ADHD More Common if Grandmother Used DES During Pregnancy

MedicalResearch.com Interview with:

Marianthi-Anna Kioumourtzoglou ScD Assistant Professor Environmental Health Sciences Mailman School of Public Health Columbia University 

Dr. Kioumourtzoglou

Marianthi-Anna Kioumourtzoglou ScD
Assistant Professor
Environmental Health Sciences
Mailman School of Public Health
Columbia University 

MedicalResearch.com: What is the background for this study?

Response: The prevalence of neurodevelopmental disorders, like attention deficit/hyperactivity disorder (ADHD) has been increasing. One of the hypothesized risk factors for increased risk for neurodevelopmental disorders is a class of chemicals known as endocrine disrupting chemicals (EDCs). These chemicals are known to interfere with the endocrine system, i.e. the system that uses hormones to control and coordinate metabolism, reproduction and development. Several high production volume chemicals, ubiquitously present in commercial products, are known or suspected endocrine disruptors. Because of their widespread use in consumer products, the population-wide exposure to known and suspected EDCs is very high.

Recently, there has been increased attention in the potential effects of EDCs on neurodevelopment that span multiple generations. Animal studies have provided evidence that exposure to EDCs, such as phthalates and bisphenol A (BPA), alter the behavior and social interactions in mice in three to five generations after exposure. However, evidence of such multi-generational impacts of EDC exposure on neurodevelopment in humans is unavailable, likely because of the lack of detailed information on exposures and outcomes across generations.

For this study we leveraged information from a nationwide cohort, the Nurses’ Health Study II (NHSII), to investigate the potential link between exposure to diethylstilbestrol (DES) and third generation ADHD, i.e. ADHD among the grandchildren of the women who used DES while pregnant. DES is a very potent endocrine disruptor that was prescribed between 1938 and 1971 to pregnant women thought to prevent pregnancy complications. In the United States, between 5 and 10 million women are estimated to have used DES, although the exact number is not known. DES was banned in 1971, when was linked to vaginal adenocarcinomas (a rare cancer of the reproductive system) in the daughters of the women who had used it during pregnancy. Since then, DES has been also linked to multiple other reproductive outcomes in DES daughters, as well as with some reproductive outcomes in the grandchildren of the women who used it, such as hypospadias and delated menstrual regularization. However, to our knowledge, no study to date has evaluated the association between DES, or any other EDC, and multigenerational neurodevelopment.

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Zika Birth Defects More Severe When Mothers Infected During First Trimester

MedicalResearch.com Interview with:

This image depicts a posterior view of a patient’s back, captured in a clinical setting, upon presenting with this blotchy rash. After a diagnostic work-up, it was determined that the rash had been caused by the Zika virus. Note: Not all patients with Zika get a rash CDC image

This image depicts a posterior view of a patient’s back, captured in a clinical setting, upon presenting with this blotchy rash. After a diagnostic work-up, it was determined that the rash had been caused by the Zika virus.
Note: Not all patients with Zika get a rash
CDC image

Professor Bruno Hoen, M.D., Ph.D
Dept of Infectious Diseases, Dermatology, and Internal Medicine
University Medical Center of Guadeloupe 

MedicalResearch.com: What is the background for this study?

Response: Zika virus (ZIKV) infection during pregnancy has been identified only recently to cause severe birth defects, including microcephaly, other brain defects, and the congenital Zika syndrome. However, the magnitude of this risk was not clearly defined, with discrepancies between observational data from Brazil and the U.S. Zika Pregnancy Registry. We implemented a cohort study of pregnant women who have been exposed to ZIKV throughout the outbreak that hit the Caribbean in 2016.
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Autoantibodies Generated By Zika Virus May Explain Some Consequences of Infection

MedicalResearch.com Interview with:

Slobodan Paessler, D.V.M., Ph.D. Associate Professor, Department of Pathology; Director, Galveston National Laboratory Preclinical Studies Core;  Director, Animal Biosafety Level 3, Institute for Human Infections and Immunity; Member, Center for Biodefense & Emerging Infectious Diseases University of Texas Medical Branch  Galveston, TX

Dr. Paessler

Slobodan Paessler, D.V.M., Ph.D.
Professor, Department of Pathology;
Director, Galveston National Laboratory Preclinical Studies Core;
Director, Animal Biosafety Level 3, Institute for Human Infections and Immunity;
Member, Center for Biodefense & Emerging Infectious Diseases
University of Texas Medical Branch
Galveston, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika virus infection is associated with various developmental issues for human embryos such as reduced head growth, reduced brain tissue growth, and damage to brain or eyes. We wanted to better understand if some of these birth defects are caused directly by the Zika virus or maybe by the host response to infection.

