Tag: pregnancy

Promising Zika Vaccine Protects Foetus in Animal Trial

Mosquito
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US researchers have shown that a Zika virus vaccine candidate is effective at preventing the Zika virus passing from mother to foetus in preclinical animal studies, according to a new study published in npj Vaccines.

“The vaccine has been shown to be safe for non-pregnant humans, but of course we need to know if it is safe and effective for the people at greatest risk: pregnant women and their fetuses,” said first author In-Jeong Kim, PhD, a viral immunologist at Trudeau Institute. “Our proof-of-concept studies conducted at Trudeau and Texas Biomed show very promising results that the vaccine given before pregnancy will provide high levels of protection for mothers and babies.”

The 2015–2016 Zika outbreak in Brazil and other countries in the Americas caused a surge in miscarriages and a constellation of birth defects, called Congenital Zika Syndrome, including abnormally small heads and neuro-developmental disorders.

“It’s important to test vaccines before the next large outbreak, because there will be another,” said senior author Jean Patterson, PhD, a virologist at Texas Biomed. “Zika is part of a family of viruses known to go through cycles. These viruses tend to spread rapidly through naïve populations that have never been exposed to the virus before, then infections drop down for years because most people have been exposed. As more and more people are born, there is a new group of naïve individuals in which the virus can once again wreak havoc. We want to help break that cycle.”

The purified, inactivated Zika vaccine (ZPIV) candidate was been tested in non-pregnant animals, showing it effectively clears the virus from blood. In Phase 1 human trials, it has been shown to be safe and elicit a protective immune response.

However for ethical and safety reasons, it is not possible to test whether the vaccine protects women and their foetuses from both infection and severe malformations, so animal models are used as a substitute.

Researchers tested the vaccine in pregnant mice and marmosets, respectively. The mouse studies, led by Dr Kim and Marcia Blackman, PhD, a viral immunologist at Trudeau, showed the vaccine prevented around 80% of foetal malformations, and neutralising antibodies were detected in foetal blood samples eight days after infection.

“We were able to detect maternal antibodies in the fetus during pregnancy and the results suggest the antibodies play a critical role in protecting fetuses from Zika virus,” Dr Kim said.

Marmosets are more sensitive to Zika infection than other nonhuman primates; previous research showed foetuses were aborted within two weeks of maternal infection.

In this study, four marmosets were immunised with the ZPIV vaccine and then exposed to Zika virus after they became pregnant. Only 1 of 12 offspring tested positive for Zika virus, demonstrating more than 90% effectiveness.

“Because the animals became pregnant at different times, our study was able to show the vaccine confers protection for at least 18 months after vaccination, which is important for showing long-lasting immunity,” Dr Patterson said.

The researchers are already testing what happens when the vaccine is administered during pregnancy.

“These studies add evidence that the Zika vaccine WRAIR developed not only protects animals against Zika virus infection, but also the congenital defects that mimic what has been observed in people,” says Kayvon Modjarrad, MD, PhD, who leads the US Army Zika vaccine programme. “Together with the early phase clinical trials, we believe these data lend even more support that this vaccine platform is a viable approach for countering the persistent threat of Zika.”

Source: Texas Biomedical Research Institute

After a Pregnancy, Natural Killer Cells Suppress Tumours

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After a pregnancy, breast cells call in Natural Killer T (NKT) cells as reinforcements to prevent tumours from arising, according to a study published in Cell Reports. This finding from the lab of Associate Professor Camila dos Santos at Cold Spring Harbor Laboratory (CSHL) illuminates a new way in which pregnancy reduces the risk of breast cancer.

Two lines of defence exist in the immune system: the innate response, which involves immune cells that attack any foreign molecule they encounter, and the adaptive response, which consists of immune cells that respond specifically to calls for help. NKT cells are a unique subset of cells that are present throughout the body which can participate in both responses. 

