Previous meta-analyses looking at the use of antidepressants during pregnancy and risk of neurodevelopmental disorders in children were conducted nearly a decade ago and limited by small study numbers and a lack of controlling for additional factors. This new meta-analysis provides the best evidence to date that the small increase in risk of autism or ADHD in the children of women who used antidepressants when pregnant identified in many studies is not caused by the medication.

“We know many parents-to-be worry about the potential impact of taking medication during pregnancy; our study provides reassuring evidence that commonly used antidepressants do not increase the risk of neurodevelopmental disorders such as autism and ADHD in children. While all medications carry risks, so too does stopping antidepressants during pregnancy due to an increased risk of relapse. Therefore, for women with moderate-severe depression, doctors and patients must carefully weigh the potential risks and benefits of continuing antidepressant treatment during pregnancy against the potential harms of untreated depression,” says author Dr Wing-Chung Chang, University of Hong Kong.

He continues, “Although our study found a small increase in the risk of autism and ADHD in the children of women who had used antidepressants during pregnancy, it also found that this risk disappeared when we accounted for other factors. The increased risk was also seen in the children of fathers who took antidepressants and of mothers with antidepressant use before, but not during, pregnancy. Together, this suggests that it is not the antidepressants themselves causing an increased risk in autism and ADHD but it is more likely to be due to other factors, including genetic predisposition to conditions such as ADHD, autism, and mental health conditions.”

Authors pooled data from 37 studies which included more than 600,000 pregnant women taking antidepressants and almost 25 million pregnancies with no antidepressant use.

Before controlling for key factors such as mental health conditions, the analysis found that antidepressant use by the mother during pregnancy was associated with a 35% increased risk of ADHD and a 69% increased risk of autism. However, this became greatly reduced or non-significant in analyses that better controlled for confounding factors. Use of antidepressants during pregnancy by the father was associated with a 46% increase in the risk of ADHD and a 28% increase in the risk of autism.

Among studies with analyses restricted to mothers with mental health disorders, all selective serotonin reuptake inhibitors (SSRIs) were found to not be associated, only amitriptyline/nortriptyline remained associated with increased ADHD and autism risk. Amitriptyline/nortriptyline are currently considered second or third options as treatments for depression and are often prescribed for treatment-resistant depression. Therefore, women treated with these may have more severe, chronic, or complex underlying mental health conditions than those receiving more common antidepressants, which could be influencing the association between amitriptyline/nortriptyline and increased ADHD and autism risk.

The study found no difference in risk between high and low doses of antidepressants.

“The evidence suggests a link between either parent having a mental health condition and a slightly higher risk of ADHD or autism. In addition to genetic factors, this link could be explained by the home and social environment as ongoing family stress, changes in how the family functions, and differences in how parents behave and care for their children may influence neurodevelopment. There is a need to ensure both parents have access to support and treatment for mental health conditions; for their own sake and to support neurodevelopment of their child,” says Dr. Joe Kwun-Nam Chan, University of Hong Kong.

The researchers note some limitations of their study, including that data on important factors such as socioeconomic status, lifestyle risk factors and low birth weight was lacking in the studies. Additionally, there was only a small number of studies looking at antidepressant use in specific trimesters or exact doses and dose changes, which makes it harder to draw conclusions about these. Finally, women who are prescribed antidepressants tend to have more severe depression than those who are not, so some bias may remain even after controlling for mental health status.

Writing in a linked Comment, Lisa Vitte, Emmanuel Devouche and Gisele Apter from University Rouen Normandy (France), who were not involved in the study, say, “Chang and colleagues’ study adds knowledge and confirms some of the pre-existing knowledge on the use of antidepressants during pregnancy: that they should continue to be taken as they protect maternal mental health and do not harm fetal development. This result is of considerable impact after many contradictory and controversial studies.”

There was no funding source for this study. The study was conducted by researchers from the University of Hong Kong.

