Murphy Ciara N, Cluver Catherine A, Walker Susan P, Keenan Emerson, Hastie Roxanne, MacDonald Teresa M, Hannan Natalie J, Brownfoot Fiona C, Cannon Ping, Tong Stephen, Kaitu'u-Lino Tu'uhevaha J
Department of Obstetrics & Gynaecology, Mercy Hospital for Women, The University of Melbourne, Heidelberg, VIC 3084, Australia.
Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia.
J Clin Med. 2022 Feb 9;11(4):901. doi: 10.3390/jcm11040901.
Fetal growth restriction (FGR), when undetected antenatally, is the biggest risk factor for preventable stillbirth. Maternal circulating SPINT1 is reduced in pregnancies, which ultimately deliver small for gestational age (SGA) infants at term (birthweight < 10th centile), compared to appropriate for gestational age (AGA) infants (birthweight ≥ 10th centile). SPINT1 is also reduced in FGR diagnosed before 34 weeks' gestation. We hypothesised that circulating SPINT1 would be decreased in co-existing preterm preeclampsia and FGR. Plasma SPINT1 was measured in samples obtained from two double-blind, randomised therapeutic trials. In the Preeclampsia Intervention with Esomeprazole trial, circulating SPINT1 was decreased in women with preeclampsia who delivered SGA infants ( = 75, median = 18,857 pg/mL, IQR 10,782-29,890 pg/mL, < 0.0001), relative to those delivering AGA ( = 22, median = 40,168 pg/mL, IQR 22,342-75,172 pg/mL). This was confirmed in the Preeclampsia Intervention 2 with metformin trial where levels of SPINT1 in maternal circulation were reduced in SGA pregnancies ( = 95, median = 57,764 pg/mL, IQR 42,212-91,356 pg/mL, < 0.0001) compared to AGA controls ( = 40, median = 107,062 pg/mL, IQR 70,183-176,532 pg/mL). Placental Growth Factor (PlGF) and sFlt-1 were also measured. PlGF was significantly reduced in the SGA pregnancies, while ratios of sFlt-1/SPINT1 and sFlt1/PlGF were significantly increased. This is the first study to demonstrate significantly reduced SPINT1 in co-existing FGR and preeclamptic pregnancies.
胎儿生长受限（FGR）若在产前未被检测到，是可预防死产的最大风险因素。与适于胎龄（AGA）婴儿（出生体重≥第10百分位数）相比，在足月分娩小于胎龄（SGA）婴儿（出生体重＜第10百分位数）的妊娠中，母体循环中的SPINT1会减少。在妊娠34周前诊断出的FGR中，SPINT1也会减少。我们假设，同时存在早产子痫前期和FGR时，循环中的SPINT1会降低。在两项双盲随机治疗试验获取的样本中测量了血浆SPINT1。在埃索美拉唑治疗子痫前期试验中，与分娩AGA婴儿的女性相比（n = 22，中位数 = 40,168 pg/mL，四分位间距22,342 - 75,172 pg/mL），分娩SGA婴儿的子痫前期女性循环中的SPINT1降低（n = 75，中位数 = 18,857 pg/mL，四分位间距10,782 - 29,890 pg/mL，P＜0.0001）。这在二甲双胍治疗子痫前期2试验中得到证实，与AGA对照组相比（n = 40，中位数 = 107,062 pg/mL，四分位间距70,183 - 176,532 pg/mL），SGA妊娠中母体循环中的SPINT1水平降低（n = 95，中位数 = 57,764 pg/mL，四分位间距42,212 - 91,356 pg/mL，P＜0.0001）。还测量了胎盘生长因子（PlGF）和可溶性血管内皮生长因子受体-1（sFlt-1）。SGA妊娠中PlGF显著降低，而sFlt-1/SPINT1和sFlt1/PlGF的比值显著升高。这是第一项证明同时存在FGR和子痫前期妊娠时SPINT1显著降低的研究。