CSHL graduate student Amritha Varshini Hanasoge Somasundara said that after a pregnancy: “There is an increase in this specific [NKT] cell type, and only in the mammary gland. We don’t see the expansion everywhere else in the body, even though NKT cells are present everywhere else in the body.”

The team sought to uncover the reason behind the larger number of NKT cells were doing in the breast tissue. Hanasoge discovered that in mice, breast epithelial cells, which line lactation ducts, produce a specific protein called CD1d after pregnancy. If the cells did not present CD1d, no increase in NKT cells was seen in the tissue; the epithelial cells became cancerous and grew into tumours. Hanasoge and dos Santos think that CD1d molecules are calling in NKT cells to monitor the epithelial cells in the breast tissue after pregnancy. If they become cancerous, the NKT cells can quickly kill them to prevent tumour growth.

The team’s findings establish a novel link between pregnancy and the immune system in preventing breast cancer. They want to know how these findings can be translated into humans and what other factors may influence an abundance of NKT cells in breast tissue, such as aging and menopause, which are both associated with increased breast cancer risk.

Discussing the results, Associate Professor dos Santos said: “One of the hypotheses that we are working on now is: do pregnancies later on in life bring in the same expansion of the same subtypes of immune cells as pregnancies that took place early in life?”

Source: Cold Spring Harbor Laboratory

Smoking During Pregnancy Can Impact a Subsequent Pregnancy

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University of Southampton researchers have found that the link between smoking at the start of pregnancy and having a smaller baby may extend to future pregnancies.

The research team studied data between 2003 and 2018 for nearly 17 000 mothers who received antenatal care for their first two pregnancies. 

The findings, published in PLOS One, showed that, compared to non-smokers, women who smoked at the start of their first pregnancy were more likely to have a baby born smaller than expected in their second pregnancy. This held true even where they quit by the start of their second pregnancy.

The link between smoking during a pregnancy and that baby’s birth weight is well established. However, until now there has been limited evidence on the impact of maternal smoking on following pregnancies.

This study found that for women who smoked but did not smoke at the start of either pregnancy, there was no extra risk of a small for gestational age (SGA) baby in the second pregnancy compared to non-smokers. A mother who smoked ten or more cigarettes a day at the start of both of her first two pregnancies had the highest odds of SGA birth.

Study leader Dr Nisreen Alwan, Associate Professor at the University of Southampton, said: “It is important to encourage women to quit smoking before pregnancy and to not resume smoking after the baby is born. Resources that support mothers to quit and maintain smoking cessation are needed.”

First author Elizabeth Taylor said: “Women who smoke between pregnancies can reduce the risk of having a SGA baby by stopping smoking before the start of their next pregnancy. The period between pregnancies is when most mothers have close contact with health and care professionals and may require support to stop smoking.”

It is hoped that these findings and future research will encourage healthcare professionals and commissioners to provide better support to women before and between pregnancies, helping them to quit smoking, leading to better health for both mothers and children.

Source: University of Southampton

Cannabis Use in Pregnancy Predisposes Children to Stress and Anxiety

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Women who use cannabis during pregnancy, such as for stress and anxiety relief, may inadvertently predispose their children to stress susceptibility and anxiety, according to a study published in PNAS.

As cannabis continues to be legalised worldwide, many people mistakenly believe that cannabis use is without significant health risks. In line with this softening public opinion, cannabis has emerged as one of the most consumed recreational drugs of abuse during pregnancy, however the impact of maternal cannabis use on foetal and childhood development is unclear.

“We know that cannabinoid signaling plays a role in modulating stress, which is why some people use cannabis to reduce anxiety and relax,” said first author Professor Yoko Nomura at CUNY Graduate Center and Queens College. “But our study shows that in utero exposure to cannabis has the opposite effect on children, causing them to have increased levels of anxiety, aggression, and hyperactivity compared to other children who were not exposed to cannabis during pregnancy.”

