Understanding high rates of stillbirth and neonatal death in a disadvantaged, high-migrant district in France: A perinatal audit.

INTRODUCTION: The objective of this study is to investigate factors associated with risks of perinatal death in a disadvantaged, high-migrant French district with mortality rates above the national average. MATERIAL AND METHODS: The study design is a perinatal audit in 2014 in all 11 maternity units in the Seine-Saint-Denis district (25 037 births). The data come from medical chart abstraction, maternal interviews and peer assessor confidential review of deaths. A representative sample of live births in the same district, from the 2010 French Perinatal Survey, was used for comparisons (n = 429). The main outcome measures were stillbirth and neonatal death (0-27 days) at ≥22 weeks of gestation. RESULTS: The audit included 218 women and 227 deaths (156 stillbirths, 71 neonatal deaths); 75 women were interviewed. In addition to primiparity and multiple pregnancy, overweight and obesity increased mortality risks (50% of cases, adjusted odds ratios [aOR] 1.7, 95% confidence interval [CI] 1.1-2.8, and aOR 1.9 [95% CI 1.1-3.2], respectively) as did the presence of preexisting medical/obstetric conditions (28.6% of cases, aOR 3.2, 95% CI 2.0-5.3). Problems accessing or complying with care were noted in 25% of medical records and recounted in 50% of interviews. Assessors identified suboptimal factors in 73.2% of deaths and judged 33.9% to be possibly or probably preventable. Care not adapted to risk factors and poor healthcare coordination were frequent suboptimal factors. Possibly preventable deaths were higher (P < .05) for women with gestational diabetes or hypertension (44.6%) than women without (29.0%). CONCLUSIONS: Preventive actions to improve healthcare referral and coordination, especially for overweight and obese women and women with medical and obstetrical risk factors, could reduce perinatal mortality in disadvantaged areas.

Intensity of perinatal care for extremely preterm babies and outcomes at a higher gestational age: evidence from the EPIPAGE-2 cohort study.

BACKGROUND: Perinatal decision-making affects outcomes for extremely preterm babies (22-26 weeks' gestational age (GA)): more active units have improved survival without increased morbidity. We hypothesised such units may gain skills and expertise meaning babies at higher gestational ages have better outcomes than if they were born elsewhere. We examined mortality and morbidity outcomes at age two for babies born at 27-28 weeks' GA in relation to the intensity of perinatal care provided to extremely preterm babies. METHODS: Fetuses from the 2011 French national prospective EPIPAGE-2 cohort, alive at maternal admission to a level 3 hospital and delivered at 27-28 weeks' GA, were included. Morbidity-free survival (survival without sensorimotor (blindness, deafness or cerebral palsy) disability) and overall survival at age two were examined. Sensorimotor disability and Ages and Stages Questionnaire (ASQ) result below threshold among survivors were secondary outcomes. Perinatal care intensity level was based on birth hospital, grouped using the ratio of 24-25 weeks' GA babies admitted to neonatal intensive care to fetuses of the same gestation alive at maternal admission. Sensitivity analyses used ratios based upon antenatal steroids, Caesarean section, and newborn resuscitation. Multiple imputation was used for missing data; hierarchical logistic regression accounted for births nested within centres. RESULTS: 633 of 747 fetuses (84.7%) born at 27-28 weeks' GA survived to age two. There were no differences in survival or morbidity-free survival: respectively, fully adjusted odds ratios were 0.96 (95% CI: 0.54 to 1.71) and 1.09 (95% CI: 0.59 to 2.01) in medium and 1.12 (95% CI: 0.63 to 2.00) and 1.16 (95% CI: 0.62 to 2.16) in high compared to low-intensity hospitals. Among survivors, there were no differences in sensorimotor disability or ASQ below threshold. Sensitivity analyses were consistent with the main results. CONCLUSIONS: No difference was seen in survival or morbidity-free survival at two years of age among fetuses alive at maternal hospital admission born at 27-28 weeks' GA, or in sensorimotor disability or presence of an ASQ below threshold among survivors. There is no evidence for an impact of intensity of perinatal care for extremely preterm babies on births at a higher gestational age.

