Twin and triplet pregnancy is a high-risk situation, with increased risk of mortality and morbidity for both mother and babies. It is, therefore, essential that high-quality antenatal care is provided to optimise outcomes and identify and manage complications effectively. A number of additional elements of care are advised, which requires more monitoring and contact with healthcare professionals with appropriate expertise. In addition, women should be provided with accurate and relevant information and emotional support to mitigate against the anxiety and stress of these high-risk pregnancies. Early care focuses on determining chorionicity and screening for fetal complications, whereas later care concentrates on identifying and managing preterm birth, growth restriction, maternal complications, and planning for delivery. Unfortunately, the evidence base for managing these challenging pregnancies is often lacking, and a number of areas of further research is required.
Introduction
The incidence of multiple births in the developed world has risen mainly from an increase in use of assisted conception but also from increasing maternal age at conception . Multiple pregnancy is a high-risk situation for both mother and babies.
Women who have multiple pregnancies are at higher risk of miscarriage, anaemia, hypertensive disorders, haemorrhage, operative delivery, and postnatal illness, including postnatal depression . Maternal mortality is more than double that of singleton gestations , and are often overshadowed by fetal considerations. This is reflected in the literature, with only one study from the developed world addressing this association .
Adverse outcomes for fetuses and babies of multiple pregnancies occur more often . Premature birth is the main cause , but fetal growth restriction, fetal abnormality, and complications of shared placentation are important contributory factors. Cerebral palsy is increased six-fold among twins and 24-fold among triplets with causes not restricted to prematurity .
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 is logical to propose that, although some of the care that should be provided is no different to that required for all pregnancies, a number of additional elements of care necessitates more monitoring and increased contact with the healthcare team .
Additionally, the increased risk may have a psychosocial and economic effect on women and their families, and may heighten anxiety, resulting in a specific need for more information and support in pregnancy.
In this paper, we aim to summarise the additional elements of antenatal care required to identify complications and optimise outcomes in multiple pregnancy, but will not address how to manage the complications once detected and diagnosed.
Existing guidelines
Internationally, in the developed world, a number of national documents and guidelines relate to various aspects of care of multiple pregnancy . The most comprehensive and systematic review of 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 the antenatal period’ published in 2011. I was personally a member of the Guidelines Development Group , and make reference to that guideline in this chapter.
Existing guidelines
Internationally, in the developed world, a number of national documents and guidelines relate to various aspects of care of multiple pregnancy . The most comprehensive and systematic review of 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 the antenatal period’ published in 2011. I was personally a member of the Guidelines Development Group , and make reference to that guideline in this chapter.
Early pregnancy
Ideally, multiple pregnancy should be diagnosed early. Obstetric sonography in early pregnancy has become widespread, and is advocated to improve gestational dating and thus reduce induction of labour for post-mature pregnancy. It also improves early detection of multiple pregnancy . Early detection of multiple pregnancy and accurate dating in multiple pregnancy is desirable for several reasons: (1) it allows accurate amnionicity and chorionicity determination; (2) this, in turn, allows appropriate planning of care, including discussion about screening for aneuploidy and other fetal complications, such as fetal abnormality, twin-to-twin transfusion syndrome and fetal growth restriction; (3) it allows labelling of each fetus according to lateral or vertical orientation to enable consistent assessment when serial ultrasound monitoring is undertaken, and when undertaking or interpreting screening and diagnostic tests and; (4) it allows time for discussion about the risks of higher order multiple pregnancy and consideration of multi-fetal reduction (in settings where this is acceptable).
Appropriate amnionicity and chorionicity determination is key to providing optimal antenatal care and, if it cannot be determined, the woman should be referred for specialist review to clarify the matter; if still indeterminate, the pregnancy should be treated as monochorionic until proven otherwise.
It is known that labelling twins by assigning numbers (twin 1 and twin 2) and allocating the label twin 1 to the fetus closest to the cervix in early pregnancy, does not accurately determine which will be the leading twin, as the pregnancy progresses, or indeed the birth order. This is particularly true for laterally orientated twins (i.e. left and right twins) where 8.5% change presenting order between first and last scan and 20.3% delivered by caesarean compared with 5.9% delivered vaginally change birth order (i.e. the twin labelled twin 2 delivers first) . Correct labelling according to orientation in relation to the mother as lateral maternal left and maternal right, or vertical upper and lower, is better than assigning a fetus number, as it enables consistency with longitudinal biometric assessment, accuracy when interpreting screening results, and undertaking invasive diagnostic tests where necessary, and avoids misconception about birth order, ensuring that the parents and the paediatric team are aware of the possibility of peripartum switch (i.e. possible change in birth order).
