Mixed evidence on the link between maternal influenza during pregnancy and autism spectrum disorder

Could flu during pregnancy raise risk for autism?

Researchers at the Center for Infection and Immunity (CII) at Columbia University's Mailman School of Public Health found no evidence that laboratory-diagnosis alone of maternal influenza during pregnancy is associated with risk of autism spectrum disorder (ASD) in the offspring. They did, however, find a trend toward risk in mothers with a laboratory diagnosis of influenza and self-reported symptoms of severe illness. This trend did not achieve statistical significance.

The study is the first to assess the risk for ASD based on laboratory-verified maternal influenza infection, not just survey data or medical records. Results appear in the journal mSphere. 

The researchers analyzed questionnaires and blood samples from 338 mothers of children with ASD and 348 matched controls, as part of the Autism Birth Cohort Study, a prospective birth cohort in Norway. Blood samples were collected from mothers at mid-pregnancy and after delivery. Mothers also reported on their cold and flu symptoms during pregnancy.

Positive blood tests for past influenza A or influenza B infection were not associated with increased ASD risk. However, when researchers combined reports of influenza-like illness with the blood test results, they found a substantial, albeit statistically insignificant, increased risk of ASD. While random error could be responsible for the finding, the authors caution against dismissing it outright due to the magnitude of the association: children born to mothers with laboratory-verified flu and matching symptoms had nearly double the odds of later being diagnosed with ASD compared to women without flu and symptoms.

"Symptoms are important because they may indicate the extent to which the mother's immune system is fighting the flu," says first author Milada Mahic, a post-doctoral research scientist at Center for Infection and Immunity and the Norwegian Institute of Public Health. "If infection is contributing to increased risk, it likely comes from inflammation related to maternal immune system response rather than the flu infection itself. Further research is warranted." 

The flu-ASD finding aligns with past research suggesting that admission to hospital for maternal viral infection in the first trimester and maternal bacterial infection in the second trimester is associated with increased risk of ASD. 

In other recent studies from the Autism Birth Cohort Study, researchers reported that women actively infected with genital herpes during early pregnancy had twice the odds of giving birth to a child later diagnosed with ASD. Another new study reports maternal fever during pregnancy may raise risk for the child developing ASD. 

"The fetal brain undergoes rapid changes that make it vulnerable to a robust maternal immune response," says senior author W. Ian Lipkin, director of CII and John Snow Professor of Epidemiology at the Mailman School. "That said, mothers should not conclude that having an infection during pregnancy means that their child will develop autism. It may simply be one among many risk factors."

Autism risk linked to fever during pregnancy

Fever during pregnancy may raise the risk for autism spectrum disorder (ASD) in the child, according to a study led by scientists at the Center for Infection and Immunity (CII) at Columbia University's Mailman School of Public Health. The effect was most pronounced in the second trimester, raising odds for ASD by 40 percent. Risk of an ASD was increased by over 300 percent for the children of women reporting three or more fevers after the twelfth week of pregnancy.

The study is the most robust to date to explore the risk of ASD associated with fevers across the entire span of pregnancy, and of the capacity of two different types of commonly used anti-fever medications--acetaminophen and ibuprofen--to address that risk. Risks were minimally mitigated among the children of women taking acetaminophen for fever in the second trimester. Although there were no cases of ASD among children of mothers who took ibuprofen, a nonsteroidal anti-inflammatory drug, researchers could not ascertain whether risk was mitigated due to the extremely small number of women using this particular drug for fever. Results of the study appear in the journal Molecular Psychiatry.

The researchers followed 95,754 children born between 1999 and 2009, including 583 cases of ASD identified in Norway through the Autism Birth Cohort (ABC) Study. Mothers of 15,701 children (16 percent) reported fever in one or more four-week intervals throughout pregnancy, similar to rates reported in the U.S. ASD risk was increased by 34 percent when mothers reported fever at any time during pregnancy, and by 40 percent in the second trimester. The risk increased in a dose-dependent fashion from 1.3-fold with one or two fever episodes after the twelfth prenatal week to 3.12-fold with three or more episodes.

"Our results suggest a role for gestational maternal infection and innate immune responses to infection in the onset of at least some cases of autism spectrum disorder," says first author Mady Hornig, associate professor of Epidemiology and director of Translational Research at CII.

Questionnaire analysis did not indicate an association between risk and maternally-reported symptoms of infection in individual organ systems that might implicate specific infectious agents. An ongoing study is testing blood samples collected at mid-pregnancy and at birth to explore the possible role of specific infectious agents and the contribution of distinctive patterns of immune response among mothers and children to understand the mechanisms creating vulnerability.

"Future work should focus on identifying and preventing prenatal infections and inflammatory responses that may contribute to autism spectrum disorder," says senior author W. Ian Lipkin, John Snow Professor of Epidemiology and director of CII.

How do preemies perform in school?

Parents of prematurely born babies often fear their children may go on to struggle in school, but findings from a new large-scale study from the Institute for Policy Research at Northwestern University and Northwestern Medicine should reassure parents.

The large-scale study found that two-thirds of babies born at only 23 or 24 weeks were ready for kindergarten on time. Unexpectedly, nearly two percent of them even achieved gifted status in school. While these extremely premature babies often scored low on standardized tests, preterm infants born 25 weeks or later performed only slightly lower than full-term infants. In fact, as the length of pregnancy increased after 28 weeks, the differences in test scores were negligible.

The study will be published June 12 in JAMA Pediatrics.

"What excites me about this study is that it changes the focus for the clinician and families at the bedside from just focusing on the medical outcomes of the child to what the future educational outcomes might be for a child born early," said first author Dr. Craig Garfield, associate professor of pediatrics and of medical social sciences at Northwestern University Feinberg School of Medicine.

The longitudinal study analyzed more than 1.3 million babies born in Florida from 1992 to 2002 with gestational ages of 23 to 41 weeks who later entered Florida public schools between 1995 and 2012. The scientists matched the babies' vital statistic records with their Florida public school records to examine the association between being born early and educational performance.

"Many studies look at premature babies but very few of them look at their educational outcomes into middle school in such a large population," said Garfield, who also is an attending pediatrician at Ann & Robert H. Lurie Children's Hospital of Chicago. "What's special about this study is it speaks to the importance of administrative data sets and the ability to combine different data sets in ways that allow us to ask questions and get answers about how our children are doing in the long-run."

"While some people might be troubled that very premature infants tend to score well below their full-term peers on standardized tests, I believe that the glass is more than half-full," said senior author David Figlio, director of the Institute for Policy Research at Northwestern University. "Most infants born at 23 to 24 weeks still demonstrate a high degree of cognitive functioning at the start of kindergarten and throughout school."

While this study's data is strong, it does not account for some of these infants' medical issues related to preterm birth or provide information about why these children performed well in school, such as their biological make-up or if they received extra support from family or schools, Garfield said. Nevertheless, most babies born prematurely ended up performing reasonably well on standardized tests through middle school.

"Our future work in this area will focus on what parents and service providers can do to help future premature children to achieve their full potential," Garfield said.

Common periodontal pathogen may interfere with conception in women

According to a study carried out at the University of Helsinki, Finland, a common periodontal pathogen may delay conception in young women. This finding is novel: previous studies have shown that periodontal diseases may be a risk for general health, but no data on the influence of periodontal bacteria on conception or becoming pregnant have been available.

"Our results encourage young women of fertile age to take care of their oral health and attend periodontal evaluations regularly", says periodontist and researcher Susanna Paju, University of Helsinki.

Study population comprised 256 healthy non-pregnant women (mean age 29.2 years, range 19 to 42) who had discontinued contraception in order to become pregnant. They were enrolled from the general community from Southern Finland. Clinical oral and gynecological examinations were performed. Detection of major periodontal pathogens in saliva and analysis of serum and saliva antibodies against major periodontal pathogens as well as a vaginal swab for the diagnosis of bacterial vaginosis at baseline were carried out.

Subjects were followed-up to establish whether they did or did not become pregnant during the observation period of 12 months.

Porphyromonas gingivalis, a bacterium associated with periodontal diseases, was significantly more frequently detected in the saliva among women who did not become pregnant during the one-year follow-up period than among those who did. The levels of salivary and serum antibodies against this pathogen were also significantly higher in women who did not become pregnant.

Statistical analysis showed that the finding was independent of other risk factors contributing to conception, such as age, current smoking, socioeconomic status, bacterial vaginosis, previous deliveries, or clinical periodontal disease.

Women who had P. gingivalis in the saliva and higher saliva or serum antibody concentrations against this bacterium had a 3-fold hazard for not becoming pregnant compared to their counterparts. Increased hazard was nearly to 4-fold if more than one of these qualities and clinical signs of periodontitis were present.

"Our study does not answer the question on possible reasons for infertility but it shows that periodontal bacteria may have a systemic effect even in lower amounts, and even before clear clinical signs of gum disease can be seen", says Dr. Paju. "More studies are needed to explain the mechanisms behind this association."