Intensity of perinatal care, extreme prematurity and sensorimotor outcome at 2 years corrected age: evidence from the EPIPAGE-2 cohort study.

BACKGROUND: Emerging evidence suggests intensity of perinatal care influences survival for extremely preterm babies. We evaluated the effect of differences in perinatal care intensity between centres on sensorimotor morbidity at 2 years of age. We hypothesised that hospitals with a higher intensity of perinatal care would have improved survival without increased disability. METHODS: Foetuses alive at maternal admission to a level 3 hospital in France in 2011, subsequently delivered between 22 and 26 weeks gestational age (GA) and included in the EPIPAGE-2 national prospective observational cohort study formed the baseline population. Level of intensity of perinatal care was assigned according to hospital of birth, categorised into three groups using 'perinatal intensity' ratios (ratio of 24-25 weeks GA babies admitted to neonatal intensive care to foetuses of the same GA alive at maternal admission to hospital). Multiple imputation was used to account for missing data; hierarchical logistic regression accounting for births nested within centres was then performed. RESULTS: One thousand one hundred twelve foetuses were included; 473 survived to 2 years of age (126 of 358 in low-intensity, 140 of 380 in medium-intensity and 207 of 374 in high-intensity hospitals). There were no differences in disability (adjusted odds ratios 0.93 (95% CI 0.28 to 3.04) and 1.04 (95% CI 0.34 to 3.14) in medium- and high- compared to low-intensity hospitals, respectively). Compared to low-intensity hospitals, survival without sensorimotor disability was increased in the population of foetuses alive at maternal admission to hospital and in live-born babies, but there were no differences when considering only babies admitted to NICU or survivors. CONCLUSIONS: No difference in sensorimotor outcome for survivors of extremely preterm birth at 2 years of age was found according to the intensity of perinatal care provision. Active management of periviable births was associated with increased survival without sensorimotor disability.

Risk of autoimmune diseases and human papilloma virus (HPV) vaccines: Six years of case-referent surveillance.

BACKGROUND: Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization. OBJECTIVES: To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France. METHODS: Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11-25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barré syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008-2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations. RESULTS: With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41-0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results. CONCLUSION: Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.

Dengue epidemics and adverse obstetrical outcomes in French Guiana: a semi-ecological study.

OBJECTIVE: To determine whether dengue epidemics are associated with an increase in adverse obstetrical outcomes. METHODS: Semi-ecological study combining individual data on obstetrical events from the perinatal registry and aggregated exposure data from the epidemiologic surveillance of dengue in Cayenne, French Guiana between 2004 and 2007. RESULTS: After adjustment for individual risk factors, analysis showed that an epidemic level of dengue transmission during the first trimester was associated with an increased risk of post-partum haemorrhage and preterm birth. The associated risks seemed to depend on the epidemic level. CONCLUSIONS: Despite its limitations, this study suggests that dengue in the first trimester may be related to preterm birth and to post-partum bleeding, thus leading to specific hypotheses that should be tested in prospective studies.

Sociodemographic characteristics of mother's population and risk of preterm birth in Chile.

BACKGROUND: Preterm birth is a global problem in Perinatal and infant Health. Currently is gaining a growing attention. Rates of preterm birth have increased in most countries, producing a dramatic impact on public health. Factors of diverse nature have been associated to these trends. In Chile, preterm birth has increased since 90. Simultaneously, the advanced demographic transition has modified the characteristics of woman population related to maternity. The principal objective of this study is to analyze some sociodemographic characteristics of the maternal population over time, and their possible association to rates of preterm birth. The second aim is to identify groups of mothers at high risk of having a preterm child. METHODS: This population-based study examined all liveborn singletons in Chile from 1991 to 2008; divided in three periods. Preterm birth rates were measured as % births <37 weeks of gestation. Logistic regression assessed the risk of preterm birth associated with mother's age, parity, and marital status, expressed as crude and adjusted odds ratios. RESULTS: Over time, rates of preterm birth increased in overall population, especially during the third period (2001-2008). In the same time, characteristics of maternal population changed: significant increase of extreme reproductive ages, significant decrease in parity and increase in mothers living without a partner. Risk of preterm birth remained higher in groups of mothers: <18 and >38 years of age; without a partner; primiparas and grandmultiparas. However, global increase in preterm birth was not explained by the modification of socio demographics characteristics of maternal population. CONCLUSIONS: Some socio demographic characteristics remained associated with preterm birth over time. These associations allowed identifying five groups of mothers at higher risk to have a preterm child in the population. Increase in overall preterm birth affected all women, even those considered at "low sociodemographic risk" and the contribution of more recent period (2001-2008) to this increase is greater. Then, studied factors couldn't explain the increase in preterm birth. Further research will have to consider other factors affecting maternal population that could explain the observed trend of preterm birth.

