NHS Choices

Could statins prevent breast cancer returning?

NHS Choices - Behind the Headlines - Thu, 02/06/2016 - 16:28

"Statins could be used in the treatment of breast cancer," Sky News report. Findings from a new study suggest the potential involvement of cholesterol in the recurrence of breast cancer following treatment.

The researchers hope their discovery could pave the way towards new treatment targets, and say that the effect of cholesterol-lowering drugs (such as statins) now needs to be examined. 

The research centred on what is known as oestrogen receptor-positive (or "ER+") breast cancers – where cancer growth is stimulated by the hormone oestrogen; these account for the majority of cases. Hormonal treatments such as tamoxifen can be used to block the effects of oestrogen. However, in some cases, these cancers build up resistance to the lack of oestrogen and can return. This study aimed to investigate why this happens and suggests that one of the answers may lie in cholesterol.

The findings suggest that specific cholesterol molecules (25-HC and 27-HC) are produced in the absence of oestrogen, which may stimulate further tumour growth. This may be one of the reasons behind cancer resistance.

Current evidence suggests the most effective method for reducing your risk of breast cancer reoccurrence is to follow standard healthy living advice: stop smoking, exercise regularly, eat a healthy dietmaintain a healthy weight and moderate your alcohol consumption.


Where did the story come from?

The study was carried out by researchers from a number of institutions, including the London Institute of Cancer Research, University of Oslo and the Department of Biochemistry, Royal Marsden Hospital in London. It was funded by the Breast Cancer Now Toby Robins Research Centre and NHS Trust funding.

The study was published in the peer-reviewed scientific journal Breast Cancer Research. It is available on an open-access basis and is free to read online here.

The UK media's headlines are slightly premature by suggesting that the study has already assessed the effect of statins on breast cancer recurrence, which isn't the case. However, the main body of the news articles were more accurate, with the papers acknowledging that most of the research was in the lab, and therefore has not yet been tested on humans.


What kind of research was this?

This was a laboratory study, which aimed to identify the biological pathways that could be responsible for some oestrogen receptor-positive (ER+) breast cancers becoming resistant to hormone treatments. ("ER" is used due to the American spelling of oestrogen: estrogen).

Eighty percent of breast cancers are reported to carry oestrogen receptors and, while current hormone treatments such as aromatase inhibitors are effective at blocking the action of oestrogen, many patients relapse. Previous research had indicated that cholesterol-producing pathways may be involved. 

Laboratory studies like this are useful early stage research for getting an indication of biological processes and how things work at a cellular level. They can pave the way towards the development of new treatments, or using existing treatments in new ways to treat different diseases. However, clinical trials would need to be conducted to understand whether proposed treatments are firstly safe, and then effective, for this purpose in humans.


What did the research involve?

The researchers aimed to identify novel mechanisms of resistance to oestrogen deprivation. They first cultured five different types of ER+ breast cancer cells. These were grown in the absence of oestrogen until their growth rate was no longer dependent on the hormone.

They then analysed the changes in gene activity and protein production that occurred in this setting of oestrogen deprivation.

On finding increased activity of the cholesterol-producing pathway, they assessed the effect that the cholesterol molecules 25-HC and 27-HC had on cancer cell growth, and also looked at what happened when they interrupted the genes needed to produce them.

They then verified their findings in two cohorts of people with ER+ breast cancer who had been treated with aromatase inhibitors or tamoxifen.


What were the basic results?

Overall, the researchers found that ER+ breast cancer cells grown in the absence of oestrogen show increased activity of cholesterol-producing pathways. The cholesterol molecules 25-HC and 27-HC can mimic oestrogen and stimulate cancer growth instead.

When they interfered with the genes needed to produce these cholesterol molecules using small interfering RNAs (siRNAs – artificially made packets of genetic material), they observed a 30-50% drop in cancer cell growth.

Gene analysis of samples from the cohort of people with ER+ patients who had been treated with aromatase inhibitors showed that poor response to treatment was associated with increased expression of four enzymes that are required to make cholesterol molecules.


