The effect of antenatal betamethasone on cord blood concentrations of retinol-binding protein, transthyretin, transferrin, retinol, and vitamin E

We assessed the effect of short-term (less than or equal to 1 week) and prolonged (greater than 1 week) exposure to antenatal betamethasone on umbilical cord serum concentrations of retinol-binding protein (serum t 1/2 = 12 h), transthyretin (t 1/2 = 2 days), transferrin (t 1/2 = 8 days), retinol (vitamin A), and vitamin E in appropriate-for-gestational-age preterm newborn infants of less than 36 weeks' gestation. A group of 30 infants whose mothers received a single course of betamethasone less than or equal to 1 week prior to delivery had significantly elevated mean retinol-binding protein and transthyretin but not transferrin concentrations when compared with a group of 30 gestational age- and birth weight-matched infants with no exposure to antenatal betamethasone. A group of eight infants whose mothers received multiple (more than two) weekly courses of betamethasone prior to delivery had significantly elevated mean serum concentrations of all three proteins when compared with eight gestational age- and weight-matched control infants with no betamethasone exposure. Serum retinol and vitamin E concentrations were measured in a group of 21 infants exposed to short-term prenatal betamethasone and were significantly greater than in a group of 21 control infants without steroid exposure. We conclude that antenatal steroids increase the umbilical cord serum concentrations of retinol-binding protein, transthyretin, transferrin, retinol, and vitamin E. The effect on the various serum proteins is dependent on the duration of exposure to steroids.     

Cardiac effects of a single course of antenatal betamethasone in preterm infants

AIM: To show the effects of a single course of antenatal betamethasone on cardiac measurements and systolic functions in premature newborn infants. METHODS: Seventy six newborn infants with a gestational age of 25-33 weeks were included in the study. They were first classified according to their gestational age: 25-29 weeks (n = 28) and 30-33 weeks (n = 48). They were then reclassified as betamethasone positive (mother received one course of betamethasone) or betamethasone negative (mother did not receive any antenatal glucocorticoid treatment). Cross sectional M mode echocardiographic scans were performed during the first three postnatal days and at the end of the first and third weeks. Left interventricular septum (IVS), left ventricular posterior wall (LVPW), left ventricular end diastolic (LVED), and left ventricular end systolic (LVES) dimensions, aortic root (AO), and left atrial diameters (LAs) were measured. The IVS to LVPW ratio was calculated to identify asymmetrical septal hypertrophy. RESULTS: In neither group was any statistically significant difference noted in IVS, LVED, LVES, LVPW, LA, and AO measurements during the three cardiac ultrasonography scans. Systolic function, as assessed by fractional shortening, was not significantly different in infants who received betamethasone antenatally, in either age group. There was no difference in the IVS/LVPW ratios between those who received antenatal steroid and those who did not for the 25-29 week and 30-33 week groups during these three consecutive scans. CONCLUSION: One course of antenatal betamethasone did not affect the cardiac wall thicknesses and systolic function in premature infants.     

Maternal glucocorticoid therapy and reduced risk of bronchopulmonary dysplasia

Because of substantial clinical and laboratory evidence of the efficacy of glucocorticoids in the treatment of acute pulmonary surfactant deficiency in preterm newborns, we explored the hypothesis that maternal antenatal glucocorticoid receipt is followed by reduced risk of bronchopulmonary dysplasia (BPD). A sample of 223 intubated infants weighing less than 1751 g birth weight provided 76 infants with BPD (defined by both oxygen requirement and compatible chest radiograph) and 147 who had neither BPD characteristic by day 28 of life. When compared to babies who received a complete and timely course of antenatal glucocorticoids, those whose mothers received no glucocorticoids were at prominently increased risk of BPD (odds ratio = 3.0; 95% confidence interval = 1.1, 8.2). Babies whose mothers received a partial course of glucocorticoids were not at increased risk of BPD (odds ratio = 1.3; 95% confidence interval = 0.4, 4.3). Stratification by gender and birth weight at 1 kg showed a benefit of therapy in all strata except that of extremely low birth weight male infants. These data support the hypothesis that maternal antenatal glucocorticoid therapy offers very low birth weight infants protection against BPD.     

