The Significance of Epidermal Growth Factor in Noninvasively Obtained Amniotic Fluid Predicting Respiratory Outcomes of Preterm Neonates

Abstract

Preterm premature rupture of membranes (PPROM) interrupts normal lung development, resulting in neonatal respiratory morbidity. Although post-PPROM risks have been researched, only a few studies have investigated noninvasively obtained amniotic fluid (AF) to predict neonatal outcomes. In this study, we aimed to determine whether epidermal growth factor (EGF) in vaginally-collected AF is a significant predictor of neonatal respiratory outcomes after PPROM. We analyzed EGF in vaginally-obtained AF from 145 women with PPROM at 22−34 weeks of gestation. The following neonatal outcomes were included: respiratory distress syndrome, surfactant need, duration and type of respiratory support, and bronchopulmonary dysplasia. We found that EGF concentration was associated with gestational age, and its medians were lower in neonates with respiratory morbidities than unaffected ones. EGF concentrations gradually declined, the lowest being in the most clinically ill patients. EGF < 35 pg/mL significantly predicted the odds of severe respiratory outcomes. EGF in noninvasively collected AF may be a reliable predictor for respiratory outcomes of preterm neonates with PPROM before 34 weeks of gestation. The results of our study may have implications for further research both in noninvasive amniotic fluid analysis and the management of patients after PPROM.

Keywords: amniotic fluid; epidermal growth factor; noninvasive method; preterm birth; preterm premature rupture of membranes; respiratory outcomes.

Figure 1

EGF concentrations in the amniotic fluid according to gestational age. Y–axis is displayed with breaks to include all values of EGF, even outliers, using the ggbreak R package [33].

Figure 2

Median amniotic fluid EGF concentrations in neonates with respiratory outcomes compared with neonates without outcomes, (p < 0.001 for all assays): (a) Median EGF concentrations with RDS vs. no RDS were 68.25 pg/mL vs. 124.29 pg/mL (p < 0.001), respectively; (b) median EGF concentrations for severe RDS were 48.70 pg/mL vs. 63.80 pg/mL of moderate RDS vs. 88.20 pg/mL of mild RDS vs. 124.00 pg/mL of no RDS (p < 0.001); (c) median EGF concentrations in infants with a need for respiratory support was 69.85 pg/mL compared with 121.88 pg/mL in infants without RS (p < 0.001); (d) median EGF concentrations depending on the duration of RS were as follows: 122.00 pg/mL with no RS, 93.50 pg/mL with ≤24 h RS, 81.10 pg/mL with 24–96 h RS, and 47.70 pg/mL with ≥96 h RS (p < 0.001); (e) median EGF concentrations with a different type of ventilation or no RS were: mechanical ventilation vs. noninvasive RS vs. no RS—46.10 pg/mL vs. 77.10 pg/mL vs. 120.00 pg/mL (p < 0.001), respectively; (f) median EGF concentrations with BPD vs. no BPD were 29.90 pg/mL vs. 86.06 pg/mL (p = 0.0016), respectively; (g) median EGF concentrations in newborns with surfactant need vs. no need for surfactant were 45.36 vs. 93.33 pg/mL (p < 0.001), respectively. RDS—respiratory distress syndrome; RS—respiratory support; BPD—bronchopulmonary dysplasia.

Figure 2

Median amniotic fluid EGF concentrations in neonates with respiratory outcomes compared with neonates without outcomes, (p < 0.001 for all assays): (a) Median EGF concentrations with RDS vs. no RDS were 68.25 pg/mL vs. 124.29 pg/mL (p < 0.001), respectively; (b) median EGF concentrations for severe RDS were 48.70 pg/mL vs. 63.80 pg/mL of moderate RDS vs. 88.20 pg/mL of mild RDS vs. 124.00 pg/mL of no RDS (p < 0.001); (c) median EGF concentrations in infants with a need for respiratory support was 69.85 pg/mL compared with 121.88 pg/mL in infants without RS (p < 0.001); (d) median EGF concentrations depending on the duration of RS were as follows: 122.00 pg/mL with no RS, 93.50 pg/mL with ≤24 h RS, 81.10 pg/mL with 24–96 h RS, and 47.70 pg/mL with ≥96 h RS (p < 0.001); (e) median EGF concentrations with a different type of ventilation or no RS were: mechanical ventilation vs. noninvasive RS vs. no RS—46.10 pg/mL vs. 77.10 pg/mL vs. 120.00 pg/mL (p < 0.001), respectively; (f) median EGF concentrations with BPD vs. no BPD were 29.90 pg/mL vs. 86.06 pg/mL (p = 0.0016), respectively; (g) median EGF concentrations in newborns with surfactant need vs. no need for surfactant were 45.36 vs. 93.33 pg/mL (p < 0.001), respectively. RDS—respiratory distress syndrome; RS—respiratory support; BPD—bronchopulmonary dysplasia.