Article

Management during the first 72h of age of the periviable infant: An evidence-based review

Seminars in perinatology (Impact Factor: 2.68). 02/2014; 38(1):17-24. DOI: 10.1053/j.semperi.2013.07.004
Source: PubMed

ABSTRACT

After NICU admission the extremely immature newborn (EIN) requires evaluation and support of each organ system, and the integration of all those supports in a comprehensive plan of care. In this review, I attempt to analyze the evidence for treatment options after the initial transition, during the first 3 days of life, which have been shown to improve survival or short- or long-term morbidity. This review revealed several things: there is little available evidence from studies that have included significant numbers of EINs; interventions affecting different organ systems need to be co-ordinated as any intervention will have multiple effects; and future advances in treatment of this group of patients will require the installation of permanent research networks to have enough power to perform many studies needed to improve outcomes.

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Management during the rst 72 h of age of the periviable
infant: An evidence-based review
Keith J. Barrington, MB ChB
Sainte Justine University Hospital Center, 3175 Cote Ste Catherine, Montréal, Québec, Canada H3T 1C5
article info
Keywords:
Extreme prematurity
Fluid balance
Survival
Intra-ventricular hemorrhage
Bronchopulmonary dysplasia
Necrotizing enterocolitis
abstract
After NICU admission the extremely immature newborn (EIN) requires evaluation and
support of each organ system, and the integration of all those supports in a comprehensive
plan of care. In this review, I attempt to analyze the evidence for treatment options after
the initial transition, during the rst 3 days of life, which have been shown to improve
survival or short- or long-term morbidity. This review revealed several things: there is little
available evidence from studies that have included signicant numbers of EINs; inter-
ventions affecting differen t organ systems need to be co-ordinated as any intervention will
have multiple effects; and future advances in treatment of this group of patients will
require the installation of permanent research networks to have enough power to perform
many studies needed to improve outcomes.
& 2014 Elsevier Inc. All rights reserved.
1. Introduction
After the immediate transition period of the extremely
immature newborn (EIN) and admission to the NICU, occa-
sional infants succumb quickly as a result of profound
immaturity of several systems. They may be very difcult
to ventilate and oxygenate, or have profound cardiovascular
failure, or severe metabolic disturbance with metabolic
acidosis and uncontrollable hyperglycemia. More commonly,
a period of relative stability follows admission, which is then
followed by the advent of complications in the respiratory,
cardiovascular, and metabolic domains.
I will discuss the potential interventions that may be
effective during this period of relative stability, which have
been shown to improve outcomes in the very preterm infant.
I will discuss these issues by system, but with the clear
understanding that any intervention aimed at one system
will affect other systems. Ventilator practices affect cardio-
vascular function; uid management affects nutrition, and
has respiratory and cardiovascular effects. This complexity of
responses requires that we consider innovative research
approaches for the future.
2. Fluids, electrolytes, and renal function
Renal vascular resistance is high immediately after birth, and
falls rapidly in the rst 24 h. This fall is associated with a
major increase in glomerular ltration rate, and urine output,
which is usually clinically evident as an increasing diuresis
by the end of the rst 24 h of life. After this transition,
preterm renal function is marked by a low ability to excrete
a sodium load, but little restriction of maximal water
clearance.
There are few studies on which to base a decision regarding
total uid management in the extremely immature newborn.
The skin of the very immature infant is very permeable, and
huge trans-epidermal water losses occur if they are placed in
a dry environment, the evaporation of water from the skin of
the infant leads to cooling due to the latent heat of vapor-
ization, and it may be impossible to keep the EIN warm in
a dry environment under a radiant heater. Most centers have
now moved to placing EINs in incubators, although there is
no RCT evidence that this is preferable to being under a
radiant heater, it seems likely to be the case. If a radiant
heater is used it must be combined with an arrangement to
0146-0005/14/$ - see front matter & 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1053/j.semperi.2013.07.004
E-mail address: keith.barrington@umontreal.ca
S EMINARS IN P ERINATOLOGY 38 (2014) 17 24
Page 1
keep the humidity around the infant at a high concentration,
such as covering the infant with plastic.
One problem with keeping EINs in a high humidity environ-
ment is that whenever they are accessed to give care (for
example by opening the incubator portholes) the humidity
drops precipitously. This is even more evident when the
roof of an incubator with a retractable cover is lifted.
Therefore further methods to reduce trans-epidermal water
loss have been examined, including using ointments
2
or
semi-permeable membranes.
