Description of the condition

Postnatal mood disorders are heterogeneous (Brockington 2004) and range from postnatal blues that affect 15% to 80% of postnatal women (Beck 2006; Pitt 1973), to postpartum psychosis that affects one in 2000 women (Kendell 1987). The Diagnostic and Statistical Manual of Mental Disorders (DSM) (APA 2000) defines postnatal depression as a major depressive episode with postpartum onset if the onset is within four weeks postpartum. It distinguishes postpartum depressive episodes from the 'baby blues', which affect up to 80% of women during the first 10 days postpartum, but are transient and do not impair functioning (APA 2000; Cox 2003). The DSM IV and International Classification of Diseases (ICD‐10) criteria concur that postnatal depression can last for any length of time between two weeks and one year postpartum, and is differentiated from normal postpartum emotional adjustment by the pattern of symptoms, and the severity and consistency with which they occur (Cox 1987a; Cox 2003; Gibbon 2004). The DSM is published by the American Psychiatric Association (APA) and provides a common language and standards for classification of mental disorders. It is used mostly in the United States. The ICD‐10, produced by the World Health Organization, is another standard of classification and is mainly used in Europe. Symptoms of postnatal depression include mood lability, sleep disturbances such as waking at night or early rising not related to the baby, appetite disturbances and weight loss, ‘thought blocking’ and mental sluggishness, suicidal ideation, and preoccupation with infant well‐being ranging from over‐concern to frank delusions. Delusions are associated with an increased risk of harm to the infant (Austin 2008; Brockington 2004). Although not classified as a distinct syndrome, the ICD10 classifies depression after childbirth as “mild (four symptoms), moderate (five symptoms) or severe (five symptoms or more, plus agitation, feelings of worthlessness or guilt or suicidal thoughts or acts)” (Fisher 2009).

Whether postnatal depression is distinct from major depression, or just coincidental timing of a major depressive episode with the postnatal period is an area of speculation (Brockington 1996; Steiner 1990). The major life changes associated with the transition to motherhood are an obvious potential stressor, and cause emotional disruption in even the most resilient of women (Beck 2006). However, it is unlikely that the most important precipitating factors of an episode of postnatal depression are particular to pregnancy and its aftermath (Brockington 1996; Hanley 2009). Whilst the prevalence of depression in postnatal women is similar to the incidence in the general female population, there is a three‐fold increase in the incidence of depression in the first five weeks postpartum (Cox 1993). Approximately one‐third of women who develop postnatal depression may experience symptoms in the first four weeks; two‐thirds will develop them between 10 and 14 weeks; and cases who present later are often misdiagnosed or missed altogether (Hanley 2009). Three longitudinal studies from both high‐income countries (US and UK) and low‐ and middle‐income countries (Brazil) have found an increase in the incidence and symptoms of postnatal depression around three months postpartum, with a second peak occurring around nine months postpartum (Gjerdingen 2011; Lobato 2011; Nott 1987). Nott 1987 even suggests that the incidence of new cases of postnatal depression was highest three to nine months postpartum, which is outside of the period when women would have regular contact with postpartum clinical services and depression screening.

The problem for prevention and treatment lies in the lack of consensus regarding the aetiology, definition, and tools for detection of this condition. Consequently, the study and management of  women with "melancholia" after childbirth (Brockington 1996) has fallen between several disciplines ‐ that of primary care, obstetrics, and psychiatry. Also, there are multiple pathways towards an episode of postnatal depression, and different women will find alternative modes of treatment and/or support to be effective (Austin 2008; NHMRC 1999).

Description of the intervention

The overall hypothesis of this review is that certain dietary deficiencies in a pregnant or postnatal woman's diet may cause postnatal depression. Hence, correcting these deficiencies with dietary supplements could prevent postnatal depression.

The intervention considered was dietary supplements given before the onset or diagnosis of postnatal depression. Examples include omega‐3 fatty acids, iron, calcium, vitamin B12 (cobalamin), riboflavin (B2), vitamin B6 (pyridoxine), folate, S‐adenosyl‐methionine (SAMe) and vitamin D (Freeman 2009). Dietary supplements were defined as any vitamin, mineral or compound that exists naturally and could be reasonably expected to be part of the normal human diet. Intervention with supplementation would be expected to correct a current or potential deficit in these vitamins, minerals or other compounds.