The labels have been added to this press release as part of a project run by the Academy of Medical Sciences seeking to improve the communication of evidence. For more information, please see: http://www.sciencemediacentre.org/wp-content/uploads/2018/01/AMS-press-release-labelling-system-GUIDANCE.pdf. If you have any questions or feedback, please contact The Lancet press office at pressoffice@lancet.com

Quotes from Authors cannot be found in the text of the Article but have been supplied for the press release. The Comment quote is taken directly from the linked Comment.

https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(26)00089-1/fulltext

Pain and fever are common in early pregnancy and the options to manage them have been limited. Studies have raised safety concerns regarding acetaminophen while data on the safety of NSAIDs—which include widely used medications such as ibuprofen, diclofenac, and naproxen—has remained inconclusive.

The new study used data from the Southern Israeli Pregnancy Registry (SiPREG) to analyze 264,858 singleton pregnancies between 1998 and 2018, of which 20,202 (7.6%) were exposed to NSAIDs during the first trimester—most commonly ibuprofen (5.1%), diclofenac (1.6%), and naproxen (1.2%). Major congenital malformations were identified from linked clinical, hospitalization, and termination records. The researchers adjusted risks for maternal and pregnancy characteristics including maternal age, ethnicity, diabetes, obesity, folic acid use, and the reason for NSAID use.

NSAID exposure was not associated with major congenital malformations overall (8.2% vs. 7.0% in unexposed pregnancies; matched adjusted relative risk = 0.99), nor with malformations in specific organ systems including the cardiovascular, musculoskeletal, central nervous system, gastrointestinal, and genitourinary systems. No association was observed for any individual drug, and dose-response analyses found no significant link between cumulative NSAID exposure and birth defect risk.

“Our results provide reassuring evidence that NSAID use in early pregnancy is not associated with major birth defects,” the authors say. “These findings can help both pregnant women and physicians make informed decisions about managing pain and fever in early pregnancy.”

Dr. Daniel adds, “We used data from SiPREG, a large pregnancy registry in southern Israel that tracks medication use and pregnancy outcomes, including birth defects identified not only at birth, but also in pregnancy terminations and during the first year of life.”

“We examined whether common pain relievers from the NSAID group, such as ibuprofen, are linked to birth defects. We found no increased risk overall or for specific types of birth defects.”

Dr. Ariel Hasidim notes, “One of the most interesting parts of this research was finding a careful way to deal with gaps in real-world data. One key issue was that some people may have used common medicines like ibuprofen without it being recorded, which could affect the results. We tackled this head-on by using a special analysis to see whether and how this missing information might have influenced our findings.”

Paper available in PLOS Medicine: https://plos.io/4mGgtZ9

Citation: Hasidim AA, Ben Shitrit I, Idan D, Michael T, Levy A, Pariente G, et al. (2026) First-trimester nonsteroidal anti-inflammatory drugs exposure and risk of major congenital malformations: A retrospective register-based cohort study. PLoS Med 23(5): e1005063. https://doi.org/10.1371/journal.pmed.1005063

Author countries: Israel

Funding: The author(s) received no specific funding for this work.

The paper published online today highlights that ^99mTc-maraciclatide has potential as:

• A novel non-invasive diagnostic test, particularly for superficial peritoneal endometriosis (SPE), which cannot be reliably detected by conventional imaging techniques and currently requires laparoscopic surgery for definitive diagnosis
• A tool to enable disease monitoring, eliminating uncertainty around disease recurrence
• A marker of treatment response, empowering the development of novel therapies

^99mTc-maraciclatide is a gamma-emitting radiotracer that binds to αvβ3 integrin, which is upregulated during angiogenesis (new blood vessel formation), a cardinal feature of inflammatory diseases. The DETECT study describes, for the first time, the use of ^99mTc-maraciclatide as a potential tool for the visualisation and diagnosis of endometriosis.

Key findings:

• The DETECT study demonstrated a high correlation between locations of maraciclatide uptake and laparoscopy across all types of endometriotic lesions, including superficial peritoneal endometriosis (SPE). SPE is the earliest stage of endometriosis, which is found in 80 per cent of all laparoscopically diagnosed disease
• Imaging with ^99mTc-maraciclatide visualised endometriosis, detecting disease missed by conventional imaging methods
• Imaging results were concordant with the surgical presence or absence of endometriosis in 16/19 cases, with endometriosis imaged in 14/17 surgically positive participants, including two cases of thoracic endometriosis
• No false positives were reported in this study
• ^99mTc-maraciclatide imaging was able to detect lesions across all endometriosis subtypes supporting the applicability of the scan to various patient groups
• ^99mTc-maraciclatide was well tolerated and patient acceptability was high

Dr Tatjana Gibbons, lead author on the paper and investigator on the study from the Nuffield Department of Women’s and Reproductive Health, University of Oxford added, 

“These exciting findings indicate that maraciclatide offers a highly promising diagnostic and monitoring tool, particularly for superficial peritoneal endometriosis, which is the most common and yet the hardest type of endometriosis to identify.

“We are hugely grateful to the patients who have participated in the DETECT study without whom investigating this diagnostic approach would not have been possible.”

Professor Christian Becker, Co-Director of the Endometriosis CaRe Centre in Oxford, co-lead on the study and joint senior co-author on the paper, added:

“Novel, non-invasive diagnostic tests for endometriosis are a global research priority. The diagnostic challenge of endometriosis, which presents with varied and non-specific symptoms, is exacerbated by an absence of clinically validated biomarkers and the limitations of currently available imaging techniques. If these Phase II results are reproduced in the Phase III studies, maraciclatide has the potential to be an extremely valuable tool, as it could both reduce diagnostic delays and provide a validated endpoint for the development of new therapeutics.”

David Hail, CEO of Serac Healthcare, commented:

“The completion and publication of this clinical study marks a pivotal achievement for Serac Healthcare. These data, from a representative patient population, including women receiving hormone therapy, provide  evidence of maraciclatide’s anticipated real-world performance.

“With FDA Fast Track Designation and agreed Phase III study designs, we are now advancing to validate these findings in larger trials and progress to regulatory submission.”

Professor Krina Zondervan, Co-Director of the Endometriosis CaRe Centre, Head of Department at the Nuffield Department of Women’s and Reproductive Health, Co-theme Lead for the NIHR Oxford Biomedical Research Centre’s Surgical Innovation Theme, co-lead on the study and joint senior co-author on the paper, said:

“Superficial peritoneal endometriosis, the most prevalent subtype of endometriosis, currently evades reliable detection, leaving women no choice for diagnosis other than invasive surgery. If these results are confirmed in larger Phase III studies, imaging with maraciclatide could transform clinical research and practice and potentially empower the development of treatments for women across the globe.”

The study was co-led by Professor Christian Becker, Co-Director of the Endometriosis CaRe Centre in Oxford, together with Professor Krina Zondervan, Co-Director of the Endometriosis CaRe Centre and Head of Department at the Nuffield Department of Women’s and Reproductive Health at the University of Oxford. The study was funded by the  NIHR Oxford Biomedical Research Centre and Serac Healthcare. Scans were performed at the Royal United Hospital, Bath.

About the Phase 2 trial:

This was an exploratory, open-label, single-centre, phase 2 study evaluating preoperative imaging in 20 individuals with suspected or confirmed pelvic or thoracic endometriosis using a SPECT-CT, with intravenous ^99mTc-maraciclatide. The primary outcome was alignment of radiological and surgical findings in those patients completing both imaging and surgery. The surgical report on lesion type and location was compared to images for alignment.

Ten of the participants with SPE had prior imaging with traditional modalities (transvaginal (TV) ultrasound and/or MRI) in the last 12 months, none of which had detected SPE.

Phase III multi-centre international studies are due to start later this year.

That is the key finding from a new Washington State University study showing that recurring inflammation linked to the disease can sensitize the nervous system, driving lasting pain.

The work helps explain one of the most frustrating aspects of endometriosis, a condition in which tissue similar to the uterine lining grows outside the uterus. It affects more than 10% of reproductive-aged women, or roughly 190 million people worldwide, and often causes severe pelvic pain and infertility.

