National and international guidelines on the management of twin pregnancies a comparative review

In addition, some recommendations related to the management of twin gestations are often missing from the clinical guidelinesdedicated to twin pregnancies and are instead included in the

National and international guidelines on the

management of twin pregnancies: a comparative reviewOmer Weitzner, MD; Jon Barrett, MD; Kellie E Murphy, MD; John Kingdom, MD; Amir Aviram, MD; Elad Mei-Dan, MD;Liran Hiersch, MD; Greg Ryan, MD; Tim Van Mieghem, MD; Nimrah Abbasi, MD; Nathan S Fox, MD;

Andrei Rebarber, MD; Vincenzo Berghella, MD; Nir Melamed, MD, MSc

Twin gestations are associated with increased risk of pregnancy complications However, high-quality evidence regarding the management oftwin pregnancies is limited, often resulting in inconsistencies in the recommendations of various national and international professionalsocieties In addition, some recommendations related to the management of twin gestations are often missing from the clinical guidelinesdedicated to twin pregnancies and are instead included in the practice guidelines on specific pregnancy complications (eg, preterm birth) of thesame professional society This can make it challenging for care providers to easily identify and compare recommendations for the man-agement of twin pregnancies This study aimed to identify, summarize, and compare the recommendations of selected professional societiesfrom high-income countries on the management of twin pregnancies, highlighting areas of both consensus and controversy We reviewedclinical practice guidelines of selected major professional societies that were either specific to twin pregnancies or were focused on pregnancycomplications or aspects of antenatal care that may be relevant for twin pregnancies We decided a priori to include clinical guidelines from 7high-income countries (United States, Canada, United Kingdom, France, Germany, and Australia and New Zealand grouped together) and from

2 international societies (International Society of Ultrasound in Obstetrics and Gynecology and the International Federation of Gynecology andObstetrics) We identified recommendations regarding the following care areas: first-trimester care, antenatal surveillance, preterm birth andother pregnancy complications (preeclampsia, fetal growth restriction, and gestational diabetes mellitus), and timing and mode of delivery Weidentified 28 guidelines published by 11 professional societies from the 7 countries and 2 international societies Thirteen of these guidelinesfocus on twin pregnancies, whereas the other 16 focus on specific pregnancy complications predominantly in singletons but also include somerecommendations for twin pregnancies Most of the guidelines are recent, with 15 of the 29 guidelines published over the past 3 years Weidentified considerable disagreement among guidelines, primarily in 4 key areas: screening and prevention of preterm birth, using aspirin toprevent preeclampsia, defining fetal growth restriction, and the timing of delivery In addition, there is limited guidance on several importantareas, including the implications of the “vanishing twin” phenomenon, technical aspects and risks of invasive procedures, nutrition and weightgain, physical and sexual activity, the optimal growth chart to be used in twin pregnancies, the diagnosis and management of gestationaldiabetes mellitus, and intrapartum care.This consolidation of key recommendations across several clinical practice guidelines can assisthealthcare providers in accessing and comparing recommendations on the management of twin pregnancies and identifies high-priority areasfor future research based on either continued disagreement among societies or limited current evidence to guide care

Key words: American College of Obstetricians and Gynecologists, antenatal care, aspirin, clinical, comparison, delivery, expert, growthrestriction, growth retardation, guidelines, International Federation of Gynecology and Obstetrics, International Society of Ultrasound inObstetrics and Gynecology, management, multifetal, multiple, National Institute for Health and Care Excellence, practice, preeclampsia,prenatal care, prenatal screening, preterm, professional, recommendations, review, Royal College of Obstetricians and Gynaecologists,societies, Society of Obstetricians and Gynaecologists of Canada, summary, twin, twins

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From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada (Drs Weitzner, Aviram, and Melamed); Department of Obstetrics and Gynecology, McMaster University, Hamilton, Canada (Dr Barrett); Ontario Fetal Centre, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto, Canada (Drs Murphy, Kingdom, Ryan, Van Mieghem, and Abbasi); Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, North York General Hospital, University of Toronto, Toronto, Canada (Dr Mei-Dan); Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Dr Hiersch); Icahn School of Medicine at Mount Sinai, New York, NY (Drs Fox and Rebarber); Maternal Fetal Medicine Associates, PLLC, New York, NY (Drs Fox and Rebarber); and Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA (Dr Berghella).

