INTRODUCTION — Multiple births contribute disproportionately to perinatal and neonatal mortality and morbidity. (See "Perinatal mortality", section on 'Multifetal pregnancies'.)
The complications, outcome, and pediatric management of multiple births are reviewed here.
The following issues related to multiple births are discussed elsewhere in the program:
●Twin pregnancy including antenatal management. (See "Twin pregnancy: Overview" and "Twin pregnancy: Labor and delivery".)
●Monoamniotic twin pregnancy. (See "Monoamniotic twin pregnancy (including conjoined twins)".)
●Triplet pregnancy. (See "Triplet pregnancy".)
INCIDENCE — Twins and triplets naturally occur in approximately 1 in 80 and 1 in 8000 pregnancies, respectively, in the United States [1,2]. The incidence of spontaneous twins varies by country and is lower in Canada and South China [3,4].
Multiple pregnancies account for an increasing proportion of total pregnancies in the developed world because of older maternal age and the expanded use of fertility treatments [5,6]. In the United States, 36 percent of twin pregnancies and 77 percent of triplet and higher order pregnancies occur after infertility treatment [5]. (See "Twin pregnancy: Overview", section on 'Epidemiology'.)
Data regarding the incidence of multiple births in the United States is provided by the Multiple Births site for the National Center for Health Statistics, Center for Disease Control and Prevention. In the United States, both twin births and higher order multiple births appeared to be declining. Twin birth rate peaked in 2014 and for triplets and higher order pregnancies peaked in 1998 [7]. The decline in triplet and higher order multiple birth rates is due to changes in assisted reproductive technology. (See "Strategies to control the rate of high order multiple gestation", section on 'Limiting the multiple gestation risk of assisted reproductive technology'.)
TERMINOLOGY
●Zygosity
•Dizygotic (DZ), resulting from the fertilization of separate ova during a single ovulatory cycle
•Monozygotic (MZ), resulting from a single fertilized ovum that subsequently divides into two or more separate individuals. (See "Twin pregnancy: Overview", section on 'Relationship between chorionicity, amnionicity, and zygosity'.)
●Chorionicity – Chorionicity is determined by the number of chorionic (outer) membranes that surround the fetuses in a multiple pregnancy (figure 1).
•Monochorionic pregnancy – One membrane
•Dichorionic pregnancy – Two membranes
•Trichorionic pregnancy – Three membranes three, the pregnancy is trichorionic. (See 'Discordant growth' below and 'Twin-twin transfusion syndrome' below and "Twin pregnancy: Overview", section on 'Relationship between chorionicity, amnionicity, and zygosity'.)
●Amnionicity – Amnionicity is the number of amnions (inner membranes) that surround fetuses in a multiple pregnancy (figure 1). (See 'Monoamniotic twins' below and "Monoamniotic twin pregnancy (including conjoined twins)".)
•Monoamniotic pregnancy – One amnion (so that all fetuses share an amniotic sac)
•Diamniotic pregnancy – Two amnions
•Triamniotic pregnancy – Three amnions
ETIOLOGY OF MULTIPLE BIRTHS — The etiology of monozygotic (MZ) twinning is unknown. Dizygotic (DZ) twinning appears to result from ovulation of multiple follicles or transfer of multiple embryos during in vitro fertilization. The etiology and risk factors associated with dizygotic twinning are discussed separately. (See "Twin pregnancy: Overview", section on 'Epidemiology'.)
RISK FACTORS FOR COMPLICATIONS — Factors that increase the risk of complications in surviving infants of multiple births include:
●Monochorionic twins and dichorionic triplets – Monochorionic twin pregnancies (which are monozygotic) and dichorionic triplet pregnancies carry higher risks because the fetuses share a common placenta, which is associated with an increased risk of discordant growth and twin-twin transfusion. (See 'Discordant growth' below and 'Twin-twin transfusion syndrome' below and "Twin pregnancy: Overview", section on 'Relationship between chorionicity, amnionicity, and zygosity'.)
●Monoamniotic twins – Complications in monoamniotic twins include those seen in monochorionic twins (ie, discordant growth and twin-twin transfusion) and in addition, cord entanglement and conjoined twins, which only occur in monoamniotic twins. (See 'Monoamniotic twins' below and "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Fetal and neonatal'.)
