Category: Obstetrics & Gynaecology

New Study Finds Depression Risk with Hormonal Contraceptive Use

The possibility that contraceptive pills might have negative effects on mental health and even lead to depression has long been debated. Now, evidence published in Epidemiology and Psychiatric Sciences shows that contraceptive pills are in fact linked to depression, with teenage girls at particularly increased risk.

This study is one of the largest and widest-ranging to date, following more than a quarter of a million women from UK Biobank from birth to menopause.

The researchers collected data about women’s use of contraceptive pills, the time at which they were first diagnosed with depression and when they first experienced symptoms of depression without receiving a diagnosis. The method of contraception studied was combined contraceptive pills, which contain progestogen and oestrogen. Progestogen prevents ovulation and thickens the cervical mucus to prevent sperms from entering the uterus, while oestrogen thins the uterine lining to hinder the implantation of a fertilised egg.

“Although contraception has many advantages for women, both medical practitioners and patients should be informed about the side-effects identified in this and previous research,” says Therese Johansson at Uppsala University, one of the researchers leading the study.

According to the study, women who began to use contraceptive pills as teenagers had a 130% higher incidence of symptoms of depression, while the corresponding increase among adult users was 92%.

“The powerful influence of contraceptive pills on teenagers can be ascribed to the hormonal changes caused by puberty. As women in that age group have already experienced substantial hormonal changes, they can be more receptive not only to hormonal changes but also to other life experiences,” Johansson says.

The researchers were also able to see that the increased incidence of depression declined when the women continued to use contraceptive pills after the first two years. However, teenage users of contraceptive pills still had an increased incidence of depression even after stopping using the pill, which was not observed in adult users of contraceptive pills.

“It is important to emphasise that most women tolerate external hormones well, without experiencing negative effects on their mood, so combined contraceptive pills are an excellent option for many women. Contraceptive pills enable women to avoid unplanned pregnancies and they can also prevent illnesses that affect women, including ovarian cancer and uterine cancer. However, certain women may have an increased risk of depression after starting to use contraceptive pills.”

The findings of the study point to a need for healthcare professionals to be more aware of possible links between different systems in the body, such as depression and the use of contraceptive pills. The researchers conclude that it is important for care providers to inform women who are considering using contraceptive pills of the potential risk of depression as a side-effect of the medicine.

“Since we only investigated combined contraceptive pills in this study, we cannot draw conclusions about other contraceptive options, such as mini pills, contraceptive patches, hormonal spirals, vaginal rings or contraceptive rods. In a future study, we plan to examine different formulations and methods of administration. Our ambition in comparing different contraceptive methods is to give women even more information to help them take well-informed decisions about their contraceptive options,” Johansson says.

Source: Uppsala University

Researchers Advise Stopping Heparin Use for Pregnant Women with Thrombophilia and Miscarriage Risk

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Heparin, commonly prescribed to pregnant women with an inheritable blood clotting condition and a history of recurrent miscarriage does not help to reduce their miscarriage risk, new research has found. The UK-led international study was published in The Lancet.

Researchers are now advising doctors to stop offering the anticoagulant heparin to women and birthing people with inherited thrombophilia, an inherited condition which increase clotting risk.

Despite the lack of evidence and guidance, doctors often prescribe heparin to women with recurrent miscarriage and inherited thrombophilia. It’s costly for health services, and inconvenient for women who must inject the drug daily and are more likely to experience bruising as a result.

The results show that a daily injection of heparin does not improve the chance of a live birth for women who have previously had two or more miscarriages and confirmed inherited thrombophilia, when compared to standard care.

Led by Professor Siobhan Quenby at the University of Warwick, the ALIFE2 trial recruited women from 40 hospitals in Europe and the US.

326 women with inherited thrombophilia and recurrent miscarriage were split into 2 groups; 164 received heparin across the course of their pregnancy, starting from as soon as possible after a positive pregnancy test and ending at the start of labour. 162 were not offered the medication.

All women received standard obstetrician-led care and all women were encouraged to take folic acid.

The rate of live births for each group was roughly the same: 116 women (71.6%) treated with heparin had a baby born alive after 24 weeks’ pregnancy. 112 women (70.9%) in the standard care group had a baby born alive after 24 weeks’ pregnancy.

