Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 305–317

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Best Practice & Research ClinicalObstetrics and Gynaecology

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11

Optimal antenatal care for twin and tripletpregnancy: The evidence base

Leanne Bricker, MB.BCh, MRCOG, Consultant inFetal and Maternal Medicine *

Liverpool Women’s NHS Foundation Trust, Crown St, Liverpool L17 8UF, UK

Keywords:twin pregnancytriplet pregnancymultiple pregnancyantenatal careevidence base

* Tel.: þ44 (0) 151 702 4271; Fax: þ44 (0) 151 7E-mail address: Leanne.Bricker@lwh.nhs.uk.

1521-6934/$ – see front matter � 2013 Elsevier Lthttp://dx.doi.org/10.1016/j.bpobgyn.2013.12.006

Twin and triplet pregnancy is a high-risk situation, with increasedrisk of mortality and morbidity for both mother and babies. It is,therefore, essential that high-quality antenatal care is provided tooptimise outcomes and identify and manage complications effec-tively. A number of additional elements of care are advised, whichrequires more monitoring and contact with healthcare pro-fessionals with appropriate expertise. In addition, women shouldbe provided with accurate and relevant information and emotionalsupport to mitigate against the anxiety and stress of these high-risk pregnancies. Early care focuses on determining chorionicityand screening for fetal complications, whereas later care concen-trates on identifying and managing preterm birth, growth re-striction, maternal complications, and planning for delivery.Unfortunately, the evidence base for managing these challengingpregnancies is often lacking, and a number of areas of furtherresearch is required.

� 2013 Elsevier Ltd. All rights reserved.

Introduction

The incidence of multiple births in the developed world has risen mainly from an increase in use ofassisted conception but also from increasing maternal age at conception [1]. Multiple pregnancy is ahigh-risk situation for both mother and babies.

Women who have multiple pregnancies are at higher risk of miscarriage, anaemia, hypertensivedisorders, haemorrhage, operative delivery, and postnatal illness, including postnatal depression [2].

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Maternal mortality is more than double that of singleton gestations [3], and are often overshadowed byfetal considerations. This is reflected in the literature, with only one study from the developed worldaddressing this association [4].

Adverse outcomes for fetuses and babies of multiple pregnancies occur more often [5]. Prematurebirth is the main cause [6], but fetal growth restriction, fetal abnormality, and complications of sharedplacentation are important contributory factors. Cerebral palsy is increased six-fold among twins and24-fold among triplets with causes not restricted to prematurity [7].

It is generally accepted that, in pregnancy, antenatal care is a pre-requisite for optimising outcomes.This premise is no different for multiple pregnancies but, given the higher risk of complications, it islogical to propose that, although some of the care that should be provided is no different to thatrequired for all pregnancies, a number of additional elements of care necessitates moremonitoring andincreased contact with the healthcare team [8].

Additionally, the increased risk may have a psychosocial and economic effect on women and theirfamilies, and may heighten anxiety, resulting in a specific need for more information and support inpregnancy.

In this paper, we aim to summarise the additional elements of antenatal care required to identifycomplications and optimise outcomes in multiple pregnancy, but will not address how to manage thecomplications once detected and diagnosed.

Existing guidelines

Internationally, in the developed world, a number of national documents and guidelines relate tovarious aspects of care of multiple pregnancy [9–14]. The most comprehensive and systematic reviewof the published literature is the UK National Institute of Health and Clinical Excellence (NICE)guideline entitled ‘Multiple pregnancy: the management of twin and triplet pregnancies in theantenatal period’ published in 2011. I was personally a member of the Guidelines Development Group[2], and make reference to that guideline in this chapter.

Early pregnancy

Ideally, multiple pregnancy should be diagnosed early. Obstetric sonography in early pregnancy hasbecome widespread, and is advocated to improve gestational dating and thus reduce induction oflabour for post-mature pregnancy. It also improves early detection of multiple pregnancy [15]. Earlydetection of multiple pregnancy and accurate dating in multiple pregnancy is desirable for severalreasons: (1) it allows accurate amnionicity and chorionicity determination; (2) this, in turn, allowsappropriate planning of care, including discussion about screening for aneuploidy and other fetalcomplications, such as fetal abnormality, twin-to-twin transfusion syndrome and fetal growth re-striction; (3) it allows labelling of each fetus according to lateral or vertical orientation to enableconsistent assessment when serial ultrasound monitoring is undertaken, and when undertaking orinterpreting screening and diagnostic tests and; (4) it allows time for discussion about the risks ofhigher order multiple pregnancy and consideration of multi-fetal reduction (in settings where this isacceptable).

Appropriate amnionicity and chorionicity determination is key to providing optimal antenatal careand, if it cannot be determined, the woman should be referred for specialist review to clarify thematter; if still indeterminate, the pregnancy should be treated as monochorionic until provenotherwise.

It is known that labelling twins by assigning numbers (twin 1 and twin 2) and allocating the labeltwin 1 to the fetus closest to the cervix in early pregnancy, does not accurately determine which willbe the leading twin, as the pregnancy progresses, or indeed the birth order. This is particularly truefor laterally orientated twins (i.e. left and right twins) where 8.5% change presenting order betweenfirst and last scan and 20.3% delivered by caesarean compared with 5.9% delivered vaginally changebirth order (i.e. the twin labelled twin 2 delivers first) [16]. Correct labelling according to orientationin relation to the mother as lateral maternal left and maternal right, or vertical upper and lower, isbetter than assigning a fetus number, as it enables consistency with longitudinal biometric

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assessment, accuracy when interpreting screening results, and undertaking invasive diagnostic testswhere necessary, and avoids misconception about birth order, ensuring that the parents and thepaediatric team are aware of the possibility of peripartum switch (i.e. possible change in birthorder).

Screening for fetal complications

Down’s syndrome and other aneuploidies

Down’s syndrome and other aneuploidy screening in multiple pregnancy is complicated because ofthe following issues: (1) there is a higher risk of aneuploidy; (2) the sensitivity (i.e. detection rate) ofscreening tests is probably lower compared with singleton screening; (3) the false–positive rate ishigher; (4) the likelihood of being offered invasive diagnostic testing is higher as is the risk of com-plications of invasive diagnostic testing; and (5) in the event of an affected fetus, the options arecomplex, including selective reduction and risks to the surviving normal fetus or fetuses. The publishedliterature on first-trimester screening in multiple pregnancy is of poor quality, and no studies havebeen published on second-trimester screening in multiple pregnancy.

Of nine studies that evaluated first-trimester screening, three evaluated combined screening(nuchal translucency, maternal age, other maternal factors, serum screening–beta-human chorionicgonadotropin, and pregnancy-associated plasma protein-A) [17–19], three evaluated nuchal traslu-cency and maternal age [17,20,21], and six evaluated nuchal translucency alone [20–25]. Two of thesestudies included triplets [22,23], but did not report separate data for twins compared with triplets. Oneonly evaluated monochorionic twins [20]. For twins, all methods have high sensitivities, but combinedscreening overall performs best and should be offered. For dichorionic twin pregnancies, risks shouldbe calculated for each fetus. For triplets, there are no nomograms for serum screening, and thereforenuchal translucency and maternal age is the only available screening [2].

Women need to be fully informed about the higher risks with screening, and need to be aware thatdecision-making and options are complex if the screening test is positive. This requires experiencedprofessionals providing information and counselling before the screening test, and indeed afterwards ifthe result is positive. Furthermore, if the test is positive and the woman opts for invasive diagnostictesting, this should be carried out by a specialist who has the expertise to subsequently carry outselective termination of pregnancy if required [26].

If first-trimester screening is not possible (e.g. the woman presents too late), no published evidenceis available on which to base recommendations, but the NICE guideline [2] recommends offeringsecond-trimester serum screening for twins. For triplet pregnancy, no options are available for second-trimester screening.

Structural abnormalities

Structural abnormalities, particularly cardiac abnormalities, are more common in twin and higherorder pregnancies. This is mainly because of the higher incidence of abnormalities in monozygotictwins (owing to the unusual nature of the cleavage of the conceptus) compared with dizygotic twins[27,28].

The management of these pregnancies, where one fetus has an abnormality, is complex. Timelydiagnosis enables more choices, time to prepare, optimising fetal surveillance depending on theanomaly, involvement of other specialists (e.g. genetics team, paediatric surgeons) and appropriatebirth planning (e.g. place, timing and mode), including access to intrauterine therapy where it ispossible.

Published evidence about screening for structural abnormalities in twin or higher order pregnan-cies is limited. Logic suggests that the scan will take longer and that visualisation at scan may belimited, depending on fetal position, but there is little reason to expect mid-trimester ultrasound to besignificantly less ormore effective inmultiple pregnancy. The limited evidence suggests detection ratesfor twin pregnancy is similar to published data for singletons [27,29,30]. Therefore, routine anomaly

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screening by ultrasound between 18–20 þ 6 weeks gestation as in singleton pregnancy isrecommended.

Abnormalities specific to monozygotic twins are midline, such as holoprosencephaly and neuraltube defects, and cardiac abnormalities. Therefore, the value of fetal echocardiography in addition toroutine anatomy scan is questioned. As not all monozygotic twins aremonochorionic, this policy wouldneed to be applied to all twins irrespective of chorionicity unless one were to undertake fetal sexingand exclude discordant sex twins, which can complicate matters (as couples may not want to know thesex of their babies). A Scandinavian study of twin pregnancies [29] in which women had a package ofscans (nuchal translucency scan, anomaly scan at 19 weeks, fetal echocardiography at 21 weeks, and acervical length at 23 weeks), found that 0.5% of the fetuses had cardiac anomalies, 80% of which weredetected at the 19-week anomaly scan (i.e. before fetal echocardiography), and therefore concludedthat formal fetal echocardiography is not justified.

Twin-to-twin transfusion syndrome

About 10–15% of monochorionic pregnancies with shared placentation develop twin-to-twintransfusion syndrome (TTTS), in which outcome is significantly improved if treated with laser abla-tion. Given the availability of treatment, it is important to screen for TTTS to allow timely access to thistreatment.

It is worth noting that the chronic form of TTTS (most common form) usually presents between 16and 24 weeks gestation, and treatment is recommended from 16 weeks gestation; therefore, earlierscreening would need to be effective to advocate its use.

First-trimester parameters for TTTS screening have been evaluated in several studies. These includenuchal translucency [31–34], crown, rump length, or both [32,34], or ductus venosus Doppler bloodflow [34,35]. They all show low sensitivity and variable specificity. As these parameters are not pre-dictive, and there is potential to cause unnecessary anxiety, first-trimester screening for TTTS is notadvised.

Although it is known that serial ultrasound scans are necessary to identify TTTS by looking for theobvious features, the lack of published evidence about how often to undertake the scans or what pre-clinical features to look out for, are worrying. Two second-trimester studies have addressed pre-clinicalfeatures, looking specifically at inter-twin membrane folding [31] and amniotic fluid discordance [36].Both these features have been shown to have better sensitivity than the aforementioned first-trimesterparameters; poor specificity, however, should warrant a step up in frequency of scans but alsocontinued vigilance in those pregnancies without these features. The NICE guideline recommends ascan every 2 weeks from 16–24 weeks to screen for TTTS, but a step up to weekly scans if inter-twinmembrane folding or liquor discordance occurs [2].

Intra-uterine growth restriction

Fetuses of multiple pregnancies are at increased risk of being small for gestational age (SGA) and, ifplacental dysfunction exists, growth restriction (IUGR). Both SGA and IUGR fetuses and babies havepoorer perinatal outcomes and, therefore, identifying growth problems is important.

Symphysis–fundal height measurement is not effective in identifying growth problems in twinpregnancy [37], and serial ultrasound scans are required to identify small babies but also a significantsize difference between fetuses.

The problemwith interpreting the published literature to inform the best parameters to use is thatcriteria for abnormality and definitions of SGA or IUGR or growth discordance are variable, and one isoften not comparing like with like. The NICE guideline development group reviewed 26 studies ofultrasound parameters in twin pregnancies, including various fetal biometric measurements andestimated fetal weight (EFW), based on formulae of ultrasound parameters, Doppler ultrasound of theumbilical cord, and composite screening strategies [2]. They acknowledge that most of the evidence islow or very low quality, but concluded that (1) any single fetal biometric parameter was a poorpredictor of IUGR or birthweight discordance; (2) an EFW at or less than the 10th centile is amoderately useful predictor of intrauterine growth restriction, defined as birthweight at or less than

