The effect of vitamin D and calcium supplementation on inflammatory biomarkers, estradiol levels and severity of symptoms in women with postpartum depression: a randomized double-blind clinical trial.

Objectives: Postpartum depression (PPD) is a major depressive disorder. Vitamin D deficiency may play a role in PPD pathogenesis. This study was designed to determine the effect of vitamin D and calcium supplementation on the severity of symptoms and some related inflammatory biomarkers in women with PPD.Materials and Methods: Eighty-one women with a PPD score >12 participated in this study. A total of 27 patients were randomly assigned into three groups (1:1:1 ratio) to receive either 50,000 IU vitamin D3 fortnightly + 500 mg calcium carbonate daily; or 50,000 IU vitamin D3 fortnightly + placebo of calcium carbonate daily, or placebo of vitamin D3 fortnightly + placebo of calcium carbonate daily (placebo group) for 8 weeks. At the baseline and end of the study, the severity score of PPD, levels of 25-hydroxy vitamin D, calcium, tumor necrosis factor-alpha (TNFα), interleukin 6 (IL6) and estradiol were measured.Results: The PPD score had more reduction in the vitamin D + calcium and vitamin D + calcium placebo groups than that of the placebo group (-1.7 ± 3.44, -4.16 ± 5.90 and 0.25 ± 2.81, respectively; p = 0.008). The effect of vitamin D on the PPD score was larger when vitamin D was given alone than given together with calcium (p = 0.042 and p = 0.004, respectively). No significant differences in estradiol, IL6 and TNFα were observed between the three groups.Discussion: Vitamin D may be effective in improving the clinical symptoms of PPD; however, the mechanism of the effect might not entirely operate through inflammatory and/or hormonal changes.

A prospective study to explore the relationship between MTHFR C677T genotype, physiological folate levels, and postpartum psychopathology in at-risk women.

BACKGROUND: The etiology of postpartum psychopathologies are not well understood, but folate metabolism pathways are of potential interest. Demands for folate increase dramatically during pregnancy, low folate level has been associated with psychiatric disorders, and supplementation may improve symptomatology. The MTHFR C677T variant influences folate metabolism and has been implicated in depression during pregnancy. OBJECTIVE: To conduct a prospective longitudinal study to explore the relationship between MTHFR C677T genotype, folate levels, and postpartum psychopathology in at-risk women. HYPOTHESIS: In the first three months postpartum, folate will moderate a relationship between MTHFR genotype and depression, with TT homozygous women having more symptoms than CC homozygous women. METHODS: We recruited 365 pregnant women with a history of mood or psychotic disorder, and at 3 postpartum timepoints, administered the Edinburgh Postnatal Depression Scale (EPDS); Clinician-Administered Rating Scale for Mania (CARS-M) and the Positive and Negative Symptom Scale (PANSS) and drew blood for genotype/folate level analysis. We used robust linear regression to investigate interactions between genotype and folate level on the highest EPDS and CARS-M scores, and logistic regression to explore interactions with PANSS psychosis scores above/below cut-off. RESULTS: There was no significant interaction effect between MTHFR genotype and folate level on highest EPDS (p = 0.36), but there was a significant interaction between genotype, folate level and log(CARS-M) (p = 0.02); post-hoc analyses revealed differences in the effect of folate level between CC/CT, and TT genotypes, with folate level in CC and CT having an inverse relationship with symptoms of mania, while there was no relationship in participants with TT genotype. There was no significant interaction between MTHFR genotype and folate level on the likelihood of meeting positive symptom criteria for psychosis on the PANSS (p = 0.86). DISCUSSION: These data suggest that perhaps there is a relationship between MTHFR C677T, folate level and some symptoms of postpartum psychopathology.

Relationship between vitamin D deficiency and both gestational and postpartum depression.

INTRODUCTION: Introduction: vitamin D deficiency (VDD) has been associated with depressive symptoms in pregnancy and postpartum, which can result in increased adverse outcomes in the maternal-infant segment. A possible explanation in the literature is VDD relationship with genetic and neurological mechanisms. Objective: to evaluate VDD relationship with gestational and postpartum depression. Methods: this review followed the recommendations proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Research was conducted in electronic databases, PubMed and LILACS, including studies of the analytical type (cross-sectional and longitudinal), systematic reviews, meta-analyses, and controlled clinical trials carried out in humans; inclusion and exclusion criteria were applied. Results and conclusions: in this systematic review, eight articles were analyzed comprising 8,583 women from seven different countries. Among the selected articles, six found an association between VDD and gestational and postpartum depression. Considering the data collection, it was possible to conclude that there is a probable relationship between VDD and a higher predisposition to gestational and postpartum depression. Also, we concluded that vitamin D supplementation has proven to be a promising strategy for reducing the risk of depressive symptoms.

