Functional residual capacity and passive compliance measurements after antenatal steroid therapy in preterm infants

Studies in preterm animal models have shown that antenatal corticosteroids enhance lung maturation by improving a variety of physiologic variables, including lung volumes. Changes in lung volume of preterm infants treated with a full course of antenatal steroids have not been investigated. We hypothesized that a full course of antenatal steroids would significantly increase functional residual capacity (FRC) in treated vs. untreated preterm infants. The objective of our study was to compare FRC and respiratory mechanics in steroid treated vs. untreated preterm infants. FRC and passive respiratory mechanics were prospectively studied within 36 hr of life in 20 infants (25-34 weeks of gestation) who had received a full course of antenatal steroids and in 20 matched untreated preterm infants. FRC was measured with the nitrogen washout method, and respiratory mechanics with the single-breath occlusion technique. Preterm infants who received steroids (n = 20; mean birth weight = 1,230 g; gestational age = 28.8 weeks) had a significantly higher FRC (29.5 vs. 19.3 mL/kg; P < 0.001) than untreated infants (n = 20; birth weight = 1,202 g; gestational age = 28.5 weeks). Passive respiratory system compliance was also increased in treated vs. untreated infants (P < 0.05). In conclusion, FRC and passive respiratory system compliance were significantly improved in preterm infants (25-34 weeks gestation) treated with a full course of antenatal steroids, compared to matched untreated infants. Although this study was not randomized, it confirms that antenatal steroids have important effects on pulmonary function that may contribute to a decreased risk of respiratory distress syndrome in treated preterm infants.     

Placental transfer of maternal rubella antibodies to full-term and preterm infants

Summary Premature infants are vulnerable to infections, partly because of the low transplacental transfer of maternal antibodies. The present study investigated the placental transfer of maternal rubella-specific antibodies to full-term and preterm infants. The study group consisted of 133 healthy, native Israeli mothers and their 159 newborns. Of these, 69 were full-term infants (gestational age >37 weeks) of 69 mothers, and 90 were preterm infants (gestational age <35 weeks) of 64 mothers. Antibody titers against rubella were measured in maternal and umbilical cord blood samples by hemagglutination inhibition and microneutralization techniques. There was no significant difference in the level of protection and in geometrical mean titers by hemagglutination between the full-term and preterm groups. Conversely, significant differences in geometric mean titers of neutralizing antibodies were found between full-term and preterm infants, e.g., 65.9 and 39.8, respectively (P<0.001). Very low birth weight preterm infants are at greater risk of rubella infection during the first year of life, due to the diminished transfer of neutralizing maternal antibodies. Therefore, earlier vaccination of this group may be beneficial.     

Sweat-testing in preterm and full-term infants less than 6 weeks of age

Our objective was to examine the characteristics of preterm and full-term infants < or = 6 weeks old that influence the success of obtaining sufficient sweat for diagnosis of CF, and corresponding sweat chloride concentrations. A retrospective chart review of 119 sweat tests was performed on 103 preterm and full-term infants < or = 6 weeks of age. Bivariate and multivariate regression analyses were used to determine the predictors of successful sweat testing and characteristics influencing sweat chloride concentrations. Adequate amounts of sweat (> or = 75 mg) were obtained for analysis in 73.8% of initial attempts in the infant group. The following characteristics were associated with increased odds of obtaining a quantity not sufficient (QNS) for sweat chloride concentration measurement: African-American race, infant weight < 2,000 g, preterm birth, and postmenstrual age (PMA) < 36 weeks. With a multivariable logistic model, the only significant predictors were African-American race (7.3, 2.4-21.7) and PMA < 36 weeks (17.9, 4.2-75.9). Sweat chloride concentration in non-CF individuals is inversely related to both gestational age and age at testing, and this effect is additive in a linear regression model. In conclusion, sweat collection can be reliably performed in infants > or = 36 weeks postmenstrual age, > 2,000 g, and > 3 days postnatal age. Maturational factors have a mild impact on sweat chloride concentration.     

Evaluation of renal glomerular and tubular functional and structural integrity in neonates

BACKGROUND: Renal cells are not fully differentiated at birth, representing a major risk in preterm infants. We evaluated glomerular and tubular functional integrity as well as structural integrity of renal tubules among healthy full-term and preterm infants as well as diseased preterm infants. METHODS: A total of 50 newborns (10 healthy full-term, 10 healthy preterm, and 30 diseased preterm, at 38.9 +/- 1.10, 34.2 +/- 0.92, and 32 +/- 2.47 weeks gestational age, respectively) were included in the present study. Glomerular function was assessed by measuring urinary levels of both microalbumin and immunoglobulin G as well as serum creatinine levels, whereas the proximal tubular function was investigated by measuring the urinary levels of both alpha1-microglobulin and beta2-microglobulin as well as retinol-binding protein. Also, distal tubular reabsorption capacity was investigated by assessing fractional excretion of sodium. Moreover, the structural integrity of renal proximal tubules was studied by measuring the urinary activities of both the brush-border membrane enzyme leucine-aminopeptidase (LAP) and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase. The preceding investigations were done on both the first and third days of life of all 50 newborns. RESULTS: Glomerular and tubular function and structure was relatively impaired at birth among both healthy and diseased preterm as well as healthy full-term neonates and improved rapidly thereafter. The diseased preterm neonates showed worse renal function and structure with minimal improvement regardless of the underlying sickness. CONCLUSION: Renal insufficiency and renal immaturity could be evaluated using enzymuria and low- and high-molecular-weight proteinuria as noninvasive methods.     

Moment analysis of multibreath nitrogen washout in healthy preterm infants

Moment analysis (MA) of multibreath nitrogen washout (MBNW) has not previously been applied to newborn infants. The aim of the present study was to adapt this method to healthy preterm infants using an improved technique suitable for small infants, and to determine reference values of MA. Twenty healthy preterm infants with a mean birth weight (± SD) of 1,666 ± 402 g and a mean gestational age of 31.3 ± 2.1 weeks were studied during their first 7–28 days of life. Computerized bedside equipment with very low dead space was constructed. The limits of normal variability were determined from results of duplicate studies. Outcome variables included functional residual capacity (FRC), the first-to-zeroth moment ratio (M₁/M₀), the second-to-zeroth moment ratio (M₂/M₀), and the lung clearance index (LCI). The starting point for MA had considerable impact on the results. Mean M₁/M₀ and M₂/M₀ were 2.18 ± 0.18 and 8.71 ± 1.24, respectively. No significant relation between moment ratios and weight, gender or age was found. Intrasubject coefficients of variation (CV) for M₁/M₀ (7.9 ± 5.9%) and for M₂/M₀ (12.1 ± 9.1%) and intersubject CV for M₁/M₀ (8%) and M₂/M₀ (14%) were similar to those reported in children and adults. Mean lung clearance index was 10.8 ± 1.4 and intra- and intersubject CVs were 11.3 ± 8.9% and 13%, respectively. Mean functional residual capacity (FRC) was 22.5 ± 2.1 ml/kg. Mean intra- and intersubject CVs for FRC were 8.3% and 9%, respectively. We conclude that the MBNW test can be performed by a simple bedside method and that MA appears to be a suitable method for measuring gas mixing in preterm infants. Pediatr. Pulmonol. 1998; 25:52–58. © 1998 Wiley-Liss, Inc.     

Decline of hepatitis a antibodies during the first 7 months of life in full-term and preterm infants

Summary In a previous study we have shown that transplacental transfer of hepatitis A antibodies to preterm infants does not differ from that observed in full-term infants. This follow-up study was designed to investigate the decline of hepatitis A virus (HAV) antibodies during the first 7 months of life in full-term and preterm infants, in an endemic region for hepatitis A. Two hundred and fifty newborn infants— 147 full-term and 103 preterm infants—were enrolled. Blood samples from the infants were taken at birth, and at 3 and 7 months of age. Anti-HAV titers were determined by ELISA. A concentration of ≥1∶20 mlU/ml was considered protective. Protective hepatitis A antibodies were present at birth in 48.3% of all full-term and 49.5% of all premature infants. By the age of 7 months only 13% of full-term and 21.7% of preterm infants still had protective titers. For the seropositive full-term infants the geometric mean titers (GMT) were 15,698, 6,107 and 345 at birth, 3 months and 7 months, respectively, and for preterm infants, 10,378, 2,307 and 225 at birth, 3 months and 7 months, respectively. Significant differences in GMT between preterm and full-term infants were found at birth and at 3 monts of age (P<0.05). In a region endemic for hepatitis A, low levels of anti-HAV at 7 months of age may justify trials on infant vaccination since this is the most effective way to eliminate hepatitis A from circulation.     

