Is CDH Genetic? - Guest Speaker Meaghan Russell, MPH, PhD

Meet our guest speaker...

Meaghan Russell, MPH, PhD
Pediatric Surgical Research Laboratories
MassGeneral Hospital for Children

Click here to go to the CDH Q&A on Genetics!

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Because there is a massive amount of misinformation and inaccurate medical advice being posted lately on Facebook on different pages and groups and many parents seem confused about CDH and genetics and the possible causes of Congenital Diaphragmatic Hernia we have asked geneticist and CDH expert, Meaghan Russell, to guestspeak here on our Facebook page to answer any questions that you may have about possible causes, current research, familial CDH, etc.

Please post your questions as comments to this note and she will answer as her schedule allows. 

*** Please note that Meaghan cannot give medical advice or diagnosis your cherub via the internet! ***


 
Meaghan Russell and Mauro Longoni at the 2011 CDH Conference


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View videos from Meaghan's lectures at the CDH conference at http://www.cdhconference.org or http://www.youtube.com/cdhsupport

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FROM PNAS- http://www.pnas.org/content/109/8/2978.full

"Congenital diaphragmatic hernia candidate genes
derived from embryonic transcriptomes"

Congenital diaphragmatic hernia (CDH) is a common (1 in 3,000 live
births) major congenital malformation that results in significant
morbidity and mortality. The discovery of CDH loci using standard
genetic approaches has been hindered by its genetic heterogeneity.
We hypothesized that gene expression profiling of developing
embryonic diaphragms would help identify genes likely to be
associated with diaphragm defects. We generated a time series of
whole-transcriptome expression profiles from laser captured em-
bryonic mouse diaphragms at embryonic day (E)11.5 and E12.5
when experimental perturbations lead to CDH phenotypes, and
E16.5 when the diaphragm is fully formed. Gene sets defining
biologically relevant pathways and temporal expression trends
were identified by using a series of bioinformatic algorithms. These
developmental sets were then compared with a manually curated
list of genes previously shown to cause diaphragm defects in
humans and in mouse models. Our integrative filtering strategy
identified 27 candidates for CDH. We examined the diaphragms of
knockout mice for one of the candidate genes, pre–B-cell leukemia
transcription factor 1 (Pbx1), and identified a range of previously
undetected diaphragmatic defects. Our study demonstrates the
utility of genetic characterization of normal development as an in-
tegral part of a disease gene identification and prioritization strat-
egy for CDH, an approach that can be extended to other diseases
and developmental anomalies.

Click here to go to the CDH Q&A on Genetics!

CDC Study Links 2 Antibiotics to Birth Defects

http://health.usnews.com/articles/health/healthday/2009/11/02/cdc-study-links-2-antibiotics-to-birth-defects.html

CDC Study Links 2 Antibiotics to Birth Defects
No added risk was found, however, for most commonly used infection-fighters

Posted November 2, 2009

By Jennifer Thomas
HealthDay Reporter

MONDAY, Nov. 2 (HealthDay News) -- Taking antibiotics during pregnancy does not raise the risk for most birth defects, though there are some exceptions, new research has found.

Penicillin, which is the most commonly used antibiotic during pregnancy, as well as erythromycin, cephalosporins and quinolones, other widely prescribed antibiotics, were not associated with increased risk for about 30 different birth defects.

However, the study found that two types of antibiotics were linked with a higher risk for several birth defects: nitrofurantoins and sulfonamides, sometimes called "sulfa drugs," which are prescribed for urinary tract and other infections.

Women whose children had anencephaly, a fatal malformation of the skull and brain, were three times more likely to have taken sulfonamides, the study found. Sulfonamides were also tied to an increased risk for such heart defects as hypoplastic left heart syndrome and coarctation of the aorta, choanal atresia (a blockage of the nasal passage), transverse limb deficiency and diaphragmatic hernia, an abnormal opening in the diaphragm that results in severe breathing difficulties.

