Triplet pregnancy

INTRODUCTION — Triplets and other higher order multiple gestations are associated with significantly increased risks of maternal and neonatal morbidity compared with twin and singleton gestations. The increased neonatal risks are primarily related to iatrogenic or spontaneous preterm birth: two thirds of triplet pregnancies in the United States deliver before 34 weeks compared with one-fifth of twin pregnancies and 2 percent of singleton pregnancies [1].

This topic will discuss the potential complications associated with triplet gestations and obstetric management of these pregnancies.

PRIMARY PREVENTION OF TRIPLETS AND HIGHER ORDER PREGNANCIES — The ideal outcome of assisted reproductive technology is the birth of a single, healthy neonate. Progress toward this goal has been made as a result of improvements in ovulation induction, embryo evaluation, and patient selection, including limiting the number of embryos transferred based on maternal age and embryo quality/availability for cryopreservation. Strategies to reduce the occurrence of triplets and higher order multiple births are reviewed in detail separately:

●(See "Strategies to control the rate of high order multiple gestation".)

●(See "Multifetal pregnancy reduction and selective termination".)

PREVALENCE — In areas where medically assisted conception (ie, assisted reproductive technology [ART]) is widely available, the rate of triplet and higher order multiple births is higher than the naturally occurring rate. ART, particularly in vitro fertilization (IVF) and controlled ovarian hyperstimulation with gonadotropins, account for almost 80 percent of triplet and higher order multiple births [2]. Triplet and higher order multiple births accounted for 78.9 per 100,000 births in the United States in 2022 [3] but only 32.3 per 100,000 births in 1977 (before IVF) [4]. However, the 2022 rate of triplet births was down approximately 60 percent from the 1998 peak (193.5 per 100,000 births) and was the lowest rate in three decades as a result of transfer of fewer embryos and an increase in fetal reduction procedures. (See "Assisted reproductive technology: Pregnancy and maternal outcomes", section on 'Multiple gestation incidence and risks' and "Strategies to control the rate of high order multiple gestation" and "Multifetal pregnancy reduction and selective termination".)

CLINICAL PRESENTATION AND DIAGNOSIS — Diagnosis of triplet pregnancy is based on ultrasound examination, which is generally initially performed for assessment of gestational age or fetal cardiac activity. An increased likelihood of triplet pregnancy may be suspected based on use of assisted reproductive technology to conceive and/or uterine size that is large for dates.

COUNSELING — Pregnant people with triplet pregnancies should be counseled about the following issues.

●Maternal, fetal, and neonatal risks are increased in these pregnancies. Potential risks (eg, preterm birth, preeclampsia, fetal growth discordance) and their management should be discussed. Consultation with a maternal-fetal medicine specialist can be helpful. (See 'Potential complications' below and 'Perinatal mortality and morbidity' below.)

Underlying maternal medical conditions that are exacerbated by the physiological changes of the pregnant state are more severely impacted by carrying a triplet gestation. For example, in a study of five triplet pregnancies, maternal median peak cardiac output was 8.44 L/min and occurred at 32 to 36 weeks [5], whereas the mean maternal peak cardiac output in singleton pregnancies is 6.1 L/min at the same gestational age [6]. Thus, triplet pregnancy can be a severe challenge and even life-threatening for pregnant people with some cardiac abnormalities (eg, cardiomyopathy, mitral stenosis).

●Multifetal reduction decreases the likelihood of spontaneous preterm birth and other obstetrical and neonatal complications. In a meta-analysis of observational studies, pregnancy reduction from triplets to twins was associated with reductions in pregnancy loss, birth before 36 weeks, cesarean birth, low birth weight infants, and neonatal deaths compared with expectant management, and the rates were similar to those in spontaneously conceived twin pregnancies [7]. (See "Multifetal pregnancy reduction and selective termination".)

●The pregnancy will need close maternal and fetal surveillance, including frequent ultrasound examinations to monitor fetal growth and well-being and frequent office visits, particularly after 20 weeks of gestation, due to the increased risk for maternal complications. (See 'Ultrasound examination' below and 'Office visits' below.)

●Antenatal hospitalization because of pregnancy complications is common. There is a high probability of cesarean birth since vaginal birth of triplets is generally avoided. (See 'Delivery' below.)

●Carrying a triplet pregnancy and caring for triplet offspring can be physically demanding. There are also potential psychosocial and financial impacts of caring for triplets [8,9]. Connecting the patient to local groups of triplet parents can be useful, especially near the time of birth and postpartum. These groups can provide support and practical information.

●The advisability of planning birth at a hospital with an on-site level III neonatal intensive care unit should be discussed, given the likelihood of preterm birth. (See "Neonatal complications of multiple births".)

Many other issues are the same as in any pregnancy. (See "Prenatal care: Initial assessment" and "Prenatal care: Second and third trimesters" and "Prenatal care: Patient education, health promotion, and safety of commonly used drugs".)

BASIC ANTEPARTUM CARE

Ultrasound examination — Frequent ultrasound examination is essential for monitoring triplet pregnancies. Standard office procedures for monitoring growth and viability of singleton pregnancies, such as measuring the fundal height and listening to the fetal heart rate, are not as effective for detecting problems in triplets. Ultrasound is also the only means for monitoring triplets for complications, such as congenital anomalies and twin-twin transfusion.

