̽��ֱ�� of Cambridge - Department of Obstetrics and Gynaecology

Newborn babies at risk from bacteria commonly carried by mothers

cjb250 — Wed, 29 Nov 2023 16:00:11 +0000

Streptococcus agalactiae (known as Group B Streptococcus, or GBS) is present in the genital tract in around one in five women. Previous research by the team at the ̽��ֱ�� of Cambridge and Rosie Hospital, Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, identified GBS in the placenta of around 5% of women prior to the onset of labour. Although it can be treated with antibiotics, unless screened, women will not know they are carriers.

GBS can cause sepsis, a life-threatening reaction to an infection, in the newborn. Worldwide, GBS accounts for around 50,000 stillbirths and as many as 100,000 infant deaths per year.

In a study published today in Nature Microbiology, the team looked at the link between the presence of GBS in the placenta and the risk of admission of the baby to a neonatal unit. ̽��ֱ��researchers re-analysed data available from their previous study of 436 infants born at term, confirming their findings in a second cohort of 925 pregnancies.

From their analysis, the researchers estimate that placental GBS was associated with a two- to three-fold increased risk of neonatal unit admission, with one in 200 babies admitted with sepsis associated with GBS – almost 10 times the previous estimate. ̽��ֱ��clinical assessment of these babies using the current diagnostic testing identified GBS in less than one in five of these cases.

In the USA, all pregnant women are routinely screened for GBS and treated with antibiotics if found to be positive. In the UK, women who test positive for GBS are also treated with antibiotics – however, only a minority of pregnant women are tested for GBS, as the approach in the UK is to obtain samples only from women experiencing complications, or with other risk factors.

There are a number of reasons why women in the UK are not screened, including the fact that detecting GBS in the mother is not always straightforward and only a small minority of babies exposed to the bacteria were thought to become ill. A randomised controlled trial of screening for GBS for treatment with antibiotics is currently underway in the UK.

Dr Francesca Gaccioli from the Department of Obstetrics & Gynaecology at the ̽��ֱ�� of Cambridge said: “In the UK, we’ve traditionally not screened mothers for GBS, but our findings – that significantly more newborns are admitted to the neonatal unit as a result of GBS-related sepsis than was previously thought – profoundly changes the risk/benefit balance of universal screening.”

To improve detection, the researchers have developed an ultrasensitive PCR test, which amplifies tiny amounts of DNA or RNA from a suspected sample to check for the presence of GBS. They have filed a patent with Cambridge Enterprise, the ̽��ֱ�� of Cambridge’s technology transfer arm, for this test.

Professor Gordon Smith, Head of Obstetrics & Gynaecology at the ̽��ֱ�� of Cambridge, said: “Using this new test, we now realise that the clinically detected cases of GBS may represent the tip of the iceberg of complications arising from this infection. We hope that the ultra-sensitive test developed by our team might lead to viable point-of-care testing to inform immediate neonatal care.”

When the researchers analysed serum from the babies’ umbilical cords, they found that over a third showed greatly increased levels of several cytokines – protein messengers release by the immune system. This suggests that a so-called ‘cytokine storm’ – an extreme immune response that causes collateral damage to the host – was behind the increased risk of disease.

̽��ֱ��research was funded by the Medical Research Council and supported by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.

Reference
Gaccioli, F, Stephens, K & Sovio, U et al. Placental Streptococcus agalactiae DNA is associated with neonatal unit admission and fetal pro-inflammatory cytokines in term infants. Nature Microbiology; 29 Nov 2023; DOI: 10.1038/s41564-023-01528-2

One in 200 newborns is admitted to a neonatal unit with sepsis caused by a bacteria commonly carried by their mothers – much greater than the previous estimate, say Cambridge researchers. ̽��ֱ��team has developed an ultra-sensitive test capable of better detecting the bacteria, as it is missed in the vast majority of cases.

