Multiple Pregnancy (Twin and Triplet Management)

Multiple pregnancy is a high-risk condition in which perinatal mortality and morbidity are markedly increased compared with singleton pregnancy. The cornerstone of management is accurate determination of chorionicity and amnionicity in the first trimester, because monochorionic placentation carries a spectrum of complications not seen in dichorionic pregnancy (twin-to-twin transfusion syndrome, twin anemia-polycythemia sequence, selective fetal growth restriction). Drawing on ACOG Practice Bulletin No. 231 (2021), ISUOG Practice Guidelines (2025), SMFM Consult Series #72 (2024), NICE NG137, and RCOG Green-top Guideline No. 51, this review addresses diagnostic thresholds, surveillance frequency, indications for fetal intervention, and timing of delivery in twin and triplet pregnancies.

Definition and epidemiology

The incidence of multiple pregnancy has increased significantly in the last forty years due to the widespread use of assisted reproductive techniques (ART) and advanced maternal age. In US data, the twin birth rate increased by 76% between 1980 and 2009, from 18.9 per thousand to 33.3 per thousand; With the widespread use of single embryo transfer practices, the rate decreased by 4% between 2014 and 2018, to 32.6 per thousand (ACOG PB 231, 2021).

Approximately 30% of twins are monozygotic (single egg) and 70% are dizygotic; About two-thirds of monozygotic twins are monochorionic. The spontaneous twinning rate varies ethnically and geographically: it reaches 0.6% in Asian populations, 1–2% in Europe-USA-Australia, and 4% in Africa. After IVF, even with single embryo transfer, the rate of monozygotic twins is higher than the natural rate, at approximately 1.5% per live birth (Hum Reprod 2025, DOI 10.1093/humrep/deaf128).

The clinical determinant is chorionicity rather than zygosity. Monochorionic pregnancies carry an approximately 3-fold increased risk of perinatal mortality and an approximately 10-fold increased risk of prenatal neurological lesions compared to dizygotic twins. The prevalence of major congenital anomalies is also directly related to chorionicity: approximately 1/30 in dichorionic pregnancy, 1/15 in monochorionic diamniotic (MCDA) pregnancy, and 1/4 in monoamniotic (MCMA) pregnancy (ISUOG 2025).

Chorionicity and amnionicity determination

Chorionicity determination is the single most important first step in the management of multiple pregnancy and should be performed before 13+6 weeks of gestation, using as much ultrasound evidence as possible (ISUOG 2025; SMFM #72, GRADE 1B). After fourteen weeks, the reliability of chorionicity determination drops significantly, so early screening is critical.

• Dichorionic (DCDA): Lambda (λ) or twin-peak sign — triangular projection of thick chorionic tissue extending towards the placenta, thick membrane, and separate placental masses.
• Monochorionic (MCDA): T-sign (null lambda) — fusion of the membrane with the placenta at right angles, without protrusion of chorionic tissue; thin double amnion layer.

In monochorionic pregnancies, amnionicity can be distinguished from approximately the 8th week of gestation, when the amniotic sac becomes visible (ISUOG 2025). When a monoamniotic pregnancy is detected, the patient should be referred to a tertiary fetal medicine center.

Gestational age determination should also be standardized: in spontaneous pregnancies, before 13+6 weeks, the greater of two CRL measurements is taken as the basis, and after 14 weeks, the head circumference (HC) of the larger twin is taken as basis; Embryo age and transfer date are used in IVF pregnancies (ISUOG 2025). Consistent labeling of fetuses (lateral-vertical orientation, placenta placement, cord entry site) should be clearly documented so that the same fetus can be followed throughout follow-up.

Monitoring frequency

Monitoring intensity differs markedly according to chorionicity. Because the risk of complications is lower in dichorionic pregnancies, growth monitoring every four weeks is sufficient, whereas monochorionic pregnancies require much more frequent surveillance due to the risk of TTTS and TAPS. Guidelines are largely aligned on this point.

At each monochorionic follow-up ultrasound, amniotic fluid on both sides of the membrane, fetal bladder fullness, and ideally umbilical artery Doppler should be evaluated to screen for TTTS (SMFM #72, GRADE 1C). Middle cerebral artery peak systolic velocity (MCA-PSV) measurement for TAPS screening should be added to routine monochorionic monitoring from 16–20 weeks (SMFM #72, GRADE 1C; ISUOG recommends starting measurement from 20 weeks).