●Assessment of gestational age – In individuals who became pregnant as a result of an assisted reproductive technique, ultrasound examination of the pregnancy is generally first performed at six weeks of gestation, which is when the fetal heartbeat may first be detected. Online calculators (eg, the pregnancy due date and gestational age calculator [10]) and apps are available for calculating the estimated date of delivery and gestational age based on one of the following dates, as appropriate: date of ovulation, date of egg retrieval, date of insemination, or date of cleavage stage (day 3) or blastocyst (day 5) transfer. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight", section on 'Assigning an estimated date of delivery to pregnancies conceived by assisted reproduction'.)

In naturally conceived triplet pregnancies, assessment of gestational age and determination of the estimated date of delivery is the same as for singletons. (See "Prenatal assessment of gestational age, date of delivery, and fetal weight".)

●Determining chorioamnionicity – Determination of chorionicity and amnionicity, which is ideally performed between 8 and 13 weeks of gestation, is critical for risk assessment, counseling, and pregnancy management. For example, a dichorionic triamniotic triplet pregnancy is at risk for twin-twin transfusion syndrome (TTTS) and twin-anemia polycythemia sequence (TAPS), which worsen the perinatal prognosis; however, close fetal monitoring for these conditions and therapeutic intervention can improve outcome [11,12]. The procedure for and interpretation of chorioamnionicity is similar to that in twin pregnancies. (See "Twin pregnancy: Overview", section on 'Assessment of chorionicity and amnionicity' and "Twin-twin transfusion syndrome: Screening, prevalence, pathophysiology, and diagnosis" and "Twin anemia-polycythemia sequence (TAPS)".)

●Screening for congenital anomalies – The initial first-trimester ultrasound examination may detect abnormalities potentially associated with an adverse outcome. These include congenital anomalies, crown-rump length discordance (which can be associated with aneuploidy or TTTS), and enlarged nuchal translucency (NT; which can be associated with aneuploidy, some congenital anomalies, or TTTS). (See "Diagnosis and outcome of first-trimester growth delay" and "Enlarged nuchal translucency and cystic hygroma".)

At approximately 20 weeks of gestation, we perform a detailed ultrasound examination to survey the fetal anatomy in all triplet pregnancies. The examination is more challenging than in singletons because three fetuses need to be examined, a clear anatomic survey of each fetus can be difficult to obtain and may require a repeat examination, and any anomalies that are identified need to be associated with the correct fetus.

Structural abnormalities, particularly cardiac abnormalities, are more common in triplet pregnancies, mainly because of the higher incidence of abnormalities in monozygotic siblings (owing to the cleavage of the conceptus) compared with dizygotic siblings. Anomalies are generally discordant among the triplets, so management needs to consider both issues specific to the anomalous triplet(s) and the effects of the anomalies and their management on the nonanomalous triplet(s). (See "Twin pregnancy: Routine prenatal care", section on 'Screening for congenital anomalies'.)

●Labeling the triplets – It is important to use a consistent strategy for identifying and labeling each triplet over serial ultrasound examinations in the second and third trimesters. Each triplet may be identified based on its sex and orientation relative to the other triplets, although the orientation can change. Documentation of the sites of placental implantation (anterior, posterior, lateral) and the sites and types of placental cord insertion (eg, marginal versus central; normal versus velamentous) is also useful for labeling. Triplets may not deliver in the order expected from antenatal ultrasound (termed perinatal switch), especially when delivered by cesarean.

●Second- and third-trimester ultrasound monitoring – We base the timing and frequency of second- and third-trimester ultrasound examinations on chorionicity and amnionicity.

•Monochorionic triamniotic and dichorionic triamniotic triplets – Any multiple gestation with a shared chorionic sac (figure 1) places the involved fetuses at risk for TTTS, selective growth restriction, and TAPS. We follow an ultrasound protocol similar to that commonly used for monitoring monochorionic twin pregnancies (table 1) [13]. (See "Twin-twin transfusion syndrome: Screening, prevalence, pathophysiology, and diagnosis", section on 'Our approach to monitoring' and "Selective fetal growth restriction in monochorionic twin pregnancies".)

In a series of 152 monochorionic triamniotic triplet pregnancies, TTTS was the most common antenatal complication related to chorionicity and occurred in 27.6 percent of these pregnancies [14]. Selective fetal growth restriction was the second most common antenatal complication related to chorionicity and occurred in 16.4 percent. TAPS occurred in 4.6 percent.

•Monochorionic monoamniotic or dichorionic diamniotic triplets – Any multiple gestation with a shared amniotic sac (monoamniotic component) (figure 2) places the involved fetuses at high risk of cord entanglement and death from cord compression. Experts suggest admitting patients with this type of placentation to the hospital at 26 weeks of gestation to facilitate performance of one hour of continuous fetal heart rate monitoring every eight hours. (See 'Cord entanglement in monoamniotic multiples' below.)

We suggest not using Doppler velocimetry of umbilical cord vessels for routine monitoring of monoamniotic twins to detect altered flow suggestive of cord entanglement and compression [15]. Although high blood velocity in the umbilical vein [16,17], a notch in the umbilical artery waveform [18], or persistent absent end-diastolic flow [19] may suggest compromise of the fetoplacental circulation, these findings have poor specificity.

Multiple gestations with a shared amniotic sac are also at risk for TTTS, selective growth restriction, and TAPS. Ultrasound monitoring for these conditions is the same as that described above for triplets with a shared chorionic sac (monochorionic triamniotic and dichorionic triamniotic triplets).

