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FDA orders the market withdrawal of the only US premature birth drug

The move marks the first time the FDA has formally forced the removal of a drug

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The Food and Drug Administration has ordered the immediate market withdrawal of the only drug intended to prevent premature births in the US.

The drug, which remained available on the market for years despite data showing it was not effective, was the only drug approved in the US to help reduce the risk of early births in women with a history of preterm deliveries, according to ABC News.

The decision to withdraw it follows efforts by the pharmaceutical company Covis Pharma to keep Makena on the market while additional studies emerged.

In recent months, however, the drugmaker bowed to FDA pressure, proposing a “winding down” period of several months so that women taking the drug could complete their treatment.

The FDA rejected the proposal and said that the action against Makena and several generic versions should take effect immediately.

The decision by FDA Commissioner, Robert Califf, and the agency’s chief scientist marks the first time the FDA has formally forced the removal of a drug that it initially approved based on promising early data.

In all prior cases, drugmakers voluntarily pulled medications after the FDA made clear it intended to order removal.

The injectable drug is a synthetic version of the hormone progesterone, which helps the uterus sustain pregnancy.

The FDA expedited Makena’s approval in 2011 based on a study suggesting it reduced rates of premature birth in women who had previously had trouble bringing a pregnancy to term.

However, results from a 1,700-participant study conducted in late 2018 showed the drug neither reduced premature births — as originally thought — nor resulted in healthier outcomes for babies.

The FDA has been working to get the drug off the market since then, though Covis repeatedly appealed for more time to conduct further research.

In October, the company failed to convince a panel of outside FDA advisers that the drug should stay on the market for certain women.

Menopause

High street bakery chain Gail’s reveals menopause plan

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Gail’s has unveiled a menopause action plan offering new workplace support to thousands of staff ahead of legal reforms due in 2027.

The high street bakery chain will offer new benefits including 24/7 digital GP access and a new employee assistance programme, according to The Times.

It will also explore new online training for staff, including specific training for management.

Gail’s people director Miranda Burgum told The Times: “All we’re trying to do is talk freely and for it not to be a forbidden subject. It’s helping our managers and teams understand that this isn’t a taboo.”

“We’re going to develop the education with our managers, so it will be threaded through all our policies

“It will look at induction training, it will look at the types of people we need to make sure that we make reasonable adjustments for.

“And if somebody needs some sort of risk assessment, we’re going to be looking at [that].”

The move comes ahead of reforms due to be introduced in spring 2027 under the Employment Rights Act.

UK employers with 250 or more employees will be legally required to publish and update official menopause action plans.

The plans are intended to support employers to take effective action to improve workplace gender equality and support employees experiencing menopause.

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Pregnancy

Paracetamol use may impact future fertility, studies suggest

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Paracetamol use in pregnancy was not linked to autism or ADHD, while separate research found reproductive differences in girls exposed before birth.

One study analysed health records from more than 120,000 children and found no increased risk of autism following prenatal paracetamol exposure.

A separate analysis of nearly 100,000 children also found no increased risk of ADHD among those born to mothers who used the painkiller during pregnancy.

Researchers from the Hong Kong Hospital Authority examined electronic health records covering pregnancies between January 2001 and December 2023.

The autism analysis included 124,333 children, who were nine years old on average and split almost evenly between males and females. There were 3,445 autism diagnoses, representing 2.8 per cent of the group.

The ADHD analysis involved 97,285 children, who were seven years old on average and also split evenly between males and females. There were 5,168 ADHD diagnoses, representing 5.3 per cent.

Women prescribed paracetamol during pregnancy were more likely to be older and have pre-existing conditions including psychiatric disorders, as well as reasons for taking the drug such as infection, fever or chronic pain.

No association was found between prenatal paracetamol exposure and either autism or ADHD.

The findings did not differ according to the trimester in which paracetamol was taken or whether use was intermittent or daily. Advanced maternal age, defined as pregnancy in women over 35, did not alter the findings.

The researchers wrote: “Paracetamol remains a safe and essential analgesic [pain reliever] and antipyretic [fever reducer] during pregnancy, whereas alternatives, such as NSAIDs and opioids carry well-documented risks.

“Unwarranted reluctance to use paracetamol could lead to undertreatment of pain and fever, or the use of more harmful alternatives, both posing risks to the pregnancy and developing fetus.”

The authors said women should assess paracetamol use with guidance from their doctor.

