Determinants of fetal growth and body proportionality

Previous studies of fetal growth and body proportionality have been based on error-prone gestational age estimates and on inappropriate comparisons of infants with dissimilar birth weights. Based on a cohort of 8719 infants with validated (by early ultrasonography) gestational ages and indexes of body proportionality standardized for birth weight, potential maternal and fetal determinants of fetal growth and proportionality were assessed. Maternal history of previous low birth weight infants, pregnancy-related hypertension (particularly if severe), diabetes, prepregnancy weight, net gestational weight gain, cigarette smoking, height, parity, and fetal sex were all significantly associated with fetal growth in the expected directions. Consistent with previous reports, maternal age, marital status, and onset or total amount of prenatal care had no significant independent effects. Fetal growth ratio (relative weight for gestational age), pregnancy-related hypertension, fetal sex, and maternal height were the only significant determinants of proportionality. Infants who were growth-retarded, those with taller mothers, those whose mothers had severe pregnancy-related hypertension, and males tended to be longer and thinner and had larger heads for their weight, although these variables explained only a small fraction of the variance in the proportionality measures. Among infants with intrauterine growth retardation, gestational age was not independently associated with proportionality (in particular, late term and post-term infants did not tend to be more disproportional), a finding that does not support the hypothesis that earlier onset of growth retardation leads to more proportional growth retardation. The results raise serious questions about previous studies of proportionality, particularly those suggesting a nutritional etiology for proportional intrauterine growth retardation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low birth weight and intrauterine growth retardation in Filipino infants

Low birth weight, prematurity, and intrauterine growth retardation represent important health tasks for neonates. Pregnancy outcome risk categories based on combinations of these variables and a measure of body proportions were developed and tested with respect to how well they predict poor growth during infancy. Data were collected during a prospective community-based survey of births representative of the Cebu region of the Philippines. In the sample of 2139 births for which there were available birth weight and gestational age data, 20% of infants were classified as growth retarded and 12% were low birth weight. Low birth weight, the more conservative category, was a better predictor of small infant size at 12 months of age than intrauterine growth retardation. Rohrer's index, which captures information about patterns of intrauterine growth, improves the positive predictive value of categories based either on intrauterine growth retardation or low birth weight. Infants who had an adequate Rohrer's index, ie, were well proportioned at birth, were smaller at 12 months of age than infants who had a low Rohrer's index, ie, had weight deficits relative to their lengths at birth. Important questions about the value of the intrauterine growth retardation classification are raised by the results.     

Neurology and behaviour of growth-retarded neonates. Relation to biochemical placental function tests in late pregnancy

Serial estimations of maternal urinary oestriol, serum cystine aminopeptidase (S-CAP), and human chorionic somatomammotrophin (S-HCS) were done in a prospective study on 29 pregnancies in which intrauterine growth retardation was diagnosed in the third trimester by the gravidogram method and/or serial ultrasound measurements of the fetal biparietal diameter. The series was divided into 2 growth-retarded groups: (i) severe growth retardation with birth weight less than -2 SD from the mean for gestational age (N = 14); (ii) moderate growth retardation with birth weight between -1 and -2 SD from the mean for gestational age (N = 15). These were compared with a control group of 18 normal pregnancies and infants. A modified Prechtl neurological examination and the Brazelton Neonatal Behavioural Assessment Scale (NBAS) were done in the neonatal period at full-term age. Both categories of growth-retarded infants showed lower muscle tonus than the controls. The severely growth-retarded infants showed fewer optimal items in the neurological examination; they also showed poorer capacity for orientation to external stimuli, inferior motor function, and less physiological stability in NBAS than the controls. The abnormal biochemical placental tests were significantly correlated to low Apgar scores (urinary oestriol), to low excitability (S-CAP) and to poor motor function (S-HCS). The neurological and behavioural condition of the neonate seemed to be more closely associated to the extent of growth retardation than to the occurrence of abnormal biochemical placental tests.     

