Mediterranean diet

Of interest, the Mediterranean diet characterised by high intakes of fruit, vegetables, olive oil, fish, legumes, and cereals and low intakes of potatoes and sweets, is associated with reduced risk of Spina bifida in offspring compared with maternal intake not on Mediterranean diet.²⁸ The Mediterranean diet also correlated with higher levels of serum and RBC folate, serum vitamin B12 and lower plasma homocysteine.

Western diet

Maternal consumption of the Western diet (e.g. high in meat, pizza, legumes, and potatoes, and low in fruits) increases the risk of offspring with a cleft lip and/or cleft palate by approximately twofold.²⁹ The authors postulated low folate levels in the Western diet may account for this association and, therefore, recommend dietary and lifestyle profiles should be included in preconception screening programs.

Fish and heavy metal exposure in pregnancy

Fish is an important part of dietary intake. It contains a number of essential nutrients such as eicosopentaenoic acid (EPA) and docosohexaenoic acid (DHA), important for development of the fetal brain and retina, and is rich in iodine, iron, choline, selenium, and trace elements important for pregnancy and fetal growth. Also meta-analysis of the literature indicates maternal diet high in fish may reduce the risk of inflammatory conditions such as rheumatoid arthritis, atopy and asthma in the newborn, although more evidence is required.^{30, 31}

Health benefits of fish may counterbalance any adverse effects of mercury exposure on the developing nervous system.³² All fish contains some mercury in their flesh, mostly in the form of organic methyl mercury (MeHg), a known neurotoxin which can cause developmental delay, neurological problems and damage to the developing central nervous system (CNS). The quantity of MeHg present in fish varies depending on the dietary habits and age of the fish, and is particularly concentrated in the larger predatory fish at the top of the food chain.

Foods Standards Australia New Zealand (FSANZ) has useful advice on mercury in fish.³³ FSANZ found that most fish is safe for all population groups to eat 2–3 serves per week and recommends that pregnant women, women planning pregnancy and young children continue to consume a variety of fish as part of a healthy diet, but limit their consumption of the larger predatory fish such as shark, marlin, broadbill and swordfish (containing highest levels of MeHg) to no more than 1 serve per fortnight with no other fish to be consumed during that fortnight. For orange roughy (also sold as sea perch) and catfish, the FSANZ advice is to consume no more than 1 serve per week, with no other fish being consumed during that week.³³

The FSANZ ‘Advice on Fish Consumption’ has been specifically developed for the Australian population and suggests that women in other countries check with their local authorities as mercury content of fish varies from country to country depending on the environmental exposure, patterns of fish consumption in the community and other food sources consumed containing mercury.

Vitamin A deficiency

Vitamin A deficiency is common in developing countries such as Indonesia and Nepal due to poor nutritional intake where daily or weekly supplementation may be necessary as deficiency of vitamin A causes night-blindness, anaemia and other problems.⁶⁴ However, in women with adequate nutritional intake, vitamin A supplementation can cause toxicity, especially doses >10 000IU/day, and should be avoided. Toxic levels can cause miscarriage and birth defects. Note: beta-carotene intake is very safe.

Vitamin C deficiency

It is not clear if taking vitamin C supplementation in pregnancy is safe, because a Cochrane review found in a trial that vitamin C supplementation was linked with a moderate risk of pre-term birth, although more studies are required to confirm this adverse effect.⁶⁵ Vitamin C deficiency is linked with complications in pregnancy such as pre-eclampsia, anaemia and intrauterine growth retardation, and so women should be encouraged to eat foods rich in vitamin C such as fruit.

