4 Research recommendations

The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of research recommendations is detailed in the full guideline (see section 1).

4.1 Information and emotional support

Does additional information and emotional support improve outcomes in twin and triplet pregnancies?

Why this is important

The guideline review identified insufficient evidence to determine the clinical and cost effectiveness of several specific aspects of information giving and emotional support in twin and triplet pregnancies. The evidence that was identified was generally of low quality. Outstanding research questions include:

  • What is the effectiveness of information and emotional support in improving maternal satisfaction and psychological wellbeing, and in increasing the uptake of breastfeeding?

  • Should different information and support be offered according to the chorionicity of the pregnancy?

Well-designed prospective studies (including randomised controlled trials or observational studies, and qualitative research to elicit views and experiences of women with twin and triplet pregnancies) should be conducted to inform future NICE guidance.

4.2 Specialist care

Does specialist antenatal care for women with twin and triplet pregnancies improve outcomes for women and their babies?

Why this is important

Important issues for women with twin and triplet pregnancies in the antenatal period include access to care (including the implications of having to travel to a particular location to receive care) and the possibility of transfer to hospital during pregnancy or labour. Current evidence is limited, of low quality, and originates from a healthcare system that is different from the NHS (in particular, from a system where midwives are not involved in providing care). None of the studies identified in the guideline review made a direct comparison between specialist twin or triplet antenatal care and routine antenatal care (that is, care offered to women with singleton pregnancies).

Although health economic analysis conducted for the guideline demonstrated cost effectiveness of a range of models of specialist antenatal care, the recommendations reflect the clinical experience of the Guideline Development Group rather than strong evidence to support a particular model of care. Further research is, therefore, needed to evaluate the clinical and cost effectiveness of different models of specialist antenatal care for women with twin and triplet pregnancies. This includes evaluating the best mix of resources and skills in multidisciplinary antenatal care services, and identifying the most effective components of care.

Research should cover the roles of different healthcare professionals (including midwives, since their role is not addressed in any existing studies). It should also investigate maternal, perinatal and neonatal morbidity and mortality associated with different models of specialist care, and also long-term outcomes. Maternal outcomes to be considered include satisfaction with care and psychological wellbeing because the increased risks associated with twin and triplet pregnancies may lead to maternal anxiety or even depression. The chorionicity of the pregnancy should also be considered as a factor influencing components of specialist care. The outcomes of such research could identify particular models of care to be implemented in the NHS, which would affect service delivery and organisation (for example, by specifying a need for additional staff or further training for existing staff, both of which have cost implications).

In making this research recommendation the Guideline Development Group recognises that future research needs to provide data relevant to the current clinical context in England and Wales. The research should use cluster randomised trials or observational studies.

4.3 Monitoring for intrauterine growth restriction

What is the pattern of fetal growth in healthy twin and triplet pregnancies, and how should intrauterine growth restriction be defined in twin and triplet pregnancies?

Why this is important

Although the guideline review found some studies relating to the identification of intrauterine growth restriction in twin and triplet pregnancies, the larger existing studies are retrospective in design and, therefore, of low quality. No evidence-based growth charts specific to twin and triplet pregnancies are available for use in the diagnosis of intrauterine growth restriction. The evidence for the effectiveness of tests for diagnosis of intrauterine growth restriction according to chorionicity of the pregnancy is limited.

There is, therefore, a need for large, prospective cohort studies to develop fetal growth charts specific to twin and triplet pregnancies. This would allow definition and diagnosis of clinically significant intrauterine growth restriction using true growth velocity and trajectories, rather than estimated fetal weight and discrepancy. The charts should distinguish between growth patterns in monochorionic, dichorionic and trichorionic pregnancies, and the research should evaluate clinical outcomes associated with particular growth patterns.

4.4 Preventing preterm birth

What interventions are effective in preventing spontaneous preterm birth in women with twin and triplet pregnancies, especially in those at high risk of preterm birth?

