Maturity of the neonatal foal.

The immature foal frequently represents a significant management challenge to even the most experienced clinician. The clinical course typically involves complications to a range of body systems,including the musculoskeletal, respiratory, and gastrointestinal systems. Before the commencement of treatment, it is important to provide the owner with an estimation of short-term and long-term survival, expected costs, and possible complications. Formulation of an accurate prognosis can be a difficult task but is aided by knowledge not only of normal maturation but of the factors that affect this process.

Preterm birth makes the immature intestine sensitive to feeding-induced intestinal atrophy.

Preterm birth and formula feeding predispose to small intestinal dysfunction, which may lead to necrotizing enterocolitis (NEC). In piglets, we tested whether the physiological and environmental transitions occurring at birth affect the response of the immature intestine to enteral feeding. Pig fetuses (106 days gestation, term = 115 days) were prepared with esophageal feeding tubes and fed either sow's colostrum (n = 8) or infant formula (n = 7) in utero. After 24 h of oral feeding, the pig fetuses were delivered by cesarean section and their gastrointestinal morphology and function were compared with those of preterm newborn (NB) littermates that were not fed (n = 8) or fed colostrum (n = 7) or formula (n = 13) for 24 h after birth. Before birth, both colostrum and formula feeding resulted in marked increases in intestinal mass, brush-border enzyme activities, and plasma glucagon-like peptide 2 concentrations, to levels similar to those in NB colostrum-fed piglets. In contrast, NB formula-fed piglets showed reduced intestinal growth, decreased brush-border enzyme activities, and intestinal lesions, reflecting NEC. NB formula-fed pigs also showed impaired enterocyte endocytotic function and decreased antioxidative capacity, whereas brush-border enzyme mRNA levels were unaltered, relative to NB colostrum-fed pigs. Our results indicate that the feeding-induced growth and enzyme maturation of the immature intestine are not birth dependent. However, with a suboptimal diet (milk formula), factors related to preterm birth (e.g., microbial colonization and metabolic and endocrine changes) make the immature intestine sensitive to atrophy and development of NEC.

Neonatal antecedents for cerebral palsy in extremely preterm babies and interaction with maternal factors.

BACKGROUND: Preterm delivery is associated with an increased risk of cerebral palsy (CP). The greatest risk is for infants born <28 weeks' gestation. AIMS: To identify significant neonatal risk factors for CP and explore the interactions between antenatal and neonatal risk factors, among extremely preterm infants of 27 weeks' gestation or less. STUDY DESIGN: Nested case control design. METHODS: Infants born between 1989 and 1996, at 24-27 weeks' gestation, were evaluated: 30 with CP at 2 years corrected age and 120 control infants matched for gestation age. Neonatal variables were compared using matched analyses with the interaction between antenatal and neonatal factors being examined using logistic regression analyses. RESULTS: Risk factors for CP on matched analyses included patent ductus arteriosus requiring surgical ligation, peri-intraventricular haemorrhage, moderate to severe ventricular dilatation, periventricular leukomalacia (PVL) and need for home oxygen. Independent neonatal predictors were ventricular dilatation (OR 7.3; 95% CI 1.6, 32.3), PVL (OR 29.8; 95% CI 5.6, 159.1) and home oxygen use (OR 3.4; 95% CI 1.2, 9.4). No interaction terms in the logistic models were significant between the previously identified pregnancy risk factors of absence of antenatal steroids and intrauterine growth restriction and the neonatal risk factors. CONCLUSIONS: PVL is the most powerful independent predictor of CP in extremely preterm infants of 27 weeks' gestation or less and appears to be uninfluenced by antenatal factors.

Risk factors for cerebral palsy in preterm infants.

