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Less postnatal steroids, more bronchopulmonary dysplasia: a population-based study in very low birthweight infants.

OBJECTIVE: To study the association between reduced use of postnatal steroids for bronchopulmonary dysplasia (BPD) in very low birthweight (VLBW) infants and oxygen (O(2))-dependency at 28 days of age and at 36 weeks postmenstrual age. DESIGN: Large national database study. SETTING: The Israel National VLBW Neonatal Database. PATIENTS: The sample included infants born between 1997 and 2004, of gestational age 24-32 weeks, who required mechanical ventilation or O(2) therapy. Four time periods were compared: 1997-8 (era 1, peak use), 1999-2000 (era 2, intermediate), 2001-2 (era 3, expected reduction) and 2003-4 (era 4, lowest). The outcome variable "oxygen dependency" was based on clinical criteria. Multivariate regression models were used to account for confounding variables. RESULTS: Steroid use fell significantly from 23.5% in 1997-8 to 11% in 2003-4 (p<0.005). After adjustment for relevant confounding variables, the odds ratio for O(2) therapy at 28 days in era 4 versus era 1 was 1.75, 95% confidence interval (CI) 1.47 to 2.09 and 1.41, 95% CI 1.15 to 1.73 at 36 weeks postmenstrual age. The mean duration of O(2) therapy increased from 25.3 days (95% CI 23.3 to 26.3) in era 1, to 28.0 days (95% CI 26.6 to 29.4) in era 4. Survival increased from 78.5% in era 1 to 81.6% in era 4 (p<0.005). CONCLUSIONS: The use of steroids has fallen considerably since the awareness of the adverse effects of this treatment. This change has been temporally associated with increased O(2) dependency at 28 days of age and at 36 weeks postmenstrual age. The prolongation of O(2) therapy was modest in degree.

Bronchopulmonary Dysplasia↗

Serotonin levels and platelet uptake during premenstrual tension.

Premenstrual tension was studied in 16 females, using both biochemical and psychological parameters during the pre- and postmenstrual phases. Uptake of serotonin (5-HT) and the levels of 5-HT in platelet-rich plasma and platelet-poor plasmas were determined. Degrees of distress experienced pre- and postmenstrually were quantified via the Moos menstrual distress questionnaire. The mean Vmax was significantly lower during the premenstrual (tension) phase (8.2 +/- 0.9 pmol/min) as compared to the postmenstrual (normal) phase (14.4 +/- 3.2 pmol/min). There was no significant difference in the Km values. A highly significant (p less than 0.001) reduction in the levels of 5-HT in platelet-rich plasma (-23.2%) and platelet-poor plasma (-19.1%) was found during the premenstrual phase. There were correlations between the kinetic parameters of 5-HT uptake and some of the Moos symptoms.

Adolescent↗

Effect of plasma from premenstrual syndrome and control patients on human platelet and rat brain synaptosome monoamine oxidase B activity.

The present study determined the kinetic properties of platelet monoamine oxidase (MAO) in patients with premenstrual syndrome (PMS) and control subjects during the pre- and postmenstrual intervals. In addition, we investigated the effects of plasma obtained during the pre- and postmenstrual intervals from both subject groups on MAO activity in washed human platelets and rat brain synaptosomes. The Vmax of platelet MAO in postmenstrual PMS patients was significantly less than that during the premenstrual phase. Plasma from both subject groups (10-100 microliters) inhibited platelet and synaptosomal MAO in a dose-dependent manner to approximately the same degree at each time interval. The results indicate that although human plasma contains endogenous substances which inhibit MAO activity, alterations in their concentration are probably not responsible for the previously reported transient changes in platelet MAO activity in PMS.

Animals↗

The role of maternal factors, postnatal nutrition, weight gain, and gender in regulation of serum IGF-I among preterm infants.

