Multifetal pregnancy (Twins Pregnancy)

Twins pregnancy, zygosity and chorionicity, amniocity, complications, management, delivery

1. Multiple Pregnancy Dr Nishma Bajracharya FCPS Resident, 1 st year, KMH

2. Introduction Two or more fertilization events Single fertilization followed by splitting of zygote Combination of both

3. Incidence Global incidence: 4/1000 births Hellin’s Law : Twins: 1/80 singleton births Triplets: 1:80 2 Quadruplets: 1:80 3 Conjoined twins: 1 : 60,000

4. Impact Twins account for 17% of all preterm births 24% of low birth-weight infants (<2,500 g) and 26% of very-low-birth-weight infants (<1,500 g) (ACOG,2004) Women with twin pregnancy are 6 times more likely to be hospitalized with complications

5. Dizygotic / non-identical twins ( binovular , fraternal, 2 egg twins) ~ two third of twins. fertilization of two independently released ova by two different sperm. In all polyzygotic multiple pregnancies, each zygote develops its own amnion, chorion and placental circulation, and hence will be polychorionic . not true twins

6. Monozygotic twins ( uniovular , identical or single egg twins) ~One third of twins. arise from the splitting of a single fertilized egg within the first 14 days after fertilization. Always same sex (Identical) does not necessarily result in equal sharing of genetic material , so they may be discordant for genetic mutations , or may have the same genetic disease but with marked variability in expression. teratogenic event

7. MONOZYGOTIC TWINS DIZYGOTIC TWINS PLACENTA 1 or 2 PLACENTA 2 PLACENTA COMMUNICATING VESSELS PRESENT ABSENT INTERVENING MEMBRANE VARIABLE 2 AMNION, 2 CHORION SEX IDENTICAL MAY DIFFER GENETIC FEATURES SAME DIFFER SKIN GRAFTING ACCEPTANCE REJECTION ADULT USUALLY IDENTICAL NOT IDENTICAL

8. Etiology Maternal age Race and heredity : Black race Parity: Increasing parity (2.7% in 4 th pregnancy) Heredity Pituitary Gonadotropin ART: Ovulation induction with FSH and gonadotropin / chlomiphine Greater the number of embryos transfered , the greater the risk of multiple pregnancy

9. Determination of zygosity / chorionicity Chorionicity can be identified in the first trimester with sonography Before 10 weeks sonographic findings to determine chorionicity . Number of 1.gestational sacs 2.amniotic sacs within the chorionic cavity 3.yolk sacs.

10. 1. Number of Gestational Sacs Each gestational sac forms its own placenta and chorion: 2 gestational sacs: DC twin 1 gestational sac with 2 identified heartbeats: MC twin

11. 2. Number of Amniotic Sacs Within the Chorionic Cavity Diamniotic twins: separate and distinct amnions before 10w the separate amnions of a diamniotic pregnancy will not have enlarged sufficiently to contact each other and create the inter-twin septum. TAS: Each single amnion is extremely thin and delicate: very difficult to see TVS: often successful in differentiating separate amnions.

12. 3. Number of Yolk Sacs 2 yolk sacs are seen in the extra-embryonal coelom: diamniotic 1 yolk sac --in most cases indicate monoamniotic twins -- when there are dual embryos: a follow-up 1st T scan to definitively assign amnionicity .

13. After 10 weeks These sonographic signs are no longer present: gestational sacs are no longer distinctly separable, and the inter-twin membrane is formed. Findings: 1.Genitalia 2. Placental number 3. Chorionic peak sign 4. Membrane characteristics .

14. Number of Distinct Placentas 1 placental mass: MC 2 distinct, separate placentas: DC Presence or Absence of the Chorionic Peak (twin peak or lambda sign) Projecting zone of tissue of similar echotexture to the placenta Triangular in cross-section and wider at the chorionic surface of the placenta, extending into, and tapering to a point within, the inter twin membrane. Most often identifies DC MC: absence of the twin peak sign.