How did the researchers interpret the results?

The researchers concluded: "Our observations suggest that enzymes within the cholesterol biosynthesis pathway may be associated with acquired resistance to AI [aromatase inhibitors] therapy. Our study highlights the need to evaluate the lowering of cholesterol on the impact of endocrine therapy."



The study aimed to identify biological pathways that could be the reason why some ER+ breast cancers relapse after oestrogen-blocking treatment.

It seems that one of the answers for treatment resistance lies in increased activity of cholesterol-producing pathways in the absence of oestrogen. The cholesterol molecules mimic oestrogen and stimulate further tumour growth.

The researchers hope that their research could potentially highlight a new pathway, which could be used as a target for therapeutic treatment in the future. Dr Lesley-Ann Martin from the research team told the media, "This is hugely significant. Testing the patient's tumour for 25-HC or the enzymes that make it may allow us to predict which patients are likely to develop resistance to hormone therapy, and tailor their treatment accordingly."

While this may be an important discovery, and could hopefully pave the way to more targeted treatments, the research has so far only been performed in cells in the lab. Cholesterol-blocking treatments such as statins may have new potential in the management of some people with ER+  breast cancers, but they have not yet been tested for this use.

Further laboratory studies are likely to be needed to test the effect of statins upon cancer growth. If these results are positive, this may lead to clinical trials to test whether statins have the same effect in people as they do on cancer cell growth in the lab. This will identify which women could benefit from statin involvement in their breast cancer treatment, and to see if there are any long-term side effects.

Current evidence suggests that the most effective methods to reduce your risk of breast cancer reoccurrence is to follow standard healthy living advice: stop smoking, exercise regularly, eat a healthy dietmaintain a healthy weight and moderate your alcohol consumption.

Links To The Headlines

Statins Could Stop Breast Cancer Return – Study. Sky News, June 1 2016

Statins 'could be valuable addition to breast cancer treatment'. The Guardian, June 1 2016

Statins could prevent breast cancer returning, study suggests. The Daily Telegraph, June 1 2016

Statins could provide hope for millions of breast cancer sufferers. Daily Mirror, June 1 2016

Statins offer new way to beat breast cancer – for good. The Times, June 1 2016 (subscription required)

Links To Science

Simigdala N, Gao Q, Pancholi S, Roberg-Larsen H, et al. Cholesterol biosynthesis pathway as a novel mechanism of resistance to estrogen deprivation in estrogen receptor-positive breast cancer. Breast Cancer Research. Published online June 1 2016

Categories: NHS Choices

Migraines linked to increased heart disease risk in women

NHS Choices - Behind the Headlines - Wed, 01/06/2016 - 14:30

"Women who suffer migraines have a 50 per cent greater chance of developing a major heart … problem," the Daily Mail reports.

Individual risks to women remain small, but because migraines are so widespread, this could be an issue of concern at a public health level.

A study of more than 100,000 women from the US found that those who reported getting migraine headaches had a 50% higher risk of having or dying from a heart attackstroke or heart disease.

Doctors already knew migraine is linked to stroke, as we discussed back in 2009, especially migraine with aura.

This is when a migraine is preceded by warning signs and symptoms, such as visual problems or feeling dizzy. We don't know whether migraine is a direct cause of these problems.

Although a 50% increased risk sounds like a lot, you have to take into account the baseline (absolute) risk.

Only 1.2% of all the women in the study had a major cardiovascular disease event like a heart attack or stroke, so increasing that by 50% takes the risk to 1.8%, or around a 1 in 50 chance.

The authors are calling for research to find out more about whether treatment that reduces the incidence of migraines can also reduce the risk of heart attacks and strokes.

A related editorial makes the point that we also have to be sure that preventative treatments for heart disease, such as statins, don't actually make the problem worse for women with migraines.

Where did the story come from?

The study was carried out by researchers from Charité-Universitätsmedizin in Germany, Harvard Medical School, the Harvard TH Chan School of Public Health, and the Washington University School of Medicine in the US.