Vitamin D deficiency

Severe vitamin D deficiency can cause maternal osteomalacia and lead to significant morbidity in the mother and fetus. The prevalence of vitamin D deficiency in pregnant women is high and this can have serious health ramifications in the mother and child.^{66, 67} Pregnant women who are deficient in vitamin D can lead to reduced weight gain and pelvic deformities that prevent normal delivery. For the fetus, vitamin D deficiency is linked with poor fetal growth, low birth weight, neonatal hypocalcemia with and without convulsions, neonatal rickets, defective tooth enamel, and pre-disposition to childhood rickets, particularly in breastfed, dark skinned children.^{68, 69, 70} Deficiency is common in populations residing in geographically prone areas such as southern Australia (e.g. Melbourne) and in some high-risk communities such as migrants, women wearing veiled clothing, and people who spend more time indoors.⁷¹ Ninety percent of the body’s vitamin D is produced by the skin from sunlight (ultraviolet B light) exposure of non-covered skin without sunscreen, with only 10% coming from dietary sources. It is essential to restore vitamin D deficiency in mothers by advising safe sun exposure which is dependent on geographical areas and pigmentation of the skin (the darker the skin the more sun that is required), and supplement with cholecalciferol if needed, but this needs to be done cautiously to avoid vitamin D toxicity. Excessive vitamin D may cause hypercalcemia and fetal harm. Doses within RDI are safe. According to a Cochrane review of the literature, there is not enough evidence to date to evaluate the effects of vitamin D supplementation in pregnancy.⁷² Vitamin D is excreted in milk in limited amounts, and with excessive use can cause toxicity in infants. If pharmacological supplementation is required, it is essential to monitor calcium levels in the infant and get maternal vitamin D checked regularly.

Folate deficiency

Folate is one of the most important nutrients for healthy fetal development. Pregnant women and the growing embryo require higher levels of folate for cell replication and growth. Rapidly dividing cells in the embryo fail to produce healthy DNA if folate levels are low. The recommended daily intake for folate is increased significantly by 50% in pregnancy. It is recommended that every woman planning a pregnancy should take 500mcg folate a few months prior to pregnancy and in the 1st trimester although recent studies indicate that folate supplementation in the 2nd trimester may help prevent pre-eclampsia.⁷³ Low folate levels are associated with increased risk of spontaneous abortion, anaemia, low birth weight and congenital malformations such as neural tube defects (NTD), oral clefts and cleft palate, and cardiovascular and urinary tract malformations.^{74, 75} Overall, nutritional deficiency in the pregnant woman (not just folate deficiency) can increase the risk of orofacial cleft. Increasing intakes of vegetables, protein, fibre, fruit, ascorbic acid, iron, vitamin Bs and magnesium also reduce the risk of orofacial cleft.^{76, 77}

Folate is essential for fetal brain and spinal cord development. A Cochrane review evaluated 4 trials of folate supplementation involving 6425 women. Peri-conceptional folate supplementation significantly reduced the incidence of NTD (relative risk 0.28, 95% confidence interval 0.13 to 0.58) without significant harmful effects such as miscarriage, ectopic pregnancy or stillbirth. The authors also found multivitamins were not associated with any additional beneficial preventative effects of NTDs even when given with folate.⁷⁸

Iron deficiency

The recommended daily intake for iron is increased significantly, by 50%, in pregnancy. Iron deficiency is linked with infertility, anaemia, increased risk of infection, fatigue, and behavioural and cognitive development problems.^{84, 85, 86} It is possible that fetal oxygenation is compromised with iron deficiency.⁸⁵ While the benefits are clear for iron supplementation, if the mother demonstrates serum iron deficiency with or without anaemia, at this stage, there is not enough evidence to recommend routine iron supplementation in all pregnant women.⁸⁷

Zinc deficiency

Zinc is an essential trace element and plays an important role in normal growth and development, protein synthesis and cellular integrity. Zinc deficiency can adversely effect pregnancy outcome, such as pre-term birth, intrauterine growth retardation, poor fetal bone growth and prolong labour.^{88, 89} Zinc deficiency is common in low socioeconomic groups with poor nutritional intake and in third world countries. A trial of zinc supplements in HIV pregnant women improved infant mortality, birth weight and duration of pregnancy.⁹⁰ Its benefit was related to improving immune status.

