stress can also affect the maternal oxygen supply and fetal uptake. The most preventable cause is maternal smoking. Cigarette smoking by expectant mothers has been shown to have a wide variety of deleterious effects on the developing fetus. Among the negative effects are carbon monoxide induced tissue hypoxia and placental insufficiency which causes a reduction in blood flow from the uterus to the placenta thereby reducing the availability of oxygenated blood to the fetus. Placental insufficiency as a result of smoking has been shown to have a causal effect in the development of pre-eclampsia. While some previous studies have suggested that carbon monoxide from cigarette smoke may have a protective effect against preeclampsia, a recent study conducted by the Genetics of Pre-Eclampsia Consortium in the United Kingdom found that smokers were five times more likely to develop pre-eclampsia. Nicotine alone has been shown to be a teratogen which affects the autonomic nervous system, leading to increased susceptibility to hypoxia-induced brain damage. Maternal anemia in which smoking has also been implicated is another factor associated with IH/BA. Smoking by expectant mothers causes a decrease in maternal nucleated red blood cells, thereby reducing the amount of red blood cells available for oxygen transport. Utero-placental hypoxia is associated with abnormal placental implantation, impaired vascular remodeling and vascular diseases. It is also associated with pregnancies complicated by gestational hypertension, intrauterine growth restriction, and pre-eclampsia. Post-placental hypoxia is associated with mechanical obstructions of the umbilical cords, reduced uterine artery flow, progressive fetal cardiac failure, and genetic anomalies. The perinatal brain injury occurring as a result of birth asphyxia, manifesting within 48 hours of birth, is a form of hypoxic ischemic encephalopathy. Diagnosis Treatment Treatment of infants with birth asphyxia by lowering the core body temperature is now known to be an effective therapy to reduce mortality and improve neurological outcome in survivors, and hypothermia therapy for neonatal encephalopathy begun within 6 hours of birth significantly increases the chance of normal survival in affected infants. There has long been a debate over whether newborn infants with birth asphyxia should be resuscitated with 100% oxygen or normal air. It has been demonstrated that high concentrations of oxygen lead to generation of oxygen free radicals, which have a role in reperfusion injury after asphyxia. Research by Ola Didrik Saugstad and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead