ORIGINAL PAPER

V. Kavvadia A. Greenough G. Dimitriou R. Hooper

Comparison of the effect of two uid input regimens
on perinatal lung function in ventilated infants
of very low birthweight
Received: 20 April 1999 / Accepted: 16 June 1999
Abstract Fluid overload worsens respiratory failure; conversely, uid restriction has been
associated with a higher survival rate without chronic lung disease. We therefore
hypothesised that uid restriction in the perinatal period might improve lung function in
ventilated, prematurely born infants of very low birthweight. As a consequence, we
compared in a randomised trial the eect of two uid regimes on perinatal lung function.
On one regime infants were to receive 60 ml/kg on day 1, increasing to 150 ml/kg by day
7, and on the other regime approximately 25% less uid was to be prescribed. Lung
function was assessed by measurement of functional residual capacity (FRC) and
compliance. Measurements were made daily on days 1 to 5 and then on day 7. Ninety
infants, median gestational age 28 weeks (range 2333), were included in the study. There
were no signicant dierences between the two groups regarding their gestational age or
birthweight, or in the proportions who received antenatal steroids or postnatal surfactant.
The infants on the restricted regime received signicantly less uid (P < 0.01). The only
signicant dierences in lung function between the two groups, however, were that the
infants on the restricted regime had a higher mean compliance on day 3, but thereafter the
dierence was reversed. Colloid intake, however, unfavourably aected lung function,
total colloid intake being negatively correlated with both the area under the curve of
birth-adjusted FRC (P 0.003) and compliance (P 0.001).
Conclusion We conclude that early uid restriction appears to have very little impact on
perinatal lung function.
Key words Fluid balance Lung function Very low birthweight
Introduction
Infants who are uid-overloaded are more likely to
develop a symptomatic patent ductus arteriosus (PDA)
than those without a uid overload [3]. Infants with a
PDA, compared to those without, have worse lung
function [8, 21] and a higher incidence of subsequent
chronic lung disease (CLD) [18, 28]. Fluid restriction in
the rst weeks of life has been reported to increase
survival without chronic lung disease [23]. It seems likely,
therefore, that early restriction of uid input might
improve lung function in the perinatal period. The aim of
this study was to test that hypothesis by comparing the
eect of two uid regimes on perinatal lung function.
Materials and methods
Infants born prematurely with a birthweight of 1500 g, without
major congenital anomalies and requiring mechanical ventilation
from the rst 6 h after birth, were eligible for entry into a study
assessing the impact of uid input on the development of CLD. All
such infants, if informed written consent was given by their parents,
Eur J Pediatr (1999) 158: 917922 Springer-Verlag 1999
A. Greenough (&) V. Kavvadia G. Dimitriou
Children Nationwide Regional Neonatal Intensive Care Centre,
4th oor, Ruskin Wing, King's College Hospital,
London SE5 9RS, UK
e-mail: anne.greenough@kcl.ac.uk
Tel.: +44-171-3463037; Fax: +44-171-9249365
R. Hooper
Dept of Public Health, Kings College Hospital,
London SE5 9RS, UK
were randomised to receive one of two uid regimes during the
perinatal period (Table 1). On the restricted uid regime
(restricted), compared to the control regime (control), the infants
were to be prescribed approximately 25% less maintenance uid.
As part of the study, lung function measurements were attempted
daily for ve days and then at seven days in the rst 90 patients
enrolled in the study.
Fluid input on either uid regime was only increased if the
infants had lost more than 10% of their birthweight and there were
no signs of uid overload, such as hyponatraemia (serum sodium
<135 mmol/l). Infants who developed renal failure [urine output
less than 1.0 ml/(kg h) except on day 1 when the urine output had
to be less than 0.5 ml/(kg h)] without evidence of dehydration
were restricted to a uid input equal to their urine output plus
insensible losses. Infants who were small for gestational age were
admitted to the study on day 2 of the randomised uid regime and
progressed accordingly. An extra 30 ml/(kg day) of maintenance
uids was given while an infant received phototherapy. Hypoten-
sion was treated initially with up to two boluses of a colloid or
crystalloid solution; if that failed to improve the blood pressure, a
dopamine infusion was commenced. Inotropes were used as rst
choice for blood pressure support if there was evidence of myo-
cardial ischaemia. Infants who were hypoglycaemic (blood glucose
level less than 2.5 mmol/l) were preferentially given a more con-
centrated dextrose solution rather than an increased volume load.
