Using virtual-reality simulation to ensure basic competence in hysteroscopy.

BACKGROUND: Hysteroscopy is a technically challenging procedure. Specialty curricula of obstetrics and gynaecology appraise hysteroscopy for trainees but there is no present evidence-based training program that certifies the fundamental technical skills before performance on patients. The objectives of this study were to develop and gather validity evidence for a simulation-based test that can ensure basic competence in hysteroscopy. METHODS: We used the virtual-reality simulator HystMentor™. Six experts evaluated the feasibility and clinical relevance of the simulator modules. Six modules were selected for the test and a pilot study was carried out. Subsequently, medical students, residents, and experienced gynaecologists were enrolled for testing. Outcomes were based on generated simulator metrics. Validity evidence was explored for all five sources of evidence (content, response process, internal structure, relations to other variables, consequences of testing). RESULTS: Inter-case reliability was high for four out of five metrics (Cronbach's alpha ≥ 0.80). Significant differences were identified when comparing the three groups' performances (p values < 0.05). Participants' clinical experience was significantly correlated to their simulator test score (Pearson's r = 0.49, p < 0.001). A single medical student managed to achieve the established pass/fail score (6.7% false positive) and three experienced gynaecologists failed the test (27.3% false negative). CONCLUSIONS: We developed a virtual-reality simulation-based test in hysteroscopy with supporting validity evidence. The test is intended to ensure competency in a mastery learning program where trainees practise on the simulator until they are able to pass before they proceed to supervised training on patients.

Cytokines associated with necrotizing enterocolitis in extremely-low-birth-weight infants.

BACKGROUND: The goal was to identify cytokines associated with necrotizing enterocolitis (NEC). Based on our earlier reports of decreased tissue expression of transforming growth factor (TGF)-ß, we hypothesized that infants with NEC also have low blood TGF-ß levels. We further hypothesized that because fetal inflammation increases the risk of NEC, infants who develop NEC have elevated blood cytokine levels in early neonatal period. METHODS: Data on 104 extremely-low-birth-weight infants with NEC and 893 without NEC from 17 centers were analyzed. Clinical information was correlated with blood cytokine levels on postnatal day 1 (D1), D3, D7, D14, and D21. RESULTS: Male gender, non-Caucasian/non-African American ethnicity, sepsis, lower blood TGF-ß and interleukin (IL)-2 levels, and higher IL-8 levels were associated with NEC. The NEC group had lower TGF-ß levels than controls since D1. The diagnosis of NEC was associated with elevated IL-1ß, IL-6, IL-8, IL-10, monocyte chemoattractant protein-1/CC-motif ligand-2, macrophage inflammatory protein-1ß/CC-motif ligand-3, and C-reactive protein. CONCLUSION: Clinical characteristics, such as gender and ethnicity, and low blood TGF-ß levels are associated with higher risk of NEC. Infants who developed NEC did not start with high blood levels of inflammatory cytokines, but these rose mainly after the onset of NEC.

Joint analysis of SNPs and proteins identifies regulatory IL18 gene variations decreasing the chance of spastic cerebral palsy.

Cerebral palsy (CP) is a permanent disorder, affecting 2-3 per 1,000 live born children, disturbing movement and posture. Spastic limbs affects about 70-80% of the CP children, and this group is the target of our study. CP is considered a multifactorial condition believed to be provoked by, for example, preterm birth, infection during pregnancy, neural disorders, and genetics, to mention some. Interestingly, the cytokine network is believed to be involved in many of these disorders. In this study, including 203 spastic CP cases and 167 controls, we measured the levels of 25 cytokine proteins, and genotyped 159 SNPs in their gene loci. Using logistic regression, we estimated the genetic association of SNP genotypes to spastic CP. In addition, fitting a Tobit regression model for each protein and each SNP in the respective gene loci, we estimated three regression coefficients corresponding three different effects of the genetic variation on the protein level. Intriguingly, two IL18 loci SNPs (rs549908:A>C and rs1290349:C>A) showed a protective effect against spastic CP, and interestingly both were associated to a decreased epidemiological expression of IL-18 protein. By joining protein data to genetic information, we have provided new data suggesting IL18's involvement in the pathogenesis of spastic CP.

