Antibody kinetics in infants exposed to Chikungunya virus infection during pregnancy reveals absence of congenital infection.

To search for serological evidence of congenital infection in apparently healthy neonates born to women infected with the Chikungunya virus (CHIKV) during pregnancy, monitoring for CHIKV-specific antibodies was performed within the CHIMERE cohort study (Reunion island, 2006-2008). CHIKV-specific antibody kinetics showed no evidence of asymptomatic congenital infection as neonates were tested negative for CHIKV-specific IgM antibodies at birth and 368 infants with CHIKV-specific IgG antibodies seroreversed completely (mean seroreversion time: 7.7 months). Seroreversion time of transplacental CHIKV IgG antibodies was inversely correlated with the stage of pregnancy at which exposure took place and end-term small for gestational infants seroreversed earlier.

Clear amniotic fluid aspiration syndrome: A novel description of an old entity.

BACKGROUND: Clear amniotic fluid aspiration syndrome (CAF-AS) is a very rare event occurring in 0.25% of our term clear amniotic fluids deliveries. The study's aims were: 1. to characterize the risk factors and outcomes associated with Clear Amniotic Fluid Aspiration Syndrome and 2. to compare the outcomes of Clear Amniotic Fluid Aspiration to Meconium Aspiration. METHODS: This was an observational study over a 22-year period in a single level-3 medical center. Compared were parturient/labor characteristics and neonatal outcomes in cases with suspected Clear Amniotic Fluid Aspiration to cases suspected for Meconium Aspiration. RESULTS: Out of 79,620 term deliveries there were 66,705 (83.8%) clear amniotic fluids and 12,915 (16.2%) meconium stained amniotic fluid (MSAF). Of neonates born with clear amniotic fluid, 166 (0.25%) were diagnosed with Clear Amniotic Fluid Aspiration Syndrome (CAF-AS), while 202 (15.7%) of those born with MSAF, were diagnosed with aspiration syndrome (MSAF-AS). Both conditions had comparable rates of mild manifestation (67.5% vs 69.2%, p = 0.63). Persistent pulmonary hypertension (PPH) occurred 5 times less in CAF-AS than MSAF-AS (4% vs 20%, OR 0.17, P< 0.0001) Both conditions presented similar rates of surfactant without PPH (11.1% vs 13.4%, p = 0.87). There was 1 postnatal death in CAF-AS vs 10 in MSAF. CONCLUSION: CAF-AS were quantitatively quite similar in terms of need of actual active intervention of the neonatologists in the delivery room (166 vs 202, i.e. in terms of numbers of cases and not prevalence) to MSAF-AS.We identified in these cases two major specific causes: hyperkinetic explosive deliveries in multiparas and long-lasting episodes of maternal hypotension due to epidural/spinal anaesthesia during labor. Out of 140 million births per year in the world, it should be of concern that 3 million cases are neglected nowadays. Future studies should evaluate if this CAF-AS should benefit from a more active intervention such as immediate endotracheal suction at birth, this clear fluid being very easy to suction.

Prenatal and neonatal phenotype of Larsen of La Réunion Island syndrome (B4GALT7-linkeropathy).

