Impact of prenatal estimation of the risk of respiratory distress in neonates with congenital pulmonary malformations on the choice of delivery site.

BACKGROUND: The vast majority of prenatally diagnosed congenital pulmonary malformations (CPM) remain asymptomatic at birth. The maximal value of the CPM volume ratio (CVRmax) predicts the risk of neonatal respiratory distress (NRD), and should allow for better assessment of the level of expertise needed at the delivery site. AIM: This study evaluated the level of maternity units currently chosen for the delivery of CPMs, and determined the impact of the choice of delivery site based on the CVRmax, with a threshold of 0.4 cm2. METHODS: Data were extracted from the French prospective MALFPULM cohort, with inclusion between March 2015 and June 2018. RESULTS: The final study population consisted of 383 women. Deliveries in level 1 or 2 maternity units (n = 98, 25%) involved CPMs with lower CVRmax (p<0.001), causing fewer signs of prenatal compression (p = 0.025). Among the 62 children (16%) who presented with NRD, only seven (11%) were born in level 1 or 2 units (p = 0.0078). Choosing the maternity level according to the CVRmax would have increased the number of births in level 1 or 2 maternity hospitals by 70%. In these maternity units, the percentage of children with NRD would have increased from 8% in the actual distribution to 10% in the new strategy. CONCLUSION: Our results showed an overuse of level 3 maternity hospitals for the delivery of newborns with a prenatal diagnosis of CPM. The use of CVRmax should enable a reduction in the use of expertise centers without an adverse impact on newborns.

Respiratory morbidity in children with congenital heart disease.

OBJECTIVE: To evaluate the respiratory outcome in children with congenital heart disease (CHD), considering recent management procedures and the CHD pathophysiology. DESIGN AND SETTING: Clinical and functional respiratory outcome were evaluated in 8-year-old children with isolated CHD followed up from birth in the prospective population-based EPICARD cohort. PATIENTS: Children were assigned to two groups, based on the pathophysiology of the CHD: CHDs with left-to-right shunt (n = 212) and CHDs with right outflow tract obstruction (n = 113). RESULTS: Current wheezing episodes were observed in 15% of the children with isolated CHD and left-to-right shunt, and 11% of the children with isolated CHD and right outflow tract obstruction (not significant). Total lung capacity (TLC) was the only respiratory function parameter that significantly differed between the two groups. It was lower in children with left-to-right shunt (88.72 ± 0.65% predicted) than in those with right outflow tract obstruction (91.84 ± 0.96, p = 0.006). In multivariate analysis, CHD with left-to-right shunt (coeff. [95% CI]: -3.17 [-5.45; -0.89]) and surgery before the age of 2 months (-6.52 [-10.90; -2.15]) were identified as independent factors associated with significantly lower TLC values. CONCLUSION: Lower TLC remains a long-term complication in CHD, particularly in cases with left-to-right shunt and in patients requiring early repair. These findings suggest that an increase in pulmonary blood flow may directly impair lung development.

Prenatal natural history of congenital pulmonary malformations: MALFPULM population-based cohort study.