It was funded by the US National Institutes of Health.

The study was published in the peer-reviewed British Medical Journal (BMJ) on an open access basis, so it's free to read online.

There is also a related editorial written by independent experts, who provide an interesting insight into the study's implications.

The UK media's coverage was accurate, with many sources stressing that the risk to individual women was small.

But this tone of reassurance was ignored by many of the headline writers – for example, the Daily Express' headline, "Suffer with migraines? Female sufferers 'more likely' to DIE from heart disease and stroke".

Many of the headlines were unnecessarily alarming, not least because stress and anxiety are known triggers for migraines.

The Daily Telegraph said the study suggested that statins might reduce risk for people with migraines, which is misleading, as the potential role of statins was not investigated in this study.

What kind of research was this?

This was a prospective cohort study of 115,541 women taking part in the ongoing US Nurses' Health Study.

Prospective cohort studies, especially of this size and length, can be useful ways to identify links and trends in health.

However, observational studies like this one cannot prove that one factor – in this case, migraine – causes another (heart attack or stroke).

What did the research involve?

Researchers used data from a big ongoing study of women's health in the US, which began in 1989.

Women aged 25 to 42 at baseline were asked a wide range of questions about their health and lifestyle, and were followed up every two years until June 2011.

After adjusting their figures to take account of confounding factors, researchers looked to see whether women who said they had been diagnosed with migraine were more likely to have had or died from cardiovascular disease, including heart attack and stroke.

Women were asked about migraine at the start of the study and twice in follow-up questionnaires.

They were asked about cardiovascular disease every two years. Women with cardiovascular disease in 1989 were not included in this study.

The wide range of confounding factors the researchers took into account included:

  • age
  • high cholesterol
  • diabetes
  • high blood pressure
  • smoking
  • alcohol
  • exercise
  • whether a woman had gone through the menopause
  • family history of heart attack
  • use of widely used medications, such as hormone replacement therapy (HRT), oral contraceptive pills, paracetamol, aspirin, and non-steroidal anti-inflammatory drugs (NSAIDs)

The researchers used these factors to construct models to test their results and take account of known risks for heart disease and stroke.

What were the basic results?

Of the 115,541 women in the study, over the course of 22 years follow-up:

  • 17,531 (15%) had migraine
  • 1,329 (1.2%) had a heart attack, stroke, angina, or needed a procedure to reopen the blood vessels
  • 223 (0.2%) died of cardiovascular disease

After adjusting for confounding factors, the chances of getting major cardiovascular disease were 50% higher for women with migraine than women without (adjusted hazard ratio 1.5, 95% confidence interval 1.33 to 1.69). The link was stronger for stroke than heart attack.

Women who had migraine were more likely to be overweight, smoke, and have high blood pressure and cholesterol.

However, these factors did not explain the raised risk of heart attack and stroke, as the researchers had already adjusted their figures to account for them.

How did the researchers interpret the results?

The researchers said they found "consistent associations" between migraine and cardiovascular disease, which "persisted" after adjustment for traditional cardiovascular risk factors.

They said there is now an "urgent need" to understand what's behind the link, so they can look at treatments to prevent heart attacks and strokes in women with migraine.

The researchers also suggested that people with migraine should have their overall cardiovascular risk assessed, so they can be advised about any steps they can take to reduce it – for example, reducing blood pressure if it's too high, or stopping smoking if they smoke.


This study shows a strong link between migraine and cardiovascular disease, extending the link already found between migraine and stroke. However, many questions remain.

We don't know if the results are relevant to men who have migraines, as all the people in the study were women. We also don't know if the results apply to non-white populations, as most of the women in the study were white.

Previous studies on stroke have shown that the group at highest risk is who get an "aura" before a migraine – sensation(s) that tells them the migraine is on its way.

But this study did not ask people about aura, so we don't know whether it's only people with aura who are at risk of heart disease.

We don't know what causes the increased risk of cardiovascular disease for people with migraine.