Infertility is a major concern, and increasing healthcare resources are needed for infertility treatments. More attention should be paid to the potential effects of common periodontal diseases on general health. Young women are encouraged to take care of their oral health and maintain good oral hygiene also when they are planning pregnancy, suggests Dr. Paju.

Medical advice from risk-averse health professionals may contribute to some women's decisions to stop cycling to work during pregnancy, meaning they miss out on the potential benefits of the active commute

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Medical advice from risk-averse health professionals may contribute to some women's decisions to stop cycling to work during pregnancy, meaning they miss out on the potential benefits of the active commute. A recent study in the Journal of Transport & Health reveals the reasons why women decide to stop or continue cycling to work when they are pregnant, including often ambiguously worded or overly-cautious advice from medical guidelines, midwives and obstetricians.

More people than ever are commuting to work by bicycle in London. According to data from the 2011 census, the city saw a 144% increase in cycle-commuting over the previous decade. This has big health benefits, for the health of the individual cyclist as well as for public health more broadly, as it helps people move more as part of their everyday activities.

Moderate intensity exercise provides benefits during pregnancy for mother and baby. In the UK, the National Institute for Clinical Excellence (NICE) and the National Health Service (NHS) both recommend pregnant women engage in daily exercise to help manage common discomforts, reduce pregnancy complications like preeclampsia, reduce discomfort and improve mood. But when it comes to cycling, the advice dries up: there are no clear recommendations women can use to decide whether to continue cycling.

"Despite the clear health benefits of cycling and the push to get more people commuting by bike, especially in cities like London, the medical advice on cycling during pregnancy remains murky," commented Davara Lee Bennett, the author of the new study. "My research aimed to explore why women do -- and don't -- cycle to work when they're pregnant, with a view to supporting informed decision-making -- including, if women so wish, rocking the rust off their chains, and bringing their bikes out from under the stairs and into the light."

Bennett conducted three individual interviews and held three focus group discussions: with a group of women who had stopped cycling early, a group that had carried on into later pregnancy and a mixed group. She recorded and transcribed all of them, and analyzed the transcripts line-by-line to develop themes. The resulting factors that affected women's decisions fell into a few main areas: physical obstacles and enablers, perceptions of risk and of pregnancy itself, and advice.

The idea of risk was a key factor in decisions about continued cycling: women adjusted their cycling practices to minimize risk, taking partners' support or concern into account. Although some women had positive encounters with health professionals, the medical advice they received was often noncommittal or risk-averse.

During pregnancy, depending on women's proportions and the type of bike, the growing belly can feel physically restrictive. Some women stopped cycling because of this, while others found comfort from their daily aches and pains when they commuted by bike. Either way, more comfortable bikes helped: women preferred Dutch-style, upright designs with a low crossbar and a wide, supportive seat.
Perceptions of pregnancy also had an impact on women's decisions: some preferred to abandon their active commute, opting for a more peaceful state, while others continued to cycle in a bid to remain connected to their authentic selves.

"Understanding the obstacles to women's cycling during pregnancy can support the development of safer cycling infrastructure and informed medical guidelines, ultimately offering more women the opportunity to benefit from an active commute," said Bennett. "By addressing some of the more socially prohibitive public discourses on the topic, I hope that my research will not just enable informed decision-making by women, but also encourage more constructive support and advice for women from health professionals."

Pregnancy after breast cancer does not increase chance of recurrence

"These data provide reassurance to breast cancer survivors that having a baby after a breast cancer diagnosis may not increase the chance of their cancer coming back. For many young women around the world who want to grow and expand their families, it's very comforting news," said Erica L. Mayer, MD, MPH, ASCO Expert.

Findings from a retrospective study of 1,200 women provide reassurance to breast cancer survivors who are contemplating pregnancy. In the study, women who became pregnant after an early breast cancer diagnosis, including those with estrogen receptor (ER)-positive tumors, did not have a higher chance of cancer recurrence and death than those who did not become pregnant.

The study will be featured in a press briefing today and presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.

Breast cancer is the most common cancer in women of reproductive age. Taking into account current trends toward delaying childbearing, breast cancer in young women may occur before the completion of reproductive plans. Although half of young women with newly diagnosed breast cancer report interest in having children, less than 10% become pregnant after treatment.1 In fact, of all cancer survivors, breast cancer survivors are the least likely to have a baby after diagnosis.

Doctors and patients have long been concerned that pregnancy could increase the chance of breast cancer recurrence, particularly for women with ER-positive disease. Because ER-positive breast cancer is fueled by estrogen, the fear is that hormone levels during pregnancy could coax any occult cancer cells -- those that may remain in the body after treatment -- to grow.

Another concern regarding pregnancy in women with ER-positive cancer is the need to interrupt adjuvant (post-surgery) hormone therapy before trying to achieve a pregnancy. Such hormone therapy helps prevent cancer recurrence, and it is recommended that women receive it for at least 5 years and in some cases up to 10 years. "Our findings confirm that pregnancy after breast cancer should not be discouraged, even for women with ER-positive cancer," said lead study author Matteo Lambertini, MD, a medical oncologist and ESMO fellow at the Institut Jules Bordet in Brussels, Belgium.

"However, when deciding how long to wait before becoming pregnant, patients and doctors should consider each woman's personal risk for recurrence, particularly for women who need adjuvant hormone therapy."

With 1,207 patients, this is the largest study to investigate the safety of pregnancy after breast cancer and the only to address this question specifically in women with ER-positive breast cancer (the most common type of breast cancer), according to the authors.

This study included women who were diagnosed with non-metastatic breast cancer before 2008, under the age of 50. The majority (57%) had ER-positive cancer, and more than 40% had poor prognostic factors, such as large tumor size and cancer spread to the axillary lymph nodes. Among the 1,207 patients included in the study, 333 of the women became pregnant, and 874 did not (as per the case-control study design, researchers matched each patient who became pregnant with three patients who had similar cancer characteristics but did not become pregnant).

The median time from diagnosis to conception was 2.4 years. Women with ER-positive breast cancer tended to achieve pregnancy later than those with ER-negative disease; 23% of patients with ER-positive disease had a pregnancy beyond 5 years from diagnosis as compared to 7% in those with ER-negative tumors.

Key Findings

After a median follow-up of about 10 years from cancer diagnosis, there was no difference in disease-free survival between women who became pregnant and those who did not, irrespective of ER status. Secondary analyses showed that there was no difference in disease-free survival compared to women who did not become pregnant, irrespective of whether women completed the pregnancy or had an abortion, became pregnant less than two years or more than two years from breast cancer diagnosis, and whether patients had breastfed.

Among survivors of ER-positive cancer, there was also no difference in overall survival between women who became pregnant and those who did not. Survivors of ER-negative breast cancer who became pregnant had a 42% lower chance of dying than those who did not become pregnant.
"It's possible that pregnancy could be a protective factor for patients with ER-negative breast cancer, through either immune system mechanisms or hormonal mechanisms, but we need more research into this," said Dr. Lambertini.

Although there was limited data on breastfeeding in this study (64 patients, with 25 women who reported having breastfed their newborn), the results suggest that breastfeeding is feasible, even after breast surgery.

Next Steps

Although large, this study had limited information on the use of assisted reproductive technologies (such as in vitro fertilization) in breast cancer survivors, and HER2 status was unknown for about 80% of the women. Further research is also needed to study the effect of pregnancy on health outcomes of women with BRCA mutations, a group that generally develops breast cancer at a younger age. A large clinical trial (the POSITIVE study) is under way investigating the impact of interrupting adjuvant hormone therapy to allow for pregnancy in women with ER-positive breast cancer. This study will also provide further insight on the impact of reproductive technologies and breastfeeding.

This study was partly supported by grants from Les Amis de l'Institut Bordet (grant number 2012-09) and the European School of Oncology (ESO). The International Breast Cancer Study Group (IBCSG) study, which provided patient information for this study, was partially funded by the National Institutes of Health (grant number CA-753562).

1Letourneau JM, et al. Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer. 2012 Mar 15;118(6):1710-7
 

 

 

Cesarean patients sent home with more narcotic pain medications than needed

cesarean childbirth are prescribed more opioid (narcotic) pain medications than needed upon release from the hospital, a Vanderbilt University Medical Center (VUMC) study shows.

The study, published online today in Obstetrics and Gynecology and in print in July, studied 179 cesarean patients from VUMC over an eight-week period to examine the variation in opioid prescribing and consumption after cesarean delivery, the most common major surgical procedure performed in the United States.

"What we found is that prescribers, partly in order to expedite a patient's release from the hospital, have kind of a one-size-fits-all prescription model for patients when they are discharged from the hospital," said Sarah Osmundson, M.D., assistant professor of Obstetrics and Gynecology in the Division of Maternal-Fetal Medicine and the first author of the study, 'Postdischarge Opioid Use After Cesarean Delivery.' What we've learned is that this method may undertreat a few patients, but likely overtreats the vast majority of patients.

"There's so much attention around excess opioids and the growing problem with opioid addiction, and the question came up, how much are patients really using when they go home," Osmundson said. "Anecdotally, I was hearing that patients were using one to two tablets once they were home, but they went home with a prescription for 30 tablets. The big question for us is what is happening after discharge and can we modify that to reduce the amount of excess opioids prescribed."

