Alejandro Jenik

A Randomized, Double-Blind, Placebo-Controlled Trial of the Effects of Prophylactic Theophylline on Renal Function in Term Neonates With Perinatal Asphyxia

Background. The kidney is the most damaged organ in asphyxiated full-term infants. Experiments in rabbits and rats have shown that renal adenosine acts as a vasoconstrictive metabolite in the kidney after hypoxemia and/or ischemia, contributing to the fall in glomerular filtration rate (GFR) and filtration fraction. Vasoconstriction produced by adenosine can be inhibited by the nonspecific adenosine receptor antagonist, theophylline. Gouyon and Guignard performed studies in newborn and adult rabbits subjected to normocapnic hypoxemia. Their results clearly showed that the hypoxemia-induced drop in GFR could be avoided by the administration of low doses of theophylline. Objective. This study was designed to determine whether theophylline could prevent and/or ameliorate renal dysfunction in term neonates with perinatal asphyxia. Setting. Buenos Aires, Argentina. Study Design. We randomized 51 severe asphyxiated term infants to receive intravenously a single dose of either theophylline (8 mg/kg; study group: n = 24) or placebo (control group: n = 27) during the first 60 minutes of life. The 24-hour fluid intake and the urine volumes formed were recorded during the first 5 days of life. Daily volume balances (water output/input ratio and weights) were determined. Severe renal dysfunction was defined as serum creatinine elevated above 1.50 mg/dL, for at least 2 consecutive days after a fluid challenge, or rising levels of serum creatinine (.3 mg/dL/day). The GFR was estimated during the second to third days of life by endogenous creatinine clearance (mL/minute/1.73 m2) and using Schwartzs formula: GFR (mL/minute/1.73 m2) = .45 × length (cm)/plasma creatinine (mg/100 mL) during the first 5 days of life. Tubular performance was assessed as the concentration of β2-microglobulin (β2M) determined by enzyme immunoassay, on the first voided urine 12 hours after theophylline administration. The statistical analysis for the evaluation of the differences between the groups was performed with Studentst and χ2 tests as appropriate. Results. During the first day of life, the 24-hour fluid balance was significantly more positive in the infants receiving placebo compared with the infants receiving theophyline. Over the next few days, the change in fluid balance favored the theophyline group. Significantly higher mean plasma values were recorded in the placebo group from the second to the fifth days of life. Severe renal dysfunction was present in 4 of 24 (17%) infants of the theophylline group and in 15 of 27 (55%) infants of the control group (relative risk: .30; 95% confidence interval: .12–.78). Mean endogenous creatinine clearance of the theophylline group was significantly increased compared with the creatinine clearance in infants receiving placebo (21.84 ± 7.96 vs 6.42 ± 4.16). The GFR (estimated by Schwartzs formula) was markedly decreased in the placebo group. Urinary β2M concentrations were significantly reduced in the theophylline group (5.01 ± 2.3 mg/L vs 11.5 ± 7.1 mg/L). Moreover, 9 (33%) patients of the theophylline group versus 20 (63%) infants of the control group had urinary β2M above the normal limit (<.018). There was no difference in the severity of the asphyxia between infants belonging to the theophylline and control groups in regards of Portmans score. Except for renal involvement, a similar frequency of multiorganic dysfunction, including neurologic impairment, was observed in both groups. The theophylline group achieved an average serum level of 12.7 μg/mL (range: 7.5–18.9 μg/mL) at 36 to 48 hours of live versus traces (an average serum level of .87 μg/mg) in the placebo group. Conclusions. Our data suggest that prophylactic theophylline, given early after birth, has beneficial effects on reducing the renal dysfunction in asphyxiated full-term infants. A single dose of 8 mg/kg of theophylline within the first postnatal hour in term neonates with severe perinatal asphyxia results in a significant decrease in serum creatine and urinary β2M, together with a significant increase in the creatine clearance. The potential clinical relevance of the data would be the avoidance of the contributory role of hypoxemia in the development of acute renal failure. Additional studies will be necessary before the use of theophylline in asphyxiated newborns can be considered for clinical practice.

Does the recommendation to use a pacifier influence the prevalence of breastfeeding

OBJECTIVE To evaluate whether the recommendation to offer a pacifier once lactation is well established reduces the prevalence or duration of breastfeeding. STUDY DESIGN A multicenter, randomized, non-inferiority, controlled trial comprising 1021 mothers highly motivated to breastfeed whose newborns regained birth weight by 15 days. They were assigned to offer versus not to offer pacifiers. Primary outcome was prevalence of exclusive breastfeeding at 3 months. Main secondary outcomes were the prevalence of exclusive and any breastfeeding at different ages and duration of any breastfeeding. RESULTS At 3 months, 85.8% infants in the offer pacifier group and 86.2% in the not offer pacifier group were exclusively breastfeeding (risk difference, 0.4%; 95% CI, -4.9%-4.1%), satisfying the pre-specified non-inferiority requirement of -7%. Furthermore, the recommendation to offer a pacifier did not produce a significant decrease in the frequency of exclusive and any breastfeeding at different ages or in the duration of lactation. CONCLUSIONS The recommendation to offer a pacifier at 15 days does not modify the prevalence and duration of breastfeeding. Because pacifier use is associated with reduced incidence of sudden infant death syndrome, the recommendation to offer a pacifier appears safe and appropriate in similar populations.

The pacifier debate.

