“A glass of wine every day in pregnancy could be good for your baby,” is the entirely incorrect headline in The Daily Telegraph today. Other newspapers reported that drinking while pregnant does ‘no harm’, these claims are also misleading.

The news is based on a new study investigating the link between alcohol exposure before birth and childhood balance, which is considered an important sign of children’s development. Previous research has found that alcohol consumption during pregnancy is linked to poorer outcomes on several markers of neurodevelopment, but the effect on balance is uncertain.

Researchers found no evidence of an adverse effect of low-to-moderate maternal alcohol consumption on childhood balance. They also found moderate alcohol exposure seemed to have a beneficial effect compared to no alcohol. However, the researchers say that this positive effect is possibly due to them not being able to fully adjust for the fact that higher alcohol use was linked to social advantage.

This study adds to knowledge about the effects of alcohol in pregnancy on children’s balance. However, uncertainty remains over whether there is a ‘safe’ level of alcohol consumption during pregnancy. For this reason, current guidance suggests that women avoid alcohol completely during the first three months of pregnancy. If women choose to drink after this time, they should not drink more than one to two units of alcohol once or twice per week, and avoid binge drinking altogether. Contrary to media suggestions, this study does not change this advice.

Where did the story come from?

The study was carried out by researchers from the University of Bristol and University Hospital Bristol NHS Foundation Trust and was funded by the UK Medical Research Council, the Wellcome Trust, the University of Bristol and the Alcohol Education and Research Council (AERC). The study was published in the peer-reviewed, open access medical journal, BMJ Open.

The Telegraph’s headline was incorrect and potentially dangerous. While the researchers found a positive effect of alcohol in one measure, they clearly and categorically said that this likely to be a statistical blip. This headline also ignores the fact that the research was into just one aspect of children’s development and that alcohol consumption was measured at only one point in time.

Because of these limitations, women should stick to the existing advice on alcohol in pregnancy. Fortunately, in its online edition, the Telegraph used a more accurate headline. All other newspapers’ headlines suggested that drinking in pregnancy was “OK”, or does “no harm” – and are also misleading.

What kind of research was this?

This was a prospective cohort study that aimed to determine whether there was a link between alcohol exposure during pregnancy and balance in 10-year old children. Although this is the ideal study design to address this question, cohort studies can only show association, and cannot prove a cause-and-effect relationship. This is because other factors (confounders) may be responsible for any association seen.

This problem is demonstrated by this study. Despite the fact that the researchers collected information on a number of socioeconomic factors, and adjusted for them in their analyses, they conclude that the associations seen are probably due to not fully being able to adjust for social advantage.

What did the research involve?

The researchers used information on 6,915 children and their parents, who were participating in the Avon Longitudinal Study of Parents and Children.

This study used children who were born singly (who were not twins or another multiple birth) between April 1991 and December 1992, who had undergone balance assessment at 10 years of age and for whom they had information on the mother’s alcohol intake.

The balance assessment evaluated three types of balance:

• dynamic balance: time to cross a 2m balance beam, walking heel to toe 
• static balance, eyes open: heel to toe balance on a beam, eyes open and standing on one leg, eyes open. Both balances were held for a maximum of 20 seconds
• static balance, eyes closed: heel to toe balance on a beam, eyes closed and standing on one leg, eyes closed. Both balances were held for a maximum of 20 seconds

Children were said to have ‘good balance’ if they were in the top 25% fastest times for crossing the balance beam (good dynamic balance), if they maintained the static balances with their eyes open for 20 seconds (good static balance with eyes open), and if they were in the top 25% longest times for holding the static balances with eyes closed (good static balance with eyes closed).

Alcohol exposure was measured by asking mothers and fathers to self-report their alcohol intake at 18 weeks of pregnancy.

At 18 weeks of pregnancy, mothers reported both their current consumption and their consumption prior to pregnancy. For each time point, the mothers reported the total number of glasses (defined as a pub measure of spirits, half a pint of larger or cider, a small glass of wine) consumed per week, categorised into none (0 glasses), low (1-2 glasses), moderate (3-7 glasses), and high (more than 7 glasses) consumption. Mothers were also asked how many days in the previous month they had drunk the equivalent of at least four units of alcohol (binge drinking). Similarly, fathers reported alcohol consumption and binge drinking.

Information on other factors that could explain any association seen (confounders) was also collected. These included marital status, crowding index (number of people in the household and number of rooms), home ownership, parity (the number of previous children the mother has), maternal education, ethnicity, maternal age, maternal social class, smoking, cannabis use, caffeine consumption, number of stressful maternal life events during pregnancy, and maternal depression.

The researchers looked to see whether there was a link between alcohol exposure during pregnancy and the balance ability of 10-year old children after adjusting for these potential confounders.

What were the basic results?

Few mothers reported drinking heavily during pregnancy, with 95.5% of mothers reporting no alcohol consumption to moderate alcohol consumption.

In general, higher total levels of maternal alcohol consumption were associated with higher socioeconomic status and higher maternal age, whereas higher levels of binge drinking were associated with lower socioeconomic status and lower maternal age.

No evidence was found of an adverse effect of maternal alcohol consumption on childhood balance.

• There was no association between any level of alcohol consumption during pregnancy and childhood dynamic balance.
• Compared to no alcohol consumption at 18 weeks of pregnancy, moderate maternal alcohol consumption was significantly associated with good static balance with both eyes open and eyes closed.
• There was no significant difference in static balance (eyes open or eyes closed) between no alcohol, low alcohol or high alcohol (the only significant association seen was for moderate alcohol).

Regular heavy maternal binge drinking (more than 10 times per month) was also associated with good static balance (eyes shut) in children. There was no significant association between any other level of binge drinking, or any other measure of balance.

Paternal drinking during the first three months was associated with good static balance (eyes open) in children, with fathers that reported drinking less than one glass per week, at least one glass per week and at least one glass per day having children with better static balance than those that reported never drinking.

The researchers then analysed the data differently, using a technique called “Mendelian randomisation”. This approach is based on the assumption that a person’s DNA is not linked to socioeconomic status.

It is known from previous research that particular variations in a gene that codes for alcohol dehydrogenase (an enzyme that breaks down alcohol) predisposes people to lower alcohol consumption. The researchers looked at this variant. Mothers carrying this variant consumed less alcohol before, during and after pregnancy.

There was no evidence that mothers carrying this variant had children with poorer balance, which is not what would be expected if alcohol exposure improves balance. The researchers use this result to suggest that the previous association between maternal alcohol consumption and balance outcomes may have been due to the fact that the current analysis could not completely adjust for socioeconomic status.

How did the researchers interpret the results?

The researchers suggest that the most correct interpretation of their results is that they, “provide no strong evidence of an effect, either beneficial or detrimental, of moderate maternal alcohol use during pregnancy on offspring balance.”

Conclusion

This large, well-designed prospective study has found no evidence that moderate maternal alcohol consumption at 18 weeks of pregnancy has an adverse effect on offspring balance at age 10.

The study is limited by the fact that, as a cohort study, it cannot show a cause-and-effect relationship. This is because other confounding factors may be responsible for any association seen.

Despite the fact that the researchers collected information on a number of socioeconomic factors, and adjusted for them in their analyses, they conclude that the small benefits seen for some outcomes with some drinking patterns are probably due to not fully being able to adjust for social advantage.

Also, maternal and paternal alcohol use was self-reported and alcohol use during pregnancy was assessed at only one point in time, which could be subject to bias. The researchers also reported that the balance measures used had low test-retest reliability.

Although the results of this study will add to knowledge about the effects of alcohol in pregnancy on one particular developmental outcome, uncertainty remains over what is a ‘safe’ level of alcohol consumption during pregnancy.

Current guidance suggests that women avoid alcohol completely during the first three months of pregnancy due to increased risk of miscarriage, and if they choose to drink after this time, should not drink more than one to two units of alcohol once or twice per week, and avoid binge drinking altogether. This study does not change this advice.

For more advice, read Can I drink alcohol when pregnant.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.

Links To The Headlines

A glass of wine a day in pregnancy could be good for your baby. The Daily Telegraph. June 18 2013

Moderate drinking during pregnancy 'does not harm baby's development'. The Guardian. June 18 2013

Pregnant women told moderate drinking will not harm the baby. The Independent. June 18 2013

Mums-to-be 'CAN have a glass of wine a day without harming their child's development'. Daily Mail. June 18 2013

Glass of wine per day OK during pregnancy, study claims. Daily Mirror. June 18 2013

Glass of wine does no physical harm, pregnant women told. The Times. June 18 2013

Links To Science

Humphriss R, et al. Prenatal alcohol exposure and childhood balance ability: findings from a UK birth cohort study. BMJ Open. Published online June 18 2013

“Lego characters are getting angrier – and could be harming children's development,” reports the Daily Mail.

Its report is based on a study that asked over 250 adults in the US to rate the emotion on the faces of more than 600 different Lego minifigures (affectionately known as "minifigs"). It found that most faces are happy, but that anger is also a common expression. Initially very different heads were produced, with the first face from 1975 being rated as sad, and the next few produced in the late 1970s and early 80s rated as happy.

Over time, the proportion of happy faces has declined. This increase has been partially driven by an increasing tendency towards cross-branding, such as Star Wars Lego, with some minifigs representing "baddies", rogues and warriors from these films.