INTRODUCCIÓN: Introducción: la deficiencia de vitamina D (VDD) se ha asociado a síntomas depresivos en el embarazo y el posparto, lo que puede resultar en un aumento de los resultados adversos en el segmento materno-infantil. Una posible explicación en la literatura es la relación de la VDD con mecanismos genéticos y neurológicos. Objetivo: evaluar la relación de la VDD con la depresión gestacional y posparto. Métodos: esta revisión siguió las recomendaciones propuestas por los Elementos de Informes Preferidos para revisiones sistemáticas y metaanálisis. La investigación se llevó a cabo en bases de datos electrónicas, PubMed y LILACS, incluyendo estudios de tipo analítico (sección transversal y longitudinal), revisiones sistemáticas, metaanálisis y ensayos clínicos controlados realizados en seres humanos; se aplicaron criterios de inclusión y exclusión. Resultados y conclusiones: en esta revisión sistemática se analizaron ocho artículos que comprenden a 8716 mujeres de siete países diferentes. Entre los artículos seleccionados, seis encontraron asociación entre la VDD y la depresión gestacional y posparto. Teniendo en cuenta la recopilación de datos, fue posible concluir que existe una relación probable entre la VDD y una mayor predisposición a la depresión gestacional y posparto. También llegamos a la conclusión de que la suplementación con vitamina D ha demostrado ser una estrategia prometedora para reducir el riesgo de síntomas depresivos.

Levels of n-3 and n-6 Fatty Acids in Maternal Erythrocytes during Pregnancy and in Human Milk and Its Association with Perinatal Mental Health.

Omega-3 long-chain polyunsaturated fatty acid (n-3 FA) status may be associated with mood disorders. Here, we evaluated the potential association between antenatal depression/anxiety and n-3/n-6 FA in (a) maternal erythrocytes and (b) human milk. In addition, we explored associations between n-3/n-6 FA in erythrocytes and in human milk and postpartum depression, while controlling for antenatal depression. Twenty-seven pregnant women diagnosed with a current major depressive disorder (MDD; n = 9), anxiety disorder (AD; n = 10) or a mixed anxiety-depression disorder (MADD; n = 8), and 40 healthy controls were included. n-3/n-6 FA were determined in maternal erythrocytes in gestational week 32 and in human milk in postpartum week 1. In the first week postpartum, the Edinburgh-Postnatal-Depression-Questionnaire was used to assess postpartum depression. Results show that women with M(A)DD had significantly lower erythrocyte levels of total n-3 FA, EPA, DHA and DGLA, and significantly higher n-6 DPA, and n-6:n-3, AA:EPA and n-6 DPA:DHA ratios compared to healthy controls. No significant associations between antenatal depression or anxiety and n-3/n-6 FA in human milk were found. After controlling for antenatal mental health, n-3/n-6 FA in maternal erythrocytes or in human milk were not significantly associated with postpartum depression. In conclusion, antenatal depression, alone or with an anxiety disorder, was associated with lower n-3 FA levels and higher n-6:n-3 FA ratios in maternal erythrocytes during gestation. This study provides some insights into the associations between n-3/n-6 FA levels during pregnancy and lactation and perinatal mental health.

On maternal Post-Partum/Natal depression. A global underrecognized problem and the need for better Treatment strategies.

BACKGROUND: Maternal Postpartum (PPD) or Postnatal Depression (PND) is believed to be the commonest medical complication postpartum. Evidence suggests a significantly higher prevalence of the disease compared to the often reported 10-15%. METHOD: Studies were identified by accessing several databases including PubMed/Medline, PubMed Central, EBSCO, and PsycINFO. RESULTS: Vitamin D (VD) deficiency, hormonal levels alteration (estrogen, progesterone, testosterone, oxytocin, and prolactin), thyroid dysfunction, and increased oxidative stress, play a critical role in PPD etiopathogenesis and pathophysiology. CONCLUSIONS: Treatment strategies should include an integrated approach of antidepressants and psychotherapy, melatonin, diet, sleep improvement, exercise, VD and antioxidants supplementation, and economic and social support.

