Management of Multiple Pregnancy

1. Management of Multiple Pregnancy 부산백병원 산부인과 김영남

2. Ref. • Evidence-based care of women with a multiple pregnancy • Dodd JM, Best Pract Res Clin Obstet Gynaecol. 2005 • Management of Multiple pregnancy: Prenatal care-Part I • Management of Multiple pregnancy: Prenatal care-Part II • Management of Multiple pregnancy: Labor and Delivery • Ayres A, Obstet Gynecol Surv. 2005 • Chapter 39 Multiple gestation, Williams obstetrics,22nd ed.

3. Incidence • More than 3 % in USMartin and colleques, 2002 • 1.4 per 100 birth in KoreaKorean birth certificate, 1996 • In Our Hospital (1997 – 2004) 2007

4. Trend of Increasing rates of multiple pregnancy (between 1980 and 2001, in US) 77 percent rise in twin deliveries 459 percent rise in high-order multiple births • Twining rates per 1000 births (1986)

5. Types and Genesis of Twining Dizygotic Monozygotic By timing of division < 3 day 4- 8 day > 8 day > 12 day Dichorionic Diamnionic Dichorionic Diamnionic Monochorionic Diamnionic Monochorionic Monoamnionic Conjoined

6. Management in Pre-Pregnancy • Risks associated with assisted reproductive techniques • Ovulation induction; 20-40% increase the risk of Multiple pregnancy • Clomiphen; 1.83% – 17% • hMG-hCG; 18% - 53.5% • Number of embryos or zygotes transferred following ART • risk of multiple pregmancy; 1.4% - single embryo transfer with IVF •  17.9% - two embryo transfer • 24.1% - four embryo transfer • RCTs comparing single-embryo transfer with double-embryo transfer • ; single transfer women – less likely to become pregnant (RR 0.69, 95% CI 0.51 – 0.93) but, reduced risk of a twin pregnancy (RR 0.12, 95% CI 0.03 – 0.48) & low infant birthweight (RR 0.17, 95% CI 0.04 – 0.79) • Infertility treatment increase both dizygotic and monozygotic (but, more dizygotic)

7. Management in Pre-Pregnancy • Women who are offered ART should be provided with adequate counseling about the increased risk of multiple pregnancy and the potential complication • All pregnant women should be advised to take periconceptual folate supplementationto reduce the risk of fetal neural tube defects

8. Antepartum Management

9. 다태임신의 예후 1. 일반적인 예후 1) 자연유산 ↑ 2) 주산기 사망률 ↑ 3) 선천성 기형 ↑(특히 일란성) ; 쌍둥이 형성 자체의 결과, 혈관연결에 의한 혈류교환의 결과, 자궁 내 밀집현상의 결과 4) 출생 체중: ; 저체중아----태아발육부전 및 조산 때문 ; 체중 간 불일치----이란성; 태반의 불균형, 유전적 성향, 제대이상, 태아기형 등 일란성; 할구의 불균등 분배, 태반 내 혈관연결, 기형 등 5) 재태기간 감소:태아수 증가함에 따라 제태기간은 감소 ; 쌍태임신의 1/2에서 조산경험 ; 평균 제태기간- 쌍태임신; 35주, 세쌍둥이; 32주, 네쌍둥이 30주, 다섯쌍둥이 29주 6) 조산 ; 조산으로 인한 신생아 사망 및 이환율 증가 ; 태아성장의 불일치가 있는 경우, 심각한 주산기 사망 및 이환율 보임 7) 지연임신(prolonged pregnancy):쌍태임신의 경우, 임신 40주가 경과 시 지연임신으로 간주

10. Perinatal mortality • Multiple births contribute up to 10% of all perinatal mortality rate - 10 greater than singleton - At all weeks of gestation, associated with an increase in the risk of both stillbirth and neonatal death • Increased mortality associated with monochorionic twin compared with dichorionic twin • A review of 1051 twin pair ;monochorionicity (OR 2.0; 95%CI 1.2-3.4) & discordant birth weight (OR 4.3; 95%CI 2.5-7.3) as factors associated with twin dying in utero.

