Types of IUGR

IUGR infants can be subdivided according to whether they are stunted or wasted (or both). Stunted infants have been chronically undernourished in utero, resulting in a proportionate reduction in both skeletal and soft tissue growth. Wasted infants have normal linear growth but reduced tissue mass resulting in a low ponderal reflecting later onset, primarily in the third trimester (Rosso and Winick, 1974; Campbell, 1974; Villar and Belizan, 1982; Villar et al, 1989). Whether this heterogeneity in body composition and aetiology has a differential impact on the risk of mortality and morbidity will be explored.

Low birth weight and mortality

Large population-based studies of neonatal and postneonatal mortality (all causes).

The relative risks of neonatal and postneonatal death among infants of different birth weights have been reviewed previously (Ashworth and Feachem, 1985). Birth weights of 3500-4500 g were associated with the lowest risk. In these large population-based studies, infants were grouped in 500 g intervals whatever their gestational age. Preterm infants, however, are generally regarded as being at greater risk of death in the first year of life, especially neonatal death, than term infants of comparable birth weight (Behrman et al, 1971; Mata, 1978; Victora et al, 1987). Previously calculated relative risks may therefore overestimate the risks for term IUGR infants in developing countries. Therefore for this review, additional data sets have been sought and median values recalculated. This has been done separately for populations with a LBW prevalence of < 7.5% (assumed to reflect preterm births) and for populations where the prevalence of LBW is > 15%. The latter has been suggested as a proxy for IUGR prevalence (World Health Organization, 1995).

Table 1 presents neonatal mortality data from 9 populations in which the majority of LBW infants can be expected to have been preterm. Despite a 30-year span and large reductions in overall neonatal mortality during this period, for any birth-weight interval the relative risks of neonatal death are remarkably consistent across studies. Table 2 gives comparable data for populations where the majority of LBW infants can be expected to be IUGR. Population sizes are much smaller and no national data sets were located. The results are less consistent among the 4 populations, but all show an increased risk of neonatal mortality with decreasing birth weight.

Comparable birth-weight-specific mortality data for the postneonatal period are given in Tables 3 and 4. For populations where most LBW infants would be expected to be preterm, the relative risks by birth weight are again very consistent (Table 3). This is less so for populations where LBW infants are presumed IUGR (Table 4).

An alternative approach to ascertain birth-weight-specific mortalities for IUGR infants is to identify studies where gestational ages are specified. Five such studies were located and 8 data sets for term infants extracted (Tables 5 and 6). All were from the USA, and all except two data sets were restricted to neonatal mortality. By comparing Tables 2 and 5, the results of the two approaches regarding neonatal risk can be compared. Focusing on birth weights 2000-2499 g, the relative risk of neonatal death compared to birth weights 2500-2999 g, ranges from 2.7-5.6 for term infants of known gestation (Table 5) and from 1.4-4.5 for infants presumed to be term (Table 2). For infants presumed to be preterm (Table 1) the risk ranges from 2.8-4.5.

Similarly for postneonatal mortality in infants 2000-2499 g, the relative risk ranges from 2.0-2.2 for term infants of known gestation (Table 6) and from 0.8-2.3 for infants presumed to be term (Table 4). For infants presumed to be preterm (Table 3), the relative risk ranges from 1.8-2.3.

Table 7 compares the median relative risks for neonatal and postneonatal mortality by birth weight derived from the approaches described above. These population-based comparisons indicate that

i) term LBW infants have increased risks of neonatal and postneonatal death compared with infants of adequate birth weight (ABW),

ii) term LBW infants have risks of neonatal and postneonatal death that are of a broadly similar magnitude to those of preterm infants of the same birth weight,

iii) in the 2000-2499 g birth-weight category which accommodates most LBW infants in developing countries, there is a 4-fold increased risk of neonatal death compared with infants 2500-2999 g, and a 2-fold greater risk of postneonatal death (composite median values for the 10 neonatal 'term' studies and the 5 postneonatal 'term' studies).

