Breastfeeding, Mixed, or Formula Feeding at 9 Months of Age and the Prevalence of Iron Deficiency and Iron Deficiency Anemia in Two Cohorts of Infants in China.

OBJECTIVE: To assess associations between breastfeeding and iron status at 9 months of age in 2 samples of Chinese infants. STUDY DESIGN: Associations between feeding at 9 months of age (breastfed as sole milk source, mixed fed, or formula fed) and iron deficiency anemia (IDA), iron deficiency, and iron sufficiency were determined in infants from Zhejiang (n = 142) and Hebei (n= 813) provinces. Iron deficiency was defined as body iron < 0 mg/kg, and IDA as iron deficiency + hemoglobin < 110 g/L. Multiple logistic regression assessed associations between feeding pattern and iron status. RESULTS: Breastfeeding was associated with iron status (P < .001). In Zhejiang, 27.5% of breastfed infants had IDA compared with 0% of formula-fed infants. The odds of iron deficiency/IDA were increased in breastfed and mixed-fed infants compared with formula-fed infants: breastfed vs formula-fed OR, 28.8 (95% CI, 3.7-226.4) and mixed-fed vs formula-fed OR, 11.0 (95% CI, 1.2-103.2). In Hebei, 44.0% of breastfed infants had IDA compared with 2.8% of formula-fed infants. With covariable adjustment, odds of IDA were increased in breastfed and mixed-fed groups: breastfed vs formula-fed OR, 78.8 (95% CI, 27.2-228.1) and mixed-fed vs formula-fed OR, 21.0 (95% CI, 7.3-60.9). CONCLUSIONS: In both cohorts, the odds of iron deficiency/IDA at 9 months of age were increased in breastfed and mixed-fed infants, and iron deficiency/IDA was common. Although the benefits of breastfeeding are indisputable, these findings add to the evidence that breastfeeding in later infancy identifies infants at risk for iron deficiency/IDA in many settings. Protocols for detecting and preventing iron deficiency/IDA in breastfed infants are needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00642863 and NCT00613717.

Impact of Fetal-Neonatal Iron Deficiency on Recognition Memory at 2 Months of Age.

OBJECTIVE: To assess the effects of fetal-neonatal iron deficiency on recognition memory in early infancy. Perinatal iron deficiency delays or disrupts hippocampal development in animal models and thus may impair related neural functions in human infants, such as recognition memory. STUDY DESIGN: Event-related potentials were used in an auditory recognition memory task to compare 2-month-old Chinese infants with iron sufficiency or deficiency at birth. Fetal-neonatal iron deficiency was defined 2 ways: high zinc protoporphyrin/heme ratio (ZPP/H > 118 µmol/mol) or low serum ferritin (<75 µg/L) in cord blood. Late slow wave was used to measure infant recognition of mother's voice. RESULTS: Event related potentials patterns differed significantly for fetal-neonatal iron deficiency as defined by high cord ZPP/H but not low ferritin. Comparing 35 infants with iron deficiency (ZPP/H > 118 µmol/mol) to 92 with lower ZPP/H (iron-sufficient), only infants with iron sufficiency showed larger late slow wave amplitude for stranger's voice than mother's voice in frontal-central and parietal-occipital locations, indicating the recognition of mother's voice. CONCLUSIONS: Infants with iron sufficiency showed electrophysiological evidence of recognizing their mother's voice, whereas infants with fetal-neonatal iron deficiency did not. Their poorer auditory recognition memory at 2 months of age is consistent with effects of fetal-neonatal iron deficiency on the developing hippocampus.

Depressed nNOS expression during spine transition in the developing hippocampus of FMR1 KO mice

Nitric oxide (NO), synthesized as needed by NO synthase (NOS), is involved in spinogenesis and synaptogenesis. Immature spine morphology is characteristic of fragile X syndrome (FXS). The objective of this research was to investigate and compare changes of postnatal neuronal NOS (nNOS) expression in the hippocampus of male fragile X mental retardation 1 gene knockout mice (FMR1 KO mice, the animal model of FXS) and male wild-type mice (WT) at postnatal day 7 (P7), P14, P21, and P28. nNOS mRNA levels were analyzed by real-time quantitative PCR (N = 4-7) and nNOS protein was estimated by Western blot (N = 3) and immunohistochemistry (N = 1). In the PCR assessment, primers 5’-GTGGCCATCGTGTCCTACCATAC-3’ and 5’-GTTTCGAGGCAGGTGGAAGCTA-3’ were used for the detection of nNOS and primers 5’-CCGTTTCTCCTGGCTCAGTTTA-3’ and 5’-CCCCAATACCACATCATCCAT-3’ were used for the detection of β-actin. Compared to the WT group, nNOS mRNA expression was significantly decreased in FMR1 KO mice at P21 (KO: 0.2857 ± 0.0150, WT: 0.5646 ± 0.0657; P < 0.05). Consistently, nNOS immunoreactivity also revealed reduced staining intensity at P21 in the FMR1 KO group. Western blot analysis validated the immunostaining results by demonstrating a significant reduction in nNOS protein levels in the FMR1 KO group compared to the WT group at P21 (KO: 0.3015 ± 0.0897, WT: 1.7542 ± 0.5455; P < 0.05). These results suggest that nNOS was involved in the postnatal development of the hippocampus in FXS and impaired NO production may retard spine maturation in FXS.

Depressed nNOS expression during spine transition in the developing hippocampus of FMR1 KO mice.

Nitric oxide (NO), synthesized as needed by NO synthase (NOS), is involved in spinogenesis and synaptogenesis. Immature spine morphology is characteristic of fragile X syndrome (FXS). The objective of this research was to investigate and compare changes of postnatal neuronal NOS (nNOS) expression in the hippocampus of male fragile X mental retardation 1 gene knockout mice (FMR1 KO mice, the animal model of FXS) and male wild-type mice (WT) at postnatal day 7 (P7), P14, P21, and P28. nNOS mRNA levels were analyzed by real-time quantitative PCR (N = 4-7) and nNOS protein was estimated by Western blot (N = 3) and immunohistochemistry (N = 1). In the PCR assessment, primers 5'-GTGGCCATCGTGTCCTACCATAC-3' and 5'-GTTTCGAGGCAGGTGGAAGCTA-3' were used for the detection of nNOS and primers 5'-CCGTTTCTCCTGGCTCAGTTTA-3' and 5'-CCCCAATACCACATCATCCAT-3' were used for the detection of ß-actin. Compared to the WT group, nNOS mRNA expression was significantly decreased in FMR1 KO mice at P21 (KO: 0.2857 ± 0.0150, WT: 0.5646 ± 0.0657; P < 0.05). Consistently, nNOS immunoreactivity also revealed reduced staining intensity at P21 in the FMR1 KO group. Western blot analysis validated the immunostaining results by demonstrating a significant reduction in nNOS protein levels in the FMR1 KO group compared to the WT group at P21 (KO: 0.3015 ± 0.0897, WT: 1.7542 ± 0.5455; P < 0.05). These results suggest that nNOS was involved in the postnatal development of the hippocampus in FXS and impaired NO production may retard spine maturation in FXS.