●Order of delivery, as the first infant delivered has a lower risk of morbidity and mortality compared with subsequent infants. Data from twin births demonstrate that first-born infants have a lower risk of mortality and morbidity than the second twin. (See "Twin pregnancy: Overview", section on 'Neonatal and infant morbidity and mortality'.)
●Fetal death (See 'Fetal death: Complications for survivor' below.)
NEONATAL COMPLICATIONS AND RISK FACTORS — The complications discussed in the following sections contribute to the higher perinatal mortality and morbidity observed in multiple order births compared with singleton births at the same gestational age [7,8].
Preterm birth — The most common risk of multiple gestations is spontaneous preterm delivery, which is associated with increased perinatal mortality and short-term and long-term complications associated with immaturity [9-12]. These include hypothermia, respiratory abnormalities, patent ductus arteriosus, intracranial hemorrhage, hypoglycemia, necrotizing enterocolitis, infection, and retinopathy of prematurity. (See "Short-term complications of the preterm infant" and "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality".)
The risk of preterm delivery is greater with multiple than with singleton pregnancies
[13,14]. It increases from approximately 60 percent with twin gestations to >90 percent with triplet and quadruplet gestations and approaches 100 percent with quintuplet gestations [7]. Similarly, the incidence of birth weight <1500 g and gestational age <34 weeks increases with the order of multiples, from approximately 10 percent with twins to approximately 100 percent with quintuplets and higher order multiples (table 1).
As a result, a higher proportion of infants from multiple births are at risk for the complications associated with very low birth weight or prematurity.
Although data are limited and inconsistent, there is evidence that suggests preterm infants from multiple births are at increased risk for death and significant morbidity (eg, respiratory distress syndrome) compared with singletons born at the same gestational age [11,15,16].
Fetal (intrauterine) growth restriction — Fetal growth restriction (FGR; also referred to as intrauterine growth restriction) is defined as a fetus who does not fully achieve expected in utero growth potential. There is a higher rate of FGR in multiple compared with singleton births, which contributes to perinatal morbidity and mortality [8,17,18]. (See "Infants with fetal (intrauterine) growth restriction" and "Twin pregnancy: Overview", section on 'Fetal complications'.)
The growth of twins is not significantly different from that of singletons in the first and second trimesters. However, it appears that the rate of growth after 30 weeks gestation of twins of uncomplicated pregnancies is slower than that of singleton fetuses. Because of the decreased growth rate in the third trimester and the increased rate of preterm birth with increasing gestations, the average birth weight decreases as the number of fetuses increases. In the United States in 2019, the proportion infants with birth weight <2500 g increased from approximately 55 percent in twins to >90 percent in triplets and quadruplets and the proportion of infants with birth weight <1500 increased from approximately10 percent in twins to 34 percent in triplets and 61 percent in quadruplets (table 1) [7]. (See "Twin pregnancy: Routine prenatal care", section on 'Screening for fetal growth restriction and discordance'.)
Discordant growth — Discordant growth reflects the difference in birth weight between the largest and smallest infant of a multiple birth pregnancy. Increasing discordant growth is associated with increasing risk of neonatal death and morbidity [19-23].
Discordant growth is most commonly defined as the difference in weight between the largest and smallest infants calculated as a percentage of the birth weight of the larger infant [24]. Using this definition for twin births, discordance of <15 percent (considered concordant growth) occurs in 75 percent of twin gestations; discordance of 15 to 25 percent occurs in 20 percent of twin gestations, and discordance of ≥25 percent occurs in 5 percent of twin gestations.
For triplets and higher order multiple births, the same definition is commonly used, but it does not account for the birth weight of the middle infant(s). An alternative definition for triplets and higher order multiple births is symmetric growth when the birth weight of the middle infant is within 25 percent of the average of the largest and smallest infant. If the average is below this, the set is considered low skew; and above, high skew [25].
The potential mechanisms that contribute to discordance include differences in genetic potential, intrauterine crowding, unequal sharing of placental mass, and placental insufficiency [26].
The increasing risk of mortality and morbidity with discordance is illustrated by the following:
●From an analysis of a large data base of twin births, neonatal mortality (rate per 1000 live births) for the smaller twin increased with increasing discordance, from approximately 4 percent with concordant growth to 20 to 40 percent with discordance of ≥25 percent [21]. Discordance of ≥30 percent was also associated with increased neonatal mortality for the larger twin.
