Development refers to functional maturation and is assessed in terms of four domains – gross motor, fine motor, cognitive or social adaptive and language. The brain is the major organ responsible for development in all domains, hence it is crucial to monitor development in the early years of life

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Clinical application of basic concepts

In spite of normal brain function, the developmental delay could be due to the affection of other systems. Gross motor delay could be due to musculoskeletal problems and language delay from hearing impairment.

1. The initial two years of life are crucial for brain development and also to a small extent up to five years. Thus major defects in development manifest early in life though minor defects such as learning disabilities may be detected later. Thus it is important to monitor development in the early years of life.
2. Beyond five years of age, school performance can detect aberrations if any. Grossly, developmental assessment at the age of three months can detect major abnormality arising out of antenatal or perinatal events, at one year of age, autism spectrum disorder and hearing impairment can be made out and further confirmed at eighteen months of age.
3. Developmental delay in two or more domains is referred to as global developmental delay. It is important to decide whether the delay is static (milestones are achieved at the same slow speed) suggests one-time damage or progressive (development speed is slowing down and so worsening) indicates ongoing damage.

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Case-based discussion

Case 1: Down syndrome

The mother of a one-year-old infant complained about her child not able to sit without support, did not speak any words and was not gaining weight well. On further enquiry, their mother was 35-years-old when he was born after full-term with normal delivery but his birth weight was only 2 kg.

He did not cry at birth but had spontaneous breathing on stimulation and was normal thereafter. The mother on direct questioning said that he appeared to be a bit slow in his activity but it did not bother her much. He had been constipated. He held his head at 6 months and rolled over at 10 months.

He recognised her at 3 months of age, could reach for the object by 6 months of age, he is very social and goes to anyone who picks him up and is a loving happy child.

Diagnosis

1. History suggests that he has a developmental delay in all four domains that are static and so it must be due to one-time damage.
2. There has been no significant problem at birth and so the cause of this delay must be antenatal factors.
3. This mother was delivered at the age of 35 years that carries a high risk of chromosomal disorder. Physical examination revealed weight 7 kg, length 70 cm, head O 40 cm, dysmorphic features suggestive of Down syndrome, microcephaly, generalised hypotonia, developmental quotient around 50%, no other neurological abnormality, grade 3 systolic murmur, no other abnormality in hear or any other systems.
4. This child has a static global developmental delay with a congenital heart defect and dysmorphic features suggest a diagnosis of Down syndrome.

Conclusion

It can be confirmed with chromosomal analysis and parents must be counselled about avoiding future pregnancies. In fact, they should have been counselled before or during early pregnancy about prenatal tests to diagnose such defects. There is no specific treatment but the child can do better with physiotherapy and occupational therapy.

At present, heart defect does not need any intervention except periodic monitoring for timely action. He may need diet advice and relief for constipation.

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Case 2: IUGR

The mother of a one-year-old infant complained about the developmental delay in her child. He had started rolling over at 11 months of age, barely reached for the object, could recognise his mother and other family members but had no vocalisation. He was generally irritable and constipated.

Diagnosis

1. This child was born after full-term with normal delivery in a primipara at the age of 22 years and had no problem at birth but his weight was 1.5 kg.
2. The mother suffered from severe vomiting during the first three months and later developed eclampsia for which she had to be hospitalised. History suggests severe intrauterine growth restriction as a result of maternal illness during pregnancy.
3. As there was no significant birth problem, the cause of developmental delay must be due to antenatal factors and one of such factors could be poor nutrition right from early fetal life.
4. Any other cause needs to be considered based on physical examination.
5. Physical examination showed weight as 6 kg, length 68 cm, head O 39 cm, signs of calorie malnutrition and anaemia, irritable child, generalised hypotonia with poor muscle mass, and no localising signs in any other systems.

Conclusion

This child is severely malnourished – wasted (very poor weight) and stunted (poor length) with microcephaly suggesting severe malnutrition that must have started very early in fetal life as also evident by history.

So this child’s developmental delay is due to severe fetal malnutrition IUGR. There is no need for any investigations. Treatment is to improve nutrition, though this child will remain short and small in stature and also will have some brain dysfunction.

However, with improved nutrition and adequate stimulation, this child’s disability can be minimised to the extent possible. It is important to realise that it is only when malnutrition sets in so early in fetal life that results in developmental delay.

Otherwise, any severe malnutrition resulting after birth is not likely to affect brain function severely though mild defects such as learning disabilities may manifest especially if malnutrition started early during infancy.

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Case 3: Lack of stimulation

A one-year-old adopted child presented with developmental delay. Parents had taken custody of this child two months ago and were concerned about this child not standing without support and not speaking.

