Screening, Management and Delivery in Twin Pregnancy

Key words

twins - monochorionic - dichorionic - monoamniotic - TTTS

Introduction

Issues and Objectives, Identification and Evaluation of the Evidence

Recommendations

This is a brief version of the AWMF S2e guideline “Monitoring and Management of Twin Pregnancies” (https://www.awmf.org/leitlinien/detail/ll/015-087.html).

The AWMF guideline is an adaptation of the ISUOG and NICE guidelines [1] [2] [3] as well as systematic literature research. It was written to create a very condensed readable practical version and to make the guideline known.

Twin pregnancies can be classified as dichorionic diamniotic (DC DA), monochorionic diamniotic (MC DA) and monochorionic monoamniotic (MC MA).

Twin pregnancies can be concordant (both twins are affected) or discordant (only one twin is affected) for chromosomal defects, malformations, growth restriction and hemodynamic disorders.

Chorionicity is the prognostically most significant parameter. MC twins have significantly higher risks of intrauterine morbidity and mortality than DC twins.

General Information regarding Twin Pregnancies

Dating of Twin Pregnancies

• The gestational age of twin pregnancies should be determined at a crown-rump length (CRL) of 45–84 mm (11^+ 0 to 13^+ 6 weeks of gestation) [4].

• For spontaneously conceived twins, the larger CRL should be used to estimate the gestational age [5].

• Twin pregnancies conceived after in vitro fertilization should be determined based on the date of egg collection – or the age of the embryo (in days) at implantation [4].

Determination of Chorionicity and Amnionicity of Twin Pregnancies

Prior to 13^+ 6 weeks of gestation, chorionicity should be determined by

• assessment of the membrane thickness at the site of insertion of the amniotic membrane into the placenta,

• idetermination of the T-sign or lambda sign,

• as well as the number of placenta masses.

An ultrasound image showing chorionicity should be archived in the records for future reference [2] [6].

• The second opinion of a specialized center should be obtained if it is not possible to determine chorionicity in a routine setting by transabdominal or transvaginal ultrasound.

• If the determination of chorionicity is also not possible there, the pregnancy should be treated as an MC pregnancy [2].

• Amnionicity should also be determined and documented when chorionicity is established.

• MC MA pregnancies should be referred to a specialized center with related management experience [1] ([Fig. 1]).

Fig. 1 First-trimester ultrasound images of: a dichorionic diamniotic twin pregnancy, in which the twins are separated by a thick layer of fused chorionic membranes, and b a monochorionic diamniotic twin pregnancy in which the twins are separated only by two thin amniotic membranes. Source: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V (AWMF). Leitlinie zur Überwachung und Betreuung von Zwillingsschwangerschaften. Online: https://www.awmf.org/leitlinien/detail/ll/015-087.html; Stand: 05.10.2020. [rerif]

Twin Fetus Labeling

• The labeling of twin fetuses should follow a reliable and uniform strategy and be clearly documented (maternity log, patient documentation).

• Several parameters should be used for this (e. g. which is to the front, the side, the position, the location of the placenta and umbilical insertion, and the sex) [3] [7].

The Perinatal Switch Phenomenon

Not all clearly labeled fetuses are actually delivered in that order (switch phenomenon).

Routine Monitoring of Twin Pregnancies using Ultrasound

• In any general ultrasound examination of twins, the following parameters should be assessed in both twins with 20 weeks or more of gestational age:

  • biometry, estimated weight and difference of estimated fetal weights (%), amniotic fluid volume (deepest vertical pocket, DVP) and umbilical artery Doppler.

  • An estimated weight difference ≥ 25 % indicates selective fetal growth restriction, sFGR, for which referral to a specialized center is indicated [8].

• Uncomplicated twin pregnancies should receive first-trimester screening, a detailed second-trimester malformation ultrasound (organ screening), and subsequently serial growth measurements and Doppler ultrasound examinations every 4 weeks.

• Complicated DC twins should be examined more often, depending on the circumstances and their severity [3].