Association between blood spot transforming growth factor-ß and patent ductus arteriosus in extremely low-birth weight infants.

Permanent ductal closure involves anatomic remodeling, in which transforming growth factor (TGF)-ß appears to play a role. Our objective was to evaluate the relationship, if any, between blood spot TGF-ß on day 3 and day 7 of life and patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Prospective observational study involving ELBW infants (n = 968) in the National Institute of Child Health and Human Development Neonatal Research Network who had TGF-ß measured on filter paper spot blood samples using a Luminex assay. Infants with a PDA (n = 493) were significantly more immature, had lower birth weights, and had higher rates of respiratory distress syndrome than those without PDA (n = 475). TGF-ß on days 3 and 7 of life, respectively, were significantly lower among neonates with PDA (median 1,177 pg/ml [range 642-1,896]; median 1,386 pg/ml [range 868-1,913]) compared with others without PDA (median 1,334 pg/ml [range 760-2,064]; median 1,712 pg/ml [range 1,014-2,518 pg/ml]). The significant difference persisted when death or PDA was considered a composite outcome. TGF-ß levels were not significantly different among subgroups of infants with PDA who were not treated (n = 51) versus those who were treated medically (n = 283) or by surgical ligation (n = 159). TGF-ß was not a significant predictor of death or PDA (day 3 odds ratio [OR] 0.99, 95 % confidence interval [CI] 0.83-1.17; day 7 OR 0.88, 95 % CI 0.74-1.04) on adjusted analyses. Our results suggest that blood spot TGF-ß alone is unlikely to be a reliable biomarker of a clinically significant PDA or its responsiveness to treatment.

Maternal age and body mass index as risk factors for rectovaginal colonization with group B streptococci.

OBJECTIVE: To examine the effect of including maternal age and body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) as additional risk factors in the traditional risk-based strategy at term pregnancies consisting of previous early-onset group B streptococcus (GBS) disease, GBS bacteriuria during pregnancy, maternal temperature of 38.0°C or more intrapartum, and rupture of membranes of 18 h or longer. METHODS: A secondary analysis of a Danish cohort including 902 pregnant women. Exposures were maternal age and pre-pregnancy BMI. Outcome was rectovaginal GBS colonization at the time of labor. The logistic regression analysis adjusted for parity, gestational age, vaginal delivery, and smoking. RESULTS: The GBS prevalence was 17% in the entire population, 35% among participants older than 40 years, and 23% among those with a BMI of 25 or greater. Including maternal "age > 40" as an additional risk factor increased the sensitivity of the risk-based strategy from 21% to 26% and decreased the specificity from 90% to 87%. Inclusion of "BMI ≥ 25" increased the sensitivity from 21% to 57% and decreased the specificity from 90% to 59%. CONCLUSIONS: Maternal age and BMI might be included as additional risk factors in risk-based programs for identification of GBS-positive laboring women to receive intrapartum antibiotics prophylaxis.

Amniotic fluid chemokines and autism spectrum disorders: an exploratory study utilizing a Danish Historic Birth Cohort.

INTRODUCTION: Elevated levels of chemokines have been reported in plasma and brain tissue of individuals with Autism Spectrum Disorders (ASD). The aim of this study was to examine chemokine levels in amniotic fluid (AF) samples of individuals diagnosed with ASD and their controls. MATERIAL AND METHODS: A Danish Historic Birth Cohort (HBC) kept at Statens Serum Institute, Copenhagen was utilized. Using data from Danish nation-wide health registers, a case-control study design of 414 cases and 820 controls was adopted. Levels of MCP-1, MIP-1α and RANTES were analyzed using Luminex xMAP technology. Case-control differences were assessed as dichotomized at below the 10th percentile or above the 90th percentile cut-off points derived from the control biomarker distributions (logistic regression) or continuous measures (tobit regression). RESULTS AND CONCLUSION: AF volume for 331 cases and 698 controls was sufficient for Luminex analysis. Including all individuals in the cohort yielded no significant differences in chemokine levels in cases versus controls. Logistic regression analyses, performed on individuals diagnosed using ICD-10 only, showed increased risk for ASD with elevated MCP-1 (elevated 90th percentile adjusted OR: 2.32 [95% CI: 1.17-4.61]) compared to controls. An increased risk for infantile autism with elevated MCP-1 was also found (adjusted OR: 2.28 [95% CI: 1.16-4.48]). Elevated levels of MCP-1 may decipher an etiologic immunologic dysfunction or play rather an indirect role in the pathophysiology of ASD. Further studies to confirm its role and to identify the potential pathways through which MCP-1 may contribute to the development of ASD are necessary.

Cytokine profiles of preterm neonates with fungal and bacterial sepsis.

BACKGROUND: Information on cytokine profiles in fungal sepsis (FS), an important cause of mortality in extremely low birthweight (ELBW) infants, is lacking. We hypothesized that cytokine profiles in the first 21 d of life in ELBW infants with FS differ from those with bacterial sepsis (BS) or no sepsis (NS). METHODS: In a secondary analysis of the National Institute of Child Health and Human Development Cytokine study, three groups were defined-FS (≥1 episode of FS), BS (≥1 episode of BS without FS), and NS. Association between 11 cytokines assayed in dried blood spots obtained on days 0-1, 3 ± 1, 7 ± 2, 14 ± 3, and 21 ± 3 and sepsis group was explored. RESULTS: Of 1,066 infants, 89 had FS and 368 had BS. As compared with BS, FS was more likely to be associated with lower birthweight, vaginal delivery, patent ductus arteriosus, postnatal steroids, multiple central lines, longer respiratory support and hospital stay, and higher mortality (P < 0.05). Analyses controlling for covariates showed significant group differences over time for interferon-γ (IFN-γ), interleukin (IL)-10, IL-18, transforming growth factor-ß (TGF-ß), and tumor necrosis factor-α (TNF-α) (P < 0.05). CONCLUSION: Significant differences in profiles for IFN-γ, IL-10, IL-18, TGF-ß, and TNF-α in FS, BS, or NS in this hypothesis-generating secondary study require validation in rigorously designed prospective studies and may have implications for diagnosis and treatment.

Pre-, peri- and neonatal risk factors for autism.

OBJECTIVE: To identify pre-, peri- and neonatal risk factors for pervasive developmental disorders (PDD). METHODS: We searched the Medline database through March 2011 for relevant case-control and population-based studies on pre-, peri- and neonatal hazards related to PDD, including autism. We identified 85 studies for this review. Data were extracted systematically and organized according to risk factors related to family history, pregnancy, gestational age, delivery, birth milestones and the neonate's condition at birth. RESULTS: During the prenatal period, risk factors for PDD were advanced maternal or paternal ages, being firstborn vs. third or later, maternal prenatal medication use and mother's status as foreign born. During the perinatal and neonatal periods, the risk factors for PDD were preterm birth, breech presentation, planned cesarean section, low Apgar scores, hyperbilirubinemia, birth defect and a birthweight small for gestational age. The influence of maternal pre-eclampsia, diabetes, vomiting, infections and stress during pregnancy requires further study in order to determine risk for PDD. DISCUSSION: Despite evidence for the association of some pre-, peri- and neonatal risk factors associated with PDD, it remains unclear whether these risks are causal or play a secondary role in shaping clinical expression in individuals with genetic vulnerability. A plausible hypothsesis is that improvements in obstetric and neonatal management have led to an increased rate of survivors with pre-existing brain damage. Given the variety of risk factors, we propose that future studies should investigate combinations of multiple factors, rather than focusing on a single factor.

Cytokines and posthemorrhagic ventricular dilation in premature infants.

