high risk pregnancy 4/e samplechapter

1053

C H A P T E R 5 9

Multiple Pregnancy JODIE M. DODD , ROSALIE M. GRIVELL ,

and CAROLINE A. CROWTHER

INTRODUCTION Multiple pregnancy rates vary worldwide, from a low of 6.7 per 1000 births in Japan to 40 per 1000 births in Nigeria. The frequency of twin births in tertiary centers ranges from 1 in 25 to 1 in 100, refl ecting the hospital referral population rather than the true population rate. The incidence of mono-zygous twinning is relatively constant at 3.5 per 1000 births. 1

Dizygous twinning rates and higher-order birth rates vary widely and are affected by age, parity, racial background, and the use of assisted reproductive techniques. This chapter discusses the general and obstetric risks associated with mul-tiple pregnancy. Problems specifi c to multiple pregnancy are discussed in Chapter 23 .

RISKS Multiple pregnancy is associated with more maternal and fetal risks than singleton pregnancy.

Maternal Risks ( Table 59 – 1 ) Increased Symptoms of Early Pregnancy Nausea and vomiting are three times more common in mul-tiple than in singleton pregnancies, 2 , 3 with higher levels of pregnancy hormones implicated. 4

Increased Risk of Miscarriage Both threatened and actual miscarriage are more common in multiple pregnancy, 2 with the rate of missed abortion approximately twice as high as the 2% rate seen in singletons at 10 to 14 weeks ’ gestation. 5

Vanishing Twin Syndrome Twins and higher-order multiple gestations are more often conceived than born. During the fi rst trimester, arrest of development and subsequent reabsorption of one or more of the fetuses may occur. This event can be seen ultrasono-graphically and is known as the “ vanishing twin ” phenom-enon. 6 First-trimester vaginal bleeding may be related to this syndrome. Whereas the prognosis for the remaining fetus after loss of a co-twin at this early stage of pregnancy is

generally considered to be good, 6 more recent reports suggest an increase in the risk of low birth weight in the surviving twin. 7 – 9

Minor Disorders of Pregnancy The extra weight carried with a multiple pregnancy exag-gerates the minor symptoms of pregnancy. Backache, breathlessness, diffi culty walking (especially toward the end of pregnancy), and pressure problems (e.g., varicose veins) are more common in multiple pregnancy.

Anemia Anemia is thought to be more frequent in multiple than in singleton pregnancy. However, the greater increase in blood volume compared with the red cell mass decreases the hemoglobin concentration, producing a more pronounced decrease in hemoglobin than in seen in singleton preg-nancy. 10 Mean corpuscular hemoglobin concentration, used as a measure of anemia, does not differ in multiple versus singleton pregnancy. In a retrospective case-control study comparing hemoglobin concentration in twin and singleton gestations matched for parity, no statistically signifi cant dif-ferences in third-trimester hemoglobin levels were identifi ed between the two groups. 11 The lower levels identifi ed in the fi rst and second trimesters of pregnancy in twins compared with singletons refl ected lower values in multiparous women with a twin pregnancy. Fetal demands in a multiple preg-nancy are greater, particularly for folate, and megaloblastic anemia has been reported.

Preterm Labor and Delivery Preterm birth (birth < 37 wk) occurs in over 50% of all twin pregnancies, 12 – 15 with approximately 10% of these births occurring prior to 32 weeks ’ gestation. 12 , 14 The mean dura-tion of pregnancy decreases as the number of fetuses in utero increases. The risks to the mother of a preterm birth relate to the need for hospitalization and the possible use of toco-lytic therapy, with potential side effects. Preterm prelabor rupture of the membranes occurs more frequently in multiple gestations and is often followed by preterm labor and birth.

Hypertension The incidences of pregnancy-induced hypertension, pre-eclampsia, and eclampsia are all increased in multiple

Videos corresponding to this chapter are available online at www.expertconsult.com.

1054 SECTION SIX • Prenatal—General

pregnancy. 2,16,17 A primigravid woman with a twin preg-nancy has a 5 times greater risk of severe preeclampsia than one with a singleton pregnancy, and for a multigravid woman, the risk is 10 times greater. 18 Some report a higher risk of hypertension with monozygotic twins, 19 but others do not. 20 , 21

Antepartum Hemorrhage Antepartum hemorrhage as a result of either placenta previa 22 or placental abruption 23 – 25 is increased in multiple gestations.

Hydramnios Hydramnios is suspected clinically in up to 12% of multiple pregnancies 26 and is associated with an increased risk of preterm labor. 27 Acute polyhydramnios may occur, particu-larly with monochorionic twins, often with signifi cant abdominal discomfort for the mother. This is often associ-ated with twin-twin transfusion syndrome (TTTS) (see Chapter 23 ).

Possible Need for Prenatal Hospitalization With the increased risk of threatened preterm labor, hyper-tension, fetal growth restriction, and minor disorders of pregnancy, women with a multiple pregnancy often require hospital admission, sometimes for prolonged periods, during the prenatal period. For the mother, prolonged separation from her family is often a disruptive and stressful experience. Specifi c complications of twinning, such as TTTS or single fetal death, may require hospitalization.

Single Fetal Death in Twins The risk of single fetal death in a multiple pregnancy is 2% to 6%. Psychological trauma may be considerable and is enhanced by concerns about the health of the surviving fetus or fetuses. The mother who experiences fetal death of one twin during the antepartum period must adjust to a future without one of the twins while developing a bond with the surviving twin. The mother also must adjust to the additional

risk of death and morbidity from cerebral and renal lesions for the surviving twin (see Chapter 23 ).

Risk of Operative Vaginal Birth Compared with a vaginal singleton birth, there is an increased likelihood of operative delivery for one or both twins, with the associated maternal risks of trauma, infection, and hemorrhage.

Increased Likelihood of Cesarean Birth Twins are more frequently born by cesarean section than are singletons, either as an elective procedure or as an emer-gency procedure before or after the birth of the fi rst twin. Presentation and gestational age infl uence this likelihood. 28

Postpartum Hemorrhage The risk of postpartum hemorrhage is greater in multiple pregnancy because of the increased placental site, uterine overdistention, and a greater tendency to uterine atony. 29 , 30

Postnatal Problems Learning to cope with the demands of two or more infants can be stressful. A higher percentage of depression is reported in mothers of twins. 31 Given the increased perinatal mortality rate among higher-order multiple pregnancies, the problems of coping with the loss of one or more infants may be an added burden in the postnatal period.

