Neonatal complications of multiple births

INTRODUCTION — Multiple births contribute disproportionately to neonatal mortality and morbidity. (See "Perinatal mortality", section on 'Multifetal pregnancies'.)

The neonatal complications of multiple births are reviewed here. Complications related to preterm birth (which are the main neonatal consequences of multiple gestation pregnancy) are reviewed in detail separately. (See "Overview of short-term complications in preterm infants" and "Overview of the long-term complications of preterm birth".)

Maternal complications and obstetric management of multiple gestation pregnancies are discussed is separate topic reviews:

●(See "Twin pregnancy: Overview".)

●(See "Twin pregnancy: Routine prenatal care".)

●(See "Twin pregnancy: Management of pregnancy complications".)

●(See "Twin pregnancy: Labor and delivery".)

●(See "Monoamniotic twin pregnancy (including conjoined twins)".)

●(See "Triplet pregnancy".)

INCIDENCE — Multiple pregnancies account for an increasing proportion of total pregnancies in the developed world because of older maternal age and the expanded use of assisted reproductive technologies [1,2]. In the United States, approximately one-third of twin pregnancies and more than three-quarters of triplet and higher order pregnancies occur after infertility treatment [1]. (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, multiple births appear to be declining. The twin birth rate peaked at 3.4 percent in 2014 and declined slightly to 3.1 percent in 2021 [3]. Rates for triplets and higher order births have declined from approximately 15 per 10,000 births the late 1990s to 8 per 10,000 births in 2021 [3]. 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 — The following terms are used to describe the number of oocytes (zygosity), outer membranes (chorionicity), and inner membranes (amnionicity) in multiple gestation pregnancies. The relationship between zygosity, chorionicity, and amnionicity is summarized in the figure (algorithm 1) and discussed in greater detail separately. (See "Twin pregnancy: Overview", section on 'Relationship between chorionicity, amnionicity, and zygosity'.)

●Zygosity

•Dizygotic (DZ; sometimes called fraternal twins), resulting from the fertilization of separate oocytes during a single ovulatory cycle

•Monozygotic (MZ; sometimes called identical twins), resulting from a single fertilized oocyte that subsequently divides into two or more separate individuals

●Chorionicity – Chorionicity is determined by the number of chorionic (outer) membranes that surround the fetuses in a multiple pregnancy (figure 1).

•Monochorionic – One membrane

•Dichorionic – Two membranes

•Trichorionic – Three membranes

●Amnionicity – Amnionicity is the number of amnions (inner membranes) that surround fetuses in a multiple pregnancy (figure 1).

•Monoamniotic – One amnion (so that all fetuses share an amniotic sac) (see "Monoamniotic twin pregnancy (including conjoined twins)")

•Diamniotic – Two amnions

•Triamniotic – Three amnions

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 (TTTS)' below.)

●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 'Other perinatal complications' below and "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Fetal and neonatal outcomes'.)

●Number of multiples – The risk of preterm birth prematurity-related complications increases with increasing number of multiples (table 1) [3].

●Preterm birth – The risk of prematurity related complications increases with decreasing gestational age. (See "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality" and "Overview of short-term complications in preterm infants" and "Overview of the long-term complications of preterm birth".)

●Order of delivery – The risk of morbidity and mortality is higher in the second-born infant (and subsequent infants) compared with the first infant delivered. The reasons for this are multifactorial and are likely related to lower birth weight; higher frequency of malpresentation, cord prolapse, and abruption; and a higher frequency of obstetric maneuvers at delivery of the second-born and subsequent infants. (See "Twin pregnancy: Overview", section on 'Neonatal/infant morbidity and mortality'.)

●Fetal death – Fetal death of one twin increases the risk of complications in the surviving twin. (See 'Fetal death: Complications for survivor' below.)

NEONATAL COMPLICATIONS — The complications discussed in the following sections contribute to the higher mortality and morbidity observed in multiple order births compared with singleton births [4,5].