OBJECTIVES: To assess prenatal changes in the volume of congenital pulmonary malformations (CPM) and examine whether these changes differ in lesions that appear cystic on ultrasound compared with hyperechoic lesions, and to study the relationship between CPM volume and risk of fetal compression. METHODS: We conducted a nationally representative, multicenter, prospective cohort study, which included 579 ultrasound examinations in 176 pregnant women with a diagnosis of fetal CPM, between March 2015 and November 2016. Several ultrasound examinations were performed between diagnosis and delivery, including measurement of CPM volume. We modeled changes in CPM volume ratio (CVR) as a function of gestational age, overall and for cystic/mixed vs hyperechoic malformations, and examined the association between CVR and signs of compression during pregnancy. RESULTS: When modeling CVR changes over time, there was a statistically significant decrease in CVR with increasing gestational age (P < 0.001), but the pattern of change differed according to CPM phenotype at first ultrasound examination: cystic/mixed CPM were characterized by a monotonic decrease in CVR with increasing gestational age (P = 0.002), whereas hyperechoic CPM showed an initial increase in CVR up to 27 weeks of gestation, followed by a decrease thereafter (P < 0.001). Peak CVR values were predicted as early as 21-22 weeks for cystic/mixed CPMs compared with 25-26 weeks for hyperechoic malformations. Regardless of CPM phenotype, fetuses that showed no sign of compression at any point had substantially lower CVR at first CVR measurement, and the CVR remained relatively constant thereafter. Among the subpopulation of fetuses with no sign of compression at first CVR measurement, the odds of a subsequent compression was 7-fold higher (adjusted odds ratio, 7.0; 95% CI, 1.6-29.9) if initial CVR was > 0.4 vs CVR ≤ 0.4 cm2 . CONCLUSIONS: Predicted changes in CVR during pregnancy differ between cystic and hyperechoic malformations. This may be the result of different pathophysiological mechanisms or differences in the timing of occurrence of these different types of CPM. CVR measured at the initial diagnostic ultrasound examination was strongly associated with the odds of subsequent compression. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Colorectal cancer screening: factors associated with colonoscopy after a positive faecal occult blood test.

BACKGROUND: Contextual socio-economic factors, health-care access, and general practitioner (GP) involvement may influence colonoscopy uptake and its timing after positive faecal occult blood testing (FOBT). Our objectives were to identify predictors of delayed or no colonoscopy and to assess the role for GPs in colonoscopy uptake. METHODS: We included all residents of a French district with positive FOBTs (n = 2369) during one of the two screening rounds (2007-2010). Multilevel logistic regression analysis was performed to identify individual and area-level predictors of delayed colonoscopy, no colonoscopy, and no information on colonoscopy. RESULTS: A total of 998 (45.2%) individuals underwent early, 989 (44.8%) delayed, and 102 (4.6%) no colonoscopy; no information was available for 119 (5.4%) individuals. Delayed colonoscopy was independently associated with first FOBT (odds ratio, (OR)), 1.61; 95% confidence interval ((95% CI), 1.16-2.25); and no colonoscopy and no information with first FOBT (OR, 2.01; 95% CI, 1.02-3.97), FOBT kit not received from the GP (OR, 2.29; 95% CI, 1.67-3.14), and socio-economically deprived area (OR, 3.17; 95% CI, 1.98-5.08). Colonoscopy uptake varied significantly across GPs (P=0.01). CONCLUSION: Socio-economic factors, GP-related factors, and history of previous FOBT influenced colonoscopy uptake after a positive FOBT. Interventions should target GPs and individuals performing their first screening FOBT and/or living in socio-economically deprived areas.

Screening for fetal spina bifida at the 11-13-week scan using three anatomical features of the posterior brain.

OBJECTIVE: To evaluate the contribution of examination of specific anatomical features of the fetal posterior brain on mid-sagittal first-trimester ultrasound examination to the early detection of open spina bifida. METHODS: Four independent observers reviewed a series of 260 mid-sagittal first-trimester ultrasound images from 52 cases of open spina bifida and 208 normal fetuses. The following analysis was performed by each reviewer for each image: Herman score calculation, intracranial translucency score (CFEF-IT) calculation and determination of presence or absence of three anatomical criteria: intracranial translucency (IT), caudal displacement of the brainstem and cisterna magna. The sensitivity and the false-positive rate for spina bifida detection were calculated for each of the latter three criteria. A secondary analysis was performed on the subset of images achieving a Herman score ≥ 7. RESULTS: The highest detection rate for spina bifida was achieved by non-visualization of the cisterna magna, with associated sensitivity of 50-73% and 39-76%, respectively, for all images and for the subset of images achieving a Herman score ≥ 7. Posterior shift of the brainstem achieved the highest detection rate (86%), but for a single reviewer only. The level of variation in performance between observers was also greatest for this sign. Absence of IT was associated with a lower detection rate for all observers. Overall, an abnormal posterior brain presenting at least one of these three criteria was associated with a detection rate ranging from 50 to 90%. CONCLUSION: In the detection of spina bifida, non-visualization of the cisterna magna achieved the best screening performance. Both non-visualization of the IT and posterior shift of the brainstem were associated with acceptable but lower detection rates. A prospective evaluation of changes in the posterior brain is needed to allow assessment of the most pertinent criteria for first-trimester screening for spina bifida.

Prevalence and risk factors of bacterial vaginosis during the first trimester of pregnancy in a large French population-based study.

OBJECTIVES: Bacterial vaginosis is a risk factor for preterm delivery. Its prevalence and risk factors in Europe are not well known. Our objective was to assess both in early pregnancy. STUDY DESIGN: As part of the PREMEVA randomized controlled trial, this population-based study included 14,193 women screened before 14 weeks' gestation for bacterial vaginosis in the 160 laboratories of the Nord-Pas-de-Calais region in France. Bacterial vaginosis was defined by a Nugent score ≥ 7. Data were collected about maternal tobacco use, age, education, and history of preterm birth. We estimated the prevalence of bacterial vaginosis and used a multilevel logistic regression model to identify significant risk factors for it. RESULTS: Among the 14,193 women assessed before 14 weeks' gestation, the prevalence of bacterial vaginosis was 7.1% (95% CI: 6.6-7.5%). In the multivariate analysis, smoking during pregnancy tobacco (adjusted OR: 1.38; 95% CI: 1.19-1.60), maternal age 18-19 years (adjusted OR: 1.40; 95% CI: 1.01-1.93), and educational level (completed only primary school: adjusted OR: 1.77; 95% CI: 1.35-2.31; completed only secondary school: adjusted OR: 1.27; 95% CI: 1.10-1.48) were independent risk factors for bacterial vaginosis. History of preterm delivery was not an independent risk factor of bacterial vaginosis: adjusted OR: 1.15; 95% CI: 0.90-1.47. CONCLUSION: In a large sample of women in their first trimester of pregnancy in France, the prevalence of bacterial vaginosis was lower than rates reported in other countries, but risk factors were similar: young age, low level of education, and tobacco use during pregnancy. These results should be considered in future strategies to reduce preterm delivery.

Visualization of intracranial translucency at the 11-13-week scan is improved after specific training.

OBJECTIVE: To evaluate the ability to confidently identify intracranial translucency (IT) in a clinical practice and following specific training of 10 operators. METHODS: Two experienced observers reviewed 11-13-week nuchal translucency (NT) images for IT visibility in (1) a series of 50 randomly selected images obtained by 10 skilled operators certified by the Collège Français d'Echographie Foetale (CFEF) (retrospective analysis) and (2) a series of 315 images obtained by 10 different operators following specific training for IT visualization (prospective analysis). We calculated proportions of images for which IT was deemed visible and the agreement between the two observers. Data were also stratified by Herman and CFEF quality-score intervals. RESULTS: In the retrospective analysis, IT was visualized by both reviewers in 52% of images, with a moderate level of agreement (κ = 0.63). The rate of IT visualization by both reviewers increased very slightly to 56-58% when only considering images with the best NT quality-control scores. Following specific training of the operators the proportion of images for which both reviewers could identify the fourth ventricle increased to 85%, but the level of agreement remained moderate (κ = 0.66). When considering images with the best NT quality-control scores, IT visualization by both reviewers increased to 91-92%. CONCLUSIONS: In a clinical practice that focuses on NT measurement IT cannot be visualized in a substantial proportion of the images obtained, which limits the utility of this approach for the early prenatal diagnosis of open spina bifida. However, the ability to identify the fourth ventricle significantly increases following specific training.

Survey of prenatal screening policies in Europe for structural malformations and chromosome anomalies, and their impact on detection and termination rates for neural tube defects and Down's syndrome.