11. Antepartum Management Ultimate goals • to prevent the delivery of markedly preterm fetuses • to identify growth restriction in 1 or both fetuses • to expedite their delivery before they become moribund • to deliver the fetuses atraumatically • to have expert anesthesia and neonatal care available

12. Antepartum Management Determination of chorionicity • Best performed in the first trimester with Ultrasound • 1. Numbers of G-sac • 2. Detection of the ‘lambda sign’ or ‘twin peak’ • ; best seen between 10-14 weeks, disappear after 20 weeks • 3. Measurement of membrane thickness, using a cut-off value of 2 mm Describe as DCDA / MCDA / MCMA twin

13. Antepartum Management Nutrition and Weight Gain • Increased requirements for calories, protein, minerals, and vitamins • 35- to 40-lb total weight gain is recommended • additional 150 kcal/day above the level for singleton pregnancy • take 60 - 100 mg of ironand300 ㎍ of folateafter the 12th week of gestation

14. Antepartum Management Antenatal screening • Increased hypertensive disorders in pregnancy • 5 times greater in primigravid women • 10 times greater in multiparous women than singleton pregnancy -> frequent antenatal attendance allows the early detection of hypertension • Gestational diabetes screening; conflicting evidence to support the practice • Increased risk of antepartum hemorrhage from both placenta previa and abruption

15. Antepartum Management Nuchal translucency screening • No RCT about NT in multiple pregnancy • Reports from a study of 448 women with a twin pregnancy • ; NT + maternal age • => yield similar sensitivity & false-positive rates for women with a dichorionic pregnancy as those for women with a singleton pregnancy. • Sebire N, British Journal of Obstetrics and Gynaecology, 1996 • The false-positive rate of screening is higher in women with a monochorionic twin pregnancy than in singleton pregnancies, with discordance for nuchal translucency measures a possible indicator of early onset twin–twin transfusion syndrome. • Nicolaides K, 1999

16. Antepartum Management Routine fetal anomaly ultrasound at 18–20 weeks • Twins have an increased risk of congenital abnormalities • ->midtrimester ultrasound examination between 18 and 20 weeks gestation. • ; A retrospective review of 245 women with a twin pregnancy • -> congenital malformation in 4.9% of cases • Edwards M, Ultrasound in Obstetrics and Gynecology, 1995

17. Antepartum Management Preterm labor • Higher risk of preterm birth • ; rates varying from 30 to 50%. • Trend to increasing preterm birth ; from 40.9% (1981) to 55.0% (1996), in US • Greater risk of preterm birth • for monochorionic twin than dichorionic twins (9.2% of monochorionic vs. 5.5% of dichorionic twins, before 32 weeks) • for higher-order multiple pregnancies (up to 80% in triplet gestations) • In our hospital

18. Antepartum Management Preterm labor 1. Cervical assessment • Cervical length of less than 25 mmat 24 weeks in twins; • ; predictor of spontaneous preterm birth at < 32 weeks (OR 6.9), < 35 weeks (OR 3.2), and < 37 weeks (OR 2.8) • ; its clinical usefulness as a routine evaluation is questionable because of the lack of proven treatments affecting outcome 2. Fetal fibronectin • The presence of fetal fibronectin in cervical secretions ; • ; positive test at 28 weeks to predict preterm birth before 35 weeks • => 50% sensitivity, 92% specificity, 62.5% positive predictive value, 87.3% negative predictive value • it is unclear if this knowledge can result in effective interventions that could reduce preterm labor and birth

19. Antepartum Management Preterm labor 3. Cervical cerclage • Prophylactic cervical cerclage in preventing preterm birth in multiple pregnancies • ; no benefit • ; the routine use of cerclage cannot be recommended. 4. Prophylactic tocolytic agents • The use of prophylactic beta-mimetic agents to prevent preterm birth • ; no benefit in reducing the incidence of preterm labor and birth • ; their use is not advocated • Complications occur more often with the use of tocolytic therapy in multiple gestations than in singletons • ; cardiovascular complications (34.4% vs. 4.0%) • ; the result of a greater increase in plasma volume and cardiac output

