Journal of Neonatal-Perinatal Medicine

Objectives: Mild hypothermia has been shown to be neuroprotective for newborn infants with hypoxic ischemic encephalopathy (HIE). In this study, we examined the effects of deep hypothermia on systemic and brain temperature changes during whole-body or selective head cooling in an animal model of perinatal HIE.

Methods: Twelve piglets were studied under anesthesia and artificial ventilation. Five ultra-sensitive, flexible, titanium, thermocouple probes were used for continuous temperature recording from five brain regions, two kidney regions; the thoracic aorta, the wall of the small intestine, and the rectal lumen using single sensor probes for each. Changes in temperatures from the 10 sites were recorded continuously during baseline, 20 minutes of hypoxic-ischemic injury; 60 minutes whole-body cooling (n=6) or selectively the head cooling (n=6); and 60 minutes of re-warming.

Results: Deep hypothermia with whole-body cooling led to uniform drops in temperature in the five brain regions, maintaining a constant gradient across the superficial and deep brain regions. Deep hypothermia with selective head cooling led to larger drops in superficial than in the deep brain temperatures. Deep whole-body hypothermia led to sharp drops in core body, kidney and small intestinal temperatures; the latter dropping to −11.27°C ± 3.72°C below baseline compared to −3.32°C ± 1.52°C below the baseline with deep hypothermia for selective head cooling (P<0.001).

Conclusions: Deep hypothermia with whole-body cooling can lead to severe core hypothermia especially of the kidney and small intestines, which get cooled far in excess of the aortic blood. Reduced kidney and small intestinal blood flow, and a direct cooling effect from lying on the cooling mattress may be responsible for rapid cooling of the kidney and the intestines. These findings underscore the need to target the core temperatures to strict ranges, as specified in the published hypothermia trials, especially during the transportation of infants to centers providing therapeutic hypothermia.

A neonatal piglet model was used to determine IL6, IL8 and CRP responses to asphyxia and subsequent volume infusion. Mechanically ventilated swine (n=37, age: 8 ± 2 days, weight: 2.2 ± 0.7 kg) were progressively asphyxiated by changing the ventilator gases until heart rate < 100 bpm and mean arterial blood pressure < 20 mmHg. After 5 minutes of ventilatory resuscitation, piglets were randomized to receive volume infusion with either 5% Albumin (ALB), Normal Saline (NS), or no volume (SHAM). IL6, IL8 and CRP were measured at baseline, at the end of asphyxia (ASPYHXIA), and 2 hrs after resuscitation (RESUSCITATION). IL6 (median and [25–75 percentiles] pg/ml) increased from 163 [55,193] at baseline, to 263 [196,393] at ASPHYXIA, and 441 [309,875] at RESUSCITATION (p<0.001). Both IL8 and CRP were similar to baseline at all time intervals. Animals randomized to volume (ALB and NS) vs. SHAM had higher IL6 levels following RESUSCITATION (749 [383,1163] vs. 303 [204,465], p<0.02). In this model of severe neonatal asphyxia, serum IL-6 was elevated following volume infusion. The lack of change in IL8 and CRP suggests selectivity in the immediate inflammatory responses following asphyxia and volume resuscitation.

Background: Vascular endothelial growth factor (VEGF) is a known mediator of angiogenesis. It has been shown to induce vascular proliferation and permeability via nitric-oxide-mediated mechanism during hypoxia. VEGF exerts its effects by binding to two receptors; VEGFR-1 and VEGFR-2.

Objectives: To test the hypothesis that serum concentration of the soluble receptor sVEGF-R1 is increased in infants with hypoxic ischemic encephalopathy (HIE); and such an increase correlates with the severity of encephalopathy.

Study design: Serum samples of 30 full term newborns diagnosed with HIE and 20 controls were obtained within the first 6 hours of life and kept at −70°C. Concentrations of sVEGFR-1 were measured by the enzyme-linked immunosorbent assay double sandwich method. Values were correlated with the severity of HIE at birth and with outcomes measured at 4 weeks of age.

Results: The concentrations of sVEGFR-1 in HIE patients were increased when compared to control subjects. Patients with the least Apgar scores had the most increase in sVEGFR-1. sVEGFR-1 at a cut off 11.0 ng/ml had 100% sensitivity & 100% specificity for detection of HIE. The concentrations of sVEGFR-1 did not differ among patients with different degrees of HIE nor in patients with different short term clinical outcomes. Two stepwise regression analyses showed that both degree and outcome of HIE depend upon Apgar score and the liver enzyme alanine transaminase.

Conclusion: sVEGFR1 is upregulated early in neonates with HIE. It does not correlate with the severity of encephalopathy or the short term outcomes.

Persistent pulmonary hypertension of the newborn (PPHN) is a life threatening condition associated with an increased risk of neurological impairment. Magnesium sulfate (MgSO $_{4}$ ) is an alternative and low cost treatment for PPHN. Despite more appropriate and available therapies MgSO $_{4}$ is still widely used, especially in developing countries, but long-term follow-up is unknown. In a retrospective controlled study we evaluated whether MgSO $_{4}$ therapy for PPHN was associated with increased neuro-developmental impairments at follow-up, as compared to a control group. Population consisted of 33 infants treated for PPHN with MgSO $_{4}$ only (study group) and 32 healthy term infants (control group). Extensive neuro-developmental follow-up examination was performed at 18 months and 5 years of age. Rate of major impairments and minor impairments were evaluated and compared to the literature.

