in keeping with other
reports, we found that hind milk has significantly more fat and less carbohydrate than fore milk, regardless of
stage of lactation. However, protein concentration in fore and hind milk differed with stage of lactation: at 7 days,
there was no difference between fore and hind milk; but at 3 months there was more protein in hind milk
(p=0.009). Between 7 days and 3 months of lactation, in fore milk, the concentration of fat remained stable,
carbohydrate increased and protein decreased; in hind milk there were significant increases in fat and
carbohydrate, but a significant decrease in protein.
Conclusions
In contrast to previous research, we did not observe any association between maternal BMI and breast milk
macronutrient content at any of the time points studied. Our data suggest that breast milk composition is
regulated independent of maternal BMI.
References (include acknowledgement here if appropriate)
1
Michaelsen, K. F. J Pediatr Gastroenterol Nutr. 1990 11(2); p. 229-39
Senior author supporting presentation on day of meeting: Professor Neena Modi
Title (Upper case)
DOES THE SENSITIVITY OF PULSE OXIMETRY SCREENING DEPEND ON THE TYPE OF CRITICAL
CONGENITAL HEART DISEASE? AN ADJUNCT TO THE PULSE OXIMETRY SCREENING DEBATE.
Authors (Presenting author underlined. If no author is a Society member please provide the name of the
member introducing the author to the Society)
I. Mawson, P. Babu, G. Fox, J. Simpson
Corresponding author e-mail address:
John.simpson@gstt.nhs.uk
Institution(s)
Neonatal and Cardiology Departments, Evelina London Children’s Hospital, Guy’s and St Thomas’ NHS
Foundation Trust.
Introduction (include hypothesis)
The aim was to investigate the sensitivity of newborn pulse oximetry (Pulsox) screening for each type of critical
congenital heart disease (CCHD). The hypothesis was that Pulsox screening sensitivity varies depending on the
type of CCHD being identified and depending on the threshold used for further investigation. A meta-analysis in
1
2012 described Pulsox screening’s sensitivity as moderate, with high specificity and low false positive rates.
Due to small numbers of infants with CCHD in studies little data is available on Pulsox sensitivity by diagnosis.
Methods (include source of funding and ethical approval if required)
Retrospective review of admission pre-ductal oxygen saturations of infants with antenatally diagnosed CCHD
delivered at a cardiac neonatal unit between 2010- 2014. Saturations were recorded at median of <1hr (range
<1-9hrs) after delivery. Data was stratified by CCHD diagnosis and analysed according to three different oxygen
saturation thresholds, ≤90%, ≤92%, and ≤95%. Sensitivities (with 95% confidence intervals) of Pulsox screening
using each threshold were calculated using Microsoft Excel for the whole data set and for each CCHD diagnosis.
Calculations were repeated for a group representing infants well enough for postnatal ward care.
Results
276 neonates were identified. 208 (78.2%) were clinically well, admission to the neonatal unit occurred purely
due to antenatal CCHD diagnosis. In this group Pulsox was more sensitive using ≤95% threshold at 71.6%(65.577.8%) compared to ≤92% (52.3%(45.6-59.2%))and ≤90% (46.2%(39.4-52.9%)). The 95% confidence intervals
(95%CI) for Pulsox sensitivities using a threshold of ≤90% and ≤92% did not overlap with the 95%CI of the
Pulsox sensitivity using ≤95%. Pulsox sensitivity was increased by 37.5-52.7% using ≤95% threshold compared
to ≤90% for hypoplastic left heart (HLH), tetralogy of fallot (TOF) and interrupted aortic arch (IAA). Using the
highest threshold (≤95%) Pulsox sensitivity for aortic stenosis (AS) was 20%(0.0-55.1%), pulmonary stenosis
was 36.4%(7.9-64.8%), and coarctation was 41.5%(26.4-56.5%) whereas sensitivity for pulmonary atresia (PA)
at threshold ≤90% was 66.7%(40.0-93.3), TGA 83.9%(74.7-93.0%) and TAPVD 100.0%(100.0-100.0%).
Conclusions
Pulsox sensitivity is influenced by CCHD diagnosis and is highest using ≤95% threshold (overall and especially
for HLH, IAA and TOF). In coarctation, AS and PS, the minority of cases were detected irrespective of saturation
threshold. TGA, PA and TAPVD would be detected in the majority regardless of the threshold.
References (include acknowledgement here if appropriate)
1. Thangaratinam S, Brown K, Zamora J, et al. “Pulse oximetry screening for critical congenital heart defects in
asymptomatic newborn babies: a systematic review and meta-analysis.” The Lancet 2012;379:2459-64
Senior author supporting presentation on day of meeting: Dr G. Fox
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