In a paper published in the Journal of Clinical Investigation, WSU scientist Kanako Hayashi and collaborators found that repeated cycles of inflammation can trigger lasting changes in the brain, amplifying and sustaining pain over time.

“We’re showing that this is not just a local gynecological disease,” said Hayashi, a professor in WSU’s School of Molecular Biosciences. “Once the system is sensitized, the brain keeps responding, even if the original lesions are gone.”

Endometriosis has long puzzled researchers because pain does not reliably match the extent of disease. Some patients with widespread lesions report little discomfort, while others with minimal tissue growth experience debilitating symptoms.

“That mismatch tells us something more complex is happening,” Hayashi said. “It’s not just the lesions themselves. It’s how the body and the nervous system respond over time.”

To investigate, the research team designed a model that mimics repeated menstrual cycles. Most previous studies induced endometriosis-like conditions only once. Hayashi’s group instead introduced multiple cycles, simulating the repeated backflow of menstrual tissue called retrograde menstruation, thought to contribute to the disease.

Mice exposed to repeated cycles showed heightened sensitivity and lasting changes in the nervous system. Inflammation increased in the pelvic region, and signals traveled along nerve pathways to the spinal cord and brain, where researchers observed clear signs of neuroinflammation.

“That repeated stimulation acts like turning up the volume again and again,” Hayashi said. “Eventually, the system becomes hypersensitive. Even small signals can feel very painful.”

To strengthen the findings, the team also analyzed tissue samples from rhesus macaques with naturally occurring endometriosis through a collaboration with the Oregon National Primate Research Center. No primate experiments were conducted at WSU.

The results help explain why pain can persist even after lesions are removed. Once the brain’s pain-processing circuits are sensitized, they can continue to generate pain signals independently.

“It becomes a feedback loop,” Hayashi said. “The body is sending signals to the brain, and the brain is reinforcing those signals back to the body.”

The study also points toward new approaches for treatment. Rather than focusing only on removing lesions or suppressing hormones, therapies could target inflammation in the nervous system. In the study, both a commonly used hormonal drug and an immunomodulating compound reduced pain sensitivity and brain inflammation in the mouse model, even without shrinking lesions.

“We now have a system where we can follow the entire process from the beginning,” Hayashi said. “That gives us a powerful way to develop better treatments and, hopefully, detect the disease earlier.”

“These findings are clinically valuable for they show us that this injectable extended-release buprenorphine formulation is safe to use in pregnancy and results in better opioid abstinence outcomes compared to sublingual buprenorphine,” said Nora D. Volkow, M.D., director of NIH’s National Institute on Drug Abuse (NIDA). “This is especially relevant in the context of the ongoing opioid overdose crisis and public health emergency.”

Illicit opioid use and untreated OUD can have dire consequences during pregnancy, including risk of fatal overdose for the mother and the development of neonatal opioid withdrawal syndrome (NOWS) and other adverse consequences for the baby. Treating OUD in pregnancy with sublingual buprenorphine is effective, but it has disadvantages, including risk of misuse, potentially poor adherence, and daily fluctuating blood levels known as peak-trough effects that may inadequately mitigate opioid-related cravings and withdrawal, leading to continued opioid use. The researchers in this study wanted to see if using a weekly formulation of subcutaneous (under-the-skin), extended-release buprenorphine injections during pregnancy—with the option of a monthly formulation for postpartum participants who were not breastfeeding—might promote as good or better opioid abstinence rates and NOWS outcomes.

In the multicenter trial, 140 pregnant adults were randomized to receive either injectable extended-release or sublingual buprenorphine (with or without naloxone). The trial, supported by the NIDA Clinical Trials Network as part of the NIH Helping to End Addiction Long-term ® Initiative (NIH HEAL Initiative^®), was the first randomized trial testing extended-release buprenorphine for OUD in pregnancy and postpartum.

