When a woman becomes pregnant her body undergoes major changes. These affect her body shape, physiology and metabolism as she provides for the developing fetus. Changes include increased blood volume, heart rate, blood pressure, lung function and urine production by her kidneys; the movement of the digestive tract reduces. Good nutrition and lifestyle is important to give ‘the best possible’ pregnancy outcome for mother and baby.

Possible complications of pregnancy include the mother developing high blood pressure (gestational hypertension), diabetes (gestational diabetes), infections, a long labour and the need for a caesarean birth. The baby may have a low birthweight, be small for the date after conception, have a low Apgar score at birth or need to be admitted to a special care neonatal unit. The Apgar score rates the baby’s color, heart rate, response to stimulation of the sole of the foot, muscle tone, and respiration.

We present some of the evidence from Cochrane systematic reviews about complementary and alternative treatments related to pregnancy. This evidence comes from carefully researched reviews of information about clinical trials done to evaluate medical treatments. Studies are only included in these reviews if they meet pre-defined criteria.

Good nutrition is important to give ‘the best possible’ pregnancy outcome for mother and baby.Vitamin B12 and folic acid are needed for normal development of body tissues (DNA synthesis), particularly by rapidly-turning-over cells such as red blood cells as these are constantly being replaced.  Oxygen is carried around the body by the haemoglobin in red blood cells. Iron is an essential part of haemoglobin. Folic acid is an essential B-vitamin that comes from the diet. Fresh green leafy vegetables, organ meats, legumes, nuts and cereals with added folic acid are all good sources of folate. Cooking and processing can however destroy much of the folic acid in food so supplements may be needed to maintain a woman’s folic acid levels during the entire pregnancy.

Low folate levels around the time of becoming pregnant are related to increased chances of their babies having defects in the developing spinal cord. These abnormalities can lead to the baby being born with spina bifida where the spinal vertebral covering in the lower back region generally is incomplete.

The best sources of iron are meat, liver, shellfish, egg yolk, dried fruit and nuts, and legumes. A deficiency causes lethargy and tiredness, a pale colour, feeling cold and even shortness of breath.Magnesium is an essential mineral needed in relatively large amounts. Many enzymes in the body need magnesium to be effective. Enzymes are proteins that the body produces to help (catalyse) its metabolism and body function. Magnesium occurs widely in many foods including dairy products, breads and cereals, vegetables and meats.Zinc also plays a critical role in many of the body’s functions. For pregnant women, zinc may be important for a normal birth. It is obtained in the diet from meat, liver, eggs, seafood (particularly shellfish) also nuts, legumes, green beans, mushrooms, yeast and whole grains. This is complex however as whole grains, corn and rice also reduce the body’s ability to absorb zinc from the diet.

During pregnancy extra vitamin A is needed for the mother, for the growth of the baby and to provide the baby withsome reserves when it is newborn. Vitamin A is important for the skin, other epithelial surfaces such as the airways and gut and for resistance against infections. In the diet, the richest sources of vitamin A are liver, fish liver oils, herrings, sardines, tuna and dairy products (milk, cheese, butter, ice cream). Plant foods in the diet provide beta-carotene and other carotenoids that the body uses to produce vitamin A. Common sources of these include carrots, yellow squash, dark leafy vegetables, corn, tomatoes, oranges, papayas and mangoes.