Foods rich in zinc are found in pecans, wholegrains, lima beans, almonds, walnuts, hazelnuts, sardines and chicken. A Cochrane review of 17 randomised controlled trials (RCTs) involving over 9000 women and their babies demonstrated zinc supplementation resulted in a significant reduction in pre-term birth by 14%, reduced need for caesarean section and in 1 trial demonstrated reduced need for induction of labour, but did not reduce the risk of babies with low birth weight.⁹¹ In a study held in Bangladesh, babies of women who took 30mg/day of elemental zinc during pregnancy were less likely to develop acute diarrhoea by 16%, dysentery by 64% and impetigo by 47%, compared with mothers on placebo.⁹²

Iodine deficiency

Iodine is an essential trace element for the production of thyroid hormones T3 and T4. Studies indicate mild deficiency of iodine is common in pregnant women.⁹³ Sources of iodine include ocean fish, spinach, seaweed (such as kelp), garlic, watercress, citrus fruit, cereals, nuts (cashews), egg yolk and iodised salt. Researchers suggest pregnant women need to increase their intake of iodine and, if deficient, should consider supplementation from 100–200mcg/day.

A high frequency of iodine deficiency is known to occur in Australia, with almost 20% of pregnant women having a moderate to severe iodine deficiency. Mild deficiency occurred in almost 30% of women.⁹⁴

Maternal iodine deficiency is known to cause neonatal cretinism. A suboptimal iodine intake by pregnant females without overt deficiency may compromise fetal development, even in the absence of cretinism, leading to developmental delays in the infant.⁹⁵

It is possible to prevent cretinism with iodine supplementation pre-conception, and also if supplementation is given before the end of the 2nd trimester.⁹⁶

Depression as a risk factor for GDM

Among low-income pregnant women, those with diabetes (pre-existing of gestational) were twice as likely to suffer peri-natal depression and more likely to have post-partum depression after adjustment for other confounding factors, according to a retrospective cohort study.⁹⁷

Lifestyle and GDM

Lifestyle risk factors play a role in the development of diabetes in any person and these include stress management, sunshine for vitamin D, dietary factors, exercise and sleep strategies. (See Chapter 13 for diabetes and Chapter 22 for sleep.)

Exercise and GDM

An analysis of 21 765 women as part of the Nurses Health study II found that women who perform regular exercise, especially brisk walking 30 minutes daily, before pregnancy have a significantly reduced risk of developing GDM, by up to 34%, when compared with women who did the least amount of exercise.⁹⁸

Diet and GDM

Diet factors play a significant role in the control of diabetes, with wholegrain carbohydrates and low GI diets being particularly helpful.

Low GI diet and GDM

A low GI diet can effectively halve the need to use insulin compared with a high GI diet, according to a recent randomised study.⁹⁹

A Cochrane review identified 3 trials including 107 women.¹⁰⁰ Two trials assessed low versus high GI diets for pregnant women. Women on low GI diets, had less large-for-gestational-age infants and lower maternal fasting glucose levels. The other trial assessed high fibre versus control diet but the trial did not report on the outcomes. The reviewers concluded based on these findings that whilst ‘a low glycaemic index diet was seen to be beneficial for some outcomes for both mother and child, results from the review were inconclusive’.¹⁰⁰

Weight gain and GDM

Women of reproductive age should be encouraged to maintain a normal healthy weight as weight gain and maternal obesity is associated with increased risk for diabetes, adverse pregnancy and neonatal outcome.¹⁰¹ See the maternal obesity section earlier in this chapter.

Cinnamon and GDM

Cinnamon has been reported to enhance insulin sensitivity. (See Chapter 13 for diabetes information.)

Nutrients and GDM

Nutrients in GDM may be of some help, such as fish oil and chromium supplementation, to improve insulin sensitivity, although great care is required, especially with high doses, as there are no adequate studies in pregnancy. (See Chapter 13 for diabetes information.)

Stress and PE

Work stress is a significant predictor and risk factor for developing PE.¹⁰³ In a trial on pregnant normotensive women, heart rate increased and mean arterial blood pressure rose by more than 2.9mmHg, and in some up to 10mmHg on work days.¹⁰⁴ Higher blood pressures occurred in women experiencing greater job stress.

