Journal List > Perinatology > v.29(3) > 1102886

Kim, Kim, Jung, Kim, Song, Lee, Kim, and Kim: The Effect of Macrolide Therapy on Bronchopulmonary Dysplasia in UreaplasmaPositive Very Low Birth Weight Infants

Abstract

Objective

Ureaplasma has been demonstrated the cause of short and long-term morbidities of preterm infants, especially such as bronchopulmonary dysplasia (BPD). This study aims to evaluate the influence of Ureaplasma on neonatal morbidities and the effect of macrolide treatment in very low birth weight (VLBW) infants.

Methods

We performed a retrospective review of clinical records of VLBW infants born between 2015 and 2016. Their endotracheal aspirate and gastric juice were obtained immediately after birth and tested for Ureaplasma. Therapeutic macrolides were administered according to the clinical judgment, not routinely, in Ureaplasma-positive infants. Neonatal morbidities were compared using individual matching analysis between Ureaplasma-positive and negative groups, and with macrolides administration.

Results

A total of 144 infants with the mean (±standard deviation) gestational age of 28+3 (±3+3) weeks and birth weight of 1,051.9 (±290.0) g were included, and 30 (20.8%) were Ureaplasma-positive. Ureaplasma-positive group was associated with higher incidence of respiratory distress syndrome (RDS, P=0.039) and severe neurologic injury (SNI; intraventricular hemorrhage ≥grade 3 or periventricular leukomalacia, P=0.013). However, Ureaplasma-positive group was not associated with the risk of BPD (P=0.706). In the subgroup analysis for Ureaplasma-positive infants, there was no difference in the incidence of morbidities according to the macrolides administration.

Conclusion

Although Ureaplasma has no independent role in the development of BPD, Ureaplasma-positive VLBW infants were more likely to have RDS and SNI. The macrolides administered in Ureaplasma -positive was not effective to reduce neonatal morbidities.

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Table 1.
Demographic Characteristics
  Value (n=144)
Gestational age (weeks) 28.3±3.3
Birth weight (g) 1,051.9±290.0
Male 67 (46.5)
Multiple births 51 (35.4)
Maternal age (years) 33.3±3.88
PROM 52 (36.1)
Histologic chorioamnionitis 52 (36.1)
Pre-eclampsia 24 (16.7)
Cesarean section 89 (61.8)
Antenatal steroid use 110 (76.3)
Apgar score at 1 minute 5.4 (2-7)
Apgar score at 5 minutes 7.4 (1-8)
IUGR 38 (26.3)
Ureaplasma-positive 30 (20.8)
RDS 86 (59.7)
PDA requiring treatment 77 (53.4)
Moderate to severe BPD 43 (29.9)
Severe BPD 36 (29.8)
Postnatal steroid therapy 35 (24.3)
Length of oxygen supply (days) 71.2±45.8
Severe neurologic injury 15 (10.4)
NEC (≥stage 2) 14 (9.7)
LOS 39 (27.1)
ROP requiring treatment 24 (16.7)
Hospital stay (days) 71.4±45.6
Mortality after 36 weeks of PMA 2 (1.4)

Values are presented as mean±standard deviation, mean (interquartile range), or number (%). Abbreviations: PROM, premature rupture of membranes; IUGR, intrauterine growth retardation; RDS, respiratory distress syndrome; PDA, patent ductus arteriosus; BPD, bronchopulmonary dysplasia; NEC, necrotizing enterocolitis; LOS, late-onset sepsis; ROP, retinopathy of prematurity; PMA, postmenstrual age.

