PDF(Pubmed)
Abstract：
Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival.
To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks\' gestation to mitigate lethal pulmonary hypoplasia.
Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies.
Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks\' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age.
The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement.
The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks\' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks).
Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden.
ClinicalTrials.gov Identifier: NCT03101891.
To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks\' gestation to mitigate lethal pulmonary hypoplasia.
Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies.
Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks\' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age.
The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement.
The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks\' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks).
Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden.
ClinicalTrials.gov Identifier: NCT03101891.
摘要：
■怀孕期间早期羊水过少，由于胎儿双侧肾发育不全，导致新生儿致命的肺发育不全。通过连续羊膜输注恢复羊水可能促进肺发育，使生存。
■评估在妊娠26周前开始连续羊膜输注以减轻致命性肺发育不全的新生儿结局。
■预期，2018年12月至2022年7月在美国9个胎儿治疗中心进行的非随机临床试验.据报道，由于孤立的胎儿双侧肾脏发育不全而没有其他确定的先天性异常，有21对母胎对的证实羊水过多。
注册参与者在妊娠26周前开始超声引导下经皮羊膜输注等渗液，个体化输注频率，以维持胎龄正常的羊水水平。
■主要终点是出生后婴儿存活至14天或更长时间的透析通路。
该试验基于对18对母胎对的中期分析而提前终止，尽管已证实干预措施的有效性，但仍关注新生儿发病率和死亡率超出主要终点。有17例活产(94%)，分娩时的中位胎龄为32周，4天（IQR，32-34周）。所有参与者在妊娠37周前分娩。在17例活产婴儿中，有14例（82％）获得了主要结局（95％CI，44％-99％）。与生存到主要结局相关的因素包括较高的羊膜输注（P=0.01），胎龄大于32周（P=0.005），出生体重较高（P=0.03）。17名活着出生的新生儿中，只有6名（35％）在接受腹膜透析时存活到出院，中位年龄为24周（范围，12-32周）。
■系列羊膜输注减轻了致命性肺发育不全，但与早产相关。较低的出院生存率凸显了独立于肺功能的额外死亡负担。需要更多的长期数据来充分表征存活新生儿的结局，并评估发病率和死亡率负担。
■ClinicalTrials.gov标识符：NCT03101891。
■评估在妊娠26周前开始连续羊膜输注以减轻致命性肺发育不全的新生儿结局。
■预期，2018年12月至2022年7月在美国9个胎儿治疗中心进行的非随机临床试验.据报道，由于孤立的胎儿双侧肾脏发育不全而没有其他确定的先天性异常，有21对母胎对的证实羊水过多。
注册参与者在妊娠26周前开始超声引导下经皮羊膜输注等渗液，个体化输注频率，以维持胎龄正常的羊水水平。
■主要终点是出生后婴儿存活至14天或更长时间的透析通路。
该试验基于对18对母胎对的中期分析而提前终止，尽管已证实干预措施的有效性，但仍关注新生儿发病率和死亡率超出主要终点。有17例活产(94%)，分娩时的中位胎龄为32周，4天（IQR，32-34周）。所有参与者在妊娠37周前分娩。在17例活产婴儿中，有14例（82％）获得了主要结局（95％CI，44％-99％）。与生存到主要结局相关的因素包括较高的羊膜输注（P=0.01），胎龄大于32周（P=0.005），出生体重较高（P=0.03）。17名活着出生的新生儿中，只有6名（35％）在接受腹膜透析时存活到出院，中位年龄为24周（范围，12-32周）。
■系列羊膜输注减轻了致命性肺发育不全，但与早产相关。较低的出院生存率凸显了独立于肺功能的额外死亡负担。需要更多的长期数据来充分表征存活新生儿的结局，并评估发病率和死亡率负担。
■ClinicalTrials.gov标识符：NCT03101891。