Importantly, the study did not look at what impact the faces had on a child’s emotions. It is a great stretch to say that they may be “harming children’s development”.

You could also make the point that children actually enjoy an angry villain. Children’s fiction is full of infamous examples, ranging from Captain Hook to Voldemort.

A final piece of advice, provided by Lego, is that parents who are concerned “can always just switch heads with another figure”.

Where did the story come from?

The study was carried out by researchers from the Human Interface Technology Laboratory New Zealand at the University of Canterbury, and the Industrial Research Institute for Automation and Measurements in Poland. No sources of funding were reported.

The study appears to be a written summary of a presentation to be given at a scientific conference on how humans interact with objects that are designed to represent personalities. It is unclear whether the study has been peer-reviewed.

The media coverage has tended to overinterpret the findings of this research, with the lead researcher’s suggestion that angry faces could affect a child’s emotional development being accepted uncritically.

Also, The Guardian reports that “there were risks involved in exposing children to a variety of emotions, with small fans likely to remember the anger and fear in their figurines' faces, as well as their happier moments”. It is not clear how the paper came to include this statement, as the study did not assess children at all. In fact, only The Daily Telegraph explicitly reported in its text that the study only included adults.

The BBC News coverage includes a balancing comment from the author that it is "hard to derive a causal relationship" between angry toys and children's behaviours.

What kind of research was this?

This was a cross-sectional study looking at people’s perception of the emotion shown on Lego figures’ faces. The researchers were interested in whether the types of faces on Lego figures had changed over the last 35 years, and if perception of the face varies if the whole body of the figure is shown. The researchers are from a laboratory that looks at “developing and commercialising technology that improves human computer interaction”, with the ultimate goal of improving users’ experience.

Therefore, the study did not really focus on health issues or child development as such. It suggested that their study may help other researchers to understand the effect of the figures’ appearance on users over time, and also to inform design of other faces in game and toys.

What did the research involve?

The researchers took a sample of Lego figure faces over the years, and asked people what emotions the face expressed to see if the types of expression changed over time.

The researchers photographed all 3,655 Lego minifigures released between 1975 and 2010. They identified 628 heads with different faces used on these figures, and identified the year in which the head was first introduced. They used all of these faces in their study. They also randomly selected 100 heads and a minifigure with that head for use in their survey. They excluded six heads where the face was largely obscured, for example by a helmet. They also presented one figure (a Harry Potter figure) with two different skin colours – the traditional Lego yellow or a “natural” peach-coloured skin tone.

The researchers recruited 264 adults in the US through a website that enables people and businesses to ask other people to do tasks that computers are not capable of doing (called Human Intelligence Tasks).

They used the website to present the isolated faces and minifigures in a random order, with 30 people asked to rate each face. The participants were asked to rate which of these six emotions each face expressed:

• anger
• fear
• disgust
• happiness
• sadness
• surprise

They were asked to rank on a five-point scale (similar to a Likert scale) how intensely the face showed the emotion, ranging from “weak” to “intense”. The participants could rate as many of the faces as they liked and they were paid one cent per face they rated.

For each face, the researchers identified the dominant emotion for each face by finding which emotion was most commonly reported as being present. The researchers then looked at whether the figures’ faces had changed in the emotions shown over time. They also looked at whether presenting a face with the body of the figure changed perception of the face’s emotion.

What were the basic results?

The researchers found that each face was reported as expressing about four different emotions on average. The dominant emotion on most faces was happiness (324 faces) followed by anger (192 faces).

The number of different faces produced has increased over time, from fewer than five faces each year up to 1988, to more than 90 in 2010. From the early 1990s there was an increase in the variety of facial emotions shown by the minifigures. In 1975, the faces produced were all rated as sad, while in 1978 and 1980 all were rated as happy. However, in these years, only very few faces were produced. The proportion of happy faces released in each year decreased over time as more different and more varied faces were introduced.

If the figure’s body was shown as well as the face, anger tended to be reported more frequently, and disgust, sadness and surprise less frequently.

The minifigure’s skin colour did not affect which emotion was perceived on the face.

How did the researchers interpret the results?

The researchers concluded that “toy design has become a more complex design space in which the imaginary world of play does not only consist of a simple division of good versus evil, but a world in which heroes are scared and villains can have a superior smile”. They suggest that face designers should take care in designing the expressions and to test their effect “since toys play an important role in the development of children”. However, they also say that to appeal to users the faces need to offer a wide range of emotions “that connect to the complex interaction scenarios of today’s users”.

Conclusion

Overall, this research suggests that Lego figures’ faces have changed over time. This is a finding that is unlikely to surprise parents (or big kids of a certain age). The default minifig of old (described in the study as having an “enigmatic smile”) is now just part of a much larger family of minifigs including pirates, Star Wars “imperial stormtroopers” and ninjas.

So, as more faces have been produced it is unsurprising that a larger variety of emotions has been shown on the faces – particularly as minifigs now more commonly represent warriors. This study only assessed adults’ responses to the faces, and children’s perceptions of the faces may differ.

The study did not look at how children perceived the faces’ emotions or what impact the faces had on a person’s own emotions. The study doesn’t tell us anything about how the faces might potentially impact the health or development of children or adults playing with the figures. Therefore, it is a great stretch to say that they may be “harming children’s development” or are a “possible cause for concern”.

As the Lego manufacturer suggested in The Guardian, parents who might be concerned “can always just switch heads with another figure” (however, wary parents may want to consider the emotional effects of decapitating their children’s toys).

There are also studies suggesting that playing with Lego – or other toys designed to stimulate creativity, planning and building skills – can play a positive role in a child’s development.

Read more about why play is important.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Lego faces are getting angrier, study finds. The Guardian, June 12 2013

Do Lego Minifigures' have anger-management issues? Toy's faces are becoming less cheerful and more grumpy, fearful and disdainful, finds study. Daily Mail, June 13 2013

Lego faces are angrier now, study shows. The Daily Telegraph, June 13 2013

Links To Science

Bartneck, C, Obaid, M, Zawieska, K Agents with faces – What can we learn from Lego Minifigures? (PDF 1.7Mb) Proceedings of the 1st International Conference on Human-Agent Interaction. 2013

"Generation XXL" is the headline on the front page of Metro, as the results of a new study show that hospital admissions related to obesity in children have soared in recent years.

The study looked at English hospital admissions over a 10-year period for obese children and teenagers. It found that hospital admission rates for obesity and obesity-related health problems among children and young people have risen more than fourfold in the last decade, particularly among girls and teenagers.

Most admissions were not for obesity itself but for complications of obesity, including asthma, sleep apnoea (disturbed breathing during sleep), and pregnancy complications. The number of children having weight loss surgery has also risen sharply, with most operations being performed in teenage girls. However, the figures have remained low. There was just one admission in 2000 and 31 in 2009.

As the authors point out, some of this increase could be attributed to greater awareness and improved diagnosis of obesity-related conditions. Nevertheless, this reliable study makes disturbing reading and highlights the possibility that the "obesity epidemic" in children may be leading to health problems far earlier than previously expected.

Where did the story come from?

The study was carried out by researchers from Imperial College London, UK and the University of South Carolina, US. It was published in the peer-reviewed open access journal PLOS ONE. Its authors are funded by a number of public institutions, including the UK National Institute for Health Research.

The research was covered fairly in the media, with several reports including comments from independent experts. Somewhat surprisingly, none of the papers' coverage chose to denigrate the main group identified – obese teenage mums-to-be. The coverage may have been guided by a press release from Imperial College London that sensibly and accurately outlined the research.

What kind of research was this?

This study looked at national trends in hospital admissions associated with obesity and weight loss surgery among children and young people in England between 2000 and 2009.

The authors point out that although the recent steep rise in childhood obesity appears to be levelling off, national surveys suggest that about three in 10 children between the ages of two and 15 are overweight, and 14-20% are obese.

Obese children are at increased risk of conditions such as type 2 diabetes, asthma and sleep apnoea, while emerging evidence suggests they may also be at risk of cardiovascular disease.

The health consequences of childhood obesity could translate into large increases in demand for healthcare services, placing already stretched services under increased financial pressure.

What did the research involve?

The researchers used information from a national database which records all single episodes of NHS hospital admissions in England, including NHS-funded treatment performed in private hospitals. The database is called Hospital Episode Statistics and is freely available for everyone to look at.

For every admission, the database gives the main reason for admission (the primary diagnosis) and other health conditions that may contribute to the condition (the secondary diagnosis) using international disease codes. It also includes information such as gender and the age of the patient, as well as any procedures performed.

The researchers used data on planned or emergency obesity admissions in all children aged 5-19 between 2000 and 2010. The data included admissions for the management of obesity where obesity was the primary diagnosis and admissions for other health problems where obesity was thought to be a contributory factor (secondary diagnosis). They also identified children and young people who underwent weight loss (bariatric) surgery.

Three age bands – 5-9, 10-14 and 15-19 – were created to reflect key stages of childhood development, with children under the age of five excluded. They obtained population estimates for these three age groups for 2000-09 in England, stratified by sex. They then calculated the age- and sex-specific admission rates per million children for all years.

What were the basic results?

Between 2000 and 2009, researchers found that hospital admission rates in 5-19 year olds for total obesity-related diagnoses increased more than fourfold from 93 (95% confidence interval [CI] 86-100) per million children, to 414 (95% CI 410.7-417.5) per million children.

