Vanishing twin syndrome among ART singletons and pregnancy outcomes

Study question: Among babies born by ART, do singleton survivors of a vanishing twin have lower birth weight than other singletons? Summary answer: Vanishing-twin syndrome was associated with lower birth weight among ART singletons; a sibship analysis indicated that the association was not confounded by maternal characteristics that remain stable between deliveries. What is known already known: Previous studies indicate that ART singletons with vanishing-twin syndrome have increased risk of adverse pregnancy outcomes, compared with other ART singletons. The potential contribution of unmeasured maternal background characteristics has been unclear. Study design, size and duration: This was a Norwegian population-based registry study, including 17,368 mothers with 20,410 ART singleton deliveries between January 1984 and December 2013.Participants/materials, setting, methods: The study population included 17,291 ART singletons without vanishing-twin syndrome, 638 ART singletons with vanishing-twin syndrome, and 2,418 ART singletons with uncertain vanishing-twin status. We estimated differences in birth weight and gestational age comparing ART singletons with vanishing-twin syndrome first to all ART singletons without vanishing-twin syndrome, and subsequently to their ART siblings without vanishing-twin syndrome, using random- and fixed-effects linear regression, respectively. The corresponding comparisons for the associations with preterm birth and small-for-gestational age (SGA) were conducted using random-and fixed-effects logistic regression. The sibling analysis of preterm birth included 587 discordant siblings, while the sibling analysis of SGA included 674 discordant siblings.Main results and the role of chance: ART singletons with vanishing-twin syndrome had lower birth weight when compared to all ART singletons without vanishing-twin syndrome, with an adjusted mean difference (95% CI) of -116 grams (-165, -67). When we compared ART singletons with vanishing-twin syndrome to their ART singletons sibling without vanishing-twin syndrome, the adjusted mean difference was -112 grams (-209, -15). ART singletons with vanishing-twin syndrome also had increased risk of being born SGA, with an adjusted odds ratio (95% CI) of 1.48 (1.07, 2.03) compared to all ART singletons without vanishing twin-syndrome, and 2.79 (1.12, 6.91) in the sibship analyses. ART singletons with vanishing-twin syndrome were also more likely to be born preterm, although this difference did not reach statistical significance.Limitations, reasons for caution: We did not have information on maternal socio-economic status, but this factor is accounted for in the sibship analyses. We have no information on whether fresh or frozen embryos were replaced.Wider implications of the findings: The reduction in birth weight and increased SGA in ART singletons with vanishing-twin syndrome may suggest the presence of harmful intrauterine factors with long-term health impact. While vanishing twins are not routinely observed in naturally conceived pregnancies, loss of a twin is potentially a risk factor for the surviving fetus in any pregnancy. This could be further explored in large samples of naturally conceived pregnancies with the necessary information. Study funding/competing interest(s): The authors of this study are supported in part by the UK Medical Research Council, US National Institute of Environmental Health Sciences, and the Norwegian Research Council. The authors have no conflicts of interest.