Association of antepartum vitamin D deficiency with postpartum depression: a clinical perspective.

OBJECTIVE: Postpartum depression affects up to 20 % of new mothers within the first 12 months of parturition. 25-Hydroxyvitamin D (25(OH)D) has known importance in bone health, but it may also play an important role in other functions, including reproduction and fertility, immune function and mental health. This clinical commentary reviews literature evaluating 25(OH)D deficiency during pregnancy and the incidence of postpartum depressive symptomatology. DESIGN: Narrative review, summary and recommendations. SETTING/PARTICIPANTS: A literature search revealed five relevant studies of antepartum women, three based in the USA, one in Turkey and one in Iran. RESULTS: Three of the five studies measured serum 25(OH)D concentrations during the first or second trimester and discovered an association with 25(OH)D deficiency and depressive symptoms postpartum. One study determined an almost significant (P=0·058) inverse relationship with first-trimester 25(OH)D concentration and depressive symptoms postpartum, and the last study, which was a secondary analysis, did not find an association. CONCLUSIONS: The Endocrine Society recommends routine vitamin D supplementation during pregnancy and lactation due to increased metabolic demand in the mother, but a recent Cochrane review recommended against screening. Vitamin D should be the target of more studies during pregnancy and the postpartum period since it appears to have an important role for both medical and mental health. Vitamin D supplementation is a relatively safe and cost-effective intervention during pregnancy, and it may prove to be important in the prevention of postpartum depression.

Traditional Chinese acupuncture and postpartum depression: A systematic review and meta-analysis.

BACKGROUND: Acupuncture, a key component of traditional Chinese medicine, is a form of alternative medicine in which thin needles are inserted into the body commonly for pain relief. To date, the role of traditional Chinese acupuncture in mood disorders in the postpartum period is unclear. Thus, this study aimed to review the effectiveness of acupuncture in patients with postpartum depression (PPD). METHODS: We searched databases such as PUBMED, EMBASE, and Cochrane Controlled Trials Register until September 2018. Meta-analysis was performed using Comprehensive Meta-Analysis 2.0 software. The mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) were calculated to evaluate the results of each comparison. RESULTS: A total of 887 PPD patients from 12 randomised controlled trials were included in the quantitative meta-analysis, with 443 patients in the treatment group and 444 patients in the control group. Patients in the acupuncture group had significantly better performances assessed by the Hamilton Depression Scale than those in the control group, and the pooled MD was -1.27 (95% CI: -2.55 to 0.01; p = 0.05, I = 83%) in the random-effect model. In addition, significantly better performance in the effective rate was observed in the acupuncture group than in the control group, and the pooled RR was 1.20 (95% CI: 1.09 to 1.33; p < 0.0001, I = 46%). However, in subgroup analysis for the acupuncture therapy alone, only effective rate showed a significantly better performance. CONCLUSION: Traditional Chinese acupuncture seems to be effective in improving some symptoms of PPD, although the evidence is uncertain. Therefore, further studies following standardized guidelines with a low risk of bias are needed to confirm the effectiveness of acupuncture in the treatment of PPD.

Imbalance between Omega-6 and Omega-3 Polyunsaturated Fatty Acids in Early Pregnancy Is Predictive of Postpartum Depression in a Belgian Cohort.

While studies revealed that the omega-3 polyunsaturated fatty acids (n-3 PUFA) and their mediators would be able to regulate several biological processes involved into the development of postpartum depression (PPD), evidence from observational studies remains mixed. The aim of the present study was to investigate the association between maternal erythrocyte n-3 PUFA, measured in early pregnancy, and the risk of PPD. A Belgian cohort of 72 healthy women was screened. Erythrocyte fatty acids were analysed using gas chromatography. PPD was assessed using the Bromley Postnatal Depression Scale by phone interview one year after delivery. We observed a significant negative association between docosahexaenoic acid (DHA) levels and the risk of postpartum depression in the adjusted model (p = 0.034). Higher n-6/n-3 and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratios were significantly associated with an increased odds of PPD (p = 0.013 and p = 0.043, respectively). Women with an omega-3 index <5% had a 5-fold increased risk of depressive episode than did those with an omega-3 index ≥5% (OR 5.22 (95%CI 1.24-21.88)). A low n-3 PUFA status, alone and combined with high n-6 PUFA status, in early pregnancy was associated with a greater risk of PPD. Management of maternal n-3 PUFA deficiency can be a simple, safe and cost-effective strategy for the prevention of this major public health issue.

