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Abstract：
OBJECTIVE: Monochorionic twins with twin-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP) are at increased risk of neurodevelopmental impairment (NDI). This meta-analysis aimed to identify the prevalence of and perinatal risk factors for NDI in TTTS survivors treated with FLP.
METHODS: We performed a search in PubMed, EMBASE, Scopus and Web of Science, from inception to 13 February 2021, for studies evaluating perinatal risk factors for NDI in children diagnosed prenatally with TTTS managed by FLP. Data on severity of TTTS at the time of diagnosis, defined according to the Quintero staging system, FLP-related complications and perinatal outcomes were compared between children with a history of TTTS treated with FLP with and those without NDI, which was defined as performance on a cognitive or developmental assessment tool ≥ 2 SD below the mean or a defined motor or sensory disability. A random-effects model was used to pool the mean differences or odds ratios (OR) with the corresponding 95% CIs. Heterogeneity was assessed using the I2 statistic.
RESULTS: Nine studies with a total of 1499 TTTS survivors were included. The overall incidence of NDI was 14.0% (95% CI, 9.0-18.0%). The occurrence of NDI in TTTS survivors was associated with later gestational age (GA) at FLP (mean difference, 0.94 weeks (95% CI, 0.50-1.38 weeks); P < 0.0001, I2 = 0%), earlier GA at delivery (mean difference, -1.44 weeks (95% CI, -2.28 to -0.61 weeks); P = 0.0007, I2 = 49%) and lower birth weight (mean difference, -343.26 g (95% CI, -470.59 to -215.92 g); P < 0.00001, I2 = 27%). Evaluation of different GA cut-offs showed that preterm birth before 32 weeks was associated with higher risk for NDI later in childhood (OR, 2.25 (95% CI, 1.02-4.94); P = 0.04, I2 = 35%). No statistically significant difference was found between cases with and those without NDI with respect to Quintero stage of TTTS, recipient or donor status, development of postlaser twin anemia-polycythemia sequence, recurrence of TTTS and incidence of small- for-gestational age or cotwin fetal demise.
CONCLUSIONS: TTTS survivors with later GA at the time of FLP, earlier GA at delivery and lower birth weight are at higher risk of developing NDI. No significant association was found between Quintero stage of TTTS and risk of NDI. Our findings may be helpful for parental counseling and highlight the need for future studies to understand better the risk factors for NDI in TTTS survivors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
METHODS: We performed a search in PubMed, EMBASE, Scopus and Web of Science, from inception to 13 February 2021, for studies evaluating perinatal risk factors for NDI in children diagnosed prenatally with TTTS managed by FLP. Data on severity of TTTS at the time of diagnosis, defined according to the Quintero staging system, FLP-related complications and perinatal outcomes were compared between children with a history of TTTS treated with FLP with and those without NDI, which was defined as performance on a cognitive or developmental assessment tool ≥ 2 SD below the mean or a defined motor or sensory disability. A random-effects model was used to pool the mean differences or odds ratios (OR) with the corresponding 95% CIs. Heterogeneity was assessed using the I2 statistic.
RESULTS: Nine studies with a total of 1499 TTTS survivors were included. The overall incidence of NDI was 14.0% (95% CI, 9.0-18.0%). The occurrence of NDI in TTTS survivors was associated with later gestational age (GA) at FLP (mean difference, 0.94 weeks (95% CI, 0.50-1.38 weeks); P < 0.0001, I2 = 0%), earlier GA at delivery (mean difference, -1.44 weeks (95% CI, -2.28 to -0.61 weeks); P = 0.0007, I2 = 49%) and lower birth weight (mean difference, -343.26 g (95% CI, -470.59 to -215.92 g); P < 0.00001, I2 = 27%). Evaluation of different GA cut-offs showed that preterm birth before 32 weeks was associated with higher risk for NDI later in childhood (OR, 2.25 (95% CI, 1.02-4.94); P = 0.04, I2 = 35%). No statistically significant difference was found between cases with and those without NDI with respect to Quintero stage of TTTS, recipient or donor status, development of postlaser twin anemia-polycythemia sequence, recurrence of TTTS and incidence of small- for-gestational age or cotwin fetal demise.