OBJECTIVE: To identify crucial factors that precipitate cerebral palsy by controlling confounding factors in logistic regression analyses. DESIGN AND PATIENTS: We retrospectively investigated a cohort of all 922 infants with gestational ages of less than 34 weeks (22-33 weeks), who were admitted to our neonatal intensive care unit between 1990 and 1998. Thirty (3.7%) were diagnosed to have cerebral palsy. We analyzed the prenatal and postnatal clinical variables of the cerebral palsy cases and compared them with 150 randomly selected controls. RESULTS: Risk factors for cerebral palsy identified in univariate analysis were: twin pregnancy, long-term ritodrine tocolysis, respiratory distress syndrome, air leak, surfactant administration, intermittent mandatory ventilation, high frequency oscillation, lowest PaCO2 levels, prolonged hypocarbia during the first 72 h of life, and postnatal steroid therapy. In a conditional multiple logistic model, long-term ritodrine tocolysis, prolonged hypocarbia and postnatal steroid therapy remained associated with an increased risk of cerebral palsy after adjustment for other antenatal and postnatal variables (OR [Odds Ratio] = 8.62, 95% CI [Confidence Interval], 2.18-33.97; OR = 7.81, 95% CI, 1.42-42.92; OR = 21.37, 95% CI, 2.01-227.29, respectively). CONCLUSIONS: Our results suggest that long-term ritodrine tocolysis underlines the development of cerebral palsy. Further assessments of the effect of ritodrine on fetal circulation and nervous system are required. Moreover, possible alternatives to systemic postnatal steroids are needed, and carbon dioxide levels should be more strictly controlled.

Is there an association between low birth weight and caries in the primary dentition?

OBJECTIVES: An association between low birth weight and caries in the primary dentition has been suggested but not demonstrated. This study analyzed this association using data from a probability sample of US children 2-6 years of age. METHODS: Data from the Third National Health and Nutrition Examination Survey (NHANES III) were used. Variables included decayed and filled primary surfaces (dfs), birth weight, gestational age, and Apgar score (a surrogate measure of fetal well-being); maternal age, education, income; number of previous births, marital status, the existence of pregnancy complications, and cigarette smoking during the pregnancy. Data were analyzed using SUDAAN 8.0.2. RESULTS: Bivariate Poisson regression showed that children of mothers who were unmarried (incidence density ratio, IDR = 3.28), with less education (IDR = 1.43), who were 17 years of age or younger at birth (IDR = 1.51), and had 2 or fewer prenatal visits (IDR = 1.65) had a significantly ( p <0.05) greater risk of caries than the reference groups. Children of mothers with pregnancy-related hypertension (IDR = 0.14) had less than 20% the risk of caries than the reference group. Blacks (IDR = 1.37) and Mexican-Americans (IDR = 2.38) had greater risk of caries than whites, and children of low (IDR = 2.57) and middle income (IDR = 2.00) level families had higher caries risks than those of upper income families. Multivariate Poisson regression found only race-ethnicity, age, and income level to be statistically significant. CONCLUSIONS: This study did not support the association between low birth weight and caries of the primary dentition.

Inhaled nitric oxide in the treatment of persistent pulmonary hypertension/ hypoxic respiratory failure in neonates: an update.

Persistent pulmonary hypertension (PPHN) and subsequent hypoxic respiratory failure is seen in association with numerous diseases and conditions in the neonate. This includes infections such as group B streptococcus, meconium aspiration syndrome, perinatal asphyxia, congenital diaphragmatic hernia, congenital heart disease, and as an idiopathic phenomenon. Conventional therapy of persistent pulmonary hypertension is discussed, as well as integrated with current treatment modalities such as surfactant replacement therapy and high frequency ventilation. The molecular action of nitric oxide including its relationship to neonatal cardiopulmonary transition at birth and the human neonatal clinical experience with term infants from 1992 to the present is explored. Also, the current use of inhaled nitric oxide in preterm infants is reviewed. Additionally, the follow-up of infants treated with inhaled nitric oxide is summarized, and novel therapies including inhaled prostacyclin and other pulmonary vasodilators such as sildenafil are introduced.

Infections of cefotaxime-resistant and cefmetazole-susceptible Escherichia coli and Klebsiella pneumoniae in children.