Maternal Mortality Women with a multiple pregnancy have a twofold increase in the risk of death compared with women with a singleton gestation. 32

Fetal Risks ( Table 59 – 2 ) Stillbirth and Neonatal Death Multiple pregnancy contributes approximately 10% of total perinatal mortality, 14 , 33 being up to 10 times greater than in

T A B L E 5 9 – 1

Maternal Risks Associated with Multiple Pregnancy

Increased symptoms of early pregnancy Increased risk of miscarriage Vanishing twin syndrome Minor disorders of pregnancy Anemia Preterm labor and delivery Hypertension Antepartum hemorrhage Hydramnios Possible need for prenatal hospitalization Single fetal death in twins Increased risk of an operative vaginal birth Increased likelihood of cesarean birth Postpartum hemorrhage Postnatal problems Maternal mortality

T A B L E 5 9 – 2

Fetal Risks Associated with Multiple Pregnancy

Stillbirth or neonatal death Single fetal death in twins Preterm labor and delivery Intrauterine growth restriction Congenital anomalies Congenital anomaly in one twin Twin reversed arterial perfusion sequence Conjoined twins Cord accident Zygosity Monoamniotic twins Hydramnios Twin-twin transfusion syndrome Risk of asphyxia Operative vaginal birth, especially for the second twin Twin entrapment Cerebral palsy

CHAPTER 59 • Multiple Pregnancy 1055

singletons. 26,34,35 If late abortion, late neonatal death, and infant death are included the mortality, the risk is further doubled. Cause-specifi c perinatal mortality in twins is higher for every major cause of death, and at all weeks of gestation, compared with singletons. 36

Higher mortality rates are reported for monochorionic compared with dichorionic twins, 37 – 39 although not in all studies. 40 For dichorionic twins, the risk of death increased throughout gestation, whereas the risk for monochorionic twins reached a maximum at 28 weeks ’ gestation and then remained constant. 40 In a review of 1051 twin pairs, factors associated with one or both twins dying in utero related to monochorionicity (odds ratio [OR] 2.0; 95% confi dence interval [CI] 1.2 – 3.4) and discordant birth weight (OR 4.3; 95% CI 2.5 – 7.3), after correcting for gestational age at birth. 41

Single Fetal Death in Twins See Chapter 23 .

Preterm Labor and Birth Preterm birth ( < 37 completed wk) is the major contributor to the poor perinatal outcomes observed in multiple preg-nancy. The preterm birth rate in twin pregnancy is consis-tently reported to be above 50%, 13 – 15,33 the risk increasing to in excess of 80% among triplet pregnancies. 14,42,43

The median gestational age at birth for monochorionic twins is 36 weeks compared with 37 weeks for dichorionic twins. However, 9.2% of monochorionic twins are born before 32 weeks ’ gestation compared with 5.5% of dichori-onic twins ( Fig. 59 – 1 ). 5

Intrauterine Growth Restriction The incidence of small – for – gestational age infants (birth weight < 10th percentile for gestational age standards in pregnancy) is common in multiple pregnancy, with up to 50% of infants having birth weight below 2500 g. 14 These infants are at increased risk for perinatal mortality and morbidity. 44 – 47

Fetal Problems Specifi c to Multiple Pregnancy Major congenital abnormalities are more common in mul-tiple pregnancies than in singletons, with rates reported as 4.9%. 48 Several fetal problems are specifi c to multiple preg-nancy, including conjoined twins (discussed later), twin reversed arterial perfusion sequence, monoamniotic twins, and TTTS (see Chapter 23 ).

Conjoined Twins Conjoined twins is a congenital abnormality that occurs only in multiple pregnancy and affects 1 in 200 monozy-gotic twins. 49

Cord Accident Preterm birth, preterm prelabor rupture of the membranes, hydramnios, malposition, and malpresentation are more likely to increase the risk of a cord accident in multiple pregnancies than in singleton pregnancies.

Chorionicity Chorionicity has an important effect on pregnancy outcome. Two thirds of monozygous twins are monochorionic and are at increased risk for mortality and morbidity compared with dichorionic twins. Risk factors include increased risk of TTTS, congenital anomalies, single fetal death in utero, and acute hydramnios (see Chapter 23 ).

Hydramnios Hydramnios may occur in one gestational sac in both TTTS and the “ stuck twin ” phenomenon (see Chapter 23 ). It may be caused by fetal anomalies such as upper gastroin-testinal tract atresias, congenital heart anomalies. or hydrops fetalis. In some cases of gross hydramnios in both sacs, no causal factor is evident. Hydramnios is a major cause of preterm birth and the associated perinatal mortal-ity rate is high. 27

Risk of Asphyxia The risk of mortality as a result of asphyxia in a twin is four to fi ve times than in a singleton. 50 Important risk factors include the increased occurrence of intrauterine growth restriction, cord prolapse, and hydramnios.

Operative Vaginal Birth, Especially for the Second Twin The likelihood of operative birth is increased, especially for the second twin, who may require internal podalic version. Operative birth is associated with an increased risk of birth trauma, low Apgar scores, and hyperbilirubinemia compared with a normal vaginal birth.

Twin Entrapment Twin entrapment is rare and reported to occur in 1 in 817 twin pregnancies. 51 The risk of fetal death of the fi rst twin is high, as is the risk of fetal hypoxia in both twins. Twin entrapment is associated with monoamniotic twins.

Cerebral Palsy The prevalence of cerebral palsy in triplets is 47 times greater and in twins 8 times greater than in singletons. 52 Lower gestational age at birth is associated with a greater risk of cerebral palsy. 53

FIGURE 59 – 1 Gestational age at birth for monochorionic and dichorionic twin pregnancies. (From Sebire N, Thornton S, Hughes K, et al: The prevalence and consequence of missed abortion in twin pregnancies at 10 – 14 weeks of gestation. Br J Obstet Gynaecol 1997;104:847 – 848.)

