Indian J Pediatr (December 2011) 78(12):1485–1490

DOI 10.1007/s12098-011-0442-9

ORIGINAL ARTICLE

Growth and Neurosensory Outcomes of Preterm Very Low

Birth Weight Infants at 18 Months of Corrected Age
Pradeep Kumar Sharma & M. Jeeva Sankar &
Savita Sapra & Rohit Saxena & C. Venkat Karthikeyan &
Ashok Deorari & Ramesh Agarwal & Vinod Paul

Received: 20 August 2010 / Accepted: 29 April 2011 / Published online: 16 July 2011
# Dr. K C Chaudhuri Foundation 2011

Abstract Results During the period from July 2006 through June
Objective To determine the growth and neurosensory out- 2007, there were 141 neonates born at gestation ≤32 wks
comes of infants with birth weight ≤1,500 g or gestation or birth weight ≤1,500 g. Seven infants had major
≤32 wks at 18 months corrected age. This prospective malformations, 30 died before discharge, 36 had residence
cohort study was conducted at a Level III neonatal unit in >20 km and parents of four had refused consent. The
India. The neonates with birth weight ≤1,500 g or gestation remaining 64 neonates were enrolled for follow up. The
≤32 wks were included in the study. mean gestation and birth weight were 31(2.4) wks and 1208
Methods The infants were followed up at 3,6,9,12 and (365) g respectively. There were 38 (59%) small for
18 months corrected age. Weight, length and head circumfer- gestation infants. Fifty-five infants completed 18 months
ence were plotted on WHO multisite growth reference study follow up for growth outcomes. Seventeen (30.9%; 95% CI
(MGRS) charts. Neurological examination was conducted by 18.3% to 43.5%) infants were undernourished, 28(50.9%;
Amiel-Tison method, hearing was evaluated with brainstem 95% CI 37.3% to 64.6%) were stunted, 8(14.5%; 95% CI 0
auditory evoked responses, vision assessed with Teller acuity to 24) were wasted and 14(25.4%; 95% CI 13.6% to
cards, and development assessed with Developmental Assess- 37.3%) had microcephaly. Infants with birth weight
ment Scales for Indian Infants II. <1,000 g (n=17) were significantly more affected. Ten
(58.8%; p<0.01) were undernourished, 13(76.5%; p<0.01)
were stunted and 10(58.8%; p<0.01) had microcephaly.
R. Saxena
Department of Ophthalmology, Complete formal neurological evaluation for development,
All India Institute of Medical Sciences, hearing and vision was done in 31 infants. Six of these 31
New Delhi, India (19.3%; 95% CI 4.6% to 34.1%) infants had one or more
major disabilities. These included cerebral palsy (n=3),
S. Sapra
Department of Pediatrics, developmental delay (development quotient <70, n=3), and
All India Institute of Medical Sciences, deafness (n=3).
New Delhi, India Conclusions Very low birth weight infants are at a high risk
P. K. Sharma : M. J. Sankar : A. Deorari : R. Agarwal (*) :
of neurosensory disability and growth failure. There is a
V. Paul need to create a nation-wide database of these infants for
Division of Neonatology, Department of Pediatrics, neurodevelopment and growth outcomes.
All India Institute of Medical Sciences,
WHO Collaborating Centre for Training and Research, Keywords Neurodevelopment . Growth
Ansari Nagar,
New Delhi 110029, India
e-mail: ra.aiims@gmail.com
Introduction
C. V. Karthikeyan
Department of Otorhinolaryngology,
All India Institute of Medical Sciences, There has been an impressive improvement in survival
New Delhi, India of very low birth weight neonates in the last two
1486 Indian J Pediatr (December 2011) 78(12):1485–1490