●In another large dataset, smaller preterm twins with birth weight <1500 g and discordance of ≥30 had higher mortality rates and were more likely to have significant morbidities (necrotizing enterocolitis, severe retinopathy of prematurity [ROP], bronchopulmonary dysplasia, and neurodevelopmental impairment) than smaller twins without discordance [23]
Congenital anomalies — Congenital anomalies are more common in multiple births, primarily due to increased risk in monozygotic (MZ) twins [27]
Early malformations — The following malformations that occur early in gestation are more common in MZ twins. This suggests that they are caused by the same factor that results in MZ twinning [27].
●Anencephaly (see "Anencephaly").
●Holoprosencephaly (see "Overview of craniofacial clefts and holoprosencephaly").
●Exstrophy of the cloaca malformation sequence (see "Clinical manifestations and initial management of infants with bladder exstrophy").
●VATER association (a constellation of malformations, including vertebral, anal, cardiac, tracheoesophageal, renal, and limb defects).
●Sacrococcygeal teratoma. (See "Sacrococcygeal teratoma".)
●Sirenomelia (see "Closed spinal dysraphism: Pathogenesis and types", section on 'Caudal regression or sacral agenesis').
●Conjoined twins (see 'Conjoined twins' below).
Only one twin is affected by the malformation in the majority of cases. In the 5 to 20 percent of cases in which twins are concordant for the defect, one twin often is more severely affected.
Placental vascular anastomoses — Anomalies due to abnormal placental vascular anastomoses occur in fetuses who share a common placenta (eg, monozygotic and monochorionic twins). The anastomoses can be artery-to-artery, vein-to-vein, and artery-to-vein.
Twin-twin transfusion syndrome
●Pathophysiology – Twin-twin transfusion syndrome (TTTS) results from unbalanced blood flow caused by artery-to-vein anastomoses, which are present in the placenta of the majority of monochorionic multiple pregnancies [28,29]. With preferential blood flow in severe cases, one twin becomes the donor and the other is the recipient, which may result in wide discordance in fetal growth [28]. (See "Twin-twin transfusion syndrome: Screening, prevalence, pathophysiology, and diagnosis", section on 'Pathophysiology'.)
●Clinical features
•Recipient twin – The recipient twin, the larger fetus in the amniotic sac with polyhydramnios, typically has a large umbilical cord, abdominal circumference, kidneys, and bladder. Polycythemia in the recipient fetus can lead to thrombosis or hyperbilirubinemia after birth. Excessive volume can lead to cardiovascular decompensation with cardiomegaly, tricuspid regurgitation, and ventricular hypertrophy; hydrops fetalis may also develop [30]. (See "Nonimmune hydrops fetalis", section on 'Twin gestation'.)
•Donor twin – The donor twin is the smaller fetus and is in the oligohydramniotic sac. This fetus may have severe growth restriction with anemia, hypovolemia, and renal insufficiency. Severe oligohydramnios can lead to adherence of the donor twin to the uterine wall ("stuck twin"), and to complications including pulmonary hypoplasia and deformations.
●Management – If needed, neonatal management includes resuscitation at birth and respiratory and cardiovascular support. (See "Neonatal resuscitation in the delivery room".)
•Recipient twin – In the recipient twin, a partial exchange transfusion may be required to treat significant polycythemia. In addition, neuroimaging may be needed to detect central nervous system (CNS) injury. (See "Neonatal polycythemia", section on 'Partial exchange transfusion'.)
•Donor twin – In the donor twin, rapid establishment of intravascular access may be necessary for volume expansion to treat hypotension, correct hypoglycemia, and transfuse packed red blood cells to treat anemia.
The fetal management of TTTS is discussed separately. (See "Twin-twin transfusion syndrome: Management and outcome".)
●Outcome – The prognosis of untreated severe TTTS in utero is poor; perinatal mortality rates of 70 to 100 percent are reported. Survivors have significant morbidity including neurologic, cardiac, and renal impairment. With advances in obstetrical management of TTTS (ie, fetoscopic laser ablation), mortality has decreased, and survivors have improved long-term outcome, as discussed separately. (See "Twin-twin transfusion syndrome: Management and outcome", section on 'Outcome of TTTS treated with laser ablation'.)