In our study we demonstrate that the Zika virus infection induces autoimmune response against the C1q protein. This protein is a very important immune protein as well as one of the essential proteins for healthy brain development. Attacking the C1q protein upon exposure with the Zika virus could contribute to the development of autoimmune disorders and birth defects.  Continue reading

Small Increased Risk of Cardiac Birth Defects With ADHD Drug During Pregnancy

MedicalResearch.com Interview with:

Krista F. Huybrechts, M.S., Ph.D. Assistant Professor of Medicine at Harvard Medical School Epidemiologist in the Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women’s Hospital. Boston, MA 02120

Dr. Krista Huybrechts

Krista F. Huybrechts, MS PhD
Assistant Professor of Medicine
Division of Pharmacoepidemiology and Pharmacoeconomics
Brigham and Women’s Hospital
Harvard Medical School
Boston, MA 02120  

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In recent years, use of stimulant medications in adults, including women of reproductive age, has increased substantially.

However, data regarding the safety of stimulant medications in early pregnancy are sparse and conflicting.  For example, two recent cohort studies failed to detect an association between use of methylphenidate in early pregnancy and overall or cardiac malformations, while another found an 81% increased risk of cardiac malformations, although the estimate was imprecise.

Given the rapidly increasing use of stimulant medications during pregnancy and among women of reproductive age who may become pregnant inadvertently, there is an urgent need to better understand their safety.

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Stress of 911 Linked To Decrease In Male Babies Born With Birth Defects

MedicalResearch.com Interview with:
Parvati Singh B. Tech, MBA, MPA
PhD student, Department of Public Health,
University of California, Irvine and
Dr. Tim Bruckner, first author

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study builds upon earlier research by our group which showed that male fetal deaths rose and the number of liveborn males fell after the 9/11 attacks. Here we show that, in California, the number of live born males with birth defects fell after 9/11.

This finding appears consistent with the notion that frail male gestations, such as those with defects, may have been lost in utero as a result of the stress induced by the 9/11 attacks.

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Maternal Obesity Linked To Increased Risk of Congenital Malformations in Offspring

MedicalResearch.com Interview with:
Dr. Martina Persson

Clinical Epidemiology Unit
Department of Medicine Solna
Karolinska University Hospita

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It is well known that obesity increases risks of several maternal, fetal and neonatal complications including congenital malformations. However, it has not been clear if risks of malformations are increased also in offspring of normal weight mothers or if risks increase with degree of maternal obesity.

In this study, we found progressively increasing risks of major congenital malformations in the offspring with a mother’s overweight and obesity severity.

MedicalResearch.com: What should readers take away from your report?

Response: The most sensitive period of fetal organ development is the first eight weeks of gestation and it is during this time a mother´s BMI may influence risks of malformations. Thus, it is important to try to obtain a normal bodyweight before conception.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Our results should be confirmed in other populations and mechanisms behind the increased risks of malformations associated with maternal obesity should be further explored.

MedicalResearch.com: Is there anything else you would like to add?

Response: Obesity is a major health problem in many countries in the world. Preventive measures to halt the obesity epidemic should be implemented at all levels of society.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Lithium Use in Pregnancy and Risk of Fetal Cardiac Malformations

MedicalResearch.com Interview with:

Elisabetta Patorno, MD, DrPH Assistant Professor of Medicine, Harvard Medical School Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital

Dr. Patorno

Elisabetta Patorno, MD, DrPH
Assistant Professor of Medicine, Harvard Medical School
Division of Pharmacoepidemiology and Pharmacoeconomics,
Department of Medicine, Brigham and Women’s Hospital

MedicalResearch.com: What is the background for this study?

Response: Lithium, a widely used medicine to treat bipolar disorder, has been associated with a 400 fold increased risk of Ebstein’s anomaly, a congenital malformation of the heart, and a 5 fold increased risk of cardiac defects overall in infants when taken early in pregnancy, based on the results from the International Register of Lithium Babies in the 1970’s. Beyond this data, most of the information on the safety of lithium during pregnancy accumulated in the last 40 years is based on case reports and small studies with conflicting results. Despite these concerns and the limited information, lithium remains a first-line treatment for the 1% of women of reproductive age with bipolar disorder in the U.S. population, due to its recognized efficacy during pregnancy and the postpartum period, and due to the presence of a larger body of evidence showing increased risk of congenital malformations for other mood stabilizers, such as valproate.

