Anna Karin Edstedt Bonamy

Increased Risk of Barrett's Esophagus Among Individuals Born Preterm or Small for Gestational Age

BACKGROUND & AIMS Gastroesophageal reflux is common in infants during their first year of life, especially in those born preterm or small for gestational age (SGA). We assessed whether being born preterm or SGA increased the risk of developing Barretts esophagus (BE) in adulthood. METHODS We performed a population-based case-control study of patients with BE (cases) that were diagnosed at 2 Swedish hospitals from January 1, 1986, through December 31, 2005. We identified the birth hospital of the cases; data on perinatal characteristics such as gestational age at birth and birth weight were collected from original birth records. We also obtained and collected information on the 3 singleton live births, of the same sex, born after each case at the same maternity ward (controls). In total, we analyzed data from 331 cases and 852 matched controls. We used conditional logistic regression to determine odds ratios (ORs), determined 95% confidence intervals (CIs), and adjusted for potential confounding factors. RESULTS Compared with infants born with a normal birth weight (3000-3999 g), infants with low birth weight (<2500 g) were at increased risk of BE (adjusted OR, 8.22; 95% CI, 2.83-23.88). This was mainly due to an effect of SGA rather than preterm birth. Specifically, compared with infants with normal birth weight for gestational age (25th-75th percentiles), the odds of BE among very SGA infants (<3rd percentile) was nearly tripled (adjusted OR, 2.95; 95% CI, 1.35-6.44). CONCLUSIONS On the basis of a population-based study of patients with BE in Sweden, infants born SGA have a 3-fold increase in risk for developing BE as adults, compared with infants of normal birth weight for gestational age.

Use of magnesium sulfate before 32 weeks of gestation: a European population-based cohort study

Objectives The use of magnesium sulfate (MgSO4) in European obstetric units is unknown. We aimed to describe reported policies and actual use of MgSO4 in women delivering before 32 weeks of gestation by indication. Methods We used data from the European Perinatal Intensive Care in Europe (EPICE) population-based cohort study of births before 32 weeks of gestation in 19 regions in 11 European countries. Data were collected from April 2011 to September 2012 from medical records and questionnaires. The study population comprised 720 women with severe pre-eclampsia, eclampsia or HELLP and 3658 without pre-eclampsia delivering from 24 to 31 weeks of gestation in 119 maternity units with 20 or more very preterm deliveries per year. Results Among women with severe pre-eclampsia, eclampsia or HELLP, 255 (35.4%) received MgSO4 before delivery. 41% of units reported use of MgSO4 whenever possible for pre-eclampsia and administered MgSO4 more often than units reporting use sometimes. In women without pre-eclampsia, 95 (2.6%) received MgSO4. 9 units (7.6%) reported using MgSO4 for fetal neuroprotection whenever possible. In these units, the median rate of MgSO4 use for deliveries without severe pre-eclampsia, eclampsia and HELLP was 14.3%. Only 1 unit reported using MgSO4 as a first-line tocolytic. Among women without pre-eclampsia, MgSO4 use was not higher in women hospitalised before delivery for preterm labour. Conclusions Severe pre-eclampsia, eclampsia or HELLP are not treated with MgSO4 as frequently as evidence-based medicine recommends. MgSO4 is seldom used for fetal neuroprotection, and is no longer used for tocolysis. To continuously lower morbidity, greater attention to use of MgSO4 is needed.

Preterm arteries in childhood: Dimensions, intima-media thickness, and elasticity of the aorta, coronaries, and carotids in 6-y-old children born extremely preterm