Researchers examined placental gene expression and early childhood behaviour and physiology in a long-term study of 322 mother-child pairs who were drawn from an ongoing New York City-based study of stress in pregnancy started in 2009. When the children were approximately six years old, hormone levels were measured via their hair samples, electrocardiogram recordings were used to measure heart function during a stress-inducing condition, and behavioural and emotional functioning was assessed based on surveys administered to the parents.

The children of mothers who used cannabis during pregnancy showed higher anxiety, aggression, hyperactivity, and levels of the stress hormone cortisol, compared to children of non-cannabis users. Maternal cannabis use was also associated with a reduction in the high-frequency component of heart rate variability, which normally reflects increased stress sensitivity. In addition, RNA sequencing of placental tissue collected at birth in a subset of participants revealed that there was an association between maternal cannabis use and lower expression of immune-activating genes, including pro-inflammatory cytokines. The cannabis-related suppression of several placental immune-gene networks predicted higher anxiety in the children.

“Pregnant women are being bombarded with misinformation that cannabis is of no risk, while the reality is that cannabis is more potent today than it was even a few years ago. Our findings indicate that using it during pregnancy can have long-term impact on children,” said senior author Yasmin Hurd, PhD. “The study results underscore the need for nonbiased education and outreach to the public and particular vulnerable populations of pregnant women regarding the potential impact of cannabis use. Disseminating this data and accurate information is essential to improving the health of women and their children.”

Source: The Mount Sinai Hospital

Moderate Caffeine Intake May Reduce Gestational Diabetes Risk

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Pregnant coffee lovers can breathe a sigh of relief, as consuming a low amount of caffeine during pregnancy could help to reduce gestational diabetes risk, according to a new study published in JAMA Network Open.

“While we were not able to study the association of consumption above the recommended limit, we now know that low-to-moderate caffeine is not associated with an increased risk of gestational diabetes, preeclampsia, or hypertension for expecting mothers,” said the study’s lead author Stefanie Hinkle, PhD, an assistant professor of Epidemiology at the University of Pennsylvania.

The current recommendation from the American College of Obstetricians and Gynecologists (ACOG) is that pregnant women limit their caffeine consumption to less than 200 mg (about two cups) per day. The recommendations are based on studies that suggest potential associations with pregnancy loss and foetal growth at higher caffeine levels. However, there remains limited data on the link between caffeine and maternal health outcomes.

To better understand this association, researchers studied prospective data from 2529 pregnant participants from 2009 to 2013.

At enrollment and at each visit thereafter, women reported their weekly intake of caffeinated coffee, caffeinated tea, fizzy drinks, and energy drinks. Concentrations of caffeine were also measured in the participants’ plasma at 10 to 13 weeks into their pregnancies. The researchers then matched their caffeine consumption with primary outcomes: clinical diagnoses of gestational diabetes, gestational hypertension, and preeclampsia.

The research team found that caffeine at 10 to 13 weeks gestation was not related to gestational diabetes risk. During the second trimester, drinking up to 100 mg of caffeine per day was associated with 47% less diabetes risk. No statistically significant differences in blood pressure, preeclampsia, or hypertension between those who did and did not consume caffeine during pregnancy.

The findings are in line with research that found an association between and improved energy balance and decreased fat mass, the researchers noted. However, other constituents of coffee and tea such as phytochemicals could be the cause.

The group’s previous work has however shown that caffeine consumption during pregnancy, even in amounts less than the recommended 200 mg per day, was associated with smaller neonatal anthropometric measurements, according to Prof Hinkle.

“It would not be advised for women who are non-drinkers to initiate caffeinated beverage consumption for the purpose of lowering gestational diabetes risk,” she said. One meta-analysis found that any amount of caffeine was a risk to the foetus. “But our findings may provide some reassurance to women who already are consuming low to moderate levels of caffeine that such consumption likely will not increase their maternal health risks.”

