Michael Sgro

Cyclosporine excretion into breast milk.

Although many female patients of childbearing age who are receiving cyclosporine have successful pregnancies, these women may be advised not to breast-feed. During recent years, cases of uneventful pregnancies and subsequent successful breast-feeding have been reported in the literature. The infants blood cyclosporine concentration was usually very low. Based on these findings and the lack of detectable adverse effects, some investigators have suggested that women on cyclosporine may breast-feed, challenging the conventional view that cyclosporine is contraindicated during breast-feeding. Here, we report our experience with cyclosporine use during breast-feeding in five mother-infant pairs. We show a wide range of infant exposures to the drug in milk, noting that one of the infants had therapeutic blood concentrations of cyclosporine despite relatively low concentrations of the drug in milk.

Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels

Background:Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden.Methods:Systematic reviews and meta-analyses were undertaken of national prevalence, mortality, and kernicterus due to Rh disease and EHB. We applied a compartmental model to estimate neonatal survivors and impairment cases for 2010.Results:Twenty-four million (18% of 134 million live births ≥32 wk gestational age from 184 countries; uncertainty range: 23–26 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800–477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000–131,000), with a 24% risk for death (114,100; uncertainty range: 59,700–172,000), 13% for kernicterus (75,400), and 11% for stillbirths. Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. Kernicterus with Rh disease ranged from 38, 28, 28, and 25/100,000 live births for Eastern Europe/Central Asian, sub-Saharan African, South Asian, and Latin American regions, respectively. More than 83% of survivors with kernicterus had one or more impairments.Conclusion:Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries.

Pregnant Women’s Knowledge of Influenza and the Use and Safety of the Influenza Vaccine During Pregnancy

INTRODUCTION We wished to assess pregnant womens knowledge of influenza, vaccine safety during pregnancy and breast feeding, and the recommendations for use of the influenza vaccine in pregnancy. METHODS We performed a cross-sectional survey of postpartum women during influenza season in 2006. RESULTS Pregnant womens overall knowledge of these subjects was poor. Most women (95%) knew that influenza is highly contagious, but almost 90% incorrectly believed that pregnant women have the same risk of complications as non-pregnant women. Only one half of the women were aware of national recommendations for vaccination during pregnancy and that the vaccine is safe during pregnancy and breast feeding, and 80% incorrectly believed that the vaccine can cause birth defects. Only 20% of women had been offered the vaccine during the current pregnancy or a prior pregnancy. CONCLUSIONS Pregnant womens knowledge about influenza vaccine recommendations and safety during pregnancy is poor. There is substantial room for improvement among prenatal care providers in both patient education and offering the vaccine.

Routine Immunization Practices: Use of Topical Anesthetics and Oral Analgesics

BACKGROUND. Immunization pain is a global public health issue. Despite an abundance of data that demonstrate the efficacy of local anesthetics for decreasing immunization pain, their adoption in practice has not been determined. Our objective was to evaluate analgesic use during childhood immunization. PATIENTS AND METHODS. We used a cluster-sampling survey of pediatricians in the greater Toronto area (who administer immunizations) and multiparous women. By using a self-administered survey, pediatricians reported frequency of analgesic use in their practice for 2 phases of immunization: injection (needle puncture and vaccine administration) and postinjection (hours to days postvaccination). By using an interviewer-administered face-to-face survey, mothers reported analgesic practices for their children. RESULTS. Of 195 eligible pediatricians, 140 (72%) responded. During the injection phase, 58% rarely or never used analgesics compared with 11% for the postinjection phase. During injection, the local anesthetics lidocaine-prilocaine and tetracaine were used at least sometimes in 12% and 2% of the practices, respectively, whereas acetaminophen and ibuprofen were used in 81% and 46%, respectively. Postinjection, acetaminophen and ibuprofen were used in 89% and 56% of practices. Of 257 eligible mothers, 200 (78%) participated. During injection, analgesics were used in 25% of immunizations (acetaminophen [87%], ibuprofen [7%], and lidocaine-prilocaine [6%]). Postinjection, analgesics were used in 33% of immunizations (acetaminophen [86%] and ibuprofen [14%]). CONCLUSIONS. A minority of pediatricians and mothers use topical local anesthetics during childhood immunization despite evidence to support their use. Oral analgesics are used more commonly, but this practice is not consistent with scientific evidence. Knowledge-translation strategies are needed to increase the use of local anesthesia.

