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ORIGINAL ARTICLE
Year : 2022 | Volume
: 8
| Issue : 3 | Page : 137-144
Association between iron-deficiency anemia and antenatal depression in a semi-urban population of south India: A cross-sectional study
Roopa Satyanarayan Basutkar1, Pooja Sudarsan1, Chris Elizabeth Vinod1, Resia Varghese1, Divya Perumal2, Ponnusankar Sivasankaran1
1 Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Tamil Nadu, India
2 Department of Obstetrics and Gynecology, Government District Headquarters Hospital, JSS Academy of Higher Education and Research, Ooty, Tamil Nadu, India
Correspondence Address:
Dr. Ponnusankar Sivasankaran
Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty - 643 001, The Nilgiris, Tamil Nadu
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/ijam.ijam_133_21
Introduction: Iron-deficiency anemia (IDA) during pregnancy affects the glial cells of the brain of mother, which results in altered neuronal myelination with dysregulation. Although several factors could lead to antenatal depression, IDA is an emerging etiology. The primary objective of this study is to determine the relationship between IDA and antenatal depression among pregnant women.
Materials and Methods: This cross-sectional study was conducted at Government Head Quarters and Hospital, in Udhagamandalam. A total of 210 pregnant women in the second trimester were enrolled and categorized into iron-deficient anemia and noniron-deficient anemia groups based on their hematological results. The risk of depression was assessed using the validated Edinburgh Depression Scale (EDS). A Chi-square test for categorical variables and an independent t-test for continuous variables were used. A Pearson's correlation analysis was performed to check the association of EDS scores with participants' demographic characteristics and hematological parameters. Regression analysis was conducted to predict the outcome variable.
Results: The distribution of depression was significantly varied between the groups. EDS score was significantly higher in the IDA group in comparison with the non-IDA group (12.78 ± 3.40 vs. 8.82 ± 3.12; P = 0.005; 95% confidence interval 2.94–4.87). The odds of developing antenatal depression are 12 times higher in the iron-deficient group, P < 0.001.
Conclusions: Our findings suggest that IDA acts as an independent factor in influencing antenatal depression.
The following core competencies are addressed in this article: Medical knowledge, Patient care, Practice-based learning and improvement.
Keywords: Anemia in pregnancy, antenatal depression, Edinburgh Depression Scale, iron-deficiency anemia, preterm birth
Iron is an important micronutrient present in our body and is responsible for many vital functions such as oxygen transport, metabolic processes, regulation of cell growth, and cell differentiation.[1] The likelihood of depression occurring is heightened during the period of pregnancy but generally goes unrecognized and untreated. The prevalence rate of perinatal depression varies globally.[1],[2] Iron-deficiency anemia (IDA) may contribute to perinatal depression. Iron and ferritin are found to be heterogeneously distributed in the brain. Its deficiency in the glial cells can cause altered myelination of neuronal cells along with impaired neurotransmitter metabolism, leading to delay in motor maturation and alternation in the development of the brain.[3],[4],[5] The physiological drop in hemoglobin (Hb) in mid-trimester, which is due to the increased need for fetal blood circulation, is one of the possible contributing factors to antenatal depression.[6]
The prevalence of IDA in pregnant Indian women is the highest in the world and ranges from 9.18% to 36.7%.[7] If this condition is left untreated, it could lead to several obstetric complications such as premature birth, low birthweight, and morphological changes in the fetus that delays the development and intensify the chance of the mother getting postpartum depression.[8],[9],[10],[11] These complications can be prevented through early detection and management.[12],[13] The present study was conducted to find out the association between IDA and antenatal depression among pregnant women in their second trimester of gestation in India.
