International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
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IJCRR - Vol 08 Issue 05, March, 2016

Pages: 33-36

Date of Publication: 13-Mar-2016


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STRESS DURING PREGNANCY AND LACK OF CALCIUM AND FOLIC ACID INCREASES RISK OF AUTISM SPECTRAL DISORDER IN OFFSPRING

Author: Nandini Vaz Fernandes

Category: Healthcare

Abstract:The idea that preconception environmental exposures may be involved in Autism Spectrum Disorders (ASD) etiology arose in the 1970s from a retrospective case-control study of ASD that found a statistically significant difference in parental occupational exposure to chemicals during the preconception period 1. ASD are neurodevelopmental disorders characterized by varying deficits in social interactions, communication, and learning, as well as stereotypic behaviors. Over the past years, research into environmental risk factors for autism has grown dramatically, bringing evidence that an array of non-genetic factors acting during the prenatal period may influence neurodevelopment 2. The present study was therefore undertaken to investigate the potential prenatal risk factors for ASD. A total number of 184 individuals were studied. In the present study, factors that have demonstrated significant increases in ASD risk, include advanced maternal age and stress during pregnancy while folic acid and calcium supplement intake was found to be reducing the risk of ASD. Factors that showed insignificant increase in frequency or no association with ASD were intake of medications, fall, respiratory problems and bleeding during pregnancy.

Keywords: ASD, Maternal stress, Maternal age, Folic acid

Full Text:

INTRODUCTION Autism spectrum disorders (ASDs) are complex conditions, with combinations of milder social abnormalities and communication impairment and less rigid interest restrictions. Genetic factors may be the most significant cause for autism spectrum disorders. Others factors may alter this underlying genetic liability such as sex, IQ, and prenatal and perinatal injury1 . From the earlier research works, it is known that ASD is not caused by a single factor. Both genetic and environmental factors have the potential to increase the risk of ASD. The present study was undertaken to investigate potential prenatal and perinatal factors risk factors for ASD.

SUBJECTS AND METHOD To achieve the objective of the study, 184 individuals were surveyed. The individuals surveyed were divided into ASD group and control group. The sample population included ASD group consisting of 92 ASD subjects and control group constituted by 92 subjects of similar age group but with no history of ASD. For achieving the objectives of the study a Proforma was designed to collect information about Prenatal and perinatal factors studied included medications taken, supplements taken during pregnancy, maternal stress, respiratory problems, fall during pregnancy and bleeding during pregnancy. The data collected using the proforma was tabulated and analyzed. For quantitative data, mean and standard deviation were computed. The statistical significance of associations between the various qualitative parameters was evaluated through Fisher’s exact test (two tail).

RESULT ASD subjects studied had a mean age of 9.02 ± 3.26 years. The mean age of detection of the ASD subject’s studied was 2.7 ±1.76 years with a variance of 3.11. The following prenatal factors were studied.

1. Maternal Age: We observed that with advanced maternal age, the risk of having a child with ASD increase. Age of pregnancy in different age intervals of both control and ASD is tabulated (Table 1). The frequency of ASD was higher in maternal age intervals of 31-35 and 36-40 years. The mean maternal age during pregnancy of the ASD subject’s studied was 27.8 ± 5.36 years and a variance of 28.7. The results indicate a significantly higher frequency of 26.09% ASDs in children born to mothers in age interval of 31 – 35 (P = 0.0306) as compared to the control.

2. Intake of medication during pregnancy and ASD: The present study showed an increase in the frequency of ASD in offspring of mothers who consumed medication during the first trimester of pregnancy. The study indicates that higher frequency of 39.13% of history of intake of medication in the mothers of ASD as compared to the control (28.57%). The difference was found to be statistically insignificant (P=0.4312).

3. Stress during pregnancy and ASD: Stress on mothers during pregnancy was another factor studied. Mothers of the subjects were interrogated for physical and mental stress during their pregnancy, in both the control and ASD group. The frequency of stress during pregnancy was found to be higher in mothers of ASD group as compared to those in the control group. The difference is found to be statistically significant (P=0.0257).

4. Respiratory problems during pregnancy and ASD: To evaluate the role of the hypoxic condition of a mother during pregnancy, we analyzed the sample population for respiratory problems during pregnancy. The present study found no correlation between respiratory problems during pregnancy and ASD.