In the UK, we’ve traditionally not screened mothers for GBS, but our findingsprofoundly changes the risk/benefit balance of universal screening

Francesca Gaccioli

Arteida MjESHTRI

Pregnant woman holding her stomach

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Risk of premature birth from smoking while pregnant more than double previous estimates

cjb250 — Wed, 27 Sep 2023 23:01:31 +0000

̽��ֱ��study, published today in the International Journal of Epidemiology, also found that smoking meant that the baby was four times more likely to be small for its gestational age, putting it at risk of potentially serious complications including breathing difficulties and infections.

But the team found no evidence that caffeine intake was linked to adverse outcomes.

Women are currently recommended to stop smoking and limit their caffeine intake during pregnancy because of the risk of complications to the baby. For example, smoking during pregnancy is associated with an increased risk of fetal growth restriction, premature birth and low birthweight, though it has also been linked to a reduced risk of preeclampsia (high blood pressure during pregnancy).

High caffeine intake has also been shown to be associated with lower birthweights and possibly fetal growth restriction. Caffeine is more difficult to avoid than cigarette smoke as is found in coffee, tea, chocolate, energy drinks, soft drinks, and certain medications.

Studies looking at the links between smoking, caffeine and adverse pregnancy outcomes tend to rely on self-reported data to estimate exposure, which is not always reliable. A more objective measure is to look at levels of metabolites in the blood – chemical by-products created when substances such as tobacco and caffeine are processed in the body.

Researchers at the ̽��ֱ�� of Cambridge and the Rosie Hospital, part of Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, recruited more than 4,200 women who attended the hospital between 2008 and 2012 as part of the Pregnancy Outcome Prediction (POP) study. ̽��ֱ��team analysed blood samples taken from a subset of these women four times during their pregnancies.

To assess exposure to cigarette smoke, the team looked at levels of the metabolite cotinine, which can be detected in blood, urine, and saliva. Only two out of three women with detectable levels of cotinine in every blood sample were self-reported smokers, showing that this measure is a more objective way of assessing smoking behaviour.

A total of 914 women were included in the smoking analysis. Of these, 78.6% were classified as having no exposure to smoking while pregnant, 11.7% as having some exposure and 9.7% as having consistent exposure.

Compared to women who were not exposed to smoking while pregnant, those with consistent exposure were 2.6 times more likely to experience spontaneous preterm birth – more than double the previous estimate of 1.27 from a meta-analysis of studies – and 4.1 times as likely to experience fetal growth restriction.

Babies born to smokers were found to be on average 387g lighter than babies born to non-smokers – that is, more than 10% smaller than the weight of an average newborn. This increases the risk that the baby will have a low birth weight (2.5kg or less), which in turn is linked to an increased risk of developmental problems as well as poorer health in later life.

Unlike in previous studies, however, the team found no evidence that smoking reduced the risk of pre-eclampsia.

Professor Gordon Smith, Head of the Department of Obstetrics and Gynaecology at the ̽��ֱ�� of Cambridge, said: “We’ve known for a long time that smoking during pregnancy is not good for the baby, but our study shows that it’s potentially much worse than previously thought. It puts the baby at risk of potentially serious complications from growing too slowly in the womb or from being born too soon.

“We hope this knowledge will help encourage pregnant mums and women planning pregnancy to access smoking-cessation services. Pregnancy is a key time when women quit and if they can remain tobacco free after the birth there are lifelong benefits for them and their child.”

Smoking cessation is offered routinely to all pregnant women and the NHS has local smoking cessation services for anyone, pregnant or not. Further information is available on the NHS website.

To assess caffeine intake, they researchers looked for the metabolite paraxanthine, which accounts for 80% of caffeine metabolism and is both less sensitive to recent intake and more stable throughout the day.

915 women were included in the caffeine analysis. Of these women, 12.8% had low levels of paraxanthine throughout pregnancy (suggesting low caffeine intake), 74.0% had moderate levels and 13.2% had high levels. There was little evidence of an association between caffeine intake and any of the adverse outcomes.

