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.
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.”
In an article in the BMJ, authors argue that menstrual changes after COVID vaccination are plausible and should be investigated.
Listed common side effects of COVID vaccination include a sore arm, fever, fatigue, and myalgia. However, changes to periods and unexpected vaginal bleeding are not listed, and primary care clinicians and those in the reproductive health field are seeing more and more people who have experienced these events shortly after vaccination.
More than 30 000 reports of these events had been made to the UK;s surveillance scheme for adverse drug reactions by 2 September 2021, across all COVID vaccines currently offered.
Most post-vaccination changes to periods return to normal, and there is no evidence that COVID vaccination adversely affects fertility. In clinical trials, there were similar rates for unintended pregnancies in vaccinated and unvaccinated groups. In fertility clinics, fertility measures and pregnancy rates are similar in vaccinated and unvaccinated patients. The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) says that there are few reported that
Menstrual changes have been reported after both mRNA and adenovirus vectored COVID vaccines, suggesting that, if there is a connection, it is likely to be a result of the immune response to vaccination rather than a specific vaccine component. Human papillomavirus (HPV) vaccinations have also been associated with menstrual changes. Indeed, the menstrual cycle can be affected by immune activation from various stimuli, including viral infection: one study found about a quarter of menstruating women with COVID experienced menstrual disruption.
Biologically plausible mechanisms linking immune stimulation with menstrual changes include immunological influences on the hormones driving the menstrual cycle or effects mediated by immune cells in the lining of the uterus, which are involved in the cyclical build-up and breakdown of this tissue. Research may also help understand the mechanism.
Though the period changes are short lived, there is need for adequate research. Vaccine hesitancy among young women is largely driven by false claims that COVID vaccines could harm their chances of future pregnancy. Failing to thoroughly investigate reports of menstrual changes after vaccination is likely to fuel these fears. If a link between vaccination and menstrual changes is confirmed, this information will allow people to plan for potentially altered cycles. Clear and trusted information is particularly important for those who rely on being able to predict their menstrual cycles to either achieve or avoid pregnancy.
In terms of management, the Royal College of Obstetricians and Gynaecologists and the MHRA recommend that anyone reporting a change in periods persisting over several cycles, or new vaginal bleeding after the menopause, should be managed according to the usual clinical guidelines for these conditions.
The authors conclude by stating there is an important lesson in that the effects of medical interventions on menstruation should not be an afterthought in future research. In clinical trials, participants are unlikely to report changes to periods unless specifically asked, so in future trials, information about menstrual cycles and other vaginal bleeding should be actively solicited.
Adenomyosis, a cause of painful menstrual cramps and heavy bleeding, is more common than generally appreciated, and many hysterectomies could be avoided with alternative treatment, suggests a review of the literature published in JAMA Network.
Adenomyosis is a gynaecologic condition characterised by ectopic endometrial tissue within the uterine myometrium. Up to a third of all women have adenomyosis, which should be considered in the differential diagnosis of abnormal uterine bleeding and/or pelvic pain, the researchers noted. It is considered a common uterine condition, but often goes undiagnosed until it results in a hysterectomy.
However, the findings suggest that surgery may be preventable for some women. The researchers identified a range of medical therapies and uterine-sparing procedures that can alleviate symptoms without resorting to hysterectomy.
“Many women come to me and say the only solution they’ve ever been offered is a hysterectomy. Other low-cost, low-risk options such as medical management or less invasive options have existed for more than 20 years,” said lead author Kimberly A Kho, MD.
Modern ultrasound and MRI imaging, combined with a pelvic examination, can often spot the condition, she added. Dr Kho and colleagues encouraged greater awareness of this condition – along with endometriosis – including among school nurses, who are frequently the first contact for young women who begin menstruating. Society may inaccurately teach women that heavy bleeding and pain during periods are normal, but these symptoms can worsen if left untreated, leading to lower quality of life, pain in sexual intercourse, and fertility problems. “Physicians often consider adenomyosis to be a condition of women in their 40s and 50s because that’s when they have their uteruses removed and receive a diagnosis, but it develops much earlier,” said Dr Kho. “Improved clinical awareness is needed to ensure appropriate patient care and encourage additional studies to improve the understanding of adenomyosis.”
Though there are no FDA-approved therapies specifically indicated for treating adenomyosis, the condition can still be managed by using medications developed for contraception, or for symptoms such as fibroids or endometriosis. The authors noted the need for further research, including what ages and ethnicities are most commonly affected, and what could be learned from the condition about uterine cancers.
In a new study, John Hopkins researchers have found that the periods before pregnancy and in between pregnancies are crucial times to address preeclampsia risk factors like obesity, diabetes and hypertension.