Fibre and PE

High dietary fibre plays an important role in the prevention of PE. A study of over 1500 pregnant women found that women consuming more than 21.2g/day of fibre were associated with reduced risk of PE by up to 70% and mean concentrations of triglycerides was higher and high density lipoprotein (HDL) cholesterol was lower compared with women consuming less than 11.9g of fibre daily.¹⁰⁵

Salt and PE

Whilst a low salt diet is recommended for the prevention of hypertension, there is currently insufficient evidence to advise reduction of dietary salt during pregnancy for the prevention of PE and its complications.¹⁰⁶

Antioxidants and PE

Findings from a Cochrane review could not recommend the use of antioxidants for the prevention of PE¹⁰⁷ although another Cochrane review found women taking vitamin supplements ‘may be less likely to develop pre-eclampsia and more likely to have a multiple pregnancy’.¹⁰⁸

Vitamins C and E and PE

Inadequate dietary intake of vitamin E during pregnancy is associated with PE and low birth weight. A Cochrane review found in trials that pregnant women supplemented with vitamin E in combination with other supplements compared with placebo were at reduced risk of developing clinical PE, however, the data was too few to recommend supplementation in pregnancy at this stage.¹⁰⁹

One double-blind RCT of 283 women at risk of PE (previous history of PE or placental blood flow abnormalities) were assigned to 1000mg/day of vitamin C and 400IU/day of vitamin E or placebo at 16-22 weeks gestation.¹¹⁰ Vitamin supplementation correlated with a significant 21% reduction in plasma markers reflecting endothelial and placental function. Plasma ascorbic acid increased 32% on average, and the α-tocopherol level increased by 54%. PE developed in 17% of placebo recipients but in only 8% of women given vitamins. Furthermore, small-for-gestational-age infants were less frequent, although less significant in the vitamin-supplemented group. Subsequent research demonstrated similar findings.^{111, 112}

Another study found 1000mg of vitamin C or 400IU of vitamin E did not reduce the risk of PE compared with placebo, however, the synthetic form of vitamin E was used in this study.¹¹³ Women should be encouraged to eat foods high in vitamin E found in vegetable oils, nuts, cereals and some leafy green vegetables.

However, a recent study warns against peri-conception use of vitamin E supplements with high dietary vitamin E intake above 14.9mg/day as it increased the risk of congenital heart defects (CHDs) in offspring by nine fold.¹¹⁴

Folate and PE

A prospective cohort study of 2951 women at 12–20 weeks gestation found supplementation with multivitamins containing folic acid in the 2nd trimester reduced the risk of developing PE.⁷³

Mineral supplementation for PE

Herbs for PE

Nausea and vomiting

Nausea and vomiting may occur in the early stages of pregnancy and can be quite intense and disabling for the mother. In some mothers, nausea and vomiting persist throughout the whole pregnancy. HG occurs in 0.5–2% of pregnant women, although up to 85% of women will experience some level of nausea. When symptoms are severe, some women require hospitalisation and intravenous fluid therapy to avoid dehydration.

Many trials have compared the use of vitamin B6 and ginger with anti-emetic medication. A Cochrane review of the literature found anti-emetic medication to reduce the frequency of nausea but there is little research that explores adverse fetal outcome from this medication and it can cause side-effects such as drowsiness in the mother. The reviewers found evidence for ginger, acupressure (of pericardium P6) and vitamin B6 in reducing severity of nausea and vomiting.¹²²

Lifestyle and miscarriage

A large UK population case-control study identified risk factors for 1st trimester miscarriage and found lifestyle factors and stress play an important role in increasing the risk of miscarriage.¹³⁵ The findings of this case-control population-based study are summarised in Table 32.1.^18,135

Table 32.1 Lifestyle and behavioural risk and protective factors for miscarriage

Stress and miscarriage

Stress is a risk factor for miscarriage, particularly with stressful and traumatic events. Stress may contribute to hormonal imbalance such as lowered progesterone and raised cortisol levels through neuroendocrine pathways.