Long-Term Neurodevelopment of Children Exposed In Utero to Ciclosporin After Maternal Renal Transplant

AbstractBackground: Immunosuppressant therapy is essential in the prevention of organ transplant rejection. Objective: To evaluate the long-term neurodevelopmental outcomes of children following in utero ciclosporin (cyclosporine) exposure after maternal renal transplantation. Methods: A cohort study with matched controls using a prospectively collected database was conducted to assess neurocognitive and behavioral outcomes using standardized measures. Thirty-nine children exposed in utero to ciclosporin therapy following maternal renal transplantation were assessed (15 single pregnancies, 24 multiple pregnancies) and compared with 38 matched unexposed children. Intelligence, visuomotor abilities, and psychologic adjustment were measured using the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Beery Developmental Test of Visual-Motor Integration (VMI-4) and the Wide Range Assessment of Visual Motor Abilities (WRAVMA), and the Child Behavior Checklist (CBCL), respectively. Statistical analysis, including regression, was performed to determine the significant predictors for the main outcome, full-scale IQ (FIQ). Results: There were no significant differences in FIQ, verbal IQ (VIQ), performance IQ (PIQ) or behavioral outcomes between exposed and unexposed children or between single and multiple delivery groups. Thirty-three percent of exposed children were premature versus 0.5% in unexposed controls (p < 0.01). Prematurity was associated with low birthweight, high rates of perinatal complications, and instrumental deliveries. Relative to full-term children, premature, low birthweight children in the ciclosporin-exposed group had significantly lower FIQ and VIQ scores (101.04 vs 111.31 [p = 0.008] and 102.31 vs 113.08 [p = 0.021], respectively). Maternal IQ and socioeconomic status were positive and significant predictors for children’s IQ (p < 0.001 and p = 0.03, respectively). There were no statistically significant differences in exposed children’s IQ who were and were not breastfed. Conclusion: In this cohort, there was no association between in utero exposure to ciclosporin and long-term neurocognitive and behavioral development in children after maternal renal transplantation. Maternal IQ and socioeconomic status are positive predictors for children’s intelligence. However, maternal renal transplantation and associated co-morbidity is associated with higher rates of premature delivery and consequent poorer neurocognitive and behavioral outcomes. Proper management of maternal morbidity and improved obstetric care may improve the child’s profile.

Incidence of Chronic Bilirubin Encephalopathy in Canada, 2007–2008

BACKGROUND AND OBJECTIVES: Despite the implementation of screening guidelines to identify infants at risk for hyperbilirubinemia, chronic bilirubin encephalopathy (CBE) continues to be reported worldwide in otherwise healthy infants. The incidence of CBE in Canada is unknown. The objectives of this study were to establish the incidence of CBE in Canada and identify epidemiological and medical risk factors associated with its occurrence. METHODS: Data on infants were collected prospectively through the Canadian Pediatric Surveillance Program. Infants born between January 1, 2007 and December 31, 2008 were included if they either had symptoms of CBE and a history of hyperbilirubinemia, or if they presented in the newborn period with severe hyperbilirubinemia and an abnormal MRI finding as per the reporting physician. RESULTS: During the study period, 20 cases were identified; follow-up data were available for 14 of these. The causes for the hyperbilirubinemia included glucose-6-phosphate dehydrogenase deficiency (n = 5), sepsis (n = 2), ABO incompatibility and other red blood cell antibodies (n = 7). Fifteen infants had abnormal brain MRI findings during the neonatal period. At follow-up, 5 infants developed classic choreoathetoid cerebral palsy, 6 had spectrum of neurologic dysfunction and developmental delay (as described by the reporting physician), and 3 were healthy. CONCLUSIONS: CBE continues to occur in Canada at an incidence that appears to be higher than previously reported.

Impact of Patient Education on Knowledge of Influenza and Vaccine Recommendations Among Pregnant Women

OBJECTIVE To determine whether providing an information pamphlet in the antenatal clinic improves womens knowledge about influenza and vaccine recommendations during pregnancy. METHODS An information pamphlet was distributed in the antenatal clinic during the fall of 2007. A cross-sectional survey was carried out in women on the postpartum floor in the fall of 2006 and again in the fall of 2007 (before and after implementation of the pamphlet) to assess womens knowledge. Results were compared to assess knowledge transfer. RESULTS Knowledge improved with the use of the educational pamphlet. Most women in both years (>90%) correctly answered that influenza is a serious infection. However, significantly more women in 2007 correctly answered that pregnant women have a higher risk of complications from influenza (34.6% in 2007 vs. 12.1% in 2006, P < 0.001), that the influenza vaccine is safe for use during pregnancy (80.2% vs. 55.2%, P < 0.001) or breastfeeding (75.3% vs. 60.3%, P = 0.001), and that the vaccine does not cause birth defects (90.1% vs. 79.3%, P = 0.04). After implementation of the information pamphlet, a significantly higher proportion of women knew the correct recommendations for influenza vaccination during pregnancy (63.2% vs. 39.7%, P < 0.001). Vaccination rates increased from 19% in 2006 to 56% in 2007. CONCLUSIONS Providing an information pamphlet in the antenatal clinic improved pregnant womens knowledge about influenza and vaccine safety during pregnancy and about recommendations for influenza vaccination during pregnancy. Knowledge transfer in this area may help to increase vaccination rates.

