Association of serum angiogenic factors with bronchopulmonary dysplasia. The ANGIODYS cohort study.

OBJECTIVES: Angiogenic factors may be involved in lung development. To evaluate the relations between maternal and cord blood angiogenic factors (sFlt-1, placental growth factor [PlGF], soluble endogline [sEng], transforming growth factor ß [TGF-beta]) and their association with moderate and severe bronchopulmonary dysplasia (BPD) in very preterm growth-restricted infants. STUDY DESIGN: Prospective monocentric cohort study. Twenty-four mother-child dyads featuring antepartum preeclampsia, intra-uterine growth restriction (IUGR) and birth before 30 weeks' gestation were included. This ensured a 80% power to test whether sFlt-1 maternal levels would be twice as high in cases of BPD as in the absence of BPD. MAIN OUTCOME MEASURES: Four pro/anti-angiogenic factors from two pathways (sFlt-1, PlGF and sEng, TGF-beta) were measured in maternal serum before delivery (at the time of hospitalization or the day of birth) and in neonates' cord blood. Neonatal outcome was moderate to severe BPD, defined as oxygen requirement for at least 28 days and persistent need for oxygen or ventilatory support at 36 weeks' postmenstrual age. RESULTS: sFlt-1 levels were positively correlated in maternal serum and cord blood (rs = 0.83, p < .001) but levels of PlGF and TGF-beta and its receptor sEng were not. Among all the factors studied in cord and maternal blood, none was associated with BPD. CONCLUSIONS: In IUGR preterm babies born before 30 weeks' gestation from preeclamptic mothers, serum sFlt-1, PlGF and sEng, TGF-ß levels were not correlated with BPD. The increased BPD risk in preterm neonates born from preeclamptic mothers cannot be related to high sFlt-1 levels.

Bronchopulmonary dysplasia in neonates born to mothers with preeclampsia: Impact of small for gestational age.

BACKGROUND AND OBJECTIVES: Small for gestational age and preeclampsia have both been described as risk factors for bronchopulmonary dysplasia in preterm neonates, but their respective role in the occurrence of bronchopulmonary dysplasia is debated. We evaluated the relation between small for gestational age and bronchopulmonary dysplasia in neonates born to mothers with preeclampsia. We hypothesized that low birth weight is still associated with bronchopulmonary dysplasia in this homogeneous population. METHODS: Retrospective single-center cohort study including 141 neonates born between 24 and 30 weeks' gestation to mothers with preeclampsia. The main outcome measure was moderate to severe bronchopulmonary dysplasia at 36 weeks' postmenstrual age. Neonates born small for gestational age (birthweight < 10th percentile on the AUDIPOG curves) were compared to those with appropriate birthweight for gestational age by bivariable analyses and logistic regression models, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Bronchopulmonary dysplasia rates were 61.5% (32/52) and 27.4% (20/73) for small for gestational age and appropriate birthweight for gestational age neonates (p < .001). On adjustment for gestational age and other confounding factors, the risk of moderate to severe bronchopulmonary dysplasia was greater for small for gestational age than appropriate birthweight for gestational age neonates (adjusted OR = 5.9, 95% CI [2.2-15.4]), as was the composite outcome death or moderate to severe bronchopulmonary dysplasia (adjusted OR = 4.7, 95% CI [1.9-11.3]). CONCLUSIONS: Small for gestational age was associated with bronchopulmonary dysplasia in very preterm neonates born to mothers with preeclampsia. REGISTRATION NUMBER: CNIL no. 1747084.

Impact of fetal growth restriction on neurodevelopmental outcome at 2 years for extremely preterm infants: a single institution study.

AIM: We evaluated the impact of fetal growth restriction on neurodevelopmental outcomes at 2 years corrected age for infants born before 27 weeks gestational age. METHOD: Data on infants born before 27 weeks gestational age between 1999 and 2008 (n=463), admitted to a tertiary neonatal unit in Paris, were used to compare neurological outcomes at 2 years for infants with birthweight lower than the 10th centile and birthweight of at least the 10th centile, using intrauterine reference curves. Outcomes were cerebral palsy (CP) and the Brunet-Lézine assessment of cognitive development, which provides age-corrected overall and domain-specific (global and fine motor skills, language and social interaction) developmental quotients. Models were adjusted for perinatal and social factors. RESULTS: Seventy-two percent of infants were discharged alive. Eighty-three percent (n=268) were evaluated at 2 years. Six percent had CP. Fetal growth restriction was not associated with the risk of CP. After adjustment, children with a birthweight lower than the 10th centile had a global developmental quotient 4.7 points lower than those with birthweight of at least the 10th centile (p<0.001); differences were greatest for fine motor and social skills (-4.7, p=0.053 and -7.3, p<0.001 respectively). INTERPRETATION: In extremely preterm children, fetal growth restriction was associated with poorer neurodevelopmental outcomes at 2 years, but not with CP.