28

Gestational age (weeks)

32 36 4024

Fre

quen

cy (

%)

30

0

5

10

15

20

25


MANAGEMENT OPTIONS Prepregnancy The rate of multiple pregnancy for women undergoing ovu-lation induction is increased to 20 to 40%. For clomiphene, the twinning rate is 9% to 14%. 54 Appropriate counseling about this increased risk should be provided to women who are offered this treatment. The risk of multiple pregnancy from assisted reproductive techniques correlates with the number of embryos or zygotes transferred, increasing from 1.4% with single embryo transfer to 17.9% with two embryos, and 24.1% after transfer of four embryos. 55 Simi-larly, after gamete intrafallopian transfer, the rate of multiple pregnancy is 18.7% after transfer of two oocytes and 25.8% after transfer of three oocytes. 55 The rate of multiple preg-nancy at 20 weeks ’ gestation after zygote intrafallopian transfer with three zygotes is 27%. 56

The best way to reduce the risk of multiple pregnancy is to reduce the number of embryos, zygotes, or oocytes trans-ferred after full discussion of the risks (of multiple preg-nancy) and benefi ts (of high successful pregnancy rates) with the couple. Three randomized, controlled trials compared single versus double embryo transfer, 57 – 59 and another com-pared double embryo transfer with transfer of four embryos. 60 When single embryo transfer was compared with double embryo transfer, fewer women became pregnant (relative risk [RR] 0.69; 95% CI 0.51 – 0.93), but the risks of twin pregnancy (RR 0.12; 95% CI 0.03 – 0.48) and low birth weight (RR 0.17; 95% CI 0.04 – 0.79) were markedly reduced. 61 No statistically signifi cant differences were iden-tifi ed for outcomes relating to singleton pregnancy, preg-nancy loss at less than 20 weeks ’ gestation, extrauterine pregnancy, or preterm birth at less than 37 weeks. 61 When the transfer of two embryos was compared with the transfer of four embryos, no statistically signifi cant differences were seen in the number of women who became pregnant with a multiple or singleton pregnancy or the risk of pregnancy loss. 60 In view of the risks associated with multiple preg-nancy, the Royal College of Obstetricians and Gynaecolo-gists (RCOG) has issued guidelines indicating that consideration should be given to transferring only a single embryo. 62

Periconceptual folate supplementation is recommended as a general measure for all women to reduce the risk of neural tube defects. 63

Prenatal Overall Care Regular prenatal attendance for pregnancy care is accepted practice. The variation in visit frequency, the health care provider, and screening program seen in practice are of unproven value. Specialized multidisciplinary twin clinics have been advocated, and some nonrandomized cohort data suggest that perinatal outcome can be improved by intensive preterm birth education, continuity of care providers, and individualized care. 64 – 66 Prospective randomized data are lacking.

Frequent prenatal visits permit extra vigilance in the early detection of pregnancy-induced hypertension. 67 Routine screening for gestational diabetes is often performed, with some reports suggesting an increased risk in twins 68 and

others suggesting no increased risk. 69 Antepartum hemor-rhage can be neither predicted nor prevented by additional prenatal visits or any other strategy. In addition, iron and folate supplementation is frequently advised from the begin-ning of the second trimester for women with multiple preg-nancy, although the evidence to support this practice is limited. 10 , 11

Diagnosis of Chorionicity by Early Ultrasound Amnionicity and chorionicity can be determined by ultra-sound. 70 This knowledge may be useful in predicting which pregnancies are at greater risk for TTTS, and for monoam-niotic twins, cord entanglement, or to differentiate TTTS from a twin pregnancy complicated by growth restriction. Similarly, this knowledge may be useful in the management of twin pregnancy when one twin has a major congenital malformation and selective termination is considered or in the management of pregnancy after a single fetal death. 71 Screening for amnionicity and chorionicity is best performed in the fi rst trimester, although it is not always easy, even for a skilled ultrasonographer. 72

Monochorionic twins are the same sex and have one pla-cental mass, with a thin dividing membrane (two amnions, no chorions) and a T insertion. 41 , 73 Because the dividing membrane is so thin, it is often diffi cult to identify, and the pregnancy may be misidentifi ed as monoamniotic. Visual-ization of the dividing membrane is facilitated by searching over the fetal chin or away from the fetal body and around the limbs. A dichorionic placenta essentially eliminates the diagnosis of TTTS.

The dividing membrane is thicker in dichorionic twins (containing two layers of amnion and two layers of chorion). Measuring the membrane thickness by ultrasound, using a cutoff of 2 mm to characterize a dichorionic or monochori-onic placenta, 74 has been described as a good, but subopti-mal, test for determining chorionicity. 72 High interobserver and intraobserver variation, together with differences related to gestational age and sampling site, lead to suboptimal accuracy of the determination of chorionicity. 73 Ultrasonic detection of the lambda sign 69 (an echogenic V-shaped cho-rionic projection of tissue between the dividing membranes in dichorionic placentation) is reported as more reliable, especially if the scan is performed at 10 to 14 weeks ’ gesta-tion ( Fig. 59 – 2 ). 75 As gestational age increases, the lambda sign is more diffi cult to see, and after 20 weeks, it may disap-pear. The lambda sign is also known as the “ twin peak ” sign. 76 Given the prognostic value for later risks of preg-nancy, attempting to establish the chorionicity of the placenta between 10 and 14 weeks ’ gestation may be appropriate.

Accuracy rates for determining chorionicity with fi rst-trimester ultrasound, determined by subsequent pathologic examination, are reported as up to 96% with transabdominal sonography 77 and up to 100% with transvaginal sonography. 32

No prospective clinical studies show that knowledge of chorionicity should alter subsequent clinical management or whether pregnancy outcome can be improved by changes in clinical care. Despite this, many practitioners increase antenatal surveillance in women with a monochorionic pregnancy.


as a screening tool for trisomy 21 are similar to those reported for singleton pregnancies. 78 In monochorionic twin pregnancies, the false-positive rate of screening is higher than that reported in singleton pregnancies, and discordance in nuchal translucency measurements raise the possibility of early-onset TTTS. 79 The incorporation of nasal bone assess-ment has more limited sensitivity in screening for chromo-somal anomalies and is technically more diffi cult to achieve in multiple pregnancies. 80