Decreased interleukin-10 in tracheal aspirates from preterm infants developing chronic lung disease

The inability to balance pulmonary injury with healing may predispose preterm infants to chronic lung disease (CLD). It is postulated that the production of interleukin (IL)-10, an anti-inflammatory cytokine, is gestationally influenced and that CLD-prone infants may have a reduced ability to produce IL-10. METHODS: Tracheal fluid (TF) was collected at least twice weekly from 48 mechanically ventilated infants within the first 7 d of life while intubated. RESULTS: A total of 87 TF specimens were obtained. None of the 11 CLD infants (24-31 wk of gestation) had TF IL-10 levels above 4 pg/ml (0/20 TF specimens), while 14 (70%) of the 20 non-CLD preterm infants (27-36 wk of gestation) had IL-10 levels above 5 pg/ml in one or more of their TF specimens (18/48 TF specimens, p < 0.001). Only the 5 term infants who were ventilated for severe lung disease had raised IL-10 levels (17 infants, 5/19 TF specimens). IL-10 levels, if detected, (range 6-938 pg/ml) tended to be higher with increasing gestation (Spearman's rho coefficient = 0.43; p = 0.003). TF IL-10 detection was not associated with hyaline membrane disease, antenatal steroids or influenced by TF sample volume. Overall IL-8 levels were wide ranging but towards the end of week 1 the levels were significantly higher in CLD infants (CLD: median 34 184 ng/ml, preterm non-CLD: median 699 ng/ml, p < 0.001, term: 2961 ng/ml, p = 0.028). CONCLUSION: A gestationally influenced low IL-10 may predispose preterm infants to persistent pulmonary inflammation of CLD.     

Comparing alloimmunization in preterm infants after transfusion of fresh unmodified versus stored leukocyte-reduced red blood cells.

PURPOSE: To compare the occurrence of red blood cell (RBC), platelet (PLT), and white blood cell (WBC) antibodies in preterm infants after transfusions. METHODS: A randomized, blinded trial was conducted in which preterm infants were transfused either with stored RBCs, prepared by prestorage leukocyte reduction and transfused throughout 42 days of storage to limit donor exposure (n = 18), or with fresh RBCs prepared without leukocyte reduction and transfused within 7 days after collection from as many donors as needed to guarantee freshness (n = 17). Nontransfused preterm infants of comparable birth weight were control subjects (n = 11). RESULTS: No RBC antibodies were detected in serial blood samples taken during the first 6 months of life. Similarly, no definite WBC antibodies were found, although weak reactivity was detected transiently in sera from two infants. Accordingly, RBC and WBC antibody production did not differ among groups. In all, 11% of the transfused the infants exhibited platelet antibodies: 14% of the infants given stored leukocyte-reduced RBCs and 7% of the infants given fresh nonleukocyte-reduced RBCs (difference not statistically significant). CONCLUSIONS: Preterm infants rarely produce antibodies to blood cell antigens after RBC transfusions, regardless of whether the exposure is to fresh unmodified RBCs from several donors or to stored leukocyte-reduced RBCs from a limited number of donors. Therefore, efforts to limit donor exposures or to remove WBCs from blood components cannot be justified simply for purposes of preventing alloimmunization in neonates.     

Antenatal steroids are associated with a reduction in the incidence of cerebral white matter lesions in very low birthweight infants

AIMS: To investigate whether antenatal steroids reduce the incidence of cerebral white matter lesions in very low birthweight infants. METHODS: A total of 224 newborn infants of < 31 weeks gestational age and weighing < 1500 g was studied between January 1998 and June 2000. Obstetric and neonatal information was obtained from the case notes. The study population was subdivided into two groups according to antenatal steroid exposure. A complete course of treatment consisted of two doses of 12 mg each of betamethasone given at an interval of 12-24 hours. Infants in group 1 were born to mothers who had not received betamethasone, or were delivered within 24 hours of receiving the first dose of steroid. Infants in group 2 were born to mothers who had received one or more complete courses of betamethasone and were delivered > 24 hours after receiving the first dose of steroid. RESULTS: The two groups contained statistically similar proportions of boys and girls, and the infants had similar birth weights and survival rates. Those in group 2, compared with those in group 1, had a lower gestational age (p = 0.02) and a lower incidence of white matter lesions on cranial ultrasound scans (p = 0.03). Stepwise logistic regression analysis showed that gestational age (p = 0.0002) and a complete course of antenatal steroids (p = 0.02) had independent effects on cerebral white matter lesions. CONCLUSIONS: These observations suggest that a complete course of antenatal steroids may have a protective effect against cerebral white matter lesions in very low birthweight infants.     

