Frenotomy with breastfeeding support versus breastfeeding support alone for infants with tongue-tie and breastfeeding difficulties: the FROSTTIE RCT

Article history

The research reported in this issue of the journal was funded by the HTA programme as project number 16/143/01. The contractual start date was in April 2018. The draft report began editorial review in April 2022 and was accepted for publication in September 2022. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Copyright statement

Copyright © 2023 Knight et al. This work was produced by Knight et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaption in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – NIHR Journals Library, and the DOI of the publication must be cited.

2023 Knight et al.

Objective

The objective of this research was to investigate whether frenotomy is clinically and cost-effective to promote continuation of breastfeeding at 3 months in infants with breastfeeding difficulties diagnosed with tongue-tie.

Design

The FROSTTIE trial was a multicentre, randomised, controlled parallel group trial conducted in England.

The trial was registered with the International Standard Randomised Controlled Trial Register (ISRCTN 10268851).

Patient and public involvement

The research question was initially prioritised by the NIHR Health Technology Assessment programme, including patient and public involvement (PPI). In order to obtain the perspective of a wide group of women with recent breastfeeding experience and/or experience of tongue-tie, we included a PPI co-applicant from the Breastfeeding Network, who consulted with other Network members, and also established a Public Advisory Group. These two groups helped design the study processes and materials, and advised throughout the trial.

Participants

Setting

The trial was conducted in 12 infant feeding services in England (see Appendix 1).

Informed consent and recruitment

Information about the trial was made widely available throughout the infant feeding units in the form of posters and leaflets (with QR codes to the trial website). Written information about the trial was available to all women at participating centres when they attended for breastfeeding support. In some sites, materials were also available on the postnatal ward.

Potential participants were identified by the infant feeding service staff from the population of infants with breastfeeding difficulties referred to NHS infant feeding services through volunteer breastfeeding supporters, other breastfeeding counsellors, midwives or through self-referral by parents.

As standard, following referral to the infant feeding service, infant feeding was observed (either in person or via video conferencing) and tongue assessment conducted, and mothers received advice on positioning and attachment. Initial discussions may have taken place in person or virtually via telephone or video conferencing if this was what was being offered as part of routine care. The tongue-tie diagnosis was made according to usual hospital practice, which may have included using any suitable tool. However, all babies whose parents consented for their participation in the trial had an assessment of their tongue-tie made using the Bristol Tongue Assessment Tool (BTAT). 14

Following diagnosis of a tongue-tie associated with breastfeeding difficulties, a verbal explanation and written information (the Parent Information Leaflet) was provided to the parent(s) either as a hardcopy in person or via post, electronically via email or by being directed to the study website. The parent(s) were allowed as much time as they needed to consider the information, and the opportunity to question staff before deciding whether they consented for their baby to participate in the study. Written or remote verbal informed consent was obtained.

Written or verbal informed consent also included optional consent for linkage of their baby’s data to routine data sources to allow the potential for further follow-up beyond the funded trial.

Intervention

Infants were randomised via a web randomisation portal to either:

1. frenotomy with standard breastfeeding support (intervention arm), or

2. no frenotomy with standard breastfeeding support (comparator arm).

Breastfeeding support included as a minimum: an initial assessment of breastfeeding, for example using the LATCH (Latch, Audible swallowing, Type of nipple, Comfort, Hold) tool15 or Baby Friendly Initiative assessment tool, and advice on positioning and attachment and at least one follow-up visit, together with drop-in clinic advice as required, but available on more than 1 day a week. Assessments and breastfeeding support were provided face-to-face in person or virtually using video conferencing or telephone dependent on what was being offered as part of routine care.

Intervention arm: infants who were randomised to frenotomy with breastfeeding support underwent frenotomy according to usual hospital practice. Frenotomy was carried out by the usual trained practitioner for participating hospitals using their normal technique. The babies had an immediate postfrenotomy observed feed. Parents received further advice on positioning and attachment together with standard postfrenotomy advice concerning bleeding and other postfrenotomy adverse events. Parents were provided with details about how to access rapid breastfeeding support in the event of ongoing feeding difficulties and an appointment for at least one follow-up visit.

Comparator arm: infants randomised to breastfeeding support only did not undergo frenotomy, but received further advice on positioning and attachment. Parents were provided with details about how to access rapid breastfeeding support in the event of ongoing feeding difficulties and an appointment for at least one follow-up visit.