Pregnancy Reduction Couples who are faced with the dilemma of a triplet or higher-order multiple pregnancy have several options. Ter-mination of the entire pregnancy generally is not acceptable to women, particularly those with a history of infertility. Attempting to continue the pregnancy with all of the fetuses is associated with inherent problems related to preterm birth, survival, and long-term morbidity. Reduction in the number of fetuses by selective termination has been advo-cated in an attempt to reduce the risk of adverse obstetric and perinatal outcomes. 81 The procedure is described in Chapter 23 . Many prospective, nonrandomized studies have compared pregnancy outcome after multifetal pregnancy reduction in twins conceived spontaneously or after assisted reproduction 82 – 84 with multifetal pregnancy reduction in expectantly managed triplet pregnancies. 84 – 87 A systematic review assessed the effects of multifetal pregnancy reduction on fetal loss, preterm birth, and perinatal and infant mortal-ity and morbidity rates in women with triplet and higher-order multiple pregnancies. 88 , 89 When pregnancy was reduced to twins, the reported outcomes appeared compa-rable with those in twins conceived spontaneously or those conceived with assisted reproductive techniques ( Table 59 – 3 ). 88 , 89 Counseling these women is further complicated by the varying preterm delivery rates and their consequences ( Table 59 – 4 ). No randomized, controlled trials have assessed multifetal reduction. The available nonrandomized studies provide limited insight into the benefi ts and risks associated with fetal reduction procedures. 88 , 89 Although a randomized, controlled trial would provide the most reliable evidence, selective termination may not be acceptable to couples, par-ticularly those with a history of infertility, and consequently, recruitment to such a trial may be exceptionally diffi cult.

Fetal Anomaly Scanning Given the increased risk of congenital abnormalities, an anomaly scan of each fetus by an ultrasonographer with appropriate expertise is suggested, usually between 18 and

FIGURE 59 – 2 Ultrasonography to establish chorionicity. A , Monochorionic twin pregnancy. B, Dichorionic twin pregnancy showing the lambda sign ( arrow ).

A

B

T A B L E 5 9 – 3

Pregnancy Outcomes in Multifetal Pregnancy Reduction

OUTCOME (% OF PREGNANCIES)

TRIPLETS UNREDUCED (%)

TRIPLETS REDUCED TO TWINS (%)

TWINS UNREDUCED (%)

TWINS REDUCED TO SINGLETONS (%)

Miscarriage rate 20.2 8.6 7.8 5.6

Very preterm birth 22.1 * 9.3 * 13.8 † 13.3 †

From Dodd J, Crowther C: Reduction of the number of fetuses for women with triplet and higher order multiple pregnancies (Cochrane Review). In Cochrane Library. Chichester, UK, John Wiley & Sons, Issue 4, 2003.

* < 32 wk. † < 34 wk.

Nuchal Translucency Screening The use of nuchal translucency screening for aneuploidy in singleton gestation is widespread, and it has been used to screen women with twin pregnancy. In a study of 448 women with twin pregnancy, nuchal translucency was mea-sured for each fetus and combined with maternal age to derive a risk estimate. 78 The detected nuchal translucency was greater than the 95th percentile for gestational age (using crown-rump length derived from singletons) in 7.3% of fetuses, including 88% of those with trisomy 21. These fi ndings suggest that in dichorionic twin pregnancies, the sensitivity and false-positive rate of fetal nuchal translucency


20 weeks ’ gestation. In centers offering routine ultrasound scanning at this stage of pregnancy, undetected multiple pregnancy should be diagnosed. Early diagnosis allows appropriate counseling and planning for future care and has been reported to reduce perinatal loss related to twin preg-nancy. 90 Conjoined twins can be diagnosed if an ultrasound scan is performed at this stage.

In one series, prenatal ultrasonography, including cardiac screening limited to the four-chamber view, resulted in the detection of up to 39% of all major congenital anomalies in twins. 91 However, none of the cardiac lesions was detected. Of major noncardiac anomalies, 55% were detected, as were 69% of major anomalies that could alter prenatal manage-ment. 91 In a retrospective study of 245 women with twin pregnancy, ultrasound screening for fetal anomalies identi-fi ed a 4.9% prevalence of congenital malformations. 48 For the detection of each individual anomaly, sensitivity was 82%, specifi city was 100%, positive predictive value was 100%, and negative predictive value was 98%. 48

Conjoined Twins Conjoined twins are usually diagnosed antenatally. 92 Deter-mination of the conjoined site permits multidisciplinary dis-cussion before birth as to the prognosis and the possibility of surgical correction and allows full involvement of the parents. Unless birth is necessary for other reasons, preterm cesarean section is recommended. The use of one course of steroids to stimulate fetal lung maturity is advisable. Some test for fetal lung maturity before birth. Many obstetricians recommend elective cesarean delivery at 38 weeks; however, this procedure can be diffi cult technically. Some recommend a classic incision, although this increases the maternal risks, particularly of uterine scar rupture in subsequent pregnancy. At delivery, two neonatal teams should be available, with the neonatal surgical team and operating room on standby.

Preterm Labor Preterm labor and subsequent birth presents the greatest risk for fetal morbidity and mortality. Maternal counseling as to the signs and symptoms of preterm labor may be of value.

If uterine activity is noted, the woman should go to the hospital promptly.

It is diffi cult to predict which patients will have preterm labor. Cervical assessment by either digital 93 – 95 or ultrasound examination 96 – 99 has been suggested as a useful way to evalu-ate the risk of preterm delivery. How frequently such an assessment should be made (e.g., weekly, every 2 weeks, monthly) is uncertain, and whether such assessment is more benefi cial than harmful is not known. Cervical assessment allows calculation of the cervical score (cervical length [in centimeters] – cervical dilation [in centimeters]). A cervical score of 2 or less at or before 34 weeks ’ gestation has a posi-tive predictive value of 75% for preterm birth, 94 with other authors reporting that a cervical score of 0 or less has a posi-tive predictive value of 75% for preterm birth. 95 As part of a study of the prediction of preterm delivery, cervical length was prospectively assessed by ultrasound in 147 women with a twin pregnancy. 96 A short cervix ( < 25 mm) was consis-tently associated with spontaneous preterm birth at less than 32 weeks ’ gestation (OR 6.9; 95% CI 2.0 – 24.2), less than 35 weeks ’ gestation (OR 3.2; 95% CI 2.3 – 7.9), and less than 37 weeks ’ gestation (OR 2.8; 95% CI 1.1 – 7.7). 96

The presence of fetal fi bronectin in cervical secretions has been used to predict preterm birth. 96 , 99 In multiple preg-nancy, a positive fetal fi bronectin test result at 28 to 30 weeks was associated with preterm birth before 32 weeks ’ gestation. 96 A positive fetal fi bronectin test result at 28 weeks ’ gestation predicted birth before 35 weeks, with sen-sitivity, specifi city, positive predictive value, and negative predictive value of 50.0%, 92.0%, 62.5%, and 87.3%, respectively. 99 The ability of fetal fi bronectin to predict very preterm birth requires ongoing prospective evaluation to determine whether such prediction can lead to effective interventions that would reduce the risk of preterm birth.

