̽��ֱ�� of Cambridge - Ken Ong

Largest ever genetic study of age of puberty in girls shows links with weight gain

cjb250 — Mon, 01 Jul 2024 09:00:22 +0000

In the largest study of its kind to date, an international team led by researchers at the Medical Research Council (MRC) Epidemiology Unit, ̽��ֱ�� of Cambridge, studied the DNA of around 800,000 women from Europe, North America, China, Japan, and Korea.

Published on 1 July in Nature Genetics, the researchers found more than 1,000 variants – small changes in DNA – that influence the age of first menstrual period. Around 600 of these variants were observed for the first time.

̽��ֱ��age at which girls hit puberty and start having periods normally occurs between ages 10 to 15, though this has been getting earlier and earlier in recent decades. ̽��ֱ��reasons for this are not fully understood. Early puberty is linked with increased risk of a number of diseases in later life, including type 2 diabetes, cardiovascular disease, and certain cancers. Later puberty on the other hand, has been linked to improved health in adulthood and a longer lifespan.

Just under half (45%) of the discovered genetic variants affected puberty indirectly, by increasing weight gain in early childhood.

Corresponding author Professor John Perry said: “Many of the genes we’ve found influence early puberty by first accelerating weight gain in infants and young children. This can then lead to potentially serious health problems in later life, as having earlier puberty leads to higher rates of overweight and obesity in adulthood.”

Previous work by the team – together with researchers at Cambridge’s MRC Metabolic Diseases Unit – showed that a receptor in the brain, known as MC3R, detects the nutritional state of the body and regulates the timing of puberty and rate of growth in children, providing a mechanism by which this occurs. Other identified genes appeared to be acting in the brain to control the release of reproductive hormones.

̽��ֱ��scientists also analysed rare genetic variants that are carried by very few people, but which can have large effects on puberty. For example, they found that one in 3,800 women carry variants in the gene ZNF483, which caused these women to experience puberty on average, 1.3 years later.

Dr Katherine Kentistou, lead study investigator, added: “This is the first time we’ve ever been able to analyse rare genetic variants at this scale. We have identified six genes which all profoundly affect the timing of puberty. While these genes were discovered in girls, they often have the same impact on the timing of puberty in boys. ̽��ֱ��new mechanisms we describe could form the basis of interventions for individuals at risk of early puberty and obesity.”

̽��ֱ��researchers also generated a genetic score that predicted whether a girl was likely to hit puberty very early or very late. Girls with the highest 1% of this genetic score were 11 times more likely to have extremely delayed puberty – that is, after age 15 years. On the other hand, girls with the lowest 1% genetic score were 14 times more likely to have extremely early puberty – before age 10.

Senior author and paediatrician Professor Ken Ong said: “In the future, we may be able to use these genetic scores in the clinic to identify those girls whose puberty will come very early or very late. ̽��ֱ��NHS is already trialling whole genome sequencing at birth, and this would give us the genetic information we need to make this possible.

“Children who present in the NHS with very early puberty – at age seven or eight – are offered puberty blockers to delay it. But age of puberty is a continuum, and if they miss this threshold, there’s currently nothing we have to offer. We need other interventions, whether that’s oral medication or a behavioural approach, to help. This could be important for their health when they grow up.”

̽��ֱ��research was supported by the Medical Research Council and included data from the UK Biobank.

Reference
Kentistou, KA & Kaisinger, LR, et al. Understanding the genetic complexity of puberty timing across the allele frequency spectrum. Nat Gen; 1 July 2024; DOI: 10.1038/s41588-024-01798-4

Genes can indirectly influence the age at which girls have their first period by accelerating weight gain in childhood, a known risk factor for early puberty, a Cambridge-led study has found. Other genes can directly affect age of puberty, some with profound effects.

Many of the genes we’ve found influence early puberty by first accelerating weight gain in infants and young children. This can then lead to potentially serious health problems in later life

John Perry

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Portrait of a young girl writing in her diary

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One in 500 men carry extra sex chromosome, putting them at higher risk of several common diseases

cjb250 — Fri, 10 Jun 2022 07:56:38 +0000

In a study published in Genetics in Medicine, researchers analysed genetic data collected on over 200,000 UK men aged 40-70 from UK Biobank, a biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants. They found 356 men who carried either an extra X chromosome or an extra Y chromosome.