Ailments most closely associated with low levels of vitamin A include measles, diarrhoea and respiratory disease. In a number of developing countries women may have both vitamin A and iron deficiencies. Vitamin C in the body is essential for producing collagen, part of the connective tissue that binds and joins the body structures together. It is also involved in the body’s defence mechanisms against infections. Vitamin C also helps the body to absorb and use iron and activates folic acid for the formation of red blood cells. We cannot make our own vitamin C so an adequate dietary intake is needed to maintain body stores. Vitamin C is found in many fruits and vegetables with high levels in guava, blackcurrants, citrus fruits, strawberries, green or mild and hot peppers, tomatoes, potatoes and broccoli. Vitamin C deficiency is rarely reported in individuals with a healthy standard diet.Vitamin D comes both from the diet (fish liver oils, egg yolk) and sunlight. Vitamin D deficiency is most likely in women who are vegetarian and who remain indoors or whose clothing leaves little exposed skin, particularly in relatively sunless climates. This is because it is produced from the effect of sunlight on the skin or is obtained in the diet by eating fish oils, beef and liver, butter and egg yolk. This vitamin is needed for strong bones.Vitamin E is a combination of eight different fat soluble compounds obtained from plants (alpha-tocopherol is the most active form of vitamin E). Vitamin E is found in wheat germ oil and other vegetable oils, nuts, some cereals and some leafy green vegetables. Synthetic forms of vitamin E are most commonly used in vitamin supplements. Vitamin E is an antioxidant reducing harmful free radicals.

There are Cochrane reviews available on eight possible supplements. They look particularly at maintaining the mother’s levels of vitamins and minerals.

ROUTINE IRON AND FOLATE SUPPLEMENTATION DURING PREGNANCY

Pregnancy makes large demands on a woman’s body with increases in her blood volume, heart rate, blood pressure, lung function and urine production. Haemoglobin and serum iron levels fall as pregnancy progresses. Approximately 65% of the body’s iron is in the haemoglobin of red blood cells. Most of the remainder is stored in cells as an iron-protein complex (ferritin). Oxygen is carried around the body by the haemoglobin in red blood cells and iron is an essential part of haemoglobin.

During pregnancy the mother also needs folic acid for producing red blood cells, as they are constantly being replaced, and for the growth of the baby. Folic acid is an essential B-vitamin that comes from the diet.

Iron deficiency and anaemia during pregnancy is a major health problem in many developing countries. Women may have an inadequate diet and have other factors such as malaria and worm (helminthic) infections and poor sanitation and drinking water which contribute to the increased risk of illness and death of mothers and their newborn babies. If a pregnant woman has low haemoglobin levels she may also be more likely to give birth prematurely and have a low birthweight baby. Iron deficiency and anaemia in newborn infants can impair the infant’s cognitive and intellectual development and physical growth (WHO 2001).

What is known

For women in industrialized countries, such as the US, 30 mg per day is likely to be sufficient. International recommendations for pregnant women who are not anaemic are for a daily dose of 60 mg of iron for at least six months of the pregnancy; using higher doses if for shorter periods and in areas where iron deficiency is common. The supplement should include 400 µg of folic acid.

International organisations advocate routine iron and folic acid supplements for every pregnant woman in areas where anaemia is common. This requires the organisational infrastructure to do this, and the supplements to be available with costs met. One way is for the supplement to be taken less frequently than one daily.

Supplemental iron can cause gastrointestinal distress with constipation or diarrhea, nausea and vomiting, especially on an empty stomach and taking higher doses.

High haemoglobin levels (greater than 130 g/L) have been associated with pregnancy complications including high blood pressure (pre-eclampsia), convulsions, (eclampsia), low birthweight and premature births.

What the synthesised research says

The great majority of studies with daily iron supplementation were carried out in industrialized countries, with minor representation from African, Asian and Latin American countries. It was the intermittent iron and folic acid antenatal supplementation trials that came from developing countries.

Comparing women taking iron alone to those who had no supplement or a non-active placebo (from 29 trials, seven of high quality) Taking daily iron supplementation during pregnancy did not affect the birthweight of the newborn (from 5 trials with 925 women) or the number of infants born with low birthweight (from 3 trials with 1147 women).

The women receiving iron alone or iron with folic acid had higher haemoglobin levels at term; were less likely (31% versus 55%) to have iron deficiency at term (from 6 trials with 1108 women) or to be anaemic (from 13 trials including 1696 women) or have iron-deficiency anaemia at term (4.9% versus 15.5%) (five trials with 940 women). This was the case whether supplementation started early or at any time in pregnancy.

