Treatment and outcome of congenital nephrotic syndrome.

BACKGROUND: Recommendations for management of Finnish-type congenital nephrotic syndrome (CNS) followed by many teams include daily albumin infusions, early bilateral nephrectomy, dialysis and transplantation. We aimed to assess the treatment and outcome of patients with CNS in France. METHODS: We conducted a nationwide retrospective study on 55 consecutive children born between 2000 and 2014 treated for non-infectious CNS. RESULTS: The estimated cumulative incidence of CNS was 0.5/100 000 live births. The underlying defect was biallelic mutations in NPHS1 (36/55, 65%), NPHS2 (5/55, 7%), PLCE1 (1/55, 2%), heterozygous mutation in WT1 (4/55, 7%) and not identified in nine children (16%). Fifty-three patients (96%) received daily albumin infusions from diagnosis (median age 14 days), which were spaced and withdrawn in 10 patients. Twenty children (35%) were managed as outpatients. Thirty-nine patients reached end-stage kidney disease (ESKD) at a median age of 11 months. The overall renal survival was 64% and 45% at 1 and 2 years of age, respectively. Thirteen children died during the study period including four at diagnosis, two of nosocomial catheter-related septic shock, six on dialysis and one after transplantation. The remaining 13 patients were alive with normal renal function at last follow-up [median 32 months (range 9-52)]. Renal and patient survivals were longer in patients with NPHS1 mutations than in other patients. The invasive infection rate was 2.41/patient/year. CONCLUSIONS: Our study shows: (i) a survival free from ESKD in two-thirds of patients at 1 year and in one-half at 2 years and (ii) a significant reduction or even a discontinuation of albumin infusions allowing ambulatory care in a subset of patients. These results highlight the need for new therapeutic guidelines for CNS patients.

Kidneys in 5-year-old preterm-born children: a longitudinal cohort monitoring of renal function.

BackgroundBeing aware of the impact of low birth weight on late-onset hypertension, our aim was to describe systolic blood pressure (sBP) and renal function in 3-5-year-old preterm-born children and to determine which perinatal factors or childhood factors were associated with an altered renal function at 5 years in these children.MethodsThis was a prospective longitudinal cohort study of children born at 27-31 weeks of gestation and included at birth and examined at 3, 4, and 5 years of age. The primary outcome was renal function at 5 years: BP, estimated glomerular filtration rate, and albuminuria.ResultsOne hundred and sixty five children were examined, of whom 93 (56.4%) were male. Gestational age was 29.2±1.4 weeks and birth weight was 1,217±331 g. Overall, 25% children had sBP ≥90th percentile at age 3 and 4 years and 11% at 5 years. In multivariate analysis, sBP ≥90th percentile at 5 years was associated with the use of antenatal steroids (OR=0.19(0.05;0.65)). There was a significant association between protein intake on day 28 and sBP at 5 years (ß=2.1±1.0, P=0.03). Glomerular filtration rate at 5 years was significantly decreased in case of hyaline membrane disease or necrotizing enterocolitis. High urine albumin was not predictable from one year to another.ConclusionIn preterm-born children, sBP was often high and neonatal protein intake was associated with increased blood pressure during childhood.

Breaking bad news in prenatal medicine: a literature review.