The researchers found that rates of illicit opioid abstinence during pregnancy, as measured by urine drug screens, were significantly higher for those receiving weekly extended-release buprenorphine and were non-inferior postpartum compared to participants receiving sublingual buprenorphine.  While the percentage of participants experiencing non-serious maternal adverse events did not differ between the types of treatments, they were more commonly rated as medication-related in the extended-release group during pregnancy. Serious maternal adverse events were less common in the extended-release group throughout the trial. NOWS outcomes did not differ between the treatment groups.

“We knew that injectable extended-release buprenorphine leads to superior rates of illicit opioid abstinence in non-pregnant adults, but there had been no completed randomized clinical trial testing its use during pregnancy,” said principal investigator and lead author John Winhusen, Ph.D., professor of Psychiatry and Behavioral Neuroscience at the University of Cincinnati College of Medicine. “It is exciting to share the results of this trial, which have immediate clinical application: this longer-acting medication can safely and more effectively support treatment and recovery in pregnant patients.”

The Simplified Adolescent Factors for Endometriosis (SAFE) score uses a questionnaire to identify at-risk patients and fast track specialist referrals for further investigation.

Professor Gita Mishra AO, Centre Director of UQ’s Australian Women and Girls’ Health Research Centre, said the test could prevent years of waiting for a diagnosis.

“The test uses 6 questions to detect girls or young women at risk of endometriosis and in need of further assessment,” Professor Mishra said.

“Identifying which patients should be referred and treated is challenging and improving how patients are diagnosed is a major priority.

“By detecting endometriosis earlier – ideally in adolescents as soon as they begin their periods – we hope the tool will reduce the average 6-8-year diagnostic delay so we can start treatment as early as possible.’’

Endometriosis is an often-crippling condition where tissue, similar to the inner lining of the uterus, grows outside of it.

The condition has no cure and affects up to 11 per cent of Australian women of reproductive age.

Using the questionnaire, young women are asked if they experience pelvic pain often, if they’ve sought treatment for pelvic pain, taken painkillers for pelvic pain, experienced heavy menstrual bleeding or painful periods, and have a family history of endometriosis.

The SAFE score works on a point‑based system and would help guide referrals in primary care.

The more risk factors identified, the higher a woman’s score and the greater likelihood of the condition.

The tool was designed using data from more than 9000 women from the Australian Longitudinal Study on Women’s Health, with researchers identifying risk factors for endometriosis.

“This simple tool can be used in women of any age, but we have carefully chosen age-appropriate questions to target adolescents,” Professor Mishra said.

“Long delays in diagnosis can be due to unclear symptoms, lack of awareness, misdiagnosis, and normalisation of menstrual pain which impacts quality of life.

“The condition often involves surgery to confirm diagnosis, although experts are working to change this so the condition can be picked up through ultrasound or MRI.

“We need to be able to detect endometriosis early because our research found most women were diagnosed in their late twenties, often when they are trying to fall pregnant.

“Early diagnosis is critical because it can change treatment of fertility issues later on.

“The usual treatment route is ovulation induction, but this is not as effective as IVF for women with endometriosis.’’

Next steps will evaluate the tool in clinical settings, assess its practicality in Brisbane GP, endometriosis and pelvic pain clinics, and explore if an app can be developed.

March is Endometriosis Awareness Month, signified internationally by the colour yellow.

The research is published in eClinicalMedicine.

When they analyzed 2012–2024 information on 45,619 babies born at 24–32 weeks’ gestation at 1,111 hospitals in an international network, along with information from the UK National Neonatal Research Database and a literature review, investigators found that on average, less than half of infants had been exposed to preterm magnesium sulfate in middle-income countries, and approximately three-quarters in high-income countries. Even within high-income countries, there were large discrepancies in care. Preterm steroids were used more frequently with less variation, although treatment gaps were still apparent.