OBJECTIVE: To determine in extremely low-birth-weight infants if elevated blood interferon-γ (IFN-γ), interleukin (IL)-1ß, IL-18, tumor necrosis factor-α (TNF-α), and transforming growth factor-ß are associated with need for shunt following severe intraventricular hemorrhage (IVH) or with ventricular dilation following milder grades/no IVH. STUDY DESIGN: Whole blood cytokines were measured on postnatal days 1, 3, 7, 14, and 21. Maximum IVH grade in the first 28 days, and shunt surgery or ventricular dilation on subsequent ultrasound (28 days' to 36 weeks' postmenstrual age) were determined. RESULTS: Of 902 infants in the National Institute of Child Health and Human Development Neonatal Research Network Cytokine study who survived to 36 weeks or discharge, 3.1% had shunts. Of the 12% of infants with severe (grade III to IV) IVH, 26% had a shunt associated with elevated TNF-α. None of the infants without IVH (69%) or with grade I (12%) or II (7%) IVH received shunts, but 8.4% developed ventricular dilation, associated with lower IFN-γ and higher IL-18. CONCLUSION: Statistically significant but clinically nondiscriminatory alterations in blood cytokines were noted in infants with severe IVH who received shunts and in those without severe IVH who developed ventricular dilation. Blood cytokines are likely associated with brain injury but may not be clinically useful as biomarkers for white matter damage.

Polymerase chain reaction for Group B Streptococci (GBS) at labor highly correlates with vaginal GBS load.

OBJECTIVE: To explore factors associated with a high vaginal GBS load during labor considering (1) the recto-vaginal GBS load at 35-37 weeks' gestation determined by culture and (2) the vaginal GBS colonization determined by a polymerase chain reaction (PCR) assay during labor. METHODS: From an unselected cohort of 902 pregnant women, we obtained (1) recto-vaginal swabs for culture of GBS at 35-37 weeks' gestation (GBSrectovag-36), (2) vaginal swabs for GBS PCR detection at labor (PCRvag-labor), and (3) vaginal swabs for culture of GBS at labor (GBSvag-labor). The GBS load was classified semi quantitatively according to a culture protocol without prior broth enrichment of the swab samples: none (0), few (+), some (++), or many (+++) GBS colonies. RESULTS: Among 902 unselected pregnant women, 859 (95%) had a vaginal swab culture taken at labor, which was classified semi quantitatively. High load GBSvag-labor (+++) were found in 31 participants. GBSrectovag-36 showed a sensitivity of 90% (28/31) and a PPV of 23% (28/121), whereas PCRvag-labor had a sensitivity of 98% (30/31, non-significant difference) and a PPV of 42% (30/71, p < .01). PCR at labor had a lower sensitivity (78%) for detection of vaginal colonization with GBS at labor (any load) compared to recto/vaginal colonization with GBS at 36 weeks (92%). Vaginal colonization with GBS at 36 weeks seemed to have a lower sensitivity for detecting GBS in vagina at labor for high load (48%) and for any load (39%). CONCLUSION: PCR at labor has higher detection rate (non-significant) and PPV in identification of laboring women with a high load of vaginal GBS compared with recto-vaginal culture at 36 weeks' gestation.

Cytokines and neurodevelopmental outcomes in extremely low birth weight infants.

OBJECTIVE: To determine if selected pro-inflammatory and anti-inflammatory cytokines and/or mediators of inflammation reported to be related to the development of cerebral palsy (CP) predict neurodevelopmental outcome in extremely low birth weight infants. STUDY DESIGN: Infants with birth weights ≤1000 g (n = 1067) had blood samples collected at birth and on days 3 ± 1, 7 ± 1, 14 ± 3, and 21 ± 3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on 5 cytokines (interleukin [IL] 1ß; IL-8; tumor necrosis factor-α; regulated upon activation, normal T-cell expressed, and secreted (RANTES); and IL-2) reported to be most predictive of CP in term and late preterm infants. RESULTS: IL-8 was higher on days 0-4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, tumor necrosis factor-ß, soluble IL rα, macrophage inflammatory protein 1ß) were found to be altered on days 0-4 in infants who developed CP. CONCLUSIONS: CP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin.

T cell cytokines and the risk of blood stream infection in extremely low birth weight infants.