The number of opioid overdose deaths in the United States has quadrupled in 15 years, a dramatic result of the current opioid abuse epidemic. The rise correlates with a sharp increase in the amount of legal prescription opioids dispensed. Most individuals using prescription opioids for non-medical purposes have obtained them from family members or friends who have been prescribed the medications.

For the study, starting on postoperative day 14 until they had stopped taking the medication, women were asked weekly about the number of opioid pills used, the amount remaining and their pain experience. The state's Substance Monitoring Program was used to ascertain prescription-filling details.

Michael Richardson, M.D., associate professor of Anesthesiology and a co-author, said more attention needs to be paid to patients' opioid use while they are still inpatients in the hospital to better predict their use after going home. "Our data suggest that providers are not currently considering in-hospital opioid use to determine the amount of opioid prescribed at discharge," Richardson said. "If the patient is not using very much in the hospital, why should they go home with a prescription for 30 oxycodone tablets?"

The study authors also found that many patients with a 30-day prescription believe they are supposed to take the pills until they are all gone, when in fact, they only need to take them when absolutely needed. Normally over-the-counter pain relievers such as ibuprofen or Tylenol are sufficient in controlling post cesarean pain.

The study found that most women (83 percent) used opioids after discharge for an average of eight days, and of the women who filled their prescriptions (92 percent) 74 percent had unused tablets. This amounted to about 2,540 unused 5 mg oxycodone tablets over the study period, Richardson said, and about 19,000 excess oxycodone per year from cesareans at VUMC alone.

And the majority (63 percent) stored their pills in an unlocked location in their home, which is another cause for concern, Osmundson said.

"Large studies show that the most common source for misused opioids are ones that are prescribed legally and to the appropriate person," Osmundson said. "We know that these are falling into the wrong hands and that people frequently use opioids prescribed to a friend or family member. One way to tackle the opioid epidemic is not to have excess opioids around, which is unlikely to happen, or to minimize what we're currently prescribing, which is doable," she said.

There's a balance, though, Richardson added. "You don't want to underprescribe either. In Tennessee a health care provider can't just call in a refill for opioids, so if you underprescribe when the patient is sent home from the hospital, someone has to pick up a paper prescription, and that's inconvenient for many patients.

Osmundson and Richardson say that they plan further study to determine whether in-hospital opioid use can guide postdischarge prescribing to reduce opioids without undertreating pain.

"If we can find a more nuanced way to prescribe, we can do a lot to reduce the excess opioids out there," Osmundson said.

Antidepressants during pregnancy associated with increased autism risk

The use of antidepressants, especially selective serotonin reuptake inhibitors, during the final two trimesters of pregnancy was associated with increased risk for autism spectrum disorder in children, according to an article published online by JAMA Pediatrics.

Antidepressants (ADs) are widely used during pregnancy to treat depression. Autism spectrum disorder (ASD) is a neurodevelopmental syndrome characterized by altered communication, language and social interaction and by particular patterns of interests and behaviors. Few studies have investigated the effect of AD use during pregnancy on the risk of ASD in children. A better understanding of the long-term neurodevelopmental effects of ADs on children when used during gestation is a public health priority.

Anick Bérard, Ph.D., of the University of Montreal, Canada, and coauthors used data on all pregnancies and children in Québec between January 1998 and December 2009. The authors identified 145,456 full-term singleton infants born alive. Of the infants, 1,054 (0.72 percent) had at least one ASD diagnosis; the average age at first ASD diagnosis was 4.6 years and the average age of children at the end of follow-up was 6.2 years. Boys with ASD outnumbered girls 4 to 1.

The authors identified 4,724 infants (3.2 percent) who were exposed to ADs in utero; 4,200 (88.9 percent) infants were exposed during the first trimester and 2,532 (53.6 percent) infants were exposed during the second and/or third trimester. There were 31 infants (1.2 percent) exposed to ADs during the second and/or third trimester diagnosed with ASD and 40 infants (1.0 percent) exposed during the first trimester diagnosed with ASD, according to the results.

The use of ADs during the second and/or third trimester was associated with an 87 percent increased of ASD (32 exposed infants), while no association was observed between the use of ADs during the first trimester or the year before pregnancy and the risk of ASD.

Results indicate the increased risk of ASD was observed with selective serotonin reuptake inhibitors (22 exposed infants) and with the use of more than one class of AD during the second and/or third trimester (five exposed infants). In children of mothers with a history of depression, the use of ADs during the second and/or third trimester was associated with an increased risk for ASD in the study (29 exposed infants).

The authors suggest several mechanisms may account for the increased risk of ASD associated with maternal use of ADs during pregnancy. Limitations to the study include its use of prescription filling data, which may not reflect actual use. The data also contained no information on maternal lifestyle.

"Further research is needed to specifically assess the risk of ASD associated with antidepressant types and dosages during pregnancy," the study concludes.

Using antidepressants during pregnancy greatly increases the risk of autism, Professor Anick Bérard of the University of Montreal and its affiliated CHU Sainte-Justine children's hospital revealed today. Prof. Bérard, an internationally renowned expert in the fields of pharmaceutical safety during pregnancy, came to her conclusions after reviewing data covering 145,456 pregnancies. "The variety of causes of autism remain unclear, but studies have shown that both genetics and environment can play a role," she explained. "Our study has established that taking antidepressants during the second or third trimester of pregnancy almost doubles the risk that the child will be diagnosed with autism by age 7, especially if the mother takes selective serotonin reuptake inhibitors, often known by its acronym SSRIs." Her findings were published today in JAMA Pediatrics.

Bérard and her colleagues worked with data from the Quebec Pregnancy Cohort and studied 145,456 children between the time of their conception up to age ten. In addition to information about the mother's use of antidepressants and the child's eventual diagnosis of autism, the data included a wealth of details that enabled the team to tease out the specific impact of the antidepressant drugs. For example, some people are genetically predisposed to autism (i.e., a family history of it.) Maternal age, and depression are known to be associated with the development of autism, as are certain socio-economic factors such as being exposed to poverty, and the team was able to take all of these into consideration. "We defined exposure to antidepressants as the mother having had one or more prescription for antidepressants filled during the second or third trimester of the pregnancy. This period was chosen as the infant's critical brain development occurs during this time," Prof. Bérard said. "Amongst all the children in the study, we then identified which children had been diagnosed with a form of autism by looking at hospital records indicating diagnosed childhood autism, atypical autism, Asperger's syndrome, or a pervasive developmental disorder. Finally, we looked for a statistical association between the two groups, and found a very significant one: an 87% increased risk." The results remained unchanged when only considering children who had been diagnosed by specialists such as psychiatrists and neurologists.

The findings are hugely important as six to ten percent of pregnant women are currently being treated for depression with antidepressants. In the current study, 1,054 children were diagnosed with autism (0.72% of the children in the study), on average at 4.5 years of age. Moreover, the prevalence of autism amongst children has increased from 4 in 10,000 children in 1966 to 100 in 10,000 today. While that increase can be attributed to both better detection and widening criteria for diagnosis, researchers believe that environmental factors are also playing a part. "It is biologically plausible that anti-depressants are causing autism if used at the time of brain development in the womb, as serotonin is involved in numerous pre- and postnatal developmental processes, including cell division, the migration of neuros, cell differentiation and synaptogenesis - the creation of links between brain cells," Prof. Bérard explained. "Some classes of anti-depressants work by inhibiting serotonin (SSRIs and some other antidepressant classes), which will have a negative impact on the ability of the brain to fully develop and adapt in-utero"

The World Health Organization indicates that depression will be the second leading cause of death by 2020, which leads the researchers to believe that antidepressants will likely to remain widely prescribed, including during pregnancy. "Our work contributes to a better understanding of the long-term neurodevelopmental effects of anti-depressants on children when they are used during gestation. Uncovering the outcomes of these drugs is a public health priority, given their widespread use," Prof. Bérard said.

Recommendations for use of aspirin to prevent preeclampsia

To prevent preeclampsia, new research suggests that low-dose aspirin should be given prophylactically to all women at high risk (those with diabetes or chronic hypertension) and any woman with two or more moderate risk factors (including obesity, multiple gestation and advanced maternal age).

Preeclampsia, a potentially dangerous complication of pregnancy characterized by high blood pressure and a high level of protein in the urine or other end organ affects, complicates between three and seven percent of the births in the U.S. One in seven preterm births and one in 10 maternal deaths in the U.S. can be directly attributed to preeclampsia. Currently, the only intervention that has been shown to reduce the risk of preeclampsia is the use of prophylactic low-dose aspirin.

The research is entitled 'A Cost-Benefit Analysis of Low-Does Aspirin Prophylaxis for the Prevention of Preeclampsia in the United States' was published research in Obstetrics & Gynecology.
 