Screening for fetal complications
Down’s syndrome and other aneuploidies
Down’s syndrome and other aneuploidy screening in multiple pregnancy is complicated because of the following issues: (1) there is a higher risk of aneuploidy; (2) the sensitivity (i.e. detection rate) of screening tests is probably lower compared with singleton screening; (3) the false–positive rate is higher; (4) the likelihood of being offered invasive diagnostic testing is higher as is the risk of complications of invasive diagnostic testing; and (5) in the event of an affected fetus, the options are complex, including selective reduction and risks to the surviving normal fetus or fetuses. The published literature on first-trimester screening in multiple pregnancy is of poor quality, and no studies have been 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 chorionic gonadotropin, and pregnancy-associated plasma protein-A) , three evaluated nuchal traslucency and maternal age , and six evaluated nuchal translucency alone . Two of these studies included triplets , but did not report separate data for twins compared with triplets. One only evaluated monochorionic twins . For twins, all methods have high sensitivities, but combined screening overall performs best and should be offered. For dichorionic twin pregnancies, risks should be calculated for each fetus. For triplets, there are no nomograms for serum screening, and therefore nuchal translucency and maternal age is the only available screening .
Women need to be fully informed about the higher risks with screening, and need to be aware that decision-making and options are complex if the screening test is positive. This requires experienced professionals providing information and counselling before the screening test, and indeed afterwards if the result is positive. Furthermore, if the test is positive and the woman opts for invasive diagnostic testing, this should be carried out by a specialist who has the expertise to subsequently carry out selective termination of pregnancy if required .
If first-trimester screening is not possible (e.g. the woman presents too late), no published evidence is available on which to base recommendations, but the NICE guideline recommends offering second-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 higher order pregnancies. This is mainly because of the higher incidence of abnormalities in monozygotic twins (owing to the unusual nature of the cleavage of the conceptus) compared with dizygotic twins .
The management of these pregnancies, where one fetus has an abnormality, is complex. Timely diagnosis enables more choices, time to prepare, optimising fetal surveillance depending on the anomaly, involvement of other specialists (e.g. genetics team, paediatric surgeons) and appropriate birth planning (e.g. place, timing and mode), including access to intrauterine therapy where it is possible.
Published evidence about screening for structural abnormalities in twin or higher order pregnancies is limited. Logic suggests that the scan will take longer and that visualisation at scan may be limited, depending on fetal position, but there is little reason to expect mid-trimester ultrasound to be significantly less or more effective in multiple pregnancy. The limited evidence suggests detection rates for twin pregnancy is similar to published data for singletons . Therefore, routine anomaly screening by ultrasound between 18–20 + 6 weeks gestation as in singleton pregnancy is recommended.
Abnormalities specific to monozygotic twins are midline, such as holoprosencephaly and neural tube defects, and cardiac abnormalities. Therefore, the value of fetal echocardiography in addition to routine anatomy scan is questioned. As not all monozygotic twins are monochorionic, this policy would need to be applied to all twins irrespective of chorionicity unless one were to undertake fetal sexing and exclude discordant sex twins, which can complicate matters (as couples may not want to know the sex of their babies). A Scandinavian study of twin pregnancies in which women had a package of scans (nuchal translucency scan, anomaly scan at 19 weeks, fetal echocardiography at 21 weeks, and a cervical length at 23 weeks), found that 0.5% of the fetuses had cardiac anomalies, 80% of which were detected at the 19-week anomaly scan (i.e. before fetal echocardiography), and therefore concluded that formal fetal echocardiography is not justified.
Twin-to-twin transfusion syndrome
About 10–15% of monochorionic pregnancies with shared placentation develop twin-to-twin transfusion syndrome (TTTS), in which outcome is significantly improved if treated with laser ablation. Given the availability of treatment, it is important to screen for TTTS to allow timely access to this treatment.
It is worth noting that the chronic form of TTTS (most common form) usually presents between 16 and 24 weeks gestation, and treatment is recommended from 16 weeks gestation; therefore, earlier screening would need to be effective to advocate its use.
First-trimester parameters for TTTS screening have been evaluated in several studies. These include nuchal translucency , crown, rump length, or both , or ductus venosus Doppler blood flow . They all show low sensitivity and variable specificity. As these parameters are not predictive, and there is potential to cause unnecessary anxiety, first-trimester screening for TTTS is not advised.
