Chapter 32 Pregnancy disorders
Introduction
Pregnancy is a special time in a woman’s life that should be enjoyed with good health. Due to a surge of hormones and rapid physical changes by the body, a number of distressing symptoms may arise, especially if the woman is unprepared. Many women conceive without planning a pregnancy, so it is not always possible to be prepared for a pregnancy. Hence it is vital that women optimise their health as soon as they make the decision to plan a pregnancy.
Complementary and alternative medicines (CAMs) are frequently used in pregnancy, more than prescription medicines, according to Australian research.1 These CAMs include massage (49%), vitamin and mineral supplements (30%) and yoga (18.4%) which are not likely to be harmful in pregnancy. The study highlighted more than three-quarters had used at least 1 complementary therapy 8 weeks prior to the study; one-third had used complementary medicine to alleviate a physical symptom such as headache, cough or cold with a 95% positive response to treatment compared with 6.8% of women on prescription medicine to treat a complaint.
Studies in the Netherlands found up to 36% of women were using herbs in pregnancy and up to 43% during breastfeeding.2 The most commonly used herbs in pregnancy include red raspberry leaf, ginger, chamomile3 and also echinacea and cranberry.2 Less commonly used supplements were fish oil, herbal teas, blue cohosh, acidophilus, ombeshi plums, homeopathic drops, peppermint and St John’s wort.
Symptoms of pregnancy
A number of problems can develop during pregnancy, including the following:4
Mind–body medicine
Sleep
A good nights sleep of up to 8 hours a night is essential in pregnancy and post-partum to help reduce fatigue, depression, mood disturbances and exhaustion. Recent evidence also suggests that a good nights sleep also contributes to shorter labour and an easier delivery.5 Women who slept for less than 4–5 hours per night were more likely to have caesarean deliveries and experience longer labour times compared with women who were well rested.5
Psychosocial and psychological factors
Many women experience anxiety during pregnancy and fear of pain, especially with a vaginal delivery. Studies suggest that personality factors such as general anxiety, neuroticism, low self-esteem and vulnerability, and dissatisfaction with their partners, violence in the relationship, lack of social support and unemployment will contribute and amplify pregnancy related anxiety.6, 7 Strategies such as increasing supports, meditation, counselling and cognitive behaviour therapy (CBT) should be aimed at reducing maternal anxiety and addressing issues with the partner. Even a telephone-based peer support line can make a significant difference in preventing postnatal depression among women at high risk.8
Duration between births
Women should be advised to avoid conceiving too quickly after giving birth to avoid subsequent birth complications. A large scale study of 89 000 women found shorter intervals between births (i.e. of less than 6 months between first and second pregnancy) was an independent risk factor for pre-term birth and neonatal death in the second pregnancy.9
Physical activity/exercise
It is clear that daily exercise benefits pregnant women both physically and emotionally but what is not certain is the level of intensity that is safe for pregnancy. A prospective study of 148 pregnant women examined whether vigorous exercise undertaken by recreational exercisers had any impact on infant birth weight and gestational age at birth.10 The researchers found there were no differences between the different exercise groups in pregnancy outcome, and duration or frequency of vigorous exercise was not associated with any adverse outcome for the infant, such as mean birth weight.
Regular exercise maintains and improves fitness during pregnancy, including aerobic exercise. However, larger and better trials are needed before confident recommendations can be made about the benefits and risks, such as pre-term birth, of more vigorous exercise in pregnancy.11
Environmental factors
Pollution
Pollution is a public health issue and can cause adverse health outcomes in pregnancy. A large Australian study of 28 000 births recorded during the study period found exposure to low levels of air pollution from vehicle exhausts, particularly in the 1st trimester, resulted in more premature births before 37 weeks gestation, the risk increasing by 15–26%.12 This association was strongest in winter and less in autumn compared with summer.
Smoking
Smoking should be completely avoided in pregnancy for its known adverse pregnancy outcomes that include intrauterine growth retardation, failure to thrive, low birth weight, premature death, fetal anomalies, and predisposition to asthma (maternal and child). Giving up smoking prior to pregnancy is preferred, although even ceasing early in the pregnancy (before 15 weeks gestation) can also be of benefit and reduce the risk of spontaneous pre-term birth and infants who are small for gestational age, according to a prospective cohort study.13
Smokers demonstrate lower levels of folate compared with non-smokers with similar dietary folate intake which may explain some of the negative pregnancy outcomes.14 Passive smoking is also harmful.