Received April 5, 2023; revised May 20, 2023; accepted May 22, 2023.

J.B., A.A., E.A.D., G.R., T.V.M., N.A., and N.M are coauthors of the Society of Obstetricians and Gynaecologists of Canada guidelines on twin pregnancies The other authors report no con flict of interest.

N.M holds the Waugh Family Chair in Twin Fetal Medicine Research at the Sunnybrook Health Sciences Centre and the University of Toronto None of the funding agencies had any role in the idea, design, analyses, interpretation of data, writing of the manuscript, or decision to submit the manuscript Corresponding author: Nir Melamed, MD, MSc nir.melamed@sunnybrook.ca

0002-9378/$36.00
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https://doi.org/10.1016/j.ajog.2023.05.022

MONTH 2023 American Journal of Obstetrics & Gynecology 1

Twin gestations, accounting for>3% of

pregnancies in the United States and

Canada,1,2are associated with increased

risk of common pregnancy

complica-tions such as preterm birth, hypertensive

disorders of pregnancy, gestational

dia-betes mellitus, cesarean delivery, and

fetal growth restriction.3e7 Therefore,

twin pregnancies are associated with

considerable risk to both mothers and

their developing fetuses.8 Indeed, twin

births account for a disproportionately

high rate of neonatal morbidity and

healthcare resource utilization,9 and

mothers with twins are at>4-fold risk of

severe acute morbidity compared with

those with a singleton pregnancy.10,11

proper use of preventive strategies,

adequate maternal and fetal surveillance,

and optimization of timing and mode of

delivery are all key components of

antepartum and intrapartum care of

twin pregnancies, with the ultimate goal

of minimizing morbidity and mortality

in this high-risk group of pregnancies

However, the underlying quality of

evidence to guide the management of

twin pregnancies is generally poor in

comparison with singleton pregnancies,

in part because twins have been

under-represented in clinical trials This deficit

has been acknowledged in a recent

statement by the Society for

Maternal-Fetal Medicine on the state of science

on multifetal gestations.12 The limited

research data have made it challenging to

either provide or agree upon clear

evidence-based recommendations for

the management of twin pregnancies,

resulting in considerable variation and

inconsistencies in the recommendations

worldwide.13e21 Such inconsistencies

may cause unnecessary confusion for

care providers and perpetuate variations

in the management of twin pregnancies

between centers and countries Another

important challenge that care providers

are often faced with is that some key

recommendations for twin gestations

are often included within practice

guidelines on specific topics (eg,

guide-lines on preterm birth or fetal growth

restriction, which are predominantly

focused on singleton pregnancies, butalso include some recommendations fortwins) rather than being included in theclinical practice guideline on twin preg-nancies issued by the same professionalsociety This resource gap makes itchallenging for busy care providers toeasily identify, compare, and access therecommendations of the various pro-fessional societies on the management oftwin pregnancies Summarizing recom-mendations from different guidelinesinto a single document would make iteasier for care providers to access rec-ommendations and identify areas ofconsensus and disagreement betweenguidelines In addition, such a resource

research community to topics withinsufficient guidance or evidence, andthat might therefore merit additionalresearch

Our goal was to identify, summarize,and compare the recommendations ofselected professional societies fromhigh-income countries on the manage-ment of twin pregnancies, highlightingareas of both consensus and controversy

Methods

Eligibility criteria and search strategy

We included clinical practice guidelines

of selected major professional societiesthat were either specific to twin preg-nancies or were focused on pregnancycomplications or aspects of antenatalcare that may be relevant for twin preg-nancies We decided a priori to includeclinical guidelines from 7 high-income

United Kingdom, France, Germany, andAustralia and New Zealand groupedtogether), and from 2 international so-cieties (International Society of Ultra-sound in Obstetrics and Gynecology[ISUOG] and the International Federa-tion of Gynecology and Obstetrics[FIGO])