Artery-to-artery shunts (acardiac twins) — Artery-to-artery anastomoses, which are less common than arteriovenous connections, lead to severe abnormalities when the perfusion pressure of one twin overtakes that of the other, resulting in reversed arterial flow. Blood from the donor twin enters the recipient's iliac vessels so that the lower part of the body is perfused more than the upper part. This disorder is known as the twin reversed arterial perfusion (TRAP) sequence and causes acardius fetal malformation, which results in lack of a functioning heart in the recipient twin (acardiac twin). Acardia is lethal in the affected recipient twin. The heart of the donor or pump twin is typically structurally normal. However, the added circulatory burden often leads to cardiomegaly and heart failure that may progress to hydrops fetalis [31] (see "Nonimmune hydrops fetalis", section on 'Twin gestation'). This results in a mortality rate of 50 to 75 percent in the donor twin [32].
The diagnosis and fetal management of the TRAP sequence are discussed separately. (See "Twin reversed arterial perfusion (TRAP) sequence".)
Deformations — Deformations due to uterine crowding occur in both monozygotic and dizygotic multifetal pregnancies and are discussed separately. (See "Lower extremity positional deformations".)
Monoamniotic twins — Monoamniotic twin pregnancies result from division of a single fertilized oocyte, and the fetal membranes consist of one amnion and one chorion (figure 1). Although all multiple births are associated with an increased risk for neonatal complications and death compared with singleton births, monoamniotic twins are at increased risk of perinatal mortality and morbidity because of unique complications associated with sharing a single amniotic sac. (See "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Outcomes'.)
Conjoined twins — Conjoined twins occur when MZ twins fail to separate into two individuals as division occurs at or after day 13 postfertilization [33]. The conjunction ranges from simple joining of ectodermal tissues to the extreme case when one twin is contained within the other. The incidence ranges from 1 in 50,000 to 1 in 100,000 live births [33,34]. The ratio of females to males is 3:1.
●Diagnosis – The diagnosis of conjoined twins is often made on prenatal ultrasound scan performed as early as the 12th week of gestation. Typical features include a fixed position of the fetal heads, inability to detect separate bodies or skin contours, and the lack of separating membranes [33].
●Classification – Conjoined twins are classified by the site of their most prominent union, which is ventral or dorsal in 87 and 13 percent, respectively. The abnormality is named with the suffix pagus, which means fixed.
The distribution of ventral unions is as follows [35]:
•Cephalopagus – 11 percent
•Thoracopagus – 19 percent
•Omphalopagus – 18 percent
•Ischiopagus – 11 percent
•Parapagus (pelvis and variable trunk) – 28 percent
The distribution of the less frequent dorsal unions is as follows:
•Craniopagus – 5 percent
•Rachiopagus (vertebral column) – 2 percent
•Pygopagus (sacrum) – 6 percent
●Management – Management of conjoined twins begins when the diagnosis is made. Elective termination is often advised when there is a cardiac or cerebral fusion, as separation is rarely successful, and is often considered if severe deformities are anticipated after separation. If the pregnancy is continued, elective cesarean delivery is planned after lung maturation. (See "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Conjoined twins'.)
After birth, surgical separation can be performed or, depending upon the extent of the abnormality, nonoperative comfort care may be provided. Separation is performed emergently if one of the twins is dead, threatens the survival of the other twin, or has a life-threatening condition Elective separation allows stabilization of the infants, and extensive evaluation and planning. The survival rate for elective separation is approximately 80 percent for both twins, and is lower for emergency separation [33,36-38].
Other complications
●Cord entanglement – Cord entanglement may result in fetal loss or neurologic morbidity in surviving infants [39,40]. (See "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Cord entanglement' and "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Delivery'.)
●Congenital anomalies – Increased risk of congenital anomalies compared with dizygotic twins (26 versus 6 percent) and singletons due to increased risk of early malformations including conjoined twins and placental vascular anastomoses, which result in discordant growth usually caused by TTTS. (See 'Early malformations' above and 'Placental vascular anastomoses' above.)
Fetal death: Complications for survivor — Spontaneous fetal death in multiple births is common, particularly with monochorionic multiple births. The risk and management of fetal death in twin pregnancies are discussed separately. (See "Twin pregnancy: Overview", section on 'Vanishing twins' and "Twin pregnancy: Management of pregnancy complications", section on 'Death of one twin'.)
