B12 and Folic Acid —

Ray and colleagues raise an important point on folic acid fortification. This is a very contentious subject, with well developed battle grounds.

Folic acid fortification is advocated to prevent or reduce the incidence of foetal neural tube defects in babies. A terrible blight for those afflicted.

Folic acid fortification was universally introduced in Canada in 1998 , the result was a 50% reduction in foetal neural tub defects.

However why has the figure not dropped to zero?

The authors show that 35% of neural tube defects in Canada may be a result of maternal deficiency of vitamin B12.

7.4% of pregnant women tested in a study in Ontario had a reduced serum B12 concentration.

Clearly an important trial is required here of vitamin folic acid and folic acid plus B12 supplementation

Ray et al 2008 High rate of maternal vitamin B12 deficiency nearly a decade after Canadian folic acid flour fortification QMJ vol 101 475-477. .

Birth Defects —

Neural tube defects and oral clefts are among the most common congenital malformations with prevalences of 10-15 per 10,000 and 20 per 10,000 live births, Periconceptional supplementation with folic acid reduces the risk of neural tube defects. What has been less defined is the effect of folic arid supplementation on other birth defects, such as cleft lip. with or without cleft palate.

Wilcox and colleagues report a population based case-control study from Norway, which shows that supplementation with folic acid in the periconceptional period reduces the risk of cleft lip, with or without cleft palate, in newborn. Supplementation with 100 ug of folic acid for three months around conception was associated with a 40% reduction in the prevalence of cleft lip, with or without cleft palate, at birth. The study supports findings from other recent studies, including a large meta-analysis.

400 ug folic acid per day may well prevent a large proportion ot neural rube defects. even suboptimal fortification (for example. 180 ug/day in the US) greatly reduces neural tube defect rates.’

Three public health policies have been suggested.

for women to eat a diet rich in naturaJ folates. However, it is difficult to reach this dose with diet alone, and folate in the diet has lower bio-availability than synthetic folic acid.
The second is for women to take supplements of folic acid in the periconceptual period. But low compliance and high rates of unplanned pregnancy limit this approach, fewer than 50% of women followed the recommendations.
The third fortification of staple foods (such as wheat, corn flour, or rice).
The World Health Organization has recommended supplementation with 400 ug of folic acid in the peri-conceptual period. Fortification of food is mandatory in an increasing number of countries Countries differ substantially ) in their choices of preventive strategy.

“Further support for mandatory fortification of food comes from a cohort study showing that simply recommending women planning pregnancy to take folic acid is not enough to substantially reduce the prevalence of neural tube defects at birth.

However, in many European countries mandatory fortification has been limited by theoretical concerns. These include the potential of masking symptoms of vitamin B12 deficiency, interactions with certain drugs (amifolales). and other unrecognised adverse effects such as idiosyncratic reactions to folic acid even in small amounts

But mandatory folic acid fortification to achieve around 180 rig/day on average and 1000 pg/day at maximum appears to holds little risk of complications.

Fortification could also reduce the burden of major disorders such as cardiovascular diseases and dementia. The risks of these disorders increase with high plasma concentrations of homo-cysteine, which folic acid supplementation can reduce in humans. The definitive evidence in large long standing controlled trials studying the benefits of supplements in cardiovascular disease and dementia have yet to be obtained .

The underlying problem is a lack of knowledge of what basic defect is involved in the aetiology of these birth defects. Karen Liu has shown that in mice with a glycogen synthase kinase ( GSK-3β) defect developed defective fusion of the palate and sternum. Giving Rapamycin at an early stage in development prevented cleft palate.and later in the pregnancy the sternal defects. Rapamycin stabilizes the glycogen synthase kinase.

Another problem is the population at risk. The potential mother of a wanted baby is likely to follow this advise.

Breast Milk —

The World Health Organisation and the American Academy of Pediatrics advocate exclusive breast feeding for the first 6 months and partial for up to 1 to 2 years.

The best way to achieve this has still to be identified. In a paper from Singapore

Su and colleagues have studied the effect of antenatal breast feeding education compared with routine hospital car (Su et al 2007Antenatal education and postnatal support strategies for improving rates of exclusive breast feeding randomised controlled tial British Medical Journal vol 335, 596-9

The combination of antenatal breast feeding education and post natal support significantly improve the rate of mothers breast feeding their babies.