Sex chromosomes determine our biological sex. Men typically have one X and one Y chromosome, while women have two Xs. However, some men also have an extra X or Y chromosome – XXY or XYY.

Without a genetic test, it may not be immediately obvious. Men with extra X chromosomes are sometimes identified during investigations of delayed puberty and infertility; however, most are unaware that they have this condition. Men with an extra Y chromosome tend to be taller as boys and adults, but otherwise they have no distinctive physical features.

In today’s study, the researchers identified 213 men with an extra X chromosome and 143 men with an extra Y chromosome. As the participants in UK Biobank tend to be ‘healthier’ than the general population, this suggests that around one in 500 men may carry an extra X or Y chromosome.

Only a small minority of these men had a diagnosis of sex chromosome abnormality on their medical records or by self-report: fewer than one in four (23%) men with XXY and only one of the 143 XYY men (0.7%) had a known diagnosis.

By linking genetic data to routine health records, the team found that men with XXY have much higher chances of reproductive problems, including a three-fold higher risk of delayed puberty and a four-fold higher risk of being childless. These men also had significantly lower blood concentrations of testosterone, the natural male hormone. Men with XYY appeared to have a normal reproductive function.

Men with either XXY or XYY had higher risks of several other health conditions. They were three times more likely to have type 2 diabetes, six times more likely to develop venous thrombosis, three times as likely to experience pulmonary embolism, and four times more likely to suffer from chronic obstructive pulmonary disease (COPD).

̽��ֱ��researchers say that it isn’t clear why an extra chromosome should increase the risk or why the risks were so similar irrespective of which sex chromosome was duplicated.

Yajie Zhao, a PhD student at the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge, the study’s first author, said: “Even though a significant number of men carry an extra sex chromosome, very few of them are likely to be aware of this. This extra chromosome means that they have substantially higher risks of a number of common metabolic, vascular, and respiratory diseases – diseases that may be preventable.”

Professor Ken Ong, also from the MRC Epidemiology Unit at Cambridge and joint senior author, added: “Genetic testing can detect chromosomal abnormalities fairly easily, so it might be helpful if XXY and XYY were more widely tested for in men who present to their doctor with a relevant health concern.

“We’d need more research to assess whether there is additional value in wider screening for unusual chromosomes in the general population, but this could potentially lead to early interventions to help them avoid the related diseases.”

Professor Anna Murray, at the ̽��ֱ�� of Exeter, said: “Our study is important because it starts from the genetics and tells us about the potential health impacts of having an extra sex chromosome in an older population, without being biased by only testing men with certain features as has often been done in the past.”

Previous studies have found that around one in 1,000 females have an additional X chromosome, which can result in delayed language development and accelerated growth until puberty, as well as lower IQ levels compared to their peers.

̽��ֱ��research was funded by the Medical Research Council.

Reference
Zhao, Y et al. Detection and characterisation of male sex chromosome abnormalities in the UK Biobank study. Genetics in Medicine; 9 Jun 2022; DOI: 10.1016/j.gim.2022.05.011

Around one in 500 men could be carrying an extra X or Y chromosome – most of them unaware – putting them at increased risk of diseases such as type 2 diabetes, atherosclerosis and thrombosis, say researchers at the universities of Cambridge and Exeter.

Even though a significant number of men carry an extra sex chromosome, very few of them are likely to be aware of this

Yajie Zhao

Rost-9D (Getty Images)

3D illustration XY-chromosomes

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Study identifies hundreds of genes that influence timing of puberty and alter risk of several cancers

cjb250 — Mon, 24 Apr 2017 15:15:26 +0000

̽��ֱ��study, published today in Nature Genetics and led by researchers from the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge and other scientists in the international ReproGen consortium, also found new genetic evidence linking earlier timing of puberty to higher risk of several cancers known to be sensitive to sex-hormones in later life, including breast, ovary and endometrial cancers in women, and prostate cancer in men. These influences remained after controlling for body weight, which is important as body weight itself influences both the timing of puberty and the risk of some cancers.