The researchers developed a decision model to evaluate the risks, benefits and costs of four different approaches to aspirin prophylaxis -- no prophylaxis, prophylaxis per recommendations of the American College of Obstetricians and Gynecologists (only for a narrow segment of pregnant women -- namely, those with a history of preeclampsia necessitating delivery before 34 weeks gestation and those with preeclampsia in more than one prior pregnancy), prophylaxis per the U.S. Preventive Task Force recommendations, and universal prophylaxis for all women.

The researchers concluded, "Both the U.S. Preventive Task Force approach and universal prophylaxis would reduce morbidity, save lives, and lower health care costs in the United States to a much greater degree than the approach currently recommended by ACOG."

Having more children slows down aging process

A study by Simon Fraser University researchers suggests that the number of children born to a woman influences the rate at which her body ages.

The study led by health sciences professor Pablo Nepomnaschy and postdoctoral researcher Cindy Barha found that women who give birth to more surviving children exhibited longer telomeres. Telomeres are the protective tips found at the end of each DNA strand and are indicative of cellular aging. Longer telomeres are integral to cell replication and are associated with longevity.

The study assessed the number of children born to 75 women from two neighbouring indigenous rural Guatemalan communities, and their telomere lengths. The participants' telomere lengths were measured at two time points 13 years apart, through salivary specimens and buccal swabs. This is the first study to examine the direct association between the number of children and telomere shortening in humans over time.

According to Nepomnaschy, the study findings contradicts life history theory which predicts that producing a higher number of offspring accelerates the pace of biological aging. "The slower pace of telomere shortening found in the study participants who have more children however, may be attributed to the dramatic increase in estrogen, a hormone produced during pregnancy," says Nepomnaschy who also spearheads the Maternal and Child Health Laboratory at the SFU Faculty of Health Sciences. "Estrogen functions as a potent antioxidant that protects cells against telomere shortening."

The social environment that the study participants live in may also influence the relationship between their reproductive efforts and the pace of aging. "The women we followed over the course of the study were from natural fertility populations where mothers who bear numerous children receive more social support from their relatives and friends," explains Nepomnaschy. "Greater support leads to an increase in the amount of metabolic energy that can be allocated to tissue maintenance, thereby slowing down the process of aging."

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Link to study: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146424

Why fish intake by pregnant women improves the growth of a child's brain

Researchers at Tohoku University's School of Medicine have found an explanation for the correlation between eating fish during pregnancy, and the health of the baby's brain.

Dietary lipid contains fatty acids such as omega-6 and omega-3, which are essential nutrients for many animals and humans. The research group, led by Professor Noriko Osumi, found that a balanced intake of lipids by pregnant women is necessary for the normal brain formation of the unborn child.

In an animal study, the researchers noticed that when female mice were fed an omega-6-rich/omega-3-poor diet, their offsprings were born with a smaller brain and showed abnormal emotional behavior in adulthood.

This is significant because people in many countries these days have similarly poor dietary patterns and tend to consume more seed oils that are rich in omega-6 fatty acids and less fish rich in omega-3 fatty acids.

According to Professor Osumi, the brain abnormality found in the offsprings of mice used in the study, was caused by a premature aging of fetal neural stem cells that produce brain cells. The premature aging was promoted by an imbalance of oxides of omega-6 and omega-3 fatty acids. The offsprings also showed higher anxiety levels, even though they were raised on nutritionally optimized diets from an early lactation period.

A diet that contains a good balance of omega-6 and omega-3 fatty acids is known to improve the development of brain functions; this is based on earlier researches that evaluated the effects of maternal intake of an omega-3-poor diet on brain function in children.

The new study took this premise further and focused on the effects of dietary lipids on the brain formation. The results reveal why omega-6 and omega-3 balance is important for future brain function, and reinforces earlier suggestions that more fish intake by women during pregnancy can advantageously affect the child's health.

Women who eat more potatoes before pregnancy may have higher rates of gestational diabetes

Women who eat more potatoes before pregnancy may have higher rates of gestational diabetes--the form that occurs during pregnancy--compared to women who consume fewer potatoes, suggests a National Institutes of Health (NIH) study. The researchers propose that substituting potatoes with other vegetables, legumes or whole grains may help lower gestational diabetes risk. The findings appear in The BMJ (formerly the British Medical Journal).

Gestational diabetes is a common pregnancy complication that causes high blood sugar levels in the mother. The disorder can lead to future health problems for mother and child. Previous studies have linked foods with a high glycemic index, a measure of the ability to raise blood sugar levels, to a higher risk of gestational or type 2 diabetes. However, until the current study, the effect of potatoes, a common, high-glycemic food, on the development of gestational diabetes was unknown.

Researchers from NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and Harvard University evaluated more than 15,000 women in the Nurses' Health Study II. They analyzed records from 1991 to 2001 of women who had no history of illness before pregnancy and had not had gestational diabetes before. Every four years, the women filled out a questionnaire on the kinds of foods they had eaten during the previous year. For potatoes, the women were asked if they had consumed baked, boiled, or mashed potatoes, fries or potato chips, with possible responses ranging from "never" to "six or more times a day."

The researchers found that women who ate more potatoes had a higher risk of gestational diabetes. They estimated reductions in gestational diabetes risk by substituting the following foods for two servings of potatoes per week:

• 9 percent for other vegetables
• 10 percent for legumes
• 12 percent for whole grain foods

The authors cautioned, however, that because their study was not designed to prove cause and effect, their results do not prove conclusively that potato consumption directly leads to gestational diabetes. They added that their results need to be confirmed by other studies.

 

Eating soy may protect women from health risks of BPA

Consuming soy regularly may protect women who are undergoing infertility treatments from poor success rates linked to bisphenol A exposure, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Bisphenol A (BPA) is a chemical found in a variety of food containers, including polycarbonate plastic water bottles and can linings. BPA can mimic estrogen, one of the two main sex hormones found in women. Biomonitoring studies by the U.S. Centers for Disease Control and Prevention estimate that more than 96 percent of Americans have BPA in their bodies.

As of 2014, nearly 100 epidemiological studies have been published tying BPA to health problems, including reproductive disorders, according to the Society and IPEN's Introductory Guide to Endocrine-disrupting Chemicals.

"Our study is the first to show a possible interaction between soy and BPA in humans," said first author Jorge E. Chavarro, MD, ScD, of Harvard T.H. Chan School of Public Health, Brigham and Women's Hospital, and Harvard Medical School in Boston, MA. "This is consistent with research in mice that found a soy-rich diet could protect against reproductive health problems associated with BPA exposure. More research is needed to determine why soy has this effect in humans."

The researchers examined the relationship between BPA exposure, diet and success rates among 239 women who underwent at least one in vitro fertilization (IVF) cycle at the Massachusetts General Hospital Fertility Center between 2007 and 2012. The women participated in the Environment and Reproductive Health (EARTH) Study, an ongoing prospective cohort study designed to evaluate the role of environmental factors and nutrition in fertility. The EARTH Study was funded by the National Institutes of Health's National Institute of Environmental Health Sciences.

Participants' urine samples were analyzed to measure BPA exposure. The women, who were between the ages of 18 and 45, completed a lifestyle questionnaire that included questions about how frequently they ate soy-based foods. Among the participants, 176 consumed soy foods.

Among women who did not eat soy foods, those with higher levels of BPA in their urine had lower rates of embryo implantation, fewer pregnancies that progressed to the point where the fetus could be seen on an ultrasound, and fewer live births than women with lower levels of BPA in their bodies. In comparison, BPA concentrations had no impact on IVF outcomes in women who routinely ate soy.

"Although it is recommended that women trying to get pregnant reduce their exposure to BPA, our findings suggest that diet may modify some of the risks of exposure to BPA, a chemical that is nearly impossible to completely avoid due to its widespread use," said senior author Russ Hauser, MD, ScD, MPH of Harvard T.H. Chan School of Public Health, Massachusetts General Hospital, Harvard Medical School in Boston, MA.

"Additional research could help identify other diet and lifestyle changes that may modify the effects of not only BPA exposure, but also exposure to other chemicals," Chavarro added. "In order to fully appreciate risks to human health, we need to design studies that adequately assess both diet and environmental chemical exposures."

The benefits of chocolate during pregnancy

In a study to be presented at the Society for Maternal-Fetal Medicine's annual meeting, The Pregnancy Meeting™, in Atlanta, researchers will present findings from a study titled, High-flavanol chocolate to improve placental function and to decrease the risk of preeclampsia: a double blind randomized clinical trial.

In light of previous studies showing conflicting results regarding the role of chocolate consumption during pregnancy and the risk of preeclampsia, this study set out to evaluate the impact of high-flavanol chocolate. Researchers conducted a single-center randomized controlled trial of 129 women with singleton pregnancy between 11 and 14 weeks gestation who had double-notching on uterine artery Doppler. The pregnant women selected were randomized to either high-flavanol or low-flavanol chocolate. A total of 30 grams of chocolate was consumed daily for 12 weeks and women were followed until delivery. Uterine artery Doppler pulsatility index was at baseline and 12 weeks after randomization. Preeclampsia, gestational hypertension, placenta weight, and birthweight were also evaluated.