“Our study has highlighted the international disparities in how two key treatments to protect pre-term babies are implemented. These gaps aren’t because of a lack of evidence,” said corresponding author Hannah B. Edwards, MA, MSc, of the University of Bristol, in the UK. “Lessons can be learned from successful implementation programs like PReCePT, which has transformed use of magnesium sulphate in pre-term births in England. The bigger-picture goal should now be to ensure that no matter where a baby is born, their mother has access to the evidence-based treatments that offer the best start in life.”

URL upon publication: https://onlinelibrary.wiley.com/doi/10.1002/ijgo.70832

Vaccination against COVID-19 and influenza are recommended during pregnancy by the World Health Organization (WHO) and Norway, as pregnant women and their newborns have an increased risk of severe outcomes from these diseases. For at-risk groups, the WHO recommends a vaccination target of 75% for both infections.

These findings emphasise the need for more targeted strategies and better integration of vaccinations into routine pre-natal care for pregnant women in Norway, along with comprehensive surveillance of maternal vaccination.

In Norway, the influenza vaccine is provided during the influenza season, while the COVID-19 vaccine is available year-round. Generally, both vaccines are recommended to pregnant women during the second and third trimester. Pregnant women in Norway access these vaccines through self-initiated appointments with healthcare professionals; the influenza vaccine is provided at a cost, while the COVID-19 vaccine is free.

Significant variation in coverage depending on month of delivery and timing during pregnancy

Stecher et al. looked at how many pregnant women received the influenza and COVID-19 vaccines during the 2023/24 influenza season, at what stage of pregnancy they received the vaccine, and whether uptake differed by age group or region.

A total of 53,161 women were included in the study. Researchers drew data from two Norwegian national registries, with the study population comprising all women who delivered in Norway between 1 October 2023 and 30 September 2024, as identified in the Medical Birth Registry Norway (MBRN). The records and birth data from MBRN were then linked to data from the Norwegian Immunisation Registry (SYSVAK).

Despite universal recommendations for vaccination during pregnancy, coverage in the influenza season 2023/24 was low at 29.9% and 12.1% for influenza and COVID-19, respectively, while only 11.4% of pregnant women received both vaccines.

For the influenza vaccine, 22.3% of women were vaccinated in the second or third trimester. Coverage increased from 16.4% in October to 26.4% in November, and levelled off thereafter. It was highest among women delivering in February at 50.8%, declining afterwards. Coverage for the COVID-19 vaccine followed a similar pattern to influenza, with 10.1% of women receiving the vaccine in the second or third trimester.

Low vaccination rates despite high trust in health authorities

There were considerable differences across regions and age groups, despite the population’s high level of trust in health authorities and recommendations, and the authors point to practical and psychological barriers to vaccination. The lowest uptake was among women aged 25 years or younger. Regionally, the Oslo and Vestland counties had the highest vaccination coverage, while the lowest coverage was found in Northern Norway.

Stecher et al. suggest removing financial barriers, improving accessibility, and exploring information sources on vaccines trusted by women to address hesitancy. The authors also cite international evidence supporting the integration of free vaccination into routine pre-natal care, with vaccination coverage for whooping cough among pregnant women improving when the vaccine was introduced into Norway’s maternal immunisation programme.

Similar challenges globally, including limited surveillance systems and inconsistent integration, highlight the importance of coordinated efforts to promote maternal immunisation in Europe and worldwide.

There is no new evidence that would require changes to the current long-standing recommendation, the Agency stressed. It cited a recent systematic review and meta-analysis published in The Lancet Obstetrics, Gynaecology & Women’s Health which found no evidence linking paracetamol to autism, ADHD or intellectual disability in children.

‘Paracetamol remains an important option to treat pain or fever in pregnant women,’ said EMA’s Chief Medical Officer, Steffen Thirstrup. ‘Our advice is based on rigorous assessment of the available scientific data and we have found no evidence that taking paracetamol during pregnancy causes autism in children.’

The unusual decision to issue a statement – which announces no change in advice and no new evidence to review – comes in response to misinformation which falsely linked the common pain reliever with developmental changes. This idea was repeated by senior politicians in the United States in recent months, sparking widespread concern worldwide.

