Multiple pregnancy: antenatal care for twin and triplet pregnancies

1. Multiple pregnancy: antenatal care for twin and triplet pregnancies professor Dr Esraa AL-Maini

2. Introduction The incidence of twinning ranges from 4 per 1000 births in Japan to as frequent as 54 per 1000 in some regions of Nigeriais 1- more prevalent in pregnancies with advancing maternal age (strongest at 30–39 years) (presumed to be secondary to the rise in follicle‐stimulating hormone concentrations ( spontaneous dizygous) 2- Familial predisposition to multiple ovulations (usually dizygoustwinning) may occur and is presently best explained by an autosomal dominant inheritance pattern 3-monozygotic constant incidence of approximately 3.9 per 1000. The incidence of multiple births has risen in the last 30 years.The combined effects of delayed childbearing and high uptakes of assist reproductive technologies at advanced maternal age have been responsible for this rise .

3. Up to 24% of successful IVF procedures result in multiple pregnancies. • increase is due to assisted reproductive technologies,such as superovulation (using antioestrogens or gonadotrophins)and in vitro fertilization (IVF) with embryo transfer. • There is evidence that the number of multiple pregnancies is influenced by the number of embryo transfers and, as such, the number of multiple pregnanciesassociated with IVF has reduced since the recommendation that embryo transfer numbers be reduced. • In addition, epidemiological evidence suggests that assisted reproduction techniques increase the incidence of monozygous twinning by up to eightfold . This is particularly associated with the techniques of ‘blastocyst hatching’. • Monochorionic twins comprise 20% of spontaneous and 5% of iatrogenic twin gestations.

4. maternal mortality associated with multiple births is 2.5 times that for singleton births. • This high perinatal fetal loss and morbidity is largely attributed to : • the increased risk of prematurity and also intrauterine growth restriction (IUGR) with associated iatrogenic prematurity (irrespective of chorionicity. Cerebral palsy is approximately three times more common in twins and 10 times more common in triplets compared with singletons. Multiple pregnancy may be classified according to: Number of fetuses: twins, triplets, quadruplets, etc. Number of fertilized eggs: zygosity. Number of placentae: chorionicity. Number of amniotic cavities: amnionicity.

5. Twin pregnancy may be dizygotic (70%) or monozygotic (30%). • Dizygotic twins (non-identical) occur from ovulation and subsequent fertilization of two oocytes. • This results in dichorionicdiamniotic twins, where each fetus has its own placenta and amniotic cavity. Although they always have two functionally separate placentae (dichorionic), the placentae can become anatomically fusedtogether and appear to the naked eye as a single placental mass. • They always have separate amniotic cavities (diamniotic) and the two cavities are separated by a thick three-layer membrane (fused amnion in the middle with chorion on either side; The fetuses can be either same-sex or different-sex pairings.

6. Monozygotic (identical) pregnancies result from fertilization of a single ovum with subsequent division of the zygote. • If the zygote splits shortly after fertilization with in 3days , the twins will each have a separate placenta and thus will be dichorionicdiamniotic in 10%

7. Monochorionicdiamniotic (20%) pregnancies occur when division of the zygote occurs between days four and eight post fertilization Splitting after formation of the inner cell mass. • The vast majority of monochorionic twins have two amniotic cavities (diamniotic) but the dividing membrane is thin, as it consists of a single layer of amnion alone • Monochorionicmonoamniotic (1%) pregnancy occurs when division occurs between days 8 and 12 post fertilization and finally conjoined twins occur when division of the zygote happens after day 13 after formation of embryonic disc

9. Conjoined twins: Classified according to anatomic location of incomplete splitting Thoracopagus anterior pygopagus-posterior craniopagus-cephalic ischiopagus-caudal

11. Maternalhomeostatic responses All the normal physiological adaptations, such as increased cardiac output, glomerular filtration rate and renal blood flow, are further increased in a multiple pregnancy. Women with twins increase their plasma volume by one‐third more than women with singletons. Red cell mass increases approximately 300 mL more than in singleton pregnancies but because this is disproportionately less than the increase in plasma volume, haemoglobin and haematocrit values fall.

12. . Maternal iron stores are diminished in 40% of women with twins routine haematinic supplementation is recommended (usually as combined iron sulfate and folic acid supplementation) • . Hyperemesisgravidarum is more common in multiple pregnancies and is managed as in singleton pregnancies.Severe cases may respond to maternal steroid therapy and require pyroxidine (B6) supplementation. • The majorityof minor pregnancy complications such as backache, symphysis pubis dysfunction, oedema, varicose veins, haemorrhoids and stria are all increased as a result of both the physical effects of greater uterine size and greater placental hormone production . • Hypertensive disease of pregnancy and pre‐eclampsia are up to 10 times more common in multiple compared with singleton pregnancies but are managed once • diagnosed on standard principles (as in singletons).