There were no clear benefits to women on iron supplements in terms of having lower risks of high blood pressure, bleeding (haemorrhage), or preterm birth. Any benefits for the newborn baby were not clearly evident in the trials included in this synthesis.

Comparing women taking iron with folic acid daily to those who had no supplement or a non-active placebo (from eight trials, one of high quality)
Newborn babies were not clearly different in terms of birthweight, deaths (perinatal mortality) or admission to special care units.

The women did have higher haemoglobin levels (from 4 trials with 179 women) and were less likely to be anaemic at term (from 2 trials with 346 women).

A lowered risk of women’s developing high blood pressure, of bleeding (haemorrhage), or of giving birth preterm was not proven by these trials.

When the supplement was given less often than daily (seven trials, one of high quality) There was no evidence of clear differences in birthweight and women getting iron supplements were just as likely to have a baby with low birthweight (from 3 trials with 650 women).

Haemoglobin levels and the number of women who were anaemic were not clearly different.

Women who routinely received weekly iron and folic acid supplementation during pregnancy were more likely to experience vomiting (16% versus 9%), which is likely to be because a dose given weekly is 2 or 3 times higher than the daily dose.

How it was tested

The researchers made a comprehensive search of the medical literature. They found 40 randomised controlled trials that met pre-set criteria for inclusion.

Side effects and general cautions

Women receiving daily oral iron supplementation were more likely to report side-effects (6 trials with 1099 women) of any kind than women taking placebo or no supplement (26% versus 12%). Taking iron supplements has been linked with diarrhoea, constipation, nausea and vomiting or heartburn but this was not clear from these trials.

The information from the trials suggests that women who routinely take daily iron supplementation during pregnancy are more likely to have high haemoglobin levels (haemoconcentration) at term than those taking placebo or not taking any iron supplements at all (33% versus 10%) (from 8 trials with 1222 women).

The role of folic acid supplementation around the time of conception was not addressed in this review.

Note: Low levels of haemoglobin are below 95 g/L; anaemia at term is a haemoglobin less than 110 g/L; high haemoglobin levels are greater than 130 g/L.

Sources

Pena-Rosas JP, Viteri FE. Effects of routine oral iron supplementation with or without folic acid for women during pregnancy. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004736. DOI: 10.1002/14651858.CD004736.pub2.

World Health Organization. Iron deficiency anemia assessment prevention and control: a guide for program managers. Geneva: World Health Organization, 2001:132.WHO, CDC. Assessing the iron status of populations.

Report of a joint World Health Organization/Centers for Disease Control and Prevention technical consultation on the assessment of iron status at the population level. Geneva, Switzerland: World Health Organization and Centers for Disease Control and Prevention, 2005:1-30.

TAKING FOLATE SUPPLEMENTS AT CONCEPTION - TO PROTECT THE BABY AGAINST BRAIN AND SPINAL ABNORMALITIES (NEURAL TUBE DEFECTS)

A baby's brain and spinal cord develop from a fetal structure called the neural tube. This tube develops within the first month after fertilization (by the sixth week after the last menstrual period).

If the neural tube does not completely close, the infant may not survive and the defect can cause severe mental and physical impairments or disability (congenital defects). For example, spina bifida is the incomplete closure around the spine so that part of the spinal cord or its protective membrane (meninges) is exposed. Surviving children may have incontinence, reduced mobility and sensation, learning difficulties. The severity of the impairments depends on where the defect is, its size, the extent of neural tissue damage and the degree of increased fluid in the brain (hydrocephalus). Newborn infants with neural tube defects may also have facial clefts, limb reduction defects, heart defects involving the main blood vessels coming out from the heart and urogenital defects.

Although these defects can be identified in the second trimester of pregnancy and pregnancies may be terminated, the defects cause a lot of grief. Having a pregnancy with neural tube defects is associated with a greatly increased risk of it happening again in following pregnancies.