20. Antepartum Management Preterm labor 5. Prenatal corticosteroids • The use of corticosteroids ( < 34 weeks) is recommended • Fetal Lung Maturation • Pulmonary maturation is synchronous in twin gestations, measured by L/S ratio • The data concerning acceleration of fetal lung maturation in twin pregnancies is conflicting. • At each biweekly interval from 31 to 36 weeks, twin L/S ratios were significantly greater than those of singletons • No significant difference in the incidence of RDS (38% vs. 35%) or in the use of mechanical ventilation (41% vs. 39%) between groups

21. Antepartum Management Fetal growth • The growth of twin • < 28 to 30 weeks ; similar to singletons > 30 weeks; starts to lag behind the growth of singletons By 36 weeks, the mean birth weight of twins is 2500 g (2800 g for singletons) • The birth weight discordance calculation • ; Bwt (large) – Bwt(small) • Bwt (large) • Perinatal morbidity and mortality in twin pregnancies is related to intrapair birth weight discordance • As the weight discordance increase, the perinatal mortality increase

22. Labor and Delivery Timing of birth • The lowest risk of perinatal mortality and morbidity; between 36 and 38 weeks • After 38 weeks gestation, the perinatal death rate and intrauterine growth restriction of twin pregnancies increase substantially • In a single RCT from Japan, Women were randomised at 37 weeks gestation either to induction of labor or to continued expectant management • ; No statistically significant differences • The ideal time of delivery for an uncomplicated twin pregnancy is still uncertain. • However, the literature appears to support delivery by 38 weeks of gestation

23. Antepartum Management Mode of birth • Women with a twin pregnancy are more likely to give birth by caesarean, with gestational age and fetal presentation influencing this decision • First twin vertex/second twin vertex • the most common presentation of twins • the general recommendation is for vaginal birth, even for infants of estimated very low birthweight (less than 1500 g) • First twin vertex/second twin non-vertex • no consensus as to the most appropriate mode of birth • The only small RCT, planned vaginal or planned caesarean birth showed no differences in neonatal outcome • For the second non-vertex twin of birthweight less than 1500 g, some reports recommend caesarean birth to reduce the risk of birth trauma • First twin non-vertex • Caesarean section is often performed

24. Antepartum Management General care in labor • Monitored continuously by an external monitor, a trained obstetric attendant should be present with the patient throughout the labor. • 2. Blood and blood component products should be immediately available. • 3. An intravenous access with a large-bore catheter should be in place during the labor and delivery process. • 4. An appropriate intravenous antibiotic should be administered for group B Streptococcus prophylaxis if indicated. • 5. Delivery of the multiple gestation should be in an operating room or in a delivery room • 6. Ultrasound should be in the delivery room to determine the lie, presentation, and position of the second twin after the delivery of the first fetus. • 7. An experienced anesthesiologist/anesthetist • 8. a trained pediatrician or neonatologist skilled in neonatal resuscitation • 9. an obstetrician who is skilled in evaluating the presentation and position of the second twin and also in intrauterine manipulation to expedite the delivery of the second twin should attend the delivery.

