From womb to world—is it time to revisit our current guidelines for treatment of antenatal depression? Supporting the next generation to have the best start to life

This viewpoint examines the significant impact of antenatal depression on maternal and infant health, highlighting the limitations of current treatment guidelines that primarily recommend psychotherapy and antidepressants. It argues for the inclusion of nutritional interventions based on both the growing literature demonstrating the risks of a nutrient-poor diet on maternal and infant health as well as the emerging evidence from the New Zealand-conducted NUTRIMUM trial, which demonstrated that supplementing with vitamins and minerals during pregnancy can significantly improve maternal mental health and birth outcomes. The intent of the paper is to advocate for an update to the guidelines from the Royal Australia and New Zealand College of Psychiatrists (RANZCP) and the Royal Australia and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) to incorporate nutrition as a key component in the treatment of antenatal depression, thereby enhancing the wellbeing of both mothers and their infants.

Antenatal depression in New Zealand

Antenatal depression affects between 15% and 21% of pregnant women worldwide¹ and increases the risk of pregnancy and birth complications, as well as postnatal depression.² In New Zealand, 11.9% of women experience antenatal depression in their third trimester based on scoring ≥13 on the Edinburgh Postnatal Depression Scale (EPDS), with higher rates reported in Māori, Pacific and Asian women compared with women of European ancestry.³

Current treatment options

The recommended psychological treatments for pregnant women with depression are typically psychological therapies,⁴ with research showing they can be effective in reducing perinatal depression.⁵ However, women often cannot access these treatments due to cost, time constraints, stigma and childcare challenges.⁶ There are also mixed findings on whether women at high risk for depression respond to these interventions sufficiently to prevent the development of postnatal depression.⁷

For those with more severe depression symptoms or where psychological interventions have failed or are unsuitable, antidepressant medication is advised, after discussion of the risks and benefits, based on clinical best practice guidelines set by RANZCP and RANZCOG.^4,8,9 Dispensing data, along with longitudinal observations, indicate about 3% of women in New Zealand take an antidepressant during pregnancy.¹⁰

While a recent umbrella meta-analysis reported that adverse health outcomes associated with psychotropic medications are suggestive at best,¹¹ there is no clear evidence antidepressants are reducing the risks associated with untreated depression down to levels observed in pregnancies of nondepressed individuals. Despite assurances on the absence of serious adverse effects and the low clinical significance of observed effects, pregnant women are often reluctant to use psychiatric medications. This reluctance persists even though the risks of stopping medication and inadequately treated maternal psychiatric illness are deemed higher for the infant than continuing the medications,¹² with dispensing rates dropping during the pregnancy period.¹³ As such, the impact of antenatal depression on maternal and infant outcomes, coupled with implementation challenges with current treatments, underscores the need for research into alternative interventions.

Maternal nutrition has been overlooked

Over the past two decades, research has demonstrated poor nutrition during pregnancy is a risk factor linked to mental health challenges for both mothers and their offspring. Poor nutritional intake, including high consumption of ultra-processed foods in pregnancy, has been associated with higher risk of maternal anxiety, stress and depression during pregnancy.¹⁴ In contrast, consumption of whole foods such as fruit, nuts and seafood has been associated with decreased rates of postpartum depression.¹⁵ The risks are not confined to just maternal outcomes. For example, maternal high adherence to a “healthy dietary pattern” is significantly associated with lower rates of anxiety and depression symptom trajectories in children from 3 to 8 years¹⁶ and lower likelihood of the offspring developing autism at 8 years.¹⁷ In contrast, high consumption of a “Western diet” during pregnancy is associated with higher trajectories of inattention and hyperactivity from 3 to 10 years in offspring.^18,19

Most pregnant women in New Zealand don’t adhere to nutritional guidelines. The Growing Up in New Zealand cohort reported that 3% of pregnant women in New Zealand fully adhered to the Ministry of Health’s Food and Nutrition Guidelines in Pregnancy, with 25% consuming the recommended daily number of servings of vegetables and fruit (≥6).²⁰ Changing diets in women during pregnancy, especially reducing consumption of ultra-processed foods, may have a positive effect on the mental health of the next generation. For example, overseas initiatives have shown mothers receiving adequate nutrition during pregnancy, especially from fish, leads to better mental health outcomes for their offspring.²¹ Indeed, pregnancy is the most cost-effective time for any government to allocate its resources for prevention.

