Multiple pregnancy

What is a multiple pregnancy?

Multiple pregnancy occurs when two or more ova are fertilised to form dizygotic (non-identical) twins or a single fertilised egg divides to form monozygotic (identical) twins.

In dizygotic multiple pregnancies, each fetus has its own placenta (either separate or fused), amnion and chorion. In monozygotic multiple pregnancies, the situation is more complex depending on the timing of the division of the ovum:

• Embryo splits at 3 days: two chorions, two amnions.

• Embryo splits at 4-7 days: single placenta, one chorion, two amnions.

• Embryo splits at 8-12 days: single placenta, one chorion and one amnion (rare - 1-2% of monochorionic pregnancies). ¹

• Embryo splits at 13 days: conjoined twins (Siamese twins) - very rare.

In monochorionic twin pregnancies, one twin can receive a reduced blood supply and have a slower growth rate (twin-twin transfusion). Sometimes, one fetus dies and forms a mummified fetus papyraceous or is reabsorbed.

Triplet pregnancies can be monochorionic, dichorionic or trichorionic. Chorionicity and amnionicity in multiple pregnancies affect the risks and therefore management of the pregnancy and so are assessed in early scans.

Multiple pregnancy epidemiology

The incidence of twin pregnancy varies worldwide, from a low incidence of 6.7 per 1,000 births in Japan, to the highest in Nigeria of 40 per 1,000 births.² Generally the rate of monozygotic twins is relatively constant at 3.5 per 1,000 births; however, the rate of dizygous twins varies with the age, parity and ethnicity of the mother, and the use of assisted reproductive techniques.

According to the Office for National Statistics, the rate of multiple pregnancy in England and Wales in 2021 was 14 per 1,000 births.³ Of these multiple pregnancies, 98.8% were twin pregnancies.

The incidence of multiple pregnancy has increased in the UK from a rate of around 10 per 1,000 births in 1980 to the current level, mainly due to the use of assisted reproductive techniques such as in vitro fertilisation (IVF). Trends towards increasing maternal age also contribute (twins are more common at later ages).¹

Due to a recognition of the increased risk to both mother and baby of multiple pregnancy, the Human Fertilisation and Embryology Authority (HFEA) set targets to reduce the rates of double embryo transfers and hence the numbers of multiple pregnancy. In 2003, the HFEA restricted triple embryo transfers. In 2007, their 'One at a time' campaign encouraged clinics to transfer one embryo and freeze any remaining embryos for good prognosis IVF patients. Later consensus agreements required clinics to meet multiple birth targets and develop strategies to reduce their rates.

These measures have been very successful. The average multiple birth rate from IVF in the UK has decreased from around 28% in the 1990s, to 6% in 2019. The overall IVF success rate has continued to increase, potentially due to improved embryo selection.⁴

Risk factors⁵

For dizygotic twinning include:

• Previous multiple pregnancy.

• Family history (maternal side).

• Increasing maternal age.

• Geography. The rate of multiple birth is 1.3 per 1000 births in Japan, and up to 50 per 1000 births in Nigeria.

• Different ethnic groups may have different rates of multiple pregnancy; the reasons are complex and may relate to diet, endogamy, and access and attitudes towards fertility treatment.

• Assisted conception.

Multiple pregnancy symptoms (presentation)

• Nearly all multiple pregnancies are now diagnosed in the first trimester by ultrasound. However, some twins die and are absorbed in the first half of pregnancy ('the disappearing twin' syndrome) and early scanning increases awareness of this phenomenon.

• Early symptoms may include hyperemesis and other exaggerated pregnancy-related symptoms. The uterus may be palpated abdominally earlier than 12 weeks of gestation.

• In the second half of pregnancy, may present with large-for-dates uterine size, higher than expected weight gain, more than two fetal poles on palpation and two or more fetal heart rates heard on auscultation.

Antenatal care¹

Multiple pregnancy is associated with higher risk to both mother and babies. Specific risks are discussed further below in the 'Complications' section. Therefore, antenatal care involves more intensive monitoring and protocols are different to those for a singleton pregnancy.