Larsen of La Réunion Island syndrome (LRS) is an autosomal recessive condition associated with multiple large joint dislocations, clubfeet, severe dwarfism, and distinctive facial features. LRS is caused by a recurrent homozygous variant in B4GALT7 gene with a founder effect in La Réunion population. Proteoglycans (PG) that are a major component of the extracellular matrix, are composed of a core protein connected to a glycosaminoglycans side chain via a tetrasaccharide linker region. B4GALT7 encodes galactosyltransferase I, one of the enzymes involved in the biosynthesis of the linker region. Conditions caused by pathogenic biallelic variants in genes implicated in the synthesis of the tetrasaccharide linker of PG are known as linkeropathies. Prenatal features are rarely described in this group of chondrodysplasias. We present a series of 12 unpublished patients having LRS and describe the perinatal phenotype. All the patients had a prenatal growth restriction with brevity of limbs. The other features revealed by ultrasounds were increased nuchal translucency at 10-12 weeks of gestation (50 %), feet abnormalities (clubfeet or metatarsus varus) (25 %), dislocation affecting at least one large joint (elbow, knee, wrist) (25 %). Bilateral bowing of femora was noted for two fetuses. Fibular hypertrophy was noted for one fetus. Prenatal helical computed tomography (CT) performed in three pregnancies showed additional data such as bowing of the forearm bones, proximal radio-ulnar synostosis, or dislocation of large joints. Prenatal sonographic and helical CT findings led to the prenatal diagnosis of LRS in four patients. We confirm that the neonatal clinical picture of LRS has an important overlap with that reported in patients with B4GALT7 deficiency outside La Réunion Island and other linkeropathies. The core of the phenotypic spectrum combines low birth height, micromelia, hypermobility, dislocation of at least one large joint, facial features with prominent eyes, microstomia, depressed nasal bridge, and midface hypoplasia. Other clinical features include clubfeet (33%), bifid thumb in one patient, and cardiac abnormalities in two patients. Radiological findings include radio-ulnar synostosis (75%), metaphyseal flaring, precocious carpal ossification, and a Swedish key appearance of the proximal femora. Finally, we also report radiological features rarely described in B4GALT7-linkeropathies, including bowing of the femora and fibular hypertrophy. Our results confirm the phenotypic continuum of LRS within linkeropathies with some additional findings, including a high frequency of clubfeet usually described in B3GALT6-linkeropathies, the presence of congenital heart diseases usually described in B3GAT3-linkeropathies, and a high frequency of metaphyseal flaring usually reported in B3GALT6 or XITLT1-linkeropathies. This is the first study that describes the perinatal phenotype in a cohort of patients with LRS. This study can help improve the prenatal diagnosis of the linkeropathies and add this group of conditions to the differential diagnosis of chondrodysplasias with multiple dislocations. In view of the founder effect for LRS in La Réunion Island, this disease should be suspected in fetuses with growth restriction and micromelia. Thus in case of LOH which include B4GALT7 identified in SNP-array, we recommend performing a targeted Sanger sequencing for the recurrent mutation c.808C > T; p. (Arg270Cys).

Congenital heart defects in La Réunion Island: a 6-year survey within a EUROCAT-affiliated congenital anomalies registry.

OBJECTIVES: This study compares the prevalence and perinatal mortality of congenital heart defects on La Réunion with European (EUROCAT) standards. METHODS AND RESULTS: Data were extracted from a EUROCAT-affiliated congenital malformations registry, covering 88,025 births during the period 2002-2007, on the whole island territory. A total of 512 congenital heart defects were registered, including 424 live births, 18 foetal deaths from 16 weeks of gestation, and 70 terminations of pregnancy. The total prevalence of congenital heart defects was 5.8 per 1000 births and live birth prevalence was 4.8 per 1000. The total prevalence of non-chromosomal congenital heart defects was 5.1 per 1000 births, of which 3% were perinatal deaths, 33.3% prenatally diagnosed, and 11.6% termination of pregnancy. Severe non-chromosomal congenital heart defects - excluding ventricular septal defects, atrial septal defects, and pulmonary valve stenosis - occurred in 2.1 per 1000 births, of which 10.3% were perinatal deaths, 59.1% prenatally diagnosed, and 24.3% termination of pregnancy. Of the severe congenital heart defects, the rates of single ventricle (0.20‰), Ebstein anomaly (0.11‰), common arterial trunk (0.25‰), and atrioventricular septal defect (0.62‰) exceeded averages found in Europe, although coarctation of the aorta was infrequent. Conversely, rates of ventricular septal defects, atrial septal defects, and pulmonary valve stenosis were inferior to European standards. Slightly less than half of the congenital heart defects of chromosomal origin were associated with Down syndrome. CONCLUSION: In La Réunion, the total prevalence of congenital heart defects is far inferior to that found in Europe. The difference can be attributable to lower prevalences of mild congenital heart defects.

