**6. Prevention of brain injury**

Prevention of brain damage requires knowledge of the etiologies underlying injury, awareness of the availability of preventive measures, and timely employment of them to address the underlying cause. In addition, situations that may aggravate existing or evolving brain injury need to be anticipated, recognized, and appropriate evidence-based care provided that is capable of improving outcome.

**Maternal and paternal medical history and lifestyle:** Maternal nutrition and trace element status, the health and age of both parents at conception, and other factors related to current developmental origins of health and disease (DOHaD) concepts are all relevant to prevention [4, 95]. The risk of fetal brain injury is decreased where mothers maintain a good diet, add folic acid and iron plus required prenatal supplements (vit. D, calcium), avoid smoking and the detrimental effects of alcohol and drugs, and exposure to TORCH infections is prevented. There are benefits to becoming a mother earlier rather than later in life, and from both parents having lifestyles that promote physical health and mental wellness especially at conception.

**Antenatal care** is central to optimizing the fetal environment, monitoring maternal health, detection of entities that require intervention or forward planning, and enabling pregnancy to progress to term. Care should ensure that fetal growth progresses normally, all indicated US and lab studies are done, necessary referrals are made, and parents prepared appropriately. Prevention of brain injury centers on labor and delivery, but relies on attention to multiple factors throughout pregnancy. The fetal brain probably benefits most from prevention of avoidable preterm delivery, and therapy such as antenatal steroid use to mature the fetal lung when prematurity is inevitable. Post maturity with the inherent risks of placental failure and increased fetal morbidity must be avoided, especially where at risk situations exist such as gestational diabetes. Prior cesarean section requires special planning and supervision, to avoid uterine complications that can jeopardize fetal wellbeing.

**Monitoring during pregnancy:** Confirmation by US of gestational age reduces premature delivery; monitoring of fetal growth parameters anticipates intrauterine growth retardation, and can identify placental anomalies that increase morbidity. Genetic screening can detect anomalies linked to brain defects; termination of pregnancy is a care option when a fetus is known to have a major anomaly. Surveillance for a broad range of maternal illnesses is possible with investigative protocols and preventive entities available to optimize maternal care and fetal health, and select appropriate timing, mode and location of labor/delivery.

**Advance consultation** with obstetric and neonatal referral centers should occur where necessary to obtain advice regarding priorities for care and delivery.

**Transport** with the fetus in utero should occur if care at a higher level is required to optimize the logistics of delivery and provide for a good neonatal outcome [2].

**Intrapartum care:** Guidelines exist in most jurisdictions based on the evidence base for best practice in obstetric management where the health of the mother and/or fetus becomes at risk. Monitoring of maternal and fetal wellbeing requires entities that provide for anticipation, detection and management of complications, particularly those linked to maternal emergencies and/or generate fetal distress; e.g. placental insufficiency, failure or abruption, hemorrhage, hypo or hypertension, uterine tachysystole or rupture, obstructed labor, or cord compromise. Importantly, a non-reassuring electronic fetal heart rate pattern, or changes in FHR reflecting alteration in fetal cardiac function, usually occurs prior to brain metabolism being affected sufficiently for neurological damage to begin. Hence, recognition of a 'non-reassuring' tracing, a 'sentinel event' involving fetal heart function, or a pattern known to be associated with pathology (e.g. cord compression) [84], allows prompt assessment, and instigation of interventions required to relieve compromised fetal oxygenation, expedite instrumental delivery, or do an emergency cesarean section.

**Staff with the required skills** must be available to comprehensively resuscitate any sick newborn, and promptly address residual morbidity after delivery. Skill with assisted ventilation is important, as prevention of detrimental hyperoxia and hypocarbia reduces brain injury risk in premature infants, and improves outcome in any sick neonate where hypoxia and ischemia have occurred [67]. After appropriate resuscitation, all the care entities required to minimize the possibility of a brain injury being sustained, or an existing intrapartum injury compounded, must be provided. Priorities to do this include: support of respiration and the circulation; provision of a neutral thermal environment, appropriate hydration and nutrition; prophylactic antibiotics and management of proven infections; hematological and biochemical surveillance; and neuroradiological monitoring. Good communication and support of the physical and mental wellbeing of both parents must be ensured.