Prediction of moderate and high grade vesicoureteral reflux after a first febrile urinary tract infection in children: construction and internal validation of a clinical decision rule.

PURPOSE: Urinary tract infection leads to a diagnosis of moderate or high grade (III or higher) vesicoureteral reflux in approximately 15% of children. Predicting reflux grade III or higher would make it possible to restrict cystography to high risk cases. We aimed to derive a clinical decision rule to predict vesicoureteral reflux grade III or higher in children with a first febrile urinary tract infection. MATERIALS AND METHODS: We conducted a secondary analysis of prospective series including all children with a first febrile urinary tract infection from the 8 European participating university hospitals. RESULTS: A total of 494 patients (197 boys, reflux grade III or higher in 11%) were included. Procalcitonin and ureteral dilatation on ultrasound were significantly associated with reflux grade III or higher and then combined into a prediction model with an ROC AUC of 0.75 (95% CI 0.69-0.81). Given the prespecified constraint of achieving at least 85% sensitivity, our model led to the clinical decision rule, for children with a first febrile urinary tract infection cystography should be performed in cases with ureteral dilatation and serum procalcitonin level 0.17 ng/ml or higher, or without ureteral dilatation (ie ureter not visible) when serum procalcitonin level is 0.63 ng/ml or higher. The rule had 86% sensitivity (95% CI 74-93) with 47% specificity (95% CI 42-51). Internal cross-validation produced 86% sensitivity (95% CI 79-93) and 43% specificity (95% CI 39-47). CONCLUSIONS: A clinical decision rule was derived to enable a selective approach to cystography in children with urinary tract infection. The rule predicts high grade vesicoureteral reflux with approximately 85% sensitivity and avoids half of the cystograms that do not find reflux grade III or higher. Further validation is needed before its widespread use.

Trends in gestational age and birth weight in Chile, 1991-2008. A descriptive epidemiological study.

BACKGROUND: Gestational age and birth weight are the principal determinants of newborn's health status. Chile, a middle income country traditionally has public policies that promote maternal and child health. The availability of an exhaustive database of live births has allows us to monitor over time indicators of newborns health. METHODS: This descriptive epidemiological study included all live births in Chile, both singleton and multiple, from 1991 through 2008. Trends in gestational age affected the rate of prevalence (%) of preterm births (<37 weeks, including the categories < 32 and 32-36 weeks), term births (37-41) and postterm births (42 weeks or more). Trends in birth weight affected the prevalence of births < 1500 g, 1500-2499 g, 2500-3999 g, and 4000 g or more. RESULTS: Data from an exhaustive register of live births showed that the number of term and postterm births decreased and the number of multiple births increased significantly. Birth weights exceeding 4000 g did not vary.Total preterm births rose from 5.0% to 6.6%, with increases of 28% for the singletons and 31% for multiple births (p for trend < 0.0001). Some categories increased even more: specifically preterm birth < 32 weeks increased 32.3% for singletons and 50.6% for multiple births (p for trend 0.0001).The overall rate of low birth weight infants (<2500 g) increased from 4.6% to 5.3%. This variation was not statistically significant for singletons (p for trend = 0.06), but specific analyses exhibited an important increase in the category weighing <1500 g (42%) similar to that observed in multiple births (43%). CONCLUSIONS: The gestational age and birth weight of live born child have significantly changed over the past two decades in Chile. Monitoring only overall rates of preterm births and low-birth-weight could provide restricted information of this important problem to public health. Monitoring them by specific categories provides a solid basis for planning interventions to reduce adverse perinatal outcomes.This epidemiological information also showed the need to assess several factors that could contribute to explain these trends, as the demographics changes, medical interventions and the increasing probability of survival of extremely and very preterm child.

