1.1 Intrauterine Growth Retardation (IUGR)

IUGR refers to foetal growth that has been constrained by an inadequate nutritional environment in utero and, thus characterizes a newborn that has not attained its growth potential. These infants are disadvantaged before they enter the world. Although the classification of IUGR is still based on insufficiently standardized reference data,⁶ there are three distinct groups, as depicted in Figure 1.2. The reference curve in this figure is the 10^th percentile of a reference population and takes into account gestational age.

Newborns in Group 1 are born after at least 37 weeks of gestation and weigh less than 2,500 g at birth. In most populations this is the largest group of newborns affected by intrauterine growth retardation. Group 2 newborns are preterm and weigh less than the 10^th percentile at birth. Newborns in Group 3, a smaller group, weigh less than the 10^th percentile (fall below the curve) but have a birthweight greater than 2,500 g.

In most circumstances in developing countries, it is not possible to determine the gestational age of an infant. Also, reference curves adjusted for gestational age are not widely employed. Therefore, low birthweight (< 2,500 g) is often used as a proxy for IUGR. Incidence rates of low birthweight help to characterize nutritional status during foetal life for populations, but they do not go far enough. This is because the incidence of low birthweight among preterm infants will overestimate poor growth due to nutritional causes (Group 2). On the other hand, incidence rates of low birthweight among term infants will underestimate poor growth due to nutritional causes in term infants because not all infants falling below the 10^th percentile reference curve are captured (that is, Group 3). In this report we focus on the largest group of IUGR infants, those in Group 1, because this is the only group for which reasonably good data are available.

FIGURE 1.2: Different types of intrauterine growth retardation (IUGR)

Source: Adapted from 7.

Comparing Prevalences and Numbers

Table 1.1 presents a picture of IUGR globally and by region, as far as available data permit. (Statistical methods are described in Appendices 3 and 4.) In the year 2000 it is estimated that 11.0% of newborns in developing countries, or 11.7 million infants, have low birthweight at term.^a These children are born undernourished with little chance of fully catching up. This is a major global human development problem with profound short - and long-term consequences for individuals, communities, and whole populations. Population-wide interventions aimed at preventing foetal growth retardation are urgently needed in many developing countries.

^a Low birthweight at term is also referred as “IUGR-LBW” in some publications.

Low birthweight at term is especially common in South Central Asia, where 20.9% of newborns are affected; this sub-region accounts for about 80% of all affected newborns worldwide. Low birthweight is also common in Middle and Western Africa, where 14.9% and 11.4% of infants have low birthweight at term, respectively. Data are not sufficient to prepare estimates for other parts of Africa. Low birthweight at term is less common in Latin America and the Caribbean than in other parts of the developing world. Incidence rates average 6.5% for this region as a whole and 6.2% for South America.

In all regions the total number of newborns with IUGR is higher than the number affected by low birthweight. IUGR, defined as all newborns falling below the reference curve in Figure 1.2, probably affects about 24% or approximately 30 million newborns per year in developing countries.^{b, 7}

^b This estimate is based on total live births for 1995.

These estimates suffer from important qualitative and quantitative constraints owing to limitations of the available data. In some regions only a small proportion of infants are born in a health care facility where birthweight can be measured. However, the estimates represent a valid attempt to quantify the magnitude and geographical distribution of foetal undernutrition for advocacy and public health purposes. The limitations point to the need to improve the availability and quality of gestational age and birthweight data.

TABLE 1.1: Estimated incidence of low birthweight and expected number of affected newborns, 2000

Sources: 8 (incidence of LBW); 7 (incidence of LBW at term); Number of newborns affected was obtained by applying incidence estimates to the total number of live births, obtained from 9.

Notes: Data for LBW and LBW at term refer to birthweights < 2,500 g. n/a = not available because coverage of live births < 80%.

^a Groups defined in Figure 1.2.

^b Excludes Japan.

^c Excludes Australia and New Zealand.

^d Weighted average of incidences in each country

Causes

In developing countries, the major determinants of growth retardation in utero are nutritional: inadequate maternal nutritional status before conception, short maternal stature (principally due to undernutrition and infection during childhood), and poor maternal nutrition during pregnancy (low gestational weight gain, primarily due to inadequate dietary intake). Maternal nutrition during pregnancy is especially important. Low pregnancy weight gain may account for more than 14% of growth retardation in utero; further, in populations with a high prevalence of short stature, low maternal height accounts for about 18.5%.¹⁰ Prevalence rates are high where pre-pregnancy weight-for-height is low - undernourished women obtain a greater benefit than other women from a given gestational weight gain.¹¹

Diarrhoeal diseases, intestinal parasitosis, and respiratory infections are common in developing countries and may also have an important impact on IUGR. These illnesses may be associated with an impaired foetal growth of, on average, 45 g per birth.¹² Where it is endemic, malaria is a major determinant of IUGR. Infants born to women with placental malaria have a mean deficit in birthweight of about 170 g.¹³ Furthermore, the effects of cigarette smoking are becoming a significant factor in some developing countries.¹⁴

The immediate causes of IUGR often operate simultaneously with more deeply rooted underlying and basic causes. These causes relate to the care of women, access to and quality of health services, environmental hygiene and sanitation, household food security, educational status, and poverty.

In industrialized countries, cigarette smoking is the most important determinant of IUGR, followed by low gestational weight gain and low pre-pregnancy body mass index.¹² The etiological roles of pre-eclampsia, short stature, genetic factors, and alcohol and drug use during pregnancy are well established but are quantitatively less important. In industrialized countries, the contribution of socioeconomic factors to IUGR incidence remains unknown after controlling for the factors discussed above.¹⁴

The etiological roles of micronutrients in IUGR remain to be clarified in developing and industrialized countries. Some have argued that randomized trials are required to define the possible effects of folate, iron, calcium, vitamins D and A, magnesium, and zinc, especially in developing countries.¹⁵ Others argue that the use of multiple vitamin and mineral supplements by women in developing countries is an important strategy to improve micronutrient status and benefit women’s health, pregnancy outcome, and child health.¹⁶ The NAS suggests that a strategy to promote increased consumption of multiple micronutrients simultaneously would be more effective than the promotion of a select few.¹⁷

Consequences

It has been estimated that for term infants weighing 2,000-2,500 g at birth, the risk of neonatal death is four times higher than for infants weighing 2,500-3,000 g, and ten rimes higher than for infants weighing 3,000-3,500 g.¹⁸ In developing countries with a high prevalence of low weight at birth, IUGR infants account for the majority of neonatal deaths. Although the association between IUGR and increased mortality is strongest during the immediate neonatal period (seven days), it extends beyond this time. Furthermore, there is an increased risk of diarrhoea in term infants below 2,500 g and an increased risk of pneumonia in IUGR infants in developing countries.¹⁸

IUGR has significant long-term consequences on body size, composition, and muscle strength. IUGR newborns in industrialized countries partially catch up relative to controls during the first two years of life. However, this is usually not enough to compensate for prenatal growth retardation. These infants will be about 5 cm shorter and 5 kg lighter in adulthood.^19-21 In Guatemala, IUGR newborns also showed partial catch-up during the first two years of life and then maintained their achieved place in the growth distribution. Guatemalan IUGR infants were shorter, lighter, and weaker than non-IUGR controls as adolescents and young adults and were also about 5 cm shorter and 5 kg lighter as adults.²²

Some, but not all, studies evaluating neurodevelopmental outcomes in IUGR infants have shown the presence of neurological dysfunction, particularly in males of low socioeconomic status. Neurological dysfunction is associated with attention deficits, hyperactivity, clumsiness, and poor school performance.²³ The effects on cognitive development and behaviour in the first six years of life are still unclear, although deficits in cognition have been found in children with very low birthweights.²⁴

Most immune functions have been shown to be impaired in IUGR infants. The greater the foetal growth retardation, the greater the impairment of the immune competence. This impairment may be sustained through childhood.^25-27 One study links disproportionate foetal growth to altered immunoglobulin E concentrations in adult life,²⁸ and another links it to autoimmune thyroid disease.²⁹

There is evidence of associations between retarded foetal growth and blood pressure, noninsulin-dependent diabetes, coronary heart disease, and cancer in adult life. Barker’s foetal origins of disease hypothesis posits that nutritional insults during critical periods of gestation and early infancy, followed by relative affluence, increase the risks of chronic diseases in adulthood as described in Box 1.1.¹ The nutrition transition - that is, the shirts in dietary patterns and lifestyle that have resulted from urbanization and rapid economic development - may accelerate the emergence of adult consequences of early undernutrition.³⁰