Data from twins have shown that single fetal death in the late second or during the third trimester is associated with increased morbidity and mortality of the co-twin [41-43]. Based on case series and reports, the following complications have been observed in patients who survived after the fetal death of a co-twin [44]:
●Increased risk of prematurity and fetal growth restriction
●CNS injury including cerebral palsy [45,46] (see "Cerebral palsy: Epidemiology, etiology, and prevention", section on 'Multiple births')
●Renal failure due to renal cortical necrosis [47,48]
●Small bowel atresia
●Gastroschisis
●Limb amputation
NEONATAL MANAGEMENT
Initial management — Neonatal management of multiple births should include preparation for problems that can occur more frequently in multiple births, including prematurity, fetal growth restriction, congenital anomalies, discordant growth, twin-twin transfusion, and conjoined twins. (See 'Neonatal complications and risk factors' above.)
Prior to delivery, the obstetrical team should provide information that identifies additional high risk factors so that the pediatric team can anticipate the needs of the infants in the delivery room, and whether the infant will require neonatal intensive care. If there is adequate time and there are concerns regarding neonatal outcome for one or more of the infants, antenatal counseling prior to delivery allows the team caring for the infants to know the wishes of the parents/caregivers depending on clinical circumstances. (See "Neonatal resuscitation in the delivery room", section on 'High-risk delivery' and "Neonatal resuscitation in the delivery room", section on 'Antenatal counseling'.)
The following information should be relayed to the teams providing neonatal care:
●What is the gestation of the pregnancy at the time of the anticipated delivery?
●Were antenatal corticosteroids administered to mothers at risk for delivery at a gestation ≤34 weeks?
●Is there evidence of fetal growth restriction? (See 'Fetal (intrauterine) growth restriction' above and "Infants with fetal (intrauterine) growth restriction" and "Fetal growth restriction: Screening and diagnosis".)
●Is the multiple pregnancy monochorionic? (See 'Terminology' above and "Twin pregnancy: Overview", section on 'Relationship between chorionicity, amnionicity, and zygosity'.)
•If the pregnancy is monochorionic, is there discordant growth or twin-twin transfusion syndrome? (See 'Neonatal complications and risk factors' above.)
●Is there evidence of congenital anomalies? (See 'Congenital anomalies' above.)
●Was there fetal demise, and if so when did it occur? (See 'Fetal death: Complications for survivor' above.)
●Is there any special concern about any of the fetuses?
The management in the delivery room and nursery includes:
●Adequate skilled personnel – An adequate number of healthcare providers who have the necessary skill sets to evaluate and initiate resuscitation procedures, so that there are dedicated personnel assigned to care for each individual infant in the delivery room.
●Premature infants – Management of multiples born prematurely should proceed as for singleton preterm births. This includes equipment and personnel to maintain body temperature and provide additional respiratory and cardiac support for each infant as needed in the delivery room and transport to the neonatal intensive care unit (NICU). (See "Neonatal resuscitation in the delivery room", section on 'Preterm infants'.)
●Infants with fetal growth restriction should be evaluated for anticipated complications such as hypothermia, hypoglycemia, and polycythemia. (See "Infants with fetal (intrauterine) growth restriction", section on 'Delivery room management'.)
●Infants should be thoroughly examined for congenital malformations. (See 'Congenital anomalies' above and "Birth defects: Approach to evaluation".)
●Monochorionic twins, especially those with discordant birth weights, should be evaluated for twin-twin transfusion syndrome, including a determination of hematocrit. Problems specific to the donor and recipient twins should be evaluated and treated. (See 'Twin-twin transfusion syndrome' above.)
Supporting breastfeeding — Human milk is recognized as the optimal feeding for all infants because of its proven health benefits for infants and their mothers. Although challenging, mothers of multiple infants can successfully breastfeed. Mothers who wish to breastfeed should be supported, and additional guidance given to optimize the feeding of the newborn infants in regards to milk production, feeding schedule, and positioning of infants. The rate of initiation and duration of breastfeeding in mothers of multiple births increased when mothers received prenatal consultation that includes information on the benefits of breast milk and strategy for successful breastfeeding [49,50]. (See "Infant benefits of breastfeeding" and "Maternal and economic benefits of breastfeeding".)
Mothers of multiple births encounter a variety of unique breastfeeding barriers and challenges, which result in lower breastfeeding rates compared with mothers of singleton births [51]. Counseling may include the following:
●Human milk for preterm infants – Infants of multiple gestations are often premature and may be unable to breastfeed. Mothers who want to breastfeed preterm need to establish and maintain milk production by milk expression. Their expressed breast milk can be given to their infants by gavage feeds, cup, or bottle. Milk expression and breastfeeding the premature infant are discussed in greater detail separately. (See "Breast milk expression for the preterm infant" and "Breastfeeding the preterm infant".)
