Neonatal Neurology

By: Michelle G. Sy, MD

Last Edited: May 25, 2025

Development of the Nervous System

Discovering that your new baby has a neurologic or neuro-developmental condition is not easy, and it can bring a lot of unknowns to your life. Neurological disorders occur when an injury or other problem affects this development before, during or shortly after birth. These can include a baby’s brain, spinal cord, nerves and muscles.

These high-risk newborns can be born with neurological disorders that develop in the womb during pregnancy or, their condition can be due to complications during or after delivery that increase their risk of developing a neurological disorder.

How does a fetus develop a brain and the importance of the "First 1000 Days"

Stages of brain development before birth. From Nutton, Georgina & Silburn, Sven & Arney, Fiona & Moss, Bonnie. (2011). The first five years: Starting early. Early Childhood Series No. 2. 2011.

The first 1,000 days of human development is a critical time for children’s brain. The first 1,000 days refers to a child's life from conception until they reach 2 years of age (24 months). Research shows that 80 percent of a child’s brain development occurs within the first 1,000 days of life – making it important for lifelong health, learning, and success.

Just a couple of weeks after you conceive, the embryo forms a neural plate. This is the basic plan for the nervous system. The neural plate elongates and folds on itself forming the neural tube. The upper part of the tube becomes the brain, while the lower portion elongates further to eventually become the spinal cord.

At 6-7 weeks, the neural tube closes. At which point, the brain separates into three parts: front brain, midbrain, and hindbrain. The brain will grow at a rate of 250,000 neurons per minute for the next 21 weeks. In the first trimester, the brain will grow millions of neurons, which connect across synapses to direct movement and growth. Such that by the end of the first trimester, the 3-part brain will have developed specialized parts, and fold into the left and right halves of the brain. Different areas of the brain play different roles and will soon be able to communicate with each other through these synapses to coordinate all aspects of functioning. Among the major areas are the following:

Cerebrum
- largest part of the brain and contains the cerebral cortex and the frontal and temporal lobes of the brain.
- responsible for thinking, feeling, and memory.
Cerebellum
- also called the "little brain"
- responsible for directing the body’s motor control, balance, movement and coordination
- currently known to influence the learning process, working memory, language and emotional regulation.
Brain stem
- controls the vital functions that keep the body alive.
- mainly direct involuntary systems like heartbeat, blood pressure, and breathing, and digestive processes
Pituitary gland
- in charge of releasing most of the hormones in the body that direct the metabolism, ovulation, growth, and more.
Hypothalamus
- regulates body temperature, hunger and thirst cues, sleep, and emotions

In the second trimester, the fetal brain continue to grow and begins to recognize and react to the external world.

The nervous system has developed enough to detect loud noises from outside. You may feel the baby startle when there’s a sudden loud noise or move to your voice. The fetal brain stem is almost entirely developed by the end of the second trimester and will controls the heart rate, breathing, and blood pressure. The fetus continues to make other movements such as kicking, stretching, swallowing and sucking and will continue to develop the full range of fetal movements. These movements are coordinated and directed by the cerebellum with the brain stem. The fetus will begin experiencing sleep cycles, and brainwaves that occur during sleep, controlled by the hypothalamus, begin occurring around week 28.

During the third trimester – the final 13 to 14 weeks of gestation – fetuses’ brains grow exponentially and triple in size. The body shifts energy to the brain to accommodate the neurological growth spurt. As the brain size increases, it develops critical structures and connections that will be relied upon for life. The cerebrum will begin to develop grooves and ridges. By the time a fetus is term, the brain will resemble that of an adult. Premature infants or those born before 37 weeks of pregnancy, have a higher risk of a neurological disorder.

The first 1,000 days of life are a critical period for children’s development, often referred to as the “golden interval”. From Gonçalves JdL, Arnez MFM and Paula-Silva FWGd (2024) How the First 1,000 Days of Life Can Shape a Child’s Future Health?. Front. Young Minds. 12:1386240. doi: 10.3389/frym.2024.1386240

Although the complex parts of the brain continue to grow and develop through the end of pregnancy, development ends around the age of 25. For a term infant, critical areas of brain development continue until the end of the first 1000 days or until 2 years old. A child's brain's capacity and structure are shaped at an exponential rate with 80% of the brain developing within the first 1000 days.