Table 1. Relative risks of neonatal mortality by birthweight compared to birthweight of 2500-2999g. Selected countries with LBW prevalence < 7.5%

*Birth weight (g)*	*UK (1993)*	*Belgium (1986-87)*	*USA California (1977)*	*USA (1986-87)*	*USA (1980)*	*USA (5 regions) (1974-75)*	*Norway (1967-68)*	*USA Oregon (1959-66)*	*USA (1960)*
1000-1499	99.6^a	49.6	52.7	34.0	46.7	99.6^a	41.0	47.5	55.0
1500-1999	10.4	15.9	13.5	12.9	13.5	17.5	16.6	20.6	19.6
2000-2499	2.8	3.3	3.0	3.7	4.0	3.8	4.5	4.4	4.4
2500-2999	1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0	1.0
3000-3499	0.5	0.4	0.3	0.4	0.5	0.5	0.4	0.4	0.4
3500-3999	0.4	0.4	0.3	0.3	0.3	0.3	0.2	0.3	0.3
4000-4499	0.4	0.4	0.3	0.3	0.4	0.4	0.2	0.2	0.4
4500+	0.4	0.4	0.4	0.9	0.9	0.4	0.4	0.3	0.8
Neonatal mortality rate^b	4.1	4.8	5.1	5.6	7.3	8.2	8.5	13.8	16.9
% LBW	6.5^c	4.9	7.0^d	5.9	6.0	6.1	5.2	5.2	6.8
No. of births	673,000 all	229,000 single	290,000 single	7.4 million single	3.5 million single/all races	234,000 single	700,000 all	40,000 white/single	3.6 million white
Reference	Platt and Pharoah, 1995	Buekens et al, 1995	Williams and Chen, 1982	Buekens et al, 1995	Buehler et al, 1987	Starfield et al, 1982	Erickson and Bjerkedal, 1982	Behrman et al, 1971	Chase, 1969

^aincludes all births <1500g
^bneonatal mortality rate: Deaths per 1000 live births except for Williams and Chen (1982) (per 1000 vaginal births) and Erickson and Bjerkedal (1982) (per 1000 total births)
^c1992 figure
^d estimated from Erickson and Bjerkedal (1982).

Table 2. Relative risks of neonatal mortality by birthweight compared to birthweight of 2500-2999 g. Selected countries with LBW prevalence >15.0%

*Birth weight (g)*	*USA (Denver) (1974-80)*	*India (Delhi) (1969-72)*	*India (N. Arcot) (1969-75)*	*Guatemala (Santa Maria Cauque) (1964-72)*
1000-1499	32.8	94.6	16.7^a	^-
1500-1999	9.4	30.9	4.4	27.3
2000-2499	2.1	4.5	1.4	3.4
2500-2999	1.0	1.0	1.0	1.0
3000-3499	0.3	1.1	0.8	0
3500-3999	0.3	1.1	0.6	-
4000-4499	0	1.1	1.4	-
4500+	0	1.1	1.4	-
Neonatal mortality rate^b	17.5	21.2	34.8	39.0
% LBW	15.2	23.2	31.9	41.7
No. of births	14,400 all	4,590 single	4,220 single	416 single
Reference	Koops et al, 1982	Ghosh et al, 1979	Rao and Inbaraj, 1978	Mata, 1978

^aincludes all births <1500g
^bneonatal mortality rate: Deaths per 1000 live births

Table 3. Relative risks of postneonatal mortality by birthweight compared to birthweight of 2500-2999g. Selected countries with LBW prevalence < 7.5%

*Birth weight (g)*	*UK (1993)*	*Norway (1967-1968)*	*USA (1980)*	*USA (5 regions) (1974-75)*	*USA (1960)*
1000-1499	14.7^a	2.6	9.3	12.2^a	6.3
1500-1999	3.8	3.0	4.2	3.7	3.5
2000-2499	2.3	1.8	2.1	1.9	1.9
2500-2999	1.0	1.0	1.0	1.0	1.0
3000-3499	0.6	0.6	0.6	0.6	0.6
3500-3999	0.4	0.5	0.4	0.5	0.5
4000-4499	0.4	0.4	0.4	0.5	0.5
4500+	0.4	0.5	0.4	0.5	0.5
Postneonatal mortality rate^b	2.1	3.2	3.7	4.3	5.4
% LBW	6.5^c	5.2	6.0	6.1	6.8
No. of births	673,000 all	700,000 all	3.5 million single/all races	234,000 single	3.6 million white
Reference	Platt and Pharoah, 1995	Erickson and Bjerkedal, 1982	Buehler et al, 1987	Starfield et al, 1982	Chase, 1969

^aincludes all births <1500g
^bpostneonatal mortality rate: Deaths per 1000 neonatal survivors, except for Erickson and Bjerkedal (1982) (per 1000 total births) and Platt and Pharoah (1995) and Starfield et al (1982) (per 1000 live births)
^c1992 figure