13. Consideration should be given to low‐dose aspirin prophylaxis • but there are no national/international recommendations to this effect. • Maternal pregnancy‐related hypertension remains a significant cause of maternal morbidity (and mortality) in multiple pregnancies and a significant cause of iatrogenic preterm delivery, increasing perinatal morbidity and mortality. • This occurs in 15–20% of twin pregnancies, 25% of triplets and up to 60% of higher‐order multiple pregnancies

14. Postnatally, the physical difficulties and socioeconomic impact of coping with the demands of two or more babies are considerable. • Postnatal depression is more common in women nursing twins than singletons . • With the high perinatal loss rates there are often associated • problems of postnatal grieving and bereavement. • Families of women who give birth to babies after a multiple pregnancymay require additional social support

15. Woman-centred care • Treatment and care should take into account women's needs and preferences.Women with twin and triplet pregnancies should have the opportunity to make informed decisions about their care and treatment, in partnership with their healthcare professionals. • If women do not have the capacity to make decisions, healthcare professionals should follow the the Department of Health's advice on consent Good communication between healthcare professionals and women is essential.

16. General care • 1-Information and emotional support • 2-Explain sensitively the aims and possible outcomes of all screening and • 3-diagnostic tests to women with twin and triplet pregnancies to minimise their anxiety. • 4-Diet, lifestyle and nutritional suppleme Give women with twin and triplet pregnancies the same advice about diet, • lifestyle and nutritional supplements as in routine antenatal care • 5-Be aware of the higher incidence of anaemia in women with twin and triple pregnancies compared with women with singletone • 6- Perform a full blood count at 20–24 weeks to identify women with twin and • 7-triplet pregnancies who need early supplementation with iron or folic acid, and repeat at 28 weeks as in routine antenatal care 

17. Special Clinical care for women with twin and triplet pregnancies should be provided by a multidisciplinary team consisting of: a core team of named specialist obstetricians, specialist midwives andultrasonographers, all of whom have experience and knowledge of managing twin and triplet pregnancies an enhanced team for referrals, which should include: a perinatal mental health professional a women's health physiotherapist an infant feeding specialist a dietitian. 

18. Coordinate clinical care for women with twin and triplet pregnancies to: minimise the number of hospital visits provide care as close to the woman's home as possible provide continuity of care within and between hospitals and the community. The core team should offer information and emotional support specific to twin and triplet pregnancies at their first contact with the woman and provide ongoing opportunities for further discussion and advice including: antenatal and postnatal mental health and wellbeing antenatal nutrition the risks, symptoms and signs of preterm labour and the potential need for corticosteroids for fetal lung maturation likely timing and possible modes of delivery breastfeeding parenting.

19. 1-Determining gestational age and chorionicity -women with a twin pregnancy should be offered an ultrasound examination between11 +0 weeks and 13+6 weeks of gestation (crown–rump length 45-84 mm) to assess; 1- Fetal viability 2-Gestational age 3-Chorionicity 4- Exclude major congenital malformations. Chorionicity should be determined at the time the twin pregnancy is detected by ultrasound based upon ( 90%100%accuracy ) 1-The number of placental masses, 2-The appearance of the membrane attachment to the( placenta twin peak sign) 3-The membrane thickness.(no. of layers ,thick or thin) This scan is best performed before 14 weeks of gestation.

20. If transabdominal ultrasound scan views are poor because of 1-A retroverted uterus 2- A high body mass index (BMI), use a transvaginal ultrasound scan to determine chorionicity. If a woman with a twin or triplet pregnancy presents after 14 weeks 0 days, determine chorionicity at the earliest opportunity by ultrasound using all of the following: 1-The number of placental masses 2-The lambda or T-sign 3-Membrane thickness 4-Discordant fetal sex (16-20 weeks)for medical reasons

21. -A photographic (thermal copy) record should be taken and placed in the patients notes documenting the ultrasound appearance of the membrane attachment to the placenta( may need another opinion ,) as chorionicity is best determined before 14 weeks of gestation. • -On ultrasound, the fetuses in twin pregnancies should be assigned nomenclature (i.e. upper and lower, or left and right) and this should be clearly documented in the womans case notes • -Women should informed monochorionic twin pregnancies have higher fetal loss rates than dichorionic twin pregnancies, mainly due to second trimester loss and, overall, may have a higher risk of associate neurodevelopmental morbidity

22. This is because chorionicity is relevant to: ●● counselling parents in relation to the risk of perinatal morbidity and mortality ●● counselling parents in relation to their risk of genetic and structural abnormalities; ●● invasive testing and the management of discordant congenital anomaly; ●● feasibility of multiple fetal pregnancy reduction; ●● risk of complications that may occur in a multiple pregnancy and potential sequelae ; ●● early detection and management of feto‐fetal transfusion syndrome.

23. ZYGOSITY: Monochorionic twins by definition are monozygotic, Discordant‐sex twins are dizygous. while in dichorionic concordant‐sex twins the chance of dizygosity is 75–80% In the remaining 50%, zygosity cannot be determined without DNA fingerprinting, such as the polymerase chain reactionTechnique Not only are parents curious but knowledge of zygosity influences the twins’ rearing, their sense of identity, their genetic risks and their transplantation compatibility. However, it is not routine to offer this incurrent practice in UK. Rarely there may be indications for zygosity testing in utero on invasive

24. 2-Miscarriage Twins have a high incidence of spontaneous early pregnancyloss. 12% of human conceptions start as twins ,are found at least twice as commonly in the first trimester as at birth. First‐trimester early pregnancy loss and resorption of one previously indefinable twin on ultrasound is known as the ‘vanishing twin’ phenomenon and is estimated to occur in up to 20% of twin pregnancies Spontaneous first‐trimester loss of one or more fetuses in high‐order pregnancies is estimated to occur approximately 50% of the time.(up to 13weeks ) When one twin dies in utero in mid‐trimester (13-20), a papyraceous fetus (the squashed paper‐like remains of the baby) may be found alongside the placenta after delivery. In some cases, this is onlyidentifiable histopathologically

25. In dichorionic twins, the second or third trimester after 20 weeks intrauterine death of one fetus may be associated with the onset of labour, although in some cases the pregnancy may continue uneventfully and even result in delivery at term. Careful fetal and maternal monitoring is required .By contrast, fetal death of one twin in monochorionic twins may result in immediate complications in the survivor. These include death or brain damage with subsequent neurodevelopmental handicap. Acute hypotensive episodes, secondary to placental vascular anastomoses between the two fetuses, result inhaemodynamic volume shifts from the live to the dead fetus. The acute release of vasoactive substances into the survivor’s circulation may also play a role. Death or handicap of the co-twin occurs in up to 30% of cases.

26. 3-Screening for Down’s syndrome -Should be done by health care professional with experience with care for twin and counseling . -Inform women about the complexity of decisions they may need to make depending on the outcomes of screening, including different options according to the chorionicity of the pregnancy - map the fetal positions

27. Womenwith dizygous twins can be counselled that the chance of their pregnancy producing a child with Down’s syndrome is theoretically double their age‐related risk, where as women with monozygous twins simply have their age‐related risk that both twins will be aneuploid. Serum screening is, in general, inapplicable to multiple pregnancies

28. second trimester serum screening for Down’s syndrome in triplet pregnancies not used Offer women with twin and triplet pregnancies who have a high risk of Down’s syndrome referral to a fetal medicine specialist in a tertiary level fetal medicine centre of women with a multiple pregnancy

29. Women with twins who wish to have aneuploidy screening should be offered use the combined screening test (nuchal translucency, beta-human chorionic gonadotrophin, pregnancy- associated plasma protein-A) at approximately 11 weeks 14) calculate the risk of Down’s syndrome per pregnancy • In dichorionic twins, the risk of aneuploidy is that ofeach of the individual fetuses. • In monochorionic twinpregnancies, the risk of aneuploidy is the averagebetween the twins

30. In women with twin pregnancies who miss or who have unsuccessful first trimester screening for aneuploidy, second trimester screening by the quadruple test(alpha feto protein ,B HCG ,E2 Inhibin 14-21) should be offered (Result is awaited) Down’s syndrome in twins, but the results of large prospective studies are awaited . Screening for Down’s syndrome using a maternal plasma sample to perform cell‐free DNA sequencing also known as non‐invasive prenatal testing (NIPT), IN monochorionic twins should be equally reliable as in singletons. In monochorionic twin pregnancies, higher failure rate and lower accuracy compared with MONO small study

31. Invasive test   consider second trimester serum screening and explain to the woman the potential problems of such screening. These include the increased likelihood of pregnancy loss associated with double invasive testing (amniocentesis) because the risk of Down's syndrome cannot be calculated separately for each baby Invasive procedures in twins and other higher‐order multiple pregnancies are potentially complex techniques and should only be performed in fetal medicine referral centres The in utero topography (placental and membranes) is mapped using ultrasound. The location of the fetuses, the placental site(s) and the plane of the dividing septum in three dimensions should be noted and recorded. Such is a prerequisite for interpretation of discordant results and for selective termination of pregnancy.