Glucose homeostasis in the newborn

Hepatic glucose production by glycogenolysis and gluconeogenesis is essential to maintain blood glucose levels, and the glucose-6-phosphatase system catalyses the terminal step of both pathways. Developmental delays in the postnatal up-regulation of hepatic glucose-6-phosphatase enzyme activity are common in preterm infants. Two groups of infants have been identified with failure of developmental regulation of glucose homeostasis. Firstly, up to 20% of preterm infants about to be discharged home are at risk of hypoglycaemia if a feed is delayed. Cortisol, corticotrophin and epinephrine levels are higher in the infants with severe and persistent hypoglycaemia, but insulin, glucagon and human growth hormone do not differ from normoglycaemic infants. Secondly, preterm infants with an inadequate glycaemic response to glucagon (30% at the time of discharge home) have relative fasting hyperglycaemia, hyperinsulinaemia, increased insulin:glucagon ratios and a lower insulin sensitivity index. Hormonal dysfunctions in preterm infants may contribute to failures in postnatal expression of hepatic enzymes.     

The effects of repeated antenatal glucocorticoid therapy on the developing brain

Antenatal glucocorticoid (GC) therapy improves infant outcome following preterm birth. As approximately 50% of women given a first course of antenatal GCs remain undelivered 7-14 d later, many clinicians administer further courses. GCs are known to be neurotoxic and there is concern that exposure during early development may have adverse effects on the immature brain. The aim of this investigation was to compare magnetic resonance (MR) indices of brain maturation in infants exposed to repeated antenatal GC therapy and born at or close to term, with non-GC exposed control infants. MR images were obtained during quiet sleep without sedation. T1 weighted volume images were obtained in the sagittal plane and T1, T2 weighted spin echo and inversion recovery images in the transverse plane. Brain volume and surface area were calculated from segmented image slices, and a measure of the complexity of cortical folding, the whole cortex convolution index (WCCI), from computerized analysis of a vector coded contour following algorithm. Analysis of covariance was used to compare the two groups after allowing for the effect of postmenstrual age. There were 10 infants in the GC group (range of antenatal GC exposure, 3-11 courses) and 6 controls. Each GC course comprised two 12-mg IM doses of betamethasone 24 h apart. GC exposed infants had a significantly lower WCCI (p = 0.001) and smaller surface area (p = 0.02), after allowing for postmenstrual age. There was no significant difference in brain volume (p = 0.5). Repeated antenatal GC exposure results in measurable differences in brain maturation when compared with gestational age matched non-GC exposed controls. The clinical relevance of these observations is not known.     

Antenatal glucocorticoids increase early total thyroxine levels in premature infants

BACKGROUND: Hypothyroxinemia is associated with adverse neonatal outcomes including white matter damage, cerebral palsy, poor neurodevelopment and death. It has become increasingly important to understand the natural history and modifiers of thyroid function in the premature infant. It is standard obstetrical practice to offer antenatal glucocorticoids to pregnant women with threatened preterm delivery. Few studies have investigated the effect of antenatal glucocorticoids on neonatal thyroid function. OBJECTIVE: To examine the association between antenatal exposure to glucocorticoids and early total thyroxine (T4) levels among extremely premature infants. METHODS: We studied 521 infants born at 4 medical centers. Entry criteria included a gestational age of 23-28 weeks and a serum thyroxine level obtained in the first postnatal week. Receipt of antenatal glucocorticoids was recorded as none, partial, or complete. A complete course consisted of two doses of betamethasone or four doses of dexamethasone within a 48-hour period between 2 and 7 days of delivery. Early total T4 levels were obtained from state-mandated newborn screening programs. RESULTS: Controlling for potential maternal, perinatal and neonatal confounding variables, infants exposed to a complete course of antenatal glucocorticoids had total T4 levels 0.8 microg/dl higher than their peers who were not exposed to a complete course of antenatal glucocorticoids (p = 0.03). CONCLUSIONS: Extremely premature infants who received a complete course of antenatal glucocorticoids had significantly higher total thyroxine levels in the first postnatal week. Maternal, perinatal, and early neonatal variables did not completely explain this association. We speculate that antenatal glucocorticoids influence early neonatal thyroid function.     