The nurses recorded all uid input (crystalloid and colloid) hourly
on observation charts. This was then totalled for each 24 h. Urine
was collected on nappies or, for the smaller babies, on cotton wool
balls. As soon as the infant voided, the nappy or cotton wool ball
was weighed to determine the amount of urine passed. This was
then totalled for each 24-h period. Infants were weighed at least
daily on bed scales.
Lung volume was assessed by measuring functional residual
capacity (FRC) using a helium gas dilution technique and a spe-
cially designed infant circuit with a volume of 95 ml [7]. The FRC
system contained a re-breathing bag, the system reservoir, enclosed
in an airtight cylinder. A non-intubated infant breathed through a
face mask and this was connected to the re-breathing bag via a
three-way valve. The endotracheal tube of a ventilated infant was
connected to the re-breathing bag via the three-way valve and the
ventilator was connected to a side port in the cylinder. The infant
could be ventilated directly or, once the position of the three-way
valve was changed, breathe from the re-breathing bag while re-
ceiving positive pressure support by changes in pressure within the
cylinder, resulting in compression of the re-breathing bag. The
FRC system contained a helium analyser (Equilibrated Biosystems
Inc. Series 7700, Melville, NY) with a digital display. The helium
concentration was recorded prior to and at 15-s intervals during the
measurement. Equilibration was assumed when there was no
change in the helium concentration over a 30-s interval. The initial
and equilibration helium concentrations were used in the calcula-
tion of FRC. The FRC results were corrected for oxygen
consumption, assumed to be 7 ml/(kg min) [12], and the results
were then corrected to body temperature under pressure-saturated
conditions. FRC was estimated twice on each occasion, with an
interval of 10 min between measurements. The FRC was expressed
as the mean of the paired measurements. The coecients of
repeatability of FRC measurements in ventilated and non-venti-
lated infants are 5.7 ml/kg [6] and 3.9 ml/kg [7] respectively.
Compliance was measured by the occlusion technique. In ven-
tilated infants, a pneumotachograph was inserted between the end
of the endotracheal tube and ventilator circuit. In non ventilated
infants the pneumotachograph was inserted into a face mask which
was placed over the infant's nose and mouth. The pneumotacho-
graph (Mercury F1OL-GM Instruments, Kilwinning, Scotland)
was attached to a Validyne dierential pressure transducer (range
2 cmH
2
O). The ow signal from the pneumotachograph was
integrated to give the volume (Gould Integrator model 13-4615-70).
Airway pressure was measured from the pneumotachograph using
a Validyne pressure transducer (50 cmH
2
O). Airway occlusion
was produced by occluding the distal end of the pneumotacho-
graph; in ventilated infants this was done during a very temporary
disconnection from the ventilator. Airway occlusion was performed
at end-inspiration; this provoked the Hering Breuer reex and
hence a temporary apnoea, indicated by a plateau in the airway
pressure trace. Compliance was calculated from the inspiratory
volume immediately prior to the occlusion divided by the height of
the airway pressure plateau during the occlusion. The means of the
results of compliance from 10 occlusions were calculated. In ven-
tilated infants who were paralysed or apnoeic, compliance was
measured by relating the volume change of a positive pressure in-
ation, maintained until no further volume change occurred, to the
change in airway pressure. Again the means of the results of 10
such inations were calculated.
Sample size
Comparison of data from 45 patients in each group allowed us,
with 90% power at the 5% level, to detect a dierence in FRC of
4 ml/kg between the lung volumes of the infants in the two groups.
Thus, the results from the rst 45 consecutive patients entered into
each group, who had serial measurements attempted in the rst
week, were analysed.