Randomisation and blinding

The infants entered into the trial were randomised 1 : 1 to either intervention or comparator arm. Multiples (twins or higher-order multiples) were randomised to the same arm. Stratified block randomisation (using variable block sizes) was performed via a secure 24-hour web-based randomisation system [hosted by the National Perinatal Epidemiology Unit (NPEU) Clinical Trials Unit (CTU), University of Oxford] stratified by infant’s age (<2 and ≥2 weeks) at randomisation and mother’s parity (primiparous or multiparous) within the centre. A telephone back-up system was available 24 hours a day (365 days per year).

A statistician independent of the trial generated the stratified block randomisation (using variable block sizes) schedule and the Senior Trials Programmer wrote the web-based randomisation program; both were independently validated. The implementation of the randomisation procedure was monitored by the Senior Trials Programmer and independent statistician throughout the trial and reports provided to the Data Monitoring Committee (DMC).

Parents were blinded to the allocation for the first 20 participants, following which the trial was conducted unblinded. Blinding consisted of parents being asked not to directly observe the procedure (tongue-tie examination with or without frenotomy) immediately before a postprocedure breastfeed. The request for a change to an unblinded design was made by the funder as it was felt to be a barrier to recruitment.

Internal pilot

We conducted an internal pilot during the first 6 months of the trial, when 266 recruits were predicted, to test recruitment and retention assumptions. The pre-defined stop–go criteria were as follows:

1. recruitment 75% or more (N ≥ 199) – continue directly with the main trial

2. recruitment 50–75% (133 ≤ N < 199) – recruit more centres and review in 6 months

3. recruitment < 50% (N < 133) – undertake an urgent detailed review of options with Trial Steering Committee (TSC) to subsequently recommend to the funder.

The pilot was restarted in September 2019, following removal of blinding, but was never completed due to a pause in recruitment between March and May 2020 because of the COVID-19 pandemic, and subsequent closure of the trial by the funder.

Outcomes

Sample size

It was assumed that a 10% absolute increase in the rate of breastfeeding represented the minimal clinically important difference that should be detectable by the trial; and breastfeeding rates will remain high in this motivated population. Thus, assuming a breastfeeding rate of 70% in the control group and 80% in the intervention group, at 90% power with a 5% level of significance, and allowing for 5% loss to follow-up, with a further 5% increase to account for between-group contamination required a sample size of 870. Given the final sample size achieved with complete primary outcome data (n = 163), the study had 31% power to detect this difference, assuming the same control group rate.

Statistical analyses

Statistical analyses were carried out according to a pre-specified Statistical Analysis Plan finalised prior to unblinding. For the primary analysis for all primary and secondary outcomes infants, we compared the outcomes of all infants allocated to frenotomy with breastfeeding support with all those allocated to breastfeeding support, regardless of deviation from the protocol or treatment received (referred to as the ITT population). Demographic and clinical data were summarised with counts and percentages for categorical variables, means [standard deviations (SDs)] and medians [with interquartile range (IQR) or simple range] for continuous variables. For binary outcomes, risk ratios (RRs) and confidence intervals (CIs) were calculated using log binomial regression or Poisson regression with a robust variance estimator. Continuous outcomes were analysed using linear or median (quantile) regression for normally distributed and skewed variables, respectively. Analyses were adjusted for stratification factors at randomisation where possible (centre, infant’s age at randomisation and mother’s parity). 18 Both unadjusted and adjusted risk ratios (aRRs) are presented, with the primary inference based on the adjusted estimates. Two-sided statistical testing was performed throughout. A 5% level of statistical significance was used, and 95% CIs are presented.

Data collection

Baseline information was collected on sociodemographic and other characteristics at trial entry, including the following:

1. infant birthweight

2. infant current weight

3. estimated date of delivery

4. current feeding practices (e.g. expressed breastfeeding, use of infant formula)

5. assessment of the degree of tongue-tie using the BTAT

6. mother’s prior beliefs about frenotomy: using a 3-point Likert scale, the opinions of mothers of infants recruited to the trial were measured at the time of recruitment on their prior belief of the potential benefit of frenotomy

7. EQ-5D-5L

8. mother’s pain while feeding during the previous 24 hours: measured using visual analogue scale of the SF-MPQ, modified into a Likert-type scale (scores ranging from 0 to 10)16

9. exclusive breastmilk feeding: exclusive breastmilk feeding in the previous 24 hours

10. exclusive direct breastfeeding: exclusive breastfeeding directly from the breast with no bottle feeds of expressed milk in the previous 24 hours

11. pre-trial entry breastfeeding support received.

The following data were collected from the clinician performing the frenotomy on the day of the procedure:

1. in-person BTAT assessment if the baseline assessment was done virtually that is not face-to-face

2. intervention undertaken according to randomisation schedule and technique used

3. bleeding following frenotomy or frenulum tear

4. postprocedure adverse events (tongue cut, salivary duct damage).