Referral

Twin pregnancies should be referred to obstetricians for shared care, due to the higher risk they present. There should be a special care baby unit (SCBU) available. Clinical care for women with twin and triplet pregnancies should be provided by a team of named specialist obstetricians, specialist midwives and ultrasonographers, all of whom have experience and knowledge of managing twin and triplet pregnancies. Further enhanced care may be needed for some women by specialist physiotherapists, dieticians, mental health professionals and infant feeding specialists. A tertiary-level fetal medicine centre referral is indicated for:

• Monochorionic monoamniotic twin pregnancies.

• Monochorionic monoamniotic triplet pregnancies.

• Monochorionic diamniotic triplet pregnancies.

• Dichorionic diamniotic triplet pregnancies.

Pregnancies complicated by any of the following:

• Asymmetrical fetal growth.

• Fetal anomaly.

• Death of one fetus.

• Twin-twin transfusion syndrome (TTTS).

• Conjoined twins and triplets.

Scanning

Women with multiple pregnancies should be offered a first-trimester ultrasound scan when approximately 11 weeks 0 days to 13 weeks 6 days:

• This is to estimate gestational age, determine chorionicity and screen for Down's syndrome.

• Ideally these should all be performed at the same scan.

• Chorionicity should be determined using the number of placental masses, the lambda or T-sign and membrane thickness. The risks are greater if the fetuses share a placenta (monochorionic), so it is important that this is established early.

Scanning to screen for structural anomalies takes place as per singleton pregnancies (at 18 to 21 weeks), but the procedure takes longer.

Multiple pregnancies should be monitored carefully for intrauterine growth restriction (IUGR) and for feto-fetal transfusion syndrome (FFTS). The latter is a risk in monochorionic (shared placenta) twin pregnancies, where it is termed the twin to twin transfusion syndrome (TTTS) and in monochorionic or dichorionic triplet pregnancies.

• Differences in fetal weight should be monitored using two or more parameters at each ultrasound scan from 20 weeks.

• Women with uncomplicated dichorionic twin pregnancies should be scanned at 20, 24, 28, 32 and 36 weeks.

• Women with uncomplicated monochorionic diamniotic twin pregnancies should be scanned at 16, 18, 20, 22, 24, 28, 32 and 34 weeks.

• Monochorionic twins should be scanned fortnightly to detect TTTS from 16 to 24 weeks of gestation.

• Women with uncomplicated trichorionic triamniotic triplet pregnancies should be scanned at 20, 24, 26, 28, 30, 32 and 34 weeks.

• Women with uncomplicated monochorionic triamniotic and dichorionic triamniotic triplet pregnancies should be scanned at 16, 18, 20, 22, 24, 26, 28, 30, 32 and 34 weeks.

• If there is a 25% or greater difference in size between twins or triplets, this is a clinically important indicator of IUGR. A referral to a tertiary level fetal medicine centre should be offered.

First-line management of TTTS is usually laser surgery of inter-twin vascular placental anastomoses where the syndrome develops before 26 weeks of gestation. Other options include serial amnioreduction, septostomy and selective feticide.^{6 7}

Prenatal diagnosis

National Institute for Health and Care Excellence (NICE) guidelines advise that women should be informed about the greater likelihood of Down's syndrome in twin and triplet pregnancies before screening. They should be made aware of the different options for screening and the higher false-positive rate of screening tests in twin and triplet pregnancies. As a result of this they have a greater likelihood of being offered invasive testing and of complications occurring from this testing. Screening should be performed between approximately 11 weeks 0 days and 13 weeks 6 days:

• The fetal positions should be noted.

• The risk per pregnancy in monochorionic pregnancies and for each baby in dichorionic and trichorionic pregnancies should be calculated.

• Women whose risk of Down's syndrome exceeds 1:150 should be offered a referral to a fetal medicine specialist in a tertiary-level fetal medicine centre.

• Twin pregnancies should use the 'combined test' and consider second-trimester serum screening if the woman books too late for first-trimester screening. Explain the potential problems (particularly the increased likelihood of pregnancy loss associated with double invasive testing because the risk cannot be calculated separately for each baby).

• Triplet pregnancies should use nuchal translucency and maternal age. They should not use second-trimester serum screening.

If one fetus is detected as abnormal, selective termination (if desired) must be accurately targeted. Selective termination in monochorionic pregnancies particularly risks co-twin sequelae.

Maternal health

There is a higher incidence of anaemia in women with twin and triplet pregnancies. FBC should be taken at 20-24 weeks to identify a need for early supplementation with iron or folic acid. This should be repeated at 28 weeks as in routine antenatal care.