Source: Penn Medicine

Cannabis Use during Pregnancy is on the Rise

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As cannabis becomes increasingly legalised, for medical or recreational purposes, its use during pregnancy is increasing, along with the potential for abuse or dependence.

A new study, published in JAMA Psychiatry, explored the magnitude and nature of cannabis use disorders during pregnancy by examining hospital discharge codes. Most of those hospitalisations were for childbirth.

The study found that the proportion of hospitalised pregnant patients identified with cannabis use disorder (defined as cannabis use with clinically significant impairment or distress) rose 150% from 2010 to 2018.

Largest such study so far
“This is the largest study to document the scale of cannabis use disorder in prenatal hospitalisations,” said study co-author Claudia Lugo-Candelas, PhD, assistant professor of clinical medical psychology in Columbia University’s Department of Psychiatry. She notes the study found that pregnant patients with the condition had sharply higher levels of depression, anxiety, and nausea – results of clinical concern.  

“It’s a red flag that patients may not be getting the treatment they need,” Dr Lugo-Candelas said.

Some pregnant patients use cannabis instead of prescribed medications, thinking it’s a safer choice as cannabis legalisation has eased safety fears. However, both the American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG) have recommended against using cannabis while pregnant, chiefly because of known and unknown fetal effects. Concerns for maternal effects focus on smoking or vaping risks, not mental health.

The study identified 249 084 hospitalised pregnant patients with cannabis use disorder, who were classified into three sub-groups: those with cannabis use disorder only; those with use disorders for cannabis and other controlled substances; and those with cannabis use disorder and other non-controlled substances (alcohol, tobacco). Data was matched against equivalent patients without any substance use disorders.

Mood disorders more common
Researchers found that those with the cannabis condition were more likely to be younger (ages 15 to 24), Black non-Hispanic, and to not have private insurance.

Researchers analysed patients records for depression, anxiety, trauma, and ADHD, and a broader category of mood-related disorders. Medical conditions measured included chronic pain, epilepsy, multiple sclerosis, nausea, and vomiting.

All disorder sub-groups had elevated rates of nearly every factor studied. Patients with cannabis use disorder alone had triple the levels of depression and anxiety than patients with no use conditions. Mood-related disorders affected 58% of those with cannabis use disorder compared to 5% without.

“The least other substance use you have, the more that cannabis use makes a difference,” Dr Lugo-Candelas said. “That’s really striking.”

High levels of were also seen in the cannabis use disorder hospitalisations, but whether that was due to patients using cannabis to mitigate nausea, or due to cannabis use, which can cause a vomiting syndrome, or a symptom of pregnancy is unknown. Study co-author Angélica Meinhofer, PhD, assistant professor of population health sciences at Weill Cornell Medicine, noted that many states allow medical use of cannabis for nausea and vomiting.

While screening for cannabis during pregnancy could help, doctors could be reluctant to ask about use due to mandatory reporting rules. Patient education could help get them treatment earlier, especially with co-occurring psychiatric problems.

“Hopefully these findings will motivate better conversations between pregnant patients and their health care providers,” said Meinhofer.

The authors stress they aren’t arguing for or against cannabis use in pregnancy. Research on prenatal effects of the disorder is still largely lacking, though frequent use has been linked to low birth weight and other adverse outcomes. Their study, the researchers say, instead underscores the need to further explore the disorder and its links to psychiatric and medical conditions.

The increase of cannabis use by pregnant patients demands immediate investigation. “This is a population that’s showing a level of distress that is very, very high,” said Dr Lugo-Candelas. “Care and attention need to be rolled out.”

Source: Columbia University Irving Medical Center

UN Urges Group B Streptococcus Vaccine to Protect Babies

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There is an urgent need for vaccines against Group B streptococcus, a major cause of preterm births, disability and infant mortality worldwide, according to a UN-backed report published on Wednesday.

Group B streptococcus (GBS) is a gram-positive bacteria that colonises the gastrointestinal and genitourinary tract. It can be transmitted in utero, is linked to around 150 000 infant deaths each year, more than half a million preterm births and significant long-term disability.