The following data were collected from the mother at the routine follow-up visit (approximately 1 to 2 weeks posttrial entry):

1. mother’s pain while feeding during the previous 24 hours: measured using visual analogue scale of the SF-MPQ, modified into a Likert-type scale (scores ranging from 0 to 10)16

2. exclusive breastmilk feeding in the previous 24 hours

3. exclusive breastfeeding directly from the breast with no bottle feeds of expressed milk in the previous 24 hours

4. type of breastfeeding support received (in person or virtual)

5. frenotomy/repeat frenotomy (defined as any further procedure on tongue-tie)

6. bleeding following frenotomy or frenulum tear

7. postprocedure adverse events (tongue cut, salivary duct damage): measured by specific questions

8. maternal anxiety or depression as indicated by the anxiety and depression dimension of EQ-5D-5L

9. maternal health-related quality of life (HRQoL): as elicited by the EQ-5D-5L.

Data on the primary outcome (any breastmilk feeding in the previous 24 hours at age 3 months) were collected from mothers by automated text message. The following data were collected using maternal self-report via a follow-up link (by smart phone, tablet, computer, postal questionnaire or telephone) when the infant was 3 months of age:

1. mother’s breastfeeding self-efficacy: measured using the Breastfeeding Self-Efficacy Scale – Short Form19

2. mother’s pain while feeding during the previous 24 hours: measured using visual analogue scale of the SF-MPQ, modified into a Likert-type scale (scores ranging from 0 to 10)16

3. total number of contacts with any breastfeeding supporter since first referral and specific means of support used (in person or virtual)

4. infant weight

5. exclusive breastmilk feeding in the previous 24 hours

6. exclusive breastfeeding directly from the breast with no bottle feeds of expressed milk in the previous 24 hours

7. age when child last received breastmilk, to determine when and whether switch to exclusive formula feeding had occurred20

8. time spent breastfeeding in previous 24 hours: time in minutes/hours

9. frenotomy/repeat frenotomy

10. bleeding following frenotomy or frenulum tear

11. postprocedure adverse events (tongue cut, salivary duct damage): measured by specific questions

12. mother or infant previously diagnosed with COVID-19

13. maternal anxiety or depression as indicated by the anxiety and depression dimension of EQ-5D-5L

14. maternal HRQoL: as elicited by the EQ-5D-5L

15. maternal and infant NHS health-care resource use: collected on general practice visits and hospital admissions.

Data on any breastmilk feeding at 6 months were collected from mothers by automated text message.

Adverse event reporting

Non-serious adverse events were not routinely recorded as the procedure is part of standard clinical practice. However adverse events that were part of the study outcomes [bleeding following frenotomy (unless excessive) or frenulum tear and postprocedure adverse events (tongue cut, salivary duct damage)] were collected as part of standard follow-up.

All serious adverse events (SAEs) were reported immediately, at least within 24 hours; except the following SAEs, which were foreseeable SAEs and were subject to SAE reporting procedures:

1. admission or extension of hospital stay due to the following:

   1. breastfeeding difficulties

   2. poor milk supply in the mother

   3. weight loss or poor weight gain in the baby

   4. jaundice.

Economic evaluation

A within-trial cost-consequences analysis (CCA) with a time horizon of a 3-month follow-up was conducted from a NHS perspective as the primary analysis for the economic evaluation. In this case, results were presented as benefits and health-care costs in disaggregated format for both mothers and their infants in each treatment arm. 21 Costs included frenotomy and breastfeeding support-related costs, primary care, community care, secondary care and non-NHS related costs. The benefits considered in the CCA were the primary outcome of any breastmilk feeding at 3 months according to maternal self-report, maternal anxiety and depression measured using the relevant EQ-5D-5L domain22 and HRQoL measured using the EQ-5D-5L at different time points.

In a secondary analysis, a within-trial cost-utility analysis (CUA) from the mother’s perspective with a time horizon up to 3 months was also conducted. Quality-adjusted life-years (QALYs), were used to measure benefits in the CUA with mean difference in costs and QALYs were synthesised using the incremental cost-effectiveness ratio (ICER) expressed as incremental costs per QALYs gained over the trial period. 23 The ICER was compared to the standard cost-effectiveness threshold as recommended by NICE to determine value for money. 24

Governance and monitoring

A monitoring plan for the trial, including responsibilities, was developed prior to the start of recruitment. In person monitoring of all sites was carried out to identify barriers and facilitators to recruitment and the findings of the visits summarised to guide ongoing actions to enhance recruitment.

The trial was supervised on a day to day basis by a Project Management Group. A TSC was convened including an independent chair, four other independent members, a PPI representative(s), the NPEU CTU Director and the Chief Investigator. A DMC independent of the applicants and of the TSC reviewed the progress of the trial annually and provided advice on the conduct of the trial to the TSC.