All of which confirms the benefit of education and support in nutrition. Mothers are particularly sensitive to advise to care for their baby.

Pregnancy, Lactation, and Weaning
Breastfeeding

Hoddinott et al have written a very timely clinical review of breast feeding in the BMJ of 19th April 2008.

Breast feeding is crucial to infant health in developing countries, but there are possible longer term benefits to act against subsequent obesity, high blood pressure, cholesterol, and cancer.

The World Health Organization (WHO) recommends exclusive breast feeding, that is breast milk only, with no water, other fluids, or solids for six months, with supplemental breast feeding continuing for two years and beyond.

In the UK and the United States, breast feeding rates have been low for decades and can seem remarkably resistant to change.

Formula milk is just a food, whereas breast milk is a complex living nutritional fluid that contains anti-bodies, enzymes, and hormones, all of which have health benefits. In addition, some methods of delivering formula milk expose the baby to serious risks of infection. Early intake of colustrum, which is rich in antibodies, is especially important in developing countries, and the small volume of colostrum helps to prevent renal overload when the newborn baby is adjusting its fluid balance

In countries with poor services , contaminated drinking water , low immunisation rates and reduced immunity babies readily die. And each baby is born from a pregnancy where the mother is at risk. Exclusive breast feeding could prevent 1.3 million deaths in children under 5 years.

Good education and training for new mothers would make such a difference to the breast feeding rates

Breast fed babies may not grow at the same rate as bottle fed babies so new growth charts may need to be constructed to avoid unfavourable comparisons.

Hoddinott et al 2008 Breast feeding BMJ vol 336, 881-7

Codeine and Milk —

In the Lancet of August 23rd 2008 there is an fascinating debate on a report from 2006 also in the Lancet ( Lancet 2006 vol 368 p 704 . In the original case report the death of a neonate was attributed to the mother taking codeine. The mother was an ultra rapid converter of codeine to morphine and the morphine passed in the breast milk to the baby. The new letter by Bateman et al challenges their conclusions suggesting that the concentration and amount of codeine and morphine in the milk could never achieve lethal amounts to the baby. The original authors reply and disagree saying that the metabolism of the baby is different from the adult and that the infant was vulnerable to small doses of morphine.

They both make good case for their point of view.

For the nutritionist the important message is that the mother is the source of the constituents of the breast milk. Care and attention should be taken about what the breast feeding mother eats and drinks and is given in non nutritional substances, drugs, alcohol etc.

The baby is very dependent and vulnerable,

Lancet 2008 vol 372 pp 625-626

Ferner 2008 did the drug cause death? Codeine and breast feeding Lancet vol 372 pp 606-7

Coffee —

In a study reported in the BMJ and accompanied with an Editorial the effect of caffeine intake during pregnancy is discussed

There are two variables which are important for the mother.

The metabolism of caffeine depends on genetic and environmental factors. Caffeine is metabolised in the liver primarily by CYP1A2 and NAT2, and people can be classified as slow or fast metabolisers. The foetuses of women who are slow metabolisers will be exposed to more caffeine than the foetuses of fast metabolisers with an equivalent caffeine intake.

Caffeine is rapidly absorbed and crosses the placenta freely. After ingestion of 200 mg caffeine, intervillous blood flow in the placenta has been found to be reduced by 25%. Cytochrome P450 1A2, the principal enzyme involved in caffeine metabolism, is absent in the placenta and the foetus. The amount of caffeine and metabolites available to the foetoplacental unit therefore depends on the maternal caffeine metabolism, which shows marked variation between individuals, Variations in caffeine metabolic activity have been found to be more closely associated with foetal growth restriction than have blood caffeine concentrations.

Coffee and tea contain a variety of chemical compounds, but most of the health concerns relate to caffeine. One cup of coffee contains about 100 mg of caffeine and a cup of tea about half of this amount; the exact amount varies according to cup size, brewing methods, and brands of coffee or tea. Caffeine is also present in cola, chocolate, cocoa, and some drugs. Most of the caffeine that adults consume comes from coffee, but in the present study 60% of the caffeine that pregnant women consumed came from tea.