̽��ֱ��work was supported by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre and the Medical Research Council.

Reference
Selvaratnam, RJ et al. Objective measures of smoking and caffeine intake and the risk of adverse pregnancy outcome. International Journal of Epidemiology; 28 Sept 2023; DOI: 10.1093/ije/dyad123

Cambridge researchers have found that women who smoke during pregnancy are 2.6 times more likely to give birth prematurely compared to non-smokers – more than double the previous estimate.

We’ve known for a long time that smoking during pregnancy is not good for the baby, but our study shows that it’s potentially much worse than previously thought

Gordon Smith

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Surviving birth

lw355 — Thu, 10 Dec 2020 09:00:28 +0000

Researchers at one of the busiest maternity hospitals in the world aim to help more women survive complications giving birth.

Additional routine ultrasounds benefit mothers and babies, and could be cost saving, study finds

cjb250 — Wed, 17 Apr 2019 07:52:22 +0000

These are some of the conclusions of the Pregnancy Outcome Prediction study published this week in PLOS Medicine led by researchers at the ̽��ֱ�� of Cambridge.

Undiagnosed breech presentation — when a baby’s buttocks or feet emerge first at birth — increases the risk of perinatal morbidity and mortality. In current practice, fetal presentation is assessed by palpation of the maternal abdomen, but the sensitivity of this approach varies by practitioner. By routinely using ultrasound screening, undiagnosed breech presentation in labour could be avoided, lowering the risk of morbidity and mortality for both mother and baby.

In the new study, researchers performed research screening ultrasounds at 36 weeks’ gestation in 3879 women having first pregnancies in England. A total of 179 women (4.6%) were diagnosed with breech presentation by the research scan. However, in over half of these cases (55%) there was no prior suspicion that the baby was presenting in the breech position.

Making the diagnosis at 36 weeks allowed women to opt for an attempt at turning the baby, called external cephalic version. For the women who declined this procedure, or where it was unsuccessful, a planned caesarean section was arranged. None of the women opted to attempt a vaginal breech birth, which is known to be associated with an increased risk of complications, particularly in first pregnancies.

Across the UK, the analysis estimated that routine scanning could prevent around 15,000 undiagnosed breech presentations, more than 4,000 emergency caesarean sections and 7 to 8 baby deaths per year. If a scan could be done for less than £12.90 then it could be cost-saving to the NHS. This could be possible once midwives are instructed how to perform the simple technique, using inexpensive portable equipment.

Professor Gordon Smith from the Department of Obstetrics and Gynaecology at the ̽��ֱ�� of Cambridge, who led the study, said: “We believe the study highlights an opportunity to identify women at increased risk of a complicated birth. It seems likely that screening for breech presentation near term could be introduced in a cost-effective manner and this should be considered by the NHS and other health systems.”

̽��ֱ��research was funded by the National Institute for National Institute for Health Research.

Reference
Wastlund, D et al. Screening for breech presentation using universal late-pregnancy ultrasonography: A prospective cohort study and cost effectiveness analysis. PLOS Medicine; 16 April 2019; DOI: 10.1371/journal.pmed.1002778

Adapted from a press release from PLOS

Offering universal late pregnancy ultrasounds at 36 weeks’ gestation eliminates undiagnosed breech presentation of babies, lowers the rate of emergency caesarean sections, and improves the health of mothers and babies.

It seems likely that screening for breech presentation near term could be introduced in a cost-effective manner and this should be considered by the NHS and other health systems

Gordon Smith

Fotorech

Pregnant woman

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Baby’s sex affects mother’s metabolism and may influence risk of pregnancy-related complications

cjb250 — Thu, 12 Jul 2018 13:00:37 +0000

̽��ֱ��findings, published today in JCI Insight, help to explain, for example, why male babies in the womb may be more vulnerable to the effects of poor growth, and why being pregnant with a girl may lead to an increased risk of severe pre-eclampsia for the mother.