Cytokines mediate the host immune response to infectious micro-organisms. The objective of this study was to determine whether immune regulatory interleukins (IL-4, IL-5, IL-6, and IL-10) and inflammatory cytokines (Interferon-γ [INF-γ], tumor necrosis factor-ß [TNF-ß], IL-2, and IL-17) are associated with an increased risk of developing blood stream bacterial/fungal infection (BSI) in extremely low birth weight (ELBW) infants. ELBW infants from 17 NICHD Neonatal Research Network centers without early onset sepsis were studied. Cytokines were measured from blood on days 1, 3, 7, 14, and 21 after birth. 996 ELBW infants contributed a minimum of 4080 unique measurements for each cytokine during the five sampling periods. Infants with BSI had lower levels of the inflammatory cytokines IL-17 (p=0.01), and higher levels of the regulatory cytokines, IL-6 (p=0.01) and IL-10 (p<0.001). Higher levels of regulatory cytokines relative to pro-inflammatory cytokines were associated with increased risk of BSI even after adjusting for confounding variables. In ELBW infants, the ratio of immune regulatory cytokines to inflammatory cytokines was associated with development of BSI. Altered maturation of regulatory and inflammatory cytokines may increase the risk of serious infection in this population.

Risk factors for cerebral palsy in children born at term.

OBJECTIVE: To provide an overview of current research on risk factors for cerebral palsy (CP) in children born at term and hypothesize how new findings can affect the content of the CP registers worldwide. DESIGN: A systematic search in PubMed for original articles, published from 2000 to 2010, regarding risk factors for CP in children born at term was conducted. METHODS: Full text review was made of 266 articles. MAIN OUTCOME MEASURES: Factors from the prenatal, perinatal and neonatal period considered as possible contributors to the causal pathway to CP in children born at term were regarded as risk factors. RESULTS: Sixty-two articles met the criteria for an original report on risk factors for CP in children born at term. Perinatal adverse events, including stroke, were the focus of most publications, followed by genetic studies. Malformations, infections, perinatal adverse events and multiple gestation were risk factors associated with CP. The evidence regarding, for example, thrombophilic factors and non-CNS abnormalities was inconsistent. CONCLUSIONS: Information on maternal and neonatal infections, umbilical cord blood gases at birth, mode of delivery and placental status should be collected in a standardized way in CP registers. Information on social factors, such as education level, family income and area of residence, is also of importance. More research is needed to understand the risk factors of CP and specifically how they relate to causal pathways of cerebral palsy.

Low serum interleukin-17 is associated with preterm delivery.

OBJECTIVE: To study maternal serum interleukin-17 (IL-17) during normal pregnancy and evaluate the association with preterm delivery. DESIGN: Prospective study. SETTING: Aarhus University Hospital, Denmark. POPULATION: Three cohorts: (a) low-risk cohort of 1,069 women who had serum drawn in weeks 12 and 19, (b) subgroup of the low-risk cohort, consisting of 40 women, who had serum drawn at 12, 19, 26, 33 and 39 weeks of gestation and (c) a symptomatic cohort of 93 women admitted with symptoms of preterm delivery at a gestational age of 24(+ 0) weeks to 33(+ 6) weeks. METHODS: Serum IL-17 determined by an in-house developed multiplex sandwich immunoassay. MAIN OUTCOME MEASURES: Preterm delivery <37(+0) weeks gestation. RESULTS: Serum IL-17 did not change during normal pregnancy. At admission to hospital, women with preterm contractions had significantly decreased serum IL-17 as compared with normal pregnancies (median <4 [interquartile ranges, IQR, <4-10 pg/ml] vs. 174 pg/ml [IQR, 92 - 485 pg/ml]); this difference was enhanced and highly significant for women delivering preterm versus term (median <4 [IQR, <4-7.9 pg/ml] vs. median 6.0 [IQR, <4-221 pg/ml]; p-value 0.03). Serum IL-17 was also lower in women with preterm prelabor rupture of membranes. A slightly, but not statistically significant decrease was found in weeks 12 and 19 in low-risk women who subsequently delivered preterm. CONCLUSION: Maternal serum IL-17 may be involved in preterm delivery.