Omega‐3 polyunsaturated fatty acids are found in oily fish and seafood as docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA). During the last century, the diets of industrialised societies have contained significantly lower amounts of omega‐3 fatty acids, and relatively higher levels of omega‐6 polyunsaturated fatty acids Simopoulos 2008). There also appears to be a correlation between fish consumption rates and depression, with lower reported incidence of depression in people from Hong Kong, China, and Japan compared with Western countries (Hibbeln 2002). Lower rates of fish consumption have also been correlated with higher rates of postnatal depression (Rees 2005). Women have been found to be depleted in omega‐3 polyunsaturated fatty acids during gestation and breastfeeding as there is preferential diversion of omega‐3 fats to the baby (Huang 2013). It has been hypothesised that if low omega‐3 levels are associated with depression, one reason women are more vulnerable to depression postnatally is due to depletion of their omega‐3 fatty acids (Rees 2005). A previous non‐Cochrane systematic review (Wojcicki 2011) looked at the association between omega‐3 fatty acid supplementation and the risk of perinatal depression. It reviewed 10 articles and found that six found no association, two found mixed results and two found a positive association between omega‐3 supplementation and reduced risk of perinatal depression. This review included longitudinal cohort studies, randomised controlled trials and pilot trials. All of the randomised controlled trials included mixed populations of depressed and non‐depressed women on entry into the studies so none of these studies could be classified as purely investigating a prevention effect of omega‐3 fatty acids on postnatal depression. One of the pilot studies in which women were excluded at entry if they were depressed showed no preventive effect of omega‐3 fatty acids on perinatal depression (Marangell 2004).

Other dietary deficiencies may play a part in postnatal depression. In one study, iron treatment resulted in a 25% improvement in previously iron‐deficient mothers’ depression and stress scales, whereas anaemic mothers who received placebo did not improve (Beard 2005). Anaemia is a risk factor for postnatal depression (Corwin 2003), hence postpartum haemorrhage may also be a cause of postnatal depression. Albacar (Albacar 2011) found an association between low ferritin 48 hours after delivery and postpartum depression. S‐adenosyl‐L‐methionine, alone or in combination with pharmacologic antidepressants, has been effective in the treatment of major depression (Mischoulon 2002). One prospective study examined the relationship of dietary consumption of folate and B vitamins during pregnancy with the risk of postpartum depression (Miyake 2006). There was no measurable association between intake of folate, cobalamin, or pyridoxine and the risk of postpartum depression. Compared with riboflavin intake in the first quartile, only riboflavin consumption in the third quartile was independently related to a decreased risk of postpartum depression. In another study, nulliparous women, between 11 and 21 weeks' gestation, were randomised to receive either placebo or 2000 mg elemental calcium per day as participants in the NIH‐sponsored Calcium for Preeclampsia Prevention (CPEP) trial. The study found there was a trend toward less depression in calcium‐supplemented women (Harrison‐Hohner 2001). An association has been found between low vitamin D serum levels and depression in older persons (Hoogendijk 2008). If reduced vitamin D levels are linked to depression then it is not unreasonable that correcting a deficiency may be helpful for postnatally depression women.

Hence, certain nutritional deficiencies such as low levels of DHA found in seafood, calcium, B vitamins, vitamin D, and iron have been investigated in relation to postnatal depression but so far this research has been inconclusive (Hanley 2009; Miller 2002). Further research into the biological aetiology of postnatal depression is required, as studies to date have been quasi‐experimental, or randomised controlled trials with small sample sizes of varying methodological quality (Dennis 2009; Miller 2002).

How the intervention might work

Dietary supplementation individually or in combination could be shown to indicate a significant effect in preventing postnatal depression.

Specific hypotheses for how each intervention works are related to the particular intervention. For instance, iron supplements may prevent iron deficiency anaemia, hence preventing maternal lethargy and concomitant depression. But iron deficiency also affects electrophysiological recordings and neurotransmitter metabolism with no direct association to anaemia (Beard 2005). Correcting iron deficiency may normalise neural functioning through direct electrochemical mechanisms. S‐adenosyl‐L‐methionine is involved in methylation of biological proteins which are integral to neural functioning of neurotransmitters, phospholipids, and cellular receptors and channels (Mischoulon 2002). Folate also is involved in methylation of homocysteine and a deficiency may have a similar effect biochemically to a deficiency of S‐adenosyl‐L‐methionine (Freeman 2009). Omega‐3 fatty acids are known to affect neurotransmitters, peptides, releasing factors, hormones, and a variety of physiological and cognitive processes. Fatty acids also may exert a controlling function in the modulation of neuronal membrane fluidity (Yehuda 1999). Nuclear receptors for vitamin D exist in neurons and glial cells. Vitamin D is involved in the biosynthesis of neurotrophic factors, and at least one enzyme involved in neurotransmitter synthesis. Vitamin D can also inhibit the synthesis of inducible nitric oxide synthase and increase glutathione levels, suggesting a role for the hormone in brain detoxification pathways (Garcion 2002).

The hypothesis upon which this review is based is that postnatal depression can be linked to, or contributed to by a dietary deficiency in one or more compounds, and that replacement of these compounds can prevent postnatal depression. It is also likely that women undergoing pregnancy and childbirth require increased amounts of these compounds compared with non‐pregnant women. What is regarded as normal intake outside of pregnancy and childbirth would be insufficient for the extra dietary requirements of pregnancy and childbirth.

