Association between fetal growth restriction and stillbirth in twin compared with singleton pregnancies
Authors: Martínez‐Varea A. , Prasad S. , Domenech J. , Kalafat E. , Morales‐Roselló J. , Khalil A. 
Published: April 2024

Objectives

Twin pregnancies are at higher risk of stillbirth compared to singletons. Fetal growth restriction (FGR) is a major cause of perinatal mortality, but its impact on twins vs singletons remains unclear. The primary objective of this study was to investigate the association of FGR and small‐for‐gestational age (SGA) with stillbirth in twin compared with singleton pregnancies. A secondary objective was to assess these associations stratified by gestational age at delivery. Furthermore, we aimed to compare the associations of FGR and SGA with stillbirth in twin pregnancies using twin‐specific vs singleton birth‐weight charts, stratified by chorionicity.

Methods

This was a retrospective cross‐sectional study of pregnancies receiving obstetric care and giving birth between 1999 and 2022 at St George's Hospital, London, UK. The exclusion criteria included triplet and higher‐order pregnancies, those resulting in miscarriage or live birth at ≤ 23 + 6 weeks, termination of pregnancy and missing data regarding birth weight or gestational age at birth. Birth‐weight data were collected and FGR and SGA were defined as birth weight <5th and <10th centiles, respectively. While standard logistic regression was used for singleton pregnancies, the association of FGR and SGA with stillbirth in twin pregnancies was investigated using mixed‐effects logistic regression models. For twin pregnancies, intercepts were allowed to vary for twin pairs to account for intertwin dependency. Analyses were stratified by gestational age at delivery and chorionicity. Statistical significance was set at P ≤ 0.001.

Results

The study included 95 342 singleton and 3576 twin pregnancies. There were 494 (0.52%) stillbirths in singleton and 41 (1.15%) stillbirths in twin pregnancies (17 dichorionic and 24 monochorionic). SGA and FGR were associated significantly with stillbirth in singleton pregnancies across all gestational ages at delivery: the odds ratios (ORs) for SGA and FGR were 2.36 ((95% CI, 1.78–3.13), P < 0.001) and 2.67 ((95% CI, 2.02–3.55), P < 0.001), respectively, for delivery before 32 weeks; 2.70 ((95% CI, 1.71–4.31), P < 0.001) and 2.82 ((95% CI, 1.78–4.47), P < 0.001), respectively, for delivery between 32 and 36 weeks; and 3.85 ((95% CI, 2.83–5.21), P < 0.001) and 4.43 ((95% CI, 3.16–6.12), P < 0.001), respectively, for delivery after 36 weeks. In twin pregnancies, when stratified by gestational age at delivery, both SGA and FGR determined by twin‐specific birth‐weight charts were associated with increased odds of stillbirth for those delivered before 32 weeks (SGA: OR, 3.87 (95% CI, 1.56–9.50), P = 0.003 and FGR: OR, 5.26 (95% CI, 2.11–13.01), P = 0.001), those delivered between 32 and 36 weeks (SGA: OR, 6.67 (95% CI, 2.11–20.41), P = 0.001 and FGR: OR, 9.54 (95% CI, 3.01–29.40), P < 0.001) and those delivered beyond 36 weeks (SGA: OR, 12.68 (95% CI, 2.47–58.15), P = 0.001 and FGR: OR, 23.84 (95% CI, 4.62–110.25), P < 0.001). However, the association of stillbirth with SGA and FGR in twin pregnancies was non‐significant when diagnosis was based on singleton charts (before 32 weeks: SGA, P = 0.014 and FGR, P = 0.005; 32–36 weeks: SGA, P = 0.036 and FGR, P = 0.008; after 36 weeks: SGA, P = 0.080 and FGR, P = 0.063).

Conclusion

Our study demonstrates that SGA and, especially, FGR are associated significantly with an increased risk of stillbirth across all gestational ages in singleton pregnancies, and in twin pregnancies when twin‐specific birth‐weight charts are used. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.