Study on Cause-Effect Relationship of Antenatal Maternal Emotional State with Neurodevelopmental Disorders

Neuro developmental disorders (NDDs) include developmental brain dysfunction, which can manifest as neuropsychiatric problems or impaired motor function, learning, language or non-verbal communication i.e. intellectual disability, attention deficit hyperactivity disorder, communication disorders, epilepsy, emotional disorders, etc. This study wants to throw light on the fact that mother and fetus are one entity and whatever affects the mother will affect the child. The aim of the study is to find the cause-effect relationship of antenatal maternal emotional state with neurodevelopmental disorders. A sample of 60 cases was obtained with neurodevelopmental disorders (NDDs) which had a stressful antenatal maternal emotional history. Proper diagnostic tools such as Vanderbilt ADHD diagnostic parent rating scale, Screen for child anxiety related emotional disorders (SCARED), developmental screening test (DST), Vinland social maturity scale (VSMS) and basic IQ tests like draw a man test, gazelle drawing, Seguine Form Board (SFB) test, etc. were used for the specific diagnosis of each NDD. Details regarding the antenatal history were elicited such as family stressors, financial problems, interpersonal relationships and any other stressful events. Not only the stressful event/situation but also the type of response/emotions given by the mother during pregnancy period was elicited. The most common emotion causing NDDs was anxiety/worry/fear in the antenatal period and was about 41.66%. In most cases there was intermingling of different emotions also. study, the


Introduction
 Neuro developmental function is a basic process needed for learning and productivity. Its dysfunction reflects disruptions of neuro anatomic structure or psychophysiologic function and places a child at-risk for developmental, cognitive, emotional, behavioural, psychosocial and adaptive challenges. Therefore, neuro developmental disorders (NDDs) include developmental brain dysfunction, which can manifest as neuropsychiatric problems or impaired motor function, learning, language or non-verbal communication i.e. intellectual disability, attention deficit hyperactivity disorder, communication disorders, epilepsy, emotional disorders, etc.
Need of the study:  The prevalence of NDDs was found to be nearly 12% in Indian children aged 2 -9 years. Nearly 1 in every 8 children might be suffering from at least one of the NDDs "as given in India bioscience news 2018" (Urvashi, 2018).  Every child's development starts from the mother's womb itself. Therefore, every developmental disorder has to be considered from antenatal period.  Today's antenatal check-ups are only focusing on the physical factors affecting the mother.  In recent years there is no much concern over the behavioural or emotional teratogenicity and its possible effects on the offspring even though several studies have found a correlation between prenatal stress and child development.  This study also tries to throw light on the probable risk factors so that it can be avoided and necessary measures can be taken to avoid such effects in the offspring.  This study may motivate every system of medicine to find a therapeutic aid to treat such developmental disorders where cause lies in the emotional level.
Does the environment affect CNS during fetal development?  Early influences, particularly those producing toxic levels of stress modify gene expression (epigenetic change) which is a result of environmental insults.
 According to Kleigman (2015), "Neuronal plasticity permits the CNS to recognize neuronal networks in response to environmental stimulation, both positive and negative. Thus experience (environment) has a direct effect on the physical and therefore functional properties of the brain (genetics)".  According to Inderbir Singh & Pal (1976), "Apart from this, a major part of the nervous system develops by around 4 months of gestation and therefore V. Sreekumar, V. C. Kurup the environment of the fetal can affect the development of its nervous system as well" (p. 297). How antenatal maternal emotional states affect the offspring? The "prenatal environment" (the environment inside the uterus) of the developing child is important because everything experienced by the mother is experienced by the fetus as well. The hormones produced in a mother during any emotions passes through the placenta and will alter the character of the developing child's physiology.
According to Anindya Kumar Gupta, Monica Mongia, & Ajoy Kumar Garg, (2017), "It is also said that the fetus develops a range of behavioural responses from early gestation itself and therefore the behavioural teratogenicity is very important" (p. 91-94).
Animal studies: [According to Vivette Glover, (1997)]  The hypothalamo-pituitary adrenal (HPA) axis has been shown to be affected, showing increased responsiveness to a particular stimulus. For example, stressing the mother monkey, by exposure to unpredictable noise, resulted in the offspring having raised basal cortisol levels, and a raised adrenocorticotropin response during stress (Clarke et al, 1994). Similar findings have been obtained with rodents.  Henry et al. (1994) have shown that prenatal stress of the mother caused an elevated corticoster one response in the offspring during exposure to a novel environment. Levels of both glucocorticoid type I and type II receptors were reduced in the hippocampus at 90 days, showing a possible mechanism for the long-lasting effects on the HPA axis. Human studies:  According to Vivette Glover, (1997), "Lou et al, 1994 conducted a study and examined the links between life events, or prenatal stressors, and fetal brain development. They compared the 70 most stressed with 50 controls from the sample. They found that both antenatal stress contributed significantly to a lower gestational age, lower birth weight, and smaller head circumference when corrected for birth weight. Prenatal stress also significantly worsened the scores on the neonatal neurological examination" (p-105-6).  According to Schulz, Pearson, Neeley, et al., (2011). "Studies indicate that brain development, specifically that of the hippocampal system which is heavily involved in learning and memory, is adversely affected by prenatal stress and stress hormones during gestation, creating lasting effects on learning and memory" (p. 340). According to Tandu-Umba et al., (2014) "It is also proposed that emotional stress or insult incites an adaptive response involving the hypothalamic pituitary-adrenal axis, with release of various immune (Interleukins 1, 6, and Tumor Necrosis Factor-alpha), hormonal (prostaglandins) and neurohormonal (corticotrophin-releasing hormone, hence cortisol and catecholamines) mediators along with heavy production of free radicals or reactive oxygen species (ROS) which will cause oxidation of essential macromolecules and DNA" (p. 361-370).
Acoording to Lobo et al., (2010). "this in turn will result in alteration of vital cell functions along with systemic inflammatory state, causing long term effects" (p. 118-126) Different emotions have different hormones According to Vineetha Sreekumar, (2017). "Not only stress but also all the negative and positive emotions of a mother during pregnancy has some effects in the offspring. It is said so because during each emotion the hormones produced are different."  Acetylcholine is active when a person is angry which then trigger one to feel anxious or depressed and later leading to sudden outburst of tears.
 Norepinephrine or noradrenalin is high at the time of panic or anxiety.  Epinephrine is increased during emotions of fear, anger, amusement.  Estrogen level is high at the time of anxiety.  Serotonin levels are decreased at the time of depression and sensitivity.  GABA (gamma-butyric acid) becomes low when a person is anxious.  Oxytocin is called "love hormone" and so it is lowered when there is no good interpersonal relationship.
Role of Homoeopathic medicine  According to Rajalakshmi (2016). "In Homoeopathy, holistic means treating the individual as a whole and not just the different parts. Homoeopathy looks at the root of the problem. If there is a behavioural issue the Homoeopath will first look at the circumstances that led to the behaviour. For example if the child has temper tantrums it may be due to a hypersensitivity to the environment or some internal discomfort."  The history taking is also a very important aspect of the Homoeopathic consultation. Here the entire history including the state of the mother during pregnancy is taken. Homoeopathy helps with emotional healing.  Homoeopathy believes in restoring homeostasis or external and internal equilibrium and harmony. Nanoparticles of Hypericum were used. It was found that both the extract and the nanoparticles significantly reduced stress induced behavioural and oxidative damage. The effect of Hypericum nanoparticle was more than that seen with the V. Sreekumar, V. C. Kurup extract. The study showed significant improvement in memory and recall that was stress induced.