They say the increase was largely due to rising admissions in which obesity was mentioned as a secondary diagnosis. In just over a quarter (26.7%) of admissions, obesity was the main reason for admission (primary diagnosis), while for the remaining three-quarters (73.3%) obesity was a secondary diagnosis (contributing to the condition they were admitted for).

The researchers also found that:

• the average age of admission to hospital over the study period was 14 years
• admissions were more common in girls than boys (56.2% v 43.8%)
• the most common reasons for admission where obesity was a secondary diagnosis were sleep apnoea, asthma and complications of pregnancy
• the number of bariatric surgery procedures rose from one per year in 2000 to 31 in 2009, with the majority performed in obese girls (75.6%) aged 13-19 years

How did the researchers interpret the results?

The researchers point out that hospital admissions for obesity in children and young people have increased more than fourfold in the last decade, with more and more NHS resources being used to treat conditions associated with obesity.

They say public health action is needed both to quantify the scale of the problem more clearly and reverse the "obesity epidemic", thereby reducing the number of admissions caused by obesity.

Conclusion

This study is useful for monitoring national trends in the number of child hospital admissions for obesity and obesity-related conditions over the past decade.

However – as the authors point out – the study has some limitations. The quality of the data used relies on the accuracy of disease coding, and it is possible that obesity as a secondary diagnosis may sometimes be omitted. But this would lead to an underestimate of children admitted for obesity-related conditions, rather than the reverse.

Also, the big increase in obesity-related admissions may partly reflect increased awareness and improved diagnosis, rather than rising incidence of obesity.

The authors also point out that compared with admission rates for other common childhood diseases, admission rates for obesity are still small. Nevertheless, the results of this study make disturbing reading, and indicate that some of the health consequences of obesity may be felt in childhood as well as adulthood.

If you are worried that your child is obese, you need to take action now. If you don't, it is highly likely that your child's obesity will persist into adulthood, which can cause a range of serious complications.

Your GP or practice nurse can assess your child's weight and provide further advice on lifestyle changes. They may also be able to refer you to a local weight management programme for children, such as those run by the Weight Management Centre, MEND and Carnegie Weight Management.

These programmes are often free to attend through your local health authority, and typically involve a series of weekly group workshop sessions with other parents and their children. These workshops will teach you more about the diet and lifestyle changes that will help your child achieve a healthy weight.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

NHS swamped by fourfold rise in obese children cases. Metro, June 12 2013

Child obesity hospital admissions quadruple. The Daily Telegraph, June 12 2013

Rise in child obesity-related hospital admissions. BBC News, June 13 2013

Childhood obesity cases up four-fold in a decade: Nearly 21,000 aged five to 19 treated in hospital for weight-related conditions. Daily Mail, June 12 2013

Links To Science

Jones Nielsen JD, Laverty AA, Millett C, et al. Rising Obesity-Related Hospital Admissions among Children and Young People in England: National Time Trends Study. PLOS ONE. Published online June 12 2013

“A new test can reliably tell if an unborn baby has Down’s syndrome without putting it at risk,” Metro reports.

Screening for Down’s syndrome is currently offered to all pregnant women.

However, the current screening test has a false positive rate (that is, the results suggest a problem when the foetus is in fact healthy) of around 3-4%.
This means many women have needless invasive testing, using chorionic villus sampling (CVS) or amniocentesis. Both of these procedures carry around a one in 100 risk of causing a miscarriage.

If the false positive rate of the screening test could be reduced this would reduce the number of women who need invasive testing, resulting in fewer miscarriages.

This new screening technique involves analysing the small amounts of foetal DNA found in the mother’s blood stream.

After testing 1,005 women, researchers found the new technique had a much lower false positive rate (around 0.1%). This means many fewer normal pregnancies had an unnecessary invasive diagnostic test with the new test. However, in about 2% of women the new test did not produce a result, meaning that the conventional screening technique had to be used.

These results are promising, but until the findings are replicated in larger studies, it is unlikely the current national screening procedures will be changed.

Where did the story come from?

This research was carried out at King’s College Hospital and University College Hospital in London.

It was published in the peer-reviewed journal, Ultrasound in Obstetrics and Gynecology.

It was funded by The Fetal Medicine Foundation: a research, education and training charity. The Foundation is funded by an associated private clinic, which carries out ultrasound scans for pregnant women and donates all profits to the Foundation, and by private donations.

The research was covered by many news sources and generally, the findings were reported reasonably. However, there are a few inaccuracies.

Many of the news sources suggest the new test can pick up more foetuses with the conditions (is more sensitive) than the existing test. While previous studies have suggested that this might be the case, this was not the case in the current study. Both tests picked up the same number of cases where the screening tests were performed successfully.

However, the new test did not work on the blood sample for one pregnancy that turned out to be affected by Down’s syndrome, which was picked up by the existing screening test. Larger studies may provide a better estimate of how sensitive the new test is.

Some reports, including the BBC and Daily Mail correctly state that the current screening programme includes both an ultrasound scan and a blood test, but, The Daily Telegraph only states that ultrasound is used.

What kind of research was this?

This was a study looking at a new screening test for detecting three specific chromosomal abnormalities called ‘trisomies’ early in pregnancy. It compared this new test against an existing screening test. Both tests require women with at risk pregnancies to have an invasive diagnostic test to confirm the results.

Initial studies have suggested that the new screening test could reduce the number of women who needed to have the invasive diagnostic test, but still identify most of the affected foetuses.

In trisomies, foetuses carry all or part of an extra chromosome 21 (called trisomy 21 or Down’s syndrome), or chromosome 18 (called trisomy 18 or Edwards’ syndrome), or chromosome 13 (called trisomy 13 or Patau syndrome). These conditions are rare but Down's syndrome is the most common. All three conditions have a large impact on the health and development of the foetus, with the effects of Down’s syndrome generally less severe than the other two syndromes. Many babies with Edwards’ or Patau syndrome will miscarry or be still born, and those that survive to birth rarely live for longer than a year.

Currently, women are offered screening for Down’s syndrome in the first trimester of pregnancy. This screening involves what is called the “combined test” which includes an ultrasound scan to measure the thickness of the soft tissue at the back of the foetus’ neck and taking a blood sample to measure certain proteins in the mother’s blood. The results of this test and the mother’s age are used to calculate the risk of the foetus being affected by Down’s syndrome. The combined screening test picks up about 90% of foetuses with Down’s syndrome. This test also sometimes identifies foetuses with trisomy 13 or 18.

Women whose screening test results show that they are at higher risk of having an affected foetus are offered a diagnostic test to check whether the fetus does have Down’s syndrome. However, this confirmation involves an invasive procedure, either chorionic villus sampling or amniocentesis to collect cells from the foetus that are found in the placenta or in the fluid surrounding the foetus. The combined screening test picks up about 90% of foetuses with Down’s syndrome. This test also sometimes identifies foetuses with trisomy 13 or 18. The problem with both of these invasive procedures is that they is that they carry around a one in a 100 chance of causing a miscarriage.

Not all foetuses the combined test identifies as having an increased risk of Down’s syndrome have the condition. About 5% of pregnancies which are not affected by Down’s syndrome will have a combined test result suggesting they are at risk, they are called false positives.

Researchers would like to have a test returning fewer false positives, to reduce the number of women who have invasive testing unnecessarily.

The new screening test assessed in this study is based on testing the small amounts of foetal genetic material (DNA) found in the mother’s blood stream. This is now possible due to advances in DNA technology.

What did the research involve?

The researchers enrolled 1,005 pregnant women attending their clinic in London who were not having twins and were at the right time in their pregnancy to offer the screening tests.

Women in the study were between 20 and 49 years old. Most had conceived naturally (85.7%), with 11.6% having conceived by IVF and 2.7% having conceived after taking drugs to promote ovulation.

They took blood samples from the women at 10 weeks into their pregnancy to perform the new DNA-based screening test and part of the existing screening test (called the combined test), and at 12 weeks they performed the ultrasound needed as part of the combined test.

The analysis of the blood samples for the new DNA-based screening test was done in the US. The parents had counselling before the tests to explain what they were and what the implications of the findings might be. Both the existing and new screening tests evaluate how much risk a woman has of having a foetus affected by one of the three conditions.

For trisomy 18 and 21, the doctors relied on the results of the new DNA-based screening test to counsel the parents about their risk of having an affected baby and what their options were if they were at high risk. For example, if the DNA-based test suggested the women had low risk of these conditions, the women were reassured that their risk was low regardless of the result of the combined test.

For trisomy 13, because affected foetuses often have many abnormalities detected by ultrasound, which is part of the existing screening test but not the new screening test, the doctors used the results of both tests.

If the DNA-based screening test found that the foetus was at low risk, but the combined test suggested they were at very high risk, the parents were still advised to consider having invasive diagnostic testing. If the DNA-based test did not give a result then the result for the combined test was used.

Women who were not identified as being at high risk, or not found to have a trisomy on diagnostic testing, went on to have the usual second trimester ultrasound scan that looks for problems in the developing foetus.

What were the basic results?

The DNA-based test gave a result in about 95% of women (957 women), and failed on the first attempt in about 5%. The failed tests were repeated on a second blood sample for most of the women (40 out of 48 women) – they worked in this second sample for 27 of these 40 women.