•Trichorionic triamniotic triplets – Trichorionic triamniotic placentation (figure 3) is associated with more favorable perinatal outcomes than triplet pregnancies in which the fetuses share an amniotic sac or placenta/chorion [20,21]. Growth restriction is still a major concern, so starting at 20 weeks, ultrasound examination is generally performed every three to four weeks to monitor fetal growth. (See "Fetal growth restriction: Evaluation".)

Monitoring for TTTS and TAPS is unnecessary since the placenta is not shared.

Office visits — In the first half of pregnancy, office visits can be scheduled per usual obstetric standards for singleton pregnancy. We see patients weekly beginning at 24 weeks of gestation to closely monitor for signs/symptoms of preeclampsia and preterm labor. However, there is limited evidence that weekly visits improve outcomes. Others have recommended visits at 20, 24, 28, 32, and 34 weeks for trichorionic triamniotic triplets and at 20, 22, 24, 26, 28, 30, 32, and 34 weeks for monochorionic triamniotic and dichorionic triamniotic triplets [22]. Weekly visits are appropriate from 34 weeks until birth, which is typically scheduled by 35+6 weeks. (See 'Delivery' below.)

Physical and sexual activity — There is no consensus about physical activity for pregnant people carrying triplets given a lack of definitive data. Our activity recommendations are, in general, similar to those for pregnant people with singleton gestations, especially prior to 20 weeks of gestation. (See "Exercise during pregnancy and the postpartum period".)

After approximately 20 weeks of gestation, many pregnant people with uncomplicated triplet pregnancy will want to limit physical activity because of fatigue and physical discomfort; in the mid-to-late second trimester, the uterus enlarges to a size comparable to that of a singleton at term. These individuals can rest and reduce activity in and outside of the home, as needed.

Sexual intercourse does not appear to increase the risk of preterm birth [23]; abstinence is not necessary.

Weight gain — Evidenced-based weight gain and nutritional guidelines for triplet pregnancies are lacking. We use the following gestational weight gain targets, which reflect the higher end of National Academy of Medicine (formerly the Institute of Medicine [IOM]) gestational weight gain guidelines for twin pregnancies that go to term [24]:

●Body mass index (BMI) 18.5 to 24.9 kg/m² (normal weight) – 25 kg (54 lbs)

●BMI 25.0 to 29.9 kg/m² (overweight) – 23 kg (50 lbs)

●BMI ≥30.0 kg/m² (obese) – 19 kg (42 lbs)

However, almost no triplet pregnancies go to term. A more clinically practical recommendation is maternal weight gain of approximately 0.7 kg (1.5 lbs) per week and >16.2 kg (36 lbs) by 24 weeks of gestation since weight gain below this threshold has been associated with lower birth weights in triplets [25].

Some authorities believe that these gestational weight gain targets are too high. The target described above for pregnant patients with obesity is particularly controversial. For pregnant patients with obesity and a singleton gestation, gestational weight gain lower than that recommended by the National Academy of Medicine may be associated with better maternal and perinatal outcomes, and this may also be true for pregnant patients with obesity and triplet gestations.

Gestational weight gain and loss in pregnant patients with obesity is discussed in more detail separately, but available data are from singleton pregnancies. (See "Gestational weight gain", section on 'Overweight and obese pregnant people'.)

Micronutrients — Our recommendations for daily micronutrient supplementation are based on existing data for twin pregnancies, as described by the Society for Maternal-Fetal Medicine (table 2) [26]. One or two multivitamins or one prenatal vitamin may be consumed daily. The content of vitamins varies depending on the product selected. (See "Nutrition in pregnancy: Dietary requirements and supplements", section on 'Supplements and dietary intake that can be harmful'.)

Preeclampsia prophylaxis — Low-dose aspirin should be initiated between 12 and 28 weeks (optimally before 16 weeks) and continued daily until delivery. (See 'Preeclampsia' below.)

Aneuploidy screening and diagnosis — We suggest offering genetic counseling to all pregnant people with triplet gestations to discuss their risk of aneuploidy in one or more fetuses. The risk of aneuploidy in a trizygotic triplet pregnancy is higher than in a singleton or dizygotic twin pregnancy since there are three independent fetal risks for aneuploidy. The pregnancy trisomy 21 risk of a 28-year-old individual carrying a trizygotic triplet pregnancy is similar to the pregnancy trisomy 21 risk of a 35-year-old individual carrying a singleton [27]. Thus, the conventional application of advanced maternal age as applied to aneuploidy risk may be considered to be a maternal age ≥28 years at the estimated date of delivery.

●Screening – The distribution of NT measurements is the same in triplets as it is in singletons, so NT can be used to screen for trisomy 21 and other anomalies [28]. Increased NT (defined as greater than the 95^th percentile for gestational age) has been validated as a screening test for trisomy 21 and trisomy 18 in triplets based on one study [29]. In this study, five of six aneuploid fetuses had increased NT (three cases of trisomy 21, one of trisomy 18, and one of monosomy of chromosome X; a mosaic 45,X/46,XX was missed). (See "Enlarged nuchal translucency and cystic hygroma", section on 'Clinical significance'.)