The result was that there was no difference in preeclampsia, gestational hypertension, placental weight or birthweight in the two groups; however, the uterine artery Doppler pulsatility index (a surrogate marker of blood velocity in the uterine, placental and fetal circulations) in both groups showed marked improvement that was much greater than expected in general population.

"This study indicates that chocolate could have a positive impact on placenta and fetal growth and development and that chocolate's effects are not solely and directly due to flavanol content," explained Emmanuel Bujold, M.D., one of the researchers on the study who will present the findings. Dr. Bujold and Dr. Sylvie Dodin, principal investigator of the trial, are with the Université Laval Québec City, Canada.

Pregnancy in older age increases stroke, heart attack risk years later

Women who become pregnant at age 40 or older face a greater risk of stroke and heart attack later in life than women who become pregnant at a younger age, according to research presented at the American Stroke Association's International Stroke Conference 2016.

"We already knew that older women were more likely than younger women to experience health problems during their pregnancy," said Adnan I. Qureshi, M.D., lead researcher and director of the Zeenat Qureshi Stroke Institute in St. Cloud, Minnesota. "Now, we know that the consequences of that later pregnancy stretch years into the future."

Qureshi added that this finding was especially important because more women are choosing to have children after they turn forty.

Researchers reviewed data from 72,221 women aged 50 to 79 enrolled in the Women's Health Initiative Study. Of those, 3,306 women reported pregnancies at an advanced age, and researchers compared their rates of stroke, heart attack and cardiovascular death over the next 12 years with women who were pregnant at a younger age.

Researchers found that compared to pregnancy at a younger age, pregnancies at age 40 and older increased the risk of:

• Ischemic stroke (clot caused), the most common type of stroke, from 2.4 percent to 3.8 percent;
• Hemorrhagic stroke (brain bleed), from 0.5 percent to 1 percent;
• Heart attack from 2.5 percent to 3 percent; and
• Death from all forms of cardiovascular disease from 2.3 percent to 3.9 percent.

When researchers checked for well-known risk factors for cardiovascular disease, including high blood pressure, diabetes and high cholesterol, they found these factors explained most of the higher risk the older pregnant women faced. However, these established risk factors did not explain the link between advanced age pregnancy and stroke caused by a brain bleed. Researchers said this link needs further research. Hemorrhagic stroke accounts for about 13 percent of all strokes, according to the American Heart Association's 2016 Statistical Update.

Qureshi also noted that the only cardiovascular risk factor that did not increase with later pregnancies in the study population was smoking. Older pregnant women were less likely to smoke than younger women.

The age of last pregnancy has not been considered a risk factor for stroke, heart attack and other cardiovascular diseases. "However, women with a late pregnancy need to be aware of their increased risk and take steps to improve their cardiovascular health," he said. "And their doctors need to remain vigilant years later in monitoring these women's risk factors through physical examination and, perhaps more tests and earlier interventions to prevent stroke and other cardiovascular events."

Couples’ pre-pregnancy caffeine consumption linked to miscarriage risk, daily multivitamin before and after conception greatly reduces miscarriage risk.

A woman is more likely to miscarry if she and her partner drink more than two caffeinated beverages a day during the weeks leading up to conception, according to a new study from researchers at the National Institutes of Health and Ohio State University, Columbus. Similarly, women who drank more than two daily caffeinated beverages during the first seven weeks of pregnancy were also more likely to miscarry.

The study was published online in Fertility and Sterility.

“Our findings provide useful information for couples who are planning a pregnancy and who would like to minimize their risk for early pregnancy loss,” said the study’s first author, Germaine Buck Louis, Ph.D., director of the Division of Intramural Population Health Research at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

The researchers analyzed data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study, which was established to examine the relationship between fertility, lifestyle and exposure to environmental chemicals. The LIFE Study enrolled 501 couples from four counties in Michigan and 12 counties in Texas, from 2005 to 2009.

For the current study, researchers compared such lifestyle factors as cigarette use, caffeinated beverage consumption and multivitamin use among 344 couples with a singleton pregnancy from the weeks before they conceived through the seventh week of pregnancy.

The researchers reported their results using a statistical concept known as a hazard ratio, which estimates the chances of a particular health outcome occurring during the study time frame. For example, the researchers evaluated caffeinated beverage consumption in terms of the daily likelihood of pregnancy loss over a given time period. A score greater than 1 indicates an increased risk for pregnancy loss each day following conception, and a score less than 1 indicates a reduced daily risk.

Of the 344 pregnancies, 98 ended in miscarriage, or 28 percent. For the preconception period, miscarriage was associated with female age of 35 or above, for a hazard ratio of 1.96 (nearly twice the miscarriage risk of younger women). The study was not designed to conclusively prove cause and effect. The study authors cited possible explanations for the higher risk, including advanced age of sperm and egg in older couples or cumulative exposure to substances in the environment, which could be expected to increase as people age.

Both male and female consumption of more than two caffeinated beverages a day also was associated with an increased hazard ratio: 1.74 for females and 1.73 for males. Earlier studies, the authors noted, have documented increased pregnancy loss associated with caffeine consumption in early pregnancy. However, those studies could not rule out whether caffeine consumption contributed to pregnancy loss or was a sign of an unhealthy pregnancy. It’s possible, the authors wrote, that these earlier findings could have been the result of a healthy pregnancy, rather than caffeine consumption interfering with pregnancy. For example, the increase in food aversions and vomiting associated with a healthy pregnancy led the women to give up caffeinated beverages.

Because their study found caffeine consumption before pregnancy was associated with a higher risk of miscarriage, it’s more likely that caffeinated beverage consumption during this time directly contributes to pregnancy loss.

“Our findings also indicate that the male partner matters, too,” Dr. Buck Louis said. “Male preconception consumption of caffeinated beverages was just as strongly associated with pregnancy loss as females’.”

Finally, the researchers saw a reduction in miscarriage risk for women who took a daily multivitamin. During the preconception period, researchers found a hazard ratio of 0.45 — a 55-percent reduction in risk for pregnancy loss. Women who continued to take the vitamins through early pregnancy had a hazard ratio of 0.21, or a risk reduction of 79 percent. The authors cited other studies that found that vitamin B6 and folic acid — included in preconception and pregnancy vitamin formulations — can reduce miscarriage risk. Folic acid supplements are recommended (link is external) for women of childbearing age, as their use in the weeks leading up to and following conception reduces the risk for having a child with a neural tube defect.

Study supports fish consumption during pregnancy

A new study supports the theory that the detrimental effects of low-level exposure to mercury may be outweighed by the beneficial effects of fish consumption.

The study finds little evidence of harm in infants whose mothers had low fish consumption and low mercury exposure. In fact, infants of mothers with higher mercury exposure during pregnancy and who consumed more fish had better attention and needed less special handling during a newborn exam. This likely was due to the beneficial nutritional effects of fish consumption, according to the researchers.

"The better neurobehavioral performance observed in infants with higher mercury biomarkers should not be interpreted as a beneficial effect of mercury exposure, which is clearly neurotoxic," says Kim Yolton, PhD, a researcher at Cincinnati Children's Hospital Medical Center and senior author of the study. "It likely reflects the benefits of polyunsaturated fatty acid intake that also comes from fish and has been shown to benefit attention, memory, and other areas of development in children. In our study, mercury exposure was very low, primarily due to consumption of fish low in mercury, so the detrimental effects might have been outweighed by the beneficial effects of fish nutrition."

The study is published online in Neurotoxicology and Teratology.

The researchers assessed the neurobehavior of 344 5-week-old infants using a standard neurobehavioral scale. Gestational mercury exposure was measured in maternal blood and infant umbilical cord blood. The researchers collected fish consumption information from the mothers and estimated polyunsaturated fatty acid intake based on the type and amount of fish consumed.

Eighty-four percent of mothers reported eating fish during pregnancy but only about two ounces per week on average. Those infants with higher prenatal mercury exposure showed asymmetric, or unequal reflexes. But when fish consumption was taken into account, those whose mothers consumed more fish had better attention and needed less special handling.

In 2014, the FDA and EPA updated their advice to consumers to encourage women to eat more fish (eight to 12 ounces per week) than had previously been recommended and to select fish with the lowest mercury levels. These include salmon, shrimp, pollock, light canned tuna, tilapia, catfish, and cod. They also suggested avoiding fish with the highest mercury levels, including tilefish, shark, swordfish, and mackerel.

"The important thing for women to remember is that fish offers excellent nutritional qualities that can benefit a developing baby or young child," says Dr. Yolton. "Moms just need to be thoughtful about which fish they eat or provide to their child."

Oily fish eaten during pregnancy may reduce risk of asthma in offspring

Oily fish eaten during pregnancy may reduce risk of asthma in offspring

Children born to mothers who eat salmon when pregnant may be less likely to have doctor diagnosed asthma compared to children whose mothers do not eat it, new research has shown.

The study, led by Professor Philip Calder of the University of Southampton, was presented at the recent Experimental Biology Congress in San Diego.