Feasibility and safety of AS-3 red blood cells for neonatal transfusions

OBJECTIVES: Most extremely low birth weight (<1 kg) infants receive red blood cell (RBC) transfusions. RBCs stored up to 42 days can be transfused safely in small volumes to preterm infants; however, because the formulation of RBC anticoagulant/preservative solutions differs, clinical studies are required to document the safety of each solution before widespread use. Our goal was to study the feasibility and safety of AS-3 anticoagulant/preservative solution to preterm infants. STUDY DESIGN: Two clinical studies were conducted in sequence: (1) a randomized trial to compare RBC transfusions given as stored (< or =42 days) AS-3 RBCs (11 infants) versus fresh (< or = 7 days) citrate, phosphate, dextrose, and adenine RBCs (10 infants) and (2) a subsequent evaluation of the safety of stored AS-3 RBCs in 33 additional preterm infants given 120 AS-3 RBC transfusions. RESULTS: Results of both the randomized study and the subsequent evaluation documented that AS-3 RBCs stored < or =42 days and transfused in small volumes (15 mL/kg) were safe for RBC transfusions of preterm infants. Donor exposure was significantly reduced, clinical transfusion reactions were rare, and post-transfusion blood hematocrit, pH, and plasma Na, K, Ca, lactate, and glucose measurements were similar when AS-3 and citrate, phosphate, dextrose, and adenine RBC transfusions were compared. CONCLUSIONS: AS-3 RBCs can be used safely for small-volume RBC transfusions for preterm infants.     

Endogenous pulmonary surfactant metabolism is not affected by mode of ventilation in premature infants with respiratory distress syndrome

OBJECTIVE: To determine if high frequency oscillatory ventilation (HFOV) decreases surfactant production in premature infants with respiratory distress syndrome (RDS). STUDY DESIGN: We randomized 19 infants <28 weeks of gestation to either HFOV (n = 8) or conventional ventilation (CV, n = 11) at 24 hours of life. After a 24-hour continuous infusion of uniformly labeled carbon 13 glucose (U-(13)C(6)) glucose, we measured (13)C enrichment in surfactant phosphatidylcholine (PC) in tracheal aspirate samples using gas chromatography/mass spectrometry. We calculated the fractional synthetic rate (FSR) of surfactant PC from labeled glucose and its half-life of clearance (T(1/2)). RESULTS: FSR did not differ between groups (4.7% +/- 2.7%/day CV vs 4.2% +/- 3.1%/day HFOV, P =.7). T(1/2) was 79 +/- 18 hours in the CV group and 76 +/- 23 hours in the HFOV group (P =.7). Neither degree of ventilatory support nor supplemental oxygen exposure correlated with surfactant metabolic indices. Three of 4 infants who died from RDS within the first month of life had a shorter T(1/2) than 14 of 15 infants who survived. CONCLUSION: Surfactant metabolism is similar in preterm infants ventilated with HFOV and CV. Shortened surfactant half-life may characterize a subset of preterm infants with lethal RDS.     

早产儿视网膜病危险因素分析(英文)

目的：早产儿视网膜病(ROP)是儿童视觉损害及致盲的重要原因之一。众多的研究表明低出生体重和低胎龄是ROP发病的主要危险因素。该文旨在探讨除出生体重和胎龄外,影响ROP发生的其他危险因素。方法：根据胎龄、出生体重进行配对,合并ROP的早产儿和未合并ROP的早产儿各32例进行对照研究,对20种可能的危险因素进行Logistic回归性分析。结果：氧疗时间(DOT)、最高动脉氧分压(MaxPaO2)、妊娠高血压(PIH)、生后3 d内最低pH值(MinpH)的比值比(OR)值分别为2.764、2.175、1.935、2.417(P<0.01)。建立的早产儿ROP危险因素主效应模型是Logit(P)=β0+1.265 DOT+1.034MaxPaO2+0.936 PIH-1.273 MinpH (χ2=25.634,P<0.01)。结论：氧疗时间长、高氧血症、妊娠高血压和酸中毒为ROP的高危因素。     

