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.

Detection of adolescent suicidality in primary care: an international utility study of the bullying-insomnia-tobacco-stress test.

AIM: General practitioners (GPs) are ideally placed to identify suicidality in adolescents. However, adolescents are often reluctant to confide in their GPs about these problems, and GPs are not comfortable when questioning them about suicide. We previously proposed the BITS test, a set of four opening and four additional questions, to alert doctors about possible suicidality in an adolescent. We validated its use in the identification of suicidality ("frequent suicidal ideation or suicide attempts at one time or another)" in 15-year-old adolescents in a school setting. The objective of the present study was to assess the detection utility of this method in 13-to-18-year-olds in primary care. METHODS: We carried out a screening utility study in general practices in 17 French-speaking sites in four countries and three continents. Each GP was instructed to use the bullying, insomnia, tobacco, stress (BITS) test with five to ten 13-to-18-year-old adolescents, consulting consecutively, for any reason. They subsequently asked them questions about their suicidality. RESULTS: One hundred and two GPs tested a total of 693 adolescents; 13.0% of the adolescents (girls 15.4%, boys 9.9%) reported suicidality (1.6% known, 11.4% previously unknown). A score of at least 3 on the BITS scale was associated with suicidality (sensitivity: 65.9, specificity: 82.5%). CONCLUSIONS: The BITS test is a pragmatic instrument, alerting the GP to an adolescent's previously unknown suicidability, whatever the reason for consultation.

Risk Factors for Very Preterm Births in French Guiana: The Burden of Induced Preterm Birth.

Background Early preterm births are still represented as a major public health problem in French Guiana. The objective of the present study was to study factors associated with early preterm birth in French Guiana. Methods A monocentric age-matched case control study was conducted at the sole level 3 maternity in French Guiana. In utero fetal deaths and multiple pregnancies were not included. Cases were defined as giving birth prematurely between 22 and 32 weeks of pregnancy. Controls were defined as women delivering on term. For each case three controls were matched on age. In utero deaths, medical pregnancy interruptions and multiple pregnancies (a known major cause of preterm delivery) were excluded from the study. Sociodemographic variables, medical and obstetrical history, the complications of the current pregnancy, and the results of the last vaginal swab before delivery were recorded in the second or the third trimester. Thematic conditional logistic regression models were computed. Results Overall 94 cases and 282 matched controls were included. Preterm delivery was spontaneous in 47.9% (45/94) of the cases and induced in 52.1% (49/94).A history of preterm birth was associated with both spontaneous and induced preterm delivery. The absence of health insurance was associated with spontaneous early preterm delivery AOR (adjusted odd ratio) = 9.1 (2.2-38.3), p = 0.002 but not induced preterm delivery adjusted odd ratio (AOR) = 2.1 (0.6-6.7), p = 0.2. Gravidic hypertension, placenta praevia, intrauterine growth retardation and mostly preeclampsia (66%, 32/49) were linked to induced preterm delivery but not spontaneous delivery. Gardnerellavaginalis and group B Streptococcus infections were significantly associated with induced early preterm delivery but not spontaneous early preterm delivery. Conclusions Social factors were associated with spontaneous early preterm delivery, suggesting that efforts to reduce psychosocial stressors could lead to potential improvements. Vaginal infections were also associated with induced preterm labor suggesting that early diagnosis and treatment could reduce induced early preterm delivery. Preeclampsia was a major contributor to induced early preterm delivery. Reliable routine predictors of preeclampsia are still not available which makes its prevention impossible in first pregnancies.

Risk factors for premature birth in French Guiana: the importance of reducing health inequalities.

