Table 1 Summary of representative drug or physical intervention trials to reduce IVH or improve neurological outcomes in humans
Drug(s) or intervention | Dosage | Mechanism | Data class | Degree of IVH reduction | Neurological outcome improvement | References |
|---|---|---|---|---|---|---|
Antenatal betamethasone | Single 2-dose (12 mg each); 24 mg | May reduce endothelial proliferation, vascular density, and increase pericyte vascular coverage [270] | Class 2, Class 2, Class 2, Class 2, Class 1, Class 2, Class 1 | IVH reduction from 6 to 47 h, slowly increased 48 h ≥ 10 days); beneficial for women < 34 weeks GA; decreased IVH from 22–29 GA; decreased IVH even with incomplete course | Not significant, not examined in study; associated improved neurological outcome | |
Antenatal betamethasone/dexamethasone | Meta-study with unknown dosing | May reduce endothelial proliferation, vascular density, and increase pericyte vascular coverage | Class 2 | Beneficial for women peri-viable ages 23–26 weeks GA | Not examined | [274] |
Prophylactic indomethacin (oral or IV) | Oral 0.2 mg/kg daily for 3 days; 0.1 mg/kg IV for daily for 2 days | Inhibits cyclooxygenase-mediated production of prostaglandins, promotes germinal matrix vascular maturation | Class 2, Class 1, Class 1 | 50–80% reduction in IVH | Higher verbal scores in 3-8 yr old boys | |
Ibuprofen | Oral 5–10 mg/kg daily for 3 days | Inhibits cyclooxygenase-mediated production of prostaglandins | Class 2, Class 1 | Mixed results: 0–80% reduction in IVH | Not examined | |
Neonatal Ethamsylate | 12.5Â mg/kg daily for 4Â days | Inhibits cyclooxygenase-mediated production of prostaglandins; possibly increases platelet aggregation | Class 1, Class 1, Class 1 | Reduction in IVH | No decrease in mortality (possibly increased), no improvement in cognitive outcomes | |
Inhaled nitric oxide | Inhaled at 20Â ppm | Mediates rapid vasodilation by stimulating guanylate cyclase, subsequent reduced phosphorylation of myosin, and relaxes smooth muscle cells | Class 1, Class 1 | No reduction in IVH | No significant neurological improvement | |
Phenobarbital | IV injections of 20–30 mg/kg loading dose, followed by 3–7 days of maintenance doses | Acts on GABA receptors and is thought to stabilize blood pressure and may protect against free radicals | Class 2, 3 | Mixed results from 12 clinical trials; overall does not appear to reduce severe IVH or ventricular dilatation | Did not seem to attenuate neurological impairments | [282] |
Prophylactic surfactant | Bolus or infusion delivery via endotracheal tube (e.g., 5Â ml/kg) | Replenishes insufficient surfactant production in premature neonates in order to increase pulmonary compliance, increase alveolar gas exchange, and decrease hypoxia | Class 1, Class 1, Class 1 | No reduction in IVH (though there was decrease in neonatal morbidity) | Not examined | |
Postnatal corticosteroids (typically dexamethasone) | 0.12–0.5 mg/kg/day for several days | May reduce endothelial proliferation, vascular density, and increase pericyte vascular coverage | Class 1, Class 1 | Possible trend towards reduction of neonatal IVH | Unclear neurological improvement | |
Magnesium (magnesium sulfate) | 4–6 g IV MgSO4 loading dose, 2–4 g/h for 12–24 h | Tocolytic mechanisms include competition for calcium, prevent release of acetylcholine, and activation of myosin light chain kinase, which blocks myometrial contractions; neuroprotective effects may include stabilization of rapid blood pressure fluctuations, increased cerebral blood flow, and decreased neuroinflammation | Class 1, Class 1, Class 1, Class 2 | No effect on IVH reduction | Possible neurological protection | |
Cesarean delivery | 22–37 weeks gestational age planned delivery | Prevention of stresses associated with vaginal delivery | Class 2, Class 2 | 35% reduction in IVH in < 30 week preterm neonates | Not examined | |
Delayed cord clamping | Delayed clamping usually performed 60–75 s (compared with 30–45 s) | Proposed mechanisms include cardiovascular transition with ventilation, establishment of red blood cell volume, decreased need for blood transfusion | Class 1, Class 1, Class 3, Class 3 | Up to 50% reduction in preterm IVH; benefits unclear in term neonates | May improve fine motor and social domains at 4 years in low-risk children [293] |