Multiple Gestation: Complicated Twin, Triplet, and High-Order Multifetal Pregnancy

Clinical Management Guidelines for Obstetrician-Gynecologists Number 56, October 2004

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Purpose of this document

Since 1980 65% increase in frequency of twins 500% increase in triplet and high-order births increased use of ovulation induction agents and assisted reproductive technology(ART) In 2002, multifetal gestations 130,000 infants in the US Although multifetal births account for only 3% of all live births, they responsible of a disproportionate share of perinatal morbidity and mortality all survivors of preterm multifetal birhts have an increased risk of mental and physical handcap.

Purpose of this document

To address the risks associated with these pregnancies Present on evidence-based approach to management when possible

Background
Infant and Maternal Morbidity Infant
1/5 of Triple pregnancy & of quadruplet pregnencies 1 child with a major long-term handicap (eg. Cerebral palsy) Triple pregnancies : cerebral palsy 17 times of singleton pregnancies Twin pregnancies : 4times of singleton pregnancies Growth restricted preterm infants NICU admission of twin(18days), of triples(30days), all quadruplets (58days)

Background
Infant and Maternal Morbidity Maternal
maternal morbidity and associated health care costs period of hospitalization 6 times Complication : preeclampsia, preterm labor, preterm premature rupture of membranes, placental abruption, pyelonephritis and postpartum hemorrhage Hospital costs 40%

Background
Table 1. Morbidity and Mortality in Multiple Gestation

Charecteristic Average birth weight Average gestational age at delivery Percentage with growth restriction Percentage requiring admission to neonatal intensive care unit Average length of stay in neonatal intensive care unit Percentage with major handicap Risk of cerebral palsy Risk of death by age 1year

Twins 2,347g 35.3wk 14-25 25 18days 4times more than singletons 7 times higher than singletons

Triplets 1,687g 32.2wk 50-60 75 30days 20 17times more than singletons 20 timesgigher than singletons

Quadruplets 1,309g 29.9wk 50-60 100 58days 50 -

Background
Role of Assisted Reproductive Technology
In 1980, 37/100,000 triple or more By 2002, 184/100,000 : result of the increased use of ART and ovulation-induction agents during this period one unexpected complication of ART : high incidence of monochorionic twins - one group evaluated 218 ART pregnancies and found the incidence of monochorionicity : 3.2% - other studies : reported an incidence of monochorionicity ranging 1%~5% in association with both ART and ovulation induction

Background
Role of Assisted Reproductive Technology

Monozygotic twinning increase the incidence of high order multiple gestation complicates fetal growth and development and can lead to rare complications(twin-twin transfusion syndrome or acardiac twinning) increases the morbidity of a pregnancy reduction procedure.

Background
Maternal Age

The a prior risk of a poor perinatal outcome in a high-order multiple gestation : increased by the womans age Growing proportion of older women successfully undergoing fertility treatment increase in pregnancies complicated adult-onset disease (HTN, DM, labor abnormalities, cesarean delivery) Increased maternal age (eg. Down syndrome) increases the risk of fetal trisomies

Background
Prenatal Diagnosis

Amniocentesis Chorionic villous sampling : technically difficult to accomplish in patients with multiple gestation

Complications of Pregnancy

Gestational Diabetes Hypertension and Preeclampsia Other pregnancy Complication

Complications of Pregnancy
Gestational Diabetes

Incidence twin pregnancies : higher than in singleton pregnancies (3~6%) triplet pregncncies : higher than in twin pregnancies (22~39%) Diagnosis & management of gestational diabetes in multiple gestation remain unexamined - The best time of testing, the ideal number of daily calories, the optimal
weight gain , whether women treated with oral hypoglycemic agents for polycystic ovary syndrome should continue taking them. The best form of insulin to use the best method of fetal surveillance and the ideal time for delivery are all currently unknown -

Complications of Pregnancy
Hypertension and Preeclampsia
Preeclampsia
twin gestations X 2.6 times of singleton gestations triplet gestations twin gestations

Significantly more likely to occur earlier and to be severe <35wks : gestational hypertension (12.4times in twin) preeclampsia (6.7times in twin) hypertension with diastolic BP >110 (2.2 times in twin) Multiple gestations by ART : greater risk of develop in hypertensive complications than spontaneous multiple gestations (unknown)

Complications of Pregnancy
Hypertension and Preeclampsia

High-order multiple gestations : more likely to develop atypical preeclampsia - hypertension (50%) edema (38%) proteinuria (19%) epigastric pain (60%) HELLP : hemolysis, elevated liver enzymes, low PLT (56%) Multifetal reduction : may decrease the risk of preeclampsia Management of hypertension complications in high-order multiple gestations has not been studied prospectively Placental abruption : 8.2 times

Complications of Pregnancy
Other pregnancy Complication
acute fatty liver : severe coagulopathy, hypoglycemia, hyperammonemia can lead to fetal or maternal death halt the disease process by delivery but postpartum period : complicated by pancreatitis or diabetes insipidus or both Sx : anorexia, nausea, vomiting, malaise beginning late in pregnancy and developing over several days of weeks vague and nonspecific concurrent evidence of preeclampsia (1/3 of affected women) delayed Dx.

Complications of Pregnancy
Other pregnancy Complication
Pulmonary embolism Factors multiple pregnancy (m/c) cesarean delivery delivery < 36wks BMI (body mass index) 25 maternal age 35 Treatment Prompt and sustained anticoagulation ( confirmed thrombosis or thromboembolism)
- Because the volume of distribution is increased to a much greater degree in multiple gestations than in singleton gestations, it may be difficult to achieve a therapeutic level of anticoagulation

form of anticoagulation chosen should be readily reversible

- Because high - order multiple gestations are at significantly increased risk of preterm labor, c/sec and bleeding complications (eg. Abruption)

Complications of Pregnancy
Other pregnancy Complication

others
Pruritic urticarial papules and pustules - dermatosis that most commonly affects primigravid women in the 3rd trimester - starts in abdominal striae * striae : in multiple gestations (m/c) d/t wt. gain, abdominal distension

Complications of Pregnancy
Multifetal Reduction and Selective Fetal Termination
High-order multiple gestation creates a medical and ethical dilemma

The risks associated with a quadruplet or higher pregnancy clearly outweigh the risks associated with fetal reduction Perinatal outcome after fetal reduction Noted an overall postprocedure pregnancy loss rate: 11.7% Very early preterm (ig. 25~28wks) delivery rate : 4.5% Chance of losing either an additional fetus or the whole pregnancy Chance of early preterm delivery Increased according to the starting number of fetuses Fetuses 6 : lost before 24wks of gestation 23% delivered at 37wks 20%

Complications of Pregnancy
Multifetal Reduction and Selective Fetal Termination
Fetal reduction of a high-order multiple pregnancy has been associated with an increased risk of intrauterine fetal growth restriction (IUGR) Monochorionicity : complicate the reduction procedure one fetus of a monochorionic twin pair is inadvertently reduced sudden hypotension and thrombotic phenomena death of damage of the remaining twin fetus Selective fetal termination is the application of the fetal reduction technique to the selective termination of an anomalous of aneuploid fetus that is part of a multiple gestation The risks of this procedure are higher than those associated with multifetal reduction

Clinical Considerations and Recommendations

Can preterm labor be predicted in multiple gestation? Are there interventions that can prolong pregnancy in multiple gestation ? How is preterm labor managed in multiple gestation? How should restriction of discordant growth be diagnosed and managed in multiple gestation? How is the death of one fetus managed? Is there a role for routine antepartum fetal surveillance? How is delayed delivery of the second twin managed? How are problems caused by monochorionic placentation managed? Are there special considerations for timing of delivery in multiple gestations? Are there special considerations for route of delivery of multiple gestation

Clinical Considerations and Recommendations

Can preterm labor be predicted in multiple gestation?

Cervical length Measurement by ultrasonography - Shortened cervix : predictive of preterm delivery in twin pregnancies - Cx length < 25mm (at GA 24wks) : best predictor of delivery before GA 32, 35 and 37wks. twin gestations (m/c) Cervical Length Measurement by Digital Examination - by experienced examiner - Less objective than USG, not allow assessment of the internal os

Clinical Considerations and Recommendations

Can preterm labor be predicted in multiple gestation?

Fetal Fibronectin - high-molecular-weight extracellular matrx glycoprotein - normally found in fetal membranes, placental tissues and amniotic fluid. - in cervical-vaginal fluids>50ng/ml : abnormal predict preterm delivery in singleton gestations Home Uterine Activity Monitoring

Clinical Considerations and Recommendations

Are there interventions that can prolong pregnancy in multiple gestation?