Analysis
For the purpose of data analysis, FRC, compliance and uid intake
were each adjusted by dividing by birthweight. FRC and compli-
ance measurements could not always be obtained on all the days, so
two approaches to data analysis were used. Firstly, results on each
of days 2, 3, 4, 5 and 7 were analysed separately using analysis of
covariance to compare the groups and all available data on a given
day. A Bonferroni correction was applied to adjust for performing
ve separate analyses. Secondly, results in the two groups were
compared using repeated measures analysis of covariance applied
to those infants for whom there was an FRC measurement and a
compliance measurement on each of days 2, 3, 4, 5 and 7. FRC on
day 1 was used as a covariate in all analyses of subsequent FRC
measurements. The same approach was used for analysis of the
compliance measurements. Body weights in the two groups were
compared in a similar way. Analysis of covariance was used on
Table 1 Comparison of the re-
commended uid input and the
amount of uid actually re-
ceived on the restricted and
control regimes (medians and
ranges). On each day, infants
on the restricted regime received
signicantly less crystalloid
(P < 0.01) and total uid
(P < 0.01) than those on the
control regime
Day Restricted regime Control regime
``Recommended''
intake (ml/kg)
Total received (ml/kg) ``Recommended''
intake (ml/kg)
Total received (ml/kg)
Crystalloid Colloid Crystalloid Colloid
1 40 44 (2795) 11 (052) 6070 67 (30129) 20 (048)
2 4060 54 (27160) 0 (045) 90 91 (30211) 11 (050)
3 70 83 (46178) 0 (065) 110 122 (30271) 10 (080)
4 90 106 (42222) 0 (038) 120 141 (43301) 0 (039)
5 110 113 (30266) 0 (033) 140 147 (43271) 0 (039)
6 130 142 (45266) 0 (040) 150 169 (45284) 0 (029)
7 150 151 (45266) 0 (051) 150 179 (60301) 0 (059)
918
each day separately and repeated measures analysis of covariance
employed where data for each of days 1 to 7 were available;
birthweight was used as the covariate. It was expected that there
would be some variation in uid intake in both groups; therefore,
the correlations of the total crystalloid and colloid intakes per ki-
logram of birthweight (summed over the seven-day period) with the
areas under the curve of birthweight-adjusted FRC and compliance
measurements over the seven days were also examined.
Patients
Parents of all but one eligible infant gave consent for their infant to
take part in the trial (i.e. 90 of 91 consented). There were no sta-
tistically signicant dierences between the characteristics of the
two groups (Table 2). All the infants throughout the study were
nursed in humidied closed incubators except for the rst few
hours of life when arterial and central lines were being placed.
During ventilation all the infants were supported by 3 cmH
2
O of
positive end-expiratory pressure (PEEP) and had shouldered en-
dotracheal tubes. We have previously demonstrated that there is
minimal or usually no leak around such tubes in premature infants
[13]. Sodium supplementation was withheld until day 2, although
patency of arterial lines was maintained using 0.45% saline infu-
sions run at 0.5 ml/h. The level of sodium supplementation was
subsequently altered in an attempt to ensure that the serum sodium
level was between 135 and 145 mmol/l. Regular diuretic therapy
was only used after the rst week and to treat incipient right heart
failure.
Results
Despite randomization, infants allocated to the re-
stricted uid regime tended to be of higher birthweight
(non-signicant) and more mature than infants allocated
to the control uid regime (Table 2). Similar numbers of
infants in each group received inotropes 11 in both
groups on day 1, 14 in both groups on day 2, 9 in both
groups on day 3, and 7 and 6 respectively on day 4.
Infants on the restricted regime, as was intended,
received signicantly less crystalloid in total than those
on the control regime (P < 0.01) (Table 1). The total
colloid intake did not dier signicantly between the two
groups. In spite of the dierent uid regimes, body
weight over the course of the follow-up period was not
found to dier between the groups (the dierence at
baseline having been adjusted for in the analysis)
(Table 3). Urine output was signicantly higher on days
3, 4 and 6 in infants receiving the control regime
(Table 4).