Evolution of the QT interval in premature infants: a preliminary study

BACKGROUND: The association between long QT interval and sudden infant death syndrome has been clearly established. Several studies have been conducted to determine the evolution of the QT interval in childhood from birth, but only in full-term newborns. However, data on the QT interval in pre-term infants are extremely scarce. The objective was to describe the development of the QT interval in premature infants. Material and methods In a prospective monocentric study in a neonatal intensive care unit, pre-term newborns born before 37 weeks of gestation without congenital heart disease, family history of long QT, unstable haemodynamic status, or administration of drugs inducing QT interval prolongation were included with parental consent. An electrocardiogram was recorded in similar conditions weekly until discharge in each child. The corrected QT was calculated with Bazett's formula. RESULTS: In all, 309 echocardiograms were recorded in 87 children, with gestational age ranging from 24-36 weeks. QT first increased after birth in very premature infants - less than 30 weeks of gestation - and then started to decrease, whereas it only decreased in more mature infants. When plotted against postmenstrual age, QT first increased, and then decreased after 32 weeks. Discussion Our data suggest that the QT interval varies with postmenstrual age in very premature infants, reaching a peak at 32 weeks. These developmental changes may induce specific vulnerability to QT-lengthening medications in premature infants. This study underlines the need for specific pharmacological studies in this population.     

Static compliance of the respiratory system in healthy infants

We recorded static deflation pressure-volume (PV) curves from near TLC to FRC in 49 healthy, sedated, spontaneously breathing infants of 1 to 104 wk of age. Respiratory activity was transiently inhibited by inflating the respiratory system several times to a volume at an airway pressure of 30 cm H2O (V30). Passive deflation from V30 to FRC was then interrupted by multiple brief occlusions at the airway opening, in order to measure static recoil pressures. The expired volume from V30 to FRC was defined as V30E. Compliance of the respiratory system (Crs) was calculated as the slope of the linear portion of the PV curve from 5 to 15 cm H2O. Crs and V30E increased with increasing body length (p < 0.001). After adjustment for body length, males had greater Crs values than did females (p < 0.01). V30E was smaller in female infants (p < 0.05) and in infants whose mothers smoked during pregnancy (p < 0.04). Specific compliance (Crs/V30E) declined with increasing age (p < 0.01), but there were no differences related to sex or maternal smoking. We conclude that static deflation PV curves can be recorded in the age range from 1 to 104 wk, and that maternal smoking may produce hypoplastic lungs.     

Lung function tests in neonates and infants with chronic lung disease of infancy: functional residual capacity

This is the second paper in a review series that will summarize available data and discuss the potential role of lung function testing in infants and young children with acute neonatal respiratory disorders and chronic lung disease of infancy. The current paper addresses the expansive subject of measurements of lung volume using plethysmography and gas dilution/washout techniques. Following orientation of the reader to the subject area, we focus our comments on areas of inquiry proposed in the introductory paper to this series. The quality of the published literature is reviewed critically, and recommendations are provided to guide future investigation in this field. Measurements of lung volume are important both for assessing growth and development of lungs in health and disease, and for interpreting volume-dependent lung function parameters such as respiratory compliance, resistance, forced expiratory flows, and indices of gas-mixing efficiency. Acute neonatal lung disease is characterized by severely reduced functional residual capacity (FRC), with treatments aimed at securing optimal lung recruitment. While FRC may remain reduced in established chronic lung disease of infancy, more commonly it becomes normalized or even elevated due to hyperinflation, with or without gas-trapping, secondary to airway obstruction. Ideally, accurate and reliable bedside measurements of FRC would be feasible from birth, throughout all phases of postnatal care (including assisted ventilation), and during subsequent long-term follow-up. Although lung volume measurements in extremely preterm infants were described in a research environment, resolution of several issues is required before such investigations can be translated into routine clinical monitoring.     

Thyroid function in seventy-five healthy preterm infants thirty to thirty-five weeks of gestational age: a prospective and longitudinal study during the first year of life.