The risk of other pregnancy complications, including miscarriage, babies with low birth weight, placental abruption, premature birth or pre-eclampsia, was about the same for both groups.

As expected, bruising easily was reported by 73 (45%) of women in the group taking heparin (mostly around injection-sites) and only 16 (10%) in the standard care group.

Professor Siobhan Quenby says, “Based on these findings, we don’t recommend the use of Low Molecular Weight Heparin for women with recurrent pregnancy loss and confirmed inherited thrombophilia.”

“We also suggest that screening for inherited thrombophilia in women with recurrent pregnancy loss is not needed. Patients and doctors will always value knowing about any factor which could be associated with recurrent miscarriage, but the association between inherited thrombophilia and recurrent miscarriage isn’t proven: a recent review of research showed that thrombophilia is as common in the general population as it is in women with recurrent miscarriage.”

“Many women with recurrent miscarriage around the world are tested for inherited thrombophilia and are treated with heparin daily. Research now shows that this screening is not needed, the treatment isn’t effective, and it is giving false hope to many by continuing to offer it as a potential preventive treatment.”

Twenty-eight percent of women who participated in the trial lost their badly wanted pregnancies, and these unexplained losses will be the focus of further study, as our researchers continue to search for answers and treatment to prevent early pregnancy loss.

Source: Medical Xpress

Low Maternal Vitamin D Levels may Increase Schizophrenia Risk of Offspring

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Neuroscientists published in the Journal of Neurochemistry, shows that maternal levels of vitamin D are key in the development of dopaminergic neurons, which are thought to be involved in schizophrenia.

Professor Darryl Eyles has built on past research out of his laboratory at the Queensland Brain Institute linking maternal vitamin D deficiency and brain development disorders, such as schizophrenia, to understand the functional changes taking place in the brain.

Schizophrenia is associated with many developmental risk factors, both genetic and environmental. While the precise neurological causes of the disorder are unknown, what is known is that schizophrenia is associated with a pronounced change in the way the brain uses dopamine, the neurotransmitter often referred to as the brain’s ‘reward molecule’.

Professor Eyles has followed the mechanisms that might relate to abnormal dopamine release and discovered that maternal vitamin D deficiency affects the early development and later differentiation of dopaminergic neurons.

The team at the Queensland Brain Institute developed dopamine-like cells to replicate the process of differentiation into early dopaminergic neurons that usually takes place during embryonic development.

They cultured the neurons both in the presence and absence of the active vitamin D hormone. In three different model systems they showed dopamine neurite outgrowth was markedly increased. They then showed alterations in the distribution of presynaptic proteins responsible for dopamine release within these neurites.

“What we found was the altered differentiation process in the presence of vitamin D not only makes the cells grow differently, but recruits machinery to release dopamine differently,” Professor Eyles said.

Using a new visualisation tool known as false fluorescent neurotransmitters, the team could then analyse the functional changes in presynaptic dopamine uptake and release in the presence and absence of vitamin D.

They showed that dopamine release was enhanced in cells grown in the presence of the hormone compared to a control.

“This is conclusive evidence that vitamin D affects the structural differentiation of dopaminergic neurons.”

Leveraging advances in targeting and visualising single molecules within presynaptic nerve terminals has enabled Professor Eyles and his team to further explore their long-standing belief that maternal vitamin D deficiency changes how early dopaminergic circuits are formed.

The team is now exploring whether other environmental risk factors for schizophrenia such as maternal hypoxia or infection similarly alter the trajectory of dopamine neuron differentiation.

Eyles and his team believe such early alterations to dopamine neuron differentiation and function may be the neurodevelopmental origin of dopamine dysfunction later in adults who develop schizophrenia.

Source: University of Queensland

Cannabis Use in Pregnancy Reduces Birth Weights

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With growing legalisation and recreational use of cannabis comes a change in attitudes. Research has shown that dispensaries often recommend cannabis for the easing of pregnancy symptoms, especially morning sickness.

Growing evidence links cannabinoid consumption during pregnancy with poor child outcomes, though the exact effects on the developing foetus remain unclear. In a study published in Frontiers in Pediatrics, researchers in the US have now examined how timing of cannabis exposure during pregnancy impacts foetal development.

