Oxidative Stress in Pregnancies Complicated by Diabetes

LAPPAS M; LEIVA A; PARDO F; SOBREVÍA L; JAWERBAUM A

Oxidative Stress in Applied Basic Research and Clinical Practice

Springer

Lugar: New york; Año: 2014; p. 47 - 79

The embryonic and fetal period is wrought with oxidative challenges, which can impact development (Chap. 1 ). These lead to long-lasting consequences in neonatal life and beyond. This book will evaluate the continuum of perinatal to postnatal oxidative stress and address possible therapeutic strategies to mitigate the deleterious effects. In the prenatal period, maternal constitutive or acquired exposure to oxidative injury can result in pathology that impacts both the mother and the fetus. The examples of diabetes (Chap. 3 ) and maternal smoking (Chap. 4 ) will be discussed in the book. In the instance of Down syndrome (Chap. 7 ), the adverse oxidant environment resulting from excess manganese superoxide dismutase leads to abnormal organogenesis and development. Maternal infection (Chap. 2 ) and poor placentation can result in adverse neonatal effects related to oxidative stress. In terms of poor placentation, a fetus may present with intrauterine growth restriction and have oxidative stress-mediated maladaptation of organs and tissues (Chap. 6 ). This is well illustrated in adults born to malnourished mothers during the Dutch famine. It is thought that the resultant intrauterine growth restriction and thrifty substrate utilization predisposed these infants to develop diabetes, hypertension, and obesity, or syndrome X, as adults at a higher proportion than in normally grown infants. These observations raise the question of whether this predisposition could also occur in preterm infants who have abnormal growth and poor nutrition during a critical period of development. Onset of preterm labor may also be determined by oxidative stress. The evidence for this is discussed in Chap. 5. Postnatally, there are many consequences of the extrauterine environment on a premature or sick host. A baby born prematurely will have decreased oxidative defenses and, therefore, will be more susceptible to oxidative stress as tissues and organs are still developing. The eyes are particularly vulnerable to changes in hyperoxia, leading to abnormal retinal blood vessel proliferation or retinopathy of prematurity (Chap. 8 ). The relationship between oxidative stress and the development of this condition was found only after physicians had instituted the use of liberal oxygen delivery to prevent equally adverse consequences related to hypoxemia, illustrating the double-edged sword of oxygen. Necrotizing enterocolitis is another condition that may result from enhanced oxidative stress in the gut of an immature infant (Chap. 9 ).Enhanced oxidative burden is not restricted to preterm infants; several conditions lead to adverse oxidative stress in term infants including the prenatal hypoxia. This has caused a reevaluation of how we resuscitate infants in the delivery room (Chap. 11 ).The dire consequences of oxidative stress can lead to brain injury (Chap. 14 ), pain (Chap. 16 ), and seizures (Chap. 20 ). Oxidative stress can also lead to aggravation of pulmonary vasoreactivity as in persistent pulmonary hypertension of the neonate (PPHN), as discussed in Chap. 10 . One of the key discoveries of the last century was nitric oxide (NO). Its use was shown to prevent or ameliorate pulmonary hypertension in the neonate. In fact, use of inhaled NO has improved the survival of infants with pulmonary hypertension and may promote alveolar development. Nevertheless,it is well known that NO in the presence of oxygen can generate the peroxynitrite radical. In animal models, this combination results in pulmonary toxicity, perhaps explaining why inhaled NO has been fraught with challenges in preterm infants since these vulnerable hosts may not have sufficient antioxidant defenses. AlthoughNO is not recommended for use in prematures, surfactant that is used to alleviate respiratory distress syndrome also has significant antioxidative properties as discussed (Chap. 12 ). Another common concern in neonates is hyperbilirubinemia (Chap. 15 ). Interestingly, this provides antioxidant defenses to the neonate in the transition to a relatively hyperoxic environment but carries a risk of significant toxicity. Once we understand the impact of oxidative stress in the uterus, placenta, fetus,and neonates, we need to develop strategies to mitigate these effects. General mechanisms of how oxidative stress affects the neonate and how glutathione is involved are explored in Chap. 13 . Also, we gain a better understanding of how endogenous antioxidant defenses develop (Chap. 17 ). This sets the stage for the development of antioxidant therapies (Chap. 18 ) and for understanding the importance of nutrition to antioxidant protection (Chap. 19 ). The development of new therapeutic interventions to prevent and obviate oxidative stress is also examined (Chap. 22 ).Overall, the examples in this book illustrate that the perinatal and neonatal periods are an important time of vulnerability to oxidative stress and that the effects of excess oxidative stress can lead to lifelong adverse events (Chap. 21 ). It is the hope that, with a better understanding of the mechanisms by which reactive oxygen species impact the fetal and neonatal host, therapeutic interventions can be developed to obviate such effects.