If cervical change is noted, hospital admission is the most generally accepted management. Routine hospital admission and subsequent rest, however, seem to offer little benefi t in delaying labor. 100 , 101 It is unknown whether prophylactic tocolysis is of value in this identifi able group at high risk for preterm birth.

T A B L E 5 9 – 4

Likelihood of Preterm Delivery and Subsequent Preterm Mortality and Neurodevelopmental Morbidity Rates in Unreduced Triplets and Triplets Reduced to Twins

24 WK 26 WK 28 WK 30 WK 32 WK

OUTCOME URT TWN URT TWN URT TWN URT TWN URT TWN REFERENCE

Percentage of pregnancies undelivered at a given gestation

80 90 75 87 70 87 65 87 55 82 86

Percentage survival if delivered at a given gestation (95% CI)

21 (16 – 25) 62 (58 – 65) 88 (68 – 90) 96 (95 – 97) 99 (97 – 99) 167

Percentage with no NDM ( “ no disability ” ) if delivered at a given gestation (95% CI)

30 * (8 – 58) 55 * (35 – 75) 70 * (62 – 88) Proportion of survivors with “ no disability ” continues to rise with gestation at delivery, but no accurate current data are available for each gestational period > 28 wk. *

168 , 169

CI, confi dence interval; NDM, neurodevelopmental morbidity; TWN, triplets reduced to twins; URT, unreduced triplets. * Mortality and neurodevelopment morbidity assessed at 4 yr in survivors.


Several prenatal interventions have been tried to reduce the risk of preterm birth in multiple pregnancies and have been evaluated by randomized clinical trials. These include prophylactic cervical cerclage, 102 , 103 prophylactic β -mimetic agents, 104 – 106 prophylactic progesterone therapy, 107 – 109 bedrest in the hospital, 100 , 110 and home uterine activity moni-toring. 111 , 112 However, none of these haa proved to be of value in reducing the incidence of preterm birth and the associated high perinatal mortality rate in multiple pregnancy.

Prophylactic cervical cerclage in twin pregnancy does not show benefi t when the results of randomized trials are reviewed. 113 It seems prudent to reserve the insertion of a cervical suture for women with evidence of cervical incom-petence. Prophylactic tocolytic agents are occasionally used in multiple pregnancy. Systematic review of randomized trials of prophylactic β -mimetics does not show a benefi t in the incidence of preterm labor, 114 and their use cannot be recommended.

Prophylactic progesterone has been advocated as a treat-ment for women at risk for preterm birth from multiple pregnancy. Two randomized trials have been identifi ed evaluating the use of 17 α -hydroxyprogesterone caproate in women with a twin pregnancy, 108 , 109 and a single trial involv-ing women with a triplet pregnancy. 107 To date, there is little evidence to support its use, with no demonstrated benefi t in either the risk of preterm birth or the neonatal health outcomes. 115 , 116

Admission of women with an uncomplicated twin preg-nancy to the hospital for rest does not reduce the risk of preterm birth. The Cochrane Systematic Review of random-ized trials of routine hospitalization for rest shows an increased likelihood of preterm birth in women who were admitted compared with control subjects who continued normal activity at home. 100 Hospital admission for rest in an uncomplicated twin pregnancy should be considered only if the woman requests admission. Women may request hospi-tal admission for several reasons, including discomfort, dif-fi culty coping at home, or living a signifi cant distance from the hospital.

The value of hospital admission for rest in triplet or higher-order multiple pregnancy is uncertain. Only two small randomized studies have been conducted, with no demonstrable benefi t. 110 , 117

Home uterine activity monitoring (HUAM) has been sug-gested to permit the diagnosis of preterm labor at an early stage, allowing successful tocolysis and fewer preterm births. A small randomized trial of 45 women reported these ben-efi ts. 112 However, in subgroup analysis of the 844 twin gesta-tions in a multicenter trial comparing HUAM with weekly or daily nursing contact, HUAM did not reduce the risk of preterm birth. 111 HUAM, when combined with daily nursing contact, did result in more unscheduled visits and increased use of tocolytics.

A course of prenatal corticosteroids should be given to improve fetal outcome in women with multiple pregnancy who are considered at increased risk for preterm birth at less than 34 weeks, if birth is planned, or if there is a high risk of birth within the next 48 hours. 118 Whether a larger dose of corticosteroids than that given in singleton pregnancies would be more benefi cial in twin gestations has been sug-gested but not adequately assessed. 118 For women who

remain undelivered after 7 days following corticosteroids, repeat doses may be recommended, because they have been shown to reduce the occurrence and severity of neonatal lung disease and other serious health problems in the early neonatal period. 119 However, these benefi ts are associated with a reduction in some measures of weight and head cir-cumference at birth, and there is still insuffi cient evidence on the longer-term benefi ts and risks. 119 , 120

Fetal Assessment Fetal assessment during pregnancy includes regular ultra-sound to determine fetal growth and well-being. The recom-mended frequency of scanning varies (e.g., from every 2 wk from 24 wk ’ gestation to every 3 – 4 wk from 20 wk ’ gesta-tion). Umbilical artery Doppler improves pregnancy outcome in high risk pregnancy and is often included as part of routine fetal assessment. 121 Some centers suggest obtain-ing biophysical profi les from 30 weeks ’ gestation, although the evidence to support this strategy is not strong.