Body size and neonatal hypoglycemia in intrauterine growth retardation

The relationship between blood glucose and body physique of 233 (42 hypo-and 191 normologycemic) intrauterine growth-retarded neonates was analyzed using different body measurements and indices of body proportions. Classification by combination of weight and length deficit for fetal age revealed that the disproportionately retarded infants (deficit in weight for age > 30%; deficit in length for age less than equal to 15%) were particularly prone to hypoglycemia. The lowest incidence of hypoglycemia was observed in the group with severe proportionate retardation (weight deficit for age > 30%; length deficit for age > 15%). Among the indices of body proportions ponderal index (W/L3), and percentage deviation from the expected weight for length turned out to be a sensitive predictor of the risk of hypoglycemia. The majority of hypoglycemia neonates were underweight for length and a considerable number of normoglycemic infants were overweight for length. These findings point to the significance of soft tissue wasting rather than low birth weight for gestational age itself, in the development and diagnosis of neonatal hypoglycemia. The significance of anthropometry in the classification of different types of intrauterine growth impairment, as well as in predicting specific hazards after birth is discussed.     

Activities of lipase and trypsin in duodenal juice of infants small for gestational age

In 18 low birth weight infants, small for gestational age, with different degrees of intrauterine growth retardation the activities of pancreatic lipase and trypsin and the concentrations of bile acids were measured in preprandially aspirated duodenal juice. The results were compared to those of 24 low birth weight infants, appropriate for gestational age, with comparable birth weights and postnatal ages. The activities of both measured pancreatic enzymes were negatively correlated with the degree of intrauterine growth retardation, expressed as the difference between the individual birth weight and the weight of the 10th percentile of the intrauterine growth curve (lipase: r = -0.697, p less than 0.001; trypsin: r = -0.739, p less than 0.001). The activity of trypsin in the small for gestational age infants was within the range of that found in the infants appropriate for gestational age. However, the lipase activity was decreased in infants who presented with growth retardation of greater than 400 g/kg birthweight. The concentrations of bile acids were similar in both groups (4.60 +/- 2.51 and 4.55 +/- 2.26 mmol/L, respectively) and sufficient for activating the bile salt stimulated lipase in human milk. The data suggest that in intrauterine growth retarded infants the lipase activity in the duodenal juice can be a limiting factor for optimal fat digestion. This should be considered in the nutritional management of such infants.     

Impact of maternal drug dependency on birth weight and head circumference of offspring

The impact of maternal opiate dependency on birth weight and head circumference of offspring was studied in 150 mother-infant pairs and 150 controls. Mean birth weight and head circumference of drug-dependent offspring were reduced symmetrically compared with drug-free controls of similar socioeconomic status. Although mean gestational ages and rates of prematurity were similar, intrauterine growth retardation occurred in 20% of passively addicted infants vs 4% of controls. A longer period of methadone maintenance was associated with longer gestation and increased birth weight, while higher methadone dosages were associated with higher birth weights and larger head circumferences. Smoking was associated with reduced birth weight by an average of 160 g per pack of cigarettes smoked per day; longer duration of smoking was associated with reductions in both birth weight and head circumference. These data suggest therapeutic strategies to improve these fetal growth characteristics and perhaps improve neurobehavioral outcome of drug-dependent newborns.     

Catch up Growth in Preterm Infants

Seventy-one surviving infants were followed up from birth to 24 weeks of postnatal age. Their mean gestational age was 32 weeks with a range of 26–36 weeks and a standard deviation of 2.1 weeks. Their mean birth weight was 1.805 kg with a range of 0.675–2.5 kg and a standard deviation of 0.408 kg. Their weights, lengths and head circumferences were measured at birth, 6, 12 and 24 weeks. Curves for the mean weight, length and head circumference were produced and superimposed on the available intrauterine and extra-uterine growth charts. The growth curves of the preterm infants did not show the flattening noted in the intrauterine curves towards term. The curve of the mean weight of the preterm infants started at the 50th centile for Gairdner & Pearson (1971) at birth to drop below that shortly after birth. At 40 weeks of postconceptional age the mean weight curve of preterm infants crossed the 50th centile and continued above it to reach the 90th centile at 60 weeks. The curves of mean length and head circumference started below the 50th centile at birth and crossed it at 40 weeks and continued above it to approach the 90th centile at 60 weeks. Growth velocity was calculated as a relative gradient using the straight line equation (y=a+bx), where y is the weight, length or head circumference, and x is the independent variable and here it is the group mean of the parameter at the corresponding ages. Catch up growth is taken as a relative gradient significantly greater than one. The first 24 weeks of postnatal life are defined as a period of catch up growth with the first 8 weeks as an interval of maximum head velocity.     