• Uncomplicated MC twin pregnancies should receive first-trimester screening and a detailed second-trimester malformation ultrasound (organ screening) and, from 16 weeks of gestation onwards, examined serially every 2 weeks with growth measurements, amniotic fluid volume determination (DVP) and Doppler ultrasound.

• Depending on the circumstances and their severity complicated MC twins should be examined more frequently [3] [9] [10] ([Fig. 2], [3]).

Fig. 2 Algorithm of ultrasound monitoring (completed weeks of pregnancy) for uncomplicated dichorial twin pregnancies. Source: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V (AWMF). Leitlinie zur Überwachung und Betreuung von Zwillingsschwangerschaften. Online: https://www.awmf.org/leitlinien/detail/ll/015-087.html; Stand: 05.10.2020. [rerif]

Fig. 3 Algorithm of ultrasound monitoring (completed weeks of pregnancy) for uncomplicated monochorionic twin pregnancies. DVP: deepest vertical pocket; PI: pulsatility index; MCA-PSV: peak systolic velocity (V_max of middle cerebral artery); A. umb: umbilical artery; MCA: middle cerebral artery; EFW: estimated fetal weight. Source: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V (AWMF). Leitlinie zur Überwachung und Betreuung von Zwillingsschwangerschaften. Online: https://www.awmf.org/leitlinien/detail/ll/015-087.html; Stand: 05.10.2020. [rerif]

Screening for Chromosomal Abnormalities in Twin Pregnancy

• First-trimester screening for chromosomal abnormalities in twins should include maternal age, nuchal translucency (NT) and serum biochemistry (free beta-hCG and PAPP-A).

• If necessary, it should be combined with sonographic markers for chromosomal defects such as the nasal bone, tricuspid regurgitation and ductus venosus (NB, TR, DV) [2] [11] [12] [13].

• In the case of a “vanishing twin”, first-trimester screening for fetal trisomy should take into account maternal age, fetal NT measurement and serum beta-hCG (without PAPP-A) level.

• PAPP-A should only be used if it has been adjusted for the interval between the estimated gestational age at fetal death and blood collection [14].

• First-trimester screening for chromosomal defects in twins may include cell-free fetal (placental) DNA.

• However, the detection rates of the non-invasive prenatal test (NIPT) for chromosomal defects in twins are lower than for single pregnancies [2] [15].

• Ultrasound between 11–13^+ 6 weeks of pregnancy should include early structured malformation diagnosis including NT [16] [17].

• Twins are more likely to have an increased risk of chromosomal abnormalities after first-trimester screening (combined test) than singletons.

Invasive prenatal Diagnosis in Twin Pregnancy

• The abortion rate after invasive diagnostics is about 2–3.8 % for CVS and 1.5–3.1 % for AC [18] [19] [20] [21].

• Screening and invasive diagnostic procedures are more complex for twins compared to singletons;

• therefore such procedures should be performed by experienced physicians.

• The consultation should include the risks of puncture, possible discordance for aneuploidy, potential management strategies and the risks of embryo reduction or selective fetocide [1] [3].

• CVS should be the preferred method for DC twins as it can be employed earlier than amniocentesis.

• Early diagnosis of aneuploidy is particularly important in twin pregnancies, as the risk of selective fetocide is lower in the first trimester than in the second [22].

• The localization of the fetuses and placentas should be carefully mapped in order to allow clear assignment.

• DC twins should be sampled individually.

• If MC twins are also sampled separately, a heterokaryotype can be detected in the case of discordant chromosomal defects (e. g. for trisomies 21, 18, 13, Turner syndrome and triploidy described above).

Implications of NT or CRL Discordance in the first Trimester

• The management of twin pregnancies with NT discordance ≥ 20 % or CRL discordance ≥ 10 % between 11–13^+ 6 of gestation should be discussed with experts in fetal medicine [23] [24].

Ultrasound Screening for structural Anomalies in Twin Pregnancy

• Twin fetuses are to be examined for the presence of severe malformations during first-trimester ultrasound.

• Organ screening should be performed at about 20 (18–22) weeks of gestation [2] [17] [25], including fetal echocardiography [26] [27].

