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.
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.”
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.
Researchers have developed a topical antibody-based contraceptive for use by women, which works like a glue, clumping and trapping sperm.
Over 40 percent of pregnancies worldwide are unintended, even though multiple forms of contraception are available. As well as fuelling population growth, unintended pregnancies can negatively impact the physical, mental and economic wellbeing of mothers.
To address these problems, researchers from Boston University School of Medicine and ZabBio have developed an anti-sperm monoclonal antibody, the Human Contraception Antibody (HCA), which laboratory tests showed was safe and had potent sperm agglutination (clumping) and immobilisation activity.
“HCA appears to be suitable for contraceptive use and could be administered vaginally in a dissolvable film for a woman-controlled, on-demand birth control method,” explained senior author Deborah Anderson, PhD, professor of Medicine.
In order to assess its applicability as a topical contraceptive, the team tested HCA over a wide range of concentrations and under different physiologically relevant conditions in vitro. HCA was mixed with sperm from normal, healthy volunteers and then tested. Sperm became immobilised within 15 seconds, becoming stuck together. The researchers also found that HCA did not seem to cause vaginal inflammation in lab tissue culture tests.
Thanks to its safety and efficacy, HCA could fill current gaps in the contraception field. “HCA could be used by women who do not use currently available contraception methods and may have a significant impact on global health,” said Prof Anderson. HCA is currently being tested in a Phase I Clinical Trial.
The researchers also believe that a combination of HCA with other antibodies such as anti-HIV and anti-HSV antibodies could make a multipurpose prevention technology, a product that would both serve as a contraceptive and prevent sexually transmitted infections.
These findings appear online in the journal EBioMedicine.
Journal information: Gabriela Baldeon-Vaca et al, Production and characterization of a human antisperm monoclonal antibody against CD52g for topical contraception in women, EBioMedicine (2021). DOI: 10.1016/j.ebiom.2021.103478
Scientists have found that significant amounts of THC and CBD, the two main components of cannabis enter the embryonic brain of mice in utero and impair the mice’s ability as adults to respond to fluoxetine (Prozac).
The study suggests that when the developing brain is exposed to THC or CBD, normal interactions between endocannabinoid and serotonin signaling may be diminished as exposed individuals become adults.
“Hemp-derived CBD is a legal substance in the US, and we are in a time of increasing state-level legalisation of cannabis. Therefore, use of cannabis components have increased across most levels of society, including among pregnant women. The study marks the beginning of an effort to understand the effects of THC and CBD on the endogenous cannabinoid system (ECS) in the developing brain and body,” explained Hui-Chen Lu, director of the Linda and Jack Gill Center and professor in the Department of Psychological and Brain Sciences in the IU Bloomington College of Arts and Sciences.
Researchers studied four groups of pregnant mice. Some received daily moderate doses of either THC, CBD, or a combination of equal parts THC and CBD; a control group had placebo injections throughout pregnancy. Using mass spectrometry, IU psychological and brain sciences professor Heather Bradshaw tested embryos and found that CBD and THC both could cross the placenta and reach the embryonic brain.
“The surprising part is that maternal exposure to CBD alone — a drug that is often considered as safe and harmless and is a popular ‘natural’ therapy for morning sickness — resulted in a lasting impact on adult mice offspring,” Lu said. “Both prenatal THC and CBD exposure impaired the adult’s ability to respond to fluoxetine. The results suggest taking a cautious approach to using CBD during pregnancy.”
There is however some evidence for CBD’s effectiveness in treating chronic pain and anxiety, though currently the only FDA-approved indication for CBD is the treatment of severe seizure disorders.
“We still know very little about the effects of CBD on the developing brain,” Prof Lu said.
The new paper is one of the first studies to see the potential negative impact of CBD on the developing brain and later behaviours. However observational studies in the 1980s saw increased anxiety and depression in offspring of mothers who used the lower-strength cannabis available at the time. Since women may take cannabis products for nausea and vomiting, this has relevance for public health awareness.
Study co-author Ken Mackie, Gill Chair of Neuroscience at IU Bloomington, said researchers know that prenatal cannabis exposure may increase the risk for anxiety and depression, so it is important to evaluate the response to a class of drug used to treat anxiety and depression.