decades.[1] These infants are at high risk of lifelong Follow Up

problems including developmental delay, visual and
hearing problems; behavioral problems and learning The infants were evaluated at 3 months±2 wks, 6 months±
disabilities. With increasing survival of these infants due 2 wks, 9 months±4 wks, 12 months±4 wks and 18 months±
to advances in perinatal medicine, it might be predicted 6 wks of corrected age.
that the incidence of chronic morbidity and long term
sequelae would also increase. This increasing number of Growth
disabled infants will affect the resources of family and
society.[2] Weight was taken on an electronic weighing scale (Zeal
There is paucity of data on long term outcome of very products) with an error of ±1 g after removal of clothes
low birth weight patients from developing countries and shoes. Length was measured with an infantometer.
including India. There is only one large study from Pune Head circumference was measured with nonstretchable
on long term follow up of low birth weight babies.[3–5] fiberglass tape at the maximum occipitofrontal diameter.
They have reported that low birth weight babies are The Z-score were calculated according to The WHO
significantly disabled compared to the normal controls. Multicentre Growth Reference Study (MGRS) growth
But only less than one-third infants in this study were very charts.[7]
low birth weight.
The data from developed countries currently cannot be Neurological Assessment
extrapolated to the population in the developing countries
as we have more small for gestational age infants and The infants were evaluated for development in the high risk
their genetic make-up and the environment in which they clinic by the principal investigator. Any seizures or
are reared, the level of care and infrastructure are involuntary movements were recorded. The tone was
different. Therefore, there is a need for follow up studies assessed by standard neurological examination and
from such settings to assess the long term outcome of Amiel-Tison method.[8]
very low birth weight infants. In the present study, the
authors followed a cohort of infants born with birth Eye Evaluation
weight ≤1,500 g or gestation ≤32 wks at a tertiary care
center till 18 months of corrected age for growth and The ophthalmologist evaluated the infants for vision,
neurosensory outcomes. squint, cataract and optic atrophy. The objective visual
assessment was done with the Teller Acuity Card.

Material and Methods Hearing Evaluation

The study was conducted at a high risk clinic of the First a screening brainstem auditory evoked response
neonatal unit of a tertiary care hospital in north India. It (BERA) was done. If abnormal, it was confirmed with a
was a cohort study. Infants were enrolled from July 2006 repeat test. The babies were sedated with oral chloral
through June 2007 and were followed up till February hydrate 50 mg/kg 30 min before the procedure. The test
2009. The inclusion criteria were birth weight ≤1,500 g was done by a trained technician in a sound-proof
or gestation ≤32 wks. The exclusion criteria were major audiometry room. Deafness was defined as severe to
malformation, death before discharge and residence more profound hearing loss requiring hearing aids.[9]
than 20 km from the study site.
Developmental Assessment
Baseline Assessment
The mental development index (MDI) and psychomotor
The demographic profile and neonatal morbidity were development index (PDI) were calculated by the clinical
recorded in a predesigned proforma. The gestational age psychologist using Developmental Assessment Scales for
was calculated from the last menstrual period (LMP) or Indian Infants (DASII).[10] The scale consists of 67 items
first trimester sonogram, if LMP not available. It was for assessment of motor development and 163 items for
assessed by Expanded New Ballard Score.[6] In case of assessment of mental development. Motor scale assesses
discrepancy of more than 2 wks, the latter was taken as the control of gross and fine motor muscle groups. Mental scale
gestational age. assesses cognitive, personal and social skills development.
Indian J Pediatr (December 2011) 78(12):1485–1490 1487