Study Setting
A sample of 60 cases was obtained from Sarada Krishna Homoeopathic Medical College, Kanniyakumari with neurodevelopmental disorders (NDDs) which had a stressful antenatal maternal emotional history.

Selection of Samples
A sample size of 60 cases with neurodevelopmental disorders (NDDs) which had a stressful antenatal maternal emotional history were selected using purposive sampling technique. For that every child will be screened for neurodevelopmental disorders using basic diagnostic tools and cases with stressful antenatal maternal emotional history will be selected from it through detailed case taking.

Inclusion Criteria
 Patients of paediatric age group between 6 yrs and 18 yrs.

Exclusion Criteria
 Patients with antenatal maternal history of some other physical causes like exposure to radiation or chemicals.

Study Design
Observational study.

Brief of Procedures
Every case is subject to screening using basic diagnostic tools and those cases identified with NDDs will be sent for detailed case taking which includes the mothers's antenatal emotional aspect as well. Out of this a sample of 60 cases with neurodevelopmental disorders (NDDs) which had a stressful antenatal maternal emotional history. All details regarding the antenatal history was properly elicited such as family stressors, financial problems, interpersonal relationships and any other stressful events. Not only the stressful event/situation but also the type of response/emotions given by the mother during pregnancy period was elicited. All cases were not just diagnosed as NDDs but were specifically diagnosed using proper diagnostic tools such as Vanderbilt ADHD diagnostic parent rating scale, Screen for child anxiety related emotional disorders (SCARED), developmental screening test (DST), Vinland social maturity scale (VSMS) and basic IQ tests like draw a man test, gazelle drawing, Seguine Form Board (SFB) test etc. Apart from the antenatal history, details regarding the occupation of the parents, economic status, religion, age/sex of the affected child were also collected. Finally the data collected is analyzed properly and tabulated. Psychology

Data Collection
Data is obtained from the patient, patient's mother and other bystanders through interview technique. The diagnosis is done through proper screening and assessment of the patient using proper diagnostic tools.

Data Analysis
Data is presented using charts and Tables 1-5.