Why it is important to do this review

Postnatal depression is the most common complication of childbirth, which not only impacts maternal well‐being, but also infant and child development, and family cohesion (Fisher 2009; Harpham 2005). A large systematic review of postnatal depression in low‐ and middle‐income countries identified a pooled prevalence of common postnatal mental disorders of 19.8% (Fisher 2012). Prevalence of postnatal depression has been estimated to be between 10% and 20% worldwide, although rates vary within and between countries (Affonso 2000; O'Hara 1996). Furthermore, the recurrence rate of postnatal depression is significant (25% to 68%) (Dalton 1982; Wisner 2004). Women who have suffered from postnatal depression are also twice as likely to suffer from further episodes of depression over a five‐year period (Cooper 1995).

Postnatal depression can cause impaired maternal‐infant interactions (Cooper 1998; Murray 1996) and negative perceptions of infant behaviour (Mayberry 1993) that have been linked to attachment insecurity (Hipwell 2000; Murray 1992). Other effects on the infant include cognitive developmental delay (Deave 2008; Hipwell 2000), social/interaction difficulties (Cummings 1994; Murray 1999), impaired expressive language development (Cox 1987), attention‐ (Breznitz 1988), and long‐term behavioural problems (Beck 1999). Infants of depressed mothers have been shown to have a statistically significant poorer growth than infants of non‐depressed mothers at the third month postpartum (Adewuya 2008). Child abuse/neglect (Buist 1998) and marital stress resulting in separation or divorce (Boyce 1994; Holden 1991) are other reported outcomes. Effective treatment for postnatal depression may not be sufficient to improve the developing mother‐child relationship (Forman 2007). Hence in this aspect, prevention is better than treatment.

Several Cochrane reviews have considered various strategies for the prevention and treatment of postnatal depression. However, to date there appears to be no effective strategy for the prevention of postnatal depression among these reviews. One intervention that might be effective in preventing postnatal depression is telephone‐based peer support among women at high risk (Dennis 2009).

Intensive, professionally‐based postpartum support for at‐risk women appears promising (Dennis 2004); however, antenatal interventions do not appear to be effective (Austin 2008). One review reported that synthetic progestogens could double the incidence of postnatal depression (Dennis 2008a). Oestrogens and natural progesterone have not been tested in a randomised trial. In terms of other alternative therapies, massage and/or acupuncture have not been demonstrated to improve antenatal depression immediately after treatment or prevent postnatal depression (Dennis 2008b). One systematic review found that some psychosocial and psychological interventions for treating postpartum depression appear to be effective in reducing Edinburgh Postnatal Depression Scale (EPDS) scores; however, the methodological quality of the included trials was not strong, and the long‐term effectiveness is unclear (Dennis 2007a). There is not enough evidence to demonstrate that these interventions can treat antenatal depression (Dennis 2007b). This is despite the fact that women prefer to have counselling with someone who was non‐judgmental, rather than receive pharmacological interventions (Dennis 2006).

Antidepressants given postpartum cannot be recommended for prevention of postnatal depression as there is a lack of clear evidence (Howard 2005). There is also little evidence for using antidepressants for the treatment of postnatal depression (Hoffbrand 2001), although this is certainly the current standard accepted practice among clinicians. Another issue regarding the acceptability of antidepressants as a treatment for postnatal depression is their transfer from mother to infant through breastfeeding, although most antidepressants are believed to be safe with breastfeeding (Kendall‐Tackett 2007). Antidepressants given in the third trimester have been associated with transient neonatal withdrawal syndrome, which includes jitteriness, muscle weakness, and respiratory difficulties (Oberlander 2004). There are concerns regarding unknown effects of antidepressants on the fetus and infant as well. There is a paucity of information on the concentrations of different drugs that are excreted in breast milk and their associated toxicity profiles (Fortinguerra 2009; Hanley 2009). Some significant areas of concern exist with antidepressant use in pregnancy, particularly some evidence of higher risk of preterm birth, neonatal adaptation difficulties, and congenital cardiac malformations with paroxetine (Udechuku 2010).

Compared to other treatments, dietary supplements are an inexpensive, readily available form of intervention and are generally free of side effects. Furthermore, there is marketing of over‐the‐counter dietary supplements in pharmacies and supermarkets for the purpose of preventing postnatal depression, without clear evidence of benefit. On examining the literature there appear to be no concerns mentioned with regard to micronutrient supplementation in pregnancy where it is recommended to correct specific deficiencies (Shah 2009). Concerns have been raised concerning excessive consumption of vitamin A. However, excessive dietary intake of vitamin A has been associated with teratogenicity in humans in less than 20 reported cases over 30 years (Azaïs‐Braesco 2000). This review is not intended to address the effects of excessive or supra‐physiological doses of dietary supplements. It is intended only to address the effects of correcting dietary deficiencies.

Postnatal depression has a high recurrence rate and treatments may not improve the mother‐infant relationship. The symptoms of postnatal depression are generally assumed to have a deleterious effect on mother‐infant interaction, as mothers experience low energy levels and ambivalence towards the baby. This in turn inhibits their ability to provide a nurturing, responsive environment for their infants and children (Hanley 2009; Pedros‐Rosello 2007). Hence the focus of this review will be on interventions that may prevent this condition.