“We show that even when marijuana use occurred only in the first trimester of pregnancy, birth weight was significant reduced, by more than 150g on average,” said senior author Dr Beth Bailey, professor and director of population health research at Central Michigan University“If that use continued into the second trimester, newborn head circumference was significantly decreased as well.”

Continued exposure results in largest deficiencies

“These findings are important as newborn size is one of the strongest predictors of later child health and development,” added study first author Dr Phoebe Dodge.

Recent work, including the research by Dodge et al., has shown significant effects of cannabis use on newborn size. “Size deficits were largest among newborns exposed to marijuana throughout gestation,” Bailey explained. The babies born after continued in-utero exposure were nearly 200g lighter, and their head circumference was nearly 1cm less than that of babies who had not been exposed. Pregnancy cannabis use did not significantly predict newborn length in this study.

The effects the scientists observed have also shed light on patterns of use. Their study showed that occasional use, such as for first trimester morning sickness, may reduce fetal growth in the same way as continued use throughout pregnancy. The same is true for other use in early stages, including cases when someone uses cannabis not knowing they are pregnant.

Quitting before pregnancy is best recommendation

The authors pointed out that in their study they did not have information about how much or how often participants used cannabis. Their results were based on whether people did or did not use it at certain times in pregnancy. Therefore, the study could not establish if there was a connection between heavy use and more pronounced outcomes in newborn growth.

More studies are needed to determine whether timing or amount of use is most important when it comes to effects on newborn size, they wrote.

 “The best recommendation is that women should be advised to quit marijuana use prior to becoming pregnant,” Dodge said. However, quitting as soon as possible after getting pregnant is the second-best option to avoid long term adverse health and developmental outcomes. “There are some benefits of quitting among those who begin pregnancy using marijuana,” she continued.

Source: EurekAlert!

Limited Evidence for Menstrual Changes After COVID Vaccination

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Results from a Swedish study of nearly three million women and girls published by The BMJ found that there was no evidence of an increased risk of post-COVID vaccination menstrual changes that were significant enough for healthcare interaction.

The researchers found only weak and inconsistent associations were found between COVID vaccination and contact with healthcare for postmenopausal bleeding. These were even less consistent for menstrual disturbance and premenstrual bleeding.

These findings do not provide any substantial support for a causal association between COVID vaccination and diagnoses related to menstrual or bleeding disorders, say the researchers.

Many women have reported changes to their periods after a COVID vaccination, such as the number of days they bleed and the heaviness of the flow. Self-reporting may capture events that normally would not result in a healthcare contact but may still be sufficiently disturbing to be relevant for the affected women. But calculating the strength of a potential association based on self reports can be unreliable.

To address this, researchers in Sweden drew on high quality health registry data to evaluate the risks of menstrual disturbance and bleeding after COVID vaccination in 2 946 448 women and girls aged 12-74 years from December 2020 to February 2022.

Contact with healthcare included primary care visits, specialist outpatient visits, and days of hospital stay related to menstrual disturbance or bleeding before or after menopause.

Risks were assessed by vaccine (Pfizer-BioNTech, Moderna, or Oxford-AstraZeneca) and dose (unvaccinated and first, second, and third dose) over two time windows (1-7 days, considered the control period, and 8-90 days).

In the main analysis, more than 2.5 million (88%) of women received at least one covid-19 vaccination and over 1.6 million (64%) of vaccinated women received three doses during the study period.

The highest risks for bleeding in postmenopausal women were seen after the third dose in the 1-7 days risk window (28%) and in the 8-90 days risk window (25%).

Adjusting for socioeconomic factors, previous healthcare use, and for several specific medical conditions had only a modest effect on these results.

Analyses of individual vaccines and risk of postmenopausal bleeding suggested a 23-33% increased risk after 8-90 days with Pfizer-BioNTech, and Moderna after the third dose, but a less clear association with Oxford-AstraZeneca.

In premenopausal women, weak associations were found for menstrual disturbance or bleeding after vaccination with any dose (13% or 8% after 1-7 days and 6% or 1% after 8-90 days, respectively). However, adjusting for other factors almost completely removed these weak associations, suggesting that a causal effect is unlikely.

These are observational findings and the authors point to several limitations, including the fact that the time between onset, start of symptoms, and date of healthcare contact might be considerable, making the interpretation of effect of different risk windows challenging. 

But this was a large study with near complete follow-up, using mandatory data from nationwide registers.

