Biological effects of anti-RANKL antibody administration in pregnant mice and their newborns.

Denosumab, a fully human monoclonal antibody that neutralizes receptor activator of nuclear factor-κB ligand (RANKL) and blocks osteoclast differentiation, has received approval in Japan for use as an anti-resorptive drug for osteoporosis and skeletal-related events (SREs) in patients with solid cancer. Denosumab is contraindicated during pregnancy, though the effects of blocking RANKL activity on pregnant mothers and their newborns are unclear. We used mice to investigate the effects of an anti-RANKL antibody on maternal and newborn health. Mothers injected with the anti-RANKL antibody had increased bone mass as compared with the controls, while osteoclast number and the level of tartrate-resistant acid phosphatase (TRAP) in serum were increased at the end of pregnancy. Newborn mice exposed to the antibody in utero were normally born, but showed increased bone mass and died within 48 h after birth. None of the newborns were found to have milk in their stomachs, suggesting that they died due to a maternal defect in lactation. Consistent with this, anti-RANKL antibody-injected mothers displayed impaired mammary gland development. However, fostering by healthy surrogate mothers rescued only 33% of the antibody-exposed newborns, suggesting that neonatal mortality was due, at least in part, to an intrinsic defect in the newborns. Our findings show that anti-RANKL antibody administration during pregnancy results in not only an undesirable increase in bone mass, but also has harmful effects on newborn survival.

Gentamicin Exposure and Sensorineural Hearing Loss in Preterm Infants.

OBJECTIVE: To evaluate the impact of gentamicin exposure on sensorineural hearing loss (SNHL) in very low birth weight (VLBW) infants. METHODS: Exposure to gentamicin was determined in infants born between 1993 and 2010 at a gestational age < 32 weeks and/or with a birthweight < 1500 g, who presented with SNHL during the first 5 years of life. For each case, we selected two controls matched for gender, gestational age, birthweight, and year of birth. RESULTS: We identified 25 infants affected by SNHL, leading to an incidence of SNHL of 1.58% in our population of VLBW infants. The proportion of infants treated with gentamicin was 76% in the study group and 70% in controls (p = 0.78). The total cumulated dose of gentamicin administered did not differ between the study group (median 10.2 mg/kg, Q1-Q3 1.6-13.2) and the control group (median 7.9 mg/kg, Q1-Q3 0-12.8, p = 0.47). The median duration of gentamicin treatment was 3 days both in the study group and the control group (p = 0.58). Maximum predicted trough serum levels of gentamicin, cumulative area under the curve and gentamicin clearance were not different between cases and controls. CONCLUSION: The impact of gentamicin on SNHL can be minimized with treatments of short duration, monitoring of blood levels and dose adjustment.

Relation of nitrate contamination of groundwater with methaemoglobin level among infants in Gaza.

A descriptive, cross-sectional and analytical study was carried out in 3 areas of the Gaza Strip, Palestine, in 2002, to determine the factors associated with high methaemoglobin (Met-Hb) levels in infants and the relationship with nitrate concentration in drinking water wells. Drinking water sources were likely to be the main factor for high levels of Met-Hb. Out of 338 infants attending for vaccination, having supplemental feeding, use of boiled water and age 3-6 months were associated with high Met-Hb levels. The highest mean Met-Hb level was in Khan-Younis, where the highest mean nitrate concentration was recorded in drinking water. The results emphasize the importance of exclusive breastfeeding for infants < 6 months old, and the choice of a suitable source of water for these infants.

[Rickets prophylaxis under current recommendations]. / Profilaktyka przeciwkrzywicza u niemowlat w swietle obowiazujacych zalecen.

AIM OF THE STUDY: We analysed the compliance of current recommendations concerning rickets prevention in Poland. MATERIAL AND METHODS: The study group consisted of 65 infants hospitalised because of emergency problems. In each case, the medical history included prophylaxis of rickets and feeding pattern. In most cases (80%) we measured calcium, phosphate, and alkaline phosphatase in the serum. RESULTS: Vitamin D3 was overdosed in 70% of infants. 14% of children were diagnosed as rachitic in outpatient department before hospitalisation, but neither the clinical symptoms nor the laboratory test confirmed the diagnosis. This confirms the observation, that rickets is diagnosed too often, usually on the basis of isolated craniotabes in young infants. CONCLUSION: In the context of changing recommendations for prophylaxis of rickets, we recommend more careful prescribing of vitamin D3 preparations.

Neonatal hypernatraemic dehydration and malnutrition associated with inadequate breastfeeding and elevated breast milk sodium.

The advantages of breastfeedng to both the mother and infant are well recognised. In rare instances if breasteding is inadequate or if the sodium content bast milk is high, malnutrition and hypernatraemia can result. A 15 days old exclusively breastfed baby presented with inadequate weight gain. On evaluation, he was found to have hypernatraemia and mother's breast milk showed high sodium concentrations. The infant needed parenteral fluid for correction of dehydration and hypernatraemia. His serum sodium and breast milk sodium of the other of the mother returned to normal gradually. He started gaining weight on exclusive breastfeeds. The present paper describes the case report and brief review of the literature.