A search of the computerized database at the National Taiwan University Hospital was made for cefotaxime-resistant and cefmetazole-susceptible isolates of Escherichia coli and Klebsiella pneumoniae (which may be extended-spectrum beta-lactamase-producing strains) in pediatric wards and intensive care units between 1999 and 2001. Fourteen infectious episodes attributed only to study bacteria were identified, including 7 episodes of bacteremia. Nine patients (64.3%) had underlying medical conditions: 3 were premature babies, 3 were immunodeficient, 2 had malignancy, and 2 had a congenital heart disease with active heart failure even after surgery. Among the 7 patients with bacteremias, 5 may be catheter-related; 6 were treated with carbapenems and 1 was treated with cefmetazole successfully, with or without the removal of the catheter. Before the acquisition of the infection, a history of stay in an intensive care unit within 4 weeks was noted in 10 cases (71.4%); a history of use of extended-spectrum cephalosporins within 4 weeks was also noted in 6 cases (42.9%). Cefmetazole, with or without an aminoglycoside, was clinically effective in 6 cases (42.8%). Except for 1 episode of pneumonia that ended in mortality, all of the infectious episodes were successfully treated. The mortality rate was 7.1%.

Preterm birth, low birth weight, and risk for esophageal adenocarcinoma.

BACKGROUND & AIMS: Gastroesophageal reflux is common among preterm infants and those who are small for gestational age, and it is a strong risk factor for adenocarcinoma of the esophagus. METHODS: In a cohort of 3364 individuals born preterm and/or small for gestational age between 1925 and 1949, we assessed the long-term risk for esophageal cancer. RESULTS: The standardized incidence rate ratio for esophageal adenocarcinoma was increased more than 7-fold in the cohort (standardized incidence rate ratio, 7.27; 95% confidence interval, 1.98-18.62), and a birth weight <2000 g was associated with a more than 11-fold increase in risk (standardized incidence rate ratio, 11.5; 95% confidence interval, 1.39-41.5). CONCLUSIONS: The associations may be spurious, but if not, they may be explained by increased gastroesophageal reflux during infancy among infants born preterm and/or small for gestational age.

Childhood asthma hospitalization risk after cesarean delivery in former term and premature infants.

BACKGROUND: Cesarean delivery modifies infant gut bacterial flora composition, which may result in hindered tolerance to allergenic substances, thereby increasing the risk of asthma in accordance with the hygiene hypothesis. Results of previous studies regarding an association between birth route and asthma are conflicting, and these studies have not evaluated some potential confounding effects, including prematurity and maternal asthma. OBJECTIVE: To determine whether cesarean delivery in full-term and premature infants increases the risk of subsequent childhood asthma hospitalization. METHODS: We conducted a case-control study using the Washington State Birth Events Record Database linked to statewide hospitalization data. The study included 2,028 children hospitalized for asthma (cases) and 8,292 age-matched controls. RESULTS: Cesarean delivery was modestly associated with an increased risk of asthma hospitalization (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.04-1.39). However, when analyzed separately, there was an association between cesarean delivery and asthma hospitalization in premature infants (OR, 1.90; 95% CI, 1.09-3.02) but not in full-term infants (OR, 1.15; 95% CI, 0.97-1.34). CONCLUSIONS: Cesarean delivery was associated with subsequent asthma hospitalization only in premature infants. Because mothers with asthma are reported to have increased rates of cesarean delivery and premature delivery, other factors in addition to the hygiene hypothesis, including genetic and in utero influences associated with maternal asthma, may contribute to the increased risk of asthma in premature infants.

Prevalence of cranial scan abnormalities in preterm twins in relation to chorionicity and discordant birth weight.