Within this period, a child's auditory and visual sensory systems, learning abilities, memory functions, and information processing systems are formed. Infant brains can create 1,000 new neural connections every second throughout this time. This process of myelination abruptly increases at 32 weeks gestation and is most active in the first 2 postnatal year.

The brain does not develop all at the same time. Instead, it is composed of multiple anatomical regions and processes, each with unique developmental trajectories. The first 2-3 years of life outside the womb is involved in the growth and pruning of these processes.

Systems involved in mediating reward, affect, and mood begin their development prenatally, continuing at a brisk pace until at least age 3 years.The hippocampus, which is crucial for mediating recognition and spatial memory begins its rapid growth phase at approximately 32 weeks gestation, continuing for at least the first 18 postnatal months. The prefrontal cortex, which orchestrates more complex processing behaviors, such as attention and multi-tasking, has the onset of its growth spurt in the first 6 postnatal months

Brain development is time-sensitive and involve areas with specific growth trajectories that is critical for promoting behaviors served by the individual regions. More importantly, the time-coordinated development of brain areas are designed to work together as circuits that mediate complex behaviors.

This is why the first 1000 days is critical in enhancing the full brain potential of a child, and is the window of opportunity to prepare them for a wider range of neuro-developmental capabilities. From the moment babies begin growing in their mothers’ wombs until they are 2 years old, children are the most sensitive to interactions with the environment.

Some ways to take full advantage of the first 1000 days are the following

1. Prepare for a healthy pregnancy. Proper nutrition and supplementation does not only start during pregnancy. It is best done as a preparation for this life changing event. Folate supplementation can help prevent neural tube defects (NTDs). Iron supplementation for menstruating women can help prevent iron deficiency anemia and improve oxygen capacity, especially important during pregnancy. A healthy lifestyle with proper nutrition, hydration, good hygiene and exercise helps prepare the body get the needed substrates for a baby's mental development.

2. Avoid toxic substances. Toxins that can adversely affect the fetus include not only smoking and alcohol. Ingestion of ultra-processed foods such as those with high sugar and oil content, preservatives, artificial compounds and even food containers made with more volatile chemicals can contribute to poor health outcomes for the fetus. Other toxic chemicals can make their way into the mother's blood stream and into the fetus's body by absorption when substances are applied to the skin and scalp and by inhalation of fumes.

3. Avoid high and prolonged stress. While certain forms of stress is beneficial to our survival, increased stress causes increased stress hormones and stress response in the body. Certain parts of the developing fetal brain can be susceptible or sensitive to undue levels of these chemicals, which can cause short and long term consequences. Having a good support system prior and throughout pregnancy can help reduce maternal stress levels.

4. Be intentional parents. Once a baby is born, a full range of environmental factors can now influence an infants development directly. From nutrition and ability to feed, hygiene and health practices, sleep routines, interpersonal and social relationships, physical activities, interplay with nature and so much more, these will shape a child's development and serve as a foundation for their later years. Therefore, it is important for parents to provide the best possible care for their babies from the moment of conception and throughout the first 2 years of life. Making the healthiest possible choices during this period can put children on the best path to being healthy as they grow up!

The High-Risk Newborn

A "High-Risk Pregnancy" is one in which a woman and her fetus face a higher-than-normal chance of experiencing problems. These risks may be due to factors in the pregnancy itself, or they may stem from preexisting maternal conditions, such as very young or older maternal age, and maternal medical conditions.

A 'High-Risk Newborn' refers to a newborn baby who has a greater chance of experiencing health issues or complications and require specialized medical care. These infants are exposed to conditions that endanger their survival and have greater chance of morbidity or mortality due to conditions surrounding birth.

High-risk newborn infants need more frequent follow-up assessments to ensure that all expected developmental stages are achieved in the expected time window. Often, more visits are needed for those with a specific neuro-developmental problem at the time of discharge from the NICU, or if new neuro-developmental problem was detected at a regular follow-up visit. These newborns at risk for neuro-developmental delay should be assessed regularly during the early rapid development in the first 2 years or withing the first 1000 days of life.