Perceived morbidity and community burden after a Chikungunya outbreak: the TELECHIK survey, a population-based cohort study.

BACKGROUND: Persistent disabilities are key manifestations of Chikungunya virus (CHIKV) infection, especially incapacitating polyarthralgia and fatigue. So far, little is known about their impact on health status. The present study aimed at describing the burden of CHIKV prolonged or late-onset symptoms on the self-perceived health of La Réunion islanders. METHODS: At 18 months after an outbreak of Chikungunya virus, we implemented the TELECHIK survey; a retrospective cohort study conducted on a random sample of the representative SEROCHIK population-based survey. A total of 1,094 subjects sampled for CHIKV-specific IgG antibodies in the setting of La Réunion island in the Indian Ocean, between August 2006 and October 2006, were interviewed about current symptoms divided into musculoskeletal/rheumatic, fatigue, cerebral, sensorineural, digestive and dermatological categories. RESULTS: At the time of interview, 43% of seropositive (CHIK+) subjects reported musculoskeletal pain (vs 17% of seronegative (CHIK-) subjects, P < 0.001), 54% fatigue (vs 46%, P = 0.04), 75% cerebral disorders (vs 57%, P < 0.001), 49% sensorineural impairments (vs 37%, P = 0.001), 18% digestive complaints (vs 15%, P = 0.21), and 36% skin involvement (vs 34%, P = 0.20) on average 2 years after infection (range: 15-34 months). After controlling for confounders such as age, gender, body mass index or major comorbidities in different Poisson regression models, 33% of joint pains were attributable to CHIKV, 10% of cerebral disorders and 7.5% of sensorineural impairments, while Chikungunya did not enhance fatigue states, digestive and skin disorders. CONCLUSIONS: On average, 2 years after infection 43% to 75% of infected people reported prolonged or late-onset symptoms highly attributable to CHIKV. These manifestations carry a significant burden in the community in the fields of rheumatology, neurology and sensorineural health.

Adverse reactions and drug-drug interactions in the management of women with postmenopausal osteoporosis.

The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions and drug-drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug-drug interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits of treatment itself, i.e., the prevention of osteoporotic fracture.

From knowledge to planning considerations: a matrix to assess health needs for the perinatal network in eastern Paris.

BACKGROUND: Regionalization of perinatal care is required throughout networks to reduce perinatal morbidity and mortality and to organize access to health services for high-risk new borns, such as in the eastern Paris in 2007. Our study sought to design a matrix to build a perinatal knowledge base for assessing health needs and facilitating public health planning process for the perinatal network in eastern Paris. METHODS: Our matrix listed as its columns 'perinatal stages' from conception through the age of 6 years, whereas the rows covered components related to public health planning (i.e. target population, perinatal risk factors and health services). For each situation, the matrix lists require information and potential data sources to measure health status and health services. RESULTS: Our matrix structures the cyclical process for building knowledge for action. The eastern Paris has a population of 670,000. Its nine maternity units are distributed into three levels of care, a level-3 unit opened up in June 2007. A total of 16,400 deliveries occur every year in the nine units; 2500 women living in the eastern area deliver outside the area. CONCLUSION: Our matrix is useful for building a comprehensive perinatal knowledge base depending upon perinatal stages and health-care dimensions. It should imply stakeholders in collecting, synthesizing and analysing massive amounts of data. It can be adapted to any health network or local health policy.

Predictors of the risk of cognitive deficiency in very preterm infants: the EPIPAGE prospective cohort.

