Armstrong-Buisseret Lindsay, Godolphin Peter J, Bradshaw Lucy, Mitchell Eleanor, Ratcliffe Sam, Storey Claire, Heazell Alexander E P
1Nottingham Clinical Trials Unit (NCTU), Building 42, University of Nottingham, University Park, Nottingham, NG7 2RD UK.
2Maternal and Fetal Health Research Centre, 5th Floor (Research), St Mary's Hospital, Oxford Road, Manchester, M13 9WL UK.
Pilot Feasibility Stud. 2020 Feb 13;6:23. doi: 10.1186/s40814-020-0561-z. eCollection 2020.
Biomarkers of placental function can potentially aid the diagnosis and prediction of pregnancy complications. This randomised controlled pilot trial assessed whether for women with reduced fetal movement (RFM), intervention directed by the measurement of a placental biomarker in addition to standard care was feasible and improved pregnancy outcome compared with standard care alone.
Women aged 16-50 years presenting at eight UK maternity units with RFM between 36 and 41 weeks' gestation with a viable singleton pregnancy and no indication for immediate delivery were eligible. Participants were randomised 1:1 in an unblinded manner to standard care and a biomarker blood test result revealed and acted on (intervention arm) or standard care where the biomarker result was not available (control arm). The objectives were to determine the feasibility of a main trial by recruiting 175-225 participants over 9 months and to provide proof of concept that informing care by measurement of placental biomarkers may improve outcome. Feasibility was assessed via the number of potentially eligible women, number recruited, reasons for non-recruitment and compliance. Proof of concept outcomes included the rates of the induction of labour and caesarean birth, and a composite adverse pregnancy outcome.
Overall, 2917 women presented with RFM ≥ 36 weeks, 352 were approached to participate and 216 (61%) were randomised (intervention = 109, control = 107). The main reason for not approaching women was resource/staff issues ( = 1510). Ninety-seven women declined the trial, mainly due to not liking blood tests ( = 24) or not wanting to be in a trial ( = 21). Compliance with the trial interventions was 100% in both arms. Labour was induced in 97 (45%) participants (intervention = 49, control = 48), while 17 (9%) had planned caesarean sections (intervention = 9, control = 8). Overall, 9 (8%) babies in the intervention arm had the composite adverse pregnancy outcome versus 4 (4%) in the control arm.
A main trial using a placental biomarker in combination with delivery, as indicated by the biomarker, in women with RFM is feasible. The frequency of adverse outcomes in this population is low, hence, a large sample size would be required along with consideration of the most appropriate outcome measures.
ISRCTN, ISRCTN12067514; registered 8 September 2017.
胎盘功能生物标志物可能有助于妊娠并发症的诊断和预测。这项随机对照试验评估了对于胎动减少（RFM）的女性，除标准护理外，基于胎盘生物标志物测量进行干预是否可行，以及与单纯标准护理相比是否能改善妊娠结局。
年龄在16至50岁之间、孕36至41周时因RFM就诊于英国8个产科单位、单胎妊娠存活且无立即分娩指征的女性符合条件。参与者以1:1的比例非盲随机分组，分为接受标准护理且生物标志物血液检测结果已知并据此采取行动的组（干预组）和生物标志物结果未知的标准护理组（对照组）。目标是在9个月内招募175至225名参与者以确定一项主要试验的可行性，并提供概念验证，即通过测量胎盘生物标志物指导护理可能改善结局。通过潜在符合条件的女性数量、招募的数量、未招募的原因和依从性来评估可行性。概念验证结局包括引产率和剖宫产率，以及综合不良妊娠结局。
总体而言，2917名孕≥36周出现RFM的女性中，352名被邀请参与，216名（61%）被随机分组（干预组 = 109名，对照组 = 107名）。未邀请女性参与的主要原因是资源/人员问题（ = 1510）。97名女性拒绝试验，主要原因是不喜欢血液检测（ = 24）或不想参加试验（ = 21）。两组对试验干预的依从性均为100%。97名（45%）参与者接受了引产（干预组 = 49名，对照组 = 48名），17名（9%）进行了计划剖宫产（干预组 = 9名，对照组 = 8名）。总体而言，干预组9名（8%）婴儿出现综合不良妊娠结局，对照组为4名（4%）。
对于RFM女性，使用胎盘生物标志物并结合生物标志物指示的分娩方式进行一项主要试验是可行的。该人群中不良结局的发生率较低，因此，需要大样本量并考虑最合适的结局指标。
ISRCTN，ISRCTN12067514；2017年9月8日注册。