Management of Twin Pregnancy discordant for Fetal Anomaly

• Twin pregnancies discordant for fetal anomaly should be referred to a fetal medicine center [2].

Selective Fetocide in Twin Pregnancy

• In the case of anomalies in a discordant DC twin pregnancy, embryo reduction can be performed, preferably in the first trimester, by ultrasound-guided intracardiac injection of potassium chloride or lidocaine [22].

• When the diagnosis is made in the second trimester, women might opt for late selective termination in the third trimester, if If legally possible, in order not to endanger the survivor in case of preterm birth [1].

• Selective fetocide in monochorionic twins is performed by cord occlusion, intrafetal laser ablation or radiofrequency ablation [1] [2] [22] [28] [29] [30].

Screening for Risk of Preterm Birth in Twin Pregnancy

• Ultrasound cervical length measurement is the preferred screening method for preterm birth of twins;

• a cervix length of < 25 cm in the second trimester should be used as a cut-off [1] [31].

Fetal Growth Restriction

Fetal Growth Restriction (FGR, Intrauterine Growth Restriction, IUGR) in twins is found in both MC and DC twins.

Complications frequently affecting MC twins with FGR are Twin to Twin Transfusion Syndrome (TTTS), Twin Reversed Arterial Perfusion Sequence (TRAP) and Twin Anemia Polycythemia Sequence (TAPS).

Screening, Diagnosis and Management of Fetal Growth Restriction

Diagnostic Criteria and Investigations for selective Fetal Growth Restriction (sFGR)

• A single estimated weight < 3 rd percentile in a twin, independent of chorionicity defines sFGR.

• At least 2 of the following 4 parameters must be met for MC twins (fetal weight of one fetus < 10^th percentile, abdominal circumference < 10^th percentile, EFW difference ≥ 25 %, umbilical artery PI of the smaller fetus > 95^th percentile).

• For DC twins, at least 2 of the following 3 parameters must be met (fetal weight of one fetus < 10^th percentile, EFW differential ≥ 25 %, umbilical artery PI of the smaller fetus > 95^th percentile) [32].

• Monitoring should be intensified in MC twins with a weight discrepancy ≥ 20 % as this is associated with increased intrauterine mortality and perinatal morbidity [33] [34].

• The estimated weight discordance should be calculated using the following formula:

• (weight of the larger twin – weight of the smaller twin) × 100/weight of the larger twin [1].

• A search for the underlying causes of sFGR should include the following examinations: ultrasound scan, Doppler sonography, genetic familly history and testing, infection screening [35].

• In MC twin pregnancies, sFGR is mainly due to unequal placental sharing [36].

Screening for FGR in Twin Pregnancy

• A combination of head, abdomen and femur measurements is best used to estimate fetal weight [37].

• If the difference in the estimated fetal weights is ≥ 25 %, the patient should be referred to a Level 1 Perinatal Medicine Center [1].

Classification of sFGR in MC Twin Pregnancy

In MC DA twins sFGR is classified based on the end-diastolic flow profile of the umbilical arteries: [38].

• Type I: EDF-positive

• Type II AREDF

• Type III: cyclical/intermittent AREDF

EDF: end-diastolic flow
AREDF: absent or reversed end diastolic flow ([Fig. 4])

Fig. 4 Classification of selective fetal growth restriction in monochorionic twin pregnancies. In Type I, the umbilical artery waveform shows a positive end-diastolic flow, while in Type II there is persistent absent or reverse end-diastolic flow (AREDF). In Type III there is a cyclical/intermittent AREDF pattern alternating with positive flow. Source: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V (AWMF). Leitlinie zur Überwachung und Betreuung von Zwillingsschwangerschaften. Online: https://www.awmf.org/leitlinien/detail/ll/015-087.html; Stand: 05.10.2020. [rerif]

Management of Twin Pregnancy complicated by sFGR

• DC twin pregnancies with sFGR should be monitored like singletons with FGR [1].

• There is limited evidence available to guide the management of MC twins affected by sFGR.

• Possible options include: conservative management followed by early delivery, laser ablation, or cord occlusion of the growth-restricting twin (in order to protect the other twin) [39].

