Category: Obstetrics & Gynaecology

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IVF Babies Have Better Quality of Life as Adults

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Being conceived via assisted reproductive technology (ART), such as IVF, could boost quality of life in adulthood, according to the results of a new study published in Human Fertility. The findings offer reassuring news for people who have been conceived with ART, and those who need to use the technology to conceive.

“Our findings suggest that being ART-conceived can provide some advantages on quality of life in adulthood, independent of other psychosocial factors,” said lead author Karin Hammarberg of Monash University. “Together with previous evidence that adults conceived by ART have similar physical health to those who were naturally conceived, this is reassuring for people who were conceived with ART—and those who need ART to conceive.”

In the more than four decades since the first birth following in vitro fertilization (IVF) in 1978, more than 8 million children have been born as a result of ART. In that time, many studies have evaluated the physical health, development and psychosocial well-being of ART-conceived children compared with those naturally conceived (NC). But currently, there is less known about the health and quality of life of adults who were conceived by ART.

The study recruited 193 young adults conceived through ART and 86 through NC. These participants completed questionnaires, which included a standardised quality of life measure (World Health Organization Quality of Life – Brief Assessment [WHOQoL-BREF]), when aged 18–28 years (T1) and again when aged 22–35 years (T2). The WHOQoL-BREF assesses four domains of quality of life: 1) physical 2) psychosocial 3) social relationships and 4) environment.

The researchers looked at the associations between factors present at T1 (mode of conception, the mother’s age when the participant was born, sexual orientation, family financial situation in secondary school, perceptions of own weight, number of close friends, frequency of vigorous exercise and quality of relationships with parents) and the scores on the four domains of WHOQoL-BREF at T2.

After making statistical adjustments to account for other psychosocial factors present in young adulthood, the results showed that being ART-conceived was strongly linked with higher scores (better quality of life) on both the social relationships and environment WHOQoL-BREF domains at T2. In addition, having less psychological distress, a more positive relationship with parents, a better financial situation, and perceptions of being about the right weight at T1 were associated with higher scores on one or more WHOQoL-BREF domains at T2.

“Children conceived via ART are nowadays a substantial part of the population—and it’s important to continue to evaluate the long-term effects of ART on their physical health and well-being as they progress through adolescence into adulthood,” said Hammarberg. “When accounting for other factors present in young adulthood, being ART-conceived appears to confer some advantages in quality of life. Perhaps unsurprisingly, we also found that, independently of how the person was conceived, having a better relationship with parents, less psychological distress, and a better family financial situation in young adulthood contributed to a better adult quality of life.”

This is the first study to explore the contributions of being conceived with ART and psychosocial factors present in young adulthood to the quality of life of adults. While the findings are reassuring, they should be interpreted with caution because many of those who took part in the first study did not take part in the follow-up study.

Source: Taylor & Francis

Categories : COVID Obstetrics & GynaecologyTags :

COVID Vaccination During Pregnancy Does not Cause Complications

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COVID vaccination during pregnancy is not associated with a higher risk of pregnancy complications, according to a large scale Swedish and Norwegian study published in the journal JAMA.

The study, which comprised almost 160 000 pregnancies, found there to be no increase in the risk of preterm birth, growth retardation, low Apgar scores at birth or the need for neonatal care after vaccination against COVID during pregnancy.

“The results are reassuring and can hopefully make pregnant individuals more willing to get vaccinated,” said co-first author Anne Örtqvist Rosin, researcher at the Department of Medicine, Karolinska Institutet.

Studies have shown that, compared to non-pregnant peers, pregnant women are at risk of serious COVID requiring intensive care with a higher risk of death. Preterm births are also more likely in pregnant women with severe COVID. COVID vaccines have been available in Sweden and Norway since January 2021, and in May 2021 Sweden recommended all pregnant individuals to have a COVID jab, followed in August by Norway.

“We’re still seeing that vaccination rates are lower than in the rest of the population, so it’s likely that there’s some concern about how the vaccines affect the pregnant individual and the foetus,” explained Dr Örtqvist Rosin. “When the vaccines were produced, pregnant women were not included in the large clinical studies, and until now there have been no population-based data about any risk there might be to them.”