Though he seemed to understand spoken words. He did not mind being picked up by strangers. Otherwise, he appeared to be happy, feeding well and had gained one kg weight in the last two months.

Diagnosis

1. Apparently, they were not informed about earlier milestones but were told that the child was normal. History suggests that this child is lagging behind in milestones and his present development is like a 9-month-old child.
2. However, there are no clues to probable cause. Physical examination showed a weight of 8 kg, length of 72 cm, head O of 42 cm, and no other significant abnormality.
3. This child’s weight and length are appropriate for 9 months and his head O is on the lower limit of normal. However, his head O at birth was not noted, it is not sure whether this head O represents microcephaly.
4. His milestones are not much behind the expected level and considering that this child was reared for the first 10 months in a shelter home, there may have been lack of interaction and it could explain the mild delay, especially in speaking.

Conclusion

Development occurs first in the receptive domain and then follows with expressive ability. This child did respond to spoken words which means that he had developed receptive language.

Thus our impression would favour a normal child with a lack of stimulation in early infancy. It is expected that this child would pick up lagging milestones within a short time with interaction with parents.

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Case 4: Vitamin D deficiency rickets

A one and half-year-old child presented with complaints of not being able to walk without support. He was born after a  full-term with normal delivery, birth weight of 3 kg and had been normal without any significant problems.

He was exclusively breastfed for the first 6 months and then was started on complementary feeds while continuing breastfeeds that he takes even now.

Diagnosis

1. He gained weight well in the first year but had not gained only 800 gm in the last 6 months. He had achieved all milestones in time during the first 6 months but had started sitting without support only at one year and then standing at 14 months.
2. The doctor had said that it was within normal limits. But now that he was not able to walk without support, his parents were worried. His other milestones were all normal as he could speak words with meaning and respond appropriately to his age.
3. History suggests a well-nourished child without any disease is lagging behind only in gross motor milestones sometime after the first 6 months and his other domains are all normal.
4. So he has isolated delay in gross motor milestones starting sometime after the age of 6 months in spite of normal brain function.

Conclusion

Obviously, the fault lies in the musculoskeletal system and not in the peripheral neurological system as he can stand and so does not have any paresis. Acquired motor delay in a well-nourished child is often due to vitamin D deficiency rickets contributed by a predominantly milk diet.

Physical examination showed a weight of 11.5 kg, length of 78 cm, head O 48 cm, signs of rickets, and no other abnormality. Diagnosis of vitamin D deficiency rickets was confirmed by biochemical (low or normal serum Ca, low serum P and high serum alkaline phosphatase) and radiological tests (cupping and fraying at the epiphyseal end of bones with demineralisation).

He needs a therapeutic dose of vitamin D-6 lakhs unit to heal rickets and repeated twice more to replenish the store. Ideally, vitamin D supplements every day for the next three months would be ideal but often lacks compliance and so a massive dose is often prescribed.

His parents should be counselled about diet. He may have been addicted to breast milk and hence consumes mainly milk without much solid food.

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Case 5: Autism spectrum disorder

A two-year-old child presented with an inability to speak and did not respond age-appropriately. Though his motor milestones were normal. He was born after full-term with normal delivery and had achieved all the milestones in time except speech development.

When consulted about this delay, the doctor had said that such a delay was familial in this child as his uncle also was a late talker. They were advised to check their hearing ability which was found to be normal. But now a year had passed without any improvement and so parents were worried.

Diagnosis

1. On direct questioning, it was realised that he was hyperactive, often kept on moving without purpose, engrossed in activities with repeated manoeuvres, had no eye to eye contact, would not respond when called by his name and would not follow any orders.
2. However, he would sit for a long time in front of the television. Unfortunately, this aspect remained ignored. So this child has a communication disorder with attention deficit.
3. Physical examination confirmed his abnormal behaviour but had no abnormality in any other system.
4. Diagnosis of Autism spectrum disorder was confirmed by standard tests done by psychologists – DSM 5 – developmental manual test. He would need long term therapy under the guidance of a developmental paediatrician.

Conclusion

Surely he would improve at least to some extent but only with strong commitment from his parents. Ideally, he should have picked up at about one year. A simple screening test for autism spectrum disorder is to see whether the child responds to his name being called for at least by one year.

If there is no response, one should check hearing ability and brain function in other domains and if found to be normal, such a child should be referred to a developmental paediatrician. If diagnosed early and treated properly, there would be a much better outcome.

There are no drugs for such a problem though occasionally hyperactivity may need some medications.

