Abstract：
Preterm delivery is associated with cardiovascular remodeling and dysfunction in children and adults. However, it is unknown whether these effects are caused by the neonatal consequences of preterm birth or if these are already present in utero.
We evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or preterm prelabor rupture of membranes and the association of these changes with the presence of intra-amniotic infection and/or inflammation.
In this prospective cohort study, fetal echocardiography and amniocentesis were performed at admission in singleton pregnant women with preterm labor and/or preterm prelabor rupture of membranes between 24.0 and 34.0 weeks\' gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non-intra-amniotic infection and/or inflammation, n=54). Controls (n=48) were outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes. Intra-amniotic infection was defined by a positive amniotic fluid culture or positive 16S ribosomal RNA gene. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by our group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor. Fetal cardiac morphology and function was evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or preterm prelabor rupture of membranes and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or preterm prelabor rupture of membranes or cardiac pathology. The data were adjusted for the estimated fetal weight below the 10th percentile and for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared.
From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 (28.7%) were in the intra-amniotic infection and/or inflammation group and 54 (37.8%) were in the non-intra-amniotic infection and/or inflammation group. A total of 48 (33.6%) fetuses were included in the control group. Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 [interquartile range, 0.72-1.16] in the intra-amniotic infection and/or inflammation group; 0.79 [0.66-0.92] in the non-intra-amniotic infection and/or inflammation group; and 0.69 [0.56-0.83] in controls; P<.001) and diastolic dysfunction (tricuspid A duration 0.23 seconds [0.21-0.25], 0.24 [0.22-0.25], and 0.21 [0.2-0.23]; P=.007). Systolic function was similar among groups. Higher values of amniotic fluid troponin I (1413 pg/mL [927-2334], 1190 [829-1636], and 841 [671-959]; P<.001) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%; P=.005) in fetuses with preterm labor or preterm prelabor rupture of membranes when compared with the control group. The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group.
Fetuses with preterm labor or preterm prelabor rupture of membranes showed signs of cardiac remodeling and subclinical dysfunction, which were more pronounced in those exposed to intra-amniotic infection and/or inflammation. These findings support that the cardiovascular effects observed in children and adults born preterm have, at least in part, a prenatal origin.
We evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or preterm prelabor rupture of membranes and the association of these changes with the presence of intra-amniotic infection and/or inflammation.
In this prospective cohort study, fetal echocardiography and amniocentesis were performed at admission in singleton pregnant women with preterm labor and/or preterm prelabor rupture of membranes between 24.0 and 34.0 weeks\' gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non-intra-amniotic infection and/or inflammation, n=54). Controls (n=48) were outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes. Intra-amniotic infection was defined by a positive amniotic fluid culture or positive 16S ribosomal RNA gene. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by our group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor. Fetal cardiac morphology and function was evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or preterm prelabor rupture of membranes and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or preterm prelabor rupture of membranes or cardiac pathology. The data were adjusted for the estimated fetal weight below the 10th percentile and for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared.
From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 (28.7%) were in the intra-amniotic infection and/or inflammation group and 54 (37.8%) were in the non-intra-amniotic infection and/or inflammation group. A total of 48 (33.6%) fetuses were included in the control group. Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 [interquartile range, 0.72-1.16] in the intra-amniotic infection and/or inflammation group; 0.79 [0.66-0.92] in the non-intra-amniotic infection and/or inflammation group; and 0.69 [0.56-0.83] in controls; P<.001) and diastolic dysfunction (tricuspid A duration 0.23 seconds [0.21-0.25], 0.24 [0.22-0.25], and 0.21 [0.2-0.23]; P=.007). Systolic function was similar among groups. Higher values of amniotic fluid troponin I (1413 pg/mL [927-2334], 1190 [829-1636], and 841 [671-959]; P<.001) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%; P=.005) in fetuses with preterm labor or preterm prelabor rupture of membranes when compared with the control group. The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group.
Fetuses with preterm labor or preterm prelabor rupture of membranes showed signs of cardiac remodeling and subclinical dysfunction, which were more pronounced in those exposed to intra-amniotic infection and/or inflammation. These findings support that the cardiovascular effects observed in children and adults born preterm have, at least in part, a prenatal origin.
