Study of Pregnancy And Neonatal Health (SPAN)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)304 enrolled

Overview

This study will conduct a randomized trial among women with gestational diabetes (GDM). Study of Pregnancy And Neonatal health (SPAN), TIMing of dElivery (TIME) is a randomized trial that will recruit up to 3,450 pregnant women with uncontrolled GDM and randomize the timing of their delivery. Women with GDM who are approached for the trial and are found eligible but do not consent to participating in randomization for delivery will be asked to consent for chart review only (estimated additional n=3,000). The primary objective is to determine the best time to initiate delivery for GDM-complicated deliveries (defined as the time when risk of illness and death for the newborn is the lowest) between 37-39 weeks.

This is a randomized clinical trial under an adaptive design nested in a larger observational study, among women who are diagnosed with uncontrolled gestational diabetes mellitus (GDM). Women from multiple clinical sites around the United States will be recruited into the study (n=3,450). Women with GDM who are approached for the trial and are found eligible but do not consent to participating to randomization for delivery will be asked to consent for chart review only (estimated additional n=3,000). The primary objective is to determine the optimal time to initiate delivery for GDM complicated deliveries (defined as the time when neonatal morbidity and perinatal mortality risk is the lowest) between 37-39 weeks (n=3,450 women). Newborn developmental and behavior outcomes, and anthropometric measures will also be assessed as secondary outcomes, as well as an exploratory analysis to investigate whether there are clinical, non-clinical or biochemical factors such as glucose measures that will further assist in refining the interval for optimizing time of GDM complicated deliveries relative to neonatal morbidity and perinatal mortality.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Interventions

ChildbirthPROCEDURE

Induction or planned cesarean

Eligibility

Sex: FEMALEMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

INCLUSION CRITERIA: Aim 3 (GDM randomized trial, TIME) inclusion criteria: Women inclusion criteria: 1. Age ≥ 18 Years 2. Verified diagnosis of Gestational Diabetes Mellitus (GDM) with abnormal glucose levels\*\*\* or meeting other criteria for poor control, specifically any one of the following: Estimated fetal weight ≥90th percentile (LGA), Polyhydramnios, and or Demonstrate noncompliance or nonadherence as defined clinically, including missing visits, not keeping accurate log, etc. \*\*\*One or more elevated fasting blood glucoses OR three or more elevated post-prandial blood glucoses after receiving education about appropriate diet and lifestyle modification (e.g. physical activity) 3. Accurate gestational age as verified by ultrasound 4. Singleton gestation 5. English or Spanish speaker 6. Plans to deliver at the study site hospital 7. Ability to provide informed consent to be randomized to initiation of delivery EXCLUSION CRITERIA: Aim 3 (GDM randomized trial, TIME) exclusion criteria: 1. Pre-gestational diabetes\* \*will be defined as diabetes diagnosis before pregnancy OR before 13 weeks of gestation with a documented fasting plasma glucose ≥ 126 mg/dL, random plasma glucose ≥ 200 mg/dL, 2 hour post glucose ≥ 200 mg/dL during an oral glucose tolerance test (75 g glucose load), or hemoglobin A1c ≥ 6.5%.110. 2. Previous stillbirth defined as fetal demise ≥ 20 weeks of gestation 3. Self-reported history of alcohol dependency disorder and/or other drug/substance dependency in the past year 4. Teratogen exposure (e.g. cyclophosphamide, valproic acid, warfarin) 5. Known infectious diseases associated with neonatal morbidity (e.g. malaria, cytomegalovirus, rubella, toxoplasmosis, syphilis or Zika virus) 6. Genetic disorders, aneuploidy and known major fetal anomalies 7. Fetal demise 8. Pregnancies with concurrent conditions and other indications for earlier delivery will also be excluded. 9. Participation in another interventional study that influences management of labor and delivery or perinatal morbidity or mortality

Locations (8)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Ochsner Baptist

New Orleans, Louisiana, United States

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Duke University Perinatal Research Center

Durham, North Carolina, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Intermountain Healthcare

Murray, Utah, United States

University of Utah

Salt Lake City, Utah, United States

INOVA Fairfax Hospital

Falls Church, Virginia, United States

Outcomes

Primary Outcomes

Composite of Neonatal Morbidity and Perinatal Mortality

Time frame: Hospital discharge

Occurrence of Antepartum, intrapartum or neonatal death (Component of primary outcome)

