Search

Objective: Research suggests that postnatal catch-up growth after fetal growth restriction (FGR) occurs frequently. Yet, postnatal growth in singletons may be influenced by multiple factors. Identical twins with discordant prenatal growth, termed selective FGR (sFGR), can be regarded as a natural experiment eliminating these sources of bias. Design: Observational cohort study. Methods: Monochorionic twins with sFGR born between 2002 and 2017 (aged 3-17 years) were eligible. Growth measurements (height, weight, head circumference, and body mass index) were performed at follow-up. Detailed growth curves documented by a systematic primary care system in the Netherlands were collected. Measurements were converted to standard deviation scores (SDSs). A mixed-effects model was used to assess within-pair SDS difference and individual height SDS relative to target height SDS. Results: Forty-seven twin pairs (94 children) were included at a median age of 11 (interquartile range 8-13) years. At the last measurement, smaller twins at birth had a lower height SDS [-0.6 vs -0.3, P < .001, median difference 0.5 (95%CI 0.4-0.7)], lower weight SDS [-0.5 vs -0.1, P < .001, median difference 0.8 (95%CI 0.5-1.0)], and lower head circumference SDS [-0.5 vs 0.2, P < .001, median difference 0.8 (95%CI 0.6-0.9)] compared to larger twins. These differences persisted until the age of 17. Smaller twins showed rapid catch-up growth in the first 2 years and reached their target height range between 8 and 11 years. Conclusions: Identical twins with discordant prenatal growth maintain a modest but significant difference in height, weight, and head circumference, indicating a persistent, inhibitory effect of an adverse intrauterine environment on childhood growth. [ABSTRACT FROM AUTHOR]

Lifelong health is thought to be partially set during intrauterine life by persistent epigenetic changes induced by the prenatal environment. To evaluate this hypothesis, we initiated a prospective longitudinal study in monochorionic (MC) twins: the TwinLIFE study. MC twins are monozygotic, thus in origin genetically identical, and share a single placenta. Although MC twins have many environmental factors in common, in one-third of the MC twin pairs, one fetus has significantly less access to nutrients and resources during pregnancy than its co-twin often resulting in a significant discordance in prenatal growth. Hence, MC twins constitute a unique natural experiment to study the influence of the prenatal environment on health. In TwinLIFE, we will chart intrapair differences in DNA methylation focusing on mesenchymal stromal cells isolated from cord as an advanced proxy of epigenetic dysregulation relevant for long-term health consequences. Next, we will follow up the MC twins for growth, cardiovascular and neurodevelopmental outcomes during childhood and evaluate the impact of an epigenetic signature at birth on future health. The current target is to include 100 MC twin pairs, but we aim to continue enrollment after procuring additional funding. TwinLIFE will not only address an unmet clinical need in the high-risk group of MC twins, but may also advance early-life strategies to prevent adverse growth, cardiovascular and neurodevelopmental outcomes in the general population. [ABSTRACT FROM AUTHOR]

As twin-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR) are both prevalent complications of monochorionic (MC) twin pregnancies, its coexistence is not uncommon. The aim of this study is to evaluate the short and long-term outcome in TTTS with and without sFGR prior to fetoscopic laser coagulation. All TTTS cases treated with laser surgery at our center between 2001–2019 were retrospectively reviewed for the presence of sFGR, defined as an estimated fetal weight (EFW) <10th centile. We compared two groups: TTTS-only and TTTS + sFGR. Primary outcomes were perinatal survival and long-term severe neurodevelopmental impairment (NDI). Of the 527 pregnancies eligible for analysis, 40.8% (n = 215) were categorized as TTTS-only and 59.2% (n = 312) as TTTS + sFGR. Quintero stage at presentation was higher in the TTTS + sFGR group compared to the TTTS-only group (57% compared to 44% stage III). Separate analysis of donors showed significantly lower perinatal survival for donors in the TTTS + sFGR group (72% (224/311) compared to 81% (173/215), p = 0.027). Severe NDI at follow-up in long-term survivors in the TTTS-only and TTTS + sFGR group was present in 7% (13/198) and 9% (27/299), respectively (p = 0.385). Both sFGR (OR 1.5;95% CI 1.1–2.0, p = 0.013) and lower gestational age at laser (OR 1.1;95% CI 1.0–1.1, p = 0.001) were independently associated with decreased perinatal survival. Thus, sFGR prior to laser surgery is associated with a more severe initial presentation and decreased donor perinatal survival. The long-term outcome was not affected. [ABSTRACT FROM AUTHOR]

The human umbilical cord (hUC) is the lifeline that connects the fetus to the mother. Hypercoiling of the hUC is associated with pre- and perinatal morbidity and mortality. We investigated the origin of hUC hypercoiling using state-of-the-art imaging and omics approaches. Macroscopic inspection of the hUC revealed the helices to originate from the arteries rather than other components of the hUC. Digital reconstruction of the hUC arteries showed the dynamic alignment of two layers of muscle fibers in the tunica media aligning in opposing directions. We observed that genetically identical twins can be discordant for hUC coiling, excluding genetic, many environmental, and parental origins of hUC coiling. Comparing the transcriptomic and DNA methylation profile of the hUC arteries of four twin pairs with discordant cord coiling, we detected 28 differentially expressed genes, but no differentially methylated CpGs. These genes play a role in vascular development, cell-cell interaction, and axis formation and may account for the increased number of hUC helices. When combined, our results provide a novel framework to understand the origin of hUC helices in fetal development., (© 2024 Todtenhaupt et al.)