IGF-I is important for somatic growth and development of the human fetus and neonate. IGF-I also plays an important role in normal vascularization of human retina, as it has been suggested that insufficient IGF-I may be a factor in the development of retinopathy of prematurity. The principal regulator of the bioavailability of IGF-I in the circulation is IGF binding protein 3 (IGFBP-3). The aim of this study was to study factors associated with postnatal serum concentrations of IGF-I and of IGFBP-3 in preterm infants from birth to an age corresponding to 40 wk postmenstruation. We conducted a prospective, longitudinal study in which we measured serum IGF-I and IGFBP-3 concentrations in 76 preterm infants from birth (postmenstrual ages 23-32 wk) until discharge from hospital around 40 wk. Information regarding nutrition, weight gain, maternal factors, and treatment with corticosteroids were collected weekly. Variables found to be associated with postnatal change over time of serum IGF-I and IGFBP-3 were postmenstrual age (p<0.001), weight gain (standard deviation score) (p<0.001), and enteral intake of protein (p<0.001). Male gender was associated with lower IGF-I levels (p<0.001). The relationship between protein intake and IGF-I (and also between protein intake and IGFBP-3) was positive, as was the relationship between weight gain and IGF-I (and between weight gain and IGFBP-3). These results indicate that the degree of prematurity, low enteral protein intake, male gender, and slow weight gain are associated with a slower postnatal increase of IGF-I in preterm infants.

Birth Weight↗

Early postnatal dexamethasone therapy for the prevention of chronic lung disease.

OBJECTIVE: To test the hypothesis that early postnatal dexamethasone will reduce the incidence of death or chronic lung disease (CLD) in ventilated extremely low birth weight premature infants. DESIGN: Multicenter randomized double-blinded controlled clinical trial. SETTING: A total of 42 neonatal intensive care units in the Vermont Oxford Network. PARTICIPANTS: Infants weighing 501 to 1000 g were eligible for enrollment at 12 hours of age if they needed assisted ventilation, had received surfactant replacement therapy, were physiologically stable, had no obvious life-threatening congenital anomaly, and had blood cultures obtained and antibiotic therapy initiated. INTERVENTION: Infants were randomly assigned to dexamethasone or saline placebo. Intravenous dexamethasone was administered for 12 days according to the following dosing schedule: 0.5 mg/kg/d for 3 days, 0.25 mg/kg/d for 3 days, 0.10 mg/kg/d for 3 days, 0.05 mg/kg/d for 3 days. Infants in either group could receive treatment with selective late postnatal steroids beginning on day 14 of life if they were on assisted ventilation with supplemental oxygen greater than 30%. OUTCOME MEASUREMENTS: The primary outcome measure was CLD or death at 36 weeks postmenstrual age. RESULTS: The study was stopped before completion of sample size goals because of concern about serious side effects in the early steroid treatment group. A total of 542 infants were enrolled (early treatment N = 273, control N = 269). The 2 groups had similar demographic characteristics. No differences were noted in the primary outcome of CLD or death at 36 weeks postmenstrual age (early treatment 50% vs control: 53%, relative risk: 0.93; 95% confidence interval [CI]: 0.79-1.09). Fewer infants who received early steroid treatment had a patent ductus arteriosus (relative risk: 0.78; 95% CI: 0.63-0.96), and fewer infants in the early steroid group received indomethacin therapy (relative risk: 0.74; 95% CI: 0.64-0.86) or late steroid treatment (relative risk: 0.69; 95% CI: 0.58-0.81). However, more infants who received early steroid treatment had complications associated with therapy including an increase in hyperglycemia (relative risk: 1.29; 95% CI: 1.13-1.46) and an increase in the use of insulin therapy (relative risk: 1.62; 95% CI: 1.36-1.94). A trend toward increased gastrointestinal hemorrhage (relative risk: 1.55; 95% CI: 0.92-2.61), gastrointestinal perforation (relative risk: 1.53; 95% CI: 0.89-2.61), and an increased systolic blood pressure (relative risk: 1.34; 95% CI: 0.97-1.85) was noted. In infants receiving cranial ultrasound examinations, a marginal increase in periventricular leukomalacia was noted in the early steroid treatment group (relative risk: 2.23; 95% CI: 0.99-5.04). Infants who received early steroid therapy had fewer days in supplemental oxygen but experienced poor weight gain. CONCLUSIONS: A 12-day course of early postnatal steroid therapy given to extremely low birth weight infants did not decrease the risk of CLD or death at 36 weeks postmenstrual age and was associated with an increased risk of complications and poor weight gain.

Anti-Inflammatory Agents↗

Regional brain development in serial magnetic resonance imaging of low-risk preterm infants.

OBJECTIVE: MRI studies have shown that preterm infants with brain injury have altered brain tissue volumes. Investigation of preterm infants without brain injury offers the opportunity to define the influence of early birth on brain development and provide normative data to assess effects of adverse conditions on the preterm brain. In this study, we investigated serial MRI of low-risk preterm infants with the aim to identify regions of altered brain development. METHODS: Twenty-three preterm infants appropriate for gestational age without magnetic resonance-visible brain injury underwent MRI twice at 32 and at 42 weeks' postmenstrual age. Fifteen term infants were scanned 2 weeks after birth. Brain tissue classification and parcellation were conducted to allow comparison of regional brain tissue volumes. Longitudinal brain growth was assessed from preterm infants' serial scans. RESULTS: At 42 weeks' postmenstrual age, gray matter volumes were not different between preterm and term infants. Myelinated white matter was decreased, as were unmyelinated white matter volumes in the region including the central gyri. The gray matter proportion of the brain parenchyma constituted 30% and 37% at 32 and 42 weeks' postmenstrual age, respectively. CONCLUSIONS: This MRI study of preterm infants appropriate for gestational age and without brain injury establishes the influence of early birth on brain development. No decreased cortical gray matter volumes were found, which is in contrast to findings in preterm infants with brain injury. Moderately decreased white matter volumes suggest an adverse influence of early birth on white matter development. We identified a sharp increase in cortical gray matter volume in preterm infants' serial data, which may correspond to a critical period for cortical development.

Brain↗

Formation and enlargement of the paranasal sinuses in normal and cleft lip and palate human fetuses.

OBJECTIVE: Comparisons of paranasal sinus morphology between humans with and without cleft lip and palate (CLP) have yielded conflicting opinions regarding size differences. Although postnatal samples have been investigated, no studies have compared paranasal sinus volumes between cleft and noncleft human fetuses. METHOD: The nasal cavities of 20 'normal' and 9 CLP human fetuses (8-21 weeks' postmenstrual age) were examined to assess prenatal volumetric changes of the maxillary sinuses, anterior and posterior ethmoidal air cells, and sphenoidal sinuses. Lengths and volumes of right and left maxillary and sphenoidal sinuses were calculated from histologically prepared sections using a computer reconstruction technique, and regression equations were generated to assess the enlargement rates. RESULTS: All paranasal sinuses were found among both normal and CLP specimens in the same locations and in similar age ranges. However, greater shape asymmetry was noted for all sinuses in CLP compared to normal specimens. In the normal sample, results indicated significant (p < .05) correlations between right or left maxillary sinus length (R2 = 0.49, 0.54) and volume (R2 = 0.67, 0.68), and increasing postmenstrual age, but no significant (p > .05) correlations were observed for right or left sphenoidal sinus length or volumes and postmenstrual age. Maxillary sinus length changes were best described by second-order polynomial regression equations, and volume changes were best described by logarithmic equations. When individual right or left sinuses of CLP specimens were compared to the mean of the normal sample, one maxillary sinus was significantly (p < .05) larger, and 9 maxillary sinuses were not significantly (p > .05) different. Sphenoidal sinus lengths and volumes of CLP specimens were within the same range compared to these dimensions for the normal sample. CONCLUSION: Results on normal specimens indicate that maxillary sinuses exhibit second-trimester length and volume increases, whereas sphenoidal sinuses are more variable. This study suggests a similar timing of sinus formation in normal and CLP fetuses, but shape asymmetries are frequently detected among CLP specimens. In particular, the sphenoidal sinuses may be altered in shape and size by adjacent, hypertrophic cartilaginous structures in CLP fetuses. These results indicate that the maxillary sinuses of CLP fetuses are not deficient in size compared to noncleft fetuses.

