Preterm Premature Rupture of Membranes: A Constant Challenge in Perinatal Medicine?

Secondly, neonatologists must be aware of the fact that persistent pulmonary hypertension may aggravate the clinical course of affected very preterm neonates with respect to cardiopulmonary function. Several therapeutic options are currently available for persistent pulmonary hypertension in very preterm infants [9, 11]. Apart from cardiopulmonary problems, contractures not being a major challenge actually for neonatal intensive care, but potentially causing some long-term problems must be anticipated [1]. Thus, careful follow-up in affected very preterm neonates seems reasonable. As various therapeutic options for treatment of pulmonary hypertension in very preterm neonates have been proposed, which require high treatment standards, pregnant woman suffering from early PPROM should be allocated to centers being adequately staffed and equipped for diagnosis and treatment of affected very preterm neonates [4]. For further prenatal counselling, the overall survival rate in affected neonates should be discussed. In the paper from the Netherlands, a survival rate of very preterm neonates, who were admitted to neonatal intensive care, was in the range of 70 to 76 % still indicating a serious prognosis. However, overall prognosis for survival of very preterm has been substantially improved compared with the data published one or 2 decades ago [2, 7]. The major result from the German trial with enrollment of very low birth weight infants is given by the fact that an increased risk for BPD must be anticipated in very low birth weight infants after PPROM. Thus, strategies for preventing BPD in infants at highest risk should include all current therapeutic options. The authors of the GNN study further conclude that the diagnosis of PPROM is not primarily associated with an increased mortality or other major neonatal complications. Given the data of both trials, there still is an ongoing discussion as to expectant or intentional treatment in obstetrics should be preferred in case of PPROM. One study from Japan enrolling very preterm neonates after PPROM with an expectant management within 14 days was associated with impaired neonatal outcomes. Mortality was mainly attributed to sepsis and related complications. However, the Japanese data imply on the other hand that prenatal steroid administration was an excellent tool in improving prognosis after PPROM occurring beyond 26 weeks gestational age [3]. Thus, it can be concluded from this study, that survival depends also on obstetrical management. Two recently published observational studies have focused on the outcome of very preterm respectively of very low birth weight infants after preterm premature rupture of fetal membranes (PPROM). One single center study from the Netherlands enrolling 160 women with PPROM before 24 weeks gestational age, who admitted to the Rotterdam Medical Center between 2002 and 2011, were analyzed [14]. In parallel, there was a publication from the German Neonatal Network (GNN) enrolling about 6,000 very low birth weight infants, whose data were analyzed under the aspect of PPROM as a potential risk factor for adverse neonatal outcomes [5]. The major result from the first study conducted in the Netherlands was the finding that neonatal outcome largely depends on the time of PPROM. Neonates born after a PPROM diagnosed beyond 20 completed weeks gestational age had a greater likelihood to survive compared with those being born after PPROM with onset before 20 weeks gestational age. There was a 24 % difference in survival in favor of the first group, which was highly significant. On the other hand, using a quite different approach, the GNN-consortium aimed at investigating risk factors for adverse neonatal outcome including PPROM. Definitions of neonatal variables in both papers were comparable. It could be demonstrated that PPROM as a primary cause of preterm birth was not an independent risk factor for sepsis and other related neonatal complications. In the GNN cohort, gestational age, i. e. the degree of immaturity, was the major risk factor for developing early onset sepsis. The only adverse diagnosis in the German cohort associated with PPROM was an increased risk of bronchopulmonary dysplasia (BPD) by an odds ratio of 1.25, reaching just the level of statistical significance. However, all other major neonatal adverse outcome variables were not associated with PPROM. What do both aforementioned studies mean for clinical practice in the actual discussion of the scientific community? The key message of the trial from the Netherlands is to provide a useful basis for prenatal counselling of parents facing the delivery of a very preterm neonate with PPROM. As birth weight and gestational age was comparable in preterms with PPROM before and after 20 weeks, there are 2 major robust conclusions to be drawn from this study: Firstly, the prognosis of very preterm neonates born after PPROM < 20 weeks is worse than in the group with PPROM > 20 weeks. L. Gortner