The new screening test suggested that among the 984 women:

• 967 had very low risk (<0.01%) for all three trisomies
• 11 were at high risk (>99%) for trisomy 21 only
• five were at high risk (>99%) for trisomy 18 only
• one had an increased risk (34% risk) for trisomy 13 only

One woman whose pregnancy was at high risk for trisomy 21 had a miscarriage before her planned diagnostic test. The remaining 16 women whose pregnancies were identified as being at increased risk for trisomy all had CVS for diagnostic testing. Fifteen were confirmed as having the trisomy they had been predicted as being at high risk for.

One pregnancy predicted as being at high risk of trisomy 18 was not found to have a trisomy on diagnostic testing. This foetus was 20 weeks old at the time the paper was written and appeared to be normal in the second trimester ultrasound.

Assuming this foetus did not have trisomy 18, this would mean that the new test had a false positive rate of 0.1% – so one in 1,000 women without a trisomy pregnancy would be offered invasive testing.

One foetus did not have results for the DNA-based test but was found to be at high risk of trisomy 21 from the combined test and so had CVS and was found to have trisomy 21.

Overall, the combined screening test identified 5% of women (49 women) to be at increased risk of trisomy 21 (over 1% risk). Sixteen of these women were found to have a trisomy pregnancy on diagnostic testing.

This meant the test had a false positive rate of 3.4%, meaning that 34 in 1,000 women with a normal pregnancy would be offered invasive testing.

All of the cases of trisomy 13, 18, and 21 identified as being at increased risk by the DNA-based test were also identified as being at increased risk by the combined test.

The one pregnancy incorrectly identified as being at high risk of trisomy 18 by the new DNA-based test was not identified as being at increased risk on the combined test.

As well as the 16 women who had invasive diagnostic testing due to a high-risk result in the new screening test, invasive diagnostic testing was also carried out on four who had no result on the new test but were at high risk on the combined test, and 12 who had a low risk on both tests.

Most of the pregnancies without high risk on the screening tests or diagnostic testing (968 women) had not reached term at the time the paper was published. So it is not clear if any trisomies were missed in these pregnancies.

How did the researchers interpret the results?

The researchers concluded that routine use of the new screening test for trisomies 21, 18 and 13 at 10 weeks into pregnancy is feasible, and gives fewer false positive results than the existing screening test for trisomy 21. The results of the screening test still needed to be confirmed by invasive diagnostic testing.

Conclusion

The current study suggests that screening for trisomies 13, 18, and 21 using a DNA based maternal blood test may identify similar numbers of affected foetuses to the current screening test. However, the new screening test appears to be better at ruling out the condition in women with normal pregnancies, this means that fewer women would be offered unnecessary invasive diagnostic testing.

There are a few important points to note:

• Not all women in this study had given birth when the study was published, and these babies will need to be assessed to make sure that no cases of trisomy were missed.
• If this test does become more widely used, it is unlikely to be used on its own to screen for these trisomies. It is more likely to be used as part of an overall screening strategy for these conditions. For example, combined testing could be used in cases where the new test did not provide a result, and ultrasound is likely to continue to be used to identify those foetuses with abnormalities. It will be important to assess the overall potential effect of whatever screening strategy is proposed.
• The current test only looked at women at 10 weeks into their pregnancy, other studies would be needed to determine whether the test performed similarly at other stages in pregnancy.
• These three conditions are relatively rare, and therefore only a few women in this study had them. Larger studies are needed to confirm these findings, and the newspapers suggest that such studies are ongoing. These studies will also need to confirm what level of risk on this new test should be considered high, and prompt an offer of diagnostic testing.
• Invasive diagnostic testing is still needed to confirm the results, as although the false positive rate is much lower with the new test, it does still have some false positives – where a foetus is predicted as being at high risk but found to be unaffected.

The cost of the test (currently not conducted by labs in the UK) is quoted at £400 in the papers. This is likely to be too high a cost for all 700,000 pregnancies per year in the UK.

The researchers mention the possibility of only using the test in women who tested positive on the current screening test but before the invasive diagnostic test. This could cut down on the number of the new tests needed, and also reduce the need for invasive testing for some of the women who test positive on the combined test.

Alternatively, the news reports suggest the researchers hope the cost of the new test may fall.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Blood test for Down's syndrome detection hailed. The Independent, June 7 2013

New Down’s syndrome test offers ‘major increase in detection rate’. Metro, June 7 2013

New Down's syndrome blood test which can reliably detect if an unborn baby has genetic condition is to go on trial at two hospitals. Daily Mail, June 7 2013

New Down's syndrome blood test more reliable, say researchers. The Guardian, June 7 2013

New Down’s Syndrome blood test to go on trial. The Daily Telegraph, June 7 2013

Early Down's test 'more sensitive'. BBC News, June 7 2013

Links To Science

Gil MM, Quezada MS, Bregant B, et al. Implementation of maternal blood cell-free DNA testing in early screening for aneuploidies. Ultrasound in Obstetrics & Gynecology. Published online June 7 2013

"Babies practise frowning in the womb so they can show when they are unhappy after birth," reports the Daily Mirror.

The story comes from a small study that looked at '4-D' ultrasound scans of the facial movements of 15 unborn babies during the later stages of pregnancy. These 4-D scans combine detailed 3-D images over time. They can provide a real-time moving image of the baby while it’s still in the womb.

The researchers found that the babies, as they matured, showed more complex facial expressions including more complete signs of pain and distress. These signs included lowered brows, a wrinkled nose and parted lips. It is important to highlight that the study did not show that the babies were actually in pain.

The researchers’ theory is that the babies were just practising these expressions. As any sleep-deprived parent will tell you, crying is a newborn’s main method of communication. It may be the case that the babies were pulling faces to prepare for life after birth, which is an interesting, but still unproven, hypothesis.

Where did the story come from?

The study was carried out by researchers from the University of Durham and Lancaster University. There is no information about external funding. The study was published in the peer-reviewed open-access journal PLoS One.

The study was covered fairly in the media. Most papers pointed out the researchers’ conclusions that the unborn babies were not actually in pain – just practising “the faces they’ll need out in the big bad world” as the Daily Mail put it.

What kind of research was this?

This was a study of the facial movements of 15 foetuses during weeks 24 to 36 in the womb. Researchers aimed to show that foetal facial expression becomes increasingly complex from the second (around weeks 14 to 27) to third trimester (weeks 28 onwards) of pregnancy. In particular, they set out to test the theory that, as healthy foetuses mature, their facial movements can express recognisable signs of pain or distress.

They say that, with advances in treatments for babies still in the womb, the question of identifying foetal facial expressions, especially those of pain, is becoming increasingly important.

What did the research involve?

Researchers used 4-D ultrasound scans to observe the facial expressions of 15 healthy foetuses – eight girls and seven boys – during the second and third trimesters of pregnancy.

The faces and upper bodies of the unborn babies were scanned for 10 minutes at 24, 28, 32 and 36 weeks of pregnancy. The unborn babies were not stimulated during these observation periods.

Using an accepted system of coding, researchers had previously identified 19 facial movements that could be observed on foetuses and coded from the 4-D scans. In particular, they identified six facial movements shown to have a significant relationship to pain and distress and which have been used to identify pain in various populations. These were:

• lowering the brows
• nose wrinkling
• raising of upper lip
• deepening of nasolabial furrows (the furrows are the ‘smile lines’ running from the nostrils to each corner of the mouth)
• lips parting
• mouth stretch

They defined a combination of these expressions as the "pain/distress gestalt" (a "gestalt" is a combination where the whole is greater than the sum of its parts). In this case, researchers defined this as a pattern of co-ordinated movements that would be viewed by an observer as expressing pain or distress. This "gestalt", they say, is supported by previous research into facial expressions.

Using the coding system, the researchers analysed how often all 19 facial movements occurred simultaneously or within a second of each other. In particular, they wanted to know how often facial expressions included in the “pain/distress gestalt” occurred together.

They used standard statistical methods to analyse their results.

What were the basic results?

The researchers say the foetuses made “significant progress” towards more complex facial expressions, involving more co-occurring movements, as their gestational age increased. In particular, their analysis of facial movements thought to make up the “pain/distress gestalt” became more complete as the foetuses matured.

For example, at 24 weeks, three of the facial movements identified with pain expression co-occurred in only 5% of the “facial events” while, at 36 weeks, co-occurrence was observed in more than one-fifth (21.2%). However, the co-occurrence of five or more of these facial movements was rare at any age (0% at 24 weeks and 0.5% at 36 weeks).

How did the researchers interpret the results?

The researchers say the study shows it is possible for foetuses to show facial behaviours that can be determined as an expression of pain or distress. As the foetus matures, the combination of movements associated with pain or distress increases.

The researchers suggest that rather than indicating pain, the development of these expressions may have a role in preparing the foetus for life outside the womb and the need to alert carers to pain experiences. They theorise that the increasingly complex facial expressions, rather than a sign of distress, are actually a sign of healthy development. As such, the researchers suggest that they could be used to identify normal and abnormal development.

Conclusion

This study contributes to a fascinating field of research – the development of foetal facial expression. However, its conclusion that babies in the womb gradually develop complex facial expressions that indicate pain is based on observations of only a very small number of foetuses. Similarly, the researchers’ hypothesis that babies are “practising” pain/distress expressions for life once they are born remains a theory and one that would be extremely hard to prove.

It is also important to highlight that the study did not show that the unborn babies were actually feeling pain in the womb. The scanning was taking place when the mothers were at rest, in cases of healthy pregnancy, so there would be no particular reason for any of the babies to be in pain or distress.