Time frame: Antepartum pregnancy period through Newborn Discharge

Incidence of moderate or higher neonatal respiratory support within 72 hours after birth (Component of primary outcome)

Including any of the following: Nasal cannula \>/= 2 LPM (liters per minute), Nasal continuous positive airway pressure (NCPAP), NIPPV; (non-invasive intermittent positive pressure ventilation; Note that NIPPV is more general than Bilevel positive airway pressure (BiPAP) i.e. BiPAP is a form of NIPPV, as is non-invasive NAVA, synchronized NIPPV, non-synchronized NIPPV, some ventilators can do nasal IMV in certain situations, etc.), Mechanical ventilation, High frequency ventilation, and ECMO/ECLS (extracorporeal mechanical support/extracorporeal life support)

Time frame: Delivery through Newborn Discharge

Occurrence of Pneumonia (Component of primary outcome)

Confirmed by X-ray or positive blood culture

Time frame: Delivery through Newborn Discharge

Occurrence of Meconium aspiration syndrome (Component of primary outcome)

Respiratory distress in an infant born through meconium-stained amniotic fluid with X-ray findings consistent with meconium aspiration syndrome, and whose symptoms could not be otherwise explained

Time frame: Delivery through Newborn Discharge

Occurrence of Sepsis (Component of primary outcome)

The diagnosis of sepsis will require the presence of a clinically ill infant in whom systemic infection is suspected with a positive blood, CSF, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal X-ray confirming infection.

Time frame: Delivery through Newborn Discharge

Occurrence of Neonatal encephalopathy (Component of primary outcome)

Defined by Shankaran et al. 2005

Time frame: Delivery through Newborn Discharge

Occurrence of Intracranial hemorrhage (Component of primary outcome)

Intraventricular hemorrhage grades III and IV, subgaleal hematoma, subdural hematoma, or subarachnoid hematoma

Time frame: Delivery through Newborn Discharge

Occurrence of Seizures (Component of primary outcome)

Time frame: Delivery through Newborn Discharge

Occurrence of Birth trauma (Component of primary outcome)

Bone fractures, brachial plexus palsy, other neurologic injury, retinal hemorrhage, or facial nerve palsy

Time frame: Delivery through Newborn Discharge

Occurrence of Hypotension requiring pressor support (Component of primary outcome)

Time frame: Delivery through Newborn Discharge

Occurrence of hypertrophic cardiomyopathy (Component of primary outcome)

Time frame: Delivery through Newborn Discharge

Incidence of neonatal intensive care unit (NICU) > 1 day (24 hours) stay

NICU stay \> 1 day (24 hours)

Time frame: Delivery through Newborn Discharge

Secondary Outcomes

Incidence of respiratory support less than moderate

Hood oxygen and Nasal cannula \<2 LPM (liters per minute); Other than room air (No support)

Time frame: Delivery through Newborn Discharge

Duration of any respiratory support

Time frame: Delivery through Newborn Discharge

Duration of moderate respiratory support

Time frame: Delivery through Newborn Discharge

Occurrence of Transient tachypnea of the newborn

Time frame: Delivery through Newborn Discharge

Occurrence of Respiratory distress syndrome in Neonates

Both a clinical diagnosis and whether required surfactant

Time frame: Delivery through Newborn Discharge

Occurrence of Hypoglycemia in neonates

Glucose \< 35 mg/dl) and whether required IV therapy

Time frame: Delivery through Newborn Discharge

Occurrence of Hyperbilirubinemia in Neonates

Requiring phototherapy or exchange transfusion in Neonates

Time frame: Delivery through Newborn Discharge

Occurrence of Polycythemia in Neonates

Both a clinical diagnosis and whether required partial exchange transfusion

Time frame: Delivery through Newborn Discharge

Incidence of Therapeutic hypothermia

Head or body cooling

Time frame: Delivery through Newborn Discharge

Incidence of Transfusion of blood products or blood in neonates

Data from ClinicalTrials.gov

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Time frame: Delivery through Newborn Discharge

Occurrence of neonatal intensive care unit (NICU) or intermediate care unit admission