Preeclampsia, a common pregnancy complication, is characterised by high blood pressure and signs of damage to the liver, kidneys or other organs. It usually starts after 20 weeks of pregnancy in women whose blood pressure had previously been normal. .
The team, led by S. Michelle Ogunwole, MD, a fellow in the Division of General Internal Medicine, and Wendy Bennett, MD, MPH, associate professor of medicine, both at the Johns Hopkins University School of Medicine, published their findings in the Journal of the American Heart Association.
Dr Ogunwole said: “Preconception health care is really important as it’s a window of opportunity to think about your future health. We encourage patients to work on chronic disease issues before their pregnancies and between their pregnancies.”
A woman who develops preeclampsia during her first pregnancy has a higher risk of the condition recurring in a second or any successive pregnancies, she said.
“As an internist concerned about maternal outcomes, I am interested in what health care providers can do to help women reduce their risk of preeclampsia, including being a big proponent of preconception counseling,” said Dr Ogunwole.
The team compared two sets of women who were participating in the Boston Birth Cohort. Since 1998, the cohort has looked at a broad array of early life factors and their effects on pregnancy, infancy and child health outcomes. The researchers wanted to understand the differences between women who developed preeclampsia and those who did not, and how a first case of the condition affects subsequent pregnancies. Dr Ogunwole’s team studied 618 women to gain “rich maternal health data among racially and ethnically diverse pregnant women.”
“We wanted to make sure that we’re asking questions in a population that looks like the populations we serve,” she says. “I’m interested in the life course of women and pregnancy complications that can shape the trajectory of their future health.”
The researchers found that obesity, diabetes, high blood pressure, gestational diabetes and preterm birth were common factors in women who had preeclampsia during both first and second pregnancies, or who developed the condition during gestation with a second or later child.
“We know that improving weight will improve other conditions, so we advise that women create healthier lifestyles before and between pregnancies,” said Dr Ogunwole. “Whether you have another pregnancy again or not, you can still improve your overall health.”
Future research should hopefully include larger trials to confirm their results. Dr Ogunwole also plans to study the structural barriers that may prevent women from engaging in healthy lifestyles and develop strategies to improve long-term health outcomes for women.
A study found no increases in preterm births or stillbirths during the first year of the COVID pandemic, which will help alleviate concerns around pregnancy and COVID. The large study of more than 2.4 million births in Ontario is published in CMAJ (Canadian Medical Association Journal).
Infection, inflammation, stress, medical or pregnancy-induced disorders, genetic predisposition, and environmental factors are risk factors for stillbirth and preterm birth, although in many instances the exact mechanism is not yet known.
During the COVID pandemic, reports emerged of declining rates of preterm births in countries such as the Netherlands, Ireland and the United States, while the United Kingdom, Italy, India while others reported increases in stillbirths and some variability in preterm birth rates. However, most studies were limited by their small size.
To identify a possible shift, the study researchers analysed Ontario births over an 18-year period and compared these trends in the prepandemic period (2002–2019) with the pandemic period (January to December 2020).
“We found no unusual changes in rates of preterm birth or stillbirth during the pandemic, which is reassuring,” said Dr Prakesh Shah, a paediatrician-in-chief at Sinai Health and professor at University of Toronto, Toronto, Ontario.
It is possible that measures related to the pandemic and compliance with them could affect preterm birth rates in different settings. Thus, the researchers examined birth outcomes in the public health units with higher SARS-CoV-2 positivity rates (Toronto, Peel Region, York Region and Ottawa), and also compared urban and rural births and those in neighbourhoods with different average income levels.
“In some areas and in certain people, the restrictions could be beneficial, and in other settings or individuals, restrictions could have the opposite effect,” said Dr Shah.
International studies are now underway to help understand the impact of COVID on pregnancy and childbirth around the globe.
Long hours and delaying pregnancy to after 35 increase complication risk for female surgeons’ pregnancies. Photo by JESHOOTS.COM on Unsplash
A survey of female surgeons found that 48 percent had experienced major pregnancy complications, with even higher risks for those with more operation hours per week in the last trimester of pregnancy.
Women are entering the surgical field in increasing numbers but they continue to face well-known challenges related to childbearing. Surveys have documented pregnancy-related stigma, unmodified work schedules, brief maternity leave options, and little support for childcare and lactation needs after delivery. Due to a lack of childcare options in developed countries, many female trainees delay pregnancy until after 35, already a risk factor for pregnancy complications, researchers from Brigham and Women’s Hospital and elsewhere surveyed 1175 surgeons and surgical trainees from across the US to study their or their partner’s pregnancy experiences. They found that 48 percent of surveyed female surgeons experienced major pregnancy complications, with those who operated 12-or-more hours per week during the last trimester of pregnancy at a higher risk compared to those who did not. Their findings are published in JAMA Surgery.