OBJECTIVE: The purpose of this study was to determine the incidence of ultrasonographically detected cerebral white matter lesions (WMLs) in preterm twins at birth in relation to chorionicity, discordant weight and twin-twin transfusion syndrome (TTTS). METHODS: In this retrospective study, perinatal, neonatal, and cranial scan data of 85 monochorionic (MC) and 94 dichorionic (DC) twin pregnancies (341 infants) delivered between 24 and 34 weeks of gestation were collected. Data were analysed according to chorionicity, discordant birth weight (>20%), single intrauterine death and TTTS. RESULTS: The cerebral WML was seen in 14% of preterm twins. Monochorionic infants had higher risks of WML than DC twin (odds ratio 7.1; 95% CI 3.28-15.8). In MC group, discordant weight (37%), TTTS (38%), single intrauterine death (67%) had higher incidence of cerebral WML than concordant weight infants (7%). Similarly, incidence of WML was higher in DC discordant compared with concordant weight infants (13% versus 2%; P < 0.05). CONCLUSION: Monochorionic infants had a seven-fold higher incidence of cerebral WML than DC infants. Discordant birth weight, TTTS and survivor of co-twin demise are an independent risk of cerebral white matter lesion.

Prognostic value of umbilical artery Doppler studies in unselected preterm deliveries.

OBJECTIVE: To evaluate the prognostic value of umbilical artery Doppler studies in premature deliveries. METHODS: In this cohort study of 582 singleton pregnancies delivered between 24 and 35 weeks of gestation, we evaluated the ratio of peak-systolic to end-diastolic (S/D) blood flow velocities in the umbilical artery of all the patients. The correlations among the results of the Doppler studies, short-term neonatal complications, and the infants' neurodevelopmental outcome at 2 years were studied by univariable and multivariable methods. RESULTS: The prevalences of either neonatal death or cerebral palsy among the 266 (45.7%) growth restricted fetuses were 3.4% (3/88) in pregnancies with a S/D ratio below the 95th percentile, 4.9% (5/103) in pregnancies with a S/D at or above the 95th percentile, and 17.3% (13/75) in those with absent or reversed end-diastolic blood flow in the umbilical artery (P for trend = .001). The corresponding figures in the 316 pregnancies with adequate fetal growth were 6.4% (15/234) and 4.3% (3/69) among pregnancies with a S/D ratio below and at or above 95th percentile, respectively, whereas no cases of either neonatal death or cerebral palsy were recorded in the 13 pregnancies with adequate fetal growth and absent or reversed end-diastolic blood flow velocity (P for trend = .28; chi(2) for heterogeneity of linear trends compared with growth-restricted infants = 7.02, P = .008). In logistic regression, in pregnancies complicated by fetal growth restriction, absent or reversed end-diastolic blood flow in the umbilical artery was still associated with an increased risk of either neonatal death or cerebral palsy even after adjustment for gestational age and proportion of expected birth weight, (odds ratio 3.2, 95% confidence interval 1.18-8.66, P = .02). CONCLUSION: Absent or reversed end-diastolic flow in the umbilical artery is an independent predictor of either neonatal death or cerebral palsy in preterm growth-restricted fetuses. In the absence of fetal growth restriction, umbilical artery Doppler study was associated with none of the infant outcome parameters studied.

Assessment of lung volumes in children and adolescents: comparison of two plethysmographic techniques.

Thoracic gas volume (Vtg) can be measured with body plethysmography by either repetitive panting or one single inspiratory effort against a shutter occluding the airways. The panting technique is preferred, but may be demanding. We aimed to assess the precision of these two methods and the degree of agreement between them. Vtg and functional residual capacity (FRC) were measured in 155 subjects with a standard, commercially available plethysmograph, acting as a variable-pressure, constant-volume device when Vtg is determined. Total lung capacity (TLC) and residual lung volume (RV) were calculated subsequent to a full vital capacity manoeuvre. For non-asthmatic healthy subjects, the standard deviations (SD) of the differences between two replicate measurements of FRC, TLC and RV were respectively 0.16, 0.13 and 0.14 litres with the panting technique, and 0.18, 0.18 and 0.23 litres with the single inspiratory effort technique. In percentage of the respective lung volumes, the corresponding 1.96 SDs were 20%, 8% and 40% with the panting technique and 23%, 12% and 67% with the single inspiratory effort technique. Between the two techniques, 95% limits of agreement were 21% for FRC, 11% for TLC and 58% for RV. The variability of Vtg and FRC accounted for most of the variability of TLC and RV. In conclusion, the panting and the single inspiratory effort technique produced results that were comparable in magnitude, however with a better precision with the panting technique. The single inspiratory effort technique can be used as an alternative if the panting technique fails.

