Impact of Maternal Infection on Foetal Growth and Nutrition

by Andrew Tomkins, Susan Murray, Patricia Rondo and Suzanne Filteau, Centre for International Child Health, Institute of Child Health, University of London, United Kingdom.

The Disadvantages of Being Born Small

Fetal growth and birth weight are increasingly being considered as crucial markers of future health status during infancy, childhood and adult life. For many years it has been recognised that children with a low birth weight (<2.5 kgs) have an increased risk of infection and death during the neonatal period and infancy. There are broadly two types of low birth weight (LBW) - those babies that are prematurely born (pre-term) and those that are small for their gestational age, often termed IUGR (intrauterine growth retarded). Most published population data on the prevalence of LBW in developing countries does not distinguish between pre-term babies and babies with IUGR. Where studies have separated the two types, it appears that IUGR is by far the commoner form of LBW. Those babies which are born prematurely and are also small for their gestational age have the worst prognosis. Several studies have also emphasised the importance of low birth weight on cognitive function, psycho-motor development and physical growth in childhood. There is now increasing evidence that LBW is associated with an increased prevalence of diseases such as diabetes, hypertension, ischaemic heart disease and stroke in adult life.

The Multiple Causes of IUGR

Many studies have been performed comparing the characteristics of mothers whose babies have IUGR with those whose babies have appropriate weights for their gestational age (AGA). The relative importance of the various risk markers in determining birth weight varies between populations and communities, and there is a considerable problem of ‘confounding’. Nevertheless there are certain key groups of maternal risk markers which require consideration in making policies and plans to reduce the prevalence of IUGR.

Table of Maternal Risk Markers for IUGR

1. Anthropometry (e.g, maternal height, body mass index, pre-pregnancy weight)
2. Demographic (e.g, maternal age, socio-economic status)
3. Obstetric (e.g. parity, birth interval)
4. Diet (e.g. intake of protein, energy and micronutrients)
5. Physical activity (e.g, intensity of physical work and posture during the different stages of pregnancy)
6. Toxic exposures (e.g. cigarettes, coffee, alcohol)
7. Maternal morbidity (e.g. toxaemia of pregnancy, infection)

Maternal Infection and Foetal Nutrition

There are several mechanisms by which fetal growth may be affected by infection in the mother. Firstly, the mother herself may be subjected to a series of infections which influence her own nutrition, making supplies of nutrients less available to the fetus. Secondly, the placenta may not transfer nutrients satisfactorily as a result of a variety of disease conditions including disorders of the feto-placental circulation, with reduction of blood flow. Thirdly, the fetus itself may be infected such that growth and development are impaired. Prevention of IUGR requires programmes which focus on all three areas.

Infection and Maternal Nutrition

The relationship between infection and nutrition is well recognised. Epidemiological studies have emphasised the impact of malaria, diarrhoea and AIDS on maternal nutrition. Pelvic inflammatory disease, severe reproductive tract infections and urinary infections may also be important. Clinical studies have emphasised that there are characteristic mechanisms which explain the reason why mothers become malnourished during infection.

Firstly, dietary intake may be reduced. Decreased appetite (anorexia) is a common feature of many infections and is caused by several factors. Pyrexia, pain, shortness of breath and general malaise may all cause anorexia. It is now recognised that many infections have a biochemical effect on the appetite by releasing chemical messengers called cytokines which suppress the appetite centre in the brain. In addition, certain infections, particularly those causing febrile responses, may be treated by culturally determined practices such as avoidance of certain foods.

Secondly, nutrient absorption may be decreased. Characteristically this occurs with a number of intestinal parasites such as ascaris which decrease absorption of energy, protein and micronutrients such as iron and vitamin A in particular.

Thirdly, the metabolic stress of infection may increase the requirements for nutrients by the mother herself. For every one degree centigrade rise in body temperature, there is, on average, an increase of 10% in the requirements for energy, protein and micronutrients. During systemic infection there may be quite profound changes in the distribution of micronutrients such as vitamin A, iron and zinc with a decrease in the blood levels of these nutrients. This has obvious implications for transfer of nutrients from mother to the fetus. There has been little attention to the impact of infection on iodine metabolism, of crucial importance to fetal development. Fourthly, there may be nutrient losses. These may characteristically occur with intestinal parasites such as hookworm which can cause severe loss of iron and protein. Chronic diarrhoeal syndromes may cause losses of zinc and potassium; both are important for intrauterine development.

In addition to the impact of infection on the nutritional status of the mother herself, there may be a striking change in blood flow to the placenta during febrile conditions, with a negative impact on nutrient flow from mother to fetus.

Placental Dysfunction

Some infections can alter the structure of the placenta such that nutrient transfer is impaired. Perhaps the most important is malaria infection. Several studies have shown that women infected with malaria give birth to babies with lower birth weights than those without infection. Recent studies on prophylaxis against malaria using tablets or bednets have shown a trend towards a higher mean birth weight among those in the ‘protected’ groups. The placenta and membranes may be infected from a variety of sources, such as ascending infections from the vagina to the amniotic sac and a wide range of organisms reaching the placenta in the maternal blood. Their impact on birth weight, however, is not known.

