The High-Risk Infant

Keywords

• acardiac fetus

• chimeric

• conjoined twins

• diamnionic

• dichorionic

• dizygotic

• endoparasitic twins

• exoparasitic twins

• fission theory

• fusion theory

• monoamniotic

• monochorionic

• monozygotic

• superfecundation

• superfetation

• TRAP

• TTTS

• twin reversed arterial perfusion syndrome

• twin-twin transfusion syndrome

Monozygotic vs Dizygotic Twins

Identifying twins as monozygotic or dizygotic is useful in determining the relative influence of heredity and environment on human development and disease. The previous assumption that twins not of the same sex are dizygotic can no longer be held as true. Sex discordance, placentation, and determination of amnionicity and chorionicity are not reliable ways of determining zygosity. Detailed blood typing, gene analysis, or tissue (human leukocyte antigen) typing can be used for zygosity testing (an exception being blood typing in cases of chimeric twins, where one or both twins contain distinct cell lines from multiple zygotes). Physical and cognitive differences may still exist between monozygotic twins because of other factors. The in utero environment may have been different. Additionally, differences may exist in the mitochondrial genome, in posttranslational gene product modification, and in the epigenetic modification of nuclear genes in response to environmental factors.

Incidence

The incidence of spontaneous twinning is highest among blacks and East Indians, followed by northern European whites, and is lowest in the Asian races. Differences in the incidence of twins worldwide mainly involve dizygotic twins. The incidence of monozygotic twins (3-5 per 1,000) is unaffected by racial or familial factors. Until recently, monozygotic twinning rates remained stable across continents and cultures. In 2014 the U.S. final natality report recorded a twin rate of 33.9 per 1,000 live births, which was a new high for the nation. Increases in monozygotic and dizygotic twinning have been associated with advanced maternal age (AMA) and the use of assisted reproductive technologies (ART). The rate of triplets and higher-order multiple births is 113.5 per 100,000 live births in the United States and continues to decline. The use of single-embryo transfer in ART has decreased the numbers of triplet births and higher-order multiples. However, a doubling of monozygotic twinning and an increase in atypical twinning have been reported. The incidence of dizygotic multifetal gestation is also increasing, attributed to treatment of infertility with ovarian stimulants (clomiphene, gonadotropins).

Etiology

Polyovular pregnancies are more frequent beyond the 2nd pregnancy, in older women, and in families with a history of dizygotic twins. They may result from simultaneous maturation of multiple ovarian follicles, but follicles containing 2 ova have also been described as a genetic trait leading to twin pregnancies. Twin-prone women have higher levels of gonadotropin. Polyovular pregnancies occur in many women treated for infertility.

The occurrence of monozygotic twins appears to be independent of heritable factors. The etiology of monozygotic twinning is unknown, but there are 2 prevailing theories. In the classic fission theory , twinning results from the splitting of a single conceptus, with the timing of splitting resulting in differing amnionicity and chorionicity (i.e., the earlier the fission occurs, the more likely the twins are to be diamniotic dichorionic) ( Fig. 117.2 ). However, this theory fails to account for several forms of atypical twinning, including the occurrence of diamniotic dichorionic monozygotic twinning after single-embryo transfer in the late blastocyst state, phenotypically-discordant monozygotic twins, and asymmetrically attached conjoined twins. An alternate fusion theory of twinning has been proposed to account for this discrepancy, in which the inner cell masses of trophectoderm fuse after the initial 2-cell splitting stage ( Fig. 117.3 ).

Atypical Twinning

Conjoined twins (1 in 50,000 pregnancies and 1 in 250,000 live births) are obligate monozygotes . Theoretically, they result from later fission of a single zygote (10-14 days) or from fusion of 2 zygotes (as proposed for asymmetrically attached conjoined twins). The majority of conjoined twins are female. The prognosis for symmetrically conjoined twins depends on the possibility of surgical separation, which in turn depends on the extent to which vital organs are shared. The site of connections varies: thoracoomphalopagus (28% of conjoined twins), thoracopagus (18%), omphalopagus (10%), craniopagus (6%), and incomplete duplication (10%). The term parasitic twin has historically been used to describe the smaller and less completely developed member of a pair of conjoined twins; this parasitic twin has typically had embryonic demise but remains vascularized by the surviving independent twin (the autocyte ). For asymmetrically attached conjoined twins in whom one twin is dependent on the cardiovascular system of the intact autocyte ( exoparasitic twins , 1 in 1 million live births) survival of the autocyte depends on the feasibility of excising the exoparasitic twin. For endoparasitic twins ( fetus in fetu, 1 in 500,000 live births) in whom one (or more) fetus exists as a benign mass in the autocyte, survival of the autocyte is unaffected.

Superfecundation, or fertilization of an ovum by an insemination that takes place after one ovum has already been fertilized, and superfetation, or fertilization and subsequent development of an embryo when a fetus is already present in the uterus, have been proposed as explanations for differences in size and appearance of certain twins at birth.

Complications

Problems of twin gestation include polyhydramnios, hyperemesis gravidarum, preeclampsia, premature rupture of membranes (PROM), vasa previa, velamentous insertion of the umbilical cord, abnormal presentation (breech), and premature labor. Monoamniotic twins have a high fatality rate because of obstruction of the circulation secondary to intertwining of the umbilical cords.

Compared with the 1st-born twin, the 2nd twin is at increased risk for respiratory distress syndrome and asphyxia. Twins are at risk for intrauterine growth restriction, twin-twin transfusion syndrome, and congenital anomalies, which occur predominantly in monozygotic twins. Anomalies are a result of compression deformation of the uterus from crowding (hip dislocation), vascular communication with embolization (ileal atresia, porencephaly, cutis aplasia) or without embolization (acardiac twin), and unknown factors (conjoined twins, anencephaly, meningomyelocele).