[Inflammatory Biomarkers and Postpartum Depression: A Systematic Review of Literature]. / Biomarqueurs de L'inflammation et Dépression du Post-Partum: Une Revue Systématique De la Littérature.

OBJECTIVE: Postpartum Depression (PPD) affects over 15% new mothers. Its etiology is multifactorial and still partly unknown. Some hypotheses suggest a link with inflammation. This review aims to explore the existence of inflammatory biomarkers associated with PPD. The possibility of potential adjunct treatments, linked with these biomarkers, will be discussed. METHOD: The systematic review of literature was performed using in PubMed, PsycInfo and Embase, and 25 articles were included. Various biomarkers were identified. The most often studied are C-reactive protein (CRP), interleukins 6 and 10, tumor necrosis factor-alpha and interferon-gamma. RESULTS: Although few results appear as significant during the various testing times, the dosage of some inflammation biomarkers, including CRP, at the very end of pregnancy or immediately after delivery could predict PPD. Interactions between inflammation and the corticotropic axis could explain PPD onset. Epigenetic mechanisms could lead to pro-inflammatory state. Several therapeutics provide interest due to their anti-inflammatory property. CONCLUSIONS: Further studies are needed to assess these biomarkers value as predictive factors of PPD and to consider adjunct treatments to antidepressants. If this value is confirmed, the inflammatory marker dosage, in particular CRP, could help to provide early screening of women at risk of PPD, parallel of the clinical evaluation. A zinc supplementation could then be offered.

OBJECTIF: La Dépression du Post-Partum (DPP) affecte plus de 15% des nouvelles mères. Son étiologie est plurifactorielle et encore partiellement méconnue. Certaines hypothèses posent l'idée d'un lien avec l'inflammation. L'objectif de cette revue est d'explorer l'existence de biomarqueurs de l'inflammation associés à la DPP. Puis sera discutée la possibilité de compléments thérapeutiques éventuels, en lien avec ces biomarqueurs. MÉTHODE: La revue systématique de la littérature a été réalisée à partir de PubMed, PsycInfo et Embase. Vingt-cinq articles ont été inclus. Différents biomarqueurs ont été identifiés. Les plus étudiés sont la C-Réactive Protéine (CRP), les Interleukines 6 et 10, le Tumor Necrosis Factor-alpha et l'Interferon Gamma. RÉSULTATS: Alors que peu de résultats apparaissent comme significatifs aux différents temps, le dosage de certains biomarqueurs de l'inflammation, notamment la CRP, en toute fin de grossesse ou juste après l'accouchement pourrait être une piste de recherche intéressante avec une orientation prédictive de la DPP. Les interactions entre inflammation et axe corticotrope peuvent expliquer la survenue de la DPP. Des phénomènes épigénétiques pourraient conduire à un état pro-inflammatoire. Plusieurs thérapeutiques offrent des pistes intéressantes grâce à leur propriété anti-inflammatoire. CONCLUSIONS: Davantage d'études sont nécessaires afin d'évaluer l'intérêt de ces biomarqueurs comme facteur prédictif de la DPP et d'envisager des traitements complémentaires à l'antidépresseur. Si cet intérêt était confirmé, le dosage de marqueur de l'inflammation, notamment la CRP, pourrait aider au dépistage précoce des femmes à risque de DPP, parallèlement à la clinique. Une supplémentation en Zinc pourrait alors être proposée.

Anaemia and depletion of iron stores as risk factors for postpartum depression: a literature review.

PURPOSE: Iron-deficiency and anaemia are common in pregnant and postpartum women because of increasing iron demand and blood loss. Many women also enter pregnancy with pre-depleted iron stores. We reviewed the evidence linking anaemia and/or iron-deficiency to postpartum depression (PPD). METHODS: We identified seventeen studies in four databases including randomized-controlled trials (RCTs) and observational studies assessing the impact of anaemia, iron-deficiency and iron supplementation on the risk of PPD. We extracted data on sample size, geographical region, obstetrical complications, measures of depression, haemoglobin, iron levels and intake of iron supplementation and critically appraised the results from the studies. RESULTS: Eight out of ten studies found higher risk for PPD (r - 0.19 to -0.43 and ORs 1.70-4.64) in anaemic women. Low ferritin in the postpartum period but not during pregnancy was associated with increased risk of PPD. Iron supplementation in the postpartum period decreased risk of PPD in four out of five studies, whereas it did not protect from PPD if given during pregnancy. Limitations include study heterogeneity, discrepancy of prevalence of PPD and usage of a screening tool for evaluation of PPD. CONCLUSION: Anaemia and/or iron-deficiency may contribute to PPD in at-risk women. Further studies should elucidate the association between these entities.

