Factors affecting growth Intrauterine growth retardation
Antenatal detection of fetal growth retardation Fetal loss
Congenital defects Teratogens Management Prenatal infections
Congenital rubella
Congenital cytomegalovirus (CMV) Herpesvirus hominis
Human immunodeficiency virus (HIV) Varicella-zoster virus
Fetal growth
The birth weight at term of a baby of an elite well-nourished mother anywhere in the world is more than 3 kg. Any newborn baby whose birth weight is less than 2.5 kg is classified as being oflow birth weight. Delivery before full-term or 37 completed weeks of gestation is one cause of a neonate being of low birth weight; such an infant is a preterm baby. A term infant of low birth weight is one who is small-for-gestational dates (SFD).
Preterm low-birth-weight babies are usually appro-priate for gestational dates but some are both preterm and small-for-gestational dates~ Any newborn infant weighing 1.5 kg or less is called a very-Iow-birth-weight baby (VLBW), and one weighing 1 kg or less is an extremely-Iow-birth-weight baby (ELBW).
Factors affecting growth
Most normal fetuses have similar rates of growth during the first two trimesters of pregnancy. Slowing of fetal growth usually occurs in the last trimester when
Congenital varicella Perinatal varicella Syphilis
Tuberculosis
Congenital tuberculosis Toxoplasmosis
Trypanosomiasis
Congenital African trypanosomiasis Congenital Chagas disease Malaria
Pregnancy and malaria Congenital malaria
Protection of pregnant women References
one-third of the birth weight is acquired. Factors affecting fetal growth are to be found in the fetus, the mother or the environment.
Environmental factors
Women living at high altitude, such as the Andes in Colombia, are shorter and lighter than their sisters at sea-level, and tend to give birth to low-birth-weight babies. Low social class women have the highest frequency of small-for-gestational dates babies related to a number of adverse maternal factors.
Maternal factors
Nutrition A baby's birth weight is influenced by the size of the mother. Small women tend to give birth to low-birth-weight babies. Maternal size is an indicator of the quality of nutrition the mother had as a girl.
Improving the nutrition of girls leads to increase in birth weights of their babies, as observed in emigrant Japanese in America.
Birth weight shows a greater relationship to the weight of the mother before pregnancy than to weight gained during pregnancy. In a study in Uganda, maternal weight of less than 55 kg was associated with an increase in the number of low-birth-weight infants compared with heavier women.1 For a given maternal weight, mothers who are taller give birth to heavier babies than shorter women. Thin mothers who give birth to small-for-dates babies are less able to mobilize their fat stores than mothers of normal weight babies.
Energy intake during pregnancy influences fetal growth in thin women, as demonstrated in Birmingham Asian mothers receiving food supplements in the last trimester of pregnancy. Heavier babies were born to thin mothers who had shown poor weight gain and little increase in triceps skin fold thickness earlier in pregnancy. Well-nourished mothers of similar height did not benefit. 2
Maternal undernutrition must be severe before fetal growth is affected. Observations during the acute famine in Holland in 1944-5, showed that fetal growth was affected when maternal food intake was under 1500 calories a day during the last trimester of pregnancy.
There was a decrease of 300 to 400 g in birth weight and these infants had a significant increase in mortality during their first three months but with no long-term effects in the survivors. Women who were in their first trimester of pregnancy during the famine had more stillbirths or premature deliveries with increased death rate.
Chronic undernutrition of mothers is common in developing countries. Fetal tissues take priority over the mother's body when there is an energy deficit. Supple-menting the diet of malnourished mothers who are protein or energy deficient can increase the baby's weight at birth. In a study in Guatemala, dietary supplementation of malnourished mothers in the latter half of pregnancy reduced the incidence of low-birth-weight babies by 40 per cent. 3 The greatest gains were associated with increased calorie intake. The effects on birth weight may be more marked if a food supplement is given at an earlier stage of pregnancy and if it is sustained throughout gestation as shown by the studies in the Gambia4• (See pp. 324-35). High-protein food supplements alone have proved harmful in some preg-nancies, increasing the risk of deliveries before 30 weeks of gestation and of neonatal death.5 But a supplement enriched with protein will not be harmful if recom-mended dietary allowances are followed within the framework of a regular diet.
Some mothers of small-for-gestational dates babies have an eightfold increased risk of another SFD infant in subsequent pregnancies.
Fetal growth 159
Age Young teenage mothers and women over 35 years of age tend to have low-birth-weight babies.
Parity First babies usually weigh less than their siblings.
Chronic disease Impaired transfer of nutrients through the placenta occurs in mothers with hypertension, pre-eclampsia, renal disease and poorly controlled diabetes mellitus.
Alcohol and smoking The adverse effects of cigarette smoking on the placenta are probably mediated through nicotine and carbon monoxide and lead to chronic fetal deficiency of oxygen and retardation of intrauterine growth. These result in a decrease in birth weight and an SFD baby.
The daily consumption of 45 ml of absolute alcohol by a pregnant woman will lead to slow fetal growth, increase in preterm delivery and fetal malformations.
Alcoholic mothers who drink 90 ml of absolute alcohol daily tend to produce babies with features of the fetal-alcohol syndrome - severe stunting, microcephaly, mental retardation and typical facies of maxillary hypoplasia, short palpebral fissures, ptosis, squint and hairy face.
Fetal factors
Boys are born heavier than girls by about 140 g at full-term, because of their faster growth after 36 weeks of gestation.