U.S. 55-57% of all multiple gestations : delivered preterm - 49%-63% of these infants <2,500g 12% of twin pregnancies 36% of triplet pregnancies 60% of quadruplet pregnancies Are bore before GA 32wks Factors of preterm birth - lower and upper genital tract infection - Uterine overdistension - Cervical incompetence - Maternal medical complications, maternal stress - Fetal, placental or uterine abnormalities

Clinical Considerations and Recommendations

Are there interventions that can prolong pregnancy in multiple gestation?

Management Prophylactic cerclage : not prolong gestation or improve perinatal outcome in either study Routine Hospitalization : Bed rest in the hospital does not prolong twin gestation Restriction of Activities and Rest at Home

Clinical Considerations and Recommendations

How is preterm labor managed in multiple gestation?

Tocolytics - -mimetic therapy : maternal and fetal cardiac stress and gestational diabetes - occur more frequently in multiple gestation even without mimectic therapy - Increased risk of developing pulmonary edema- resulting in severe respiratory distress when tocolytic agents, steroids and intravenous fluid are administered together - should be used judiciously Cortiosteroids Not been examined

Clinical Considerations and Recommendations

How should growth restriction or discordant growth be diagnosed and managed in multiple gestation?
Discordant fetal growth (common in multiple gestation ) Definition : a 15~25% reduction in the estimated fetal weight of the smaller fetus when compared with the largest Causes structural or genetic fetal anomalies, discordant infection, an unfavorable placental implantation, umbilical cord insertion site, placental damage (ie. Partial abruption ) complication related to monochorionic placentation site ( ie. Twin-twin transfusion syndrome ) - occur more frequently in high-order multiple gestations Expected in multiple gestations especially those resulting from ovulation induction or the implantation of 3 embryos when the fetuses are not genetically identical and may be of different sexes.

Clinical Considerations and Recommendations

How should growth restriction or discordant growth be diagnosed and managed in multiple gestation?
Associated with - structural malformations - stillbirh - IUGR , preterm delivery, cesarean delivery of nonreassuring fetal heart tracing - Umbilical arterial pH <7.1 - admission to the NICU, respiratory distress syndrome, neonatal death<7days of delivery If 2 fetuses are discordant but both have normal estimated weights and grow appropriately of their own growth curves not indicate a pathologic process

Clinical Considerations and Recommendations

How is the death of one fetus managed?

Fetal loss cause - 1st-trimester losses : not determined - the later losses : twin-twin transfusion syndrome, severe IUGR , placental insufficiency, placental abruption Fetal monitoring protocol: not predict most of these losses Authorities disagree about the preferred antepartum surveillance method and management once a demise has occurred. Some investigators: advocated immediate delivery of the remaining fetuses If the death is the result of an abnormality of the fetus itself rather than maternal or uteroplacental pathology and the pregnancy is remote from term expectant management

How is the death of one fetus managed?

The most difficult cases : those in which the fetal demise occurs in 1 fetus of a monochorionic twin pair 100% of monochorionic placentas contain vascular anastomoses that link the circulations of the 2fetuses the surviving fetus is at significant risk of sustaining damage caused by the sudden , severe and prolonged hypotension that occurs at the time of the demise or by embolic phenomena that occurs later.

Clinical Considerations and Recommendations

How is the death of one fetus managed?

There may not be any benefit in immediate delivery (esp. if the surviving fetuses are very preterm and other wise healthy) pregnancy to continue may provide the most benefit. DIC (disseminated intravascular coagulopathy) remains a theoretical risk, rarely occurs Fibrinogen and fibrin degradation product levels can be monitored serially until delivery and delivery can be expedited if DIC develops

Clinical Considerations and Recommendations

Is there a role for routine antepartum fetal surveillance

The most effective fetal surveillance system : Not known Nonstress test(NST), fetal Biophysical profile(BPP) At present, antepartum fetal surveillance in multiple gestation is recommended in all situations in which surveillance would ordinarily be performed in a singleton pregnancy (eg. IUGR, maternal disease, decreased fetal movement)

Clinical Considerations and Recommendations

How are problems caused by monochorionic placentation managed?

Twin-Twin Transfusion Syndrome In the 2nd trimester (m/c) Etiology : the result of uncompensated arteriovenous anastomoses in a monochorionic placenta, which lead to greater net blood flow going to one twin at the expense of the other Effect - Donor twin : anemic & growth restricted - appears stuck to one spot in the uterus because the lack of anmiotic fluid in its sac precludes movement - Recipient twin : plethoric and much larger, hydramnios - rapidly lead to premature rupture of membranes, preterm labor or early mortality (d/t heart failure in either of the fetuses)

Clinical Considerations and Recommendations

How are problems caused by monochorionic placentation managed?