15. Dichorionic Twins (Two placentas) Lambda sign Monochorionic Twins (One placenta) T sign

16. Inter-Twin Membrane Characteristics DC : 2 layers of amnion and 2 layers of chorion. Thicker > 2 mm more reflective MC: ≤ 2mm In 2nd T: Number of membranes may be counted, and if there are > 2, then dichorionicity is strongly suggested

17. Dichorionic Diamniotic twin: a triangular projection of chorionic tissue emanating from fused dichorionic placentas and extending between layers of the intertwin membrane. Dichorionic twin in the first trimester: a thick inter twin membrane

18. Monochorionic Twins thin intertwin membrane Monochorionic Twins (One placenta) T sign

19. Pregnancy complications 2 to3 fold increased than singletons Threatened and spontaneous abortions (vanishing twin) 7.3 % risk in multiple pregnancy versus 0.9 % in singleton ( Joo , 2012) Hyperemesis Severe anemia Hypertensive disorders of pregnancy: 3 to 4 fold increase Gestational diabetes Antepartum hemorrhage: abruption Preterm premature rupture of the membranes Operative delivery PPH : 3-4 fold increase Increased maternal mortality

20. Fetal complications Congenital Malformations- 406/10000 in twins versus 238/10000 singletons ( Glinianaia and associates, 2008) Low birthweight- due to restricted fetal growth and preterm delivery Preterm birth Monochorionic pregnancy complications Perinatal asphyxia Fetal death, Cord accidents Increased perinatal mortality

21. Unique fetal complications Monoamniotic twins- 1 in 20 monochorionic twins are monoamniotic Associated with high fetal death rate from cord entanglement, congenital anomalies, preterm birth, or twin- twin transfusion syndrome Diamniotic twins can become monoamniotic if the dividing membrane ruptures

22. Aberrant twinning mechanisms

23. Conjoined twins

24. External parasitic twins- grossly defective fetus or merely fetal parts attached externally to a relatively normal twin Believed to result from demise of the defective twin with its surviving tissues attached to and vascularized by its normal twin Fetus in fetu - early in development, one embryo may be enfolded within its twin Classically vertebral or axial bones are found in these fetiform mases, supported by their host by a few large parasitic vessels

25. Monochorionic twins with vascular anastomoses Two amniotic sacs and a common surrounding chorion anatomical sharing of the two fetal circulations through anastomoses of placental arteries and veins Artery to artery anastomoses are most common and are identified on the chorionic surface of the placenta- 75% Vein to vein and artery to vein– approx. 50%

26. Deep artery to vein connections can extend from capillary bed of a given villus, creating a common villous compartment or third circulation Depending on the degree to which they are hemodynamically balanced, severity occurs With significant pressure or flow gradients, a shunt will develop between fetuses Chorioinic feto fetal transfusion result in several clinical syndromes

27. Twin-Twin Transfusion syndrome 5 – 17 % of monochorionic twin Mortality irrespective of gestational age is 60-70% Mechanism: deep A-V vascular anastomosis

28. Blood is transfused from donor twin to its recipient sibling – donor is anemic and growth may be restricted Recipient becomes polycythemic , with circulatory overload and may manifest as hydrops Classic TTTS results from unidirectional flow through AV anastomoses Deoxygenated blood from donor placental artery- pumped into a cotyledon shared by recipient. Once oxygen exchange is completed in the chorionic villus, oxygenated blood leaves the cotyledon via a placental vein of the recipient twin

29. Clinically important TTTS is frequently chronic, results from significant volume differences Presents in mid pregnancy, donor fetus- oliguric due to decreased renal perfusion – develops oligohydramnios Recipient- polyhydramnios Stuck twin, polyhydramnios- oligohydramnios – syndrome (poly- oli )

30. Diagnosis Society for maternal- fetal medicine (2013) Two criteria- 1.presence of a monochorionic diamniotic pregnancy 2. Hydramnios defined if the largest vertical pocket > 8 cm in one twin and oligohydramnios < 2cm in the other twin. Quintero staging: Stage 1 – Oligo/poly sequence and bladder seen in donor twin, normal Doppler studies Stage 2 - Oligo/poly sequence; donor bladder not seen; normal Doppler studies.