What is known

There are striking geographical variations, both between and within countries, in the prevalence of newborn babies with neural tube defects. In places where the prevalence is high there are marked social class differences, with neural tube problems occurring more often in pregnancies of women with low social determinants of health.

Based on observational studies of individual women (case studies), communities (cohorts) and in non-randomised studies, higher dietary intakes of folate or multivitamin or folic acid supplements taken by the mother before pregnancy and in the first two months of pregnancy are associated with decreased risks of having a baby with neural tube defects.

In many countries this has led to dietary advice and counseling for women who are likely to become pregnant to increase their consumption of folate-rich foods, or folate-fortified foods, and information strategies and marketing to raise community awareness. Some basic foods are fortified with extra folate, such as flour or breakfast cereal.

Most national policy statements have opted for 0.4 mg/day of folate as the recommended intake for women contemplating pregnancy or of child-bearing age.

What the synthesised research says

The review of trials found that folate, taken as a supplement before pregnancy and in the first two months, effectively protects against neural tube defects. Folate did not increase the risk of miscarriage, a pregnancy outside the uterus (ectopic pregnancy) or giving birth to a stillborn baby. Folate may increase the chance of multiple pregnancies. Amounts of folate from 0.36 to 4 mg each day were effective.

Multivitamins alone did not give the same protection. Nor did they add to the protective effects of folate supplements.

Providing printed material within communities increased the awareness of low folate and neural tube defects by 4%, (odds ratio 1.37); from 12% of women of child-bearing age who were aware beforehand.

How it was tested

The researchers searched the medical literature thoroughly and found four controlled trials. A total of 6425 women were randomized to receive folate supplements or not around the time of conception. Periconceptional folate supplementation reduced the number (prevalence) of neural tube defects substantially (relative risk (RR) 0.3). This reduction was similar whether or not she had had a previously affected fetus or infant). The number of women needed to treat (NNT) with folate to prevent one neural tube defect is 847.

One high-quality trial of the benefits of dissemination of information about folate, a community randomised trial, involved six communities, matched in pairs, where 1197 women were interviewed prior to the intervention and 1206 women of child-bearing age were interviewed following the intervention. After the intervention, there was an increase in folate awareness but not all of these women (by 70%) were aware that folate was required periconceptionally for effective prevention of neural tube defects.

Side effects and general cautions

Evidence on the effectiveness of multivitamins, with or without folate, in preventing recurrent neural tube defects is available from two trials only.

An increase in multiple pregnancies is possible with folate as shown by a consistent trend in three trials. The number of women needed to treat with folate for one additional set of twins was 175, compared with 847 to prevent one neural tube defect. 

The trials did not have sufficient numbers of women to identify any differences in other major birth defects. Nor could they provide information on overconsumption of folate, interactions of folate with prescription drugs, or the effects of production and sale of foods fortified with extra folate on older people or children and adolescents (who would receive additional folate over a long period of time, with possibly adverse effects in some cases but also with possible cardiovascular benefits midlife).

Source

J Lumley, L Watson, M Watson, C Bower. Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. The Cochrane Database of Systematic Reviews 2001, Issue 3. Art. No.: CD001056. DOI: 10.1002/14651858.CD001056.

MAGNESIUM SUPPLEMENTATION IN PREGNANCY

Magnesium is one of the essential minerals needed by humans in relatively large amounts. Enzymes are proteins that the body produces to help (catalyse) its metabolism and body function. Many enzymes in the body need magnesium to be effective. Good food sources of magnesium are dairy products, breads and cereals, vegetables and meats. Healthy women who eat varied diets are unlikely to lack magnesium. Magnesium supplementation during pregnancy has been reported to reduce the risk of a mother developing high blood pressure and body swelling (pre-eclampsia) and poor fetal growth.

What is known

Many women especially those from disadvantaged backgrounds have less than the recommended daily amount of magnesium in their diet.

