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Indian Pediatr 2017;54: 629-634 |
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Physical Growth, Morbidity Profile and
Mortality Among Healthy Late Preterm Neonates
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Priyanka Gupta, Ritu Mital, Bimlesh Kumar, Ajeet
Yadav, Mohit Jain and Amit Upadhyay
From Department of Pediatrics, LLRM Medical College,
Meerut, UP, India
Correspondence to: Dr Amit Upadhyay, Head, Department
of Pediatrics, LLRM Medical College, Meerut, Uttar Pradesh, India.
Email: [email protected]
Received: April 01, 2016;
Initial Review: July 14, 2016;
Accepted: May 19, 2017.
Published online:
June 04, 2017.
PII:S097475591600062
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Objective: To compare the physical growth outcomes, morbidity
profile and mortality at an age of 12 months among late preterm (34
0/7to 36 6/7) neonates to term (37 0/7to 41 6/7) neonates.
Study design: Prospective cohort
study.
Setting: A tertiary care
center of Northern India during 2014-2015.
Participants: 200 apparently
healthy late preterms and term infants, followed up to 12 months of age.
Main outcome measures: Physical
growth parameters, morbidity profile and mortality.
Results: At mean age of 12
months, mean (SD) weight, length and head circumference of late preterms
were 7.4 (0.8) kg, 69.2 (2.5) cm and 43.0 (1.1) cm, respectively; which
were significantly lower than that of the full term infants [8.7 (1.6)
kg, 72.2 (3.1) cm and 44.2 (1.1) cm] (P< 0.001). On univariate
analysis, late preterm group was associated with higher odds (95% CI) of
being underweight [5.6 (3.4, 5.5)], stunted [3.5 (2.1, 5.8)] and wasted
[3.6 (1.9, 6.9)]. On multivariate analysis, only adjusted odds of late
preterms becoming underweight by one year was significant [OR 4.1; 95%
CI (1.6, 10.4)]. Feeding difficulties, jaundice and re-hospitalization
rates were significantly higher in the late preterm group. The median
(IQR) episodes per baby for late preterms as compared to terms for
diarrhea [1.84 (0,3) vs 1.14 (0,2) (P <0.001)], and fever
[1.33 (0,2) vs. 0.95 (0,2) (P = 0.01)] were higher.
Conclusion: Healthy late preterms
are at significantly higher risk of being underweight in the first year
of life, in addition to having significantly higher morbidity.
Keywords: Prematurity, Prognosis, Stunting,
Underweight, Wasting.
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L ate preterm (LPT) infants accounts for nearly 8%
of all births and almost 74% of all preterm births [1]. They are at
increased risk for having higher morbidities and mortality in the
neonatal period as well as adverse neurodevelopmental outcomes as
compared to full term (FT) infants [2-4]. Late preterms have also been
shown to have higher health care utilization rates [5],
re-hospitalization rates and mortality by 1 year of age [6,7]. However,
majority of them do not require admission in neonatal intensive care
unit (NICU) soon after birth. Such infants are often left out from the
ambit of follow-up and growth monitoring. Few retrospective studies from
developed countries have reported that even such apparently healthy
looking late preterms have higher morbidity and mortality in the initial
years of life [3]. A recent study from India has compared the short term
outcomes of late preterms, [8] but there is no Indian data on longer
follow-up of such infants. With this background, we designed this cohort
study with the objective of follow-up of apparently healthy asymptomatic
late preterm infants till 1 year of age and assess them for physical
growth, morbidity and mortality.
Methods
This cohort study was conducted after obtaining
approval from Institutional Ethical Committee of the LLRM Medical
College, Meerut, Uttar Pradesh in Northern India. All neonates born
between April 2014 and August 2014 were assessed for eligibility, and
enrolled neonates were followed till 1 year of age. Informed written
consent in local language (Hindi) was obtained from mother and/or father
of the enrolled infant. Healthy late preterms (born between 34 0/7to
366/7 gestational age) [9]
appropriate for gestational age (AGA) neonates delivered in the
hospital, who did not require resuscitation or admission in the NICU for
more than 48 hours and resided within 20 km radius of institution
premises were included as cases. We excluded multiple births, those with
major congenital anomalies, and those with families who were reluctant
for institutional follow-up for any reason. Control group constituted
the next born healthy term infant (370/7to
416/7weeks) who did not
require resuscitation or admission in NICU for more than 48 hours, and
consented for follow-up.
Gestational age was documented in completed weeks
from the date of mother’s last menstrual period (LMP) or antenatal
ultrasonography of first trimester. If LMP or ultrasonography were not
available, gestational age was estimated using New Ballard Score [10].