●Milk production – Mothers of multiples should be counseled that they can provide adequate milk for their all their infants and that emptying the breast on a regular and frequent basis enhances milk production. The volume of milk released by mothers of twins is consistently twice that of mothers of singletons, and mothers of triplets are capable of producing 3 L of milk when the infants are 2.5 months of age [52]. There also are case reports of mothers able to produce sufficient milk to exclusively feed breast milk to quadruplets [53,54]
Donor human milk may be while mothers increase their milk production. Strategies to optimize milk production are discussed separately. (See "Breast milk expression for the preterm infant", section on 'Specific measures to optimize milk production'.)
●Feeding schedule ‒ Twins may breastfeed simultaneously, separately on an individual demand schedule, or separately on a modified demand schedule where one infant is fed on demand and the other follows immediately afterwards [51]. If the infants are fed individually, it is best to alternate breasts between the infants so that each breast receives balanced stimulation from the different infants.
●Feeding positions ‒ Simultaneous feeding saves time for the mother. Three positions are commonly used for simultaneous feeding [51].
•Double football – An infant's head is supported in each of the mother's hands with the infant's body lying under each of the mother's arms. This position is preferred if the infant does not have good head control as it allows the mother to provide additional head support (picture 1).
•Double cradle – Each infant is held like a singleton in the cradle position and the infants' bodies cross over the mother's abdomen.
•Combination – One infant is held in the cradle position and the other in the football position.
●Discharge planning — Lactation support should include development of a breastfeeding plan in partnership with the parents/caregivers, minimizing separation of the mother from her infants, and providing assistance to the parents/caregivers when the infants are discharged separately [55,56]. Because of the time commitment and intensity of feeding, mothers often require additional outside help that can focus on household chores and ancillary support so that mothers can focus on breastfeeding. If the mother desires, she can express milk so that other caregivers can feed the infant.
Family/caregiver support — Psychosocial support is needed to address the increased emotional stress, financial burden, and care issues that parents/caregivers of multiple births experience.
●Multiple birth parents/caregivers are at risk for depression or anxiety disorders [57-59]. Death of a twin or higher multiple contributes to depression and anxiety about the care of the surviving infant(s) [60].
●Preterm birth is also common in multiple gestations, is often associated with illness, and is an additional source of parental/caregiver stress [61]. Stress and anxiety may be increased by the separation of the mother from her infants if they require further hospitalization beyond the mother's discharge or transfer from the delivery hospital to a NICU at another institution.
●Multiple births have a major financial impact on the family/caregivers and society. Costs increase with decreasing gestational age predominantly due to neonatal intensive care [62].
●Parents/caregivers often experience difficulties in caring for twins or higher order multiples [63]. Although additional caregivers are frequently needed, the assistance provided by other family members/caregivers may be affected by socioeconomic status or cultural factors. Organizations of parents/caregivers of multiples may provide helpful coping strategies.
●Parents/caregivers of children with congenital anomalies and other disabilities need additional ongoing support and guidance.
OUTCOME
Neonatal mortality and major morbidity — Neonatal mortality and risk of major morbidity are similar for infants of multiple births compared with matched singleton births. In a large retrospective cohort study using databases from nine countries of preterm triplets and singletons matched for gestational age, sex, and country of birth born between 2007 and 2013, rates of death or severe morbidity were comparable (23.4 versus 24 percent) [64]. Severe morbidity was defined as severe neurologic injury, treated retinopathy of prematurity, or bronchopulmonary dysplasia. In this study, infants with major congenital anomalies were excluded.
However, the perinatal and infant mortality rates (IMR) of infants are higher in multiple than singleton pregnancies because of the higher-risk profile of multiple births with increased rates of prematurity, growth abnormalities, obstetric complications, and congenital anomalies.
Neurodevelopmental outcome
It remains uncertain whether survivors of twin and higher order multiple pregnancies are at increased risk for long-term neurodevelopmental impairment compared with individuals from singleton births after adjusting for confounding factors (eg, prematurity, and fetal growth restriction). In a systematic review of the literature, the reported increased risk of neuromotor impairment appeared to be partly due to the lower birth weight and gestational age of twins [65]. However, data were inconsistent, and there also were limitations of the studies included in the review, such as failure to adequately control for confounding factors and small number of patients. In a subsequent report, very preterm twin and singleton (gestational age <32 weeks) survivors had similar cognitive and neuropsychological outcomes with the exception of a lower verbal intelligence quotient at five years of age [66].