Therapy - therapeutic amniocenteses of the recipient twins amniotic sac is most frequently used favorably changing intraamniotic pressure and, thus, placental intravascular pressure, allowing redistribution of placental blood flow and normalization of amniotic fluid volume in each sac. - abolishing the placental anastomoses by endoscopic laser coagulation or selective feticide by umbilical cord occlusion ( only for very early, severe cases) - immediate delivery : gestational age is such that survival is

Clinical Considerations and Recommendations

How are problems caused by monochorionic placentation managed?

Rare Complications Acardiac or acephalus twin - heart failure (d/t abnormal division of the zygote at the time of twinning) : Pump twin is supplying blood flow to both its own body and that of its abnormal twin, death from heart failure is a common complication - Tx : Close monitoring with consideration of early delivery or selective feticide of the abnormal co-twin by umbilical cod occlusion if heart failure develops conjoined twin (at the head, thorax, abdomen, or spine and often share organs ) - Tx : directed by their chance of long-term survival - close monitoring, c/sec delivery

Clinical Considerations and Recommendations

Are there special considerations for timing of delivery in multiple gestations ?

The nadir of perinatal mortality for twin pregnancies occurs at approximately 38 completed weeks of gestation and 35 complete weeks of gestation for triplets Quadruplet and other high-order multiple gestation is not known Fetal and neonatal morbidity and mortality : Twin >GA37wks, triple>GA35wks If the fetuses are appropriate in size for gestational age with evidence of sustained growth and there is normal amniotic fluid volume and reassuring antepartum fetal testing in the absence of maternal complication (ie. Preeclampsia, gestational diabetes) the pregnancy can be continued.

Clinical Considerations and Recommendations

Are there special considerations for timing of delivery in multiple gestations ?

If the woman is experiencing morbidities that would improve with delivery but do not necessarily mandate delivery (eg. Worsening dyspnea, inability to sleep, severe dependent edema, painful superficial varicosities) delivery may be considered at these gestational age. Determination of fetal pulmonary maturity before delivery may be necessary for twin and other multiple gestations if prenatal care was late, if the woman desires a scheduled delivery, or if the pregnancy is complicated by preterm labor or preterm premature rupture of membranes Several reports - noted that GA>31-32wks the biochemical markers of pulmonary maturity (lecithin/sphingomyelin ratio or fluorescence polarization immunoassay) are higher in twin pregnancies than in singleton pregnancies at comparable gestational ages

Clinical Considerations and Recommendations

Are there special considerations for route of delivery for multiple gestations?
Determined by the position of the fetuses, the ease of fetal heart rate monitoring and maternal and fetal status Data are insufficient to determine the best route of delivery for high-order multiple gestations There are retrospective case series that validate vaginal delivery as a potential mode of delivery, especially for triplet gestations But delivered by c/sec

Summary of Recommendations
The following recommendations are based on limited of inconsistent scientific evidence (Level B) Tocolytic agents should be used judiciously in multiple gestation Women with high-order multiple gestations should be queried about nausea, epigastric pain and other unusual 3rd-trimester symptoms because they are at increased risk to develop HELLP syndrome, in many cases before symptoms of preeclampsia have appeared. The higher incidence of gestational diabetes and hypertension in high-order multiple gestations warrants screening and monitoring for these complication .

Summary of Recommendations
The following recommendations are based primarily on consensus and expert opinion (Level C) The national Institutes of Health recommends that women in preterm labor with no contraindication to steroid use be given one course of steroids regardless of the number of fetuses Cerclage, hospitalization, bed rest, or home uterine activity monitoring have not been studied in high order multiple gestations, and, therefore should not be ordered prophylactically. There currently is no evidence that their prophylactic use improves outcome in these pregnancies Because the risks of invasive prenatal diagnosis procedures such as amniocentesis and chorionic villus sampling are inversely proportional to the experience of the operator, only experienced clinicians should perform these procedures in high-order multiple gestation .

Summary of Recommendations

Women should be counseled about the risks of high order multiple gestation before beginning ART Management of discordant growth restriction of death of one fetus in a high-order multiple gestation should be individualized, taking into consideration the welfare of the other fetus (es)