Preterm birth — The most common neonatal complication of multiple gestations is preterm delivery [6,7]. Preterm birth is associated with increased risk of infant mortality and short- and long-term prematurity-related complications [8-11]. These include respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), sepsis, patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP). (See "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality" and "Overview of short-term complications in preterm infants" and "Overview of the long-term complications of preterm birth".)

The risk of preterm birth increases with the number of multiples (table 1) [3]. For example, the risk of early preterm birth (ie, birth before 34 weeks completed gestation) is approximately 2 percent for singleton gestations, 20 percent for twin gestations, 65 percent for triplet gestations, and >95 percent for quadruplet or higher order gestations [3].

Although data are limited and inconsistent, there is evidence that suggests preterm infants from multiple births are at increased risk for mortality and morbidity (eg, RDS, BPD) compared with singletons born at the same gestational age (GA) [10,12,13]. However, in a large retrospective cohort study using databases from nine countries comparing preterm triplets with singletons matched for GA, sex, and country of birth, mortality rates were the same in both groups (6 percent in each) [14]. Rates of severe morbidity (defined as severe neurologic injury, treated ROP, or BPD) were also similar in both groups (18 percent in each).

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 [4,15,16]. (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 approximately 10 percent in twins to 34 percent in triplets and 61 percent in quadruplets (table 1) [3]. (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 (BW) between the largest and smallest infants of a multiple birth pregnancy. Greater degrees of discordance are associated with higher risk of neonatal morbidity and mortality [17-21]. (See "Twin pregnancy: Management of pregnancy complications", section on 'Growth restriction and discordance'.)

Discordant growth is defined by the difference in BW between the smaller and larger infant, most commonly calculated as a percentage of the larger infant’s BW [22]. For twin births, discordance of <15 percent is within the range considered normal and is seen in approximately three-quarters 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 BW of the middle infant(s). An alternative definition for triplets and higher order multiple births is symmetric growth when the middle infant’s BW 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 [23].

The potential mechanisms that contribute to discordance include differences in genetic potential, intrauterine crowding, unequal sharing of placental mass, and placental insufficiency [24].

Several studies have found that discordance is associated with increased risk of neonatal mortality and morbidity. In a study that analyzed data on all twin births in the United States from 1995 through 1997, the infant mortality rate among discordant twins who were ≥30 percent smaller than the larger twin was 43 deaths per 1000 live births, a rate that was more than 10-fold higher than that of nondiscordant twins (4 deaths per 1000 live births) [19]. In another large study, smaller preterm twins with birth weight <1500 g and discordance of ≥30 percent had higher mortality rates and were more likely to have significant morbidities (NEC, severe ROP, BPD, and neurodevelopmental impairment) than smaller twins without discordance [21].

Congenital anomalies — Congenital anomalies are more common in multiple births, primarily due to increased risk in monozygotic (MZ) twins [25].

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 [25].

●Anencephaly (see "Anencephaly").

●Holoprosencephaly (see "Overview of craniofacial clefts and holoprosencephaly").

●Cloacal exstrophy (see "Body stalk anomaly and cloacal exstrophy: Prenatal diagnosis and management", section on 'Cloacal 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 "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Conjoined twins').

In most cases, only one twin is affected by the malformation. In the 5 to 20 percent of cases in which both twins are affected, one twin often has a more severely defect.

Deformations — Deformations due to uterine crowding occur in both monozygotic and dizygotic multifetal pregnancies and are discussed separately. (See "Lower extremity positional deformations".)

Twin-twin transfusion syndrome (TTTS) — TTTS results from unbalanced blood flow through placental intertwin vascular anastomoses that leads to hypovolemia in one twin (donor twin) and hypervolemia in the other (recipient twin). The diagnosis and antenatal management of TTTS are discussed in detail separately. (See "Twin-twin transfusion syndrome: Screening, prevalence, pathophysiology, and diagnosis" and "Twin-twin transfusion syndrome: Management and outcome".)