Vitamin D deficiency and depressive symptoms in the perinatal period.

Depression affects 1 in 7 women during the perinatal period. Women with vitamin D deficiency may be at an increased risk for depression. This study investigated the relationship between maternal and cord blood 25-hydroxyvitamin D (25OHD) and maternal depressive symptoms over the perinatal period. Study objectives were to examine variations and relationships between maternal and cord blood vitamin D levels and maternal depressive symptoms over the perinatal period. At a large medical center in southern California, pregnant women (N = 126) were recruited for this longitudinal cohort study. Depressive symptoms (Edinburgh Postnatal Depression Screen, EPDS) and vitamin D status (25OHD) were measured at three time points in the perinatal period: time 1 (T1; N = 125) EPDS and 25OHD were collected in early pregnancy; time 2 (T2; N = 96) EPDS was conducted in the third trimester with blood collected at time of delivery; and time 3 (T3; N = 88) was collected postpartum. A significant inverse relationship between vitamin D status and depressive symptoms was observed between 25OHD and EPDS scores at all time points in this sample (T1 = - 0.18, P = 0.024; T2 = - 0.27, P = 0.009; T3 = - 0.22, P = 0.019). This association remained after controlling for confounders. Low cord blood 25OHD levels were inversely associated with higher EPDS scores in the third trimester (r = - 0.22, P = 0.02). Clinicians may want to consider screening women diagnosed with vitamin D deficiency for depression and vice versa. Vitamin D may represent an important biomarker for pregnant and postpartum women diagnosed with depression. Further studies examining underlying mechanisms and supplementation are needed.

Vitamin D deficiency and depressive symptoms in pregnancy are associated with adverse perinatal outcomes.

Prenatal vitamin D deficiency and prenatal depression are both separately associated with adverse perinatal outcomes; however, to our knowledge no studies have investigated the effects of having both risk factors. Our objective was to determine to what extent vitamin D deficiency predicts adverse perinatal outcomes and whether elevated depressive symptoms in pregnancy places women at additional increased risk. This study was a secondary data analysis of prospective data collected from a cohort of pregnant women (N = 101) in an obstetric clinic of a large medical center. Maternal vitamin D deficiency (serum 25(OH)D ≤ 20 ng/ml) and depressive symptoms (Edinburgh Postnatal Depression Scale, EPDS) were assessed in early pregnancy. A composite of four adverse perinatal outcomes (low birth weight, preterm birth, small-for-gestational age, and preeclampsia) were abstracted from medical charts. Nineteen of the 101 women had one or more adverse perinatal outcome and 84% with an adverse outcome (16/19) were not White. Both prenatal and time of delivery vitamin D deficiency were associated with developing an adverse outcome compared to those vitamin D sufficient (prenatal relative risk 3.43; 95% CI 1.60-7.34, p = 0.004; delivery time relative risk 5.14, 95% CI 2.68-9.86, p = 0.004). These both remained significant after adjusting for BMI. A higher rate of adverse outcome was found when women had both prenatal vitamin D deficiency and elevated depressive symptoms (EPDS ≥ 10). Sixty percent with both risk factors had an adverse perinatal outcome versus 17% with only one or neither risk factor (relative risk 3.60; 95% CI 1.55-8.38, p = 0.045), worthy of investigation with larger samples. Together, prenatal vitamin D deficiency and elevated depressive symptoms in pregnancy may increase risk for adverse perinatal outcomes, especially in racial minorities. Obstetric providers should consider routine prenatal depression screening. The impact of vitamin D supplementation to reduce risk for adverse perinatal outcomes should be studied in prospective trials. Our results suggest that supplementation early in pregnancy might be especially beneficial for depressed women.

The Relationship Between Vitamin D and Postpartum Depression in Reproductive-Aged Iranian Women.

