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62 CPD ACTIVITY FROM PAGE 61 omega-3s required to prevent preterm birth. HANDI suggests women with singleton pregnancies take a supplement with at least 500mg DHA daily from 12 weeks until delivery, to specifically reduce the risk of a preterm (<37 weeks) and early preterm birth (<34 weeks). The supplement doesn’t need to be more than 1000mg DHA plus EPA overall, as higher doses don’t appear to provide extra benefit. The microbiome The maternal gastrointestinal microbiome (the genetic material of all microbes inhabiting the gut) changes in composition and diversity throughout the pregnancy.24 The metabolic output from digestion by the maternal microbiota (communities of commensal, symbiotic and pathogenic microorganisms) of diet, pharmaceuticals and toxins can subsequently be passed to the developing foetus and the breast- feeding neonate. While the gut microbiota resembles that of healthy non-pregnant controls in the first trimester, by third trimester the structure and composition of the community resembles a disease- associated dysbiosis that differs between women.25 Foetal immune pathways rapidly mature during the first 1000 days. The foetus is challenged by adverse environmental insults, such as infection or malnutrition. The in-utero environment shapes the foetal immune system. In normal pregnancies this is partly due to exchange of molecules from the maternal intestinal microbiota via the placenta.26 It’s likely that antenatal immunostimulation contributes to maturation of immune responses in the neonate that may predispose to development of allergic diseases later in life.27,28 Aside from immunity, the maternal intestinal microbiota plays an important role in growth and development of mother and baby by increasing energy yield from the maternal diet from digestion of complex carbohydrates and vitamin synthesis.26 Maternal malnutrition from loss of macro- and micronutrients leads to stress responses in both the mother and foetus. These stressors directly affect function of the placenta and immune development of the foetus.29 Malnutrition not only increases the risk of opportunistic infection in the mother but also decreases the availability of essential maternal immunoglobulins for the foetus.29 Increased infection in the mother will further increase her hypothalamic pituitary axis mediated stress responses.26,29 Contact with a high diversity of bacteria is important for the healthy development of the infant and protection against allergic diseases is reliant on contact with diverse bacteria. Probiotic supplementation is one approach used to intentionally modify the gut microbiota in an attempt to influence health risks. Meta-analyses of RCTs produce conflicting results for use of probiotic supplements during pregnancy and early infant life to prevent atopic dermatitis. Broad variability in study design, species of probiotic bacteria used and timing of the intervention (ie, pre- or after birth) contribute to the conflicting results.30,31,32 Most studies were carried out in the last two months of the pregnancy, which may miss the critical window available to influence foetal immune responses and development of allergic disease. A 2015 meta-analysis did find that probiotic supplementation, particularly mixed probiotics, during pregnancy and directly to the neonate, significantly reduced the risk of developing eczema but no other atopic diseases, including asthma, wheezing or rhinoconjunctivitis.33 The currently running New Zealand ‘Probiotics in Pregnancy Study’ (PiP Study) aims to assess whether supplementation of women from early pregnancy (14-16 weeks gestation) and while breastfeeding with Lactobacillus rhamnosus HN001 (6 × 109 colony-forming units per day (cfu/day)), reduces infant eczema and atopic sensitisation at one year.34 The study will also assess the effect of HN001 supplementation on maternal gestational diabetes mellitus, bacterial vaginosis, group B streptococcal vaginal colonisation before birth, and postpartum depression and anxiety.34 Barthow et al identified two studies with only mothers receiving probiotics (from 36 weeks gestation and during breastfeeding). Both demonstrated a positive effect on eczema at two years. The effect was similar to when probiotics were administered directly to the infant.28 Therefore, probiotic supplementation for the breastfeeding mother may also be important to reduce the risk of atopic disease developing later in the infant. Probiotic supplementation may also improve health outcomes for the mother, with meta-analyses suggesting supplementation decreased the risk of gestational diabetes and pre-eclampsia.35.36 The nature of the maternal vaginal, oral and epidermal microbiota impacts the microbiota of the developing infant. Robertson and colleagues evaluated healthy vaginal microbiota in urban dwelling women from high-income countries. They found these were typically dominated by one of four species of Lactobacillus.24 They suggested that aside from hormonal changes, immune system changes, particularly at mucosal surfaces, may cause changes in maternal vaginal microbiota. The vaginal microbiota is the source of the infant’s gut microbiota when delivery is vaginal, while the gut microbiota of infants delivered via caesarean more closely resembles the mother’s skin. Emerging evidence also suggests that vaginal microbes may interact with the developing foetus to ‘program’ prenatal growth and duration of pregnancy.37 Vaginal infections such as bacterial vaginosis are associated with the inflammatory cascade of preterm birth.24 Research into the benefits of probiotic supplementation on maternal and neonatal health is an immense area. Probiotics are generally considered safe but rare reports of some species of Lactobacilli being associated with sepsis in children and endocarditis in adults exist.28 Gomez-Arrango and colleagues reviewed probiotic use in pregnancy and recommended caution in patients with immunosuppression or increased risk of sepsis due to a leaky gut or significant gastrointestinal disease.38 Risk factors for allergy in babies include having a biological parent or sibling with existing or history of allergic rhinitis, asthma, eczema, or food allergy. Recommendations of the World Allergy Organisation for evidence-based use of probiotics to prevent allergy in at- risk children born to otherwise healthy women include:39 “... using probiotics in pregnant women at high risk for allergy in their children, because considering all critical outcomes, there is a net benefit resulting primarily from prevention of eczema (conditional recommendation, very-low- quality evidence)”. The recommendation cannot be generalised to women with compromised immune system function. Another recommendation suggested: “... using probiotics in women who breastfeed infants at high risk of developing allergy, because considering RETAIL PHARMACY • MAY 2021