AIM: To assess cerebral lesions and other medical as well as social characteristics as predictors of risk of mild and severe cognitive deficiencies in very preterm infants. METHODS: As part of the EPIPAGE population-based prospective cohort study, perinatal data and cognitive outcome at 5 years of age were recorded for 1503 infants born before 33 weeks of gestation in nine regions of France in 1997. Mild cognitive deficiency was defined as a Mental Processing Composite score on the Kaufman Assessment Battery for Children test of between 70 and 84, and severe cognitive deficiency as a score of <70. RESULTS: After controlling for cerebral lesions and other medical as well as social factors, low parental socio-economic status and lack of breastfeeding were significant predictors of mild and severe cognitive deficiencies, whereas presence of cerebral lesions, being small for gestational age and having a large number of siblings were predictors of severe cognitive deficiency. CONCLUSION: Predictors of poor cognitive outcome in very preterm infants are low social status, lack of breastfeeding, presence of cerebral lesions on ultrasound scan, being born small for gestational age and having a high number of siblings. Social factors predicted both mild and severe cognitive deficiencies, whereas medical factors predicted mostly severe cognitive deficiencies.

Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study.

AIM: The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population-based cohort of very preterm infants. METHOD: As part of EPIPAGE, a population-based prospective cohort study, perinatal data and outcome at 5 years of age were recorded for 1812 infants born before 33 weeks of gestation in nine regions of France in 1997. RESULTS: The study group comprised 942 males (52%) and 870 females with a mean gestational age of 30 weeks (SD 2 wks; range 24-32 wks) and a mean birthweight of 1367 g (SD 393 g; range 450-2645 g). CP was diagnosed at 5 years of age in 159 infants (prevalence 9%; 95% confidence interval [CI] 7-10%), 97 males and 62 females, with a mean gestational age of 29 weeks (SD 2 wks; range 24-32 wks) and a mean birthweight of 1305 g (SD 386 g; range 500-2480 g). Among this group, 67% walked without aid, 14% walked with aid, and 19% were unable to walk. Spastic, ataxic, and dyskinetic CP accounted for 89%, 7%, and 4% of cases respectively. The prevalence of CP was 61% among infants with cystic periventricular leukomalacia, 50% in infants with intraparenchymal haemorrhage, 8% in infants with grade I intraventricular haemorrhage, and 4% in infants without a detectable cerebral lesion. After controlling for cerebral lesions and obstetric and neonatal factors, only male sex (odds ratio [OR] 1.52; 95% CI 1.03-2.25) and preterm premature rupture of membranes or preterm labour (OR 1.72; 95% CI 0.95-3.14) were predictors of the development of CP in very preterm infants. INTERPRETATION: Cerebral lesions were the most important predictor of CP in very preterm infants. In addition, infant sex and preterm premature rupture of membranes or preterm labour were also independent predictors of CP.

Hospitalization for severe bacterial infections in children after exposure to NSAIDs: a prospective adverse drug reaction reporting study.

BACKGROUND: NSAIDs are widely used to treat fever and pain in children, but their possible role in the progression of some bacterial infections is controversial. OBJECTIVE: This study was performed to analyse reported cases of severe bacterial infection associated with NSAID exposure in children admitted for this reason to a general paediatric department. METHODS: This study was based on the reporting system of hospital admissions for severe bacterial infections in children after NSAID exposure, and followed the recommendations of the European Guidelines of Pharmacovigilance for medicines used in a paediatric population. Data were prospectively collected and reported by active daily surveillance in the department from November 2002 to November 2005. RESULTS: Thirty-two cases of severe bacterial infections (cellulitis, soft tissue abscesses, parapneumonic empyema, necrotizing pneumonia, adenophlegmon [fever and a tender, warm and easily compressible neck mass] and lateral or retropharyngeal abscesses) were identified in children who had received NSAIDs, principally ibuprofen, in an exposure window of 15 days before the beginning of the signs of infection. Staphylococcus aureus, group A streptococci and Streptococcus pneumoniae were identified. Seven (22%) children required surgical treatment, and four (13%) were hospitalized in an intensive care unit. CONCLUSIONS: The frequency of hospitalization for severe bacterial infection as a possible adverse effect of NSAID use was 0.6% (95% CI 0.4, 0.9) of all admissions during the study period. The frequency of severe bacterial infections after exposure to NSAIDs was elevated (one case per month) in the department studied. Further work is necessary to confirm these findings, given the potential for recruitment and protopathic biases in our study.

Predictive factors of preterm delivery in French Guiana for singleton pregnancies: definition and validation of a predictive score.