Without naming those who have perpetuated the myth, the EU regulator pushed back against the baseless medical claim which has potential to cause distress and avoidable physical suffering for pregnant women with a fever.

The EMA said it has a large amount of data from pregnant women who used paracetamol during pregnancy, over a very long period of time, and has seen no evidence of any risk of malformations in the developing foetus or in newborns.

‘When needed, paracetamol can be used during pregnancy. As with any medicine for acute treatment, it should be used at the lowest effective dose, for the shortest possible time and as infrequently as possible,’ the EMA statement said. ‘Pregnant women should speak to their healthcare professional if they have questions about any medication during pregnancy.’

The findings were published on January 16, 2026 in The Lancet Obstetrics, Gynaecology, & Women’s Health journal.

As background, the authors noted, “Concerns have emerged about the impact of paracetamol use in pregnancy on child neurodevelopment, particularly in relation to autism spectrum disorder. We aimed to synthesize available evidence to investigate associations between prenatal paracetamol exposure and autism spectrum disorder, attention-deficit hyperactivity disorder (ADHD), and intellectual disability.”

The authors concluded, “This systematic review and meta-analysis found no evidence that maternal paracetamol use during pregnancy increases the risk of autism spectrum disorder, ADHD, or intellectual disability among children. The null findings remained consistent when analyses were harmonized to studies with longer follow-up, those employing sibling comparisons, and those at low risk of bias.”

They included 43 studies in this systematic review, and 17 studies in the meta-analysis.

The largest and most rigorous studies, specifically those with sibling comparisons, provided strong evidence that paracetamol-use during pregnancy is not a cause of autism, ADHD or intellectual disabilities.

Sibling comparison studies are designed to compare outcomes between siblings with different exposures (one sibling exposed to a drug, the other not) to control for shared genetic and environmental factors, and helping to isolate an accurate effect of exposure.

They reported that, when considering sibling comparison studies, paracetamol exposure during pregnancy was not associated with the risk of autism spectrum disorder (p=0·45), ADHD (p=0·31), or intellectual disability (p=0·63).

They also reported finding no association between paracetamol use during pregnancy and autism spectrum disorder (p=0·78), ADHD (p=0·49), or intellectual disability (p=0·28) when considering only studies at low risk of bias.

Low-risk-of-bias studies have strong designs, methods, and reporting, meaning their results are considered valid and reliable.

“This absence of association persisted when considering all studies with adjusted estimates and those with more than 5 years of follow-up,” they noted.

In an COMMENT appearing with the study, the authors said, “For now, this study reinforces that the strongest epidemiological evidence does not support a link between paracetamol use during pregnancy and neurodevelopmental harm, confirming that, when clinically-indicated, paracetamol remains an important and evidence-supported option for the management of fever and pain during pregnancy, particularly in settings where untreated maternal infection and fever pose well-established risks to fetal survival and neurodevelopment.

Researchers surveyed 422 clinicians who regularly prescribe birth control and found that only about a third of those who were aware of the option prescribe it. The providers said they were concerned about their patients’ ability to self-inject, the medication’s availability at pharmacies, and the lack of standardized approaches to counseling and prescribing it.

The study is the first to document the barriers that prevent widespread adoption of self-administered injectable contraception. It was published Jan. 8 in the journal Obstetrics & Gynecology.

“Since most physicians don’t know that this is an option, patients don’t know about it,” said Jennifer Karlin, MD, PhD, a UCSF associate professor of Family and Community Medicine and the paper’s senior author. “It’s safe, effective, and puts the control in patients’ own hands. We should be talking about and offering it to patients without biases.”

Depot medroxyprogesterone acetate (DMPA) is an injectable form of progestin, which is a synthetic form of the natural hormone progesterone. The drug prevents pregnancy for up to three months by stopping ovulation, thickening cervical mucus, and thinning the uterine lining.

DMPA is available in two injectable forms: an intramuscular injection, marketed under the name Depo Provera, that can only be administered by a provider, and one that is injected just under the skin. This subcutaneous version can be easily self-injected, like the now popular injectable GLP-1 weight-loss drugs.