Thyroid function was evaluated in 75 healthy preterm infants, 30-35 weeks of gestational age. Serum thyrotropin (TSH), thyroxine (T(4)), triiodothyronine (T(3)), free T(4) (immunochemoluminescence) and reverse triiodothyronine (rT(3)) (radioimmunoassay) were measured in the mother and in the cord at delivery and in the preterm infants at 1 hour, 24 hours, 1 week, 3 weeks, 2 months, 4 months, 6 months, and 12 months of postnatal age. These values were compared to those of healthy full-term infants of the same postnatal age (22 at 24 hours from our hospital and from previously reported data at others times). Mean 24-hour TSH values were significantly lower (p < 0.001) in preterm than in full-term infant populations (12.38 +/- 6.13 microIU/mL versus 22.02 +/- 13.28 microIU/mL); however, all TSH values of preterm infants were in the range of the full-term values. Mean 24-hour free T(4) values were similar in preterm and full-term infants (1.88 +/- 0.46 ng/dL versus 2.01 +/- 0.54 ng/dL) and all preterm infants had free T(4) values within the range of those of full-term infants at 24 hours. Mean T(4) and T(3) values were significantly lower in preterm than in full-term neonates at 1 hour and 24 hours of age. Mean 24-hour rT(3) values were significantly higher in preterm than in full-term newborns. From 1 week onwards, all thyroid function values were in the same range in both populations. In conclusion, individual thyroid function was similar in healthy preterms and full-terms from the first 24 hours of life. Normative data in preterm infants during the first year of life applying the latest luminescence techniques currently used worldwide are reported.     

Progressive decline in plethysmographic lung volumes in infants: physiology or technology?

During the last 30 years, there has been an unexplained trend toward declining values for plethysmographic assessments of lung volume at functional residual capacity (FRC) in infants. The aim of this study was to compare data collected from healthy infants using contemporary equipment with published reference data and to explore reasons for discrepancies. Lung volumes were measured in 32 healthy infants (age, 4-93 weeks; weight, 3.9-12.4 kg) using a new, commercially available infant plethysmograph. Mean (SD) FRC was 19.6 (3.4) ml/kg (within subject coefficient of variation 3.4 [2.3%]), which was on average 7.0 [3.5] ml/kg and 2.3 [1.2] SD (Z) scores lower than the recently collated reference data from an American Thoracic Society task force. A total of 66% of these healthy infants had a FRC that was below the predicted normal range. Comparison of equipment, software, and protocols with those from previous reports revealed the importance of minimization of dead space and of adequate subtraction of all compressible occluded volume when calculating FRC in infants. These findings emphasize the need to establish reference data for lung function tests in infants that are appropriate for the equipment and protocols in current use.     

Total respiratory system compliance in asymptomatic infants with cystic fibrosis

Total respiratory system compliance (Crs) was assessed by the weighted spirometer method in 11 asymptomatic infants (mean age, 11.1 months) with cystic fibrosis (CF) who had normal chest radiographs. In addition to Crs, functional residual capacity (FRC), respiratory rate (RR), and mixing index (MI) were measured. There was no significant difference in FRC between normal controls (n = 36) and CF infants (190 +/- 69 versus 186 +/- 63 ml; p less than 0.8), although the CF group had a higher RR (32 +/- 7 versus 37 +/- 7 BPM; p less than 0.05) and a lower MI (45 +/- 7 versus 40 +/- 8%; p less than 0.05), reflecting an abnormal distribution of ventilation. The lower Crs (9.0 +/- 3.4 versus 5.7 +/- 2.8 ml/cm H2O; p less than 0.01) and the lower specific compliance, Crs/FRC (0.049 +/- 0.013 versus 0.029 +/- 0.007 1/cm H2O; p less than 0.0001), in the CF group were the parameters that best distinguished the normal control and CF infants. We conclude that the measurement of Crs represents a noninvasive method for detecting early pulmonary function abnormalities in CF infants.     