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10th centile; (3) the best cut-off for inter-twin birthweight discordance is an EFW difference of 25% ormore; (4) the best EFW is derived when applying a formula that includes at least two biometricparameters; (5) the best predictor of IUGR or discordance between twins is an ultrasound carried outwithin 28 days of birth; (6) strong evidence supporting the routine use of umbilical artery Doppler forthe prediction of IUGR or birthweight discordanceis lacking; and (7) strong evidence that any com-posite screening strategy detects IUGR in twin pregnancy is lacking. No studies addressed the value ofamniotic fluid volume assessment or middle cerebral artery Doppler examination. No studiesaddressed timing and frequency of scanning. They acknowledge that no evidence was available toguide the management of triplet pregnancies, but it seems logical to apply the conclusions to triplets.On the basis of the detailed review, the group recommended that EFW discordance should becalculated using two biometric parameters from 20 weeks gestation, scans should be undertaken atintervals of less than 28 days, a 25% or greater EFW discordance should be considered significant, andumbilical artery Doppler should not be used to monitor for IUGR or birthweight differences in twinand triplet pregnancies [2].

Since the publication of the NICE guideline [2], a large UK cohort study of 2161 twin pregnancies(302 monochorionic and 1859 dichorionic twin pregnancies) has shown that EFW discordance is ac-curate in predicting birthweight discordance, both EFW and birthweight discordance are good pre-dictors of adverse outcome, and that the optimal cut off for the prediction of perinatal mortality,irrespective of chorionicity or individual fetal size, is an EFW discordance of 25% or more [38].

Screening for maternal complications

Hypertensive disorders of pregnancy

Womenwithmultiple pregnancy have a two to three times higher risk of developing a hypertensivedisorder in pregnancy (i.e. gestational hypertension, pre-eclampsia or eclampsia) [39]. In addition, if itoccurs, it is more likely to occur earlier and be severe. In preventing a hypertensive disorder, The UKNICE guideline for hypertension in pregnancy [40] recommends that womenwith one high-risk factoror at least two moderate risk factors take oral low-dose aspirin (75 mg daily) from 12 weeks gestationuntil birth [40]. Multiple pregnancy is considered a moderate risk factor. To detect hypertensive dis-orders, it is recommended that a woman’s blood pressure is measured and urine tested for protein ateach antenatal contact [2].

Gestational diabetes

Gestational diabetes results from relative insulin insufficiency secondary to the diabetogenic effectof placental hormones (e.g. human placental lactogen, progesterone and cortisol). The larger placentalmass of multiple pregnancy, increases the amount of these placental hormones and, therefore, theo-retically the risk of developing gestational diabetes. In practice, however, evidence is conflicting aboutwhether the occurrence of gestational diabetes is increased in multiple pregnancy, and whether it isadvisable to screen [41–43]; this area warrants further research.

Other maternal complications

Almost all other complications of pregnancy are increased in multiple pregnancy, such as placentapraevia, obstetric cholestasis, and antepartum haemorrhage. Indeed, all minor ailments of pregnancyare worse too. The management of these complications and ailments is, however, no differentcompared with management in singleton pregnancies.

Prediction and prevention of preterm labour

Preterm delivery, caused by spontaneous preterm labour, preterm prelabour rupture of membranes,or by iatrogenic factors, is themost important fetal complication of multiple pregnancy, as it is themostcommon cause of adverse outcome. Over a one-half of twins and almost all triplets are born before 37

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weeks gestation, and 15–20% of neonatal unit admissions are caused by preterm birth of twins andtriplets. The cause of preterm labour is probablymultifactorial. The optimal methods for prediction andprevention remain the subject of continuing debate.

Prediction

Several factors and tests associated with diagnostic accuracy as a predictor of spontaneous pretermbirth in twin and triplet pregnancies have been studied, namely ultrasonographic cervical lengthmeasurements, fetal fibronectin test (FFT), home uterine activity monitoring, past obstetric history ofpreterm birth, and composites of these approaches.

A systematic review of 21 studies [44] comprising 3523 twin pregnancies concluded that trans-vaginal cervical length at 20–24 weeks’ gestation is a good predictor of spontaneous preterm birth inasymptomatic women with twin pregnancies. The NICE guideline having reviewed all the evidence,including the aforementioned systematic review, concluded that a cervical length of less than 25mmat18–24 weeks gestation is a good predictor of spontaneous preterm delivery in twin pregnancy [2]. Twostudies of sonographic cervical length in triplet pregnancy also concluded that a cervical lengthmeasurement of less than 25mm at 14–20 weeks gestation is a good predictor of spontaneous pretermbirth in triplet pregnancy [45,46].