Cartilage↗

The characteristics of 100 women presenting to a gynecological clinic with premenstrual complaints.

100 women consecutively referred to a gynaecological clinic with premenstrual problems were prospectively assessed by daily completion of a set of visual analogue scales (VAS). The relationship of their symptoms to menstrual cycle phase was quantified by calculating the percentage change in symptom intensity between the premenstrual week and the postmenstrual week and also during menstruation itself. The results indicated that the physical symptoms of breast discomfort and swelling were more closely related to menstrual cycle phase than were the psychological symptoms of tension, irritability or lethargy and depression. Only 32 of the women showed reduction of the premenstrual psychological symptoms by 75% or more during the postmenstrual week, while the corresponding degree of physical symptom relief was recorded by 62 women. For almost half the women, adverse mental symptoms reached their peak after the onset of menstrual bleeding. Significantly fewer of the women with almost total (75% or more) relief of their psychological symptoms postmenstrually had a history of psychiatric treatment, marital breakdown, or more than three children, compared with those whose symptoms were less completely relieved. The results suggest that a large proportion of women who experience premenstrual symptoms suffer a premenstrual and/or menstrual exacerbation of problems which are present throughout the cycle and are therefore unlikely to respond to hormonal manipulation.

Adult↗

Early detection of delayed myelination in preterm infants.

Myelination of the central nervous system can be demonstrated with magnetic resonance imaging. The influence of periventricular-intraventricular hemorrhage and periventricular leukomalacia on cerebral myelination was studied using magnetic resonance imaging. The subjects were 33 preterm infants of less than 30 weeks' gestation studied at 44 weeks' postmenstrual age: 11 infants with periventricular-intraventricular hemorrhage, 7 with periventricular leukomalacia, and 15 without periventricular-intraventricular hemorrhage or periventricular leukomalacia. There were no differences in mean gestational age and birth weight between the three groups. However, infants without periventricular-intraventricular hemorrhage or periventricular leukomalacia had significantly less respiratory distress syndrome. At 44 weeks postmenstrual age, infants with periventricular leukomalacia had a significantly delayed myelination pattern (stage M2) in comparison with infants without periventricular-intraventricular hemorrhage or periventricular leukomalacia and infants with periventricular-intraventricular hemorrhage (stages M3 and M4). The latter two groups had myelination stages that were similar to those of healthy term infants at 44 weeks' postmenstrual age. The results demonstrate that periventricular leukomalacia causes delayed myelination of the cerebrum, whereas periventricular-intraventricular hemorrhage does not.

Brain↗

[Supplementation of maternal milk with calcium and phosphorus for the feeding of premature neonates weighing 1500 g or less. How long should it be continued?].

Feeding four preterm infants weighing less than or equal to 1,500 g with human milk supplemented with calcium (160-200 mg/kg/day) and phosphorus (80-200 mg/kg/day) until term postmenstrual age was reached, and suitable levels of plasma calcium, phosphorus and alkaline phosphatase and urinary excretion index of calcium and phosphorus were attained. When such a supplementation was suppressed at 38-40 weeks of postmenstrual age a rapid onset of biochemical disturbances was observed: a rise of plasma calcium (p less than 0.025) and alkaline phosphatase (p less than 0.0025) with a decrease of plasma phosphorus (p less than 0.005) and of urinary phosphate excretion (p less than 0.002). Reincorporation to former supplemented regime results in quick recovery of these parameters. Authors can assert that the necessity of calcium and phosphorus supplementation of human milk for less than or equal to 1.500 g preterm infant feeding exceeds the term postmenstrual age if suitable calcium and phosphorus levels are to be obtained.

Alkaline Phosphatase↗

Association between alcoholic and caffeinated beverages and premenstrual syndrome.