The age placement of the item at the total score rank of the Table 1 Baseline characteristics (n=64)
scale is noted as the child’s developmental age. This Characteristics Results
converts the child’s total scores to motor and mental
development quotients, respectively by comparing them Birth weight (g) 1208±365
with his chronological age and multiplying it by 100. <1000 20 (31)
ðDMoQ ¼ MoA=CA  100 and DMeQ ¼ MeA=CA  100Þ. ≥1000 44 (69)
The composite DQ is derived as an average of DMoQ and Gestation (wks) 31.6±2.4
DMeQ. <28 6 (9)
The infants were followed in a multidisciplinary ≥28 58 (91)
approach involving a team of pediatricians, child Intrauterine growth category
psychologist, pediatric neurologist, ophthalmologist, Appropriate for gestational age 24 (37)
otorhinolaryngologist, physiotherapist, occupational ther- Small for gestational age 38 (59)
apist, medical social worker, and a dietician for the Large for gestational age 2 (3)
management of these infants. Males 35 (55)
Mothers’ age (years) 28.2±4.1
Parity
Results Primipara 28 (47)
Multipara 32 (53)
During the period from July 2006 through June 2007, Mother’s education (years)
there were 1977 live births in the present hospital. A ≤12 26 (43)
total of 111 (78.7%) of 141 babies, born at ≤32 wks >12 34 (57)
gestation or birth weight ≤1,500 g survived to dis- Family income (Indian rupees per month) 13985±12714
charge. Seven babies had major malformations. Parents <10000 28 (47)
of four infants refused consent for participation in the ≥10000 32 (53)
study for follow up and 36 were staying more than Pregnancy induced hypertension 27 (42)
20 km away from the study site. The remaining 64 Cesarean section 48 (75)
infants were enrolled for follow up. Of them, five died Multiple gestation 12 (19)
and four were lost to follow up. Accordingly, 55 infants Antenatal steroids 41 (66)
underwent assessment for neurological examination and Surfactant use 8 (13)
growth, while 31 had complete formal evaluation Premature rupture of membranes >24 h 7 (11)
including development, hearing and vision. The mean Chorioamnionitis 2 (3)
age at last follow up was 19.0 ± 2.7 months. The mean Severe birth asphyxia (Apgars <3 at 5 min) 1 (2)
birth weight and gestation of the enrolled infants were Postnatal steroids 4 (7)
1,208 ± 365 g and 31.6 ± 2.4 wks, respectively. There
a
were 20 (31%) extremely low birth weight infants. Data expressed as mean ± SD or n(%); 64 neonates and 60 mothers:
There were 35 (54.7%) males and 38 (59%) small for multiple pregnancies 6, 2 deaths during neonatal period
date infants (Table 1).
Growth Outcomes in Small for Gestational
Age (SGA) Infants
Growth
The SGA neonates had more severe growth retardation
One-third infants were undernourished at 18 months of compared to their AGA counterparts. More than half were
corrected age. Half were stunted and one-fourth had stunted, nearly 40% were undernourished and one-third had
microcephaly (Table 2). microcephaly (Table 3).
There was improving trend in weight and head
Growth Outcomes in Infants with Birth Weight <1,000 g circumference with age. The prevalence of undernutrition
decreased by almost 50% from 3 months to 18 months
Half were undernourished and had microcephaly and two- corrected age.
thirds were stunted. The weights for age, height for age,
weight for height and head circumference Z- scores were Major Disability Six Infants Had Major Disability (Table 4).
significantly lower in these infants. None Had Blindness or Epilepsy
1488 Indian J Pediatr (December 2011) 78(12):1485–1490

Table 2 Growth outcomes at

18 months of corrected age by Growth parameter Birth weight <1,000 g (n=17) Birth weight≥1,000 g (n=38)
birth weight (n=55)
Z score
Weight for age −2.3±1.2 −1.1±1.3
Length for age −2.9±1.7 −2.0±1.3
Weight for length −1.1±0.9 −0.2±1.4
HC for age −2.2±1.7 −0.9±1.0
Undernutrition (weight for age <2SD) 10 (58.8) 7 (18.4)
Stunting (length for age <2SD) 13 (76.5) 15 (39.5)
Date expressed as n (%), Wasting (weight for length <2SD) 3 (17.6) 5 (13.2)
Mean ± SD
Microcephaly (HC for age <2SD) 10 (58.8) 4 (10.5)
HC Head circumference

Major Disability in Infants with Birth Weight <1,000 g nary dysplasia had recurrent episodes of wheezing and were
on inhaled bronchodilators.
There were 11 infants with birth weight less than 1,000 g who There were five infants who had died after discharge. All
underwent complete evaluation for neurosensory disability. these deaths occurred at home.
Four (36.4%) had major disability. Three (27.3%) had
cerebral palsy and development quotient less than 70.
Discussion
Major Disability in Small for Gestational Age (SGA)
Infants With improvement in neonatal services across the
country there is a greater survival of very low birth
There were 18 small for gestational age (SGA) infants. Five weight babies; hence in the number of infants with
had major disability. Three had cerebral palsy and develop- disabilities which can cause considerable burden on the
mental delay. Two had deafness. There was no statistically families and the society.3 This becomes even more
significant difference between the two groups for the important for countries with limited resources. Therefore,
incidence of any major disability. there is a need to objectively document the burden of
disability in prospective studies. In an attempt to address
Post Discharge Morbidity and Mortality this issue, the authors assessed the neuromorbidity and
growth outcomes at 18 months of corrected age of
There were five babies who required hospitalization after infants born with birth weight ≤1,500 g or gestation
discharge from the NICU. Two infants with bronchopulmo- ≤32 wks. Since birth weight is not the only criterion to
assess maturity due to a high incidence of intrauterine
growth retardation in less developed countries and the
Table 3 Incidence of major neurological disabilities at 18 months of gestational assessment is not feasible in all the settings
corrected age where mothers do not remember their last menstrual
period dates or use lunar calendars and first trimester
Major disability1 Affected n(%)
ultrasonography is not a routine, the authors have taken
Any disability2 6/31(19.3) both the birth weight and gestation as the criteria for
Cerebral palsy3 3/55 (5.4) maturity.
Developmental delay2 3/31 (9.7)
Deafness2 3/31 (9.7) Neurosensory Disability