32. In monochorionic twins, sample only one fetus by either amniocentesis or chorionic villous sampling (CVS). However, rare cases of heterokaryotypicmonochorionic twins may be missed (occurring in <1%). So, amniocentesis on both amniotic sacs is worthy of consideration if monochorionic twins are 1-discordant for structural anomalies 2-nuchal translucencies or growth.

33. In dichorionic twins, there has been controversy CVS is less desirable than amniocentesis for performing karyotyping. Because of problems with contamination 2% miss dsaignosis So limited to CVS to high‐risk cases such as - monogenic disease or -there is an aneuploidy risk of greater than 1 in 50. RCOG guidelines amniocentesis as the preferred option for karyotyping in dichorionic twins. to be weighed against the increased risks of selective reduction at increased gestational ages.

34. When performing fetal blood sampling, the intrahepatic vein may be sampled to avoid confusing the cord origins in twins. The overall pregnancy‐loss rate was 2-3%

35. 4-Screening for structural abnormalities Monozygous twins have a 50% increase in structural abnormalities per baby. In particular, they have twice the frequency of congenital heartdisease (a fourfold increase per pregnancy). monochorionic twins should undergo a routine detailed ultrasound scan between 18 and 20+6weeks of gestation which includes extended views of the fetal heart anatomy (as recommended in the Fetal Anomaly Screening Programme screening of a singleton fetus). Consider scheduling ultrasound scans in twin and triplet pregnancies at a slightly later gestational age than in singleton pregnancies and be aware that the scans will take longer to perform. 30-45 minut

36. In dichorionic twins discordant for fetal anomaly, Selectivetermination of pregnancy by the induction of asystole using an abortifacient is associated with an 8% loss rate, with lower rates if the procedure is performed before 16 weeks’ gestation Selective termination of monochorionic twins cannot be performed using injection of an abortifacient as this would lead to death of the healthy twin due to sharingof the circulation along vascular anastomoses. However, a variety of cord occlusion techniques has been developed to render selective termination feasible, associated increased risk of co‐twin demise and co‐twin morbidity when these Survival rates of the co‐twin vary between 70 and 80% in reported single‐centre series

37. What is the optimum ultrasound regimen for twin pregnancies? uncomplicated dichorionic twin pregnancies at least eight antenatal appointments with a healthcare professional from the core team. At least two of these appointments should be with the specialist obstetricianevery 4weeks from 16 to 36 weeks , Offer additional appointments without scans at 16 and 34 weeks. Fetal ultrasound assessment should take place every 2 weeks in uncomplicated monochorionic pregnancies from 16 +0 weeks onwards until delivery at least nine antenatal appointments (30-34 escape ) Offer women with uncomplicated monochorionictriamniotic and dichorionictriamniotic triplet pregnancies at least 11 antenatal trichorionictriamniotic triplet pregnancies at least seven antenatal appointments . Offer an additional appointment scan at 16 weeks. Women with twin and triplet pregnancies involving a shared amnion should be offered individualised care from a consultant in a tertiary level fetal medicine centre

38. Monitoring for intrauterine growth restriction Ultrasound is the primary tool for monitoring growthin multiple pregnancies for several reasons. The risk ofIUGR (~25%) is higher than in singleton pregnancy in two‐thirds of cases growth will be discordant (affecting one twin only). In addition, abdominal palpation andsymphysis–fundal height measurement are unreliable as indices of growth in individual fetuses as they reflect total intrauterine growth. There is no proven agreement on the ideal frequency of ultrasound examination. However, it is common policy to scan dichorionic twins at up to 4‐weekly intervals from 24 weeks’ gestation with or without Doppler measurements as indicated.

39. Monochorionic twins are oftenscanned more frequently, at 2‐weekly intervals, from16 weeks onwards, (significant overlap in diagnosis between early twin–twin transfusion syndrome and selective IUGR.) singleton biometric charts should be used. Many centres use the measurement of discordancy inestimated fetal weight Consider a 25% or greater difference in size between twins or triplets as a clinically important indicator of intrauterine growth restriction and offer referral to a tertiary level fetal medicine centre. This parameter has some predictive value in monochorionic twins for bad outcome in feto‐fetal transfusion syndrome and stillbirth but not in dichorionic twin . Do not use umbilical artery Doppler ultrasound to monitor for intrauterine growth restriction or birth weight differences in twin or triplet pregnancies.