Abbreviations: AD, Alzheimer disease; ASD, autism spectrum disorder; MIA, maternal immune activation; PD, Parkinson disease

Proposed causal chain of events with maternal immune activation in humans, leading to a wide spectrum of neuronal dysfunctions and behavioral phenotypes observable in the juvenile, adult, or aged progeny. From Scher, M. S. (2022). A Bio-Social Model during the First 1000 Days Optimizes Healthcare for Children with Developmental Disabilities. Biomedicines, 10(12), 3290. https://doi.org/10.3390/biomedicines10123290

Causes and Risk Factors of Neonatal Neurological Disorders

We know that the neuro-development of infants is affected by multiple factors, such as heredity, biology and environment and this can be especially influenced by events during the first 1000 days when the brain is fast developing.

Neurological disorders in newborn infants may be inherited from one or both parents, or the child has an abnormality in his or her genetic material. Infants can be born with a chromosomal anomaly causing Trisomy syndromes. Certain metabolic disorders such as phenylketonuria and congenital hypothyroidism can cause neurological problems. These are often detected at birth through newborn screening, however, many conditions that cause neurologic disorders are not included.

Neurological conditions can also be caused by improper growth within the brain or spinal cord. Premature and low birth weight babies are particularly at risk for disorders of the brain. Immaturity of the brain, spine, blood vessels, lack of nutritional requirements for brain growth make the nervous system vulnerable to certain conditions.

Other factors that contribute to are maternal health and toxin exposure, labor and delivery complications, and congenital infections.

During and after birth, several issues can lead to the development of a neurological disorder. These include:

Asphyxia, hypoxia or ischemia. This means there is a lack of adequate oxygen before, during, or immediately following birth.
Infections. Unsterile deliveries can cause bacteria to enter through the umbilical cord or a mother with genital tract infection can harbor bad bacteria or pathogenic bacteria that can enter causing sepsis, meningitis and other infections.
Hemorrhage. Injury to the head or vitamin K deficiency can cause bleeding inside the brain.
Immune disorders and other medical conditions. Prolonged NICU stay for medical conditions, as well as the immature immune system of a newborn can bring about consequences to the developing nervous system.

Types of Neonatal Neurological Disorders

While there are several neurological problems a newborn may have, these are the more common conditions:

Neonatal seizures: These occur due to a variety of conditions and may range in severity.
Encephalopathy: This refers to your baby's general level of alertness due to a neurological condition causing feeding and breathing difficulties related to decreased consciousness.
Intracranial hemorrhage: Bleeding can occur in several parts within the skull. It may be within or outside the brain tissue. An intraventricular hemorrhage occurs most in premature newborns.
Congenital neurological defects: These are mostly related to brain and spinal cord malformations, and are present at birth. This could range from obvious malformations such as neural tube defects that affect the spinal cord and brain and cause hydrocephalus, to disorders that become apparent at an older age when they develop symptoms, to malformations that do not have obvious symptoms but are incidental findings in neuro-diagnostic tests.
Periventricular leukomalacia: This is a common neurological condition that affects preterm infants and is related to an injury to the periventricular white matter, a very specific area of the brain.
Hypotonia: An infant may be floppy or have low muscle tone. This is a form of muscle weakness and may be due to a variety of neuromuscular conditions. This can be associated with difficulty breathing and feeding.
Neurometabolic disorders: Our body requires a variety of biochemical reactions to function, moreso with our brains. Any disruption in this process can lead to changes in neurological function. While the disorder is largely genetic in origin, the disorder in neuro-metabolism can be due to enzyme and protein defects, or neuro-chemical production, breakdown and receptor abnormalities.

Incidence of neuro-developmental disorders among high risk newborns is significantly high. Depending on the condition or neurologic disorder they had, adverse neuro-developmental outcomes can vary from mild motor and language delay to global delay, hearing and visual impairments, seizures and also long-term intellectual impairment, academic underachievement, and learning difficulties.