A team led by researchers at the Department of Obstetrics and Gynaecology, NIHR Cambridge Biomedical Research Centre, performed detailed scientific studies of more than 4,000 first time mothers and analysed samples of placenta and maternal blood.

They found that the genetic profile of the placentas of male and female babies were very different in relation to the baby’s sex. Many of the genes that differed according to the sex of the baby in the placenta had not previously been seen to differ by sex in other tissues of the body.

̽��ֱ��team found that one of these uniquely sex-related placental genes controlled the level of a small molecule called spermine. Spermine is a metabolite – a substance involved in metabolism – that plays an important role in all cells and is even essential for the growth of some bacteria.

Female placentas had much higher levels of the enzyme that makes spermine, and mothers pregnant with baby girls had higher levels of a form of spermine in their blood compared to mothers pregnant with baby boys.

Placental cells from boys were also found to be more susceptible to the toxic effects of a drug that blocked spermine production. This provided direct experimental evidence for sex-related differences in the placental metabolism of spermine.

̽��ֱ��researchers also found that the form of spermine which was higher in mothers pregnant with a girl was also predictive of the risk of pregnancy complications: high levels were associated with an increased risk of pre-eclampsia (where the mother develops high blood pressure and kidney disease), whereas low levels were associated with an increased risk of poor fetal growth.

̽��ֱ��patterns observed were all consistent with previous work which has shown that boys may be more vulnerable to the effects of fetal growth restriction and that being pregnant with a girl may lead to an increased risk of severe preeclampsia.

“In pregnancy and childbirth, the sex of the baby is at the forefront of many parents’ minds, but we do not even think of the placenta as having a sex. This work shows that the placenta differs profoundly according to sex,” says Professor Gordon Smith from the ̽��ֱ�� of Cambridge, who led the study.

“These differences alter elements of the composition of the mother’s blood and may even modify her risk of pregnancy complications. Better understanding of these differences could lead to new predictive tests and possibly even new approaches to reducing the risk of poor pregnancy outcome.”

̽��ֱ��work was supported by NIHR Cambridge Biomedical Research Centre and the Medical Research Council.

Reference
Gong, S et al. Placental polyamine metabolism differs by fetal sex, fetal growth restriction, and preeclampsia. JCI Insight; 12 July 2018; DOI: 10.1172/jci.insight.120723

̽��ֱ��sex of a baby controls the level of small molecules known as metabolites in the pregnant mother’s blood, which may explain why risks of some diseases in pregnancy vary depending whether the mother is carrying a boy or a girl, according to new research from the ̽��ֱ�� of Cambridge.

In pregnancy and childbirth, the sex of the baby is at the forefront of many parents’ minds, but we do not even think of the placenta as having a sex

Gordon Smith

Jerry Lai

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Zika warnings lead to ‘significant’ increase in demand for abortions in Latin America

cjb250 — Wed, 22 Jun 2016 21:00:51 +0000

However, in many of these countries, abortion is either illegal or highly restricted, leaving pregnant women with few options and potentially driving women to use unsafe methods, access abortion drugs without medical supervision or visit underground providers.

On 17 November 2015, the Pan American Health Organization (PAHO) issued an alert about the Zika virus in Latin America. Although the virus, spread by mosquitos, causes only mild symptoms, it can have serious complications for unborn children, ranging from eye and hearing defects through to microcephaly (abnormally small heads) and other severe fetal brain defects. Following the PAHO alert, several countries issued health advisory warnings, including urging women to avoid pregnancy.

For several years, one option for women seeking an abortion in Latin America has been Women on Web, a non-profit organisation that provides medical abortion outside the formal healthcare setting through online telemedicine, in countries where safe abortion is not universally available. A team of researchers from the US and UK analysed data on requests for abortion through the website between 1 January 2010 and 2 March 2016 in 19 Latin-American countries, assessing whether requests for abortion increased beyond expected trends following the PAHO alert.