For each country or international ciety, we identified twin-specific clinicalguidelines, and reviewed clinical guide-lines on the following topics for recom-mendations specific to twin pregnancies:

so-preterm birth, hypertensive tions of pregnancy, fetal growth restric-tion, prenatal screening for genetic and

complica-structural anomalies, ultrasound inpregnancy, and nutrition in pregnancy.Guidelines were identified through thefollowing approaches: (1) a detailed re-view of all relevant guidelines on thewebsite of the specific society; (2) asearch in PubMed and Google usingthe following key words: (guideline OR

OR practice OR consensus) AND (twin

“preterm labor” OR “preterm labour”

OR progesterone OR cerclage OR pertension OR hypertensive OR pre-eclampsia OR aspirin OR growth ORrestriction OR retardation OR screening

hy-OR genetic hy-OR prenatal hy-OR ultrasound

OR sonographic OR nutrition ORweight OR obesity OR exercise OR ac-tivity); and (3) a search in the Interna-tional Guideline Library website.The last search was undertaken onFebruary 10, 2023 When>1 version of aguideline on a specific topic was identi-fied, only the most recent version of thisguideline was included

Areas of antenatal and intrapartumcare

We decided a priori to identify mendations regarding the followingareas of antenatal and intrapartum care

recom-in twrecom-in pregnancies: (1) first-trimestercare—including dating, labeling, cho-rionicity, prenatal genetic screening andtesting, “vanishing” twins, and intra-uterine fetal demise; (2) antenatal sur-veillance—including the frequency of

screening for structural anomalies, andnutritional and lifestyle recommenda-

screening with cervical-length ment, preventive interventions (cerclage,progesterone, pessary, tocolysis), andadministration of antenatal corticoste-roids; (4) other pregnancy complicationsincluding preeclampsia, fetal growth re-striction, and gestational diabetes melli-tus; and (5) timing and mode of delivery

measure-We chose not to include dations on complications unique to

transfusion syndrome, twin polycythemia sequence, twin reversed

arterial perfusion, selective fetal growth

restriction, and single fetal demise)

complex diagnosis and management

processes and may warrant a separate

recommendations

Data extraction

The clinical guidelines documents were

reviewed in detail by 2 independent

re-viewers (O.W and N.M.)

Recommen-dations regarding any of the areas of care

listed above were extracted and

tabu-lated Then, for each area of care, the

recommendations of the various

soci-eties were compared, to identify areas of

consensus and controversy Areas with

good agreement, considerable

disagree-ment, or insufficient guidance were

flagged in the last column by a green

mark, respectively Given the difficulty in

quantifying agreement, these 3

cate-gories of agreement were determined by

the authors in a qualitative and

subjec-tive manner, with the main goal of

facilitating for the readers the identi

fi-cation of areas where the variation

be-tween societies is greatest

Results

Description of the clinical guidelines

We identified 28 guidelines published by

11 professional societies from the 7

countries and 2 international societies

included in the current review (Table 1)

Thirteen of these guidelines are focused

on twin pregnancies, whereas the other

16 mostly focus on complications in

singletons but include certain specific

recommendations for twin pregnancies

Most of the guidelines are recent, with 15

and 22 of the 28 guidelines published

over the past 3 and 5 years, respectively

First-trimester care and prenatal

genetic screening

first-trimester care and prenatal genetic

screening are summarized inTable 2

Dating and labeling

The dating method is addressed in 4

guidelines (Canada, Germany, ISUOG,

and FIGO), all of which recommend that

pregnancy dating be based on the

crownerump length of the larger twin(Table 2) Five guidelines (Canada,United Kingdom, Germany, ISUOG, andFIGO) describe the approach for twinlabeling, recommending that it be based

on the lateral or vertical orientation andinclude as many parameters as possible

Only the Canadian guidelines mend that in laterally oriented twins, thetwin on the maternal right be labeled as

recom-A and that the naming be maintained forall subsequent scans irrespective ofchange in location to maintain consis-tency, especially for complex pregnan-cies that need to be referred for invasiveinterventions (Table 2)