Perinatal bile acid metabolism: bile acid analysis of meconium of preterm and full-term infants

Background Our purpose was to evaluate the metabolism of bile acids in the fetus by analyzing the bile acid composition of meconium of preterm (less than 30 weeks’ gestational age) and full-term infants and comparing the results with the bile acid composition of feces of preterm and full-term infants 6 days after delivery. Methods The concentrations of individual bile acids were determined by gas chromatography-mass spectrometry after solvolysis and hydrolysis of bile acid conjugates. Results In meconium, the main bile acids were chenodeoxycholic and hyocholic acids. The main bile acid of feces from preterm infants at 6 days of age was the same as that of meconium. We also detected large amounts of secondary bile acids, especially deoxycholic acid and ursodeoxycholic acid. The ratio of cholic acid relative to chenodeoxycholic acid in meconium of preterm and full-term infants and in feces of preterm infants was less than 1, 0.36, 0.55, and 0.55, respectively. The percentage of chenodeoxycholic acid relative to total bile acids in meconium of preterm (P < 0.05) and full-term (P < 0.01) infants was significantly higher than that in feces of 6-day-old full-term infants. Conclusions More than half of the main pathway, at least, for bile acid synthesis in preterm infants may be the acidic pathway until the infants reach about 7 days of age.     

Cord plasma adiponectin: a 20-fold rise between 24 weeks gestation and term

Adiponectin is an adipocyte-derived hormone with profound insulin-sensitizing, antiinflammatory, and antiatherogenic effects. Apart from its obvious potential as a mediator of adult metabolic syndrome, adiponectin could have a significant role in regulating fetal growth.We measured plasma adiponectin concentrations by ELISA in cord vein of 197 infants. Of them, 122 were born preterm (gestational age, 22-32 wk), and 75 at term (49 from a healthy and 26 from a diabetic pregnancy, with similar findings, and thus all data from term infants pooled).Mean adiponectin concentrations increased from less than 1 microg/ml at 24 wk gestation to approximately 20 microg/ml at term. One week increase in gestational age corresponded in preterm infants to 43% increase (95% confidence interval 34-53%; P < 0.0001) in adiponectin and term infants to 21% increase (12-31%; P < 0.0001). In preterm infants, one unit increase in birth weight sd score corresponded to 42% increase (22-66%; P = 0.0001) in adiponectin, and females had 57% higher adiponectin concentrations (0-146%; P = 0.05) than males. These differences were not seen in term infants. Adiponectin levels were lower in preterm infants with recent (<12 h) exposure to maternal betamethasone but were unrelated to mode of delivery, preeclampsia, or impaired umbilical artery flow.In conclusion, adiponectin concentrations in fetal circulation show a 20-fold rise between 24 wk gestation and term and, in preterm infants are associated with birth weight sd score, sex, and glucocorticoid exposure. Adiponectin may play an important role in regulating fetal growth and explaining its links to the metabolic syndrome and its consequences during adult life.     

Lung function in 6-20 month old infants born very preterm but without respiratory troubles.

Lung function results of 21 healthy infants born very prematurely are reported. The median gestational age was 29 weeks, but none had developed respiratory distress or required any form of respiratory support in the neonatal period. Lung function was assessed by measurements of thoracic gas volume (TGV) and airway resistance (Raw) plethysmographically, and of functional residual capacity (FRC) using a helium gas dilution technique. Two separate measurements were made between 6 and 20 months of age; all infants were measured once in the first and once in the second year of life. Regression equations were calculated for TGV, Raw, and FRC related to weight, height, and postnatal age. These data provide a new set of values for very preterm infants, in part small for gestational age, without neonatal respiratory trouble.     

The limits of physiological anemia in the African neonate

In order to determine the limits of physiological anemia in the African neonate, the hematological values of 402 healthy neonates were determined. It was observed that although the African neonate had much lower hematological values at birth when compared with their North American and European counterparts, the eventual nadir reached is approximately the same. The hematocrit, hemoglobin and red blood cell count of preterm infants on the first day of life were comparable to those of full-term and postterm infants. However, the preterm infants had a more precipitous drop in these values and, consequently, reached a nadir much lower than full-term and postterm infants. The nadir was reached between 6 and 8 weeks in each group. In all three groups, recovery was spontaneous and preceded by a rise in reticulocyte count. It is also significant that by 16 weeks of life, no significant difference exists between the values for preterm, full-term and postterm infants.     

