Weeks In Infants Research Articles

Addition of extended zidovudine to extended nevirapine prophylaxis reduces nevirapine resistance in infants who were HIV-infected in utero

In the Post-Exposure Prophylaxis of Infants (PEPI)-Malawi trial, most women received single-dose nevirapine (NVP) at delivery, and infants in the extended study arms received single-dose NVP along with 1 week of daily zidovudine (ZDV), followed by either extended daily NVP or extended daily NVP and ZDV up to 14 weeks of age. Although extended NVP prophylaxis reduces the risk of postnatal HIV transmission, it may increase the risk of NVP resistance among infants who are HIV-infected despite prophylaxis. We analyzed 88 infants in the PEPI-Malawi trial who were HIV-infected in utero and who received prophylaxis for a median of 6 weeks prior to HIV diagnosis. HIV genotyping was performed using the ViroSeq HIV Genotyping System. At 14 weeks of age, the proportion of infants with NVP resistance was lower in the extended NVP and ZDV arm than in the extended NVP arm (28/45, 62.2% vs. 37/43, 86.0%; P = 0.015). None of the infants had ZDV resistance. Addition of extended ZDV to extended NVP was associated with reduced risk of NVP resistance at 14 weeks if prophylaxis was stopped by 6 weeks (54.5 vs. 85.7%, P = 0.007) but not if prophylaxis was continued beyond 6 weeks (83.3 vs. 87.5%, P = 1.00). Addition of extended ZDV to extended NVP prophylaxis significantly reduced the risk of NVP resistance at 14 weeks in infants who were HIV-infected in utero, provided that HIV infection was diagnosed and the prophylaxis was stopped by 6 weeks of age.

Pattern and determinants of BCG immunisation delays in a sub-Saharan African community

BackgroundChildhood immunisation is recognised worldwide as an essential component of health systems and an indispensable indicator of quality of care for vaccine-preventable diseases. While performance of immunisation programmes is more commonly measured by coverage, ensuring that every child is immunised at the earliest/appropriate age is an important public health goal. This study therefore set out to determine the pattern and predictors of Bacille de Calmette-Guérin (BCG) immunisation delays in the first three months of life in a Sub-Saharan African community where BCG is scheduled at birth in order to facilitate necessary changes in current policy and practices for improved services.MethodsA cross-sectional study in which immunisation delays among infants aged 0-3 months attending community-based BCG clinics in Lagos, Nigeria over a 2-year period from July 2005 to June 2007 were assessed by survival analysis and associated factors determined by multivariable logistic regression. Population attributable risk (PAR) was computed for the predictors of delays.ResultsBCG was delayed beyond three months in 31.6% of all eligible infants. Of 5171 infants enrolled, 3380 (65.4%) were immunised within two weeks and a further 1265 (24.5%) by six weeks. A significantly higher proportion of infants born in hospitals were vaccinated in the first six weeks compared to those born outside hospitals. Undernourishment was predictive of delays beyond 2 and 6 weeks while treated hyperbilirubinaemia was associated with decreased odds for any delays. Lack of antenatal care and multiple gestations were also predictive of delays beyond 6 weeks. Undernourishment was associated with the highest PAR for delays beyond 2 weeks (18.7%) and 6 weeks (20.8%).ConclusionsBCG immunisation is associated with significant delays in this setting and infants at increased risk of delays can be identified and supported early possibly through improved maternal uptake of antenatal care. Combining BCG with subsequent immunisation(s) at 6 weeks for infants who missed the BCG may be considered.