What the synthesised research says

Taking magnesium supplements did not have a clear benefit for either mother or baby. Magnesium in a wide range of doses was given by mouth starting before the 25th week of gestation.

Six trials indicated no effect of magnesium treatment on miscarriage, stillbirth or neonatal mortality. The frequencies of preterm birth, low birth weight and small for gestational age were also not altered.

The cluster trial where women received magnesium or non-active placebo according to where they were treated did report a lower frequency of preterm or small low birthweight babies with the women taking magnesium during pregnancy. The women taking magnesium were less likely to need hospitalisation or experience bleeding during pregnancy than women taking a non-active placebo.

Taking magnesium did not reduce how long labour was.

How it was tested

The researchers made a comprehensive search of the medical literature. They found seven trials involving 2689 women with normal or high-risk pregnancies. Six of these trials randomly allocated a total of 1704 women to either an oral magnesium supplement or a control group, while the largest trial with 985 women randomised by where the women received treatment (a cluster design).

The highest quality trial of 400 women also did not find any benefit for a pregnant woman taking magnesium, on blood pressure, pre-eclampsia or other pregnancy outcomes. All women in this trial received a multivitamin and mineral preparation containing 100 mg magnesium.

Side effects and general cautions

Gastrointestinal side effects (diarrhoea and gastric irritation) were reported with magnesium and placebo in the four trials that reported them. No serious adverse effects were evident on mother or baby with magnesium supplements.

Source

Makrides M, Crowther CA. Magnesium supplementation in pregnancy. The Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD000937. DOI: 10.1002/14651858.CD000937.

ZINC SUPPLEMENTATION IN PREGNANCY BEING UPDATED

Zinc plays a critical role in many of the body’s functions. For pregnant women, zinc may be important for a normal pregnancy and birth. It is obtained in the diet from meat, liver, eggs, seafood (particularly shellfish) also nuts, legumes, green beans, mushrooms, yeast and whole grains. This is complex however as whole grains, corn and rice also reduce the body’s ability to absorb zinc from the diet.

What is known

Some health conditions such as HIV and AIDS, recurrent infections and sickle cell anaemia are associated with low zinc levels. Serum levels may not reflect the true status of zinc in the body and white blood cell (leucocytes) measures may give a better indication of body zinc levels.

What the synthesised research says

Routinely taking a zinc supplement during pregnancy reduced the number of women giving birth preterm births (five trials with 2539 women) or having caesarean section (three trials with 1747 women) (odds ratio 0.7). In one small trial involving 54 women appreciably fewer of the women on zinc supplement needed labor to be induced (odds ratio 0.2).

The number of women with high blood pressure during pregnancy was no different overall when taking zinc supplements.

How it was tested

The researchers made a comprehensive search of the medical literature and found seven trials involving healthy pregnant women. Some trials specifically selected women who were likely to have low zinc levels and in one trial pregnant women were selected on the basis of proven low plasma zinc levels.

The 1571 pregnant women were randomly assigned to receive either zinc supplementation or no supplement or non-active treatment (placebo). Elemental zinc was given by mouth at a dose of 20 to 62 mg, starting from at least 26 weeks gestation.

Side effects and general cautions

No adverse effects for mother or baby were apparent with zinc supplementation.

Zinc can interact with other minerals and medicines.

This review has been withdrawn from Issue 3, 2006 of The Cochrane Library because it is out-of-date. An updated version of the review will be published in 2007. This summary will then be updated accordingly.  

Source

Mahomed K. Zinc supplementation in pregnancy. The Cochrane Database of Systematic Reviews 1997, Issue 3. Art. No.: CD000230. DOI: 10.1002/14651858.CD000230.

This review was withdrawn from Issue 3, 2006 of The Cochrane Library.  

