Raghuraman Nandini, Porcelli Bree, Temming Lorene A, Macones George A, Cahill Alison G, Tuuli Methodius G, Dicke Jeffrey M
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
J Matern Fetal Neonatal Med. 2020 Jan;33(1):42-48. doi: 10.1080/14767058.2018.1484095. Epub 2018 Jun 27.
Betamethasone (BMZ) is commonly administered to patients with fetal growth restriction (FGR) and abnormal umbilical artery Doppler (UAD) velocimetry due to the increased risk of preterm delivery; however, the clinical impact of UAD changes after BMZ exposure is unknown. To test the hypothesis that lack of UAD improvement after BMZ administration is associated with shorter latency and greater neonatal morbidity in patients with FGR. This was a retrospective cohort study of pregnancies complicated by FGR and abnormal UAD between 24 and 33 weeks gestation. Abnormal UAD included the following categories of increasing severity: elevated (pulsatility index >95%), absent end diastolic flow (EDF), or reversed EDF improvement was defined as any improvement in category of UAD within two weeks of BMZ. Sustained improvement was defined as improvement until the last ultrasound before delivery, whereas transient improvement was considered as unsustained. The was latency, defined as interval from betamethasone administration to delivery. were gestational age at delivery, umbilical artery pH, and a composite of neonatal morbidity (intubation, necrotizing enterocolitis, ionotropic support, intraventricular hemorrhage, total parenteral nutrition, neonatal death). Outcomes were compared between (a) patients with and without UAD improvement and (b) patients with sustained and unsustained improvement, using univariable, multivariable and time-to-event analyses. Of the 222 FGR pregnancies with abnormal UAD, 94 received BMZ and had follow-up ultrasounds. UAD improved in 48 (51.1%), with 27 (56.3%) having sustained improvement. Patients with hypertension and drug use were less likely to have UAD improvement. Patients without UAD improvement had shorter latency (21.5 days [interquartile range (IQR) 8,45] versus 35 [IQR 22,61], = .02) and delivered at an earlier gestational age (34 weeks [IQR 31,36] versus 37 [IQR 33,37], < .01) than those with improvement. There were no differences in umbilical artery pH between groups. Composite neonatal morbidity was higher in patients without UAD improvement, but this was not statistically significant after adjusting for confounders (aOR 2.0; 95% CI 0.08-5.1). There were no differences in outcomes between patients with sustained versus unsustained improvement. UAD improved in half of patients following BMZ. Lack of UAD improvement was associated with shorter latency and earlier gestational age at delivery, but no difference in composite neonatal morbidity. UAD response to BMZ may be useful to further risk stratify FGR pregnancies.
由于早产风险增加，倍他米松（BMZ）常用于治疗胎儿生长受限（FGR）和脐动脉多普勒（UAD）测速异常的患者；然而，BMZ暴露后UAD变化的临床影响尚不清楚。为了验证这一假设，即BMZ给药后UAD缺乏改善与FGR患者的潜伏期缩短和更高的新生儿发病率相关。这是一项对妊娠24至33周合并FGR和UAD异常的回顾性队列研究。UAD异常包括以下严重程度增加的类别：升高（搏动指数>95%）、舒张末期血流缺失（EDF）或反向EDF。改善定义为BMZ给药后两周内UAD类别有任何改善。持续改善定义为直到分娩前最后一次超声检查时仍有改善，而短暂改善则视为未持续改善。潜伏期定义为从倍他米松给药到分娩的间隔时间。结局指标包括分娩时的孕周、脐动脉pH值以及新生儿发病率的综合指标（插管、坏死性小肠结肠炎、离子支持、脑室内出血、全胃肠外营养、新生儿死亡）。使用单变量、多变量和事件时间分析，比较了（a）UAD有改善和无改善的患者之间以及（b）持续改善和未持续改善的患者之间的结局。在222例合并UAD异常的FGR妊娠中，94例接受了BMZ并进行了随访超声检查。48例（51.1%）UAD有改善，其中27例（56.3%）持续改善。高血压和药物使用的患者UAD改善的可能性较小。UAD无改善的患者潜伏期较短（21.5天[四分位间距（IQR）8,45]对35天[IQR 22,61]，P = 0.02），且分娩时孕周较早（34周[IQR 31,36]对37周[IQR 33,37]，P < 0.01），而有改善的患者则不然。两组之间脐动脉pH值无差异。UAD无改善的患者综合新生儿发病率较高，但在调整混杂因素后无统计学意义（调整后比值比2.0；95%置信区间0.08 - 5.1）。持续改善和未持续改善的患者之间结局无差异。BMZ治疗后一半患者UAD有改善。UAD缺乏改善与潜伏期缩短和分娩时孕周较早相关，但综合新生儿发病率无差异。UAD对BMZ的反应可能有助于进一步对FGR妊娠进行风险分层。