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Case 6: Spastic cerebral palsy with remote symptomatic epilepsy

The mother of a one-year-old child complained of the child's inability to hold the head, not recognising her, and no smile or cooing.

Diagnosis

1. This child was born after full-term cesarean section delivery done for fetal distress.
2. The child did not cry at birth, required oxygenation and ventilation for the next 4 days, had few seizures on D2, was on IV fluids and subsequently fed through a nasogastric tube.
3. He also developed sepsis which was treated with antibiotics.
4. He was discharged on D 20. He was prescribed anticonvulsant drugs.
5. He had three more episodes of seizures and had poor weight gain.
6. He was on physiotherapy without much benefit.
7. History clearly suggests severe hypoxic-ischaemic birth injury resulting in severe developmental delay and seizure disorder.
8. Physical examination showed a malnourished infant with global developmental delay, microcephaly and severe spasticity with signs of bilateral upper motor neuron lesion.
9. It confirms the diagnosis of spastic cerebral palsy with remote symptomatic epilepsy (due to one-time damage) and severe malnutrition.

Conclusion

In such a typical presentation, there is no need for neuro-imaging as it does not add to any more relevant information. Neuro-imaging is reserved in a child with cerebral palsy only in absence of microcephaly, significant birth history or presence of a family history of a similar problem.

Treatment is palliative in the form of physiotherapy to prevent contractures, occupational therapy and anti-epileptic medications, nutritional rehabilitation and care of non-neurological problems such as constipation, gastro oesophagal reflux, skin and bladder care and vitamin D supplements. Prognosis in such a child is poor.

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Case 7: Spastic diplegic cerebral palsy

A two-year-old child presented with delayed standing and an inability to walk without support. He was born after 30 weeks of gestation with normal delivery.

He did not cry at birth and required resuscitation with a bag and mask and oxygenation. He also required tube feeding for one week but thereafter was discharged.

Diagnosis

1. He was under regular follow-up and had gained initial milestones a bit more delayed than normal.
2. He held his head at 5 months, rolled over at 7 months, and sat at 10 months.
3. Cognitive and language milestones were also developed a bit late but he was talking now at two years of age and also had a normal understanding. He had no other complaints.
4. This history suggests mild global delay that has improved to near normal except for the inability to walk without support at 2 years of age which is disproportionately delayed.
5. We may have to find an answer on physical examination. Physical examination showed normal nutritional status with cognition and language development within normal limits, bilateral upper motor neuron signs in lower limbs but not in upper limbs.
6. There were no other abnormalities. Bilateral pure motor UMN lesion without sensory loss rules out spinal disease. As pyramidal fibres innervating both lower limbs are affected, the lesion in the brain is periventricular.
7. The lesion is static and so the diagnosis is spastic diplegic cerebral palsy.

Conclusion

This must have resulted from the probable milder grade of periventricular haemorrhage. This type of cerebral palsy has near-normal brain function.

There is no need for neuro-imaging as it is unlikely to give any more relevant information. Physiotherapy would improve this child and the prognosis is good.

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Case 8: Inborn error of metabolism

A child was born after a full-term and normal delivery and was presented with developmental delay. The child had cried immediately and there was no problem at birth.

He was discharged on D 3 with exclusive breastfeeding. However, on D 5, he developed an acute episode of vomiting followed by seizures and unconsciousness for which he was hospitalised.

Diagnosis

1. There was no fever. He was put on IV fluids and anti-convulsant drugs and some investigations were sent. Over the next 2 days, he improved and looked normal. Pending reports, he was discharged without any medicines.
2. However, he returned with similar events within the next two days.
3. This history rules out any birth injury as his problems started only after four days. Sudden onset of severe neurological symptoms in an apparently normal neonate and then quickly recovery within two days on IV fluids, suggest inborn error of metabolism.

Conclusion

In such a disorder, an abnormal metabolite is formed from one of the constituents of ingested feed due to a lack of a specific enzyme and this abnormal metabolite is toxic to the brain.

Specific abnormality can be diagnosed only on detailed metabolic investigations. If not recognised in time, it results in ongoing brain damage that is fatal.

Even if an abnormality is diagnosed and an offending agent from the ingested feed is withdrawn, irreversible damage may have occurred and one can hope to prevent further damage.

Ideally, such diseases are best diagnosed by neonatal screening to prevent damage but can be considered mostly if an index case exists in the family.

However neonatal screening is carried out routinely in western countries for more than 20 such diseases, selected on the basis of their incidence in the community. In India, many centres have started neonatal screening programs for 5-6 common diseases and are cost-effective considering the common prevalence of these diseases in the community.

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Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.