Background: The aim of this study was to evaluate the relationship between vitamin D and postpartum depression in reproductive-aged Iranian women. Methods and Results: This study was conducted on 120 women (60 with postpartum depression and 60 without) in Izeh, Iran. A socio-demographic questionnaire and Beck Depression Scale were used for data collection. The ELISA method was used for measuring 25-OH vitamin D (ng). The participants were classified according to their vitamin D level as follows: 25-OH-D < 10ng/ml considered as severe deficiency, 10-20n g/ml as moderate insufficiency, 20-30 ng/ml as mild insufficiency and >30ng/ml as normal. Data were analyzed using the independent t-test or Mann-Whitney test, chi-square and logistic regression test. The mean level of vitamin D of women with postpartum depression was lower than that in normal women (16.89±7.05 vs. 21.28±7.13, p=0.001). More than 53% of women with postpartum depression had vitamin D <20 ng/ml compared to 31.7% of women with no depression (p=0.005). Moreover, 16.7% of women with postpartum depression had vitamin D < 10ng/ml compared to only 6.7% in the normal group (p = 0.005). Women with vitamin D less than 20ng/ml compared to vitamin D > 20ng/ml were 3.30 times more likely to have postpartum depression (OR: 3.3, CI: 1.32-8.24, p= 0.01). Discussion: There is a significant relationship between a low level of vitamin D and postpartum depression among reproductive-aged Iranian women. Health policy makers should pay attention to the measuring vitamin D level as one of the primary tests of pregnant women.

Effects of zinc and magnesium supplements on postpartum depression and anxiety: A randomized controlled clinical trial.

Postpartum anxiety and depression are prevalent disorders. The authors of this study aimed to determine the effects of zinc and magnesium supplements on depressive symptoms and anxiety in postpartum women referred to three governmental, educational hospitals in Tabriz, Iran during 2014-2015. In this triple-blind, randomized, controlled clinical trial, the participants were randomly assigned to the zinc sulfate, magnesium sulfate, and placebo groups (n = 33 per group). The intervention groups received a 27-mg zinc sulfate tablet or 320-mg magnesium sulfate tablet per day for 8 weeks, whereas the control group received a placebo tablet each day during the same period. The Edinburgh Postnatal Depression Scale and the Spielberger State-Trait Anxiety Inventory were completed before and 8 weeks after the intervention. Blood samples were drawn from each participant to determine serum levels of zinc and magnesium before intervention at 48 hours after delivery. Also, a 24-hour dietary questionnaire was used during the first and last 3 days of the intervention. Adjusting for baseline scores as well as zinc and magnesium serum levels, no significant difference was observed between groups 8 weeks after delivery in mean scores of depressive symptoms (p = .553), state anxiety (p = .995), and trait anxiety (p = .234). This study concluded magnesium and zinc did not reduce postpartum anxiety and depressive symptoms.

The role of diet and nutritional supplementation in perinatal depression: a systematic review.

This article presents a systematic literature review on whether dietary intake influences the risk for perinatal depression, i.e. depression during pregnancy or post-partum. Such a link has been hypothesized given that certain nutrients are important in the neurotransmission system and pregnancy depletes essential nutrients. PubMed, EMBASE and CINAHL databases were searched for relevant articles until 30 May 2015. We included peer-reviewed studies of any design that evaluated whether perinatal depression is related to dietary intake, which was defined as adherence to certain diets, food-derived intake of essential nutrients or supplements. We identified 4808 studies, of which 35 fulfilled inclusion criteria: six randomized controlled trials, 12 cohort, one case-control and 16 cross-sectional studies, representing 88 051 distinct subjects. Studies were grouped into four main categories based on the analysis of dietary intake: adherence to dietary patterns (nine studies); full panel of essential nutrients (six studies); specific nutrients (including B vitamins, Vitamin D, calcium and zinc; eight studies); and intake of fish or polyunsaturated fatty acids (PUFAs; 12 studies). While 13 studies, including three PUFA supplementation trials, found no evidence of an association, 22 studies showed protective effects from healthy dietary patterns, multivitamin supplementation, fish and PUFA intake, calcium, Vitamin D, zinc and possibly selenium. Given the methodological limitations of existing studies and inconsistencies in findings across studies, the evidence on whether nutritional factors influence the risk of perinatal depression is still inconclusive. Further longitudinal studies are needed, with robust and consistent measurement of dietary intake and depressive symptoms, ideally starting before pregnancy.

Vitamin D levels and perinatal depressive symptoms in women at risk: a secondary analysis of the mothers, omega-3, and mental health study.

BACKGROUND: Vitamin D insufficiency may be associated with depressive symptoms in non-pregnant adults. We performed this study to evaluate whether low maternal vitamin D levels are associated with depressive symptoms in pregnancy. METHODS: This study was a secondary analysis of a randomized trial designed to assess whether prenatal omega-3 fatty acid supplementation would prevent depressive symptoms. Pregnant women from Michigan who were at risk for depression based on Edinburgh Postnatal Depression Scale Score or history of depression were enrolled. Participants completed the Beck Depression Inventory (BDI) and Mini International Neuropsychiatric Interview at 12-20 weeks, 26-28 weeks, 34-36 weeks, and 6-8 weeks postpartum. Vitamin D levels were measured at 12-20 weeks (N = 117) and 34-36 weeks (N = 112). Complete datasets were available on 105 subjects. Using regression analyses, we evaluated the relationship between vitamin D levels with BDI scores as well as with MINI diagnoses of major depressive disorder and generalized anxiety disorder. Our primary outcome measure was the association of maternal vitamin D levels with BDI scores during early and late pregnancy and postpartum. RESULTS: We found that vitamin D levels at 12-20 weeks were inversely associated with BDI scores both at 12-20 and at 34-36 weeks' gestation (P < 0.05, both). For every one unit increase in vitamin D in early pregnancy, the average decrease in the mean BDI score was .14 units. Vitamin D levels were not associated with diagnoses of major depressive disorder or generalized anxiety disorder. CONCLUSIONS: In women at risk for depression, early pregnancy low vitamin D levels are associated with higher depressive symptom scores in early and late pregnancy. Future investigations should study whether vitamin D supplementation in early pregnancy may prevent perinatal depressive symptoms. TRIAL REGISTRATION: https://clinicaltrials.gov/ REGISTRATION NUMBER: NCT00711971.

Docosahexaenoic Acid Status in Pregnancy Determines the Maternal Docosahexaenoic Acid Status 3-, 6- and 12 Months Postpartum. Results from a Longitudinal Observational Study.

BACKGROUND: Essential fatty acid status as well as docosahexaenoic acid (DHA, 22:6n-3) declines during pregnancy and lactation. As a result, the DHA status may not be optimal for child development and may increase the risk for maternal postpartum depression. The objective of this study was to assess changes in the maternal fatty acid status from pregnancy to 12 months postpartum, and to study the impact of seafood consumption on the individual fatty acid status. METHODS: Blood samples and seafood consumption habits (gestation week 28, and three-, six- and 12 months postpartum) were collected in a longitudinal observational study of pregnant and postpartum women (n = 118). Multilevel linear modeling was used to assess both changes over time in the fatty acid status of red blood cells (RBC), and in the seafood consumption. RESULTS: Six fatty acids varied the most (>80%) across the four time points analyzed, including the derivative of the essential α-linoleic acid (ALA, 18:3n-3), DHA; the essential linoleic acid (LA, 18:2 n-6); and the LA derivative, arachidonic acid (AA, 20:4n-6). Over all, a large variation in individuals' DHA- and AA status was observed; however, over the 15-month study period only small inter-individual differences in the longitudinal trajectory of DHA- and AA abundance in the RBC were detected. The median intake of seafood was lower than recommended. Regardless, the total weekly frequency of seafood and eicosapentaenoic acid (EPA, 20:5n-3)/DHA-supplement intake predicted the maternal level of DHA (µg/g RBC). CONCLUSION: The period of depletion of the maternal DHA status during pregnancy and lactation, seem to turn to repletion from about six months postpartum towards one year after childbirth, irrespective of RBC concentration of DHA during pregnancy. Seafood and EPA/DHA-supplement intake predicted the DHA levels over time. TRIAL REGISTRATION: www.helseforskning.etikkom.no 2009/570/REC, project number: 083.09.

Long-chain polyunsaturated fatty acid status during pregnancy and maternal mental health in pregnancy and the postpartum period: results from the GUSTO study.