A separate study involving 685 pregnant women without pre-existing conditions and 302 infant daughters found associations between prenatal paracetamol exposure and differences in reproductive organs and hormone levels.

Researchers from Copenhagen University Hospital enrolled the women during their first trimester and assessed them during the first trimester, third trimester and again when their babies were three months old.

At around three months, infants experience a temporary rise in reproductive hormones sometimes called mini-puberty.

Pregnant participants completed questionnaires every two weeks about their use of pain medicines including paracetamol. Infant girls underwent ultrasound scans of their reproductive organs and blood tests to measure hormone levels.

Researchers also examined a separate group of 1,210 girls followed from infancy to adolescence whose mothers reported paracetamol use during the third trimester.

Three-month-old girls exposed to paracetamol before birth had an average 40 per cent smaller ovarian volume, 13 per cent smaller uterine volume and 23 per cent fewer ovarian follicles.

Girls exposed during the first trimester also had lower levels of Anti-Müllerian hormone, a marker of ovarian function.

Among the older girls, those exposed before birth were more likely to have smaller uteruses at puberty and smaller ovaries during their teenage years.

Dr Margit Bistrup Fischer, lead study author and postdoctoral researcher in the Department of Growth and Reproduction at Rigshospitalet hospital in Denmark, said: “Animal studies have demonstrated that impaired formation of ovarian follicles can lead to reduced fertility and earlier reproductive aging.

“Whether the differences observed in our study have implications for fertility and age at menopause in humans remains unknown and will require long-term follow-up of the girls in our cohort.”

She cautioned that women who had used paracetamol during pregnancy “should not be alarmed by our findings”, as the study found associations rather than direct causation and outcomes for individual women and children are unclear.

“Importantly, our study does not evaluate whether [acetaminophen] causes reproductive problems, nor does it provide evidence that prenatal exposure affects future fertility or age at menopause,” she said.

“Although we observed similar associations in an independent cohort, long-term follow-up is needed to determine whether these early-life differences have any clinical significance later in life.”

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Insight

Research uncovers potential new target for breast cancer therapy

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Targeting CD1d altered immune cells slowed tumour growth and improved immunotherapy responses in mouse models of breast cancer, researchers found.

The findings suggest blocking the molecule could make the environment around breast tumours more favourable to anti-cancer immune responses.

Further work is needed to understand how these immune changes occur and how the approach could be safely used in patients.

Researchers from King’s College London, the Francis Crick Institute and University College London investigated how immune cells inside breast tumours influence cancer growth.

They focused on myeloid cells, a group of immune cells found in large numbers within tumours that can either support an immune attack against cancer or contribute to tumour growth and immune evasion.

The team examined CD1d, a molecule found on the surface of myeloid and other immune and tissue cells that helps regulate immune responses.

When CD1d was genetically removed from cells in a mouse model of breast cancer, the mice were more resistant to tumour growth. Researchers also saw changes in myeloid cell populations, including increased activity among cells that can help attack cancer.

The team then blocked CD1d using an antibody and again observed changes in myeloid cells and slower tumour growth. Blocking CD1d also improved responses to immunotherapy in the mouse model.

Researchers used single-cell RNA sequencing, a technique that examines gene activity in individual cells, to investigate the immune changes in more detail.

They identified a population of myeloid cells called monocytes that expressed genes associated with inflammation, an important part of the immune response. These cells were particularly important in restricting tumour growth in the mouse models.

A similar pattern of gene activity was identified in data from human breast cancer tumours. Its presence in myeloid cells was associated with positive responses to immunotherapy in breast cancer patients.

However, the findings in people were based on gene expression data and did not test CD1d-targeting treatment in patients.

Professor Patricia Barral, professor of immunobiology at King’s College London and senior author of the study, said: “Many breast cancers do not respond well to current immunotherapies.

“Our findings reveal a previously unrecognised mechanism by which immune cells within tumours are regulated.

“While CD1d is best known for helping immune cells recognise lipid molecules, we found that it also plays a role in shaping the behaviour of myeloid cells within tumours.

“These findings suggest that targeting the immune cells that surround and support tumours could boost anti-cancer immunity and potentially improve treatment responses in the future.”

Researchers now plan to investigate how the immune changes occur and how they can be safely harnessed in patients.

They also want to examine whether targeting CD1d could enhance existing treatments and influence treatment responses in different cancer types.

The work was supported by UKRI BBSRC, Breast Cancer Now and the Cancer Research UK City of London Centre.

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