Lactoferrin Supplementation to Prevent Nosocomial Infections in Preterm Infants

THE STUDY BY MANZONI AND COLLEAGUES 1 IN THIS ISsue of JAMA represents an important step toward preventing infections that currently pose a major hurdle for preterm infants. The findings give insight into the role of lactoferrin in preventing infection, helping to define its importance in breast milk as well as the effect of daily supplementation with bovine lactoferrin (BLF) in preterm infants. The incidence of late-onset ( 72 hours of age) bloodstream infections in very low-birth-weight (VLBW) infants ( 1500 g) is approximately 20% and is complicated by high mortality and neurodevelopmental impairment. In the United States, nearly 65 000 VLBW infants are born each year, which translates into approximately 13 000 infections, 2300 deaths, and neurodevelopmental impairment in 3000 survivors. For the smallest infants of extremely low birth weight (ELBW) ( 1000 g), neurodevelopmental impairment occurs in 45% of those who survive bacteremia and 57% of those who survive fungemia. For VLBW infants, bloodstream infections increase hospital treatment costs and length of stay. Manzoni and colleagues performed a multicenter, double-blind, placebo-controlled, randomized trial in VLBW infants comparing administration of BLF alone or in combination with Lactobacillus rhamnosus GG (LGG) to placebo. Invasive infections (blood or cerebrospinal or peritoneal fluid) were significantly lower in the treatment groups (5.9% for BLF and 4.6% for BLF plus LGG, vs 17% for placebo). This effect was strongest for infants weighing less than 1000 g (11.3% for BLF and 11.1% for BLF plus LGG, vs 36.7% for placebo). There was an effect on infection-related mortality for both treatment groups (0% for BLF and 0.7% for BLF plus LGG, vs 4.8% for placebo), whereas the incidence of necrotizing enterocolitis was decreased in the BLF plus LGG group only (0% vs 6% in infants receiving placebo). The effect of BLF and BLF plus LGG was significant for ELBW infants (n=167), as well as those weighing less than 750 g (n=39) and of 27 weeks or fewer gestation (n=118), but not for infants weighing between 1000 and 1500 g (n=307). This may be explained in part by the dosing used in the study. The infants did not receive dosing based on their weight, but rather all infants received 100 mg per day; therefore, smaller infants received a higher dose per kilogram per day. For example, for infants weighing 500, 1000, and 1500 g, the dose per kg would be 200, 100, and 67 mg/kg, respectively. Extremely low-birth-weight infants also received study drug for 6 weeks compared with only 4 weeks for infants weighing 1000 to 1500 g. Thus, supplementation of BLF between 100 and 200 mg/kg per day and possibly for a longer period may be needed for all patients. Additionally, doses higher than 200 mg/kg per day may have a greater effect and need to be further studied. Post hoc analysis revealed that BLF decreased grampositive and fungal infections. This demonstrates the probable interaction of lactoferrin with the gastrointestinal tract microflora effecting common gram-positive skin and central venous catheter bloodstream infections, as central venous catheter days and time to reach full enteral feedings were similar between groups. While BLF did not change fungal colonization, it prevented progression to infection, thus potentially allowing fungi to maintain their symbiotic role in the gut and helping to maintain a balanced microflora. Fluconazole prophylaxis has demonstrated efficacy in reducing invasive Candida infections in single and multicenter randomized controlled trials. However, intravenous immunoglobulin products and colony-stimulating factors have not proven effective in preventing infections, largely because many elements of the immune system are underdeveloped in preterm infants. Lactoferrin has many functions and is a key link in several immune processes. This may in part explain the large effect demonstrated by Manzoni et al. Lactoferrin is the major whey protein in human milk and is involved in innate host defenses having antimicrobial and immunomodulation activities as well as promoting a mature and healthy gut. Bovine lactoferrin has activity against gram-positive and gram-negative bacteria, fungi, and viruses such as rotavirus, enterovirus, and adenovirus. This includes antilipopolysaccharide (against gram-negative

Soluble Vascular Endothelial Growth Factor Receptor 1 in Tracheal Aspirate Fluid of Preterm Neonates at Birth May Be Predictive of Bronchopulmonary Dysplasia/Chronic Lung Disease

We tested the hypothesis that soluble vascular endothelial growth factor receptors are involved in the development of bronchopulmonary dysplasia/chronic lung disease. Neonates with a birth weight of < or =1500 g and/or < or =30 weeks' gestation, with respiratory failure, requiring O(2) and mechanical ventilation within 24 hours, were eligible. Tracheal aspirate fluid samples were collected from 65 neonates before surfactant and/or assisted mechanical ventilation (baseline), at 3 and 7 days after birth, and weekly thereafter until extubation. Samples were analyzed for total vascular endothelial growth factor, soluble vascular endothelial growth factor receptor 1 and 2 levels and compared in infants with bronchopulmonary dysplasia/chronic lung disease (n = 31) versus those with no bronchopulmonary dysplasia/chronic lung disease (n = 34). Mean gestational age and birth weight were lower in infants with bronchopulmonary dysplasia/chronic lung disease. At baseline, vascular endothelial growth factor levels in the tracheal aspirate fluid were significantly lower, whereas soluble vascular endothelial growth factor receptor 1 levels were higher in the bronchopulmonary dysplasia/chronic lung disease infants compared with infants with no bronchopulmonary dysplasia/chronic lung disease. Vascular endothelial growth factor levels progressively increased from baseline to 4 weeks in all of the infants developing bronchopulmonary dysplasia/chronic lung disease. Conversely, soluble vascular endothelial growth factor receptor 1 declined in both groups from baseline to 5 weeks of age. Similarly, soluble vascular endothelial growth factor receptor 2 declined from baseline to 5 weeks in the control infants, but there were significant increases at 3 and 4 weeks in infants developing bronchopulmonary dysplasia/chronic lung disease. We speculate that low vascular endothelial growth factor levels in tracheal aspirate fluid, concurrent with elevated soluble vascular endothelial growth factor receptor 1 levels on the first day of life, are biological markers for the development of bronchopulmonary dysplasia/chronic lung disease in very low birth weight infants requiring O(2) and assisted mechanical ventilation.

Population pharmacokinetics of lamivudine in human immunodeficiency virus-exposed and -infected infants.

This study aimed to determine lamivudine disposition in infants and to construct an appropriate dose adjustment for age, given the widespread use of lamivudine for both the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) and the treatment of HIV-infected infants. Using a pooled-population approach, the pharmacokinetics of lamivudine in HIV-exposed or -infected infants from four Pediatric AIDS Clinical Trials Group studies were assessed. Ninety-nine infants provided 559 plasma samples for measurement of lamivudine concentrations. All infants received combination antiretroviral therapy including lamivudine dosed at 2 mg/kg of body weight every 12 h (q12h) for the first 4 to 6 weeks of life and at 4 mg/kg q12h thereafter. Lamivudine's apparent clearance was 0.25 liter/h/kg at birth, doubling by 28 days. In the final model, age and weight were the only significant covariates for lamivudine clearance. While lamivudine is predominantly renally eliminated, the serum creatinine level was not an independent covariate in the final model, possibly because it was confounded by age. Inclusion of interoccasion variability for bioavailability improved the individual subject clearance prediction over the age range studies. Simulations based on the final model predicted that by the age of 4 weeks, 90% of infant lamivudine concentrations with the standard 2 mg/kg dose of lamivudine fell below the adult median concentration. This population pharmacokinetic analysis affirms that adjusting the dose of lamivudine from 2 mg/kg to 4 mg/kg q12 h at the age of 4 weeks for infants with normal maturation of renal function will provide optimal lamivudine exposure, potentially contributing to more successful therapy.

Small-for-gestational-age infants classified by customized or population birthweight centiles: impact of gestational age at delivery