OBJECTIVE: Studies have demonstrated a relationship between lower omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) status and anxiety and depression. It is uncertain whether similar associations occur in pregnant women, when anxiety and depression could have long-term effects on the offspring. We examined the associations between plasma LC-PUFA status during pregnancy and perinatal mental health. METHOD: At 26-28 weeks' gestation, plasma LC-PUFAs were measured in mothers of the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort study, who were recruited between June 2009 and September 2010. Maternal symptoms of anxiety and depression were assessed with the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) during the same period and at 3 months' postpartum. The STAI-state subscale was used as a continuous measure of current anxiety, while EPDS scores ≥ 15 during pregnancy or ≥ 13 postpartum were indicative of symptoms of probable depression. RESULTS: In adjusted regression analyses (n = 698), lower plasma total omega-3 PUFA concentrations (ß = -6.49 STAI-state subscale scores/unit increase of omega-3 fatty acid; 95% CI, -11.90 to -1.08) and higher plasma omega-6:omega-3 PUFA ratios (ß = 6.58 scores/unit increase of fatty acid ratio; 95% CI, 1.19 to 12.66), specifically higher arachidonic acid (AA):docosahexaenoic acid, AA:eicosapentaenoic acid, and AA:docosapentaenoic acid ratios, were associated with increased antenatal anxiety (P < .05 for all), but not postpartum anxiety. There was no association between plasma PUFAs and perinatal probable depression. CONCLUSIONS: No association was found with probable depression in pregnancy or postpartum. Lower plasma omega-3 fatty acids and higher omega-6:omega-3 fatty acid ratios were associated with higher antenatal anxiety, but not postpartum anxiety. Replication in other studies is needed to confirm the findings and determine the direction of causality. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01174875.

Is essential fatty acid status in late pregnancy predictive of post-natal depression?

OBJECTIVE: We tested the hypothesis that abnormal levels of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) during late pregnancy are associated with antenatal and post-natal depression. METHOD: We interviewed a sample of more than 900 women in late pregnancy. We assessed whether they met criteria for depression on a standardized measure of post-natal depression [the Edinburgh Post-natal Depression Scale (EPDS)] and met DSM-IV criteria for major depression and/or were in receipt of antidepressant medication. Blood was collected at that time to generate data on nine PUFA variables. Sample members were re-interviewed post-natally to determine depressive experience in the 3 months following the birth of their baby. RESULTS: Univariate associations were demonstrated between pre-natal depression categorized using DSM criteria and measures of blood fatty acids including total omega-3, the ratio of omega-6 to omega-3, docosahexaenoic acid (DHA) omega-3 and DHA plus eicosapentaenoic acid (EPA) omega-3. Such associations were not found post-natally, but different associations were quantified between EPDS-diagnosed depression and total omega-6, total omega-3 and EPA omega-3. In multivariate analyses, slight associations were maintained between EPDS and lower omega-3, lower EPA and higher omega-6 when neuroticism, stress during pregnancy, a lifetime episode of depression and older age were included in the analysis. CONCLUSION: Findings in such a large sample indicate that PUFA status in late pregnancy is only slightly linked with the risk of post-natal depression when depression was quantified by the EPDS. There were no associations between post-natal depression diagnosed by DSM criteria and any fatty acid variables.

Perinatal depression and omega-3 fatty acids: a Mendelian randomisation study.

BACKGROUND: There have been numerous studies investigating the association between omega-3 fatty acids (FAs) and depression, with mixed findings. We propose an approach which is largely free from issues such as confounding or reverse causality, to investigate this relationship using observational data from a pregnancy cohort. METHODS: The Avon Longitudinal Study of Parents and Children (ALSPAC) cohort collected information on FA levels from antenatal blood samples and depressive symptoms at several time points during pregnancy and the postnatal period. Conventional epidemiological analyses were used in addition to a Mendelian randomisation (MR) approach to investigate the association between levels of two omega-3 FAs (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) and perinatal onset depression, antenatal depression (AND) and postnatal depression (PND). RESULTS: Weak evidence of a positive association with both EPA (OR=1.07; 95% CI: 0.99-1.15) and DHA (OR=1.08; 95% CI: 0.98-1.19) with perinatal onset depression was found using a multivariable logistic regression adjusting for social class and maternal age. However, the strength of association was found to attenuate when using an MR analysis to investigate DHA. LIMITATIONS: Pleiotropy is a potential limitation in MR analyses; we assume that the genetic variants included in the instrumental variable are associated only with our trait of interest (FAs) and thus cannot influence the outcome via any other pathway. CONCLUSIONS: We found weak evidence of a positive association between omega-3 FAs and perinatal onset depression. However, without confirmation from the MR analysis, we are unable to draw conclusions regarding causality.