Abstract：
Singletons born after fetal growth restriction (FGR) are at increased risk of poor neurodevelopmental outcomes. Studies of singletons with FGR usually compare outcomes with those without FGR, a comparison that is inherently biased by obstetrical, parental, and genetic factors. We aim to compare neurodevelopmental outcomes between the smaller and larger twin in a population of discordant identical twins who shared a single placenta (monochorionic diamniotic), naturally eliminating these confounders.
This study is part of the cohort study LEMON of monochorionic diamniotic twins with selective FGR. All monochorionic diamniotic twins with selective FGR who were born in Leiden University Medical Center (Leiden, Netherlands) between March 1, 2002, and Dec 31, 2017, were eligible for inclusion. Twin pregnancies that were complicated by twin-twin transfusion syndrome, twin anaemia polycythaemia sequence, or monoamnionicity were excluded. Cognitive performance was evaluated with two standardised psychometric age-appropriate tests, producing a full-scale intelligence quotient (FSIQ). Motor functioning was assessed with a standardised neurological examination. A composite outcome of neurodevelopmental impairment (NDI) was used, subdivided into mild NDI (defined as FSIQ <85, minor neurological dysfunction or cerebral palsy grade 1, or mild visual or hearing impairment) and severe NDI (defined as FSIQ <70, severe neurological dysfunction, or severe visual or hearing impairment).
Between Jan 25, 2021, and March 15, 2022, 47 twin pairs were enrolled in the study and underwent neurodevelopmental assessment. The median gestational age at birth was 33·9 weeks (IQR 31·3-36·0) for the 47 included twin pairs, with median birthweights of 1400 g (1111-1875) in the smaller twin and 2003 g (1600-2680) in the larger twin. The median age at neurodevelopmental assessment was 11 years (8-13). Median FSIQ was 94 (86-101) for the smaller twin and 100 (92-108) for the larger twin (p<0·0001). More smaller twins had mild NDI (17 [36%] of 47) than did the larger twins (five [11%] of 47; odds ratio 4·8 [95% CI 1·6-14·1]; p=0·0049). There was no difference in the proportion of children with severe NDI (two [4%] of 47 in both groups, p=1·0).
As mild NDI can impede children in their daily functioning, we recommend standardised long-term follow-up, including neurodevelopmental testing, for monochorionic diamniotic twins with selective FGR to facilitate early identification of children at risk.
The Dutch Heart Foundation.
This study is part of the cohort study LEMON of monochorionic diamniotic twins with selective FGR. All monochorionic diamniotic twins with selective FGR who were born in Leiden University Medical Center (Leiden, Netherlands) between March 1, 2002, and Dec 31, 2017, were eligible for inclusion. Twin pregnancies that were complicated by twin-twin transfusion syndrome, twin anaemia polycythaemia sequence, or monoamnionicity were excluded. Cognitive performance was evaluated with two standardised psychometric age-appropriate tests, producing a full-scale intelligence quotient (FSIQ). Motor functioning was assessed with a standardised neurological examination. A composite outcome of neurodevelopmental impairment (NDI) was used, subdivided into mild NDI (defined as FSIQ <85, minor neurological dysfunction or cerebral palsy grade 1, or mild visual or hearing impairment) and severe NDI (defined as FSIQ <70, severe neurological dysfunction, or severe visual or hearing impairment).
Between Jan 25, 2021, and March 15, 2022, 47 twin pairs were enrolled in the study and underwent neurodevelopmental assessment. The median gestational age at birth was 33·9 weeks (IQR 31·3-36·0) for the 47 included twin pairs, with median birthweights of 1400 g (1111-1875) in the smaller twin and 2003 g (1600-2680) in the larger twin. The median age at neurodevelopmental assessment was 11 years (8-13). Median FSIQ was 94 (86-101) for the smaller twin and 100 (92-108) for the larger twin (p<0·0001). More smaller twins had mild NDI (17 [36%] of 47) than did the larger twins (five [11%] of 47; odds ratio 4·8 [95% CI 1·6-14·1]; p=0·0049). There was no difference in the proportion of children with severe NDI (two [4%] of 47 in both groups, p=1·0).
As mild NDI can impede children in their daily functioning, we recommend standardised long-term follow-up, including neurodevelopmental testing, for monochorionic diamniotic twins with selective FGR to facilitate early identification of children at risk.