VITAMIN A SUPPLEMENTATION IN PREGNANCY

Vitamin A can be obtained from the diet both as vitamin A and as carotenoids, usually beta-carotene, that are changed in the body to vitamin A. Preformed Vitamin A occurs naturally only in animals and the richest sources are liver, fish oils, herring, sardines, tuna and dairy products (milk, cheese, butter, ice cream). Between 25 and 35% of the vitamin A in the diet comes from plants, including carrots, yellow squash, dark leafy vegetables, corn, tomatoes, oranges, papayas and mangoes.

What is known

Extra vitamin A is required for the growth of the fetus during pregnancy, for providing the newborn infant with sufficient reserves and for the mother herself. From WHO information, pregnant women have a daily requirement of 370 micrograms, which increases to 450 micrograms during breast feeding.

Vitamin A deficiency may be common in many developing countries and be accompanied by low iron levels. A low dietary vitamin A can cause night-blindness, anaemia with decreased haemoglobin levels and other problems. Infections most closely associated with vitamin A deficiency include measles, diarrhoea and respiratory disease. Currently, WHO recommends routine vitamin A supplementation during pregnancy or at any time during breast feeding in areas where vitamin A deficiencies are common (endemic). It is not clear whether this strategy has other beneficial effects such as reduction in maternal mortality, prevention of anaemia or infection or has any harmful effects. Very high levels of supplementation over a long period of time during pregnancy can cause miscarriage and birth defects, but the above doses are safe.

What the synthesised research says

A large trial in Nepal (see below) reported a clear reduction in deaths from any cause, including from an infection, up to 12 weeks after birth when the women took vitamin A or beta-carotene supplements during pregnancy. Fetal or early infant survival was not improved.

In a number of trials no clinical benefits other than improved vitamin A or haemoglobin levels were examined. In an Indonesian trial, vitamin A and iron given together increased women’s haemoglobin levels; additional iron supplementation increased the stored iron levels even more.

In one Malawi trial, involving a total of 115 pregnant women, vitamin A supplements did not improve women’s haemoglobin levels even when considering initial vitamin A deficiency or iron deficiency anaemia. In the second Malawi trial the pregnant women involved were at a similar stage of pregnancy, had similar levels of vitamin A and iron and of infection (infective status). Giving a vitamin A supplement (5000 IU or double) did not alter their blood levels of vitamin A although their vitamin level stores in the liver were more likely to be maintained if the woman took vitamin A supplementation. Taking vitamin A did not affect their iron levels or indications of infection.

For 29 Asian women living in the UK, giving 8000 IU vitamin A in addition to 800 IU vitamin D raised vitamin A blood levels (compared with taking only 1000 IU vitamin D). The newborn babies’ birthweights and physical measurements were no different.

How it was tested

The researchers made a comprehensive search of the medical literature and found five trials involving a total of 23,426 pregnant women from Nepal, Indonesia, Malawi and the UK. The women were randomly assigned to receive Vitamin A supplementation alone or in combination with other micro-nutrients or a control group which could be non-active (placebo), no treatment or another intervention (for example iron).

The trial conducted in South-East Nepal was by far the largest, involving more than 20 000 births. A total of 44 646 women at reproductive age were in different areas visited by local field workers that were randomised to a weekly single oral supplement of vitamin A (23,300 IU) and beta-carotene (42 mg) or non-active tablets (placebo). Women received supplements for at least five months before conception to be included in the study of pregnancy outcomes.

A trial conducted in 20 rural villages in West Java in Indonesia included 305 women who were 16 to 24 weeks pregnant. Their haemoglobin levels were between 8.0 and 10.9 g/dl. Women were randomly assigned to receive daily supplements: one group received Vitamin A (8000 IU Vitamin A) and placebo iron tablets, the second group received iron (60 mg iron as ferrous sulphate) and placebo Vitamin A, the third group received both the Vitamin A and iron supplements and the fourth group received the placebos only.

The first trial in Malawi involved women attending a teaching hospital antenatal clinic. They were given daily supplements of either Vitamin A (10,000 IU) or placebo. All women routinely received daily iron (30 mg) and folate (400 micrograms) and were treated for malaria.