It is far too soon to say whether, with future research, foetal facial expressions could one day be used to help doctors distinguish between normal and abnormal development.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on twitter.

Links To The Headlines

Babies practise crying in the womb, Durham researchers claim. BBC News, June 6 2013

Unborn babies practise the faces they'll need out in the big bad world! Scans show them grimacing and wrinkling their noses. Daily Mail, June 6 2013

Babies learn to grimace in the womb to prepare for pain after birth. Daily Mirror, June 6 2013

Unborn Babies Can Show Pain in The Womb. Sky News, June 6 2013

Links To Science

Reissland N, Francis B, Mason J. Can Healthy Fetuses Show Facial Expressions of “Pain” or “Distress”? PLoS One. Published online June 5 2013

The Daily Mail reports on the warning for pregnant women that household chemicals could pose a threat to their babies. ‘Don’t paint the nursery and avoid non-stick frying pans’ the Mail continues. 

The news is based on advice to pregnant or breastfeeding women in a report from the Royal College of Obstetricians and Gynaecologists (RCOG).

The report, titled ‘Chemical exposure during pregnancy: dealing with potential, but unproven, risks to child health’ warns that pregnant and breastfeeding women could be exposed to harmful chemicals through:

• food packaging
• ordinary household products
• medicines
• personal care items such as moisturisers

It is important to stress that the advice is framed in a safety-first approach. There is no credible evidence that any of the items listed above pose a threat to birth outcomes.

A large amount of uncertainty exists because carrying out studies to assess these risks is difficult. This is because virtually all pregnant women are exposed to certain chemicals as they are found in everyday products.

The report provides a list of recommendations and examples of how women can avoid these potentially harmful chemicals (such as to minimise purchasing household furniture, frying pans or cars – see below for more details).

However, these recommendations are based on little evidence of any risk to the child. It recommends women put ‘safety first’ and assume a risk is present even when it may be small or proven not to be harmful.

Reassuringly, the report does say that one option is for mothers to do nothing and acknowledges that it may be difficult to avoid certain exposures.

The advice has prompted criticism by some, arguing that causing stress during pregnancy could do more damage than a theoretical, and as yet unproven, risk of chemical exposure.

Who are RCOG?

The Royal College of Obstetricians and Gynaecologists (RCOG) is a professional membership organisation based in the UK. According to their website, they encourage the study and advancement of the science and practice of obstetrics and gynaecology (women’s reproductive health). They do this through education and training for their members as well as publication of clinical guidelines and reports for patients and practitioners working in this area.

According to the RCOG press release, the report has been produced by an RCOG Scientific Advisory Committee. It says these papers are up to date reviews of emerging or controversial scientific issues of relevance to obstetrics and gynaecology and that the papers are intended to raise awareness of such issues.

Why has this report been produced?

According to the report, no official advice or guidelines exist that inform women who are pregnant or breastfeeding of the potential risks that some chemical exposures could pose for their babies.

Co-author of the paper, Dr Michelle Bellingham from the University of Glasgow, says, ‘there is much conflicting anecdotal [single observations] evidence about environmental chemicals and their potentially adverse effects on developing babies.’

She adds, ‘The information in this report is aimed at addressing this problem and should be conveyed routinely in infertility and antenatal clinics so women are made aware of key facts that will allow them to make informed choices regarding lifestyle changes.’

What evidence did the report look at?

The report states there is some evidence linking exposure to some chemicals during pregnancy with negative birth outcomes. Encouragingly, it emphasizes that this evidence is only of an association and there is no evidence that one causes the other (causality). It also says that some studies show no association between chemical exposure and disease. This evidence is not provided in detail but links to the primary research are included in the report.

The report mentions that other studies looking at this issue have investigated the effects of chemicals on pregnant animals. However, as the report points out, it is often difficult to interpret animal research and caution should be exercised when trying to generalise these findings to humans. In part, because in some of these studies the animals are exposed to levels of chemicals that would never occur in a real world human setting.

The focus of the report, it says, was to provide examples of where chemical exposures can be avoided.

What recommendations did the report make?

The report recommends the best approach for pregnant women is ‘safety-first’. It says this is ‘to assume there is a risk present even when it may be minimal or eventually unfounded.’

Other recommendations provided in the report include:

• use fresh food rather than processed food wherever possible
• reduce use of food and drink in cans or plastic containers
• minimise the use of personal care products such as moisturisers, cosmetics, shower gels and fragrances
• minimise the purchase of newly produced household furniture such as fabrics, non-stick frying pans, and cars while pregnant or breastfeeding
• avoid paint fumes and all pesticides, such as fly spray
• only take over-the-counter medicines when necessary
• do not assume safety of all ‘natural’ named products

Despite this list of recommendations, the report acknowledges that it may be difficult for mothers to deal with the uncertainty of chemical exposure risks and that one option is do nothing.

How has the report been received?

It is fair to say that the report has not been universally well received. Many commentators have criticised the findings as being needlessly alarmist without providing any credible evidence of a threat posed by everyday chemical exposure. Ultimately the report, in the words of the critics, provides little in the way of useful advice.

Tracey Brown, of the Sense About Science charitable trust was quoted by BBC News as saying “Pregnancy is a time when people spend a lot of time and money trying to work out which advice to follow, and which products to buy or avoid. The simple question parents want answered during pregnancy is: 'Should we be worried?'

"What we need is help in navigating these debates about chemicals and pregnancy. Disappointingly, the RCOG report has ducked this."

Conclusion

Nervous mothers-to-be may want to take on board RCOG’s recommendations, though as previously mentioned, the evidence to back up these recommendations is lacking. It is important not to lose sight of established harms that are known to cause damage to a pregnancy:

• smoking
• drinking alcohol
• using drugs
• certain types of medication, such as medications used to treat epilepsy
• eating certain foods, such as pate or liver

Read more about health and wellbeing in pregnancy in the NHS Choices Pregnancy and baby guide.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Food packaging and furniture: What to avoid when you're pregnant. The Independent, June 5 2013

A mum-to-be? Don't paint the nursery and avoid non-stick frying pans: Pregnant women warned over risk to baby from exposure to chemicals. Daily Mail, June 5 2013

Expectant mothers told not to paint the nursery or use non-stick frying pans in case of chemical exposure. The Daily Telegraph, June 5 2013

Chemicals: a worry for pregnant women? BBC News, June 5 2013

Pregnancy safety advice prompts criticism. BBC News, June 5 2013

Pregnant Women Warned Of Chemical Exposure. Sky News, June 5 2013

Pregnant women warned over household products. ITV News, June 5 2013

“Mothers’ diets may harm IQs of two babies in three,” warns The Independent. The newspaper reports on its front page that iodine deficiency is widespread among pregnant women.

Iodine is recognised to play a role in the healthy development of the baby’s brain and nervous system while in the womb and the World Health Organization recommends that pregnant women eat iodine-rich foods.

Severe lack of iodine is one of the leading causes of brain damage in the developing world. But a new study, reported in most of the media today, suggests that even mild-to-moderate iodine deficiency during pregnancy may be associated with poorer cognitive function in the child.

In this large study, the iodine levels of pregnant women were measured, and their child’s IQ at age eight and reading ability at age nine were tested.

The researchers found that children of women who didn’t get enough iodine were more likely to be in the lowest quartile for verbal IQ, reading accuracy and reading comprehension. However, there was no significant difference in overall IQ.

A study of this kind has limitations, for example the fact that it relies on measurements being taken at a single point in time. Also, although the researchers adjusted for many factors that may have influenced the relationship (for example, parental lifestyle and socioeconomic factors), the study cannot prove a direct cause and effect relationship between a mother’s iodine consumption during pregnancy and her child’s cognitive ability. It is also not clear whether the differences seen in the children’s verbal and reading skills would translate into ‘real-world’ problems for these children.

Nevertheless, the study does highlight the need for pregnant women to get enough iodine during pregnancy.

Where did the story come from?

The study was carried out by researchers from the University of Surrey and the University of Bristol. No specific funding was reported for the current study, but researchers were supported by the Waterloo Foundation, the Commission of the European Communities, the US National Oceanographic and Atmospheric Administration and Wassen International. The latter is a company that makes and sells iodine supplements. However, none of these organisations had any role in how the study was conducted or how the collected data was interpreted.

This study used information taken from a much larger ongoing cohort study known as the Avon Longitudinal Study of Parents and Children (ALSPAC), which is looking at the health outcomes of children born during the 1990s. The ALSPAC study is supported by the Medical Research Council, the Wellcome Trust and the University of Bristol.

The study was published in the peer-reviewed medical journal The Lancet.

The media reporting is generally representative of the study, although the Mail Online headline writers got into a serious muddle. When they first published the story they used the headline “Drinking organic milk in pregnancy is 'vital for the baby's future brain power'". This was then changed later in the day – "Drinking organic milk in pregnancy could be harming baby’s IQ".

Neither claim is supported by this study. The study did not assess women’s dietary iodine intake from different sources. So it is not possible to say how many women drank organic milk and whether those who did were more likely to be in the iodine deficient group.

What kind of research was this?

The researchers say that the World Health Organization considers iodine deficiency to be “the single most important preventable cause of brain damage” worldwide. Iodine has a role in regulating the thyroid gland, and thyroid hormones have a role in brain and nervous system development. 