Drinking coffee and tea correlate with other lifestyle factors like smoking, work load, and perhaps also dietary habits

The results show that faster metabolisers have a higher risk than women with a slower clearance rate who have the same caffeine intake. This indicates that it is not caffeine but one of its metabolites that causes harm—this notion is supported by another study based on biomarkers for caffeine exposure. Slow metabolisers with a high intake of caffeine may not be comparable with fast metabolisers with a similar intake.

In the linked cohort study, the CARE Study Group reports that consuming caffeine during pregnancy is associated with an increased risk of foetal growth restriction. For 100-199 mg caffeine a day the odds ratio was 1.2 . for 200-299 mg a day 1.4. and for over 300 mg a day l.5..

What advice should we give to women who are or intend to become pregnant. The authors suggest that every effort should be made to stop pregnant women consuming caffeine or to reduce intake greatly,

The accompanying editorial does not totally agree with the advise about how much to reduce caffeine intake, but the general drift is that caffeine intake is to be watched.

CARE study Group Maternal caffeine intake during pregnancy and risk of foetal growth restriction: a large prospective observational study BMJ vol 337, pp1334-8

Olsen and Bech 2008 Caffeine intake during pregnancy should be minimised but not replaced with unhealthy alternatives BMJ volume 337, pp 1305-1306

Energy expenditure and Pregnancy —

This study looked at resting metabolic rate, activity energy expenditure, total energy expenditure and physical activity pattern, that is, duration and intensity (in metabolic equivalents, METs) of activities performed in late pregnancy compared with postpartum in healthy, well-nourished women living in Switzerland.

The subjects were 27 healthy women aged 23–40 years at 38.2 1.5 weeks of gestation and 40.0 7.2 weeks postpartum.

The RMR during late pregnancy was 7480 kJ per day, that is, 1320 760 kJ per day (21.4%) higher than the postpartum resting metabolic rate (P<0.001). Absolute changes in resting metabolic rate were positively correlated with the corresponding changes in body weight (r=0.61, P<0.001). Resting metabolic rate per kg body weight was similar in late pregnancy vs postpartum (P=0.28). Activity energy expenditure per kg during pregnancy and postpartum was 40 13 and 50 20 kJ/kg, respectively (P=0.001). There were significant differences in daily time spent at physical activity pattern, that is, duration and intensity (in metabolic equivalents),

Energy expenditure in healthy women living in Switzerland increases in pregnancy compared with the postpartum state. Additional energy expenditure is primarily attributed to an increase in resting metabolic rate , which is partly compensated by a decrease in Activity energy expenditure. The decrease in physical activity-related energy costs is achieved by selecting less demanding activities and should be taken into account when defining extra energy requirements for late pregnancy in Switzerland.

Keywords:

pregnancy, energy expenditure, requirements, physical activity, exercise

K Melzer et al (2009 ) Pregnancy-related changes in activity energy expenditure and resting metabolic rate in Switzerland . European Journal of Clinical Nutrition, 63, 1185–1191.

Malnutrition —

The Lancet has embarked on an immensely important series on Maternal and Childhood under nutrition s

BlackRL et al 2008, Maternal and child undernutrition: global and regional exposures and health consequence. The Lancet vol 371, 243-260.

There are also important leaders in the same edition

Morbidity and mortality in families in Iraq p177

Maternal health and child undernutrition: an urgent opportunity R Horton p 179

The challenge of hunger J Sheeran p 180

Nutrition interventions need improved operational capacity Heikens et al p 181

Maternal and child undernutrition is highly prevalent in low-income and middle-income countries, resulting in substantial increases in mortality and overall disease burden. In this paper, new analyses are presented to estimate the effects of the risks related to measures of undernutrition, as well as to suboptimum breastfeeding practices on mortality and disease

They discussed their findings as

Maternal short stature and low body mass index in pregnancy and lactation. Maternal short stature is a risk factor for mother and baby in the delivery as the pelvis is small.

Childhood underweight, stunting and wasting.