A study of the FFT in twin pregnancies showed no association between a positive test and risk ofspontaneous preterm delivery [47]. When combined with cervical length assessment, FFT can predictpreterm delivery [48,49].

A systematic review of six randomized trials of home uterine activity monitoring showed thisintervention to be ineffective in predicting spontaneous preterm delivery [50].

An effective predictor is a history of previous preterm delivery [51], although this is not helpful inprimigravidae.

Prevention

Interventions that have been studied to prevent spontaneous preterm labour and hence delivery intwin and triplet pregnancies include bed rest, progesterone (intramuscular or vaginal), cervical cerc-lage, and tocolytics (oral betamimetics). Sexual abstinence has never been studied in multiplepregnancy.

A systematic review of seven randomised-controlled studies (RCTs) (five of twins and two oftriplets) of bed rest found no evidence to support this intervention to reduce preterm delivery [52].

Several RCTs have evaluated the clinical effectiveness of progesterone (intramuscular or vaginal)compared with placebo in the prevention of preterm birth in women with twin [53–57] and tripletpregnancies [58,59]. None have shown this intervention to be effective. A systematic review and meta-analysis of individual patient data from five RCTs considering the effect of vaginal progesterone inwomen with asymptomatic short cervix (defined as 25 mm or less on midtrimester ultrasound)included only 52 twin pregnancies [60]. Although a significant reduction in preterm birth occurred insingleton pregnancy, no such effect was reported in twin pregnancies.

One RCT [61] and one observational study (prospective) of twin pregnancies [62], and four obser-vational studies (retrospective) of triplet pregnancies [63–66] evaluated the effectiveness of cervicalcerclage in the prevention of preterm birth. None showed this intervention to be effective.

A systematic review of five RCTs evaluating the effectiveness of betamimetics found no evidence tosupport this intervention to reduce preterm delivery [67].

Therefore, in the absence of an effective intervention, routine screening to predict preterm deliveryis not recommended in twin and triplet pregnancy.

Use of corticosteroids

It is well known that antenatal corticosteroids reduce neonatal complications in preterm babies[68]. Although corticosteroids are considered to be less effective in multiple pregnancy [68], thequestion arises, given the substantial risk of preterm delivery in multiple pregnancy, whether giving an

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untargeted course of steroids routinely at a given gestation or whether giving multiple courses atregular intervals may be beneficial. The problem with giving a single course routinely would be thattime of administration may be remote from delivery and the effect dampened. An RCT (21% of recruitswere twin pregnancies) showed that multiple courses compared with a single course does not improveoutcomes, but are associated with potential harm (i.e. lower birth weight and head circumference)[69]. On this basis, it is better to avoid untargeted routine single or multiple courses of steroids, and toadvocate targeted steroids when indicated (i.e. when preterm labour or birth is imminent [2]). This willenable a shift in focus towards informing all womenwith twin and triplet pregnancies of the increasedrisk of preterm birth, the benefits of targeted steroids, and providing information about symptoms andsigns to be aware of so that they can present in a timely manner.

Planning delivery

It is not within the scope of this paper to address timing or mode of delivery but, in addition todiscussing risks of preterm delivery and preparing women for this eventuality, a number of twin andtriplet pregnancies will have uncomplicated progression, and a crucial aspect of optimal antenatal careis to ensure an informed discussion occurs relating to place, timing and mode of delivery. This shouldinclude discussing risks and benefits of vaginal delivery compared with caesarean section, pain reliefoptions, who will be present at the delivery (often more personnel than in singleton pregnancy), andthe potential for specialist neonatal care even if delivery is not preterm.

Other aspects of care

Information and emotional support

The risks of multiple pregnancy, and the additional elements of antenatal care required to mitigateand identify them, can lead to a certain level of anxiety for the woman and her partner or family. Intoday’s world, women also have access to a wide range of information from various sources (e.g.internet and media), some of which may be poor or misleading. It is important to ensure that womenare given good information and are guided to reputable sources of further information, and have theopportunity to clarify matters that are unclear to them. They should be encouraged to explore socio-economic issues related to caring for and supporting more than one child. This process of informationgiving is ongoing, and can be delivered in a number of formats.

Nutritional supplements, diet and lifestyle advice

In multiple pregnancy, as the metabolic rate of the mother is greater than in singleton pregnancy, ithas been suggested that a high-calorie diet may help maintain her nutritional state. The counterargu-ment is thatboostingweightgainmightnot beadvantageous.ACochrane reviewfoundnoRCTs toadvisewhether specific dietary advice for womenwith multiple pregnancy does more good than harm [70].