The use of umbilical artery Doppler studies in the assess-ment of twin pregnancy was evaluated in three randomized, controlled trials. 122 – 124 Giles and colleagues 122 randomly allo-cated 526 women with a twin pregnancy at 25 weeks ’ gesta-tion to biometry only or to biometry and umbilical artery Doppler waveform at 25, 30, and 35 weeks ’ gestation. This study of close antenatal surveillance identifi ed a lower than expected fetal mortality rate from 25 weeks ’ gestation in both the biometry alone and the combined biometry and Doppler groups.

Maternal Education and Support During the prenatal period, the couple will need specifi c information and support to help prepare for the birth and care of the ï r infants. 125 The most likely mode of birth, care in labor, and the use of analgesia, especially epidural, should be discussed. 126 Many countries have multiple pregnancy support groups. The opportunity to contact a local group during the prenatal period, attend meetings, and make per-sonal contact with other families who have had a multiple birth is recommended.

Labor and Delivery Birth in a hospital is accepted practice, 127 with many advis-ing birth in a tertiary unit, when possible. Induction of labor may be indicated for complications such as pre-eclampsia or growth restriction. The benefi t of elective birth at 37 weeks ’ gestation to reduce the risk of antepartum stillbirth as a result of intrauterine growth restriction is controversial.

Retrospective data suggest that the lowest rate of perinatal mortality and morbidity in twin pregnancies occurs at 36 to 38 weeks ’ gestation, with the risk of adverse outcome increas-ing as gestation advances. 36,128 – 131 The recent Cochrane Sys-tematic Review of the role of elective birth in twin pregnancy from 37 weeks ’ gestation 132 identifi ed a single small random-ized, controlled trial from Japan assessing elective birth with continued expectant management. 133 This study identifi ed no statistically signifi cant differences. However, the sample size was underpowered to detect meaningful differences, and insuffi cient data are available to support the practice of elec-tive birth from 37 weeks ’ gestation in women with an


otherwise uncomplicated twin pregnancy. A multicenter randomized, controlled trial is in progress, coordinated by the Maternal Perinatal Clinical Trials Unit at the University of Adelaide, to assess the optimal timing of birth in women with twin pregnancy at term. 134

Intrapartum blood loss is greater in multiple pregnancy, as is the risk of postpartum hemorrhage. An intravenous access line should be inserted early in labor and blood obtained to estimate maternal hemoglobin or hematocrit and to hold serum for cross-matching, if needed later.

For a vaginal birth, both twins should be monitored con-tinuously. 127 Initially, only external fetal monitoring will be possible. When feasible, a scalp electrode should be placed on the fi rst twin, with continuation of external monitoring of the second twin. The use of a twin fetal heart rate monitor allows simultaneous recording of the two fetal heart rate tracings. If continuous monitoring of the second twin is impossible, some recommend cesarean section because of the higher risk of fetal asphyxia in twins, which may go undetected without adequate monitoring.

Epidural analgesia is widely used, providing the mother with adequate pain relief, and minimizes the risk that she will push before full dilation occurs. 127 In addition, adequate analgesia is provided in the event that operative birth, internal podalic version of the second twin, or cesarean delivery is needed. The widespread use of epidural anesthe-sia often negates the need for emergency general anesthesia with the complications discussed earlier, although it may still be needed for emergency cesarean section for fetal distress.

The optimal mode of birth in multiple pregnancy is con-troversial. 135 For triplets and higher-order multiple gesta-tions, the most frequent mode of delivery is cesarean section, 136 – 138 although no randomized studies are available to support this mode of birth over vaginal birth. Reports suggest that the risk of lower Apgar scores in higher-order multiple gestations is reduced with cesarean delivery 42 , 139 ; in addition, there are fewer perinatal deaths. 42

Neonatal respiratory disease was more common in twins born by cesarean section at 36 to 38 weeks than in those born vaginally at 38 to 40 weeks. 140 Another report sug-gested higher perinatal mortality rates with cesarean deliv-ery, primarily as a result of respiratory distress syndrome. 141 This has led to the suggested role of prophylactic cortico-steroid administration prior to elective cesarean section. 142

The Cochrane Systematic Review of the mode of birth for the second twin 143 identifi ed a single randomized trial 144 comparing planned vaginal birth with planned cesarean birth for the second, nonvertex twin. This study highlighted the need for further evidence from randomized, controlled trials to inform practice. To provide more reliable informa-tion about the optimal mode of birth for women with twin pregnancy, a randomized, controlled trial (Twin Birth Study) is in progress, coordinated by the University of Toronto ’ s Centre for Mother, Infant, and Child Research. 145

Based on the literature on twin pregnancy, some recom-mendations can be made. The mode of birth is often affected by the presentation of the twins, which may be divided into the following three groups: ● First twin vertex, second twin vertex. ● First twin vertex, second twin nonvertex. ● First twin nonvertex.

First Twin Vertex, Second Twin Vertex The most common presentation of twins is vertex-vertex. In this case, most obstetricians recommend vaginal birth, 146 – 149 and the literature supports vaginal birth, even of very low – birth weight infants ( < 1500 g). 147,150,151

First Twin Vertex, Second Twin Nonvertex For twins presenting as fi rst twin vertex, second twin non-vertex, opinion is divided as to the optimal mode of birth. Some recommend elective cesarean delivery, reporting reduced neonatal mortality and morbidity rates for the second twin. 146 , 152 Others suggest that there is no increase in neonatal risk associated with vaginal birth of the second twin weighing 1500 g or more, either as breech presentation after internal podalic version if the fetus does not have a longitudinal lie or as cephalic presentation after external cephalic version. 153 – 158 The only randomized study found no difference in neonatal outcome in 60 nonvertex second twins at 35 weeks ’ gestation or more. Study subjects were randomly allocated to either vaginal delivery or cesarean section. 144 , 159 Assessment of whether vaginal breech delivery is appropriate is necessary using the standard criteria for singleton birth. These include exclusion of cephalopelvic disproportion, estimated fetal weight of less than approxi-mately 3500 g, and the fi nding of a fl exed fetal head on ultrasound.

For a nonvertex second twin of very low birth weight ( < 1500 g), the mode of birth is controversial. Some reports recommend cesarean delivery to minimize birth trauma to the preterm infant, 147,153,155,158,160 whereas others show no neonatal benefi t and emphasize that vaginal delivery has reduced risks for the mother. 151 No randomized studies have compared vaginal and cesarean birth in these infants.

