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Indian Pediatr 2013;50:
573-467 |
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Growth and Neurodevelopmental Outcome of VLBW
Infants at 1 Year Corrected Age
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M Modi, S Saluja, N Kler, A Batra, A Kaur, P Garg, A Soni and *P
Suman
From Departments of Neonatology, and *Pediatrics, Center for Child
Health, Sir Ganga Ram Hospital, New Delhi.
Correspondence to: Dr Manoj Modi, Department of Neonatology, Center
for Child Health, Sir Ganga Ram Hospital, New Delhi, India.
Email: [email protected]
Received: May 18, 2012;
Initial review: June 8, 2012;
Accepted:
October 31, 2012.
PII:
S097475591200427
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Objectives:
To evaluate growth
and neurodevelopmental outcome of very low birth weight infants (VLBW)
and compare with term normal birth weight infants (NBW) till 12 months
corrected age.
Design: A prospective cohort study
Setting: Tertiary care neonatal unit in northern
India
Subjects: 37 VLBW infants and 35 NBW
infants born between January 2007 and December 2007.
Interventions: Anthropometric measurements were
recorded and Z-scores were computed serially at birth, discharge, 40
weeks post menstrual age (PMA), and at 1, 3, 6 and 12 months of
corrected age. Developmental quotient (DQ) at 12 months corrected age
was assessed.
Results: Z-scores for weight, length and head
circumference (HC) at birth were -1.21(±0.92), -0.98(±1.32) and
-0.70(±1.14), respectively for VLBW infants and -0.37(±0.72),
-0.11(±0.96) and 0.05(±0.73) respectively for NBW infants. VLBW infants
had a significant drop in all Z-scores by discharge (P<0.001).
There was a catch up to birth scores by 12 month age. VLBW infants had
significantly lower Z-scores for weight, length and HC at one year
corrected age as compared to NBW infants (P =0.01, 0.04 and
0.001, respectively). DQ at 12 months was significantly lower in VLBW
infants (91.5+7.8) than NBW infants (97.5±5.3) (P <0.001).
DQ of small for gestational age (SGA) and appropriate for gestational
age (AGA) VLBW infants was comparable.
Conclusion: VLBW infants falter in their growth
during NICU stay with a catch-up later during infancy. In comparison to
NBW infants, they continue to lag in their physical growth and
neurodevelopment at 1 year of corrected age.
Key words: Development, Neonate, Outcome, Very low birth weight.
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V
ery low birth weight (VLBW) infants are at higher
risk of poor growth and neurodevelopmental outcomes, due to associated
adverse perinatal risk factors and postnatal morbidities. Several
studies have reported high incidence of growth failure and poor
neurological outcome during infancy and childhood [1-3]. There have been
a few studies from India, reporting growth and neurodevelopment of low
birth weight infants [4-6]. However, there is paucity of data on these
outcomes of VLBW infants. Recently, Mukhopadhyay, et al. [7] have
reported neurodevelopmental outcome of VLBW infants from northern India.
We planned this study with an objective to evaluate
growth and neurodevelopmental outcome of VLBW infants at 12 months of
corrected age and compare it with term, normal birth weight (NBW)
infants.
Methods
All VLBW infants, admitted to our NICU from January
2007 to December 2007 were enrolled and prospectively followed till one
year corrected age. Gross congenital malformation was an exclusion
criteria. This study was approved by the Institutional Review Board and
Hospital Ethics Committee. Parental consent was obtained at the time of
enrolment. Gestational age was recorded as per obstetrical estimates
based on first trimester ultrasono-graphy or if not available, by date
of last menstrual period. Weight was taken at birth, on electronic
weighing scale with accuracy of ± 5 gram, with baby being unclothed.
Length and head circumference (HC) were taken first at 12-24 hrs of age
using standard techniques. Subsequently, measurements were repeated at
discharge and then at 40 weeks, 1, 3, 6, and 12 months of corrected age.
To improve follow up, periodic reminders were sent to parents through
telephonic calls and postal mails.
All VLBW infants were started on enteral feeds as
soon as possible after birth. Parenteral nutrition (PN) was initiated on
first day of life, if infant was not receiving total enetral feeds. Most
infants with birth weight <1250 grams and all with a birth weight <1000
grams received partial parenteral nutrition along with incremental
enteral feeds. As per the unit practice during the study period, PN was
initiated with protein and lipid at 1 gm/kg with daily increments by 1
gm/kg to maximum protein 3.5-4 gm/kg and lipid 3 gm/kg. Target calorie
through PN was 70-90 Cal/kg/day. PN was continued till feed volume
reached 100 ml/kg/day. Enteral feeds were increased gradually to a
volume of 180 mL/kg/day. Human milk was preferred; where not available,
LBW formula was used. Once infant reached 100 mL/kg/day of enteral
feeds, expressed breast milk was fortified with human milk fortifier to
make caloric content of 80 Cal/100 mL, to achieve a target calories
110-130 cal/kg/day. Developmentally supportive care was routinely
provided to all the neonates. Special care was taken for environment
including noise level, light, positioning and nesting. Kangaroo mother
care was offered, once infants were hemodynamically stable. Early
stimulation and intervention, tailored to the infant’s need was provided
during NICU stay and during follow up. A cohort of term, birth weight ( ³2500
grams) infants born during same period, who had uneventful antenatal and
postnatal course, was enrolled for comparison. Their anthropometric
measurements were taken at birth and then at 1, 3, 6 and 12 months of
chronological age.