Selective fetal growth restriction (sFGR)

Selective FGR is defined by an estimated fetal weight (EFW) below the 10th percentile in one fetus and intertwin EFW discordance ≥25%; EFW below the 3rd percentile in one twin alone is also diagnostic (ISUOG 2025). Discordance is calculated as [(larger−smaller)/larger]×100. In monochorionic pregnancies, at least 2 of the criteria EFW <10th percentile, AC <10th percentile, discordance ≥25%, and UA-PI >95th percentile are required; in dichorionic pregnancies, at least 2 of 3 criteria are required. For the early/late distinction, onset before 32 weeks in dichorionic pregnancies and before 24 weeks in monochorionic pregnancies is considered early.

The prognosis and management of monochorionic sFGR are determined by the Gratacós classification based on the umbilical artery end-diastolic flow pattern:

• Type I (positive EDF): Good prognosis; Over 90% survival, approximately 4% in-utero mortality. It is usually managed conservatively with close monitoring.
• Type II (persistent absent/reversed EDF): High risk; The risk of intrauterine death reaches 29% and the rate of neurological sequelae reaches approximately 15%.
• Type III (cyclic/intermittent AREDF): Risk of unpredictable sudden fetal death 10–20%; approximately 20% neurological morbidity in the surviving twin. It is the most difficult group to manage due to the fluctuation in the Doppler pattern.

Twin-to-twin transfusion syndrome (TTTS)

TTTS is a serious condition resulting from unstable vascular anastomoses in the placenta, complicating approximately 10–15% of monochorionic pregnancies. Diagnosis is based on ultrasonographic demonstration of the oligohydramnios-polyhydramnios sequence. Deepest vertical pocket (DVP) in donor fetus ≤2 cm; DVP ≥8 cm (≤20 weeks) or ≥10 cm (>20 weeks) in the recipient fetus is considered the threshold (ISUOG 2025). For early polyhydramnios before sixteen weeks, a threshold of 6 cm is used. The Quintero chart of SMFM #72 is based on a >8 cm threshold for the recipient, regardless of the week.

The basis of treatment is fetoscopic laser coagulation. SMFM #72 (2024) recommends fetoscopic laser as standard treatment in Stage II–IV TTTS between 16–26 weeks (GRADE 1A) . In Stage I TTTS, an expectant approach with at least weekly follow-up is appropriate in asymptomatic cases (GRADE 1B); While approximately 78% intact survival was reported in expectant follow-up, those who progressed and received laser treatment had a rate of 71%, and no significant difference in outcome was detected between immediate laser and expectant management in Stage I. If symptoms of maternal polyhydramnios are evident, laser may be considered. For presentations earlier than seventeen weeks and later than 26 weeks, the approach is individualized (GRADE 1C). All TTTS cases should be referred to a fetal intervention center.

In the post-laser literature, survival of both fetuses is reported to be 50–70%, and survival of at least one fetus is reported to be 86–93%; The average post-laser birth week in the NAFTNet cohort was approximately 33 weeks. In double-surviving MCDA pregnancies after uncomplicated, resolved TTTS, birth is planned at 34–36 weeks (GRADE 1B/1C).

Twin anemia-polycythemia sequence (TAPS)

TAPS is intertwin hemoglobin discordance that develops as a result of chronic fetofetal blood transfer via small diameter (<1 mm) placental anastomoses without significant amniotic fluid discordance. While it occurs spontaneously in approximately 3–5% of monochorionic pregnancies, the rate of iatrogenic TAPS after standard fetoscopic laser can reach 16% (15.6% in the Solomon control arm; reduced to 2.9% with the Solomon technique).