Follow-up of Twin Pregnancy complicated by sFGR

• In DC twin pregnancy complicated by sFGR, fetal Doppler examinations should be performed approximately every two weeks.

• Fetal Doppler examinations should be performed at least every week for MC twin pregnancies.

• Management of MC DA twin pregnancies affected by sFGR is complex and should be performed at a Perinatal Center [39].

• The timing of delivery should be based on the evaluation of interval growth, fetal Doppler findings and/or CTG and, if available, computerized CTG analysis [1].

Management of the surviving Twin after Demise of the Cotwin

• When a single intrauterine demise occurs in an MC pregnancy, the woman should be referred to a Perinatal center,

• A Doppler examination of the middle cerebral artery should be performed with measurement of maximum velocity (V_max) in order to estimate the probability of fetal anemia [1] [40].

When one MC twin dies in utero, the surviving twin may then lose part of its circulating volume to the dead twin, leading to potentially severe hypotension in the survivor, which can lead to hypoperfusion of the brain and other organs, potentially causing brain damage or death [41].

The following complications can occur after a single intrauterine demise of an MC or DC twin [41] [42]:

• Death of a cotwin 15 % and 3 %

• Preterm delivery 68 % and 3 %

• Abnormal cranial image of the cotwin 34 % and 16 %

• Neurodevelopmental impairment of the surviving cotwin 26 % and 2 %

• Brain damage is usually the result of a hypoxic-ischemic lesion that results in the development of cystic periventricular leukomalacia, infarction of the middle cerebral artery, or damage to the basal ganglia, thalamus and/or cortex.

• Pre- and postnatal imaging including high-resolution ultrasound and, if necessary, an MRI should be performed.

• Additionally, there should be long-term pediatric follow-up [43].

• If there is strong suspicion that the surviving twin may have suffered serious neurological damage, late termination of pregnancy should be considered as an option [1].

Complications unique to Monochorionic Twin Pregnancy

Complications that occur exclusively in MC twin pregnancies are TTTS, TAPS and TRAP sequence, monoamniotic pregnancies and conjoined twins.

Twin-to-Twin-Transfusion Syndrome (TTTS)

TTTS Staging

• The Quintero staging system is the most widely used classification system of TTTS [44].

• This system is not always predictive of the outcome and is not always chronological, e. g. Stage I can lead directly to Stage III or intrauterine fetal death [1] ([Fig. 5], [Table 1]).

Fig. 5 Sonographic image of TTTS with a polyhydramnion of the recipient and b oligohydramnios of the donor. Source: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V (AWMF). Leitlinie zur Überwachung und Betreuung von Zwillingsschwangerschaften. Online: https://www.awmf.org/leitlinien/detail/ll/015-087.html; Stand: 05.10.2020. [rerif]

Table 1 Staging system modified according to Quintero [44].

stage	classification
I	oligohydramnios-polyhydramnios sequence donor: DVP < 2 cm recipient: DVP > 8 cm (≤ 20 weeks gestation), > 10 cm (> 20 weeks gestation)
II	donor: urinary bladder not visible in ultrasound
III	absent or reversed umbilical-arterial diastolic flow absent or reversed a-wave in ductus venosus pulsatile umbilical-venous flow in one of the twins
IV	hydrops in one or both twins

DVP, deepest vertical pocket (amniotic fluid depot).

Screening for TTTS

• In MC twin pregnancy, screening for TTTS should start at 16 weeks of gestation, with scans repeated every 2 weeks thereafter [1].

• If TTTS is diagnosed, the patient should be referred to a specialized center as soon as the following criteria are met:

• Donor: DVP < 2 cm

• Recipient: DVP > 8 cm (≤ 20 weeks gestation) or > 10 cm (> 20 weeks gestation) [1] [3]

• MC twin pregnancies with amniotic fluid discordance should be checked on a weekly basis to rule out progression to TTTS [1].

TTTS Therapy

• Laser ablation is the treatment of choice for TTTS.

• Patients with TTTS should be referred promptly to a center providing this therapy [45] [46] [47].

• Conservative management with close monitoring may be considered for Quintero Stage I without maternal complications due to a massive polyhydramnion or short cervix [1] [48].