Other considerations include:
●Extremely preterm multiple births – Data are inconsistent regarding the neurodevelopmental outcome of the most extremely preterm infants, defined as either gestational age (GA) <28 weeks or those with a birth weight (BW) ≤1000 g [67-69]. It appears that differences noted during early childhood may attenuate with age.
●Growth discordance – Case series report an increased risk of adverse neurodevelopmental outcome in smaller twins or triplets with growth discordance including monochorionic twins [68,70,71]. However, preterm birth <33 weeks had a greater effect on neurodevelopmental outcome than fetal growth discordance.
●Cerebral palsy – The risk of cerebral palsy may also be increased in survivors of multiple births and is discussed separately. (See "Cerebral palsy: Epidemiology, etiology, and prevention", section on '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
●Introduction – Multiple births contribute disproportionately to perinatal and neonatal mortality and morbidity. Additional risk factors for perinatal mortality and morbidity include monoamniotic pregnancy (eg, cord entanglement), second or higher birth order, and death of another fetus during the late second or third trimester. (See 'Neonatal mortality and major morbidity' above and 'Neonatal complications and risk factors' above.)
●Risk factors for complications associated with multiple births – Risk factors for perinatal mortality and morbidity for multiple births include monoamniotic pregnancy (eg, cord entanglement), second or higher birth order, and death of another fetus during the late second or third trimester. (See 'Risk factors for complications' above.)
●Neonatal complications associated with multiple births
•Prematurity – Prematurity is the most common neonatal complication of multiple births; its incidence increases as fetal number increases. (See 'Preterm birth' above.)
•Fetal growth restriction – FGR is more common in multiple order than in singleton pregnancies. FGR is due primarily to either uterine crowding, or uteroplacental insufficiency. Selective or discordant growth restriction is more common in monochorionic multiple births, in which fetuses share a common placenta. Increasing discordance is associated with increasing mortality and morbidity (eg, twin-twin transfusion). (See 'Fetal (intrauterine) growth restriction' above and 'Twin-twin transfusion syndrome' above.)
•Congenital anomalies – Congenital anomalies are more common in multiple births primarily due to increased risk in monozygotic twins. Causes of congenital anomalies include early malformations, anomalies due to abnormal placental vascular anastomoses in monochorionic pregnancies (eg, acardiac twins), and deformations due to uterine crowding. (See 'Congenital anomalies' above.)
●Management – Neonatal management includes being prepared for the issues that occur more commonly at the birth of multiple infants. Prior to delivery, the obstetrical team should provide information that identifies additional high-risk factors so that the pediatric team can anticipate the needs of the infants in the delivery room. In the delivery room, there should be adequate staffing of skilled providers to provide care for each individual infant. The care of the infants is individualized depending on the presence of complications due to prematurity (eg, hypothermia, respiratory distress), FGR (hypothermia, hypoglycemia, and polycythemia), and twin-twin transfusion, and the presence of severe congenital anomalies. (See 'Neonatal management' above.)
●Breastfeeding support – Although challenging, mothers of twins and triplets can successfully breastfeed. Mothers who wish to breastfeed should be supported, and additional guidance should be given to optimize the feeding of her newborn infants in regards to milk production, timing, and positioning of infants. (See 'Supporting breastfeeding' above.)
●Psychosocial support – Psychosocial support is needed to address the increased emotional stress, financial burden, and care issues that parents of multiple births experience. (See 'Family/caregiver support' above.)
●Outcome
•Mortality – Neonatal mortality and morbidity rates are higher in multiple than in singleton births because of increased rates of in multiple than singleton pregnancies because of the higher-risk profile of multiple births with increased rates of prematurity, growth abnormalities, obstetric complications, and congenital anomalies.(See 'Neonatal mortality and major morbidity' above and 'Neonatal complications and risk factors' above.)
•Neurodevelopmental outcome – It is unclear whether twins are at increased risk for long-term neurodevelopmental impairment after adjusting for confounding factors. However, it appears that risk of cerebral palsy may be increased in survivors of multiple births, especially in those exposed to a fetal demise. (See 'Outcome' above and 'Fetal death: Complications for survivor' above.)