OBJECTIVES: French Guiana has the highest birth rate in South America. This French territory also has the highest premature birth rate and perinatal mortality rate of all French territories. The objective was to determine the premature birth rate and to identify the prevalence of risk factors of premature birth in French Guiana. METHODS: A retrospective study of all births in French Guiana was conducted between January 2013 and December 2014 using the computerized registry compiling all live births over 22 weeks of gestation on the territory. RESULTS: During this period 12 983 live births were reported on the territory. 13.5% of newborns were born before 37 (1755/12 983). The study of the registry revealed that common sociodemographic risk factors of prematurity were present. In addition, past obstetrical history was also important: a scarred uterus increased the risk of prematurity adjusted odds ratio =1.4, 95%CI (1.2-1.6). Similarly, obstetrical surveillance, the absence of preparation for birth or of prenatal interview increased the risk of prematurity by 2.4 and 2.3, the excess fraction in the population was 69% and 72.2%, respectively. CONCLUSIONS: Known classical risk factors are important. In the present study excess fractions were calculated in order to prioritize interventions to reduce the prematurity rate.

High mortality due to congenital malformations in children aged < 1 year in French Guiana.

BACKGROUND: In French Guiana, pregnant women may be exposed to infectious, environmental, and social risks leading to congenital malformation. The objective of the study was to study mortality rates from congenital malformations among infants < 1 year and to compare them with those in mainland France. METHODS: We used the CEPI DC (INSERM) database, which compiles annual data from death certificates in all French territories using the International Classification of Diseases. Annual deaths for French Guiana and mainland France between 2005 and 2015 were compiled. The age category studied was children less than 1 year and deaths from congenital malformations, deformations and chromosomal abnormalities were compiled. Crude risk ratios and 95% confidence intervals were calculated to quantify the excess risk of disease in French Guiana. RESULTS: In French Guiana between 2005 and 2015 there were 666 deaths of children aged < 1 year, among which, 132 (19.8%) were due to congenital malformations and chromosomal anomalies. Overall the risk ratio of death from congenital malformations and chromosomal anomalies between French Guiana and mainland France was 2.7 (1.5-4.7), P < 0.001 for neurological congenital malformations it was 4.8 (1.2-19.7), P = 0.01 and for congenital malformations of the circulatory system it was 3.3 (1.5-6.9), P = 0.001. CONCLUSIONS: The incidence of death from congenital malformations or chromosomal anomalies in French Guiana was significantly higher than in mainland France. Explanations for this may be infections, genetic causes, nutritional causes, and toxic causes that are prevalent. There is a need to identify factors that predispose children born in French Guiana to having a higher risk of congenital malformations and chromosomal anomalies.

A prospective matched study on symptomatic dengue in pregnancy.

Dengue fever is an increasing problem worldwide, but consequences during pregnancy remain unclear. Much of the available literature suffers from methodological biases that compromise the validity of clinical recommendations. We conducted a matched cohort study during an epidemic in French Guiana to compare events and pregnancy outcomes between two paired groups of pregnant women: women having presented with symptomatic dengue during pregnancy (n = 73) and women having had neither fever nor dengue during pregnancy (n = 219). Women in each arm were matched by place of follow up, gestation weeks at inclusion, and place of residence. Dengue infection was considered to be confirmed if viral RNA, N S1 antigen, the seroconversion of IgM antibodies or the presence of IgM was detected in collected samples. According to the 2009 WHO classification, 27% of the women with symptomatic dengue had at least one clinical or biological warning sign. These complications occurred after the 28th week of gestation in 55% of cases. The medical history, socioeconomic status and demographic characteristics were included in multivariate analysis. Exposure to dengue during pregnancy was not significantly associated with prematurity, small for gestational age infants, hypertension or emergency caesarian section. Maternal dengue with warning signs was a risk factor for peripartum hemorrhage with adjusted relative risk = 8.6(95% CI = 1.2-62). There was a near significant association between dengue and in utero death (p = 0.09). This prospective comparative study underlined the importance of taking into account potential confounders between exposure to dengue and the occurrence of obstetrical events. It also confirms the need for increased vigilance for pregnant women with dengue, particularly for women who present with severe dengue.

Estimating the Risk of Vertical Transmission of Dengue: A Prospective Study.