BACKGROUND: The diagnosis of a fetal anomaly in perinatal medicine forces expectant parents and healthcare providers to face the difficult process of breaking bad news. OBJECTIVES: This exploratory literature review was aimed at providing a medical and psychological view of the psychological experience in expectant parents and physicians in the context of prenatal diagnosis of a fetal anomaly. METHOD: An exploratory search of PubMed and PsycINFO/PsycARTICLES databases performed by an interdisciplinary team composed of a physician and psychologists. Search terms were: prenatal diagnosis AND bad news; prenatal diagnosis AND psychological consequences; prenatal diagnosis AND psychological sequelae; prenatal diagnosis AND fetal abnormality. The processing of selected articles followed a standardised five-step procedure. RESULTS: A total of 860 articles were screened of which 32 were retained for analysis. Four main themes emerged from the explanatory content analysis: (1) parents' subjective experience; (2) physicians' subjective experience; (3) encounters between expectant parents and professionals; and (4) ethical challenges in breaking bad news in prenatal medicine. CONCLUSION: Expectant parents go through a complex and multidimensional experience when the diagnosis of a fetal anomaly is disclosed. Simultaneously, physicians consider breaking bad news as a very stressful event and are poorly prepared in this regard. A better knowledge of factors underlying psychological adjustment of the parental dyad and on the subjective experience of physicians delivering these diagnoses could enable better adaptation for both patients and professionals.

ANTENATAL DETERMINANTS OF PARENTAL ATTACHMENT AND PARENTING ALLIANCE: HOW DO MOTHERS AND FATHERS DIFFER?

Parental (parent-to-infant) attachment and parenting alliance are defined as two important components of psychoaffective adjustment to the parental role. This study aimed to build a predictive model of parental attachment and parenting alliance for mothers and fathers using partial least squares-structural equation modeling. Specifically, we were interested in assessing how adult romantic attachment, marital quality, and psychological distress influenced parental attachment (parent-to-infant) and parenting alliance. Forty heterosexual couples completed questionnaires during the third trimester of pregnancy and 2 months after childbirth. Results showed that adult romantic attachment, marital quality, and psychological distress were important antenatal determinants of parental attachment and parenting alliance, although they behaved differently for mothers and fathers. Hence, different predictive models were therefore proposed for mothers and fathers. Mothers' attachment to the child was influenced by internal factors as adult attachment dimensions; for fathers, it also depended on mothers' antenatal attachment to the child and on marital quality. Concerning parenting alliance, both mothers and fathers depended on own and partner's variables. Antenatal variables are important for what occurs during the transition to parenthood in terms of parenting adjustment and act differently for mothers and fathers. It thus is important to assess the psychological functioning of both mothers and fathers.

Efficacy of antenatal corticosteroids according to maternal and perinatal factors: a retrospective cohort study.

OBJECTIVE: The aim of this study is to evaluate the impact of multiple pregnancies, maternal obesity, and preeclampsia on the effect of antenatal steroids on neonatal respiratory distress syndrome (RDS). STUDY DESIGN: The retrospective cohort study was performed in a level III maternity ward. Population was composed of mother-infant pairs. We included inborn infants < 34 weeks gestation, hospitalized in our neonatal intensive care unit, and mothers delivering before 34 weeks gestation and hospitalized before delivery. Primary measurement outcome was RDS. RESULTS: A total of 1,173 subjects were included: 535 mothers and 638 preterm infants. Antenatal corticosteroid (ACS) doses and pulmonary surfactant doses were negatively correlated (r = -0.15, p = 0.0002). Multiple logistic regression: lower gestational age and cesarean section were significantly associated with RDS in single pregnancies (odds ratio [OR], 95% confidence interval [CI]): 2.0 (1.7-2.4) and 3.6 (1.8-7.1), respectively; only gestational age was associated with RDS in twin or higher-order pregnancies: 2.7 (1.9-4.1) and 1.8 (0.6-5.4), respectively. Preterm infants of obese women did not receive more pulmonary surfactant than other preterm infants: OR = 0.67 (0.13-1.40), neither did those born to women with hypertension or preeclampsia. CONCLUSION: More ACS doses were associated with less pulmonary surfactant doses. Cesarean section and low gestational age increased the risk of RDS, independently from ACS administration, but maternal obesity and multiple pregnancies did not.

Impact of neonatal factors and nutrition on kidney size in 5-year-old preterm-born children.