5. Maternal infection during pregnancy and ASD: Infection of the mother may be also a source of impeding the growth of the fetus, which can be a potential risk factor for ASD in offspring. The present study found no correlation between maternal infections during pregnancy and ASD (P = 0.6887).

6. Fall during pregnancy and ASD: This factor was studied to see if the physical impact of fall during pregnancy can be a potential risk factor. The frequency of ASD was higher in 13.04% of the mothers who had a fall during pregnancy as compared to the control. However, the difference was found to be statistically insignificant (P=0.1226).

7. Intake of supplements during pregnancy and ASD: Different types of supplements are necessary for growth and development of the fetus. The vital supplements include vitamins, folic acid, iron, and calcium. The present study tried to evaluate the effect of not consuming folic acid or calcium or both. Most of the mothers of ASD subjects had not consumed folic acid and calcium supplements (52%) as compared to the control (5.5%). The difference was found to be statistically highly significant (P=0.0039).

8. Bleeding during Pregnancy: The present study found no correlation between maternal bleeding during pregnancy and ASD (P = 0.4898).

DISCUSSION The present study evaluated the risk that a child will develop autism increases monotonically with the age of the mother. This study revealed that maternal age during pregnancy is a very crucial factor in determining the neurological development of the fetus. This study indicates a significantly higher frequency of 26.09% of ASDs in children born to mothers in age interval of 31 – 35 (P = 0.0306) as compared to the control. The present study is consistent with the findings of Croen LA et al,3 Kolevzon A et al.,4 and Gardener5 which state that older parents may be statistically more likely to have children with autism. Study of Sandin S et al.,6 reports that children of mothers older than 35 years had 30% increased the risk for autism.

Association of medication during pregnancy with autism risk is indicated in the study of Gardener4 . According to his study, maternal medication use was associated with a 46% increased risk. The present study, however, does not agree with the study of Gardener4 . This study shows a higher frequency of 39.13% of the mothers in ASD group had taken medication during pregnancy as compared to the control (28.57%). However, the difference was found to be statistically insignificant (P=0.4312). Strongest evidence of maternal hypertension and ASD risk is indicated in the studies of Gardener4 .

The important revelation of this study was the association of maternal stress during pregnancy and increased the risk of ASD. The frequency of stress during pregnancy was found to be significantly higher in mothers of ASD group as compared to those in the control group (P=0.0257). Studies of Rai D et al.,7 also revealed that exposure to stressful life events during the prenatal period is associated with an increased risk of offspring ASD.

Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. The nutritional supplements taken were found to be having a positive influence in decreasing the ASD risk, as per the present study. Most of the mothers of ASD subjects had not consumed all supplements (21.74%) as compared to the control. This study reinforces the findings of Schmidt R. J et al.,8 which indicated that women who consume the recommended daily dosage of folic acid, the synthetic form of folate or vitamin B-9, during the first month of pregnancy may have a reduced risk of having a child with autism. Studies of Lyall K, et al.,2 also support that higher maternal intake of certain nutrients and supplements like folic acid has been associated with a reduction in ASD risk. Vitamin D deficiency – eitherduring pregnancy or early childhood – may be an environmental trigger for ASD in individuals genetically predisposed for the broad phenotype of autism9 .

The factors with the strongest evidence against a role in autism risk included maternal bleeding, intake of medications, respiratory problem and fall during pregnancy. However, meta-analysis of Gardner10 identified fetal distress as potential risk factors for ASD and showed significant 81% elevated risk of ASD in relation to maternal bleeding during pregnancy. The mechanism underlying the suggested association with maternal medication use is also unclear, due to the variety of medications consumed during pregnancy and assessed in these studies.

Heterogeneity in some studies may be on account of methodological limitations that have impaired the precision and validity of results of most studies include small sample size, non-normal control groups, broad disease definition, and retrospective parental recall of exposures which may result in the high possibility of recall bias. Thus, the rising prevalence of ASD, coupled with the severe emotional and financial impact on the families, underscores the need for large, prospective, population-based studies with the goal of elucidating the modifiable risk factors, particularly those during the prenatal period.

