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Study Associates Gene with Cerebral Palsy and Death in Very Preterm Babies

In a study to be presented on Feb. 6 at 2:45 p.m. CST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting ™, in New Orleans, researchers will report that a variant in SERPINE1, a gene involved in inflammation and blood clotting, is associated with cerebral palsy and death in very preterm babies. This gene has been associated with increased risk of cerebral palsy in one previous study of preterm babies.

Previous genetic studies of very preterm babies have suggested several genetic variations that might predispose to brain injury and developmental problems. However, different studies have had different results.

This study, titled Genetic Predisposition to Adverse Neurodevelopmental Outcome After Early Preterm Birth: A Validation Analysis, was a collaborative effort between the Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units and Neonatal Research Networks.

Researchers evaluated two different populations of very early preterm births (earlier than 32 weeks) with the goal of confirming the same genetic risk factors in both groups. The first population of preterm births was enrolled in a large Neonatal Research Network study, and the other group was of births that were enrolled in a Maternal Fetal Medicine Units Network study of magnesium sulfate before preterm birth for prevention of cerebral palsy.

Results revealed a variant in the gene SERPINE1, a gene involved in inflammation and blood clotting, was associated with cerebral palsy and death after early preterm birth in both populations of preterm babies.

“Preterm birth is the leading cause of childhood brain injury in otherwise normal children. The earlier a baby is born, the higher the risk of brain injury. However, even among the tiniest preemies, some babies develop quite normally, while others have devastating brain injury and life-long disability,” said Erin Clark, M.D., the study’s author. “The reason for this difference in outcomes is not well understood. Genetics may allow identification of babies at increased risk so that we can target those babies for prevention and treatment strategies. These results add to the evidence that genes may play a role in risk of brain injury and death in preterm babies.”

Clark, assistant professor of Maternal Fetal Medicine, University of Utah School of Medicine’s Department of Obstetrics and Gynecology, also noted that additional research is necessary to further evaluate genes that may influence risk and to determine how to apply these results to clinical care.

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A copy of the abstract is available at http://www.smfmnewsroom.org and below.  For interviews please contact Vicki Bendure at Vicki@bendurepr.com 202-374-9259 (cell), or Meghan Blackburn at Meghan@bendurepr.com, 540-687-5099 (office) or 859-492-6303 (cell).

The Society for Maternal-Fetal Medicine (est. 1977) is the premiere membership organization for obstetricians/gynecologists who have additional formal education and training in maternal-fetal medicine.  The society is devoted to reducing high-risk pregnancy complications by sharing expertise through continuing education to its 2,000 members on the latest pregnancy assessment and treatment methods. It also serves as an advocate for improving public policy, and expanding research funding and opportunities for maternal-fetal medicine. The group hosts an annual meeting in which groundbreaking new ideas and research in the area of maternal-fetal medicine are shared and discussed.  For more information visit www.smfm.org.

Financial Disclosure:  The authors did not report any potential conflicts of interest.

 

Abstract 15: Genetic Predisposition to Adverse Neurodevelopmental Outcome After Early Preterm Birth: A Validation Analysis

Author: Erin A. S. Clark, The Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units and Neonatal Research Networks, Bethesda, MD  

Objective: Validate genetic risk loci associated with adverse neurodevelopment after early preterm birth.

Study Design: We previously conducted a large candidate gene association study in a cohort of 1013 extremely low birth weight infants (<1000 gms). The case-control analysis utilized samples in the NICHD Neonatal Research Network’s DNA Bank and evaluated 1634 SNPs in 145 genes in hypothesized causal pathways, with emphasis on inflammation, angiogenesis, and brain development. Cases were children who died by age 1 or who were diagnosed with CP or neurodevelopmental delay (Bayley II MDI or PDI <70) by 18-22 months. Controls were survivors with normal neurodevelopment. The outcomes of CP, combined CP or death, mental delay (MDI<70), and motor delay (PDI<70) were evaluated. Twenty-five SNPs with P<0.01 for one or more outcomes in the previous analysis were selected for validation in this analysis. Validation samples were derived from an RCT of magnesium sulfate before anticipated early preterm birth (<32 weeks) for prevention of cerebral palsy (CP). Case/control definitions were equivalent to the primary cohort, with the exception that neurodevelopmental outcomes were evaluated at 24 months. As in the primary analysis, four outcomes were evaluated. Cases and controls were matched for race and infant sex; covariates included gestational age at birth, small for gestational age, maternal education level, treatment group, and antenatal corticosteroids. Significance in the validation cohort was defined as P<0.05.

Results: The validation cohort included 364 infants, 170 cases and 192 controls. Three genetic loci from the primary analysis were significantly associated with the outcomes CP, CP/death and mental delay after early preterm birth in the validation analysis (Table).

Conclusion: Genetic loci involved in inflammation and brain development are associated with CP, CP/death, and mental delay after early preterm birth in primary and validation genetic analyses.

Table

Une étude montre que les injections de progestérone ne réduisent pas l’accouchement prématuré dans les grossesses de jumeaux

Résumé récipiendaire du prix March of Dimes au congrès SMFM

Dans une étude devant être présentée le 14 février entre 8 et 10 heures, au 33e congrès annuel de la Society for Maternal-Fetal Medicine, The Pregnancy Meeting™, les chercheurs présenteront des résultats suggérant que le 17P, une forme de progestérone, n’est pas efficace pour prévenir l’accouchement prématuré chez les femmes enceintes de jumeaux, et il pourrait même être nocif.

Study Suggests That Genetic Predisposition to Brain Injury After Preterm Birth is Sex-Specific

In a study to be presented on February 14 between 1:15 p.m., and 3:30 p.m. PST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting ™, in San Francisco, researchers will report that variation in a gene involved in inflammation is associated with developmental problems after preterm birth in females, but not males.

Study Finds That Caloric Restriction and Exercise Help to Prevent Weight Gain and Other Pregnancy Complications in Obese Women

In a study to be presented on February 15 between 1:15 p.m., and 3:30 p.m. PST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting ™, in San Francisco, researchers will report findings that suggest that consistent physical activity and healthier lifestyle changes beginning in a woman’s first trimester can prevent excessive weight gain in obese pregnant women (with a Body Mass Index greater than 30), helping to avoid preterm delivery, hypertension and gestational diabetes.

Largest Population Based Study Finds Better Outcome for Frozen Embryo Replacement vs. IVF

In a study to be presented on February 14 between 1:15 p.m., and 3:30 p.m. PST, at the Society for Maternal-Fetal Medicine’s annual meeting, The Pregnancy Meeting ™, in San Francisco, California, researchers will present findings showing perinatal outcomes of frozen/thawed embryo replacement (FER) have better outcomes compared to fresh in vitro fertilization (IVF), but worse outcomes compared to the non-IVF general population.

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