摘要：
背景：早产与儿童和成人的心血管重塑和功能障碍有关。然而,目前尚不清楚这些影响是由早产的新生儿后果引起的，还是这些影响已经存在于子宫内。
目的：我们评估了因早产或早产胎膜破裂入院的母亲胎儿的胎儿心脏形态和功能，以及这些变化与羊膜腔内感染和/或炎症的关系。
方法：在这项前瞻性队列研究中，在妊娠24.0至34.0周之间早产和/或早产胎膜破裂的单胎孕妇入院时进行胎儿超声心动图和羊膜穿刺术（羊膜腔内感染和/或炎症组，n=41）且无羊膜腔内感染和/或炎症（非羊膜腔内感染和/或炎症，n=54）。对照组（n=48）是没有早产或早产胎膜破裂的门诊孕妇。羊膜腔内感染由羊水培养阳性或16S核糖体RNA基因阳性定义。羊膜腔内炎症的定义是使用我们小组先前报告的羊水白细胞介素-6截止水平>1.43ng/mL在早产胎膜破裂和>13.4ng/mL在早产。使用超声心动图评估胎儿心脏形态和功能，测量早产或早产胎膜破裂妇女羊水中的肌钙蛋白-I和N末端脑钠肽前体浓度，并与20个因早产或早产胎膜破裂或心脏病理学以外的原因获得的羊水Biobank样本进行比较。当比较羊水生物标志物时，数据针对估计的胎儿体重低于10百分位数，以及入院时早产胎膜破裂以及羊膜穿刺术的胎龄进行了调整。
结果：从2018年到2021年，包括143个胎儿；95个胎儿来自诊断为早产或早产胎膜破裂的母亲。其中，羊膜腔内感染和/或炎症组41例（28.7%），非羊膜腔感染和/或炎症组54例（37.8%）。对照组共纳入48例(33.6%)胎儿。早产和/或早产胎膜破裂的胎儿有亚临床心脏向心性肥大的迹象（左壁厚度中位数为0.93[四分位距，羊膜腔内感染和/或炎症组0.72-1.16]；非羊膜腔内感染和/或炎症组0.79[0.66-0.92]；对照组0.69[0.56-0.83]；P<.001）和舒张功能障碍（三尖瓣A持续时间0.23秒[0.21-0.25]，0.24[0.22-0.25],和0.21[0.2-0.23]；P=.007）。组间收缩功能相似。羊水肌钙蛋白I值较高（1413pg/mL[927-2334]，1190[829-1636],和841[671-959];P<.001)和N末端脑钠肽前体检测(35.0%,17%,和0％；与对照组相比，早产或早产胎膜破裂的胎儿P=.005）。在羊膜腔内感染和/或炎症组中发现最高的N末端脑钠肽前体浓度。
结论：早产或胎膜早破的胎儿表现出心脏重塑和亚临床功能障碍的迹象，在暴露于羊膜腔内感染和/或炎症的人群中更为明显。这些发现支持在早产的儿童和成人中观察到的心血管影响，至少在某种程度上,产前起源。
目的：我们评估了因早产或早产胎膜破裂入院的母亲胎儿的胎儿心脏形态和功能，以及这些变化与羊膜腔内感染和/或炎症的关系。
方法：在这项前瞻性队列研究中，在妊娠24.0至34.0周之间早产和/或早产胎膜破裂的单胎孕妇入院时进行胎儿超声心动图和羊膜穿刺术（羊膜腔内感染和/或炎症组，n=41）且无羊膜腔内感染和/或炎症（非羊膜腔内感染和/或炎症，n=54）。对照组（n=48）是没有早产或早产胎膜破裂的门诊孕妇。羊膜腔内感染由羊水培养阳性或16S核糖体RNA基因阳性定义。羊膜腔内炎症的定义是使用我们小组先前报告的羊水白细胞介素-6截止水平>1.43ng/mL在早产胎膜破裂和>13.4ng/mL在早产。使用超声心动图评估胎儿心脏形态和功能，测量早产或早产胎膜破裂妇女羊水中的肌钙蛋白-I和N末端脑钠肽前体浓度，并与20个因早产或早产胎膜破裂或心脏病理学以外的原因获得的羊水Biobank样本进行比较。当比较羊水生物标志物时，数据针对估计的胎儿体重低于10百分位数，以及入院时早产胎膜破裂以及羊膜穿刺术的胎龄进行了调整。
结果：从2018年到2021年，包括143个胎儿；95个胎儿来自诊断为早产或早产胎膜破裂的母亲。其中，羊膜腔内感染和/或炎症组41例（28.7%），非羊膜腔感染和/或炎症组54例（37.8%）。对照组共纳入48例(33.6%)胎儿。早产和/或早产胎膜破裂的胎儿有亚临床心脏向心性肥大的迹象（左壁厚度中位数为0.93[四分位距，羊膜腔内感染和/或炎症组0.72-1.16]；非羊膜腔内感染和/或炎症组0.79[0.66-0.92]；对照组0.69[0.56-0.83]；P<.001）和舒张功能障碍（三尖瓣A持续时间0.23秒[0.21-0.25]，0.24[0.22-0.25],和0.21[0.2-0.23]；P=.007）。组间收缩功能相似。羊水肌钙蛋白I值较高（1413pg/mL[927-2334]，1190[829-1636],和841[671-959];P<.001)和N末端脑钠肽前体检测(35.0%,17%,和0％；与对照组相比，早产或早产胎膜破裂的胎儿P=.005）。在羊膜腔内感染和/或炎症组中发现最高的N末端脑钠肽前体浓度。
结论：早产或胎膜早破的胎儿表现出心脏重塑和亚临床功能障碍的迹象，在暴露于羊膜腔内感染和/或炎症的人群中更为明显。这些发现支持在早产的儿童和成人中观察到的心血管影响，至少在某种程度上,产前起源。