Nitrofurantoins were also associated with multiple birth defects, including anophthalmia and microphthalmos (eye defects) and several congenital heart defects. Mothers whose children were born with a cleft lip or cleft palate were twice as likely to have taken nitrofurantoins, the study found.

But pregnant women should not be overly worried if they need an antibiotic to treat an infection during pregnancy, stressed the study's lead author, Krista Crider, a geneticist with the National Center on Birth Defects and Developmental Disabilities, part of the U.S. Centers for Disease Control and Prevention.

"The most important message is that most commonly used antibiotics do not seem to be associated with the birth defects we studied," Crider said.

The findings are published in the November issue of Archives of Pediatrics & Adolescent Medicine.

Crider and her colleagues analyzed data on more than 13,000 women whose babies had one of more than 30 birth defects, including cleft palate, heart or limb defects and anencephaly. They compared the women's rates of antibiotic usage, from the month leading up to pregnancy through the end of the first trimester, with that of almost 5,000 women whose children did not have a birth defect. The data was culled from the National Birth Defects Prevention Study, which began in 1997 and includes about 30,000 women from 10 states.

Information on the impact of many prescription drugs on developing fetuses is sorely lacking, Crider pointed out. Much of that stems from the fact that ethical considerations preclude conducting drugs trials in pregnant women, she said.

Though many antibiotics have been used safely for decades, resistant strains of bacteria are forcing doctors to use a wider array of antibiotics. For some, little data exist.

The researchers found that about 30 percent of women took an antibiotic between the three months prior to conception and the end of the pregnancy.

Even antibiotics that generally were safe were found to be associated with a few specific birth defects. Women whose babies were born with a certain type of limb malformation were three times more likely to have taken penicillin. Erythromycin, cephalosporins and quinolones were also associated with an increased risk for one or two specific birth defects.

However, the researchers said they did not know if the birth defects were caused by the antibiotics or the underlying infection.

One expert said women need to remember the good antibiotics can do mom and baby, as well. Though many pregnant women want to avoid taking any drugs during pregnancy, infections pose a risk to mother and baby and often need to be treated, said Dr. Jennifer Wu, an obstetrician-gynecologist at Lenox Hill Hospital in New York City.

"Untreated infections during pregnancy can lead to severe consequences, such as maternal sepsis [blood infection] and preterm labor," Wu said. "Yet many patients are afraid to take medications such as antibiotics during pregnancy."

The study "supports the evidence that antibiotics are safe for pregnant women," she said. "It is reassuring for doctors and patients to have more data on necessary drugs for pregnancy."

Crider also stressed that the chances of having a baby with a birth defect remain small, even if an antibiotic has been linked to an elevated risk. For example, the risk of having a child with hypoplastic left heart syndrome is about one in 4,200. Sulfonamides were associated with a three-fold increase, making the likelihood about one in 1,400, she said.

Brand names for nitrofurantoins include Furadantin, Macrobid and Macrodantin. Bactrim and Septra are among the brand names of sulfonamides.

Given the data, Crider said, women should be cautious about taking either of those types of drugs during pregnancy and should discuss other options with their physicians,.

According to the study, the overall risk for having a child with a birth defect is about three percent.

The study did not look at chromosomal defects, including Down syndrome.

More information

The U.S. Centers for Disease Control and Prevention has more on birth defects.

CHERUBS 2008 CDH Conference Guest Speakers - Meaghann Russell, MPH and Mauro Longoni, MD

CHERUBS 2008 International Member Conference for families affected by Congenital Diaphragmatic Hernia.

Meaghann Russell, MPH and Mauro Longoni, MD (MassGeneral CDH Clinic, Boston, MA) speech on CDH and Genetics.

This only includes the speech. This does not include questions, comments or dialogue with members (you have to attend our conference to hear and participate in that!).


Part 1



Part 2



Part 3



Part 4



Part 5



Part 6

For information on this year's conference you can visit http://www.cherubsconference.org

For information on CHERUBS and CDH please visit http://www.cdhsupport.org