40. Indications for referral to a tertiary level fetal medicine centre Seek a consultant opinion from a tertiary level fetal medicine centre for: monochorionicmonoamniotic twin pregnancies monochorionicmonoamniotic triplet pregnancies monochorionicdiamniotic triplet pregnancies dichorionicdiamniotic triplet pregnancies pregnancies complicated by any of the following: discordant fetal growth fetal anomaly discordant fetal death feto-fetal transfusion syndrome

41. The standard principle of management of IUGR (i.e. delivery when the risks of continued intrauterine life outweigh those of extrauterine existence) needs modification in twin pregnancy to account for the risks to both twins. The latency between absent end‐diastolic flow velocity in IUGR in twins is longer before ‘pre‐terminal’ factors precipitate delivery than in singleton pregnancies. this latency is longest in monochorionic twins.  cessation of fetal growth with pre‐terminalarterial cerebral, peripheral and intracardiacarterial and venous Doppler studies may warrant deliveryat 26 weeks in a singleton fetus.

42. Discordant IUGR at such an early gestation in dichorionic twins might better be managed by allowing the severely affected IUGR fetus to die in utero, sparing the healthy fetus the risks of iatrogenic prematurity. In monochorionic twins, such decisions are even more complex. There is some evidence that the presence or absence of umbilical artery Doppler flow during diastole is indicative of prognosis. Positive end‐diastolic velocities indicate the best prognostic group when there is significant discordancy between monochorionic twins in terms of growth.

43. Absent end‐diastolic velocity indicates an intermediate risk group and so‐called intermittent absent end‐diastolic velocity indicates the worst prognostic group ( perinatal morbidity ) monochorionic the ‘larger’ twin may have the highest morbidity in terms of neurodevelopmentalsequelae. In some cases (of early onset) it may be necessary to consider selective cord occlusion rather than delivery of the whole pregnancy(are difficult decisions )evoking Management in a tertiary centre

44. Maternal complications Hypertension Measure blood pressure and test urine for proteinuria to screen for hypertensive disorders at each antenatal appointment in twin and triplet pregnancies as in routine antenatal careAdvise women with twin and triplet pregnancies that they should take 75 mg of aspirin1 daily from 12 weeks until the birth of the babies if they have one or more of the following risk factors for hypertension: first pregnancy ,age 40 years or older ,pregnancy interval of more than 10 years BMI of 35 kg/m2 or more at first visit family history of pre-eclampsi , Preterm labour Preterm labour 52.2% of multiple births deliver before 37 weeks, The median gestational ages at delivery in twins and triplets is 37 and 34 weeks, respectively and This is the major cause of neonatal death in multiple pregnancies:

45. mortality rates are up to seven times higher in twins than singleton pregnancies; in triplets and higher‐order pregnancies, rates of nearly 40 per 1000 live births have been recorded . • Parents should be informed of the symptoms and signs of threatened preterm labour and the advisability of earlypresentation.

46. The risk is not clearly defined. 1-Certainly (as in polyhydramnios) there is increased uterine distension 2-There is also focus on the potential maternal–fetal endocrine interaction, which may predispose to this increased risk Identification of twin pregnancies at risk of preterm birth may improve outcome if effective interventions are used. More reliable than screening

47. Management of preterm labour in multiple Prediction One of the most promising methods of prediction of spontaneous labour in twins is the measurement of maternal cervical length using transvaginal ultrasound. Between 23 and 24 weeks gestation, the mean maternal cervical length is similar to that of singleton pregnancies (38 mm). At this gestation, a cervical length of 25 mm or less will have a positive for delivery prior to 34 weeks. Do not use fetal fibronectin testing nor home uterine activitity nor cervical length (with or without fetal fibronectin) routinely to predict the risk of spontaneous preterm birth in twin or triplet pregnancies.

48. Prevention Do not use the following interventions (alone or in combination) routinely to prevent spontaneous preterm birth in twin or triplet pregnancies: bed rest at home or in hospital intramuscular or vaginal progesterone cervical cerclage oral tocolytics.

49. here is no evidence that prophylactic measures, either physical fitting of an Arabin cervical pessary, or pharmacological, prevent spontaneous preterm labour in multiple pregnancies. There is no specific preventive measure (aside from fetal reduction in higher‐order multiple pregnancies

50. Management  1-The use of β2‐sympathomimetic infusions in multiple pregnancy, along with steroids and fluid overload, are known risk factors for the rare but potentially fatal complication of pulmonary oedema( active tocolysis has been abandoned) 2-equally use of oral nifedipine or intravenous atosiban (an oxytocin receptor antagonist) only leads to a relatively modest prolongation of gestation data is sparse.