MethodsStudy design and setting
A cross-sectional, observational study was carried out in a secondary care hospital. It was conducted for 8 months from December 2018 to July 2019 recruiting 210 singleton pregnant women in their second trimester using simple random sampling. The World Health Organization, classification was used: mild anemia (Hb levels 9–10.9 g/dL), moderate anemia (Hb levels 7–8.9 g/dL), and severe anemia (Hb levels <7 g/dL). In this study, the participants with mild-to-moderate IDA were included since the symptoms of depression are manifested at this stage.[13] Patients with severe IDA were not included since; its physical symptoms (fatigue, loss of energy, appetite, and sleep changes) can confound the identification of antenatal depression.[14] Data were collected from the medical records of the participant and depression was assessed using the Validated Tamil version of the Edinburg Depression Scale.[15] Edinburgh Depression Scale (EDS) is a 10-item questionnaire that has a significant level of sensitivity and specificity in identifying depression. A score <8 rules out the possibility of depression. Scores 9–13 indicate the possibility of depression. A participant is considered to have probable depression for scores ≥14.[16],[17],[18]
Inclusion and exclusion criteria
Primary screening was done based on the eligibility criteria. Pregnant women aged 18–45 years at the time of consent, in their 13th–28th weeks of gestation, were recruited for the study. The participants who were already on routine medication such as folic acid (0.5 mg), FeSo4 (100 mg of elemental iron), and Vitamin B Complex tablet were included. Moderate anemic (Hb: 7–-9.9 g/dL) and nonanemic (Hb: ≥11 g/dL) was the targeted population.
Pregnant women with chronic diseases, a history of high-risk pregnancy, hemoglobinopathy, and autoimmune diseases were excluded from the study. Participants who came with mental health concerns or those on any antidepressants were also eliminated from the study, as this would interfere with the study outcome measures.
The written informed consent form was collected. All procedures involving human subjects were approved by the Institutional Review Board, JSS College of Pharmacy, Udhagamandalam (JSSCP/IEC/04/2018-19). The study has been registered by the Clinical Trials Registry (CTRI) of India (CTRI/2018/11/016461).
Data collection
Randomization
Pregnant women in their second trimester of pregnancy were allocated into IDA and Non-IDA groups randomly based on their levels of Hb measurements as per the inclusion and exclusion criteria.
A specially designed data collection form was used, which had closed and opened end questions to collect the sociodemographic details, medical and medication history, supplement intake, and obstetric details. It was also used to collect the anthropometric measurements, physical examination, and vital parameters that were recorded at study enrollment. The data were collected prospectively as a single encounter from each participant in their second trimester of pregnancy from their respective medical records and who had confirmed their pregnancy with ultrasonography results. Blood samples were collected for laboratory measurement which was followed by the assessment of depression scores using the EDS.
Laboratory measurement
Five milliliters of venous blood was withdrawn from the study participants into a sterile tube and was centrifuged for 30 min at room temperature. Serum was separated and analyzed on the same day. Hb was estimated using Drabkin's method, while the remaining parameters were estimated using a fully automated hematology analyzer.
Data analysis
Sample size calculation was performed based on the study conducted by Dama et al.[19] as their demographic's details are relatable to the South Indian study population. To demonstrate a significant difference at 80% power and 5% level of significance with groups (IDA patients and non-IDA patients) ratio being 1:2, approximately 210 participants were required, i.e., 70 participants in the IDA patients' group and 140 participants in the non-IDA patients' group for adjusted odds ratio (OR) 2.51. The sample size has been adjusted for the dropout rate (approximately 15%) that may occur during the study. It was calculated using Open-Source Epidemiologic Statistics for Public Health (OpenEpi).
Descriptive analysis was performed for demographic characteristics. Categorical variables were expressed as percentages and continuous variables as unadjusted means with standard deviations. For normally distributed data, parametric tests were used to measure the differences in variables among the groups. A Chi-square test for categorical variables and an independent t-test for continuous variables were used. Skewed data were analyzed using Mann–Whitney U-test. A Pearson's correlation analysis was performed to check the association of EDS scores with participants' demographic characteristics and hematological parameters. Regression analysis was conducted to predict the outcome variable. A simple linear model was prepared based on the inferences obtained from multivariate linear regression. The effect of each variable on the outcome was adjusted at a significance of P < 0.05. OR was calculated using binary logistic regression. All analysis was conducted using the IBM SPSS statistical software (V.21.0; SPSS Inc, Chicago, Illinois, USA).
ResultsParticipant recruitment status
Two hundred and fifty-one pregnant women in their second trimester of pregnancy were recruited through simple random sampling and assessed for eligibility and 210 of the pregnant women fulfilled the inclusion criteria and provided consent to be a part of the study [Figure 1]. A total of 210 study participants were assigned to the IDA group and the non-IDA group. Forty-one participants were excluded due to illiteracy, denial, comorbidities, and mild and severe anemia.