Impact of intrauterine growth retardation and body proportionality on fetal and neonatal outcome

Previous prognostic studies of infants with intrauterine growth retardation (IUGR) have not adequately considered the heterogeneity of IUGR in terms of cause, severity, and body proportionality and have been prone to misclassification of IUGR because of errors in estimation of gestational age. Based on a cohort of 8719 infants with early-ultrasound-validated gestational ages and indexes of body proportionality standardized for birth weight, the consequences of severity and cause-specific IUGR and proportionality for fetal and neonatal morbidity and mortality were assessed. With progressive severity of IUGR, there were significant (all P less than .001) linear trends for increasing risks of stillbirth, fetal distress (abnormal electronic fetal heart tracings)O during parturition, neonatal hypoglycemia (minimum plasma glucose less than 40 mg/dL), hypocalcemia (minimum Ca less than 7 mg/dL), polycythemia (maximum capillary hemoglobin greater than or equal to 21 g/dL), severe depression at birth (manual ventilation greater than 3 minutes), 1-minute and 5-minute Apgar scores less than or equal to 6, 1-minute Apgar score less than or equal to 3, and in-hospital death. These trends persisted for the more common outcomes even after restriction to term (37 to 42 weeks) births. There was no convincing evidence that outcome among infants with a given degree of growth retardation varied as a function of cause of that growth retardation. Among infants with IUGR, increased length-for-weight had significant crude associations with hypoglycemia and polycythemia, but these associations disappeared after adjustment for severity of growth retardation and gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heterogeneous growth and mental development of intrauterine growth-retarded infants during the first 3 years of life

Postnatal growth and development were studied in two groups of term infants with intrauterine growth retardation (IUGR) and one group of infants with normal birth weight up to 3 years of age (total sample, 205 infants). Infants with IUGR were classified as having low ponderal index (IUGR-LPI) or adequate ponderal index (IUGR-API). At birth, the two groups of infants with IUGR had similar birth weight, but length and head circumference measurements were significantly different. Overall, the IUGR-API infants remained lighter and shorter and had smaller head circumferences up to 30 months of age. The IUGR-LPI infants experienced catch-up growth in weight during the first months, because of greater fat deposition. At 24 months of age, the IUGR-API infants scored below the others on mental items. At 3 years of age the IUGR-API infants had the lowest values on seven of eight developmental measures and on the composite score; at these two time periods, the group with normal birth weight scored the highest, and the IUGR-LPI infants obtained intermediate values. It is concluded that infants with IUGR tend to follow postnatal growth and developmental patterns that are associated with their physical characteristics at birth.     

Epidemiology of inguinal hernia in preterm neonates

We have studied the epidemiology of inguinal hernias in preterm infants. Inguinal hernias occur with increased frequency in infants less than or equal to 32 weeks' gestational age or less than or equal to 1,250 g birth weight. Among infants less than or equal to 32 weeks' gestational age, intrauterine growth retardation significantly increases the risk for development of inguinal hernias, especially in male infants. Our data demonstrate a previously unrecognized association between neonatal inguinal hernia and intrauterine growth retardation.     

