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1.  Sociodemographic characteristics of mother’s population and risk of preterm birth in Chile 
Reproductive Health  2013;10:26.
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.
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.
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.
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.
PMCID: PMC3662587  PMID: 23680406
Preterm birth; Maternal population; Risk factor; Sociodemographic characteristics
2.  Predictors of Chikungunya rheumatism: a prognostic survey ancillary to the TELECHIK cohort study 
Long-lasting relapsing or lingering rheumatic musculoskeletal pain (RMSP) is the hallmark of Chikungunya virus (CHIKV) rheumatism (CHIK-R). Little is known on their prognostic factors. The aim of this prognostic study was to search the determinants of lingering or relapsing RMSP indicative of CHIK-R.
Three hundred and forty-six infected adults (age ≥ 15 years) having declared RMSP at disease onset were extracted from the TELECHIK cohort study, Reunion island, and analyzed using a multinomial logistic regression model. We also searched for the predictors of CHIKV-specific IgG titres, assessed at the time of a serosurvey, using multiple linear regression analysis.
Of these, 111 (32.1%) reported relapsing RMSP, 150 (43.3%) lingering RMSP, and 85 (24.6%) had fully recovered (reference group) on average two years after acute infection. In the final model controlling for gender, the determinants of relapsing RMSP were the age 45-59 years (adjusted OR: 2.9, 95% CI: 1.0, 8.6) or greater or equal than 60 years (adjusted OR: 10.4, 95% CI: 3.5, 31.1), severe rheumatic involvement (fever, at least six joints plus four other symptoms) at presentation (adjusted OR: 3.6, 95% CI: 1.5, 8.2), and CHIKV-specific IgG titres (adjusted OR: 3.2, 95% CI: 1.8, 5.5, per one unit increase). Prognostic factors for lingering RMSP were age 45-59 years (adjusted OR: 6.4, 95% CI: 1.8, 22.1) or greater or equal than 60 years (adjusted OR: 22.3, 95% CI: 6.3, 78.1), severe initial rheumatic involvement (adjusted OR: 5.5, 95% CI: 2.2, 13.8) and CHIKV-specific IgG titres (adjusted OR: 6.2, 95% CI: 2.8, 13.2, per one unit increase). CHIKV specific IgG titres were positively correlated with age, female gender and the severity of initial rheumatic symptoms.
Our data support the roles of age, severity at presentation and CHIKV specific IgG titres for predicting CHIK-R. By identifying the prognostic value of the humoral immune response of the host, this work also suggest a significant contribution of the adaptive immune response to the physiopathology of CHIK-R and should help to reconsider the paradigm of this chronic infection primarily shifted towards the involvement of the innate immune response.
PMCID: PMC3672753  PMID: 23302155
3.  Trends in gestational age and birth weight in Chile, 1991–2008. A descriptive epidemiological study 
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.
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.
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%).
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.
PMCID: PMC3573962  PMID: 23116061
5.  Prediction of High-Grade Vesicoureteral Reflux after Pediatric Urinary Tract Infection: External Validation Study of Procalcitonin-Based Decision Rule 
PLoS ONE  2011;6(12):e29556.
Predicting vesico-ureteral reflux (VUR) ≥3 at the time of the first urinary tract infection (UTI) would make it possible to restrict cystography to high-risk children. We previously derived the following clinical decision rule for that purpose: cystography should be performed in cases with ureteral dilation and a serum procalcitonin level ≥0.17 ng/mL, or without ureteral dilatation when the serum procalcitonin level ≥0.63 ng/mL. The rule yielded a 86% sensitivity with a 46% specificity. We aimed to test its reproducibility.
Study Design
A secondary analysis of prospective series of children with a first UTI. The rule was applied, and predictive ability was calculated.
The study included 413 patients (157 boys, VUR ≥3 in 11%) from eight centers in five countries. The rule offered a 46% specificity (95% CI, 41–52), not different from the one in the derivation study. However, the sensitivity significantly decreased to 64% (95%CI, 50–76), leading to a difference of 20% (95%CI, 17–36). In all, 16 (34%) patients among the 47 with VUR ≥3 were misdiagnosed by the rule. This lack of reproducibility might result primarily from a difference between derivation and validation populations regarding inflammatory parameters (CRP, PCT); the validation set samples may have been collected earlier than for the derivation one.
The rule built to predict VUR ≥3 had a stable specificity (ie. 46%), but a decreased sensitivity (ie. 64%) because of the time variability of PCT measurement. Some refinement may be warranted.
PMCID: PMC3247275  PMID: 22216314
6.  Special Care and School Difficulties in 8-Year-Old Very Preterm Children: The Epipage Cohort Study 
PLoS ONE  2011;6(7):e21361.
To investigate school difficulties, special care and behavioral problems in 8 year-old very preterm (VPT) children.