Why this is important

The guideline review considered several interventions aimed at preventing spontaneous preterm birth in women with twin and triplet pregnancies, including cervical cerclage, tocolytic drugs and sexual abstinence. The existing evidence for the effectiveness of cervical cerclage is of low quality (mostly originating from observational studies). The existing evidence in relation to tocolytics is also limited: there is evidence for the effectiveness of betamimetics, but no randomised controlled trials were identified for the effectiveness of ritodrine, magnesium sulphate or nifedipine. No evidence was identified for the effectiveness of sexual abstinence alone in preventing preterm birth.

Further research in the form of randomised controlled trials is, therefore, needed to evaluate the effectiveness of cervical cerclage, tocolytics other than betamimetics, and sexual abstinence. Future research should place particular emphasis on women at high risk of preterm birth in twin and triplet pregnancies. Some evidence suggested that a cervical length of less than 25 mm at 18–24 weeks of gestation in twin pregnancies or 14–20 weeks of gestation in triplet pregnancies, or a history of preterm labour in singleton pregnancies, increases the risk of spontaneous preterm birth in twin and triplet pregnancies. The evidence was limited in quality and additional research into the predictive accuracy of these factors would inform future NICE guidance. All research into the prevention of preterm birth should report spontaneous preterm birth separately from other preterm births. Data should also be reported separately for twin and triplet pregnancies, for different chorionicities, and for different gestational ages at birth (that is, less than 28 weeks, between 28 and less than 32 weeks, and 32–37 weeks).

4.5 Indications for referral to a tertiary level fetal medicine centre

What is the incidence of monochorionic monoamniotic twin and triplet pregnancies, and what clinical management strategies are most effective in such pregnancies?

Why this is important

Monochorionic monoamniotic twin pregnancies occur rarely, as do all triplet pregnancies (fewer than 200 women give birth to triplets each year in England and Wales). Across the guideline, the evidence relating to such pregnancies was very limited in quantity and quality, with monochorionic monoamniotic pregnancy often listed as an exclusion criterion in studies reviewed for the guideline. Monochorionic monoamniotic pregnancies and triplet pregnancies are associated with greater complexity and risks to the woman and babies than other pregnancies considered in the guideline. The lack of evidence for effective clinical management of these pregnancies influenced the Guideline Development Group to recommend referral to a tertiary level fetal medicine centre for monochorionic monoamniotic twin pregnancies and complicated triplet pregnancies (including monochorionic and dichorionic triplet pregnancies).

Further research to determine the incidence of monochorionic monoamniotic pregnancies and triplet pregnancies of different chorionicities would inform future provision of NHS services, as would research into the most effective models for clinical management of such pregnancies. Studies could include national audits of clinical care and outcomes in such pregnancies before and after publication of the guideline. They should also include consideration of the impact of referral (or non-referral) to a tertiary level fetal medicine centre on perinatal psychological and emotional wellbeing of women and their partners.

4.6 Timing of birth

What is the incidence of perinatal and neonatal morbidity and mortality in babies born by elective birth in twin and triplet pregnancies?

Why this is important

The existing evidence in relation to perinatal and neonatal outcomes associated with elective birth in twin and triplet pregnancies is limited in quantity and quality. Evidence suggests a consistently higher fetal death rate (at all gestational ages) in monochorionic twin pregnancies than in dichorionic twin pregnancies. It is uncertain whether elective birth in monochorionic twin pregnancies at 1 week earlier than recommended in the guideline (that is, from 35 weeks 0 days) would reduce fetal death rates significantly without increasing adverse neonatal outcomes significantly (for example, immaturity of the babies' respiratory systems). The research could be conducted through national audits of perinatal and neonatal morbidities in babies born by elective birth in twin and triplet pregnancies, taking account of the chorionicity of the pregnancy and gestational age at birth. If data from more than one study were available, then the technique of meta-regression might be useful for determining the optimal timing of birth precisely (according to gestational age).

  • National Institute for Health and Care Excellence (NICE)