The researchers linked Sweden’s Pregnancy Register and Norway’s Medical Birth Register to each country’s vaccination register to obtain data on if and when pregnant individuals were vaccinated and with which vaccine. The study included a total of 157 521 individuals who gave birth between January 2021 and January 2022, of whom 18% had been vaccinated. It was found that vaccinated individuals were at no higher risk than unvaccinated of developing one of the studied complications.

The majority of the pregnant individuals included in the study were vaccinated after week 12 in accordance with current recommendations, and 95% received an mRNA vaccine. This should be factored in when interpreting the results, which were similar for the different mRNA vaccines regardless of whether one or two doses were given. Vaccination during the third trimester and vaccination with the Moderna vaccine was associated with a slightly lower risk of needing neonatal care.

A possible benefit of vaccination during pregnancy is that the antibodies generated pass through the placenta, conferring a certain degree of protection against COVID to the newborn baby.

“We’re now planning to study how long this protection lasts, and if SARS-CoV-2 infection or vaccination during pregnancy has any other lasting effects on the child’s health,” said joint last author Professor Olof Stephansson at the Karolinska Institutet .

Source: Karolinska Institutet

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WHO Warns of Lethal Tranexamic Acid Mix-ups in Intrathecal Administration

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The World Health Organization is alerting health care professionals about the risk of lethal administration errors that can potentially occur with tranexamic acid (TXA) injection. There have been reports of TXA being mistaken for obstetric spinal anaesthesia used for caesarean deliveries resulting in inadvertent intrathecal administration.

Intrathecal TXA is a potent neurotoxin and neurological sequelae are manifested, with refractory seizures and 50% mortality. The profound toxicity of intrathecal TXA was described in 1980. In a 2019 review, Patel et al. identified 21 reported cases of inadvertent intrathecal injection of TXA since 1988, of which 20 were life-threatening and 10 fatal. It appears that mortality risk is greater after caesarean delivery. Sixteen were reported between 2009 and 2018.

WHO recommends early use of intravenous TXA within three hours of birth in addition to standard care for women with clinically diagnosed postpartum haemorrhage (PPH) following vaginal births or caesarean section. TXA should be administered at a fixed dose of 1g in 10 ml (100 mg/ml) IV at 1 ml per minute, with a second dose of 1g IV if bleeding continues after 30 minutes. In South Africa, the incidence of maternal bleeding after caesarean delivery has been characterised as a national emergency, and obstetric haemorrhage remains the third most common cause of maternal mortality at 17%.

However, problems can arise as TXA is frequently stored in close proximity with other medicines, including injectable local anaesthetics indicated for spinal analgesia (eg, for caesarean section). The presentation of some of the local anaesthetics is similar to the TXA presentation (transparent ampoule containing transparent solution), which can be administered in error instead of the intended intrathecal anaesthetic, and resulting in serious undesirable adverse effects.

Obstetricians from several countries have recently reported inadvertent intrathecal TXA administration and related serious neurological injuries. In a South African clinical alert, Bishop et al. highlighted the different appearances of TXA used in state and private hospitals, with one example in private hospitals appearing very similar (white label, red text) at first glance to spinal bupivacaine and stored in the same container. Applicable recommendations were provided by the authors.

TXA is a lifesaving medicine, however, this potential clinical risk should be considered and addressed by all operating theatre staff. Reviewing of existing operating theatre drug handling practice is required in order to decrease this risk, such as storage of TXA away from the anaesthetic drug trolley, preferably outside the theatre.

Source: World Health Organization

Categories : COVID Obstetrics & GynaecologyTags :

Severe COVID Raises Risk of Pregnancy Complications

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A University of Oxford study of over 4000 pregnant women indicates that severe COVID in pregnancy increases the risk of pre-labour caesarean birth, a very or extreme preterm birth, stillborn birth, and the need for admission to a neonatal unit.  