OBJECTIVE: The aim of this article is to evaluate the influence of neonatal factors on kidney size in 5-year-old preterm-born children. STUDY DESIGN: Preterm-born children were examined at 5 years with kidney ultrasound. RESULT: A total of 20 children were evaluated. Their gestational age (GA) was 29.3 ± 1.5 weeks, birth weight 1,321 ± 323 g. On Day 28, protein intake was (median, range) 2.8 (1.7-3.6 g/kg) g/kg, protein/total calories ratio 2.8 (range, 1.7-3.3 g/100 kcal) g/100 kcal. At 5 years, their systolic blood pressure was 97 mm Hg (range, 84-115 mm Hg). All had normal estimated glomerular filtration rate. Protein intake on Day 28 and protein/calories ratio on Day 28 were associated with a low total relative renal volume, respectively, ß = - 37 ± 15, p = 0.03; ß = - 50 ± 19, p = 0.03, after adjustment on GA, neonatal morbidities, and body mass index (multivariate linear regression). Kidney size was not associated with protein intake at 5 years. CONCLUSION: Improving protein prescription in the neonatal period could have an impact on kidney size in childhood in preterm-born children.

Kidney outcomes in Shiga toxin-associated hemolytic uremic syndrome in childhood: A retrospective single-center study from 1999 to 2017: Kidney outcomes in typical hemolytic uremic syndrome in childhood.

BACKGROUND: Shiga toxin-associated hemolytic uremic syndrome (STECHUS) is the main cause of acute kidney injury in children and may be responsible for adverse outcomes despite an apparent quiescent period. OBJECTIVE: To describe the medium- and long-term kidney outcomes of pediatric STECHUS in a French region. METHODS: A single-center, descriptive, retrospective study of STECHUS cases that occurred at Besançon University Hospital between 1999 and 2017 in children up to 17 years of age was conducted. The primary study endpoint was the proportion of chronic kidney disease (CKD) cases at 5 years of follow-up. RESULTS: We included 98 consecutive patients. Among the 71 patients at the 5-year follow-up, we found 24 (34 %) patients with no adverse kidney outcome, 18 (25 %) with moderate adverse kidney outcome, and one (1.4 %) with severe adverse kidney outcome. Among the 96 patients at 1 year from the diagnosis, these figures were, respectively, 25 (26 %), 51 (53 %), and two (2 %); and among the 38 patients at 10 years, they were, respectively, nine (24 %), 12 (32 %), and one (3 %). The glomerular filtration rate level and oliguria-anuria beyond 8 days at baseline were significantly associated with more severe kidney outcomes at 10 years (p = 0.03 and 0.005, respectively). Two patients died during the acute phase. Overall, 33 patients (34 %) were lost to follow-up. CONCLUSION: Adverse kidney outcomes may appear many years after an episode of STECHUS despite an apparent quiescent period. Regular long-term monitoring is required. The challenge is to reduce the proportion of patients lost to follow-up with potentially severe adverse kidney outcomes and no evaluation or treatment.

Socioeconomic deprivation and hospital length of stay: a new approach using area-based socioeconomic indicators in multilevel models.

BACKGROUND: Socioeconomic deprivation is not easily measurable in hospital information systems. However, its identification is essential, as it is associated with morbidity and hospital length of stay (LOS). We aimed at studying the feasibility of using routinely recorded individual and area-based socioeconomic indicators, and assessing their relation with LOS. METHODS: In a cross-sectional study we collected area-based socioeconomic deprivation indicators from French census databases and individual ones from the 2009 medical and administrative databases of a French referral maternity hospital. The principal outcome was the LOS for delivery. Individual level socioeconomic deprivation indicators included preferential insurance scheme (health insurance allocated to poor persons). Nine area-based socioeconomic deprivation indicators were aggregated at the census tract and commune levels. The relation between socioeconomic deprivation and LOS was studied using multilevel models. The well-documented relation between socioeconomic deprivation and preterm delivery was firstly studied in these models as a validation step. RESULTS: The linkage between aggregated and individual data was possible for the 3471 women included. The median LOS was 5 days. In multivariable analysis adjusted for age (P=0.02), twinning (P=0.0001), delivery mode (P<0.0001), drug addiction (P<0.0001), diagnosis-related group severity level (P<0.0001), and unemployment rate (P=0.002) were associated with an increased LOS. CONCLUSIONS: Identifying deprived patients in hospital databases using routinely collected area-based indicators is feasible. The relation of these latter with LOS is consistent with previous studies. Further multicenter investigations are needed to confirm the interest of using such indicators for cost and morbidity predictions.

