Tag: pregnancy

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Secrets of Pregnant Mothers’ ‘Super Antibodies’ Revealed

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Pregnant mothers have the ability to confer greater immunity to the vulnerable developing foetus with ‘super antibodies’. Now, a far-reaching study published in Nature provides a surprising explanation of how this actually works, and what it could mean for preventing death and disability from a wide range of infectious diseases.

The findings suggest the amped-up antibodies that expecting mothers produce could be mimicked to create new drugs to treat diseases as well as improved vaccines to prevent them.

“For many years, scientists believed that antibodies cannot get inside cells. They don’t have the necessary machinery. And so, infections caused by pathogens that live exclusively inside cells were thought to be invisible to antibody-based therapies,” said Sing Sing Way, MD. “Our findings show that pregnancy changes the structure of certain sugars attached to the antibodies, which allows them to protect babies from infection by a much wider range of pathogens.”

“The maternal-infant dyad is so special. It’s the intimate connection between a mother and her baby,” says John Erickson, MD, PhD, first-author of the study.

Drs Way and Erickson are both part of Cincinnati Children’s Center for Inflammation and Tolerance and the Perinatal Institute, which strives to improve outcomes for all pregnant women and their newborns.

Erickson continues, “This special connection starts when babies are in the womb and continues after birth. I love seeing the closeness between mothers and their babies in our newborn care units. This discovery paves the way for pioneering new therapies that can specifically target infections in pregnant mothers and newborns babies. I believe these findings also will have far-reaching implications for antibody-based therapies in other fields.”

How mothers make super antibodies
The new study identifies the specific change in the sugar. During pregnancy, the “acetylated” form of sialic acid (one of the sugars attached to antibodies) shifts to the “deacetylated” form. This subtle molecular shift lets immunoglobulin G (IgG) take on an expanded protective role by stimulating immunity through receptors that respond specifically to deacetylated sugars.

“This change is the light switch that allows maternal antibodies to protect babies against infection inside cells,” Dr Way said.

“Mothers always seem to know best,” Dr Erickson added.

Revved-up antibodies can be produced in the lab
The research team pinned down the key biochemical differences between antibodies in virgin mice compared to pregnant ones. They also identified the enzyme naturally expressed during pregnancy responsible for driving this transformation.

Further, the team successfully restored lost immune protection by supplying lab-grown supplies of the antibodies from healthy pregnant mice to pups born to mothers that were gene-edited to lack the ability to remove acetylation from antibodies to enhance protection.

Hundreds of monoclonal antibodies have been produced as potential treatments for various disorders, including COVID, with a variety of results.

Dr Way said this molecular alteration can be replicated to change how antibodies stimulate the immune system to fine-tune their effects. This potentially could lead to improved treatments for infections caused by other intracellular pathogens including HIV and respiratory syncytial virus (RSV), a common virus that poses serious risks to infants.

Another reason to accelerate vaccine development
“We’ve known for years the many far-reaching benefits of breastfeeding,” Dr Erickson said. “One major factor is the transfer of antibodies in breastmilk.”

The study shows that nursing mothers retain the molecular switch, passing through the antibodies to their newborns.

Additionally, Dr Way says the findings underscore the importance of receiving all available vaccines for women of reproductive age – as well as the need for researchers to develop even more vaccines against infections that which are especially prominent in women during pregnancy or in newborn babies.

“The immunity needs to exist within the mother for it to be transferred to her child,” Dr Way said. “Without natural exposures or immunity primed by vaccination, when that light switch flips during pregnancy, there’s no electricity behind it.”

Source: Cincinnati Children’s Hospital Medical Center

Categories : Obstetrics & GynaecologyTags :

Study Confirms Analgesics during Pregnancy Carries Risks for Newborns

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Researchers have called for a reassessment of medical advice on analgesic use during pregnancy after a new study published in BMJ Open found that pregnant women using over-the-counter analgesics are about 1.5 times more likely to have a baby with health issues.

The study found elevated risks for preterm delivery, stillbirth or neonatal death, physical defects and other problems compared with the offspring of mothers who did not take such medications.

Between 30% and 80% of women globally use non-prescription analgesics in pregnancy for pain relief. However, there is presently great variation in evidence for safety of use during pregnancy, with some drugs considered safe and others not.

“We would encourage a strong reinforcement of the official advice for pregnant women.”

Aikaterini Zafeiri, first author of the study

The study analysed data from more than 151 000 pregnancies over 30 years (1985–2015) which contained medical notes for non-prescribed maternal consumption of five common analgesic. These were paracetamol, aspirin, and non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac, naproxen and ibuprofen – either as single compounds or in combinations.

Overall, 29% of women have taken over-the-counter analgesics during pregnancy, a figure which more than doubled to 60% during the last seven years of the 30-year study period.