As such, they say: “We observed weak and inconsistent associations between SARS-CoV-2 vaccination and healthcare contacts for postmenopausal bleeding, and even less consistent for menstrual disturbance, and premenstrual bleeding.”

They add: “These findings do not provide any substantial support for a causal association between SARS-CoV-2 vaccination and healthcare contacts related to menstrual or bleeding disorders.”

Source: The BMJ

Preterm Births Concern Raised Over New Maternal RSV Vaccine

Experts have called for further scrutiny of a new Pfizer vaccine given during pregnancy to prevent respiratory infection in infants, after trials of a similar GSK vaccine were stopped after increased preterm birth and infant deaths. Pfizer says its vaccine is safe and effective, but experts contacted as part of an investigation published by The BMJ say that Pfizer’s trial data should be reviewed in light of the trend for preterm births seen in GSK’s trial.

Pfizer’s maternal RSV vaccine aims to protect infants from severe illness caused by the respiratory syncytial virus (RSV). RSV is very common but can be fatal, especially in young children. In 2019, an estimated 3.6% of all deaths worldwide in children aged 1-6 months were due to RSV, with 97% of these deaths occurring in low and middle income countries.

The vaccine has not yet been approved for use, but a decision by the US Food and Drug Administration is expected by August. The European Medicines Agency is also set to make a decision about the vaccine later this year.

In February 2022, GSK halted vaccination in its phase 3 trials of its maternal RSV vaccine after finding an increased risk of preterm birth in vaccinated mothers, mainly in low and middle income countries.

Pfizer published the results of an interim analysis of its phase 3 trial last month, saying that the vaccine was effective against medically attended severe RSV in children and that no safety concerns were identified.

And while the difference in preterm births in the Pfizer trials was not statistically significant, the results have raised concerns about a possible increase in preterm births, and now experts are calling for further analyses of the data and post-approval monitoring of the vaccine should the FDA approve it.

“My interpretation of all these data is that there may be a safety signal for preterm births that should be followed up on,” said Klaus Überla, director of the Virological Institute of the University Hospital Erlangen and member of the RSV working group of the Standing Committee on Vaccination (STIKO), which develops national recommendations for the use of licensed vaccines in Germany. 

And a scientist at the National Institutes of Health (NIH) said the Pfizer data should be analysed using more sensitive measures such as average birth weight and subgroup analyses to detect possible signals.

Meanwhile, Cody Meissner, professor of paediatrics and medicine at the Dartmouth Geisel School of Medicine and consultant in the US Centers for Disease Control and Prevention (CDC)’s maternal RSV working group, predicts that possible adverse effects such as premature births will be “closely monitored” in assessment programs by FDA and CDC.  “We need a safe vaccine,” he added.

Pfizer did not respond when asked about a possible increase in preterm births associated with its vaccine, but told The BMJ that “no imbalance of neonatal deaths was observed” in its phase 3 trial. 

In a linked editorial, researchers point to challenges for RSV vaccine development and the main approaches to protection currently being pursued. 

They argue that, while the burden of illness caused by RSV is substantial worldwide, it is particularly important that new vaccines and other prevention strategies are available to infants in low and middle income countries, where the greatest illness and deaths occur.

And they say further research is urgently needed “to identify the best prevention strategies for low and middle income countries, where affordability is paramount and timing of administration is complicated by the lack of predictable seasonal RSV epidemics.”

Source: EurekAlert!

Sons Born to Women with PCOS Can Also Encounter Health Problems

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Sons of women with polycystic ovary syndrome (PCOS) have a twofold increased risk to develop obesity, according to a study published in Cell Reports Medicine. The findings highlight a previously unknown risk of passing PCOS-related health problems across generations through the male side of a family, say the the researchers from Karolinska Institutet.

PCOS is caused by overproduction of testosterone by the ovaries and affects around 15% of women of childbearing age worldwide, impacting fertility. In addition, the disease is associated with various health problems such as diabetes, obesity, and mental illness. 

Daughters of women with PCOS have a fivefold risk of developing the same disease. Although it is not yet clear how sons of women with PCOS are affected, research suggests that they are more likely to have weight and hormone problems

The researchers used both registry data and mouse models in the newly published study to determine if and how PCOS-like traits are passed from mothers to their sons. Just over 460 000 sons born in Sweden between July 2006 and December 2015 were included in the registry study. Of these, roughly 9000 had mothers with PCOS. The researchers then identified which of the children were obese. 