Table 4. Relative risks of postneonatal mortality by birthweight compared to birthweight of 2500-2999 g. Selected countries with LBW prevalence >15.0%

*Birth weight (g)*	*India (Delhi) (1969-72)*	*India (N. Arcot) (1969-75)*	*Guatemala (Santa Maria Cauque) (1964-72)*
1000-1499	9.3	4.5^a	-
1500-1999	5.3	2.3	7.0
2000-2499	2.3	1.1	0.8
2500-2999	1.0	1.0	1.0
3000-3499	0.7	0.6	0.5
3500-3999	07	0.5	-
4000-4499	0.7	0	-
4500+	0.7	0
Postneonatal mortality rate^b	25.3	51.6	60.0
% LBW	23.2	31.9	41.7
No. of births	4,590 single	4,220 single	416 single
Reference	Ghosh et al, 1979	Rao and Inbaraj, 1978	Mata, 1978

^aincludes all births <1500g
^bpostneonatal mortality rate: Deaths per 1000 neonatal survivors.

Table 5. Risks of neonatal mortality by birthweight for term infants

*Birth weight (g)*	*USA (1980)*	*USA (California) (1980-81)*	*USA (1980)*	*USA^a (Oregon) (1959-66)*	*USA (Denver) (1958-68)*	*USA^a (California) (1970-76)*
1000-1499	-	17.5	-	-	-	59.2
1500-1999	-	13.1	-	17.9^b	18.1	18.7
2000-2499	5.6	4.7	3.0	4.4	2.7	4.4
2500-2999	1.0	1.0	1.0	1.0	1.0	1.0
3000-3499	0.4	0.4	0.6	0.4	0.5	0.4
3500-3999	0.3	0.3	0.5	0.5	0.6	0.3
4000-4499	0.3	0.2	0.5	0.1	1.9	0.5
4500+	0.5	0.3	1.4	0	1.9	-
Neonatal mortality^c	1.7	1.7	3.0	3.5	4.8	10.5
Gestation (weeks)	40-41	38-41	40-41	40	38-42	38-40
No. of births	861,000 white single	213,500 white male	122,000 black single	15,500 white	9,500 all	1 million single
Reference	Sappenfield et al, 1987	Binkin et al, 1985	Sappenfield et al, 1987	Behrman et al, 1971	Lubchenco et al, 1972	Williams et al, 1982

^aestimated from 250g birthweight intervals
^b1750-1999g
^cneonatal mortality rate: Deaths per 1000 live births for the gestations specified.

Table 6. Relative risks of postneonatal mortality by birthweight for term infants

*Birthweight (g)*	*USA (1980)*	*USA (1980)*
1000-1499	-	-
1500-1999	-	-
2000-2499	2.2	2.0
2500-2999	1.0	1.0
3000-3499	0.5	0.6
3500-3999	0.4	0.5
4000-4499	0.3	0.3
4500+	0.3	0.8
Postneonatal mortality^a	2.4	5.2
Gestation (weeks)	40-41	40-41
No. births	861,000 white single	122,000 black single
Reference	Sappenfield et al, 1987	Sappenfield et al, 1987

^aPostneonatal mortality rate: deaths per 1000 neonatal survivors

Table 7. Median relative risks of neonatal and postneonatal mortality by birthweight

*Postneonatal*	*preterm & term^a*	*mostly preterm^b*	*mostly term^c*	*only term^d*
Birthweight (g)
1000-1499	50.0	49.6	32.8	38.3
1500-1999	18.0	15.9	18.3	18.0
2000-2499	4.0	3.8	2.7	4.4
2500-2999	1.0	1.0	1.0	1.0
3000-3499	0.5	0.4	0.5	0.4
3500-3999	0.4	0.3	0.4	0.4
>4000	0.4	0.4	0.7	0.4
^a median values (n= 13 studies) from Ashworth and Feachem (1985)
^bmedian values from Table 1 (n = 9 studies)
^cmedian values from Table 2 (n = 4 studies)
^dmedian values from Table 5 (n = 6 studies)
*Postneonatal*	*preterm & term^e*	*mostly preterm^f*	*mostly term^g*	*only term^h*
Birthweight (g)
1000-1499	6.1	9.3	6.9	-
1500-1999	3.4	3.7	5.3	-
2000-2499	1.8	1.9	1.1	2.1
2500-2999	1.0	1.0	1.0	1.0
3000-3499	0.6	0.6	0.6	0.5
3500-3999	0.5	0.5	0.6	0.4
>4000	0.5	0.4	-	0.3
^emedian values (n = 8 studies) taken from Ashworth and Feachem (1985)
^fmedian values from Table 3 (n = 5 studies)
^gmedian values from Table 4 (n = 3 studies)
^hmedian values from Table 6 (n = 2 studies)