25. Antepartum Management General care in labor • Intrapartum blood loss and postpartum haemorrhage • ; intravenous access with blood available for cross-matching • When the plan is for vaginal birth, continuous electronic fetal monitoring is recommended • Epidural analgesia is widely available • Experienced obstetrician, with the availability of a paediatrician, neonatal nurse and anaesthetist • After the birth of the first twin, the lie of the second twin should be assessed and, if not longitudinal, converted to such by internal podalic version or external cephalic version followed by amniotomy. • An infusion of Syntocin should be available in the event of uterine inertia. • Active management of the third stage of labor with an oxytocic agent is advocated after the birth of the second twin • TIME INTERVAL BETWEEN DELIVERIES • If there is continuous fetal and uterine monitoring, a time restriction for the delivery interval between the first and second twins is not necessary • However, the cesarean section rate was higher in the group in which the interval was 15 minutes compared with the group with the interval 15 minutes (18% vs. 3%)

26. 다태임신의 특이한 합병증 1) 단일양막성 쌍둥이(monoamnionic twins) - 일란성 쌍태아의 약 1% - 매우 높은 태아 사망률, 제대간의 꼬임현상이 주된 사망원인 2) 결합쌍둥이(conjoined twins) - 일명 샴쌍둥이(Siamese twins) (1) 앞 쪽: 가슴붙은 쌍둥이(thoracopagus) (2) 뒤 쪽: 엉덩붙은 쌍둥이(pygopagus) (3) 둔부: 머리붙은 쌍둥이(craniopagus) (4) 미부: 좌골붙은 쌍둥이(ischiopagus) 3) 쌍둥이간 수혈증후군(twin-to-twin transfusion syndrome) 4) 무심장 쌍둥이(acardiac twin); Twin reversed-arterial-perfusion(TRAP) sequence 5) 불일치 쌍둥이(discordant twin) 6) 일측태아의 사망

27. Congenital Anomaly of One Twin • Occur more frequently than single pregnancy • in particular neural tube defects, bowel atresia, and cardiac anomalies, chromosomal anomalies • Major malformations - 2.12%(twin) Vs 1.05% (single) • Minor malformations - 4.13% (twin) vs 2.45% (single) • Higher in monozygotic than dizygotic (3.1% vs 1.9%) • Option of management • continuation of the entire pregnancy • termination of the entire pregnancy • selective termination of the anomalous fetus • For women with a monochorionic twin, selective termination carries an additional risk of pregnancy loss when compared with dichorionic twin pregnancy

28. Monoamniotic Twins • less than 2% of monozygotic • risk ofcord entanglement, subsequent perinatal mortality (half of the cases) • ; unpredictable, no effective monitoring method • Current care • ; based on cases, with no RCTs to inform practice. • ; Frequent monitoring will not prevent sudden fetal death • ; No consensus of the optimal timing and mode of birth • ; Prophylactic preterm birth may not be indicated

29. Twin–Twin Transfusion Syndrome (TTTS) • Incidence; 4 - 35% of monochorionic twin • Mechanism • ; Vascular anastomosis (usually deep arteriovenous anastomosis) • ; unidirectional blood flow in anastomosis (imbalanced blood flow) • ; resulting in discordance in fetal size and amniotic fluid volume • -> donor twin – oligohydramnios, recipient twin – polyhydramnios • ; in severe oligo-polyhydramnios syndrome, • Stuck twin (oligo-); pulmonary hypoplasia, growth restriction, contracture • Poly-; PROM, fetal hydrops

30. TWIN–TWIN TRANSFUSION SYNDROME (TTTS) • Diagnosis • monochorionic twin gestation with placental vascular anastomoses • same-sex fetuses • intertwin birth weight difference 20% • polyhydramnios of the larger twin, oligohydramnios of the smaller twin • hemoglobin difference of 5 g/dL Perinatal outcome • The overall perinatal survival rate; 21% - 65% • Affecting factors; gestational age at diagnosis, the gestational age at delivery, the severity of the disease, ie, presence of hydrops fetalis.