“We discovered that sons of women with PCOS have a twofold increased risk of obesity and of having high levels of “bad” cholesterol, which increases the risk of developing insulin resistance and type 2 diabetes later in life”, says study leader Elisabet Stener-Victorin, professor at Karolinska Institutet. 

These findings were confirmed in the mouse study, where the researchers examined male offspring of female mice that before and during pregnancy were fed either a standard diet or a diet rich in fat and sugar, and were exposed to high levels of the male sex hormone dihydrotestosterone during pregnancy to mimic the pregnancy of normal weight individuals and obese women with PCOS. 

The male mice were then fed a standard diet until adulthood when their fat distribution and metabolism were examined. 

“We could see that these male mice had more fat tissue, larger fat cells, and a disordered basal metabolism, despite eating a healthy diet”, says Elisabet Stener-Victorin.

To investigate the reproductive function of the offspring and whether physiological characteristics can be passed on from generation to generation, the first-generation male mice were mated with healthy female mice that were not exposed to male sex hormones or a diet rich in fat and sugar. The whole process was repeated in the second generation to reach the third generation which is the first generation that was not affected by the mother condition.  
 
“Through these experiments, we can show that obesity and high levels of male hormones in the woman during pregnancy can cause long-term health problems in the male offspring. Their fat tissue function, metabolism, and reproductive function deteriorate, which in turn affects future generations”, says Qiaolin Deng, associate professor at the same department and one of the researchers behind the study.
 
“These findings are important because they highlight the risk of passing health problems down through the male side of a family, highlight the risk of passing this kind of health problem, and they may help us in the future to find ways to identify, treat and prevent reproductive and metabolic diseases at an early stage,” says Elisabet Stener-Victorin.

Source: Karolinska Institutet

Labour Induction in 39th Week Does not Decrease Risk of Needing Caesarean

In recent years, experts have debated the benefits of labour induction once at a certain stage of pregnancy. But a new US study suggests that inducing labour at the 39th week of pregnancy for those having their first births with a single baby in a head down position, or low risk, doesn’t necessarily reduce the risk of caesarean births. In fact, for some, it may even have the opposite effect if hospitals don’t take a thoughtful approach to induction policies.

“Some people in the field have suggested that after 39 weeks of gestation, medical induction should be standard practice,” said lead author Elizabeth Langen, MD, a high-risk maternal fatal medicine physician and researcher at University of Michigan Health Von Voigtlander Women’s Hospital, of Michigan Medicine.

“We collaborated with peer hospitals to better understand how labour induction may influence caesarean birth outcomes in real world maternity units outside of a clinical trial. In our study sample, we found inducing labour in this population of women and birthing people did not reduce their risk of caesarean birth.”

The new research, published in the American Journal of Perinatology, was based on more than 14 135 deliveries in 2020 analysed through a statewide maternity care quality collaborative registry.

Results conflict with national trial findings

The study was conducted in response to published research in 2018 from a multicentre trial known as “ARRIVE” (A Randomized Trial of Induction Versus Expectant Management.)

Findings from ARRIVE indicated that medical induction at 39 weeks gestation in first time low risk pregnancies resulted in a lower rate of caesarean deliveries compared to expectant management – or waiting for labour to occur on its own or for a medical need for labour induction.

Michigan researchers mimicked the same framework used in the national trial and analysed data from the collaborative’s data registry, comparing 1558 patients who underwent a proactively induced labour versus 12 577 who experienced expectant management. However, their results failed to support a link between elective induced labour in late pregnancy and a reduction in caesarean births.

In fact, results from the general Michigan sample were contradictory to the ARRIVE trial: Women who underwent elective induction were more likely to have a caesarean birth compared with those who underwent expectant management (30% versus 24%.)

In a subset of the sample, matching patient characteristics for a more refined analysis, there were no differences in c-section rates. Authors noted that time between admission and delivery was also longer for those induced.

Expectantly managed women were also less likely to have a postpartum haemorrhage (8 % versus 10 %) or operative vaginal delivery (9 % versus 11 %), whereas women who underwent induction were less likely to have a hypertensive disorder of pregnancy (6 % versus 9%.) There were no other differences in neonatal outcomes.

