Impairment of the Developing Human Brain in Iron Deficiency:Correlations to Findings in Experimental Animals and Prospects for Early Intervention Therapy

Due to the necessity of iron for a variety of cellular functions, the developing mammalian organism is vulnerable to iron deficiency, hence causing structural abnormalities and physiological malfunctioning in organs, which are particularly dependent on adequate iron stores, such as the brain. In early embryonic life, iron is already needed for proper development of the brain with the proliferation, migration, and differentiation of neuro-progenitor cells. This is underpinned by the widespread expression of transferrin receptors in the developing brain, which, in later life, is restricted to cells of the blood–brain and blood–cerebrospinal fluid barriers and neuronal cells, hence ensuring a sustained iron supply to the brain, even in the fully developed brain. In embryonic human life, iron deficiency is thought to result in a lower brain weight, with the impaired formation of myelin. Studies of fully developed infants that have experienced iron deficiency during development reveal the chronic and irreversible impairment of cognitive, memory, and motor skills, indicating widespread effects on the human brain. This review highlights the major findings of recent decades on the effects of gestational and lactational iron deficiency on the developing human brain. The findings are correlated to findings of experimental animals ranging from rodents to domestic pigs and non-human primates. The results point towards significant effects of iron deficiency on the developing brain. Evidence would be stronger with more studies addressing the human brain in real-time and the development of blood biomarkers of cerebral disturbance in iron deficiency. Cerebral iron deficiency is expected to be curable with iron substitution therapy, as the brain, privileged by the cerebral vascular transferrin receptor expression, is expected to facilitate iron extraction from the circulation and enable transport further into the brain

Consequences of vanishing twins in IVF/ICSI pregnancies

BACKGROUND: Spontaneous reductions are a possible cause of the increased morbidity in IVF singletons. The aim of this study was to assess incidence rates of spontaneous reductions in IVF/ICSI twin pregnancies and to compare short- and long-term morbidity in survivors of a vanishing co-twin with singletons and born twins. METHODS: We identified 642 survivors of a vanishing co-twin, 5237 singletons from single gestations and 3678 twins from twin gesta-tions. All children originated from pregnancies detected by transvaginal sonography in gestational week 8. By cross-linkage with the national registries the main endpoints were prematurity, birth weight, neurological sequelae and mortality. RESULTS: Of all IVF singletons born, 10.4 % originated from a twin gestation in early pregnancy. Multi-ple logistic regression analyses adjusted for maternal age, parity and ICSI treatment showed for birth weight <2500 g an odds ratio (OR) of 1.7 [95 % confidence interval (CI) 1.2–2.2] and for birth weight <1500 g OR 2.1 (95 % CI 1.3–3.6) in singleton survivors of a vanishing twin versus singletons from single gestations; corresponding figures were seen for preterm birth. This increased risk was almost entirely due to reductions that occurred at>8 weeks gestation. We found no excess risk of neurological sequelae in survivors of a vanishing co-twin versus the singleton cohort; however, OR of cerebral palsy was 1.9 (95 % CI 0.7–5.2). Furthermore, we observed a correlation between onset of spontane-ous reduction, i.e. the later in pregnancy the higher the risk of neurological sequelae (r = –0.09; P = 0.02). Adjusted OR of child death within the follow-up period was 3.6 (95 % CI 1.7–7.6) in the survivor versus the singleton cohort