Don’t Forget the Bones: Incidence and Risk Factors of Metabolic Bone Disease in a Cohort of Preterm Infants

Abstract

Metabolic bone disease of prematurity (MBD) is a condition of reduced bone mineral content (BMC) compared to that expected for gestational age (GA). Preterm birth interrupts the physiological process of calcium (Ca) and phosphorus (P) deposition that occurs mostly in the third trimester of pregnancy, leading to an inadequate bone mineralization during intrauterine life (IUL). After birth, an insufficient intake of Ca and P carries on this alteration, resulting in overt disease. If MBD is often a self-limited condition, in some cases it could hesitate the permanent alteration of bone structures with growth faltering and failure to wean off mechanical ventilation due to excessive chest wall compliance. Despite advances in neonatal intensive care, MBD is still frequent in preterm infants, with an incidence of 16–23% in very-low-birth-weight (VLBW, birth weight <1500 g) and 40–60% in extremely low-birth-weight (ELBW, birth weight <1000 g) infants. Several risk factors are associated with MBD (e.g., malabsorption syndrome, parenteral nutrition (PN), pulmonary bronchodysplasia (BPD), necrotizing enterocolitis (NEC), and some chronic medications). The aim of this study was to evaluate the rate of MBD in a cohort of VLBWI and the role of some risk factors. We enrolled 238 VLBWIs (107 male). 52 subjects were classified as increased risk (G1) and 186 as standard risk (G2) according to serum alkaline phosphatase (ALP) and phosphorus (P) levels. G1 subjects have lower GA (p < 0.01) and BW (p < 0.001). Moreover, they need longer PN support (p < 0.05) and invasive ventilation (p < 0.01). G1 presented a higher rate of BPD (p = 0.026). At linear regression analysis, BW and PN resulted as independent predictor of increased risk (p = 0.001, p = 0.040, respectively). Preventive strategies are fundamental to prevent chronic alteration in bone structures and to reduce the risk of short stature. Screening for MBD based on serum ALP could be helpful in clinical practice to identify subjects at increased risk.

Neurodevelopment Outcomes in Very-Low-Birth-Weight Infants with Metabolic Bone Disease at 2 Years of Age

“…To diagnose MBD in accordance with the radiological alterations described by Koo's score [13], we use X-ray imaging interpreted by a single radiologist (to minimize the possibility of bias). The prevalence of MBD in our present study was 21%, showing similarity with previous reports [1,6,7,12].…”

“…MBD is a multifactorial disease characterized primarily by inadequate bone matrix mineralization and biochemical alterations in the metabolism of phosphorus and calcium [6,7]. The data in this report indicate that VLBW infants diagnosed with MBD are at an increased risk of neurodevelopmental delay at 2 years of corrected age.…”

“…MBD often occurs in preterm infants 6-8 weeks after birth [4]. The pathogenesis of MBD remains unclear and is likely to be multifactorial [6,7]. It has been established that MBD is associated with rickets and fractures, low peak bone mass, and poorer respiratory outcomes [1,7].…”

Association of Preterm Birth and Low Birthweight with Bone Fractures during Childhood

“…These ultra‐preterm infants are at the highest risk for metabolic bone disease of prematurity, as the fetal accumulation of minerals occurs mainly in the third trimester of pregnancy. ( 26 ) Furthermore, despite improvements in modern neonatal intensive care, these infants are still at high risk of severe neonatal morbidity, including necrotizing enterocolitis, long‐term parenteral nutrition and poor nutrition, and extrauterine growth delay. A similar tendency was also shown in previous studies as increased rates of fractures during infancy in extremely preterm newborns.…”

Vitamin D Status of Preterm Newborns at Approximately 4 Weeks of Age in Shenzhen, China: A Retrospective Observational Cohort Study Conducted Across Two Centers

“…intravenous feeding of multivitamins in preterm children with lower GAs, as well as the increased oral VD consumption in infants with an increase in alkaline phosphatase concentration 2 weeks after delivery. [21][22][23] Furthermore, the univariate analysis indicated a strong correlation between VDI and PIH (P<0.05). However, the multivariable analysis revealed that the association between the two variables was not statistically significant (P>0.05), potentially attributable to the presence of multiple confounding factors.…”