An 18-month follow-up study of growth-retarded neonates. Relation to biochemical tests of placental function in late pregnancy and neurobehavioural condition in the newborn period

Serial estimations of maternal urinary oestriol, serum cystine aminopeptidase (S-CAP), and human chorionic somatomammotrophin (S-HCS) were studied prospectively in 29 pregnancies complicated by intrauterine growth retardation. The newborn growth-retarded infants were examined by neurological and behavioural techniques. Growth variables and neurological and developmental findings were compared with those in 18 healthy controls at 5, 10 and 18 months of age. The growth-retarded infants caught up with regard to body size from 5 months of age, although the severely retarded infants (birth weight ? ?2 SD) differed from the controls with regard to weight and head circumference at 18 months of age. Abnormal maternal oestriol excretions were negatively correlated to weight and length during the follow-up period. Infants who had been severely growth-retarded at birth were neurologically below optimal level at 10 months of age, compared to the controls. There were no significant differences between the growth-retarded infants and the controls with regard to psychomotor development, as assessed by a screening test and by Griffiths' method. Significant correlations were found between abnormal biochemical placental tests (especially urinary oestriol and S-CAP) and psychomotor development. Significant correlations also appeared between neonatal orientation and motor behaviour and some Griffiths' scales at 18 months of age. No relationship was found between the neurological condition in the neonatal period and the neurological findings and development at follow-up.     

Second-generation consequences of small-for-dates birth

This is the first reported study of birth outcomes of a group of women whose own birth weights and gestational ages had been previously recorded. Births occurring from 1972 to 1983 among 1154 Swedish women, born from 1955 to 1965, were studied. Women who were themselves small for gestational age (SGA) at birth were at increased risk of giving birth to a SGA infant (odds ratio = 2.21, 95% confidence interval = 1.41, 3.48). Women who had been SGA had an even greater increase in risk of giving birth to a preterm infant (odds ratio = 2.96, 95% confidence interval = 1.47, 5.94). Women who were preterm at birth were not at increased risk of giving birth to either preterm (odds ratio = 0.65, 95% confidence interval = 0.15, 2.74) or SGA (odds ratio 1.21, 95% confidence interval = 0.62, 2.38) infants. It is concluded that the long-term effects of intrauterine growth retardation may extend to the next generation; women who had been SGA should be considered at increased risk to give birth to both growth-retarded and preterm infants.     

Increased energy expenditure and fecal fat excretion do not impair weight gain in small-for-gestational-age preterm infants.

In order to optimize the nutrition of high-risk premature infants beyond the early postnatal period, a more precise knowledge of individual nutritional requirements is needed. We therefore studied the influence of intrauterine growth retardation on energy expenditure and nutrient utilization determined by indirect calorimetry and fecal fat excretion (steatocrit) in nineteen premature infants who were appropriate-for-gestational-age (AGA; mean gestational age 29.9+/-0.3 weeks, mean birth weight 1.30+/-0.05 kg) and thirteen small-for-gestational-age (SGA) premature infants [mean gestational age 32.4+/-0.5 weeks, mean birth weight 1.024+/-0.07 kg (i.e., below the 10th percentile)] during the first and second month of life. All infants were clinically stable during the study period. In nine SGA infants we observed a significantly higher steatocrit compared to twelve AGA infants (29+/-1 vs. 17+/-1% p = 0.0001). SGA infants (n = 12) also showed a slightly (albeit statistically not significantly) higher energy expenditure than AGA infants (n = 15) (58.7+/-1.9 vs. 53.6+/-1.5 kcal/kg per day, p = 0.054). Despite the increased fat excretion and higher energy expenditure, SGA infants gained weight more rapidly during the study period than AGA infants (20+/-1 vs. 17+/-1 g/kg per day, p = 0.026). We conclude that influences of intrauterine growth retardation on energy expenditure and nutrient utilization persist during the first weeks of extrauterine life. However, these metabolic changes do not impair the capability of SGA infants for extrauterine catch-up growth if adequate nutrition is provided.     