Exercise-induced bronchoconstriction in school-age children born extremely preterm.

BACKGROUND: School children born preterm often show airway hyperresponsiveness to methacholine or histamine. Less attention has been paid to their airway response to exercise, an important point because of the role of exercise in the child's daily life. The aim of this study was to describe the characteristics of, and potential determinants to, the airway response to exercise in children born extremely preterm. METHODS: Forty-two nonasthmatic nonatopic children born before 32 wk gestation were compared with 27 healthy nonasthmatic nonatopic term children at age 7. Spirometry and respiratory impedance were measured at baseline and repeated after a single-step 6-min treadmill exercise in a climate-controlled room. RESULTS: The preterm group showed significant broncho-constriction induced by exercise. Prematurity, but not low baseline lung function, neonatal oxygen supplementation, mechanical ventilation, chronic lung disease, or maternal smoking, was a determinant of exercise-induced bronchoconstriction. CONCLUSION: Children born extremely preterm present significant exercise-induced airway obstruction at age 7. The response has different characteristics from that occurring in asthmatics and is likely to express airway noneosinophilic inflammation.

Increased albuminuria in 4-year-old preterm-born children with normal height.

OBJECTIVE: To determine risk factors for high blood pressure (BP), increased markers of glomerulosclerosis, and tubular dysfunction in 4-year-old preterm-born children. STUDY DESIGN: The study group was a longitudinal cohort of 119 children with BP, albuminuria, and ß2 microglobulin measurements obtained during the neonatal period and at age 4 years. RESULTS: Systolic BP was >95(th) percentile in 15 (12.6%) of the children at age 4 years and lower in those born small for gestational age compared with those born appropriate for gestational age. Preterm-born 4-year-olds with height <-1 SD had lower systolic and diastolic BP, and 14.4% of the 4-year-olds had albuminuria. Albuminuria was less prevalent in the 4-year-olds with height <-1 SD than in those with height ≥-1 SD (6.8% vs 19.3%; P=.04). Mean albuminuria level was 1.0±0.7 mg/mmol in 4-year-olds with height <-1 SD and 1.4±1.3 mg/mmol in those with height ≥-1 SD. In multivariate analysis, albuminuria level was increased by 0.4±0.2 mg/mmol in preterm-born children with normal height at age 4, and by 0.5±0.2 mg/mmol in females, after adjustment for gestational age, sex, neonatal morbidity, and intrauterine growth restriction. These results were unchanged after adjustment for body mass index. CONCLUSION: Normal height at age 4 years may be associated with an increased risk for glomerulosclerosis in preterm-born children.

The influence of fetal growth reference standards on assessment of cognitive and academic outcomes of very preterm children.