The researchers say that changes to dairy farming after the 1930s increased the amount of iodine in milk in the UK. After this and due to the reduction in cases of goitre associated with thyroid problems in the UK it was considered that iodine intake in the UK was sufficient.

However, some more recent UK studies have suggested that mild iodine deficiency may be quite common among adolescent schoolgirls and pregnant women.

The current study used data collected from participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort study to see whether there was an association between pregnancy iodine levels and child cognitive performance. The researchers speculated that women with lower iodine levels during pregnancy would have children with poorer cognitive outcomes.

What did the research involve?

The ALSPAC cohort was eligible to all pregnant women in southwest England with a due date between April 1991 and December 1992.

A total of 14,541 pregnant women were enrolled and 13,988 of their children survived for at least 12 months.

The researchers selected 1,040 women for whom they could measure iodine in the first trimester of pregnancy (up to 12 weeks) and their child’s IQ when they were eight years old.

Iodine was measured in a single urine sample. Urinary iodine levels are said to be a good indicator of iodine levels in the body as 90% of ingested iodine is excreted into the urine. However, the results would have been more accurate if the researchers had been able to measure iodine based on 24-hour urine collection.

To try to reduce the impact of this issue, the researchers looked at the iodine-to-creatinine ratio, which is said to be a good way to get a more accurate iodine measurement. The researchers defined adequate iodine as an iodine-creatinine ratio of 150 micrograms or more per litre. Iodine deficiency was sub-categorised as mild-to-moderate (50 to 150) or severe (less than 50).

Child IQ at the age of eight was assessed using a validated scale (the Wechsler Intelligence Scale for Children). At the age of nine psychologists also assessed children’s reading speed, accuracy and comprehension. 

The researchers looked at the association between pregnancy iodine status and IQ at the age of eight and reading at the age of nine. They adjusted analyses for a wide range of confounders including:

• mother’s age
• mother’s ‘parenting score’ (assessed by looking at cognitive stimulation of the baby, parental education and socioeconomic status)
• home environment, including baby’s emotional and cognitive environment
• family adversity
• stressful events during pregnancy
• infant birth weight and prematureness
• breastfeeding history
• maternal smoking and alcohol intake
• other dietary factors during pregnancy, including intakes of omega-3 fatty acids and iron

What were the basic results?

The researchers found that, overall, the women in the study had an average (median) urinary iodine concentration of 91 micrograms per litre, and average iodine-to-creatinine ratio of 110 micrograms per litre. About two-thirds of women in the study (67%) were iodine deficient in pregnancy. None of the women was using an iodine supplement.

Compared with mothers with adequate pregnancy iodine, those with iodine deficiency were significantly younger and less educated, but had less exposure to stressful life events in pregnancy.

Compared with children of women with adequate pregnancy iodine levels and after adjustment for confounders, children of women with iodine deficiency were at significantly higher risk of:

• having a verbal IQ score in the lowest quartile (odds ratio 1.58, 95% confidence interval (CI) 1.09 to 2.30)
• having a reading accuracy score in the lowest quartile (odds ratio 1.69, 95% CI 1.15 to 2.49)
• having a reading comprehension in the lowest quartile (odds ratio 1.54, 95% CI 1.06 to 2.23)

However, there was no significant association between pregnancy iodine deficiency and performance IQ or overall IQ score – only verbal IQ. There was also no significant association between iodine deficiency and reading score or number of words read per minute – only reading accuracy and comprehension.

How did the researchers interpret the results?

The researchers say that their results demonstrate the importance of having adequate iodine intake during early pregnancy. They say that the results “emphasise the risk that iodine deficiency can pose to the developing infant, even in a country classified as only mildly iodine deficient”. The researchers consider iodine deficiency during pregnancy to be an important public health issue that needs attention.

Conclusion

This is a valuable study that demonstrates that in this subsample of a large cohort of pregnant women in the UK, the majority had inadequate iodine levels during pregnancy.

They also found that this deficiency was associated with poorer verbal IQ in their children at the age of eight, and reading accuracy and comprehension at the age of nine.

The study benefits from its relatively large sample size, from the fact that it followed participants up over time and from the fact that it adjusted for extensive confounding factors.

However, there are some limitations to this study:

• As the researchers say, several 24-hour urine collections would have been the ideal way to measure iodine levels, rather than a single measure, but this would be impractical in a large-scale study.
• It would also be useful to continue to reassess the children’s IQ and reading performance at different time points, particularly as the associations were only found for certain measures of IQ and reading ability. Related to this, it is also unclear what impact these differences in verbal IQ and reading accuracy and comprehension would have had on the children’s learning and school performance. Children’s IQs are not thought to be fixed for life but can change over time.
• Studies in other population samples from other countries would be valuable.

The researchers note that a randomised controlled trial assessing the effect of iodine supplementation in pregnant women on child cognitive ability in areas with mild-to-moderate iodine deficiency would be valuable. They say that they hope to run such a trial in the UK, as current evidence from trials in this area is weak. 

Overall, the study highlights the need for pregnant women to obtain sufficient iodine during pregnancy. The World Health Organization recommends that pregnant and breastfeeding women consume 250 micrograms of iodine a day.

Dietary sources of iodine include dairy products and fish. Pregnant or breastfeeding women who are unable or unwilling to eat these types of iodine-rich dietary sources may need supplements.

If you are pregnant or breastfeeding and are concerned about your iodine levels, speak to your GP or midwife before taking supplements. Supplements will not be suitable for every woman.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Mothers' diets may harm IQs in two-thirds of babies. The Independent, May 22 2013

Iodine deficiency 'may lower UK children's IQ'. BBC News, May 22 2013

Women who drink organic milk in pregnancy could be harming their baby's IQ. Mail Online, May 22 2013

Enough iodine vital in pregnancy – study. The Guardian, May 22 2013

Links To Science

Bath SC, Steer CD, Golding J, et al. Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC) . The Lancet. Published online May 22 2013

"Bed-sharing 'raises cot death risk fivefold'," BBC News reports. The news has featured in much of the media, with headlines based on a large analysis of previous studies into the risk of cot death, or sudden infant death syndrome (SIDS), associated with bed-sharing.

Bed-sharing is where babies sleep in the same bed as their parents. It has long been known that bed-sharing with a parent who smokes or has consumed drugs or alcohol increases the risk of SIDS.

This new study aimed to see if bed-sharing still increased the risk of SIDS in the absence of these risk factors.

The researchers found a fivefold increase in the risk of SIDS associated with bed-sharing in breastfed babies who were under three months old, had parents who did not smoke, and when the mother had not had any alcohol or drugs.

The risk of SIDS was even higher when the parents smoked, drank or used drugs.

It is important to note that the researchers did not conclude that babies should not be brought into their parents' bed for comfort and feeding, only that they should not sleep in the same bed as their parents.

It is also important to be aware that the overall risk of SIDS is very small and it is a rare condition. However, there are simple steps parents can take to reduce the risk of SIDS (see box), and it is well worth following this potentially life-saving advice.

Where did the story come from?

The study was carried out by an international team of researchers from the London School of Hygiene and Tropical Medicine, the University of Glasgow and the Medical Research Council, UK; the Children's University Hospital, Ireland; the University of Auckland, New Zealand; and the University of Muenster, Germany.

No external sources of funding were reported, although the original research this report is based on was funded by a number of governmental bodies, charities and trusts.

The study was published in the peer-reviewed open access medical journal, BMJ Open.

The story was well reported by the media. 

What kind of research was this?

This study combined information from individuals in five large case-control studies. These studies had collected data on babies who died from SIDS (cases) and babies of a similar age who were still alive (controls).

The researchers were interested in bed-sharing specifically. The research aimed to resolve the uncertainty over whether there is a risk of SIDS associated with bed-sharing in breastfed babies where neither parent smoked. 

What did the research involve?

The researchers combined individual data from studies in the UK, Europe and Australasia. In total, information was collected for 1,472 babies who died from SIDS and 4,679 control infants, all under one year of age. Control infants were randomly selected normal infants of a similar age, from a similar location and born at a similar time.

The researchers estimated the risk associated with bed-sharing in relation to breastfeeding, smoking, and the mother's recent alcohol consumption or illegal drug use. This was after they had controlled for other important risk predictors, including:

• whether the baby slept in the parents' room or elsewhere
• the position in which the baby was put to sleep
• mother's age
• mother's relationship status
• the number of children the mother had had previously
• the baby's birth weight

What were the basic results?

The researchers found that 22.2% of cases and 9.6% of controls reported a history of bed-sharing. Bed-sharing increased the risk of SIDS fivefold (adjusted odds ratio [OR] 5.1, 95% confidence interval [CI] 2.3 to 11.4) compared with room-sharing (assuming the baby was placed on his or her back in a cot in the parents' room) when:

• neither parent smoked
• the mother did not drink
• the baby was less than three months old
• the baby was breastfed, and
• there were no other risk factors

The researchers estimate that the absolute risk of SIDS for room-sharing infants was 0.00008 (eight per 100,000) when neither parent smoked and the baby was less than three months old, breastfed, and had no other risk factors.

Bed-sharing increased the absolute risk of SIDS by 0.15 per 1,000. This means the absolute risk from bed-sharing was 0.00023 (0.23 per 1,000).

Bed-sharing, smoking and alcohol use all increased the risk of SIDS. However, the risks associated with bed-sharing decreased as the baby got older.

