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:

* Birth weight \<1000 gm
* Gestational age \<30 completed weeks
* Intention to manage the infant with non-invasive respiratory support (i.e. no endotracheal tube), where either:

  * the infant is within the first 7 days of life and has never been intubated or has received less than 24 hours of total cumulative intubated respiratory support;
  * the infant is within the first 28 days of life, has been managed with intubated respiratory support for 24 hours or more and is a candidate for extubation followed by non-invasive respiratory support.

Exclusion Criteria:

* Considered non-viable by clinician (decision not to administer effective therapies)
* Life-threatening congenital abnormalities including congenital heart disease (excluding patent ductus arteriosis)
* Infants known to require surgical treatment
* Abnormalities of the upper and lower airways
* Neuromuscular disorders
* Infants who are \>28 days old and continue to require mechanical ventilation with an endotracheal tube
B: Inclusion Criteria:

1. Gestational age between 24 to 34 and 6/7 weeks assessed by the obstetrical team from dating of last menstural period or ultrasound and weight \>1000 g for the initial treatment of RDS or \<35 weeks post extubation or for apnea of prematurity
2. Infants with RDS who will need NRS as initial therapy or after extubation and for apnea of prematurity, 3. written informed consent.

Exclusion Criteria:

1. Significant morbidity apart from RDS including: cardiac disease (not including patent ductus arteriosus \[PDA\]), congenital malformation, or if they had cardiovascular or respiratory instability because of sepsis, anemia or severe intraventricular hemorrhage (IVH),
2. Parents refuse consent.
3. Unavailability of suitable ventilator.
C: Inclusion Criteria:

* All inborn VLBW infants (birthweight less than 1500 g and Gestational Age \< 32 wks) with signs of RDS, spontaneously breathing and only supported by N-CPAP, will be randomized within the first 2 hours of life to receive two different Non Invasive Ventilation (NIV) strategies.

Exclusion Criteria:

* Apneic or severely depressed newborns requiring invasive ventilation, within two hours from birth
* Newborns with genetic disease and/or with major congenital malformations
* Newborns for whom it was not obtained informed consent within two hours from birth
D: 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

Answer: D