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Meta-Analysis
. 2022 Jun 1;139(6):1155-1167.
doi: 10.1097/AOG.0000000000004789. Epub 2022 May 2.

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis

Ashlee K Koch  1 , Renée J Burger, Ewoud Schuit, Julio Fernando Mateus, Maria Goya, Elena Carreras, Sckarlet E Biancolin, Eran Barzilay, Nancy Soliman, Stephanie Cooper, Amy Metcalfe, Abhay Lodha, Anna Fichera, Valentina Stagnati, Hiroshi Kawamura, Maria Rustico, Mariano Lanna, Shama Munim, Francesca Maria Russo, Anwar Nassar, Line Rode, Arianne Lim, Sophie Liem, Katherine L Grantz, Karien Hack, C Andrew Combs, Vicente Serra, Alfredo Perales, Asma Khalil, Becky Liu, Jon Barrett, Wessel Ganzevoort, Sanne J Gordijn, R Katie Morris, Ben W Mol, Wentao Li
Affiliations
Meta-Analysis

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis

Ashlee K Koch et al. Obstet Gynecol. .

Abstract

Objective: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies.

Data sources: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded.

Methods of study selection: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs.

Tabulation, integration, and results: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward.

Conclusion: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone.

Systematic review registration: PROSPERO, CRD42018090866.

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Conflict of interest statement

Financial Disclosure Elena Carreras is a member of the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA (EU Framework Partnership Agreement ID: 3HP-HP-FPA ERN-01-2016/739516). One included research project was supported, in part, by the Division of Population Health, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and, in part, with federal funds for the NICHD Fetal Growth Studies – Dichorionic Twins under Contract Numbers: HHSN275200800013C; HHSN275200800002I; HHSN27500006; HHSN275200800003IC; HHSN275200800014C; HHSN275200800012C; HHSN275200800028C; and HHSN275201000009C. Katherine L. Grantz has contributed to this work as part of her official duties as an employee of the United States federal government. Wessel Ganzevoort reports government funding (ZonMW 843002825) and free-of-charge test kits from Roche Diagnostics. Sanne J. Gordijn disclosed that money was paid to their institution from ZonMW, Roche (in-kind kits unrestricted and shipping and handling of material), and SCEM (conference payment to research fund). They also received funding from Dublin Maternity Hospital (payment for travels for Charter Day lecture). In addition, they report holding government funding (ZonMW 852002034) and free-of-charge test kits from Roche Diagnostics. R. Katie Morris disclosed money was paid to her through a consultancy to a company that designs neonatal vital signs monitors (SUREPULSE), and money was paid to her institution from the NIHR. Ben W. Mol is supported by a NHMRC Investigator grant (GNT1176437), and reports consultancy for ObsEva and research funding from Ferring and Merck. The PREDICT study received funding from The Danish Medical Research Council, The Fetal Medicine Foundation, The Copenhagen University Hospital's Research Fund, The Aase and Ejnar Danielsens Fund, The Augustinus Fund, The Ivan Nielsen Fund, The Doctor Sofus Carl Emil Friis, and wife Olga Doris Friis' Fund, The Simon Fougner Hartmanns Family Fund, The Danish Medical Society in Copenhagen, and The A.P. Moeller Foundation. The other authors did not report any potential conflicts of interest.

Figures

Fig. 1.
Fig. 1.
MOOSE (Meta-analysis of Observational Studies in Epidemiology) flowchart for assessment of studies for eligibility. *Items not mutually exclusive. MCMA, monochorionic–monoamniotic; TRAP, twin reversed arterial perfusion; TTTS, twin–twin transfusion syndrome; FGR, fetal growth restriction. Koch. Time of Delivery in Twins With Growth Disorders. Obstet Gynecol 2022.
Fig. 2.
Fig. 2.
Prospective risk of stillbirth from expectant management vs risk of neonatal mortality from delivery at weekly intervals from 34 weeks of gestation in dichorionic twin pregnancies, by birth weight centile and level of growth discordance. Statistically significant results are shown in bold in Table 1. All neonates (A), small-for-gestational age neonates (birth weight less than the 10th percentile) (B), and appropriate-for-gestational age neonates (birth weight at the 10th percentile or greater) (C). Koch. Time of Delivery in Twins With Growth Disorders. Obstet Gynecol 2022.
Fig. 3.
Fig. 3.
Prospective risk of stillbirth from expectant management vs risk of neonatal mortality from delivery at weekly intervals from 34 weeks of gestation in monochorionic twin pregnancies, by birth weight centile and level of growth discordance. Statistically significant results are shown in bold in Table 2. All neonates (A), small-for-gestational age neonates (birth weight less than the 10th percentile) (B), and appropriate-for-gestational age neonates (birth weight at the 10th percentile or greater) (C). Koch. Time of Delivery in Twins With Growth Disorders. Obstet Gynecol 2022.
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