Clinical trial NCT02968628: Effect of Maternal Diabetes on Brain Development, as Measured by Neonatal Electroencephalogram (EEG)
Official title: Effect of Maternal Diabetes on Brain Development, as Measured by Neonatal Electroencephalogram (EEG)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes in Pregnancy
Diabetes, Gestational
Infant, Newborn, Diseases
Perinatal Disorders of Growth and Development
Lead sponsor: University of Rochester
Sponsor class: OTHER
First posted: 2016-11-18
Enrollment: 39
Sex: ALL
Minimum age (years): 24
Maximum age (years): 120
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will be a convenience sample, comprised of singleton neonates born at or after 35 weeks post-menstrual age at the University of Rochester Medical Center (URMC). Cases will be infants of mothers with either a diagnoses of pre-gestational diabetes or gestational diabetes whose provider recommends treatment with insulin or oral glycemic agents. Controls will be neonates whose mothers had normal glucose testing during gestation and pre-pregnancy BMI of \<30. All subjects will be otherwise healthy, as defined by the exclusion criteria. There is no intended racial, ethnic or gender distribution of these neonates.

Brief summary: 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. .


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Interburst Interval on cEEG
timeFrame: Single EEG between 24 hours of life and 5 days of life
measure: Lower Margin Amplitude on aEEG
timeFrame: Single EEG between 24 hours of life and 5 days of life
Secondary outcomes:
measure: Number of Delta Brushes on cEEG
timeFrame: Single EEG between 24 hours of life and 5 days of life
measure: Bandwidth on aEEG
timeFrame: Single EEG between 24 hours of life and 5 days of life
Other outcomes:
Locations:
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
Study officials:
affiliation: University of Rochester
name: Laura M Price, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: Ronnie Guillet, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: