During the 18-month study period, 187 inborn, preterm, VLBW infants were admitted to the NICU. Of these 187 infants, 23 died and 3 were transferred to the cardiovascular intensive care unit at CMC before 36 weeks’ postmenstrual age and were excluded from the study. The clinical characteristics of the remaining 161 infants are shown in Table 1. The majority of infants were singleton, born by cesarean delivery, appropriate for gestational age, and did not have PDA, NEC, BPD, or late-onset sepsis. None of the infants had early-onset sepsis. Of the 161 infants, 157 received at least 48 hours of antibiotics and the median antibiotic DOT received was 11 (IQR, 5.5–19.5).
Table 1
Characteristics of the study population
Number of infants | 161 |
Gestational age (weeks, mean ± SD) | 28.5 ± 1.97 |
Delivery by caesarean section | 124 (77%) |
Singleton, twin, triplet gestation | 117 (73%), 39 (24%), 5 (3%) |
Male gender | 81 (50%) |
Birth weight (grams; mean ± SD) | 1130 ± 229 |
Birth length (cm; mean ± SD) | 37 ± 3 |
Ponderal index (mean ± SD) | 2.22 ± 0.28 |
Intrauterine growth restriction | 14 (9%) |
Small for gestational age | 9 (6%) |
CRIB-II score (mean ± SD) | 7.4 ± 2.9 |
Antibiotic exposure (median; IQR)* | 11 (5.5–19.5) |
Bronchopulmonary dysplasia | 29 (18%) |
Patent ductus arteriosus | 40 (25%) |
Necrotizing enterocolitis (Bell stage ≥ 2) | 8 (5%) |
Late-onset sepsis | 1 episode, 19 (12%); 2 episodes, 9 (6%) |
SD, standard deviation; cm, centimeter; IQR, interquartile range |
*Antibiotic exposure defined as days of therapy (DOT). |
Of the 161 infants, 155 (96%) had at least 1 follow-up visit to the CMC Low Birth Weight Follow-up clinic. Complete weight and length data were available for 151 (94%) infants at ∼2-month visit, 134 (83%) infants at ∼4 months, 136 (84%) infants at ∼6 months, and 129 (80%) infants at ∼12 months. Weight alone was available for an additional 1 infant at 2 months, 1 infant at 4 months, 3 infants at 6 months, and 1 infant at 12 months.
The weight and length z-scores at birth were within the standard range for gestational age by the Fenton curves, with the average weight and length z-scores being 0.074 ± 0.91 and 0.096 ± 0.93, respectively. The weight and length z-scores decreased by an entire standard deviation from birth to 36 weeks corrected age, to -0.98 ± 0.92 and − 1.18 ± 0.82, respectively. After 36 weeks corrected age, there was a steady increase toward a normal average z-score of zero for both weight and length, although the length z-score remained lower than the weight z-score. At 2 months corrected age, there was an elevated weight-for-length z-score of 0.997 ± 1.08 but by 12 months corrected age, the average weight-for-length z-score approached zero.
Univariate linear regression was performed to evaluate the impact of antibiotic exposure as well as demographic features and clinical diagnoses on growth patterns (Table 2, 3). There was a negative correlation between antibiotic exposure and weight delta z-score at only 36 weeks and 2 months corrected age. A negative correlation with weight z-scores also was seen at 36 weeks corrected age in males, at 2 months corrected age for late-onset sepsis, at 36 weeks, 2 months, and 4 months for total days of TPN, and at 36 weeks and 2 months for total days NPO. CRIB-II score and BPD had a negative relationship with change in weight z-score at multiple time points (Table 2). A positive correlation with weight z-scores was seen in infants who were SGA, especially at 4, 6, and 12 months corrected ages. Gestational age showed a persistently strong positive correlation with weight delta z-score, indicating that infants born later in gestation had improved catch-up weight gain through the first-year post-term.
Table 2
Weight delta z-scores from birth to subsequent age points by univariate linear regression analysis#
| Weight Delta Z-score at Age of Evaluation |
∼36 weeks | ∼2 months | ∼4 months | ∼6 months | ∼12 months |
No. of infants | 161 | 151 | 134 | 136 | 129 |
Gestational age | 0.274* | 0.477* | 0.446* | 0.445* | 0.479* |
Mode of delivery | 0.270*+ | 0.177*+ | 0.121 | 0.130 | 0.111 |
Multiple gestation | 0.091 | 0.081 | 0.034 | 0.022 | 0.025 |
Gender | -0.208**♦ | -0.111 | -0.072 | -0.091 | -0.040 |
IUGR | 0.052 | 0.194* | 0.163 | 0.164 | 0.162 |
SGA | 0.059 | 0.078 | 0.191* | 0.247* | 0.250* |
CRIB-II score | -0.206** | -0.379** | -0.334** | -0.310** | -0.321** |
Antibiotic exposure | -0.375* | -0.295* | -0.151 | -0.080 | -0.119 |
BPD | -0.294** | -0.262** | -0.195** | -0.127 | -0.209** |
PDA | -0.138 | -0.107 | -0.077 | -0.053 | -0.112 |
NEC | -0.174 | -0.023 | 0.051 | 0.069 | 0.035 |
Late-onset sepsis | -0.074 | -0.192** | -0.129 | -0.052 | -0.075 |
TPN (total days) | -0.397** | -0.356** | -0.206** | -0.131 | -0.127 |
Total days of NPO | -0.367** | -1.313** | -0.177 | -0.092 | -0.109 |