Demographic characteristics
The demographic characteristics of the study participants are listed in [Table 1]. Variables such as income, education, occupation, marital status, gravidity, abortion, social habits of husband, concurrent use of iron supplements, and consanguinity were equally distributed between the groups.
Table 1: Demographic characteristics of 210 study participants in the iron-deficiency anemia group and noniron-deficiency anemia group groupsThe results of physical examination and vital signs are listed in [Table 2]. The participants in the study had a mean gestation age of 21.90 ± 5.18. No statistically significant difference was seen in a physical examination and vital signs results in both the groups.
Table 2: Physical and vital sign examination of 210 study participants in the iron-deficiency anemia and noniron-deficiency anemia groupsHowever, some factors, such as diet and depression, showed a significant difference among IDA and non-IDA groups. The distribution of depression was significantly varied between the groups [Figure 2]. There were significantly higher cases of antenatal depression in the iron-deficient group (92.9 vs. 59.3; P = 0.00; 95% confidence interval [CI] 0.00–0.01). Iron-deficient pregnant women showed a significantly higher EDS score in comparison with the non-IDA group (12.78 ± 3.40 vs. 8.82 ± 3.12; P = 0.005; 95% CI 2.94–4.87).
Figure 2: Classification of antenatal depression in IDA and non-IDA groups. IDA: Iron-deficiency anemiaThe hematological parameters and complete blood count measured during their visit are presented in [Table 3]. A statistically significant difference in the hematological parameters in IDA and non-IDA group was observed.
Table 3: Complete blood count and selected blood chemistries in iron-deficiency anemia and noniron-deficiency anemia groupsPearson's correlation was performed between EDS scores and various variables since the variables were normally distributed [Table 4]. The strength of association between Hb and mean cell hemoglobin concentration (MCHC) with EDS scores was found to be moderately negative. Hence, the EDS scores increase with a moderate decrease in the Hb and MCHC levels. The hematocrit, ferritin, serum iron, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were also weakly correlated with EDS scores. However, a positive correlation was observed between total iron-binding capacity and EDS scores.
Table 4: Correlation between Edinburgh Depression Scale scores and various variablesThe results of multiple linear regression analysis are listed in [Table 5]. Although several independent variables were included in the analyses, predictor is such as ferritin (r = –0.50), consanguinity (r = –0.15), and income r = 0.12) correlates best with EDS scores (dependent variable); P < 0.05. Hence, it is likely that these variables will best predict EDS scores. The t-tests associated with the B-value are statistically significant at P < 0.05, which indicates that the predictors are making a significant contribution to the linear model.
Table 5: Prediction of the Edinburgh Depression Scale score by the independent variables using multivariable linear regression analysisThe logistic regression model was statistically significant, P < 0.001. The model explained 22% (Nagelkerke R2) of the variance in depression and correctly classified 70.5% of cases. The iron-deficient pregnant population was 12 times more likely to develop depression than the noniron-deficient pregnant population [Table 6].
Table 6: Binary logistic regression analyses showing independent variables associated with Edinburgh Depression Scale score as the dependent variable in study population Discussion IDA during pregnancy remains a widespread public health concern in most developing countries and even developed countries.[20],[21] Studies investigating the association between IDA and depression during the antenatal period are scarce; hence, we have reported a comparison of our study with the only available literature on this association[19],[22] In this study, we have included the pregnant women between 13 and 28 weeks of gestation period due elevated fetal blood circulation.
The inferential statistics using Pearson's correlation test yielded a strong association between maternal iron status and depression outcomes. The findings of this are dissimilar to a study conducted by Tran et al., where reverse causality was found to be significant among pregnant women because the magnitude of the effect of depression could not be detected due to the smaller sample size.[23]
By analyzing the demographic characteristics of nonanemic and anemic patients, all were equally distributed in both the groups at a P < 0.05, which is consistent with the literature.[19],[22] In terms of gravidity (P = 0.01), it was found to be significantly different in both groups this is different from Yilmaz et al.[21] as their age group for recruitment had extended to a maximum of 43 years.