Hydrocortisone use in ventilated extremely preterm infants decreased bronchopulmonary dysplasia with no effects on neurodevelopment after two years.

AIM: We assessed the outcomes of ventilated extremely premature infants treated with late postnatal corticosteroids from 2005-2008, according to permissive or restrictive policies in two centres. METHODS: This retrospective study included inborn infants below 27 weeks of gestational age who were ventilator dependent after 14 days. Centre P permitted postnatal corticosteroids but centre R restricted their use. The effects on infants were assessed in hospital and after two years using multivariable analysis. RESULTS: We compared 62 infants from centre P, including 92% who received hydrocortisone, and 48 infants from centre R, including 13% who received betamethasone. Infants from both centres had comparable baseline characteristics and perinatal management, but bronchopulmonary dysplasia (BPD) rates were significantly lower in centre P (30% versus 71%, p < 0.001) and this centre was significantly associated with a younger post-conceptional age at oxygen weaning, with an adjusted hazard ratio (aHR) of 0.45 and an aHR of 0.51at discharge. At two years of corrected age, 18% of centre P infants and 30% of centre R infants showed poor neurodevelopmental outcome (p = 0.18). CONCLUSION: Using hydrocortisone after 14 days on ventilated extremely preterm infants was associated with decreased BPD, with no apparent effects on neurodevelopment at two years of corrected age.

Does the antenatal detection of fetal growth restriction (FGR) have a prognostic value for mortality and short-term morbidity for very preterm infants? Results from the MOSAIC cohort.

OBJECTIVE: We investigated the impact of antenatal diagnosis of fetal growth restriction (FGR) on the risks of mortality and morbidity for very preterm infants given actual birthweight percentiles. METHODS: Data on 4608 live born infants 24-31 weeks of gestational age (GA) in 10 European regions in 2003 were used to compare in-hospital mortality, bronchopulmonary dysplasia (BPD) and severe neurological morbidity by birthweight percentiles and antenatal diagnosis of FGR. Other covariates were GA, sex, multiplicity, maternal complications, antenatal corticosteroids, birth in a level III center and region. RESULTS: Sixteen percent (n = 728) of all infants and 72%, 30% and 6%, respectively, of those with birthweight percentiles <10th, 10th-24th and ≥25th had an antenatal diagnosis of FGR. After adjustment for clinical factors, antenatal diagnosis of FGR was not associated with mortality for infants with a birthweight ≥10th percentile (OR [95% CI]: 0.9 [0.5-1.9] and 1.0 [0.6-1.8] for birthweights between the 10th-24th percentile and ≥25th percentile, respectively), but infants with a birthweight <10th percentile had higher mortality (OR [95% CI]: 2.4 [1.0-5.8]). No association was observed at any birthweight percentile with BPD or severe neurological morbidity. CONCLUSION: Antenatal diagnosis of FGR did not influence risks of mortality or morbidity when birthweight was ≥10th percentile; however, mortality risk was higher in antenatally detected infants with birthweight below the <10th percentile.

Impact of fetal growth restriction on mortality and morbidity in a very preterm birth cohort.