Serum insulin-like growth factor 1 and serum growth-promoting activity during the first postnatal year in infants with intrauterine growth retardation

Follow-up from birth to age 12 months was obtained in 21 infants born with intrauterine growth retardation. Serum insulin-like growth factor 1 was measured by radioimmunoassay. The bioassayable growth-promoting activity of the serum was measured as the "thymidine activity" on lectin-activated lymphocytes at 5 days and 1, 3, 6, 9, and 12 months, and was compared with control values. Depending on their length at age 12 months, the intrauterine growth retardation infants were divided into three groups: at or above the average (n = 8, group A), between the mean and -2 SD (n = 7, group B), or less than -2 SD (n = 6, group C). No differences in nutritional indexes or in head circumference were found between the three groups. Insulin-like growth factor 1 was significantly lower at age 5 days in intrauterine growth retardation than in control infants. It increased slowly in groups A and B to reach the control values at age 9 and 12 months. In group C it remained significantly subnormal at 1 yr of age. Thymidine activity was also significantly lower at age 5 days in intrauterine growth retardation compared with control infants. It increased sharply at age 1-3 months in groups A and B but remained significantly lower in group C up to 1 yr of age. Although individual values of insulin-like growth factor 1 and thymidine activity were closely correlated, the increase of length during the first postnatal year correlated significantly with the thymidine activity levels at 1 and 3 months but not with the insulin-like growth factor 1 levels at 1, 3, and 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Catch-up growth, muscle and fat accretion, and body proportionality of infants one year after newborn intensive care

We studied catch-up growth, muscle and fat accretion, and body proportionality at 4 and 12 months of age corrected for prematurity in 30 very low birth weight (VLBW) (less than 1500 gm), 30 low birth weight (LBW) (1500 to 2499 gm) and 30 normal birth weight (greater than or equal to 2500 gm) infants who required newborn intensive care. At 4 and 12 months, the VLBW infants had significantly lower mean weight and length (p less than 0.01), but not lower occipitofrontal circumference percentiles, than the LBW and normal birth weight groups, and showed no catch-up weight or length growth between 4 and 12 months. All three groups had significant increases in mean upper mid-arm circumferences, mid-arm muscle circumferences, and arm muscle areas between 4 and 12 months. Mean mid-arm muscle circumferences and arm muscle areas were similar among the three groups at 4 months but became significantly stratified by birth weight groups by 12 months, with VLBW infants having the lowest mean value. In contrast, analysis of fat stores by triceps skin-fold thickness and arm fat area demonstrated no significant increases in any group between 4 and 12 months, except for arm fat area in the LBW group. The VLBW infants had significantly less fat than normal birth weight infants at 4 and 12 months. All three groups had proportional growth at both visits, as assessed by mid-arm circumference/head circumference ratio and weight-length percentile for age. The VLBW infants were significantly lighter for their length than normal birth weight infants. We conclude that VLBW infants have no first-year catch-up growth, remaining smaller than higher birth weight infants, although appropriately proportional. Somatic growth during the first year is due more to muscle than to fat accretion, especially in VLBW infants.     

Extrauterine growth retardation in premature infants in Shanghai: a multicenter retrospective review

Intrauterine growth retardation (IUGR) represents the degree of body growth and development decided by genes and by placental function. Extrauterine growth retardation/restriction (EUGR) refers to severe nutritional deficits during the first weeks of life that result in growth that is less than expected based on intrauterine growth rates (growth values ≤10th percentile of intrauterine growth expected in accordance with the estimated gestational age). The deficits affect not only weight but also head circumference and height. As is well known, a nutrition support team (NST) is a multidisciplinary team comprised of physicians, nurses, dietitians, pharmacists, social workers, and medical technologists who provide nutritional management. In this study, we review 2,015 premature infants (1,209 boys and 806 girls) from four hospitals in the Shanghai area from January 1, 2003 to December 31, 2006, two of which had NSTs. The overall incidence of EUGR was 56.8% assessed by weight, while the incidence of IUGR was 26.1%. Higher incidence of EUGR was associated with lower birth weight, but higher gestational age. There was a significant relationship between EUGR incidence and NST availability (χ ² = 60.630, p < 0.001), though there was no similar finding for IUGR incidence. The incidence of EUGR was 44% in NST hospitals and 62.6% in non-NST hospitals. According to logistic regression, the following five factors were related to EUGR: male gender, gestational age at birth, birth weight, length of hospital stay, and NST availability. NSTs reduced the risk of EUGR by a magnitude of 0.47. EUGR remains a serious problem in premature infants in Shanghai, but NSTs can reduce EUGR incidence.     