Recent evidence suggests smoking during pregnancy also increased the risk of children developing behavioural problems and hyperkinetic disorder by threefold compared with non-smokers.15
Alcohol
The Australian new-draft alcohol guidelines state that for pregnant women and women planning pregnancy no drinking is the safest option.16 A British study examining the effects of low–moderate prenatal alcohol exposure on pregnancy outcome found no convincing evidence of adverse effects.17 Similar findings have been found by a Western Australian group, however, alcohol intake at higher levels, particularly heavy and binge drinking patterns, was associated with increased risk of pre-term birth even when drinking was ceased before the 2nd trimester.18 Adverse effects of alcohol exposure on the fetus include fetal alcohol syndrome (1–3 % of live births), birth defects, neurodevelopmental disorders, miscarriage, still births, pre-term births and low birth weight.
Fetal alcohol exposure can be minimised through abstaining or reducing alcohol consumption or increasing effective contraception in females who engage in risk drinking.19
Animal studies suggest dietary zinc supplementation may play a role in preventing fetal alcohol syndrome due to prenatal ethanol exposure, although more studies are required.20
Maternal obesity
It is natural for a woman to gain on average up to 18kg during pregnancy without risking complications, although the recommended weight range is from 11.5 to 16kg.21 The optimal birth weight for the infant is 3500–4500g. Women gaining weight at the lower end of the recommended range had a higher chance of low birth weight newborns weighing less than 3500g.
A study of 100 pregnant women were randomised to a program of dietary and lifestyle counselling that helped reduce excessive weight gain during pregnancy compared with the routine prenatal care group, who also had significantly more caesarean deliveries by 58.6% due to failure to progress (compared with lifestyle counselling group 25.0%, P = .02).22
Obesity is an independent risk factor for negative, adverse pregnancy outcome. It contributes to infertility, miscarriage, hypertension, increased deep vein thrombosis and pulmonary embolisms, pre-eclampsia, gestational diabetes, prematurity, congenital anomalies, fetal distress, still birth, longer labour, caesarean delivery, subsequent post-operative complications, and cardiovascular risk factors.23–26
A large scale cohort study of 54 000 pregnant women found the risk of fetal death (stillbirth) for obese women (Body Mass Index [BMI] >30) doubled by week 28 of gestation and quadrupled by week 40 compared to normal weight women.27 They found that obesity was associated with placental dysfunction.
Nutritional influences
Diet
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
Nutritional risk factors in pregnancy
The increased needs during pregnancy can vary from 12% for dietary fibre, 14% for vitamin A, 46% for vitamin B6, 50% for folate, 37% for zinc, 50% for iron, 46% for iodine, 30% for protein and 25% for essential fatty acids.34, 35
Teenage pregnancy requires special needs as a mother’s body is still growing in many instances. The ideal weight gain for teenage pregnancy is 10kg; lower weight gain can lead to lower birth weight which can be associated with greater risk of developing type 2 diabetes and hypertension later in life, as well as a weight problem.27
Routine supplementation with iron, vitamin A, C and E are not recommended in pregnancy. 36
Nutritional supplements
Fish oil for pregnancy and breastfeeding
Fish oils play an important role in pregnancy and in the development of the fetus and newborn. Pregnant women should be encouraged to eat at least 3 deep sea fish a week although there are real concerns with heavy metal toxicity in the larger predator fish (see section titled ‘Fish and heavy metals’).37 A number of studies demonstrate fish oils can significantly reduce the risk of atopy, asthma (see Chapter 5 for asthma information) and other immune-mediated diseases by positively modulating inflammation and prostaglandin effects on the newborn child. In addition, the benefits of fish oils are carried through to breastfed babies. In bottle-fed babies, the benefits are through formulas enriched with fish oils.38–42
For instance, a population-based study of 533 pregnant women from 30 weeks gestation to birth were randomly assigned to receive 4 x 1g gelatin capsules/day of fish oil (2.7g n-3 PUFAs) or 4 x 1g similar-looking capsules/day with olive oil, or no oil capsules.43 Over a 16-year follow-up of offspring, the risk of asthma was reduced by 63% and of allergic asthma by 87% in those pregnancies treated with fish oil compared with the olive oil group. This study supports a potential prophylactic role of fish oils late in pregnancy, reducing risk of asthma in the newborn.43
Women consuming fish oil supplements compared with olive oil capsules were also less likely to experience pre-term delivery and more likely to reach full term without any complications.44 The high intake of fish oils might prolong pregnancy by shifting the balance of production of prostaglandins in parturition.