Although the researchers took into account a wide range of confounding factors, it's possible that some unaccounted factors were responsible for the link.

Alternatively, a third underlying factor might cause both cardiovascular problems and migraine.

Until we fully understand what's behind the link, it's too early to know whether treatments for migraine – or any other treatments – will help reduce the risk, or could possibly make it worse.

As the editorial in the BMJ points out, aspirin – often used to prevent cardiovascular disease because of its blood-thinning properties – was found to actually increase the risk of heart attacks in women who had migraines with aura.

But we do know that everyone can reduce their risk of cardiovascular disease by stopping smoking, eating a healthy diet, maintaining a healthy weight and taking regular exercise.

Regular exercise is also known to help reduce stress levels and boost mood, which could also help to reduce the number of migraines you experience.  

Links To The Headlines

Women who suffer migraines have a 50 per cent greater chance of developing a major heart or circulation problem. Daily Mail, June 1 2016

Migraines raise risk of heart attack and early death, scientists find. The Daily Telegraph, May 31 2016

Migraines linked to heart attacks and strokes among women in latest study. Daily Mirror, May 31 2016

Suffer with migraines? Female sufferers 'more likely' to DIE from heart disease and stroke. Daily Express, May 31 2016

Links To Science

Kurth T, Winter AC, Eliassen AH, et al. Migraine and risk of cardiovascular disease in women: prospective cohort study. BMJ. Published online May 31 2016

Categories: NHS Choices

Treatment 'breakthrough' in man with advanced skin cancer

NHS Choices - Behind the Headlines - Tue, 31/05/2016 - 14:30

"Skin cancer cure hope for millions as major treatment breakthrough sees man's tumours disappear 'completely'," the Daily Mirror reports.

While the headline is premature, the case report it is based on does present interesting findings.

The study involved a man with melanoma – the most serious type of skin cancer – that had spread to other parts of the body.

He was entered into a small trial to try a combination of immunotherapy treatments, which involves stimulating the immune system to detect and kill cancer cells.

The combination of treatments essentially aimed to boost the numbers of T immune cells that could target and kill the melanoma cells.

The researchers gave the man an infusion of T cells, along with an antibody treatment that would also help boost their numbers.

The man's tumours had not responded to the two treatments when given separately, but taken together they diminished the size of the tumours in his chest.

After three years, he'd achieved complete remission – meaning all signs of the cancer had gone. He remains cancer-free five years later, at his latest check-up.

These are promising findings, but are also the results of just one case. Ten people received the same treatment combination as the man, but only he and one other achieved the same remission.

It is hoped that the researchers will build on these findings to find out who may be suitable for this treatment.

However, at this stage, it doesn't offer a "cure hope for millions", as the Daily Mirror states.

Where did the story come from?

The study was carried out by researchers from the Fred Hutchinson Cancer Research Center, the University of Washington, and the Memorial Sloan-Kettering Cancer Center, all in the US.

Funding was provided by the Cancer Research Institute and a "Stand Up To Cancer" Cancer Research Institute Cancer Immunology Dream Team Translational Research Grant.

The study was published in the peer-reviewed Journal of Experimental Medicine.

The lead author of the study serves on the advisory board of Adaptive Biotechnologies, a biotech company whose technology was used in this case.

The Daily Mirror's headline gives rather false hope to the many people and their families affected by this aggressive cancer.

However, the body of the article is generally representative of the study, and does make it clear that the results were found for just one person.

The relative success of the treatment could have been a lot clearer had they mentioned that of the 10 people who received the new treatment combination, just two achieved complete remission.

Without this context, readers might believe the treatment had a higher success rate than was actually the case.

The newspaper does provide a human angle to the story, which is often missing from typically dry case reports.

The man in question just hoped to live a couple of months more so he could see his daughter graduate from college. The success of his treatment meant that he saw her both graduate and get married a few years later.

What kind of research was this?

This case report investigated a combination of cancer treatments in a person with metastatic melanoma who had not responded to the two treatments given individually.