BackgroundPreterm birth increases risk for adult cardiovascular disease. We hypothesized that arteries in 6-year-old children born preterm are narrower, with thicker intima-media and stiffer than in peers born at term.MethodsChildren born extremely preterm (EXP, n=176, birthweights: 348-1161g) and at term (CTRL, n=174, birthweights: 2430-4315g) were included. Using ultrasonography, we determined diameters of the coronaries (CA), common carotid arteries (CCA) and aorta, the carotid intima media thickness (cIMT), and the stiffness index of the CCA and aorta.ResultsArteries were 5-10% narrower in EXP than in CTRL (p<0.005) but after adjustment for body surface area, diameter differences diminished or disappeared. EXP-children born small for gestational age exhibited similar arterial dimensions as those born appropriate for date. The cIMT was 0.38 (SD=0.04) mm and did not differ between groups. Carotid but not aortic stiffness was lower in EXP than in CTRL.ConclusionsIn 6-year-old children born extremely preterm, conduit arteries are of similar or smaller size than in controls born at term, and they have no signs of accelerated intima media thickening or arterial stiffening. While these findings are reassuring for these children and their families, the causal pathways from preterm birth to adult cardiovascular disease remain unknown.Background:Preterm birth increases risk for adult cardiovascular disease. We hypothesized that arteries in 6-y-old children born preterm are narrower, with thicker intima-media and stiffer than in peers born at term.Methods:Children born extremely preterm (EXP, n = 176, birthweights: 348–1,161 g) and at term (CTRL, n = 174, birthweights: 2,430–4,315 g) were included. Using ultrasonography, we determined diameters of the coronaries (CA), common carotid arteries (CCA) and aorta, the carotid intima media thickness (cIMT), and the stiffness index of the CCA and aorta.Results:Arteries were 5–10% narrower in EXP than in CTRL (P < 0.005) but after adjustment for body surface area, diameter differences diminished or disappeared. EXP-children born small for gestational age exhibited similar arterial dimensions as those born appropriate for date. The cIMT was 0.38 (SD = 0.04) mm and did not differ between groups. Carotid but not aortic stiffness was lower in EXP than in CTRL.Conclusion:In 6-y-old children born extremely preterm, conduit arteries are of similar or smaller size than in controls born at term, and they have no signs of accelerated intima media thickening or arterial stiffening. While these findings are reassuring for these children and their families, the causal pathways from preterm birth to adult cardiovascular disease remain unknown.

Evidence-based neonatal unit practices and determinants of Postnatal corticosteroid-use in preterm births below 30 weeks ga in Europe. A population-based cohort study

Background Postnatal corticosteroids (PNC) were widely used to treat and prevent bronchopulmonary dysplasia in preterm infants until studies showed increased risk of cerebral palsy and neurodevelopmental impairment. We aimed to describe PNC use in Europe and evaluate the determinants of their use, including neonatal characteristics and adherence to evidence-based practices in neonatal intensive care units (NICUs). Methods 3917/4096 (95,6%) infants born between 24 and 29 weeks gestational age in 19 regions of 11 European countries of the EPICE cohort we included. We examined neonatal characteristics associated with PNC use. The cohort was divided by tertiles of probability of PNC use determined by logistic regression analysis. We also evaluated the impact of the neonatal unit’s reported adherence to European recommendations for respiratory management and a stated policy of reduced PNC use. Results PNC were prescribed for 545/3917 (13.9%) infants (regional range 3.1–49.4%) and for 29.7% of infants in the highest risk tertile (regional range 5.4–72.4%). After adjustment, independent predictors of PNC use were a low gestational age, small for gestational age, male sex, mechanical ventilation, use of non-steroidal anti-inflammatory drugs to treat persistent ductus arteriosus and region. A stated NICU policy reduced PNC use (odds ratio 0.29 [95% CI 0.17; 0.50]). Conclusion PNC are frequently used in Europe, but with wide regional variation that was unexplained by neonatal characteristics. Even for infants at highest risk for PNC use, some regions only rarely prescribed PNC. A stated policy of reduced PNC use was associated with observed practice and is recommended.

Blood Pressure in 6‐Year‐Old Children Born Extremely Preterm

Background Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results We measured casual blood pressures (BPs) in a population‐based cohort of 6‐year‐old survivors of extremely preterm birth (<27 gestational weeks; n=171) and in age‐ and sex‐matched controls born at term (n=172). Measured BP did not differ, but sex, age‐, and height‐adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow‐up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week‐longer gestation. Conclusions Six‐year‐old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow‐up at older age is warranted.