No serum marker or cell-free DNA (cfDNA) screening test for aneuploidy has been validated in triplet gestations, and no study has published observed detection rates for Down syndrome and other common trisomies in triplet pregnancies. Given the rarity of triplet pregnancies and the reticence of providers to offer serum-based or cfDNA screening in this group, it is unlikely that the type of dataset now available for twins will ever be available for triplet pregnancies. However, with the limited data available and acknowledging an up to 20 percent test failure rate, the International Society for Prenatal Diagnosis (ISPD) position statement on cfDNA screening for Down syndrome in triplet gestations states cfDNA screening may be a potential option, but diagnostic testing should always be offered and the limitations of screening tests in triplet gestations should be stressed [30].

●Fetal diagnosis – Chorionic villus sampling (CVS) is one option for prenatal diagnosis of aneuploidy. This technique is particularly useful for pregnant people with high age-related risk of fetal aneuploidy who are planning multifetal pregnancy reduction. Because karyotype results generally are available prior to the reduction procedure, it is possible to identify and selectively reduce an aneuploid fetus. However, CVS is more difficult in triplet than singleton gestations, and the patient must understand that it can be difficult to be certain that all three placentas have been sampled rather than one placenta sampled twice and another missed altogether. The risk of a sampling error in triplets and higher order gestations was 1.2 percent in one study [31]. (See "Chorionic villus sampling", section on 'Multiple gestations'.)

Genetic amniocentesis is another option for prenatal diagnosis. The procedure-related pregnancy loss rate is probably similar to that after genetic amniocentesis in a singleton pregnancy. (See "Diagnostic amniocentesis", section on 'Multiple gestation'.)

Screening for neural tube defects — All triplets should undergo a focused anatomic survey of the neural tube in the second trimester, given that serum screening for neural tube defects with maternal serum alpha-fetoprotein has not been validated in triplets. (See "Neural tube defects: Overview of prenatal screening, evaluation, and pregnancy management", section on 'Ultrasound examination'.)

Screening for gestational diabetes — Since triplet pregnancies are at high risk for gestational diabetes when compared with singletons (12.8 versus 2.9 percent, respectively, in one study [32]) and a high proportion of these patients (in the author's practice) have insulin resistance related to polycystic ovary syndrome, this author agrees with others [32] who recommend screening for diabetes early in pregnancy (eg, at the first or second prenatal visit). If this screen is negative, screening is repeated at 24 to 28 weeks of gestation.

Screening tests and management of diabetes are the same as in pregnant people with singleton pregnancies and described in detail separately. (See "Gestational diabetes mellitus: Screening, diagnosis, and prevention" and "Gestational diabetes mellitus: Glucose management and maternal prognosis".)

Screening for anemia — Assessment for anemia is performed at 24 to 28 weeks along with screening for gestational diabetes. Patients with anemia should be evaluated for the cause, which is often iron deficiency. Treatment of iron deficiency anemia in pregnancy is discussed separately. (See "Anemia in pregnancy", section on 'Treatment of iron deficiency'.)

Antepartum fetal monitoring — There are no evidence-based guidelines regarding when and how often to perform antepartum fetal monitoring in triplets (see "Overview of antepartum fetal assessment"). Fetal testing is based on chorioamnionicity:

●Monochorionic triamniotic and dichorionic triamniotic triplets – We obtain a weekly biophysical profile score starting at 28 weeks of gestation because all of these pregnancies are at high risk for fetal complications because of the shared chorionic sac. Ultrasound allows identification of each fetus and thus avoids the technical difficulties encountered when performing nonstress tests in higher order multiples [33]. However, nonstress testing is an acceptable alternative.

●Monochorionic monoamniotic or dichorionic diamniotic triplets – We suggest monitoring these triplets three times daily with one hour of continuous fetal heart rate monitoring when the mother is hospitalized at approximately 26 weeks of gestation. The goal is to detect decelerations, which suggest cord entanglement with cord compression in the shared amniotic sac, and this is more readily accomplished with prolonged fetal heart rate monitoring with the biophysical profile. (See 'Cord entanglement in monoamniotic multiples' below.)

●Trichorionic triamniotic triplets – We obtain a weekly biophysical profile score beginning at 32 weeks, based on evidence that dichorionic twins are at increased risk for stillbirth with advancing gestational age [34]. (See "Overview of antepartum fetal assessment".)

When results of fetal monitoring of a singleton preterm fetus are nonreassuring, the decision to intervene is determined by whether the fetus's risk from remaining in utero exceeds that from preterm birth. In multiple gestations, an ethical dilemma arises when one fetus is in jeopardy but the others are not. These decisions are complex and should be made jointly with, at a minimum, the parents, a maternal-fetal medicine specialist, and a neonatologist.

Monitoring for preterm labor — Preterm birth is the most common cause of death and morbidity in triplet gestations. We educate patients about the signs and symptoms of preterm labor but do not perform routine digital cervical examination, fetal fibronectin screening, or home uterine activity monitoring, as these interventions have no proven benefit on pregnancy outcome. (See 'Risk for preterm birth' below.)

Role of sonographic cervical length measurement — We do not measure cervical length in triplet pregnancies. Although this is a common screening test for prediction of preterm birth in singleton and twin pregnancies, a short cervical length was not a sensitive screening test for prediction of preterm birth in triplets in the three retrospective studies that evaluated this issue [35-37]. In all of these studies, the median cervical length was over 30 mm up to approximately 24 weeks and then declined, but no threshold was useful for prediction of preterm birth. Furthermore, in contrast to singleton and twin pregnancies, the limited data on the efficacy of any intervention (eg, progesterone supplementation, cerclage) for preventing preterm birth in patients with triplets and short cervical length suggest no benefit [38-40].