胎龄≤32周早产儿低血糖的危险因素分析

目的 探讨胎龄≤32周早产儿出生后发生低血糖的危险因素。方法 回顾性纳入2017年1月至2020年6月入住新生儿重症监护病房的86例胎龄≤32周低血糖早产儿作为低血糖组,随机选取同期住院监测血糖正常的早产儿172例为对照组。采用单因素分析与多因素logistic回归分析筛选早产儿低血糖的危险因素。结果 研究期间早产儿共计515例,其中低血糖86例（16.7%）。低血糖组小于胎龄儿（SGA）、剖宫产出生、孕母高血压、产前使用激素的比例均高于对照组（P < 0.05）,而出生体重及血糖检测前已静脉使用葡萄糖的比例均低于对照组（P < 0.05）。SGA（OR=4.311,95% CI：1.285~14.462）、孕母高血压（OR=2.469,95% CI：1.310~4.652）和产前使用激素（OR=6.337,95% CI：1.430~28.095）为早产儿低血糖的危险因素（P < 0.05）,静脉使用葡萄糖（OR=0.318,95% CI：0.171~0.591）为早产儿低血糖的保护因素（P < 0.05）。结论 SGA、孕母高血压和产前使用激素可增加胎龄≤32周早产儿早期发生低血糖的风险;对胎龄≤32周早产儿,建议生后尽早静脉使用葡萄糖,以减少低血糖的发生。     

The effects of antenatal betamethasone administration on fetal heart rate and behaviour depend on gestational age

OBJECTIVE: We previously reported decreases in fetal heart rate (FHR) variability and body and breathing movements after maternal betamethasone administration. We now test the hypothesis that fetal responsiveness to betamethasone depends on the gestational age at which glucocorticoid therapy is started. DESIGN OF THE STUDY: 1-h recordings of FHR (n=350) and fetal movements (n=310) made during a 5-day period (days 0-4) were available for analysis. The recordings had been obtained from 63 pregnant women at high risk for preterm delivery who received betamethasone (two doses of 12 mg 24 h apart) between 26 and 34 weeks' gestational age (wGA). The response to betamethasone, i.e. the direction and magnitude of change in FHR and movement parameters compared with baseline (day 0), was studied in relation to gestational age at drug administration. RESULTS: Fetuses exposed to betamethasone at 29-34 wGA showed a decrease in FHR on day 1 (indicative of baroreceptor reflex), and reduced breathing activity and prolonged episodes of quiescence with a concomitant decrease in body movements on days 1 and 2. However, these changes were not observed if betamethasone administration occurred at 26-28 wGA. Betamethasone-induced reductions in FHR variability were similar in young and older fetuses. CONCLUSIONS: Age-related differential responsiveness to betamethasone was found for all studied fetal processes (body and breathing movements, FHR, and quiescence), except FHR variability. Our results suggest ontogenic changes in the mechanisms presumed to underlie these processes (glucocorticoid receptor (GR) maturation, cardiovascular and neuro-endocrine development).     

Effect of multiple courses of antenatal corticosteroids on pituitary-adrenal function in preterm infants