When asked specifically at their first antenatal clinic visit, as opposed to later in pregnancy or after labour, 84% of women using painkillers reported use during the first 12 weeks after conception. However, the duration and dose of use and medical reason for use were not recorded.

Nevertheless, given that up to 60% of women reported using over the counter analgesics, they could not all have underlying medical conditions that would cause the increased risks seen in this study.

The study found increases in the following:

  • Neural tube defects: 64% more likely.
  • Admission to a neonatal unit: 57% more likely.
  • Neonatal death: 56% more likely.
  • Premature delivery before 37 weeks: 50% more likely.
  • Baby’s condition at birth based on APGAR score of less than 7 at five minutes: 48% more likely.
  • Stillbirth: 33% more likely.
  • Birthweight under 2.5 kg: 28% more likely.
  • Hypospadias, a birth defect affecting the penis: 27% more likely.

First author of the paper, Aikaterini Zafeiri of the University of Aberdeen said: “In light of the study findings, the ease of access to non-prescription painkillers, in combination with availability of mis-information as well as correct information through the internet, raises safety concerns.

“This is especially when mis-informed or partially-informed self-medication decisions are taken during pregnancy without medical advice.

“It should be reinforced that paracetamol in combination with NSAIDs is associated with a higher risk and pregnant women should always consult their doctor or midwife before taking any over-the-counter drugs. We would encourage a strong reinforcement of the official advice for pregnant women.”

Source: University of Aberdeen

Categories : Obstetrics & GynaecologyTags :

No Added Seizure Risk from Antidepressant Use in Pregnancy

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A large Swedish study in the journal Neurology found that pregnant women taking selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs) during the first trimester of was not linked to an increased risk for neonatal seizures and epilepsy in childhood.

Any increase in seizures or epilepsy is likely due to other factors, the researchers said.

“It’s not likely the medications themselves that are causing the seizures and epilepsy in children, but rather the reasons why these women are taking the medication,” according to Kelsey Kathleen Wiggs, a PhD candidate at Indiana University in Bloomington. There are also the other background factors that differ between women who do and do not use SSRI/SNRIs.

“When it rains, it pours,” Wiggs said. “Women who are taking antidepressants in pregnancy are doing that for lots of different reasons, and they might be at risk for different things than women who aren’t taking those medications in pregnancy.”

The study found an elevated risk for neonatal seizures (risk ratio [RR] 1.41) and epilepsy in early childhood (HR 1.21) among offspring of mothers who used antidepressants in pregnancy.

Adjustment for maternal indications for SSRI/SNRI use and background factors like smoking during pregnancy revealed that they were drivers for both associations: neonatal seizures (RR 1.10); epilepsy diagnosis at 5 years (HR 0.96). Parental history of epilepsy was not found to affect the association.

The findings provide a “conclusive answer” to these concerns with using SSRI/SNRIs during pregnancy, according to Anne Berg, PhD, and Torin Glass, BM, Bch, BAO.

“[SSRI/SNRIs] have been demonstrated to have serotonergic central nervous system effects and are associated with an observable withdrawal syndrome which may be seen in the neonate following in utero exposure,” noted Drs Berg and Glass, in an accompanying editorial.

“The authors understood that with a population-based data registry and huge sample size, they had more than sufficient statistical power to detect even a modest increase in risk,” the editorialists wrote. “They tested this hypothesis and were able to reject it, definitively!”

In order to determine whether antidepressants had a causal association with infant seizures and childhood epilepsy, the researchers analysed data from national Swedish healthcare registries on a total of 1 721 274 children in Sweden born between 1996 and 2011.

Participants were divided into two groups: one group of mothers who reported use of an SSRI (fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, escitalopram) or SNRI (venlafaxine, duloxetine) during the first trimester of pregnancy (n = 24 308), and another group with no reported antidepressant use (n = 1 696 966).

Source: MedPage Today

Categories : Neurology Obstetrics & GynaecologyTags :

Scientists Discover the Neurological Basis of Food Cravings in Pregnancy

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By examining mice, which get pregnancy cravings similar to humans, scientists have identified the neurological basis of food craving during pregnancy.

During pregnancy, the mother’s body undergoes a series of physiological and behavioural changes to create an environment facilitating the embryo’s development. Frequent consumption of tasty, high calorie foods driven by the cravings contributes to weight gain and obesity in pregnancy, with possible negative consequences for the baby’s health.

“There are many myths and popular beliefs regarding these cravings, although the neuronal mechanisms that cause them are not widely known,” noted study leader March Claret, at the University of Barcelona and leader of the study published in the journal Nature Metabolism.

The researchers found that the brains of pregnant female mice undergoes changes in the functional connections of the brain reward circuits, as well as the taste and sensorimotor centres. Mice, like pregnant women, are also more sensitive to sweet food, and develop binge-eating behaviours towards high calorie foods. “The alteration of these structures made us explore the mesolimbic pathway, one of the signal transmission pathways of dopaminergic neurons. Dopamine is a key neurotransmitter in motivational behaviours,” notes Claret, member of the Department of Medicine of the UB and the Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM).

The team saw that dopamine levels and dopamine receptor (D2R) activity increased in the nucleus accumbens, a brain region involved in the reward circuit. “This finding suggests that the pregnancy induces a full reorganisation of the mesolimbic neural circuits through the D2R neurons,” noted study leader Roberta Haddad-Tóvolli. “These neuronal cells – and their alteration – would be responsible for the cravings, since food anxiety, typical during pregnancy, disappeared after blocking their activity.”

The team demonstrated that persistent cravings have consequences for the offspring, affecting the metabolism and development of neural circuits that regulate food intake, leading to weight gain, anxiety and eating disorders. “These results are shocking, since many of the studies are focused on the analysis of how the mother’s permanent habits – such as obesity, malnutrition, or chronic stress – affect the health of the baby. However, this study indicates that short but recurrent behaviours, such as cravings, are enough to increase the psychological and metabolic vulnerability of the offspring,” concluded Claret.

The conclusions of the study could contribute to the improvement of nutritional guidelines for pregnant women in order to ensure a proper prenatal nutrition and prevent the development of diseases.

Source: University of Barcelona

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

Categories : Obstetrics & GynaecologyTags :

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!

Categories : Obstetrics & Gynaecology Substance Use UncategorizedTags :

Effects of Fathers’ Prenatal Alcohol Exposure Manifests in Offspring

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Researchers have discovered that males exposed to alcohol in utero later pass on those effects to their offspring during foetal development, through reduced placental efficiency. The study appears in FASEB Journal.

Dr Michael Golding, an associate professor at Texas A&M University has spent years investigating the father’s role, with regard to drugs and alcohol, in foetal development. Studies have shown that males pass down more than just their genetics, Dr Golding said, but exactly how that process works and the its consequences are still largely unknown.

“When you look at the data from throughout human history, there’s clear evidence that there’s something beyond just genetics being inherited from the male,” Dr Golding said. “So, if that data is solid, we’ve got to start looking more at male behaviour.

“Say you had a parent who was exposed to starvation – they could pass on what you might call a ‘thriftiness,’ where their kids can derive more nutrition from less food,” he said. “That could be a positive if they grow up in a similar environment, or they could grow up in a time when starvation isn’t an issue and they might be more prone to obesity or metabolic syndromes. That kind of data is clearly present in clinical data from humans.”

Epigenetics, which is Dr Golding’s area of study of how things beyond genes, such as behaviour and environment, affect development is called. One of the big questions in the search for answers on how male prenatal behaviour can impact foetal growth has been the way these epigenetic factors manifest.

The team has shown that prenatal exposure to alcohol in males can manifest in the placenta: in mice, offspring of fathers exposed to alcohol have a number of placenta-related difficulties, including increased foetal growth restriction, enlarged placentas, and decreased placental efficiency.

“The placenta supplies nutrients to the growing foetus, so foetal growth restriction can be attributed to a less efficient placenta. This is why placental efficiency is such an important metric; it tells us how many grams of foetus are produced per gram of placenta,” said Thomas, a graduate student at Texas A&M. “With paternal alcohol exposure, placentas become overgrown as they try to compensate for their inefficiency in delivering nutrients to the foetus.”

However,while these increases happened frequently in male offspring, the frequency varied greatly based on the mother; however, the same increases were far less frequent in female offspring. Dr Golding thinks that although information is passed from the father, the mother’s genetics and the offspring’s sex are also involved.

“This is a novel observation because it says that there’s some complexity here,” Dr Golding said. “Yes, men can pass things on to their offspring beyond just genetics, but the mom’s genetics can interpret those epigenetic factors differently, and that ultimately changes the way that the placenta behaves.”

These results don’t draw a clear line in how drinking in human males prior to conception impacts foetal development, but they continue to at least point to it being a question that needs to be explored. 

Dr Golding is hoping that more questions will be asked about male prenatal behaviour so that there’s more data from which to work.

“The thing that I want to ultimately change is this stigma surrounding the development of birth defects,” Dr Golding said. “There’s information coming through in sperm that is going to impact the offspring but is not tied to the genetic code; it’s in your epigenetic code, and this is highly susceptible to environmental exposures, so the birth defects that we see might not be the mother’s fault; they might be the father’s or both, equally.”

Source: Texas A&M University