First Twin Nonvertex When the fi rst twin is nonvertex, cesarean delivery is often preferred 135 , 148 and advised, 147 although no series suggests that vaginal birth is inappropriate. It is likely that this approach is infl uenced by the data on the optimum mode of delivery in singleton breech presentations (see Chapter 63 ). By following such a policy, the risk of twin entrapment by interlocking chins or heads can be avoided.

P R O C E D U R E

TWIN BIRTH For a vaginal twin birth, at least one experienced obste-trician, anesthetist, pediatrician, and neonatal nurse should be in attendance. Depending on gestational age (e.g., if preterm) and circumstances (e.g., operative birth, abnormal cardiotocographic fi ndings), a double pediatric team (two pediatricians and two neonatal nurses) may be appropriate. For higher-order multiple births, one pediatric team should be present for each infant. Some recommend having a nurse scrubbed and the operating room prepared for emergency cesarean section.

For a vaginal birth, delivery of the fi rst twin should be as for a singleton. After the birth of the fi rst twin, an experienced obstetrician assesses the lie and presen-tation of the second twin. This assessment can be


done by vaginal examination, abdominal palpation, or transabdominal ultrasound examination. The lie should be corrected to longitudinal by external version or inter-nal podalic version. 161 External version ( Fig. 59 – 3 ) gently turns the fetus so that the vertex lies above the pelvic brim. Amniotomy can be performed if there are uterine contractions (discussed later), and then delivery is completed. Version is more likely to be successful with epidural anesthesia and when the twins are of similar weight (difference of < 500 g). 156

In two series, external version was less likely than breech extraction to result in a vaginal birth. 158 , 162 Emer-gency cesarean section and complications such as cord prolapse and fetal distress were more frequent in the external version group. Although these were not randomized studies, in view of these fi ndings, internal podalic version, if necessary, and breech delivery are recommended by some obstetricians if the lie is non-longitudinal or the breech is presenting. However, others prefer to use external cephalic version and perform amniotomy once the lie is longitudinal and there are regular uterine contractions. They advocate cesarean delivery if the lie remains nonlongitudinal. Oxytocin (Syntocinon) infusion is mandatory if there is uterine inertia, and it is normal practice in many units to have an infusion ready at the onset of the second stage of labor. Once there are contractions and the lie is longitudinal, amniotomy is performed and birth pro-ceeds with maternal effort during contractions. A scalp electrode can be applied after amniotomy to permit continuous fetal heart rate monitoring, or an external monitor can be used. Most authors advise continuous monitoring of the second twin throughout the second stage of labor, given the increased risk of intrapartum asphyxia. The risk of fetal distress and acidosis is increased if the twin-twin delivery interval exceeds 30 minutes. 163 If fetal distress develops and birth cannot be achieved safely, or if the second twin does not

descend into the pelvis, emergency cesarean delivery is necessary.

After birth of the second infant, active management of the third stage of labor is recommended with an oxytocic agent. 164 To prevent uterine atony, in many units, an oxytocin infusion is continued for 3 to 4 hours.

Internal podalic version with vaginal breech delivery remains an option for birth of the second twin when a nonlongitudinal lie persists and the membranes are intact ( Fig. 59 – 4 ). This approach involves the following steps: ● Use adequate analgesia, usually epidural, but pos-

sibly a general anesthetic. ● Place the patient in the lithotomy position. ● Provide continuous fetal heart rate monitoring.

FIGURE 59 – 3 Modifi ed external version for delivery of the second twin.

FIGURE 59 – 4 Internal podalic version.


● Use aseptic technique, and catheterize the patient. ● Ensure that a pediatrician is present. ● Determine the lie of the second twin by abdominal

palpation, internal examination, or transabdominal ultrasound examination.

● Locate a fetal foot. Confi rm that the structure is a foot rather than a wrist by palpating the heel.

● Perform an amniotomy. ● Grasp the foot, and pull down into the vagina. Grasp

both feet, if possible. ● With maternal effort during contractions, deliver the

fetus as an assisted breech.

Complications

Complications include ● Fetal anoxia. ● Diffi culty with delivery of the head with breech

presentation. ● Fetal trauma as a result of breech delivery (e.g.,

dislocated hips). ● Inadvertent delivery of a hand with shoulder

presentation. ● Placental abruption. ● Cord accident. ● Endometritis. ● Maternal trauma (e.g., ruptured uterus).

Twin Entrapment

Twin entrapment may occur if the fi rst twin is delivered as a breech and the second twin is cephalic and the head of the second twin enters the pelvis before the head of the leading twin. Some maintain that the risk of twin entrapment can be avoided by performing elec-tive cesarean section if the fi rst twin is breech and the second twin is cephalic. In an emergency, an attempt may be made to separate the locked twins by passing a hand vaginally between the chins of the fetuses and pushing the second twin upward. If this attempt fails, emergency cesarean section is necessary. Alterna-tively, an attempt may be made to push back the fi rst twin, presenting as a breech, and allow the “ second ”

twin, presenting cephalically, to deliver fi rst. Again, if this attempt fails, emergency cesarean delivery is necessary.

During cesarean section, the head of the fi rst twin is maneuvered upward, enabling birth of the second twin ’ s head and body. The “ fi rst ” twin may then be delivered. Some recommend having a second obstetri-cian available to manipulate the infants vaginally, if necessary.

If the fi rst twin is already dead, rather than cesarean birth, there is the option of decapitation of the fi rst twin, vaginal delivery of the second twin, and delivery of the head of the fi rst twin. Such a destructive procedure should be performed under general anesthesia to protect the mother from seeing it. Many believe that this option should not be used in modern obstetrics, and some would argue that abdominal delivery may be associated with a lower incidence of perinatal asphyxia for the second twin.

Complications

In twin entrapment, the risk of fetal death of the fi rst twin is high, as is the risk of fetal hypoxia for both twins. Maternal risks relate to the need for emergency cesarean section, endometritis, and the possible need for general anesthesia.

Postnatal After the birth of twins, the mother may require a prolonged hospital stay. Breast-feeding should be encouraged, and additional support is important. The provision of adequate contraception is necessary and should be discussed. Coordi-nated support to help the parents care for their infants should be available. 125

Before discharge, if extra help is not available at home, additional community support may need to be arranged. Maintaining contact with the local multiple birth support group during the puerperium is important.