Maternal complications (eg, pre-eclampsia) are more common and carers should be vigilant for early signs. Women are advised to take 75 mg of aspirin daily from 12 weeks until the birth of the babies if they have one or more of the following risk factors for hypertension:

• First pregnancy.

• Age 40 years or older.

• Pregnancy interval of more than 10 years.

• BMI of 35 kg/m² or more at first visit.

• Family history of pre-eclampsia.

Timing of delivery¹

• Women with uncomplicated monochorionic twin pregnancies should be offered elective birth from 36 weeks 0 days, after a course of antenatal corticosteroids has been advised.

• Women with dichorionic twin pregnancies should be offered elective birth from 37 weeks 0 days.

• Women with triplet pregnancies should be offered elective birth from 35 weeks 0 days, after a course of antenatal corticosteroids has been advised.

If the woman declines elective birth, weekly appointments should be offered with the specialist obstetrician. An ultrasound scan and biophysical profile assessment should be part of each appointment, with fortnightly fetal growth scans.

Intrapartum management

On admission in labour:

• Obtain intravenous (IV) access.

• Blood should be taken for group and save, as significant blood loss is more likely in multiple pregnancy.

• Monitor fetal heart rates separately and continuously. Fetal scalp electrodes are used where there is concern about the quality of the trace of twin 1.

• Check the position of the lead fetus:
  

  • This is usually confirmed by ultrasound.

  • Both fetuses may present as cephalic.

  • The first twin may be cephalic, with the second breech.

  • The first twin may be breech, with the second cephalic.

  • Both twins may be breech.

  • The second twin changes position during delivery of the first in around 20% of vaginal deliveries, so this must be planned for when choosing a vaginal delivery.⁸

Choice of mode of delivery depends on a number of factors, including amnionicity, experience of the delivery team, wishes of the mother, presentation and other risk factors. There are no clear universal guidelines. Generally a trial of vaginal delivery is usually first choice if the first twin has a cephalic presentation. Caesarean section is usually preferred if there is monoamnionicity, a non-cephalic presentation of the first twin or other risk factors.⁹ Evidence suggests where there is cephalic presentation of the first twin, vaginal delivery and caesarean section have similar outcomes.¹⁰ In the Twin Birth Study of 2013, if vaginal birth was planned this was achieved in 60% of cases.¹¹ 4% of women who delivered twin 1 vaginally required delivery by caesarean section for twin 2. Triplets and higher multiple deliveries are usually managed by caesarean section and in tertiary-level fetal medicine centres.

Vaginal delivery of twins

NICE advises that planned vaginal birth and a planned caesarean section are both safe choices if:¹

• The pregnancy is uncomplicated and has progressed beyond 32 weeks.

• There are no obstetric contraindications to labour.

• The first twin has a cephalic presentation.

• There is no significant size difference between the twins.

Where the first twin presents in a breech or transverse position, caesarean section is preferred.

In most cases, vaginal birth proceeds as normal.

• With rupture of membranes, check for prolapse of umbilical cord.

• Immediately after the first baby is born:
  

  • Determine the position of the second fetus by vaginal examination.

  • If longitudinal, once the presenting part is engaged (usually after a couple of contractions) rupture the second amniotic sac and proceed to delivery.

  • If transverse, external cephalic or internal podalic version may be attempted to bring into longitudinal position.

  • If successful, as confirmed by vaginal examination, then rupture the second amniotic sac when the fetal head is engaged.

  • If unsuccessful, deliver by caesarean section.

• Contractions can reduce after the birth of the first fetus and, if they do not quickly return, set up an IV oxytocin infusion, following which birth of the second fetus should be straightforward. The second twin will usually deliver within 20-45 minutes of the first twin.

• Where there are difficulties with the delivery of the second twin or if a bradycardia develops, a vacuum extraction (in cephalic position) or breech extraction can be used to expedite delivery without necessarily resorting to caesarean section.

• Third stage should be actively managed by intramuscular (IM) injection of Syntometrine® or Syntocinon® as the fetal head is being born, in order to avoid postpartum haemorrhage.

Complications¹

Although a naturally occurring phenomenon, multiple pregnancies are considered high-risk. There are increased risks to both mother and babies.

Maternal risks

There is an increased risk of:

• Miscarriage.

• Anaemia.

