Fetal Haptoglobin as Potential Biomaker for Increased Risk of Cerebral Palsy

MedicalResearch.com Interview with:

MedicalResearch.com Interview with:Catalin S. Buhimschi MD, MMS, MBAProfessor of Obstetrics and GynecologyDivision of Maternal Fetal MedicineDirector of ObstetricsDepartment of Obstetrics and GynecologyChicago, IL, 60612

Dr. Buhimschi

Catalin S. Buhimschi MD, MMS, MBA
Professor of Obstetrics and Gynecology
Division of Maternal Fetal Medicine
Director of Obstetrics
Department of Obstetrics and Gynecology
Chicago, IL, 60612

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

Response: In 2008, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal–Fetal Medicine Units Network published the results of a randomized controlled trial of magnesium sulfate for the prevention of cerebral palsy (CP). The results of this trial suggested that fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate to severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. As such, the search for a biomarker or a therapeutic solution to prevent CP had to continue.

We are grateful to the NICHD for giving us access to the umbilical cord blood samples retrieved at the time of birth for the infants enrolled, who were also followed for 2 years postnatally. We discovered that fetus’s ability to switch-on haptoglobin (Hp) expression in response to inflammation was associated with reduction of intra-ventricular hemorrhage (IVH) and/or death, and cerebral palsy and/or death. Fetuses unable to mount such a response in-utero had an increased risk of adverse outcomes.

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Cerebral Palsy Prevalence Has Not Decreased and Remains Higher in Black Infants

Kim Van Naarden Braun, Ph.D. Epidemiologist Developmental Disabilities Branch National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention Atlanta, GA 30341

Dr. Van Naarden Braun

MedicalResearch.com Interview with:
Kim Van Naarden Braun, Ph.D.

Epidemiologist
Developmental Disabilities Branch
National Center on Birth Defects and Developmental Disabilities
Centers for Disease Control and Prevention
Atlanta, GA  30341

Medical Research: What is the background for this study? What are the main findings?

Dr. Van Naarden Braun: Over the past five decades, remarkable improvements have been made in obstetric and neonatal care resulting in significant declines in infant mortality both in the US and abroad, particularly for infants born premature and very low birthweight. Successes in neonatal survival have been met by concerns that the occurrence of developmental disabilities, most notably cerebral palsy, would increase. By monitoring changes over time in the prevalence of cerebral palsy, we can try to understand the impact of these advances further. Our recently published study reported that the birth prevalence of cerebral palsy has not decreased from the mid-1980’s to early 2000’s.

The study also looked at whether the birth prevalence over time differed for children with cerebral palsy who were in certain racial and ethnic groups, had certain birth characteristics, or had other developmental disabilities and found that:

  • The birth prevalence of children with cerebral palsy with moderate to severe intellectual disability decreased about 2.6% each year from 1985 to 2002.
  • Birth prevalence of cerebral palsy among black children was higher than among white and Hispanic children, and this higher prevalence continued over the 17-year period.
  • Overall, there was no change over time in cerebral palsy birth prevalence among children born at certain birthweights or gestational age, but there were some differences when looking at these factors in different racial/ethnic groups.

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Adults With Cerebral Palsy Risk Multiple Chronic Diseases

Mark D. Peterson, Ph.D., M.S. University of Michigan, Medicine Department of Physical Medicine and Rehabilitation Ann Arbor, MI

Dr. Peterson

MedicalResearch.com Interview with:
Mark D. Peterson, Ph.D., M.S
.
University of Michigan, Medicine
Department of Physical Medicine and Rehabilitation
Ann Arbor, MI 

Medical Research: What is the background for this study? What are the main findings?

Dr. Peterson: Cerebral palsy (CP) is a neurodevelopmental condition caused by a disturbance to the developing fetal or infant brain. While the incidence of CP has remained stable in recent years, the mortality rate of children with Cerebral palsy has declined, suggesting that adults with Cerebral palsy represent a growing population whose healthcare needs are poorly understood.  More than half of children with Cerebral palsy are independently mobile at 8 years of age; however, a large proportion lose mobility in adulthood. These declines are attributed to pain, fatigue, and muscle weakness, and result in chronic inactivity and accelerated aging. Despite this, there have been virtually no specific surveillance efforts or even epidemiologic studies to examine the prevalence of lifestyle-related chronic diseases in adults with Cerebral palsy. Therefore, the purpose of this study was to examine estimates of chronic conditions in a large, U.S. population-representative sample of adults with CP (n=1,015 fromthe Medical Expenditure Panel Survey (MEPS) (2002-2010). We demonstrated that adults with cerebral palsy had significantly greater estimates of chronic diseases, including diabetes, asthma, hypertension and other heart conditions, stroke, emphysema, joint pain, and arthritis as compared with adults without Cerebral palsy.