Summary of changes to the study protocol

Masking of parents was removed from the trial at the funder request after a short pilot period as it was felt to be a barrier to recruitment. Following the restart after the first wave of the COVID-19 pandemic, changes were made to allow virtual assessments and breastfeeding support, and virtual BTAT assessment. Verbal consent was permitted if written consent was not possible. The COVID-19 status of mother and baby was added to the data collection.

A summary of the other changes made to the original protocol is presented in Appendix 3.

Recruitment and retention

Between March 2019 and November 2020, 169 infants were randomised; 80 to the frenotomy with breastfeeding support arm and 89 to the breastfeeding support arm. There were no substantial differences in the response rates between the intervention arms during the follow-up period (see Figure 1). The trial was stopped in November 2020 in the context of the COVID-19 pandemic due to withdrawal of breastfeeding support services, slow recruitment and crossover between arms. In the frenotomy with breastfeeding support arm 74/80 infants (93%) received their allocated intervention, compared to 23/89 (26%) in the breastfeeding support arm.

FIGURE 1.

Flow of participants.

The number of participants recruited at each site varied from 1 to 85 (see Table 1).

Characteristics of participants

Characteristics of participants were similar between the two trial arms. Infants had a mean age of 3 weeks, a mean birthweight of 3439 g and 87% were born at ≥38 weeks’ gestation. Overall 33% of infants had a BTAT score of 4 or less, 66% had exclusive breastmilk feeding in the previous 24 hours, and 40% had exclusive direct breastmilk feeding. Thirty-four per cent of infants had also received formula milk in the previous 24 hours (see Table 1). Mothers were a mean of 32 years old, 94% were of white ethnicity and 48% had a previous live birth. Only 8% were resident in the most deprived quintile of areas. Mothers reported a mean pain score of 4 out of 10 while feeding during the previous 24 hours and 42% had some anxiety or depression. More than half of women recruited to the trial believed a frenotomy would help their baby (see Table 2). Only one infant, in the breastfeeding support group, was reported to have had COVID-19.

Outcomes

Exploratory analyses

There was no significant difference (aRR 1.27, 95% CI 0.99 to 1.64) in the rate of breastmilk feeding at 3 months between the arms per protocol analysis where the 70 infants who did not receive their allocated intervention were excluded (infants in the frenotomy with breastfeeding support who had no frenotomy performed and infants in the breastfeeding only group who had a frenotomy performed) (see Table 8).

There was a significant difference in the rate of breastmilk feeding at 3 months in the as-treated analysis where infants were analysed according to the intervention received (RR 1.35, 95% CI 1.05 to 1.74), noting that for this analysis, the groups compared were not the groups originally randomised and hence this difference may be due to confounders not accounted for in the analysis (see Table 9).

Pre-specified subgroup analyses

There were no notable differences between both the arms for any of the selected subgroups except that the rate of breastmilk feeding at 3 months appeared higher in the frenotomy with breastfeeding support arm compared to the breastfeeding support arm (92% vs. 83%) before the trial paused due to the coronavirus pandemic (see Table 10). After the trial restarted, the rate was higher in the breastfeeding support arm compared to the frenotomy with breastfeeding support arm (91% vs. 81%).

Secondary analyses

There were minimal differences between infants of mothers who complied with the intervention compared to non-compliers in the breastfeeding support arm for most baseline characteristics (see Table 11). However, a higher proportion of mothers who did not comply believed that frenotomy was helpful for their baby compared to mothers who complied (39/65, 61% vs. 6/24, 25%). A higher proportion of infants in the complier group had a BTAT score >4 compared to non-compliers (21/24, 88% vs. 41/64, 64%). The rate of breastmilk feeding at 3 months was higher among non-compliers compared to compliers (59/65, 91% vs. 16/24, 73%) (see Table 12), but the results from the CACE analysis showed no evidence for a difference in rates of breastmilk feeding at 3 months between the arms (RR 1.09, 95% CI 0.53 to 1.64) (see Table 13).

Economic evaluation

Maternal HRQoL using EQ-5D-5L instrument

The distribution of response across all EQ-5D-5L dimensions at different follow-ups are presented in Table 28. A significant difference in the distribution of responses between groups was observed at the routine follow-up visit for the mobility dimension (χ² = 10.429 with p-value of 0.005). No other significant difference was observed in any of the other dimensions. Table 19 presents the results of the HRQoL analysis between trial arms at different follow-up points. The mean (SD) HRQoL at baseline was 0.773 (0.179) and 0.766 (0.162), at routine follow-up was 0.851 (0.141) and 0.824 (0.157) and at 3 months after birth was 0.850 (0.183) and 0.868 (0.117) in the frenotomy and no frenotomy groups, respectively. No statistically significant mean differences were detected in overall HRQoL at baseline, routine follow-up and 3 months after birth.