AIM: To evaluate the pituitary-adrenal function of preterm infants whose mothers received multiple courses (8 or more doses) of antenatal dexamethasone. METHODS: The pituitary-adrenal function of 14 preterm infants whose mothers received eight or more doses of antenatal dexamethasone were assessed using the human corticotrophin releasing hormone (hCRH) stimulation test when 7 days (n = 14) and 14 days old (n = 12). During each test, blood samples were taken at 0 (baseline), 15, 30 and 60 minutes after an intravenous bolus dose of hCRH (1 microg/kg). The corresponding hormone concentrations were compared between days 7 and 14, and with various associated factors. RESULTS: The baseline (0 min) plasma adrenocorticotrophic hormone concentration was significantly higher at day 14 than at day 7 (p = 0.036). None of the corresponding poststimulation (15, 30, and 60 min) hormone concentrations was significantly different between the two time epochs. When the association between the hormone concentrations and the number of antenatal dexamethasone doses received by the mothers was assessed, a significant negative correlation was observed in serum cortisol concentrations at 15 and 30 min on day 14 (r = -0.59, p = 0.04 and r = -0.60, p = 0.039, respectively). CONCLUSIONS: The absence of a significant difference in poststimulation hormone concentrations between days 7 and 14 in this cohort of infants, and the similarity of their hormone responses with those of older children and adults, suggests that no severe pituitary-adrenal suppression had occurred. None the less there was evidence of mild adrenal suppression in some of the treated infants. Vigilance in monitoring blood pressure, electrolytes and signs of adrenal suppression in infants whose mothers receive multiple courses (8 or more doses) of antenatal dexamethasone is required, as some of them might have diminished adrenal reserve.     

Lung function, arterial pressure and growth in sheep during early postnatal life following single and repeated prenatal corticosteroid treatments

BACKGROUND: Antenatal corticosteroid therapy is of great benefit to preterm infants, owing largely to effects on lung maturation. In sheep, repeated betamethasone injections given to the ewe improve lung function following preterm birth but also cause intrauterine growth restriction (IUGR). In humans and in animal models, IUGR is associated with impaired postnatal lung function. The effects on lung function of repeated prenatal betamethasone treatments and associated IUGR following term delivery are unknown. AIM AND STUDY DESIGN: To determine the effects of antenatal betamethasone treatments on postnatal arterial pressure, blood gases, ventilation, pulmonary gas volumes and compliance in serial studies of four groups of lambs until 4 weeks of age. SUBJECTS: Treatment groups were (1) maternal injections of saline at 104, 111 and 118 days of gestation, (2) a single maternal injection of betamethasone (0.5 mg/kg) at 104 days followed by saline at 111 and 118 days, (3) repeated betamethasone injections at 104, 111 and 118 days, or (4) no intervention (term is approximately 150 days). RESULTS: Repeated maternal betamethasone injections reduced birthweight and resulted in reduced postnatal body weights and arterial pressure throughout the first postnatal month. Lung function was not deleteriously affected by single or repeated maternal betamethasone treatments: blood gases, minute ventilation, lung volumes and compliance were not different between groups of lambs. CONCLUSIONS: The absence of alterations in postnatal blood gases contrasts with other models of IUGR in sheep and suggests that changes in lung structure caused by betamethasone may benefit IUGR neonates born at term.     

Hyperglycaemia as a possible marker of invasive fungal infection in preterm neonates

AIM: The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognition and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. METHODS: We performed a case-control study on neonates with birthweight less than 1250 g admitted to our tertiary-level unit during the years 1998-2004 (n = 383), comparing those with invasive fungal infection (n = 45, group A) to matched controls with late-onset sepsis caused by bacterial agents (n = 46, group B). We investigated in both groups the occurrence of hyperglycaemia (serum glycaemia > 215 mg/dl, i.e. 12 mmol/l) in the first month of life, and its temporal relationship with the episodes of sepsis. RESULTS: Hyperglycaemia occurred significantly more often in group A (21/45, 46.6%) than in group B neonates (11/46, 23.9%) (OR 1.95, 95% CI 1.235-4.432, p = 0.008). Moreover, in 19 of 21 (90.4%) neonates with hyperglycaemia in group A, the carbohydrate intolerance episode typically occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis (p = 0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia (p = 0.15). CONCLUSIONS: Hyperglycaemia is significantly more frequent in neonates who subsequently develop fungal rather than bacterial late-onset sepsis, with a typical 3-d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be carefully evaluated for systemic fungal infection whenever signs of carbohydrate intolerance occur.     