Objective: Given the high rate of premature birth in French Guiana (13.5%), and its stability in time, the aim of the present study was to define a predictive score for preterm birth in women with a unique pregnancy in order to help prioritize health resources in the local context.Methods: A retrospective study was conducted on all deliveries of unique pregnancies in French Guiana collected between 1 January 2013 and 31 December 2014 in the Registre d'Issue de Grossesse Informatisé (RIGI), a registry that collects data on live births over 22 weeks of amenorrhea on the territory. Statistically significant predictors (p < .05) of preterm delivery were included in a logistic regression model. The selected variables were chosen to be available during the first trimester. Coefficients were used to establish a score which was categorized and prospectively validated using data from 2015.Results: Seven explanatory variables, all measurable during the first trimester of pregnancy, were significantly associated with preterm birth. The predictive score divided in deciles allowed to establish sensitivity and specificity thresholds. Overall, depending on the chosen threshold the score sensitivity was low and the specificity was high. Lowering the threshold identified half of women as "at risk" for preterm birth.Conclusion: This first trimester score was insufficiently sensitive to identify individual women at risk for preterm delivery.

Clinical decision rules for evaluating meningitis in children.

PURPOSE OF REVIEW: Distinguishing between bacterial and aseptic meningitis in children is sometimes difficult. Guidelines recommend that patients with acute meningitis be systematically hospitalized and treated with antibiotics until the cerebrospinal fluid culture results are available. This strategy ensures rapid treatment for bacterial meningitis, but also involves unnecessary admissions and antibiotics for aseptic meningitis. Some authors have, therefore, proposed different combinations of predictors in clinical decision rules to distinguish as early as possible between bacterial and aseptic meningitis. To be useful, these rules must have near-100% sensitivity for bacterial meningitis, good specificity (to reduce unnecessary antibiotics and admissions), and easy bedside application. RECENT FINDINGS: The present review examines the performance and level of validation of decision rules proposed after the Haemophilus influenzae vaccination entered widespread use. Most of these rules have been validated incompletely, if at all. Only one rule incorporates the best single validated predictive marker for distinguishing between bacterial and aseptic meningitis in children: serum procalcitonin level. SUMMARY: Two rules are highly promising, meeting the three major conditions after a retrospective validation process in large samples. These rules can be applied cautiously to patients with the same inclusion and exclusion criteria as those in the derivation sets, while awaiting prospective multicenter validation studies.

Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study.

BACKGROUND: The increasing survival rates of children who are born very preterm raise issues about the risks of neurological disabilities and cognitive dysfunction. We aimed to investigate neurodevelopmental outcome and use of special health care at 5 years of age in a population-based cohort of very preterm children. METHODS: We included all 2901 livebirths between 22 and 32 completed weeks of gestation from nine regions in France in Jan 1-Dec 31, 1997, and a reference group of 667 children from the same regions born at 39-40 weeks of gestation. At 5 years of age, children had a medical examination and a cognitive assessment with the Kaufman assessment battery for children (K-ABC), with scores on the mental processing composite (MPC) scale recorded. Data for health-care use were collected from parents. Severe disability was defined as non-ambulatory cerebral palsy, MPC score less than 55, or severe visual or hearing deficiency; moderate deficiency as cerebral palsy walking with aid or MPC score of 55-69; and minor disability as cerebral palsy walking without aid, MPC score of 70-84, or visual deficit (<3/10 for one eye). FINDINGS: In total, 1817 (77%) of the 2357 surviving children born very preterm had a medical assessment at 5 years and 396 (60%) of 664 in the reference group. Cerebral palsy was diagnosed in 159 (9%) of children born very preterm. Scores for MPC were available for 1534 children born very preterm: 503 (32%) had an MPC score less than 85 and 182 (12%) had an MPC score less than 70. Of the 320 children in the reference group, the corresponding values were 37 (12%) and 11 (3%), respectively. In the very preterm group, 83 (5%) had severe disability, 155 (9%) moderate disability, and 398 (25%) minor disability. Disability was highest in children born at 24-28 completed weeks of gestation (195 children [49%]), but the absolute number of children with disabilities was higher for children born at 29-32 weeks (441 children [36%]). Special health-care resources were used by 188 (42%) of children born at 24-28 weeks and 424 (31%) born at 29-32 weeks, compared with only 63 (16%) of those born at 39-40 weeks. INTERPRETATION: In children who are born very preterm, cognitive and neuromotor impairments at 5 years of age increase with decreasing gestational age. Many of these children need a high level of specialised care. Prevention of the learning disabilities associated with cognitive deficiencies in this group is an important goal for modern perinatal care for children who are born very preterm and for their families.