The rates of major impairments in the study group at 18 months and 5 years were 6% and 11.4%, respectively, and 0% at both ages in the control group. The rates of minor impairments at the same ages were 3% and 26.9% for the study group, and 0% and 26.1% for the control group. Mean developmental quotients at 18 months were 106.6 (SD 1.6) in the study group and 118.3 (SD 1.0) in the control group (p<0.001). General intellectual index at preschool age was not significantly different between the two groups. Treatment with MgSO $_{4}$ does not increase the rate of disability, as compared to other treatments for PPHN.

Objective: We hypothesized that a single sustained inflation (SI) of the lung as a volume recruitment maneuver during high frequency oscillatory ventilation (HFO-SI) would improve pathophysiologic, inflammatory responses when compared to conventional inflation (CI) during both HFO (HFO-CI), volume targeted synchronized intermittent mandatory ventilation (SIMV+V) in spontaneously breathing newborn piglets with surfactant washout.

Design: Prospective, randomized animal study.

Subjects: Thirty-two newborn piglets.

Interventions: Animals underwent saline lavage to produce lung injury, received surfactant and randomized to one of 3 treatment groups. Lung volume recruitment (LVR) protocol followed and ventilation continued for 6 hours.

Measurements and main results: Vital signs and arterial blood gases were continuously monitored. End expiratory lung volume (ΔEELV) changes were estimated during LVR using respiratory impedance plethysmography (RIP). At baseline, post lung injury, 6 hours: serum, bronchoalveolar lavage (BAL) samples for proinflammatory cytokines were collected and static pressure volume (P/V) curves obtained. At 6 hours animals were euthanized and lungs fixed for morphometrics, histopathology. ΔEELV during LVR was greatest using SIMV+V, HFO-CI (p<0.05); HFO-SI required higher P $_{aw}$ for LVR compared to SIMV+V (p< 0.005), while ΔEELV change was lowest. Oxygenation was greatest with SIMV+V. Inflammatory responses, histopathology and morphometrics were similar.

Conclusions: Single SI during HFO is not adequate for LVR. SIMV+V and HFO-CI adequately recruited lung volumes without creating more lung injury.

Objectives: Few works address the impact of armed conflict on obstetric outcomes, largely secondary to limitations in measurement of these outcomes. In settings where hospitalized data is routinely and consistently obtained, these sources may provide rapidly accessible and valuable information on the status of women.

The objective of this work was to determine the impact of the armed conflict of February, 2004 on maternal health in rural Haiti.

Methods: Study of data from the Hospital Albert Schweitzer perinatal database from the time of conflict in February, 2004 was compared to baseline indices from the preceding year, 2003. Primary outcome measures included: maternal mortality, eclampsia, and stillbirth.

Results: In 2003, maternal deaths occurred in 0.8% of women at baseline, compared to 4% during the conflict. (p=0.03) The baseline eclampsia rates were 0.5% and rose to 14% during the 2004 conflict. (p=0.06) Surrounding hospital closures resulted in a marginally significant increase in patients from outside the hospital catchement area.

Conclusions: In areas of poverty, access to care is one of the most significant determinants of health. Peaks in maternal mortality may reflect obstructions in access to care during times of acute instability. These data may serve as markers for the social status of women, the function of the local health care system, and the international response to conflict, as experienced, by the most vulnerable members of the population.

Background: Despite a dearth of well-controlled studies comparing the gastric emptying (GE) of casein- and whey-based formulas in humans and lack of clear evidence suggesting that such a difference influences patient symptoms, prevailing opinion among healthcare professionals continues to purport that a clinically meaningful difference exists between the two.

Aim: To review the literature related to the influence of casein and whey on GE in humans.

Methods: A PubMed literature search was executed using a combination of the following search terms: gastric emptying, human, casein, and whey. Our primary interest was experimental design strategies with respect to established physiologic factors controlling GE.

Results: Our search resulted in 11 citations; 5 directly compared GE rates of casein- and whey-based formulas and 3 of the 5 suggested a difference. Critical review of these studies revealed numerous experimental design weaknesses that included: 1) lack of control over osmolality, caloric density, feeding volume and macronutrients (protein, fat, and carbohydrate), 2) small sample sizes, and 3) use of heterogeneous subjects with respect to age, symptom types, symptom severity, and general health status.

Conclusion: No convincing evidence exists to support the prevailing notion that casein- and whey-predominant formulas differently influence GE rates.

Central vascular catheterization for nutrition and monitoring is common in the current era of increasing survival of ever smaller preterm infants and their complex nutritional needs. Any foreign body in blood vessels, whether venous catheters or transvenous pacing catheters (implanted frequently in children with rhythm disorders) could put them at risk of progressive venous obstruction. Although obstruction of SVC leading to "SVC syndrome" has been widely reported in adults, it is very uncommon in children and may be associated with previous congenital heart surgery. In this case study we present SVC obstruction in a newborn infant as a complication of a central catheter. This was diagnosed by combination of clinical suspicion and typical Doppler characteristics as elucidated by application of echocardiographic skills by in-house neonatal staff.

A term newborn male who presented with hyperglycemia and metabolic acidosis was subsequently diagnosed with neonatal diabetes mellitus. We describe his hospital and out-patient course and review the current epidemiology, pathophysiology, genetics, and treatment options for these patients.