Pregnancy presents as an opportune time for dietary improvement and research shows this can be achieved;²² however, food insecurity (limited access to nutritious food due to cost) and food deserts (areas in which access to nutritious foods are limited) are global health concerns that limit women’s ability to improve their diet.^23,24 Further, multiple factors mean diet change alone may be insufficient to address existing mental health challenges, with data from high-income countries showing supplementation with multiple micronutrients (vitamins and minerals) may be necessary to prevent nutritional deficiencies during pregnancy.²⁵ However, single-nutrient studies have been largely disappointing in reducing the symptoms of perinatal depression.²⁶

Women with antenatal depression may need more micronutrients than diet provides

The NUTRIMUM trial, which ran between 2017 and 2022, aimed to study whether providing additional micronutrients could be proof of principle that the nutritional environment during pregnancy may not be adequately meeting the mental health needs of the mothers. This study adopted a broad-spectrum micronutrient approach that ensured all essential vitamins and minerals were provided in balance, recognising that no one single nutrient can address nutritional deficiencies that may be related to poor mental health. NUTRIMUM recruited 88 women, mostly from the Canterbury Region, in their second trimester of pregnancy and presenting with moderate depressive symptoms. They were randomly allocated to receive either 12 capsules (four pills, three times a day) of a broad-spectrum micronutrient supplement (Daily Essential Nutrients) or an active placebo containing iodine and riboflavin for a 12-week period.²⁷ Micronutrient doses were generally between the recommended dietary allowance (RDA) and the tolerable upper level. Retention in the study was good (81%) and compliance excellent (90%). After the randomised controlled trial (RCT) phase, all women were offered the micronutrients until the birth of their child.

The mental health outcomes from the RCT

Both groups reported similar reductions in symptoms of depression, with more than three-quarters of participants in remission at the end of the RCT. However, 69% of participants in the micronutrient group rated themselves as “much” or “very much” improved, compared with 39% in the placebo group. Also, based on clinician ratings, micronutrients significantly improved overall psychological functioning compared with the placebo. The clinician ratings considered all noted changes based on self-assessment and clinician observations, including sleep, anhedonia, mood regulation and side effects.²⁸

There were no group differences in reported side effects, and reports of suicidal thoughts, stress and anxiety dropped over the course of the study for both groups. Blood tests confirmed increased vitamin levels (vitamin C, D, B₁₂) and fewer deficiencies in the micronutrient group.²⁹ Micronutrient treatment also appeared to support a more diverse (alpha diversity) and stable (beta diversity) microbiome during pregnancy.³⁰

Naturalistic follow-up of the birth outcomes and early infant development

The infants of the mothers enrolled in the NUTRIMUM trial provided a naturalistic opportunity to investigate the effects of micronutrients on birth and infant outcomes. Due to the varying starting points in gestation of the RCT phase (12 to 24 weeks), the inclusion of an open-label phase and gestational age at birth, NUTRIMUM infants had varying days of exposure during pregnancy to the micronutrients that ranged from 0 to 6 months, although the mean was 113 days. To contextualise the outcomes, two other groups of women were monitored during pregnancy and post-birth: 1) a reference group: mothers not using the NUTRIMUM micronutrients or psychiatric medications, and 2) medication group: mothers using antidepressants during pregnancy to treat depression.

Mothers taking micronutrients had birth outcomes similar to the reference group, with no increased risks of preterm births, low birthweight or delivery complications, and on par or better than national averages in New Zealand.³¹ The one significant group difference favoured a better outcome for the micronutrient-exposed mothers, with significantly less bleeding after delivery (post-partum haemorrhage) in vaginal births (7.7% versus 30%). Compared with the infants exposed to antidepressants, the micronutrient infants had significantly higher gestational age (about 1 week difference; 5.5% premature births in the NUTRIMUM group and 20% in the antidepressant group) and greater birth length (about 2.2cm difference, and lower rates of infant resuscitation (14.5% versus 45%). The longer the infant was exposed to the micronutrients during pregnancy, the heavier and the longer the child was at birth.³¹ This means the risks conferred to the infant based on the mother’s history of depression were possibly mitigated by the micronutrients.