1
Neurosensory abnormality was defined by the presence of either These deficits are more compared to that reported by
cerebral palsy, developmental delay (development quotient <70), Chaudhari et al. from Pune in a large prospective study of
blindness (visual acuity <6/60 in the worse eye checked with Teller
acuity cards), deafness (requiring hearing aids) or epilepsy (two or low birth weight infants with 4% incidence of cerebral
more unprovoked seizures) palsy 4%.[3] This could be because there were more
Data expressed as numbers (percentages) premature babies in the present study. The present results
2
31 infants had complete formal evaluation with DASII, BERA and compare with the meta-analysis by Escobar et al., of 141
TAC follow up studies on very low birth weight babies which
3
55 infants underwent clinical neurological assessment showed a median incidence of cerebral palsy 7.7% and
Data mutually not exclusive major disability 25%.[11]
Indian J Pediatr (December 2011) 78(12):1485–1490 1489

Table 4 Growth outcomes at 18 months of corrected age by intrauterine growth category (n=55)

Growth parameter SGA (n=34) AGA (n=19) Difference in means/OR (95% CI) P value

Weight for age Z score −1.9±1.4 −0.9±1.0 1.1 (0.4–1.8) 0.00

Undernutrition 14 (41.2) 3 (15.8) 2.0 (0.7 to 6.1) 0.11
Length for age Z score −2.5±1.6 −2.0±1.2 0.6 (−0.2–1.4) 0.14
Stunting 20 (58.8) 8 (42.1) 1.2 (0.4 to 3.2) 0.17
Weight for length Z score −0.9±1.4 0.1±1.0 1.1 (0.4–1.8) 0.00
Wasting 8 (23.6) 0 (0.0) 4.1 (0.8 to 22.0) 0.07
HC for age Z score −1.5±1.5 −1.1±1.1 0.5 (−0.3–1.2) 0.20
Microcephaly 11 (32.6) 3 (15.8) 1.6 (0.5 to 5.0) 0.37

Date expressed as n (%), Mean ± SD, HC Head circumference, AGA Appropriate for gestational age, SGA Small for gestational age

Although most of the infants did not have developmental decreased by half but stunting persisted suggesting chronic
delay, they still had the development quotients much below undernutrition. Bhargava et al had similarly observed a
that for the normal infants. These infants later on may have disappearance of growth differences between small for
difficulties in doing complex activities requiring concentration gestational age and appropriate for gestational age infants
and intuition. after the age of 5 years.[12] This catch-up growth should be
Since more than half of the neonates in the present study watched cautiously as there is altered metabolic programming
had intra-uterine growth retardation, they might be rela- in intra-uterine growth retarded infants which has been shown
tively mature and the survival and outcome would have to be associated with various diseases with manifestation
varied for the corresponding birth weights. There was a during adult life. [13]
mortality of more than 20% before discharge. These The authors used WHO MGRS growth curves which
neonates were very sick with considerable morbidity and have been derived from healthy term breast-fed infants and
would have contributed to increase in major disability if may not represent very low birth weight infants. This may
survived. be one of the reasons for a very high incidence of growth
Most of the infants with major disability were sick failure reported in the present study. There is a need for
during hospital stay, requiring intensive care and multiple separate growth curves for these infants as targeting the
interventions including mechanical ventilation, blood trans- growth of normal healthy infants may lead to inadvertent
fusions, treatment for symptomatic patent ductus arteriosus, overfeeding, obesity and subsequently, increased morbidity
antibiotics for sepsis and parenteral nutrition. This may help in adult life.
us to generate data for quality improvement of perinatal
care to reduce neuromorbidity. Post Discharge Morbidity and Mortality

Growth Post discharge morbidity was a considerable problem

resulting in many infants requiring hospitalization. All
Most of the previous studies have focused on neurodevelop- these infants were extremely low birth weight and most
ment and thus, postnatal growth remained neglected, which common reasons for hospitalization were infections. The
was the major problem in the present study cohort. Nearly mortality after discharge in the present study cohort was
one-third infants were undernourished, a half were stunted similar to that reported from the authors’ institute by Maria
and one-fourth had microcephaly at 18 months corrected age. et al [14]. Sepsis was the most common cause of death. The
Nearly half of the infants with major disability were socio-economic status of the parents of these infants was
undernourished, two-thirds were stunted and one-third had looked into but none was significantly associated with
microcephaly. This highlights the importance of extreme mortality.
prematurity and in-utero growth retardation for subsequent Knowing the outcomes of very low birth weight infants
postnatal growth and neurodevelopment. is important to assess the quality of perinatal care provided.
At 3 months postnatal age more than half of the infants The authors had a multidisciplinary approach to these
were undernourished, stunted and had microcephaly. This children which included pediatricians, a trained clinical
suggests that in-utero growth retardation continues postna- psychologist, ophthalmologist, otorhinolaryngologist,
tally. There was catch-up growth with time and at 18 months dietician and a physiotherapist. The clinical assessment
of corrected age, undernourishment and microcephaly was done by a trained single observer and the outcomes
1490 Indian J Pediatr (December 2011) 78(12):1485–1490