Results
Age-wise stratification: Children with NDDs who had a stressful antenatal maternal emotional history were stratified on the basis of their age into four groups such as 6 -8, 9 -11, 12 -14, 15 -17.18 (30%) of them belonged to 6 -8 age group, 22 (36.66%) belonged to 9 -11 age group, 13 (21.66%) of them belonged to 12 -14 age group and 7 (11.66%) of them belonged to 15 -17 age group. Prevalence of NDDs with stressful antenatal emotional history was found to be highest among the children of age 9 to 11 years.
Gender difference: NDDs were more prevalent in the males than in the females. Out of the 60 children, 46 (77%) were males and 14 (23%) were females.
Different type of emotions of the mother in the antenatal period: Out of the 60 cases 25 (41.66%) had anxiety, worry or fear, 10 (16.66%) was stressed mentally, 7 (11.66%) had a feeling of lack of care, 6 (10%) did not wanted a child & attempted to abort, 5 (8.33%) were sad, wept, had helpless feeling each, 3 (5%) were depressed, had suppression of emotions & felt lonely each, 2 (3.33%) had a mental shock & unsecured feeling each, 1 (1.66%) had grief, insulted feeling & a fright each. But most of the case had a mix of many types of emotions in the antenatal period. Psychology Specific type of NDD as an outcome of stressful antenatal emotional history: From the 60 cases, 15 cases had intellectual disability, 12 were identified with ADHD, 9 had anxiety disorder and attention defiant disorder each, 7 of them had learning disability, 6 had oppositional defiant disorder, 5 were diagnosed as slow learners, 3 had epilepsy, and 1 had disruptive behavioural disorder and expressive language disorder each. It was found that in many cases more than one type of NDDs were identified in a single child or it can be said that most of the types of NDDs are co-morbidity of each others.
NDDs with stressful antenatal emotional history and socio-economic status: There was a significant difference in the prevalence of NDDs with stressful antenatal emotional history between the children belonging to poor and average socio-economic status. Out of 60 cases, 29 (48.33%) belonged to poor socio-economic status, 9 (15%) cases belonged to average socio-economic status and 22 (36.66%) cases belonged to good socio-economic status.

Discussion
According to this study the prevalence of NDDs with stressful antenatal emotional history was found to be highest among the children of age 9 to 11 years (Table 1, Figure 1). NDDs were more prevalent in males than in females i.e., 77% were males and 23% were females ( Figure 2).
The different types of emotions of mothers in the antenatal period in the study were found to be emotional states such as anxiety/worry/fear, stress, lack of care, an attempt to abort the child from unwanted pregnancy, weeping, sad, helplessness, depressed, suppression, loneliness, mental shock, unsecured feeling, grief, fright and unsecured feeling (Appendix). The most common emotion was anxiety/worry/fear in the antenatal period and was about 41.66% (Table 2, Figure 3). In most cases there was intermingling of different emotions also.
According to the study the most common cause for such negative emotions during pregnancy or antenatal period for the mother was found to be because of the problems created by the alcoholic husband and this cause was identified in almost 25 cases i.e., 41.66%. Other causes were financial stress, problems with husband's family or mother-in-laws, death of any family members, fright/any mental shock etc (Appendix).
The outcome of a stressful antenatal emotional history were found to be as different types of NDDs such as intellectual disability, ADHD, anxiety disorder, attention defiant disorder, learning disability, oppositional defiant disorder, slow learners, epilepsy, disruptive behavioural disorder and expressive language disorder ( Figure 4). In the study almost many cases had co-morbidity among themselves. Intellectual disability and ADHD was found to be the most common outcome of these (Table 3, Figure 3).
There was no much difference in the prevalence of NDDs in children belonging to poor and good socio-economic status as the percentage was 48.33% and 36.66% respectively ( Figure 5). It was estimated also from identifying the occupation of parents (Table 4, Figure 6).
Majority of the children NDDs and with a stressful antenatal emotional history belonged to the Hindu religion (75%), (18.33%) were Christians and 6.66% were Muslims (Table 5, Figure 7).      Many research studies have proven that Homoeopathy has an emotional healing ability and also have proofs to show that it has protective ability to prevent the bad effects of stress. Also that Homoeopathy can reduce genetic transmission of diseases and disorders and help in changing gene expression.

Conclusion
The study clearly shows a strong cause-effect relationship between antenatal maternal emotional state and neurodevelopmental disorders. It is found that with different negative emotions in the mother due to different causes can create different types of NDDs such as intellectuall disability, ADHD, anxiety disorders, oppositional defiant disorder, epilepsy, attention defiant disorder, learning disability, slow learners, disruptive behavioural disorder and expressive language disorder. It was found that one of the major causes for the stress in the mother was the alcoholic husband and most of them were from poor socio-economic status.
Further studies must be done to know what exactly each emotions in the mother during pregnancy can have on the offspring and its mechanism of transmission.
This study is done to stress on the importance of antenatal period for the mother not only regarding the physical health but also in the mental sphere so that more care can be given to the mother during this period. This is to highlight that "Happy mothers have healthy children".
Homoeopathy is one of the best therapeutic modalities in promoting emotional healing and also in helping the process of holistic child development in this modern day where environment promotes a faster pace of living and where stress has become a natural component of people's lives. Homoeopathy can be a helping hand for the children who grow up with the anxiety and the emotionally stressed environment.
It is of high time that every system of medicine includes the alternative system to contribute to the ways to prevent such behavioural teratogenic effect on the offspring and also to have a therapeutic solution for such emotional causes as well in order to have a healthy generation ahead.