目的:根据Gratacós分类,评估单绒毛膜(MC)双胎妊娠中选择性胎儿生长受限(sFGR)的自然史,包括脐动脉(UA)多普勒的进展/改善/稳定性以及向双胎输血综合征(TTTS)或双胎贫血红细胞增多症(TAPS)的进展。我们还旨在调查双胞胎较小死亡的风险因素。
方法:使用PubMed数据库进行了系统搜索,以确定直到2022年6月以英文发表的相关研究,Scopus,和WebofScience研究资格:我们使用了回顾性和前瞻性研究的英文报告sFGR,而没有伴随的TTTS。
方法:纳入了根据UA多普勒舒张末期血流(EDF)(Gratacós分类)研究sFGR进展和结局的文章。I型包括具有正EDF的sFGR,II型持续缺失(AEDF),和III型间歇性缺失/逆转(IARDF)。分析中未包括在sFGR之前诊断为TTTS或双胎贫血红细胞增多症序列(TAPS)的妊娠。随机效应模型用于汇集比值比(OR)和相应的95%置信区间(CI)。使用I2值评估异质性。
结果:共17项研究包括2748例MC妊娠合并sFGR。稳定性的发生率,恶化,I型UA多普勒改善为68%(95%CI26,89),23%(95%CI7-40),和9%(95%CI0.0-100),分别,II型患者为40%(95%CI18,81),50%(95%CI23,82),和10%(95%CI4,37),分别,III型为55%(95%CI2,99),23%(95%CI9,43),和22%(95%CI6,54),分别。在I型(7%)和III型(9%)之间,进展为TTTS的风险相当,在II型中发生的风险为4%(95%CI0,67),没有显著的亚组差异。TAPS的进展在I型(12%)中最高,在II型(2%)和III型(1%)之间具有可比性,没有显着亚组差异。较小的双胎死亡的危险因素是诊断时的胎龄较早(GA)(MD-2.69周,95%CI-4.94-0.45,I245%),更大的双胞胎间重量不一致(MD34%,95%CI1.35-5.38,I228%),II型和III型的UA多普勒恶化(OR3.05,95%CI1.36-6.84,I224%和OR4.5,95%CI2.31-8.77,I20.0%,分别),以及II型和III型静脉导管(DV)a波缺失/逆转(OR3.35,95%CI2.28-4.93,I20.0%和OR2.36,OR%CI1.08-5.13,I20.0%,分别)。对于II型和III型sFGR,向TTTS的进展与较小的双胞胎死亡没有显着相关。
结论:这些发现提高了我们对sFGR类型的自然史以及II型和III型sFGR中双胞胎较小死亡的预测因素的理解。当前的数据提供了重要的咨询点,并支持需要修改当前的sFGR分类系统,以包括UA和DV多普勒的变化,以更好地识别可能受益于胎儿干预的队列,未来需要进行多中心前瞻性随机试验。
This study aimed to evaluate the natural history of selective intrauterine growth restriction in monochorionic twin pregnancies based on the Gratacós classification, including progression of, improvement in, or stability of umbilical artery Dopplers and progression to twin-to-twin transfusion syndrome or twin anemia polycythemia syndrome. We also aimed to investigate risk factors for smaller twin demise.
A systematic search was performed to identify relevant studies published in English up to June 2022 using the databases PubMed, Scopus, and Web of Science STUDY ELIGIBILITY: We used retrospective and prospective studies published in English that reported on selective intrauterine growth restriction without concomitant twin-to-twin transfusion syndrome.
Articles that investigated selective intrauterine growth restriction progression and outcomes by umbilical artery Doppler end-diastolic flow (Gratacós classification) were included. Type I included selective intrauterine growth restriction cases with positive end-diastolic flow, type II included those cases with persistently absent end-diastolic flow, and type III included cases with intermittent absent or reversed end-diastolic flow. Pregnancies in which a diagnosis of twin-to-twin transfusion syndrome or twin anemia polycythemia sequence was made before the diagnosis of selective intrauterine growth restriction were not included in the analysis. A random effects model was used to pool the odds ratios and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value.
A total of 17 studies encompassing 2748 monochorionic pregnancies complicated by selective intrauterine growth restriction were included in the analysis. The incidence of stable, deteriorating, or improving umbilical artery Dopplers in type I cases was 68% (95% confidence interval, 26-89), 23% (95% confidence interval, 7-40), and 9% (95% confidence interval, 0.0-100), respectively. In type II cases, the incidence was 40% (95% confidence interval, 18-81), 50% (95% confidence interval, 23-82), and 10% (95% confidence interval, 4-37), respectively, and in type III cases, the incidence was 55% (95% confidence interval, 2-99), 23% (95% confidence interval, 9-43), and 22% (95% confidence interval, 6-54), respectively. The risk for progression to twin-to-twin transfusion syndrome was comparable between type I (7%) and type III (9%) cases and occurred in 4% (95% confidence interval, 0-67) of type II cases with no significant subgroup differences. Progression to twin anemia polycythemia syndrome was highest in type I cases (12%) and comparable between type II (2%) and III (1%) cases with no significant subgroup differences. Risk factors for smaller twin demise were earlier gestational age at diagnosis (mean difference, -2.69 weeks; 95% confidence interval, -4.94 to -0.45; I2, 45%), larger intertwin weight discordance (mean difference, 34%; 95% confidence interval, 1.35-5.38; I2, 28%), deterioration of umbilical artery Dopplers for each of type II and III cases (odds ratio, 3.05; 95% confidence interval, 1.36-6.84; I2, 24%; and odds ratio, 4.5; 95% confidence interval, 2.31-8.77; I2, 0.0%, respectively), and absent or reversed ductus venosus a-wave for each of type II and III cases (odds ratio, 3.35; 95% confidence interval, 2.28-4.93; I2, 0.0%; and odds ratio, 2.36; 95% confidence interval, 1.08-5.13; I2, 0.0%, respectively). Progression to twin-to-twin transfusion syndrome was not significantly associated with smaller twin demise for each of type II and III selective intrauterine growth restriction cases.
These findings improve our understanding of the natural history of the types of selective intrauterine growth restriction and of the predictors of smaller twin demise in type II and III selective intrauterine growth restriction cases. The current data provide vital counseling points and support the need for modifications of the current selective intrauterine growth restriction classification system to include the variations in umbilical artery and ductus venosus Dopplers to better identify a cohort that might benefit from fetal intervention for which future multicenter prospective randomized trials are needed.