Malignant melanoma is the most aggressive form of skin cancer. Metastatic means that the cancer has already spread to other parts of the body, such as the brain or lungs.

Various treatment options may be tried at this stage, such as chemotherapy, radiotherapy or biological treatments that help the body's own immune system fight the cancer cells – the latter is the focus of this study.

People with metastatic melanoma do not usually have enough tumour-specific immune cells to prevent the cancer progressing.

Progression can be slowed by transfusing T immune cells – or cytotoxic (cell-killing) T lymphocytes (CTLs) – that are able to target the melanoma cells. But complete remission is rare because the transferred T cells don't survive long.

Another option is to give an antibody treatment to block CTL-associated antigen 4 (anti-CTLA4). Blocking this antigen has been shown to boost the numbers of melanoma-specific T cells.

However, complete cancer remission is rare when giving anti-CTLA4 alone, as is giving T cells alone.

This study aimed to combine the two treatments. The researchers aimed to transfuse melanoma-specific CTLs that were first "primed" by a signalling protein called interleukin-21 (IL-21), which would help boost the numbers of these T cells.

These enhanced CTLs were combined with anti-CTLA4 to see if this would help the skin cancer patient.

What did the research involve?

This was the case of a 53-year-old man who first presented with an advanced melanoma on his right thigh that had already spread to his lymph nodes.

Despite surgery followed by immune therapy with interferon alpha, the cancer had spread to other parts of the body (metastasis) four years later.

He first received four cycles of IL-21 and the cancer progressed, then two infusions of melanoma-specific CTLs and more progression.

He then received anti-CTLA4 (ipilimumab), which initially slowed tumour growth, but four months later he had new metastases.

The man was then treated with IL-21-primed melanoma-specific CTLs, immediately followed by a single dose of ipilimumab. He was monitored for adverse events and disease progression.

What were the basic results?

Before treatment, the man had tumour masses in his chest. Twelve weeks after starting the combined treatment, the tumours started to reduce in size.

After three years, he had complete remission as defined by the state of the immune system and any solid tumours, and remained disease-free five years later.

There were no serious adverse events, apart from a transient high temperature and low white cell count at the time of infusions, which is a common side effect of chemotherapy.

However, he did lose the pigment in his eyebrows and eyelashes (vitiligo), which developed at around 12 weeks when the tumour initially reduced in size and persisted five years later.

The single patient described here represents one of 10 people treated on this combination treatment. He was one of two people who achieved ongoing complete remission.

Of the remaining eight, two achieved a partial response, three achieved a stable disease, and three experienced disease progression.   

How did the researchers interpret the results?

The researchers concluded that, "Combining CTLA4 blockade with the transfer of well-characterized, robust antitumor CTLs represents an encouraging strategy to enhance the activity of the adoptively transferred CTL and induce de novo antitumor responses.

"This strategy may hold broad promise for immune checkpoint blockade-resistant melanomas."


This is described as the first case study in humans to have successfully combined these immune treatments.

The results demonstrate that long-term cancer remission was achieved even after the cancer had previously progressed quickly when the person had been given IL-21, CTL and anti-CTLA4 separately.

These seem to be extremely encouraging findings for metastatic melanoma, a cancer with notoriously poor prognosis.

However, before the findings raise too much hope, it must be emphasised that this case report focuses on just one man.

The researchers note he is one of 10 people entered into the trial of this combination treatment, and only one other person received complete remission as well.

This means this treatment combination may not offer the hope of a complete cure for all people who have reached the advanced stages of this aggressive cancer.

It is unclear why these two people responded so positively to treatment, while the other eight did not. However, new treatment possibilities for advanced melanoma are always welcome.

It is hoped that researchers may be able to build on these encouraging results in future trials to find out which people with metastatic melanoma are likely to be suited to this treatment and would benefit the most from it – for example, by looking at characteristics of their cancer, cell profile and previous treatment.

For now, the most important message for malignant melanoma remains that prevention is better than cure.