Professor Calder presented the findings after being named as the tenth recipient of the Danone International Prize for Nutrition for his cutting edge research on fatty acid metabolism and functionality, focusing notably on the immune, inflammatory and cardiometabolic systems.

The Salmon in Pregnancy Study was a randomised controlled trial in which a group of women ate salmon twice a week from week 19 of pregnancy. Allergy tests were then performed on the children at six months and then at two to three years of age. Results were compared to a control group whose mothers did not eat salmon during pregnancy.

Professor Calder told the Congress that the early results, which are yet to be published, showed that at six months there was no difference in allergy rate between the two groups of children. However, at age two and half years, children whose mothers ate salmon while pregnant were less likely to have asthma.

These latest results are one example of Professor Calder's ground-breaking research into specific relationships between nutrition and immune-related conditions over the course of the human life course.

A particular strength of his research is its translational approach, extending the results of research in mechanistic and basic nutrition science to studies in humans, including both healthy volunteers and patients, thereby influencing the development of nutritional guidelines and innovative treatments, something with the Prize Committee have recognised.

Professor Calder's research over the years has shown that certain fatty acids - or a lack of them - are involved in a broad spectrum of common diseases ranging from diverse allergies through to atherosclerosis and inflammatory conditions such as Crohn's disease. The work carried out in this area over the last 25 years, to which Professor Calder has made important contributions, has deepened the scientific community's understanding of the underlying mechanisms that explain the relationship between nutrition and immunity, the important first step in the formulation of nutritional advice for better feeding the immune system.

Though fatty acids are at the centre of Professor Calder's work, he has also covered neighbouring areas such as pre- and probiotics, iron deficiency and amino acids, at all times with the objective of channelling the insights of nutrition science into improved public health.

Statins may shield unborn babies from mother's stress

Statins could protect the hearts of babies in the womb from the adverse effects of their mother's stress, research suggests.

Scientists have discovered that the widely-prescribed drugs help to counteract the negative impact of stress hormones on fetal growth and heart development in mice.

The therapy could lower the chances of babies being born underweight and reduce their risk of health problems in later life, including heart disease, researchers say.

Further studies are needed to assess the long-term effects of statins in pregnancy, but the drugs are already used occasionally in pregnant women and should be suitable for clinical trials, the team says.

Babies that are exposed to excessive stress hormones in the womb are often born underweight and have a greater risk of heart disease in later life.

Normally, the unborn baby is protected by a key enzyme produced by the placenta that breaks down stress hormones and greatly limits the amount of active hormones that reach the baby's blood supply.

When the expectant mother is stressed, they produce less of this enzyme and the baby is less well protected.

Scientists at the University of Edinburgh studied mice that cannot produce the enzyme as a model of maternal stress.

They found that stress hormones stop the placenta from developing normal blood vessels, which cuts back the blood supply to the growing fetus.

The developing fetus does not grow to full size as a result, and its heart function does not develop normally.

Treating the mother with a type of statin triggers production of a molecule called VEGF, which stimulates the development of blood vessels in the placenta.

By re-establishing the blood supply, the treatment promotes normal development of the heart and helps the baby to grow to a healthy birthweight, the team showed.

Around 2.5 million people in the UK take statins to lower high cholesterol.

The study is published in the journal Proceedings of the National Academy of Sciences and was funded by the Wellcome Trust. The research also received funding from the Raine Medical Research Foundation, University of Western Australia.

Professor Megan Holmes, of the University of Edinburgh's British Heart Foundation Centre for Cardiovascular Sciences, said: "These are very exciting results suggesting that there may finally be a potential therapy for women whose placenta is unable to maintain the normal growth of her baby.

"At present there is no treatment and babies may be born prematurely or small, and will be at greater risk of developing cardiovascular disease, diabetes and even psychiatric disorders later in life. Although more work needs to be done to show statins are safe in human pregnancy, these results show a new way forward for the major unmet need of fetal growth retardation."

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: "Low birthweight has been associated with maternal stress, and babies with low birthweights may be more prone to cardiovascular complications later in life.

"In this study the researchers have discovered that a drug called Pravastatin may counteract the consequences of increased levels of the stress hormone corticosterone within the placentas of mice. How Pravastatin counteracts the stress hormone is not yet understood, therefore more research is needed to see whether the drug will have the same effect in humans."

Prenatal fruit consumption boosts babies' cognitive development

Most people have heard the old adage "an apple a day keeps the doctor away." It's an old truth that encompasses more than just apples--eating fruit in general is well known to reduce risk for a wide variety of health conditions such as heart disease and stroke. But now a new study is showing the benefits of fruit can begin as early as in the womb.

The study, published in the journal EbioMedicine, found that mothers who consumed more fruit during pregnancy gave birth to children who performed better on developmental testing at one year of age. Piush Mandhane, senior author of the paper and associate professor of pediatrics at the University of Alberta's Faculty of Medicine & Dentistry, made the discovery using data from the Canadian Healthy Infant Longitudinal Development (CHILD) Study--a nationwide birth cohort study involving over 3,500 Canadian infants and their families. Mandhane leads the Edmonton site of the study.

"We wanted to know if we could identify what factors affect cognitive development," Mandhane explains. "We found that one of the biggest predictors of cognitive development was how much fruit moms consumed during pregnancy. The more fruit moms had, the higher their child's cognitive development."

The study examined data from 688 Edmonton children, and controlled for factors that would normally affect a child's learning and development such as family income, paternal and maternal education, and the gestational age of the child.

Using a traditional IQ scale as a model, the average IQ is 100 and the standard deviation is 15; two thirds of the population will fall between 85 and 115. Mandhane's study showed that if pregnant mothers ate six or seven servings of fruit or fruit juice a day, on average their infants placed six or seven points higher on the scale at one year of age.

"It's quite a substantial difference--that's half of a standard deviation," Mandhane explains. "We know that the longer a child is in the womb, the further they develop--and having one more serving of fruit per day in a mother's diet provides her baby with the same benefit as being born a whole week later."

To further build on the research, Mandhane teamed with Francois Bolduc, an associate professor in the Faculty of Medicine & Dentistry's Division of Pediatric Neurology, who researches the genetic basis of cognition in humans and fruit flies. Both researchers believe that combining pre-clinical models and epidemiological analysis is a novel approach that may provide useful new insights into future medical research.

"Flies are very different from humans but, surprisingly, they have 85 per cent of the genes involved in human brain function, making them a great model to study the genetics of memory," says Bolduc. "To be able to improve memory in individuals without genetic mutation is exceptional, so we were extremely interested in understanding the correlation seen between increased prenatal fruit intake and higher cognition."

According to Bolduc, fruit flies have a long track record in the field of learning and memory. Several genes known to be necessary in fly memory have now been found to be involved in intellectual disability and autism by Bolduc and others. In a subsequent series of experiments, he showed that flies born after being fed increased prenatal fruit juice had significantly better memory ability, similar to the results shown by Mandhane with one-year-old infants. He believes it suggests that brain function affected by fruit and the mechanisms involved have been maintained through evolution, and conserved across species.

While the findings are encouraging, Mandhane cautions against going overboard on fruit consumption as potential complications such as gestational diabetes and high birthweight--conditions associated with increased intake of natural sugars--have not been fully researched. Instead, he suggests that expectant mothers meet the daily intake recommended in Canada's Food Guide and consult with their doctors.

Mandhane also says he will continue work in the field, with plans to examine if the benefits of prenatal fruit consumption persist in children over time. He will also be looking to determine if fruit can influence childhood development related to executive functioning--in areas such as planning, organizing and working memory.

The benefits of exercise during pregnancy

Researchers collected and re-examined clinical trial data on exercise during pregnancy and whether it plays a role in preterm birth, and found that exercise is safe and does not increase the risk of preterm birth. In addition, women who exercised were less likely to have a C-section than those who did not. The study was published in the American Journal of Obstetrics & Gynecology.

Historically, women were discouraged from vigorous exercise during pregnancy because of the risk of preterm birth. "The thinking was that exercise releases norepinephrine in the body, which is a chemical that can stimulate contractions of the uterus, and thus lead to preterm birth," says senior author on the study Vincenzo Berghella, M.D., Director of Maternal Fetal Medicine and Professor at the Sidney Kimmel Medical College at Thomas Jefferson University. "But numerous studies including this new meta-analysis, have since shown that exercise does not harm the baby, and can have benefits for the mom and baby."

Dr. Berghella and his co-authors pooled data from nine randomized controlled studies - one of the strongest types studies involving human subjects - in which pregnant women were divided into two groups. Of the 2,059 women who were included in the analysis, about half (1,022 women) exercised for 35-90 minutes 3-4 times per week for 10 weeks or up until their delivery, whereas the other half, (1,037 women) engaged in no exercise.

The researchers found that there was no significant increase in preterm birth, defined as delivery before 37 weeks, in women who exercised than in those who did not. There were, however, a few benefits. Women who exercised were more likely to deliver vaginally - 73 percent of exercising women delivered vaginally whereas 67 percent of non-exercising women delivered vaginally. Likewise, there was a lower incidence of C-section in women who exercised during pregnancy - 17 percent of exercising women had a C-section versus 22 percent in those who did not. There was also lower incidence of gestational diabetes, and lower rates of high blood pressure in the exercising group.

