Non Breast-Milk-Fed Very Preterm Infants Are at Increased Risk of Iron Deficiency at 4-6-Months Corrected Age: A Retrospective Population-Based Cohort Study.

Iron supplementation is routinely recommended for breast-milk-fed preterm infants. However, the Canadian Pediatric Society recommends no additional iron supplementation for preterm infants fed primarily with iron-rich formula. Other pediatric societies don't provide specific guidance on supplemental iron for formula-fed preterm infants. This study investigated how feeding type influences iron status of very preterm infants at 4-6-months corrected age (CA). A retrospective cohort study was conducted using a population-based database on all very preterm infants (<31 weeks gestational age) born in Nova Scotia, Canada from 2005-2018. Information about feeding type, iron intake from formula, supplemental iron therapy and iron status at 4-6-months CA was extracted. Iron deficiency (ID) was defined as serum ferritin <20 and <12 µg/L at 4-and 6-months CA, respectively. Of 392 infants, 107 were "breast-milk-fed" (exclusively or partially) and 285 were "not breast-milk-fed" (exclusively fed with iron-rich formula) at 4-6-months CA. Total daily iron intake was higher in the non-breast-milk-fed group (2.6 mg/kg/day versus 2.0 mg/kg/day). Despite this, 36.8% of non-breast-milk-fed infants developed ID versus 20.6% of breast-milk-fed infants. ID is significantly more prevalent in non-breast-milk-fed infants than breast-milk-fed infants despite higher iron intake. This suggests the need to revisit recommendations for iron supplementation in non-breast-milk-fed preterm infants.

Accuracy of reticulocyte hemoglobin for diagnosing iron deficiency in former very preterm infants: a population-based cohort study.

Background: Serum ferritin (SF) is commonly used to diagnose iron deficiency (ID) but has limitations. Reticulocyte hemoglobin (Ret-He) is being increasingly used for ID diagnosis. This study aimed to assess accuracy of Ret-He for ID diagnosis in former very preterm infants (VPI) at 4-6 months corrected age (CA). Methods: A retrospective population-based cohort study was conducted on all live VPI born between 23 and 30 weeks of gestational age (GA) in Nova Scotia from 2012 to 2018. Infants underwent SF and Ret-He testing at 4-6 months CA. ID was defined using two definitions. The first defined ID as SF < 20 mcg/L at both 4- and 6-months CA, and the second as SF < 30 mcg at at both 4- and 6-months CA. The accuracy of Ret-He for identifying ID was assessed using the area under the receiver operating characteristic curve (AUC). Results: ID was present in 39.7% (62) of 156 infants in the first definition and 59.6% (93) in the second at 4-6 months CA. The AUC of Ret-He for ID diagnosis was 0.64 (p = 0.002) in the first definition and 0.59 (p = 0.04) in the second. The optimal cut-off was 29.4pg in the first and 29.7 in the second definition. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) at the 29.4 pg cut-off were 50.0%, 78.7%, 60.8%, and 70.5% for definition 1 and 44.1%, 74.6%, 71.9%, and 47.5% at the 29.7pg cut-off for definition 2. Conclusion: Ret-He had low diagnostic accuracy for ID diagnosis in former VPI. Caution is advised when using Ret-He alone for ID diagnosis. Further research is needed to establish optimal approaches for identifying ID in VPI.