Risk of immune-related diseases in childhood after intrapartum antibiotic exposure.

BACKGROUND: Intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease in newborn infants, but it influences gut microbiota development. Gut microbiota composition is, in turn, associated with immune-related diseases in childhood. OBJECTIVE: This study hypothesized that intrapartum antibiotic exposure is associated with immune-related diseases in childhood. STUDY DESIGN: We conducted a population-based cohort study of vaginally delivered children. We retrieved data on intrapartum antibiotic exposure from structured electronic medical records and obtained outcome data on childhood autoimmune, allergic, and obstructive airway diseases from comprehensive national registers. We used Cox regression analysis with adjustment for maternal and neonatal covariates and regarded death as a competing risk in the analyses. RESULTS: The study population comprised 45,575 vaginally born children of whom 9733 (21%) had been exposed to intrapartum antibiotics. Intrapartum antibiotic exposure was associated with an autoimmune disease diagnosis (adjusted hazard ratio, 1.28; 95% confidence interval, 1.02-1.62), which corresponds to 22% (95% confidence interval, 6-39) as a theoretical population-attributable fraction. Intrapartum antibiotic exposure was not associated with diagnoses of allergic (adjusted hazard ratio, 1.08; 95% confidence interval, 0.97-1.20) or obstructive airway diseases (adjusted hazard ratio, 1.04; 95% confidence interval, 0.96-1.14). CONCLUSION: Intrapartum antibiotic exposure may be associated with an increased risk for autoimmune diseases in childhood. This finding supports the efforts to develop more specific group B streptococcal disease prevention strategies in the future.

School-age children enjoyed good respiratory health and fewer allergies despite having lung disease after preterm birth.

AIM: This study explored the under-researched area of whether preterm birth or bronchopulmonary dysplasia (BPD) affected hospitalisation rates, allergies or health-related quality of life (HRQoL). METHODS: We studied 88 schoolchildren born preterm at a mean gestational age of 28.8 weeks (range 24.1-31.9) and matched term-born controls at the mean age of 11 years (range 8-14). Hospitalisations after the first discharge were recorded, skin prick allergy tests were performed and HRQoL was assessed with a parental questionnaire. RESULTS: Preterm children were hospitalised more than controls (64% versus 39%, p = 0.001), mostly before two years of age. The adjusted odds ratios (OR) for two-year-old preterm-born children being hospitalised for wheezing was 8.2 (95% CI 2.0-34.1). BPD affected 56% of the preterm children, but did not influence hospitalisations, and the positive skin prick rate was similar between the preterm and term-born children (35% versus 48%, p = 0.126). Preterm BPD children had fewer positive skin prick tests than those without BPD. HRQoL was lower in preterm than term children (81.25 ± 10.84 versus 86.80 ± 9.60, p = 0.001). CONCLUSION: Most health problems experienced by preterm-born schoolchildren occurred before two years of age and were mainly wheezing disorders. BPD decreased atopy but had no influence on hospitalisation rates.

Maternal serum alpha-1 antitrypsin levels in spontaneous preterm and term pregnancies.

Currently, there are no accurate means to predict spontaneous preterm birth (SPTB). Recently, we observed low expression of alpha-1 antitrypsin (AAT) in SPTB placentas. Present aim was to compare the concentrations of maternal serum AAT in pregnancies with preterm and term deliveries. Serum C-reactive protein (CRP) was used as a reference inflammatory marker. Two populations were studied. The first population comprised women who eventually gave birth spontaneously preterm (SPTB group) or term (control group). The second population included pregnant women shortly before delivery and nonpregnant women. We observed that serum AAT levels were higher in the SPTB group than in the controls, and a similar difference was observed when serum CRP was considered in multivariable analysis. However, the overlap in the AAT concentrations was considerable. No statistical significance was observed in serum AAT levels between preterm and term pregnancies at delivery. However, AAT levels were higher at delivery compared to nonpregnant controls. We did not observe a strong correlation between serum AAT and CRP in early pregnancy samples and at labor. We propose that during early pregnancy, complicated by subsequent SPTB, modest elevation of serum AAT associates with SPTB.

Management Practices During Perinatal Respiratory Transition of Very Premature Infants.

The present review considers some controversial management practices during extremely premature perinatal transition. We focus on perinatal prevention and treatment of respiratory distress syndrome (RDS) in immature infants. New concerns regarding antenatal corticosteroid management have been raised. Many fetuses are only exposed to potential adverse effects of the drug. Hence, the formulation and the dosage may need to be modified. Another challenge is to increase the fraction of the high-risk fetuses that benefit from the drug and to minimize the harmful effects of the drug. On the other hand, boosting anti-inflammatory and anti-microbial properties of surfactant requires further attention. Techniques of prophylactic surfactant administration to extremely immature infants at birth may be further refined. Also, new findings suggest that prophylactic treatment of patent ductus arteriosus (PDA) of a high-risk population rather than later selective closure of PDA may be preferred. The TREOCAPA trial (Prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen) evaluates, whether early intravenous paracetamol decreases the serious cardiorespiratory consequences following extremely premature birth. Lastly, is inhaled nitric oxide (iNO) used in excess? According to current evidence, iNO treatment of uncomplicated RDS is not indicated. Considerably less than 10% of all very premature infants are affected by early persistence of pulmonary hypertension (PPHN). According to observational studies, effective ventilation combined with early iNO treatment are effective in management of this previously fatal disease. PPHN is associated with prolonged rupture of fetal membranes and birth asphyxia. The lipopolysaccharide (LPS)-induced immunotolerance and hypoxia-reperfusion-induced oxidant stress may inactivate NO-synthetases in pulmonary arterioles and terminal airways. Prospective trials on iNO in the management of PPHN are indicated. Other pulmonary vasodilators may be considered as comparison drugs or adjunctive drugs. The multidisciplinary challenge is to understand the regulation of pregnancy duration and the factors participating the onset of extremely premature preterm deliveries and respiratory adaptation. Basic research aims to identify deficiencies in maternal and fetal tissues that predispose to very preterm births and deteriorate the respiratory adaptation of immature infants. Better understanding on causes and prevention of extremely preterm births would eventually provide effective antenatal and neonatal management practices required for the intact survival.

Long-Term Results of Pediatric Congenital Pulmonary Malformation: A Population-Based Matched Case-Control Study with a Mean 7-Year Follow-Up.

Symptomatic congenital pulmonary malformations (CPMs) are a group of anomalies involving the lungs. The long-term outcomes of these patients are not well known. The present research aimed to study the pulmonary function, respiratory morbidity, and health-related quality of life (QoL) of patients treated for CPMs. All children (<16 years of age) treated for CPMs in 2002−2012 (in Oulu University Hospital) were invited to the follow-up visit. Altogether, there were 22 patients, out of which 17 (77%) participated. The mean follow-up time was 6.6 (ranged from 3 to 16) years. Pulmonary function tests, diffusing capacity, respiratory morbidity, and QoL were determined as the primary outcomes. Potential residual malformations and lung anatomy were investigated using computer tomography (CT) imaging. The outcomes were compared to the age- and sex-matched healthy controls. The forced expiratory volume at 1 s (FEV1, Z-score) remained lower in operated patients compared to the healthy controls (−1.57 ± SD 1.35 vs. −0.39 ± SD −0.86, p-value 0.005). There were no differences in respiratory morbidity or QoL between the patients and the controls. The surgical approach (lobectomy vs. partial resection) did not affect lung function. A younger age (<1 year of age) at the time of the surgery seemed to result in a higher lung capacity, but the finding was not statistically significant. Patients with CPMs treated with surgery were satisfied with their wellbeing in the long-term. A lower lung function did not have an impact on their wellbeing. However, there was a slight decrease in lung function compared to the healthy controls, and a clinical follow-up of the patients was recommended.

Structural Pulmonary Abnormalities Still Evident in Schoolchildren with New Bronchopulmonary Dysplasia.

BACKGROUND: A new pattern of bronchopulmonary dysplasia (BPD) has emerged with the improved survival of preterm children. OBJECTIVES: Our aim was to characterize structural abnormalities associated with new BPD and to evaluate whether the severity of high-resolution computed tomography (HRCT) changes is associated with lung function. METHODS: HRCT scans were performed on 21 schoolchildren with a history of new BPD (mild, n = 9; moderate, n = 4; and severe, n = 8) with a mean age of 12.7 years (range: 8.7-16.7). Scans were interpreted by 2 radiologists using a structured scoring system. Spirometry (forced expiratory volume in 1 s [FEV1] and maximum mid-expiratory flow [MMEF]) and the diffusion capacity of the lung for carbon monoxide (DLCO) were measured. RESULTS: At least 1 HRCT abnormality was evident in 17 children (81%), including linear-to-triangular subpleural opacities (71%), air trapping (29%), mosaic perfusion (24%), peribronchial thickening (14%), and emphysema (14%). The HRCT score was higher in the severe BPD group (11.50; 95% CI 2.86-20.14) than in the mild or moderate BPD group (1.39; 95% CI 0.24-2.54, and 2.75; 95% CI 0.28-5.22, respectively). HRCT scores were inversely related to FEV1 (ß -4.23; 95% CI -6.97 to -1.49, p = 0.004) and MMEF (ß -3.45; 95% CI -6.10 to -0.80, p = 0.013) but not to DLCO. The duration of the initial mechanical ventilation was associated with HRCT scores (p = 0.014). CONCLUSIONS: Structural lung abnormalities are common among schoolchildren with a history of new BPD, resembling abnormalities described in the presurfactant era. HRCT abnormalities are associated with the duration of early mechanical ventilation and the severity of BPD and they are correlated with spirometry.

Intrauterine growth restriction predicts lower lung function at school age in children born very preterm.

OBJECTIVE: Children born preterm have lower lung function compared with term-born children. Intrauterine growth restriction (IUGR) may predispose individuals to chronic obstructive pulmonary disease. The purpose of this observational study was to investigate the role of IUGR as predictor of lung function at school age in children born very preterm. We further studied the difference in lung function between term-born and preterm-born children with distinct morbidities. DESIGN: Preterm-born children and age-matched and sex-matched term-born comparison groups (88 of each) were studied at the mean age of 11 years. Spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded. All preterm-born subjects with IUGR (n=23), defined as birth weight less than -2 SD, were compared with preterm-born subjects without IUGR (n=65). RESULTS: In the preterm-born children exposed to IUGR, the forced expiratory volume in 1 s (FEV1) was 5.7 (95% CI -10.2 to -1.3) and DLCO 9.2 percentage points lower (95% CI -15.7 to -2.7) than in the preterm-born children with appropriate in utero growth (expressed as percentage of predicted values). The effect of IUGR in decreasing FEV1 and DLCO remained significant after adjustment for bronchopulmonary dysplasia (BPD). Further study indicated that after adjustment with IUGR and BPD, prematurity explained reduction in FEV1 but not in DLCO. CONCLUSIONS: In children born very preterm, IUGR is an independent risk factor for a lower lung function in school age. We propose that IUGR and BPD are the major early factors predisposing the children born very preterm to lower lung function.

New BPD predicts lung function at school age: Follow-up study and meta-analysis.

New treatment practices have improved survival of preterm infants and decreased airway pathology in bronchopulmonary dysplasia (BPD). Our aim was to investigate whether preterm birth, BPD, and the severity of BPD predict lung function in school children that are born in surfactant era. We studied pulmonary function of 88 school-aged children born very preterm (gestational age <32 weeks) and paired them with 88 age- and sex-matched controls born at term. Spirometry and diffusion capacity were recorded. We also performed a meta-analysis covering the era of antenatal corticosteroid and surfactant treatment. BPD was defined as oxygen dependence for ≥ 28 days and it was severity-graded by oxygen requirement at 36 weeks postmenstrual age (mild, none; moderate, FiO2 = 0.22-0.29; severe, FiO2 ≥ 0.30). Preterm children had lower forced expiratory volume in 1 sec (FEV1 ) 86.4 ± 11.8 versus 94.9 ± 10.1 (mean % predicted ± SD; P < 0.001), and lower diffusion capacity (DLCO) 87.6 ± 13.9 versus 93.7 ± 12.0 (P = 0.005) compared with term controls. BPD group differed in both FEV1 (P = 0.037) and DLCO (P = 0.018) from those without BPD. For meta-analysis, search identified 210 articles. Together with present results, six articles met the inclusion criteria. FEV1 of no BPD, all BPD, and moderate to severe BPD groups differed from that in term controls by -7.4, -10.5, and -17.8%, respectively. According to meta-analysis and follow-up study, the adverse effects of prematurity on pulmonary function are still detectable in school-age. BPD was associated with reductions in both diffusion capacity and spirometry. New interventions are required to document a further decrease in the life-long consequences of prematurity.