Uncommonly, acute intrapartum TTTS results in the following neonatal complications; these issues and their management are discussed in separate topic reviews:

●Need for resuscitation in the delivery room (see "Neonatal resuscitation in the delivery room")

●Acute anemia and possibly hypovolemic shock in the donor twin (see "Red blood cell (RBC) transfusions in the neonate" and "Neonatal shock: Management")

●Polycythemia in the recipient twin (see "Neonatal polycythemia")

Fetal death: Complications for survivor — Spontaneous fetal death in multiple births is common, particularly with monochorionic multiple gestations. 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'.)

Studies 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 [26-28]. The following complications have been observed in infants who survived after the fetal death of a co-twin [29]:

●Higher risk of preterm birth and fetal growth restriction

●Brain injury including cerebral palsy (CP) [30,31] (see "Cerebral palsy: Epidemiology, etiology, and prevention", section on 'Multiple births')

●Renal failure due to renal cortical necrosis [32,33]

●Small bowel atresia

●Gastroschisis

●Limb amputation

Other perinatal complications

●Twin reversed arterial perfusion (TRAP) sequence – TRAP sequence is a rare, unique complication of monochorionic twin pregnancy in which a severely anomalous twin with an absent or rudimentary heart ("acardiac twin") is perfused by its co-twin ("pump twin") via retrograde flow of deoxygenated blood through arterio-arterial anastomoses. The diagnosis and fetal management of the TRAP sequence are discussed separately. (See "Twin reversed arterial perfusion (TRAP) sequence".)

●Cord entanglement – Cord entanglement occurs in most monoamniotic twin pregnancies. Severe entanglements can result in fetal loss or neurologic morbidity in surviving infants [34,35]. (See "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Cord entanglement'.)

●Conjoined twins – Conjoined twins occur when MZ twins fail to separate into two individuals. Conjoined twins are classified by the site of their most prominent union as summarized in the figure (figure 2). Additional details regarding prenatal diagnosis and antenatal management are provided separately. (See "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Conjoined twins'.)

Postnatally, patients should be cared for by a multidisciplinary team at a center experienced in management of conjoined twins. The direction of care (surgical intervention versus comfort measures only) is determined by the extent and severity of the abnormalities and the values and preferences of the caregivers. Urgent surgical intervention may be needed in select cases if one of the twins dies, threatens the survival of the other twin, or has a life-threatening condition. However, in most cases, surgical separation can be performed electively after extensive evaluation and planning. The survival rate for elective separation is approximately 80 percent for both twins, and is lower for emergency separation [36-39].

Infant mortality — Mortality rates in the neonatal period (birth through 28 days) and during infancy (birth to one year of age) are higher among infants of twin and higher order multiple pregnancies compared with individuals from singleton births [5]. In the United States, infant mortality rates according to plurality are as follows [40]:

●Singletons: 0.5 percent

●Twins: 2.2 percent

●Triplets and higher order gestations: 6.4 percent

The increased risk of infant mortality observed in multiple gestation pregnancies is largely due to the impact of preterm birth and prematurity-related comorbidities. It remains uncertain whether the increased risk of infant mortality persists after accounting for confounding factors (eg, GA, BW, comorbidities). In a large retrospective cohort study using databases from nine countries comparing preterm triplets with singletons matched for GA, sex, and country of birth, mortality rates were the same in both groups (6 percent in each) [14]. Of note, infants with major congenital anomalies were excluded for this study.

A broader discussion of the risk of infant mortality in preterm infants is provided separately. (See "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality".)

Long-term neurodevelopmental impairment (NDI) — Infants of twin and higher order multiple pregnancies are at increased risk of long-term NDI (including CP, cognitive impairment, and other developmental disabilities) compared with individuals from singleton births, largely due to the impact of preterm birth. As with mortality risk, it is uncertain whether the increased risk of NDI persists after accounting for confounding factors (eg, GA, BW, comorbidities) [41-45].

Case series report an increased risk of NDI in smaller twins or triplets with growth discordance including monochorionic twins [44,46,47]. However, preterm birth had a greater effect on risk of NDI than fetal growth discordance.

The risk CP in survivors of multiple births is discussed separately. (See "Cerebral palsy: Epidemiology, etiology, and prevention", section on 'Multiple births'.)