The authors estimate that stunting, severe wasting, and intrauterine growth restriction together were responsible for 2 2 million deaths and 21% of disability-adjusted life-years (DALYs) for children younger than 5 years. Deficiencies of vitamin A and zinc were estimated to be responsible for 0 6 million and 0 4 million deaths, respectively, and a combined 9% of global childhood DALYs. Iron and iodine deficiencies resulted in few child deaths, and combined were responsible for about 0 2% of global childhood DALYs. Iron deficiency as a risk factor for maternal mortality added 115000 deaths and 0 4% of global total DALYs. Suboptimum breastfeeding was estimated to be responsible for 1 – 4 million child deaths and 44 million DALYs (10% of DALYs in children younger than 5 years). In an analysis that accounted for co-exposure of these nutrition-related factors, they were together responsible for about 35% of child deaths and 11% of the total global disease burden. The high mortality and disease burden resulting from these nutrition-related factors make a compelling case for the urgent implementation of interventions to reduce their occurrence or ameliorate their consequences.

Maternal and child undernutrition is the underlying cause of 3-5 million deaths, 35% of the disease burden in children younger than 5 years and 11% of total global DALYs

The number of global deaths and DALYs in children less than 5 years old attributed to stunting, severe wasting,and intrauterine growth restriction constitutes the largest percentage of any risk factor in this age group

Vitamin A and zinc deficiencies have by far the largest remaining disease burden among the micronutrients considered

Iodine and iron deficiencies have small disease burdens, partly because of intervention programmes, but sustained effort is needed to further reduce their burden

Sub optimum breastfeeding, especially non-exclusive breastfeeding in the first 6 months of life, results in

1-4 million deaths and 10% of disease burden in children younger than 5 years

Maternal short stature and iron deficiency anaemia increase the risk of death of the mother at delivery accounting for at least 20% of maternal mortality

Seasonal Diet —

The diet that the Mother eats during the pregnancy must be important for the baby

So an exciting and intriguing paper from New Zealand appears in the European Journal of Clinical Nutrition examining whether seasonal variation of nutrition in pregnancy effects infant measures and the health of the baby.

The authors PE Watson and BW McDonald looked at whether there was any seasonal effect on nutrient intake during pregnancy and birth measurements, secondly if there was any relationship between maternal nutrient intake and infant birth measure according to season and thirdly to test the hypothesis that seasonal change in nutrient intake might effect health in later life of some mothers offspring.

A great idea, though in our society the super market neutralises the effect of seasons by having similar foods available all the year round.

They studied 214 pregnancies in lower Northern New Zealand.

Significant seasonal variation was found for fat, carbohydrate ,electrolytes, vitamin and trace metal intake.

There was no effect on gestational weight and head circumference. with season. There were significant effects of birth measures and specific maternal nutrients at months 4 and 7 of pregnancy.

They conclude that seasonal nutrient variation may affect foetal development.

PE Watson and BW McDonald 2007, European Journal Clinical Nutrition, vol 61, 127-1280

Sugar and Pain —

Suckling and sugar educe pain in babies Shann in Lancet 369, March 3 2007-03-28

Babies are very aware of painful procedures and events. One such is blood sampling by heel prick. Babies who at the same time are being breast fed and given a cuddle appear to be more comfortable than babies without this support. More recent studies suggest that giving sucrose in addition to breast feeding increases the effectiveness of this regime. One ml of 30% sucrose in addition to breast feeding was better than 30&% glucose.

This simple safe strategy is important. It also raises the thought of fractious babies and feeding. Does the content of the milk help sooth the baby? Or do women who have unhappy babies produce insufficient milk? Or none of the above.

Weight —

Weight and pregnancy

Pregnancy makes great demand on a woman’s body, though this is accompanied with the joy of the development of a new person.

Apparently half of pregnancies are unplanned.

World wide over 1 billion adults are overweight and 300 million clinically obese. In the USA the prevalence of obese women in the age group 20-39 years has risen from 9 % in 1960-62 to 28% in 1999—2000.

A large Swedish study of more than 200,000 pregnant women studied changes in body mass index from the beginning of the first pregnancy to the second pregnancy and maternal and perinatal outcomes.

Only, modest increases in weight of 1 to 2 units resulted in increased ill health, pre-eclampsia, diabetes, pregnancy induced hypertension and large for gestational age babies. An increase of 3 units and the more dire consequences developed, including still births.

The message is that women who are fertile and wanting babies a body mass index of 30 is an upper limit.

The association between low body mass index and infertility, prematurity and low infant birth weight is well established.

It is important that women are of normal healthy weight before and during their pregnancies.

Walsh and Murphy, Weight and pregnancy; BMJ 2007; vol 335, 169