1,3
Ointments such as Aquaphor
can reduce trans-epidermal water loss,
4
but whether they can
improve overall water balance or improve clinical outcomes
is uncertain. The only large study in ELBW infants enrolled
infants (5001000 g birth weight) starting at an average of
about 24 h of age, and showed an increase in late-onset
coagulase-negative staphylococcal sepsis during prolonged
treatment.
5
Maturation of the epithelial barrier after preterm
birth occurs rapidly, a briefer period of barrier treatment
could potentially have benets without this risk. Semi-
permeable membranes have also been tried; in a small pre
post study, TEWL appears to have been reduced, uid
requirements and peak sodium was lower, and there may
have been less BPD
6
(n ¼ 69; birth weight o1000 g), but there
is no data from RCTs examining clinical outcomes.
2.1. Total uid intake
What should the total uid intake be? Clearly this will depend
on overall uid losses. But the interaction between the
physical environment, and subsequent TEWL, and uid
administration requirements has not been well studied.
Several studies have randomly compared infants by total
volume of uid administered. The results are very inconsis-
tent. Those studies have varied in design, in particular by
how sodium intake was controlled.
Although the Cochrane review Restricted vs liberal water
intake for preventing morbidity and mortality in preterm
infants
7
suggests that restricted uid intake improves sev-
eral clinical outcomes, this result is marked by signicant
heterogeneity, also one of the better studies did not enroll
babies until the 3rd day of life,
8
and therefore is of little
relevance to this review. After the initial period of adaptation
as mentioned above, the preterm kidney has a relatively good
ability to clear a uid load. Thus there is little reason to
hypothesize that variation in total free-water administration,
within reasonable limits, will affect total body water. In fact,
one of the studies of water restriction
9
gave uids with
identical sodium concentrations in each 100 ml of the intra-
venous uid, another was designed to examine a relatively
complex protocol allowing either 10% or 15% body weight loss
and therefore varied both water and sodium intakes. These
two studies were therefore studies of combined sodium and
water restriction.
I have performed a systematic review of RCTs of different
uid administration rates starting on the rst day of life,
which I have meta-analyzed using the RevMan software,
xed-effects model I found ve controlled trials (Table 1),
three of which had similar sodium intake in each group, two
varied in both the uid and the water intake (Fig. 1). As can be
seen, the studies with varying water intake, but no difference
Table 1 Randomized trials comparing 2 levels of uid intake or 2 levels of sodium administration in the preterm.
References n Characteristics of
included infants
Comparison, uid intakes Sodium intakes Outcome
Tammela and
Koivisto
9
100 o1751 g BW, 423
weeks
50, 60, 70, 80, 90, 100, 120 Then 150 ml/kg/day vs 80,
100, 120, 150 then 200 ml/kg/day
3 mM/100 ml Na in all the uids Primary: BPD
Lorenz
12
88 7501500-g BW, day
1 of life
Designed for 10% birth weight loss vs 15%, initially,
10001500 g 70 ml/kg/day 7501000 g 80 ml/kg/day.
Thereafter varied according to weight loss
Higher in high uid group, 1 mM/kg/day on day 1
increasing to 3 in high uid group or decreasing
to 0.5 in low uid group, by day 4
No clear primary
Von Stockhausen
and Struve
13
56 Premature, day 1 of
life
60 ml/kg/day vs 150 ml/kg/day for 3 days Unclear No clear primary
Kavvadia et al.
14
168 o1501 g BW, day 1 of
life
70 increasing to 150 by day 6, 40 increasing to 150 by
day 7
Adjusted to achieve serum concentration of 135
145 mM/100 ml, no difference between groups
Survival without BPD
Costarino et al.
15
17 o1000 g, o29 weeks,
day 1 of life
Individualized, not different overall between groups 0 vs 34 mM/kg/day Risk of hypernatremia
and large uid volumes
Hartnoll et al.
16
46 2530 weeks with
RDS
Individualized, not different between groups 4 mM/kg/day Starting on day 2 vs 0 until weight
decreased by 6%
Risk of continuing oxygen
dependency
Ekblad et al.
11
20 o35 weeks 50 increasing to 110 in each group 0 Increasing to 2, vs 4 mM/kg/day No clear primary
S EMINARS IN P ERINATOLOGY 38 (2014) 17 2418
Page 2
in sodium intake showed no effect on mortality, whereas
those which varied both showed a reduction in mortality
with restricted water and sodium intake. It is noteworthy that
this second result is largely the result of a single trial with
a very high mortality in the high water/high sodium group,
9
and this subgroup shows substantial heterogeneity.