Pulmonary mechanics in normal infants and young children during first 5 years of life

To characterize lung function in young children we measured lung compliance and pulmonary conductance in 40 normal infants and children ranging in age from the newborn period to 5 years. Inspiratory and expiratory flow was measured by a pneumotachograph, esophageal pressure through a water-filled feeding tube, and functional residual capacity (FRC) by a N2 washout technique. The esophageal pressure change per breath [(mean +/- SD) 7.3 +/- 1.4 cm H2O] and specific compliance (75 +/- 13 ml/cm H2O/L-FRC) did not change with growth. Specific conductance was high (0.60 L/s/cm H2O/L-FRC) in preterm infants, decreasing rapidly with initial growth but minimally beyond 10 kg of body weight, and stabilizing at 0.10 L/s/cm H2O/L-FRC. During the age period studied, compliance increased approximately x 25 whereas conductance only rose five-fold. The changes in compliance and conductance were well correlated to FRC, body weight, and length. These findings suggest that in the last trimester of pregnancy the airways are already well developed and postnatal lung growth occurs mainly by formation of new alveoli, leading to a proportional increase in FRC and lung compliance. Postnatally, conductance increases much more slowly than FRC, resulting in a rapid drop in specific conductance.     

Relationship of symptoms to lung function abnormalities in preterm infants at follow-up.

Recurrent respiratory symptoms are common in preterm infants in the first 2 years of life. The aim of this study was to determine the lung function abnormalities associated with such symptoms. Forty preterm infants, with a median gestational age of 29 weeks were studied at a median postnatal age of 12 months. Twenty-two suffered from recurrent symptoms, defined as wheezing and/or coughing on at least 4 days per week over the previous month. Lung function was assessed by measurement of functional residual capacity (FRC), using a helium gas dilution technique, and airway resistance (Raw) and thoracic gas volume (TGV) plethysmographically. No significant difference was found in TGV between symptomatic and asymptomatic infants, but the median FRC was lower (P less than 0.01), Raw higher (P less than 0.01), and FRC:TGV ratio lower (P less than 0.001) in the symptomatic infants. These lung function abnormalities in the symptomatic infants are suggestive of gas trapping.     

Fetal growth and the function of the adrenal cortex in preterm infants

Small for gestational age preterm infants have a higher risk of neonatal morbidity compared to appropriate for gestational age preterm infants. A diminished adrenal response to stress may be involved in the higher postnatal morbidity. The adrenal cortex response in relation to fetal growth was studied by ACTH stimulation tests in 43 preterm infants (born < or = 32 wk). The cortisol and 17-hydroxyprogesterone (17-OHP) responses to 1 microg/kg ACTH were analyzed in relation to birth weight SD scores (BW-SDS) corrected for gestational age, gender, and parity. BW-SDS was significantly associated with the cortisol and 17-OHP response. Infants with the lowest BW-SDS had the lowest cortisol levels after stimulation. No effect of size at birth was found on the ratio between cortisol and 17-OHP. In addition, basal cortisone levels in a single blood sample were higher in infants with the lowest BW-SDS than in infants with higher BW-SDS, but the ratio between cortisol and cortisone was comparable in the two groups. We conclude that the response of cortisol and 17-OHP to ACTH stimulation in preterm infants is related to fetal growth. The lack of influence of fetal growth on the ratio between cortisol and 17-OHP after ACTH stimulation suggests that the activities of 21- and 11 beta-hydroxylase are not affected. The lower adrenal response to stimulation may be important in neonatal morbidity and possibly the development of disease in later life in growth-restricted preterm infants.     

Association of the growth hormone receptor d3-variant and catch-up growth of preterm infants with birth weight of less than 1500 grams

BACKGROUND: Preterm infants with very low birth weight frequently exhibit impaired longitudinal growth during the first years of life. Recently, the d3-isoform (genomic deletion of exon 3) of the GH receptor (GHR) has been linked to an increased responsiveness to GH. OBJECTIVE: Our objective was to test whether the GHRd3 isoform is associated with postnatal catch-up growth in very low birth weight preterm infants. DESIGN AND PATIENTS: We compared the postnatal growth pattern of 77 otherwise healthy preterm infants (mean gestational age, 28.5 wk; range, 23-35 wk) with a birth weight below 1500 g (mean birth weight, 941 g) to their GHR exon 3 genotype, which was analyzed by multiplex PCR. On examination, mean age of the children was 6.0 yr (range, 4.2-8.0 yr). RESULTS: Children homozygous or heterozygous for the GHRd3 allele showed a significantly higher rate of postnatal catch-up, compared with those homozygous for the full-length allele. CONCLUSIONS: Our results define the GHR exon 3 genotype as a predictor for the postnatal growth pattern of very low birth weight preterm infants. Those who carry at least one GHRd3 allele are more likely to catch-up.