Parental infertility and cerebral palsy in children.

BACKGROUND: Children born after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have been reported to have a higher risk of cerebral palsy (CP), perhaps due to the higher frequency of preterm birth, multiple births or vanishing embryo in the pregnancies. However, it has been suggested that the underlying infertility may be part of the pathway. In this study, we examined whether untreated subfecundity (measured by time to pregnancy) or infertility treatment was associated with an increased risk of CP in the offspring. METHODS: Using the Danish National Birth Cohort (1997-2003), we compared children born after 0-2 months of waiting time to pregnancy (n = 35 848) with those born after a time to pregnancy of 3-5 months (n = 15 361), 6-12 months (n = 11 528) and >12 months (n = 7387), as well as those born after IVF/ICSI (n = 3617), ovulation induction with or without intrauterine insemination (n = 3000), and unplanned pregnancies (n = 13 462). CP cases were identified through the Danish CP Register. RESULTS: In total, 165 (0.18%) children were diagnosed with CP in the entire cohort. We found no significant association between time to pregnancy and the risk of CP in children conceived spontaneously. Children born after IVF/ICSI had an increased risk of CP, even after adjustment for preterm birth and multiplicity (hazard ratio 2.30, 95% confidence interval 1.12-4.73). CONCLUSIONS: Subfecundity per se did not appear to be associated with the risk of CP in children, whereas being born after IVF/ICSI conferred an increased risk.

Mid-trimester maternal plasma cytokines and CRP as predictors of spontaneous preterm birth.

Most previous studies of maternal cytokines and preterm birth have analyzed immunologic biomarkers after the onset of labor or membrane rupture; fewer have examined the systemic (blood) immune response prior to labor onset. We carried out a case-control study nested in a large (n=5337) prospective, multi-center cohort. Cohort women had an interview, examination, and venipuncture at 24-26 weeks. Frozen plasma samples in women with spontaneous preterm birth (n=207) and approximately 2 term controls per case (n=444) were analyzed using Luminex multianalyte profiling technology. Fresh placentas were fixed, stained, and blindly assessed for histologic evidence of infection/inflammation, decidual vasculopathy, and infarction, and vaginal swabs were analyzed for bacterial vaginosis and fetal fibronectin concentration. High maternal matrix metalloproteinase-9 (MMP-9) concentration, but none of the other cytokines or C-reactive protein (CRP), was significantly associated with spontaneous preterm birth [adjusted OR=1.7 (1.1-2.4)] and showed a dose-response relation across quartiles. No association was observed, however, between maternal MMP-9 and placental infection/inflammation, bacterial vaginosis, or vaginal fetal fibronectin concentration. Our results require confirmation in future studies but suggest that a systemic immune response implicating MMP-9 may have an etiologic role in spontaneous preterm birth.

Perinatal systemic inflammatory response syndrome and retinopathy of prematurity.

Fetal and neonatal inflammation is associated with several morbidities of prematurity. Its relationship to retinopathy of prematurity (ROP) has not been investigated. Our objective was to determine the relationship between cytokine levels and ROP in the first 3 postnatal wks. Data for this study were derived from the NICHD Cytokine Study. Dried blood spots (DBS) were obtained from infants <1000 g on days 0-1, 3 +/- 1, 7 +/- 2, 14 +/- 3, and 21 +/- 3. Infants were classified into three groups-no, mild, and severe ROP. Multiplex Luminex assay was used to quantify 20 cytokines. Temporal profiles of cytokines were evaluated using mixed-effects models after controlling for covariates. Of 1074 infants enrolled, 890 were examined for ROP and 877 included in the analysis. ROP was associated with several clinical characteristics on unadjusted analyses. Eight cytokines remained significantly different across ROP groups in adjusted analyses. IL-6 and IL-17 showed significant effects in early time periods (D0-3); TGF-beta, brain-derived neurotrophic factor (BDNF), and regulated on activation, normal T cell expressed and secreted (RANTES) in later time periods (D7-21) and IL-18, C-reactive protein (CRP), and neurotrophin-4 (NT-4) in both early and later time periods. We conclude that perinatal inflammation may be involved in the pathogenesis of ROP.