Caffeine and miscarriage

Furthermore, a recent study suggests caffeine consumption of at least 2 cups daily (200mg or more) increases the risk of miscarriage by up to 40% compared with women with no intake of caffeine.¹³⁶

Nutritional factors and miscarriage

A Cochrane review of the literature found research to date indicates that pregnant women taking a daily multivitamin supplementation prior to or early in pregnancy does not reduce the risk of miscarriage or stillbirth.¹³⁷ It is likely that supplements used did not contain enough of the nutrients that can be protective. The quality of the nutrients is also important. The amount of nutrients and the type of nutrient, especially whether they were synthetic or natural, may have been an important factor in this study, which could explain this unexpected result.

Despite these findings, numerous studies have demonstrated the association between increased homocysteine and spontaneous miscarriage.^{138, 139} Folic acid and vitamin B6 and B12 take part in the metabolism of homocysteine.

Coeliac disease is associated with damaged intestinal mucosa leading to a malnourished state caused by the malabsorption of macro and micronutrients. Miscarriages are more frequently observed in those with coeliac disease.¹⁴⁰ Therefore coeliac disease must be considered in the pre-conceptional screening and treatment of patients with reproductive disorders.

Iodine deficiency is a risk factor for growth and development of up to 800 million people living in iodine deficient environments throughout the world. The effects on growth and development, called the Iodine Deficiency Disorders, includes miscarriages.^{94, 95, 96} Poor diet or diets that are vitamin deficient such as folate have been associated with an increased risk of women losing their baby early in pregnancy.¹⁴¹

Sperm and miscarriage

Older sperm are also risk factors for miscarriage. ¹⁴³

Saturated fats, riboflavin and nicotinamide and newborn CHD

Fatty acids play an important role in embryonic development, and B-vitamins riboflavin and nicotinamide play a role as co-enzymes in lipid metabolism. Vitamin B deficiency is linked with increased incidence of CHD.¹⁴⁴ A study demonstrated that maternal diets low in dietary riboflavin (<1.20mg/d) and nicotinamide (<13.5mg/d) increased the risk of a child with CHDs by twofold, especially in mothers who did not take multivitamins, and particularly those on high saturated fatty diets.¹⁴⁵ These findings were independent of dietary folate intake.

Vitamin E increases risk of newborn CHD

High vitamin E dietary intake and supplements have been associated with CHD in offspring (see under heading above, ‘Vitamins C and E and PE’).¹¹⁴

Stress and pre-term birth (PTB)

Epidemiological evidence suggests that maternal psychosocial stress, strenuous physical activity and fasting are independent risk factors for PTB and low birth weight.¹⁴⁶

Depression, anxiety, stress and PTB

Depression and anxiety are risk factors for pre-term labour. Screening of pregnant women for depression may be useful as antenatal depression is significantly associated with almost twice the risk of pre-term delivery (before 37 weeks) compared with non-depressed women, according to a cohort study of 791 women assessed at 10 weeks gestation and followed up during pregnancy.¹⁴⁷ Severe depression increased the risk by up to 2.2 times compared with women not suffering antenatal depression. The authors concluded that their findings show that pregnant women with depressive symptoms are a risk factor for PTB and exacerbated by stressful events, low educational level, and a history of fertility and obesity. It is likely excess cortisol produced in response to stress may play a role, although other factors may also contribute.

A study of 634 pregnant women revealed that depression was positively associated with underweight women (pre-pregnancy BMI below 19) and together with anxiety correlated with a higher incidence of pre-term delivery.¹⁴⁸ Anxiety also correlated with vaginal bleeding. These findings indicate that depression and anxiety are associated with spontaneous pre-term labour.

Yoga reduces risk of PTB, PE, intrauterine growth retardation

A study demonstrated yoga consisting of gentle, daily physical postures, meditation and breathing improves pregnancy outcome, significantly reduces risk of PE, intrauterine growth retardation, pre-term labour and low birth weight newborns.¹⁴⁹ No significant adverse events were reported in the yoga group. Yoga helps with relaxation, postural and stretching exercise so may have benefits in other areas of pregnancy, such as anxiety, headaches and back pain.