were also robust. The duration of follow up around Conflict of Interest None.
18 months of corrected age, picks up major disabilities
and by this time the transient tone abnormalities also Role of Funding Source None.
disappear. Later on with longer duration of follow up,
environmental effects become increasingly important. The
present study can act as a bench mark for future studies on References
neurosensory outcome and growth of very low birth weight
infants in our country. 1. Blackman JA. Neonatal intensive care: is it worth it? Developmental
There are several limitations of the present study. The sequelae of very low birth weight. Pediatr Clin N Am.
1991;38:1497–11.
number of infants followed up was small. There were 2. Vohr B, Msall ME. Neuropsychological and functional outcomes of
several children who could not undergo formal develop- very low birth weight infants. Semin Perinatol. 1997;21:202–20.
mental assessment with DASII, BERA for formal hearing 3. Chaudhari S, Kulkarni S, Barve S, Pandit A, Sonak U, Sarpotdar
assessment and Teller acuity card test for visual assessment. N. Neurologic sequelae in high risk infants—a 3 year follow up.
Indian Pediatr. 1996;33:645–53.
The authors did not include a control group for comparison. 4. Chaudhari S, Bhalerao MR, Chitale A, Pandit AN, Nene U. Pune
Longer follow up duration is required to assess subtle low birth weight study—a 6 year follow up. Indian Pediatr.
cognitive deficits, behavioral disorders and school prob- 1999;36:669–76.
lems. The authors’ unit caters to only high risk booked 5. Chaudhari S, Otiv M, Chitale A, Pandit A, Hoge M. Pune low
birth study- cognitive abilities and educational performance at
pregnancies. This may limit the external validity of the 12 years. Indian Pediatr. 2004;41:121–8.
study to centers where unbooked pregnancies and outborn 6. Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL,
babies are also cared for. The authors followed WHO Lipp R. New Ballard Score, expanded to include extremely
MGRS growth charts which are designed for term healthy premature infants. J Pediatr. 1991;119:417–23.
7. Who Multicentre Growth Reference Study Group. The child
infants and may not represent the growth of the type of growth standards. Available at: http://www.who.int/childgrowth/
infants included in the present study. Also, the effect of the standards/en/
environment on the neuromorbidity of these infants was not 8. Amiel-Tison C, Stewart A. Follow up studies during the first
measured. 5 years of life: a pervasive assessment of neurological function.
Arch Dis Child. 1989;64:496–502.
9. Watkin PM, Baldwin M. Confirmation of deafness in infancy.
Arch Dis Child. 1999;81:380–9.
10. Phatak P. Mental and motor growth of indian babies (1–30 months).
Conclusions
Final report. Baroda: Department of Child Development, MSUB.
1970: 1–85
Very low birth weight infants remain at high risk of long 11. Escobar GJ, Littenberg B, Petitti DB. Outcome among surviving
term neurosensory disability despite improvement in very low birth weight infants: a meta-analysis. Arch Dis Child.
1991;66:204–11.
NICU care and supportive therapy after discharge. The
12. Bhargava SK, Kumari S, Chaudhury P. Outcome of low birth
risk of growth failure is very high despite early weight infants. Acta Paediatr Scand. 1984;73:406–7.
aggressive parenteral nutrition and fortified formula. 13. Dover GJ. The Barker hypothesis: how pediatricians will diagnose
There is a need to correlate the growth with neuro- and prevent common adult-onset diseases. Trans Am Clin
Climatol Assoc. 2009;120:199–207.
development in these infants. A large database of very
14. Maria A, Gupta A, Aggarwal R, Sreenivas V, Paul VK, Deorari AK.
low birth weight infants from across the country with Incidence of periventricular leucomalacia among a cohort of very
longer follow up is needed. low birth weight neonates(<1500 g). Indian Pediatr. 2006;43:210–6.