POTENTIAL COMPLICATIONS

Spontaneous fetal reduction — A substantial number of triplet gestations undergo spontaneous loss of one sac in the first trimester, which is referred to as a "vanishing twin." The rate of loss correlates with the initial number of gestational sacs. In one study, spontaneous reduction of one or more gestational sacs and/or embryos occurred in 53 percent and loss of all three sacs occurred in 6 percent of 132 triplet pregnancies diagnosed before 12 weeks [41]. Most losses occurred before the ninth gestational week.

The triplet pregnancies that experienced spontaneous reduction delivered earlier than naturally occurring pregnancies with the same number of fetuses (eg, triplets-to-singletons delivered 10 days earlier than naturally occurring singletons, triplets-to-twins delivered four days earlier than naturally occurring twins) [41].

Risk for preterm birth — Preterm birth is the most common cause of death and morbidity in triplet gestations. Iatrogenic preterm birth is as common as spontaneous preterm birth in some series [42].

In 2020, 98.7 percent of triplets delivered before 37 weeks of gestation in the United States, and 65.8 percent delivered before 34 weeks of gestation [43]. Ninety-five percent of triplets were low birth weight (<2500 g), and 36 percent were very low birth weight (<1500 g). By comparison, 2.1 percent of singletons delivered before 34 weeks, and 1.1 percent weighed <1500 g. The mean gestational age of delivery for triplets is approximately 32 weeks versus 38.7 weeks in singletons [44].

Potentially useful interventions — Multiple interventions have been investigated to reduce the risk for preterm birth. None have proven efficacious; however, administration of corticosteroids and magnesium sulfate may reduce neonatal morbidity, as in singleton pregnancies.

●Antenatal corticosteroids for fetal maturation – For triplets that are not monoamniotic, we administer a course of betamethasone if we believe the clinical findings suggest an increased risk for birth within the next seven days since steroids are most effective within this time frame. Examples include patients who experience ruptured membranes or threatened preterm labor or who develop a maternal or fetal disorder that may require preterm birth within days. Routine universal steroid administration to triplet pregnancies is not warranted, as the overall frequency of birth within seven days was <10 percent before 32 weeks in one study [45]; thus, many triplet pregnancies that received an early course of steroids would need repeated courses to ensure exposure proximate to birth.

However, for monoamniotic triplets, we routinely administer a course of antenatal corticosteroids at 26 weeks when we admit the patient to the hospital for intensive fetal monitoring. These pregnancies are at high risk for early unexpected birth. (See "Monoamniotic twin pregnancy (including conjoined twins)".)

Standard betamethasone doses are administered; there is no convincing evidence that the dose should be increased with an increasing number of fetuses.

We suggest a second course of antenatal corticosteroids if it has been more than a week since the prior course, the patient is at increased risk for preterm birth within the next seven days, and the pregnancy is less than 34 weeks. We do not administer steroids after 34 weeks as no data are available on efficacy in multiple gestations late in gestation. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on '34+0 or more weeks'.)

The value of antenatal corticosteroid therapy is well-established in singleton pregnancies, but neonatal outcomes after in utero exposure to corticosteroids have not been examined in randomized trials of triplet gestations, and the magnitude of benefit in these pregnancies is less clear [46-48]. In the United States, the National Institutes of Health recommends administration of one course of antenatal corticosteroids (unless contraindicated) irrespective of the fetal number. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on 'Multiple gestation' and "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on 'Evidence of efficacy'.)

●Magnesium sulfate for neuroprotection – We suggest magnesium sulfate for neuroprotection for those triplet pregnancies at risk for imminent delivery (ie, within 24 hours) between 23+0 and 31+6 weeks. We use the Marret regimen (4 g magnesium sulfate bolus over 30 minutes with no continuous infusion [49]) because omitting the continuous infusion may reduce the risk for pulmonary edema, which may be more common in triplet pregnancies receiving this drug [50]. Other regimens (eg, 4 g bolus with 1 g/hour continuous infusion) can also be used. (See "Neuroprotective effects of in utero exposure to magnesium sulfate".)

●Delayed interval delivery – Typically, all fetuses of a triplet gestation are born within a short interval; however, in rare selected cases, the periviable birth of one or two fetuses may not require delivery of the other fetus(es) [51]. This is termed delayed interval delivery and may improve neonatal survival and reduce morbidity from very early preterm birth. Selection of candidates for delayed interval delivery and management of these rare pregnancies are reviewed separately. (See "Multifetal gestation: Approach to delayed-interval delivery".)

Unproven interventions

●Tocolytics for treatment of preterm labor – The author does not use tocolytic drugs to treat preterm contractions or preterm labor in patients with triplets. No tocolytic has been proven to improve neonatal outcomes when compared with placebo [52-55], and tocolytic use in multiple gestations results in a higher incidence of adverse events, such as pulmonary edema [56].

Others may administer a tocolytic for 48 hours to allow for administration of betamethasone. A calcium channel blocker or nonsteroidal anti-inflammatory drug, depending on gestational age, is the preferred tocolytic. (See "Inhibition of acute preterm labor".)