Antenatal diagnosis is based on Doppler (SMFM #72, GRADE 1C): MCA-PSV >1.5 MoM in the donor (anemic) fetus and MCA-PSV <1.0 MoM in the recipient (polycythemic) fetus, or intertwin delta MCA-PSV >0.5 MoM. While the classical >1.5/<1.0 criterion offers 46% sensitivity and 100% specificity, the ΔMCA-PSV >0.5 MoM criterion outperforms with 83% sensitivity and 100% specificity (Tollenaar, PMID 30125414). Definitive postnatal diagnosis is made when the hemoglobin difference between twins is ≥8 g/dL and in addition either the reticulocyte ratio is >1.7 or only small-diameter anastomoses are demonstrated in the placenta (SMFM #72; Delphi consensus, Khalil 2020, DOI 10.1002/uog.21882).

Aneuploidy and anomaly screening

Cell-free fetal DNA (cfDNA/NIPT) testing is the most accurate screening method for trisomy 21 in twin pregnancies and can be performed from 10 weeks onward; in meta-analysis, detection rates were reported as 99.0% (FPR 0.02%) for T21, 93% for T18, and 95% for T13 (ISUOG 2025). Detection rates in twins may be slightly lower than in singleton pregnancies. Alternatively, the first-trimester combined test (NT measurement at 11+0–13+6 weeks + free β-hCG + PAPP-A) may be used; in the presence of a vanishing twin, risk assessment should rely solely on NT and maternal age. Pregnancy loss rates in pregnancies undergoing invasive testing are similar in recent meta-analyses (CVS ~2.0–3.84%; amniocentesis ~2.4–3.07%). A second-trimester detailed anomaly scan is performed at 18–22 (≈20) weeks; fetal echocardiography (situs, four-chamber view, outflow tracts, aortic arch) is recommended in monochorionic pregnancies because of the increased risk of congenital heart defects.

Preterm birth and preeclampsia prophylaxis

Preterm birth is the leading cause of perinatal morbidity in multiple gestation, but evidence on prevention strategies is inconsistent and guidelines take differing stances. NICE NG137 does not recommend routine (untargeted) antenatal corticosteroid use in twin and triplet pregnancies; advocates targeted administration of steroids only in cases where preterm birth is anticipated.

The place of pharmacological prophylaxis in the short cervix (<25 mm) subgroup is not clear. Romero's meta-analysis of individual patient data showed that vaginal progesterone reduced preterm birth and perinatal morbidity (PMID 34941003), while a network meta-analysis in the same population concluded that progesterone, cervical pessary, and cerclage all provided no significant benefit (PMID 33946019). For cervical pessary, a 2025 meta-analysis (17 studies, 5704 patients) reported reductions in births <37 and <34 weeks, whereas previous randomized trials such as ProTWIN have yielded inconsistent results. Cerclage, on the other hand, carries a harm signal in terms of increasing the risk of premature birth, low birth weight and RDS in individual patient data analysis in twins with short cervix. In summary, no single superior preterm prevention strategy has been proven in multiple pregnancy; In the short cervix subgroup, the decision needs to be individualized (certainty of the evidence is low-moderate, due to inconsistency and population heterogeneity).

There is also a difference of opinion regarding the dose in preeclampsia prophylaxis. The ASPRE study showed that 150 mg/day aspirin reduced preterm preeclampsia by 60% in high-risk singleton pregnancies, but twin pregnancies were excluded (ASPRE, NEJM 2017; PMID 28657417). ACOG considers multiple pregnancy alone as a high-risk indication and recommends low-dose aspirin at 81 mg/day; Meta-analyses focusing on preeclampsia indicate that a dose of 100–150 mg/day starting at <16 weeks may be more effective. Because twin-specific randomized data are limited (ACOG 81 mg; preeclampsia literature 100–150 mg), the certainty of the evidence in this regard is moderate to low.

Birth timing

Timing of birth is the topic where there is the most significant disagreement among the guidelines in the management of multiple pregnancy. The balance point between stillbirth risk and prematurity morbidity is positioned in different weeks, with a real difference between ACOG and ISUOG/NICE.