ChorionicityAll guidelines highlight the importance

of determining chorionicity in the firsttrimester (Table 2) Six guidelinesdescribe the sonographic signs thatshould be used to determine chorio-nicity, including the number of gesta-tional sacs, the lambda and T signs (inthe cases of a single placenta), membranethickness, and fetal sex Whereas the US,

mention the number of placentas asanother sign for the determination ofchorionicity (ie, 2 placentas being anindication of dichorionic placentation),the Canadian guideline states that this isnot a reliable sign given that 3% ofmonochorionic twins have separateplacental masses (Table 2)

Prenatal genetic screeningAll guidelines recommend assessing thenuchal translucency between 11þ0 and

Although there seems to be an ment that the screening accuracy ofbiochemical markers is less accurate fortrisomy 21 twins than for singletons,some guidelines either recommend theiruse (Germany) or state that they may beconsidered (Canada, ISUOG, FIGO) orshould be offered (United Kingdom),whereas the French guideline states thattheir use is not recommended (Table 2)

agree-Six guidelines mention cell-free fetal

testing (NIPT) as an option for screeningfor trisomy 21 in twin pregnancies(Table 2) Most guidelines highlight thelimited validation of NIPT in twinscompared with singleton pregnancies

The US guidelines state that the mance of NIPT in twins is similar to thatreported in singletons, whereas otherscomment that it is associated with lowerdetection rates (Germany, ISUOG) andhigher failure rates (Australia and NewZealand) than in singletons

perfor-Invasive testingSix guidelines address the role of chori-onic villus sampling The loss rate asso-ciated with chorionic villus sampling isdescribed as 2% to 3.8% (Germany,ISUOG, FIGO) or 1% above the back-ground risk (Canada) Several guidelinesrecommend using chorionic villus sam-pling over amniocentesis in dichorionictwin pregnancies, given the earliergestational age when results will beavailable (France, Germany, ISUOG,FIGO) (Table 2) Three guidelines statethat the loss rate is similar for thetranscervical and transabdominal ap-proaches (Canada, France, ISUOG), butonly the French guideline states that thetransabdominal approach is preferred.Several guidelines state that the riskassociated with amniocentesis is higher

in twins than in singleton pregnancies(France, ISUOG, FIGO), with a loss rate

of 1.5% to 3.1% (Germany, ISUOG)(Table 2) Only 2 guidelines refer to theamniocentesis technique, stating thatthere is no difference in loss rate betweensingle- and double-uterine entry tech-niques (Canada) and that the choiceshould be left to the operator (France),although it should be noted that thedouble-uterine entry technique may in-crease the risk of injury to the dividingmembrane Some controversy existsconcerning the number of sacs thatshould be sampled when amniocentesis

is performed in monochorionic twinpregnancies Whereas the Canadianguideline recommends sampling bothsacs routinely given the (small) risk ofheterokaryotypic twins, others suggestthat routine sampling of both sacs is notalways necessary (French), especially ifchorionicity was documented before 14weeks and the fetuses are concordant forgrowth and have normal anatomy(United Kingdom, ISUOG)

Vanishing twin and fetal demiseOnly the Canadian guideline refers to the

“vanishing” twin phenomenon, stating

MONTH 2023 American Journal of Obstetrics & Gynecology 3

TABLE 1

List of the clinical guidelines included in the current review

Higher-Order Multifetal Pregnanciesa

and Gynecologists13Committee Opinion No 743 Low-Dose Aspirin Use During

SMFM Consult Series #52: Diagnosis and Management of Fetal Growth

Guideline No 428: Management of Dichorionic Twin Pregnanciesa 2022 Mei-Dan et al14

Guideline No 262: Prenatal Screening for and Diagnosis ofAneuploidy in Twin Pregnanciesa

Guideline No 373: Cervical Insufficiency and Cervical Cerclage 2019 Brown28Guideline No 398: Progesterone for Prevention of Spontaneous

Preterm Birth

Guideline No 426: Hypertensive Disorders of Pregnancy:

Diagnosis, Prediction, Prevention, and Management

NICE Clinical Guideline 137: Updated guidance for the management of

twin and triplet pregnanciesa

TABLE 1

List of the clinical guidelines included in the current review(continued)

Practice Guidelines: role of ultrasound in the prediction ofspontaneous preterm birth