In contrast the preterm kidney has a limited ability to
excrete a sodium load, and excessive sodium administration
may lead to increases in total body water and increases in
water content of vital tissues. This is true even though there
is natriuresis in the rst few days of life, at least after the rst
24 h, which accompanies the postnatal diuresis. Administra-
tion of sodium during this period may well upset the post-
natal progressive decrease in extra-cellular uid, which is
a normal phenomenon in more mature infants.
10
I performed a systematic review and meta-analysis of RCTs
in preterm infants, which compared two regimes of sodium
administration starting on the rst day of life (Table 1). The
search found ve studies, two of which are as mentioned,
also studies of varying water intake are mentioned above,
and one with very limited description of clinical outcomes
(other than death).
11
The total numbers of infants in these
trials is a disappointing 271. Nevertheless there appears to be
a reduction in mortality RR 0.44 (95% CI; 0.22, 0.90) with a
reduced sodium intake, a possible reduction in BPD, RR 0.76
(95% CI; 0.56, 1.04), and a reduction in the combined outcome
of death or BPD, RR 0.39 (95% CI; 0.23, 0.67) (Fig. 2).
The data are therefore probably best interpreted as showing
that delaying all sodium intake until after either 3 days of life
or after a 5% weight loss improves outcomes, whereas restrict-
ing free-water intake by itself has little or no effect. The major
limitation of these data being that very few extremely imma-
ture babies have been included in any of these studies.
2.2. Research needs
Further studies of optimal management of uids and electro-
lytes in EINs are warranted: they should focus on methods to
further reduce uid loss, and the potential adverse conse-
quences of any individual technique. The interaction
between physical environment uid administration and
sodium administration should be controlled and clearly
described. Good evidence regarding the water and sodium
needs of EINs nursed in high humidity environments is
urgently needed.
3. Nutrition
Over the course of the hospitalization of the very preterm
neonate, adequate nutritional intakes are important to
improve outcomes. It is now clear that both enteral and
parenteral nutrition can be commenced early without
adverse effects. Failure to do so leads to a nutritional decit
which may never be regained.
3.1. Enteral nutrition
There appears to be no good rationale for the traditional
approach of waiting for several days before introducing
enteral nutrition. Feeds should be commenced immediately
as long as there is no specic concern that the intestines are
under-perfused, such as the infant with shock requiring
inotropes. This is the practice in many European NICUs,
and can be successful. It is abundantly clear that human
milk, preferably the mothers' unpasteurized
17
milk is the
preferred food. This creates a dilemma, as mothers' milk may
not be immediately available, due to maternal illness and/or
difculties with milk production after extremely preterm
delivery. Should we wait for mother's milk or commence
donor milk feeding? If donor human milk is not available how
long should we wait, if at all, before giving articial formula?
Once feeds are started, it has become common practice to
institute several days of trophic feedings
18
; this appears to
be preferable to an equivalent period of not feeding, in terms
of nutritional advantages and no evidence of harm. A period
of trophic feeding compared to immediately starting to
increase feeds, in contrast, has only been studied in one
modestly sized trial,
19
which was stopped early. This study
however commenced after a prolonged period of being nil by
Fig. 1 Effects on mortality of studies comparing different levels of uid intake in the preterm infant starting on the rst day of
life, separated according to whether sodium intake was also varied between the groups.
S EMINARS IN P ERINATOLOGY 38 (2014) 17 24 19
Page 3
mouth (average more than 9 days) prior to starting the feeds,
and therefore has little relevance to the question of immedi-
ate commencement and increase of feed volumes. That study
found that the group with immediately increasing feeds after
a period of non-feeding, had more NEC (seven cases of 70
infants) compared to a period of trophic feeding (one case of
71 infants).
There is no other evidence that feeding patterns have any
inuence on the occurrence of NEC, different patterns of
introducing or advancing feeds appear to have no inuence
on the frequency of NEC, even among infants at high risk as
a result of intrauterine growth restriction with reversed
Doppler ow in the umbilical arteries.
20
The rate of increasing
feeds should be based on the infant's tolerance and a goal of
increasing by up to 30 ml/kg/day can be instituted without
fear of adverse effects.
21
3.2. Parenteral nutrition and macro-nutrient intake
Parenteral nutrition can be instituted immediately after birth.