Physical growth and neurodevelopmental outcome of nonhandicapped low-risk children born preterm.

BACKGROUND: Outcome studies on the effects of prematurity are increasingly restricted to extremely immature infants with birth weight below 1000 g or gestational age below 26 weeks. In contrast, studies comprising low-risk preterm infants are rare. AIM: To examine growth and neurodevelopmental outcome, 70 low-risk low birth weight (LBW) children without neurological impairment were followed from birth to 7 years of age. At 7 years of age, LBW children were compared to a matched control group born at term. METHODS: Postnatal growth was measured at 20 months in the LBW group and at 7 years in LBW and control children. At 20 months, the LBW group was assessed with the Griffiths Scales. At 7 years, LBW and control children were assessed with a neuropsychological test battery comprising tests for language, visual-perceptual, visual-motor, fine and gross motor abilities. RESULTS: At 7 years of age, the frequency of children with low (3rd-9th percentile) or subnormal (<3rd percentile) growth parameters was increased in the LBW group. The Mean Griffiths Developmental Quotient (DQ) of the preterm group was normal (102.3+/-8.4), and there were only two results below DQ 85. There was no difference between 49 children appropriate for gestational age and 21 small for gestational age (SGA) children. At 7 years of age, reduced mean test results in the range of -0.5 SDS were observed for language and visual-motor abilities in the preterm group. This was due to an increased frequency of LBW children with moderately (SDS -1.0 to -2.0 SDS) subnormal test results. Even for the slightly LBW group (2000 to 2499 g), poorer language abilities were confirmed. CONCLUSION: All LBW infants, including low-risk populations, should be included in a follow-up program in order to detect deficits early in life and begin treatment before school entry.

Neonatal outcome in discordant eutrophic twins: twin growth.

OBJECTIVE: To compare maternal characteristics and neonatal outcome in discordant twin gestations (DT) and concordant twin gestation (CT). METHOD: Maternal and neonatal data base of live twins >25 weeks' gestation (N=351 pairs) were reviewed for antepartum complications, labor beginning, mode of delivery, neonatal complications, malformations and perinatal mortality. The chi-squared analysis and Student t-tests were used to analyze the differences between discordant and concordant premature and term twin pairs, and appropriate for gestational age (AGA) twins, separately. RESULTS: DT occurred in 15.1% of all twin pregnancies. In preterm and term DT there were significantly more elective cesareans. Growth discordance among preterm and term eutrophic twins was not connected with increased neonatal death or other complications, except higher incidence of early neurological signs in term DT. CONCLUSION: We strongly believed that prematurity and not discordant growth of eutrophic twins has important influence on neonatal outcome.

Preterm birth: a cost benefit analysis.

Advances in prenatal and perinatal treatment of preterm and VLBW infants have dramatically increased the survival rate of these infants. Some interventions decrease long term sequelae associated with preterm birth, making them more cost-effective than other treatments. This paper reviews the cost-effectiveness of therapies targeted to protect the preterm brain. Birth in a center with a NICU improves survival and decreases the rate of severe neurologic disability. Administration of antenatal steroids increases survival and decreases rates of periventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, respiratory distress syndrome, and severe disability. Administration of antenatal steroids decreases costs per additional survivor. Addition of surfactant to the treatment of PT infants has also decreased treatment costs. Administration of surfactant is beneficial for symptomatic RDS but recognizes a greater benefit when given to infants younger than 30 weeks gestation prophylactically. Treatment with prophylactic indomethacin decreases the rate of intraventricular hemorrhage and results in cost savings in survivors. Postnatal administration of dexamethasone can lead to severe disability when administered before 7 to 10 days of life. Postnatal dexamethasone does not increase survival or decrease rates of chronic lung disease.