OBJECTIVE: To compare 3 methods of identifying small-for-gestational-age (SGA) status in very preterm children as related to cognitive function and academic outcome. STUDY DESIGN: There were 1038 singletons in the Epipage Study, born before 33 weeks in 1997 without severe neurosensory impairment, who were classified as SGA when birth weight was below the 10th percentile according to: (1) birth weight (bw) reference: SGA(bw)/appropriate for gestational age (AGA)(bw); (2) intrauterine (intraut) reference: SGA(intraut)/AGA(intraut); and (3) intrauterine reference customized (cust) according to individual characteristics: SGA(cust)/AGA(cust). Cognitive function was assessed by the mental processing composite (MPC) score of the Kaufman Assessment Battery for Children at age 5 and academic achievement by a parental questionnaire at age 8. RESULTS: Of the children, 15% were SGA(bw), 38% were SGA(intraut), and 39% were SGA(cust). All children SGA(bw) were also SGA(intraut) and SGA(cust). MPC was <85 in 32% of children and 27% had low academic achievement. AGA(bw)/SGA(intraut) children had a significantly increased risk of MPC <85 (adjusted OR 1.74, 95% CI 1.22-2.28) or low academic achievement (adjusted OR 1.64, 95% CI 1.05-2.55) compared with AGA(bw)/AGA(intraut) children. The SGA(cust) group was only slightly different from the SGA(intraut) group. CONCLUSIONS: An intrauterine reference identified very preterm infants at risk of poor cognitive or academic outcomes better than a birth weight reference. Customization resulted in only slight modifications of the SGA group.

Echocardiography as a guide for patent ductus arteriosus ibuprofen treatment and efficacy prediction.

OBJECTIVE: To evaluate echocardiography criteria in predicting the response to ibuprofen treatment. DESIGN: A prospective cohort study of preterm infants untreated or treated with ibuprofen for patent ductus arteriosus. SETTING: Three academic neonatal intensive care units. PATIENTS: Two hundred fifty-two preterm infants of 27-31 wks gestation. INTERVENTIONS: Ibuprofen treatment within the first 5 days of life was indicated when at least two out of four conventional echocardiography criteria were observed: ductal diameter >2 mm, left-right ductal shunt maximum velocity <2 m/sec, mean flow velocity in left pulmonary artery >0.4 m/sec, and end-diastolic flow velocity in left pulmonary artery >0.2 m/sec. MEASUREMENTS AND MAIN RESULTS: Of the infants analyzed, 135 had a closed ductus at an average age of 1.9 ± 0.9 days, and 43 had an open ductus but <2 predefined criteria. Seventy-four infants (29%) received ibuprofen on day 2.2 ± 1.1. Sixteen infants failed ibuprofen and nine had to undergo surgical ligation. The left-right ductal shunt maximum velocity criterion had the best negative predictive value for treatment response, while the ductal diameter criterion had the best positive predictive value. CONCLUSIONS: Echocardiography may be a useful tool to help patent ductus arteriosus management. A combined use of ductal diameter and left-right ductal shunt maximum velocity criteria allows a more accurate prediction of the response of infants with patent ductus arteriosus to ibuprofen treatment.

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.

The renal adverse effects of ibuprofen are not mediated by AQP2 water channels.

The aim of this study was to determine (1) whether ibuprofen treatment in very preterm infants causes an increase in the renal water channel aquaporin-2 (AQP2) activity in the collecting duct via prostaglandin synthesis inhibition and (2) whether AQP2 activity remains disturbed long after ibuprofen treatment has ended. This was a prospective study involving premature infants with a gestation age of 27-31 weeks who received treatment between December 2005 and August 2006 in a tertiary Neonatal Intensive Care Unit. Each ibuprofen-treated infant was matched to two controls. Renal glomerular and tubular function were evaluated weekly for 1 month, and urinary AQP2 was measured by immuno-dotting. In total, 166 longitudinal samples were analyzed in 36 infants. Median [interquartile range] gestational age and birthweight were 28 [27.0-29.5] weeks and 1160 [1041-1242] g, respectively. Perinatal factors were similar in both groups. Urine output was significantly decreased in the ibuprofen-treated infants during the treatment. The urinary AQP2 level decreased significantly from day 2 to day 7 in both groups and was similar thereafter for the first month of life in ibuprofen-treated and control groups. Based on our results, we conclude that ibuprofen-induced oligo-anuria is not associated with a change in AQP2 activity and that ibuprofen does not affect AQP2 activity during the first month of life in very preterm neonates.

Ibuprofen in very preterm infants impairs renal function for the first month of life.