Hypotonia at six years in prematurely-born or small-for-gestational-age children

A neurological follow up study was done of 143 full-term infants who were small for gestational age based on intrauterine growth retardation and of 49 preterm appropriate-for-gestational-age (PTAGA) infants at the age of 6 years. Findings were compared with those of a reference group of 192 full-term appropriate-for-gestational-age (FTAGA) children. In 11% of the children of both study groups, hypotonia was found without any other neurological deviancy. This type of hypotonia was absent in the reference group, whereas minor neurological dysfunction consisting of hypotonia with other neurological signs was found in all the three groups of children. No relation was found with obstetrical or neonatal variables, including severity of growth retardation and gestational age, or with weight, body height or head circumference at 6 years. The possible interference of preterm birth or intrauterine growth retardation with, and the role of placental mechanisms in, fetal and early postnatal muscle development is discussed.     

Intrauterine growth retardation and brainstem auditory-evoked response in preterm infants

Intrauterine growth retardation is frequently associated with intrauterine undernutrition, and can deleteriously affect brain function. Twenty-eight premature small for gestational age infants were compared with 28 premature appropriate for gestational age infants to determine whether intrauterine growth retardation was associated with abnormalities in the auditory pathway in the early neonatal period. The auditory pathway was studied between 4-18 wk of life by analysis of brainstem auditory-evoked potentials elicited by a 10/s 75 decibel above normal adult hearing level (dB nHL) click stimulus presented at the infants' ears. Peak latencies of components I, III and V, and interpeak latencies I-III, III-V and I-V, yielded no statistically significant differences between groups. The present study indicates that intrauterine growth-retarded premature infants may not have abnormalities of brainstem auditory-evoked response in the early neonatal period.     

Growth and development of full-term nonasphyxiated small-for-gestational-age newborns: follow-up through adolescence

Previous studies of growth and development in small-for-gestational-age (SGA) infants have been plagued by several methodologic defects, including a lack of control for socioeconomic status and parental height and an inability to distinguish among the effects of prematurity, neonatal asphyxia, and intrauterine growth retardation. An attempt has been made to overcome these defects in a study of 33 full-term, nonasphyxiated small-for-gestational-age neonates born between 1960 and 1966 and 33 matched control infants of normal birth weight. The infants were followed up and compared for physical growth and sexual, neurologic, and cognitive development at ages 13 to 19 years. Significant deficits in height, weight, and head circumference were found among the SGA cohort, even after statistical adjustment for differences in socioeconomic status and parental height. Sexual development and bone age were not delayed in the SGA group, however, indicating that the deficits in growth are permanent. On neurologic and cognitive testing, the SGA group had trends toward lower scores but scores were well within the normal range. It is concluded that full-term nonasphyxiated SGA infants have an impaired potential for physical growth, but a good prognosis for neurologic and cognitive development. Previous findings of more severe cognitive deficits are attributed to a failure to distinguish the effects of isolated intrauterine growth retardation from effects due to asphyxia.     

Mid-arm circumference/head circumference ratios for identification of symptomatic LGA, AGA, and SGA newborn infants

Mid-arm circumference/head circumference ratios (MAC/HC) and birth weights obtained in 73 neonates were studied to compare which of these growth measurements could more accurately predict risk of metabolic complications resulting from either acceleration or retardation of fetal growth. The MAC/HC ratio was more sensitive than birth weight in distinguishing symptomatic large for gestational age (LGA) infants who were born to diabetic mothers from other LGA infants who were asymptomatic, and symptomatic from asymptomatic small for gestational age infants. In addition, the MAC/HC ratio identified symptomatic appropriate for gestational age (AGA) infants born to diabetic mothers and AGA infants with signs and symptoms of growth retardation. The MAC/HC is more useful than birth weight in assessing newborn infants at risk for the metabolic complications associated with fetal growth disorders.