●Prophylactic tocolytics – There is no role for the prophylactic use of tocolytic agents in any multiple gestation, including triplets. There has been no proven reduction in the incidence of preterm birth, low birth weight, or neonatal mortality [57]. Moreover, the prolonged use of betamimetics has been linked to an increased risk of adverse maternal cardiovascular events including maternal death [58].

●Prophylactic cerclage – Prophylactic cerclage (defined as a cerclage placed only because of triplet pregnancy) in patients without a history of cervical insufficiency does not appear to prolong gestation or improve neonatal outcomes [59]. In a retrospective cohort study of over 7000 triplet deliveries in the United States with risk factors for cervical insufficiency, the cerclage and noncerclage groups had similar gestational age at delivery and risk of preterm birth at <34 and <32 weeks [60]. However, cerclage was associated with a higher risk of the composite outcome of neonatal complications (aOR 1.5, 95% CI 1.1-2.2).

In small observational studies of triplet gestations with asymptomatic cervical shortening during serial sonographic surveillance of cervical length, placement of an ultrasound-indicated cerclage for cervical length <25 mm did not result in any improvement in neonatal outcome compared with expectant management [61,62].

●Prophylactic pessary – Use of a pessary to reduce the risk of preterm birth in triplets is not recommended. The largest randomized trial of use of prophylactic pessaries in over 800 unselected multiple gestations reported the intervention did not decrease the incidence of poor perinatal outcomes [63].

●Bed rest – There is no convincing evidence that bed rest improves pregnancy outcome in triplets, and it may be harmful due to the risk for thrombosis and deconditioning. In a systematic review of six randomized trials that assessed the effectiveness of strict or partial bed rest at home or in the hospital compared with no activity restriction in patients with a multiple pregnancy (twins or triplets), the intervention did not reduce preterm birth or perinatal mortality, but the quality of evidence was low [64].

●Progesterone supplementation – Progesterone supplementation is not recommended to reduce the risk of preterm birth because of absence of data showing benefit. In an individual patient data meta-analysis of three placebo-controlled randomized trials of hydroxyprogesterone caproate supplementation of asymptomatic patients with triplet pregnancies, supplementation did not result in a statistical reduction in preterm birth <28, 32, or 34 weeks or composite adverse perinatal outcome [65]. Of note, one trial found that hydroxyprogesterone caproate resulted in a significant increase in the number of midtrimester fetal losses (13 in 56 versus 0 in 25 in the placebo group) [38]. No trials have evaluated use of vaginal progesterone to reduce the risk of preterm birth in unselected triplet gestations or in triplet gestations with short cervical length.

Preeclampsia — The frequency of preeclampsia is higher in triplet pregnancies than in singleton gestations (10 versus 3 to 5 percent) [66]. Preeclampsia occurs earlier and is more severe in multiple gestations, and HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelet count) is more likely [67].

The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support the United States Preventive Services Task Force recommendation of low-dose aspirin to reduce the occurrence of preeclampsia and its associated complications of preterm birth and intrauterine growth restriction in multifetal gestations [68,69]. Low-dose aspirin should be initiated between 12 and 28 weeks (optimally before 16 weeks) and continued daily until delivery. The daily dose ranges from 81 to 162 mg depending on the formulation available. (See "Preeclampsia: Prevention", section on 'Candidates'.)

Late fetal demise — The rate of fetal demise after 22 weeks of gestation is related to chorioamnionicity; in one study, fetal demise occurred in 0.8 percent of trichorionic triplet pregnancies (12 out of 1521) versus 2.7 percent of monochorionic triamniotic triplet pregnancies (4 out of 150) [20].

Although no study has specifically examined the outcomes of survivors of co-triplet demise, this risk likely depends on whether they shared a chorionic sac with the demised triplet. For example, monochorionic survivors of a co-twin fetal demise have higher rates of subsequent demise, preterm birth, and neurodevelopmental impairment than dichorionic survivors of a co-twin fetal demise. (See "Twin pregnancy: Management of pregnancy complications", section on 'Death of one twin'.)

After demise of one or two triplets with monochorionic placentation, injury to the surviving fetus or fetuses is thought to occur instantaneously; thus, immediate delivery will not prevent adverse outcomes related to this event [70]. We base birth timing on the usual standards for the remaining twin or singleton gestation but implement fetal surveillance with weekly biophysical profiles (nonstress tests are a reasonable alternative) and serial ultrasound growth scans.

Fetal growth restriction or discordant growth — Fetal growth is monitored by ultrasound examination; initiation and frequency are guided by the type of placentation, as described above. (See 'Ultrasound examination' above.)

We diagnose fetal growth restriction by the same criteria used for singleton pregnancies (see "Fetal growth restriction: Screening and diagnosis"). Because triplet growth starts to deviate from singleton growth in the third trimester [71-74], use of these criteria may overdiagnose impaired fetal growth. For this reason, several authors have published growth tables specific for triplet pregnancies (medians, 10^th and 90^th percentiles) [75-78]. Whether these tables perform better for detecting fetuses at increased risk of adverse fetal/neonatal outcome is unknown.

Discordant growth of multiples is usually defined as a 20 to 25 percent difference in sonographic estimated fetal weight (EFW) of the smaller compared with the larger fetus (difference of larger minus smaller EFW divided by larger EFW). Discordance may be a marker for structural or genetic anomalies, infection, twin-twin transfusion syndrome (TTTS), or placental insufficiency.