• After laser therapy, further ultrasound examinations should initially be performed weekly and every two weeks if symptoms subside [1].

Neurological follow-up for TTTS

MC twin pregnancies with TTTS have an increased risk of brain abnormalities and delayed neurological development. Both donor and recipient are at increased risk for ischemic or hemorrhagic lesions. The risk for neurological developmental disorders after laser therapy is between 4 % and 13 % and is thus about half as low as after amniotic reduction [49].

Twin Anemia-Polycythemia Sequence (TAPS)

• TAPS is based on the findings of discordant systolic V_max values of the middle cerebral artery in both fetuses [1] [50] [51].

• There is limited evidence regarding the outcome and optimal management of TAPS; therefore treatment options should be individualized and discussed with the parents [1].

• MC twins with TAPS have an increased risk of delayed neurological development.

• Cerebral imaging in the third trimester and a developmental neurological examination at the age of 2 years is recommended [52] [53] ([Table 2]).

Table 2 Antenatal and postnatal stage classification of the Twin Anemia Polycythemia Sequence (TAPS), modified according to Slaghekke and Lopriore [54] [55].

stage	antenatal staging	postnatal staging interfetal Hb differential (g/dL)
1	MCA-PSV donor 1.5 MoM and recipient < 1.0 MoM, without other signs of fetal compromise	> 8.0
2	MCA-PSV donor 1.7 MoM and recipient < 0.8 MoM, without other signs of fetal compromise	> 11.0
3	stage 1 or 2 with donor cardiac compromise umbilical artery AREDF, umbilical vein pulsatile, DV PVIV raised/a-wave negative	> 14.0
4	donor hydrops	> 17.0

Hb: hemoglobin; MCA: middle cerebral artery; MoM: multiple of median value; PSV: peak systolic velocity (V_max of middle cerebral artery).

Twin Reversed Arterial Perfusion (TRAP) Sequence

• The chances of survival of the pumping twin can be increased by using minimally invasive techniques (e. g. laser coagulation of the anastomoses as well as intrafetal methods, umbilical cord coagulation), if necessary even before 16 weeks [1] [56] [57] [58] ([Fig. 6], [7]).

Fig. 6 a Sagittal visualization of a TRAP fetus, b visualization of retrograde blood flow in the TRAP fetus. Source: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V (AWMF). Leitlinie zur Überwachung und Betreuung von Zwillingsschwangerschaften. Online: https://www.awmf.org/leitlinien/detail/ll/015-087.html; Stand: 05.10.2020. [rerif]

Fig. 7 Diagnostic algorithm for monochorionic-diamniotic twins with discordant findings. Source: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V (AWMF). Leitlinie zur Überwachung und Betreuung von Zwillingsschwangerschaften. Online: https://www.awmf.org/leitlinien/detail/ll/015-087.html; Stand: 05.10.2020. [rerif]

MC MA Twins

• Umbilical cord entanglement is almost always present in MC MA twins and does not appear to contribute essentially to morbidity and mortality [59].

Conjoined Twins

Conjoined twins are very rare and are always MC MA pregnancies. Ultrasound diagnosis in the first trimester is now common by visualization of near and fixed fetal bodies with partial fusion of the bodies ([Fig. 8]).

Fig. 8 Three-dimensional ultrasound image of a cephalopagus at 10 weeks of gestation. Source: Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V (AWMF). Leitlinie zur Überwachung und Betreuung von Zwillingsschwangerschaften. Online: https://www.awmf.org/leitlinien/detail/ll/015-087.html; Stand: 05.10.2020. [rerif]

Time of birth for twin pregnancies

Time of Birth of uncomplicated DC DA and MC DA Twins

• Uncomplicated DC twins should be delivered at between 37^+ 0–38^+ 0 weeks of gestation.

• Uncomplicated MC DA twins should be delivered at between 36^+ 0–37^+ 0 weeks of gestation [60] [61] [62] [63] [64].

Time of Birth of uncomplicated MC MA Twins

• Uncomplicated MC MA twins should be delivered at between 32^+ 0–32^+ 6 weeks of gestation [3] [65] [66].