Dr John Perry, Senior Investigator Scientist from the MRC Epidemiology Unit and senior author on the paper, says: "Previous studies suggested that the timing of puberty in childhood was associated with risks of disease decades later, but until now it was unclear if those were circumstantial observations, for example secondary to other factors such as body weight.

“Our current study identifies direct causal links between earlier puberty timing itself and increased cancer risk. This link could possibly be explained by higher levels of sex hormones throughout life, but we need to do more work to understand the exact mechanisms involved. We aim to understand these disease links and thereby contribute to the prevention of diseases in later life."

̽��ֱ��timing of puberty varies widely between individuals but tends to run closely within families. Earlier puberty timing may have advantages for some adolescents, for example for boys who engage actively in sports, but it appears to have largely negative effects on later health, such as higher risks of heart disease and some cancers.

By performing detailed assessments of genetic variants across the whole genome in 329,345 women, comprising data from 40 studies in the ReproGen consortium, UK Biobank, and consented 23andMe customers, this study identified 389 independent genetic signals for age at puberty in women. This observation was then confirmed in a further 39,543 women from the deCODE study, Iceland. Many of these genetic associations were also found to influence age at voice breaking, a comparable measure of puberty timing in men.

These findings shed light on the mechanisms that regulate puberty timing. Dr Perry adds: "These newly identified genetic factors explain one quarter of the estimated heritability of puberty timing. Our findings highlight the remarkable biological complexity of puberty timing, with likely thousands of genetic factors, in combination with numerous environmental triggers, acting together to control the timing of this key transition from childhood to adult life.”

Dr Ken Ong, also from the MRC Epidemiology Unit and joint senior author on the paper, says: "One of the more remarkable findings concerns the role of certain types of genes called imprinted genes, which are only active in your body when inherited specifically from one parent but not the other. We identified rare variants in two genes, which both lower the age of puberty when inherited from your father, but have no effect when inherited from your mother. This is intriguing as it suggests that mothers and fathers might benefit differently from puberty occurring at earlier or later ages in their children."

Reference
Felix R. Day, Deborah J. Thompson, Hannes Helgason et al. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. Nature Genetics; 24 April 2017; DOI: 10.1038/ng.3841

̽��ֱ��largest genomic analysis of puberty timing in men and women conducted to date has identified 389 genetic signals associated with puberty timing, four times the number that were previously known.

Our findings highlight the remarkable biological complexity of puberty timing, with likely thousands of genetic factors, in combination with numerous environmental triggers, acting together to control the timing of this key transition from childhood to adult life

John Perry

Jon Bunting

girl in the poppies

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Study identifies gene changes that influence timing of sexual behaviour

cjb250 — Mon, 18 Apr 2016 15:00:54 +0000

Age at first sexual intercourse is known to be influenced by social and family factors, such as peer pressure, but this study shows that genetic factors also have an influence on the timing of this sexual behaviour. It is known from other studies that first sexual intercourse at an early age is associated with adverse educational achievements, physical health and mental wellbeing.

To identify the gene differences which influence timing of sexual behavioural, the researchers at the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge analysed the genetic data of 59,357 men and 66,310 women aged between 40 and 69 years old part of UK Biobank, a national study for health research.

This analysis identified 38 gene variants that were associated with age at first sexual intercourse. Several of these gene variants were located in or near genes previously implicated in brain development and neural connections, and their analysis uncovered associations with a range of reproductive behaviours, such as age at first birth and number of children.

Dr John Perry, a senior investigator scientist at the MRC Epidemiology Unit, and a lead author of the paper, said: “While social and cultural factors are clearly relevant, we show that age at first sexual intercourse is also influenced by genes which act on the timing of childhood physical maturity and by genes which contribute to our natural differences in personality types.

“One example is a genetic variant in CADM2, a gene that controls brain cell connections and brain activity, which we found was associated with a greater likelihood of having a risk-taking personality, and with an earlier age at first sexual intercourse and higher lifetime number of children.”

In previous studies by the same team, it was found that an earlier age at puberty is linked to increased long-term risks for diseases such as diabetes, heart disease and some cancers.