The incidence of dengue worldwide is increasing rapidly. A better understanding of dengue transmission may help improve interventions against this major public health problem. The virus is mostly transmitted by vectors. There are, however, other modes of transmission, notably mother-to-child transmission or vertical transmission. We studied a prospective cohort of 54 women who had dengue while pregnant during the 2012-2013 epidemic in French Guiana to estimate the mother-to-child transmission rate and assess the clinical and biological presentation of neonatal dengue. The rate of vertical transmission was between 18.5% (95% confidence interval [CI]: 9.25-31.4) and 22.7% (95% CI: 11.5-37.8), depending on the calculation method used. Mother-to-child transmission occurred both in early and late pregnancy. There were 52 births, including three newborns who presented neonatal dengue with warning signs requiring platelet transfusion. This quantification of the mother-to-child transmission of dengue highlights three points: first, vertical transmission of dengue is not negligible; second, it is more frequent when maternal dengue occurs late during pregnancy near delivery; and third, reliable diagnostic tests must be used to allow the diagnosis of vertical transmission. Our findings indicate that if there is a known history of maternal dengue during pregnancy, or if there is fever during the 15 days before term, cord blood and placenta should be sampled after delivery and tested for the virus, and the newborn should be closely monitored during the postpartum period.

The proportion of asymptomatic infections and spectrum of disease among pregnant women infected by Zika virus: systematic monitoring in French Guiana, 2016.

Zika virus (ZIKV) infection has been associated with complications during pregnancy. Although the presence of symptoms might be a risk factor for complication, the proportion of ZIKV-infected pregnant women with symptoms remains unknown. Following the emergence of ZIKV in French Guiana, all pregnancies in the territory were monitored by RT-PCR and/or detection of ZIKV antibodies. Follow-up data collected during pregnancy monitoring interviews were analysed from 1 February to 1 June 2016. We enrolled 3,050 pregnant women aged 14-48 years and 573 (19%) had laboratory-confirmed ZIKV infection. Rash, arthralgia, myalgia and conjunctival hyperaemia were more frequently observed in ZIKV-positive women; 23% of them (95% confidence interval (CI): 20-27) had at least one symptom compatible with ZIKV infection. Women 30 years and older were significantly more likely to have symptoms than younger women (28% vs 20%). The proportion of symptomatic infections varied from 17% in the remote interior to 35% in the urbanised population near the coast (adjusted risk ratio: 1.6; 95% CI: 1.4-1.9.). These estimates put findings on cohorts of symptomatic ZIKV-positive pregnant women into the wider context of an epidemic with mainly asymptomatic infections. The proportion of symptomatic ZIKV infections appears to vary substantially between populations.

Phosphoglycerate dehydrogenase (PHGDH) deficiency without epilepsy mimicking primary microcephaly.

Phosphoglycerate dehydrogenase (PHGDH) deficiency (OMIM 256520) is a rare autosomal recessive disorder of serine synthesis, with mostly severe congenital microcephaly, caused by mutations in the PHGDH gene. Fourteen patients reported to date show severe, early onset, drug resistant epilepsy. In a cohort of patients referred for primary microcephaly, compound heterozygosity for two unreported variants in PHGDG was identified by exome sequencing in a pair of sibs who died aged 4.5 months and 4.5 years. They had severe neurological involvement with congenital microcephaly, disorganized EEG, and progressive spasticity, but never had seizures. Exome usage in clinical practice is likely to lead to an expansion of the clinical spectrum of known disorders.

Cerebral injuries associated with Zika virus in utero exposure in children without birth defects in French Guiana: Case report.