31. Stage 3 - Oligo/poly sequence; donor bladder not seen; Doppler with at least one of the following alterations: Absent or reversed diastolic flow in the umbilical artery of the donor twin Reversed flow in the ductus venosus of the donor twin Pulsatile flow in the umbilical vein of the recipient twin. Stage 4 – fetal hydops in any of the twins Stage 5 – Death of one or both twins.

32. Management and Prognosis Related to Quintero staging and gestational age at presentation > 3/4 of stage 1 cases- remains stable and regress without intervention Perinatal loss rate of 70-100 % of stage 3 or more without intervention Therapies- amnioreduction, laser ablation of vascular anastomoses, selective feticide, septostomy

33. Recommendations by RCOG TTTS should be managed in conjunction with fetal medicine centres with recourse to specialist expertise and treatment in supraregional centres . TTTS presenting before 26 weeks of gestation should be treated by fetoscopic laser ablation rather than amnioreduction or septostomy . Weekly ultrasound assessment (including examination of the fetal brain, heart and limbs) and serial measurements of UAPI, MCA- PSV and ductus venosus Doppler velocities should be performed. After 2 weeks post treatment, the ultrasound interval can be increased to every 2 weeks with documentation of adequate fetal growth (by calculating EFW). In treated TTTS pregnancies, ultrasound examination of the fetal heart should be performed by the fetal medicine specialist to exclude functional heart anomalies.

34. Serial amnioreduction Laser photocoagulation of placental vascular anastamosis

35. septostomy Selective feticide

36. Twin Anemia Polycythemia Sequence (TAPS) 3-5 % monochorionic pregnancies 13% after laser photocoagulation Significant hemoglobin differences between donor and recipient twins without the discrepancies in amniotic fluid volumes Diagnosis- MCA peak systolic velocity (PSV) > 1.5 mutiples of median in donor and <1.0 multiples of median in recipient twin Spontaneous TAPS usually occurs after 26 weeks and iatrogenic TAPS within 5 weeks after the procedure.

37. Twin Reversed Arterial Perfusion (TRAP) Sequence Aka acardiac twin Most serious complication of monochorionic multifetal gestation 1 in 35,000 pregnancies Normally formed donor twin with features of heart failure and recipient twin that lacks a heart and other structures. Hypothesis- caused by a large artery to artery placental shunt, also accompanied by vein to vein shunt.

38. Discordant growth of twin fetuses 15 % of twin gestation Diagnosis- sonographic fetal biometry to compute the estimated weight for each twin % discordancy= ( wt of larger twin- wt of smaller twin)/ wt of larger twin (20% or more) AC measurements differ more than 20mm Weight discordancy > 25-30 % predicts an adverse perinatal outcome- such as respiratory distress, intraventricular hemorrhage, seizures, sepsis etc

39. Selective growth reduction ( sGR ) sGR (growth discordance of > 20%) --Approximately 10–15% of monochorionic twins Cause- unequal placental sharing where one fetus gets blood from major placental territory than the other Stage I- Growth discordance but positive diastolic velocities in both fetal umbilical arteries. Stage II- Growth discordance with persistent absent or reversed end-diastolic velocities (AREDV) in one or both fetuses. Stage III- Growth discordance with intermittent absent or reversed end-diastolic flow in a cyclical pattern( iAREDV )

40. Recommendations by RCOG sGR in monochorionic twins requires evaluation in a fetal medicine centre . In cases of early-onset sGR in association with poor fetal growth velocity and abnormal umbilical artery Doppler assessments, selective reduction may be considered an option. surveillance of fetal growth should be undertaken at least every 2 weeks with fetal Doppler assessment (by umbilical artery and middle cerebral artery pulsatility index, and peak systolic velocity) Clinicians should be aware that there is a longer ‘latency period’ between diagnosis and delivery in monochorionic twins complicated by sGR compared with growth restriction in dichorionic twin pregnancy or singleton pregnancy.