Dr Ken Ong, a paediatrician and programme leader at the MRC Epidemiology Unit, and a lead author on the paper, added: “We have already shown that early puberty and rapid childhood growth adversely affect disease risks in later life, but we have now shown that the same factors can have a negative effect at a much younger age, including earlier sexual intercourse and poorer education attainment.”

̽��ֱ��team hope that taking account of the timing of puberty and personality type could lead to more targeted and effective approaches to health interventions and promotion of healthy behaviours.

̽��ֱ��research was funded by the MRC.

Reference
Day, FR et al. Physical and neuro-behavioural determinants of reproductive onset and success. Nat Gen; 18 April 2016; DOI 10.1038/ng.3551

Adapted from a press release from the MRC.

A study of over 380,000 people, published today in the journal Nature Genetics, has identified gene differences that influence the age of puberty, sexual intercourse and first birth.

While social and cultural factors are clearly relevant, we show that age at first sexual intercourse is also influenced by genes

John Perry

Amanda Slater

Cherries

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Opinion: Losing your virginity: how we discovered that genes could play a part

Anonymous — Fri, 15 Apr 2016 08:13:05 +0000

As far as big life decisions go, choosing when to lose your virginity or the best time start a family are probably right up there for most people. It may seem that such decisions are mostly driven by social factors, such as whether you’ve met the right partner, social pressure or even your financial situation. But scientists are increasingly realising that such sexual milestones are also influenced by our genes.

In a new study of more than 125,000 people, published in Nature Genetics, we identified gene variants that affect when we start puberty, lose our virginity and have our first child. This is hugely important as the timing of these events affect educational achievements as well as physical and mental health.

Children can start puberty at any time between eight and 14-years-old. Yet it is only in recent years that we have begun to understand the biological reasons for this. Through studies of both animals and humans, we now know that there’s a complex molecular machinery in the brain that silences puberty hormones until the right time. At this point, chemical messengers secreted from the brain begin a cascade of events, leading to the production of sex hormones and reproductive maturity.

Human genetics studies have identified many genes that are linked to individual differences in the onset of puberty. There are broadly two approaches used to map such genes – studies of patients affected by rare disorders that affect puberty and large-scale population studies. ̽��ֱ��former is helpful because it can investigate gene variants that cause extremely early or delayed/absent puberty.

In previous research, we used population studies to survey a large number of individuals using questionnaires and then genome-wide association studies to scan these same participants for common genetic differences. We could then assess whether the participants' reported age at puberty was related to particular gene variants. In this way, we have in a number of studies identified more than 100 such variants, each modifying puberty timing by just a few weeks. However, together they contribute substantially.

We now understand that both nature and nurture play a roughly equal role in regulating the timing of puberty. For example, studies have consistently shown that obesity and excessive nutrition in children can cause an early onset of puberty.

Genetic factors

However, we know far less about the biological and genetic factors behind the ages that we first have sexual intercourse or have a first child. This is because previous research has focused more on environmental and family factors than genetics. But the launch of UK Biobank, a study with over half a million participants, has greatly helped to fill this lack of knowledge.

In our new study, we used this data to survey some 125,000 people in the same way as in the puberty studies. We found 38 gene variants associated with the age of first sexual intercourse. ̽��ֱ��genes that we identified fall broadly into two groups. One category is genes with known roles in other aspects of reproductive biology and pubertal development, such as the oestrogen receptors, a group of proteins found on cells in the reproductive tract and also in behaviour control centres of the brain.

If you went through puberty early you are more likely to have many children in life. Tom Adriaenssen/wikimedia, CC BY-SA

̽��ֱ��other group includes genes which play roles in brain development and personality. For example, the gene CADM2, which controls brain activity and also has strong effects on whether we regard ourselves to be risk-takers. We discovered that this gene was also associated with losing your virginity early and having a higher number of children throughout life. Similarly, the gene MSRA, linked to how irritable we are, was also associated with age at first sexual intercourse. Specifically, people who are more irritable typically have a later encounter. However, more research is needed to show exactly how these genes help regulate the timing of the reproductive milestones.

We were also able to quantify that around 25% of the variation in these milestones was due to genetic differences rather than other factors.