CONCLUSION Many factors may have a potential for increasing the risk of ASD. ASD is influenced by both genetic and environmental factors, and the risk increases most likely due to the underlying genetic factors or an interaction of these factors with the environment. In other words, ASD is a complex disorder resulting from the combination of genetic and environmental factors. Those having genetic susceptibility may be more vulnerable to develop ASD when exposed to the environmental risk factors. In the present study, the factors with the strongest evidence for an association with autism risk included advanced maternal age and stress during pregnancy. The study also indicates that folic acid and calcium supplement intake was found to be reducing the risk of ASD. The factors with the strongest evidence against a role in autism risk included were the intake of medications, fall, respiratory problems and bleeding during pregnancy.

ACKNOWLEDGEMENT Author acknowledges the immense help received from the scholars whose articles are cited and included in references of this manuscript. The author is also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

References:

1. Freitag CM. The genetic of autistic disorders and its clinical relevance: a review of the literature. Mol Psychiatry. 2007; 2(1): 222.

2. Lyall K, Schmidt RJ, Hertz-Picciotto I. Maternal lifestyle and environmental risk factors for autism spectrum disorders. Int J Epidemiol. 2014; 43(2):443-64.

3. Croen LA., Najjar DV, Fireman B, Grether JK. Maternal and paternal age and risk of autism spectrum disorders. Arch Pediatr Adolesc Med. 2007; 161(4): 334-40.

4. Kolevzon A, Gross R, Reichenberg A. Prenatal and perinatal risk factors for autism: a review and integration of findings. Arch Pediatr Adolesc Med. 2007; 1(4):326-33.

5. Gardener H., Spiegelman D, Buka SL. Prenatal risk factors for autism: comprehensive meta-analysis. Br J Psychiatry. 2009; 195(1): 7-14.

6. Sandin S, Christina M., Hultman K A, Gross R, MacCabe JH, Reichenberg A. Advancing Maternal Age Is Associated With Increasing Risk for Autism: A Review and Meta-Analysis. J Am Acad Child Adolesc Psychiatry. 2012 May;51(5):477-486.e1. doi: 10.1016/j.jaac.2012.02.018. Epub 2012 Apr 5.

7. Rai D, Golding J, Magnusson C, Steer C, Lewis G, Dalman C. Prenatal and early life exposure to stressful life events and risk of autism spectrum disorders: population-based studies in Sweden and England. PLoS One. 2012;7(6):e38893. doi: 10.1371/ journal.pone.0038893. Epub 2012 Jun 13.

8. Schmidt RJ, Tancredi DJ, Ozonoff S, Hansen RL, Hartiala J, Allayee H, et al. Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study. Am J Clin Nutr. 2012 Jul;96(1):80-9. doi: 10.3945/ajcn.110.004416. Epub 2012 May 30.

9. Ko?ovská E, Fernell E, Billstedt E, Minnis H, Gillberg C. Vitamin D and autism: Clinical review. Research in Developmental Disabilities. 2012; 33: 5pp 1541–1550.

10. Gardener H., Spiegelman D, Buka SL. Perinatal and neonatal risk factors for autism: a comprehensive meta-analysis. Pediatrics. 2011; 128: 344–355.

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Best Article Award: 

One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

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Best Article Award

A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma COLAKOGLU entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by Arpita M. et al entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09
Late to bed everyday? You may die early, get depression
Egg a day tied to lower risk of heart disease
88 Percent Of Delhi Population Has Vitamin D Deficiency: ASSOCHAM Report

List of Awardees

Awardees of COVID-19 Research

Woman Researcher Award

A Study by Neha Garg et al. entitled "Optimization of the Response to nCOVID-19 Pandemic in Pregnant Women – An Urgent Appeal in Indian Scenario" published in Vol 12 issue 09

A Study by Sana Parveen and Shraddha Jain entitled "Pathophysiologic Enigma of COVID-19 Pandemic with Clinical Correlates" published in Vol 12 issue 13

A Study by Rashmi Jain et al. entitled "Current Consensus Review Article on Drugs and Biologics against nCOVID-19 – A Systematic Review" published in Vol 12 issue 09

Emerging Researcher Award

A Study by Madhan Jeyaraman et al. entitled "Vitamin-D: An Immune Shield Against nCOVID-19" published in Vol 12 issue 09

Study by Dheeraj Kumar Chopra et al. entitled "Lipid-Based Solid Dispersions of Azilsartan Medoxomil with Improved Oral Bioavailability: In Vitro and In Vivo Evaluation" published in Vol 12 issue 19


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