The NICE guideline group reviewed the limited literature on nutritional supplements and dietaryadvice in multiple pregnancy, and concluded that the few published studies were of low quality, andthat no evidence was available to give different advice to that given in singleton pregnancy [2]. Theyemphasised, however, that it is important to be aware of the higher incidence of anaemia, and rec-ommended checking the full blood count at 20–24 weeks to identify women who may need iron andfolic acid supplementation.

There is no evidence to inform specific advice about other lifestyle issues (e.g. work patterns, sexualactivity, and exercise in multiple pregnancy).

How and where to deliver care

It seems logical that, given the extra elements required to deliver optimal antenatal care in multiplepregnancy, this should be provided in a dedicated servicewhether it be in a clinic staffed by a dedicatedmultidisciplinary team or delivered by a core team in a specialised model.

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A Cochrane systematic review [71] identified one RCT [72] undertaken in the UK of 162 womenwith a multiple pregnancy who were randomised to receive standard antenatal care or in-terventions consisting of additional care to standard care (e.g. midwifery-led antenatal care,postnatal home visits, and antenatal preparation for parenting programme). No difference wasfound in the incidence of postnatal depression (this is the only published outcome) [73], perinatalmortality, stillbirth, neonatal mortality, and breastfeeding. The intervention group were morelikely to have caesarean delivery. No data were available for small for gestational age, pretermbirth, or maternal death. This trial was specifically designed and powered to assess maternalmental health morbidity and not fetal outcomes. The intervention was not specialist obstetric carebut rather extra midwifery support and information sharing, and therefore it does not providemuch evidence to draw conclusions about the effectiveness of specialist care in preventing adversefetal outcomes.

Evidence from other studies about the value of specialist multiple pregnancy care is conflicting.Three observational studies [74–76] and one large epidemiological study [77] have focused onspecialist antenatal care for multiple pregnancy in the USA.

Interventions, number of participants, and results of the observational studies are presented inTable 1. The intervention was different in each of the studies, but more frequent care and conti-nuity with carers was a consistent theme. Outcomes were compared with women who receivedstandard antenatal care. The specialist care had an effect on some of important outcomes,including fewer women with pre-eclampsia [76], less preterm birth [74–76] in all three studies,fewer low birthweight babies [74,76], fewer perinatal deaths [74], and less major neonatalmorbidity [76].

The epidemiological study [77] reported a trend analysis of outcomes depending onwomen’s use ofcare (i.e. frequency of antenatal care access) by analysing data from the National Centre for HealthStatistics birth and infant death records in the USA between 1981 and 1997. It found that, despiteincreased medical intervention being associated with increased preterm birth, intensive prenatal careutilisation results in lower infant mortality.

The conclusion from this limited evidence is that (1) there is a potential for bias (e.g. women atlower risk may have had better access to this care for financial, educational or other reasons); (2) it isnot clear whether it is the actual elements of care (and if so which elements) or the continuity andspecialist knowledge of the caregivers that makes the difference; and (3) as the evidence comes fromone healthcare setting (i.e. USA), where in particular there is little midwifery input, it may not bereproducible in other settings. What seems to be clear is that continuity and consistency of care by thesame experienced and knowledgeable professionals contributes to better outcomes. Further researchusing methodologies that minimise bias in different health settings is needed to corroborate thesefindings.

Given that better outcomes may result from continuity and consistency of care provided by thesame experienced and knowledgeable professionals, the NICE guideline recommends that ‘clinicalcare for women with twin and triplet pregnancies should be provided by a nominated multidisci-plinary team consisting of a core team of named specialist obstetricians, specialist midwives, andultrasonographers, all of whom have experience and knowledge of managing twin and tripletpregnancies’ [2].

The guideline goes on to specify a schedule of appointments, including timing of ultrasound scansdepending on whether twin or triplets and based on chorionicity and amnionicity, and it also specifieswhen to offer delivery (i.e. recommended timing of delivery) (Table 2). It is recognised that this is aminimum requirement or recommendation, and, if comorbidities or complications occur, there may bea need to deviate from the schedule.