Though not all cancers can be prevented, you can help reduce your risk of melanoma by ensuring that your skin and eyes are protected from the sun, and avoiding artificial sources of damaging UV rays, such as tanning lamps or beds.

Read more about how to protect your skin from the sun and reduce your risk of getting skin cancer.

Links To The Headlines

Skin cancer cure hope for millions as major treatment breakthrough sees man's tumours disappear 'completely'. Daily Mirror, May 31 2016

Links To Science

Chapuis AG, Lee SM, Thompson JA, et al. Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient. Journal of Experimental Medicine. Published online May 30 2016

Categories: NHS Choices

Leaving babies to cry 'will improve their sleep', study says

NHS Choices - Behind the Headlines - Fri, 27/05/2016 - 15:40

"Babies do sleep better if you leave them to cry," the Daily Mail reports.

A small study suggests that "graduated extinction" – better known as controlled crying in this country – increased sleep length and reduced the number of times babies woke up during the night.

Controlled crying involves waiting a set number of minutes while your baby is crying, without picking them up, to see if they drop off again.

The study compared this approach with a standard sleep education approach based on the principle of setting a standard bedtime routine, as well as a different approach known as bedtime fading.

This involves pushing back your baby's bedtime by 30 minutes if they took a while to settle the previous night.

The results suggest these two approaches work better than a sleep education only control group approach.

This didn't lead to any increases in stress to the infant or affect parental-child bonds a year later.

A problem with the study is its size – there were only 14 to 15 infants in each of the three test conditions at the start of the study.

There were even less after three months, when most of the results were analysed – only seven in each group. This isn't enough to make reliable statements about which sleep method works best.

There may not be a one-size-fits-all "trick" to getting your baby to sleep. Some babies may respond to controlled crying, others may prefer bedtime fading or a set bedtime routine.

Where did the story come from?

The study was led by researchers from Flinders University, Australia, and was funded by the Australian Rotary Health Fund, Channel 7 Children's Research Fund, and the Faculty of Social and Behavioral Sciences.

It was published in the peer-reviewed journal, Pediatrics.

The Mail's reporting was accurate, but took the findings at face value, not discussing any of the study's limitations, such as its small size, and how these could affect the findings.

What kind of research was this?

This randomised control trial (RCT) looked at two approaches to improving an infant's disturbed sleep, compared with a standard control intervention.

Many parents experience trouble getting their infant to have a good night's sleep. Struggles can include settling your infant before bed, helping them fall asleep, or frequent waking in the night.

There are a lot of approaches people suggest to help. The researchers wanted to find which one worked the best:

  • Should you comfort your child each time they cry, or show "tough love" and leave them to cry and sooth themselves?
  • Should you pick up your infant to comfort them, or is it best to only show your face but leave them where they are?
  • Is setting a standard bedtime better, or does it make more sense to be flexible, depending on how tired your baby seems to be?

These questions can leave parents confused, and sometimes feeling guilty about what's best – and they aren't the only ones.

Researchers couldn't find any clear answers from past studies they'd seen, either. They designed this trial to test two behavioural approaches against an educational-only approach to improve infants' disturbed sleep, hoping there would be a clear winner.

What did the research involve?

All families in the study answered yes to the question "Do you think your child has a sleep problem?", so they were a special group of disturbed sleepers.

Infants with mothers with significant postnatal depression scores were excluded. Most parents were graduates and middle- to high-income earners.

A total of 43 infants aged 6 to 16 months – mostly (63%) girls – were randomised to one of three sleep test groups:

  • graduated extinction (14 infants) – gradually delaying parents' responses to their infant's cry each night and each time they wake in the night. Parents were told to put their infant to bed awake, and leave within one minute. When re-entering the room, they were allowed to comfort their child, but couldn't pick them up or turn on the lights.
  • bedtime fading (15 infants) – delaying the infant's bedtime by 30 minutes each time they took more than 15 minutes to fall asleep.
  • sleep education (14 infants) – this was the control group. Parents were given information on reasons for night wakings, settling tips, and sleep cycles in infants. The graduated extinction and bedtime fading groups also received this information.