• Pre-eclampsia. (Risk for mothers of twins is three times that of singleton pregnancies and nine times greater for mothers pregnant with triplets.)

• Haemorrhage, both antepartum and postpartum.

• Operative delivery.

• Severity of symptoms of pregnancy - nausea, vomiting, heartburn, breathlessness.

• Hyperemesis gravidarum.

• Polyhydramnios.

• Postnatal illness.

• Death. Maternal mortality is 2.5 times higher for twin pregnancy than singleton pregnancy.

Risks to the fetus/baby

• There is an increased risk of stillbirth. For singleton pregnancy, the stillbirth rate is around 5 per 1,000 births, for twins the overall rate is around 12.3 per 1,000 and for triplets 31.1 per 1,000.

• There is an increased risk of preterm birth.

• Due to the increased incidence of preterm birth, there is an increased:

  • Neonatal mortality rate

  • Chance of long-term morbidity (neurodevelopmental delay, chronic lung disease.)

• Feto-fetal transfusion syndrome (FFTS). This occurs most commonly in monochorionic twins, when it is termed the twin-twin transfusion syndrome (TTTS), but also occurs in monochorionic and dichorionic triplets. It accounts for 20% of stillbirths in multiple pregnancy.

• There is an increased risk of umbilical cord entanglement, mainly in monochorionic monoamniotic twin pregnancies (rare).

• There is an increased risk of IUGR.

• There is an increased risk of congenital abnormalities (4.9% more common in multiple pregnancy than singleton pregnancy.) The risk is higher in monozygotic twins; in dizygous twins it is close to the risk in singleton pregnancy. There is a possibility that assisted reproductive techniques (ART) may cause an independent risk of congenital abnormality. Because of increasing maternal age and the use of ART, rates of multiple pregnancy have increased over the past 30 years, which has knock-on implications of more children being born with congenital abnormalities.¹² More recent studies query this and suggest that the fetus-specific risk of Down's syndrome may be lower in multiple pregnancy, although the pregnancy-specific risk is higher.¹³

• Risks are higher in monochorionic pregnancies than dichorionic pregnancies. The Northern Survey of Twin and Multiple Pregnancy in England found the stillbirth rate to be 12.2 per 1,000 births for dichorionic pregnancy compared to 44.4 per 1,000 births for monochorionic pregnancy. Neonatal death rates were 21.4 per 1,000 births for dichorionic pregnancy compared to 32.4 per 1,000 births for monochorionic pregnancy.¹⁴

Complications of multiple pregnancy do not end with birth. Language and speech delay, more general cognitive delay or motor problems, behavioural problems and difficulty in parent-child interactions all appear to be more common in multiple birth children.¹⁵

There are more likely to be feeding issues when trying to breast-feed two babies rather than one. Also, the non-medical financial, social and emotional consequences of caring for twins or higher-order multiples need to be considered.

Prevention

Clearly, the outcomes of multiple pregnancies (particularly higher-order multiples) are poorer than singleton pregnancies. Some authors have challenged this consensus, based on the argument that, if more than once child is desired via fertility treatment, the risk and costs are diminished where analysis is based on born children rather than pregnancies.¹⁶

Primary prevention should be aimed for. Limiting the number of embryos transferred in IVF and close counselling/monitoring of those using ovulation-induction therapies. The HFEA has criteria for single embryo transfer. If the woman does not fulfil them, a maximum of two embryos can be transferred per cycle. ¹⁷

Secondary prevention in the form of multifetal pregnancy reduction (MFPR) appears effective but is not acceptable to all, particularly those with a past history of infertility.¹⁸ Evidence is not gold standard, as RCTs are ethically and practically very difficult in these situations.

MFPR is performed early in pregnancy, usually between 9 and 12 weeks with a transabdominal (TA) or transvaginal (TV) ultrasound-guided injection of potassium chloride into the selected fetus(es). Usual practice is to reduce higher-order pregnancies to a twin pregnancy, although some favour reduction to a singleton pregnancy.

Risks of MFPR may include:

• Miscarriage of remaining fetus(es).

• Emotional consequences to parents.

• Infection.

Repeated Cochrane reviews have found no available data from randomised trials to inform the risks and benefits of pregnancy reduction procedures for women with a multiple pregnancy.¹⁸

Figures from the Northern Survey of Twin and Multiple Pregnancy in England in 2013 showed a rate of twin pr