Knowledge translation of the HELPinKIDS clinical practice guideline for managing childhood vaccination pain: usability and knowledge uptake of educational materials directed to new parents

BackgroundAlthough numerous evidence-based and feasible interventions are available to treat pain from childhood vaccine injections, evidence indicates that children are not benefitting from this knowledge. Unrelieved vaccination pain puts children at risk for significant long-term harms including the development of needle fears and subsequent health care avoidance behaviours. Parents report that while they want to mitigate vaccination pain in their children, they lack knowledge about how to do so. An evidence-based clinical practice guideline for managing vaccination pain was recently developed in order to address this knowledge-to-care gap. Educational tools (pamphlet and video) for parents were included to facilitate knowledge transfer at the point of care. The objectives of this study were to evaluate usability and effectiveness in terms of knowledge acquisition from the pamphlet and video in parents of newly born infants.MethodsMixed methods design. Following heuristic usability evaluation of the pamphlet and video, parents of newborn infants reviewed revised versions of both tools and participated in individual and group interviews and individual knowledge testing. The knowledge test comprised of 10 true/false questions about the effectiveness of various pain management interventions, and was administered at three time points: at baseline, after review of the pamphlet, and after review of the video.ResultsThree overarching themes were identified from the interviews regarding usability of these educational tools: receptivity to learning, accessibility to information, and validity of information. Parents’ performance on the knowledge test improved (p≤0.001) from the baseline phase to after review of the pamphlet, and again from the pamphlet review phase to after review of the video.ConclusionsUsing a robust testing process, we demonstrated usability and conceptual knowledge acquisition from a parent-directed educational pamphlet and video about management of vaccination pain. Future studies are planned to determine the impact of these educational tools when introduced in clinical settings on parent behaviors during infant vaccinations.

Arginine Is Synthesized From Proline, Not Glutamate, in Enterally Fed Human Preterm Neonates

In neonatal mammals, arginine is synthesized in the enterocyte, with either proline or glutamate as the dietary precursor. We have shown several times in piglets that proline is the only precursor to arginine, although in vitro evidence supports glutamate in this role. Because of this uncertainty, we performed a multitracer stable isotope study to determine whether proline, glutamate, or both are dietary precursors for arginine in enterally fed human neonates. Labeled arginine (M + 2), proline (M + 1), and glutamate (M + 3) were given enterally to 15 stable, growing preterm infants (GA at birth 30–35 wk) at 1–3 wk postnatal age. Enrichment in urine of the tracer amino acids and the M + 1 and M + 3 isotopomers of arginine were measured by LC-tandem mass spectrometry to determine the contribution of proline and glutamate to arginine synthesis. Plateau enrichments of arginine and proline tracers were measurable in urine. Urinary glutamate enrichment was not detected. Conversion of proline to arginine was detected. However, the M + 3 isotopomer of arginine, which would have been synthesized from glutamate, was not detected. We conclude that, in contrast to the current consensus in the literature based on in vitro studies, proline is the major contributor to arginine synthesis in human preterm infants.

Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.

We report on a male newborn infant, a compound carrier of heterozygous mutations in the FGFR3 gene causing achondroplasia and hypochondroplasia. The mother has achondroplasia and carries the common G1138 (G380R) mutation in the FGFR3 gene; the father has hypochondroplasia due to the C1620A (N540K) mutation in the same gene. The fetus was found to carry both mutations diagnosed prenatally by amniocentesis at 17.6 weeks of gestation, following maternal serum screening which showed an increased risk for Down syndrome (1:337). Detailed fetal ultrasound studies showed a large head, short limbs, and a small chest at 22 weeks of gestation. The changes were more severe than those of either achondroplasia or hypochondroplasia. The patient was born by cesarean section at 38 weeks of gestation and had rhizomelic shortness of the upper and lower limbs with excess skin folds, large head, enlarged fontanelles, frontal bossing, lumbar gibbus, trident position of the fingers, and a narrow chest with a horizontal line of demarcation at the narrowest area of the chest. Skeletal radiographs showed shortness of the long bones and flare of metaphyses. He had respiratory difficulties and was treated with nasal prongs. Seizures developed on day 2 of life and recurred on day 9 and responded to treatment with phenobarbital. Brain computed tomographic scan showed possible grey matter heterotopia, partial agenesis of the corpus callosum, and cortical dysplasia. To our knowledge, there are only two previously published cases of compound heterozygous achondroplasia-hypochondroplasia patients. The diagnosis was confirmed by DNA mutation analysis of the FGFR3 gene in both cases.