In multiple pregnancies such as twins, fetal growth is slower after 32 weeks gestation compared with sing-letons. Abnormal fetuses with genetic defects or intrauterine infections suffer growth retardation by the middle of the second trimester. Congenital defects are found in 3-5 per cent of SFD infants. Hormones, particularly thyroxine and insulin, influence growth in the latter half of pregnancy. Thyroxine deficiency results in a reduction in body length, delayed ossifi-cation of bones and impaired brain maturation. Insulin excess increases the laying down of fat in the fetus, as seen in the infant of a poorly controlled diabetic mother.
Infants of women with gestational diabetes (prediabetic women) tend to be large and have macrosomia. Lack of insulin production causes severe growth retardation.
Intrauterine growth retardation
Intrauterine growth retarded newborn infants are usually defined as those whose birth weights are less than the 3rd centile for gestational age. Body weight and gestational age distribution curves are available for boys and girls of most European populations. In the
160 Prenatal health
absence of growth charts for race-specific populations in developing countries, standards such as Fig. 2.3.1 may be used in the subtropics and tropics.
Growth retardation experiments in animals suggest that for tissue such as brain with only a limited period when cell multiplication can occur, growth restriction at this sensitive time would result in permanent stunting.
If growth restriction occurs throughout the period of brain growth, there is also permanent stunting of body growth. No satisfactory explanation has so far been found to explain the stunting of body growth in association with restricted growth during the period of brain growth.
In a large series of postmortem studies on intra-uterine growth retarded newborns (birth weight more than two standard deviations below the mean), Gruenwald6 found all organs of these babies were lighter than expected, but the brain was least affected and the liver and thymus most affected. These infants had relatively large heads, a moderate reduction in length and the greatest reduction in weight. Recent studies show that they have thinner than normal skin folds. They account for the majority of SFD infants in developed countries, are described as asymmetrically growth retarded and are the result of growth failure during the last trimester of pregnancy. Growth retarded infants with equal reduction in brain and body size, and
(a) Boys 5
4
--
----
_ /_ / / /
....
-/
....
--28 30 32 34 36
Gestation (weeks) Key:
97th centile 90th centile 50th centile 10th centile 3rd centile
---
--38 40
normal skin fold thickness are described as sym-metrically growth retarded; they are the product of chronic placental insufficiency and growth failure before the last trimester.
Intrauterine growth retardation contributes to a substantial proportion of infants of low birth weight
( <
2500 g) in some developing countries in Asia and Latin America. Fetal malnutrition is the cause of intrauterine growth retardation in these developing countries. The incidence of intrauterine growth retard-ation was reported as 24 per cent in a poor urban population of Guatemala city. 7 Many studies under-estimate the incidence of intrauterine growth retard-ation because they do not include infants whose birth weights fall below the 3rd centile but who weigh more than 2500 g.Asymmetrically and symmetrically growth retarded infants can be distinguished at birth using the formula weight/length 3 x 100, described by Rohrer8 as the ponderal index. Data from Guatemala City on 848 intrauterine growth retarded newborns analysed by the ponderal index (PI) showed 177 (20.8 per cent) had PI below the 10th percentile (indicating subacute fetal malnutrition) and 671 (79.1 per cent) had PI values above the 10th percentile (indicating chronic fetal mal-nutrition).7 The same PI analysis applied to a rural Guatemala population of 143 intrauterine growth
5
4
~
.E 3C)
~
28
(b) Girls
----
, , /-'"
30
/...-
--, --, /
-"
....
"Gestation (weeks)
--
-~--Fig. 2.3.1 Body weight and gestational age distribution curve for British boys and girls. (After Gairdner 0 and Pearson J 1985, Archives of Diseases in Childhood; 60. © Castlemead Publications).
retarded newborns, found 68.5 per cent to have chronic fetal malnutrition, and among 188 rural South African infants, 67.5 per cent were chronically malnourished in utero. Infants with chronic fetal malnutrition remain lighter, shorter, and with smaller head circumference till at least three years of age. They also score the lowest in tests of mental development from three years to school age. Villar and his colleagues make the gloomy prediction that in Latin America at least 2 million infants born every year are, already destined at birth, to remain undergrown and underdeveloped7• Similar studies are required in other developing countries to monitor and prevent chronic fetal malnutrition.
Antenatal detection of fetal growth retardation
Poor weight gain during pregnancy is common in developing countries; mothers may put on no more than 6 kg instead of the 12 kg gained by their counter-part in industrialized countries. The result of this insufficient weight gain during pregnancy is a greater risk of growth retarded babies of low birth weight.
Accurate assessment of intrauterine growth depends on the ability to measure fetal maturity and fetal size accurately. If a pregnant woman is sure of her menstrual dates, prediction of the expected date of delivery is correct to within 14 days in 90 per cent of cases. Many women in developing countries are not sure of their dates because of irregular periods or frequent pregnancies. The measurement of symphysis -fundal height plotted on a graph can detect intrauterine growth retardation as early as 28 weeks. Symphysis -fundal graphs are simple to use and indicate when to refer a patient for an ultrasound check.9 Ultra-sonography is the most accurate method of assessing fetal maturity in these circumstances. In the first trime-ster, crown-rump length is measured and in the second trimester, before 20 weeks, biparietal diameter gives accurate assessment of fetal maturity by ultrasound.