The observational follow-ups of the infants post-birth showed positive effects of micronutrients on the infants’ ability to regulate their behaviour. These results were on par with or better than the reference group, and better than those infants exposed to antidepressant treatment in utero.³² Infants exposed to micronutrients during pregnancy were significantly better at attending to external stimuli and were also better able to block out external stimuli during sleep. They showed fewer signs of stress and had better muscle tone compared with infants not exposed to micronutrients. They were better at regulating their emotional state and had fewer abnormal muscle reflexes than infants exposed to antidepressant medication in pregnancy. Reassuringly, micronutrients had no negative impact on infant temperament. Finally, the mothers who took the micronutrients during pregnancy were protected from the development of post-natal depression.³³

These positive effects of micronutrients on birth and infant outcomes are consistent with documented benefits of following a Mediterranean diet during pregnancy on perinatal outcomes.³⁴ They are also consistent with extensive research in low- and middle-income countries, demonstrating the additional benefit of multiple multi-nutrient supplementation over iron–folic acid alone on key birth outcomes such as low birthweight and preterm birth,³⁵ raising the possibility that depression in pregnancy could also be linked to multiple nutrient deficiency. Further, the overall benefits observed for the micronutrient-exposed infants compared to standard care were achieved despite the micronutrient group having a greater number of risk factors associated with poorer birth outcomes, including past history of smoking, higher rates of depression at study entry and more unplanned pregnancies, suggesting the potentially beneficial effect of micronutrient exposure to bring risks down to those observed in nondepressed mothers. Additional micronutrients might compensate for an inadequate in utero nutritional environment relative to needs as well as mitigate the negative effects that depression can have on birth and infant outcomes.

Limitations of the research

There are limitations including small sample sizes, only singleton pregnancies were included and the results apply only to mild-to-moderate symptoms of depression. The EPDS is merely a screening tool and only indicates the presence or absence of symptoms of anxiety and/or depression, so future research could utilise standard clinical interviews. In addition, the effects of the micronutrients cannot be generalised to those taking medications during pregnancy alongside micronutrients, and there were varying days of exposure to the micronutrients during pregnancy, with no exposure during first trimester, in contrast to the medication group who received the antidepressants throughout the pregnancy. There was only a small percentage of Māori and Pacific participants in NUTRIMUM (9%), and all participants identified as female; therefore, we do not know whether these results would extend across different ethnic groups and gender. Nevertheless, it is one of the largest controlled studies in pregnancy for the treatment of symptoms of antenatal depression and, as such, is relevant to treatment guidelines. There are no controlled trials of antidepressants during pregnancy to compare these results to.

Updating guidelines to include nutrition would have gains beyond just maternal mental health

Nutrition advice and possibly nutritional supplementation could be added to the current best practice guidelines, notably missing from both RANZCP and RANZCOG guidelines for management of mood disorders in the pregnancy and post-partum period.^4,8,9 Further, these results suggest that doses of antenatal over-the-counter supplements may not be sufficient to confer the advantages on birth outcomes observed in the NUTRIMUM micronutrient group, challenging the suitability of the current RDA doses for a pregnant population. Indeed, other research has shown doses of micronutrients in antenatal supplements are well below what is recommended by the American College of Obstetricians and Gynaecologists nutritional guidelines.³⁶ It also encourages a revisit of the New Zealand Ministry of Health guidelines that only identify iodine and folic acid as essential micronutrients to prescribe during pregnancy.