Z-scores for each anthropometric parameter before 40
wks Post menstrual age (PMA) were computed using Fenton’s reference [8].
Infants below 10 th centile
were categorized as small for gestational age (SGA). For term gestation
and beyond, Z-scores were computed using new WHO growth standard [9].
Neurodevelopmental assessment was done at 1 yr of corrected age, by a
single developmental pediatrician, using Developmental Assessment Scale
for Indian Infants (DASII). Motor index, mental index and combined
developmental quotient (DQ) were computed. We used revised version of
the original Baroda norms [10]. A comparison between VLBW and NBW
infants was made for each anthropometric parameter and development
quotients, at corresponding age.
Statistical analysis was done using SPSS version
17.0. Comparisons were made using independent t test, paired t
test and repeated measure ANOVA, as applicable.
Results
Flow chart of study infants is shown in Fig.
1. Baseline characteristics and morbidity profile of VLBW infants is
depicted in Table I. The mean birthweight and gestational
age of the enrolled VLBW infants were 1238 ± 176 grams and 31.2 ± 2.2
weeks, respectively. Mean birth weight and gestational age of NBW
infants were 3378 ± 598 grams and 38.5 ± 1.2 weeks, respectively.
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Fig. 1 Study flow chart.
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TABLE I Characteristics of The VLBW Infants
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Characteristics |
N = 37
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Birth weight (g)* |
1238(176)
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Gestational age (wk)* |
31.2(2.2) |
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SGA |
17 (46) |
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PIH |
12 (32) |
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Need for Ventilation
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26 (70)
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CPAP
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10 (27) |
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SIMV |
16 (43) |
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Duration of ventilation (days)#
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4 (0; 8.5)
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CPAP days
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3 (0; 5.5) |
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SIMV days |
0 (0; 2) |
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Surfactant |
9 (24) |
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Patent ductus arteriosus requiring treatment |
2 (5) |
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Intraventricular hemorrhage Grade I-II |
3 (8) |
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Cystic periventricular leucomalacia |
1 (3) |
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Culture proven Sepsis |
13 (35) |
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Necrotizing enterocolitis stage II or more |
2 (5) |
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ROP Any stage |
2 (5) |
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*Values expressed as mean (SD); #values expressed as median
(IQR)Other values expressed as n (%); No neonate has chronic
lung disease or grade III-IV intraventricular hemorrhage. |
Anthropometric parameters of VLBW and NBW infants are
depicted in Web Table I. Among VLBW infants, there was a
significant decline in all three anthropometric parameters from birth to
discharge (P <0.001). Thereafter, there was an increase in all
Z-scores during infancy (Fig. 2). After 40 wks PMA, the
difference of each anthropometric Z-score from respective birth Z-scores
was insignificant. However, all anthropometric Z-scores of VLBW infants
continued to be significantly lower than NBW infants, throughout infancy
(P<0.05).
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Fig. 2 Growth pattern of VLBW infants
from birth to 12 months.
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Developmental indices of enrolled infants are
displayed in Table II. Developmental indices of VLBW
infants were significantly lower than that of NBW infant (P<0.01).
A DQ <85 was observed in 22% of VLBW infants. Developmental indices in
AGA and SGA VLBW infants were comparable. Developmental quotient was
significantly lower in VLBW infants with 12 months head size below -1SD
than those with head size above -1SD (P<0.05) (Web Table
II).
TABLE II Developmental Indices of VLBW and NBW Infants at 12 Months
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VLBW infants (n=37) |
NBW infants (n=35) |
Mean difference (95% CI) |
P value |
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DQ |
91.5(7.8) |
97.5(5.3) |
-6.0 (-9.3 to -2.6) |
0.001 |
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Motor index |
90.1(9.6) |
96.6 (5.8) |
-6.4 (-10.5 to -2.4) |
0.002 |
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Mental index |
92.9 (8.0) |
98.4 (6.1) |
-5.5 (-9.0 to -2.0) |
0.003 |
Discussion
Majority of VLBW infants are born smaller for their
respective gestation as compared to their NBW counterparts [1,11]. We
observed that VLBW infants at birth had lower Z-scores for weight,
length and HC as compared to NBW controls. This suggests that most VLBW
infants suffer intrauterine growth failure, possibly due to adverse
perinatal factors. Amongst these infants, about 20-25% have been
reported to be small for gestational age [1,12]. The incidence of growth
restriction was higher in our cohort, with 47% of VLBW infants being
SGA, which is similar to other reports in Indian infants [6,13]. This
could be due to differences in socio-economic factors, ethnic variation
or perinatal morbidities in our cohort.