̽��ֱ��researchers found that in almost all of the countries that had issued health warnings about Zika and had legal restrictions on abortions, the number of requests for abortion through Women on Web rose significantly – effectively doubling in Brazil, Ecuador and Venezuela, and increasing by over a third in most of the other countries. In countries that had issued no health warnings, there was no statistically-significant increase.

Assistant Professor Abigail Aiken from the ̽��ֱ�� of Texas at Austin, said: “Accurate data on the choices pregnant women make in Latin America is hard to obtain. If anything, our approach may underestimate the impact of health warning on requests for abortion, as many women may have used an unsafe method or visited local underground providers.”

Dr Catherine Aiken from the Department of Obstetrics & Gynaecology at the ̽��ֱ�� of Cambridge added: “ ̽��ֱ��World Health Organization predicts as many as four million Zika cases across the Americas over the next year, and the virus will inevitably spread to other countries. It isn’t enough for health officials just to warn women about the risks associated Zika – they must also make efforts to ensure that women are offered safe, legal, and accessible reproductive choices.”

̽��ֱ��research was supported by the National Institutes of Health and the National Science Foundation.

Reference
Aiken, ARA et al. Requests for Abortion in Latin America in the Wake of Zika Virus. NEJM; 22 June 2016. DOI: 10.1056/NEJMc1605389

Declaration of interests
Rebecca Gomperts is Founder and Director of Women on Web. James Trussell serves on the Advisory Board of Women on Web. Marc Worrell is an IT Consultant for Women on Web.

Health warnings about complications related to Zika virus significantly increased demand for abortions in Latin American countries, according to a new study published today in the New England Journal of Medicine.

It isn’t enough for health officials just to warn women about the risks associated Zika – they must also make efforts to ensure that women are offered safe, legal, and accessible reproductive choices

Catherine Aiken

Pan American Health Organization

Sin Zancudos no hay Zika - Cúcuta

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Maternal obesity and diabetes in pregnancy result in early overgrowth of the baby in the womb

cjb250 — Thu, 07 Apr 2016 23:02:40 +0000

Gestational diabetes is a condition that can affect women during pregnancy, with those who are obese at greater risk. As well as affecting the mother’s health, the condition also causes the unborn child to grow larger, putting the mother at risk during childbirth and increasing the likelihood that her offspring will develop obesity and diabetes during later life. ̽��ֱ��condition can usually be controlled through a combination of diet and exercise, and medication if these measures fail.

Women are screened for the condition through a blood glucose test at around 8-12 weeks into pregnancy. Current guidelines in the UK and the USA recommend that mothers found to be at greatest risk should then be offered a full test at between 24 and 28 weeks into pregnancy; however, in practice the majority of women are screened at the 28 week mark.

Researchers at the Department of Obstetrics & Gynaecology at the ̽��ֱ�� of Cambridge analysed data from the Pregnancy Outcome Prediction study, which followed more than 4,000 first time mothers using ultrasound scans to assess the growth of their babies in the womb. They measured the abdominal and head circumference of the foetuses and compared the growth in women who developed gestational diabetes with those who did not. ̽��ֱ��results are published today in the journal Diabetes Care.

Of the 4,069 women studied, 171 (4.2%) were diagnosed with gestational diabetes at or beyond 28 weeks. ̽��ֱ��researchers found no association between the size of the child at 20 weeks and the mother subsequently developing gestational diabetes. However, they found that the foetuses of women subsequently diagnosed with gestational diabetes grew excessively prior to diagnosis, between 20 and 28 weeks. Hence, the babies were already large at the time of diagnosis, and their findings suggest that the onset of fetal growth disorder in gestational diabetes predates the usual time of screening.

̽��ֱ��researchers also studied women who were obese, as it is well recognised that maternal obesity is a risk factor for childhood obesity. Even in the absence of diabetes, the babies of obese women were also twice as likely to be big at 28 weeks. ̽��ֱ��combination of obesity and gestational diabetes was associated with an almost 5-fold risk of excessive fetal growth by the 28 week scan.