Cost-utility analysis

A summary of cost-effectiveness results comparing frenotomy with breastfeeding support with breastfeeding support only is presented in Table 21. This analysis was undertaken using a complete-case analysis with pairs of total costs and QALYs available for each trial participant. The ICER was estimated to be £6113 per QALY gained indicating that such point estimate is below current thresholds of willingness to pay for QALY gained of £20,000. However, Figure 2 displays the uncertainty around the ICER on the CEP with the joint distribution of mean differences in costs and QALYs. The chart clearly shows bootstrap replicates expanding the four quadrants of the plane indicating that CIs for the ICER in this case would be misleading and difficult to interpret. More informative is Figure 3 that suggests that at a threshold of £20,000 per QALY gained, frenotomy only reaches 50% probability of being cost-effective. Increasing this willingness to pay above that value tends asymptotically towards 60% of being cost-effective.

TABLE 21 - Summary of CUA result using complete-case analysis

Trial arm	Total number of complete cases	Total costs (2019/2020 UK £), mean (SE)	Incremental costs, mean (SE)	QALYs, mean (SE)	Incremental QALYs, mean (SE)
Breastfeeding support only	66	488 (63)	---	0.2082 (0.0036)	---
Frenotomy with breastfeeding support	71	502 (106)	14 (123)	0.2105 (0.0043)	0.0023 (0.0056)

FIGURE 2.

Bootstrap replications of mean difference in costs and effects plotted on the CEP.

FIGURE 3.

Cost-effectiveness acceptability curves indicating the probability that frenotomy is cost-effective compared to breastfeeding support only.

Site monitoring: barriers and facilitators to recruitment

Summary of main findings

The trial did not reach its pre-specified sample size and there was no evidence of differences between trial arms in any outcomes. Rates of continued breastmilk feeding were high at 3 months in both the frenotomy with breastfeeding support and breastfeeding support groups. Compared to first follow-up, pain during breastfeeding was lower at 3 months in both groups. Complications of the procedure were not uncommon, occurring in around 1 in 50 infants. There was a high rate of crossover between arms with 73% of babies in the breastfeeding support arm undergoing frenotomy. Almost two-thirds of women in the breastfeeding support without frenotomy arm whose babies went on to have a frenotomy believed at recruitment that a frenotomy would benefit their child, indicating clear evidence of lack of equipoise. A higher proportion of infants in the non-complier group had a BTAT score of 4 or below, indicating a more restricted tongue compared to compliers. Substantial uncertainty still remains about whether frenotomy with breastfeeding support is a cost-effective use of NHS resources compared with breastfeeding support only.

Limitations

The statistical power of the analysis was extremely limited due to not achieving the target sample size because of the early cessation of the trial and the high proportion of infants in the breastfeeding support arm who underwent frenotomy. Mothers recruited to the trial were more likely to be older, less likely to be of minority ethnicity and more likely to live in more affluent areas than the general population of women giving birth in the UK,6 which may further limit generalisability of the findings.

Comparison with the existing literature

Most infants in the control groups of the five previous trials identified in the Cochrane review12 also underwent frenotomy. Two studies offered frenotomy to all participants, and the other three trials, most of which compared frenotomy to standard care, reported frenotomy rates between 77% and 97%. On this basis all five trials were considered of low quality and at high risk of bias. The 73% frenotomy rate in the breastfeeding support arm that we observed in FROSTTIE is therefore very comparable, but on this basis it must also be regarded as at high risk of bias. The Cochrane review authors concluded that, in the settings where these trials were carried out, equipoise concerning frenotomy was lacking, and FROSTTIE echoes this. Equipoise was a barrier to recruitment due to both staff attitudes and parents’ expectations. Staff broadly fell into two groups. The first group felt strongly that frenotomy was an important intervention, which might aid breastfeeding, and as it had minimal risk of harm should not be denied to women whose babies were diagnosed with tongue-tie and who had breastfeeding difficulties. These staff were reluctant to randomise infants unless the infants were very young, that is before breastfeeding had really been established. It is important to note that although the Cochrane review did not identify any complications of the procedure among the 302 included infants,12 three infants in the FROSTTIE trial had significant complications (bleeding or salivary duct damage), around 1 in every 50 infants. Others have noted concerns over the potential harms of the procedure when its benefits have not been established in high-quality trials. 34

The second group of staff were very clear that expert breastfeeding support was the most important part of the intervention to assist with breastfeeding difficulties and recognised that frenotomy was not without potential harm. These staff were not willing to randomise infants to possible frenotomy until they had a substantial period of breastfeeding support, at which point women themselves were less willing to be randomised as they were desperate for any intervention which might help. Almost all staff fell into one of these two groups with few staff opinions in between.