Evidence of placental disease and poor perinatal outcome is more common in infants who are small by customized centiles, compared with population centiles. Because preterm births are more likely to be associated with placental pathology, a greater proportion of preterm births are likely to be small for gestational age (SGA) by customized centiles, compared with population centiles. Our objective was to compare the proportion of infants classified as SGA by customized and population birthweight centiles at different gestational ages at delivery. This was a retrospective observational study of 17,855 nulliparous women delivering between 1992 and 1999 at National Women's Hospital, Auckland, New Zealand. The proportion of SGA infants (birthweight less than the 10th centile) classified by customized and population birthweight centiles delivering at less than 34 weeks, 34-36(+6) weeks, and 37 weeks or longer were compared. A total of 1847 infants (10.3%) were customized SGA, compared with 2111 (11.8%) who were population SGA (relative risk [RR] 0.9, 95% confidence interval [CI] 0.8 to 0.9). Of preterm deliveries less than 34 weeks (n = 392), 29.1% were customized SGA and 17.1% were population SGA (RR 1.7, 95% CI 1.3 to 2.2). Of deliveries at 34-36(+6) weeks (n = 946), 18.0% were customized SGA and 13.7% were population SGA (RR 1.3, 95% CI 1.1 to 1.6). The converse was observed at term (n = 16,517), 9.5% classified as customized SGA and 11.5% as population SGA (RR 0.82, 95% CI 0.77 to 0.87). Of all early preterm perinatal deaths (less than 34 weeks) 31 of 72 infants (43%) were customized SGA and 23 of 72 infants (32%) were population SGA. There were no perinatal deaths or deliveries less than 34 weeks in infants who were classified as SGA by population criteria only. Customized centiles classified more infants as SGA, compared with population centiles, in preterm births but not for term births in nulliparous women.

Abnormalities in the coordination of respiration and swallow in preterm infants with bronchopulmonary dysplasia

Individual rhythms of suck, swallow, and respiration are disrupted in preterm infants with bronchopulmonary dysplasia (BPD). Integration of respiration into suck-swallow efforts is critical for establishing coordinated suckle feeding. This study quantitatively assessed the coordination of respiration and swallow in infants with and without BPD. Thirty-four preterm infants of 26 to 33 weeks’gestational age were included: 14 participants with BPD (eight males, six females) and 20 comparison participants without BDP (10 males, 10 females). Participants were studied at postmenstrual age 32 to 40 weeks and postnatal age 2 to 12 weeks using digital recordings of pharyngeal pressure, nasal thermistor flow, and thoraco-abdominal plethysmography. The coefficients of variation (COV; standard deviation/mean) of the swallow-breath (SW-BR) and breath-breath (BR-BR) intervals during swallow runs, the percentage of‘apneic swallows’(runs of ≥3 swallows without interposed breaths), and phase relationships of respiration and swallow were used to quantify rhythmic coordination and integration of respiration into feeding episodes. Apneic swallows were significantly increased after 35 weeks in infants with BPD (mean 13.4% [SE 2.4]) compared with non-BDP infants (6.7% [SE 1.8];p < 0.05), as were SW-BR phase relationships involving apnea. The BPD cohort also had significantly higher SW-BR COV and BR-BR COV than non-BPD infants, indicating less rhythmic coordination of swallowing and respiration during feeding. Results emphasize the need for frequent rests and closer monitoring when feeding infants with respiratory compromise. Quantitative assessment of the underlying rhythms involved in feeding may be predictive of longer-term feeding and neurological problems.

Blood Pressure during the First 7 Days in Premature Infants Born at Postmenstrual Age 23 to 25 Weeks

Our aims were to identify the range of blood pressure values during the first postnatal week in infants born between 23 and 25 weeks postmenstrual age who were not considered in need of treatment for hypotension, and to describe the clinical course of these untreated infants compared with those who were treated for hypotension. We reviewed retrospectively the charts of 142 consecutive inborn infants over a 6-year period. For 86 infants who survived the first postnatal week without being treated for hypotension, the mean arterial pressure (MAP) increased 0.3 mm Hg/h during the first 24 hours, 0.1 mm Hg/h from the 25th to the 48th hour, and then stabilized for the remainder of the week. MAP values < or = 25 mm Hg were not uncommon and were not associated with apparent consequences. Thirty-five infants treated for hypotension differed significantly from untreated infants in several clinical variables present at birth, suggesting a different degree of fetal compromise. Treated infants were less likely to survive (43 versus 85%; P < 0.001) or survive without a major morbidity (29 versus 53%; P = 0.013) than untreated infants. It was not apparent from our data that the treatment of hypotension was helpful.

Abnormalities in the coordination of respiration and swallow in preterm infants with bronchopulmonary dysplasia

Individual rhythms of suck, swallow, and respiration are disrupted in preterm infants with bronchopulmonary dysplasia (BPD). Integration of respiration into suck-swallow efforts is critical for establishing coordinated suckle feeding. This study quantitatively assessed the coordination of respiration and swallow in infants with and without BPD. Thirty-four preterm infants of 26 to 33 weeks' gestational age were included: 14 participants with BPD (eight males, six females)and 20 comparison participants without BDP (10 males, 10 females). Participants were studied at postmenstrual age 32 to 40 weeks and postnatal age 2 to 12 weeks using digital recordings of pharyngeal pressure, nasal thermistor flow, and thoraco-abdominal plethysmography. The coefficients of variation (COV; standard deviation/mean) of the swallow-breath (SW-BR) and breath-breath (BR-BR) intervals during swallow runs, the percentage of 'apneic swallows' (runs of >or=3 swallows without interposed breaths), and phase relationships of respiration and swallow were used to quantify rhythmic coordination and integration of respiration into feeding episodes. Apneic swallows were significantly increased after 35 weeks in infants with BPD (mean 13.4% [SE 2.4]) compared with non-BDP infants (6.7% [SE 1.8]; p<0.05), as were SW-BR phase relationships involving apnea. The BPD cohort also had significantly higher SW-BR COV and BR-BR COV than non-BPD infants, indicating less rhythmic coordination of swallowing and respiration during feeding. Results emphasize the need for frequent rests and closer monitoring when feeding infants with respiratory compromise. Quantitative assessment of the underlying rhythms involved in feeding may be predictive of longer-term feeding and neurological problems.

Higher incidence of SIDS at weekends, especially in younger infants

Background: An increased incidence of sudden infant death syndrome (SIDS) at weekends has been previously noted, although it has not been found in all studies. Where a weekend effect has...

Trends in the incidence of severe retinopathy of prematurity in a geographically defined population over a 10-year period.

To examine trends in the incidence of severe (> or =grade 3) retinopathy of prematurity (ROP) in infants with birth weight of < or =1250 g in a geographically defined population over a 10-year period. An observational study was conducted of all infants who had a birth weight < or =1250 g and were born to mothers who were resident in the county of Leicestershire, United Kingdom, during the period January 1, 1990, to December 30, 1999. Cases were identified by the Trent Neonatal Survey. The incidence of severe ROP (> or =grade 3) was compared in 2 successive 5-year periods: 1990-1994 and 1995-1999. Comparing the first 5-year period (1990-1994) with the second (1995-1999), the total number of live births fell (60 789 vs 56 564). However, there was a significant increase in the number of births with birth weight < or =1250 g (including live and dead; 615 vs 734; live births only: 455 vs 556). Survival to 42 weeks of infants who were born at < or =1250 g was significantly better in the latter time period (203 vs 302; odds ratio [OR] for death: 0.54; 95% confidence interval [CI]: 0.39-0.75). The number of cases of severe ROP was 4 times higher during the second time period compared with the first (9 vs 36). A significantly increased risk for the development of severe ROP was seen during the second time period (OR: 2.92; 95% CI: 1.37-6.20). Even after allowing for the change in gestation induced by the improved survival during the second time period, the increased risk remained (OR: 2.81; 95% CI: 1.27-6.21). There is strong evidence that the incidence of severe ROP among infants with birth weight < or =1250 g increased in the latter half of the last decade. The increased risk seems to be independent of the increase in survival.

Faecal elastase 1 levels in premature and full term infants

Background: Determination of faecal elastase 1 (FE1) is a simple, relatively inexpensive, non-invasive, highly specific and sensitive test for determining pancreatic function. Secretion of pancreatic enzymes varies during infancy, but...

Breast-Feeding among Women Exposed to Polybrominated Biphenyls in Michigan

In the early 1970s, the largest industrial accident in the United States resulted in widespread contamination of the food supply in Michigan with polybrominated biphenyls (PBBs). The chemical similarity of PBBs to compounds implicated as endocrine disruptors has raised the question of whether PBBs could affect the reproductive system. In the present analysis we examine the relation between serum measurements of PBBs and the frequency and duration of lactation. Persons who lived on or received food from farms exposed to PBBs were enrolled in a registry by the Michigan Department of Public Health. Female members of the cohort were invited to participate in a telephone survey of reproductive outcomes. The three outcomes of interest in the present analysis were a) the decision to breast-feed (yes/no); b) the duration, in months, of breast-feeding as the main source of nutrition; and c) the total duration, in months, of breast-feeding. None of the three outcomes was significantly associated with serum PBB levels, even after controlling for maternal age, previous history of breast-feeding, body mass index, maternal education, household income, history of smoking in the year before pregnancy, consumption of alcohol during the first trimester of pregnancy, history of thyroid disorder, gestational age of the infant in weeks, time to pregnancy, and year of birth.

Breast-feeding among women exposed to polybrominated biphenyls in Michigan.

In the early 1970s, the largest industrial accident in the United States resulted in widespread contamination of the food supply in Michigan with polybrominated biphenyls (PBBs). The chemical similarity of PBBs to compounds implicated as endocrine disruptors has raised the question of whether PBBs could affect the reproductive system. In the present analysis we examine the relation between serum measurements of PBBs and the frequency and duration of lactation. Persons who lived on or received food from farms exposed to PBBs were enrolled in a registry by the Michigan Department of Public Health. Female members of the cohort were invited to participate in a telephone survey of reproductive outcomes. The three outcomes of interest in the present analysis were a) the decision to breast-feed (yes/no); b) the duration, in months, of breast-feeding as the main source of nutrition; and c) the total duration, in months, of breast-feeding. None of the three outcomes was significantly associated with serum PBB levels, even after controlling for maternal age, previous history of breast-feeding, body mass index, maternal education, household income, history of smoking in the year before pregnancy, consumption of alcohol during the first trimester of pregnancy, history of thyroid disorder, gestational age of the infant in weeks, time to pregnancy, and year of birth.

Resuscitation of newborn infants with room air or oxygen

Oxygen is a toxic agent and a critical approach regarding its use during resuscitation at birth is developing. Animal data indicate that room air is efficient for newborn resuscitation. Three clinical studies have established that normal ventilation is delayed after oxygen resuscitation. Oxidative stress is augmented for several weeks in infants exposed to oxygen at birth – the long-term implications of these observations remain unclear. There are limited data regarding the use of room air during complicated resuscitations, i.e. in meconium aspiration, the severely asphyxiated infant and in the preterm infant. Thus, it is necessary to continue ongoing rigorous examination of the long-accepted practice of oxygen administration during neonatal resuscitation.

Urinary Leukotriene E4 Excretion During the First Month of Life and Subsequent Bronchopulmonary Dysplasia in Premature Infants

Inflammation plays an important role in the pathogenesis of bronchopulmonary dysplasia (BPD), but the exact nature of this inflammatory process is incompletely understood. Older infants with established BPD have higher levels of urinary leukotriene E(4) (LTE(4)) compared to healthy infants of the same age. This suggests that cysteinyl leukotrienes may play a role in the abnormalities seen in BPD. To measure urinary LTE(4) levels during the first month of life in premature infants, and to determine whether there are significant differences in premature infants who develop BPD, as compared to those who do not develop BPD. Prospective, blinded, controlled study. Neonatal ICUs of a tertiary-care university hospital. Thirty-seven premature infants (< 33 weeks of gestational age) were enrolled prospectively at birth. Urinary LTE(4) levels were measured blinded, using a standard radioimmunoassay technique at 2 days, 7 days, and 28 days of life. At 1 month of age, infants were classified as with or without BPD, based on need for supplemental oxygen, and characteristic chest radiographs. Clinical features and urinary LTE(4) were compared between the two groups. Mean +/- SD gestational age was 29 +/- 2.6 weeks. None of the infants had a family history of asthma. Thirteen of 37 infants were classified as having BPD at 28 days after birth. Mean gestational age in infants who developed BPD was 27 +/- 2.4 weeks, compared to 30 +/- 2 weeks in infants who did not develop BPD (p < 0.05). In infants with BPD, mean urinary LTE(4) levels of urinary creatinine were 1,762 +/- 2,003 pg/mg, 1,236 +/- 992 pg/mg, and 5,541 +/- 5,146 pg/mg at days 2, 7, and 28, respectively, compared to 1,304 +/- 1,195 pg/mg, 1,158 +/- 1,133 pg/mg, and 2,800 +/- 2,080 pg/mg in infants without BPD. LTE(4) levels at 2 days, 7 days, and 28 days did not correlate with the subsequent development of BPD. LTE(4) levels at day 28 were significantly higher than LTE(4) levels at day 2 and day 7 in both groups, even after correcting for gestational age or birth weight (p < 0.05). There was significant inverse correlation between LTE(4) levels at day 2 with gestational age and birth weight (p < 0.05). All 13 infants with BPD received steroid pulses, compared to 3 of 26 infants without BPD. Gestational age and use of postnatal steroid pulses, diuretics, and theophylline (for apnea of prematurity) were significantly associated with each other and with the subsequent development of BPD. Urinary LTE(4) levels measured on the second day of life in very-low-birth-weight infants inversely correlate with gestational age and birth weight. Urinary LTE(4) levels may reflect lung injury and/or inflammation in premature infants, not necessarily related to BPD as it is presently defined.

Estrogenic Activity of Phenolic Additives Determined by an In Vitro Yeast Bioassay

In the early 1970s, the largest industrial accident in the United States resulted in widespread contamination of the food supply in Michigan with polybrominated biphenyls (PBBs). The chemical similarity of PBBs to compounds implicated as endocrine disruptors has raised the question of whether PBBs could affect the reproductive system. In the present analysis we examine the relation between serum measurements of PBBs and the frequency and duration of lactation. Persons who lived on or received food from farms exposed to PBBs were enrolled in a registry by the Michigan Department of Public Health. Female members of the cohort were invited to participate in a telephone survey of reproductive outcomes. The three outcomes of interest in the present analysis were a) the decision to breast-feed (yes/no); b) the duration, in months, of breast-feeding as the main source of nutrition; and c) the total duration, in months, of breast-feeding. None of the three outcomes was significantly associated with serum PBB levels, even after controlling for maternal age, previous history of breast-feeding, body mass index, maternal education, household income, history of smoking in the year before pregnancy, consumption of alcohol during the first trimester of pregnancy, history of thyroid disorder, gestational age of the infant in weeks, time to pregnancy, and year of birth.

Enhanced in vivo IgE production and T cell polarization toward the type 2 phenotype in association with indoor exposure to VOC: results of the LARS study

AbstractThe association between indoor exposure to volatile organic compounds (VOC), prevalence of allergic sensitization and cytokine secretion profile of peripheral T cells was studied in 3 year old children of the LARS study (Leipzig Allergy Risk Children Study) to investigate the role of VOC exposure as a risk factor for the development of atopic disease.Indoor VOC exposure was measured over a period of 4 weeks in infants' bedrooms using a passive sampling system. Specific IgE antibodies to food, indoor and outdoor allergens were measured by the Pharmacia CAP system and correlated to VOC exposure (n = 120). In addition, cytokine producing peripheral T cells (interleukin(IL)-4, interferon(IFN)-γ) were measured in a subgroup of 28 children by means of intracellular cytokine staining.For the first time we were able to show that exposure to alkanes (C6, C9, C10) and aromatic compounds (toluene, o-xylene, m+p-xylene, 2-, 3- and 4-ethyl-toluene, chlorobenzene) may contribute to the risk of allergic sensitization to the food allergens milk and egg white (Odds ratios between 5.7 and 11.2). Moreover, significantly reduced numbers of CD3+/CD8+ peripheral T cells were found in children exposed to alkanes (C9-C13), naphthalene and chlorobenzene. Exposure to benzene, ethylbenzene and chlorobenzene was associated with higher percentages of IL-4 producing CD3+ T cells.Both an increase in IL-4 producing type 2 T cells and a reduction of IFN-γ producing type 1 T cells may contribute to a type 2 skewed memory in response to allergens. Therefore, we suggest exposure to VOCs in association with allergic sensitization to be mediated by a T cell polarization toward the type 2 phenotype.

Characterization of cerebral white matter damage in preterm infants using 1H and 31P magnetic resonance spectroscopy.

The biochemical characteristics of white matter damage (WMD) in preterm infants were assessed using magnetic resonance spectroscopy (MRS). The authors hypothesized that preterm infants with WMD at term had a persisting cerebral lactic alkalosis and reduced N-acetyl aspartate (NAA)/ creatine plus phosphocreatine (Cr), similar to that previously documented in term infants weeks after perinatal hypoxiaischemia (HI). Thirty infants (gestational age 27.9 +/- 3.1 weeks, birth weight 1,122 +/- 445 g) were studied at postnatal age of 9.8 +/- 4.1 weeks (corrected age 40.3 +/- 3.9 weeks). Infants were grouped according to the presence or absence of WMD on magnetic resonance (MR) images. The peak area ratios of lactate/Cr, NAA/Cr, myo-inositol/Cr, and choline (Cho)/Cr were measured from an 8-cm3 voxel in the posterior periventricular white matter (WM) using proton MRS. Intracellular pH (pHi) was calculated using phosphorus MRS. Eighteen infants had normal WM on MR imaging; 12 had WMD. For infants with WMD, lactate/Cr and myo-inositol/Cr were related (P < 0.01); lactate/Cr and pHi were not (P = 0.8). In the WMD group, mean lactate/Cr and myo-inositol/Cr were higher (P < 0.001, P < 0.05, respectively) than the normal WM group. There was no difference in the NAA/Cr, Cho/Cr, or pHi between the two groups, although pHi was not measured in all infants. These findings suggest that WMD in the preterm infant at term has a different biochemical profile compared with the term infant after perinatal HI.

The Hyperthyroid Fetus and Infant

After completing this article, readers should be able to: 1. Describe the etiology of transient and persistent neonatal hyperthyroidism. 2. Delineate the diagnostic tests for thyroid-stimulating hormone receptor antibodies. 3. Develop a treatment plan for fetal and neonatal hyperthyroidism and a management plan for subsequent pregnancies. 4. Provide guidelines for breastfeeding when the mother is receiving antithyroid medications. 5. Describe the long-term risks of neonatal hyperthyroidism. The first clinical description of neonatal hyperthyroidism was published in 1912, and the discovery of the transplacental passage of thyroid-stimulating immunoglobulins (TSI) provided an understanding for the etiology of this condition in 1964. There were, however, a few cases of persistent neonatal hyperthyroidism, initially described in 1976, that were inconsistent with the transient clinical course expected with a maternally acquired antibody. The etiology of persistent neonatal hyperthyroidism was clarified by the discovery of an activating germ-line mutation in the thyroid-stimulating hormone (TSH) receptor in 1995. When a mother has autoimmune thyroid disease, fetal and neonatal hyperthyroidism result from transplacental passage of TSI. The mother usually has a history of hyperthyroidism, but neonatal hyperthyroidism also has been reported in mothers who have hypothyroidism due to Hashimoto thyroiditis. The clinical status of the mother does not determine the infant’s risk for hyperthyroidism. The mother may have been treated with 131I or a subtotal thyroidectomy in the past and may be euthyroid or she may be receiving thyroid replacement therapy at the time of her pregnancy, but she still can be producing high titers of TSI. In a review of neonatal hyperthyroidism, mothers were clinically hyperthyroid during pregnancy in only 18 of 38 cases (47%). The prevalence of clinical hyperthyroidism in pregnancy has been reported to be 0.1% to 0.4% and is the most common endocrine disorder during pregnancy after diabetes. Clinical fetal and neonatal hyperthyroidism has been reported to occur …