We examined the association between alcohol and caffeine consumption and premenstrual syndrome (PMS). One hundred two women with PMS matched by age and race to an equal number of women without PMS were compared for differences in intake of alcoholic and caffeinated beverages, with differences determined using Student's t-tests and conditional logistic regression for matched pairs. Information on alcohol and caffeinated beverage consumption was obtained from three 24-hour dietary recall interviews conducted during the postmenstrual period and from three conducted during the premenstrual period. Results showed that no significant difference was observed in total caffeine intake or in the individual caffeinated beverages consumed during either the post-menstrual or the premenstrual period. For alcohol consumption, however, women with PMS drank 1.41 (95% confidence interval; range, 0.34-2.47) more servings per week during the postmenstrual period. Based on post-menstrual consumption, women in the heaviest drinking category (> or = 10 drinks per week) were significantly more likely to have moderate to severe PMS (P < .005) than nondrinkers. This same significant relation, but to a lesser degree, was observed based on premenstrual consumption. We conclude that because PMS is more strongly associated with alcohol consumed in the symptom-free, postmenstrual period, drinking is unlikely to be simply a response to PMS symptoms as others have previously suggested.

Alcohol Drinking↗

Association between the severity of chronic lung disease and first-year outcomes of very low birth weight infants.

OBJECTIVE: The objective of this study was to determine if there is an association between the severity of chronic lung disease in very low birth weight infants (as assessed by the duration of supplemental oxygen requirements in the neonatal period) and first-year neurodevelopmental, sensory, and growth outcomes as well as duration of neonatal hospitalization and first-year hospital readmissions. STUDY DESIGN: Retrospective chart review with matched subject groups. METHODS: The subjects of this study were very low birth weight infants born between 1987 and 1991 in a 17-county perinatal region of North Carolina. Infants were categorized into one of three groups on the basis of duration of supplemental oxygen requirements. Infants who were breathing room air by 28 days were classified as having no chronic lung disease; infants who required supplemental oxygen at 28 days but not at 36 weeks postmenstrual age were classified as having mild chronic lung disease; and infants who required supplemental oxygen at 36 weeks postmenstrual age were classified as having severe chronic lung disease. Infants were matched for birth weight, sex, and race. The matched groups (n = 174) were compared with respect to the incidence of first year adverse neurodevelopmental and sensory outcomes, growth patterns, and hospital readmissions during the first year. Results were analyzed with general linear models and logistic regression analyses. RESULTS: The incidence of any adverse neurodevelopmental or sensory outcome increased as severity of chronic lung disease increased from none (3.6%) to mild (21.4%) to severe (31.6%, p < 0.001). Growth patterns were similar in infants with no and mild chronic lung disease, but infants with severe chronic lung disease were significantly lighter (p < 0.01) and shorter (p < 0.005) at 40 weeks postmenstrual age and significantly lighter at 1 year adjusted age (p < 0.05). The duration of the initial hospitalization increased with chronic lung disease severity (p < 0.001). Infants with severe chronic lung disease were readmitted to the hospital significantly more often (p < 0.005) than infants with no chronic lung disease or mild chronic lung disease. CONCLUSIONS: Very low birth weight infants who required supplemental oxygen at or beyond 28 days were at increased risk for adverse neurodevelopmental and sensory outcomes, but only those infants who continued to require supplemental oxygen at 36 weeks were at increased risk for poor growth and readmission to the hospital.

Case-Control Studies↗

Visual development in preterm and full-term infants: a prospective masked study.

PURPOSE: To compare development of visual acuity and binocular vision in preterm and full-term infants in a prospective study that used testers masked to subject's gestational age. METHODS: Seventy-nine healthy full-term infants, mean gestational age 40 weeks, and 18 low-risk preterm infants, mean gestational age 33 weeks, were examined biweekly between the 44th and 54th weeks of postmenstrual age. Ocular alignment, convergence, fusion, grating acuity, and onset of optokinetic nystagmus (OKN) were assessed at each examination. RESULTS: The mean postnatal ages of onset of ocular alignment, convergence, fusion, grating acuity to 1.6 cycles per degree, and OKN from temporal to nasal and nasal to temporal were, respectively, 5, 7, 7, 11, 6, and 9 weeks for the full-term and 12, 13, 14, 18, 13, and 16 weeks for the preterm infants. The mean postmenstrual ages of onset for the corresponding parameters were 46, 48, 48, 51, 46, and 50 weeks for full-term and 46, 47, 48, 52, 47, and 49 weeks for preterm infants. The onset of all parameters was earlier in full-term infants than in preterm infants of the same postnatal age (P < or = 0.0001). However, no differences were found when the parameters were compared at postmenstrual ages. CONCLUSIONS: Additional visual experience of preterm infants does not influence development of visual acuity or binocular vision during the first months of life as measured from the time of conception.