Analyses of FRC and compliance on each day sep-
arately failed to nd any signicant dierences between
the uid regimes. It was possible to make compliance
and FRC measurements on each of days 2, 3, 4, 5 and 7
on 19 infants on the restricted regime and 25 on the
control regime. In the repeated measures analysis of
FRC there was no signicant main eect of uid regime
or interaction between uid regime and time (Table 5).
For compliance, however, the interaction between uid
regime and time was signicant (P < 0.05). On day
Table 2 Comparison of the patients' characteristics. Data are
given as n or median (range). PDA patent ductus arteriosus, PIP
peak inating pressure
Restricted regime Control regime
45 patients 45 patients
Gestational age (weeks) 28 (2433) 27 (2333)
Birthweight (g) 1086 (6321499) 890 (6181500)
Male 18 17
Spontaneous vaginal
delivery
18 22
Antenatal steroids 34 32
Surfactant 27 26
PDA 7 9
First 48 hours
Maximum PIP
(cmH
2
O)
19 (1434) 18 (1330)
Maximum FiO
2
0.59 (0.211.00) 0.60 (0.231.00)
Table 3 Body weight comparison of the restricted and control
groups. The body weights on each day were expressed as a
percentage of birthweight and as the median (range) for each day
Day Restricted regime Control regime
2 100 (89108) 102 (91108)
3 96 (81110) 96 (85117)
4 93 (78105) 94 (81113)
5 91 (80132) 90 (82104)
6 90 (79113) 89 (79114)
7 89 (76119) 87 (82107)
Table 4 Comparison of urine output (ml/kg) in the restricted and
control groups. Data are given as median (range)
Day Restricted regime Control regime
1 36 (7139) 37 (5188)
2 79 (18204) 100 (0177)
3 78 (38220) 114 (100204)
4 79 (22163) 116 (47172)
5 103 (38207) 115 (33192)
6 98 (37169) 121 (48193)
7 104 (59156) 121 (53192)
Table 5 Comparison of the functional residual capacity (FRC)
and compliance of the respiratory system (CRS) results of infants
on the two regimes. Data are given as median (range). The numbers
in square brackets indicate the number of patients on each study
day, measured using the occlusion technique
Day Restricted regime Control regime
FRC ml/kg
1 19.3 (5.839.8) 16.5 (6.533.4)
2 21 (5.136.3) 19.7 (7.843.9)
3 23.2 (7.937.4) 20.7 (10.639.2)
4 25.4 (2.839) 21.7 (6.932.0)
5 26.1 (5.538.8) 23.4 (10.938.5)
7 24.2 (10.340.4) 24.8 (9.734.5)
CRS ml/(cmH
2
O kg)
1 0.47 (0.161.54) [19] 0.49 (0.251.74) [13]
2 0.71 (0.201.55) [21] 0.60 (0.251.60) [22]
3 0.77 (0.161.85) [24] 0.61 (0.251.35) [24]
4 0.87 (0.181.80) [30] 0.85 (0.211.83) [25]
5 0.85 (0.321.70) [32] 0.89 (0.271.77) [24]
7 0.98 (0.262.60) [31] 1.02 (0.321.76) [30]
919
3 values for those on the restricted regime were higher
than for those on the control regime, though after day
3 this dierence was reversed (Table 5). There were no
signicant dierences between the groups in the
proportions of infants on each day in whom compliance
was measured by the occlusion technique.
There was some suggestion that total crystalloid uid
intake per kilogram of birthweight was negatively corre-
lated with the area under the curve of birthweight-ad-
justed FRC (r )0.27, P 0.079), but not with the
area under the curve of birthweight-adjusted compliance.
Total colloid intake per kilogram of birthweight was
signicantly negatively correlated with both the area
under the curve of birthweight-adjusted FRC (r =
)0.44, P 0.003) and the area under the curve of birth
weight-adjusted compliance (r )0.49, P 0.001).
For consistency, these correlations were evaluated in the
same sample as the repeated measures analyses of FRC
and compliance.