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No Increased Risk of Congenital Abnormalities Found With Paternal Use of Immunosuppressant Therapies

MedicalResearch.com Interview with:

Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital, University of Copenhagen Hellerup, Denmark

Dr. Alexander Egeberg

Alexander Egeberg, MD PhD
Gentofte Hospital
Department of Dermatology and Allergy
Denmark

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: An issue that frequently arise in clinical practice is the question from patients whether they should discontinue their therapy if they want to have children. Since immunosuppressant agents are frequently used for a number of conditions, and discontinuation could lead to disease flaring, assessment of the potential impact of such drugs on birth outcomes is important.

In our study, we examined birth outcomes in children whose father had received treatment with methotrexate, azathioprine, cyclosporine, and mycophenolate mofetil in the time leading up to conception.

Importantly, we found no increased risk of congenital abnormalities, low birth weight, or preterm birth associated with paternal treatment with these drugs.

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Neural Tube Defects in Infants Share Molecular Processes With Neurodegenerative Diseases

MedicalResearch.com Interview with:

Zhiyong Zhao, Ph.D. Associate Professor Department of Obstetrics, Gynecology & Reproductive Sciences University of Maryland School of Medicine Baltimore, MD

Dr. Zhiyong Zhao

Zhiyong Zhao, Ph.D.
Associate Professor
Department of Obstetrics, Gynecology & Reproductive Sciences
University of Maryland School of Medicine
Baltimore, MD

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Diabetes in early pregnancy can cause neural tube defects in fetus. The defects are a result of failure in neural tube closure, due to excess cell death. The aim of this study was to delineate molecular processes that induce cell death.

The main findings of this study are:
(1) Hyperglycemia disrupts protein folding. The misfolded proteins, including the ones that are associated with neurodegenerative diseases, form aggregates, indicating similar molecular processes in both fetal neural tube defects and adult neurodegenerative diseases.
(2) Protein aggregation leads to formation of a neurodegenerative disease-related cell death inducting mechanism.

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Flu Treatment With Neuraminidase Inhibitors During Pregnancy Not Linked To Birth Defects

MedicalResearch.com Interview with:

Dr. Sophie Graner Department of Women's and Childrens Health Karolinska Institute, Stockholm, Sweden

Dr. Graner

Dr. Sophie Graner
Department of Women’s and Childrens Health
Karolinska Institute, Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Pregnant women are at increased risks of severe disease and death due to influensa infection, as well as hospitalization. Also influenza and fever increase the risk of adverse pregnancy outcomes for their infants such as intrauterine death and preterm birth. Due to this, the regulatory agencies in Europe and the US recommended post exposure prophylaxis and treatment for pregnant women with neuraminidase inhibitors during the last influenza pandemic 2009-10. Despite the recommendations, the knowledge on the effect of neuraminidase inhibitors on the infant has been limited. Previously published studies have not shown any increased risk, but they have had limited power to assess specific neonatal outcomes such as stillbirth, neonatal mortality, preterm birth, low Agar score, neonatal morbidity and congenital malformations.
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Reduced Stem Cells Link Congenital Heart Disease To Impaired Brain Growth

MedicalResearch.com Interview with:

Childrens National Research Team

Children’s National Research Team

Paul D. Morton, Ph.D.
Research PostDoc and lead study author of “Abnormal Neurogenesis and Cortical Growth in Congenital Heart Disease.”
Children’s National Health System Washington, DC

Nobuyuki Ishibashi, M.D.
Director of the Cardiac Surgery Research Laboratory at Children’s National Health System and co-senior study author.

Vittorio Gallo, Ph.D.
Director of the Center for Neuroscience Research at Children’s National Health System and co-senior study author.

 

 

Richard A. Jonas, M.D.
Chief of the Division of Cardiac Surgery at Children’s National Health System and co-senior study author.

MedicalResearch.com: What is the background for this study?

Response: Congenital heart disease (CHD) is the leading birth defect in the United States and often results in an array of long-term neurological deficits including motor, cognitive and behavioral abnormalities. It has become increasingly clear that children with CHD often have underdeveloped brains. In many cases of complex CHD, blood flow to the brain is both reduced and less oxygenated, which has been associated with developmental abnormalities and delay. The cellular mechanisms underlying the impact of CHD on brain development remain largely unknown. We developed a preclinical chronic hypoxia model to define these mechanisms.

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Link Between Antidepressants During Pregnancy and Birth Defects

MedicalResearch.com Interview with:
Anick Bérard PhD FISPE

Research chair FRQ-S on Medications and Pregnancy and
Director, Réseau Québécois de recherche sur le médicament (RQRM)
and Professor, Research Chair on Medications, Pregnancy and Lactation
Faculty of Pharmacy University of Montreal and
Director, Research Unit on Medications and Pregnancy
Research Center CHU Ste-Justine 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have over 20 years of research showing that antidepressant use during the first trimester of pregnancy increases the risk of major congenital malformations. However, it still remains that controversies exist because we are not sure which of this increased risk is due to maternal depression. Therefore, we have only studied depressed pregnant women – some of them did not take antidepressant during pregnancy.