31. TWIN–TWIN TRANSFUSION SYNDROME (TTTS) • Management • Serial amnioreduction • Laser photocoagulation • Septotomy • Selective fetocide • Expectant vs. serial amnioreduction • ; higher survival rate in amnioreduction group (69% vs. 20%) • Serial amniocentsis vs. laser photocoagulation • ; In non-RCT studies, laser coagulation is associated with increased rates of successful pregnancy and intact neurodevelopmental survival. • Longer-term f/u of children wiith laser coagulation • ; median age of 21 months • ; minor neurological deficiencies - 11% • major neurological deficiencies in a further 11% of children studied

32. TWIN REVERSED ARTERIAL PERFUSION (TRAP) SEQUENCE ; Acardiac twin • Mechanism; • ; direct arterial–arterial communications • ; when the arterial pressure in one twin exceeds the other, there is a reversal of blood flow in the ‘perfused twin’ and the cotwin as the pump twin • ; The perfused twin is designated as the acardiac twin • secondary to the perfusion of ‘used’ deoxygenated blood from the donor or pump twin to the hypoxaemic perfused twin

33. TWIN REVERSED ARTERIAL PERFUSION (TRAP) SEQUENCE • Mortality • ; perfused twin – 100% • ; donor twin – 50-70 % • - with development of hydramnios and hydrops secondary to high output cardiac failure • Management • ; no RCTs to inform optimal clinical management of the TRAP sequence • ; Case series recommend fetal surveillance, • - Control of polyhydramnios or hydrops; serial amniocentesis • ; Occulusions of the circulation of the acardiac twin • ; Mid trimester hysterotomy and selective delivery of acadiac twin

34. Discordant Twin • Weight discordance usually apparent in the late second or early third trimester • In monochorionic twins • ; placental vascular anastomoses -> an imbalance in blood flow between the fetuses • In dichorionic twin • ; genetically different, in utero crowding

35. Discordant Twin • Diagnosis • The weight discordance that is clinically significant has not been well stablished. • As the weight discordance increase, the perinatal mortality increase • the risk of fetal death increased progressively when the weight discordance exceeded 25% • ; the relative risk of 2.9 at 26% to 30% discordance • 5.6 at 31% to 40% discordance • ; an intrapair weight discordance of 20% to 25% is associated with a significant risk of an adverse perinatal outcome.

36. Single Fetal Death In 1 trimester ‘vanishing twin’ ; Clinically - vaginal bleeding ; The prognosis for the remaining fetus - generally good After 1 trimester • Incidence of fetal demise; 0.5 - 6.8% • Morbidity • maternal DIC; 25% or much less • risk of death in the remaining twin; 20–25% • preterm birth • development of renal and cerebral cystic lesions in the survivor

37. Single Fetal Death • Single fetal death & Monochorionic • ; Single fetal death in utero is more frequent in monochorionic twin • ; Morbidity in surviving monochorionic cotwin • - 10 times greater than for dichorionic twin • - In review of 481 twin, • ; monochorionic – 30% neonatal death, 10% cerebral palsy • dichorionic – benign except anomaly cases • - In review of 92 twin • ; intrauterine death (26% vs. 2.4%), anemia (51.4% vs. 0%), intracranial lesion at birth (46% vs. 0%) – greater in the monochorionic twin • Specific problems; microcephaly, hydrocephaly, porencephaly, cerebral atrophy, cerebral palsy, limb reduction, intestinal atresia, renal necrosis, and pulmonary, hepatic or splenic infarction • Proposed mechanism in monochorionic twin (esp. CNS abnormalties) • ; the massive blood loss that occurs from the survivor into the more relaxed • circulation of the dead twin through vascular anastomoses

38. Single Fetal Death • Management • Optimal care for the surviving monochorionic co-twin is uncertain. • Expectant management with close maternal and fetal surveillance • Monochorionic; immediate delivery of the surviving twin does not prevent the • occurrence of central nervous system ischemic complications • Dichorionic; the outcome of the surviving twin is usually benign. • Longer-term childhood follow-up; • ; the risk of handicap or cerebral impairment in surviving co-twin • - up to 20%

39. Conclusions • Pre-pregnancy care should focus on avoiding multiple pregnancy • Early prenatal care centres on determining chorionicity and screening for fetal anomalies, • Later care focusing on the presentation, prediction and management of preterm birth, and intrauterine growth restriction. • The optimal timing and mode of birth are the focus of current multicentred RCTs.