Prematurity and neonatal noxious events exert lasting effects on infant pain behaviour

BACKGROUND: There is concern that exposure of preterm infants to noxious insults over a prolonged period may have long term effects on their developing nervous system. AIMS: To investigate medium and long term effects of heel pricks in infants over the first year of life. STUDY DESIGN: Study 1-a longitudinal study, 2 days and 4 weeks after heel prick. Study 2-a cross sectional study over the first year of life. SUBJECTS: Study 1-13 healthy preterm (PT) infants. Study 2-63 full term (FT) and 62 PT infants, divided into 3 timed groups (0-20, 21-37 and 38-52 weeks postterm and corrected for prematurity). OUTCOME MEASURES: Threshold responses (flexion withdrawal (FWR) , gross body movements (GBM) and grimace (G)) to increasing mechanical force applied with Von Frey filaments. RESULTS: Study 1-Thresholds were all significantly lower (more sensitive) from the pricked heel compared to the contralateral side at 2 days and 4 weeks. Study 2-There were significant differences in threshold between PT and FT infants at all time points for both FWR (P=0.001, <0.001, <0.001) and GBM (P=<0.001, <0.001, 0.009 respectively), the preterm infants always being lower. The threshold for the FWR in FT infants steadily increased, but the threshold for the PT infants remained the same. GBM thresholds increased during the year in both FT and PT infants, but were always significantly lower in the ex-preterm group (P<0.012). CONCLUSIONS: Either PT birth or repetitive procedures associated with such birth alters the sensitivity threshold of PT infants compared with FT infants for at least the first year of life.     

Fetal versus maternal and gestational age effects of repetitive antenatal glucocorticoids

BACKGROUND: Although single courses of antenatal glucocorticoids decrease respiratory distress syndrome and mortality, repetitive courses of antenatal glucocorticoids are being given to women at risk of preterm delivery without evidence of benefit or appreciation of potential risks. OBJECTIVES: To evaluate the effects of single and repetitive antenatal glucocorticoid exposures on fetal growth and postnatal lung function in sheep. METHODS: Pregnant ewes were randomized to three protocols that included one or three doses (at 7-day intervals) of 0.5 mg/kg of betamethasone (beta) given to the ewe or fetus beginning at gestations ranging from 104 to 128 days' gestation with delivery at 125, 135, and 146 days' gestation. Postnatal assessments included measurements of gas exchange, compliance, ventilation efficiency, static lung volume, and lung tissue and alveolar wash saturated phosphatidylcholine. RESULTS: Single or repetitive maternal beta but not fetal beta caused fetal growth retardation at delivery at 125, 135, and 146 days' gestation. Single-dose fetal beta had no effect on postnatal lung function whereas single-dose maternal beta significantly increased compliance, lung volume, and tissue and alveolar surfactant after preterm delivery. Although three-dose fetal beta improved all indicators of postnatal lung function, three-dose maternal beta resulted in larger responses. The added benefits of repetitive beta relative to a single-dose beta on postnatal lung function after preterm delivery were not as great when therapy was begun later in gestation. Postnatal lung function after delivery at 146 days' gestation (term is 150 days) was improved after repetitive maternal beta at early gestational age. CONCLUSIONS: In sheep, single or repetitive maternal beta causes growth retardation from 104 to 121 days' gestation and the growth retardation persists to term. In contrast, single or repetitive fetal beta does not cause fetal growth retardation and is less potent at improving postnatal lung function and increasing surfactant pools. There are potential benefits as well as risks for the use of repetitive antenatal glucocorticoids. Randomized, controlled trials in humans are essential given the widespread use of repetitive courses of antenatal glucocorticoids in women at risk of preterm delivery. respiratory distress syndrome, maturation, prematurity, growth retardation, surfactant.     

Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants

OBJECTIVE: This case-control study of chronic lung disease (CLD) evaluated the hypothesis that chorioamnionitis promotes CLD and interacts with other risk factors for CLD, including mechanical ventilation and postnatal infection. STUDY DESIGN: We identified a population of 193 infants who met our case criteria for CLD whose birth weights were 7 days and culture-documented sepsis. In multivariable analyses, infants were at greatest risk for CLD when they had exposure to both chorioamnionitis and either mechanical ventilation >7 days (odds ratio, 3.2; 95% confidence interval, 0.9-11) or postnatal infection (odds ratio, 2.9; 95% confidence interval, 1.1-7.4). CONCLUSIONS: We conclude that prolonged mechanical ventilation or postnatal infection increases the risk of CLD among surviving preterm infants and that these 2 factors interact with antenatal infection to further increase the risk of CLD.