The second trial was in southern Malawi. Women received daily supplements of either vitamin A 5000 IU or 10,000 IU or a placebo. In addition, all women received daily iron supplements (60 mg elemental iron with 0.25 mg folic acid) and were treated for malaria.

The UK trial involved 29 Asian women living in the UK who had low plasma vitamin A levels (retinol concentrations less than 1.24 µmol) at 28 weeks gestation. The supplemented group received 8000 IU of vitamin A and 800 IU vitamin D daily, the control group received 1000 IU ergocalciferol (vitamin D) daily from week 30 until delivery.

Side effects and general cautions

The trials were mixed in their design and the interventions used, including the type, timing, dose and duration of treatment.

Source

van den Broek N, Kulier R, Gülmezoglu AM, Villar J. Vitamin A supplementation during pregnancy. The Cochrane Database of Systematic Reviews 2002, Issue 4. Art. No.: CD001996. DOI: 10.1002/14651858.CD001996.

VITAMIN C SUPPLEMENTATION IN PREGNANCY

Vitamin C (ascorbic acid) is involved in the formation of collagen, an essential part of connective tissue that binds body structures together, and in antioxidant defense mechanisms. All our vitamin C comes from the diet yet vitamin C deficiency is rarely reported in individuals with a healthy standard diet. Vitamin C is found in many fruits and vegetables, with high levels in guava, blackcurrants, citrus fruits, strawberries, mild and hot peppers, tomatoes, potatoes and broccoli. Many people take multivitamins and vitamin C, as they are readily available over the counter.

Taking vitamin C during pregnancy has been reported to reduce the risk of developing anaemia, high blood pressure and swelling (pre-eclampsia) and poor fetal growth.

What is known

The recommended dietary intake (RDI) of vitamin C increases during pregnancy (from 30 mg per day to 60 mg per day). For a breastfeeding mother it increases even more, to 75 mg per day. This is because vitamin C passes into the breast milk.

What the synthesised research says

No clear effect was seen on pre-eclampsia (four trials, 710 women), restricted fetal growth, stillbirths or death of the newborn infant (two trials, 221 women) with routine vitamin C supplementation, either alone or in combination with other supplements. This was in women at high risk of pre-eclampsia or preterm birth, or who had severe, early-onset pre-eclampsia. 

These conclusions were based on five trials with four of these, involving 710 pregnant women looking at pre-eclampsia. Two (211 to 383 women) or three (539 women) trials contributed to the other conclusions.

Vitamin C supplementation slightly increased the number of preterm births, from three trials involving only 583 women (risk ratio 1.4).

How it was tested

The researchers made a comprehensive search of the medical literature and found five trials involving 766 pregnant women. The women were randomly assigned to receive either vitamin C supplementation, alone or in combination with other supplements; or non-active treatment (placebo), no placebo or other supplements.

All of the women involved in the trials were either at high risk of pre-eclampsia or preterm birth, or the women had established severe early onset pre-eclampsia.

Side effects and general cautions

Taking large does of vitamin C can cause diarrhoea.

The number of women involved in the studies was small (766 in total) and two trials were of poor quality and published only as abstracts.

In four of the trials women received additional supplements and medications including vitamin E, allopurinol, aspirin and fish oil.

No information was available to assess vitamin C supplementation for pregnant women who were not at risk of pre-eclampsia or pre-term births. Vitamin C supplementation using multivitamins containing vitamin C, or iron with vitamin C was excluded.

Vitamin D supplementation in pregnancy

Vitamin D is a fat soluble vitamin that comes both from the diet and from the effect of sunlight on the skin. Dietary sources include fish liver oils and oily fish, beef, liver, eggs, and fortified milk and margarine.

What is known

Vitamin D deficiency is most likely to occur in people who are vegetarians and those who either remain indoors or whose clothing leaves little exposed skin, particularly in relatively sunless climates.

What the synthesised research says

Vitamin D supplementation in the later part of pregnancy should be considered in vulnerable groups, such as Asian women living in Northern Europe, and possibly others in climates with long winters.