The presence of antenatal depression (P = 0.02) was found to be 45% in the iron-deficient group and 25% in the iron-sufficient group in the study conducted by Dama et al.[19] In the present study, the probability of study participants having depression was found to be 41.4% in the iron-deficient group and 7.9% in the iron-sufficient group. A similar difference was found in the EDS scores (P = 0.000) by Yilmaz et al.[22] This may be because a reduced level of iron can lead to hypomyelination of neurons, which results in impaired production and release of neurotransmitters such as dopamine and serotonin that play a major role in the pathogenesis of depression.[6],[7] The distribution of diet was significantly different between the groups. Nonvegetarians were higher in the non-IDA group, while the IDA group consisted of more vegetarians. A recent review of several cross-sectional studies showed that meat intake is positively correlated with an elevation in serum ferritin levels.[24],[25]
Statistically significant difference at P < 0.05 was found while comparing Hb, red blood cell, hematocrit, MCV, MCH, and MCHC levels in both groups. These findings were similar to a study conducted by Yilmaz et al.[21] Pearson's correlation showed a weak-to-moderate negative correlation for some of the hematological parameters with EDS scores. This is because a reduced level of these laboratory parameters in the blood indicates IDA, thereby causing depressive symptoms which could increase the scores on the EDS scale. The influence of risk factors on depression was minimal since the population recruited was from a similar socioeconomic background.
Several risk factors contribute to depression such as financial burden, consanguinity, domestic violence, and history of depression.[26],[27] Based on the linear regression analysis of our study; income, consanguinity, and ferritin showed a significant effect on depression. A study that was conducted on the southern Indian population suggested that consanguineous marriages are at higher risk of depression and the mechanism behind this is hypothesized to be genetic.[28] Similarly, our study supports this association with a P = 0.009. Studies conducted in South Africa[29] and Australia[30] showed a positive relationship between depression and low income among pregnant women and the findings were similar to our study results (P = 0.040).
The odds of developing antenatal depression due to IDA in pregnant women were found to be 12 times greater at P < 0.001 (95% CI: 4.14–34.74) than in the non-IDA group. IDA can increase the risk of antenatal depression by 2.51 times in accordance with the results of Dama et al.[19] The study conducted by Yilmaz et al.[22] represented the strength for depression as 25.3% and 24.4%, respectively. Our study findings portrayed the magnitude of antenatal depression to be 30.9%.
This is the first study that defined the association between IDA and antenatal depression in the Indian population. We enrolled pregnant women in the second trimester due to the increased fetal blood circulation. Furthermore, during this trimester the mothers would have adapted to the hormonal fluctuations, thereby decreasing their influence on depression. EDS was used in this study which had the added advantage of excluding the constitutional symptoms of IDA such as sleep deprivation and fatigue. Participants were from the same socioeconomic background, thereby minimizing the risk of heterogeneity. Although there are many variables affecting perinatal depression, we believe that our findings are clinically significant.
The clinical manifestations of anemia are similar to some symptoms of depression like fatigue, which was resolved by the use of the EDS scale because it excludes physical symptoms. The limitations of the study include, the reverse causality, i.e., antenatal depression could also lead to IDA was a possibility that was not ruled out in this study. Since it is a cross-sectional study, the change in depression score after correction of iron status cannot be known. However, it was managed by collecting history regarding psychiatric illness.
ConclusionsIDA is a possible risk factor for antenatal depression, which has deleterious effects on the mother and infant. Our findings suggest that the odds of developing depression were found to be greater in the iron-deficient group. Since it is the first study to be reported on the Indian population, there is an increased need for further prospective studies in larger samples. Our study emphasizes the need to create awareness among clinicians on the role of IDA in antenatal depression, thereby necessitating the need for early detection and treatment.
Acknowledgments
We would like to thank and acknowledge the support provided by the Government District Headquarters Hospital Udhagamandalam and JSS College of Pharmacy, Ooty for the assistance and facilitation provided. Express our gratitude to all the study participants.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Research quality and ethics statement
The authors of this manuscript declare that this study complies with reporting quality, formatting, and reproducibility guidelines set forth by the schedule Y guidelines of Drugs and Cosmetic rules of India and ICH GCP guidelines. The authors also attest that this study was provided by Institutional Review Board and the protocol/approval number is JSSCP/IEC/04/2018-19.
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