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)
• embryo splits at 13 days - conjoined or 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.

Normal incidence of twins is 1 in 90 pregnancies (approximately 1/3 are monozygotic) and of triplets 1 in 8100 pregnancies. However, use of in vitro fertilisation (IVF) and ovulation induction techniques has greatly increased the incidence of multiple pregnancies.¹ Figures from the North of England twin register suggest a twinning rate of 13.6-16.6/1000 maternities (or 1 in 60-74 pregnancies).²

Risk factors

For dizygotic twinning include:

• Previous multiple pregnancy
• Family history (maternal side)
• Increasing maternal age
• Racial origin (more common in women of West African ancestry, less common in those of Japanese ancestry)
• Assisted conception

• 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 gestation.
• In the second half of pregnancy, may present with large-for-dates uterine size, higher than expected weight gain, > 2 fetal poles on palpation and two or more fetal heart rates heard on auscultation.

Prenatal diagnosis^3,4

Fetal abnormality is more common in multiple pregnancies - both the maternal age specific chromosomal disorders (as increasing maternal age is a risk factor for multiple birth) and fetal anatomical disorders (monochorionic>dizygotic).

• Nuchal translucency assessment (ultrasound measurement of the translucency of the nuchal fold in the fetal neck between 10 and 14 weeks) identifies individual fetuses at high risk of trisomy.
• Serum screening is unreliable.
• Invasive prenatal diagnosis is challenging as there are at least 2 fetuses to sample correctly and should be undertaken in a tertiary referral centre. The procedure chosen will depend on chorionicity. Both amniocentesis and chorionic villi sampling (CVS) risk contamination - amniocentesis where double sac sampling occurs and CVS where chorions are not separately sampled. Procedure-related miscarriage rates appear to be similar to those for singleton pregnancies.

If one fetus is detected as abnormal, selective termination (if desired) must be accurately targeted. Selective termination in monochorionic pregnancies risks co-twin sequelae.⁵

Antenatal^4,6

• Twin pregnancies should be referred to obstetricians for shared care due to the higher risk they present.
• Women should be booked to deliver in a hospital with a SCBU.
• Early determination of chorionicity (usually based on ultrasound evaluation of presence/absence of separating membranes and thickness of these membranes) should be routine and those twins found to be monochorionic should be scanned frequently to detect twin-twin transfusion or intra-uterine growth retardation at an early stage. If suspected, these pregnancies should be referred to tertiary fetal medicine centres for further management. First line management is usually laser surgery of inter-twin vascular placental anastomoses where the syndrome develops before 26 weeks gestation. Other options include intrauterine blood transfusions, serial amnioreduction or elective delivery.⁷
• All twin pregnancies (regardless of chorionicity) are regularly scanned after about 30 weeks to monitor growth and fetal well-being with early delivery induced in cases of growth cessation and/or poor Doppler blood flow indices.
• Anaemia should be looked for and treated vigorously (may be best to have patient take folic acid and iron daily).
• Because of the extra load on the heart, some may recommend rest in the afternoon to reduce risk of toxaemia and premature labour. However, there is no clear evidence to support this.⁸ Hospital bed rest in uncomplicated cases is not recommended.
• Maternal complications such as pre-eclampsia are also more common in multiple pregnancies⁹ so antenatal carers should be vigilant for early signs.

Intrapartum^4,6

On admission in labour, obtain IV access, monitor fetal heart rates separately and check position of lead fetus:

• In 45% case both fetuses present as cephalic
• In 25% cases 1st twin cephalic, 2nd breech
• In 10% cases breech/breech or 1st twin breech/2nd cephalic

Vaginal delivery of twins

With no complicating factors, the mother can go into spontaneous labour provided the first twin has a cephalic presentation. Where the first twin presents in breech position or transversely, 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, rupture the second amniotic sac (once presenting part is engaged, usually after a couple of contractions) 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 once 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 (within 15 minutes), set up an IV oxytocin infusion following which birth of second fetus should be straightforward. The second twin should deliver within 20-45 minutes of the first twin.
• Where there are difficulties with the delivery of the second twin or if it develops a bradycardia, a vacuum extraction (in cephalic position) or breech extraction can be performed without necessarily resorting to Caesarean delivery.
• Third stage should be actively managed by IM injection of Syntometrine® or Syntocinon® as the fetal head is being born to avoid postpartum haemorrhage.
• Twin deliveries should be attended by 2 paediatricians, 2 obstetricians and an anaesthetist.

Operative delivery of twins

Vaginally delivered second twins have an increased perinatal morbidity and mortality thought due to intrapartum anoxia.¹⁰ The question of whether all women with twin pregnancies should have a Caesarean is contentious. Current NICE guidance recognises this increased risk for the second twin in uncomplicated twin pregnancies at term but felt that evidence as to whether section for the second twin improved outcome was uncertain and therefore should not be routinely offered, except as part of research.¹¹Some studies have concluded that Caesarean delivery is beneficial for the second twin with a NNT to prevent an adverse outcome of 33.¹² Other studies advocate that provided labour is actively managed in experienced centres and that complicated twin pregnancies are excluded, it continues to be a safe option.¹³

Although a naturally occurring phenomena, multiple pregnancies are considered high-risk because:

• Smaller babies - fetuses tend to be individually smaller than those in a singleton pregnancy because of greater demand for nutrients and slower in utero growth i.e. light-for-dates. Monozygotic twins tend to be smaller than dizygotic twins.
• Increased risk of prematurity - the mean gestation for twins is 37 weeks and for triplets 31 weeks.
• Higher risk of congenital abnormality associated with multiple pregnancies (x2-4 rate in singleton pregnancies).
• Higher rates of cerebral palsy found in twins (1-1.5%) and triplets (7-8%).
• Perinatal mortality rate for twins is significantly higher than singletons (x5) and even higher for triplets (x6). Rates are higher for monochorionic twins than dichorionic twins (49 versus 11.5/1000).²
• Higher rate of maternal pregnancy-related complications such as hyperemesis gravidarum, polyhydramnios, pre-eclampsia, anaemia, antepartum haemorrhage.
• Higher rate of complications in labour - malpresentation, vasa praevia, cord prolapse, premature separation of placenta, cord entanglement, postpartum haemorrhage.

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 Also the non-medical financial, social and emotional consequences of caring for twins or higher order multiples need to be kept in mind.

Clearly the outcomes of multiple pregnancies (particularly higher-order multiples) are less good compared to singleton pregnancies. A few 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. Since 2001, the Human Fertilisation and Embryology Authority has determined the maximum number of embryos to be transferred per cycle of IVF as two to limit risk of multiple pregnancies.

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.¹⁴ Evidence is not of the highest order as RCTs are ethically and practically very difficult in these situations.¹⁷
MFPR is performed early in pregnancy, usually between 9 and 12 weeks with a TA or 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 are now arguing in favour of reduction to a singleton pregnancy as the likelihood of taking home a baby is higher than remaining with a twin pregnancy.¹⁸

Risks of a triplet pregnancy compared to a triplet-reduced-to-twin pregnancy¹⁴

Risks of MFPR:

• Miscarriage of remaining fetuses (approximately the same rate as in normal twin pregnancies)
• Emotional consequences to parents
• Infection (rare)