Fish oils play an important role in the development of the nervous system and augments cognitive function, IQ, vision and behaviour in offspring to mothers supplemented with fish oils during pregnancy and breastfeeding.45–60
However, a double-blind study randomised pregnant mothers to take 10ml of either cod-liver oil or corn oil from 18 weeks gestation until 3 months after delivery.61 At 7 years of age, children were assessed and the researchers found higher maternal plasma phospholipid concentrations of alpha-linolenic acid (18:3n-3) and docosahexaenoic acid during pregnancy were correlated with enhanced cognitive function, such as sequential processing, but no significant effect was observed on global IQs or on BMI in the children.
Multi-nutrients and pregnancy
Micronutrients such as vitamins and minerals are necessary for the growing demands experienced by the pregnant mother and for the normal functioning, growth and development of the fetus. A Cochrane review of 9 trials including 15 378 women demonstrated multi-nutrient supplementation reduced the number of low birth weight and small-for-gestational-age babies and maternal anaemia, but close analyses of the data revealed no added benefit compared with iron/folic acid supplementation alone.62 Further research is required to confirm the benefits of taking multi-nutrients during pregnancy.
A systematic review and meta-analysis of the use of prenatal supplementation with multivitamins found that they decreased the risk for paediatric brain tumour, neuroblastoma and leukaemia.63
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
Medications interfering with folate
Maternal exposure to folate antagonist medication such as sulfamethoxazole-trimethoprim and anti-epileptic medication such as phenobarbital and sodium valproate may contribute to adverse pregnancy outcomes by affecting placental function, although more studies are required to confirm this finding and one needs to weigh the benefit to any potential risk.79, 80 It is important to avoid any medication and herbal medicines that may harm the fetus in pregnancy unless there is a clear risk to the mother.
Anti-epileptic medication and folate
Pregnant women who require anti-epileptic medication, many of which antagonise folate action, are at increased risk of fetal abnormalities and birth defects such as NTDs.81 Epileptic women in reproductive years should be advised to take folate peri-conceptually if on anti-epileptic medication that interferes with folate, although it is not clear what this dosage should be.
Women of child-bearing age prescribed, for example, sodium valproate should be warned about the potential risks of the drug, including teratogenesis, and should be strongly advised to ensure adequate contraception whilst taking this drug.82, 83
Minerals
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
Medical conditions associated with pregnancy or a complication of pregnancy
Gestational diabetes mellitus (GDM)
Between 1 to 14% of women develop GDM during pregnancy. Dietary advice is essential to help reduce the incidence of diabetes in pregnancy and subsequently in life. GDM can cause significant health problems, such as a very large baby, and increase the risk of negative and adverse pregnancy outcomes, such as an increased risk of induced birth and caesarean section, prematurity and increased infant morbidity and mortality. GDM is also associated with an increased risk of diabetes for mother and child later in life.
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
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.