Aging↗

Levonorgestrel plasma concentrations and hormone profiles after insertion and after one year of treatment with a levonorgestrel-IUD.

Plasma concentrations of levonorgestrel, progesterone, estradiol, FSH and LH were measured in seven volunteers who had a levonorgestrel-releasing IUD inserted postmenstrually. Blood samples were collected twice weekly during a mean of 93 days immediately postmenstrually and during a mean of 41 days over the twelfth to fifteenth month of treatment. Patterns of bleeding were studied during the first year of treatment. The IUDs used were designed to release 25 micrograms/day of levonorgestrel. The mean +/- SD plasma concentration of levonorgestrel for all subjects during the first three months was 260 +/- 68 pg/ml, and 129 +/- 28 pg/ml after one year of treatment. During the initial period of blood sampling only two of the subjects ovulated, while only two did not ovulate after one year of treatment. Intermenstrual spotting occurred during the first sixty days of treatment. Three subjects developed amenorrhea at the end of the first year. All the subjects continued the use of the IUD and no pregnancies occurred.

Adult↗

Kangaroo care is effective in diminishing pain response in preterm neonates.

OBJECTIVE: To test the efficacy of maternal skin-to-skin contact, or kangaroo care (KC), on diminishing the pain response of preterm neonates to heel lancing. DESIGN: A crossover design was used, in which the neonates served as their own controls. Subjects Preterm neonates (n = 74), between 32 and 36 weeks' postmenstrual age and within 10 days of birth, who were breathing without assistance and who were not receiving sedatives or analgesics in 3 level II to III neonatal intensive care units in Canada. INTERVENTIONS: In the experimental condition, the neonate was held in KC for 30 minutes before the heel-lancing procedure and remained in KC for the duration of the procedure. In the control condition, the neonate was in the prone position in the isolette. The ordering of conditions was random. MAIN OUTCOME MEASURES: The primary outcome was the Premature Infant Pain Profile, which is composed of 3 facial actions, maximum heart rate, and minimum oxygen saturation changes from baseline in 30-second blocks. Videotapes, taken with the camera positioned on the neonate's face so that an observer could not tell whether the neonate was being held or was in the isolette, were coded by research assistants who were naïve to the purpose of the study. Heart rate and oxygen levels were continuously monitored into a computer for later analysis. A repeated-measures analysis of covariance was used, with order of condition and site as factors and severity of illness as a covariate. RESULTS: Premature Infant Pain Profile scores across the first 90 seconds from the heel-lancing procedure were significantly (.002<P<.04) lower by 2 points in the KC condition. CONCLUSIONS: For preterm neonates who are 32 weeks' postmenstrual age or older, KC seems to effectively decrease pain from heel lancing. Further study is needed to determine if younger neonates or those requiring assistance in breathing, or older infants or toddlers, would benefit from KC, or if it would remain effective over several procedures. Given its effectiveness, and that parents of neonates in critical care units want to participate more in comforting their children, KC is a potentially beneficial strategy for promoting family health.

Blood Specimen Collection↗

Posthospitalization growth and bone mineral status of normal preterm infants. Feeding with mother's milk or standard formula.