RATIONALE: A major epidemic of Zika virus (ZIKV) infection occurred in French Guiana and West Indies. French national epidemiological surveillance estimated that 1650 pregnant women contracted the ZIKV during epidemic period from January 2016 to October 2016 in French Guiana. PATIENT CONCERNS: ZIKV infection during pregnancy is a cause of microcephaly and birth defects. DIAGNOSES: In this report, we describe 2 children with proven in utero ZIKV exposure. Their mothers were both symptomatic and ZIKV infection occurred early in pregnancy. Ultrasonography monitoring in utero did not show any abnormality for both patient. They were born at full-term, healthy, without any birth defects and no sign of congenital ZIKV infection. INTERVENTIONS: ZIKV was neither found on placenta fragments nor children blood and urine at birth. Their neurodevelopment outcomes in early-life fitted the expectations. As recommended in national guidelines, we performed cerebral MRIs at 2 months old, showing severe brain abnormalities, especially of white matter areas. After a large screening, we did not find any differential diagnosis for their brain lesions. OUTCOMES: We concluded it was due to their in utero ZIKV exposure. LESSONS: In this report, pathogenicity of ZIKV may involve mother's immunological response or metabolic disorder during the infection.

Immunosuppressive therapy after solid-organ transplantation: does the INTERMED identify patients at risk of poor adherence?

Background: Lack of adherence to medication is a trigger of graft rejection in solid-organ transplant (SOT) recipients. Objective: This exploratory study aimed to assess whether a biopsychosocial evaluation using the INTERMED instrument before transplantation could identify SOT recipients at risk of suboptimal post-transplantation adherence to immunosuppressant drugs. We hypothesized that complex patients (INTERMED>20) might have lower medication adherence than noncomplex patients (INTERMED≤20). Methods: Each patient eligible for transplantation at the University Hospital of Lausanne, Switzerland, has to undergo a pre-transplantation psychiatric evaluation. In this context the patient was asked to participate in our study. The INTERMED was completed pre-transplantation, and adherence to immunosuppressive medication was monitored post-transplantation by electronic monitors for 12 months. The main outcome measure was the implementation and persistence to two calcineurin inhibitors, cyclosporine and tacrolimus, according to the dichotomized INTERMED score (>20 or ≤20). Results: Among the 50 SOT recipients who completed the INTERMED, 32 entered the study. The complex (N=11) and noncomplex patients (N=21) were similar in terms of age, sex and transplanted organ. Implementation was 94.2% in noncomplex patients versus 87.8% in complex patients (non-significant p-value). Five patients were lost to follow-up: one was non-persistent, and four refused electronic monitoring. Of the four patients who refused monitoring, two were complex and withdrew early, and two were noncomplex and withdrew later in the study. Conclusion: Patients identified as complex pre-transplant by the INTERMED tended to deviate from their immunosuppressant regimen, but the findings were not statistically significant. Larger studies are needed to evaluate this association further, as well as the appropriateness of using a nonspecific biopsychosocial instrument such as INTERMED in highly morbid patients who have complex social and psychological characteristics (AU)

No disponible

Immunosuppressive therapy after solid-organ transplantation: does the INTERMED identify patients at risk of poor adherence?

BACKGROUND: Lack of adherence to medication is a trigger of graft rejection in solid-organ transplant (SOT) recipients. OBJECTIVE: This exploratory study aimed to assess whether a biopsychosocial evaluation using the INTERMED instrument before transplantation could identify SOT recipients at risk of suboptimal post-transplantation adherence to immunosuppressant drugs. We hypothesized that complex patients (INTERMED>20) might have lower medication adherence than noncomplex patients (INTERMED≤20). METHODS: Each patient eligible for transplantation at the University Hospital of Lausanne, Switzerland, has to undergo a pre-transplantation psychiatric evaluation. In this context the patient was asked to participate in our study. The INTERMED was completed pre-transplantation, and adherence to immunosuppressive medication was monitored post-transplantation by electronic monitors for 12 months. The main outcome measure was the implementation and persistence to two calcineurin inhibitors, cyclosporine and tacrolimus, according to the dichotomized INTERMED score (>20 or ≤20). RESULTS: Among the 50 SOT recipients who completed the INTERMED, 32 entered the study. The complex (N=11) and noncomplex patients (N=21) were similar in terms of age, sex and transplanted organ. Implementation was 94.2% in noncomplex patients versus 87.8% in complex patients (non-significant p-value). Five patients were lost to follow-up: one was non-persistent, and four refused electronic monitoring. Of the four patients who refused monitoring, two were complex and withdrew early, and two were noncomplex and withdrew later in the study. CONCLUSION: Patients identified as complex pre-transplant by the INTERMED tended to deviate from their immunosuppressant regimen, but the findings were not statistically significant. Larger studies are needed to evaluate this association further, as well as the appropriateness of using a nonspecific biopsychosocial instrument such as INTERMED in highly morbid patients who have complex social and psychological characteristics.

