■胎儿生长受限与围产期发病率和死亡率相关。早期识别具有高危胎儿的妇女可以减少围产期不良结局。
■为了评估预测胎儿生长受限和出生体重的现有模型的预测性能,如果需要的话,使用个体参与者数据开发和验证新的多变量模型。
■国际妊娠并发症预测网络中队列的个体参与者数据荟萃分析,决策曲线分析和卫生经济学分析。
■孕妇预订。现有模型的外部验证(9个队列,441,415次怀孕);国际妊娠并发症预测模型的开发和验证(4个队列,237,228次怀孕)。
■产妇临床特征,生化和超声标记。
■胎儿生长受限定义为出生体重<10分,根据胎龄和死胎进行调整,新生儿死亡或分娩前32周出生体重。
■首先,我们使用个体参与者数据荟萃分析对现有模型进行了外部验证.如果需要,我们使用随机截距回归模型开发并验证了新的国际妊娠并发症预测模型,并对变量选择进行了反向剔除,并进行了内部-外部交叉验证.我们估计了具体研究的表现(c统计量,标定斜率,对每个模型进行大范围校准),并使用随机效应荟萃分析进行汇总。使用τ2和95%预测区间量化异质性。我们使用决策曲线分析评估胎儿生长受限模型的临床实用性,和卫生经济学分析基于国家卫生与护理卓越研究所2008模型。
■在119个已发布的模型中,可以验证一个出生体重模型(Poon)。根据我们的定义,没有报道胎儿生长受限。在所有队列中,Poon模型具有良好的汇总校准斜率0.93(95%置信区间0.90至0.96),略有过拟合,平均低估出生体重90.4g(95%置信区间37.9g至142.9g)。新开发的国际妊娠并发症预测-胎儿生长受限模型包括产妇年龄,高度,奇偶校验,吸烟状况,种族,和任何高血压病史,先兆子痫,先前的死产或小于胎龄的婴儿和分娩时的胎龄。这允许以分娩时假定的胎龄范围为条件的预测。合并的表观c统计量和校准为0.96(95%置信区间0.51至1.0),和0.95(95%置信区间0.67至1.23),分别。该模型显示,预测概率阈值在1%到90%之间,净收益为正。除了国际妊娠并发症预测-胎儿生长受限模型中的预测因子外,国际妊娠并发症预测-出生体重模型包括孕妇体重,糖尿病史和受孕方式。内部-外部交叉验证队列的平均校准斜率为1.00(95%置信区间0.78至1.23),没有过度拟合的证据。出生体重平均被低估9.7g(95%置信区间-154.3g至173.8g)。
■由于结果定义的差异,我们无法从外部验证大多数已发布的模型。我们的国际妊娠并发症预测-胎儿生长受限模型的内部-外部交叉验证受到纳入队列中事件少的限制。使用已发布的国家健康与护理卓越研究所2008模型进行的经济评估可能无法反映当前的做法,由于数据匮乏,无法进行全面的经济评估。
■国际妊娠并发症预测模型的性能需要在常规实践中进行评估,它们对决策和临床结果的影响需要评估。
■妊娠并发症的国际预测-胎儿生长受限和妊娠并发症的国际预测-出生体重模型可准确预测分娩时各种假定胎龄的胎儿生长受限和出生体重。这些可用于在预订时对风险状态进行分层,计划监控和管理。
■本研究注册为PROSPEROCRD42011135045。
■该奖项由美国国家卫生与护理研究所(NIHR)卫生技术评估计划(NIHR奖编号:17/148/07)资助,并在《卫生技术评估》中全文发布。28号14.有关更多奖项信息,请参阅NIHR资助和奖励网站。
十个婴儿中就有一个出生时的年龄比他们小。三分之一这样的小婴儿被认为是“生长受限”,因为他们有并发症,如在子宫内死亡(死产)或出生后(新生儿死亡),脑瘫,或者需要长期住院。当胎儿怀疑生长受限时,他们被密切监测,并经常提前交付,以避免并发症。因此,重要的是,我们及早发现生长受限的婴儿,以便计划护理。我们的目标是提供对母亲生育生长受限婴儿的机会的个性化和准确估计,并预测婴儿在怀孕不同时间点分娩时的体重。要做到这一点,首先,我们测试了现有风险计算器(“预测模型”)在预测生长限制和出生体重方面的准确性。然后,我们开发了新的风险计算器,并研究了它们的临床和经济效益。我们通过在我们的大型数据库库(国际妊娠并发症预测)中访问单个孕妇及其婴儿的数据来做到这一点。已发布的风险计算器对生长限制有各种定义,没有人使用我们的定义来预测生长受限婴儿的机会。有人预测婴儿的出生体重。这个风险计算器表现很好,我们开发了两种新的风险计算器来预测生长受限的婴儿(国际妊娠并发症预测-胎儿生长受限)和出生体重(国际妊娠并发症预测-出生体重)。两个计算器都准确地预测了婴儿出生时生长受限的机会,和它的出生体重。出生体重低于9.7g。在预测低风险和高风险的两个母亲中,计算器表现良好。需要进一步的研究来确定在实践中使用这些计算器的影响,以及在实践中实施它们的挑战。国际妊娠并发症预测-胎儿生长受限和国际妊娠并发症预测-出生体重风险计算器都将告知医疗保健专业人员,并使父母能够就监测和分娩时机做出明智的决定。
UNASSIGNED: Fetal growth restriction is associated with perinatal morbidity and mortality. Early identification of women having at-risk fetuses can reduce perinatal adverse outcomes.