How did the researchers interpret the results?

The researchers concluded that, "Bed-sharing for sleep when the parents do not smoke or take alcohol or drugs increases the risk of SIDS. Risks associated with bed-sharing are greatly increased when combined with parental smoking, maternal alcohol consumption and/or drug use. A substantial reduction of SIDS rates could be achieved if parents avoided bed-sharing."

Conclusion

This large case-control study combined information from five studies to investigate the risk of sudden infant death syndrome (SIDS) associated with bed-sharing.

It found that bed-sharing is associated with a fivefold increase in the risk of SIDS compared with room-sharing for babies who were less than three months old, breastfed, sharing with non-smoking parents, and the mother had not had alcohol or drugs.

Smoking, alcohol and drug use are already recognised risk factors for SIDS and greatly increase the risk associated with bed-sharing.

The researchers have not concluded that babies should not be brought into the parents' bed for comfort and feeding. Rather, they advise that babies should not sleep in their parents' bed. It is also worth highlighting the very small actual risk of SIDS, both for non-sharing and bed-sharing babies.

Although this study was appropriately designed and controlled for, a number of potential factors that could affect the risk of SIDS and the causes of SIDS are not firmly established. This means that there may be other factors responsible for the observed increase in risk associated with bed-sharing.

To decrease the risk of SIDS, current advice recommends:

• putting your baby to sleep on their back – the safest place for them to sleep is in a cot in a room with you for the first six months
• do not smoke
• do not share a bed with your baby, particularly if you have been drinking or have taken drugs
• never sleep with your baby on a sofa
• do not let your baby get too hot and keep your baby's head uncovered
• if possible, breastfeed your baby

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Bed-sharing 'raises cot death risk fivefold'. BBC News, May 21 2013

Sudden infant death risk 'is five times higher if the baby sleeps in its parents' bed'. Daily Mail, May 20 2013

Sudden infant death risk greater when parents share bed with babies. The Guardian, May 20 2013

Parents warned sharing bed with babies increases risk of cot death. The Independent, May 21 2013

Sharing bed with babies raises cot death risk. The Daily Telegraph, May 20 2013

Cot Death Risks Of Babies Bed Sharing. Sky News, May 21 2013

Links To Science

Carpenter R, McGarvey C, Mitchell EA, et al. Bed sharing when parents do not smoke: is there a risk of SIDS? An individual level analysis of five major case–control studies. BMJ Open. Published online May 20 2013

“IVF advance triples couples' chances of having a baby”, The Daily Telegraph reports.

The innovation in question is actually based on an old imaging technique called time-lapse photography, where a camera is set to record a series of images at regular intervals. This technology is now available for monitoring the development of IVF embryos before they are transferred into the womb.

The researchers in this study developed a way of using the information collected to identify which embryos had a low or high chance of having an abnormal number of chromosomes (called aneuploidy). Aneuploidy can reduce the chances of embryos successfully implanting and resulting in a healthy live birth.

In this study, the researchers looked back at time-lapse imaging for embryos from 69 couples who had IVF. They wanted to know if their technique correctly identified embryos which were more likely to result in a pregnancy or live birth.

The time-lapse cameras allowed the researchers to potentially ‘screen’ embryos for risk of aneuploidy. From this, they would then be able to choose the low risk embryos for implantation.

The researchers found that 73% of the embryos their assessment would have classed as low risk resulted in a pregnancy at five to six weeks, and 61% resulted in a live birth. These rates were higher compared to the overall rate for all embryos (at any risk level), where the pregnancy rate was 42% and the live birth rate was 39%. However, it is important to restate that the new system was not used to intervene, so the results are based purely on observation.

While the results are promising, the technique is still in its early stages. Further research is needed to more widely test the technique and directly compare its results to standard methods.

Where did the story come from?

The study was carried out by researchers from CARE Fertility, an independent provider of fertility treatment and related services in the UK and Ireland. No sources of financial support were reported and the authors reported that they had no financial or commercial conflicts of interest.

The study was published in the peer-reviewed medical journal, Reproductive Biomedicine Online.

The study was well reported in the media, with BBC News coverage including an informative video to explain the technique.

However, potentially confusing figures are reported in other parts of the media.

The Times reported that the new technique “could give a 78% chance of success” while the Daily Mail reports that “Early trials show 78% of women having the test will have a healthy baby”.

The Guardian’s reporting suggests that “Doctors in Nottingham who devised the procedure say it could raise live birthrates at their clinic to 78%...” and this may be where this figure has come from.

However, this 78% figure does not come from the research paper itself, which reports that 61% of the low risk embryos successfully resulted in a live birth – not 78%.

What kind of research was this?

This study looked at whether the novel technique based on time-lapse images of IVF embryos might help select the embryos most likely to successfully produce a baby.

Until now, the researchers say that the vital decision about which IVF embryo should be selected and transferred into the mother’s womb is mainly based on between two and six observations of the developing embryo under the microscope.

To observe the embryo’s development, doctors have had to remove the culture dish containing the embryos from the very controlled environment of the incubator and place them under a microscope in the ambient air of the laboratory. This is usually only performed once a day to minimise disturbance to the embryo.

The authors of the study report that a major reason for IVF failure and miscarriage is that the implanted embryo has an abnormal number of chromosomes (aneuploidy). To accurately detect any chromosomal abnormality requires an invasive biopsy of the developing embryo, followed by genetic testing.

Currently it is not possible to reliably identify those embryos with an increased chance of aneuploidy with the normal microscopic observations of the embryo.

The current study tested a way of identifying the embryos at low risk of having abnormal numbers of chromosomal, using time-lapse imaging of the embryo. A relatively new system now allows doctors to obtain a stream of thousands of microscopic images of developing embryos (time-lapse images), without having to remove embryos from the incubator.

Using this system, the researchers previously found that embryos with an abnormal number of chromosomes take a different length of time to reach certain developmental stages than normal embryos. Based on this, they developed a method to identify those embryos at low, medium, and high risk of having an abnormal number of chromosomes.

In their current study, the researchers looked back at the results of IVF procedures where the embryos had been assessed using time-lapse imaging. They wanted to see if their method could identify those embryos which were more likely to go on to successfully implant, develop and be born.

It is important to note that the study did not actually use the method to select embryos for implantation – it only looked at what might have happened if the method had been used.

This is an appropriate first step for this type of research and, if the results are promising, the method would need to go on to be tested “for real” to select embryos, to see if it performed better than standard methods.

What did the research involve?

This study looked at the treatment outcomes for 88 embryos from 69 couples who attended the CARE Fertility clinic in Manchester between April 2011 and December 2012, and who had a known outcome from their IVF.

This meant that they knew if transfer of the embryo(s) had resulted in:

• failed implantation – where the woman had a negative pregnancy test
• clinical pregnancy – defined as the presence of a developing embryo with a heart beat at between six and eight weeks of pregnancy
• a live birth – identified through the mother completing a clinic delivery outcome form, which according to regulations is reported to the UK Human Fertilisation and Embryology Authority

The researchers excluded cases where two embryos were implanted but did not both have the same outcome, as they would not be able to tell which embryo had which outcome.

The egg cells collected from the women had been fertilised using intra-cytoplasmic sperm injection (ICSI), where a single sperm is injected directly into the egg. The fertilised eggs were then placed into the time-lapse incubator for culturing and imaging for five to six days.

The inbuilt microscope took images of the fertilised egg cell every 20 minutes. The image-analysis software recorded the precise timing of developmental events as they occurred. The embryos had been selected using standard existing methods before being transferred into the womb (that is, not using the new risk assessment method).

The researchers used this previously collected data model to assess the embryos, and grade whether the embryos were at low, medium or high risk of having an abnormal number of chromosomes. They then looked at what proportion of each of these three groups of embryos had achieved clinical pregnancy and live birth, and if this differed between the groups.

What were the basic results?

The researchers found that of the 88 embryos they assessed, 33 were at low risk for having an abnormal number of chromosomes, 51 at medium risk, and four at high risk.

Overall, 42% of the embryos successfully implanted and had a fetal heart beat at five to six weeks.

Among the low risk embryos, almost three-quarters (73%) successfully implanted and had a fetal heart beat at five to six weeks, compared to a quarter (25.5%) of medium risk embryos and no high risk embryos.

This meant that the 73% figure for low risk embryos is a relative increase of 74% compared with the rate for all embryos (42%) – what the media has translated as a ‘74% chance of successful pregnancy’.

The researchers had data on whether or not women had a live birth for 46 of the embryos (18 low risk, 26 medium risk, two high risk). The rest of the pregnancies had not reached term during the study period.

Overall, 39% of the embryo transfers resulted in a live birth. Among the low risk embryos, 61% resulted in a live birth. Among medium risk embryos, 19% resulted in live birth. None of the high risk embryos resulted in a live birth.

Therefore, the 61% figure for low risk embryos is a relative risk increase of 56% compared with the rate for all embryos (39%) – this is where media reports of the ‘increasing live birth rates to above 50%’ come from.

How did the researchers interpret the results?

The researchers say that their risk classification model using time-lapse imaging introduces a non-invasive way of selecting the embryos that are at a low risk of having an abnormal number of chromosomes. They say that this can result in higher likelihood of successful pregnancy and live birth.