This conclusion is from two trials based in the UK and France that looked at pregnancy outcomes. Fewer babies had soft skulls or low calcium levels when their mothers had taken vitamin D supplements in one of these studies involving 203 women. The effects on the number of low birthweight infants were inconsistent between the two trials.

How it was tested

The researchers made a comprehensive search of the medical literature. They found two trials involving a total of 232 women who were randomly assigned to receive vitamin D supplementation during pregnancy or no supplement. These women were considered to be at risk of Vitamin D deficiency.

Side effects and general cautions

Only a small number of women were involved in the two trials, insufficient to provide a clear effect of taking a vitamin D supplement on infant birthweights.

Vitamin D supplementation seems to have been well tolerated in the limited evidence available.

Source

Mahomed K, Gulmezoglu AM. Vitamin D supplementation in pregnancy. The Cochrane Database of Systematic Reviews 1999, Issue 1. Art. No.: CD000228. DOI: 10.1002/14651858.CD000228.

VITAMIN E SUPPLEMENTATION IN PREGNANCY

Vitamin E includes eight fat soluble and plant-derived compounds, four are referred to as tocopherols and four are known as tocotrienols (alpha, beta, gamma, delta). Natural source alpha-tocopherol is the most biologically active form of vitamin E and is found in wheatgerm oil and other vegetable oils, nuts, some cereals and some leafy green vegetables. Synthetic forms of vitamin E are also available and are commonly used in vitamin preparations. Vitamin E is an antioxidant.

What is known

In pregnant women minimal vitamin E is lost to the fetus. This means that the recommended dietary intake (RDI) of vitamin E is generally unchanged during pregnancy. Healthy adults rarely have a deficiency.

Pre-term infants and infants with low birthweights or problems with absorbing the fat in their feeds may have deficiencies. Symptoms include anaemia, high levels of the breakdown product of haemoglobin (bilirubin) and peripheral neuropathy. Vitamin E deficiency is worse with high iron levels and a high dietary intake of polyunsaturated fatty acids, which is of particular relevance for preterm infants fed formula containing high levels of iron and these fatty acids. Vitamin E supplementation may help reduce the risk of pregnancy complications such as pre-eclampsia where a woman has high blood pressure and protein in her urine in the second half of pregnancy.

What the synthesised research says

The evidence that pregnant women given vitamin E in combination with other supplements are less likely to develop pre-eclampsia is unclear. This conclusion is based on three trials involving 510 women.

No benefit was found on the risk of stillbirths, deaths of newborn babies or around the time of birth, preterm births, or clear effects on intrauterine growth restriction or birthweights. These were looked at in one or two trials, involving 40 to 383 women.

Vitamin E was given with vitamin C and additional supplements or drugs.  

How it was tested

The researchers made a comprehensive search of the medical literature and found four trials involving 566 pregnant women for inclusion in the review. Three trials looked at vitamin E supplementation compared with non-active placebo for the prevention of pre-eclampsia, one for the prevention of serious complications for mothers and for preterm births when women had established early onset pre-eclampsia.

Side effects and general cautions

Only one of the trials reported on side effects. This trial involved 56 women and reported potential side-effects of vitamin E including acne, transient weakness and skin rash.

The total number of women involved in the trials was small and two trials were not well conducted with only abstracts published.

All of the women involved were either at high risk of pre-eclampsia or had established severe early onset pre-eclampsia. This means that no information is available for healthy pregnant women on using vitamin E supplementation.

Vitamin E was not given alone but with vitamin C and additional supplements or drugs. The researchers excluded trials using a multivitamin supplement that contained vitamin E.

Source

Rumbold A, Crowther CA. Vitamin E supplementation in pregnancy. The Cochrane Database of Systematic Reviews 2005, Issue 2. Art. No.: CD004069.pub2. DOI: 10.1002/14651858.CD004069.pub2.