As evidenced from Tables 2 and 11, which show that more than half of women recruited to the trial believed that frenotomy would help their baby and that fewer than half were truly in equipoise, one of the commonest reported challenges by sites was low numbers of women willing to be randomised. One site reported that around 10 women had to be approached for everyone who expressed willingness to participate. While most women approached who did not wish to be randomised felt that frenotomy would benefit their baby and therefore were not willing to be randomised to a breastfeeding support only arm, there were a few women who strongly felt the opposite, that frenotomy was an unnecessary intervention and did not want their babies to have it. Other studies have reported that many parents feel that frenotomy is a beneficial intervention for breastfeeding difficulties and will go to considerable lengths to access the procedure;35 however, analyses of online forum posts showed more variable experiences of its outcome. 36

In many areas, capacity within infant feeding clinics and/or care pathways meant that women attended their first appointment only after they had been having difficulties with breastfeeding for some time. Only a third of babies recruited were <2 weeks old at trial entry (see Table 1). Many women felt that they had therefore already tried breastfeeding support without success, and therefore either were not willing to be randomised, or, if they were randomised to the breastfeeding support arm, they were willing only to try breastfeeding support alone for a few days before requesting frenotomy. Some sites gave women in the breastfeeding support arm ‘just in case’ appointments for frenotomy to address this concern, which had the effect of encouraging crossovers.

In the context of the COVID-19 pandemic, this was exacerbated, since parents were less willing to risk having to return for another clinic appointment and/or frenotomy when services were reduced, waiting times were longer and there were concerns over potential COVID-19 exposure by additional visits. Breastfeeding support services were known to be highly variable prior to the pandemic,11 and this was exacerbated during the pandemic, with many services ceasing completely, or moving entirely online. Almost half of women completing the 2020 national maternity survey reported that they would have liked more support with breastfeeding compared to around 30% in the 2014 and 2018 surveys. 6

Several sites had clinics that were named ‘the frenotomy clinic’ as opposed to the ‘infant feeding clinic’ or ‘breastfeeding support service’. This naming meant that parents anticipated prior to arrival that their child would undergo frenotomy at the clinic, or shortly afterwards, which again contributed to a lack of equipoise. Some sites renamed their clinics to mitigate this barrier, which was felt to be making a difference to recruitment immediately prior to trial closure.

In some sites, assessment of tongue-tie and breastfeeding support advice was undertaken very early, on the postnatal ward prior to discharge. These sites felt that women were more in equipoise concerning whether or not frenotomy might be beneficial at this time, before they had been struggling with breastfeeding for days or weeks, and therefore that recruitment in the postnatal ward setting might be more effective.

Women in both arms had high rates of breastfeeding continuation, reflecting that they were a highly motivated population. Women recruited were more likely to live in more affluent areas and were older than the general population of women giving birth,6 and almost all of those who had older children had breastfed before. All these factors are known to be associated with higher rates of breastfeeding3 and may account for the high breastfeeding rates seen rather than any impact of the intervention.

It is of concern that women reported high levels of anxiety and depression both at recruitment, and, to a lesser extent, at 3 months, indicating an important need for mental health support.

Equality diversity and inclusion

The majority of women recruited to the trial were from White ethnic groups, despite the trial being conducted at sites with substantial ethnic minority populations. Six per cent of women recruited were from Asian or mixed ethnic backgrounds, and no participants recruited were from Black ethnic minority groups. It is unclear whether this reflects better community support for breastfeeding for women from Black and other ethnic minority groups, a lack of access to hospital breastfeeding support services or differential equipoise concerning frenotomy. Mothers from Black, mixed or other ethnic minority groups are more likely to breastfeed at 6 weeks. 5 Cultural traditions have been shown to be important in women’s decisions about continuing breastfeeding37 and there is a need for tailored support,38 both of which may have influenced decisions to seek support from hospital infant feeding clinics and around the use of frenotomy.

Public and patient involvement

We included a PPI co-applicant from the Breastfeeding Network, who consulted with other Network members, and also established a Public Advisory Group. These two groups helped design the study processes and materials, and advised throughout the trial. We were also guided by a PPI member on the TSC. Patient and public involvement was challenged by the COVID-19 pandemic, and would have benefitted from greater diversity. At the time of trial closure we were planning further PPI work to determine whether there were areas of redesign that might help to address equipoise issues, but this was not carried out.