Though normal mouse behaviours were seen in many tests, one test — to determine their response to stress — had a strongly atypical result. In all groups, the mice responded normally to a stressful situation. As expected, fluoxetine increased stress resilience in mice whose mothers had received the placebo. However, the drug was ineffective in mice whose mothers had received THC, CBD or their combination.
Fluoxetine works by increasing the amount of serotonin available at brain synapses, an effect known to require the endocannabinoid system. This internal system of receptors, enzymes and molecules both mediates the effects of cannabis and plays a role in regulating various bodily systems, such as appetite, mood, stress and chronic pain.
To test if maternal exposure to THC and/or CBD impaired endocannabinoid signaling in the adult offspring, the researchers tested whether boosting the ECS with a drug would restore fluoxetine’s effectiveness. They found that the ECS boosting restored normal fluoxetine responses in mice that had received THC or CBD while their brains were developing.
Journal reference: de Sousa Maciel, I., et al. (2021) Perinatal CBD or THC Exposure Results in Lasting Resistance to Fluoxetine in the Forced Swim Test: Reversal by Fatty Acid Amide Hydrolase Inhibition. Cannabis and Cannabinoid Research. doi.org/10.1089/can.2021.0015.
A study has suggested that IVF clinics in the UK may be retrieving “far too many oocytes” and that most of them “may never be used and are probably discarded”, a finding that may well represent global practice.
Studies indicate that the optimal and safe number of oocytes needed for achieving an ongoing pregnancy is between six and 15. However, the use of egg freezing (such as to preserve fertility to a later age, known as social egg freezing), frozen embryo replacement (FER) cycles and aggressive stimulation regimes has raised this number in order to boost success rates in older women and in poor responders who produce fewer eggs. What is not known is the impact of numbers of eggs retrieved and of over-stimulation practices on the health of patients, and on their emotional state and finances.
Details of the analysis were presented online at the virtual Annual Meeting of ESHRE by Dr Gulam Bahadur from North Middlesex University Hospital, London.
More than 1.625 million eggs in the UK were retrieved from 147,274 women between 2015 and 2018. Although an average of 11 eggs was collected per patient, 16% of cycles were associated with 16-49 oocytes retrieved (per cycle) and 58 women each had over 50 eggs collected in a single egg retrieval procedure.
“Our observations suggests that the high oocyte number per retrieval procedure needs re-evaluation,” said Dr Bahadur. “In particular, this needs to focus on the side effects, including ovarian hyperstimulation syndrome and procedure-related complications, and on the fate of unused frozen oocytes and the costs associated with freezing them.
“Patients should be advised that it’s better to collect fewer eggs leading to good quality embryos which may go to term and result in a healthy baby.”
This report is based on all UK IVF clinics and relates to non-donor fertility treatment carried out between 2015 and 2018 during which 172 341 fresh oocyte retrieval cycles took place. All outcomes and patterns remained uniform over the four years.
A substantial number (n = 10 148) of cycles did not yield any oocytes. Over half (53%) of all IVF cycles were in the desired egg yield range of 6-15. In addition, a quarter of cycles yielded 1-5 eggs; 14% produced 16-25; and a minority (2%) resulted in 26-49 oocytes. The authors point out that multiple birth rates increase significantly from 6-15 oocytes onwards, which increases the risk of birth complications and low birth weight.
A total of 931 265 embryos resulted from all eggs retrieved – a fertilisation rate of 57%. Of the embryos created, more than one in five (22% or 209,080) were transferred into the uterus, while a slightly higher proportion (24% or 219, 563) were frozen.
The fate of the unfertilised oocytes (43%) is unknown, though they are usually discarded. Most of the embryos not transferred (54%) will likely be discarded after patients have paid for several years of storage.
“This comes with a financial and emotional cost,” said Bahadur. “Patients build an attachment with this frozen material and there’s insufficient counselling to support them. They should be given more information about the implications of freezing eggs and embryos.”
Researchers believe they have made a breakthrough in the science of keeping premature babies alive.
As part of her PhD work, James Cook University engineering lecturer Stephanie Baker led a pilot study that used a hybrid neural network to accurately predict how much risk individual premature babies face. This study was published in the journal Computers in Biology and Medicine.
Complications resulting from premature birth are the leading cause of death in children under five and over 50% of neonatal deaths occur in preterm infants, she said. In 2005, 12.9 million births, or 9.6% of all births worldwide, were preterm.
