Effect of Maternal Diabetes on Brain Development, as Measured by Neonatal Electroencephalogram (EEG)

Study Overview
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Brief Summary
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Alterations in the intrauterine environment can have profound effects on fetal development. Diabetes during gestation results in multiple deleterious short-term outcome differences, and is correlated with long-term developmental deficits. Multiple studies, in neonates through school-aged children, have demonstrated differences in language, attention and psychomotor development in offspring of diabetic pregnancies. Neonatal EEG is a promising and non-invasive tool for assessment of abnormal brain development or dysmaturity in this population. Multiple conventional EEG (cEEG) and amplitude-integrated EEG (aEEG) parameters change predictably with advancing gestational development and have been used to differentiate between at risk groups in neonatal studies. The investigators hypothesize that neonatal EEG can identify brain dysmaturity in infants of diabetic mothers (IDMs) compared to gestational-age matched controls. The primary aim is documentation of brain dysmaturity in IDMs using cEEG. The secondary aim is establishment of aEEG as a more accessible tool to quantify the effects of maternal diabetes on neonatal brain development. The investigators will conduct a pilot study comparing cEEG and aEEG parameters of cases to gestational-age matched controls. Cases will be IDM neonates of at least 35 weeks' gestation whose mothers were recommended treatment with either insulin or an oral glycemic agent. Video EEG recording will be planned for approximately 60 minutes and obtained between 24 hours and 5 days of life during birth hospitalization. Additional data will be extracted from maternal and neonatal medical records and a maternal questionnaire. In addition to evaluating the measures of cEEG and aEEG, this project will establish a research cohort. A subsequent study involving developmental evaluations will allow for correlation of EEG results with long-term outcomes. The ability to identify those at risk at birth would provide the opportunity to intervene in order to mitigate outcome differences, particularly in language development. More significantly, we hope to establish neonatal CNS outcome measures for future diabetic pregnancy intervention studies. .

Official Title
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Effect of Maternal Diabetes on Brain Development, as Measured by Neonatal Electroencephalogram (EEG)

Conditions
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Diabetes in Pregnancy, Diabetes, Gestational, Infant, Newborn, Diseases, Perinatal Disorders of Growth and Development

Intervention / Treatment
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* Other: Video Electroencephalogram (EEG)
* Other: Point-of Care Blood Sugar Testing
* Other: Medical Record Data Extraction
* Other: Maternal Questionnaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >/= 35 weeks post-menstrual age at delivery Dating by, or consistent with, 1st trimester ultrasound Mother able to communicate in oral and written English Available maternal obstetric record and medication history Singleton gestation Delivery at URMC attended by obstetric staff Exclusion Criteria: Maternal Exclusion Criteria: Diagnosis by obstetrician of intrauterine growth restriction (IUGR) Documentation in medical record of daily maternal cigarette smoking during 2nd or 3rd trimester Chronic maternal sedative or opiate use (>weekly use) Recreational opiate use or addiction Cocaine or amphetamine use during pregnancy ETOH abuse or concern for abuse during pregnancy (>weekly use) Other maternal conditions that may compromise fetus Psychiatric medications beyond isolated SSRI use Anti-epileptic drugs (AEDs) during gestation Magnesium exposure within 3 days of delivery Neonatal Exclusion Criteria: Blood gas pH of less than 7.1, if obtained (cord or any prior to EEG) Apgar less than 8 at 5 min CNS malformations, seizures, subgaleal or intracranial bleeds Cardiac anomalies except asymptomatic small-moderate VSD, ASD, or PDA Clinically significant malformations or chromosomal anomalies Small-for-gestational age (<10th % on Fenton growth curve) Respiratory distress ever requiring intubation or requiring CPAP support > 48 hours Hemodynamic instability requiring use of pressors or >2 bolus Culture positive sepsis Clinical concern for meningitis or encephalopathy Sedation medication or other conditions/medications affecting CNS function Clinically obtained total bilirubin more than 15 on day of EEG Scalp injury preventing placement of EEG leads Point-of-care testing (POCT) glucose <45 at time of EEG

Ages Eligible for Study
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Minimum Age: 24 Hours
Maximum Age: 120 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cases: Infants of Diabetic Mothers<br>Cases: Neonates born at or over 35 weeks gestation whose mother's were recommended to receive medication for diabetes during pregnancy. This includes pre-gestational and gestational diabetics. Interventions: Video Electroencephalogram (EEG) Point-of Care Blood Sugar Testing Medical Record Data Extraction Maternal Questionnaire | Other: Video Electroencephalogram (EEG)<br>* Single neonatal video EEG at 24 hrs to 5 days of life during birth hospitalization. Neonatal scalp leads, respiratory and nasal leads. Approximately 60 minute recording.<br>Other: Point-of Care Blood Sugar Testing<br>* One-time heel-stick point-of-care blood sugar testing at time of EEG.<br>Other: Medical Record Data Extraction<br>* Medical record data extraction from both maternal obstetric and neonatal medical record for variables known to impact EEG and neurodevelopmental outcomes.<br>Other: Maternal Questionnaire<br>* One-time maternal questionnaire related to smoking practices, ETOH consumption, level of education, and body mass index.<br>|
| Controls<br>Controls: Neonates born at or over 35 weeks gestation whose mother's had normal glycemic control testing during pregnancy. Interventions: Video Electroencephalogram (EEG) Point-of Care Blood Sugar Testing Medical Record Data Extraction Maternal Questionnaire | Other: Video Electroencephalogram (EEG)<br>* Single neonatal video EEG at 24 hrs to 5 days of life during birth hospitalization. Neonatal scalp leads, respiratory and nasal leads. Approximately 60 minute recording.<br>Other: Point-of Care Blood Sugar Testing<br>* One-time heel-stick point-of-care blood sugar testing at time of EEG.<br>Other: Medical Record Data Extraction<br>* Medical record data extraction from both maternal obstetric and neonatal medical record for variables known to impact EEG and neurodevelopmental outcomes.<br>Other: Maternal Questionnaire<br>* One-time maternal questionnaire related to smoking practices, ETOH consumption, level of education, and body mass index.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Interburst Interval on cEEG |  | Single EEG between 24 hours of life and 5 days of life | 
| Lower Margin Amplitude on aEEG |  | Single EEG between 24 hours of life and 5 days of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Delta Brushes on cEEG |  | Single EEG between 24 hours of life and 5 days of life | 
| Bandwidth on aEEG |  | Single EEG between 24 hours of life and 5 days of life |