Parents filled in sleep diaries to document their infant's sleep habits, wore ankle tags to track their night-time movements, and filled in ratings scales assessing the mother's level of depression, mood and stress.

Infants' stress levels were also monitored in the morning and afternoon, testing their saliva for the stress hormone cortisol.

Parental-reported changes in sleep patterns were obtained before the test and one week, one month, three months and one year into the test to monitor change.

A year after the tests, mothers rated their children for emotional or behavioural problems, and a series of separation and reunion tests assessed parent-child attachment.

All mothers and infants who started the test finished it through to a year, but there was data missing for approximately half (seven) of the families by the third month.

The main analysis compared the two active tests – graduated extinction and bedtime fading – with the control group, sleep education given to all, and for changes over time.

The focus was on any changes in the time it took for the infant to fall asleep (sleep latency), how often they woke in the night, and whether they woke up after falling asleep.

What were the basic results?

Three months into the intervention, a lot of sleep measures had improved across all three groups.

However, it wasn't clear whether they were statistically different across the three test conditions, or before and after the study, as they were presented as graphs.

After three months:

  • The time it took infants to go to sleep had fallen from around 18 minutes to less than 10 minutes in both graduated extinction (-12.7 minutes) and bedtime fading groups (-10 minutes). Stayed more or less the same in the control at around 20 minutes (+2 minutes).
  • Average number of times the infant woke in the night appeared to decline in all groups, but it wasn't clear if these were statistically significant compared with the education only group, or over time.
  • The time spent awake after first falling asleep fell across all groups. For graduated extinction, it fell from just under an hour at the start of the study to around 15 minutes (44.4 minutes). The control group and bedtime fading improved a little less, by 31.7 minutes and 24.6 minutes respectively.
  • Total time asleep improved for those trying graduated extinction  (+19.2 minutes) and the control group (+21.6 minutes) but there was little change for bedtime fading (+5.4 minutes).

Over the first month, maternal stress in the control group was largely unchanged, but reduced in both sleep test conditions. Maternal mood improved in all groups, most of all for bedtime fading.

At one year no effects on parent-child bonding or emotional or behavioural problems were found.

How did the researchers interpret the results?

The researchers concluded that their study showed "meaningful effects for both graduated extinction and bedtime fading".

They went on to say that, "Compared with the control group, large reductions in nocturnal wakefulness resulted from each treatment.

"Despite assertions that extinction-based methods may result in elevated cortisol, emotional and behavioural problems, and insecure parent-infant attachment; our data did not support this hypothesis."


This randomised control trial suggests two behavioural approaches to remedy disturbed sleep in infants may work better than a sleep education only control group approach.

This may be true, but may also be a chance finding or affected by bias. For example, the statistical significance of some of the results was hard to interpret, as many were presented as graphs only. This means we can't be sure that some, or even many, of the differences are down to chance.

The study was also very small, with only 14 to 15 people in each of the three test conditions at the start of the study.

There were even less after three months – only seven in each group. This isn't enough to make accurate, reliable or generalisable statements about which method works best.

Small studies like this are also more likely to throw out unusual and unrepresentative results. For these reasons, we can't say anything too solid based on it.

You may wish to experiment with different techniques to see if a specific approach suits your baby better.

If you have persistent problems getting your baby to sleep and it is beginning to have a significant impact on your quality of life and ability to function during the day, speak to your health visitor or GP.

Read more advice about helping your baby (and you) get a good night's sleep.

Links To The Headlines

Babies DO sleep better if you leave them to cry: Letting them nod off alone could help the parents, too. Daily Mail, May 27 2016

Links To Science

Gradisar M, Jackson K, Spurrier NJ, et al. Behavioral Interventions for Infant Sleep Problems: A Randomized Controlled Trial. Pediatrics. Published online May 24 2016

Categories: NHS Choices