Amino acid solutions are well tolerated, and administration
of at least 1 g /kg/day of protein can prevent catabolism, if
more is given infants can maintain an anabolic state. Imme-
diate institution of up to 3 g/kg/day has been shown to be
tolerated.
22
Because of lower uid administration rates in the
rst few days of life, it has been difcult to achieve good
calorie intake. Hyperglycemia may well follow high glucose
infusion rates, and lipids are traditionally introduced slowly
and then increased over 36 days. The safety of much higher
starting lipid doses, and the use of other innovative appro-
aches, such as supplemental enteral lipid administration, is
uncertain. Routine use of omega-3 containing lipid emulsions
has much theoretically to support it, but there is currently no
safety and efcacy data in the EIN.
3.3. Research needs
Trials comparing immediate increase of feeds, compared to
a period of trophic feeding, in infants having early institution
of enteral feeding in the rst 24 h are required. Comparisons
of different ways to administer an adequate caloric content
would also be useful. Studies of routine use of omega-3
containing lipid emulsions are required.
4. Cardiovascular support
4.1. Hypotension
Numerically low blood pressure is very common on the rst
day of life. If the standards of Watkins are used, about 50% of
extremely low-birth-weight infants will be below 10 percen-
tile at some point in the rst 24 h.
23
This occurs because the
norms were constructed from cross-sectional data, but blood
pressure varies from minute to minute. Therefore many
children will drop below statistically derived percentiles
during the early postnatal period.
24
If a more simplistic
standard, such as BW less than GA is used, even more infants
will be considered hypotensive.
25
There is little reliable
evidence that hypotension thus dened is a marker for poorer
outcomes,
26
and no evidence that treating hypotension
according to such thresholds improves outcomes.
26
Most
infants with low blood pressure have low systemic vascular
resistance and normal systemic perfusion.
27
This common
Fig. 2 Effects on (A) mortality, (B) bronchopulmonary dysplasia, and (C) combined outcome of death or bronchopulmonary
dysplasia, in studies comparing two different levels of sodium intake in preterm infants starting on the rst day of life.
S EMINARS IN P ERINATOLOGY 38 (2014) 17 2420
Page 4
hemodynamic pattern probably needs no intervention, other
than surveillance. However, the concern of some neonatolo-
gists that numerically low blood pressure may impair cere-
bral perfusion leads to some centers treating a very high
proportion of their EINs with uid boluses and inotropes.
28
4.2. Shock
Shock may occur in the extremely preterm infant in the rst
few days of life, either as a result of sepsis or asphyxia. I was
unable to nd any relevant evidence to choose among treat-
ment options: the role and place of steroids, different ino-
tropic agents, and the role of uids, and type of uids are
unknown.
4.3. PDA
Closing the PDA in the rst 3 days of life has no proven clinical
advantages. Prophylactic surgery was shown in one study to
reduce oxygen requirements at 28 days of age,
29,30
but not at 36-
weeks PMA. Prophylactic indomethacin is not universally
effective, but does frequently constrict and sometimes close
the PDA. Nevertheless it does not reduce the frequency of
BPD,
31
it does seem to reduce the risk of severe pulmonary
hemorrhage and decreases the need for later PDA ligation.
32
No
other long-term benet of closing the PDA has been shown.
33
4.4. Research needs
Studies investigating the role of the most commonly used
agents in the early life of the EIN, ie uid boluses and
dopamine are an urgent priority but they will be difcult to
perform.
34
Studies of treatment both of low blood pressure in
clinically stable infants, and infants with signs of systemic
hypoperfusion are both needed. The issues are very different
in these two clinical situations and they should be studied
separately.
5. Respiratory management
5.1. Intubation and surfactant, CPAP
Randomized controlled trials comparing prophylactic to res-
cue surfactant have clearly demonstrated a signicant benet
of prophylaxis. However in those studies the comparison is
between different timing of surfactant administration to
intubated babies. The comparison between early CPAP, with
early intubation and surfactant for rescue, and prophylactic
intubation for surfactant administration has been studied
more recently. There are now four multi-center high-quality
trials that have compared very early intubation to institution
of CPAP in very immature infants. The trials have all enrolled
babies less than 30-weeks gestation, but the exact ranges of
GA differ between the trials, as well as in some other details
(Table 2).
I have performed a meta-analysis of these trials using the
Revman software, using a xed-effects model (Fig. 2). The
overall frequency of death or BPD was lower with CPAP use
compared to routine intubation, and was marginally
Table 2 Randomized trials of effects of initial respiratory management on survival and bronchopulmonary dysplasia.
