46 Influence of Intrauterine Growth Restriction on Gene Expression of Surfactant Associated Proteins in Preterm Mice

Abstract

Background: Intra-uterine growth restriction (IUGR) is an important risk factor for perinatal morbidity and mortality in prematurity. Placental insufficiency leading to chronic fetal hypoxemia is a well known cause for IUGR. Therefore, the aim of the study was to establish a mouse model for the experimental induction of IUGR caused by reduced maternal inspiratory oxygen to obtain a chronic fetal hypoxemia. Besides auxological data for evaluation of growth restriction, pulmonary surfactant protein (SP) mRNA expression was investigated, addressing the potential impact of IUGR on lung development.Methods: Pregnant mice (C57BL/6) were randomized into two groups: dams (nϭ5) of the first group were held under hypoxic conditions (10% O2) starting at day 14 of gestation. The second group of dams (nϭ5; control) remained under normoxic conditions. All animals were fed ad libitum. At day 17.5 of gestation (term 19 -21 days) fetuses of both groups were delivered prematurely by C-section. To estimate the degree of growth restriction the following key characteristics were selected: birthweight, body length (vertex-tail), head length (rostral-occipital). Pulmonary mRNA expression of SP-A, SP-B, SP-C, SP-D was quantified using real time PCR (deltadeltaCT-method; housekeeping gene: beta-actin). Statistical analyses were performed using Mann-Whitney U test.Results: Compared to controls, hypoxic fetuses showed significantly reduced (pϽ0.0001) birthweight (-28.6%); body length (-13.8%) and head length (-7.7%). Furthermore, pulmonary mRNA expression of SP-A, B and C was significantly decreased in fetuses kept under hypoxic conditions in contrast to controls (pϽ0.05). SP-D mRNA expression was not altered.Conclusion: Maternal hypoxia revealed to be adequate for the experimental induction of IUGR. Reduced mRNA expression of SP-A, B and C in growth restricted preterm mice (day 17.5 of gestation) may indicate an impaired lung maturation.Background:Continuous positive airway pressure (CPAP) has become a preferred method of respiratory support to preterm infants, especially those with birth weights Ͻ1250 g. In a study by Sreenan et al, standard nasal cannula with flows up to 2.5 L/min were used in neonates Ͻ2.0 kg. This 'high-flow' system was shown to deliver similar positive distending pressures compared to ventilator-generated nasal CPAP, and was effective in reducing apnea of prematurity. Since that publication, 'high-flow' CPAP has become increasingly popular in our neonatal intensive care. Its use has been felt to minimize nasal irritation from conventional nasal prongs. Our usual method of CPAPdelivery is an infant flow system (IFS). The purpose of this study was to determine whether high-flow CPAP was as effective as IFS CPAP in neonates Ͻ1250 g.Methods: Preterm infants Ͻ1250 g were randomized following their first extubation to either high-flow or IFS CPAP. Those randomized to the high-flow had flow determined by the following equation: flow (L/min)ϭ0.92ϩ0.68x, where xϭweight in kg (Sreenan et al, 2001). The primary outcome was re-i...