Discussion
Despite uid restriction, on the majority of study days
infants receiving the restricted regime had very similar
lung volumes to those receiving the control regime and
there was no consistent dierence between the groups
regarding their compliance results. During the study, the
clinicians were permitted to deviate from the trial uid
regime if the infants had signs of uid overload or
dehydration, or if extra uid was required because of
hypotension, hypoglycaemia or increased insensible
losses. Nevertheless, despite variations in uid input on
each regime, there remained a statistically signicant
dierence in the amount of uid received by the two
groups, with those on the restricted regime receiving at
least 25% less uid overall. Our data, therefore, suggest
that variation in uid input levels, within the range
experienced by our study population, has only a modest
eect on lung function. It is possible that our two uid
regimes were too similar to result in marked dierences
in lung function. Our more liberal regime, however,
resembled that recommended in a number of standard
neonatal texts [4, 17] and the restricted group received at
least 25% less uid than those on the control regime.
Although more severe uid restriction might have had a
greater eect on lung function, it would have been at the
expense of increased side-eects [1, 2].
Fluid restriction has been associated with improved
survival without chronic oxygen dependency [23], but in
that study there was no statistically signicant dierence
between the groups regarding the incidence of chronic
lung disease (CLD). Similarly, Spahr et al. [20] found no
association between uid input level and CLD devel-
opment. Indeed, excessive uid input has been shown to
inuence CLD occurrence [5, 26]. In one study [26], in-
fants who developed CLD received, on average, 180 ml/
kg of crystalloid by day 3. Our results suggesting that
uid restriction has relatively little eect on perinatal
lung function are therefore not at variance with those
data [5, 20, 23, 26]. None of the previous studies [5, 20,
23, 26] apparently controlled for sodium intake. Pre-
term infants have a limited ability to excrete a sodium
load and thus an increase in sodium intake could lead to
water retention and a delay in postnatal diuresis, a fac-
tor known to inuence the development of CLD [26]. In
the ``uid trial'' in which the present population took
part, the amount of sodium prescribed was not dictated
by the study. The clinicians, however, followed the unit's
policy for all the babies and altered their sodium intake
after the rst 24 h to keep the serum sodium level within
a predetermined range. This resulted in similar numbers
of infants in each group having serum sodium levels
outside the predetermined range [15]. Thus our results
show that uid restriction, compared to a more liberal
regime when attempts are made to keep the serum so-
dium levels within a ``normal'' range, does not have a
major impact on perinatal lung function.
Infants who develop CLD gain weight rather than
experience the normal trend for weight loss in the peri-
natal period [26]. The majority of infants in this study
lost weight (Table 3) and, despite receiving dierent
uid inputs, the median weights of the two groups did
not dier signicantly on any study occasion. This
suggests that the infants were able to adjust their urine
output to compensate for the dierences in the uid
input of the two regimes; indeed those who received the
control regime tended to have higher urine outputs than
those on the restricted regime (Table 4). Another ex-
planation could have been that the clinicians had pre-
scribed large amounts of colloid in the uid-restricted
group, such that the two groups received similar vol-
umes of total uid input. This, however, did not occur;
indeed those on the control regime tended on the rst
two days to receive more colloid than those in the uid-
restricted group (Table 1), although this dierence did
not reach statistical signicance.
The two groups did not dier signicantly with regard
to their characteristics (Table 2), but those who received
the uid restriction regime tended to be one week more
mature and 200 g heavier. The lung function results were,
therefore, corrected for body weight. Routine clinical
policies were followed for the study population, such that
all had shouldered endotracheal tubes during ventilation;
we have previously demonstrated there is very little, if no
leak around such tubes [13]. In addition, all received the
same level of PEEP; this is important as the PEEP level
aects FRC [25]. Two techniques were used to assess
compliance. Compliance measured by the occlusion
technique assesses static compliance, whereas compliance
assessed using ventilator ination has been described as a
quasi-static [22] or an eective static compliance mea-
surement [27]. We would argue that, as we related the
volume change to a positive-pressure ination maintained
until no further volume change had taken place, this was
also a measure of static compliance andit was appropriate
tocombine the results of the twotechniques. Inaddition, a
similar proportion of infants in each group on each study
920
day were measured by the occlusion technique. Thus, we
feel that the lack of signicant dierences in compliance
results on most study days was genuine, particularly as
our FRC results were usually similar in the two groups.