Pre-eclampsia (PE)
Exploring diet and lifestyle are essential to lower the risk of developing PE, particularly increasing nutrient rich foods for antioxidants, vitamin E, calcium and magnesium as deficiency of these nutrients can predispose to PE. This is commonly seen in under-nourished, low socio-economic communities. A diet high in sugar and fat, cigarette smoking and low physical activity are known risk factors for PE. Stress is a contributor to PE-like hypertension. It is likely other lifestyle risk factors may also play a role in PE and strategies such as stress management, dietary changes (increasing vegetables, high fish intake), exercise and sleep restoration should assist in the management of PE (see Chapter 19 on hypertension). Calcium and magnesium appear to be particularly effective and may play an important role as therapeutic agents for PE. PE can cause serious morbidity and can lead to death in pregnant women, who should be monitored closely, including for onset and progression of chronic kidney disease.102
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
Calcium and PE
In a review of the literature of RCTs found calcium supplementation to play an important role in the prevention of PE and pre-term delivery more than any other supplement.115
A randomised placebo-controlled study of 524 healthy first-time pregnant women whose mean dietary calcium was less than RDI, found 2g of elemental calcium supplementation daily during pregnancy was associated with a significant reduced risk of PE by 69% and pre-term delivery by 49% compared with placebo.116, 117
Furthermore, a Cochrane review of the literature of 12 good quality trials supports the findings that calcium may play an important role in the prevention of PE, the authors concluding that calcium supplementation could ‘almost halve the risk of PE, and reduce the rare occurrence of the composite outcome death or serious morbidity’.118
Magnesium and PE
According to a Cochrane review magnesium supplementation during pregnancy may be able to reduce PE and fetal growth retardation.119 In a large scale international trial from 33 different countries 10 141 pregnant women were randomised to magnesium sulfate or placebo. The trial was cut short due to the positive conclusive findings demonstrating magnesium sulfate led to a significant 58% reduction of PE and 45% reduction in maternal death compared with placebo.120
Herbs for PE
Garlic and PE
Meta-analyses have demonstrated that garlic is a valid therapeutic treatment for hypertension, but its role in PE is not so clear. (See Chapter 19 for hypertension information.) A Cochrane review identified 1 study of 100 pregnant women that showed dried garlic capsules did not prevent PE compared with placebo and demonstrated no significant differences in side-effects except women on garlic reported odour.121
Hyperemesis gravidarum (HG)
Nausea and vomiting
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
Vitamin B6 and nausea
Vitamin B6 needs to be used with caution as high doses (more than 50mgs/day) and prolonged use have been associated with neurotoxicity such as peripheral neuropathy (e.g. tingling, burning and numbness of limbs), and should be stopped immediately should these symptoms develop.123, 124 Vitamin B6 should be used cautiously for therapeutic purposes and not used routinely, although a trial did suggest it may protect against tooth decay in pregnant women.125, 126
Ginger (zingiber officinale) and nausea
Ginger is a popular remedy used by pregnant women for the treatment of nausea in pregnancy. A Cochrane review of 6 RCTs involving 675 pregnant women assessed the evidence for efficacy and safety of ginger therapy for nausea and vomiting in early pregnancy.127 The authors concluded that ginger may be an effective treatment choice for nausea and vomiting associated with early pregnancy but further studies with larger numbers of women are required to confirm the promising preliminary data for the safety of this therapy. Four of the 6 RCTs showed superiority of ginger over placebo and 2 of them showed equivalence to vitamin B6 in relieving the severity and episodes of nausea and vomiting.128
Acupuncture, acupressure and nausea
A Cochrane review identified 26 trials of 3347 participants suffering nausea and vomiting and found significant reduction in the risk of nausea and need for anti-emetic medication with acupuncture point stimulation (pericardium 6) compared with sham acupuncture.129 There were minimal side-effects with this method. This treatment should be considered for pregnant women suffering severe nausea.
Cramps
Calcium and magnesium can provide effective treatment for pregnancy-induced leg cramps.131, 132, 133
Ectopic pregnancy
Ectopic pregnancy occurs in 1–2% of pregnancies and is a leading cause of pregnancy-related deaths in the 1st trimester. Whilst traditional Chinese herbal medicines are used in China to treat ectopic pregnancy, most of the trials are of poor quality.134 Surgery is highly recommended for the treatment of any ectopic pregnancy, and to exclude any predisposing factors to ectopic pregnancy, such as fallopian tube disorders.
Miscarriage
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
| Increase risk of miscarriage | Protective factors for miscarriage | No association with miscarriage |
|---|---|---|
(Source: Maconochie N, Doyle P, Prior S, Simmons R. Risk factors for first trimester miscarriage — results from a UK-population-based case-control study. BJOG 2007;114(2))
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
Congenital heart defect (CHD) in newborn
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.
Pre-term birth, low birth weight, fetal failure to thrive
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.
