Center of Fetal Medicine and Pregnancy, Department of Obstetrics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Center of Fetal Medicine and Pregnancy, Department of Obstetrics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Am J Obstet Gynecol. 2022 Jul;227(1):81.e1-81.e13. doi: 10.1016/j.ajog.2021.12.031. Epub 2021 Dec 21.
Intrauterine growth restriction is associated with an increased risk of cardiovascular changes neonatally. However, the underlying pathways are poorly understood, and it is not clear whether the dysfunction is already present in the fetus.
This study aimed to investigate fetal cardiac dimensions assessed from images at the second trimester anatomy scan from fetuses classified postnatally as small for gestational age and intrauterine growth restricted and compare them with appropriate for gestational age fetuses.
This was a substudy from The Copenhagen Baby Heart Study, a prospective, multicenter cohort study including fetuses from the second trimester of pregnancy in Copenhagen from April 2016 to October 2018. The mothers were recruited at the second trimester anatomy scan that included extended cardiovascular image documentation followed by consecutively measured heart biometry by 2 investigators blinded for the pregnancy outcome. The fetuses were classified postnatally as small for gestational age and intrauterine growth restricted according to the International Society of Ultrasound in Obstetrics and Gynecology 2020 guidelines using birthweight and with a retrospective assessment of Doppler flow. The mean differences in the cardiovascular biometry were adjusted for gestational age at the time of the second trimester scan and the abdominal circumference. The z-scores were calculated, and the comparisons were Bonferroni corrected (significance level of P<.005). Receiver operating characteristic curves were computed after performing backward regression on several maternal characteristics and biomarkers.
We included 8278 fetuses, with 625 (7.6%) of them being small for gestational age and 289 (3.5%) being intrauterine growth restricted. Both small for gestational age and intrauterine growth restricted fetuses had smaller heart biometry, including the diameter at the location of the aortic valve (P<.005), the ascending aorta in the 3-vessel view (P<.005), and at the location of the pulmonary valve (P<.005). The intrauterine growth restricted group had significantly smaller hearts with respect to length and width (P<.005) and smaller right and left ventricles (P<.005). After adjusting for the abdominal circumference, the differences in the aortic valve and the pulmonary valve remained significant in the intrauterine growth restricted group. Achievement of an optimal receiver operating characteristic curve included the following parameters: head circumference, abdominal circumference, femur length, gestational age, pregnancy associated plasma protein-A multiples of median, nullipara, spontaneous conception, smoking, body mass index <18.5, heart width, and pulmonary valve with an area under the curve of 0.91 (0.88-0.93) for intrauterine growth restricted cases.
Intrauterine growth restricted fetuses had smaller prenatal cardiovascular biometry, even when adjusting for abdominal circumference. Our findings support that growth restriction is already associated with altered cardiac growth at an early stage of pregnancy. The heart biometry alone did perform well as a screening test, but combined with other factors, it increased the sensitivity and specificity for intrauterine growth restriction.
宫内生长受限与新生儿期心血管变化的风险增加有关。然而，其潜在的途径知之甚少，也不清楚胎儿是否已经存在功能障碍。
本研究旨在探讨从胎龄小和宫内生长受限的胎儿在妊娠中期解剖扫描中获得的胎儿心脏图像评估，并将其与适合胎龄的胎儿进行比较。
这是哥本哈根婴儿心脏研究的一个子研究，这是一项前瞻性、多中心队列研究，包括 2016 年 4 月至 2018 年 10 月哥本哈根妊娠中期的胎儿。母亲在妊娠中期接受包括扩展心血管图像记录的解剖扫描时被招募，并由 2 名研究人员对心脏生物测量进行连续测量，他们对妊娠结局一无所知。根据国际超声协会 2020 年的指南，使用出生体重和回顾性评估多普勒血流，对胎儿进行小胎龄和宫内生长受限的分类。在妊娠中期扫描时的胎龄和腹围的基础上，对心血管生物测量的平均差异进行了调整。计算了 z 分数，并对其进行了 Bonferroni 校正（P<.005 为显著性水平）。对多个母体特征和生物标志物进行回归分析后，计算了接收者操作特征曲线。
我们纳入了 8278 名胎儿，其中 625 名（7.6%）为小胎龄儿，289 名（3.5%）为宫内生长受限。小胎龄儿和宫内生长受限儿的心脏生物测量均较小，包括主动脉瓣处直径（P<.005）、三血管切面升主动脉（P<.005）和肺动脉瓣处（P<.005）。宫内生长受限组的心脏长度和宽度（P<.005）以及左右心室（P<.005）明显较小。在调整腹围后，宫内生长受限组的主动脉瓣和肺动脉瓣差异仍然显著。实现最佳接收者操作特征曲线的参数包括：头围、腹围、股骨长、胎龄、妊娠相关血浆蛋白 A 中位数倍数、初产妇、自然受孕、吸烟、体重指数<18.5、心脏宽度和肺动脉瓣，曲线下面积为 0.91（0.88-0.93），用于宫内生长受限病例。
宫内生长受限胎儿的产前心血管生物测量较小，即使在调整腹围后也是如此。我们的研究结果支持在妊娠早期，生长受限与心脏生长改变有关。心脏生物测量本身作为一种筛查试验表现良好，但与其他因素结合使用时，可提高宫内生长受限的敏感性和特异性。
