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Objective:To explore the effects of prenatal dexamethasone (DEX), postnatal pulmonary surfactant (PS) and respiratory support on the lung fluid clearance in premature rabbits at gestational age (GA) of 25-28 d (full term: 31 d) and their relationship with dynamic compliance of respiratory system (Cdyn), pulmonary morphology and other parameters.Methods:In our previous publications, premature rabbits were divided into four groups according to the intervention strategy: control group, PS-only group, DEX-only group and DEX+PS group in which data of several parameters including wet-to-dry lung weight ratio (W/D), Cdyn and volume density of alveoli (Vv) were retrieved and the lung tissue sections were scanned to recalculate the ratio of perivascular sheath to vascular sectional area (S/V) and lung injury scores-edema (LIS-E). W/D, LIS-E, S/V and Vv were adjusted for birth weight (BW) (divided by BW, represented as W/D/BW, LIS-E/BW, S/V/BW and Vv/BW) and mean Cdyn (Cdyn-m) was adopted. Based on the grouping of previous studies, the intervention groups in this study were divided as DEX group and non-DEX group, and PS group and non-PS group to analyze the influence of DEX and PS on the above parameters. Two independent samples t-test, one-way analysis of variance, LSD test, Kruskal-Wallis H test, Mann-Whitney U test and Pearson correlation analysis were used for statistical analysis. Results:A total of 196 newborn rabbits receiving mechanical ventilation after birth were included in this study. (1) Effects of DEX: compared with the non-DEX group, the DEX group showed increased W/D/BW (489±69 vs 421±113, t=－2.09), LIS-E/BW (188±57 vs 138±55, t=－2.61) and Vv/BW (20.1±4.9 vs 14.2±4.7, t=－3.60), but decreased S/V (0.33±0.23 vs 0.51±0.25, t=2.23) and S/V/W/D (0.05±0.03 vs 0.07±0.04, t=2.22) at 25 d of gestation; at 26 d of gestation, W/D/BW (472±76 vs 303±44, t=－8.75), LIS-E/BW (189±63 vs 106±36, t=－5.23), Cdyn-m [(0.16±0.07) vs (0.05±0.03) ml/(kg?cmH 2O), 1 cmH 2O=0.098 kPa; t=－7.29] and Vv/BW increased (22.4±5.0 vs 12.2±3.8, t=－7.46), while S/V (0.23±0.19 vs 0.62±0.38, t=4.10), S/V/BW (15.7±12.4 vs 25.7±17.3, t=2.20), S/V/W/D (0.03±0.03 vs 0.08±0.05, t=3.92) and propensity scores decreased [(12.5±1.2) vs (15.1±1.2) scores, t=7.00]; at 27 d of gestation, Cdyn-m increased [(0.23±0.12) vs (0.16±0.07) ml/(kg?cmH 2O), t=－2.43], but S/V (0.32±0.23 vs 0.57±0.39, t=2.57) and S/V/W/D decreased (0.05±0.04 vs 0.09±0.06, t=2.55); at 28 d of gestation, W/D/BW (270±64 vs 162±33, t=－8.09), LIS-E/BW (72±32 vs 35±20, t=－5.17), S/V (0.90±0.60 vs 0.59±0.48, t=－2.81), S/V/BW (34.0±23.6 vs 15.2±12.7, t=－3.77) and Vv/BW increased (16.9±4.3 vs 9.2±2.9, t=－8.04); the differences were all statistically significant (all P<0.05). (2) Effects of PS: compared with the non-PS group, the PS group had decreased LIS-E/BW at 25, 26 and 27 d of gestation, increased Cdyn-m and Vv/BW at 25 and 27 d of gestation and higher propensity scores at 25 d of gestation (all P<0.05). (3) The correlation between gestational age and each index: gestational age was positively correlated with S/V ( r=0.31, P<0.05), but negatively correlated with W/D/BW and LIS-E/BW ( r=－0.73 and－0.63, both P<0.05). Conclusions:The pharmacological action of prenatal DEX on lung fluid clearance is mainly confined to preterm rabbits at the GA of 28 d which is supported by mechanical ventilation. Prenatal treatment with DEX and/or postnatal PS can improve the early respiratory function in preterm rabbits between GA of 25-27 d, but had no substantial impact on lung fluid clearance. The GA-related lung maturation appears to play a crucial role, in comparison with medications, in lung fluid clearance.
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The role and mechanism of vitamin D in fetal and neonatal lung development and chronic lung diseases development have raised attention in recent years. The placental transfer of vitamin D is the major source of vitamin D to the developing fetus. The lung, as a target organ for vitamin D, has its capacity for vitamin D metabolism and can form biologically active 1,25 dihydroxyvitamin D 3 in a paracrine manner to regulate lung development. Studies have shown that vitamin D is directly involved in the synthesis of lung surfactant proteins and phospholipids and promotes lung maturation such as lung epithelial-mesenchymal interactions and alveolar formation. Furthermore, it regulates immunity and improves placental function, which indirectly affects lung development. Vitamin D deficiency and vitamin D receptor polymorphisms have been found to be detrimental to the development of alveoli, and are associated with respiratory diseases such as neonatal respiratory distress syndrome and bronchopulmonary dysplasia (BPD). Experimental studies in animals have shown that antenatal vitamin D supplementation promotes lung maturation in preterm rats and postnatal vitamin D supplementation can alleviate the hyperoxia-induced inflammatory response in the lung and reduce BPD occurrence. Further high-quality research are needed to explore the dosing, timing, and impact factors of vitamin D for promoting fetal and neonatal lung maturation and clarify the mechanism of its prophylactic and therapeutic action.
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Large population-based cohort studies conducted in the industrialized countries in different eras revealed that the use of antenatal corticosteroids for extremely preterm births (EPT, <28 gestational weeks) reached 60% or higher in the mid-1990s, accompanying by steadily declined perinatal mortality to 13%-22% in EPT with gestational age ≥25 weeks in developed countries. Notably, the survival rate of EPT with 23-24 weeks of gestation was over 50% in Sweden since 2005. There's a link between the increment of antenatal corticosteroids use and steady decline of mortality in EPT in the past three decades. High-quality evidence is needed to demonstrate the impact of antenatal corticosteroids on EPT perinatal outcomes under the current healthcare background in China. This review, focusing on the progression of antenatal corticosteroid treatment for EPT, may facilitate the quality improvement of maternal-fetal and infant healthcare in China.
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Large population-based cohort studies conducted in the industrialized countries in different eras revealed that the use of antenatal corticosteroids for extremely preterm births (EPT,＜28 gestational weeks) reached 60％ or higher in the mid-1990s,accompanying by steadily declined perinatal mortality to 13％-22％ in EPT with gestational age ≥ 25 weeks in developed countries.Notably,the survival rate of EPT with 23-24 weeks of gestation was over 50％ in Sweden since 2005.There's a link between the increment of antenatal corticosteroids use and steady decline of mortality in EPT in the past three decades.High-quality evidence is needed to demonstrate the impact of antenatal corticosteroids on EPT perinatal outcomes under the current healthcare background in China.This review,focusing on the progression of antenatal corticosteroid treatment for EPT,may facilitate the quality improvement of maternal-fetal and infant healthcare in China.