Supplementation is not a replacement for nutritious food. Supporting mothers to eat nutrient-dense food should be the goal and research could evaluate the potential cost savings obtained through supporting mothers to eat more nutrient-dense foods during pregnancy on both mental and physical health issues. For example, New Zealand has one of the highest increasing rates of endometrial cancer in women under 50 in the world, the cancer most strongly associated with obesity. Educating women on the benefits of nutrition for her health and that of her offspring, provided in a culturally safe and responsive manner, could also be an opportunity to prevent later endometrial cancer.³⁷

Reducing healthcare costs

The study also points to a way to potentially reduce healthcare costs. Although the cost of the supplement studied in NUTRIMUM is a barrier for some mothers (~NZ$200/month at full dose for up to 6 months, i.e., $1200), insurance companies and government agencies could consider the cost effectiveness of such an intervention for mitigating known negative impacts of poor nutrition and untreated depression on birth outcomes. For example, the women treated with micronutrients had rates of preterm birth comparable to a typical low-risk birth (5.5%), offering an opportunity for cost savings. The incremental cost of a late preterm birth (32–36 weeks) relative to a term birth are AUD$25,417 (~NZ$28,000; birth, neonatal care, delivery costs, early intervention, schooling, primary and secondary care to 18 years).³⁸ The risk of a preterm birth of an untreated mother with depression is about 15%. Therefore, the cost savings per birth to a mother with antenatal depression treated with micronutrients: ((15%−5.5%) * $28,000) − $1200 = NZ$1,460.

With 60,000 live births in New Zealand per year, and about 12% of mothers in New Zealand experiencing antenatal depression,³ potential cost savings per annual cohort using micronutrients for these mothers: 60,000 births 12% $1,460 = ~NZ$10.5 million. These potential cost savings on preterm birth alone should encourage replication in larger and more diverse samples as well as controlled studies using micronutrients consistently throughout the pregnancy compared with standard medication care. $10.5 million per annual cohort likely underestimates cost savings as benefits were also observed in other costly health issues, such as maternal depression, post-partum haemorrhaging and infant resuscitation. Combining micronutrients with 600mg/day of docosahexaenoic acid (DHA) omega 3 fatty acids could result in even better birth outcomes and even greater cost savings.³⁹

Practical advice for clinical teams

1. Nutrition and diet

• Increase whole foods: Emphasise the consumption of whole foods such as fruits, vegetables, nuts and seafood. These foods are associated with better mental health outcomes for both mothers and their offspring. Recent guidelines indicate that during pregnancy eating at least two portions of fish a week, one of which should be oily, is advised.⁴⁰
• Reduce ultra-processed foods: Limit the intake of ultra-processed foods, which are linked to higher risks of maternal depression and negative mental health outcomes in children.
• Seek nutritional guidance: Pregnant women could be supported within the maternity services with advice from nutritionists or dietitians to ensure they are meeting their nutritional needs. This is especially important if they have limited access to nutritious foods.

2. Micronutrient supplementation

• Consider supplements: For pregnant women with mild-to-moderate depressive symptoms, healthcare providers could consider a broad-spectrum micronutrient supplement. The NUTRIMUM trial showed significant improvements in maternal mental health and infant outcomes with such supplementation. Note that combining micronutrients with psychiatric medication should only be undertaken with careful physician monitoring.

3. Access to nutritional support

• Government and insurance support: Advocate for government and insurance support to cover the costs of nutritional supplements, as they can lead to significant healthcare savings by improving birth outcomes and reducing the need for medical interventions.

4. Mental health support

• Psychotherapy and counselling: While micronutrients can help, psychotherapy and counselling remain important. Cognitive behavioural therapy and interpersonal psychotherapy are effective treatments for antenatal depression.
• Address barriers: Work on overcoming barriers to accessing mental health care, such as cost, time constraints and stigma. Online therapy options might be a viable alternative.

5. Policy and guidelines

• Update guidelines: Support efforts to update clinical and legislative guidelines to include nutrition and micronutrient supplementation as part of standard care for antenatal depression.
• Research and advocacy: Encourage further research and advocacy to explore the benefits of micronutrients and improve access to nutritional support for pregnant women.

Conclusion

The research reviewed in this viewpoint provides an evidence-based alternative for women with associated cost savings for the public health system and could be included as part of informed consent. The prenatal environment, including nutrition, sets the foundation for a child’s future. More nutritious foods and possibly additional micronutrients could provide future generations with a better start to life. Is it time to revisit current guidelines for the treatment of antenatal depression to include nutrition?