Community-based studies of mortality (all causes and cause-specific)

Smaller, community-based studies may offer certain advantages compared with the large population-based studies described above, which rely on routinely collected data. These include better estimates of gestational age and opportunities to control for potential confounding variables. If families with LBW (or IUGR) infants are more disadvantaged in terms of income, housing, parental education etc. than families of ABW infants, then they may be more exposed to infection postnatally and have inferior medical care when ill. Consequently higher mortality in LBW or IUGR infants could be due, at least in part, to their environment, rather than birth weight per se. On the other hand, smaller studies have insufficient size to allow birthweight-specific mortalities to be calculated with confidence, which limits their usefulness in estimating the potential impact on mortality of interventions to reduce IUGR.

Table 8 summarises the relative risks of mortality in LBW infants from all causes (7 studies), and from respiratory and diarrhoeal infections (4 and 3 studies respectively). Risks are calculated for birth weight as a dichotomous variable. For most, the comparison is with infants ³ 2500 g, but in one study the modal birth weight (3000-3499 g) has been used. Only 4 of the 12 studies listed were specifically of term infants. Only in 2 studies were confounding variables controlled. Where cause-specific relative risks are available within the same study, the levels of risk for diarrhoea and acute respiratory infections (ARI), appear lower than for all causes combined.

Table 8 also gives data for early childhood mortality (4 studies). The findings suggest that low birth weight continues to have an adverse effect on mortality beyond infancy.

Table 8. Summary of community-based studies of birthweight mortality

*Country (ref)*	*Design*	*Gestation*	*Age (months)*	*Sample size (deaths)*	*Birthweight (g)*	*Risk ratio (95% confidence interval)*	*Outcome*
Brazil	cohort	term	0-6	393	3000-3499	1.0
Lira et al, 1996				(12)	1500-2499	10.2 (2.2-46.7)	all causes
						6.6^a (1.4-31.2)
India	cohort	term	0-11	4590	³ 2500	1.0
Ghosh et al, 1979				(213)	2000-2499	2.6	all causes
India	cohort	term	0-11	4220	³ 2500	1.0
Rao & Inbaraj, 1978				(362)	< 2500	1.7	all causes
Guatemala	cohort	term	0-11	385	³ 2500	1.0
Mata, 1978				(24)	< 2500	1.7	all causes
Mata, 1975			12-47	(39)		1.8
Indonesia	cohort	term + preterm	0-11	687	³ 2500	1.0
Kusin et al, 1989		(9% LBW)		(83)	< 2500	3.4	all causes
Nigeria	cohort	term + preterm	0-11	4334	> 2500	1.0
Ayeni & Oduntan, 1978		(11 % LBW)		(133)	£ 2500	5.8	all causes
Brazil	cohort	term + preterm	0-11	5914	³ 2500	1.0
Barros et al, 1987		(9% LBW)		(215)	< 2500	11.0 (8.7-14.4)	all causes
						6.7 (3.0-14.9)	ARI
						2.5 (0.9-6.7)	diarrhoea
Victora et al, 1992			12-59	(29)		3.3	all causes
Brazil	case-control	term + preterm	0.25-11	1070	³ 2500	1.0
Victora et al, 1988		(9% LBW)		(357)	1500-2499	1.9^a (1.1-3.6)^b	ARI
						2.0^a (1.1-3.6)^b	diarrhoea
India	cohort	term + preterm	0-11	659	³ 2500	1.0
Datta et al, 1987		(32% LBW)		(19)	< 2500	8.0	ARI
UK	cohort	term + preterm	1-50	5522	³ 2500	1.0	bronchitis
Douglas & Mogford, 1953				(40)	< 2500	3.6	+pneumonia
USA	cohort	term + preterm		51,931	³ 2500	1.0
Read et al, 1994		(9% LBW)	1-11	(371)	1500-2499	2.4 (1.4-4.0)	infectious
			12-84	(258)		2.5 (1.3-4.5)	disease
USA	cohort	term + preterm	1-11	193,733	³ 2500	1.0
Gibson & Alexander, 1985				(93)	< 2500	7.1	diarrhoea

^aadjusted for confounders
^b90% confidence intervals.

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