It has been suggested that the postnatal growth of
VLBW infants should match intrauterine growth rates during third
trimester [14]. However, most VLBW infants experience a growth lag
during NICU stay [1,13,15]. This extra-uterine growth failure is
possibly due to neonatal morbidities, inappropriate nutritional
management or unfavourable NICU environment. Our VLBW infants had a
decline in Z-scores, from birth to discharge, by approximately 1 unit
for weight and length and 0.7 unit for head circumference. This pattern
is similar to other observations of postnatal growth of VLBW infants
during initial hospitalization [1,15,16].
After early growth failure, VLBW infants experience a
catch up in growth beyond infancy through adolescence [1,13,16,17]. We
observed a steady improvement in all anthropometric parameters of VLBW
infants from discharge to 12 months. This growth pattern is consistent
with findings of other authors, who reported a similar magnitude of
improvement in anthropometric Z-scores [1,16]. Despite a catch up to
their birth scores by 12 months age, our VLBW infants remained
significantly smaller and lighter than NBW infants. Considering the risk
of metabolic syndromes, it is debatable whether VLBW infants should
catch up to their NBW counterparts or continue to grow along their birth
centiles. A larger cohort
with long term follow up is required to address this issue.
VLBW infants have been observed to have poor
long-term neurodevelopmental outcomes [3,18]. Mean DQ at 12 months in
our VLBW cohort was 6 points lower than that of NBW infants.
Developmental quotients in our cohort were approximately 10-12 points
higher than previous observations [7,18]. In the study by Procianoy,
et al. [2], mean mental and motor indices, at 1 year of age ranged
from approximately 78 to 80. Higher DQs in our infants are possibly
related to higher gestation and lower neonatal morbidities, or a
difference in assessment tools used. The mean gestation of VLBW infants
in our study was also significantly higher than the cohort reported by
Pracianoy, et al. [2]. Mukhopadhyay, et al. [7] reported
mean mental and motor quotients at 18 months, 80.4 (±10.7) and 77.2
(±13.3), respectively. The conspicuous difference in developmental
indices of our cohort could be related to lower incidence of IVH and
other morbidities (ROP, BPD, etc.) in our cohort. Further, earlier age
at assessment in our study might have missed subtle motor and cognitive
deficits, which could unmask subsequently. For more appropriate
inferences, there is a need to evaluate long-term neurological outcome
of our VLBW cohort at a later age.
There are contradictory reports about
neuro-devlopmental outcomes of SGA infants [19-21]. We did not find a
significant difference in either motor or mental developmental index in
SGA VLBW infants, compared to AGA VLBW infants. The mean gestation of
SGA infants in our cohort was 32.8 (±1.5) weeks as compared to 29.8
(±1.70) weeks in AGA infants. The morbidities associated to lower
gestation, would possibly offset any potential benefit of AGA status of
these infants. Comparison of gestation matched AGA and SGA might
disclose any potential difference. This comparison was not possible in
our study due to smaller number of subjects.
Poor head growth has been linked to poor neurological
outcome [22,23]. To explore association of head growth and neuro-developmental
outcome, we categorized VLBW infants into two groups, with HC at 12
month below and above -1SD. During design phase of the study, it was
decided to compare infants with HC below or above-2SD. However due to
smaller number of subjects below -2 SD, a post hoc analysis was done
with a cut off of -1SD. DQ at 12 months was significantly lower for VLBW
infants with a head size below -1SD. This observation reiterates the
association of head growth to neurological outcome.
Ours was a prospective cohort study, comparing the
outcomes of VLBW infants with a simultaneously enrolled normal birth
weight cohort. In this study, we assessed both physical growth as well
as neurodevelopmental outcome of VLBW infants. Neuro-developmental
outcome was assessed using DASII, which has been validated for Indian
infants. However, the number of infants enrolled in the study was small.
There was 18% follow up loss in this study. Age at final assessment in
our study was also early wherein we may have missed minor neurological
deficit, as longer follow up duration is required to assess subtle
cognitive deficits, behavioral disorders and scholastic performance.
To summarize, our study shows that VLBW infants catch
up to their birth Z scores by infancy; however, they continue to remain
smaller and lighter as compared to normal birth weight infants.
Neurodevelopmental indices of the VLBW infants at 1 year are lower as
compared to the NBW infants. Despite advances in neonatal care, growth
and neurodevelopment of VLBW infants during initial hospitalization and
infancy remains a challenge. A multipronged approach is required to
improve growth and development of these infants.
Contributors: MM and SS conceived the idea and
designed the study. MM, BA and KA were responsible for data collection
and analysis. AS and PG helped in editing manuscript. SP and MM
performed the neurodevelopment assessment. NK supervised the study and
helped in editing the manuscript. All authors approved the final content
of the manuscript.
Funding: None; Competing interests: None
stated.
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What is Already Known?
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VLBW infants suffer a growth lag
during early infancy with a catch up during childhood and
adolescence. They have poor neurodevelopment outcome as compared
to normal birth weight infants.
What This Study Adds?
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This study highlights growth pattern and neuro-developmental
outcome of Indian VLBW infants during infancy.
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