**79**

**Author details**

improving outcome.

**7. Conclusion**

hypothermia [99, 100].

Andrew Macnab1,2

Vancouver, Canada

Stellenbosch University, South Africa

provided the original work is properly cited.

\*Address all correspondence to: andrew.macnab @ubc.ca

1 Department of Paediatrics, Faculty of Medicine, University of British Columbia,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

In future, earlier initiation of cooling after resuscitation may prove beneficial; ongoing research aims to identify other neuroprotective approaches that can be used in parallel, and evaluate potentially beneficial therapeutic agents; ways that may help reduce the incidence of IVH during rewarming are also being explored.

Many causes of fetal and neonatal brain injury are now preventable. The consequences of cerebral hypoxia and ischemia remain considerable. Evidence-based care strategies during pregnancy and for premature and sick newborns infants are

2 Stellenbosch Institute for Advanced Study, Wallenberg Research Institute at

*Pathogenesis and Prevention of Fetal and Neonatal Brain Injury*

**Controlled hypothermia** is indicated where HIE develops; the concept of cooling being beneficial stems from animal studies and the neuroprotective effects of hypothermia in children following near-drowning and during cardiac surgery. Interventions to minimize the effects of hypoxia and HIE postnatally continue to evolve; early studies of short periods of cooling had limited, contradictory results. Later studies were more promising; where cerebral hypothermia was initiated after HI insult, and before onset of secondary energy failure, newborns with moderate encephalopathy had better neurodevelopmental outcome compared to normothermic controls [96]. Neuroprotective hypothermia for neonatal encephalopathy has been the subject of systematic review [97]; it is currently the standard of care for moderate and severe HIE; improves survival without CP or other disability by 40%; and current protocols are considered near optimal. Therapy within 6 hours of age at 33–34°C, continued for 72 hours, decreases death or disability at 18 to 24 months of age and increases the number of normal survivors [8, 67, 97]. Defined obstetric antecedents indicative for cooling include umbilical cord prolapse, uterine rupture and placental abruption [98]. In cooled encephalopathic newborns, time to recovery of amplitude integrated EEG is a good predictor of outcome [8]; early MRI scans (3-6 days of life) robustly predict the predominant pattern and extent of injury, and late scans (10-14 days) long-term outcome, and the predictive value of MRI is not affected by

*DOI: http://dx.doi.org/10.5772/intechopen.93840*

*Pathogenesis and Prevention of Fetal and Neonatal Brain Injury DOI: http://dx.doi.org/10.5772/intechopen.93840*

**Controlled hypothermia** is indicated where HIE develops; the concept of cooling being beneficial stems from animal studies and the neuroprotective effects of hypothermia in children following near-drowning and during cardiac surgery. Interventions to minimize the effects of hypoxia and HIE postnatally continue to evolve; early studies of short periods of cooling had limited, contradictory results. Later studies were more promising; where cerebral hypothermia was initiated after HI insult, and before onset of secondary energy failure, newborns with moderate encephalopathy had better neurodevelopmental outcome compared to normothermic controls [96]. Neuroprotective hypothermia for neonatal encephalopathy has been the subject of systematic review [97]; it is currently the standard of care for moderate and severe HIE; improves survival without CP or other disability by 40%; and current protocols are considered near optimal. Therapy within 6 hours of age at 33–34°C, continued for 72 hours, decreases death or disability at 18 to 24 months of age and increases the number of normal survivors [8, 67, 97]. Defined obstetric antecedents indicative for cooling include umbilical cord prolapse, uterine rupture and placental abruption [98]. In cooled encephalopathic newborns, time to recovery of amplitude integrated EEG is a good predictor of outcome [8]; early MRI scans (3-6 days of life) robustly predict the predominant pattern and extent of injury, and late scans (10-14 days) long-term outcome, and the predictive value of MRI is not affected by hypothermia [99, 100].