“The way female surgeons are having children today makes them inherently a high-risk pregnancy group,” said corresponding author Erika Rangel, MD, MS, of the Division of General and Gastrointestinal Surgery. “In addition to long working hours, giving birth after age 35 and multiple gestation which is associated with increased use of assisted reproductive technologies – is a risk factor for having major pregnancy complications, including preterm birth and conditions related to placental dysfunction.”
The researchers found that over half (57 percent) of female surgeons worked more than 60 hours per week during pregnancy. Over a third (37 percent) took more than six overnight calls. Of the 42 percent of women who experienced a miscarriage (a rate twice that of the general population) three-quarters took no leave afterwards.
“As a woman reaches her third trimester, she should not be in the operating room for more than 12 hours a week,” Dr Rangel said. “That workload should be offset by colleagues in a fair way so that it does not add to the already-existing stigma that people face in asking for help, which is unfortunately not a part of our surgical culture.”
Male and female surgeons were asked to respond to the survey, which had been developed with obstetricians and gynaecologists. Nonchildbearing surgeons answered questions regarding their partners’ pregnancies. The investigators found that, compared to female nonsurgeons, female surgeons were 1.7 times more likely to experience major pregnancy complications, along with greater risk of musculoskeletal disorders, non-elective caesarean delivery, and postpartum depression, which was reported by 11 percent of female surgeons.
“The data we have accumulated is useful because it helps institutions understand the need to invest in a top-down campaign to support pregnant surgeons and change the culture surrounding childbearing,” Dr Rangel said. “We need to start with policy changes at the level of residency programs, to make it easier and more acceptable for women to have children when it’s healthier, while also changing policies within surgical departments. It is a brief period of time that a woman is pregnant, but supporting them is an investment in a surgeon who will continue to practice for another 25 or 30 years.”
Journal information: Rangel EL et al. “Incidence of Infertility and Pregnancy Complications in US Female Surgeons” JAMA Surgery DOI: 10.1001/jamasurg.2021.3301
Researchers have found that a World Health Organization (WHO) recommendation to wait at least 24 months to conceive after a previous birth may be unnecessarily long for mothers in high-income countries.
Lead researcher Dr Gizachew Tessema from the Curtin School of Population Health said that since the WHO advice was based on limited evidence from resource-limited countries, it was necessary to check the recommendation in higher-income settings. The researchers’ findings were published in journal PLOS ONE.
“We compared approximately 3 million births from 1.2 million women with at least three children and discovered the risk of adverse birth outcomes after an interpregnancy interval of less than six months was no greater than for those born after an 18-23 month interval,” Dr Tessema said.
“Given that the current recommendations on birth spacing is for a waiting time of at least 18 months to two years after livebirths, our findings are reassuring for families who conceive sooner than this.
“However, we found siblings born after a greater than 60-month interval had an increased risk of adverse birth outcomes.”
Dr Tessema said just as the current WHO recommendations are not age specific, the study’s results were not necessarily equally applicable to parents of all ages.
“Our next step with this research is to identify whether intervals between pregnancies affect the risk of adverse birth outcomes among women of different ages,” Dr Tessema said.
Dr Tessema is a perinatal and reproductive epidemiologist and conducted the study with senior author Professor Gavin Pereira, who are both from the Curtin School of Population Health and the new Curtin enAble Institute.
A strong and graded relationship between women’s heart health and pregnancy outcomes has been demonstrated by a study of more than 18 million pregnancies.
Significant metabolic and haemodynamic changes occur to a woman’s body during pregnancy, some of which can later increase the risk of cardiovascular disease. Risk factors for cardiovascular disease also impact on pregnancy outcomes. The researchers examined the presence of four cardiovascular disease risk factors in women prior to pregnancy: unhealthy body weight, smoking, hypertension and diabetes. The risk of pregnancy complications – maternal intensive care unit (ICU) admission, preterm birth, low birthweight and foetal death – rose along with the number of pre-pregnancy cardiovascular risk factors.
“Individual cardiovascular risk factors, such as obesity and hypertension, present before pregnancy have been associated with poor outcomes for both mother and baby,” said study author Dr Sadiya Khan, Northwestern University Feinberg School of Medicine, Chicago, US. “Our study now shows a dose-dependent relationship between the number of risk factors and several complications. These data underscore that improving overall heart health before pregnancy needs to be a priority.”
The study, which was published in the European Journal of Preventive Cardiology, was a cross-sectional analysis of maternal and foetal data from the US National Center for Health Statistics (NCHS), which gathers information on all live births and foetal deaths after 20 weeks’ gestation. Individual-level data was pooled from births to women aged 15 to 44 years from 2014 to 2018.
Information was collected on whether four cardiovascular risk factors were present before pregnancy: body mass index (BMI; under 18.5 kg/m2 or over 24.9 kg/m2), smoking, hypertension and diabetes. Women were categorised as having 0 to 4 risk factors. The researchers estimated the relative risks of maternal ICU admission, preterm birth (before 37 weeks), low birthweight (under 2500 g), and foetal death associated with risk factors compared with no risk factors (0). All analyses were adjusted for maternal age at delivery, race/ethnicity, education, receipt of prenatal care, parity, and birth plurality.
The analysis included a total of 18 646 512 pregnancies, with an average maternal age of 28.6 years. More than 60% of women had one or more pre-pregnancy cardiovascular risk factors, ranging from 52.5% with one risk factor and 0.02% with 4 risk factors.
Those with all four risk factors had an approximately 5.8-fold higher risk for ICU admission than those with none, 3.9-fold higher risk for preterm birth, 2.8-fold higher risk for low birthweight, and 8.7-fold higher risk for foetal death.
Graded associations were found between increasing numbers of pre-pregnancy risk factors and a higher odds of adverse outcomes. The risk ratio for maternal ICU admission compared to no risk factors was 1.12 for one risk factor, 1.86 for two risk factors, 4.24 for three risk factors, and 5.79 for four risk factors.
The analysis was repeated in women with their first pregnancy with consistent results. “We conducted this analysis since women with a complicated first pregnancy are more likely to have complications in subsequent pregnancies,” explained Dr Khan. “In addition, gestational weight gain can lead to a higher BMI going into the next pregnancy. We saw very similar results which strengthens the findings in the full cohort.”
She continued: “Levels of pre-pregnancy obesity and high blood pressure are rising and there are some indications that women are acquiring cardiovascular risk factors at earlier ages than before. In addition, pregnancies are occurring later in life, giving risk factors more time to accumulate. Taken together, this has created a perfect storm of more risk factors, earlier onset, and later pregnancies.”
Dr Khan concluded: “The findings argue for more comprehensive pre-pregnancy cardiovascular assessment rather than focussing on individual risk factors, such as BMI or blood pressure, in isolation. In reality not all pregnancies are planned, but ideally we would evaluate women well in advance of becoming pregnant so there is time to optimise their health. We also need to shift our focus towards prioritising and promoting women’s health as a society – so instead of just identifying hypertension, we prevent blood pressure from becoming elevated.”
Journal information: Wang, M.C., et al. (2021) Association of pre-pregnancy cardiovascular risk factor burden with adverse maternal and offspring outcomes. European Journal of Preventive Cardiology. doi.org/10.1093/eurjpc/zwab121.
According to a new study, antibiotic exposure early in life could alter human brain development in areas responsible for cognitive and emotional functions.
The study suggests that penicillin alters the body’s microbiome as well as gene expression, which allows cells to respond to its changing environment, in key areas of the developing brain. The findings, published in the journal iScience, suggest reducing widespread antibiotic use or using alternatives when possible to prevent neurodevelopment problems. Penicillin and related medicines, such as ampicillin and amoxicillin, are the most widely used antibiotics in children worldwide. In the United States, the average child receives nearly three courses of antibiotics before age 2, and similar or greater exposure rates occur elsewhere.
“Our previous work has shown that exposing young animals to antibiotics changes their metabolism and immunity. The third important development in early life involves the brain. This study is preliminary but shows a correlation between altering the microbiome and changes in the brain that should be further explored,” said lead author Martin Blaser, director of the Center for Advanced Biotechnology and Medicine at Rutgers.
In the study, mice were exposed to low-dose penicillin in utero or immediately after birth. Researchers found that, compared to the unexposed controls, mice given penicillin had large changes in their intestinal microbiota, with altered gene expression in the frontal cortex and amygdala. These two key brain areas are responsible for the development of memory as well as fear and stress responses.
Increasing evidence links conditions in the intestine to the brain in the ‘gut-brain axis‘. If this pathway is disturbed, it can lead to permanent altering of the brain’s structure and function and possibly lead to neuropsychiatric or neurodegenerative disorders in later childhood or adulthood.
“Early life is a critical period for neurodevelopment,” Blaser said. “In recent decades, there has been a rise in the incidence of childhood neurodevelopmental disorders, including autism spectrum disorder, attention deficit/hyperactivity disorder and learning disabilities. Although increased awareness and diagnosis are likely contributing factors, disruptions in cerebral gene expression early in development also could be responsible.”
Whether it is antibiotics directly affecting brain development or if molecules from the microbiome travelling to the brain, disturbing gene activity and causing cognitive deficits needs to be determined by future studies.