The report by the World Health Organization (WHO) and the London School of Hygiene & Tropical Medicine (LSHTM) updates 2017 estimates, and reveals that the global burden of GBS is far higher than was previously recognised.

“This new research shows that Group B strep is a major and underappreciated threat to newborn survival and wellbeing, bringing devastating impacts for so many families globally,” said Dr Phillipp Lambach, Medical Officer from WHO’s Immunization, Vaccines and Biologicals department.

The report is the first to quantify the major contribution of GBS to preterm births, and to neurological impairments such as cerebral palsy, hearing and vision loss, that can occur following infection.

Around 15% of all pregnant women worldwide, nearly 20 million annually, carry the GBS bacterium in their vagina, which can then spread to a foetus, or to newborns during labour. At present, GBS disease prevention in newborns is by administering antibiotic prophylaxis to women during labour, if the bacterium is detected during pregnancy.

However, significant health risks remain, as this intervention is unlikely to prevent most GBS-associated stillbirths, preterm births, or GBS disease that occurs later after birth.

“It is difficult to describe the breadth or depth of the grief when your child dies, or the accompanying guilt, and how it changes you, your family, and your relationships forever,” said Debbie Forwood, whose daughter Ada was stillborn after she developed a GBS infection.

Vaccine development urged
GBS burden is highest in low and middle-income countries, where screening and treatment are most challenging to implement, with regions such as sub-Saharan Africa having the highest rates of maternal GBS.
Now is the time for action, said Joy Lawn, an LSHTM Professor who contributed to the report.  While several candidate GBS vaccines are in development, none are yet available despite decades in the pipeline. The report calls for stepping up development of an effective GBS vaccine that could be administered to expectant mothers during routine pregnancy checkups.

The partners estimate more than 50 000 GBS-related deaths, and over 170 000 pre-term births, could be avoided if over 70 per cent of pregnant women were vaccinated.

Such protection could also be highly cost-effective, they added.  Net benefits from a year of maternal vaccinations could reach as high as $17 billion, accruing over several years, provided doses are affordably priced. For Ms. Forwood, this would be a bittersweet development.

“Only a GBS vaccine could have saved Ada.  When a vaccine can be widely rolled out, I will weep and scream with the unfairness that it came too late for her, and for all the other babies who are needlessly suffering and dying every year that it is delayed,” she said.

“But I will also weep with joy that in the future, many more will live, and their families will be saved from the living hell that is the death of a child.”

Source: UN News

Low Vitamin D in Pregnancy Can Raise Autism Risk

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Low maternal vitamin D intake during pregnancy can affect the development of autism in the child along with various other factors, according to a new study from the University of Turku, Finland, and Columbia University, USA.

The study, published in the Biological Psychiatry journal, included 1558 cases of autism spectrum disorder (ASD) and an equal number of matched controls born in Finland between January 1987 and December 2004, followed up until December 2015. 

Maternal vitamin D deficiency during pregnancy was linked to a 44% increased risk of ASD in the offspring, compared to women with sufficient vitamin D. 

The result persisted even when accounting for maternal age, immigration, smoking, psychopathology, substance abuse, the gestational week of blood draw, season of blood collection, and gestational age.

“The results are significant for public health as vitamin D deficiency is readily preventable,” said first author, Professor Andre Sourander from the University of Turku.

In previous work, the researchers had shown that vitamin D deficiency is also associated with increasede ADHD risk in the offspring. The serum samples were collected before the national recommendation for vitamin D supplementation during pregnancy was introduced in Finland. The current recommendation for pregnant women is a daily supplement of 10 micrograms of vitamin D throughout the year.

“Vitamin D deficiency is a major global problem,” Prof Sourander remarked.