The study, published in Acta Obstetricia et Gynecologica Scandinavica, included 4436 pregnant women hospitalised in the UK with symptomatic COVID from March 1, 2020 to October 31, 2021, of whom 13.9% of had severe COVID. As well as having increased risks of adverse pregnancy-related outcomes, women with severe infection were more likely to be aged 30 years or over, be overweight or obese, be of mixed ethnicity, or have gestational diabetes compared with those with mild or moderate infection.  

“This new analysis shows that certain pregnant women admitted to a hospital with COVID face an elevated risk of severe disease. However, it shows once again the strongly protective effect of vaccination against severe disease and adverse outcomes for both mother and baby,” said senior author Marian Knight, FMedSci, of the University of Oxford. “This study emphasises the importance of ensuring that interventions to promote vaccine uptake are particularly focused towards those at highest risk.”

Source: Wiley

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Endocrine-disrupting Chemicals Present in Many Pregnancies

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Researchers in Europe have shown that up to 54% of pregnant women in Sweden were exposed to complex mixtures of endocrine-disrupting chemicals disruptive to brain development.

While current risk assessment tackles chemicals and their allowable exposures on an individual basis, these findings show the need to take mixtures into account for future risk assessment approaches. The study was published in Science.

A growing body of evidence has shown that industrially produced chemicals have endocrine disrupting properties and can thus be dangerous to human and animal health and development. A huge number of new compounds is released every year into the environment during the production of plastic derivatives and other goods.

While exposures for individual chemicals falls below thresholds, exposure to the same chemicals in complex mixtures can still impact human health. However, all current exposure thresholds, are based on chemicals being examined individually. Therefore, an alternative strategy needed to be tested, in which the actual mixtures measured in real life exposures could be tested as such in both the epidemiological and experimental setting. The EDC-MixRisk project set out to tackle this unmet need.

“The uniqueness of this comprehensive project is that we have linked population data with experimental studies, and then used this information to develop new methods for risk assessment of chemical mixtures,” said Carl-Gustaf Bornehag, professor at Karlstad University, Project Manager of the SELMA study.

The study was conducted in three steps:

  1. A mixture of chemicals in the blood and urine of pregnant women was identified in the Swedish pregnancy cohort SELMA, associated with delayed language development in children at 30 months. This critical mixture included a number of phthalates, bisphenol A, and perfluorinated chemicals.
  2. Experimental studies uncovered the molecular targets through which human-relevant levels of this mixture disrupted the regulation of endocrine circuits and of genes involved in autism and intellectual disability.
  3. The findings from the experimental studies were used to develop new principles for risk assessment of this mixture.

“It is striking that the findings in the experimental systems well reflected what we found in the epidemiological part, and that the effects could be demonstrated at normal exposure levels for humans,” said Joëlle Rüegg, professor of environmental toxicology at Uppsala University.

“Human brain organoids (advanced in vitro cultures that reproduce salient aspects of human brain development) afforded, for the first time, the opportunity to directly probe the molecular effects of this mixture on human brain tissue at stages matching those measured during pregnancy. Alongside other experimental systems and computational methods, we found that the mixture disrupts the regulation of genes linked to autism (one of whose hallmarks is language impairment), hinders the differentiation of neurons and alters thyroid hormone function in neural tissue,” said Giuseppe Testa, principal investigator of the EDC-MixRisk responsible for the human experimental modelling.

“One of the key hormonal pathways affected was thyroid hormone. Optimal levels of maternal thyroid hormone are needed in early pregnancy for brain growth and development, so it’s not surprising that there is an association with language delay as a function of prenatal exposure,” said Barbara Demeneix, professor of physiology and endocrinology at the Natural History Museum in Paris.

By combining these techniques, the researchers were able to show that 54% of children included in the SELMA study were at risk of delayed language development (at age 30 months) as they were prenatally exposed to a mixture of chemicals at levels that were above the levels predicted to impact neurodevelopment. Yet this risk fell below the exposure limits for individual chemicals.

Source: EURION Cluster

Categories : Neurology Obstetrics & GynaecologyTags :

Reduced Antiepileptic Drug Effectiveness in Pregnancy Uncovered

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Blood levels of many commonly used antiepileptic drugs drop dramatically with the onset of pregnancy, which can result in ‘breakthrough seizures’ according to a study published in JAMA Neurology.

The findings, collected as part of the multicentre study Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), explain why many people with epilepsy start experiencing breakthrough seizures after conception, underscoring the need to increase antiseizure medication doses and closely monitor blood levels over the course of pregnancy.

A fine-tuned medication regime is critical in epilepsy. “Some people mistakenly believe that changes in the drugs’ blood concentration won’t occur until after 20 weeks of pregnancy, but our study shows how important it is to start monitoring and adjusting patients’ medication dosages early on,” said lead author Dr Page Pennelll. “Nearly half of all pregnancies in the United States are unplanned, so it is important to ensure that doctors have a clear picture of each patient’s baseline drug level even if they are not trying to conceive.”

A life-altering neurological condition, two-thirds of epilepsy cases do not have a known cause. In people with epilepsy, nerve cells in the brain are hyper-reactive, causing them to change the pattern of their electrical activity and become spontaneously active. That synchronous activation is manifested in seizures.

Epilepsy has a fraught history of diagnosis and management; people with epilepsy go undiagnosed or under-treated. First-generation drugs to control it had many dangerous side effects and were contraindicated for people who are trying to conceive.

Since then, safer medications have entered the U.S. market and become widely available, but clinicians started noticing a new problem – patients whose epilepsy was successfully managed with medications started having seizures soon after becoming pregnant.

“Identifying which antiseizure medications may have changes in concentrations and at what point in pregnancy those changes occur is important for determining which patients may need to be monitored more closely during pregnancy and after delivery,” said senior author Professor Angela Birnbaum at the University of Minnesota.

To solve the mystery, the researchers embarked on a study to analyse blood concentrations of 10 commonly used antiseizure drugs and compare them across different stages of pregnancy and after childbirth.

The study found that blood levels of seven out of 10 of the medications they examined dropped dramatically — from 29.7% for lacosamide, a commonly prescribed anticonvulsant, and up to 56.4% for lamotrigine.

In addition, the researchers noted that the drop in drug levels occurred mere days after conception.

Source: University of Pittsburgh

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Teratogenic Drug Exposures Found in 1 in 16 Pregnancies

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Researchers have found, after reviewing a database containing 3 million pregnancies, that 1 in 16 women were exposed to teratogenic drugs.

The study, published in the American Journal of Obstetrics and Gynecology, highlights the need for women and their providers to carefully examine medications taken during pregnancy.

A teratogen is a substance that interferes with the normal development of a foetus. Hundreds of such drugs have been identified, including medications to treat seizures, migraines, obesity, acne, hypertension, bipolar disease and cancer.

University of Florida researchers investigated more than 200 teratogenic drugs and evaluated their exposure among 3.4 million pregnancies identified in a national private insurance database from 2006 to 2017. Prenatal exposure was defined by the mother taking at least one teratogenic drug during pregnancy.

The researchers divided drugs into two classes based upon their known teratogenic effect. About 140 drugs were known to have definite teratogenic effects, with another 65 identified as having potential teratogenic effects. The proportion of pregnancies with exposure to definite teratogens decreased slightly over the 12-year study period from 1.9% to 1.2%, while exposures for potential teratogens increased from 3.4% to 5.3%.

“While declining exposure rates among teratogenic drugs with definite risk are encouraging, the rising prenatal exposure to drugs with potential risk calls for more assessment,”  study author Professor Almut Winterstein, PhD, RPh. “To have 1 in 16 women and their unborn baby exposed to a teratogenic medication is simply too high, and we must identify strategies to improve pregnancy outcomes.”

The study also examined age and risk for prenatal exposure to teratogenic drugs and found teenagers and women in their 40s had the greatest risk. Both groups are known to have more unintended pregnancies and the drug exposure may have been accidental, which points to the need for more information about effective birth control and family planning when using teratogenic drugs.