OBJECTIVE: To 'map' the current (2004) state of prenatal screening in Europe. DESIGN: (i) Survey of country policies and (ii) analysis of data from EUROCAT (European Surveillance of Congenital Anomalies) population-based congenital anomaly registers. SETTING: Europe. POPULATION: Survey of prenatal screening policies in 18 countries and 1.13 million births in 12 countries in 2002-04. METHODS: (i) Questionnaire on national screening policies and termination of pregnancy for fetal anomaly (TOPFA) laws in 2004. (ii) Analysis of data on prenatal detection and termination for Down's syndrome and neural tube defects (NTDs) using the EUROCAT database. MAIN OUTCOME MEASURES: Existence of national prenatal screening policies, legal gestation limit for TOPFA, prenatal detection and termination rates for Down's syndrome and NTD. RESULTS: Ten of the 18 countries had a national country-wide policy for Down's syndrome screening and 14/18 for structural anomaly scanning. Sixty-eight percent of Down's syndrome cases (range 0-95%) were detected prenatally, of which 88% resulted in termination of pregnancy. Eighty-eight percent (range 25-94%) of cases of NTD were prenatally detected, of which 88% resulted in termination. Countries with a first-trimester screening policy had the highest proportion of prenatally diagnosed Down's syndrome cases. Countries with no official national Down's syndrome screening or structural anomaly scan policy had the lowest proportion of prenatally diagnosed Down's syndrome and NTD cases. Six of the 18 countries had a legal gestational age limit for TOPFA, and in two countries, termination of pregnancy was illegal at any gestation. CONCLUSIONS: There are large differences in screening policies between countries in Europe. These, as well as organisational and cultural factors, are associated with wide country variation in prenatal detection rates for Down's syndrome and NTD.

[Socioeconomic disparities for maternal serum screening of Down's syndrome: trends between 1998 and 2003 in France]. / Disparités socioéconomiques dans le dépistage prénatal de la trisomie 21 par marqueurs sériques: évolution entre 1998 et 2003 en France.

OBJECTIVES: To compare trends in the use of and the opportunity for making an informed choice, regarding maternal serum screening for Down's syndrome. METHODS: Data were based on the national perinatal surveys of 1998 and 2003, which comprise representative samples of births in France. We used logistic regression models and likelihood ratio tests for testing the statistical significance of interactions between time trends and socioeconomic factors. RESULTS: We found a generalized increase between 1998 and 2003 in both the use of screening and in the opportunity for making an informed choice. The use of screening increased more however, for women with primary or no education (OR=3.0; 95% CI, 2.2-4.1) as compared with those with education levels beyond a high school diploma (OR: 1.8; 95% CI, 1.7-2.0). On the contrary, trends in informed choice were comparable across socioeconomic groups. Hence, disparities in the opportunity for informed choice were essentially unchanged. CONCLUSIONS: The use of serum screening, and the opportunity for informed choice regarding the test, became more widespread for women from all socioeconomic categories between 1998 and 2003. These trends were accompanied by a decrease in socioeconomic disparities in the use of screening but not in the opportunity for making an informed choice.

Injury related infant death: the impact of race and birth weight.

OBJECTIVE: To examine the effect of race and birth weight independent of other sociodemographic factors on injury related infant death using national data. SETTING: Infants born in the United States to mothers who were white (non-Hispanic), African American, Mexican American, and Native American. METHODS: Linked infant birth and death data from the National Center for Health Statistics for 1989-91 were analyzed to calculate unadjusted and adjusted odds ratios for death due to homicide or unintentional injury within the first year of life. In addition to maternal race and birth weight, the risk of death was adjusted for maternal age, prenatal care, maternal education, paternal education, marital status, birth order, interval since last pregnancy, smoking during pregnancy, and alcohol intake during pregnancy. RESULTS: Among 10.7 million births during 1989-91, 821 homicides and 2397 unintentional deaths were reported in infants. Relative to whites, African Americans were at highest risk for homicides (unadjusted and adjusted odds ratios = 3.6 (95% confidence interval = 3.1 to 4.2) and 1.6 (1.3 to 1.9), respectively) and Native Americans at highest risk for unintentional injuries (unadjusted and adjusted odds ratios = 3.8 (3.0 to 4.8) and 2.1 (1.7 to 2.6), respectively). After accounting for other sociodemographic factors, Mexican American infants appeared protected from injury (adjusted odds ratio = 0.7 (0.6 to 1.0) for homicides and 0.7 (0.6 to 0.8) for unintentional injuries). An inverse effect of birth weight was seen-as birth weight decreased, risk of homicides and unintentional injuries increased. After adjustment for the sociodemographic factors, very low birthweight babies were still at substantially increased risk of homicides with an odds ratio of 2.1 (1.4 to 3.1) and unintentional injuries with an odds ratio of 2.9 (2.4 to 3.7). CONCLUSIONS: Using a large national data-set, the effect of race as a risk factor for fatal infant injuries was mostly explained by birth weight and other sociodemographic factors. Preventable risk factors need to be identified for African Americans and Native Americans, in particular. Birth weight is an important independent risk factor; very low birthweight babies should be monitored for both homicide and unintentional injury.