Fetal Infection

Several infections which are transmitted across the placenta are associated with decreased birth weight; of these syphilis and HIV are especially important. Primary herpes infection is known to be associated with IUGR. Toxoplasmosis and cytomegalovirus may be important fetal infections which vary in different populations but their impact specifically on fetal growth is not known.

Prevention

The satisfactory prevention of maternal, placental and fetal infections requires several approaches. Firstly, it requires the education of health professionals and of the public about the recognition of symptoms, and the need for promotion of lifestyles which prevent the development of the infection in the first place. In many societies, reduction of maternal infection could be achieved by improving housing, water supplies and sanitation and facilities for hygiene, together with behavioural change to limit the spread of sexually transmitted diseases. Involvement and education of male sexual partners is essential for the protection of reproductive health in women. Such changes are crucial for the reduction of the prevalence of diseases such as syphilis, herpes, gonorrhoea, and pelvic inflammatory disease. In several African countries, the prevalence of syphillis is around 5-10% and the prevalence of gonorrhoea is over 10%. The prevalence of pelvic inflammatory disease and urinary tract infections is more difficult to define because of the non specific clinical features.

Screening during pregnancy is possible using serological techniques for syphilis and microbiological culture for gonorrhoea. New dipstick tests are under development for use in areas without laboratories. Early appropriate antibiotic treatment is required but the type of medication indicated is determined by antibiotic resistance patterns in individual populations. Increasingly, antibiotics are being used for reproductive tract infections according to symptom complexes rather than microbiological diagnosis because of the lack of laboratory facilities. The choice of antibiotic regimes needs to be defined locally and continually reviewed in the light of antimicrobial resistance, availability and acceptability of newer antibiotics.

Problems with Access to Treatment for Infection

It cannot be over emphasised that many maternal infections go untreated because of unfriendly and inaccessible health care facilities. Women’s own perceptions of their health status and of pregnancy will reflect their cultural background and their role and status within the family and community. It may not be acceptable, in some communities, for pregnant women to complain of symptoms during pregnancy. This leads to considerable levels of underreporting of disease. In others there may be the wish to consult a medical facility but there are severe constraints on the mother’s ability to travel outside the home or to take time off urgent domestic and agricultural or other wage earning activities. In the case of reproductive tract infections, there may be a strong stigma associated both with the disease itself, with genital or pelvic examination, and with attendance at clinics that are known locally as ‘STD clinics’. Inadequate privacy, poor levels of information exchange and lack of integration with other services such as child health and contraceptive services, can all contribute to a reluctance to use services which could treat maternal infection, and thereby contribute to improved fetal growth.

Several studies have emphasised the negative impact on clinic attendance rates of the introduction of user fees. All future health care programmes working on principles of ‘cost recovery’, will urgently need to address this question.

Culturally Appropriate Medication

Even when women gain access to health facilities and receive prescriptions or medications for drugs appropriate for their infection, the conflict with traditional views on suitable medications for use in pregnancy may be considerable. Thus, chloroquine treatment may be acceptable to the Mende in Nigeria because its bitter taste and white chalky consistency is analogous to traditional treatment for fever. Piperazine citrate, on the other hand, was rejected for the treatment of intestinal parasites in pregnancy by communities in S. India, because of its believed association, as a ‘hot’ medicine, with abortion. The beliefs among pregnant women in relation to disease and its appropriate treatment need to be clearly understood if health services are to have their optimum impact.

Treatments known or marketed as helpful in increasing birth weight, such as malarial prophylactics during pregnancy, are sometimes problematic themselves because these may be seen as leading to complicated labour and delivery. Indeed some traditional antenatal care may include advice on how to prevent the fetus from becoming too large. In communities where emergency obstetric care is difficult to access or is socially poorly accepted, small babies may actually be preferred.

Pre-Pregnancy Infection

In developing countries, where food availability is limited (by the climate or the budget), women are usually undernourished before pregnancy begins. Most of them are from low socio-economic classes, living in poor housing conditions. The risk of these women catching an infection is higher than for well nourished women living in a healthy environment with good standards of hygiene and sanitation. Chronic infection, especially in childhood and adolescence, can lead to malnutrition with a subsequent reduction in stature, and to deficiencies of iron, folate, zinc and vitamin A. All of these can be risk markers for IUGR. Greater attention towards promotive and preventive health of the girl child is essential in the name of equity. It is also important for the well being of her future children.

Conclusion

Satisfactory rates of fetal weight gain and development are important for health in infancy, childhood and adult life. Among the various factors affecting fetal growth, maternal infection is very important. Accessible and effective treatment for infection is vital for the general health and well-being of women. Such interventions can also prevent adverse effects on fetal growth and development. They should include attention to environment, poverty, life style, diet and provision of health services which are user friendly and efficient for women. New strategies are needed for community based management of a range of infections in women, especially reproductive tract infections. They will require sensitive consideration of cultural beliefs and practices as well as the development and delivery of health services providing effective, affordable and acceptable treatment.