Although it is known that serial ultrasound scans are necessary to identify TTTS by looking for the obvious 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-clinical features, looking specifically at inter-twin membrane folding and amniotic fluid discordance . Both these features have been shown to have better sensitivity than the aforementioned first-trimester parameters; poor specificity, however, should warrant a step up in frequency of scans but also continued vigilance in those pregnancies without these features. The NICE guideline recommends a scan every 2 weeks from 16–24 weeks to screen for TTTS, but a step up to weekly scans if inter-twin membrane folding or liquor discordance occurs .
Intra-uterine growth restriction
Fetuses of multiple pregnancies are at increased risk of being small for gestational age (SGA) and, if placental dysfunction exists, growth restriction (IUGR). Both SGA and IUGR fetuses and babies have poorer perinatal outcomes and, therefore, identifying growth problems is important.
Symphysis–fundal height measurement is not effective in identifying growth problems in twin pregnancy , and serial ultrasound scans are required to identify small babies but also a significant size difference between fetuses.
The problem with interpreting the published literature to inform the best parameters to use is that criteria for abnormality and definitions of SGA or IUGR or growth discordance are variable, and one is often not comparing like with like. The NICE guideline development group reviewed 26 studies of ultrasound parameters in twin pregnancies, including various fetal biometric measurements and estimated fetal weight (EFW), based on formulae of ultrasound parameters, Doppler ultrasound of the umbilical cord, and composite screening strategies . They acknowledge that most of the evidence is low or very low quality, but concluded that (1) any single fetal biometric parameter was a poor predictor of IUGR or birthweight discordance; (2) an EFW at or less than the 10th centile is a moderately useful predictor of intrauterine growth restriction, defined as birthweight at or less than 10th centile; (3) the best cut-off for inter-twin birthweight discordance is an EFW difference of 25% or more; (4) the best EFW is derived when applying a formula that includes at least two biometric parameters; (5) the best predictor of IUGR or discordance between twins is an ultrasound carried out within 28 days of birth; (6) strong evidence supporting the routine use of umbilical artery Doppler for the prediction of IUGR or birthweight discordanceis lacking; and (7) strong evidence that any composite screening strategy detects IUGR in twin pregnancy is lacking. No studies addressed the value of amniotic fluid volume assessment or middle cerebral artery Doppler examination. No studies addressed timing and frequency of scanning. They acknowledge that no evidence was available to guide 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 be calculated using two biometric parameters from 20 weeks gestation, scans should be undertaken at intervals of less than 28 days, a 25% or greater EFW discordance should be considered significant, and umbilical artery Doppler should not be used to monitor for IUGR or birthweight differences in twin and triplet pregnancies .
Since the publication of the NICE guideline , a large UK cohort study of 2161 twin pregnancies (302 monochorionic and 1859 dichorionic twin pregnancies) has shown that EFW discordance is accurate in predicting birthweight discordance, both EFW and birthweight discordance are good predictors 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 .
Screening for maternal complications
Hypertensive disorders of pregnancy
Women with multiple pregnancy have a two to three times higher risk of developing a hypertensive disorder in pregnancy (i.e. gestational hypertension, pre-eclampsia or eclampsia) . In addition, if it occurs, it is more likely to occur earlier and be severe. In preventing a hypertensive disorder, The UK NICE guideline for hypertension in pregnancy recommends that women with one high-risk factor or at least two moderate risk factors take oral low-dose aspirin (75 mg daily) from 12 weeks gestation until birth . Multiple pregnancy is considered a moderate risk factor. To detect hypertensive disorders, it is recommended that a woman’s blood pressure is measured and urine tested for protein at each antenatal contact .
Gestational diabetes
Gestational diabetes results from relative insulin insufficiency secondary to the diabetogenic effect of placental hormones (e.g. human placental lactogen, progesterone and cortisol). The larger placental mass of multiple pregnancy, increases the amount of these placental hormones and, therefore, theoretically the risk of developing gestational diabetes. In practice, however, evidence is conflicting about whether the occurrence of gestational diabetes is increased in multiple pregnancy, and whether it is advisable to screen ; this area warrants further research.
Other maternal complications
Almost all other complications of pregnancy are increased in multiple pregnancy, such as placenta praevia, obstetric cholestasis, and antepartum haemorrhage. Indeed, all minor ailments of pregnancy are worse too. The management of these complications and ailments is, however, no different compared 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 the most important fetal complication of multiple pregnancy, as it is the most common cause of adverse outcome. Over a one-half of twins and almost all triplets are born before 37 weeks gestation, and 15–20% of neonatal unit admissions are caused by preterm birth of twins and triplets. The cause of preterm labour is probably multifactorial. The optimal methods for prediction and prevention remain the subject of continuing debate.