The Dutch Heart Foundation.
摘要：
胎儿生长受限（FGR）后出生的单胎神经发育不良的风险增加。对具有FGR的单身人士的研究通常将结果与没有FGR的人进行比较，一种固有的产科偏见的比较，父母,和遗传因素。我们的目标是比较小双胞胎和大双胞胎之间的神经发育结果，这些双胞胎是不一致的同卵双胞胎，他们共享一个胎盘（单绒毛膜羊膜）。自然消除了这些混杂因素。
本研究是具有选择性FGR的单绒毛膜双胎的队列研究LEMON的一部分。所有出生在莱顿大学医学中心（莱顿，荷兰)在2002年3月1日至2017年12月31日期间有资格入选。双胎妊娠并发双胎输血综合征，双胎贫血红细胞增多症序列，或单羊膜性被排除。认知表现通过两个标准化的心理测量年龄测试进行评估，产生全面的智商(FSIQ)。通过标准化的神经系统检查评估运动功能。使用神经发育障碍（NDI）的复合结局，细分为轻度NDI（定义为FSIQ<85，轻度神经功能障碍或1级脑瘫，或轻度视力或听力障碍）和重度NDI（定义为FSIQ<70，重度神经功能障碍，或严重的视力或听力障碍)。在2021年1月25日至2022年3月15日之间，有47对双胞胎被纳入研究并接受了神经发育评估。47对双胎的平均出生胎龄为33·9周（IQR31·3-36·0），在较小的双胞胎中，中位出生体重为1400g（1111-1875），在较大的双胞胎中，中位出生体重为2003g（1600-2680）。神经发育评估的中位年龄为11岁（8-13岁）。小双胞胎的FSIQ中位数为94（86-101），大双胞胎的FSIQ中位数为100（92-108）（p<0·0001）。较小的双胞胎有轻度NDI（47个中的17个[36%]），而较大的双胞胎（47个中的5个[11%]；比值比4·8[95%CI1·6-14·1]；p=0·0049）。患有严重NDI的儿童比例没有差异（两组47人中有2[4％]，p=1·0）。
由于轻度NDI会妨碍儿童的日常功能，我们建议进行标准化的长期随访，包括神经发育测试,用于具有选择性FGR的单绒毛膜羊膜双胞胎，以促进早期识别有风险的儿童。
荷兰心脏基金会。
本研究是具有选择性FGR的单绒毛膜双胎的队列研究LEMON的一部分。所有出生在莱顿大学医学中心（莱顿，荷兰)在2002年3月1日至2017年12月31日期间有资格入选。双胎妊娠并发双胎输血综合征，双胎贫血红细胞增多症序列，或单羊膜性被排除。认知表现通过两个标准化的心理测量年龄测试进行评估，产生全面的智商(FSIQ)。通过标准化的神经系统检查评估运动功能。使用神经发育障碍（NDI）的复合结局，细分为轻度NDI（定义为FSIQ<85，轻度神经功能障碍或1级脑瘫，或轻度视力或听力障碍）和重度NDI（定义为FSIQ<70，重度神经功能障碍，或严重的视力或听力障碍)。在2021年1月25日至2022年3月15日之间，有47对双胞胎被纳入研究并接受了神经发育评估。47对双胎的平均出生胎龄为33·9周（IQR31·3-36·0），在较小的双胞胎中，中位出生体重为1400g（1111-1875），在较大的双胞胎中，中位出生体重为2003g（1600-2680）。神经发育评估的中位年龄为11岁（8-13岁）。小双胞胎的FSIQ中位数为94（86-101），大双胞胎的FSIQ中位数为100（92-108）（p<0·0001）。较小的双胞胎有轻度NDI（47个中的17个[36%]），而较大的双胞胎（47个中的5个[11%]；比值比4·8[95%CI1·6-14·1]；p=0·0049）。患有严重NDI的儿童比例没有差异（两组47人中有2[4％]，p=1·0）。
由于轻度NDI会妨碍儿童的日常功能，我们建议进行标准化的长期随访，包括神经发育测试,用于具有选择性FGR的单绒毛膜羊膜双胞胎，以促进早期识别有风险的儿童。
荷兰心脏基金会。