While some outcomes can be detected in young infants, many important aspects of neuro-development cannot be measured until school age. Hence, these problems can go undetected in the early years of life and eventually cause increased burden to the patient, family and society.

Regular and close follow-up of any high-risk babies with early identification of any delay and early intervention with multidisciplinary approach will help to enhance the optimal development. Assessment of growth, nutrition, development, vision, hearing and neurological status during the first 1000 days can help mitigate adverse outcomes through early intervention. Continued follow-up until school entry to adolescence can help detect cognitive problems, learning problems and behavioral problems needing additional support.

References for "Development of the Nervous System"

- National Research Council (US) and Institute of Medicine (US) Committee on Integrating the Science of Early Childhood Development; Shonkoff JP, Phillips DA, editors. From Neurons to Neighborhoods: The Science of Early Childhood Development. Washington (DC): National Academies Press (US); 2000. 8, The Developing Brain. Available from: https://www.ncbi.nlm.nih.gov/books/NBK225562/

- Cusick SE, Georgieff MK. The Role of Nutrition in Brain Development: The Golden Opportunity of the "First 1000 Days". J Pediatr. 2016 Aug;175:16-21. doi: 10.1016/j.jpeds.2016.05.013. Epub 2016 Jun 3. PMID: 27266965; PMCID: PMC4981537.

- Likhar A, Patil MS. Importance of Maternal Nutrition in the First 1,000 Days of Life and Its Effects on Child Development: A Narrative Review. Cureus. 2022 Oct 8;14(10):e30083. doi: 10.7759/cureus.30083. PMID: 36381799; PMCID: PMC9640361.

- MotherToBaby | Fact Sheets [Internet]. Brentwood (TN): Organization of Teratology Information Specialists (OTIS); 1994-. Critical Periods of Development. 2023 Feb. Available from: https://www.ncbi.nlm.nih.gov/books/NBK582659/

- Cisneros-Franco JM, Voss P, Thomas ME, de Villers-Sidani E. Critical periods of brain development. Handb Clin Neurol. 2020;173:75-88. doi: 10.1016/B978-0-444-64150-2.00009-5. PMID: 32958196.

- Ackerman S. Discovering the Brain. Washington (DC): National Academies Press (US); 1992. 6, The Development and Shaping of the Brain. Available from: https://www.ncbi.nlm.nih.gov/books/NBK234146/

Scher, M. S. (2022). A Bio-Social Model during the First 1000 Days Optimizes Healthcare for Children with Developmental Disabilities. Biomedicines, 10(12), 3290. https://doi.org/10.3390/biomedicines10123290

References for "The High Risk Newborn"

Chattopadhyay N, Mitra K. Neurodevelopmental outcome of high risk newborns discharged from special care baby units in a rural district in India. J Public Health Res. 2015 Feb 19;4(1):318. doi: 10.4081/jphr.2015.318. PMID: 25918689; PMCID: PMC4407034.

Ellison PH. Neurologic development of the high-risk infant. Clin Perinatol. 1984 Feb;11(1):41-58. PMID: 6713767.

Allen, M. C. (1993). The High-Risk Infant. Pediatric Clinics of North America, 40(3), 479–490. https://doi.org/10.1016/s0031-3955(16)38545-5

Shrestha, M. (2021). High-risk babies and neurodevelopmental outcome. In Elsevier eBooks (pp. 39–45). https://doi.org/10.1016/b978-0-12-817988-8.00004-x

Weerakul, J., Sanjaiban, M., & Intasen, S. (2021). Factors affecting the developmental outcomes of High-Risk newborns. Open Journal of Pediatrics, 11(04), 749–758. https://doi.org/10.4236/ojped.2021.114069

Brady JM, DeMauro SB. Developmental Outcomes of High-Risk Infants. In: Kline MW. eds. Rudolph's Pediatrics, 23e. McGraw-Hill Education; 2018. Accessed May 25, 2025. https://accesspediatrics.mhmedical.com/content.aspx?bookid=2126&sectionid=190244891

Other sources:

https://www.firstthingsfirst.org/

https://www.healthline.com/health/

https://flo.health/

https://study.com/

https://www.babycenter.com/

https://my.clevelandclinic.org/