UOG Journal Club: October 2018 国际妇产超声杂志俱乐部 Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth Restriction 对于随访可疑为宫内生长受限的胎儿，其妊娠期母体血流动力、胎儿生长发育及多普勒指标的变化 L. A. Roberts, H. Z. Ling, L. C. Poon, K. H. Nicolaides and N. A. Kametas Volume 52, Issue 4, pages 507–514 Journal Club slides prepared by Dr Alessandra Familiari (UOG Editor for Trainees) Translation by Dr Lijuan Sun and Prof. Qingqing Wu, ISUOG China Task Force

Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Introduction引言 Small-for-gestational-age (SGA) fetuses with birth weight < 10th percentile show increased perinatal complications.小于孕龄儿定义为出生体重小于第10百分位，已显示小于孕龄儿的围产期并发症会增加。 The risk of major adverse outcome is particularly marked in the subgroup with birth weight < 3rd percentile and in those with redistribution of the fetal circulation with increased pulsatility index (PI) in the umbilical artery (UA), reduced PI in the fetal middle cerebral artery (MCA) and reduced amniotic fluid level.尤其对于出生体重小于第3百分位、胎儿循环重新分布（表现为脐动脉搏动指数增加、大脑中动脉搏动指数下降）及羊水量减少的亚组来说，其主要不良结局的风险显著增加。 The knowledge that, in pregnancies with impaired fetal growth there is abnormal maternal cardiac function, has been utilized for screening for the risk of placental insufficiency at the routine first-trimester scan in both high- and low-risk pregnancies. 我们知道宫内生长受损的胎儿，存在母体心脏功能异常，这已常规用于高风险和低风险人群在孕早期对胎盘功能不足的筛查。

Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Aim of the study研究目的 To assess whether maternal hemodynamics, fetal biometry and Doppler indices at presentation, in women referred to a specialist clinic for the management of pregnancy with a SGA fetus, can predict the subsequent development of an abnormal fetal Doppler index or birth weight < 3rd percentile. 对于在专家门诊就诊并进行治疗的SGA胎儿，对母体的血流动力、胎儿生长发育及多普勒指标进行评估，目的是评价上述指标是否可对胎儿进一步发展为多普勒指标异常或出生体重小于第3百分位进行预测。

Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Methods方法 Prospective observational cohort study.前瞻性观察队列研究。 Maternal hemodynamic assessment was performed on initial presentation to the SGA clinic using a non-invasive bioreactance method and cardiac output (CO) (L/min), stroke volume (SV) (mL), heart rate (HR) (bpm) and peripheral vascular resistance PVR (dynes × s/cm5) were recorded. 母体的血流动力是SGA门诊首先评估的内容，使用无创生物反应法并记录如下指标：心输出量(CO) (L/min), 每博输出量(SV) (mL), 心率(HR) (bpm) 和周边血流阻力(PVR) (dynes × s/cm5) 。 Reference ranges across gestation for maternal hemodynamic and fetal variables were used and their Z-scores calculated.根据母体血流动力和胎儿变量的妊娠期参考值计算Z评分。 Estimated fetal weight (EFW) percentile and Z-score were derived from sonographic measurements. 使用超声估测胎儿体重百分位数和Z评分。 UA-PI, fetal MCA-PI, mean UtA-PI and measurement of deepest vertical pool (DVP) were assessed.测量胎儿脐动脉搏动指数、胎儿大脑中动脉搏动指数、子宫动脉平均搏动指数和羊水最大垂直深度。 Abnormal fetal Doppler index was defined as UA-PI > 95th percentile and/or MCA-PI < 5th percentile. 胎儿异常多普勒指标定义为脐动脉搏动指数大于第95百分位和/或大脑中动脉搏动指数小于第5百分位。 The consensus definition of FGR, developed through a Delphi procedure, was used to define FGR at subsequent visits. 关于FGR的定义共识通过Delphi程序开发，在接下来的研究中用于定义FGR。

Statistical analysis统计分析 Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Statistical analysis统计分析 Maternal demographics, fetal biometry, UA-PI, MCA-PI, mean UtA-PI, amniotic fluid DVP and maternal hemodynamic variables Z-scores were compared between:在下列研究组之间比较孕妇一般情况、胎儿生长发育、脐动脉搏动指数、大脑中动脉搏动指数、子宫动脉平均搏动指数、羊水最大垂直深度和母体血流动力指标Z评分。 Women with an abnormal fetal Doppler index at presentation (Group 1), 胎儿即时多普勒指标异常组（组1） Women who had developed an abnormal fetal Doppler index at a subsequent visit (Group 2), 在接下来的检查中出现胎儿异常多普勒频谱组（组2） Women who did not develop an abnormal fetal Doppler index during pregnancy (Group 3).妊娠期胎儿多普勒指标无异常组（组3） Comparisons were also made between the above parameters in women who delivered a neonate with a birth weight < 3rd percentile and those who delivered a neonate with a birth weight ≥ 3rd percentile.上述指标也在出生体重小于第3百分位组和出生体重大于第3百分位组之间进行比较，

Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Results结果 There were no significant differences in maternal demographics between groups, apart from a higher rate of women taking labetalol and methyldopa for blood-pressure control in Group 1 vs Group 3.组1和组3间进行比较，除了组1孕妇服用拉贝洛尔和甲基多巴控制血压的比例增高外，其他孕妇一般情况指标均无统计学差异。 Gestational age at presentation to the SGA clinic was similar in all groups (around 32 weeks), but there was a significant difference in EFW percentile at presentation between Groups 1 and 3. 3组间比较，SGA门诊就诊孕周相似，约为32周，但组1与组3比较，门诊超声即时估测胎儿百分位数具有统计学差异。 All three groups had a low negative Z-score for maternal CO (owing to a lower SV) and a high positive Z-score for PVR. 3组均具有负的较低的母体心输出量Z评分（由于每博输出量较低）及正的较高的周边血流阻力Z评分。

Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Results结果 Box-and-whiskers plots of Z-scores of maternal hemodynamic and fetal biometry and Doppler variables in 86 pregnancies with estimated fetal weight ≤ 10th percentile with abnormal Doppler index (UA-PI > 95th percentile and/or MCA-PI < 5th percentile) at presentation (dark box) , those that subsequently developed abnormal Doppler index (grey box) and those with normal Doppler indices throughout pregnancy (white box). 86例胎儿母体血流动力学、胎儿生长发育及多普勒指标的盒形-虚线图，黑色盒子表示超声即时估测胎儿体重小于第10百分位且胎儿多普勒指标异常（ UA-PI 大于第95百分位和/或MCA-PI小于第5百分位），灰色盒子表示随后的检查中胎儿多普勒指标异常，白色盒子表示妊娠期间多普勒指标无异常。

Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Results结果 All three groups had low negative Z-scores of logHC, logAC and FL.3组均具有负的较低的关于logHC, logAC 和 FL的Z评分. Group 1 had lower logHC Z-score than did Group 2 and lower logAC Z-score than did both Groups 2 and 3. 组1与组2比较具有较低的logHC Z评分，与组2和组3比较具有较低的logAC Z评分。 There were no differences in FL Z-scores between the groups.3组间比较FL的Z评分均无统计学意义。 All three groups had a high positive Z-score for UA-PI, with a gradual reduction from Group 1 to Group 3.3组间均具有正的较高的UA-PI Z评分，且组1至组3 Z评分依次减小。 Group 3 had a lower UA-PI Z-score compared with both Groups 1 and 2. 组3与组2、组1比较具有较低的UA-PI Z评分。 There was a gradual decline in MCA-PI Z-score from Group 3 to Group 1, with Group 3 having significantly higher MCA-PI Z-score compared with Group 1.组3至组1MCA-PI Z评分依次减小，组3与组1比较MCA-PI 显著增加。 Group 1 had a higher prevalence of DVP < 5th percentile compared with Group 3.组1与组3比较，羊水最大垂直深度小于第5百分位的发生率明显增加。 Mean UtA-PI Z-score was higher in Group 1 than in Groups 2 and 3, but the difference did not reach statistical significance.组1 与组2、组3进行比较，平均UtA-PI Z评分较高，但无统计学意义。

Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Results结果 There were modest correlations between maternal hemodynamic, fetal biometry and fetal and placental Doppler variable Z-scores.在母体血流动力学、胎儿生长发育以及胎儿和胎盘多普勒变量Z评分之间存在一定的相关性。 The Z-score of CO was correlated positively with that of MCA-PI and negatively with that of UtA-PI.心输出量Z评分与MCA-PI 呈正相关，而与UtA-PI呈负相关。 The Z-score of HR was correlated positively with those of logAC and logFL and negatively with that of UtA-PI.心率Z评分与logAC和logFL呈正相关，而与UtA-PI呈负相关。 The Z-scores of MAP and logPVR were correlated positively with that of UA-PI and negatively with those of logHC, logAC and MCA-PI. MAP 和 logPVR 的Z评分与UA-PI 呈正相关，而与logHC, logAC 和MCA-PI呈负相关。

Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Results结果 Multivariate logistic regression analysis for the prediction of delivery of a neonate with a birth weight < 3th percentile demonstrated that the addition of maternal hemodynamic variables produced a better prediction model than did the one based solely on maternal demographics, fetal biometry and Doppler indices.预测新生儿出生体重小于第3百分位的多元逻辑回归分析显示，加入母体血流动力指标比仅仅使用母体一般情况指标、胎儿生长发育和多普勒指标更能形成好的预测模型。 Multivariate logistic regression analysis for the prediction of subsequent FGR showed that maternal hemodynamic variables did not provide an improvement in the prediction model based on maternal demographics, fetal biometry and Doppler indices.预测之后发生FGR的多元逻辑回归分析显示，在母体一般情况、胎儿生长发育和多普勒指标中加入母体血流动力指标不能形成更好的预测模型。

Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Discussion讨论 All three groups at presentation were characterized by lower maternal SV and CO Z-scores and higher PVR Z-score compared with normal pregnancies.3组即时数据显示，与正常妊娠相比母体每博输出量和心输出量的Z评分较低， PVR Z评分较高。 Women with an abnormal fetal Doppler index at presentation demonstrated the lowest CO and SV Z-scores, highest PVR Z-scores, asymmetrical biometry, signs of redistribution and the highest UtA-PI Z-score. 具有异常胎儿频谱的母体其CO和SV的Z评分最低， PVR Z评分最高，胎儿发育不对称，胎儿血流重分布及UtA-PI Z评分最高。 Pregnancies that subsequently demonstrated abnormal fetal Doppler indices had no significant differences in terms of maternal hemodynamics, fetal biometry and Doppler indices, apart from higher UA-PI Z-score.在接下来的检查中出现胎儿异常多普勒频谱妊娠中，除了UA-PI Z评分较高之外，母体血流动力学、胎儿生长发育和多普勒指标均显示无统计学差异。 Pregnancies with a birth weight < 3th percentile had distinct differences compared with those with birth weight ≥ 3th percentile in terms of maternal hemodynamics and fetal Doppler indices. 出生体重小于第3百分位组与出生体重大于第3百分位组的妊娠相比，母体血流动力学和胎儿多普勒指标均存在明显差异。

Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Discussion讨论 Higher CO Z-score was associated with higher MCA-PI Z-score and lower UtA-PI Z-score 较高的CO Z评分与较高的MCA-PI Z评分、较低的UtA-PI Z评分相关。 VOLUME DEPLETION AND HIGH RESISTANCE IN THE MATERNAL CARDIOVASCULAR SYSTEM ARE ASSOCIATED WITH INCREASED PLACENTAL RESISTANCE AND FETAL GROWTH IMPAIRMENT. 容量减少及母体心血管系统的高阻力与胎盘阻力增加及胎儿生长受损相关。 CORRELATIONS ARE MODEST AND EXPLAIN ONLY A SMALL PART OF THE VARIABILITY IN FETAL BIOMETRY AND DOPPLER VARIABLES. 上述指标具有一定的相关性，但仅解释了胎儿生长发育和多普勒指标变异的一小部分。 Higher MAP and PVR Z-scores were associated with higher UA-PI Z-score and lower MCA-PI, HC and AC Z-scores 较高的MAP 和 PVR Z评分与较高的UA-PI Z评分、较低的MCA-PI、HC 和 AC Z评分相关。

Maternal hemodynamics, fetal biometry and Doppler indices in pregnancies followed up for suspected fetal growth restriction Roberts et al., UOG 2018 Discussion points讨论点 What is the possible explanation of having similar maternal hemodynamics, fetal biometry and Doppler indices between Groups 2 and 3, despite the fact that abnormal fetal Doppler indices were evident in Group 2? 组2与组3相比胎儿多普勒指标明显异常，为什么组2与组3具有相似的母体血流动力学变化、胎儿生长发育和多普勒指标？ Is it possible that Group 2 is “only” an “earlier stage” of FGR? Or does it just have a better maternal hemodynamic profile, and further insult, such as hypertension with subsequent antihypertensive treatment, worsen maternal and fetal homeostasis? 组2是否可能是FGR的早期阶段？或者它具备更好的母体血流动力和进一步的损害，比如发展为高血压及进一步的抗高血压治疗以及母体和胎儿的动态平衡受损。 Is it possible to speculate that impaired maternal cardiovascular adaptation and evidence of placental insufficiency could indicate earlier delivery in such a high-risk group in order to improve outcomes? 为了提高高危组的结局，是否可将母体心血管适应性和胎盘功能不足作为尽早结束分娩的指证。