We carried out a study aiming to determine the renal effect of ibuprofen treatment for patent ductus arteriosus (PDA) in very preterm infants during the first month of life. Infants aged 27-31 weeks gestation were enrolled from October 2004 to August 2006. They were assigned to two different groups according to ibuprofen exposure during care of their PDA status assessed by echocardiography. Infants of both groups were matched based on gestational age, Clinical Risk Index for Babies score, birth weight and inclusion center. Renal function was evaluated at baseline and weekly for 1 month. One hundred and forty-eight infants were enrolled. Glomerular filtration rate (GFR) was significantly decreased in the ibuprofen group after treatment withdrawal (GFR on day 7, ibuprofen versus no ibuprofen: 12.8 +/- 6.2 vs. 18.1 +/- 12.1 ml/min/1.73 m(2); P < 0.001). Adjusted analysis proved this decrease to be sustained during the first month of life. Tubular function was also impaired during the first month in ibuprofen-treated infants. Ibuprofen administered for PDA is associated with a decreased GFR during the first month of life. Renal function of infants receiving ibuprofen should be carefully monitored and drugs that are eliminated by glomerular filtration handled cautiously during this period.

Development of a Web-Based Formative Self-Assessment Tool for Physicians to Practice Breaking Bad News (BRADNET).

BACKGROUND: Although most physicians in medical settings have to deliver bad news, the skills of delivering bad news to patients have been given insufficient attention. Delivering bad news is a complex communication task that includes verbal and nonverbal skills, the ability to recognize and respond to patients' emotions and the importance of considering the patient's environment such as culture and social status. How bad news is delivered can have consequences that may affect patients, sometimes over the long term. OBJECTIVE: This project aimed to develop a Web-based formative self-assessment tool for physicians to practice delivering bad news to minimize the deleterious effects of poor way of breaking bad news about a disease, whatever the disease. METHODS: BReaking bAD NEws Tool (BRADNET) items were developed by reviewing existing protocols and recommendations for delivering bad news. We also examined instruments for assessing patient-physician communications and conducted semistructured interviews with patients and physicians. From this step, we selected specific themes and then pooled these themes before consensus was achieved on a good practices communication framework list. Items were then created from this list. To ensure that physicians found BRADNET acceptable, understandable, and relevant to their patients' condition, the tool was refined by a working group of clinicians familiar with delivering bad news. The think-aloud approach was used to explore the impact of the items and messages and why and how these messages could change physicians' relations with patients or how to deliver bad news. Finally, formative self-assessment sessions were constructed according to a double perspective of progression: a chronological progression of the disclosure of the bad news and the growing difficulty of items (difficulty concerning the expected level of self-reflection). RESULTS: The good practices communication framework list comprised 70 specific issues related to breaking bad news pooled into 8 main domains: opening, preparing for the delivery of bad news, communication techniques, consultation content, attention, physician emotional management, shared decision making, and the relationship between the physician and the medical team. After constructing the items from this list, the items were extensively refined to make them more useful to the target audience, and one item was added. BRADNET contains 71 items, each including a question, response options, and a corresponding message, which were divided into 8 domains and assessed with 12 self-assessment sessions. The BRADNET Web-based platform was developed according to the cognitive load theory and the cognitive theory of multimedia learning. CONCLUSIONS: The objective of this Web-based assessment tool was to create a "space" for reflection. It contained items leading to self-reflection and messages that introduced recommended communication behaviors. Our approach was innovative as it provided an inexpensive distance-learning self-assessment tool that was manageable and less time-consuming for physicians with often overwhelming schedules.

[Termination of pregnancy: A survey about its evolution in French perinatal centres]. / Évolution des demandes d'interruption médicale de grossesse : enquête auprès du centre pluridisciplinaire de diagnostic prénatal de Lorraine.