AGA, SGA and large for gestational age were defined by standard growth
charts [11]. Follow-up of infants in the two groups was planned at the
time of all routine immunizations and at 12 months of age. We
telephonically reminded all parents for their visit to hospital and for
routine immunization and follow-up. For study purpose, detailed physical
growth parameters were recorded only at 12-month visit. Morbidities were
recorded at every immunization visit, and finally at 12 months. Similar
standard of care was provided to infants in both groups.
The primary outcome of the study was physical growth
parameters: weight-for-age (WFA), length-for-age (LFA),
weight-for-length (WFL), head circumference for age (HFA), and
respective Z-scores at 12 months of age. The secondary outcomes were to
determine the morbidity profile, which was recorded in a questionnaire.
Maternal details and other potentially confounding maternal and family
covariates were noted. Socioeconomic status was classified as per the
Modified Kuppuswami Classification [12].
Naked weight was measured by calibrated digital
weighing machine (Dolphin India), with precision error of 5 gram. Length
was measured with infantometer designed to measure lengths between 0 and
100 cm with precision of 1 mm. Head circumference (HC) was measured
using a self-retracting, 0.7 cm wide, flat metal tape with black lead-in
strip (range 0-200 cm, calibrated to 1 mm). Measurements were recorded
by two invesigators throughout the duration of study. WFA, WFL, LFA and
HFA were calculated using WHO multicenter growth reference study (MGRS)
charts. Z score for these values was calculated using ‘WHO
Anthropometric Calculator’ version 3.2.2 (www.who.int/child growth/
software/en/). Those with WFA, LFA and WFL scores below -2SD were
labelled underweight, stunted and wasted, respectively [13].
At every follow-up, we examined the children and
prescribed routine immunization as per hospital schedule. Parent(s) were
asked about number of episodes of diarrhea, pneumonia, hospitalizations,
and feeding difficulties. Feeding difficulties were classified as
difficulties attributable to the infant (poor attachment/latching,
excessively sleepy infant) and those attributable to the mother (not
enough milk, flat or inverted nipples). Difficulty in initiation of
breast feeding, doctor visits seeking medical advice for feeding
difficulties, duration of exclusive breast feeding, diluted feeding and
bottle feeding were also recorded. Diarrhea, pneumonia and exclusive
breast feeding were defined as per standard WHO definitions [14-16].
Fever was defined as oral temperature more than 99.5°F or axillary
temperature over 99°F documented by a health care professional.
Hospitalization was defined as admission for >24 hours for any medical
illness.
At 12 months of age, hemoglobin (Hb) and serum
ferritin was measured in these infants. Serum ferritin was measured
using one step enzyme immunoassay sandwich method with a final
florescent detection using ferritin kit (Biomeriux Company, Marcy
l’Étoile, France).
Data were analyzed using STATA 12.0 software.
Continuous data was analyzed using student unpaired t test for
parametric data and Rank Sum test for non-parametric data. Categorical
data was compared using Chi square or Fisher exact test as applicable.
Odds ratio with 95% confidence interval was calculated for preterm and
term group. Logistic regression was done using WFA, WFL, LFA and HFA as
a dependent variable and sex of the baby, maternal weight, height,
socioeconomic status, exclusive breast feeding and re-hospitalization as
covariates. P value of <0.05 was considered significant.
Results
Fig. 1 shows the flow of participants in the
two groups. We enrolled 200 neonates in each group. Table I
compares the baseline characteristics of the two groups.
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Fig. 1 Flow of the participants in the
study.
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TABLE I Comparison of Baseline Characteristics of the Term and Late Preterm Neonates
Characteristics |
Term |
Late preterm |
|
( n=199) |
(n= 200) |
#Weight at birth (kg) |
2.8 (0.3) |
2.3 (0.3) |
#Length at birth (cm) |
49.2 (1.6) |
46.2 (1.3) |
#Head circumference (cm) |
35 (0.9) |
32 (0.9) |
#Gestational age (wks) |
38.4 (1) |
35.2 (0.8) |
Sex (male)* |
103 (51.7) |
107 (53.5) |
Vaginal delivery* |
118 (59.3) |
117 (58.5) |
Maternal age (y) |
26.1 (3.6) |
25.8 (3.7) |
$Maternal weight (kg) |
61.6 (7.3) |
63.2 (4.2) |
Maternal height (cm) |
140.1 (0.5) |
141.5 (0.5) |
Maternal Hb (g/dL) |
9.5 (1.3) |
9.6 (0.9) |
Socioeconomic status*
|
|
|
Lower |
78 (39.2) |
60 (30.3) |
Values indicate mean (SD) or *number (%); #P<0.001;
$P=0.008; MOD: mode of delivery; Hb: hemoglobin.