Twin Syndromes (TRAP, TTTS)

Placental vascular anastomoses occur with high frequency in monochorionic twins. In monochorionic placentas, the fetal vasculature is usually joined, sometimes in a very complex manner. They are usually balanced so that neither twin suffers. Artery-to-artery communications cross over placental veins, and when anastomoses are present, blood can readily be stroked from one fetal vascular bed to the other. Vein-to-vein communications are similarly recognized but are less common. A combination of artery-to-artery and vein-to-vein anastomoses is associated with the condition of acardiac fetus . This rare lethal anomaly (1 in 35,000) is secondary to the twin reversed arterial perfusion (TRAP) syndrome . In utero radiofrequency or laser ablation of the anastomosis or cord occlusion can be used to treat heart failure in the surviving twin. However, death of the autocyte is reported in up to 75% of cases. In rare cases, one umbilical cord may arise from the other after leaving the placenta, and the twin attached to the secondary cord usually is malformed or dies in utero.

In twin-twin transfusion syndrome (TTTS) , an artery from one twin acutely or chronically delivers blood that is drained into the vein of the other. The latter develops polyhydramnios, plethoric and large for dates, and the former has oligohydramnios, anemic and small ( Fig. 117.4 ). TTTS is more common in monozygotic twins and affects up to 30% of monochorionic twins. Maternal polyhydramnios in a twin pregnancy suggests TTTS. Anticipating this possibility by preparing to transfuse the donor twin or bleed the recipient twin may be lifesaving. Death of the donor twin in utero may result in generalized fibrin thrombi in the smaller arterioles of the recipient twin, possibly as the result of transfusion of thromboplastin-rich blood from the macerating donor fetus. Disseminated intravascular coagulation (DIC) may develop in the surviving twin. Table 117.2 lists the more frequent changes associated with a large shunt. Treatment of this highly lethal problem includes maternal digoxin, aggressive amnioreduction for polyhydramnios, selective twin termination, and more often, laser or fetoscopic ablation of anastomosis ( Fig. 117.5 ).

Diagnosis

A prenatal diagnosis of pregnancy with twins is suggested by a uterine size that is greater than that expected for gestational age, auscultation of 2 fetal hearts, and elevated maternal serum α-fetoprotein (AFP) or human chorionic gonadotropin (hCG) levels. It is confirmed by ultrasonography. Physical examination of twins is necessary but not sufficient to determine zygosity of twins. In the event that congenital anomalies are present or there are transfusion or transplantation considerations, genetic testing of zygosity should be performed. While noninvasive prenatal testing (NIPT) is becoming more common, the results should be interpreted with caution in multiple-gestation pregnancies until more findings are better established.

Prognosis

Most twins are born prematurely, and maternal complications of pregnancy are more common than with single pregnancies. The risk for twins is most often associated with twin-twin transfusion, ART, and early-onset discordant growth. Because most twins are premature, their overall mortality is higher than that of single-birth infants. The perinatal mortality of twins is about 4 times that of singletons, with monochorionic twins being particularly at risk. Monoamnionic twins have an increased likelihood of cord entanglement, which may lead to asphyxia. Twins are at greater risk for congenital malformations, with up to 25% of monozygotic twins being affected. Theoretically, the 2nd twin is more subject to anoxia than the 1st because the placenta may separate after birth of the 1st twin and before birth of the 2nd. In addition, delivery of the 2nd twin may be difficult because it may be in an abnormal presentation (breech, entangled), uterine tone may be decreased, or the cervix may begin to close after the 1st twin's birth.

Triplet or higher-order births are associated with an increased risk of death or neurodevelopmental impairment compared with extremely-low-birthweight (ELBW) singleton and twin infants after controlling for gestational age. The mortality for multiple gestations with ≥4 fetuses is excessively high for each fetus. Because of this poor prognosis, selective fetal reduction has been offered as a treatment option. Monozygotic twins have an increased risk of one twin dying in utero. The surviving twin has a greater risk for cerebral palsy and other neurodevelopmental sequelae.

Treatment

Prenatal diagnosis enables the obstetrician and pediatrician to anticipate the birth of infants who are at high risk because of twinning. The risk of multiple-gestation pregnancies using ART may be reduced by elective single-embryo transfers. In addition, elective delivery of twins at 37 wk (or earlier for monochorionic , monoamniotic twins) reduces the complication rate for the fetuses and the mother. Furthermore, in twin pregnancies between 32 and 39 wk of gestation, planned vaginal delivery is preferred if the 1st twin is in the cephalic presentation. Close observation and attendance by a pediatric team are indicated in the immediate neonatal period so that prompt treatment of asphyxia or fetal transfusion syndrome can be initiated. The decision to perform an immediate blood transfusion in a severely anemic “donor twin” or a partial exchange transfusion of a “recipient twin” must be based on clinical judgment.

Keywords

• Ballard scoring system

• extremely low birthweight

• extremely low gestational age newborn

• extremely preterm

• kangaroo care

• low birthweight

• neutral thermal environment

• very low birthweight

Incidence

Preterm birth , or birth before 37 wk of gestation, is fairly common. Worldwide, approximately 15 million preterm births occur annually. In the United States, approximately 10% of all births are preterm. After a prolonged period of increasing rates of preterm birth, preterm births in the United States peaked at 10.44% in 2007. From 2007 until 2014, a slow but steady decline occurred in preterm births, to 9.57% in 2014. Preliminary data show that preterm births have slightly increased since 2014, with 9.84% of all U.S. births being preterm in 2016 and a disproportionate increase in late preterm births ( Fig. 117.6 ). Of preterm births in 2016, the majority were late preterm infants, approximately 72% of preterm births, with the remaining 28% being extremely or early preterm.