41. In type I sGR , planned delivery should be considered by 34–36 weeks of gestation if there is satisfactory fetal growth velocity and normal umbilical artery Doppler waveforms. In type II and III sGR , delivery should be planned by 32 weeks of gestation, unless fetal growth velocity is significantly abnormal or there is worsening of the fetal Doppler assessment.

42. Fetal demise More in monochorionic twins Death of one fetus- early in pregnancy- vanishing twin Fetal death in a slightly more advanced gestation sometimes- can go unnoticed, and during delivery- normal appearing live infant along with dead fetus, compressed- fetus compressus Flattened remarkably through desiccation -fetus papyraceus Management- decision should be based on gestational age, cause of death and risk to surviving fetus

43. Vanishing twin in first trimester is harmless If loss occurs in 2 nd trimester, the risk of death and damage to survivor is limited to monochorionic twin, (due to vascular anastomoses) Single fetal death during late second and early third trimester presents the greatest risk to the surviving twin. Risk of preterm birth is increased After a single fetal death in a monochorionic pregnancy, the risks to the surviving twin of death or neurological abnormality are 15% and 26%, respectively.

44. Prenatal care and antepartum management All women with a twin pregnancy should be offered an ultrasound examination between 11+0 weeks and 13+6 weeks of gestation (crown–rump length 45–84 mm) to assess fetal viability, gestational age and chorionicity , and to exclude major congenital malformations. Chorionicity should be determined at the time the twin pregnancy is detected by ultrasound based upon the number of placental masses, the appearance of the membrane attachment to the placenta and the membrane thickness. This scan is best performed before 14 weeks of gestation.

45. Women with monochorionic twins who wish to have aneuploidy screening should be offered nuchal translucency measurements in conjunction with first trimester serum markers (combined screening test) at 11+0 weeks to 13+6 weeks of gestation In women with monochorionic twin pregnancies who ‘miss’ or who have unsuccessful first trimester screening for aneuploidy, second trimester screening by the quadruple test should be offered. All monochorionic twins should undergo a routine detailed ultrasound scan between 18 and 20+6 weeks of gestation which includes extended views of the fetal heart anatomy.

46. Fetal ultrasound assessment should take place every 2 weeks in uncomplicated monochorionic pregnancies from 16+0 weeks onwards until delivery. At every ultrasound examination, liquor volume in each of the amniotic sacs should be assessed and a deepest vertical pocket (DVP) depth measured and recorded, as well as the umbilical artery pulsatility index (UAPI). Fetal bladders should also be visualised . Although first presentation of TTTS is rare after 26+0 weeks of gestation, it can occur and therefore, scans should be performed at 2-weekly intervals in uncomplicated monochorionic twins until delivery From 16+0 weeks of gestation, fetal biometry should be used to calculate an EFW and the difference in EFW calculated and documented. As the risk of sGR extends to delivery, this should be performed at 2-weekly intervals until delivery.

47. At each scan from 20 weeks of gestation (at 2-weekly intervals) onwards, calculate EFW discordance using two or more biometric parameters. Calculate percentage EFW discordance using the following formula: ([larger twin EFW – smaller twin EFW]/larger twin EFW) x 100. Liquor volumes as DVP should be measured and recorded (to differentiate from TTTS). Umbilical artery Doppler evaluation in monochorionic twins with sGR allows definition of prognosis and potential morbidity. In particular, those with absent or reversed end-diastolic velocities (AREDV) and ‘cyclical’ umbilical artery Doppler waveforms (intermittent AREDV [ iAREDV ]) are at increased risk of perinatal mortality and morbidity

48. Prediction of preterm birth Cervical Length Measurement by Ultrasonography <25 mm at 24 wks -best predictor for preterm birth >35 mm at 24 wks -low risk of preterm birth

49. Prevention of preterm birth? Routine Hospitalization retrospective study have shown that bed rest in the hospital does not prolong twin gestation Prophylactic Cerclage cerclage did not prolong gestation or improve perinatal outcome Restriction of Activities and Rest at Home it has not been evaluated in a prospective randomized manner. Progesterone therapy- Weekly injections of 17 a hydroxyprogesterone caproate (17 OHPC) is not shown to be effective for multifetal gestations. Vaginal progesterone therapy (Micronized progesterone) no certain benefit