Indication for referral to tertiary level fetal medicine services

Although it is important to ensure that women can access care easily, and therefore the principleof care close to home and local expertise is important, complications of multiple pregnancy, whenidentified, require specific expertise, and it is not possible or practical to have this level of expertisein every healthcare service. When these complications do arise, clinical decision making and

Table 1Studies evaluating specialist care and clinics: characteristics, outcomes reported and significant differences reported.

Ellings et al., 1993 [74] Ruiz et al., 2001 [75] Luke et al., 2003 [76]

Quality of study Very low Very low Very low

Number of participants:specialist compared withstandard care group

89 v 51 women 30 v 41 women. 190 v 339 women.

The intervention Consistent evaluation ofmaternal symptoms andcervical status; intensivepreterm birth preventioneducation; individualisedmodification of maternalactivity; increased attentionto nutrition; and tracking ofclinic non-attenders.

Advanced practicenurse provided prenatalcare; weekly visits; homevisits; and 24-h availabilityby telephone.

Twice monthly visits;dietary prescriptionof 3000–4000 kcalper day; multimineralsupplementation;and patient education.

Maternal complicationsAnaemia X X NRBleeding at 20 weeks or over X NR XCaesarean section X X NRGestational diabetes X X XGestational hypertension NR X NRPre-eclampsia X NR Yes 8 v 17% (OR 0.41,

95% CI 0.23 to 0.75)Pre-labour rupture of membranes X NR Yes 10 v 25% (OR 0.35,

95% CI 0.20 to 0.60)Urinary tract infection X X NR

Perinatal morbidity and mortalityPreterm birth less than 37 weeks X NR Yes 23 v 42% (OR 0.45,

95% CI 0.30 to 0.68)Preterm birth less than 36 weeks NR Yes 63 v 83% (OR 0.36, 95%

CI 0.16 to 0.77).Yes 41 v 53% (OR 0.62,95% CI 0.43 to 0.89)

Preterm birth less than 30 weeks Yes 2 v 18% (OR 0.29,95% CI 0.11 to 0.76)

Yes 0 v 29%(no calculations).

Yes 3 v 9% (OR 0.29,95% CI 0.11 to 0.76)

Major neonatal morbidity NR NR Yes 17 v 32% (OR 0.44,95% CI 0.31 to 0.62)

Neonatal intensivecare unit admission

Yes 14 v 38% (OR 0.35,95% CI 0.22 to 0.55)

NR Yes 43 v 63% (OR 0.48,95% CI 0.36 to 0.64)

Very low birthweight Yes 6 v 27% (OR 0.21,95% CI 0.10 to 0.42)

X Yes 5 v 16% (OR 0.30,95% CI 0.15 to 0.61)

Small for gestational age NR NR NRPerinatal mortality Yes 1 v 8% (OR 0.06,

95% CI 0.01 to 0.53)X NR

CI, confidence interval, NR, data for this outcome not evaluated or recorded, OR, odds ratio; Yes, showed significant difference infavour of specialist care or clinic; X, data presented but no significant difference.

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choices can be complex, and it is important to recognise the need to refer to specialist fetalmedicine services with appropriate expertise. Sometimes, referral does not mean that the womencannot then return to local care where the specialist management plan is followed, and where therecan be continued liaison if necessary with the tertiary team. The NICE guideline identified com-plications that would fit this criteria as follows: high-risk aneuploidy screening result; mono-amnionicity; any triplet pregnancy where there is a shared placenta; or pregnancies complicated bydiscordant fetal growth, fetal anomaly, discordant fetal death or twin-to-twin-transfusion syn-drome [2].

Conclusion

Twin and triplet pregnancies are high risk for both mother and babies, and these sometimescomplex pregnancies require additional elements of care to identify and manage complications

Table 2Recommended schedule of antenatal appointments for uncomplicated twin and triplet pregnancy according to chorionicity andamnionicity.

Dichorionic diamniotic twins Offer women with uncomplicated dichorionic twin pregnanciesat least eight antenatal appointments with a healthcare professionalfrom the core team; at least two of these appointments should be withthe specialist obstetrician; combine appointments with scans whencrown– rump length measures from 45 mm to 84 mm (at about 11weeks 0 days to 13 weeks 6 days) and then at estimated gestationsof 20, 24, 28, 32 and 36 weeks.Offer additional appointments without scans at 16 and 34 weeks;and offer delivery from 37 weeks gestation.