The evidence base for this difference is strong. In the systematic review and meta-analysis of Cheong-See et al., including 32 studies (29,685 DC, 5,486 MC pregnancies), the risk of stillbirth and neonatal death in dichorionic twins was balanced at the 37th week; It has been shown that postponing birth until the 38th week is associated with 8.8 additional perinatal deaths per thousand. In monochorionic pregnancies, the tendency to stillbirth becomes evident after 36 weeks (Cheong-See, BMJ 2016; PMID 27599496). Koch et al.'s meta-analysis of individual patient data examining twins with growth discordance and restriction (7,474 DC + 2,281 MC pairs) found that although SGA and discordance increased the absolute risk, they did not change the optimal timing; confirmed that the risk stabilizes between 36+0–37+6 weeks in both dichorionic and monochorionic pregnancies (Koch, Obstet Gynecol 2022; PMID 35675615). Therefore, ISUOG and NICE's recommendation to deliver at earlier weeks is supported by this meta-analysis evidence; ACOG's later weeks reflect a distinct institutional stance.

Method of birth

The main evidence in determining the method of birth is the Twin Birth Study by Barrett et al. In this randomized study, which included 2804 women from twenty-five countries, no difference was found between planned cesarean section and planned vaginal birth in pregnancies with the first twin in cephalic presentation between 32+0–38+6 weeks in terms of fetal/neonatal death and serious neonatal morbidity (Twin Birth Study, NEJM 2013; DOI 10.1056/NEJMoa1214939). Two-year neurodevelopmental follow-up also showed that planned caesarean section did not benefit the child (PMID 26830380). Accordingly, if the first twin is cephalic, vaginal birth can be attempted regardless of the presentation of the second twin. Cesarean section in monoamniotic twins due to the risk of cord entanglement; In conjoined twins, cesarean section is also indicated.

Rare complications

In monoamniotic pregnancies, cord entanglement is present to some degree in almost all cases; In normally formed MCMA pregnancies, perinatal loss is approximately 6%, regardless of entanglement, and survival reaches 81–95% with aggressive follow-up. Frequent (weekly or more) fetal monitoring is recommended from 28 weeks onwards, and birth is planned at 32–34 weeks after corticosteroids.

TRAP sequence (acardiac twin) is a rare complication seen in approximately 1/35,000 of monochorionic pregnancies. In a systematic review covering 293 cases over 35 years, survival in pump twins with radiofrequency ablation (RFA) was reported as 77.9–82.6%, and this rate was found to be superior to 64.5% in expectant management (PMID 39837656). Conjoined twins are much rarer (~1/50,000–100,000) and require a planned cesarean section at the tertiary center.

Clinical summary

• Chorionicity and amnionicity are detected before 13+6 weeks with as many USG findings as possible; Lambda sign indicates dichorionic pregnancy, T-sign indicates monochorionic pregnancy. After fourteen weeks, reliability decreases.
• Monochorionic pregnancy carries a ~3-fold increased risk of perinatal mortality and a ~10-fold increased risk of neurological lesions; The prevalence of major anomaly is DCDA 1/30, MCDA 1/15, MCMA 1/4.
• Follow-up: DCDA every 4 weeks; MCDA every 2 weeks from 16 weeks (TTTS/TAPS scan with amniotic fluid + bladder + Doppler + MCA-PSV); MCMA tertiary center.
• Diagnosis of TTTS is based on the oligo-polyhydramnios sequence (donor DVP ≤2 cm, recipient ≥8 cm). Stage II–IV, 16–26 weeks → fetoscopic laser (GRADE 1A); Solomon technique reduces TAPS and recurrence.
• Diagnosis of TAPS by Doppler (donor MCA-PSV >1.5 MoM + recipient <1.0 MoM or ΔMCA-PSV >0.5 MoM); postnatal Hb difference ≥8 g/dL + reticulocyte ratio >1.7.
• Gratacós Types II–III in selective FGR carry a high risk of mortality and neurological morbidity; Requires tertiary center monitoring.
• Timing of birth — guideline difference: ACOG PB 231 recommends DCDA 38 weeks, MCDA 34–37 weeks; ISUOG/NICE recommends 37 weeks for DCDA and 36 weeks for MCDA. ISUOG/NICE's earlier stance is supported by Cheong-See (BMJ 2016) and Koch (2022) IPD meta-analysis evidence.
• If the first twin is cephalic, vaginal birth can be tried (Twin Birth Study); MCMA and conjoined twin → cesarean section.
• Evidence is inconsistent for preterm prevention (progesterone/pessary/cerclage) and aspirin dose (ACOG 81 mg; preeclampsia literature 100–150 mg); Individualization is recommended in the short cervix subgroup.

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