Ethnic differences in postmaturity syndrome in newborns. Reflections on different durations of gestation.

OBJECTIVE: To describe the prevalence, by weeks of gestation, of post-maturity signs in newborns by ethnic origins. STUDY DESIGN: Observational cohort study (2001-2018), of all consecutive singleton births delivered at Center Hospitalier Universitaire Hospitalier Sud Reunion's maternity (Reunion Island, French overseas department, Indian Ocean). The presence of clinical post-maturity signs was recorded by a week of gestation using Clifford's clinical post-maturity signs in newborns (desquamation, dry skin, wrinkling fingers and cracked skin). RESULTS: Of the 67,463 singleton births during the period, 58,503 newborns were from Reunion island, 5756 were of European origin (mainland France), and 4061 newborns from the archipelago of Comoros (North of Madagascar). Mean duration of gestation was 276 days in Caucasian women, 272 days in Comorian mothers and 273 days in Reunionese (p < .001). Post-maturity is defined by WHO as gestation greater than 293 days (41 weeks + 6 days). At 41 weeks (287 days) 12.1% of Caucasian babies presented post-maturity signs and 22.4% meconium-stained liquid versus respectively, 22.8 and 27.1% in Reunionese and 44 and 39.8% in Comorians (p < .001). CONCLUSION: Among African (Black) pregnancies, duration of gestation was approximately 7 days shorter than in Caucasian (White) pregnancies. In the Reunionese intermixed population and Comorians, the gestation was shorter by 3-4 days. Black newborns presented severe clinical post-maturity signs beginning around 40 weeks and 4-6 days, while it was 1 week later in white infants. Consequences of these differences, with respect to clinical outcomes, are discussed.

A prospective study evaluating congenital CMV infection in Mayotte and La Reunion Islands (France).

OBJECTIVES Congenital cytomegalovirus infection (cCMV) affects around 3400 newborns each year in France, of whom 700 will develop sequelae, primarily sensorineural hearing loss. Our objectives were (1) to evaluate incidence of cCMV in two French departments located in the Indian Ocean: Mayotte and La Reunion, and (2) evaluate interest and feasibility/acceptability of universal screening of cCMV at birth. MATERIAL AND METHODS We implemented a universal neonatal CMV screening in Mayotte during 7 months in 2019 and in La Reunion during one month in March 2020. Saliva swabs were collected in the first three days of life, and tested for CMV DNA by PCR. A short survey allowed evaluating whether this screening is acceptable and feasible. RESULTS: A total of 1026 newborns were screened: 854 in Mayotte and 172 in La Reunion. In Mayotte, cCMV incidence was evaluated at a minimum of 1.6 % (95 % CI 0.94-2.81). In La Reunion, cCMV incidence was evaluated at a minimum of 1.2 % (95 % CI -0.20-4.57). All cCMV infants were born to mothers with non-primary CMV infection. Only 0.7 % parents refused the screening. CONCLUSIONS cCMV incidence in Mayotte and La Reunion is higher than in metropolitan France. This diagnosis should not be overlooked, especially since the time dedicated to screening and its feeling by the parents seem to be acceptable.

Gestational weight gain and rate of late-onset preeclampsia: a retrospective analysis on 57 000 singleton pregnancies in Reunion Island.