All of the women included in this analysis were carrying a single baby (not twins), had normal weight to start with, and had no health conditions that prevented them from exercising.

"The results of this analysis support current guidelines from the American Congress of Obstetricians and Gynecologists (ACOG), which sets the recommendations for our field," says Dr. Berghella. "However, there are many reasons women pull back on exercise during pregnancy - discomfort, an increase in tiredness and feeling winded by low level exertion. This paper reinforces that exercise is good for the mom and the baby and does not hold any increased risk preterm birth."

Acetaminophen use when pregnant associated with kids' behavioral problems

Using the common pain-relieving medication acetaminophen during pregnancy was associated with increased risk for multiple behavioral problems in children, according to an article published online by JAMA Pediatrics.

Acetaminophen is generally considered safe in pregnancy and is used by a many pregnant women for pain and fever.

Evie Stergiakouli, Ph.D., of the University of Bristol, United Kingdom, and coauthors analyzed data for 7,796 mothers enrolled in the Avon Longitudinal Study of Parents and Children between 1991 and 1992 along with their children and partners. The authors examined associations between behavioral problems in children and their mothers' prenatal and postnatal acetaminophen use, as well as acetaminophen use by their partners.

Questionnaires assessed acetaminophen use at 18 and 32 weeks during pregnancy and when children were 5 years old. Behavioral problems in children reported by mothers were assessed by questionnaire when children were 7 years old.

At 18 weeks of pregnancy, 4,415 mothers (53 percent) reported using acetaminophen and 3,381 mothers (42 percent) reported using acetaminophen at 32 weeks. There were 6,916 mothers (89 percent) and 3,454 partners (84 percent) who used acetaminophen postnatally. The study reports 5 percent of children had behavioral problems.

 

Study results suggest prenatal use of acetaminophen by mothers at 18 and 32 weeks of pregnancy was associated with increased risk of conduct problems and hyperactivity symptoms in children, and maternal acetaminophen use at 32 weeks of pregnancy also was associated with higher risk for emotional symptoms and total difficulties in children.

Postnatal maternal acetaminophen use and acetaminophen use by partners were not associated with behavioral problems. Because the associations were not observed in these instances, the authors suggest that this may indicate that behavioral difficulties in children might not be explained by unmeasured behavioral or social factors linked to acetaminophen use.

Study limitations include a lack of information on dosage or duration of acetaminophen use.

"Children exposed to acetaminophen use prenatally are at increased risk of multiple behavioral difficulties. ... Our findings suggest that the association between acetaminophen use during pregnancy and offspring behavioral problems in childhood may be due to an intrauterine mechanism. Further studies are required to elucidate mechanisms behind this association as well as to test alternatives to a causal explanation. Given the widespread use of acetaminophen among pregnant women, this can have important implications on public health advice," the authors write.

But the authors also caution: "However, the risk of not treating fever or pain during pregnancy should be carefully weighed against any potential harm of acetaminophen to the offspring."

 

Unhealthy diet during pregnancy could be linked to ADHD

New research led by scientists from King's College London and the University of Bristol has found that a high-fat, high-sugar diet during pregnancy may be linked to symptoms of ADHD in children who show conduct problems early in life.

Published in the Journal of Child Psychology and Psychiatry, this study is the first to indicate that epigenetic changes evident at birth may explain the link between unhealthy diet, conduct problems and ADHD.

Early onset conduct problems (e.g. lying, fighting) and attention-deficit/hyperactivity disorder (ADHD) are the leading causes of child mental health referral in the UK. These two disorders tend to occur in tandem (more than 40 per cent of children with a diagnosis of conduct disorder also have a diagnosis of ADHD) and can also be traced back to very similar prenatal experiences such as maternal distress or poor nutrition.

In this new study of participants from the Bristol-based 'Children of the 90s' cohort, 83 children with early-onset conduct problems were compared with 81 children who had low levels of conduct problems. The researchers assessed how the mothers' nutrition affected epigenetic changes (or DNA methylation) of IGF2, a gene involved in fetal development and the brain development of areas implicated in ADHD - the cerebellum and hippocampus. Notably, DNA methylation of IGF2 had previously been found in children of mothers who were exposed to famine in the Netherlands during World War II.

The researchers from King's and Bristol found that poor prenatal nutrition, comprising high fat and sugar diets of processed food and confectionary, was associated with higher IGF2 methylation in children with early onset conduct problems and those with low conduct problems.

Higher IGF2 methylation was also associated with higher ADHD symptoms between the ages of 7 and 13, but only for children who showed an early onset of conduct problems.

Dr Edward Barker from King's College London said: 'Our finding that poor prenatal nutrition was associated with higher IGF2 methylation highlights the critical importance of a healthy diet during pregnancy.

'These results suggest that promoting a healthy prenatal diet may ultimately lower ADHD symptoms and conduct problems in children. This is encouraging given that nutritional and epigenetic risk factors can be altered.'

Dr Barker added: 'We now need to examine more specific types of nutrition. For example, the types of fats such as omega 3 fatty acids, from fish, walnuts and chicken are extremely important for neural development.

'We already know that nutritional supplements for children can lead to lower ADHD and conduct problems, so it will be important for future research to examine the role of epigenetic changes in this process.'

Exercise during pregnancy protects the next generation from age-related health risks

Exercise during pregnancy may be as effective in protecting the next generation from age-related health risks as efforts made during the offspring's own adulthood, new research suggests. Kevin Pearson, associate professor at the University of Kentucky Department of Pharmacology and Nutritional Sciences, will present preliminary findings on the long-term effects of physical activity during pregnancy at the American Physiological Society's Integrative Biology of Exercise 7 meeting in Phoenix.

Oxidative stress is damage to the body caused by an accumulation of unstable molecules called free radicals. The buildup of free radicals decreases resistance to stress and increases the risk of obesity and age-related and chronic disease. Reducing oxidative stress can help lessen the risks of conditions such as cancer, heart disease and type 2 diabetes.

The research team examined markers of oxidative stress, inflammation and insulin sensitivity in mice that were born to mothers who were exercised while pregnant. The offspring of the exercised mice had better stress resistance and improved insulin sensitivity, even into adulthood, than those born to sedentary mothers.

"To date, caloric restriction has been the most reproducible and promising intervention to improve these outcomes. An intense and expanding area of research is focused on discovering other short-term or easily achievable interventions that can have long-lasting beneficial effects," the researchers wrote.
The results of the rodent studies also have implications for human health. "Our findings highlight pregnancy as a sensitive period when positive lifestyle interventions could have significant and long-lasting beneficial effects on offspring metabolism and disease risk," wrote the research team.

Women who have their last baby after 35 are mentally sharper in old age

A new study has found that women have better brainpower after menopause if they had their last baby after age 35, used hormonal contraceptives for more than 10 years or began their menstrual cycle before turning 13.

This is the first study to investigate the association between age at last pregnancy, which can be a marker of a later surge of pregnancy-related hormones, and cognitive function in later life, said Roksana Karim, lead author of the study and assistant professor of clinical preventive medicine at the Keck School of Medicine of USC.

"Based on the findings, we would certainly not recommend that women wait until they're 35 to close their family, but the study provides strong evidence that there is a positive association between later age at last pregnancy and late-life cognition."

Postmenopausal women who had their last pregnancy after 35 had better verbal memory. Those who had their first pregnancy when they were 24 or older had significantly better executive function, which includes attention control, working memory, reasoning and problem solving.

The main hormones at play are estrogen and progesterone. In animal studies, estrogen has a beneficial impact on brain chemistry, function and structure; progesterone is linked with growth and development of brain tissue, Karim said.

The study, published this month in the Journal of the American Geriatrics Society, includes 830 women who, on average, were 60 years old. The data was adjusted for age, race and ethnicity, income, and education.

Participants were given a series of tests that included assessments of verbal memory (remembering a list of words or retelling a story after some distraction), psychomotor speed, attention and concentration, planning, visual perception, and memory.

Previous research has shown that many women experience brainpower and memory declines in their postmenopausal years. An outpouring of estrogen and progesterone, especially in later life, appears to be beneficial, Karim said.

Pregnancy, the pill and more hormones

The study found that other reproductive events were also important to later life cognition. More time between first and last period -- longer reproductive life -- proved valuable for executive function.

"Starting your period early means you have higher levels of the female sex hormone being produced by the ovaries," Karim said. "Girls are receiving the optimal levels early, so it's possible that their brain structures are better developed compared to those who are exposed to estrogen levels associated with menstrual cycles at a later age."

Use of the pill or other hormonal contraceptives for at least 10 years was beneficial for verbal memory and critical thinking ability.

"Oral contraceptives maintain and sustain a stable level of sex hormones in our blood stream," Karim said. "Stable is good."

Women who didn't carry their pregnancy to term and those who gave birth to two children had better overall cognitive ability, verbal memory and executive function when compared to women who had only one full-term pregnancy.