Best practice advice for screening, diagnosis, and management offetal growth restriction

ACOG, American College of Obstetricians and Gynecologists; AWMF, Association of the Scientific Medical Societies in Germany; CNGOF, French College of Gynaecologists and Obstetricians; FIGO, The International Federation of Gynecology and Obstetrics; ISUOG,

International Society of Ultrasound in Obstetrics and Gynecology; NICE, National Institute for Health and Care Excellence; RANZCOG, Royal Australian and New Zealand College of Obstetricians and Gynaecologists; RCOG, Royal College of Obstetricians and

Gynaecologists; SMFM, Society for Maternal-Fetal Medicine; SOGC, Society of Obstetricians and Gynaecologists of Canada.

a Guidelines that are focused on twin pregnancies.

Weitzner Summary of clinical guidelines on twin pregnancies Am J Obstet Gynecol 2023.

TABLE 2

First-trimester care and prenatal genetic screening

UnitedKingdom

136/7wk)

110/7to 136/7wk

U

twin (unless

in vitrofertilization)

CRL of largertwin (unless

in vitrofertilization)Use headcircumference

of larger twinafter 14 wk

CRL of largertwinUse headcircumference

of larger twinafter 14 wk

As many parameters as possible:

location, biometry, structuralanomalies or variants, sex,placental location, and cordinsertion

According totheir lateral orverticalorientation

As manyparameters aspossible—

location,position,placentallocation,umbilical cordinsertion site,fetal sex

According totheir lateral orverticalorientation

As manyparameters aspossible

As manyparameters aspossible

TABLE 2

First-trimester care and prenatal genetic screening(continued)

UnitedKingdom

If only 1 placenta

is visualized, usetwin peak sign vsT-sign

Fetal sex, twin peak or lambdasign, the T sign, and membranethickness

The number of placentas isunreliable because 3% ofmonochorionic twins haveseparate placental masses.b

Number ofgestationalsacs at

7e10 wk;

lambdasign at

11e14 wk

Membranethickness atthe site ofplacentalinsertion;

T-sign orlambda sign;

number ofplacentas

Membranethickness at thesite of placentalinsertion; T sign

or lambda sign;

number ofplacentas

Membranethickness atthe site ofplacentalinsertion; T sign

11e136/7wk

Recom‑mended

in the firsttrimester

Should beoffered

Lowerdetectionrate than insingletons

Notrecommen‑ded but iscurrentlybeingassessedb

considered

May beconsidered

7

seems similar tosingletons, butnumber ofreported affectedcases is small

Difficult todetermine theaccuracy fortrisomy 18 and13

NIPT is recommended and fundedfor twins in some provinces, such

as Ontario and British Columbia

May beoffered

Increased testfailure rate,fewer data onperformancethan insingletons

Can beconsidered

Detection ratesare lower thanfor singletons

Detection ratemay be lowerthan in singletons,but data are stilllimited

TABLE 2

First-trimester care and prenatal genetic screening(continued)

UnitedKingdom

Procedure-Loss rate has an excess risk of

sampling isrecommendedover amnio‑centesis,given earlierresults

Loss rate 2%

e3.8%

Chorionic villussampling isrecommendedoveramniocentesis

in dichorionictwins, givenearlier results

Loss rate 2%

e3.8%

Chorionic villussampling isrecommendedoveramniocentesis

in dichorionictwins, givenearlier results

Risk of lossseems to begreater than insingletons (2%)Chorionic villussampling isrecommendedoveramniocentesis indichorionic twins,given earlierresults

In dichorionic twins, the combination

of transabdominal and transcervicalapproaches or a transabdominal-only approach

seems to minimize the risk ofsampling errors

Transab‑

dominal route

is preferredovertranscervicalb

Risk similar fortransabdominaland transcervicalapproaches

?

Amniocentesis:

risk

Risk may beslightly higherthan insingletons

slightly higherthan insingletons,1.5%e3.1%

Risk may beslightly higherthan in singletons

2 needles isleft to theoperator

that it is associated with increased riskfor fetal structural anomalies, growthrestriction, and preterm birth in thesurviving co-twin A few guidelinesstate that fetal death of 1 twin in adichorionic twin pregnancy is asso-ciated with a 3% to 4% risk of deathand a 1% to 3% risk of neurologicinjury to the surviving twin (UnitedStates, France, ISUOG), and anincreased risk of preterm birth (Can-ada, ISUOG).