The drug has been associated with potential side effects, such as reduced bone mineral density, weight gain, and a benign brain tumor called meningioma. While the overall risk of these side effects is low, it is important that clinicians discuss the risks and benefits with their patients.

The subcutaneous version, approved in 2004, is officially labeled for administration by a clinician, but doctors have been training patients to self-inject safely for many years. Self-injectable contraception is more commonly used globally, particularly in sub-Saharan Africa. It became more widely used in the U.S. during the COVID-19 pandemic, and the study found more than half the prescribers surveyed learned about it between 2020 and 2022.

Both international and national guidelines recommend making this option accessible to all patients, but the study found that providers in states with restricted abortion access were less likely to prescribe it. Other obstacles include insufficient educational materials, lack of staff support, and limited time for consulting with patients.

To make the option more widely available, the authors recommend an education campaign for clinicians about self-administration of injectable contraceptives. They also advocate for FDA approval of the version of the injectable that can be self-administered, as well as ensuring that insurance cover it and streamlining clinic workflows.

Authors: Additional authors include Chase Clark, of UC Davis; and An-Lin Cheung, PhD, and Laura Creason, MS, of the University of Missouri-Kansas City.

Funding: The work was supported by a grant from the Society of Family Planning (SFPRF16). The authors had nothing to disclose.

About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF’s primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. UCSF School of Medicine also has a regional campus in Fresno. Learn more at https://ucsf.edu or see our Fact Sheet.

IVF patients must inject themselves with hormones daily at specific times in the weeks leading up to egg retrieval, a process that can be physically and emotionally taxing.

The team’s new system uses a hydrogel microneedle patch filled with specially engineered nanoparticles that hold and release a key IVF hormone, leuprolide, when stimulated by near-infrared light. The light can be programmed to release the drug at the desired time.

Toward personalized, programmable dosing

Current light-triggered drug delivery systems often release foreign materials into the body, posing regulatory and safety challenges.

“This is the first time that we were able to show light-triggered drug release from a nanoparticle-microneedle composite without releasing any foreign substance into the body,” said Marta Cerruti, a materials engineering professor and senior author of the study in Small.

The researchers say this key advance could accelerate clinical translation, as the delivery system leaves no nanoparticles behind in the skin.

In building their system, the team first optimized how many hormone-bearing nanoparticles could be incorporated into each microneedle without weakening its ability to penetrate skin. They then tested whether the light trigger could release the hormone into a porcine skin model over two hours. Finally, they demonstrated that even a short five-minute pulse of light released measurable levels of leuprolide into the skin, bloodstream and organs of a live rat.

“The light can also be programmed to release the drug at the specific time the drug is needed, which could differ for each individual,” said Tam, the PhD student in Cerruti’s lab who was also the lead author on this study.

“IVF success rates are at best 30 per cent, even for the youngest women. The hope is that if you take out the human error with injecting yourself and deliver the drug at times optimized for each patient, you could potentially see this success rate go up,” she said.

Beyond IVF

For IVF patients, the technology could make treatment easier, less painful and potentially more effective, but the system could also help anyone who relies on daily injections, including people with diabetes or multiple sclerosis.

Because no nanoparticles enter the body, the researchers say the platform has a clearer pathway to clinical adoption than previous systems. More work is planned to refine dosing, explore hormone release profiles and investigate commercial possibilities.

About the study

“Upconverting Nanoparticle-Loaded Microneedles for Near-Infrared Responsive Delivery of Gonadotropins to Increase Success of In-Vitro Fertilization” by Vivienne Tam, Rusvir Trana, Alfonso Nieto-Arguello, Ore-Oluwa Olasubulumi, Samuel Babity, Artiom Skripka, Fiorenzo Vetrone, Davide Brambilla, and Marta Cerruti, was published in Small.

Funding

This research was supported by Natural Sciences and Engineering Research Council (NSERC) and Vanier Canada Graduate Scholarships.