Implications for public health

An important reason why we study reproductive ageing is that these milestones impact reproductive outcomes and also broader health risks. Epidemiological studies show that individuals who go through puberty at younger ages have higher risks of many diseases of old age, such as diabetes, heart disease and breast cancer. Similarly, first sexual intercourse at an earlier age is linked to a number of adverse behavioural, educational and health outcomes.

Using a statistical genetics approach called Mendelian Randomisation, a technique that helps clarify the causal relationship between human characteristics, these studies can tell us whether such epidemiological associations are likely to be causal rather than just random associations. We managed to show that early puberty actually contributes to a higher likelihood of risk-taking behaviours, such as sexual intercourse at an earlier age. It was also linked to having children earlier, and having more children throughout life.

These findings, along with previous studies linking early puberty and loss of virginity to social and health risks, back the idea that future public health interventions should aim to help children avoid early puberty, for example by diet and physical activity and avoiding excess weight gain. Our findings predict that this would have benefits both on improving adolescent health and educational outcomes and also for future health at older ages.

John Perry, Senior Investigator Scientist, ̽��ֱ�� of Cambridge and Ken Ong, Group Leader of the Development Programme at the MRC Epidemiology Unit, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

John Perry and Ken Ong (MRC Epidemiology Unit) discuss how sexual milestones are influenced by our genes and how this can impact on broader health risks.

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Greater understanding of polycystic ovary syndrome

jeh98 — Tue, 29 Sep 2015 10:44:08 +0000

In the largest genome wide association study (GWAS) into polycystic ovary syndrome (PCOS) to date, new research conducted by scientists at the ̽��ֱ�� of Cambridge and ten other institutions, including 23andMe, has identified genetic variants and causal links associated with PCOS, some of which might be relevant to informing positive lifestyle and treatment choices for women.

Published this week in the journal Nature Communications, this study looked at genetic information from more than 200,000 women.

”We estimate that one in every five women in the UK have polycystic ovaries and therefore research such as this is critical to advance our understanding and help us to better tackle the disease.” said Dr John Perry, of the Medical Research Council (MRC) Epidemiology Unit at the ̽��ֱ�� of Cambridge, and study co-lead. “Not only did we find new genetic markers for PCOS, and confirm some linkages seen in previous studies, but our analyses also help us to understand the underlying biology of the disease in more detail.”

̽��ֱ��study found that the risk of PCOS was increased by genetic variants that are known to act by increasing body mass index (BMI) and insulin resistance. ̽��ֱ��findings indicate that therapies that counteract these mechanisms could be beneficial in women with PCOS.

“Previous studies had suggested that weight loss has only partial benefits for women with PCOS,” said Dr Ken Ong, of the MRC Epidemiology Unit and study co-lead. “We recommend that new studies should be done to test whether more intensive efforts to reduce body weight and improve insulin resistance are effective in treating women with PCOS.”

In additional to these causal links, the study also identified new genetic variants that implicate three of the four epidermal growth factor receptors, which are known targets of some modern cancer therapies. This opens up new avenues of research into future treatments in PCOS. Another new variant identified in the FSHB gene (which encodes the beta subunit of ‘follicle stimulating hormone’ FSH), indicates that low levels of FSH may also contribute to the development of PCOS.

PCOS is a condition that impacts how a woman’s ovaries work. It is very common, affecting millions of women in the UK. It is a leading cause of fertility problems and is also associated with an increased risk of developing health problems in later life, such as Type 2 diabetes and high cholesterol.

̽��ֱ��researchers used genetic information from more than 5,000 women of European ancestry who are 23andMe customers, reported having PCOS and consented to research. ̽��ֱ��study also included another 82,000 women customers of 23andMe who also consented to research but do not have the condition. Those women were used as controls for the study.

Researchers also did follow up in 2,000 other women, whose PCOS had been clinically validated, and another 100,000 women without the condition. Those women were studied by the Icelandic company deCODE, by researchers at the Erasmus Medical Center in the Netherlands, and also at the Center for Human Genetic Research at Massachusetts General Hospital in Boston, USA.

Reference:

Felix R Day, et al. "Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome" Nature Communications 6 (29 September 2015).