The growth and bone mineralization were studied in ten preterm infants fed human milk and 14 preterm infants fed cow's milk-based formula. After discharge from the hospital, at 42, 48, and 56 weeks' postmenstrual age, anthropometric measures of weight, length, occipital frontal circumference, mid-upper arm circumference, triceps, and subscapular skin folds were obtained. Blood was drawn for determinations of serum calcium, phosphorus, 25-hydroxyvitamin D, alkaline phosphatase, and albumin levels. Bone mineral analyses were performed by photon absorptiometry. Mean (+/- SD) gestational ages in nursing and formula-fed infants were similar (32.0 +/- 2.5 vs 31.5 +/- 1.5 weeks), as were their mean (+/- SD) birth weights (1.76 +/- 0.42 vs 1.52 +/- 0.30 kg). After hospitalization, both groups had similar rates of growth in weight, length, head circumference, mid-upper arm circumference, triceps, and subscapular skinfold thickness. The formula-fed group had higher serum phosphorus levels at 42 weeks, higher serum calcium levels at 48 weeks, and higher serum albumin concentrations at 56 weeks than the breast-fed group. By 56 weeks' postmenstrual age, the bone mineral content was higher in the formula-fed group. Our data suggest that after hospitalization, preterm infants fed their own mother's milk have similar growth patterns but a different bone mineralization rate compared with preterm infants fed a standard cow's milk-based formula.

Alkaline Phosphatase↗

Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms.

CONTEXT: Despite more than 2 decades of outcomes research after very preterm birth, clinicians remain uncertain about the extent to which neonatal morbidities predict poor long-term outcomes of extremely low-birth-weight (ELBW) infants. OBJECTIVE: To determine the individual and combined prognostic effects of bronchopulmonary dysplasia (BPD), ultrasonographic signs of brain injury, and severe retinopathy of prematurity (ROP) on 18-month outcomes of ELBW infants. DESIGN: Inception cohort assembled for the Trial of Indomethacin Prophylaxis in Preterms (TIPP). SETTING AND PARTICIPANTS: A total of 910 infants with birth weights of 500 to 999 g who were admitted to 1 of 32 neonatal intensive care units in Canada, the United States, Australia, New Zealand, and Hong Kong between 1996 and 1998 and who survived to a postmenstrual age of 36 weeks. MAIN OUTCOME MEASURES: Combined end point of death or survival to 18 months with 1 or more of cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness. RESULTS: Each of the neonatal morbidities was similarly and independently correlated with a poor 18-month outcome. Odds ratios were 2.4 (95% confidence interval [CI], 1.8-3.2) for BPD, 3.7 (95% CI, 2.6-5.3) for brain injury, and 3.1 (95% CI, 1.9-5.0) for severe ROP. In children who were free of BPD, brain injury, and severe ROP the rate of poor long-term outcomes was 18% (95% CI, 14%-22%). Corresponding rates with any 1, any 2, and all 3 neonatal morbidities were 42% (95% CI, 37%-47%), 62% (95% CI, 53%-70%), and 88% (64%-99%), respectively. CONCLUSION: In ELBW infants who survive to a postmenstrual age of 36 weeks, a simple count of 3 common neonatal morbidities strongly predicts the risk of later death or neurosensory impairment.

Anti-Inflammatory Agents, Non-Steroidal↗

Prenatal growth of the human vomeronasal organ.

BACKGROUND: Vomeronasal organs (VNOs) are paired epithelial structures located adjacent to the nasal septum that form in the late first trimester of human fetal development. Although VNOs have long been known to exist in fetal and adult humans, some studies continue to suggest that these structures may be degenerative or functionless. Little is known of the growth of the VNO. METHODS: The present study examined length and volume changes of the human VNO in 26 "normal" (10 female, 16 male) histologically prepared fetuses from the University of Pittsburgh and the University of Michigan across three trimesters (8-30 weeks postmenstrual age). A computer reconstruction technique was used to quantify lengths and volumes of right and left VNOs, and regression equations were generated to assess growth rates. RESULTS: A linear increase in VNO length and a logarithmic increase in VNO volume with increasing postmenstrual age was found. Volume increase was noted for both the vomeronasal epithelium and the lumen of the VNO. A comparison with most estimates of adult human VNO length suggested that further prenatal or postnatal size increase occurs. The growth curves also suggested a more rapid growth in VNO length and volume for females than for males. CONCLUSIONS: The present study demonstrates that the fetal human VNO commences volumetric increase in the early second trimester but does not achieve maximum size during fetal development. Further investigation is needed to determine whether the human VNO is sexually dimorphic in size.

Female↗