Symptomatic pelvic organ prolapse at midlife, quality of life, and risk factors.

OBJECTIVE: To estimate quality of life, prevalence, and risk factors associated with symptomatic pelvic organ prolapse (POP) among middle-aged women. METHODS: This was a cross-sectional study. A questionnaire was mailed to 3,114 women aged 50-61 years in the GAZEL cohort; 2,640 (85%) returned it. Symptomatic POP was defined by feeling a bulge from the vagina (sometimes, often, or all the time compared with never or rarely). Quality of life was determined with the Nottingham Health Profile questionnaire. Multiple linear regression was used to examine the association between frequency of POP symptoms and the quality-of-life score. Logistic regression was used to estimate the effect of risk factors on past or present symptomatic POP (current symptoms or previous surgery for POP). RESULTS: The prevalence of symptomatic POP was 3.6% (96 of 2,640) and that of surgery for POP was 2.7% (70 of 2,640). Pelvic organ prolapse symptoms were associated with difficulty defecating, lower abdominal pain, and difficulty voiding. The frequency of POP symptoms was associated with a poorer quality-of-life score in each Nottingham Health Profile domain (physical mobility, pain, emotional reaction, social isolation, energy, and sleep). Even when we took general characteristics, medical history, and lifestyle associated with quality of life into account, the global Nottingham Health Profile score was significantly impaired by POP symptoms. Factors significantly associated with past or present symptomatic POP were high body mass index and the number of vaginal deliveries. CONCLUSION: In our population of women in their 50s, POP symptoms are associated with impaired quality of life, and the number of vaginal deliveries is a risk factor for past or present symptomatic POP.

A big-data approach to producing descriptive anthropometric references: a feasibility and validation study of paediatric growth charts.

BACKGROUND: Both national and WHO growth charts have been found to be poorly calibrated with the physical growth of children in many countries. We aimed to generate new national growth charts for French children in the context of huge datasets of physical growth measurements routinely collected by office-based health practitioners. METHODS: We recruited 32 randomly sampled primary care paediatricians and ten volunteer general practitioners from across the French metropolitan territory who used the same electronic medical records software, from which we extracted all physical growth data for the paediatric patients, with anonymisation. We included measurements from all children born from Jan 1, 1990, and aged 1 month to 18 years by Feb 8, 2018, with birthweight greater than 2500 g, to which an automated process of data cleaning developed to detect and delete measurement or transcription errors was applied. Growth charts for weight and height were derived by using generalised additive models for location, scale, and shape with the Box-Cox power exponential distribution. We compared the new charts to WHO growth charts and existing French national growth charts, and validated our charts using growth data from recent national cross-sectional surveys. FINDINGS: After data cleaning, we included 1 458 468 height and 1 690 340 weight measurements from 238 102 children. When compared with the existing French national and WHO growth charts, all height SD and weight percentile curves for the new growth charts were distinctly above those for the existing French national growth charts, as early as age 1 month, with an average difference of -0·75 SD for height and -0·50 SD for weight for both sexes. Comparison with national cross-sectional surveys showed satisfactory calibration, with generally good fit for children aged 5-6 years and 10-11 years in height and weight and small differences at age 14-15 years. INTERPRETATION: We successfully produced calibrated paediatric growth charts by using a novel big-data approach applied to data routinely collected in clinical practice that could be used in many fields other than anthropometry. FUNDING: The French Ministry of Health; Laboratoires Guigoz-General Pediatrics section of the French Society of Pediatrics-Pediatric Epidemiological Research Group; and the French Association for Ambulatory Pediatrics.