Journal of Pregnancy and Child Health
Open Access

Depression is one of the main causes of disability which affects approximately 280 million people globally [1].

Antenatal depression occurs during pregnancy, and can have consequences for both the mother and the newborn. It is estimated that the prevalence in Spain and neighbouring countries is around 10-15% [2-5], and that approximately 1.8-8% of pregnant women with depression use antidepressants [6-8].

Mental health problems impact pregnancy and childbirth and might also correlate with adverse outcomes for the newborn and the baby’s development (HOWAR). One study, correlated depression in pregnant mothers under 35 years of age with hyperemesis, abortion, foetal malposition, caesarean section, and even intrauterine death [9]. Although they do not fully specify pathophysiological mechanisms, Aldane and colleagues concluded that maternal antenatal mental health disorders might be associated with a moderate increase in stillbirth and infant mortality [10].

In a systematic review comparing 20 cohort studies, Jahan, et al. conclude that untreated depression during pregnancy is associated with abortion, prematurity, Low Birth Weight (LBW, birth weight <2500 g), Small for Gestational Age (SGA), complications during delivery and postpartum depression [11].

Low birth weight is a predictor of short and long-term health. During the neonatal period, low birth weight is associated with a higher risk of infection, respiratory distress and mortality [12,13]. Later in life, it is associated with developmental delay, cardiovascular disease, and diabetes [14,15].

The aim of this study is to verify if antenatal depression has any deleterious effect on maternal and neonatal outcomes.

Study design and data collection

Retrospective, observational cohort study in pregnant women between 2012-2018 in the health region of Lleida.

Data were obtained from patients who had given birth at the Arnau de Vilanova Hospital between January 1, 2012 and December 31, 2018. The Arnau de Vilanova hospital is the only referral hospital in the region. Data were obtained from the CMBD database (Catalan acronym for minimum data set) in the E-CAP electronic medical records database, and from the Catalan health service database, which contains the electronic prescriptions made by Catalan health service professionals.

This study is part of the ILERPREGNANT project, which aims to analyse the population prevalence of diseases, drug prescription and pharmacological adherence during pregnancy [16].

Participants

Women who had delivered between January 1, 2012 and December 31, 2018. Data from the date of the last period to the date of delivery were included. This means that data from 2011 were included for women with a last period date in 2011 and a delivery date in 2012. Women from health regions other than Lleida were excluded. To evaluate the representativeness of the sample, the percentage of births studied (births registered in the Arnau de Vilanova University Hospital in Lleida) was calculated with respect to the total number of births in the health region of Lleida according to the Statistics Institute of Catalonia (Idescat) (Table 1).

Table 1: Number of births registered in Lleida sample in comparison to the Lleida health region per year

The variables recorded were as follows: Depression (yes/no), which includes a diagnostic for depression according to the International Classification of Diseases, 9th revision (ICD-9) with codes 296.20 to 296.25, 296.30 to 296.35, 300.4, or 311, and in the 10th revision (ICD-10) with codes F32.0 to F32.9, F33.0 to F33.3, F33.8, F33.9, F34.1, or F41.2; age; Body Mass Index (BMI); diabetes mellitus (ICD-10 O24.9); risk of the pregnancy; duration of the pregnancy (miscarriage, preterm, term, prolonged); caesarean section; birth weight (<2500 g=underweight, between 2500 g and 3999 g=normal weight, and ≥ 4000 g=macrosomia), 1-minute and 5-minute Apgar score; and preeclampsia. Data were also collected on prescribed antidepressant drug, dispensation date, dose and amount. Antidepressants were classified into four classes following the Anatomical Therapeutic Chemical (ATC) classification system.

Data analysis

A descriptive analysis was performed, with numerical variables described by mean and standard deviation, and categorical variables by absolute and relative frequencies. To evaluate differences between groups, we used Student's t-test or Chi-square test for numerical and categorical variables, respectively. The association of the different variables with depression was evaluated with a multivariate linear model, using percentage of depression as the response variable, and the rest of the variables as predictors. Regression coefficients and odds rations and their 95% confidence interval were calculated.

Ethics

This study was approved by the Clinical Research Ethics Committee (CREC) of the Institut d’Investigació IDIAP Jordi Gol (code 19/196-P). The study follows the tenets of the Declaration of Helsinki. The information was extracted from centralized medical files in the E-CAP database by the department of research management and health evaluation. Informed consent from participants was not required. The variables in the E-CAP database were de-identified and processed following confidentiality guarantees established by the National Law and Regulation 2016/679 of the European Parliament and of the Council on personal data protection.

Participants

Participants include a sample of 21,375 pregnant women who had given birth at the Arnau de Vilanova Hospital in Lleida between 2012 and 2018 (both included). Women who did not have a health card (n=1625) were excluded. Women with missing data in their medical records were also excluded (n=2573). The final sample consisted of 17,177 patients (Figure 1).

The average age of pregnant women during the study period was 30.5 years. A total of 436 women (2.54%) suffered from depression. In 20 women (0.13%), depression was considered gestational (Tables 2-4).

Figure 1: Sample of pregnant women.

Table 2: General characteristics of the sample.

Table 3: Depression diagnosis in pregnant women for each study year.

Table 4: Depression prevalence and relationship with other factors.

Table 3 shows percentage of depression for each year of study. The average prevalence of depression was 2.5%. Patients with depression have a higher average age, a higher body mass index, and are more often classified as high-risk pregnancy. The difference in prevalence of low birth weight is statistically significant, with 5.85% in children of patients without depression versus 11.7% of babies born to mothers with depression. No differences were found in relation to pre eclampsia, Apgar score and number of caesarean sections.