CONCLUSIONS: TTTS survivors with later GA at the time of FLP, earlier GA at delivery and lower birth weight are at higher risk of developing NDI. No significant association was found between Quintero stage of TTTS and risk of NDI. Our findings may be helpful for parental counseling and highlight the need for future studies to understand better the risk factors for NDI in TTTS survivors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
摘要：
目的：胎儿镜下激光光凝（FLP）治疗的单胎双胞胎双胎输血综合征（TTTS）的神经发育障碍（NDI）风险增加。这项荟萃分析旨在确定接受FLP治疗的TTTS幸存者中NDI的患病率和围产期危险因素。
方法：我们在PubMed中进行了搜索，EMBASE,Scopus和WebofScience,从开始到2021年2月13日，用于评估由FLP管理的产前诊断为TTTS的儿童中NDI的围产期危险因素的研究。诊断时TTTS严重程度的数据，根据Quintero分期系统定义，FLP相关并发症和围产期结局比较有TTTS病史的患儿有FLP治疗和无NDI治疗，定义为认知或发展评估工具的表现低于平均值≥2SD或定义的运动或感觉残疾。使用随机效应模型将平均差异或优势比（OR）与相应的95％CI进行汇总。使用I2统计量评估异质性。
结果：纳入9项研究，共1499名TTTS幸存者。NDI的总发生率为14.0%（95%CI，9.0-18.0%）。TTTS幸存者中NDI的发生与FLP时的孕龄（GA）有关（平均差异，0.94周（95％CI，0.50-1.38周）；P<0.0001，I2=0％），交货时较早的GA(平均差，-1.44周（95％CI，-2.28至-0.61周）；P=0.0007，I2=49％）和较低的出生体重（平均差异，-343.26g(95%CI,-470.59至-215.92g);P<0.00001,I2=27%)。对不同GA截止值的评估表明，32周之前的早产与儿童期后期NDI的高风险相关（OR，2.25（95%CI，1.02-4.94）；P=0.04，I2=35%）。在TTTS的Quintero阶段，有和没有NDI的病例之间没有发现统计学上的显着差异，接受者或捐赠者身份，激光后双胎贫血-红细胞增多症序列的发展，TTTS的复发和小胎龄或cotwin胎儿死亡的发生率。
结论：TTTS幸存者在FLP时具有较晚的GA，分娩时较早的GA和较低的出生体重发生NDI的风险较高。TTTS的Quintero阶段与NDI风险之间没有显着关联。我们的发现可能有助于家长咨询，并强调未来研究的必要性，以更好地了解TTTS幸存者NDI的危险因素。©2021国际妇产科超声学会。
方法：我们在PubMed中进行了搜索，EMBASE,Scopus和WebofScience,从开始到2021年2月13日，用于评估由FLP管理的产前诊断为TTTS的儿童中NDI的围产期危险因素的研究。诊断时TTTS严重程度的数据，根据Quintero分期系统定义，FLP相关并发症和围产期结局比较有TTTS病史的患儿有FLP治疗和无NDI治疗，定义为认知或发展评估工具的表现低于平均值≥2SD或定义的运动或感觉残疾。使用随机效应模型将平均差异或优势比（OR）与相应的95％CI进行汇总。使用I2统计量评估异质性。
结果：纳入9项研究，共1499名TTTS幸存者。NDI的总发生率为14.0%（95%CI，9.0-18.0%）。TTTS幸存者中NDI的发生与FLP时的孕龄（GA）有关（平均差异，0.94周（95％CI，0.50-1.38周）；P<0.0001，I2=0％），交货时较早的GA(平均差，-1.44周（95％CI，-2.28至-0.61周）；P=0.0007，I2=49％）和较低的出生体重（平均差异，-343.26g(95%CI,-470.59至-215.92g);P<0.00001,I2=27%)。对不同GA截止值的评估表明，32周之前的早产与儿童期后期NDI的高风险相关（OR，2.25（95%CI，1.02-4.94）；P=0.04，I2=35%）。在TTTS的Quintero阶段，有和没有NDI的病例之间没有发现统计学上的显着差异，接受者或捐赠者身份，激光后双胎贫血-红细胞增多症序列的发展，TTTS的复发和小胎龄或cotwin胎儿死亡的发生率。
结论：TTTS幸存者在FLP时具有较晚的GA，分娩时较早的GA和较低的出生体重发生NDI的风险较高。TTTS的Quintero阶段与NDI风险之间没有显着关联。我们的发现可能有助于家长咨询，并强调未来研究的必要性，以更好地了解TTTS幸存者NDI的危险因素。©2021国际妇产科超声学会。