Based on twin studies, evidence of growth restriction of one or both fetuses is a stronger predictor of adverse neonatal outcome than growth discordance alone. Management of growth restriction and growth discordance is based on the etiology. (See "Fetal growth restriction: Evaluation".)

Twin-twin transfusion — As discussed above, triplets with shared chorions are monitored for TTTS (see 'Ultrasound examination' above). Discordant amniotic fluid volume (polyhydramnios/oligohydramnios sequence) suggests TTTS. (See "Twin-twin transfusion syndrome: Screening, prevalence, pathophysiology, and diagnosis".)

Laser coagulation is an effective treatment, even in triplets. (See "Twin-twin transfusion syndrome: Management and outcome", section on 'Triplet pregnancies'.)

Twin-anemia polycythemia sequence — Twin-anemia polycythemia sequence (TAPS) is uncommon in triplets; few cases have been reported [79,80]. Treatment is the same as in twin pregnancies complicated by TAPS. (See "Twin-twin transfusion syndrome: Management and outcome", section on 'Twin anemia polycythemia sequence'.)

Cord entanglement in monoamniotic multiples — Monoamniotic placentation in any multiple gestation places the involved fetuses at high risk of cord entanglement and death from cord compression. (See "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Cord entanglement'.)

As discussed above, to reduce this risk, we admit these patients to the hospital at 26 weeks of gestation for intensive fetal heart rate monitoring (one hour of continuous monitoring every eight hours), administer a course of antenatal corticosteroids, and deliver them by cesarean at 32 to 33 weeks of gestation. (See 'Delivery' below.)

Other complications — The following pregnancy complications are also more common in triplet pregnancies than singleton pregnancies. Diagnosis and management are similar to that in singleton pregnancies with the same complication.

●Nausea and vomiting of pregnancy. (See "Nausea and vomiting of pregnancy: Clinical findings and evaluation" and "Nausea and vomiting of pregnancy: Treatment and outcome".)

●Placental abruption has been reported in 1.6 percent of triplet pregnancies versus <1 percent of singleton pregnancies [66]. (See "Acute placental abruption: Pathophysiology, clinical features, diagnosis, and consequences" and "Acute placental abruption: Management and long-term prognosis".)

●Thrombocytopenia occurs in up to one-third of triplet gestations. The most common cause is preeclampsia [81]. (See "Preeclampsia: Clinical features and diagnosis" and "Preeclampsia: Antepartum management and timing of delivery".)

●Acute fatty liver of pregnancy has been reported in up to 7 percent of triplet pregnancies versus 1 in 10,000 singleton pregnancies [82]. (See "Acute fatty liver of pregnancy".)

●Intrahepatic cholestasis of pregnancy is observed more commonly in multiple gestations. (See "Intrahepatic cholestasis of pregnancy".)

●Multiple gestation is a risk factor for uterine atony resulting in postpartum hemorrhage, transfusion, and possibly hysterectomy. (See "Overview of postpartum hemorrhage".)

●Postpartum depression and other psychological disorders are more common after a multiple birth [8,83,84]. (See "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis" and "Severe postpartum unipolar major depression: Choosing treatment".)

●Multiple gestation has been associated with an increased risk for placenta previa [85], which may be related to the large placental volume in multiples and increased exposure to assisted reproductive techniques [86]. (See "Placenta previa: Epidemiology, clinical features, diagnosis, morbidity and mortality" and "Placenta previa: Management".)

DELIVERY

Timing — Birth timing is based on amnionicity. We suggest the following:

●Monoamniotic or diamniotic triplets – These triplets are delivered by cesarean at approximately 32+4 weeks of gestation (ie, between 32+0 to 32+6 weeks) based on extrapolation of the finding that the in utero risk of fetal demise of a monoamniotic multiple gestation exceeds the risk of a postnatal nonrespiratory complication at this gestational age [87].

●Triamniotic triplets – Uncomplicated triplet pregnancies with three amniotic sacs, whether monochorionic, dichorionic, or trichorionic, are delivered between 35+0 and 35+6 weeks of gestation. Earlier delivery is indicated in complicated pregnancies; timing depends on the individual clinical scenario.

In a review commissioned by the National Institute for Health and Clinical Excellence, the committee concluded that continuing an uncomplicated trichorionic triamniotic or a dichorionic triamniotic triplet pregnancy beyond 35+6 weeks of gestation would lead to an increased risk of fetal death, based on their clinical experience as no studies on birth timing in triplets was available [88].

Route of delivery — Cesarean birth is the preferred route for all triplet gestations. A review of data from a national database found that vaginal birth of triplets was associated with an increased risk for stillbirth and neonatal and infant deaths as compared with cesarean birth [89]. This finding was supported by a multicenter retrospective United States cohort study that reported the rate for successful attempted vaginal birth was only 16.7 percent (four triplet sets), and vaginal birth was associated with a higher risk of maternal transfusion and neonatal mechanical ventilation, as well as a trend toward increased composite neonatal morbidity [90]. However, obstetricians experienced in vaginal birth of multiple gestations can consider offering patients planned vaginal birth of triplets using a shared decision-making approach [91]. (See "Anesthesia for cesarean delivery" and "Twin pregnancy: Labor and delivery", section on 'Analgesia and anesthesia'.)