Prediction
Several factors and tests associated with diagnostic accuracy as a predictor of spontaneous preterm birth in twin and triplet pregnancies have been studied, namely ultrasonographic cervical length measurements, fetal fibronectin test (FFT), home uterine activity monitoring, past obstetric history of preterm birth, and composites of these approaches.
A systematic review of 21 studies comprising 3523 twin pregnancies concluded that transvaginal cervical length at 20–24 weeks’ gestation is a good predictor of spontaneous preterm birth in asymptomatic 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 25 mm at 18–24 weeks gestation is a good predictor of spontaneous preterm delivery in twin pregnancy . Two studies of sonographic cervical length in triplet pregnancy also concluded that a cervical length measurement of less than 25 mm at 14–20 weeks gestation is a good predictor of spontaneous preterm birth in triplet pregnancy .
A study of the FFT in twin pregnancies showed no association between a positive test and risk of spontaneous preterm delivery . When combined with cervical length assessment, FFT can predict preterm delivery .
A systematic review of six randomized trials of home uterine activity monitoring showed this intervention to be ineffective in predicting spontaneous preterm delivery .
An effective predictor is a history of previous preterm delivery , although this is not helpful in primigravidae.
Prevention
Interventions that have been studied to prevent spontaneous preterm labour and hence delivery in twin and triplet pregnancies include bed rest, progesterone (intramuscular or vaginal), cervical cerclage, and tocolytics (oral betamimetics). Sexual abstinence has never been studied in multiple pregnancy.
A systematic review of seven randomised-controlled studies (RCTs) (five of twins and two of triplets) of bed rest found no evidence to support this intervention to reduce preterm delivery .
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 and triplet pregnancies . 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 in women with asymptomatic short cervix (defined as 25 mm or less on midtrimester ultrasound) included only 52 twin pregnancies . Although a significant reduction in preterm birth occurred in singleton pregnancy, no such effect was reported in twin pregnancies.
One RCT and one observational study (prospective) of twin pregnancies , and four observational studies (retrospective) of triplet pregnancies evaluated the effectiveness of cervical cerclage 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 to support this intervention to reduce preterm delivery .
Therefore, in the absence of an effective intervention, routine screening to predict preterm delivery is not recommended in twin and triplet pregnancy.
Use of corticosteroids
It is well known that antenatal corticosteroids reduce neonatal complications in preterm babies . Although corticosteroids are considered to be less effective in multiple pregnancy , the question arises, given the substantial risk of preterm delivery in multiple pregnancy, whether giving an untargeted course of steroids routinely at a given gestation or whether giving multiple courses at regular intervals may be beneficial. The problem with giving a single course routinely would be that time of administration may be remote from delivery and the effect dampened. An RCT (21% of recruits were twin pregnancies) showed that multiple courses compared with a single course does not improve outcomes, but are associated with potential harm (i.e. lower birth weight and head circumference) . On this basis, it is better to avoid untargeted routine single or multiple courses of steroids, and to advocate targeted steroids when indicated (i.e. when preterm labour or birth is imminent ). This will enable a shift in focus towards informing all women with twin and triplet pregnancies of the increased risk of preterm birth, the benefits of targeted steroids, and providing information about symptoms and signs 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 to discussing risks of preterm delivery and preparing women for this eventuality, a number of twin and triplet pregnancies will have uncomplicated progression, and a crucial aspect of optimal antenatal care is to ensure an informed discussion occurs relating to place, timing and mode of delivery. This should include discussing risks and benefits of vaginal delivery compared with caesarean section, pain relief options, who will be present at the delivery (often more personnel than in singleton pregnancy), and the 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 mitigate and identify them, can lead to a certain level of anxiety for the woman and her partner or family. In today’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 women are given good information and are guided to reputable sources of further information, and have the opportunity to clarify matters that are unclear to them. They should be encouraged to explore socioeconomic issues related to caring for and supporting more than one child. This process of information giving 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, it has been suggested that a high-calorie diet may help maintain her nutritional state. The counterargument is that boosting weight gain might not be advantageous. A Cochrane review found no RCTs to advise whether specific dietary advice for women with multiple pregnancy does more good than harm .
The NICE guideline group reviewed the limited literature on nutritional supplements and dietary advice in multiple pregnancy, and concluded that the few published studies were of low quality, and that no evidence was available to give different advice to that given in singleton pregnancy . They emphasised, however, that it is important to be aware of the higher incidence of anaemia, and recommended checking the full blood count at 20–24 weeks to identify women who may need iron and folic acid supplementation.
There is no evidence to inform specific advice about other lifestyle issues (e.g. work patterns, sexual activity, and exercise in multiple pregnancy).
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
