Calcium and Phosphorus: All You Need to Know but Were Afraid to Ask.

Inadequate intake of calcium and phosphorus during the perinatal period can result in metabolic bone disease (MBD), characterized by decreased bone mass, altered bone mineralization, and increased risk for fractures. Preterm neonates have higher risk of developing MBD. Treating MBD involves ensuring adequate calcium and phosphorus intake, early fortification, and vitamin D supplementation. Health care providers should closely monitor nutrient intake, postnatal growth, and screening of preterm neonates at risk for MBD. This review summarizes the critical roles of calcium and phosphorus in regulating bone physiology, how they regulate bone formation and resorption, and their influence on overall bone health.

Quality appraisal of clinical practice guidelines for temporomandibular joint disorders using the AGREE II instrument.

OBJECTIVE: We sought to systematically assess the quality of all clinical practice guidelines (CPGs) describing diagnosis and management of temporomandibular joint disorders (TMDs) using the Appraisal of Guidelines for Research and Evaluation instrument. STUDY DESIGN: CPGs detailing all aspects of diagnosis and management (both conservative and nonconservative) for TMDs were reviewed. RESULTS: Thirteen guidelines met inclusion criteria. The highest-scoring domain across guidelines was clarity of presentation (68.3%); the lowest-scoring domain was editorial independence (31.9%). The highest-scoring guideline described traditional Korean medicine approaches to the management of TMDs, earning a mean score of 79.2% across the six quality domains. Only three CPGs met a quality threshold of >60% in at least five domains, qualifying as 'high' per the Appraisal of Guidelines for Research and Evaluation criteria: these guidelines were the Korean medicine guidelines, Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) guidelines for diagnostic classification of TMDs, and the Japanese Society for the Temporomandibular Joint guidelines. An average intraclass correlation coefficient of 0.79 was calculated across all domains, denoting very strong agreement between independent reviewers. CONCLUSION: We identified a significant lack of quality in multiple areas of CPG development for the diagnosis and therapeutic management of TMDs, suggesting a need for new comprehensive and rigorously developed guidelines addressing TMDs.

Cycled Phototherapy Dose-Finding Study for Extremely Low-Birth-Weight Infants: A Randomized Clinical Trial.

Importance: Cycled (intermittent) phototherapy (PT) might adequately control peak total serum bilirubin (TSB) level and avoid mortality associated with usual care (continuous PT) among extremely low-birth-weight (ELBW) infants (401-1000 g). Objective: To identify a cycled PT regimen that substantially reduces PT exposure, with an increase in mean peak TSB level lower than 1.5 mg/dL in ELBW infants. Design, Setting, and Participants: This dose-finding randomized clinical trial of cycled PT vs continuous PT among 305 ELBW infants in 6 US newborn intensive care units was conducted from March 12, 2014, to November 14, 2018. Interventions: Two cycled PT regimens (≥15 min/h and ≥30 min/h) were provided using a simple, commercially available timer to titrate PT minutes per hour against TSB level. The comparator arm was usual care (continuous PT). Main Outcomes and Measures: Mean peak TSB level and total PT hours through day 14 in all 6 centers and predischarge brainstem auditory-evoked response wave V latency in 1 center. Mortality and major morbidities were secondary outcomes despite limited power. Results: Consent was requested for 452 eligible infants and obtained for 305 (all enrolled) (mean [SD] birth weight, 749 [152] g; gestational age, 25.7 [1.9] weeks; 81 infants [27%] were multiple births; 137 infants [45%] were male; 112 [37%] were black infants; and 107 [35%] were Hispanic infants). Clinical and demographic characteristics of the groups were similar at baseline. After a preplanned interim analysis of 100 infants, the regimen of 30 min/h or more was discontinued, and the study proceeded with 2 arms. Comparing 128 infants receiving PT of 15 min/h or more with 128 infants receiving continuous PT among those surviving to 14 days, mean peak TSB levels were 7.1 vs 6.4 mg/dL (adjusted difference, 0.7; 95% CI, 0.4-1.1 mg/dL) and mean total PT hours were 34 vs 72 (adjusted difference, -39; 95% CI, -45 to -32). Wave V latency adjusted for postmenstrual age was similar in 37 infants receiving 15 min/h or more of PT and 33 infants receiving continuous PT: 7.42 vs 7.32 milliseconds (difference, 0.10; 95% CI, -0.11 to 0.30 millisecond). The relative risk for death was 0.79 (95% CI, 0.40-1.54), with a risk difference of -4.5% (95% CI, -10.9 to 2.0). Morbidities did not differ between groups. Conclusions and Relevance: Cycled PT can substantially reduce total PT with little increase in peak TSB level. A large, randomized trial is needed to assess whether cycled PT would increase survival and survival without impairment in small, preterm infants. Trial Registration: ClinicalTrials.gov Identifier: NCT01944696.

