Background

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.

Methods

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).

Findings

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).

Interpretation

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.

Funding

The Dutch Heart Foundation.

中文翻译：

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选择性胎儿生长受限 (LEMON) 的长期影响：荷兰生长不一致同卵双胞胎神经发育结果的队列研究

背景

胎儿生长受限 (FGR) 后出生的单身人士神经发育不良的风险增加。对有 FGR 的单胎的研究通常将结果与没有 FGR 的结果进行比较，这种比较本质上受到产科、父母和遗传因素的影响。我们的目标是在共享单个胎盘（单绒毛膜双羊膜）的不和谐同卵双胞胎群体中比较较小和较大双胞胎之间的神经发育结果，自然消除这些混杂因素。

方法

这项研究是具有选择性 FGR 的单绒毛膜双羊膜双胞胎的队列研究 LEMON 的一部分。2002 年 3 月 1 日至 2017 年 12 月 31 日期间在莱顿大学医学中心（荷兰莱顿）出生的所有具有选择性 FGR 的单绒毛膜双羊膜双胞胎都有资格入选。排除了因双胎输血综合征、双胞胎贫血、红细胞增多症或单羊膜症而并发的双胎妊娠。认知表现通过两项标准化的心理测量适龄测试进行评估，产生全面的智商 (FSIQ)。运动功能通过标准化的神经系统检查进行评估。使用神经发育障碍 (NDI) 的复合结果，细分为轻度 NDI（定义为 FSIQ <85、轻微神经功能障碍或脑瘫 1 级、

发现

在 2021 年 1 月 25 日至 2022 年 3 月 15 日期间，47 对双胞胎被纳入研究并接受了神经发育评估。47 对双胞胎的出生时中位胎龄为 33·9 周（IQR 31·3-36·0），较小的双胞胎的中位出生体重为 1400 克（1111-1875）和 ​​2003 克（1600-2680 ) 在较大的双胞胎中。神经发育评估的中位年龄为 11 岁（8-13 岁）。较小的双胞胎的中位 FSIQ 为 94 (86-101)，较大的双胞胎为 100 (92-108) (p<0·0001)。较小的双胞胎有轻度 NDI（47 人中有 17 人 [36%]）比较大的双胞胎（47 人中有 5 人 [11%]；优势比 4·8 [95% CI 1·6–14·1]；p=0 ·0049)。患有严重 NDI 的儿童比例没有差异（两组 47 人中有 2 人 [4%]，p=1·0）。

解释

由于轻度 NDI 会阻碍儿童的日常功能，我们建议对具有选择性 FGR 的单绒毛膜双羊膜双胞胎进行标准化的长期随访，包括神经发育测试，以促进早期识别有风险的儿童。

资金

荷兰心脏基金会。