OBJECTIVE: To assess the impact of being small for gestational age (SGA) on very preterm mortality and morbidity rates by using different birthweight percentile thresholds and whether these effects differ by the cause of the preterm birth. STUDY DESIGN: The study included singletons and twins alive at onset of labor between 24 and 31 weeks of gestation without congenital anomalies from the Models of Organising Access to Intensive Care for very preterm births very preterm cohort in 10 European regions in 2003 (n = 4525). Outcomes were mortality, intraventricular hemorrhage grade III and IV, cystic periventricular leukomalacia, and bronchopulmonary dysplasia (BPD). Birthweight percentiles in 6 classes were analyzed by pregnancy complication. RESULTS: The mortality rate was higher for infants with birthweights <25th percentile when compared with the 50th to 74th percentile (adjusted odds ratio, 3.98 [95% CI, 2.79-5.67] for <10th; adjusted odds ratio, 2.15 [95% CI, 1.54-3.00] for 10th-24th). BPD declined continuously with increasing birthweight. There was no association for periventricular leukomalacia or intraventricular hemorrhage. Seventy-five percent of infants with birthweights <10th percentile were from pregnancies complicated by hypertension or indicated deliveries associated with growth restriction. However, stratifying for pregnancy complications yielded similar risk patterns. CONCLUSIONS: A 25th percentile cutoff point was a means of identifying infants at higher risk of death and a continuous measure better described risks of BPD. Lower birthweights were associated with poor outcomes regardless of pregnancy complications.

Increased incidence of necrotizing enterocolitis in premature infants born to HIV-positive mothers.

OBJECTIVE: To examine if being born to an HIV-positive mother may increase the risk of necrotizing enterocolitis in premature infants. DESIGN: Case-control study. SETTING: Neonatal unit of a level 3 perinatal centre. METHODS: : Over a period of 8.5 years, all cases of necrotizing enterocolitis occurring in premature infants admitted to the neonatal unit were identified. For each case, two controls were retrospectively chosen that matched for postmenstrual age at birth, intrauterine growth and year of birth. Perinatal characteristics were studied in all infants. MAIN RESULTS: There were 79 cases of necrotizing enterocolitis, which were compared with 158 controls. Using multivariate analysis, multiple pregnancy [odds ratio (OR), 2.29; 95% confidence interval (CI), 1.23-4.25; P = 0.009], abnormal umbilical artery velocity (OR, 2.21; 95% CI, 1.08-4.54; P = 0.030), abnormal fetal heart rate (OR, 2.14; 95% CI, 1.05-4.36; P = 0.036) and HIV-positive mother (OR, 6.63; 95% CI, 1.26-34.8; P = 0.025) were significantly more frequent in fetuses who subsequently developed necrotizing enterocolitis. CONCLUSIONS: This preliminary report suggests an association, not previously reported, between maternal HIV-positive status and an increased risk of necrotizing enterocolitis in premature infants. Despite the limitations of this study, we suggest that premature newborn infants of HIV-positive mothers should be monitored very carefully for a possible increased risk of necrotizing enterocolitis.

Lenticulostriate echogenic vessels: clinical and sonographic study of 70 neonatal cases.

BACKGROUND: Neonatal branching echogenic streaks in the basal ganglia or 'lenticulostriate vasculopathy' (LSV) has no clear comprehensive aetiology. OBJECTIVE: To provide some clinical evidence, possibly relevant to aetiology, by analysis of a large series. MATERIALS AND METHODS: Seventy cases (9 deaths, 3 post mortem) identified between 1981 and 2000 out of 9,138 neonates with routine brain sonograms (578 in a protocol for neonates from HIV+ mothers). Review of maternal/neonatal charts for clinical data and serologic status. Retrospective analysis of sonograms for grading and time course of LSV and coexistent abnormalities. RESULTS: LSV was unilateral in 31 cases (22 right), bilateral in 39. Grading separated 8 major, 27 moderate and 35 minor patterns. In 42 cases, LSV was isolated, and in 28 it was mixed with peri-intraventricular haemorrhage grades I or II and/or leucomalacia. LSV was detected in the first postnatal week in 56 instances and appeared later in 13. Disappearance occurred mostly within 2 months. Perinatal circumstances: 13 recipient monochorionic twins (polycythaemia from twin-twin transfusion syndromes), 20 HIV+ mothers (possible immunological disturbances; only 2 infected neonates), 10 congenital anomalies, 1 toxoplasmosis, 1 postnatal cytomegalovirus infection, 25 miscellaneous conditions. Numerous maternal and neonatal factors were non-contributory. CONCLUSIONS: These results do not support congenital toxoplasmosis, rubella, cytomegalovirus, and herpes (TORCH) infections as the main causative factor. Polycythaemia and various immunological disturbances may be involved, as well as infectious agents not appropriately screened by routine serodiagnoses.