OBJECTIVES: To investigate in singleton term pregnancies (≥37 weeks gestation) if applying optimal gestational weight gains (optGWG) on our population could have an effect on the incidence of late-onset preeclampsia (LOP). DESIGN: 18.5-year-observational cohort study (2001-2019). SETTINGS: Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity (French overseas department, Indian Ocean), the only maternity providing services to take care of all preeclamptic cases in an area with approximately 360 000 inhabitants. MAIN OUTCOMES AND MEASURES: Simulation rates of LOP between women achieving optimal versus inappropriate GWG (insufficient and excessive) in the non-overweight, overweight and class I-III obesity categories. RESULTS: Among 66 373 singleton term pregnancies with a live birth, and 716 LOP (≥37 weeks, LOP37), the GWG could be determined in 87% of cases. In a logistic regression model validating the independent association of optGWG, maternal ages and body mass index (BMI), primiparity, smoking habit, chronic hypertension with term preeclampsia, optGWG reduced the risk of LOP37, aOR 0.74, p=0.004. Primiparity, higher maternal BMI, chronic hypertension and higher maternal age increased the risk of LOP37. The 'protective' effect of optGWG appeared stronger in patients with overweight and obesity in a linear manner: 0.57% versus 1.07% (OR 0.53, p=0.003), overweight; class I obese (30-34.9 kg/m²), 0.70% vs 1.56% (OR 0.44, p=0.01); severe obesity (≥35 kg/m²) 0.86% vs 2.55% (OR 0.33, p=0.06). All patients with overweight/obesity together, OR 0.42, p<0.0001. CONCLUSIONS: Overweight and obesity may not result in a higher risk of developing LOP at term when a optGWG is achieved. The results of this large retrospective population cohort study suggest that targeted and strictly monitored interventions on achieving an optGWG might represent an effective method to reduce the rate of LOP and would have the potential to halve its rate in women with overweight/obesity. These findings suggest a potentially achievable pathway to actively counterbalance the morbid effects of high BMIs, so we solicit adequately powered prospective trials.

The burden to be second twin: a population-based study of 2686 twins: (2124 dichorionic). Proposal of the concept of mobility.

Objectives: To identify if there is a specific neonatal morbidity/mortality among second twins relative to first twins.Study design: A 17-year (2001-2017) population-based observational cohort of all twin newborns born in the South of Reunion island after 21 weeks.Results: Among 1062 dichorionic (DTP) and 281 monochorionic twin pregnancies (2686 newborns), twin 2 have a doubled risk to be in breech presentation and a bad Apgar at 1 mn (≤6) in vaginal deliveries. Specific to dichorionic pregnancies, twin 2 were lighter by 50-60 g than twin 1, had higher rates of intrauterine growth retardation (IUGR), OR 1.33, p = .007, a doubled risk to have congenital abnormalities OR 2.1, p = .006.Conclusion: In dichorionic twin pregnancies, second twins having a doubled prevalence of severe congenital abnormalities are not completely elucidated and deserves further research. (1) We propose that twin 2 presenting higher risks of being IUGR and much higher risks of severe malformations suggest that during pregnancy, the less mobile of the two twins is "relegated" to the back of the uterus. (2) For interventions in the delivery room, systematically the most experimented neonatologist should plan to manage the second twin because significantly twin 2 presents higher problems than twin 1.

[Vertical maternal fetal transmission of the chikungunya virus. Ten cases among 84 pregnant women]. / Transmission verticale materno-foetale du virus chikungunya. Dix cas observés sur l'île de la Réunion chez 84 femmes enceintes.

INTRODUCTION: In March 2005, an epidemic of chikungunya virus began in the southern portion of Reunion Island (French overseas district in the Indian Ocean) and spread to the northern part of the island at the end of 2005. The Reunion-South Hospital Group observed the first cases of pregnant women infected with the virus in June 2005. We report here for the first time maternal-fetal transmission of this virus. CASES: From June 2005 through the end of January 2006, 84 pregnant women had acute chikungunya infections during pregnancy. In 88% of these cases (n=74)--all involving infections relatively distant from delivery--the newborns appeared asymptomatic. Conversely, 10 newborns had severe attacks (4 with meningoencephalitis and 3 with intravascular coagulations) after birth and required prolonged neonatal hospitalization (6 in the neonatal intensive care unit with intubation and assisted ventilation). No infants died, but there was one case of severe intracerebral hemorrhage after severe thrombocytopenia. These cases were confirmed by specific serology testing or PCR or both for mothers and newborns. We note that all severe cases involved women with viremia and fever in the intrapartum period.

Neurocognitive outcome of children exposed to perinatal mother-to-child Chikungunya virus infection: the CHIMERE cohort study on Reunion Island.

