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Brief summary describing the background
and objectives of the trial
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Multiple pregnancies contribute disproportionately to preterm deliveries. Overall 52.2% of multiple births deliver before 37 weeks and 10.7% before 32 weeks. The neonatal mortality rate of twins is six to seven times that of singleton pregnancies, at 18 per 1000 live births, while neonatal mortality of triplets and higher order multiple pregnancies reaches 39.6 per 100 live births. Prematurity represents the largest cause of perinatal mortality in the world, being a major focus of attention in the main research in recent years (Chawanpaiboon et al., 2019). In a twin pregnancy, it is 3 to 4 times greater, representing 12% of preterm infants. Multiple pregnancies are at higher risk of obstetric complications, thus a substantial proportion of preterm births in multiple pregnancies are medically indicated (Marleen et al., 2021).
The reduction in the incidence of RDS and mortality was more marked in the 29- to 34-week gestation group, although the benefits in terms of decreasing the severity of RDS have also been reported in 24- to 28-week gestations. Even in unplanned preterm deliveries, the use of antenatal corticosteroids has been shown to decrease morbidity and mortality caused by RDS in many clinical trials. Initially, these effects were demonstrated mainly in singleton pregnancies and spontaneous preterm labor(Shanks AL, Grasch JL 2019).
The causes that determine preterm labor in multiple pregnancies are multifactorial. Physiological stimuli to the onset of parturition, including stretch, placental corticotrophin-releasing hormone and lung maturity factors, may be stronger in multiple pregnancies due to the increased fetal and placental mass (Mendelson et al., 2019). Pathological processes including infection and cervical insufficiency also have a role. Treatments that prevent preterm birth in singleton pregnancies, such as progesterone and cervical cerclage appear to be ineffective in multiple pregnancies (Pisacreta, & Mannella, 2022)Corticosteroids, unlike other forms of steroids, are easily transported across the placenta. They act on the airways in various ways, such as fetal lung maturation through thinning of the alveolar septa and alveolar differentiation with type 2 pneumocyte induction, which stimulates the production of surfactants (Fandiño et al., 2019). The most important fetal organ in terms of survival at birth is the lung, where corticosteroids act in the mesenchymal tissue to reduce the distances from blood vessels to the airways to allow for proper gas exchange corticosteroids. , in addition to promoting the production of surfactants, mature the pulmonary mechanisms for the elimination of fluid from the lung’s airways at birth (Hrabalkova et al., 2019).
In the fetus, cortisol plays an important role in development as it promotes the maturation of major organs in late pregnancy, including the respiratory system, kidney, gastrointestinal tract and brain. Fetal adrenal cortisol levels increase dramatically in the last six weeks before term completion and play a crucial role in later stages of organogenesis (Cole et al., 2019).
Despite these benefits, the use of corticosteroids can cause harm, including neonatal hypoglycemia (Uquillas et al., 2020). It has been shown that antenatal betamethasone results in elevated betamethasone concentrations and decreased cord blood cortisol concentrations at birth, leading to fetal hypothalamic pituitary adrenal axis suppression, persisting for up to seven days after birth. This practice results in high levels of blood glucose and C-peptide at birth and consequent hypoglycemia in the early neonatal period, which although appearing to be self-limited, has been reported to be associated with poor neurological outcomes (Takahashi et al., 2022).. |