We were able to show that among depressed pregnant women, those who took antidepressants were at increased risk of having children with malformations – especially those taking citalopram. We were also able to show that many SSRIs, SNRI and tricyclic antidepressants put women at increased risk of having children with various malformations due to their similar mechanism of action (serotonin inhibition in utero).

MedicalResearch.com: What should readers take away from your report?

Response: Depression is a serious condition that requires medical attention during pregnancy. However, given that up to 85% of depressed pregnant women have mild to moderate depression – other treatment (other than antidepressants) options need to be considered. If a woman finds out she is pregnant and is taking antidepressants however, no abrupt discontinuation is suggested and a discussion with a health care provider is advised.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Very few data on the benefits of antidepressant use during pregnancy is available within depressed pregnant women with mild to moderate depression. Our study results taken together with all the body of literature on this topic should lead to other research on the benefits and risks of other forms of treatment for depression such as psychotherapy.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Anick Bérard, Jinping Zhao and Odile Sheehy. Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: An updated analysis of the Quebec Pregnancy Cohort. BMJ Open, January 2017 DOI: 10.1136/bmjopen-2016-01337

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Women Who Can Become Pregnant Should Take Folic Acid

MedicalResearch.com Interview with:

Dr. Alex Kemper, MD, MPH, MS Member,US Preventive Services Task Force Professor of Pediatrics and Professor in Community Medicine Department of Pediatrics Duke University School of Medicine

Dr. Alex Kemper

Dr. Alex Kemper, MD, MPH, MS
Member,US Preventive Services Task Force
Professor of Pediatrics and Professor in Community Medicine
Department of Pediatrics
Duke University School of Medicine

MedicalResearch.com: What is the background for this study?

Response: Neural tube defects, where the brain or spinal cord do not develop properly in a baby, can occur early in pregnancy, even before a woman knows she is pregnant. Taking folic acid before and during pregnancy can help protect against neural tube defects. Most women do not get enough folic acid in their diets, so most clinicians recommend that any woman who could become pregnant take a daily folic acid supplement.

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High Outdoor Heat Early in Pregnancy May Raise Risk of Congenital Heart Defects

MedicalResearch.com Interview with:

Nathalie Auger MD MSc FRCPC Montréal, Québec

Dr. Nathalie Auger

Nathalie Auger MD MSc FRCPC
Montréal, Québec

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We carried out this study because congenital heart defects take a large share of birth defects, but not much is known on its risk factors.

In previous research, we found that very high temperatures in the summer were associated with a greater risk of stillbirth. We sought to determine whether elevated outdoor heat could also be linked with congenital heart defects in a sample of about 700,000 pregnancies.

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Maternal Risk of Death Elevated After Birth of Child With Major Congenital Abnormalities

MedicalResearch.com Interview with:

Eyal Cohen, MD, MSc, FRCP(C) Staff Physician, Paediatrics The Hospital for Sick Children Associate Scientist, Research Institute Child Health Evaluative Sciences Associate Professor, University of Toronto

Dr. Eyal Cohen

Eyal Cohen, MD, MSc, FRCP(C)
Staff Physician, Paediatrics
The Hospital for Sick Children
Associate Scientist, Research Institute
Child Health Evaluative Sciences
Associate Professor, University of Toronto  

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Major structural or genetic congenital anomalies affect approximately 2 percent to 5 percent of all births in the United States and Europe. Mothers of children born with major congenital anomalies face serious challenges such as high financial pressures, as well as the burden of providing care to a child with complex needs within the home setting, which can impair a mother’s health. Little is known about the long-term health consequences for the mother. We assessed whether the birth of an infant with a major congenital anomaly was subsequently associated with an increased risk of death of the infant’s mother.

The population-based study (n = 455,250 women) used individual-level linked Danish registry data for mothers who gave birth to an infant with a major congenital anomaly between 1979 and 2010, with follow-up until December 31, 2014. A comparison group was constructed by randomly sampling, for each mother with an affected infant, up to 10 mothers matched on maternal age, parity (the number of children a woman has given birth to), and year of infant’s birth. Mothers in both groups were an average age of 29 years at delivery. After a median follow-up of 21 years, there were 1,275 deaths (1.60 per 1,000 person-years) among 41,508 mothers of a child with a major congenital anomaly vs 10,112 deaths (1.27 per 1,000 person-years) among 413,742 mothers in the comparison group. Mothers with affected infants were more likely to die of cardiovascular disease, respiratory disease, and other natural causes.

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