“Preterm birth rates are increasing almost everywhere. In neonatal intensive care units, assessment of mortality risk assists in making difficult decisions regarding which treatments should be used and if and when treatments are working effectively,” said Ms Baker.
To better guide their care, preterm babies are often given a score that indicates the risk they face.
“But there are several limitations of this system. Generating the score requires complex manual measurements, extensive laboratory results, and the listing of maternal characteristics and existing conditions,” noted Ms Baker.
She said the alternative was to measure variables that do not change (eg, birthweight) that prevents recalculation of the infant’s risk on an ongoing basis and does not show their response to treatment.
“An ideal scheme would be one that uses fundamental demographics and routinely measured vital signs to provide continuous assessment. This would allow for assessment of changing risk without placing unreasonable additional burden on healthcare staff,” said Ms Baker.
She said the JCU team’s research had culminated in the Neonatal Artificial Intelligence Mortality Score (NAIMS), a hybrid neural network that relies on simple demographics and trends in heart and respiratory rate to determine mortality risk.
“Using data generated over a 12 hour period, NAIMS showed strong performance in predicting an infant’s risk of mortality within 3, 7, or 14 days.
“This is the first work we’re aware of that uses only easy-to-record demographics and respiratory rate and heart rate data to produce an accurate prediction of immediate mortality risk,” said Ms Baker.
According to Ms Baker, the technique was fast with no invasive procedures or knowledge of medical histories needed.
“Due to the simplicity and high performance of our proposed scheme, NAIMS could easily be continuously and automatically recalculated, enabling analysis of a baby’s responsiveness to treatment and other health trends,” said Ms Baker.
She said NAIMS had proved accurate when tested against hospital mortality records of preterm babies and had the added advantage over existing schemes of being able to perform a risk assessment based on any 12 hour period of data gathered during the patient’s stay.
Ms Baker said the next step in the process was partnering with local hospitals to gather more data and undertake further testing.
“Additionally, we aim to conduct research into the prediction of other outcomes in neo-natal intensive care, such as the onset of sepsis and patient length of stay,” said Ms Baker.
Journal information: Baker, S., et al. (2021) Hybridized neural networks for non-invasive and continuous mortality risk assessment in neonates. Computers in Biology and Medicine. doi.org/10.1016/j.compbiomed.2021.104521.
Babies born by caesarean section lack the same healthy bacteria as those born vaginally, but a Rutgers-led study for the first time finds that these natural bacteria can be restored.
The human microbiota, consisting of trillions of bacteria, viruses, fungi and other microorganisms, live in and on our bodies, some potentially harmful while others provide benefits. During labour and birth, women naturally impart a small group of colonisers to their babies’ sterile bodies, which helps their immune system to develop. But antibiotics and C-sections disrupt this conferring of microbes and are related to increased risks of obesity (59% increase), asthma (21% increase) and metabolic diseases. ‘Vaginal seeding‘, where a baby delivered by C-section is swabbed with their mother’s vaginal fluids at birth, is becoming increasingly popular.
According to the World Health Organization, C-section is needed in about 15 percent of births to avoid risking the life of the mother or child. However, caesarean birth rates continue to rise worldwide with recent (2016) reported rates of 24.5% in Western Europe, 32% in North America, and 41% in South America.
To see how well babies could be seeded with the mother’s microbiota after birth, the researchers followed 177 babies from four countries over the first year of their lives. Of these, 98 were born vaginally and 79 were born by C-section, 30 of which were swabbed with a maternal vaginal gauze right after birth.
Analysis showed that the microbiota of the C-section babies swabbed with their mother’s vaginal fluids was similar to that of vaginally born babies. Also, the mother’s vaginal microbiomes on the day of birth were similar to other areas of their bodies (gut, mouth and skin), indicating that maternal vaginal fluids help to colonise bacteria across their babies’ bodies.
This was the first large observational study to show that ‘vaginal seeding’ normalises the microbiome development during their first year of life. The next step would be conducting randomised clinical trials to determine if the microbiota normalisation translates into disease protection, the researchers said.
“Further research is needed to determine which bacteria protect against obesity, asthma and allergies, diseases with underlying inflammation,” said senior author Maria Gloria Dominguez Bello, a professor in the Department of Biochemistry and Microbiology in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick. “Our results support the hypothesis that acquiring maternal vaginal microbes normalises microbiome development in the babies.”