A new genetic study of over 200,000 women reveals the underlying mechanisms of polycystic ovary syndrome, as well as potential interventions.

We estimate that one in every five women in the UK have polycystic ovaries and therefore research such as this is critical to help us to better tackle the disease

John Perry

Ed Uthman

Ovum in Cumulus Oophorus, Human Ovary

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Age of puberty in girls influenced by which parent their genes are inherited from

cjb250 — Wed, 23 Jul 2014 17:00:00 +0000

̽��ֱ��findings come from an international study of more than 180,000 women involving scientists from 166 institutions worldwide, including the ̽��ֱ�� of Cambridge. ̽��ֱ��researchers identified 123 genetic variations that were associated with the timing of when girls experienced their first menstrual cycle by analysing the DNA of 182,416 women of European descent from 57 studies. Six of these variants were found to be clustered within imprinted regions of the genome.

Lead author Dr John Perry at the Medical Research Council (MRC) Epidemiology Unit, ̽��ֱ�� of Cambridge says: “Normally, our inherited physical characteristics reflect a roughly average combination of our parents’ genomes, but imprinted genes place unequal weight on the influence of either the mother’s or the father’s genes. Our findings imply that in a family, one parent may more profoundly affect puberty timing in their daughters than the other parent.”

̽��ֱ��activity of imprinted genes differs depending on which parent the gene is inherited from – some genes are only active when inherited from the mother, others are only active when inherited from the father. Both types of imprinted genes were identified as determining puberty timing in girls, indicating a possible biological conflict between the parents over their child’s rate of development. Further evidence for the parental imbalance in inheritance patterns was obtained by analysing the association between these imprinted genes and timing of puberty in a study of over 35,000 women in Iceland, for whom detailed information on their family trees were available.

This is the first time that it has been shown that imprinted genes can control rate of development after birth.

Dr Perry says: “We knew that some imprinted genes control antenatal growth and development – but there is increasing interest in the possibility that imprinted genes may also control childhood maturation and later life outcomes, including disease risks.”

Senior author and paediatrician Dr Ken Ong at the MRC Epidemiology Unit says: “There is a remarkably wide diversity in puberty timing – some girls start at age 8 and others at 13. While lifestyle factors such as nutrition and physical activity do play a role, our findings reveal a wide and complex network of genetic factors. We are studying these factors to understand how early puberty in girls is linked to higher risks of developing diabetes, heart disease and breast cancer in later life – and to hopefully one day break this link.”

Dr Anna Murray, a co-author from the ̽��ֱ�� of Exeter Medical School, adds: “We found that there are hundreds of genes involved in puberty timing, including 29 involved in the production and functioning of hormones, which has increased our knowledge of the biological processes that are involved, in both girls and boys.”

̽��ֱ��study was supported in the UK by the Medical Research Council and the Wellcome Trust.

̽��ֱ��age at which girls reach sexual maturity is influenced by ‘imprinted’ genes, a small sub-set of genes whose activity differs depending on which parent passes on that gene, according to new research published today in the journal Nature.

In a family, one parent may more profoundly affect puberty timing in their daughters than the other parent

John Perry

Mario Orellana

Race to puberty (cropped)

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How does your baby grow?

amb206 — Mon, 31 Oct 2011 13:26:28 +0000

Ten years ago Cambridge ̽��ֱ��’s Department of Paediatrics launched a major research project to study the effects of the environment on the developing foetus and young infant. ̽��ֱ��Cambridge Baby Growth Study (CBGS) recruited 2,400 pregnant mothers to take part in the research. ̽��ֱ��study represents the most in-depth study of its kind world-wide in terms of the detail it captured.

̽��ֱ��data gathered by CBGS is providing a whole community of scientists – right from physiologists to psychologists – with a rich resource for understanding more about child development and how it is affected by the environment. Researchers in Cambridge and elsewhere are using the CBGS data to produce important findings in areas such as the foetal origins of adult disease, notably diabetes, and the onset of conditions that include obesity.

In the course of the research, scientists collected biological samples from the mother and child. These included maternal blood during pregnancy, paternal DNA, cord blood, placentas, breast milk and infant serum as well as infant blood taken at intervals up to the age of two. New technologies were developed to measure hormones and chemicals in tiny spots of blood taken using the heel prick technique to minimise invasiveness.