Source: University of Turku

Consensus Statement Cautions on Paracetamol Use in Pregnancy

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A consensus statement by 13 doctors in different countries suggests that pregnant people only take paracetamol/acetaminophen if it is medically necessary, Their paper, published in the journal Nature Reviews Endocrinology, the group paracetamol/acetaminophen (APAP). 

In the same journal issue, an accompanying Editorial outlines the consensus statement and noting that its authors are not calling for a ban on the drug being used, instead they are suggesting that it be taken more cautiously by pregnant women because of a possible risk of birth defects.

Research in recent years has shown that it is possible under some circumstances for APAP to alter foetal development which can herald problems with neurological, urological and reproductive disorders in the baby – the authors found evidence of birth defects in 26 out of 29 studies. The authors call for more research into the possible problems with the drug’s use by pregnant women. They also acknowledge – as do several experts in a reaction piece published on the Science Media Centre site – that APAP is the only pain management drug available for pregnant women. And they point out that medical use of APAP is generally warranted when the mother experiences problems that can negatively impact her baby –  such as having a fever. But they also note that pregnant women’s APAP use appears to have crept up into general use as it has gained a reputation as being safe to use as an all-purpose painkiller.

The expert group and the authors of the new paper notably both point out that the recommendation does not differ from that already in use by most OB/GYNs – and similar wording generally appears on bottles of products based on APAP, such as Tylenol.

The consensus statement’s authors say their intention behind the article is to bring renewed and more focused attention to the possibility of APAP use leading to certain birth defects and the conditions under which they might arise. They note that current research has shown, for example, that the risk of harm seems to rise as the duration of APAP use goes up. In light of this, they suggest pregnant women consider using the drug for short term pain management, rather than as a long-term solution.

Source: Medical Xpress

Azithromycin Protects Pregnancies in Countries with Malaria

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A review has found that the common antibiotic azithromycin taken during pregnancy reduces low birth weight and premature births in countries where malaria is endemic.

The systematic review of 14 studies in African and Asia, published in The Lancet EClinicalMedicine, found that azithromycin, reduced low birth weight and prematurity but didn’t lower infant deaths, infections and hospital admissions.

Azithromycin, an inexpensive antibiotic widely used to treat chest and ear infections, has been specifically used in the past in pregnancy to treat STIs and, alongside other antimalarial drugs, to prevent adverse consequences of malaria on maternal and foetal outcomes and caesarean wound infections.

Murdoch Children’s Research Institute (MCRI) researcher Dr Maeve Hume-Nixon said it was not clear whether azithromycin would improve perinatal and neonatal outcomes in non-malaria endemic settings, and the potential harm on stillbirth rates needed further investigation.

Dr Hume-Nixon said these findings emphasised the importance of similar MCRI-led research currently being done in Fiji.

“This review found that there was uncertainty about the potential benefits of this intervention on neonatal deaths, admissions and infections, and potential harmful effects on stillbirth despite biological reasons why this intervention may have benefits for these outcomes,” she said.

“Therefore, results from studies like ours underway in Fiji will help to better understand the effect of this intervention on these outcomes.”

The Bulabula MaPei study is a randomised controlled clinical trial testing if azithromycin given to women in labour, prevents maternal and infant infections.

Globally, infections account for 21% of 2.4 million neonatal deaths per year and 52% of all under-five deaths, disproportionately occurring in low- and middle-income countries.

About five million cases of pregnancy-related infections occur in mothers each year as well, resulting in 75 000 maternal deaths.

MCRI Professor Fiona Russell said the large clinical trials in Africa and Asia, along with the MCRI-led trial in Fiji, were likely to inform global policy related to maternal child health and hopefully benefit infants and mothers around the world.

“Administration of azithromycin during labour may be a cheap and simple intervention that could be used to improve neonatal death rates in low and middle-income countries, alongside strengthening of maternal child health services,” she said. “This study, together with other large clinical trials, will add to evidence for the consideration of new international maternal and child health guidelines.”

Source: Murdoch Childrens Research Institute