Trial ID n GA of
subjects
Age of intubation,
control group
Initial pressure of CPAP
(CPAP group)
Indications for failure,
CPAP group
Primary outcome
SUPPORT
35
1316 2427 Weeks In DR, surfactant
within 1 h
5cmH
2
O FiO
2
40.5, CO
2
465,
hemodynamic
instability
Death or BPD
COIN
36
610 2528 Weeks 5 min, Surfactant
optional, according to
local protocol
8cmH
2
O FiO
2
40.6, pH o 7.25
with PCO
2
460,
multiple apneas
Death or BPD
VON-DRM
37
640 (Three
groups)
2629 Weeks 515 min, Immediate
surfactant, with
either INSURE (group
2) or progressive
wean (group 1)
5cmH
2
O (max 7) FiO
2
40.4 option to
intubate, 40.6
mandatory (or CO
2
465 or multiple
apneas)
Death or BPD
CURPAP
38
208 2528 Weeks o30 min, INSURE 67cmH
2
O FiO
2
40.4, CO
2
465 with
pH o 7.2 (multiple
apneas)
Need for ventilation within
the rst 5 days of life
INSURE, intubation for surfactant therapy followed by immediate extubation
S EMINARS IN P ERINATOLOGY 38 (2014) 17 24 21
Page 5
statistically signicant (RR 0.93 [95% CI; 0.86, 1.01]; Fig. 3).
Mortality was a little lower with CPAP, but not statistically
signicant (RR 0.85 [95% CI; 0.69, 1.05]). When creating sub-
groups according to whether intubated infants received
INSURE treatment or standard weaning, there was no differ-
ence between CPAP and INSURE, but a signicant (barely)
reduction in the combined outcome of death or BPD (RR 0.91
[95% CI; 0.83, 0.99]) in the comparison of CPAP to intubation
with standard weaning. There is no signicant heterogeneity.
Although there were no infants of 23-weeks GA in these trials
and only 1 included infants of 24-weeks gestation, this result
does suggest that CPAP in the delivery room, if the infant can
be stabilized without intubation, is at least as effective as
routine intubation, and that if the infant can be intubated,
attempts to rapidly wean and extubate within a short period
of time are appropriate.
6. Neurologic interventions
6.1. Preventing IVH
Antenatal steroids decrease the incidence of PDA. The only
known postnatal intervention that reduces IVH is prophylactic
indomethacin. Indomethacin given intravenously before 6 h of
age decreases both the incidence of IVH overall, and the
incidence of the more severe grades of IVH, including intra-
cerebral hemorrhag e.
39
The large st and highest quality study of
prophylactic indomethacin was unable to show a beneton
neurodevelopmental outcomes, despite a reduction in severe
(grades 3 and 4) IVH from 13% to 9% of the enrolled ELBW
infants.
39
This nding would not be unexpected if indometha-
cin has no effects on cerebral development other than a
prevention of severe IVH. From other published data, one could
estimate that a 4% reduction in severe IVH would lead to a 2%
reduction in neurodevelopmental impairment. To have suf-
cient power to demonstrate a signicant 2% reduction in
adverse outcomes, a trial would require about 9500 patients
per group, which is about 10 times larger than TIPP.
Systematic review and meta-analysis of the studies of
prophylactic indomethacin have conrmed the signicant
reduction in severe IVH, in 14 trials enrolling over 2500
infants about a 35% reduction in severe IVH has been
shown
40
RR 0.66 (95% CI; 0.53, 0.82; p ¼ 0.0001).
6.2. Improving long-term outcome
Studies of long-term neurologic and developmental outcome
are a major example of the interconnectedness of all things
in the care of the preterm infant. The major inuences on
long-term outcome are the following: (1) clinical complica-
tions during NICU stay for example, NEC, infections, BPD,
RoP, surgery of any type, inadequate nutrition, and growth
and (2) socioeconomic status of the family.
Improving long-term outcomes will require a concerted
effort to reduce each of these complications, and also early
intervention programs post-discharge, which could be tar-
geted at the families with the greatest needs.
6.3. Research needs
It is important that we ask parents whether the reduction in
severe hemorrhage is a benet that interests them, even if we
have not shown an improvement in neurodevelopmental
outcomes. They can be assured that there is no evidence of
worsened outcomes, and indeed some subgroup analyses
have shown improved outcomes. It appears to me that it is
likely that parents would prefer to have a reduced likelihood
of being faced with the diagnosis of severe IVH; a 50%
reduction in the need for PDA ligation is another signicant
benet that parents may nd worthwhile.
