Altered fetal growth, placental abnormalities, and stillbirth

BackgroundWorldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth.Methods and findingsPopulation-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small (90th percentile) for gestational age at death (stillbirth) or delivery (live birth) using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight) while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate). Five patterns were observed: placental findings associated with (1) stillbirth but not fetal growth abnormalities; (2) fetal growth abnormalities in stillbirths only; (3) fetal growth abnormalities in live births only; (4) fetal growth abnormalities in stillbirths and live births in a similar manner; (5) a different pattern of fetal growth abnormalities in stillbirths and live births.ConclusionsThe patterns of association between placental abnormalities, fetal growth, and stillbirth provide insights into the mechanism of impaired placental function and stillbirth. They also suggest implications for clinical care, especially for placental findings amenable to prenatal diagnosis using ultrasound that may be associated with term stillbirths.

背景：全球范围内，死产仍是主要致死原因之一。胎儿生长异常与胎盘异常是目前已知的死产最强且最普遍的危险因素。本研究旨在明确胎盘异常、胎儿生长与死产之间的关联模式。
方法与结果：本研究为基于人群的病例对照研究，纳入美国5个地理区域59家医院的所有死产病例以及活产儿代表性样本。采用已发表的算法，将死亡（死产）或分娩（活产）时的胎儿生长异常按胎龄分为小于第90百分位数。由围产期病理医师采用标准化方案进行胎盘检查。对数据进行加权以匹配抽样设计。本研究共纳入319例单胎死产儿以及1119例单胎活产儿，其死亡或分娩时的胎龄均≥24周，共对25项胎盘异常表现进行了分析。其中15项表现与死产显著相关。15项中的10项同时与胎儿生长异常相关：单脐动脉、脐带帆状附着、终末绒毛不成熟、胎盘后血肿、胎盘实质梗死、实质内血栓、无血管绒毛、胎盘水肿、胎盘重量、出生体重/胎盘重量比值；而15项与死产相关的表现中另有5项与胎儿生长异常无关：胎盘膜急性绒毛膜羊膜炎、绒毛膜板急性绒毛膜羊膜炎、绒毛膜板血管退行性变、绒毛周及绒毛间纤维蛋白/纤维蛋白样沉积、绒毛膜板胎儿血管血栓。本研究共观察到5类关联模式：(1)仅与死产相关、与胎儿生长异常无关的胎盘异常表现；(2)仅在死产病例中与胎儿生长异常相关的胎盘异常表现；(3)仅在活产儿中与胎儿生长异常相关的胎盘异常表现；(4)在死产病例与活产儿中以相似模式与胎儿生长异常相关的胎盘异常表现；(5)在死产病例与活产儿中呈现不同模式的胎儿生长异常关联。
结论：胎盘异常、胎儿生长与死产之间的关联模式，为胎盘功能受损及死产的发病机制提供了新的洞察视角，同时也为临床诊疗提供了参考价值，尤其是针对可通过超声实施产前诊断的胎盘异常表现，这类表现可能与足月死产相关。