Implications for practice

The results of this trial provide no evidence of benefit of frenotomy with breastfeeding support over breastfeeding support given the small sample size. The high crossover rate indicates that the trial is at high risk of bias and cannot be used to guide practice. There is nevertheless some useful information to guide counselling of women with babies with tongue-tie. Babies in the breastfeeding support group with more restricted tongue movement, as measured using the BTAT, and whose mothers were in more pain, were more likely to undergo frenotomy. Mothers in both groups had high rates of breastfeeding continuation and reported less pain when feeding at 3 months, emphasising the importance of breastfeeding support to provide advice on latch and correct positioning. Complications of frenotomy were observed in about 1 in 50 babies.

Implications for research

The FROSTTIE trial has indicated that sufficient equipoise does not exist to conduct a randomised trial of frenotomy in NHS hospital infant feeding clinic settings. Such a trial may be possible if infants are recruited early, when initially consulting for breastfeeding support, ideally within community settings. However, it is likely that other study designs will need to be considered in the UK setting, for example observational studies alongside trials of other breastfeeding interventions such as the ABA-Feed study. 39

Conclusions

This trial does not provide sufficient information to assess whether frenotomy in addition to breastfeeding support improves breastfeeding rates in infants diagnosed with tongue-tie. However, there were high breastfeeding rates in both arms. Complications of frenotomy were observed in about 1 in 50 infants. There is a clear lack of equipoise in the UK concerning the use of frenotomy, however, the effectiveness and cost-effectiveness of the procedure still need to be established. Other study designs will need to be considered to address this objective.

Funding and sponsorship

FROSTTIE was funded by the National Institute for Health and Care Research HTA Programme (project number 16/143/01) and sponsored by the University of Oxford. The funder had no role in study design or data collection, analysis and interpretation. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Independent TSC

The trial was overseen by the Trial Steering Committee (TSC) who had ultimate responsibility for considering and, as appropriate, acting on the recommendations of the DMC. The TSC included an independent chair, four independent members, a PPI representative, a co-applicant and the Chief Investigator. Membership consisted of:

Professor Pat Hoddinott, Chair, Chair in Primary Care, NMAHP Research Unit, University of Stirling

Mr Mike Bradburn, Independent member, Senior Medical Statistician, University of Sheffield

Professor Debra Bick, Independent member, Professor of Clinical Trials in Maternal Health, Warwick Clinical Trials Unit, University of Warwick

Dr Mark Johnson, Independent member, Consultant Neonatologist, Department of Neonatal Medicine, University Hospital Southampton NHS Foundation Trust

Dr Sarah McMullen, Independent member (PPI member), Head of Knowledge, National Childbirth Trust

Dr Jenny Ingram, Independent member, Senior Research Fellow, Centre for Academic Child Health, University of Bristol

Professor Marian Knight, Non-independent member, FROSTTIE Chief Investigator, Professor of Maternal and Child Population Health, National Perinatal Epidemiology Unit, University of Oxford

Professor Ed Juszczak, Non-independent member, Professor of Clinical Trials and Statistics in Medicine, Nottingham Clinical Trials Unit, University of Nottingham. During Trial conduct: Director, National Perinatal Epidemiology Unit Clinical Trials Unit (NPEU CTU), University of Oxford.

Independent DMC

The Data Monitoring Committee (DMC), independent of the applicants and the TSC, reviewed the progress of the trial and interim analysis at least annually. They provided advice on the conduct of the trial to the TSC and (via the TSC) to the NIHR HTA programme.

Membership included the following:

Professor Ben Stenson, Chair, Independent member, Consultant Neonatologist, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh

Professor Graeme MacLennan, Independent member, Director, Centre for Health-care and Randomised Trials, University of Aberdeen

Professor Mary Renfrew, Independent member, Professor in Mother and Infant Health, School of Nursing and Health Sciences, University of Dundee.

Contributions of authors

Marian Knight (https://orcid.org/0000-0002-1984-4575) (Professor, Maternal and Child Population Health) wrote the first draft of the manuscript, contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Rema Ramakrishnan (https://orcid.org/0000-0002-6784-8319) (Senior Research Fellow, Statistics) conducted the statistical analysis, contributed to the first draft of the manuscript, contributed to the interpretation of the results, and edited and approved the final version of the manuscript.

Svetlana Ratushnyak (https://orcid.org/0000-0001-7967-5112) (Research Fellow, Health Economics) conducted the economic evaluation, contributed to the first draft of the manuscript, contributed to the interpretation of the results, and edited and approved the final version of the manuscript.