A variety of studies have indicated that pacifier use lowers the risk of SIDS. Many observational studies have demonstrated a negative association between pacifier use and breastfeeding duration. However, observational studies cannot be used to determine whether the pacifier is the real cause of breastfeeding cessation. Evidence for causation can be better supplied by randomised controlled trials (RCTs). Three RCTs have been conducted on the relationship between pacifiers and breastfeeding, but each study has limitations, implying that the evidence of not causal effect can be questionated. We have recently presented the results of a large RCT which demonstrated that in mothers who are successfully breastfeeding at 2 weeks, the recommendation to offer a pacifier does not modify the prevalence of exclusive and any breastfeeding at different ages or the duration of lactation. It is therefore important that lactation consultants and international agencies reexamine their staunch position to discourage the use of pacifiers on the basis of a supposed adverse effect on the success and duration of breastfeeding.

A New Bottle Design Decreases Hypoxemic Episodes during Feeding in Preterm Infants

Oxygen saturation is lower during bottle feeding than during breastfeeding in preterm infants. Our objective was to compare two different bottle systems in healthy preterm infants before discharge in terms of SpO2 and oral feeding efficiency (rate of milk intake). Infants without supplement oxygen needs were evaluated twice on the same day during two consecutive feeds, by the same nurse. Infants served as their own controls for comparison of two systems of bottles, the order of which was randomized. The new bottles nipple design mimics moms breast in shape and feel, and the bottle vents to air when the child sucks on the nipple. The other system was the hospitals standard plastic bottle with silicone nipple. The rate of milk intake was calculated as the total volume transferred minus volume lost divided by time of feeding, mL/min. Thirty-four infants (BW: 1, 163 ± 479.1 g) were studied at 35.4 ± 1.3 weeks after-conception. SpO2 was significantly higher in infants fed with the new bottle design. Milk intake rate was significantly higher with the new bottle than with the standard bottle design. The new bottle design improves oral feeding performance in preterm infants near to discharge when compared to that of a standard bottle.

The Role of Respiratory Infection in Sudden Infant Death Syndrome (SIDS)

Abstract Introduction: The Sudden Infant Death Syndrome (SIDS) is not likely to be explained by a currently measureable presence in all cases and absence in controls, as otherwise it would have been solved already. Indeed, any proposed physiological model for SIDS causation must explain the constant mathematical and statistical properties of SIDS age and gender. We have shown previously that SIDS are characterized by a common 4-parameter lognormal age distribution sparing neonatal infants, by a nominal 50% male excess, and by a higher rate in winter than summer. We test now whether SIDS is closely related to a fulminating prodromal Acute Respiratory Infection (ARI) by a common increasing rate with the infants increasing Live Birth Order (LBO), all remaining the same, independent of the change in preferred sleeping positions of the infants, prone or supine. Methods: We use U.S. published infant mortality data from wonder.cdc.gov and other countries (Colombia, U.K., Europe, Australasia) to make comparisons between the two causes of death (ARI and SIDS) to evaluate how closely ARI resembles the characteristics of SIDS. Results: Gender: SIDS male excess 50%, ARI male excess 50%; Ages: SIDS 90% post-neonatal, ARI 96% post-neonatal; Seasonality: SIDS and ARI are higher in winter than summer; Live birth order: SIDS and ARI rates increase with increasing LBO with similar mathematical relationship. Conclusion: Our results show that all SIDS are very likely relatable to a single cause tied to a fulminating prodromal ARI in a physiologically anemic infant who is genetically (X-link recessive) susceptible to cerebral anoxia. An alternative cause of all SIDS death by a collection of subsets of different causes, such as brainstem-related respiratory abnormalities and cardiac QT abnormalities, is not supported because they cannot all have the same age-gender-seasonal-familial-distributions of SIDS, required by Cramér’s Theorem.

An Acute Respiratory Infection of a Physiologically Anemic Infant is a More Likely Cause of SIDS than Neurological Prematurity

Introduction The cause of the sudden infant death syndrome (SIDS) is perhaps the oldest of unsolved mysteries of medicine, possibly dating back to Exodus in Biblical times when Egyptian children died in their sleep as if from a plague. It occurs when infants die unexpectedly with no sufficient cause of death found in a forensic autopsy, including death scene investigation and review of medical history. That SIDS is an X-linked recessive death from infectious respiratory disease of a physiologically anemic infant and not a simple anomalous cardiac or neurological condition is an extraordinary claim that requires extraordinary evidence. If it were by a simple cause, it would have already been solved, with over 11,000 papers on SIDS listed now in PubMed. Our aim is to use mathematical models of SIDS to explain: (1) its 50% excess male death rate; (2) its 4-parameter lognormal distribution of ages at death; (3) its winter maxima and summer minima; and (4) its increasing rate with live-birth order. Methods From extensive SIDS vital statistics data and published epidemiologic studies, we developed probability models to explain the mathematical behavior of SIDS meeting the four constraints mentioned above. We, then, compare these SIDS properties to infant death from acute respiratory infection (ARI), and infant death from encephalopathy, unspecified (EU). Results Comparisons show that SIDS are congruent with ARI and are not consistent with EU and that these probability models not only fit the SIDS data but they also predict and fit the male fraction of all infant and child mortality from birth through the first 5 years of their life. Conclusion SIDS are not rejected as an X-linked disease involving ARI and are not explained by a triple risk model that has been commonly accepted by the SIDS medical community, as implicating a neurological causation process in a subset of SIDS.