Patient and Methods
Longitudinal population-based cohort in nine regions of France of VPT children and a reference group born at 39–40 weeks of gestation (WG). The main outcome measures were information about school, special care and behavioral problems using Strengths and Difficulties Questionnaire from a questionnaire to parents.
Among the 1439 VPT children, 5% (75/1439) were in a specialised school or class, 18% (259/1439) had repeated a grade in a mainstream class and 77% (1105/1439) were in the appropriate grade-level in mainstream class; these figures were 1% (3/327) , 5% (16/327) and 94% (308/327) , respectively, for the reference group. Also, 15% (221/1435) of VPT children in a mainstream class received support at school versus 5% (16/326) of reference group. More VPT children between the ages of five and eight years received special care (55% (794/1436)) than children born at term (38% (124/325)); more VPT children (21% (292/1387)) had behavioral difficulties than the reference group (11% (35/319)). School difficulties, support at school, special care and behavioral difficulties in VPT children without neuromotor or sensory deficits varied with gestational age, socioeconomic status, and cognitive score at the age of five.
Most 8-year-old VPT children are in mainstream schools. However, they have a high risk of difficulty in school, with more than half requiring additional support at school and/or special care. Referral to special services has increased between the ages of 5 and 8 years, but remained insufficient for those with borderline cognitive scores.
PMCID: PMC3132214  PMID: 21760892
7.  Adverse Reactions and Drug–Drug Interactions in the Management of Women with Postmenopausal Osteoporosis 
Calcified Tissue International  2011;89(2):91-104.
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.
PMCID: PMC3135835  PMID: 21637997
Osteoporosis; Adverse drug reaction; Drug–drug interaction; Bisphosphonate; Denosumab; SERM; Strontium ranelate; Teriparatide
8.  Perceived morbidity and community burden after a Chikungunya outbreak: the TELECHIK survey, a population-based cohort study 
BMC Medicine  2011;9:5.
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.
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.
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.
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.
PMCID: PMC3029216  PMID: 21235760
9.  Proteins, dietary acid load, and calcium and risk of postmenopausal fractures in the E3N French women prospective study 
Journal of Bone and Mineral Research  2008;23(12):1915-1922.
Excess dietary proteins and “acid ash” diets have been suspected to increase the risk of osteoporosis, but experimental and epidemiological evidence is mixed. We aimed to determine whether the association between protein intake and the overall acid-base equilibrium of the diet (as renal net acid excretion (RNAE) estimate) and fracture risk vary according to calcium intake.
Materials and Methods
During an average of 8.37 (± 1.73) years of follow up, 2408 women reported a fracture (excluding high-impact trauma) among 36,217 postmenopausal women from the E3N prospective study. We used Cox regression models to study the interaction between calcium and, respectively, proteins and RNAE, from the 1993 dietary questionnaire, for fracture risk determination, adjusting for potential confounders.
There was no overall association between fracture risk and total protein or RNAE. However, in the lowest quartile of calcium (< 400 mg/1000 kcal), high protein intake was associated with a significant increased fracture risk (RR = 1.51 for highest versus lowest quartile; 95% CI 1.17–1.94). An increasing fracture risk with increasing animal protein intake was also observed (p trend <0.0001). A similar pattern of interaction for fracture risk was observed between RNAE and calcium.
In this Western population of post-menopausal women with normal to high protein intake and fairly high calcium intake, there was no overall association between total protein or RNAE and fracture risk. However, there was some evidence that high protein – high acid ash diets were associated with an increased risk of fracture when calcium intake was low (< 400 mg/1000 kcal).
PMCID: PMC2929535  PMID: 18665794
Adult; Aged; Calcium, Dietary; metabolism; Diet; Dietary Proteins; metabolism; Female; Fractures, Bone; diagnosis; epidemiology; France; Humans; Middle Aged; Osteoporosis; drug therapy; Postmenopause; Prospective Studies; Questionnaires; Risk
10.  Collecting population-based perinatal data efficiently: the example of the Lebanese National Perinatal Survey 
We describe the methodology and the main results of the Lebanese perinatal health survey; the aim of the survey was to obtain a minimum data set on all births occurring during a short period of time. The survey was carried out during two consecutive weeks in fall 1999 and in spring 2000. All live births and stillbirths occurring during these periods in medical settings were recorded. The sample included 5231 women and 5333 newborns. Data were obtained from medical records and by interviewing the women in hospital after delivery. All maternity units and birth centers agreed to participate. Maternal characteristics, medical care during pregnancy and delivery, and pregnancy outcome were similar for the two study periods. However gestational age distribution differed between the two periods. In total, 9.0% of infants were born before 37 weeks of gestation and 7.0% weighed less than 2500 grams at birth. Wide regional variations were observed for many indicators of health, care and risk factors. For instance, the cesarean section rate varied from 16.2% in the North Region to 28.0% in Beirut. The survey protocol was successfully applied in Lebanon and may be useful in other countries that have a relatively well-developed health care system, but few sources of reliable population-based statistics on health and medical care. This type of survey may also be an appropriate instrument for collecting additional data for health policy evaluations.