Caloric density (36 weeks, kcal/ounce) | -0.024 | 0.066 | 0.022 | 0.018 | 0.006 |
IUGR, intrauterine growth restriction; SGA, small for gestational age; CRIB, Clinical Risk Index for Babies; BPD, bronchopulmonary dysplasia; PDA, patent ductus arteriosus; NEC, necrotizing enterocolitis; TPN, total parenteral nutrition; NPO, nothing per oral |
# Pearson correlation |
* Positive correlation, P < 0.05 |
+ Positive correlation with delivery by caesarean section |
** Negative correlation, P < 0.05 |
♦ Negative correlation with male gender |
Table 3
Length delta z-score from birth to subsequent age points by univariate linear regression analysis#
| Length Delta Z-score at Age of Evaluation |
| ∼36 weeks | ∼2 months | ∼4 months | ∼6 months | ∼12 months |
No. of infants | 161 | 151 | 134 | 136 | 129 |
Gestational age | 0.042 | 0.281* | 0.329* | 0.222* | 0.251* |
Delivery mode | 0.159*+ | 0.191*+ | 0.118 | 0.052 | 0.073 |
Multiple gestation | 0.015 | 0.076 | 0.061 | 0.042 | 0.086 |
Gender | -0.069 | -0.116 | -0.014 | -0.018 | -0.016 |
IUGR | 0.253** | 0.091 | 0.041 | 0.070 | 0.043 |
SGA | 0.106 | 0.039 | 0.219* | 0.283* | 0.291* |
CRIB-II score | 0.263 | 0.244** | 0.232** | 0.130 | 0.118 |
Antibiotic exposure | 0.021 | -0.144 | -0.092 | -0.040 | -0.077 |
BPD | -0.120 | -0.216** | -0.217** | -0.138 | -0.130 |
PDA | -0.153 | -0.171** | -0.151 | 0.008 | 0.018 |
NEC | -0.020 | 0.015 | -0.002 | 0.073 | 0.003 |
Late-onset sepsis | 0.244* | -0.019 | -0.056 | -0.049 | 0.007 |
TPN (total days) | 0.033 | -0.216** | -0.159 | -0.073 | -0.112 |
Caloric density (36 weeks, kcal/ounce) | -0.070 | 0.003 | 0.012 | 0.015 | 0.081 |
IUGR, intrauterine growth restriction; SGA, small for gestational age; CRIB, Clinical Risk Index for Babies; BPD, bronchopulmonary dysplasia; PDA, patent ductus arteriosus; NEC, necrotizing enterocolitis; TPN, total parenteral nutrition; NPO, nothing per oral |
# Pearson correlation |
*Positive correlation, P < 0.05 |
+ Positive correlation with delivery by caesarean section |
**Negative correlation, P < 0.05 |
Factors associated with a change in length z-score from birth to each subsequent age-point also were assessed. Antibiotic exposure had no relationship with length delta z-score at any age point. IUGR, CRIB-II score, BPD, PDA and total days of TPN all showed small negative relationships for at least one of the early age points: 36 weeks, 2 months and/or 4 months corrected age. Gestational age and SGA had a positive relationship with length delta z-score at all age points except 36 weeks’ corrected age, indicating that infants born at older gestational ages or SGA had improved catch-up growth over the first year of age.
Stepwise multivariate regression analysis was performed to predict weight delta z-scores from birth to each subsequent age point using the variables that were significant on at least one time point by univariate analysis (antibiotic exposure, gestational age, gender, delivery mode, IUGR, SGA, CRIB-II score, BPD, late-onset sepsis, total days of TPN, and total days NPO; Table 4). Antibiotic exposure was not associated with weight delta z-scores at any age point in the multivariate model. The strongest positive predictor for weight at all age points was length with the converse also true. Gestational age remained a moderate predictor of weight but not length. Total duration of TPN was a strong negative predictor for weight delta z-score from birth to 36 weeks’ corrected age. The change in z-score for weight, length, and weight-for-length between each consecutive age point had no significant predictors (data not shown).
Table 4. Weight (a) and length (b) delta z-scores from birth to subsequent age points by stepwise multivariate regression analysis#
a) The total days of parenteral nutrition showed a strong negative correlation with weight z-scores at 36 weeks’ postmenstrual age, while positive associations were seen with gestational age, length, and IUGR status. Antibiotic exposure was not significant at any time point. P-value was ≤ 0.05 for all displayed z-score values.
|
Delta Weight z-Score
|
∼36 weeks
|
∼2 months
|
∼4 months
|
∼6 months
|
∼12 months
|
No. of infants
|
161
|
151
|
134
|
136
|
129
|
Length
|
0.359
|
0.476
|
0.562
|
0.599
|
0.606
|
Gestational age
|
-
|
0.346
|
0.242
|
0.272
|
0.316
|
IUGR
|
0.137
|
0.174
|
0.138
|
0.151
|
0.119
|
Total parenteral nutrition (total days)
|
-0.349
|
-
|
-
|
-
|
-
|
Delivery mode
|
0.174
|
-
|
-
|
-
|
-
|
Late-onset sepsis
|
-
|
-0.153
|
-
|
-
|
-
|
PDA
|
-
|
0.143
|
-
|
-
|
-
|
b) Positive associations were seen with the length delta z-score and late-onset sepsis (p<0.05).
|
Delta Length z-Score
|
∼36 weeks
|
∼2 months
|
∼4 months
|
∼6 months
|
∼12 months
|
Weight delta z-score
|
0.444
|
0.568
|
0.644
|
0.674
|
0.701
|
Late-onset sepsis
|
0.152
|
-
|
-
|
-
|
-
|
# Pearson correlation