7. Improving clinical research in the extreme
preterm infant
Parents have for a long time been excluded from setting
research priorities, designing research projects, selecting
Fig. 3 Effects on the combined outcome of death or BPD in studies comparing delivery room institution of CPAP to very early
intubation.
S EMINARS IN P ERINATOLOGY 38 (2014) 17 2422
Page 6
outcome variables of interest, and monitoring ongoing trials;
this form of paternalism, academic paternalism, should be as
unacceptable as individual clinical paternalism. This must
change; our role as physicians should be to educate parents
and involve them in the neonatal research endeavor.
Research projects should investigate outcomes that parents
think are important.
8. Comprehensive protocols of care
In many areas of medicine, the use of checklists, protocols,
and algorithms have been shown to improve clinical out-
comes: from simple surgical checklists
41
to algorithms for
assisted ventilation, to complex comprehensive protocols of
care for oncological patients. Such protocols have been tested
very little in the very preterm infant. One study, with a before
and after design, showed a substantial improvement in
survival without serious brain injury in ELBW infants, with
the introduction of a checklist of admission orders.
42
Further
investigation of the use of such checklists, and comparison
of comprehensive protocols of care, could advance the
clinical science of caring for the extremely preterm infant.
Such protocols will in my opinion be essential as we move
forward. There are so many unknowns, each of which
may impact on several outcomes, and inuence how
other interventions affect those same outcomes, that to
study each variation in care, in isolation, without controlling
other interventions is unlikely to be fruitful. Current
investigational protocols for the treatment of the PDA, for
example, could be much more powerful if initial sodium
management, ventilator management, and nutrition and
uid management were also controlled in each arm of the
trial. In that way the superiority of one protocol over another
could be evaluated.
9. Research networks
Extreme prematurity is relatively infrequent, although much
more common than many conditions that are being actively
investigated in other elds of medicine. Permanent infra-
structure to support research networks should be a priority.
Networks developed to perform trials, and evaluate survival
and long-term quality of life of survivors will be essential to
permit the development of the evidence needed for the
appropriate treatment of the extremely low gestational-age
infant. No center has enough power to be able to do trials
with clinically important outcomes in this patient group.
Research networks have been enormously successful in
several domains, in particular in the care of children with
malignant disease. Such networks require a commitment of
the research community (including parents) to perform the
studies that are required, even if the opportunities for
individual academic recognition are reduced. Removing bar-
riers to prospective trials, including academic conicts of
interest and academic paternalism, will be essential for the
future of care.
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  • [Show abstract] [Hide abstract] ABSTRACT: To examine the association between intensity of perinatal care and outcome at 2.5 years' corrected age (CA) in extremely preterm (EPT) infants (<27 weeks) born in Sweden during 2004-2007. A national prospective study in 844 fetuses who were alive at the mother's admission for delivery: 707 were live born, 137 were stillborn. Infants were assigned a perinatal activity score on the basis of the intensity of care (rates of key perinatal interventions) in the infant's region of birth. Scores were calculated separately for each gestational week (gestational age [GA]-specific scores) and for the aggregated cohort (aggregated activity scores). Primary outcomes were 1-year mortality and death or neurodevelopmental disability (NDI) at 2.5 years' CA in fetuses who were alive at the mother's admission. Each 5-point increment in GA-specific activity score reduced the stillbirth risk (adjusted odds ratio [aOR]: 0.90; 95% confidence interval [CI]: 0.83-0.97) and the 1-year mortality risk (aOR: 0.84; 95% CI: 0.78-0.91) in the primary population and the 1-year mortality risk in live-born infants (aOR: 0.86; 95% CI: 0.79-0.93). In health care regions with higher aggregated activity scores, the risk of death or NDI at 2.5 years' CA was reduced in the primary population (aOR: 0.69; 95% CI: 0.50-0.96) and in live-born infants (aOR: 0.68; 95% CI: 0.48-0.95). Risk reductions were confined to the 22- to 24-week group. There was no difference in NDI risk between survivors at 2.5 years' CA. Proactive perinatal care decreased mortality without increasing the risk of NDI at 2.5 years' CA in EPT infants. A proactive approach based on optimistic expectations of a favorable outcome is justified. Copyright © 2015 by the American Academy of Pediatrics.
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