Please select the eligibility criteria that correspond to the clinical trial below.
Title: Efficacy and Safety of Methylxanthines in Very Low Birthweight Infants
Brief Summary: At least 5 of every 1000 live-born babies are very premature and weigh only 500 to 1250 grams at birth. Approximately 30-40% of these high-risk infants either die or survive with lasting disabilities. The aim of this research is to reduce this heavy burden of illness. A multi-center randomized controlled trial has been designed in which 2000 very low birth weight infants will be enrolled. Our goal is to determine whether the avoidance of methylxanthine drugs will improve survival without disability to 18 months, corrected for prematurity.

Methylxanthine drugs such as caffeine are used to prevent or treat periodic breathing and breath-holding spells in premature infants. However, there is a striking lack of evidence for the long-term efficacy and safety of this therapy. Methylxanthines block a naturally occurring substance, called adenosine, which protects the brain during episodes of oxygen deficiency. Such episodes are common in infants who are treated with methylxanthines. It is possible that methylxanthines may worsen the damage caused by lack of oxygen. Therefore, this trial will clarify whether methylxanthines cause more good than harm in very low birth weight infants.


Options:
A: Inclusion Criteria:

* Infants greater than or equal to 36 weeks EGA
* Intrauterine opioid exposure
* Primary diagnosis of NAS
* Parental permission to participate

Exclusion Criteria:

* Infants less than 36 weeks EGA
* Major congenital anomalies
* Latrogenic drug withdrawal
* Diagnosis of infection or respiratory distress
* Prior initiation of opioid replacement therapy
* Non-English speaking
* Infants with respiratory conditions
B: Inclusion Criteria:

* birthweight 500 to 1250 grams
* postnatal age day 1 to day 10
* infant considered a candidate for methylxanthine therapy by clinical staff

Exclusion Criteria:

* dysmorphic features or congenital malformations that adversely affect life expectancy or neurodevelopment
* unlikely to comply with long-term follow-up
* prior treatment with a methylxanthine
C: Inclusion Criteria:

Eligible subjects are infants currently inpatient in the NICU or Newborn Nursery at University of Massachusetts Memorial Hospital and:

* Full-term infants (\>37 wks gestational age) and late preterm infants (34-37 wks gestational age)
* Newborns at risk for NAS due to fetal-drug exposure
* At-risk infants will be infants who present with confirmed meconium and/or urine toxicology report (documented in medical chart review) for opioids (e.g., methadone, buprenorphine/subutex, oxycodone, heroin); may also have prenatal exposure to benzodiazepines, barbiturates, amphetamines, cannabinoids, alcohol, nicotine and/or caffeine.

Exclusion Criteria:

Eligible infants meeting the inclusion criteria above will be excluded from participation in the study if he/she:

* Born less than \<34 weeks.
* Has a congenital abnormality
* Has a fetal anomaly
* Has hydrocephalus or intraventricular hemorrhage \>grade 2
* Has a seizure disorder not related to drug withdrawal
* Has a clinically significant shunt
* Requires mechanical respiratory support
D: Inclusion Criteria:

* Intrauterine exposure of opiate and related drugs-morphine
* Late preterm or full term (36-42 weeks of gestation)

Exclusion Criteria:

* Major congenital anomalies
* Post-surgical cases
* Major respiratory, cardiovascular, neurological or metabolic disorders
* Less than 36 completed weeks of gestation

Answer: B