Antenatal surveillance andmanagement

Recommendations regarding natal surveillance and managementare summarized inTable 3

ante-Frequency of visits and ultrasoundexaminations

For dichorionic twins, most

sono-graphic assessment of growth and fetalwell-being every 4 weeks starting at 20

Kingdom, Germany, ISUOG, FIGO);

assessment every 3 to 4 weeks starting

at 24 to 25 weeks (Canada) or every 2weeks (France) For monochorionictwins, there was a consensus amongguidelines that sonographic assess-ment should be performed every 2weeks starting at 16 weeks, given thehigher risk of discordant growth and

twinetwin transfusion syndrome.Assessment for structural anomaliesSix guidelines recommend routineanatomic assessment at 18 to 22 weeks

of gestation, whereas 4 guidelinesrecommend that fetal anatomy also beassessed during the first-trimesterscan at 11 to 14 weeks (Table 3), andthe Canadian guidelines state that thiscan be done if the expertise is avail-able Four guidelines recommendroutine fetal echocardiography formonochorionic twins in the secondtrimester

Weight gain and lifestyle advice

We found very little guidance cerning nutrition, weight gain, physicalexercise, and restrictions (or lackthereof) regarding physical and sexualactivity (Table 3)

MONTH 2023 American Journal of Obstetrics & Gynecology 9

TABLE 3

Antenatal surveillance and management

UnitedKingdom

Every 4 wk,starting at 20 wk

Every 4 wk,starting at 20 wk

Every 4 wk,starting at 20 wk

U

Monochorionic-diamniotic twins

Every 2 wk,starting at

16 wk

Every 2 wk, starting at

16 wk

Every 2 wk,starting at

16 wk

Every 2 wk,starting at 16 wk

Every 2 wk,starting at

16 wk

Every 2 wk,starting at

16 wk

Every 2 wk,starting at

at 12e14 wk of gestation

First-trimesterscan (11e14 wk)should includeearly anatomy

Should beassessed in thefirst-trimesterscan

Should beassessed in thefirst-trimesterscan

First-trimesterscan (11e13þ6wk) shouldinclude anatomyscan

U

Late anatomy

scan

Fetal echo for

Prediction and prevention ofpreterm birth

Recommendations regarding the diction and prevention of pretermbirth are summarized inTable 4.Cervical-length screening

pre-We identified some disagreementamong guidelines regarding the use ofsonographic cervical length measure-ment to screen for spontaneous pre-term birth Whereas 5 guidelines

French guidelines recommend against

it, and the UK guidelines chose not toprovide any recommendation Therecommended timing for screening is

at the time of the routine

States, Germany) or at 18 to 24 weeks(ISUOG, FIGO), whereas the Cana-dian guideline was the only one rec-

length twice (at the anatomy scan andonce again before 24 weeks) (Table 4).Only the FIGO guidelines specifyexplicitly that screening should beperformed using the transvaginalapproach The Canadian guidelinesstate that either the transabdominal ortransvaginal approaches can be used,whereas the US guidelines recom-mend the transabdominal approach.Only 3 guidelines describe cutoffvalues that should define a short cer-vix (25 mm according to the Germanand ISUOG guidelines and 20 mmaccording to FIGO)

Prevention of preterm birthAll the guidelines (except the RoyalAustralian and New Zealand College

of Obstetricians and Gynaecologists[RANZCOG]) advise against theroutine use of progesterone, cervicalcerclage, cervical pessary, or tocolysis

(Table 4)

Two guidelines recommend vaginalprogesterone for short cervical length(25 mm) found before 24 weeks(Canada, Germany), whereas theISUOG guidelines state that it may beconsidered in this scenario

Cervical cerclage for a short cervix

is not recommended by most lines, whereas the Canadian and FIGOguidelines suggest that it may be

MONTH 2023 American Journal of Obstetrics & Gynecology 11