Gérard Bréart

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.

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. 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. 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. 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.

Dengue is a mosquito-borne disease that is common in many tropical and subtropical areas. Dengue infections can occur at any age and time in the lifespan, including during pregnancy. Few large scale studies have been conducted to determine the risk of preterm birth (PTB) and low birthweight (LBW) for infants born to women who had symptomatic dengue infection during pregnancy. This study is a retrospective cohort study using medical records from 1992–2010 from pregnant women who attended a public regional referral hospital in western French Guiana. Exposed pregnancies were those with laboratory confirmed cases of dengue fever during pregnancy. Each of the 86 exposed infants was matched to the three unexposed births that immediately followed them to form a stratum. Conditional logistic regression was used to analyze these matched strata. Three groups were examined: all infants regardless of gestational age, only infants> = 17 weeks of gestational age and their strata, and only infants> = 22 weeks of age and their strata. Odds ratios were adjusted (aOR) for maternal age, maternal ethnicity, maternal gravidity, interpregnancy interval and maternal anemia. There was an increased risk of PTB among women with symptomatic dengue; (aOR all infants: 3.34 (1.13, 9.89), aOR 17 weeks: 1.89 (0.61, 5.87), aOR 22 weeks: 1.41 (0.39, 5.20)) but this risk was only statistically significant when all infants were examined (p value = 0.03). Adjusted results for LBW were similar, with an increased risk in the exposed group (aOR All infants: 2.23 (1.01, 4.90), aOR 17 weeks: 1.67 (0.71, 3.93), aOR 22 weeks: 1.43 (0.56, 3.70)) which was only statistically significant when all infants were examined (p value = 0.05). Symptomatic dengue infection during pregnancy may increase the risk of PTB and LBW for infants. More research is needed to confirm these results and to examine the role of dengue fever in miscarriage. Previous studies have reported that dengue fever during pregnancy may be related to preterm birth and low birthweight among infants. However, few studies have used an appropriate control group to compare the risk of these outcomes for infants whose mothers had dengue fever to infants whose mothers did not. We designed this study to provide information on the amount of risk (odds ratios) and the stability of this risk (confidence intervals) of being born preterm or with low birthweight to a mother with documented dengue infection during the pregnancy. In this study there was an increased risk among pregnant women with symptomatic dengue to deliver infants who are preterm or low birthweight, but both the amount of risk and the stability of this risk were affected by the inclusion or exclusion of miscarriages (infants born before 22 weeks of gestational age) This suggests that women who are pregnant should take extra precautions to avoid dengue infections during pregnancy, since it may cause an early delivery, or the birth of a small infant.