50. Tocolytics trials showed no consistent effect on preterm birth, birth weight, or neonatal mortality. Corticosteroids recommends that all women in preterm labor who have no contraindications to steroid use be given one course of steroids, regardless of the number of fetuses

51. Labor and Delivery Timing of delivery of twins should be decided when the benefit of prolonging the pregnancy is outweighed the risk of still birth Perinatal mortality of twins starts to become significantly high after 38 weeks Uncomplicated dichorionic twins – managed expectantly and delivery can be around 38 weeks In cases of prematurity and discordant fetal well being exists, timing of delivery should be based on parameters of healthy twin. Uncomplicated monochorionic twins- delivery at around 37 weeks In case of discordant fetal well being or an anomaly, timing of delivery should be based on the condition of compromise fetus.

52. Mode of Delivery Cephalic- cephalic presentation- vaginal delivery preferred, RCT by Barrett and coworkers (2013) concluded that planned cesarean delivery does not improve neonatal outcome when both twins are cephalic Cephalic- non cephalic presentation- controversial Reports say- vaginal delivery of second non cephalic twins whose birthweight <1500gm is safe 2 nd twin- breech extraction of non cephalic twin, or internal podalic version of an unengaged cephalic second twin followed by breech extraction Following delivery of 1 st twin, the presenting part of the second twin, its size, and its relationship to the birth canal should be quickly and carefully ascertained by combined abdominal, vaginal and at times, intrauterine examination.

53. Internal podalic version- with this maneuver, a fetus is turned into a breech presentation using the hand placed into the uterus. Breech extraction is considered superior to external version because less fetal distress developed. Breech presentation of the first twin- similar as singleton breech fetus- cesarean delivery is preferred Locked twins- first fetus breech and second cephalic, breech of the first twin descends through the birth canal, the chin locks between the neck and chin of the second cephalic presenting co twin- cesarean delivery is preferred.

54. Multifetal pregnancy reduction (MFPR) Initially used as a procedure to selectively terminate fetuses with congenital abnormality or genetic d/o Now, usage to terminate one or more fetuses of a multiple gestation pregnancy while allowing some fetuses to remain alive Risks associated and ethical issues related to it are still a debate. MFPR is usually carried out through transabdominal route with USG guidance. 2-3 Meq KCL is injected to each fetus that is to be terminated into fetal thorax, asystole should be observed for 3 minutes Associated with 5-7 % risk of miscarriage.

55. Keys to remember Multiple pregnancies are at increased risk of pregnancy complications that singletons Pregnancy outcome of multiple pregnancy is mainly determined by the chorionicity First trimester USG is very reliable in determining accurate pregnancy dating, chorionicity , orientation and abnormal twin gestation Monochorionic twins should be monitored more often between 16- 24 weeks for early diagnosis of fetal transfusion syndromes Fetal growth of the multiple pregnancy should be monitored 4 weekly from 26-38 weeks

56. In case of suspected fetal transfusion syndrome, discordant growth >25 %, MCMA and higher order twins should be managed in specialized centers Uncomplicated DC twins should be delivered at 38 weeks, Uncomplicated monochorionic twins- delivery at around 37 weeks Mode of delivery is decided by presentation of presenting twin, gestation of delivery, chorionicity and fetal well being at the time of delivery MFPR is an option to improve pregnancy outcome in higher order multiples.

57. References Fernando Arias, Shirish, Amarnath. Multifetal gestation, High risk pregnancy and delivery. 4 th edition RCOG Green-top Guideline No. 51, November, 2016 Cunningham, Levono , Bloom, H Auth , Rouse,Sponge . Multifetal Pregnancy Williams obstetrics ; 24th edition ACOG practice bulletin. Clinical management guidelines for Obstetrician– Gynecologists.Number 56, October 2004

58. Thank you