Fetal Reduction of Triplet Pregnancies to Twins vs Singletons: A Meta-analysis of Survival and Pregnancy Outcome
Authors: Hessami Kamran , Evans Mark I. , Nassr Ahmed A. , Espinoza Jimmy , Donepudi Roopali V. , Sanz Cortes Magdalena , Krispin Eyal , Mostafaei Shayan , Belfort Michael A. , Shamshirsaz Alireza A. 
Published: March 2023

Fetal reduction (FR) for higher-order multiples accounted for 103.6 per 100,00 births across the United States in 2015, and the need for this service has expanded over the last 30 years. Despite improvements in neonatal care, triplet pregnancies are more likely to experience adverse outcomes, including infant mortality and morbidity, than twin or singleton pregnancies. In triplet pregnancies, prematurity is associated with an 11-fold increase and low birth weight with a 2.2-fold increase in infant deaths compared with singleton and twin prematurity pregnancies. This contributes to higher all-cause healthcare expenses for triplet pregnancies (US $407,000) versus singleton pregnancies (US $21,500). Fetal reduction has been shown to improve outcomes, including a lower risk of premature birth, in triplet pregnancies reduced to twins compared with triplet pregnancies with no FR. Another study found improved outcomes when triplet pregnancies were reduced to singleton or twin pregnancies versus expectant management. However, it remains unclear whether FR in triplet pregnancies to singleton pregnancy (RTS) improved outcomes compared with a reduction to twin pregnancies (RTT). The aim of this study was to compare perinatal outcomes and survival rates of RTS pregnancies versus RTT pregnancies, and FR in any triplet pregnancies versus expectant management.

This was a systematic review and meta-analysis based on a literature search for studies with data comparing selective RTT and RTS pregnancies. Excluded were studies with multiple pregnancies >3 fetuses, monochorionic triplets, and missing data. The primary outcome was the rate of fetal survival of RTT and RTS pregnancies, defined as a live birth >24 weeks of gestation. Secondary outcomes included gestational age (GA) at birth, birth weight, incidence of preterm birth, early pregnancy loss at <24 weeks, and neonatal death, up to 28 days after birth.

A total of 10 studies directly comparing RTT pregnancies with RTS pregnancies and another 10 studies comparing FR with no FR were included in the analysis. The studies represented 1903 RTT pregnancies and 489 RTS pregnancies. There was a significantly lower survival rate among RTT pregnancies versus RTS pregnancies (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.40–0.92; 95% prediction interval [PI], 0.36–1.03; P = 0.02; I
2 = 0%). There was a comparable risk of early pregnancy loss (OR, 0.89; 95% CI, 0.58–1.38; 95% PI, 0.54–1.48; P = 0.61; I
2 = 0%) and neonatal death (OR, 0.56; 95% CI, 0.10–3.21; P = 0.55; I
2 = 28%). RTT pregnancies had significantly lower GA (mean difference, −2.20; 95% CI, −2.80 to −1.61; 95% PI, −4.27 to −0.14; P < 0.001; I
2 = 79%) and lower birth rates (OR, 8.76; 95% CI, 5.56–13.80; 95% PI, 4.60–16.67; P < 0.001; I
2 = 0%) than RTS pregnancies. RTT pregnancies also had a greater risk of preterm birth at <34 weeks (OR, 3.04; 95% CI, 1.45–6.36; 95% PI, 0.54–17.18; P = 0.003; I
2 = 22%) and at <32 weeks (OR, 2.14; 95% CI, 1.02–4.49; 95% PI, 0.64–7.13; P = 0.04; I
2 = 0%). No difference in live birth rate was observed between RTT pregnancies and expectant management.

In conclusion, triplet pregnancies RTS pregnancies had better outcomes than RTT pregnancies, including higher fetal survival rate, higher GA at birth, lower risk of preterm birth, and higher birth weight. Understanding the potential risks and benefits of FR in triplet pregnancies is essential for obstetricians providing parental counseling.