Participants brought their babies into the research clinic at the age of 12 months and 24 months. Before these visits food diaries were sent out for completion. These diaries were coded at the MRC’s Human Nutrition Research Centre using its in-house database system. ̽��ֱ��database contains nutritional information on many thousands of different food and drinks. Macro-nutrients such as fat, protein and carbohydrates, and micro-nutrients such as vitamins and minerals were analysed. Mothers kept detailed diaries which covered meals, home-made recipes and preparation methods as well as how much their child ate; this information is enabling researchers to understand more about the complex nutritional factors which may be influencing how babies grow and develop.

CBGS began as part of a European Union research project involving centres in six European countries. Its initial remit was to focus on the study of environmental chemicals, known as endocrine disrupters, on male reproductive health, which has become a major concern in recent years. Participants were recruited at the first pre-natal hospital visit. At this point the sex of the foetus was unknown. Rather than drop around half of the recruits when it became clear which were boys and which girls, CBGS decided to retain all the children.

“To lose about 50 per cent of our recruits would have been a huge wasted opportunity. So we decided to retain the girls as well as the boys and use the data to build a resource that could tell us a tremendous amount about early years’ development and its implications for health – and about the role of nutrition in particular,” said Professor Ieuan Hughes, Head of Paediatrics at Cambridge.

CBGS has already enabled scientists to learn more about the complex and often inter-related factors that might contribute to the development of male reproductive health problems and a number of life-threatening diseases.

Data gathered from the male infants studied points to a doubling of the incidence of undescended testes since the 1960s, with around six per cent of boys at birth experiencing this problem today. ̽��ֱ��anogenital distance (distance between the anus and the genitalia) has been defined as a marker of androgen (steroid hormone) exposure. A clinical study is underway to analyse the anogenital distance in 100 infants having surgery. Cases of undescended testes are also being analysed in relation to CBGS drawn from biological samples and lifestyle information.

̽��ֱ��study has also shown that infants formula-fed at three months have higher insulin-like growth factor levels and greater gains in weight, length, fat levels and body mass index than those who were breast-fed. Preliminary data suggests that energy intake at 12 months predicts gains in body weight and fat at 24 months. Further investigations are planned to take these findings further. A Baby Milk Feeding Programme – offering advice to mothers using formula – is being piloted.

As a spin-out from CBGS, paediatricians Dr Ken Ong (Cambridge MRC Epidemiology Unit) and Dr Carlo Acerini are recruiting infants at birth who are either born small or large. Many babies born large are infants of children whose mothers either have diabetes or have developed a diabetic tendency while pregnant. “Big babies who have been exposed to higher sugar levels than others in the womb seem to grow slowly initially but are more likely to be bigger children or adults. Babies born small often grow slowly but many tend to be shorter as children or adults,” said Dr Acerini.

“We will be looking at how environmental factors, hormones and inherited factors affect growth in these babies. If we can identify early markers, we can understand and predict later growth patterns. This will help us to find out which babies are at the higher risk.”

̽��ֱ��CGBS data is also being used to promote understanding of topics such as gender identity and autism. “Working with our colleagues in fields such as psychology and psychiatry – both at Cambridge and beyond - is an important aspect of the study as it allows us to build up as full a picture as possible of human development,” said Professor Hughes.

One of the strengths of CBGS is the way in which both researchers and research nurses have worked with parents and children to foster a research community linked by a newsletter. At a party held earlier this year to mark the tenth anniversary of the study, parents had the chance to hear first-hand from experts in areas such as glucose levels and infant growth.

A substantial part of the data was gathered by a team of five research nurses whose role was vital. ̽��ֱ��expertise of these nurses is recognised by the Food Standards Agency which uses the information they gather to get accurate data on what we eat as a population and to inform government policy. For the last three years of the study funding for the nurses came from the Mothercare Group Foundation.

“We need to retain the valuable and irreplaceable resources represented by our research nurses. ̽��ֱ��generosity of the Mothercare Group Foundation has allowed us to reach this point and we are determined to realise the fruits of such investment by taking the original study forward to cover the teenage years,” said Professor Hughes.

