Demographics
Sixty-one preterm infants (33 male and 28 female infants) with a median GA of 30 ± 1.28 weeks (range, 26+ 5 weeks to 32 weeks) and a mean birth weight (BW) of 1409 ± 362 g were reviewed. They received complete oral feeds at a median PMA of 35 ± 2.1 weeks. All patients remained clinically stable and accepted the monitoring well. No one received medication for GER during hospitalization.
GER prevalence in symptomatic preterm infants
Among the 61 infants with symptoms, 34(16 female and 18 male infants, 56%) were GER-positive and 27 (44%) were GER-negative. Eighteen (53%) cases of acid reflux and 16 (47%) cases of other reflux (including weakly acidic and nonacidic reflux) occurred in GER-positive infants. Table 1 presents the GA and birth weights. There were no difference between GER positive and GER negative group classified by GA and BW (p = 0.886, 0.538 respectively). A similar result was found between acid reflux group and other reflux group classified by GA and BW (p = 0.797, 0.052 respectively).
Table 1
Cohort characteristics of patients (n = 61)
Factors
|
Grade
|
GER positive, n (%)
|
GER negative
|
acid reflux
|
other reflux
|
total
|
GA
|
< 28w
|
1(5.6%)
|
2(12.5%)
|
3(8.8%)
|
2(7.4%)
|
|
28-30w
|
7(38.9%)
|
6(37.5%)
|
13(38.2%)
|
13(48.2%)
|
|
30-32w
|
10(55.6%)
|
8(50%)
|
18(53%)
|
12(44.4%)
|
BW
|
< 1000 g
|
1(5.6%)
|
5(31.3%)
|
6(17.6%)
|
3(11.1%)
|
|
1000–1500 g
|
6(33.3%)
|
7(43.7%)
|
13(38.2%)
|
14(51.9%)
|
|
> 1500 g
|
11(61.1%)
|
4(25%)
|
15(44.2%)
|
10(37%)
|
GA: gestational age, BW: birth weight |
Among the 34 infants GER-positive for GER, 53% (18/34) had acid reflux, 26.5% (9/34) had weakly acidic reflux, and 20.6% (7/34) had nonacidic reflux. Acid reflux-positive preterm infants (10 male and 8 female infants) born at 30.12 ± 0.97 weeks of gestation (range, 28–31+ 6 weeks of gestation) had an average weight of 1530.83 ± 266.35 g (range, 973–1900 g). Eight male and eight female GER-positive infants with weak acidic or nonacidic reflux were born at 29.78 ± 1.53 weeks of gestation (range, 26+ 5-32 weeks of gestation) and had an average weight of 1336.63 ± 482.16 g (range, 695–2355 g).
Relationship between GER and the symptoms
Among the 61 infants, 26 (42.6%) had apnea, 12 (19.7%) had cyanosis, 9 (14.8%) had vomiting, 6 (9.8%) had pneumonia, and 8 (13.1%) had poor weight gain. By SSI and SAP analysis, the GER associated symptoms included apnea (52.9%), cyanosis (17.6%), vomiting (8.8%), pneumonia (5.9%), and poor weight gain (14.7%). There was no difference in the aforementioned reflux-related symptoms for those in the GER-negative and GER-positive groups according to the chi-square test (Table 2). But these symptoms were more frequent in the GER-positive group than those in the GER-negative group, indicating that GER might aggravate these symptoms (p < 0.05).