Authors point to several possible explanations for why the two studies had conflicting results. One key difference was that the Michigan study collected data after births for the purpose of quality improvement in a general population of low-risk births. The ARRIVE trial, however, used data collected in real time as part of a research study.

A significant difference between clinical trial participants and the general birthing population, Low says, may revolve around shared decision-making. Before trial enrolment, participants undergo a thorough informed consent process from trained study team members.

For the ARRIVE trial, this meant 72% of women approached to be in the study declined participation. Meanwhile, previous research has indicated that women in the general U.S. population often may feel pressured into agreeing to have their labour induced.

“Better outcomes may have occurred in the trial because the participants were fully accepting of this process,” Low said.

“Further research is needed to identify best practices to support people undergoing labour induction,” she added. “Prior to initiating an elective induction of labour policy, clinicians should also ensure resources and a process to fully support shared decision-making.”

Source: Michigan Medicine – University of Michigan

Preterm Birth and Size Linked to Adult Fibrillation Risk

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A new study published in JAMA Pediatrics showed an association between being born preterm or large for gestational age and increased risks of atrial fibrillation later in life. Being small for gestational age at birth was only associated with an increased risk of atrial fibrillation up to the age of 18.

The incidence of atrial fibrillation in the young has increased over the past few decades, from low levels.

To date there have been little or mixed findings regarding the risk of atrial fibrillation in those with adverse birth outcomes. Atrial fibrillation increases the risk of stroke and other cardiovascular conditions, and is the most common form of cardiac arrhythmia. It mainly affects the middle-aged and the elderly. The estimated incidence in the young is low, 0.12 to 0.16%.

Low incidence in the young

A collaborative study involving researchers from Karolinska Institutet has now investigated the risk of atrial fibrillation according to preterm birth and foetal growth.

“Atrial fibrillation at a young age may involve a heavy socioeconomic burden for the affected individuals and we need to learn more about the underlying causes of the disease,” says first author Fen Yang, doctoral student at Karolinska Institutet. “Our findings may highlight the need to monitor and prevent the disease in individuals with an elevated risk of atrial fibrillation.”

“We found that individuals born preterm and those who were large for gestational age at birth had a slightly higher risk of developing atrial fibrillation up to middle-age than those with corresponding normal birth outcomes,” says principal investigator Krisztina László, associate professor at the Department of Global Public Health, Karolinska Institutet, and senior lecturer at the Department of Public Health and Caring Sciences at Uppsala University. “Individuals who were small for gestational age at birth had an increased risk of atrial fibrillation up to the age of 18, but not later in adulthood.”

The risk increase was 30% for individuals born preterm, 55% for individuals who were large at birth and 71% for individuals who were both preterm and large for gestational age at birth.

Eight million participants

The results of the study are based on statistical analyses of over eight million births from Danish (1978–2016), Finnish (1987–2014) and Swedish (1973–2014) medical birth registries who were followed for incident atrial fibrillation in the national patient and cause of death registries up to 2021. The results were compared with siblings in the same families. Since the study was observational, no causal relationships could be ascertained.

The researchers say that future studies may investigate the association between preterm birth, foetal growth, and the risk of atrial fibrillation up to old age.

Source: Karolinska Institutet

Chinese Traditional Medicine in Pregnancy Linked to Increased Congenital Malformations

A new study published in the journal Acta Obstetricia et Gynecologica Scandinavica has uncovered an association between the use of traditional Chinese medicine during pregnancy and congenital malformations, including heart defects, in children.

In the prospective study, 16 751 women who received obstetrics care from hospitals in China completed a survey on their use of traditional Chinese medicine before and during pregnancy. Among foetuses, there were 273 congenital malformations.

Foetuses exposed to traditional Chinese medicine had 2.1-times higher odds of developing congenital malformations compared with those without exposure. There were significant associations with congenital malformations in women with early pregnant use of traditional Chinese medicine and for those who used two or more types of these products.

“To improve traditional Chinese medicine, we should pay more attention to its hazards – especially the identification of teratogenic ingredients – while also evaluating its therapeutic effects,” said corresponding author Jiang-Nan Wu, of Obstetrics and Gynecology Hospital of Fudan University, in China.

Source: Wiley