BACKGROUND: Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection. METHODS: The CHIMERE ambispective cohort study compared the neurocognitive function of 33 p-CHIKV-infected children (all but one enrolled retrospectively) at around two years of age with 135 uninfected peers (all enrolled prospectively). Psychomotor development was assessed using the revised Brunet-Lezine scale, examiners blinded to infectious status. Development quotients (DQ) with subscores covering movement/posture, coordination, language, sociability skills were calculated. Predictors of global neurodevelopmental delay (GND, DQ ≤ 85), were investigated using multivariate Poisson regression modeling. Neuroradiologic follow-up using magnetic resonance imaging (MRI) scans was proposed for most of the children with severe forms. RESULTS: The mean DQ score was 86.3 (95%CI: 81.0-91.5) in infected children compared to 100.2 (95%CI: 98.0-102.5) in uninfected peers (P<0.001). Fifty-one percent (n = 17) of infected children had a GND compared to 15% (n = 21) of uninfected children (P<0.001). Specific neurocognitive delays in p-CHIKV-infected children were as follows: coordination and language (57%), sociability (36%), movement/posture (27%). After adjustment for maternal social situation, small for gestational age, and head circumference, p-CHIKV infection was found associated with GND (incidence rate ratio: 2.79, 95%CI: 1.45-5.34). Further adjustments on gestational age or breastfeeding did not change the independent effect of CHIKV infection on neurocognitive outcome. The mean DQ of p-CHIKV-infected children was lower in severe encephalopathic children than in non-severe children (77.6 versus 91.2, P<0.001). Of the 12 cases of CHIKV neonatal encephalopathy, five developed a microcephaly (head circumference <-2 standard deviations) and four matched the definition of cerebral palsy. MRI scans showed severe restrictions of white matter areas, predominant in the frontal lobes in these children. CONCLUSIONS: The neurocognitive outcome of children exposed to perinatal mother-to-child CHIKV infection is poor. Severe CHIKV neonatal encephalopathy is associated with an even poorer outcome.

Low clinical burden of 2009 pandemic influenza A (H1N1) infection during pregnancy on the island of La Réunion.

BACKGROUND: Pregnant women have been identified as a group at risk, both for respiratory complications than for the admissions to the Intensive Care Unit (ICU) during the 2009 H1N1 influenza pandemic (pdm). The purpose of this prospective register-based cohort-study was to characterize the clinical virulence of the pdm (H1N1/09)v during pregnancy in La Réunion. METHODS/PRINCIPAL FINDINGS: Over a twelve-week pdm wave (13 July to 3 October 2009), 294 pregnant women presented with an influenza-like illness (ILI) to one of the three maternity departments of the South Reunion area, Indian Ocean. Out of these, 278 were checked by RT-PCR for influenza viruses (157 positive and 121 negative, of whom, 141 with pdm flu and 132 with ILIs of non pdm origin, 5 untyped). The median body temperature was higher in women experiencing pdm flu than in those with non pdm ILI (38.9 degrees C versus 38.3 degrees C, P<0.0001), without evidence linked to circulating viremia. Oseltamivir was given for 86% of pdm flu cases in a median time inferior than 48 hrs (range 0-7 days). The hospitalization rate for pdm flu was of 60% and not associated with underlying conditions. Six viral pneumonia and fourteen asthma attacks were observed among 84 hospitalized pdm flu cases, of whom, only one led to the ICU for an acute lung injury. No maternal death occurred during the pdm wave. None adverse pregnancy outcome was associated with pdm flu. No congenital birth defect, nor early-onset neonatal influenza infection was attributable to pdm flu exposure. CONCLUSIONS/SIGNIFICANCE: This report mitigates substantially the presumed severity of pandemic H1N1/09 influenza infection during pregnancy. The reasons for which the clinical burden of H1N1/09 influenza virus may differ worldwide raise questions about a differential local viral-strain effect and public health preparedness, notably in timely access to special care and antiviral treatments.