Although the ratio of the average infant's FRC to circuit
volume was approximately 0.3:1 it should be noted that
the coecients of repeatability of the measurements
in ventilated and non-ventilated infants were 5.7 and
3.4 ml/kg respectively.
The adult mature fetal, but not immature fetal, lung
is capable of actively transporting Na
+
from the alve-
olar space. Transcripts coding for the adult rat colonic
epithelial Na
+
channel are present in mature fetal and
adult alveolar epithelium [16]. If the amiloride-sensitive
electrogenic transport is abolished in airway epithelial
channels by inactivating the mouse a-epithelial sodium
channel (ENaC) gene, respiratory distress develops and
death within 40 h of birth from failure to clear the lungs
of liquid [14], demonstrating that ENaC plays a critical
role in the adaptation of the newborn lung to air
breathing [14]. aENaC in the fetal lung is regulated by
glucocorticoids [24]. Combined administration of thy-
roid-releasing hormone and dexamethasone to pregnant
rats between 16 and 18 days of gestational age induced
the expression of lung aENaC in their fetuses. We
studied a very immature group of infants, but the
mothers of the majority had received antenatal steroids,
which may have inuenced our results [24]. There was,
however, no signicant dierence in the proportions of
mothers who had received antenatal steroids between
the two groups (Table 2).
Our results suggest that uidrestrictioninthe perinatal
period has relatively little impact on lung function. There
were no signicant dierences in the lung volumes of the
two groups and, although the mean compliance of the
infants on the restricted regime was higher than mean
compliance of those on the control regime on day 3, the
reverse was subsequently true. In addition, the negative
correlation between the total crystalloid uid intake per
kilogram of birthweight and the area under the curve of
birthweight-adjusted FRC failed to reach statistical sig-
nicance and no such correlation was demonstrated with
the area under the curve of birthweight-adjusted compli-
ance of the respiratory system. We have previously dem-
onstrated that although infusion of albumin promoted
diuresis [10] compared to placebo, it did not favourably
aect lung function [11]. We now demonstrate by the re-
sults of serial measurements that colloid administration
actually adversely aected lung function. The present re-
sults, therefore, further suggest [9, 19] that clinicians
should be extremely cautious about prescribing colloid
infusions to critically ill patients.
References
1. Beard AG, Panos TC, Burroughs JC (1963) Perinatal stress and
the premature neonate. I. Eect of uid and calorie deprivation.
J Pediatr 63:361
2. Beard AG, Panos TC, Marasigan BV, Eminians J, Kennedy
HF, Lamb J (1966) Perinatal stress and the premature neonate.
II. Eect of uid and calorie deprivation on blood glucose.
J Pediatr 68:329343
3. Bell EF, Warburton D, Stonestreet B, Oh W (1980) Eect of
uid administration on the development of symptomatic patent
ductus arteriosus and congestive heart failure in premature
infants. N Engl J Med 302:598604
4. Black JA, Whiteld MF (1991) Neonatal emergencies. Butter-
worth, London
5. Brown ER, Stark A, Sosenko I, Lawson EE, Avery ME (1978)
Bronchopulmonary dysplasia: possible relationship to pulmo-
nary edema. J Pediatr 92:982984
6. Dimitriou G, Greenough A (1995) Measurement of lung
volume and optimal oxygenation during high frequency oscil-
lation. Arch Dis Child Fetal Neonatal Ed 72:F180F183
7. Dimitriou G, Greenough A, Laubscher B (1996) Lung volume
measurements immediately after extubation and prediction of
``extubation failure'' in premature infants. Pediatr Pulmonol
21:250254
8. Gerhardt T, Bancalari E (1980) Lung compliance in newborns
with PDA before and after surgical ligation. Biol Neonate
38:96105
9. Greenough A (1999) Use and misuse of albumin infusions in
neonatal care. Eur J Pediatr 157:699702
10. Greenough A, Greenall F, Gamsu HR (1988) Immediate eects
of albumin infusion in ill premature neonates. Arch Dis Child
63:307309
11. Greenough A, Emery EF, Hird MF, Gamsu HR (1993)
Randomized controlled trial of albumin infusion in ill preterm
infants. Eur J Pediatr 152:157159
12. Hey EN (1969) The relation between environmental tempera-
ture and oxygen consumption in the newborn baby. J Physiol
200:589603
13. Hird M, Greenough A, Gamsu H (1990) Gas trapping during
high frequency positive pressure ventilation using conventional
ventilators. Early Hum Dev 22:5156
14. Hummler E, Barker P, Gatzy J, Beermann F, Verdumo C,
Schmidt A, Boucher R, Rossier BC (1996) Early death due to
defective neonatal lung liquid clearance in aENaC-decient
mice. Nature Genet 12:325328
15. Kavvadia V, Greenough A, Dimitriou G, Forsling M (1998)
Complications of uid restriction in the perinatal period.