In future, earlier initiation of cooling after resuscitation may prove beneficial; ongoing research aims to identify other neuroprotective approaches that can be used in parallel, and evaluate potentially beneficial therapeutic agents; ways that may help reduce the incidence of IVH during rewarming are also being explored.

## **7. Conclusion**

*Advancement and New Understanding in Brain Injury*

appropriate timing, mode and location of labor/delivery.

wellbeing.

outcome [2].

emergency cesarean section.

**Antenatal care** is central to optimizing the fetal environment, monitoring maternal health, detection of entities that require intervention or forward planning, and enabling pregnancy to progress to term. Care should ensure that fetal growth progresses normally, all indicated US and lab studies are done, necessary referrals are made, and parents prepared appropriately. Prevention of brain injury centers on labor and delivery, but relies on attention to multiple factors throughout pregnancy. The fetal brain probably benefits most from prevention of avoidable preterm delivery, and therapy such as antenatal steroid use to mature the fetal lung when prematurity is inevitable. Post maturity with the inherent risks of placental failure and increased fetal morbidity must be avoided, especially where at risk situations exist such as gestational diabetes. Prior cesarean section requires special planning and supervision, to avoid uterine complications that can jeopardize fetal

**Monitoring during pregnancy:** Confirmation by US of gestational age reduces premature delivery; monitoring of fetal growth parameters anticipates intrauterine growth retardation, and can identify placental anomalies that increase morbidity. Genetic screening can detect anomalies linked to brain defects; termination of pregnancy is a care option when a fetus is known to have a major anomaly. Surveillance for a broad range of maternal illnesses is possible with investigative protocols and preventive entities available to optimize maternal care and fetal health, and select

**Advance consultation** with obstetric and neonatal referral centers should occur

**Intrapartum care:** Guidelines exist in most jurisdictions based on the evidence

**Staff with the required skills** must be available to comprehensively resuscitate any sick newborn, and promptly address residual morbidity after delivery. Skill with assisted ventilation is important, as prevention of detrimental hyperoxia and hypocarbia reduces brain injury risk in premature infants, and improves outcome in any sick neonate where hypoxia and ischemia have occurred [67]. After appropriate resuscitation, all the care entities required to minimize the possibility of a brain injury being sustained, or an existing intrapartum injury compounded, must be provided. Priorities to do this include: support of respiration and the circulation; provision of a neutral thermal environment, appropriate hydration and nutrition; prophylactic antibiotics and management of proven infections; hematological and biochemical surveillance; and neuroradiological monitoring. Good communication and support of the physical and mental wellbeing of both parents must be ensured.

base for best practice in obstetric management where the health of the mother and/or fetus becomes at risk. Monitoring of maternal and fetal wellbeing requires entities that provide for anticipation, detection and management of complications, particularly those linked to maternal emergencies and/or generate fetal distress; e.g. placental insufficiency, failure or abruption, hemorrhage, hypo or hypertension, uterine tachysystole or rupture, obstructed labor, or cord compromise. Importantly, a non-reassuring electronic fetal heart rate pattern, or changes in FHR reflecting alteration in fetal cardiac function, usually occurs prior to brain metabolism being affected sufficiently for neurological damage to begin. Hence, recognition of a 'non-reassuring' tracing, a 'sentinel event' involving fetal heart function, or a pattern known to be associated with pathology (e.g. cord compression) [84], allows prompt assessment, and instigation of interventions required to relieve compromised fetal oxygenation, expedite instrumental delivery, or do an

where necessary to obtain advice regarding priorities for care and delivery. **Transport** with the fetus in utero should occur if care at a higher level is required to optimize the logistics of delivery and provide for a good neonatal

**78**

Many causes of fetal and neonatal brain injury are now preventable. The consequences of cerebral hypoxia and ischemia remain considerable. Evidence-based care strategies during pregnancy and for premature and sick newborns infants are improving outcome.