"The finding that even incomplete pregnancies are beneficial was novel and surprising," said Wendy Mack, the study's senior author and professor of preventive medicine at the Keck School of Medicine. "In general, our findings are intriguing and are supported by other clinical studies and animal studies."

In humans, however, previous studies have shown that "pregnancy brain" exists, meaning researchers found that pregnant women have poorer verbal memory, word fluency and word-list learning when compared to non-pregnant women.

"The issue is the human studies haven't followed women for the long term," Mack said. "They just looked at women during pregnancy. We are not sure if we can expect to detect a positive estrogen effect at that point, as the many bodily changes and psycho-social stressors during pregnancy also can impact women's cognitive and emotional functions."

Omega-3 supplements can prevent childhood asthma

Taking certain omega-3 fatty acid supplements during pregnancy can reduce the risk of childhood asthma by almost one third, according to a new study from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) and the University of Waterloo.

The study, published in the New England Journal of Medicine, found that women who were prescribed 2.4 grams of long-chain omega-3 supplements during the third trimester of pregnancy reduced their children's risk of asthma by 31 per cent. Long-chain omega-3 fatty acids, which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are found in cold water fish, and key to regulating human immune response.

"We've long suspected there was a link between the anti-inflammatory properties of long-chain omega-3 fats, the low intakes of omega-3 in Western diets and the rising rates of childhood asthma," said Professor Hans Bisgaard of COPSAC at the Copenhagen University Hospital. "This study proves that they are definitively and significantly related."

The study used rapid analytical techniques developed and performed at the University of Waterloo to measure levels of EPA and DHA in pregnant women's blood. The University of Waterloo is one of a few laboratories in the world equipped to run such tests.

"Measuring the levels of omega-3 fatty acids in blood provides an accurate and precise assessment of nutrient status," said Professor Ken Stark, Canada Research Chair in Nutritional Lipidomics and professor in the Faculty of Applied Health Sciences at Waterloo, who led the testing. "Our labs are uniquely equipped to measure fatty acids quickly, extremely precisely, and in a cost-efficient manner."

The testing also revealed that women with low blood levels of EPA and DHA at the beginning of the study benefitted the most from the supplements. For these women, it reduced their children's relative risk of developing asthma by 54 per cent.

"The proportion of women with low EPA and DHA in their blood is even higher in Canada and the United States as compared with Denmark. So we would expect an even greater reduction in risk among North American populations," said Professor Stark. "Identifying these women and providing them with supplements should be considered a front-line defense to reduce and prevent childhood asthma."

Researchers analyzed blood samples of 695 Danish women at 24 weeks' gestation and one week after delivery. They then monitored the health status of each participating child for five years, which is the age asthma symptoms can be clinically established.

"Asthma and wheezing disorders have more than doubled in Western countries in recent decades," said Professor Bisgaard. "We now have a preventative measure to help bring those numbers down."

Currently, one out of five young children suffer from asthma or a related disorder before school age.

A new study confirms: Pregnant women should avoid liquorice

A new Finnish study supports food recommendations for families with children in that women should avoid consuming large amounts of liquorice during pregnancy. The limit for safe consumption is not known.

In the study, youths that were exposed to large amounts of liquorice in the womb performed less well than others in cognitive reasoning tests carried out by a psychologist. The difference was equivalent to approximately seven IQ points.

Those exposed to liquorice also performed less well in tasks measuring memory capacity, and according to parental estimates, they had more ADHD-type problems than others. With girls, puberty had started earlier and advanced further.

The Glaku study carried out by the University of Helsinki, the National Institute for Health and Welfare and the Helsinki and Uusimaa hospital districts compared 378 youths of about 13 years whose mothers had consumed "large amounts" or "little/no" liquorice during pregnancy. In this study a large amount was defined as over 500 mg and little/no as less than 249 mg glycyrrhizin per week. These cutoffs are not based on health effects. 500 mg glycyrrhizin corresponds on average to 250 g liquorice.

The study report was published in the American Journal of Epidemiology. The first author of the article is Academy Professor Katri Räikkönen from the University of Helsinki.

Researchers suggest that pregnant women and women planning pregnancy should be informed of the harmful effects that products containing glycyrrhizin - such as liquorice and salty liquorice - may have on the fetus.

In Finland, this is already reality. In January 2016, the National Institute for Health and Welfare published food recommendations for families with children, in which liquorice was placed in the 'not recommended' category for pregnant women. According to the recommendations, occasional consumption of small amounts such as a portion of liquorice ice cream or a few liquorice sweets is not dangerous.

Researchers underline that things should be kept in proportion. A large number of Finns have been exposed to glycyrrhizin in the womb. Glycyrrhizin is one of many factors that affect the development of a fetus but it is impossible to say whether it was glycyrrhizin expressly that affected the development of a certain individual.

As a result of animal experiments, the biological mechanism of the effects of liquorice is well known. Glycyrrhizin intensifies the effects of stress hormone cortisol by inhibiting the enzyme that inactivates cortisol. While cortisol is essential to the development of a fetus, it is detrimental in large amounts.

It has long been known that glycyrrhizin causes higher blood pressure and shorter pregnancies in humans, but such long-lasting effects on the fetus have not been proven before.

Aspirin may help prevent pregnancy loss in women with high inflammation

A daily low dose of aspirin may help a subgroup of women, those who have previously lost a pregnancy, to successfully conceive and carry a pregnancy to term, according to an analysis by researchers at the National Institutes of Health. The women who benefited from the aspirin treatment had high levels of C-reactive protein (CRP), a substance in the blood indicating system-wide inflammation, which aspirin is thought to counteract. The study appears in the Journal of Clinical Endocrinology and Metabolism.

Researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) analyzed data originally obtained from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial. The trial sought to determine if daily low-dose aspirin could prevent subsequent pregnancy loss among women who had one or two prior losses.

For the current study, researchers classified the women into 3 groups: low CRP (below .70 mg per liter of blood), mid CRP (from .70 to 1.95) and high CRP (at or above 1.95). Women within each group received either daily low-dose aspirin or a placebo. In their analysis, researchers found no significant differences in birth rates between those receiving aspirin and those receiving placebo in both the low CRP and mid CRP groups. For the high CRP group, those taking the placebo had the lowest rate of live birth at 44 percent, while those taking daily aspirin had a live-birth rate of 59 percent — a 35-percent increase. Aspirin also appeared to reduce CRP levels in the high CRP group when measured during weeks 8, 20, and 36 of pregnancy.

The authors concluded that more research is needed to confirm the findings and to examine the potential influence of inflammation in becoming pregnant and maintaining pregnancy.

Higher Dose of Vitamin D May Benefit Pregnant Women

Vitamin D is essential for strong bones and overall health, but the amount our bodies make from sunlight exposure and obtain from foods is not always enough, particularly for pregnant women.

U.S. Department of Agriculture (USDA) and University of California, Davis (UC Davis) scientists have found that a higher dose of vitamin D supplement during pregnancy may reduce inflammation. Their findings were published in the November 2016 issue of The Journal of Nutrition.

The research team included Charles Stephensen, with the USDA-Agricultural Research Service (ARS) Western Human Nutrition Research Center (WHNRC) in Davis, California; Melissa Zerofsky, a former UC Davis doctorate student; and Bryon Jacoby, a maternal fetal medicine specialist affiliated with UC Davis Medical Center. Researchers wanted to find out whether vitamin D intake levels should be higher than those common in prenatal supplements—400 international units (IU).

Severe vitamin D deficiency can contribute to osteoporosis in adults and rickets (a condition of weakened bones) in infants and children. Recent surveys also suggest that vitamin D deficiency affects up to 69 percent of American pregnant women.

Higher vitamin D levels in a person's blood may protect against certain types of cancer, strengthen the immune system, reduce diabetes risk, and play a key role in suppressing inflammation. Reducing inflammation during pregnancy is important because inflammation is associated with high blood pressure, pre-eclampsia, premature delivery and low birthweight, according to Stephensen, research leader at WHNRC's Immunity and Disease Prevention Research Unit.

In the ARS-UC Davis study, healthy women in their first trimester of pregnancy voluntarily consumed different doses of vitamin D daily. They took either a multivitamin supplement containing 400 IU vitamin D and a placebo pill, or a 400 IU vitamin D supplement and an additional 1600 IU vitamin D pill. Blood samples were analyzed for various forms of vitamin D and immune and inflammatory markers. The mothers' blood pressure and infants' birthweight were recorded.

The vitamin D dosage did not affect maternal blood pressure or infant birthweight. However, the higher daily dose, 2000 IU vitamin D, increased circulating vitamin D concentrations relative to the 400 IU per day. Higher blood vitamin D was correlated with lower circulating tumor necrosis factor-α (TNF-α), an immune substance typically associated with inflammation.

The scientists concluded that consuming 2000 IU vitamin D instead of 400 IU each day is more effective at increasing vitamin D status in pregnant women. They also found that higher levels of vitamin D increased the proportion of a specific subset of immune cells with anti-inflammatory properties that may prevent adverse effects of excess inflammation.