Pediatr Res 44:437 (abstract)
16. O'Brodovich H, Canessa C, Ueda J, Rai B, Rossier BC,
Edelson J (1993) Expression of the epithelial Na
+
channel in the
developing rat lung. Am J Physiol 265:C491C496
17. Roberton NRC (1993) Manual of neonatal intensive care.
Edward Arnold, London
18. Rojas MA, Gonzalez A, Bancalari E, Claure N, Poole C, Silva-
Neto G (1995) Changing trends in the epidemiology and
pathogenesis of neonatal chronic lung disease. J Pediatr
126:605610
19. Schierhout G, Roberts I (1998) Fluid resuscitation with colloid
or crystalloid solutions in critically ill patients: a systematic
review of randomised trials. BMJ 316:961964
20. Spahr R, Klein K, Brown D, Holzman I, McDonald H (1980)
Fluid administration and bronchopulmonary displasia: The
lack of an association. Arch Dis Child 134:958960
21. Stefano J, Abbasi S, Pearlman S, Spear M, Esterly K, Bhutani
V (1991) Closure of the ductus arteriosus with indomethacin
in ventilated neonates with respiratory distress syndrome. Am
Rev Respir Dis 143:236239
22. Suter PM, Fairley HB, Isenberg MD (1975) Optimum end
expiratory airway pressure in patients with acute pulmonary
failure. N Engl J Med 292:284289
23. Tammela OKT, Kovisto ME (1992) Fluid restriction for
preventing bronchopulmonary dysplasia? Reduced uid intake
during the rst weeks of life improves the outcome of low
birthweight infants. Acta Paediatr Scand 81:207212
24. Tchepicher S, Ueda J, Canessa CM, Rossier BC, O'Brodovich
H (1995) Lung epithelial Na channel subunits are dierently
921
regulated during development and by steroids. Am J Physiol
296:C805C812
25. Thome U, Topfer A, Schaller P, Pohlandt F (1998) The eect of
positive end expiratory pressure, peak inspiratory pressure and
inspiratory time on functional residual capacity in mechanically
ventilated infants. Eur J Pediatr 157:831837
26. van Marter LJ, Leviton A, Allred EN, Pagano M, Kuban KCK
(1990) Hydration during the rst days of life and the risk
of bronchopulmonary dysplasia in low birth weight infants.
J Pediatr 116:942949
27. Witte MK, Galli SA, Chatburn RL, Blumer JL (1988) Optimal
positive end-expiratory pressure therapy in infants and children
with acute respiratory failure. Pediatr Res 24:217221
28. Yeo C, Choo S, Ho L (1997) Chronic lung disease in very low
birthweight infants: a 5 year review. J Paediatr Child Health
33:102106
ANNOUNCEMENT
7
th
Southeast European
Symposium of
Paediatric Surgery
``Intestinal Motility Disorders''
June 23, 2000,
University of Graz, Austria/Europe
Correspondence to:
Professor Gu nther Schimpl, MD
Dept. of Pediatric Surgery
Auenbruggerplatz 34
A-8036 Graz, Austria/Europe
Tel.: +43/316/385-3762
Fax: +43/316/385-3775
E-mail: kinderchirurgie@kfunigraz.ac.at
922