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Cerebral Palsy Sometimes Due To Genetics, Not Birth Trauma

Prof. Jozef GECZMedicalResearch.com Interview with:
Prof. Jozef Gecz
NH&MRC Senior Principal Research Fellow
Professor of Human Genetics
School of Paediatrics and Reproductive Health
Faculty of Health Sciences The University of Adelaide at the Women’s and Children’s Hospital North Adelaide, SA

Medical Research: What is the background for this study? What are the main findings?

Prof. Gecz: Cerebral palsy is the most frequent movement disorder of children for many years considered to be due to brain injury. Given that cerebral palsy incidence has not changed dramatically over many years while medical care is constantly improving, we look for other causes and specifically genetic mutation. By investigating 183 children with cerebral palsy and for many also one or both of their parents we find that for at least 14% of these we can find plausible explanation in genetic mutation being involved in the causation of their cerebral palsy. Importantly, we find that 10% of these mutations are de novo, which means that these mutations are not present in the parents (specifically in their blood as that is the tissue source we tested). 4% of mutations were inherited from unaffected mothers to affected sons. Previous estimates suggested 2% genetic contribution to Cerebral palsy. We now know that it is at least 14% and likely more. If you are looking for compensation for this condition, contact an Indiana cerebral palsy lawyer.

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Cerebral Palsy Rare In Infants With Elevated Bilirubin Levels

Yvonne Wu MD Professor of Clinical Neurology and Pediatrics UCSF School of MedicineMedicalResearch.com Interview with:
Yvonne Wu MD

Professor of Clinical Neurology and Pediatrics
UCSF School of Medicine

 

Medical Research: What is the background for this study? What are the main findings?
Dr. Wu: Newborn infants commonly have elevated bilirubin levels, manifested as jaundice, because the body’s mechanisms for breaking down bilirubin have not yet fully matured.  Although high bilirubin levels are almost always well tolerated, extremely high bilirubin levels may lead to brain injury, or kernicterus, which in turn can cause a very severe form of cerebral palsy.  When bilirubin levels are extremely high, or when bilirubin levels remain high despite phototherapy, it is recommended that an exchange transfusion be performed to prevent brain injury and cerebral palsy.  The American Academy of Pediatrics (AAP) has published recommendations on when an exchange transfusion should be performed, based on bilirubin level, age of infant and other clinical factors.  However, no previous study had examined the actual risk of cerebral palsy in infants whose bilirubin levels exceeded the exchange transfusion thresholds.

Among 500,000 newborns born at Kaiser Permanente Northern California over a 17-year period, we found 1833 who had at least one bilirubin level above the AAP exchange transfusion level.  There were only 3 cases of cerebral palsy due to kernicterus in this group, even though only 42 (2.3%) of them had received exchange transfusions.  All 3 infants had bilirubin levels at least 5 mg/dL above the AAP exchange transfusion threshold and all 3 infants had 2 or more other risk factors for brain damage, including prematurity, sepsis, hypoxia and the hereditary blood disorder G6PD deficiency.  We did not identify any cases of kernicterus among otherwise well term babies, even at bilirubin levels that exceeded the AAP exchange transfusion threshold.

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Does Magnesium Help Prevent Cerebral Palsy?

Lex W Doyle MD BS MSc FRACP Professor of Neonatal Paediatrics Department of Obstetrics and Gynaecology The Royal Women’s Hospital Parkville, Victoria, AustraliaMedicalResearch.com Interview with:
Lex W Doyle MD BS MSc FRACP
Professor of Neonatal Paediatrics
Department of Obstetrics and Gynaecology
The Royal Women’s Hospital
Parkville, Victoria, Australia

Medical Research: What are the main findings of the study?

Dr. Doyle: From collectively pooling data from five large trials carried out around the world over the past 20 years, we know that magnesium sulfate given under strict medical protocols in hospital to women threatening to deliver preterm reduces the risk of cerebral  palsy in their children in early childhood.  Following  from this knowledge, magnesium sulfate is now given routinely to women, under strict medical conditions, who are threatening to deliver very early in Australia, and in other parts of the world, to try to prevent cerebral palsy in their child.  What we do not know is if magnesium sulfate used this way has any longer-term effects on the brain or on other important outcomes.

One of the initial studies that contributed to the overall evidence about cerebral palsy was carried out in Australia and New Zealand and completed more than 10 years ago.  Over 1000 women and their babies were enrolled in that study and although the rate of cerebral palsy was not substantially reduced by magnesium sulfate in our study, we showed that there were fewer children at 2 years of age who were not walking in the group whose mothers were given magnesium compared with those whose mothers were given placebo.  With this knowledge, and given the unknown longer-term benefits or risks, we re-evaluated the children from our study at school-age, between 6-11 years of age.  We thoroughly evaluated their brain function, including movement and co-ordination, thinking ability, behaviour, and school progress, as well as general health and well-being.  The basic message from our longer-term study is that magnesium sulfate, as used in our trial, does not have any substantial benefits or harms on brain or cognitive function, or any other outcome at school age.
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