S U M M A R Y O F M A N A G E M E N T O P T I O N S

Multiple Pregnancy

Management OptionsEvidence Quality and

Recommendation References

Prepregnancy

Counsel women who are undergoing assisted conception techniques about the risks of multiple pregnancy.

III/B 56

No data are available to indicate the “ ideal ” number of embryos or oocytes to replace. But, there is guidance encouraging the consideration of single embryo replacement.

Ia/A 61

Supplement folate pre- and periconception. Ia/A 63

Prenatal

Specialized twin clinics may lessen adverse outcomes. Little evidence supports other forms of prenatal care.

III/B 64 – 66

Document zygosity or chorionicity at 10 – 14 wk. But no prospective data are available on whether this documentation improves outcome.

III/B 75




Maintain increased surveillance if twins are monozygous or monochorionic.

IIb/B 165

Monochorionic twins are at increased risk for adverse outcome. But no prospective data are available on whether increased surveillance improves outcome.

Supplement iron and folate from the second trimester. IIb/B 11

Screen for hypertension. IIa/B 67

There is confl icting evidence of the value of screening for gestational diabetes.

IIa/B 68 , 69

Nuchal translucency measurement of each fetus identifi es fetuses at risk for trisomy 21, cardiothoracic abnormalities, and twin-twin transfusion syndrome.

III/B 78

Obtain routine anomaly ultrasound scan at 18 – 20 wk. III/B 48

Conjoined twins: III/B 92

● Obtain careful ultrasonographic evaluation of anatomy.

● Provide interdisciplinary discussion of therapeutic options.

Be vigilant for early symptoms of preterm labor; prompt self-referral if suspected.

Ib/A 112

Obtain possible ultrasound assessment of cervical changes and fetal fi bronectin as part of preterm delivery screening.

IIa/B 96

Provide prenatal corticosteroids if preterm birth before 34 wk is possible. Ia/A 118

There is no evidence that hospitalization prevents preterm labor and delivery.

Ia/A 100

There is no evidence that prophylactic cervical cerclage prevents preterm labor and delivery.

Ia/A 113

Obtain regular fetal ultrasound assessment of growth and umbilical artery Doppler.

Ib/A 122

Hospitalize at the woman ’ s request or if complications are detected. Ia/A 100

Consider therapeutic amniocentesis (repeated if necessary) for extreme hydramnios and maternal distress.

IIb/B 166

Provide prenatal education about the possible modes of delivery, analgesia, and care in labor.

IV/C 126

Labor and Delivery

Arrange for hospital delivery. III/B 127

Have experienced obstetrician and other health professionals on stand by.

III/B 127

Await spontaneous labor if no complications occur. Ia/A 132

Have pediatrician, neonatal nurse, and anesthetist available at delivery, with one pediatrician per infant present if preterm or operative delivery or fetal problems are anticipated.

GPP —

Maintain continuous monitoring of all fetuses during labor. III/B 127

Provide IV access. GPP —

Epidural analgesia recommended. III/B 127

Aim for vaginal delivery unless the leading twin has a nonlongitudinal lie. III/B 140 , 151

Some advocate elective cesarean delivery if the fi rst twin is not cephalic. III/B 140 , 151

Arrange for vaginal delivery of the fi rst twin, if appropriate. III/B 151

Consider synthetic oxytocin infusion for uterine inertia, especially after the fi rst twin is delivered.

GPP —

If the second twin has a longitudinal lie, perform amniotomy and deliver. III/B 161




If an infant has a nonlongitudinal lie, convert to a longitudinal lie by external version or internal podalic version.

III/B 161

Infuse oxytocin prophylactically after delivery to reduce the risk of postpartum hemorrhage.

Ia/A 163

Some advocate elective cesarean delivery for triplets and higher-order births.

IIb/B 141

Postnatal

Provide extra support while in the hospital to assist with infant care. GPP —

Offer longer in-patient stay. GPP —

Arrange support at home. GPP —

Provide adequate contraceptive advice. GPP —

GPP, good practice point.

SUGGESTED READINGS

Crowther C : Caesarean delivery for the second twin (Cochrane Review) . In Cochrane Library . Oxford , Update Software , Issue 1 , 2004 .

Crowther C : Hospitalisation for bed rest in multiple pregnancy (Cochrane Review) . In Cochrane Library . Oxford , Update Software , Issue 1 , 2004 .

Crowther CA, Harding JE: Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Cochrane Database Syst Rev 2007;3:CD003935.

Dodd J , Crowther C : Elective delivery from 37 weeks gestation in women with a twin pregnancy (Cochrane Review) . In Cochrane Library . Oxford , Update Software , Issue 1 , 2005 .

Dodd J , Crowther C : Reduction of the number of fetuses for women with triplet and higher order multiple pregnancies (Cochrane Review) . In Cochrane Library . Oxford , Update Software , Issue 1 , 2005 .

Dodd JM, Flenady VJ, Cincotta R, Crowther CA: Prenatal progesterone for prevention of preterm birth. Cochrane Database Syst Rev 2006;1:CD004947.

Hofmeyr G , Drakely A : Delivery of twins . Ballieres Clin Obstet Gynaecol 1998 ; 12 : 91 – 108 .

Keirse M , Grant A , King J : Preterm labour . In Chalmers I , Enkin M , Keirse M (eds): Effective Care in Pregnancy and Childbirth . Oxford , Oxford University Press , 1989 , pp 694 – 749 .

Neilson J , Alfi revic Z : Doppler ultrasound for fetal assessment in high risk pregnancies (Cochrane Review) . In Cochrane Library . Oxford , Update Software , Issue 1 , 2004 .

Royal College of Obstetricians and Gynaecologists (RCOG) : Consensus views arising from the 50th study group: Multiple pregnancy . London , RCOG, 2006 . Available at http://www.rcog.org.uk/fi les/rcog-corp/uploaded-fi les/StudyGroupConsensusViewsMultiplePregnancy.pdf

REFERENCES For a complete list of references, log onto www.expertconsult.com .

S U M M A R Y O F M A N A G E M E N T O P T I O N S

Multiple Pregnancy—cont’d

high risk pregnancy 4/e samplechapter

Health & Medicine