Table 2.
Clinical Outcomes between Ureaplasma-Positive Infants and Matched Controls
Ureaplasma-positive infants (n =27) Controls (n=27) P-value
Gestational age (weeks) 27.4±1.9 27.5±2.0 0.321
Birth weight (g) 1,028.5±277 1,030±273 0.667
Male 13 (48.1) 13 (48.1) 0.782
Caesarean section 13 (48.1) 17 (63.0) 0.412
PROM 22 (81.5) 11 (40.7) 0.007
Histologic chorioamnionitis 21 (77.8) 21 (77.8) 0.072
Pre-eclampsia 1 (3.7) 2 (7.4) 0.564
RDS 25 (92.6) 18 (66.7) 0.039
PDA requiring treatment      
Ibuprofen treatment 11 (40.7) 15 (55.6) 0.206
PDA ligation 4 (14.8) 6 (22.2) 0.800
Moderate to severe BPD 12 (44.4) 10 (37.0) 0.706
Severe BPD 9 (33.3) 7 (25.9) 0.655
Length of oxygen supply (days) 83.9±81.7 68.7±62.7 7 0.430
Duration of mechanical ventilation (days) 43.8±44.8 42.4±43.6 6 0.155
Duration of invasive ventilation (days) 22.4±33.5 21.4±40.3 3 0.518
Duration of noninvasive ventilation (days) 21.4±21.1 21.0±18.9 9 0.497
Postnatal steroid therapy 8 (29.6) 8 (29.6) 1.000
Cumulative dose of steroid (mg/kg) 2.1±4.5 2.1±3.9 0.402
Severe neurologic injury (IVH ≥grade 3 or PVL) 5 (18.5) 1 (3.7) 0.013
NEC (≥stage 2) 3 (11.1) 4 (14.8) 0.706
LOS 8 (29.6) 8 (29.6) 0.763
ROP requiring treatment 6 (22.2) 6 (22.2) 0.317
Hospital stay (days) 96.0±76.5 83.5±57.5 0.550
Mortality after 36 weeks of PMA 1 (3.7) 0 (0) 0.254

Values are presented as mean±standard deviation or number (%). Abbreviations: PROM, premature rupture of membranes; RDS, respiratory distress syndrome; PDA, patent ductus arteriosus; BPD, bronchopulmonary dysplasia; IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia; NEC, necrotizing enterocolitis; LOS, late-onset sepsis; ROP, retinopathy of prematurity; PMA, postmenstrual age.

P<0.05.

Table 3.
Subgroup Analysis for Ureaplasma-Positive Infants According to Macrolide Treatment (n=30)
  Macrolide (n=14) No macrolide (n=16) P-value
Gestational age (weeks) 27.3±1.6 27.4±1.9 0.227
Birth weight (g) 1,030±261 1,022±267 0.078
Male 6 (42.9) 9 (56.3) 0.464
Caesarean section 8 (57.1) 6 (37.5) 0.706
PROM 10 (71.4) 14 (87.5) 0.383
Histologic chorioamnionitis 7 (50.0) 14 (87.5) 0.032
RDS 13 (92.9) 15 (93.8) 0.724
PDA requiring treatment      
Ibuprofen treatment 8 (57.1) 3 (18.8) 0.029
Ibuprofen treatment (≥2 times) 5 (35.7) 0 (0) 0.012
PDA ligation 3 (21.4) 3 (18.8) 0.605
Moderate to severe BPD 8 (57.1) 5 (31.3) 0.153
Severe BPD 7 (50.0) 5 (31.3) 0.296
Ventilator (days) 53.5±53.0 33.0±31.1 0.169
Length of oxygen supply (days) 89.2±108 59.6±45.5 0.356
Postnatal steroid therapy 7 (50.0) 4 (25.0) 0.236
Cumulative dose of steroid 3.2±5.7 1.1±3.2 0.255
Severe neurologic injury (IVH ≥grade 3 (21.4) 2 (12.5) 0.642
3 or PVL)      
NEC (≥stage 2) 3 (21.4) 0 (0) 0.090
LOS 6 (42.9) 4 (25.0) 0.442
ROP requiring treatment 5 (35.7) 2 (12.5) 0.204
Mortality after 36 weeks of PMA 0 (0) 1 (6.3) 0.533

Values are presented as mean±standard deviation or number (%). Abbreviations: PROM, premature rupture of membranes; RDS, respiratory distress syndrome; PDA, patent ductus arteriosus; BPD, bronchopulmonary dysplasia; IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia; NEC, necrotizing enterocolitis; LOS, late-onset sepsis; ROP, retinopathy of prematurity; PMA, postmenstrual age.

P<0.05.

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