Conclusion

This study reports on a new technique using ‘time-lapse imaging’ to non-invasively identify the IVF embryos least likely to have abnormal numbers of chromosomes.

An embryo having an abnormal number of chromosomes is one of the reasons IVF can be unsuccessful.

By looking back at the results of previous IVF procedures, the study showed that embryos identified as being low risk using the new method were the most likely to result in a live birth.

To date, IVF techniques rely on removing the embryo from the incubator about once daily over the course of five to six days to view its development under the microscope. As such, current methods only allow for a few static images which cannot give a reliable indication of whether an embryo has chromosome abnormalities, and also disturb the developing embryo. To select the best embryo for implantation, biopsies of the embryo have to be taken to examine the genes. The new technique potentially offers a non-invasive way to assess the risk of chromosome abnormality using detailed time-lapse images.

The results of this study are promising, but there are some limitations:

• It only assessed the outcomes for only 69 couples who received care at one fertility service. Larger numbers of embryos would ideally need to be assessed to confirm the results. Ideally, prospective studies comparing this new technique with standard techniques would also be carried out.
• The researchers note that their methods and results may not be directly transferable to other laboratories or other types of patient populations. 

The technique, while potentially promising, is still in an early stage of development. 

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

IVF could be revolutionised by new technique, says clinic. The Guardian, May 17 2013

'Most exciting breakthrough in IVF treatment in 30 years' could triple number of births. The Independent, May 17 2013

IVF advance triples couples' chances of having a baby. The Daily Telegraph, May 17 2013

IVF test that 'trebles the chance of a baby': Photo method helps doctors implant best embryo. Daily Mail, May 17 2013

IVF 'may be boosted by time-lapse embryo imaging'. BBC News, May 17 2013

New IVF Technique Could Triple Number Of Births. Sky News, May 17 2013

IVF time lapse photographing technique breakthrough could help avoid miscarriages and triple number of births. Daily Mirror, May 17 2013

New IVF technique using time-lapse photos to increase number of healthy births. Metro, May 17 2013

Links To Science

Campbell A, Fishel S, Bowman N, et al. Retrospective analysis of outcomes after IVF using an aneuploidy risk model derived from time-lapse imaging without PGS. Reproductive BioMedicine Online. Published online May 13 2013

"Children brought up by two parents are more intelligent," is the baseless claim on the Mail Online website.

The headline fails to mention that the research the story is based on involved only mice. Not until eight paragraphs into the news story does the Mail reveal this crucial point.

The scientific study involved housing baby mice with either their mother only, with both 'parents' or with their mother and a matched female 'parent'. These baby mice were then subjected to a series of tests designed to assess their development. After the testing, researchers took tissue samples from the brains of the mice.

The researchers found that:

• male mice housed with two parents seemed to have better threat-recognition abilities than those who were raised by a single mouse mum
• female mice housed with two parents seemed to have better motor co-ordination
• being housed with two parents did seem to affect brain development, although the pattern of development differed between male and female mice

Interesting as this is, it is hard to see how it applies to human families. This study cannot be used to conclude that children raised by one parent will have behavioural differences from, or will be less intelligent than, those raised by two parents.

Where did the story come from?

The study was carried out by researchers from the University of Calgary in Canada and was funded by the Canadian Institutes of Health Research and awards from Alberta Innovates Health Solutions.

The study was published in the peer-reviewed scientific journal PLOS one, which is free to read for all on an open-access basis.

The Mail’s story exaggerates the findings of this unusual animal study. Most of the article reads as if the research were directly relevant to humans or carried out in humans. The Mail encourages this idea by illustrating the story with a picture of a couple with their toddler. It is only in the eighth paragraph of the Mail’s report that the fact that the study was in mice is revealed. The paper offers no thoughts about how relevant research on mice is to humans.

However, much of the exaggeration in the Mail’s reporting can be traced back to a press release about the research issued by the University of Calgary.

What kind of research was this?

This was animal research aiming to investigate the effect that early life experiences can have on brain development, emotions and social behaviour.

In particular, the researchers were interested in the theory that low maternal care leads to changes in the area of the brain involved with memory and emotions (the hippocampus). This may then lead to increased stress and increased sensitivity to changes in emotion and mood (emotional reactivity).

They say that previous studies have shown that when pregnant rodents have been exposed to stress the female offspring developed a smaller hippocampus. As the effect was not seen in male offspring this suggested there may be some gender difference.

This study aimed to see whether parental care offered by two rodent parents rather than one had an effect on brain cell development. Further, the researchers wanted to see whether any changes in development had an effect on the behaviour of the offspring, and whether the effect was different in male and in female offspring. 

This study may be of interest to scientists and psychologists, and offers a possible insight into the factors that may influence animal brain development and behaviour. But it is hard to determine if, or how, the results can ever be applied directly to humans.

What did the research involve?

This research involved eight-week-old female and male mice, who were fed a normal diet and housed under 12-hour light/dark conditions. They were allowed to mate freely. Pregnant females were removed and placed in different parental conditions for the duration of pregnancy, through birth and until weaning at 21 days. In total, 269 animals were involved.

The three conditions were:

• maternal-only condition – the offspring were housed with their mother only
• maternal-virgin condition – the offspring were housed with their mother and an age-matched virgin female mouse
• maternal-paternal condition – the offspring were housed with the mated male-female pair

When housed under the three conditions the researchers observed the time that the parent mice spent in parenting behaviours, such as nursing, licking and grooming, and nest building.

When the offspring were weaned at 21 days they were housed with their littermates. They then completed a series of behavioural tasks ranging from least to most stressful. The tasks included:

• different maze tasks, including water mazes
• light-dark tasks (seeing how long mice spent in light and dark compartments when allowed to navigate freely)
• horizontal ladder tests (looking at how well they walked across the differently-spaced rungs of a ladder)
• tests of social preference (looking at interest in exploring different objects that stimulated the senses)
• tests of passive avoidance (of an electric shock)
• tests of fear conditioning (observing their time spent frozen and motionless when they were exposed to different shocks and sounds)

The researchers also examined tissue samples from the brains of the offspring mice to investigate any biological differences in their brain development.

What were the basic results?

Before weaning, the researchers observed that the parenting behaviour of the mother mouse was no different in the three conditions. Nor did the displays of parenting behaviour from the virgin-female and father-mouse differ from each other in those two respective conditions.

When the researchers worked out the average time spent licking and grooming the offspring (a marker of parental attention), the offspring in the two-parent conditions (either maternal-virgin or maternal-parent) received more attention than those in the maternal-only condition.

Overall, they found effects of parenting upon offspring behaviour and brain cell development differed between male and female offspring. In the various tasks, males raised in the two-parent conditions showed more fear conditioning, by displaying more freezing behaviour than males raised in the maternal-only condition. Meanwhile, females raised in the two-parent conditions showed better co-ordination when walking across the ladder than females in the maternal-only condition. The two-parent females also displayed more interest in exploring different objects.

This suggests that being raised in an environment with the biological mother and another adult mouse (male or female), may improve or accelerate some, but not all, developmental skills.

Two-parent care also had more effect on the male mouse brain. Male offspring in both the two-parent conditions had more growth of cells in a certain part of the hippocampus (the dentate gyrus). Parenting experience didn’t seem to have an effect on the hippocampus of the female offspring. However, females raised under the two-parent conditions did show greater proliferation of the white matter (the nerve fibres) of the brain.

How did the researchers interpret the results?

The researchers say that early life experiences can have an effect on brain development and behaviour, and that this persists through life. Male and female offspring appear to be affected in different ways.

They note in the abstract of their published research article (but do not describe in detail in the main research methods or results) that some of the brain development and behavioural advantages due to two-parent upbringing can stay with the mice throughout life and can be transmitted to the next generation.

Conclusion

This animal study suggests that male and female mice raised in two-parent conditions display differences in their brain cell development and behaviour compared with mice raised with only their mother.

While there are similarities between mice and men, it would be a mistake to assume that the findings in this mice study can be applied to humans. There are many important differences between the parenting of mice and people, and many differences in biology and social development that make it impossible to translate these findings to people.

Nonetheless, this study will be of interest to scientists and psychologists and offers a possible insight into the factors that may influence animal brain development and behaviour. Future research can build on these findings.

It should not be assumed from this study that children raised by one parent will have behavioural differences from those raised by two parents. The Mail Online also mistakenly suggests that this study supports the idea that children brought up by two parents are more intelligent. Apart from the fact that it was a rodent study, the study did not examine the ‘intelligence’ of the mice, so this assumption is groundless.

The main differences observed were that male mice from two-parent families seemed to freeze more when exposed to a perceived threat, and that female mice from two-parent families were more interested in exploring objects and better at walking over a ladder. It is a distortion of the evidence to conclude from this that children from two-parent families are more intelligent.

If you are shocked by the reporting of this study, first by the University of Calgary’s press office (or to be specific, its Hotchkiss Brain Institute) and then by the Mail Online, you may want to read about a study published in 2012. It found that half of all health reporting is subject to some sort of ‘spin’ with researchers and academic press offices shouldering a large proportion of the blame.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links To The Headlines

Children brought up by two parents are more intelligent - because they develop more brain cells. Mail Online, May 2 2013

Links To Science

Mak GK, Antle MC, Dyck RH, Weiss S. Bi-Parental Care Contributes to Sexually Dimorphic Neural Cell Genesis in the Adult Mammalian Brain. PLoS One. Published online May 1 2013