Oxytocin was used in all the mothers. |
TABLE II Growth Outcomes of Late Preterms and Term Infants at 12 Months of Age
Parameter |
Term(n=157) |
Late preterms(n=158) |
P |
OR (95% CI) |
Weight (kg) |
8.7 (1.6) |
7.3 (0.7) |
<0.001 |
1.4 (1.1, 1.6) |
Length (cm) |
72.2 (3.1) |
69.2 (2.5) |
<0.001 |
3 (2.3, 3.6) |
HC (cm) |
44.2 (1.1) |
43 (1.1) |
<0.001 |
1.2 (0.9-1.4) |
*Weight gain (kg/y) |
5.9 (1.6) |
4.9 (0.7) |
<0.001 |
1(0.7-1.2) |
*Weight gain(g/wk) |
115 (26.2) |
102.2 (35.6) |
<0.001 |
12.8 (8, 17) |
*Length gain (cm/y) |
23.1 (3.4) |
23.1 (2.7) |
0.968 |
0 (-0.6, 0.6) |
*HC gain (cm/y) |
9.1 (1.3) |
10.9 (1.2) |
<0.001 |
-1.8 (-2.0,-1.5) |
Value in Mean (SD); *In first year. |
At mean age of 12 months, mean (SD) weight, length
and head circumference of late preterms were signi-ficantly lower than
that in the full term group (Table II). On univariate
analysis, as compared to term birth, late preterm birth was associated
with higher odds of being underweight, stunted and wasted. However, on
multivariate analysis only adjusted odds of being underweight was
significant (Table III). Over first year, late preterm
infants gained lesser weight as compared to full term infants. This 1
[0.7, 1.2] kg difference was statistically significant (P
<0.001). Weekly weight-gain was significantly lesser in late preterms as
compared to full term infants. Length gain was comparable in both the
groups. The mean growth of HC was more by 1.8 [1.5, 2] cm in the late
preterms as compared to full term infants. Despite this gain in HC, 34%
Late preterm remained below -2 z scores as compared to only 14% in the
term group (P < 0.0001). Their mean HC at one year also remained
significantly lower than the full term infants (Table II).
TABLE III Growth Outcomes of the Late Preterms at 12 Months of Age
Growth
|
Crude OR |
Adjusted odds |
Parameters |
(95% C.I.) |
(95% C.I.) |
Underweightb |
5.6 (3.4, 5.5) |
4.1 (1.6, 10.4)a |
Stuntingb |
3.5 (2.1, 5.8) |
1.2 (0.5, 2.7)a |
Wastingb |
3.6 (1.9, 6.9) |
1.4 (0.6, 3.7)a |
Head circumferenceb |
3.4 (1.9, 5.9) |
1.3 (0.6, 2.9)a |
a: Adjusted for sex, maternal weight, maternal height,
re-hospitalization, exclusive breastfeeding and socioeconomic
status; b: Odds ratio for late preterm infants with reference to
term infants. |
TABLE IV Morbidity Profile of Term and Late Preterm Infants Till 1 Year of Age
Variables |
Term(n=157) |
Late preterm(n=158) |
P |
Feeding related |
*Difficulty in initiation of breast feeding |
25 (15.9) |
44 (27.8) |
0.014 |
*Feeding difficulties |
29 (18.5) |
51 (32) |
|
Trouble latching |
7 (4.5) |
25 (15.8) |
0.004 |
Sleepy baby |
0 (0.00) |
6 (3.8) |
|
Not enough milk production |
19 (12.1) |
19 (12.0) |
|
Inverted nipples |
3 (1.9) |
1 (0.6) |
|
*Exclusive breast feeding for 6 months |
109 (69.4) |
92 (58.2) |
0.046 |
*Medical consultations regarding feeding difficulties |
11 (7.0) |
23 (14.4) |
0.045 |
*Bottle feeding |
59 (37.6) |
80 (50.6) |
0.023 |
*Diluted feeding
|
61 (38.9) |
58 (36.7) |
0.728 |
Morbidity profile |
#Diarrhoea episodes |
1.14 (0 -2) |
1.84 (0-3) |
0.0005 |
#Fever episodes
|
0.95 (0-2) |
1.33 (0-2) |
0.0143 |
#Prevalence of pneumonia
|
0.45 (0-1) |
0.48 (0-1) |
0.3510 |
*Jaundice requiring phototherapy
|
42 (26) |
62 (39.2) |
0.008 |
*Hospitalization
|
19 (12.1) |
40 (25.3) |
0.02 |
Hematological parameters |
**Hemoglobin (g/dL)
|
8.3 (1.1) (n = 136) |
7.9 (1.1) (n = 133) |
0.0113 |
#Serum ferritin (ng/mL)
|
90.1 (19.9-112) (n = 121) |
69.9 (1.2-80.3) (n =129) |
<0.001 |
Values indicate *Number(%); **Mean (SD) or #Median
(IQR). |
Jaundice requiring phototherapy, feeding problems and
hospitalization rates were higher in late preterms as compared to full
term group. Incidence of diarrhea and fever was also significantly
higher in the late preterm group (Table IV). Morbidity was
inversely proportional to the gestational age (Fig. 2).