Favorable Outcomes of Preterm Infants With Parenteral Nutrition-associated Liver Disease Treated With Intravenous Fish Oil-based Lipid Emulsion.

OBJECTIVES: The aim of the study was to determine the acute and long-term outcomes of preterm infants treated with an intravenous fish oil-based lipid emulsion (FishLE) for parenteral nutrition-associated liver disease (PNALD). METHODS: Preterm infants 14 days to 24 months of age with anatomic short gut or severe intestinal dysmotility, serum direct bilirubin ≥4 mg/dL, and requiring >60% calories from parenteral nutrition were eligible. Enrolled infants received 1 g ·â€Škg ·â€Šday of FishLE until resolution of direct hyperbilirubinemia or return of enteral nutrition. Acute clinical effects and biochemical markers of liver function were monitored. Growth and developmental scores at 6 and 12 months postmenstrual age (PMA) were assessed and compared with controls matched by gestational age (GA). RESULTS: Thirteen patients with mean GA of 28 ±â€Š4 weeks were treated and compared with 119 GA-matched controls. Their mean direct bilirubin was 9.8 ±â€Š6.4 mg/dL at enrollment. All infants had resolution of cholestasis after study completion. There were no acute adverse events, deaths, or liver/intestinal transplants. Weight and head circumference were similar between FishLE-treated patients and controls at 6- and 12-month PMA. Cognitive and motor scores were decreased at 6 and 12 months PMA in FishLE-treated infants. Logistic regression analysis showed that prolonged hospitalization was detrimental to cognitive and motor development, whereas treatment was not. CONCLUSIONS: The use of intravenous FishLEs in premature infants appears to be safe and reverses PNALD despite significant liver disease and intestinal failure. This therapy should be used in preterm infants with PNALD and followed long term to evaluate development.

Premature Infants 750-1,250 g Birth Weight Supplemented with a Novel Human Milk-Derived Cream Are Discharged Sooner.

OBJECTIVE: Infants may benefit from early nutritional intervention to decrease hospital stay. To evaluate the effects of adding a human milk (HM)-derived cream (Cream) product to a standard feeding regimen in preterm infants. MATERIALS AND METHODS: In a prospective multicenter randomized study, infants with birth weights 750-1,250 g were assigned to a Control or Cream group. The Control group received a standard feeding regimen consisting of mother's own milk or donor HM with donor HM-derived fortifier. The Cream group received the standard feeding regimen along with an additional HM-derived cream supplement when the HM they received was <20 kcal/oz. Primary outcomes of this secondary analysis included comorbidities, length of stay (LOS), and postmenstrual age (PMA) at discharge. RESULTS: We enrolled 75 infants (Control n = 37, Cream n = 38) with gestational age 27.7 ± 1.8 weeks and birth weight 973 ± 145 g (mean ± SD). After adjusting for gestational age, birth weight, and presence of bronchopulmonary dysplasia (BPD), the Cream group had a decreased PMA at discharge (39.9 ± 4.8 versus 38.2 ± 2.7 weeks, p = 0.03) and LOS (86 ± 39 versus 74 ± 22 days, p = 0.05). For 21 infants with BPD, these values trended toward significance for PMA at discharge (44.2 ± 6.1 versus 41.3 ± 2.7 weeks, p = 0.08) and LOS (121 ± 49 versus 104 ± 23 days, p = 0.08). CONCLUSIONS: Very preterm infants who received an HM-derived cream supplement were discharged earlier. Infants with BPD may have benefited the most.

A Longitudinal Investigation of Syndemic Conditions Among Young Gay, Bisexual, and Other MSM: The P18 Cohort Study.

The persistence of disparities in STI/HIV risk among a new generation of emerging adult gay, bisexual, and other men who have sex with men (YMSM) warrant holistic frameworks and new methodologies for investigating the behaviors related to STI/HIV in this group. In order to better understand the continued existence of these disparities in STI/HIV risk among YMSM, the present study evaluated the presence and persistence of syndemic conditions among YMSM by examining the co-occurrence of alcohol and drug use, unprotected sexual behavior, and mental health burden over time. Four waves of data, collected over the first 18 months of a 7 wave, 36-month prospective cohort study of YMSM (n=600) were used to examine the extent to which measurement models of drug use, unprotected sexual behavior, and mental health burden remained consistent across time using latent class modeling. Health challenges persisted across time as these YMSM emerged into young adulthood and the measurement models for the latent constructs of drug use and unprotected sexual behavior were essentially consistent across time whereas models for mental health burden varied over time. In addition to confirming the the robustness of our measurement models which capture a more holistic understandings of the health conditions of drug use, unprotected sex, and mental health burden, these findings underscore the ongoing health challenges YMSM face as they mature into young adulthood. These ongoing health challenges, which have been understood as forming a syndemic, persist over time, and add further evidence to support ongoing and vigilant comprehensive health programming for sexual minority men that move beyond a sole focus on HIV.