CONTEXT: Termination of pregnancy (TOP) is regulated by French law for decades. Indications of TOP may vary depending on progress performed in perinatal medicine and in diagnosis of fetal anomalies, and also according to the way malformations are perceived in society. OBJECTIVES: To determine whether the frequency and indications of TOP had varied in the Lorraine Centre for Perinatal Diagnosis from 2000 to 2012. SUBJECTS AND METHODS: Retrospective study performed on a randomized sample of medical files presented in the Lorraine Centre for Perinatal Diagnosis in years 2000, 2006 and 2012. We analyzed the number of files presented by parents-to-be, the indication motivating TOP, general characteristics of both pregnancies and mothers. We also performed a prospective enquiry among the French Centres for Perinatal Diagnosis in order to determine national rates. RESULTS: General characteristics of mothers and pregnancies were similar from 2002 to 2012. No modification in indications of TOP was measured. In Lorraine, most TOPs were performed for chromosomal abnormality. On the national level, centres for perinatal diagnosis received more requests for TOPs in the study period. There were also more TOPs for non-lethal fetal anomalies, and parents refusing TOPs though the centres had agreed with its indication. CONCLUSION: The national trends were not measured in Lorraine region.

Late Surfactant Administration in Very Preterm Neonates With Prolonged Respiratory Distress and Pulmonary Outcome at 1 Year of Age: A Randomized Clinical Trial.

IMPORTANCE: Although immature neonate survival has improved, there is an increased risk of developing bronchopulmonary dysplasia, leading to significant respiratory morbidity. Measures to reduce bronchopulmonary dysplasia are not always effective or have important adverse effects. OBJECTIVE: To evaluate the effect of late surfactant administration in infants with prolonged respiratory distress on ventilation duration, respiratory outcome at 36 weeks' postmenstrual age, and at 1 year postnatal age. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized clinical trial at 13 level III French perinatal centers. Participants included 118 neonates at less than 33 weeks' gestation who still required mechanical ventilation on day 14 (SD, 2) with fraction of inspired oxygen of more than 0.30. All survivors were eligible for follow-up. We performed an intent-to-treat analysis. INTERVENTIONS: Infants received 200 mg/kg of poractant alfa (surfactant) or air after randomization. At 1 year, after parents' interview, infants underwent physical examination by pediatricians not aware of the randomization. MAIN OUTCOMES AND MEASURES: The duration of ventilation was the primary outcome. The combined outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age and respiratory morbidity at 1 year of age were the main secondary outcome measures. RESULTS: Of the 118 infants who participated in the study, 65 (55%) were male. Fraction of inspired oxygen requirements dropped after surfactant, but not air, for up to 24 hours after instillation (0.36 [0.11] vs 0.43 [0.18]; P < .005). Severe bronchopulmonary dysplasia/death rates at 36 weeks' postmenstrual age were similar (27.1% vs 35.6%; P = .32). Less surfactant-treated infants needed rehospitalization for respiratory problems after discharge (28.3% vs 51.1%; P = .03); 39.5% vs 50% needed respiratory physical therapy (P = .35). No difference was observed for weight (7.8 [1.2] kg vs 7.6 [1.1] kg), height (69 [5] cm vs 69 [3] cm), and head circumference (44.4 [1.7] cm vs 44.2 [1.7] cm) measured at follow-up, nor for neurodevelopment outcome. CONCLUSIONS AND RELEVANCE: Late surfactant administration did not alter the early course of bronchopulmonary dysplasia. However, surfactant-treated infants had reduced respiratory morbidity prior to 1 year of age. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01039285.

Survival and morbidity of preterm children born at 22 through 34 weeks' gestation in France in 2011: results of the EPIPAGE-2 cohort study.

IMPORTANCE: Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. OBJECTIVES: To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. DESIGN, SETTING, AND PARTICIPANTS: The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. MAIN OUTCOMES AND MEASURES: Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). RESULTS: A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. CONCLUSIONS AND RELEVANCE: The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.