Effect of Delayed Cord Clamping on Systemic Blood Flow: A Randomized Controlled Trial.

OBJECTIVE: To determine whether delayed cord clamping improves systemic blood flow compared with immediate cord clamping in very preterm infants in the first 24 hours. STUDY DESIGN: Women delivering at <30 weeks' gestation at 5 tertiary centers were randomized to receive immediate cord clamping (<10 seconds) or delayed cord clamping (≥60 seconds). Echocardiography and cardiorespiratory data were collected at 3, 9, and 24 hours after birth. The primary outcome was mean lowest superior vena cava (SVC) flow. RESULTS: Of 266 infants enrolled, 133 were randomized to immediate cord clamping and 133 to delayed cord clamping. The 2 groups were similar at baseline, including mean gestation (immediate cord clamping 28 weeks vs delayed cord clamping 28 weeks) and birth weight (immediate cord clamping 1003 g vs delayed cord clamping 1044 g). There was no significant difference between groups in the primary outcome of mean lowest SVC flow (immediate cord clamping 71.4 mL/kg/min [SD 28.1] vs delayed cord clamping 70.2 mL/kg/min [SD 26.9]; P = .7). For secondary outcomes, hemoglobin increased by 0.9 g/dL at 6 hours in the group with delayed cord clamping (95% CI 3.9, 14.4; P = .0005, adjusted for baseline). The group with delayed cord clamping had lower right ventricular output (-21.9 mL/kg/min, 95% CI -39.0, -4.7; P = .01). Rates of treated hypotension, ductus arteriosus size and shunt direction, and treatment of the ductus arteriosus were similar. CONCLUSIONS: Delayed cord clamping had no effect on systemic blood flow measured as mean lowest SVC flow in the first 24 hours in infants <30 weeks' gestation. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: ACTRN12610000633088.

Screening programmes for developmental dysplasia of the hip in newborn infants

BACKGROUND Uncorrected developmental dysplasia of the hip (DDH) is associated with long term morbidity such as gait abnormalities, chronic pain and degenerative arthritis. OBJECTIVE To determine the effect of different screening programmes for DDH on the incidence of late presentation of congenital hip dislocation. METHODS Search methods: Searches were performed in CENTRAL (The Cochrane Library), MEDLINE and EMBASE (January 2011) supplemented by searches of clinical trial registries, conference proceedings, cross references and contacting expert informants. Selection criteria: Randomized, quasi-randomized or cluster trials comparing the effectiveness of screening programmes for DDH. Data collection and analysis: Three independent review authors assessed study eligibility and quality, and extracted data. MAIN RESULTS No study examined the effect of screening (clinical and/or ultrasound) and early treatment versus not screening and later treatment. AUTHORS' CONCLUSIONS There is insufficient evidence to give clear recommendations for practice. There is inconsistent evidence that universal ultrasound results in a significant increase in treatment compared to the use of targeted ultrasound or clinical examination alone. Neither of the ultrasound strategies have been demonstrated to improve clinical outcomes including late diagnosed DDH and surgery. The studies are substantially underpowered to detect significant differences in the uncommon event of late detected DDH or surgery. For infants with unstable hips or mildly dysplastic hips, use of delayed ultrasound and targeted splinting reduces treatment without significantly increasing the rate of late diagnosed DDH or surgery. .

Randomized trial of milrinone versus placebo for prevention of low systemic blood flow in very preterm infants.

OBJECTIVE: To assess the effectiveness of early prophylactic milrinone versus placebo for prevention of low systemic blood flow in high-risk preterm infants. STUDY DESIGN: Double-blind randomized placebo controlled trial of milrinone (loading dose 0.75 microg/kg/min for 3 hours then maintenance 0.2 microg/kg/min until 18 hours after birth) versus placebo. Infants born <30 weeks gestational age and <6 hours of age were eligible and were monitored with serial echocardiography, head ultrasound scanning, and continuous invasive blood pressure. Primary outcome was maintenance of superior vena cava (SVC) flow > or =45 mL/kg/min through the first 24 hours. The exit criterion was hypotension unresponsive to volume and inotropes. RESULTS: Ninety infants were enrolled, equal proportions maintained SVC flow > or =45 mL/kg/min after treatment commenced. No significant difference was observed in SVC flow, right ventricular output, and blood pressure during the first 24 hours; or grades 3 to 4 periventricular/intraventricular hemorrhage and death. Heart rate was higher and constriction of the ductus was slower in the infants randomized to milrinone. CONCLUSIONS: Milrinone did not prevent low systemic blood flow during the first 24 hours in very preterm infants, and no adverse effects were attributable to milrinone. Use of a preventative treatment with rescue model allowed comparison of an inotrope with placebo in this high-risk group of infants.