Short interpregnancy intervals and the risk of adverse birth outcomes among five racial/ethnic groups in the United States.

The authors studied the effects and population-level impact of short (< or = 12 months) interpregnancy intervals on the risks for low (<2.5 kg) birth weight and preterm (<37 weeks) delivery of liveborn singleton infants to US African American, Mexican, Native American, non-Hispanic white, and Puerto Rican mothers (n = 4,841,418) from 1989 to 1991. Statistical analyses were done by using the Mantel-Haenszel correlation statistic chi-square test and logistic regression. The proportion of livebirths associated with < or =12-month interpregnancy intervals was the lowest among non-Hispanic whites (18.5%, 95% confidence interval 18.5-18.5) and the highest among Native Americans (29.7%, 95% confidence interval 29.2-30.2). As compared with mothers with >12-month intervals, mothers with <6-month intervals had an approximately 50% to 80% increased risk of very low (<1.5 kg) birth weight delivery and a 30% to 90% increased risk of very preterm (<32 weeks) delivery. Logistic regression analyses showed that the adverse effects of short intervals were reduced by about 10% but remained for the most part significant after controlling for potential confounding by maternal age, education, parity, marital status, prenatal care, smoking, and previous preterm delivery.

Acquisition of interleukin-5 secretion by human naive T-helper cells is regulated by distinct signals from both the T-cell receptor/CD3 complex and CD2.

We developed a human naive T-helper (Th) cell differentiation model with anti-CD3 monoclonal antibody (MoAb), using a B-cell line as source of costimulation. In this system, we examined the contribution of the T-cell receptor (TCR)/CD3-derived signals and that of lymphocyte function-associated antigen-1 (LFA-1) and CD2 in regulating Th-cell subset differentiation. We found that lowering the level of anti-CD3 MoAb decreased tumour necrosis factor-alpha (TNF-alpha) production, while increasing secretion of the Th2 cytokines, interleukin-5 (IL-5) and interleukin-13 (IL-13). Secretion of interferon-gamma (IFN-gamma) was not influenced by the strength of the anti-CD3 signal. Under conditions where Th0 cells are generated, co-culture with anti-CD2 F(ab')2 MoAb led to the generation of Th cells that secreted 30-35% less IL-5, while not affecting secretion of IFN-gamma or granulocyte-macrophage colony-stimulating factor (GM-CSF). By contrast, anti-CD18 MoAb F(ab')2 inhibited IFN-gamma and GM-CSF levels only in the primary stimulation, but did not affect cytokine levels after restimulation. Neither anti-CD2 nor anti-CD18 F(ab')2 MoAbs could alter cytokine secretion profiles of peripheral blood-derived memory/effector Th cells. Our results indicate that acquisition of IL-5 secretion capability by Th cells is regulated mainly by signals transduced by the TCR/CD3 complex and by the presence of interleukin-4 (IL-4), while the CD2/LFA-3 pathway plays an additional, but minor, role. These regulatory CD2-derived signals, however, are distinct from those generated by the TCR/CD3 complex.

Epidemiology of common neurosurgical diseases in the neonate.

This article reviews the epidemiology and risk factors of posthemorrhagic hydrocephalus and neural tube defects (NTDs). Posthemorrhagic hydrocephalus is discussed in terms of risk factors for intraventricular hemorrhage. Four categories of risk factors are presented: maturational factors, antepartum factors, peripartum factors, and factors conferred by postnatal conditions. The complex epidemiology of neural tube defects is discussed in terms of person, place, and time. Interventional strategies, including antenatal screening and nutritional supplementation for NTD prevention, are reviewed.