Randomized trial of human milk cream as a supplement to standard fortification of an exclusive human milk-based diet in infants 750-1250 g birth weight.

OBJECTIVE: To evaluate whether premature infants who received an exclusive human milk (HM)-based diet and a HM-derived cream supplement (cream) would have weight gain (g/kg/d) at least as good as infants receiving a standard feeding regimen (control). STUDY DESIGN: In a prospective noninferiority, randomized, unmasked study, infants with a birth weight 750-1250 g were randomly assigned to the control or cream group. The control group received mother's own milk or donor HM with donor HM-derived fortifier. The cream group received a HM-derived cream supplement if the energy density of the HM tested <20 kcal/oz using a near infrared HM analyzer. Infants were continued on the protocol until 36 weeks postmenstrual age. Primary outcomes included growth velocities and amount of donor HM-derived fortifier used. The hypothesis of noninferiority was established if the lower bound of the one-sided 95% CI for the difference in weight velocities exceeded -3 g/kg/day. RESULTS: There were no differences between groups in baseline demographics for the 78 infants studied except racial distribution (P = .02). The cream group (n = 39) had superior weight (14.0 ± 2.5 vs 12.4 ± 3.0 g/kg/d, P = .03) and length (1.03 ± 0.33 vs 0.83 ± 0.41 cm/wk, P = .02) velocity compared with the control group (n = 39). There were no significant differences in amount of fortifier used between study groups. The 1-sided 95% lower bound of the CI for the difference in mean velocity (cream-control) was 0.38 g/kg/d. CONCLUSIONS: Premature infants who received HM-derived cream to fortified HM had improved weight and length velocity compared with the control group. HM-derived cream should be considered an adjunctive supplement to an exclusive HM-based diet to improve growth rates in premature infants.

Parathyroid hormone levels in neonates with suspected osteopenia.

AIM: The goal of this study is to describe secondary hyperparathyroidism in extremely low birthweight (ELBW) neonates and their response to enteral calcium carbonate (CaCO(3)) supplementation. METHODS: A retrospective case series was conducted on extremely low birth infants, <1000 g birthweight, who survived hospitalisation, had no major congenital anomalies and had all their care in our institution RESULTS: During this 6-year period, 231 ELBW infants survived hospitalisation at our institution. Of the 231 patients, parathyroid hormone (PTH) levels were performed in 66 of these patients (29%) and were elevated in 54 patients (82% of those tested). The timing of this testing was sporadic and was often performed after recognising osteopenia on radiography. Of the 54 patients with high PTH levels, 44 (81%) were treated with CaCO(3) and PTH levels were monitored while on therapy. The average duration of therapy was 41 ± 28 days, with 64% of PTH levels returning to normal before discharge. CONCLUSIONS: PTH is a major hormone responsible for bone resorption, and serum levels may be a useful marker in identifying ELBW neonates at risk for metabolic bone disease. ELBW neonates with secondary hyperparathyroidism may benefit from enteral supplementation with CaCO(3). Further studies are needed to better evaluate the incidence, timing and potential treatment of hyperparathyroidism in ELBW infants.

Impact of providing vitamin A to the routine pulmonary care of extremely low birth weight infants.

OBJECTIVE: The objective of this study was to determine if the continued use of vitamin A in a nursery utilizing early surfactant and nasal continuous positive airway pressure (CPAP) was warranted. STUDY DESIGN: A retrospective, cohort study of appropriately sized, preterm neonates weighing ≤1000 g at birth was conducted. Two time periods were compared: Pre-Vitamin A was composed of extremely low birth weight who were routinely cared for with early nasal CPAP (n = 76); and Post-Vitamin A (n = 102) consisted of ELBWs who were cared for similar to Pre-Vitamin A, but with the addition of vitamin A. Outcome variables included the incidence of BPD and other pulmonary and major neonatal morbidities. RESULTS: Between Pre-Vitamin A and Post-Vitamin A the incidence of moderate to severe BPD decreased by 11%, from 33% to 22% (p = 0.2). No difference was found in the number of ventilator days or in the incidence of any other neonatal morbidity or mortality, including intraventricular hemorrhage, necrotizing enterocolitis, or patent ductus arteriosus requiring surgical ligation. CONCLUSION: In a neonatal unit utilizing early surfactant followed by nasal CPAP at delivery, supplementing extremely premature neonates with vitamin A demonstrated a trend towards a decrease in the incidence of moderate to severe BPD; however, this change requires a larger sample to verify in the future.