Multiple gestations are at increased risk for uterine atony, postpartum hemorrhage, and emergency hysterectomy [92], so preparation for these potential complications is important. (See "Overview of postpartum hemorrhage".)

Anesthesia — Neuroaxial anesthesia is recommended (see "Anesthesia for cesarean delivery", section on 'Choice of anesthetic technique'). It is particularly useful for those few patients with triplets attempting a vaginal birth, as it helps to facilitate operative delivery, external or internal version, and total breech extraction.

PERINATAL MORTALITY AND MORBIDITY — Preterm birth and low birth weight are the most common causes of death and morbidity in triplet gestations. In two population-based cohort studies, overall perinatal mortality was approximately 2.5 percent [20,93], and monochorionic triplet pregnancies had a 2.6-fold greater risk of perinatal death than trichorionic triplet pregnancies (odds ratio 2.6, 95% CI 1.17-5.76) [20]. The mean/median gestational age at birth was approximately 33 weeks of gestation in both studies, and neonatal morbidity was common, consistent with the early gestational age of these births [20,93]. (See "Neonatal complications of multiple births".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Multiple gestation".)

SUMMARY AND RECOMMENDATIONS

●Overview – Pregnant people with triplet pregnancies should be counseled about the specific issues and risks associated with these pregnancies, management of complications, and the recommendation for cesarean birth. Surveillance of triplet pregnancies includes more frequent ultrasound examinations and frequent office visits (discussed below), particularly after 20 weeks of gestation, due to the increased risk of maternal morbidity and perinatal morbidity and mortality. In the second half of pregnancy, these pregnancies are at increased risk for preterm birth, preeclampsia, or fetal growth discordance when compared with singletons. Many other issues are the same as in any pregnancy. (See 'Counseling' above and 'Perinatal mortality and morbidity' above.)

●Gestational weight gain – We use the following gestational weight gain targets, which reflect the higher end of National Academy of Medicine gestational weight gain guidelines for twins (see 'Weight gain' above):

•Body mass index (BMI) 18.5 to 24.9 kg/m² (normal weight): 25 kg (54 lbs)

•BMI 25.0 to 29.9 kg/m² (overweight): 23 kg (50 lbs)

•BMI ≥30.0 kg/m² (obese): 19 kg (42 lbs)

●Prenatal care

•Ultrasound examinations

-We perform an ultrasound in the first or early second trimester to ascertain if the triplet pregnancy is trichorionic, fully monochorionic, or has a monochorionic twin pair to help guide counseling and management. (See 'Ultrasound examination' above.)

-Cervical length measurement is not a sensitive screening test for prediction of preterm birth in multiple gestations, and there is no strong evidence that any intervention (eg, progesterone supplementation, cerclage) is beneficial for preventing preterm birth in patients with multiple gestation and short cervical length. (See 'Monitoring for preterm labor' above.)

-We suggest a focused anatomic survey in the second trimester to screen for neural tube defects rather than serum screening. (See 'Screening for neural tube defects' above.)

-Fetal growth is monitored by ultrasound examination; initiation and frequency are guided by the type of placentation, as described above. (See 'Ultrasound examination' above.)

We diagnose fetal growth restriction by the same criteria used for singleton pregnancies. Discordant growth of multiples is usually defined as a 20 to 25 percent difference in sonographic estimated fetal weight (EFW) of the smaller compared with the larger fetus (difference of larger minus smaller EFW divided by larger EFW). Discordance may be a marker for structural or genetic anomalies, infection, twin-twin transfusion syndrome, or placenta-mediated disease. (See 'Fetal growth restriction or discordant growth' above.)

•Genetic counseling – We offer genetic counseling to discuss the risk of aneuploidy in one or more fetuses. No serum marker or cell-free DNA screening test for aneuploidy has been validated in this population. Increased nuchal translucency (defined as greater than the 95^th percentile for gestational age) has been validated as a screening test for trisomy 21 and trisomy 18 but not for trisomy 13. (See 'Aneuploidy screening and diagnosis' above.)

•Preeclampsia prophylaxis – We prescribe daily low-dose aspirin after 12 weeks of gestation to reduce the occurrence of preeclampsia and its associated complications (preterm birth and growth restriction). (See 'Preeclampsia' above.)

•Screening for diabetes - We screen for diabetes at the first prenatal visit and, if negative, again at 24 weeks of gestation. (See 'Screening for gestational diabetes' above.)

•Reducing newborn risks from preterm birth – Multiple interventions have been investigated to reduce the risk for preterm birth; none have proven efficacious. However, administration of corticosteroids and magnesium sulfate may reduce neonatal morbidity from preterm birth. (See 'Risk for preterm birth' above.)

●Timing of delivery – Delivery timing is based on the type of amnionicity, irrespective of lung maturity. We deliver monoamniotic and diamniotic triplets at approximately 32+4 weeks of gestation (ie, between 32+0 and 32+6 weeks). Uncomplicated triplet pregnancies with three amniotic sacs, whether monochorionic, dichorionic, or trichorionic, are delivered between 35+0 and 35+6 weeks of gestation. Earlier delivery is indicated in complicated pregnancies; timing depends on the individual clinical scenario. (See 'Delivery' above.)

●Route of delivery – We suggest delivery by cesarean (Grade 2C). (See 'Route of delivery' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges David C. Jones, MD, who contributed to an earlier version of this topic review.