UNASSIGNED: To assess the predictive performance of existing models predicting fetal growth restriction and birthweight, and if needed, to develop and validate new multivariable models using individual participant data.
UNASSIGNED: Individual participant data meta-analyses of cohorts in International Prediction of Pregnancy Complications network, decision curve analysis and health economics analysis.
UNASSIGNED: Pregnant women at booking. External validation of existing models (9 cohorts, 441,415 pregnancies); International Prediction of Pregnancy Complications model development and validation (4 cohorts, 237,228 pregnancies).
UNASSIGNED: Maternal clinical characteristics, biochemical and ultrasound markers.
UNASSIGNED: fetal growth restriction defined as birthweight <10th centile adjusted for gestational age and with stillbirth, neonatal death or delivery before 32 weeks\' gestation birthweight.
UNASSIGNED: First, we externally validated existing models using individual participant data meta-analysis. If needed, we developed and validated new International Prediction of Pregnancy Complications models using random-intercept regression models with backward elimination for variable selection and undertook internal-external cross-validation. We estimated the study-specific performance (c-statistic, calibration slope, calibration-in-the-large) for each model and pooled using random-effects meta-analysis. Heterogeneity was quantified using τ2 and 95% prediction intervals. We assessed the clinical utility of the fetal growth restriction model using decision curve analysis, and health economics analysis based on National Institute for Health and Care Excellence 2008 model.
UNASSIGNED: Of the 119 published models, one birthweight model (Poon) could be validated. None reported fetal growth restriction using our definition. Across all cohorts, the Poon model had good summary calibration slope of 0.93 (95% confidence interval 0.90 to 0.96) with slight overfitting, and underpredicted birthweight by 90.4 g on average (95% confidence interval 37.9 g to 142.9 g). The newly developed International Prediction of Pregnancy Complications-fetal growth restriction model included maternal age, height, parity, smoking status, ethnicity, and any history of hypertension, pre-eclampsia, previous stillbirth or small for gestational age baby and gestational age at delivery. This allowed predictions conditional on a range of assumed gestational ages at delivery. The pooled apparent c-statistic and calibration were 0.96 (95% confidence interval 0.51 to 1.0), and 0.95 (95% confidence interval 0.67 to 1.23), respectively. The model showed positive net benefit for predicted probability thresholds between 1% and 90%. In addition to the predictors in the International Prediction of Pregnancy Complications-fetal growth restriction model, the International Prediction of Pregnancy Complications-birthweight model included maternal weight, history of diabetes and mode of conception. Average calibration slope across cohorts in the internal-external cross-validation was 1.00 (95% confidence interval 0.78 to 1.23) with no evidence of overfitting. Birthweight was underestimated by 9.7 g on average (95% confidence interval -154.3 g to 173.8 g).
UNASSIGNED: We could not externally validate most of the published models due to variations in the definitions of outcomes. Internal-external cross-validation of our International Prediction of Pregnancy Complications-fetal growth restriction model was limited by the paucity of events in the included cohorts. The economic evaluation using the published National Institute for Health and Care Excellence 2008 model may not reflect current practice, and full economic evaluation was not possible due to paucity of data.
UNASSIGNED: International Prediction of Pregnancy Complications models\' performance needs to be assessed in routine practice, and their impact on decision-making and clinical outcomes needs evaluation.
UNASSIGNED: The International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight models accurately predict fetal growth restriction and birthweight for various assumed gestational ages at delivery. These can be used to stratify the risk status at booking, plan monitoring and management.
UNASSIGNED: This study is registered as PROSPERO CRD42019135045.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/07) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.
One in ten babies is born small for their age. A third of such small babies are considered to be ‘growth-restricted’ as they have complications such as dying in the womb (stillbirth) or after birth (newborn death), cerebral palsy, or needing long stays in hospital. When growth restriction is suspected in fetuses, they are closely monitored and often delivered early to avoid complications. Hence, it is important that we identify growth-restricted babies early to plan care. Our goal was to provide personalised and accurate estimates of the mother’s chances of having a growth-restricted baby and predict the baby’s weight if delivered at various time points in pregnancy. To do so, first we tested how accurate existing risk calculators (‘prediction models’) were in predicting growth restriction and birthweight. We then developed new risk-calculators and studied their clinical and economic benefits. We did so by accessing the data from individual pregnant women and their babies in our large database library (International Prediction of Pregnancy Complications). Published risk-calculators had various definitions of growth restriction and none predicted the chances of having a growth-restricted baby using our definition. One predicted baby’s birthweight. This risk-calculator performed well, but underpredicted the birthweight by up to 143 g. We developed two new risk-calculators to predict growth-restricted babies (International Prediction of Pregnancy Complications-fetal growth restriction) and birthweight (International Prediction of Pregnancy Complications-birthweight). Both calculators accurately predicted the chances of the baby being born with growth restriction, and its birthweight. The birthweight was underpredicted by <9.7 g. The calculators performed well in both mothers predicted to be low and high risk. Further research is needed to determine the impact of using these calculators in practice, and challenges to implementing them in practice. Both International Prediction of Pregnancy Complications-fetal growth restriction and International Prediction of Pregnancy Complications-birthweight risk calculators will inform healthcare professionals and empower parents make informed decisions on monitoring and timing of delivery.