The researchers were especially interested in prenatal exposure during more recent years, following the enactment of FDA requirements for risk mitigation strategies. Those are designed to reinforce safe medication-use behaviors, such as a pregnancy test before a teratogenic drug is started, and only a few medications require this extra safety precaution.

The 12 drugs with mitigation protocols in the study were found to be used infrequently and contributed to only a small portion of prenatal exposures. More research and regulatory action are needed to optimise the use of medications during pregnancy, the researchers concluded.

“There is much to do to address the evidence available regarding the risk-benefit of many drugs during pregnancy, and the availability of adequate risk-mitigation programs that ensure pregnancies are not unnecessarily exposed to teratogenic drugs,” Prof Winterstein said. “In the meantime, women and their providers must rely on the written information that is provided about the teratogenic risk for drugs during pregnancy.”

Source: University of Florida

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A Small Risk of Increased Congenital Abnormalities from Opioids in Pregnancy

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In a new study in the Canadian Medical Association Journal, researchers drawing on a provincial database report a small increased risk of congenital abnormalities in infants exposed to opioid medications in the first trimester of pregnancy.

Prescribed opioid pain medications are capable of crossing the placenta and have the potential to cause harm. In a study comparing placental crossing rates for various opioids, oxycodone, a commonly prescribed opioid for pain relief, was the fastest. About 2%–4% of foetuses are exposed to these drugs. To determine the association between opioid pain medications in early pregnancy and congenital abnormalities in infants, investigators analysed administrative health data from Ontario on almost 600 000 birth parent–infant pairs. 

Among the infants included in the study, 2% (11 903) were exposed in utero to opioid analgesics, such as codeine, oxycodone, hydromorphone, tramadol, and morphine. Analysis showed a small increased risk of major anomalies with exposure to tramadol and morphine, and of minor anomalies with exposure to codeine, hydromorphone and oxycodone. Specific congenital anomalies observed included gastrointestinal and genital anomalies, neoplasms and tumours, and ankyloglossia.

This study adds to the evidence from previous studies in Sweden and Norway and also from a recent study of pregnant US Medicaid beneficiaries that suggested a small increased risk of congenital anomalies, an important finding for a pregnant person who may be prescribed opioids for pain relief.

“Both the potential for harm or distress to the pregnant person as a consequence of foregoing treatment and the subsequent risk to the infant must be considered for effective treatment,” the authors concluded. “These findings further quantify harms associated with prenatal exposure to opioid analgesics to inform treatment choices for pain in pregnancy.”

Source: EurekAlert!

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Women in Labour Have Faster Gastric Emptying with an Epidural

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A study published in Anesthesiology finds gastric emptying is substantially slower during labour – but somewhat faster in women who receive an epidural for anaesthesia.

There is an ongoing debate as to whether it’s safe for women to eat solid food during labour. Physician anaesthesiologists prefer that labouring women have an empty stomach because of the lower risk for aspiration of food in case general anaesthesia for a caesarean section becomes necessary.

“These results suggest anaesthesiologists should remain cautious about permitting solid food during labour, especially when epidural analgesia is not used,” according to the report by Lionel Bouvet, MD, PhD, and colleagues of Hospices Civils de Lyon, France. 

Researchers assessed gastric emptying rates in four groups of women: 10 who were non-pregnant, 10 who were pregnant at full term (around 39 weeks) but not in labour, 10 in labour without an epidural, and 10 in labour who received an epidural for labour pain. On an empty stomach, each woman ate a light meal of yoghurt. Ultrasound scans were then used to compare the rate of stomach emptying among the four groups.

Stomach emptying was delayed for women in labour without epidural, in line with previous studies. The rate of stomach emptying from 15 to 90 minutes after eating was 52% in non-pregnant women and 45% in pregnant women at full term, compared to 31% for labouring women who received an epidural and 7% for women in labour without an epidural.

With epidural analgesia, gastric emptying occurred much faster during labour than during labour without epidural analgesia. After 90 minutes, the stomach was empty in 3 out of 10 labouring women who received an epidural, compared to 0 of 10 women in labour who had not received an epidural. By 2 hours, the stomach was empty in 6 of the women who received an epidural, compared to just 1 woman without an epidural.