Oliver Rivero-Arias (https://orcid.org/0000-0003-2233-6544) (Associate Professor, Health Economics) conducted the economic evaluation, contributed to the first draft of the manuscript, contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Jennifer Bell (https://orcid.org/0000-0001-9571-0715) (Research Fellow, Statistics) developed the statistical analysis plan, contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Ursula Bowler (https://orcid.org/0000-0002-0100-0155) (Senior Trials Manager, Clinical Trials) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Phyll Buchanan (https://orcid.org/0000-0002-1436-4396) (Public Contributor) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Claire Carter (https://orcid.org/0000-0002-0656-1146) (Infant Feeding Specialist) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Christina Cole (https://orcid.org/0000-0002-8798-2136) (Senior Trials Manager, Clinical Trials) contributed to the first draft of the manuscript, contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Oliver Hewer (https://orcid.org/0000-0002-6251-7174) (Trial Manager, Clinical Trials) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Madeleine Hurd (https://orcid.org/0000-0002-2797-2358) (Data Coordinator, Clinical Trials) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Andy King (https://orcid.org/0000-0001-7175-2718) (Head of Programming, Clinical Trials) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Ed Juszczak (https://orcid.org/0000-0001-5500-2247) (Professor, Statistics) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Louise Linsell (https://orcid.org/0000-0003-3205-6511) (Associate Professor, Statistics) developed the statistical analysis plan, contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Anna-May Long (https://orcid.org/0000-0001-6142-2117) (Consultant, Paediatric Surgery) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Linda Mottram (https://orcid.org/0000-0002-5758-7629) (Midwife, Clinical Trials) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

David Murray (https://orcid.org/0000-0001-9010-2905) (Senior Programmer, Clinical Trials) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Sam Oddie (https://orcid.org/0000-0001-8701-4912) (Consultant, Neonatology) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Maria Quigley (https://orcid.org/0000-0002-8058-6181) (Professor, Statistical Epidemiology) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Victoria Stalker (https://orcid.org/0000-0001-5157-7043) (Trial Manager, Clinical Trials) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Kayleigh Stanbury (https://orcid.org/0000-0002-8726-2411) (Head of Operations, Clinical Trials) contributed to the first draft of the manuscript, contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Richard Welsh (https://orcid.org/0000-0001-9892-7581) (Senior Software Developer, Clinical Trials) contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Pollyanna Hardy (https://orcid.org/0000-0003-2937-8368) (Director, Clinical Trials Unit) conducted the statistical analysis, contributed to the first draft of the manuscript, contributed to the development and conduct of the trial and interpretation of the results, and edited and approved the final version of the manuscript.

Ethics statement

The FROSTTIE trial protocol was approved by South Central – Oxford B Research Ethics Committee (ref. 18/SC/0580) on 10/12/2018 and the Health Research Authority (HRA) and may be found at https://www.npeu.ox.ac.uk/assets/downloads/frosttie/protocol/FROSTTIE_IRAS235355_clinical_research_protocol_v5_29Jul2020_clean_signed.pdf.

Local approval and site-specific assessments were obtained from each NHS hospital site.

Data-sharing statement

Data will be shared in accordance with the National Perinatal Epidemiology Unit Data Sharing policy. Requests for access to the data will be considered by the National Perinatal Epidemiology Unit Data Sharing committee. Access to anonymised data can be requested from general@npeu.ox.ac.uk or by contacting the corresponding author.

FROSTTIE Trial Collaborative Group

Professor Marian Knight, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford. marian.knight@npeu.ox.ac.uk

Professor Ed Juszczak, Nottingham Clinical Trials Unit, University of Nottingham. Ed.Juszczak@nottingham.ac.uk

Ms Phyll Buchanan, PPI representative, The Breastfeeding Network. phyll.buchanan@breastfeedingnetwork.org.uk

Associate Professor Oliver Rivero-Arias, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford. oliver.rivero@npeu.ox.ac.uk

Professor Sam Oddie, Bradford Royal Infirmary, Bradford Teaching Hospitals NHS Trust. sam.oddie@bthft.nhs.uk

Professor Maria Quigley, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford. maria.quigley@npeu.ox.ac.uk

Mrs Claire Carter, Registered Midwife and Infant Feeding Lead, Royal Berkshire NHS Foundation Trust (now retired). claire_carter3@hotmail.co.uk

Dr Anna-May Long, Addenbrooke’s, Cambridge University Hospitals NHS Foundation Trust. anna-may.long@addenbrookes.nhs.uk

Dr Louise Linsell, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford.

Dr Jennifer Bell, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford.

Dr Rema Ramakrishnan, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford.

Dr Pollyanna Hardy, National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford.

Disclaimers

This report presents independent research funded by the National Institute for Health and Care Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, the HTA programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, the HTA programme or the Department of Health and Social Care.