Circulating beta chemokine and MMP 9 as markers of oxidative injury in extremely low birth weight infants.

Matrix metalloproteinases (MMPs) and chemokines seem to be induced by hyperoxia in preclinical studies. We hypothesized that O2 exposure immediately after birth is associated with altered blood spot MMP 9 and beta chemokine concentrations. The following analytes were measured on blood spots on d 1 and 3 of life, using luminex technology in 1059 infants (birth weights <1000 g) in the NICHD Neonatal Research Network: MMP 9, monocyte chemoattractant protein 1 (MCP 1), macrophage inflammatory proteins (1alpha and beta), and regulated upon activation, normal t cell expressed and secreted (RANTES). Infants administered O2 continually from 6 to 24 h of life (n = 729), when compared with those with <6 h exposure (n = 330), had significantly lower mean birth weight and higher rate of respiratory distress syndrome (p < 0.002). On d 3, MCP 1 was higher and RANTES lower among infants with early prolonged O2 exposure. After adjusting for covariates, prolonged early O2 exposure retained a statistically significant association with higher MCP 1 on d 3 (p = 0.003). The consistent association between O2 exposure and MCP 1 among extremely preterm infants suggests that further investigation of its role in oxidative injury is warranted.

Lifestyle during pregnancy: neurodevelopmental effects at 5 years of age. The design and implementation of a prospective follow-up study.

BACKGROUND: It has been suggested that even mild exposure to alcohol, caffeine, smoking, and poor diet may have adverse long-term neurodevelopmental effects. In addition, there is evidence that timing of high exposures (e.g. binge drinking) can have particularly negative effects. This paper describes the design and implementation of The Lifestyle During Pregnancy Study addressing major methodological challenges for studies in this field. The study examines the effects of lifestyle during pregnancy on offspring neurodevelopment. METHODS: In 2003, we initiated a prospective follow-up of 1750 mother-child pairs, sampled on the basis of maternal alcohol drinking patterns from The Danish National Birth Cohort (DNBC), a study of 101,042 pregnancies enrolled 1997-2003. Data collection in the DNBC involved four prenatal and postnatal maternal interviews, providing detailed information on maternal alcohol drinking patterns before and during pregnancy, caffeine intake, smoking, diet, and other lifestyle, medical, and sociodemographic factors. RESULTS: At the age of 5 years, the children and their mothers participated in a comprehensive assessment of neurobehavioural development focusing on global cognition, specific cognitive functions, and behaviour. Two new tests assessing attention and speed of information processing among children were developed, and data on important potential confounders such as maternal intelligence quotient, vision, and hearing abilities were collected. Efforts were made to standardise procedures and obtain high inter-rater reliability. CONCLUSIONS: We expect that the study will illuminate the significance or lack of significance of maternal lifestyle during pregnancy and contribute to better understanding the effects of alcohol drinking during pregnancy at low to moderate consumption levels.

Urine dipstick for predicting intrapartum recto-vaginal colonisation by group B streptococci.

INTRODUCTION: In pregnant women, bacteriuria with group B streptococci (GBS) may be associated with a high degree of recto-vaginal GBS colonisation and therefore an increased risk of early-onset GBS disease. The aim of this study was to assess the performance of routine use of dipstick urine analysis during pregnancy for prediction of recto-vaginal GBS colonisation at the time of labour. METHODS: Among 902 unselected Danish pregnant women, we obtained results from 1) dipstick urine analysis, 2) urine culture carried out during pregnancy, if indicated, and 3) recto-vaginal culture at labour. The inclusion criteria were age > 18 years and gestational age ≥ 37 weeks. RESULTS: Intrapartum recto-vaginal GBS colonisation was predicted by a positive urine dipstick with 5% sensitivity only. CONCLUSION: Dipstick urine analysis had a low sensitivity for predicting intrapartum recto-vaginal colonisation with GBS. FUNDING: none. TRIAL REGISTRATION: not relevant.