Table 2
Relationship between GER and the symptoms
Symptoms
|
GER negative, n (%)
|
GER positive, n (%)
|
t/χ2
|
P
|
apnea
|
8(29.6)
|
18(52.9)
|
3.344
|
0.067
|
cyanosis
|
6(22.2)
|
6(17.6)
|
0.199
|
0.655
|
vomiting
|
6(22.2)
|
3(8.8)
|
2.148
|
0.143
|
pneumonia
|
4(14.8)
|
2(5.9)
|
1.354
|
0.245
|
poor weight gain
|
3(11.1)
|
5(14.7)
|
0.171
|
0.680
|
Risk factors for GER in the symptomatic preterm infants
As shown in Table 3, there were no significant differences in the general conditions and clinical characteristics, including sex, GA, BW, Apgar score at 1 minute, PMA at the time of the study, duration of partial parenteral nutrition, caffeine administration, duration of mechanical ventilation, length of hospital stay, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and nosocomial infection, for the GER-negative and GER-positive groups according to the independent samples t test (all p > 0.05). The durations of noninvasive auxiliary ventilation were statistically significant for the GER-negative and GER-positive groups (14.67 ± 9.1 vs 8.71 ± 7.9, p < 0.01). Infants of GER-positive group had earlier full oral feeds compared to those of GER-negative group (35.18 ± 2.16 vs 36.26 ± 1.45, p < 0.01). More probiotics was used in GER-positive group than in GER-negative group (p < 0.05). Though there was no difference of BPD between the two groups, severe BPD was more often in GER-positive group than that in GER-negative group (p < 0.05).
Table 3
Risk factors of GER negative group and GER positive group
Clinical features
|
GER negative (27)
|
GER positive (34)
|
t/χ2
|
P
|
female, n (%)
|
12(44.4)
|
16(47.1)
|
0.041
|
0.839
|
GA (weeks)
|
29.96 ± 1.41
|
29.96 ± 1.26
|
-0.001
|
0.999
|
BW (g)
|
1371 ± 327
|
1439 ± 390
|
-0.733
|
0.467
|
Apgar score at 1 min
|
7.59 ± 2.08
|
7.88 ± 1.75
|
-0.59
|
0.557
|
PMA at full oral feeds (weeks)
|
36.26 ± 1.45
|
35.18 ± 2.16
|
2.851
|
0.006
|
PMA at study (weeks)
|
35.71 ± 1.86
|
35.21 ± 1.59
|
0.939
|
0.352
|
durations of PPN (days)
|
27.37 ± 13.67
|
22.68 ± 15.50
|
1.237
|
0.221
|
caffeine administration (days)
|
17.89 ± 10.5
|
12.35 ± 11.04
|
1.988
|
0.051
|
duration of mechanical ventilation (days)
|
7.41 ± 10.5
|
3.76 ± 5.5
|
1.742
|
0.087
|
duration of noninvasive auxiliary ventilation (days)
|
14.67 ± 9.1
|
8.71 ± 7.9
|
2.740
|
0.008
|
length of hospital stay (days)
|
52.44 ± 16.81
|
48.11 ± 22.55
|
0.83
|
0.410
|
probiotics, n (%)
|
17(63.0)
|
12(35.3)
|
4.620
|
0.032
|
BPD, n (%)
|
8(29.6)
|
13(38.2)
|
0.494
|
0.482
|
severe BPD, n (%)
|
2(7.4)
|
10(29.4)
|
4.611
|
0.032
|
NEC, n (%)
|
3(11.1)
|
0
|
|
0.081*
|
nosocomial infection, n (%)
|
6(22.2)
|
7(20.6)
|
0.024
|
0.877
|
*Calculated by Fisher's Exact Test |
GA: gestational age, BW: birth weight, PMA: postmenstrual age, PPN: partial parenteral nutrition, BPD: bronchopulmonary dysplasia, NEC: necrotizing enterocolitis. |
A binary logistic regression analysis using caffeine administration, duration of mechanical ventilation, duration of noninvasive auxiliary ventilation, probiotics, severe BPD, and NEC (univariate p < 0.1) revealed that delayed full oral feeds and probiotics could decrease the GER risk (odds ratio [OR], 0.642; 95% confidence interval [CI], 0.457–0.901, p = 0.01; OR, 0.234, 95% CI, 0.069–0.794, p = 0.02). Severe BPD increased the GER risk (OR, 6.890; 95% CI, 1.125–42.209; p = 0.037) (Table 4).
Table 4
Logistic regression analysis of risk factors for GER
Risk Factors
|
B
|
Sig
|
Exp (B)
|
Exp (B) 95% CI
|
Lower
|
Upper
|
PMA at full oral feeds
|
− .443
|
0.010
|
0.642
|
0.457
|
0.901
|
probiotics
|
-1.453
|
0.020
|
0.234
|
0.069
|
0.794
|
severe BPD
|
1.930
|
0.037
|
6.890
|
1.125
|
42.209
|