Time frame: Delivery through Newborn Discharge

Duration of Neonatal hospital stay

Measured in days

Time frame: Delivery through Newborn Discharge

Birthweight

Time frame: Delivery through Newborn Discharge

Incidence of small for gestational age

Defined as \< 10th percentile using the Duryea reference

Time frame: Delivery through Newborn Discharge

Incidence of large for gestational age and macrosomia

LGA defined as \> 90th percentile using the Duryea reference and macrosomia defined as birthweight \> 4500 g

Time frame: Delivery through Newborn Discharge

Composite of Maternal Morbidity and Mortality

Maternal death, HELLP syndrome, Eclampsia, Pulmonary edema, placental abruption, blood transfusion

Time frame: Pregnancy through Discharge

Occurrence of maternal death

Time frame: Pregnancy through Discharge

Occurrence of HELLP syndrome

As defined by American College of Obstetricians and Gynecologists (ACOG)

Time frame: Pregnancy through Discharge

Occurrence of Eclampsia

As defined by American College of Obstetricians and Gynecologists (ACOG)

Time frame: Pregnancy through Discharge

Occurrence of Maternal Pulmonary edema

Chest x-ray confirmed

Time frame: Pregnancy through Discharge

Occurrence of Placental abruption

Time frame: Pregnancy through Delivery

Incidence of Maternal Blood transfusion

Time frame: Pregnancy through Discharge

Incidence of spontaneous labor

Time frame: Pregnancy through Delivery

Incidence of induced labor

Time frame: Pregnancy through Delivery

Incidence of planned cesarean

Time frame: Pregnancy through Delivery

Indication for delivery including cesarean for suspected macrosomia

Defined as estimated fetal weight \> 4500 grams

Time frame: Pregnancy through Delivery

Occurrence of Spontaneous vaginal delivery

Time frame: Pregnancy through Delivery

Occurrence of Operative vaginal delivery

Vacuum or forceps

Time frame: Pregnancy through Delivery

Occurrence of Cesarean delivery

Time frame: Pregnancy through Delivery

Indications for operative vaginal delivery

Time frame: Pregnancy through Delivery

Indication for cesarean

Time frame: Pregnancy through Delivery

Incidence of Shoulder dystocia

Time frame: Delivery through Newborn Discharge

Occurrence of Maternal lacerations

1st, 2nd, 3rd or 4th degree perineal; sulcus, vaginal wall; labial, periurethral, clitoral, abrasion, other

Time frame: Delivery through Discharge

Occurrence of Postpartum hemorrhage

Defined as any of the following: Transfusion, Non-elective hysterectomy, Use of two or more uterotonics other than oxytocin, Other surgical interventions such as uterine compression sutures, uterine artery ligation, embolization, hypogastric ligation, or balloon tamponade, and Curettage

Time frame: Delivery through Discharge

Occurrence of Maternal ICU Admission

Time frame: Delivery through Discharge

Incidence of Maternal venous thromboembolism

Deep venous thrombosis or pulmonary embolism

Time frame: Delivery through Discharge

Incidence of Chorioamnionitis

Defined as a clinical diagnosis before delivery

Time frame: Delivery through Discharge

Maternal postpartum infection

Defined as, Clinical diagnosis of endometritis, Wound reopened for hematoma, seroma, infection or other reasons, Cellulitis requiring antibiotics, Pneumonia, Pyelonephritis, Bacteremia unknown source, and Septic pelvic thrombosis

Time frame: Delivery through Discharge

Maternal hypertension

Mild and Severe (systolic and diastolic) defined by ACOG

Time frame: Delivery through Discharge

Incidence of Preeclampsia, with or without severe features

Defined by ACOG

Time frame: Delivery through Discharge

Use of antihypertensive drugs

Includes oral antihypertensive, intravenous antihypertensive, or intravenous anticonvulsant

Time frame: Delivery through Discharge

Number of hours in labor and delivery unit

Time frame: Delivery through Discharge

Duration of maternal hospital stay

Measured in Days.

Time frame: Pregnancy through Newborn Discharge

Study of Pregnancy And Neonatal Health (SPAN)

Overview

Conditions

Interventions

Eligibility

Locations (8)

Outcomes

Primary Outcomes

Secondary Outcomes