A broader discussion of the risk of NDI in preterm survivors is provided separately. (See "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors".)

OVERVIEW OF NEONATAL MANAGEMENT

Coordination between care teams — Prior to delivery, the obstetrical team should provide information to the pediatric team to identify high-risk factors (eg, congenital anomalies, fetal growth restriction [FGR], twin-twin transfusion syndrome [TTTS]) so that the pediatric team can anticipate the needs of the infants in the delivery room. If there is adequate time and there are concerns regarding the prognosis 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? (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery".)

●Is there evidence of FGR? (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 TTTS? (See "Twin pregnancy: Management of pregnancy complications", section on 'Growth restriction and discordance' and "Twin-twin transfusion syndrome: Screening, prevalence, pathophysiology, and diagnosis".)

●Are there any congenital anomalies? (See 'Congenital anomalies' above.)

●Was there fetal demise, and if so when did it occur? (See 'Fetal death: Complications for survivor' above.)

●Are there any other special concerns about any of the fetuses?

Initial management — Neonatal management of multiple births should anticipate problems that occur more frequently in multiple births, including prematurity, FGR/discordant growth, and congenital anomalies. (See 'Neonatal complications' above and "Neonatal resuscitation in the delivery room", section on 'Anticipation of resuscitation need'.)

Management in the delivery room and nursery is provided according to the same principles and practices that guide the care of all newborns. (See "Neonatal resuscitation in the delivery room" and "Overview of the routine management of the healthy newborn infant".)

Unique management issues for multiple births include:

●Adequate skilled personnel for each infant – In the delivery room, there should be adequate staffing of skilled providers to provide care for each individual infant. (See "Neonatal resuscitation in the delivery room", section on 'Training'.)

●Special care for preterm infants – For preterm multiples, management should proceed as for singleton preterm births. This includes equipment and personnel to maintain body temperature and provide additional respiratory and hemodynamic 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'.)

●Care for infants with FGR – Infants with FGR should be evaluated for anticipated complications such as hypothermia and hypoglycemia. (See "Infants with fetal (intrauterine) growth restriction", section on 'Delivery room management'.)

●Infants with TTTS should be evaluated for the associated neonatal complications (ie, anemia in the donor twin and polycythemia in the recipient twin). (See 'Twin-twin transfusion syndrome (TTTS)' 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. Studies have shown that the likelihood of initiating breastfeeding and duration of breastfeeding among mothers of multiple births increases when mothers receive prenatal consultation including information on the benefits of breast milk and strategy for successful breastfeeding [48,49]. The benefits of breastfeeding are discussed in detail separately. (See "Infant benefits of breastfeeding" and "Maternal and economic benefits of breastfeeding".)

Mothers of multiple births encounter a variety of unique breastfeeding challenges, which result in lower breastfeeding rates compared with mothers of singleton births [50]. Counseling may include the following:

●Human milk for preterm infants – Infants of multiple gestations are often born preterm and may be unable to breastfeed. Mothers who wish to breastfeed 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 for the preterm 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 while there are challenges to breastfeeding multiple infants, it is possible to provide adequate milk for their all their infants. Emptying the breast on a regular and frequent basis enhances milk production. Studies have demonstrated that the quantity and quality of breast milk produced by mothers of twins and higher multiples is adequate in most cases [50].

However, it may take time to establish adequate milk production and donor human milk may be needed in some cases. 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 [50]. 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 [50].

•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 [51,52]. 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 — It is important to provide psychosocial support to address the increased emotional stress, financial burden, and care issues that parents/caregivers of multiple births experience.

●Multiple birth parents/caregivers are at increased risk for depression or anxiety disorders [53-55]. (See "Postpartum unipolar major depression: Epidemiology, clinical features, assessment, and diagnosis", section on 'Screening'.)

●For infants born preterm and those with congenital anomalies or other disabilities, the associated care needs are an additional source of parental/caregiver stress [56]. Stress and anxiety may be increased by the separation if their infants require ongoing hospitalization after the mother's discharge.

●Multiple births have a major financial impact on the family/caregivers.

●Parents/caregivers often experience difficulties in caring for twins or higher order multiples [57]. 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.

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

●Risk factors for complications associated with multiple births – Multiple births contribute disproportionately to neonatal mortality and morbidity. Risk factors for mortality and morbidity in this population include (see 'Risk factors for complications' above):

•Monochorionic twin pregnancy or dichorionic triplet pregnancy

•Monoamniotic pregnancy (see "Monoamniotic twin pregnancy (including conjoined twins)")

•Higher number of fetuses (table 1)

•Preterm birth (see 'Preterm birth' above)

•Order of delivery (risk is higher in the second-born twin)

•Fetal death of one twin (see 'Fetal death: Complications for survivor' above)

●Neonatal complications associated with multiple births

•Preterm birth – Preterm birth and prematurity-related complications (respiratory distress syndrome [RDS], bronchopulmonary dysplasia [BPD], intraventricular hemorrhage [IVH], sepsis, patent ductus arteriosus [PDA], necrotizing enterocolitis [NEC], retinopathy of prematurity [ROP]) are the most common neonatal complications of multiple births. The risk of preterm birth increases as fetal number increases (table 1). (See 'Preterm birth' above.)

•Fetal growth restriction (FGR)/discordant growth – 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. (See 'Fetal (intrauterine) growth restriction' above and 'Discordant growth' above.)

•Congenital anomalies – Congenital anomalies are more common in multiple gestation pregnancies compared with singleton pregnancies. Malformations that occur in early gestation are more common in monozygotic twins and are likely caused by the same factor that results in monozygotic twinning. Examples include central nervous system malformations (eg, holoprosencephaly), closed spinal dysraphism, cloacal exstrophy, and sacrococcygeal teratoma. In addition, deformations due to uterine crowding later in gestation can occur in both monozygotic and dizygotic multifetal pregnancies. (See 'Congenital anomalies' above and "Twin pregnancy: Routine prenatal care", section on 'Screening for congenital anomalies' and "Lower extremity positional deformations".)

•Neurodevelopmental impairment (NDI) – Infants of twin and higher order multiple pregnancies are at increased risk of long-term NDI (including cerebral palsy [CP], cognitive impairment, and other developmental disabilities) compared with individuals from singleton births. This is largely due to the impact of preterm birth. However, it remains uncertain whether the increased risk of NDI persists after accounting for confounding factors (eg, gestational age, birth weight, comorbidities). (See 'Long-term neurodevelopmental impairment (NDI)' above and "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors" and "Cerebral palsy: Epidemiology, etiology, and prevention", section on 'Multiple births'.)

•Other – Other potential complications include:

-Twin-twin transfusion syndrome (see "Twin-twin transfusion syndrome: Screening, prevalence, pathophysiology, and diagnosis")

-Twin reversed arterial perfusion (TRAP) syndrome (see "Twin reversed arterial perfusion (TRAP) sequence")

-Cord entanglement (see "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Cord entanglement')

-Conjoined twins (see "Monoamniotic twin pregnancy (including conjoined twins)", section on 'Conjoined twins')

-Complications related to intrauterine death of one fetus (see 'Fetal death: Complications for survivor' above and "Twin pregnancy: Management of pregnancy complications", section on 'Death of one twin')

●Overview of management – Neonatal management of multiple births should anticipate problems that occur more frequently in multiple births, including prematurity, FGR/discordant growth, and congenital anomalies.

•Delivery room management – Management in the delivery room is provided according to the same principles and practices that guide the care of all newborns. 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. (See 'Initial management' above and "Neonatal resuscitation in the delivery room".)

•Breastfeeding support – Although challenging, mothers of twins and triplets can successfully breastfeed. Mothers who wish to breastfeed should receive support and additional guidance to optimize newborn feeding. (See 'Supporting breastfeeding' above.)

•Psychosocial support – It is important to provide psychosocial support to address the increased emotional stress, financial burden, and care issues that parents/caregivers of multiple births experience. (See 'Family/caregiver support' above.)