Does concurrent radiochemotherapy affect cosmetic results in the adjuvant setting after breast-conserving surgery? Results of the ARCOSEIN multicenter, Phase III study: patients' and doctors' views.

PURPOSE: To evaluate the cosmetic results of sequential vs. concurrent adjuvant chemotherapy with radiotherapy after breast-conserving surgery for breast cancer, and to compare ratings by patients and physicians. METHODS AND MATERIALS: From 1996 to 2000, 716 patients with Stage I-II breast cancers were included in a multicenter, Phase III trial (the ARCOSEIN study) comparing, after breast-conserving surgery with axillary dissection, sequential treatment with chemotherapy first followed by radiotherapy vs. chemotherapy administered concurrently with radiotherapy. Cosmetic results with regard to both the overall aspect of the breast and specific changes (color, scar) were evaluated in a total of 214 patients (107 in each arm) by means of questionnaires to both the patient and a physician whose rating was blinded to treatment allocation. RESULTS: Patients' overall satisfaction with cosmesis was not statistically different between the two arms, with approximately 92% with at least satisfactory results (p = 0.72), although differences between the treated and untreated breasts were greater after the concurrent regimen (29% vs. 14% with more than moderate differences; p = 0.0015). Physician assessment of overall cosmesis was less favorable, with lower rates of at least satisfactory results in the concurrent arm (60% vs. 85%; p = 0.001). Consequently, the concordance for overall satisfaction with cosmesis between patients and doctors was only fair (kappa = 0.62). CONCLUSION: After breast-conserving surgery, the concurrent use of chemotherapy with radiotherapy is significantly associated with greater differences between the breasts. These differences do not translate into patients' lessened satisfaction with cosmesis.

Phase III trial of concurrent or sequential adjuvant chemoradiotherapy after conservative surgery for early-stage breast cancer: final results of the ARCOSEIN trial.

PURPOSE: In 1996, we initiated the French multicenter phase III randomized trial to compare the effect on disease-free survival (DFS) of concurrent versus sequential chemotherapy (CT) and radiotherapy (RT) after breast-conserving surgery for stages I and II breast cancer. This report presents the clinical results with a median follow-up of 60 months. PATIENTS AND METHODS: Between February 1996 and April 2000, 716 patients were entered onto this trial. Adjuvant treatment began within 6 weeks after surgery. Sequential treatment of CT administered first followed by RT was compared with concurrent treatment of CT administered with RT. The CT regimen consisted of mitoxantrone (12 mg/m2), fluorouracil (500 mg/m2), and cyclophosphamide (500 mg/m2) on day 1, and it was repeated every 21 days for six courses. RT was delivered to the breast and, when indicated, to the regional lymphatics. RESULTS: There was no statistically significant difference in treatment in the 5-year DFS (80% in both groups; P = .83), locoregional recurrence-free survival (LRFS; 92% in sequential v 95% in concurrent; P = .76), metastasis-free survival (87% in sequential v 84% in concurrent; P = .55), or overall survival (90% in sequential v 91% in concurrent; P = .76). Nevertheless, in the node-positive subgroup, the 5-year LRFS was statistically better in the concurrent arm (97% in concurrent v 91% in sequential; P = .02), corresponding to a risk of locoregional recurrence decreased by 39% (hazard ratio, 0.61; 95% CI, 0.38 to 0.93). CONCLUSION: This treatment protocol remains an appealing clinical option for many women with operable breast cancer at a high risk of recurrence. Combination treatments with new drugs for breast cancer are warranted.