Gestational age in weeks
*Morbidity includes episodes of diarrhea,
pneumonia, fever and hyperbilirubinemia.
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Fig. 2 Gestation wise analysis of
morbidity and mortality.
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The mortality in the late preterm group was 7% as
compared to 4% in full term group [or (95% CI) of 2.1 (0.8, 6), P=0.1].
Mortality also had an inverse relationship with gestation age (Fig.
2).
Discussion
We observed that the healthy late preterm infants who
do not suffer from morbidities in immediate neonatal period are at
increased risk of being underweight during first year of life. Feeding
difficulties and hospitalization due to diarrhea and fever were higher
in late preterm group than full term infants while exclusive
breastfeeding rates were lower. Late preterm infants were also found to
be having lower mean Hb and serum ferritin level at one year of age.
Our study differed from earlier studies on late
preterms as only healthy late preterms were enrolled and compared to
term counterparts. Limitation of the study was the small sample size and
that the neurodevelopment outcomes were not studied. The late preterm
infants who required admission to NICU soon after birth were not
followed up as evidence is already available regarding out comes in this
population. Another limitation of the study was the follow-up loss in
about 20% of enrolled babies.
Very few studies have evaluated the early childhood
physical growth outcomes of healthy late preterms. Santos, et al.
[17] reported an increased risk for being underweight and stunted in 371
late preterms as compared with full term children at 12- and 24-months
of age. The odds of being wasted was higher at 12 months but not at 24
months of age. In our study, only the adjusted odds of being underweight
only was significant. The difference could be because our study included
only apparently healthy late preterms, while Santos, et al.
included all late preterms, including those requiring admission to NICU.
Goyal, et al. [18] in a retrospective study on 553 infants with
gestational ages ranging from 34 to 36 weeks, also demonstrated a
positive association between late preterms birth and being underweight
at one year of age. Feeding difficulties in late preterms probably makes
them more vulnerable to malnutrition, and therefore they may require
special care and extra assistance than full term infants. It would be
worth mentioning that we did not correct the late preterm babies for
gestational age on follow-up. It was not corrected for gestation, as our
unit protocol is to use corrected gestation only in babies less than 34
weeks of gestation. We agree that slightly shorter duration of growth in
late preterms can be a confounding factor when comparing growth of full
terms at 1 year of age. Other studies [17,18] comparing these two groups
also did not mention about correction for gestation age in their papers.
Increased episodes of diarrhea and fever in late
preterms may be attributed to malnutrition and feeding difficulties.
Escobar, et al. [19] reported higher risk of re-admission among
babies born between 33 to 36 weeks gestation as compared to babies born
after 37 weeks. Re-admission rates of late preterm infants have been
reported to be 1.5-3 times higher than that of term infants, and the
main reasons for re-hospitalization are jaundice and feeding
difficulties in the neonatal period [1,20,21]. Boyle, et al. [4]
in a prospective population-based study of 1146 late preterms, also
reported that they were less likely to be fed breast milk than term
infants [4].
We conclude that late preterm neonates who do not
even require admission at birth are at significantly higher risk of
growth faltering in the first year of life. They tend to have lower
weight, as compared to their term counterparts. They have higher
morbidities like feeding difficulties, jaundice, diarrhea, pneumonia and
fever as compared to full term infants in the first year of life. All
babies born as late preterm should be followed up in high- risk clinics
with special monitoring of growth and feeding difficulties.
Contributors: PG, MJ: collected and
compiled the data for the study, and drafted the manuscript: AU:
conceptualized and designed the study, finalized the manuscript. AY, BK,
RM: provided intellectual inputs from protocol stage and helped in
drafting the paper. The final version of manuscript was approved by all
authors.
Funding: None. Competing Interests:
None stated.
What is Already Known?
• Late preterms are at significant risk of
higher mortality and morbidity in the immediate neonatal period.
What This Study Adds?
• Late preterm neonates, even if they do not
require NICU admission at birth, are at significant risk of
growth faltering, feeding difficulties, and morbidity during
infancy.
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