Regarding pharmacological treatment, 14.9% of patients with depression received treatment, 71.3% drugs are selective serotonin reuptake inhibitors, followed by 12.1% serotonin-norepinephrine reuptake inhibitors, 7.89% non-selective monoamine oxidase inhibitors, and 6.58% atypical antidepressants. The most commonly prescribed drugs were paroxetine, followed by sertraline, citalopram and escitalopram. All patients diagnosed with depression received pharmacological treatment.

The regression model shows that pregnant women with depression have a significantly higher risk pregnancy, in particular in relation to low birth weight. In contrast, no significant differences were found regarding the 1-minute Apgar score, pre-eclampsia and number of caesarean sections (Figure 2).

Figure 2: Multiple linear regression: Prevalence of depression in relation to adverse variables.

This study shows a prevalence of antenatal depression of 2.54%, 14.9% patients taking one or more antidepressant. Pregnancy of women with depression was more frequently classified as very high risk (4.9) and show more risk of miscarriage (1.64). For the new born, low birth weight (OR 2.2) was significantly more common in infant from women with depression (11.8%) compared to infant from women without depression (5.87%).

Results of adverse consequences vary in the studies on antenatal depression. A meta-analysis carried out by Ghimire, et al. found an increased risk of preterm birth (RR=1.35, 95% CI 1.19–1.52), low birth weight (RR=1.86, 95% CI 1.32–2.62) and intrauterine growth retardation (RR=4.39, 95% CI 2.45–7.86) [17,18]. Lang, et al. and Nasren, et al. also reported an increased risk of low birth weight [19,20]. However, other studies have not reported this association. The systematic review and meta-analysis by Fekadu Dadi, et al. attribute the higher prevalence of depression to the economic and psycho-social situation of pregnant women. This psycho-social situation might influence the relationship observed between anxiety/depression and prematurity. Women living in disadvantaged neighbourhoods have less access to quality food and health services, fewer leisure opportunities and more social and financial stress, which might determine the adverse effects on pregnancy.

In a systematic review of 20 studies on untreated antenatal depression published in 2021, Jahan, et al. underscored the relationship with low birth weight, and also with preterm delivery, death of the newborn (in addition to other perinatal complications), and postpartum depression.

Other studies point at the causative effect of antidepressant treatment rather than depression on birth weight. Specifically, in 2016 Nezvalová-Henriksen, et al. studied the effect of exposure to SSRIs during the 2nd and 3rd trimester pregnancy, concluding that it was associated with an average decrease of 4.9 days of pregnancy and of 205 g of birth weight.

In 2017, Mitchell, et al. conducted a systematic review to compare women who had taken antidepressants during their pregnancy with women diagnosed with depression and not treated. Regarding the average weight of the newborn, 6 of 9 studies did not find significant differences, two observed a higher risk of small for gestational age due to antidepressant treatment, and one study concluded that untreated depression was a risk factor for low birth weight. Only one study analysed abortion, and it was inconclusive. Another study found that children born to mothers who adhered to antidepressants weighed 71.9 g less than children of mothers who discontinued treatment (95% Confidence Interval (CI): −115.5, −28.3 g), with a larger difference for girls (−106.4 g, 95% CI: -164.6, −48.1) than boys (−48.5 g, 95% CI: −107.2, 10.3).

Among the limitations, we should consider that in this study, 14.9% patients diagnosed with depression receive antidepressant treatment. Therefore, we have not analysed the influence of the treatment on the outcomes of the study or the adherence to it, which may condition different results. Importantly, this study has not stratified by socio-demographic variables that might affect pregnancy, but it is a population study conducted with data from a referral hospital that covers a high percentage of the population.

Antenatal depression is a risk factor for infant morbidity and mortality. In this study, maternal depression was associated with an increased risk of low birth weight, miscarriage and categorization of risk pregnancy. We underscore the relevance of early detection and treatment of depression in pregnancy. Further research is needed to evaluate the impact of depression on mother and child, taking into account severity, antidepressant treatment and other associated factors, in order to improve the management of pregnant women with depression.

The authors would like to thank Dr. Miquel Buti for his valuable contribution and help in the design and creation of the database, and Laura Azlor for her contribution in the statistical analysis. All authors have read and approved the final version of the manuscript.

All authors (M.O., M.L., J.S., D.P., M.C.S. and B.S.R.) contributed to the study conception and design. Material preparation, data collection and analysis were performed by M.O., M.L., J.S., D.P. and M.C.S. The first draft of the manuscript was written by B.S.R., M.L. and M.O.; and all authors commented on previous versions of the manuscript. All authors have read and agreed to the published version of the manuscript.

There was no funding to carry out this study. This research didn’t receive any specific grant from funding agencies in the public, commercial, or non-profit sectors.

Not applicable.

This study was approved by the ethics and clinical research committee of the “Institute for Primary Health Care Research Jordi Gol i Gurina (IDIAPJGol)” under the code 19/196-P. The study was conducted in accordance with the principles of the Declaration of Helsinki. Pseudonymized retrospective descriptive cross-sectional study adheres to Additional Provision 17.2.d LOPD-GDD for research purposes, without the need to obtain the consent of the data holders. There is a technical and functional separation between the research team and the performer pseudonymization, the data is only accessible to the research team, and technical measures have been taken to prevent such re-identification and access by third parties through the CMBD database (“Conjunt Minim de Base de Dades”), the E-CAP computerized medical history database and the Catalan Health Service database.

Available upon request to corresponding author (dperejon.lleida.ics@gencat.cat).

The authors declare no conflict of interest.

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