̽��ֱ��parents involved in CBGS saw their involvement in pioneering research as a chance to “give something back” to society and regarded the tracking of their children’s growth by professionals as an added benefit. Many parents said that taking part had been a fascinating experience and many have expressed a desire to continue with the study as their children grew up.

With so many parents willing for their children to be tracked through puberty, Professor Hughes is keen that the substantial foundation of data should be followed up with a second phase of the study.

“ ̽��ֱ��children we recruited in the first year of the study are now reaching ten and those we recruited most recently are now two years old. With our oldest children now approaching puberty, we have a unique chance to bring them back into the study in order to gather data that will enable us to address key questions about puberty – such as the onset of adult diseases and conditions,” he said.

Along with a number of centres in Europe, Professor Hughes and colleagues are currently making an application for EU funding for a large study of what has been described as the “exposome” - embracing everything that a human could be exposed to that influences health and well-being. It would include chemicals, food and genes among other factors. CBGS represents a well-documented population.

A follow-up study would enable researchers to look at the relationship between data gathered from the infants studied in the first phase (prenatal to two years old) and data gathered before and during puberty. An understanding of obesity and its prevention is one area where the study could make a valuable contribution by exploring how growth and development in early life might be related to later problems.

“Our investment in CBGS means that we are in a position to discover how we can reduce the health risks contained in our ever changing environment. Notably we will be able to learn how best to prevent the childhood obesity epidemic which is no longer just a scare mongering exercise: it’s a reality,” said Professor Hughes.

A study of infant growth, tracking 2,400 babies from gestation to the age of two, has provided data of unique depth – and is already adding to our understanding of the development of life-threatening conditions, including obesity. ̽��ֱ��Cambridge ̽��ֱ�� scientists who led the research now plan to follow the same children through another key phase of development - puberty.

Working with our colleagues in fields such as psychology and psychiatry allows us to build up as full a picture as possible of human development.

Professor Ieuan Hughes

Suzanne Smith

Weighing in for the Cambridge Baby Growth Study

Case studies

CASE STUDY 1 Lynne says: “My two daughters, who are now aged two and four, were part of the CBGS, the first child from 2007 to 2009 and the second from 2009 to 2011. I was approached to take part in the research while attending the antenatal clinic at 12 weeks’ pregnancy. I completed a detailed lifestyle questionnaire during my pregnancy and again three months after birth: this covered general health and also products used at home such as food and toiletries. I was given a detailed glucose tolerance test which gave more information than the standard prenatal test and provided some additional blood samples throughout the pregnancy. ̽��ֱ��girls' father also provided DNA samples. At birth, small samples of cord blood and placenta were taken; a sample of breast milk was also collected over the first three months. At intervals across two years, research nurses measured the girls’ growth, took abdominal ultrasounds to measure their fat and blood samples to analyse hormone levels. I kept food diaries recording details of each child’s diet at both one and two years of age. I’m keen to see the study continue so that my daughters, and others, can be followed through puberty. ̽��ֱ��girls will be able to make up their own minds whether they want to take part. I’ve kept all the newsletters so they will be able to read about the study so far. I hope they will agree to contribute to the continuation of this exciting research.”

CASE STUDY 2 Sarah says: “My son and daughter, who are now five and three, took part in the Baby Growth Study from 2006 to 2010. I was delighted to help with the research to further what we know about children’s growth and development and the factors which play a role in the health of a child. After a while we became well acquainted with the researchers and attending sessions was like catching up with old friends and it was interesting to hear about the latest developments in the project. It was great to attend the Baby Growth Study celebration party in May 2011, to meet other parents and children who were involved in the research and to hear about some of the results so far. During the study I was made more aware of potential factors which might affect children’s growth and development, such as exposure to cleaning products, hair dyes and paints. I avoided decorating my house during my pregnancies and while I was breast feeding, as a result of completing the environmental factors questionnaire! Keeping the food diaries made me think more carefully about my children’s diet. I am a GP and results of studies such as this will aid me, and fellow healthcare professionals, when advising patients in the future and will help us promote the healthiest lifestyle possible to ensure the next generation is as healthy as possible.

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