The decision to deliver uncomplicated MC MA twins between 32^+ 0–32^+ 6 weeks of gestation is based on the observation that intrauterine mortality doubles subsequently [65] [66].

The recommendation on the time of birth for MC MA twins was adopted by expert consensus due to the lack of randomized trials ([Table 3]).

Table 3 Recommended time of birth of uncomplicated dichorial (DC), monochorionic diamniotic (MC DA) and monochorionic monoamniotic (MC MA) twins according to international guidelines [3] [67] [68] [69] [70].

professional Society	DC twins	MC DA twins	MC MA twins
National Guideline Alliance (UK). Twin and Triplet Pregnancy. London: National Institute for Health and Care Excellence (UK); 2019 [3]	37+ 0 – 37+ 6	36+ 0 – 36+ 6 (after LMI)	32+ 0 – 33+ 6
Royal College of Obstetricians and Gynaecologists (RCOG) [67]	–	from 36+ 0 (after LMI)	32+ 0 – 34+ 6
American College of Obstetricians and Gynecologists (ACOG) [68]	38	34+ 0 – 37+ 6	32–34
Royal Australian and New Zealand College of Obstetricians and Gynecologists (RANZ-COG) [69]	–	up to 37	–
French College of Gynaecologists and Obstetricians (CNGOF) [70]	38 – < 40	36 – < 38+ 6	32 – < 36

LMI = Lung Maturation Induction; GW = gestation weeks (completed weeks and additional days).

Delivery Mode for Twin Pregnancies

Delivery Mode for uncomplicated DC and MC DA Twins > 32 Weeks of Gestation

• Uncomplicated twins > 32 weeks of gestation, first twin in cephalic position, without contraindications or growth discordance, can be delivered vaginally or by C-section.

• Chorionicity plays no role in delivery mode [71] [72] [73] [74] [75] [76] [77] [78].

Delivery Mode for uncomplicated DC and MC DA Twins < 32 Weeks of Gestation

• There is insufficient evidence available to offer a firm recommendation for the delivery of uncomplicated twins < 32 weeks of gestation [79] [80].

Delivery Mode for uncomplicated MC MA Twins

The recommendation on the delivery mode for MC MA twins was adopted by expert consensus due to the lack of randomized studies.

• MC MA twins should be delivered by C-section [3] ([Table 4]).

Table 4 Overview of recommendations of national professional societies on the delivery mode in uncomplicated dichorial, monochorial and monoamnial twins [3] [67] [68] [69] [70].

professional Society	DC DA twins	MC DA twins	MC MA twins
National Guideline Alliance (UK). Twin and Triplet Pregnancy. London: National Institute for Health and Care Excellence (UK); 2019 [3]	vaginal delivery under the the following conditions: uncomplicated pregnancy > 32 weeks of gestation no contraindications first child in cephalic position no significance discordance in EFW	vaginal delivery under the the following conditions: uncomplicated pregnancy > 32 weeks of gestation no contraindications first child in cephalic position no significance discordance in EFW	primary C-section
Royal College of Obstetricians and Gynaecologists (RCOG) [67]	–	planned vaginal birth	primary C-section
American College of Obstetricians and Gynecologists (ACOG) [68]	planned vaginal birth > 32+ 0 GW regardless whether twin II in cephalic or breech presentation	planned vaginal birth > 32+ 0 GW regardless whether twin II in cephalic or breech presentation	primary C-section
Royal Australian and New Zealand College of Obstetricians and Gynecologists (RANZ-COG) [69]	planned vaginal birth only when sufficient infrastructure available for continuous fetal monitoring or emergency C-section	planned vaginal birth only when sufficient infrastructure available for continuous fetal monitoring or emergency C-section	–
French College of Gynaecologists and Obstetricians (CNGOF) [70]	vaginal birth regardless of gestational age and child presentation	vaginal birth regardless of gestational age and child presentation	–

Funding

Deutsche Stiftung Frauengesundheit, Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG), Deutsche Gesellschaft für Ultraschall in der Medizin (DEGUM).

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