Monochorionic diamniotic twins Offer women with uncomplicated monochorionic diamniotic twinpregnancies at least nine antenatal appointments with a healthcareprofessional from the core team; at least two of these appointmentsshould be with the specialist obstetrician; combine appointments withscans when crown–rump length measures from 45 mm to 84 mm(at about 11 weeks 0 days to 13 weeks 6 days) and then at estimatedgestations of 16, 18, 20, 22, 24, 28, 32 and 34 weeks; and offer deliveryfrom 36 weeks gestation.

Triamniotic triamniotic triplets Offer women with uncomplicated trichorionic triamniotic tripletpregnancies at least seven antenatal appointments with a healthcareprofessional from the core team; at least two of these appointmentsshould be with the specialist obstetrician; combine appointmentswith scans when crown–rump length measures from 45 mm to 84 mm(at about 11 weeks 0 days to 13 weeks 6 days), and then at estimatedgestations of 20, 24, 28, 32 and 34 weeks [55]; offer an additionalappointment without a scan at 16 weeks; and offerdelivery from 35 weeks gestation.

Monochorionic triamniotic and dichorionictriamniotic triplets

Offer women with uncomplicated monochorionic triamnioticand dichorionic triamniotic triplet pregnancies at least 11 antenatalappointments with a healthcare professional from the core team;at least two of these appointments should be with the specialistobstetrician; combine appointments with scans when crown–rumplength measures from 45 mm to 84 mm (at about 11 weeks 0 daysto 13 weeks 6 days), and then at estimated gestations of16, 18, 20, 22, 24, 26, 28, 30, 32 and 34 weeks; and offerdelivery from 35 weeks gestation.

Any twin or triplet pregnancy wherethere is a shared amnion

Women with twin and triplet pregnancies involving a shared amnionshould be offered individualised care from aconsultant in a tertiary level fetal medicine centre.

L. Bricker / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 305–317314

effectively and optimise outcomes. This care needs to be delivered by health professionals withspecific knowledge and expertise, ensuring consistency and continuity, and this may be bestdelivered in the context of a specialist clinic or service. Early pregnancy care should include a scanto date the pregnancy accurately and to determine chorionicity. An individualised care pathwayshould be developed based on chorionicity and other risk factors specific to the woman. Screeningfor fetal complications should be offered along with specific information about the complexclinical issues and decisions that may result from such screening. Later care should focus onpresentation and management of complications, such as preterm labour, growth restriction,maternal complications, and planning for delivery. Consideration should be given to referringcomplex cases to specialists in fetal medicine. Attention should be given to relevant and accurateinformation provision and emotional support required to mitigate the stress and anxiety associ-ated with these high-risk pregnancies. Interventions for which there is no solid evidence baseshould be avoided. A number of areas of care require further research to establish a more robustevidence base, but where evidence is lacking, a more pragmatic and sensible approach isadvocated.

Practice points

� Chorionicity and amnionicity determination in the first trimester is key to planning antenatalcare in multiple pregnancy.

� Ultrasound is the mainstay of screening for fetal complications, including screening foraneuploidy, fetal structural abnormalities, fetal growth problems and, in monochorionicpregnancies, twin-to-twin transfusion syndrome.

� The evidence base for frequency of ultrasound scans is limited and, therefore, a pragmaticapproach is required.

� In the absence of an effective intervention, screening to predict preterm delivery in multiplepregnancy is not advocated.

� Focus on ensuring women are aware of signs and symptoms of preterm labour so that theycan present in time to obtain targeted corticosteroids for fetal lung maturity.

� Provide accurate, reliable and relevant information about multiple pregnancy, includingguidance about appropriate resources to access.

Research agenda

� Effectiveness of the following interventions to improve outcomes in twin and triplet preg-nancy: additional care and emotional support; care in specialist clinics or specialist services;and nutritional advice tailored to multiple pregnancy.

� Well-designed RCTs of interventions to reduce preterm birth in womenwith twin and tripletpregnancy and short cervix.

� Whether to consider multiple pregnancy a risk factor for gestational diabetes.� Optimal management when there is EFW discordance of 25% or more, including optimaltiming of delivery.

L. Bricker / Best Practice & Research Clinical Obstetrics and Gynaecology 28 (2014) 305–317 315

Conflict of interest

The author was a member of the UK NICE Guideline Development Group for the guideline number129 entitled ‘Multiple pregnancy: the management of twin and triplet pregnancies in the antenatalperiod’.

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