Pilot study of milrinone for low systemic blood flow in very preterm infants.

OBJECTIVES: To examine the hemodynamic effects of milrinone given prophylactically to very preterm infants at high risk of low superior vena cava (SVC) flow and to investigate the preliminary efficacy and safety of an optimal dose. STUDY DESIGN: This was a prospective, open-label study in two stages. The first involved dose escalation in two cohorts. Milrinone infusions of 0.25 microg/kg per minute (n = 8) and then 0.5 microg/kg per minute (n = 11) were administered from 3 to 24 hours of age. Population pharmacokinetic modeling was used to develop an optimized dose regimen. Ten infants then were loaded with 0.75 microg/kg per minute for 3 hours, followed by 0.2 microg/kg per minute maintenance until 18 hours of age. Infants were monitored for blood pressure, serial echocardiograms, and blood milrinone levels. The primary outcome was maintenance of SVC flow greater than 45 mL/kg per minute through the first 24 hours. RESULTS: Low SVC flow developed in 36% of babies at both 0.25 microg/kg per minute and 0.5 microg/kg per minute of milrinone. Blood levels on these two regimens were slow to reach the target range and accumulated above this range by 24 hours. At 0.75 to 0.2 microg/kg per minute, no infant had SVC flow below 45 mL/kg per minute, compared with 61% in historic control subjects. Four infants needed an additional inotrope to support blood pressure. Blood levels were within the target range in 9 of 10 babies. CONCLUSIONS: We used population pharmacokinetic modeling to develop an optimal dosing regimen for milrinone. The efficacy and safety in this novel preventative approach to circulatory support is encouraging but inconclusive. We do not recommend the use of milrinone in preterm infants outside a research setting.

Randomized trial of high-frequency oscillatory ventilation versus conventional ventilation: effect on systemic blood flow in very preterm infants.

OBJECTIVE: Low superior vena cava (SVC) flow is common in very preterm infants in the first day and strongly associated with periventricular hemorrhage and disability. We examined the effect of high-frequency oscillatory ventilation (HFOV) compared with conventional ventilation (CV) on SVC flow and right ventricular output. METHODS: Forty-five infants <29 weeks were randomized before 1 hour of age to HFOV or CV. Echocardiography was performed on 43 infants at 3, 10, and 24 hours of age. Infants with low SVC flow (<50 mL/kg/min) or hypotension (mean blood pressure < or =20) were treated with volume and inotrope. RESULTS: Infants allocated to HFOV (n=23) and to CV (n=20) were well matched. There was a nonsignificant trend toward more infants on HFOV having SVC flow <50 mL/kg/min (48% vs 20%) and receiving volume and inotropes (61% vs 40%). There were no significant differences in mean SVC flow or right ventricular output at 3, 10, or 24 hours. Infants on HFOV had a significantly higher calculated upper body vascular resistance at 10 hours and mean blood pressure at 24 hours. CONCLUSIONS: There were no significant adverse effects of HFOV on systemic blood flow in very preterm infants during the first 24 hours of life.

Randomized trial of dobutamine versus dopamine in preterm infants with low systemic blood flow.

OBJECTIVE: Our purpose was to determine if dobutamine or dopamine results in greater improvements in systemic blood flow in very preterm infants with low flow during the first 24 hours of life. STUDY DESIGN: A 2-center, randomized, double-blind study. Infants (n = 42) with low superior vena cava (SVC) flow (<41 mL/kg/min) in the first 12 hours were randomly assigned to receive 10 mL/kg normal saline solution, followed by 10 microg/kg/minute of dobutamine or dopamine. If low flow persisted or recurred, the inotrope was increased to 20 microg/kg/minute, with crossover to the other inotrope if treatment failed to maintain flow. RESULTS: Volume produced a more significant increase in SVC flow than dopamine (+43%). At the highest dose, dobutamine resulted in a significantly greater increase in SVC flow than dopamine (mean, +9.9 vs -3.2 mL/kg/min, P =.02). Dopamine resulted in a significantly greater increase in blood pressure. Infants receiving dobutamine only at 24 hours had a greater right ventricular output than infants receiving dopamine (mean, 295 vs 167 mL/kg/min, P <.001). Forty percent failed to increase or maintain SVC flow in response to either inotrope. No significant differences in mortality or morbidity were found. CONCLUSIONS: Dobutamine produced a greater increase in blood flow than dopamine.