Although clinical practice varies, current guidelines of the ASA and Society for Obstetric Anesthesia and Perinatology (SOAP) state that “Solid foods should be avoided in laboring patients,” reflecting a concern over the risk of aspiration in case anesthesia and surgery are needed. This new study is one of the first to systematically compare the extent of gastric emptying delay during late pregnancy and childbirth and with versus without epidural labor analgesia.

The results confirm a “statistically and clinically significant” longer time to an empty stomach among women in labour. However for those receiving epidural analgesia, stomach emptying appears to occur faster. Based on their findings, Dr Bouvet and co-authors suggest that a light solid meal “could probably be allowed” for women in labour who are receiving epidural analgesia and considered at a low risk of caesarean section within at least the next two hours.

“The report by Dr Bouvet and colleagues enables us to rethink our current practice of fasting during childbirth,” commented Anesthesiology editor Yandong Jiang, MD., PhD. “It is desirable that women giving birth with an epidural do not have the additional stress of hunger, but instead be allowed to eat a light meal.”

This contrasts with the ASA/SOAP recommendation that women in labour should consume only clear liquids to prevent aspiration, noted Mark Zakowski, MD, FASA, chair of ASA’s Committee on Obstetric Anesthesia. “This study clearly shows that stomach emptying is quite a bit slower for women in labor, and that if they eat even a light meal of about 4 ounces [about 120g] of yogurt, many will still have food in their stomach a few hours later,” Dr Zakowski said. “Since the need for emergency caesarean may arise at any time, the current ASA/SOAP guideline of clear liquids only during labour seems justified.”

Source: American Society of Anesthesiologists

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Early Menopause and Oral Contraceptive Link

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Long-term use of oral contraceptives, as well as certain methods of tubal ligation (TL), were linked to lower levels of antimüllerian hormone, a biomarker for ovarian aging, suggesting an increased risk for early menopause, according to preliminary research.

Using data from the Nurses’ Health Study II, researchers at the UMass Amherst School of Public Health and Health Sciences examined the association of oral contraceptive use and tubal ligation with antimüllerian hormone (AMH).

Published in the journal Menopause, the results were “intriguing,” according to lead author Christine Langton, PhD candidate.

“We’re one of the larger studies to have looked at both of these contraceptive methods at the same time,” says Langton, now a post-doctoral researcher at the National Institute of Environmental Health Sciences. “We feel we’re contributing to the story, and to the literature, though nothing we did was definitive. This is a piece of the puzzle.”

Early menopause, which occurs before 45, puts women at greater risk for a range of health conditions including cardiovascular disease, osteoporosis and dementia. The researchers noted that oral contraceptives change hormone levels and prevent ovulation; tubal ligation may affect blood supply to the ovaries, and certain methods of the procedure may damage the ovary and surrounding neural tissue. 

“Recently, AMH has become an established marker for the timing of menopause and was found to be strongly associated with the risk of early menopause,” the authors wrote. “Yet, the association of reproductive and lifestyle factors with AMH levels remains unclear.”

The team focused on a subset of 1420 premenopausal women in the Nurses’ Health Study prospective cohort who had provided a blood sample between 1996 and 1999. A history of their oral contraceptive use and tubal ligation began in 1989 and was updated every two years until their blood was collected.

“Women who reported that their [tubal ligation] procedure included the use of a clip, ring or band had significantly lower AMH levels compared to women who never had a TL procedure,” the researchers wrote.

One limitation is the small number of women reporting the type of tubal ligation, Langton added.

When it came to oral contraceptives, “we saw a significant inverse association – the longer the use of oral contraceptives, the lower the AMH levels were,” Langton said. “That particular finding was a little surprising to us because it didn’t completely align with what we saw when we looked at oral contraceptives and early menopause in the larger cohort” of more than 115,000 women.

Even after adjusting for factors including BMI, smoking, alcohol, number of pregnancies and breastfeeding, the inverse association between oral contraceptive use and AMH levels remained significant.

“We think further research is warranted,” Langton said.

Source: University of Massachusetts