“Our study suggests that the babies of women subsequently diagnosed with gestational diabetes are already abnormally large by the time their mothers are tested for the disease,” says Dr Ulla Sovio from the Department of Obstetrics and Gynaecology at the ̽��ֱ�� of Cambridge, the study’s first author. “Given the risk of complications for both mother and child from gestational diabetes, our findings suggest that screening women earlier on in pregnancy may help improve the short and long term outcomes for these women.

“Early screening may be particularly beneficial for obese women, as fetal growth is already abnormal by 20 weeks among these women. Any intervention aimed at reducing the risk of abnormal birthweight in the infants of obese women may need to be implemented even earlier.”

Senior author Professor Gordon Smith, also from the ̽��ֱ�� of Cambridge, adds: “We know that the offspring of women with gestational diabetes are at increased risk of childhood obesity, but so far no clinical trials have successfully demonstrated that screening and intervention in pregnancy reduces this risk. Our study suggests a possible explanation: screening and intervention is taking place when the effects of gestational diabetes are already manifested in the foetus.

“ ̽��ֱ��evidence from our study indicates that there is an urgent need for trials to assess the effect of earlier screening, both on the outcome of the pregnancy and the long term health for the offspring.”

Janet Scott, Research and Prevention Lead for the stillbirth charity Sands said: “We know from recent enquiries that failure to screen for gestational diabetes currently plays a part in a significant number of potentially avoidable stillbirths at term. Good risk assessment is crucial to avoiding harm to mothers and babies and we welcome these important findings which have real potential to inform better antenatal care for these high risk pregnancies. We are delighted to have supported this research, funded with donations from bereaved families.”

̽��ֱ��work was supported by the National Institute for Health Research (NIHR) Cambridge Comprehensive Biomedical Research Centre and SANDS (the stillbirth and neonatal death charity).

Reference
Sovio, U et al. Accelerated fetal growth prior to diagnosis of gestational diabetes mellitus: a prospective cohort study of nulliparous women. Diabetes Care; 8 April 2016; DOI 10.2337/dc16-0160

̽��ֱ��babies of obese women who develop gestational diabetes are five times as likely to be excessively large by six months of pregnancy, according to new research led by the ̽��ֱ�� of Cambridge. ̽��ֱ��study, which shows that excessive fetal growth begins weeks before at-risk women are screened for gestational diabetes, suggests that current screening programmes may take place too late during pregnancy to prevent lasting health impacts on the offspring.

Given the risk of complications for both mother and child from gestational diabetes, our findings suggest that screening women earlier on in pregnancy may help improve the short and long term outcomes for these women

Gordon Smith

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Pregnancy

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Risk of death higher if born outside working week

bjb42 — Thu, 15 Jul 2010 00:00:00 +0000

Together with colleagues from the ̽��ֱ�� of Glasgow and NHS National Services Scotland, Professor Gordon Smith of the ̽��ֱ�� of Cambridge analysed more than one million births and infant deaths in Scotland between 1985 and 2004.

They found the risk of neonatal death was 4.2 per 10,000 live births during the working week, compared with 5.6 per 10,000 at other times - a small but significant excess risk.

Although the researchers did not have access to information on the exact care provided during each birth, the study suggests the additional risk may be due to how many nurses and doctors are available at different times of day, as well as access to facilities such as operating theatres.

Addressing these issues could reduce the risk, Professor Smith says: "One approach may be to increase the provision of midwifery and obstetric staff to allow better staffing out of hours. Another may be to determine minimum levels of access to operating theatres and supporting staff at all times."

̽��ֱ��study is published this week in the British Medical Journal.

Babies born at night or at the weekend are at greater risk of dying due to lack of oxygen (anoxia) than those born during normal working hours, Cambridge researchers have found.

One approach may be to increase the provision of midwifery and obstetric staff to allow better staffing out of hours. Another may be to determine minimum levels of access to operating theatres and supporting staff at all times.

Professor Gordon Smith

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