PMCID: PMC2855854  PMID: 16911021
Adult; Birth Weight; Cesarean Section; Delivery, Obstetric; methods; Developing Countries; Educational Status; Female; Gestational Age; Health Care Surveys; methods; Home Childbirth; Humans; Infant, Newborn; Infant, Premature; Lebanon; epidemiology; Mothers; Parity; Perinatal Care; methods; Pregnancy; Pregnancy Outcome; Prenatal Care; methods; Risk Factors;  health survey ; prenatal care; delivery; pregnancy outcome; gestational age; birthweight; developing countries; Lebanon
11.  Mode of delivery and severe stress incontinence. A cross-sectional study among 2,625 perimenopausal women 
Bjog  2005;112(12):1646-1651.
To estimate the prevalence of severe stress urinary incontinence among perimenopausal women and to examine potential obstetrical risk factors.
Mail survey of female volunteers for epidemiological research.
Postal questionnaire on stress urinary incontinence (SUI).
3114 women aged 49–61 years who comprised the GAZEL cohort.
Main outcome measure
Prevalence of severe SUI defined by the response “often” or “all the time” to the question “Does urine leak when you are physically active, cough or sneeze?”
Logistic regression using data from the entire cohort to estimate the impact of risk factors. A second logistic regression using data from women who had given birth included obstetric history.
2625 women (85%) completed and returned the questionnaire The frequency of SUI reported in the preceding four weeks was: “never” 32%, “occasionally” 28%, “sometimes” 26%, “often” 10%, and “all the time” 5%. Prevalence of severe SUI was lowest among nulliparous women (7%), but it was similar among parous women regardless of birth number (14 – 17%). The prevalence of severe SUI was not associated with mode of delivery (14% for women delivered by caesarean only versus 16% for vaginal births). Significant risk factors for severe SUI were high body mass index (>30), diabetes mellitus, previous incontinence surgery, parity, and first delivery under the age of 22 years.
Pregnancy itself is a risk factor for severe SUI among women who reach the age of 50. In this age group the impact of the mode of delivery (spontaneous, forceps or caesarean) on severe SUI is slight.
PMCID: PMC2660572  PMID: 16305569
Body Mass Index; Delivery; Obstetric; adverse effects; Epidemiologic Methods; Female; France; epidemiology; Humans; Menopause; Middle Aged; Pregnancy; Pregnancy Complications; etiology; Prevalence; Questionnaires; Urinary Incontinence, Stress; epidemiology; etiology
12.  Selecting short-statured children needing growth hormone testing: Derivation and validation of a clinical decision rule 
BMC Pediatrics  2008;8:29.
Numerous short-statured children are evaluated for growth hormone (GH) deficiency (GHD). In most patients, GH provocative tests are normal and are thus in retrospect unnecessary.
A retrospective cohort study was conducted to identify predictors of growth hormone (GH) deficiency (GHD) in children seen for short stature, and to construct a very sensitive and fairly specific predictive tool to avoid unnecessary GH provocative tests. GHD was defined by the presence of 2 GH concentration peaks < 10 ng/ml. Certain GHD was defined as GHD and viewing pituitary stalk interruption syndrome on magnetic resonance imaging. Independent predictors were identified with uni- and multi-variate analyses and then combined in a decision rule that was validated in another population.
The initial study included 167 patients, 36 (22%) of whom had GHD, including 5 (3%) with certain GHD. Independent predictors of GHD were: growth rate < -1 DS (adjusted odds ratio: 3.2; 95% confidence interval [1.3–7.9]), IGF-I concentration < -2 DS (2.8 [1.1–7.3]) and BMI z-score ≥ 0 (2.8 [1.2–6.5]). A clinical decision rule suggesting that patients be tested only if they had a growth rate < -1 DS and a IGF-I concentration < -2 DS achieved 100% sensitivity [48–100] for certain GHD and 63% [47–79] for GHD, and a specificity of 68% [60–76]. Applying this rule to the validation population (n = 40, including 13 patients with certain GHD), the sensitivity for certain GHD was 92% [76–100] and the specificity 70% [53–88].
We have derived and performed an internal validation of a highly sensitive decision rule that could safely help to avoid more than 2/3 of the unnecessary GH tests. External validation of this rule is needed before any application.
PMCID: PMC2492843  PMID: 18631396
13.  Predictors of the risk of cognitive deficiency in very preterm infants: the EPIPAGE prospective cohort 
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.
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.
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.
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.
PMCID: PMC3080666  PMID: 21241364
Cognitive deficiency; Predictor; Very preterm infant

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