Wide variation in severe neonatal morbidity among very preterm infants in European regions

Objective To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates. Design Area-based cohort study of all births before 32 weeks of gestational age. Setting 16 regions in 11 European countries in 2011/2012. Patients Survivors to discharge from neonatal care (n=6422). Main outcome measures Severe neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades ≥3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics. Results 10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%–23.5%) and 13.8% including severe BPD (regional range 10.0%–23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%–18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P<0.001) and severe neonatal morbidity rates were not correlated with mortality rates (P=0.50). Conclusion Severe neonatal morbidity rates for VPT survivors varied widely across European regions and were independent of mortality rates.

Cohort study from 11 European countries highlighted differences in the use and efficacy of hypothermia prevention strategies after very preterm birth

This study investigated the different strategies used in 11 European countries to prevent hypothermia, which continues to affect a large proportion of preterm births in the region.

O-066 Admission Hypothermia In Very Preterm Infants Is Associated With Mortality – Results From The Epice Cohort

Background Strategies to prevent heat loss in the delivery room after very preterm birth have been proven effective in randomised controlled trials. Nevertheless, we hypothesise that hypothermia at admission to neonatal care is still common and contributes to mortality after very preterm birth. Methods The EPICE cohort included all births between 22+0 and 31+6 weeks of gestation in 19 regions from11 European countries in 2011–2012. We studied infants surviving to admission to neonatal care (n = 7577). The association between temperature at admission and in-hospital mortality was analysed using logistic regression. The final model adjusted for gestational age, small for gestational age (SGA), Apgarscore <7 at 5 min, infant sex and region of birth. Results Of 6639 infants with data on body temperature at admission, 1670 infants (25%) were hypothermic (<36.0° C); 6% had temperatures <35°C, 7% between 35.0 and 35.4°and 12% between 35.5 and 35.9°. Body temperature at admission was inversely related to mortality. The crude odds ratio (OR) (95% confidence interval [CI]) for mortality was 5.81(4.27–7.92) when temperature was <35°C; 3.32 (2.35–4.69) at 35.0–35.4°; and 1.61 (1.18–2.19) at 35.5–35.9°compared to normothermic infants (36.5–37.5°C). After adjustment, temperatures below 35.5°C remained significantly associated with mortality, 1.94 (1.32–2.83) at <35°C and 1.91(1.30–2.82) at 35–35.4°C compared to normothermic infants. Conclusion Hypothermia after very preterm birth contributes to mortality in modern perinatal care settings in Europe. Further studies should investigate if evidence-based heat loss prevention strategies have been implemented.

PS-017 Changes In Troponin-t After Extremely Preterm Birth

Background Cardiac Troponin-T (cTNT) has been proposed as a useful marker of PDA-severity in preterm infants. Longitudinal-data on cTNT in extremely preterm infants is scarce. Methods We included 60 infants born before 28 weeks of gestation at the Karolinska University Hospital in Stockholm Sweden and measured cTnT at 3 days (range 2–4) and 7 days (range 5–9) of age. Fourty-two infants had cTNT measured at two weeks of life (range 11–18 days). Wilcoxon signed rank-test was used to test for differences in cTnT between the different time-points. Results Mean gestational age was 26.1 weeks (range 23.0–27.9) and mean birth weight 838 g (438–1287 g). At postnatal day 3, median cTnT was 148 ng/l (range 82–386). cTnT decreased between day 3 and day 7 to 96 ng/l (68–214) (p < 0.001). Between one and two weeks of age, cTnT again increased to 144 ng/l (95–338) (p = 0.001). Thirty-four infants (57%) were treated for a hemodynamically significant PDA (hsPDA) at a mean age of 8 days (SD 3.3). Twenty-three received only pharmacological treatment, 9 had surgery after pharmacological treatment and 2 had primary surgery. cTNT did not differ at any of the three time points between infants treated for hsPDA and infants not treated. Five infants who later died had significantly higher cTnT at 7 days of age than the 55 survivors (median 175 ng/l, compared to 94 ng/l) (p = 0.01). Conclusion cTnT levels in extremely preterm infants are tenfold higher than reference values in adults. We did not find any relation between cTnT and need for PDA-treatment in this study.

161 Prenatal Nicotine Exposure Increases the Risk of Neonatal Apnea -A National Birth-Cohort Study

Infant body composition is affected by maternal obesity, which results in increased % body fat in the infant. With the rapidly increasing incidence of obesity, it is important that normative data are available for infant body composition that is not affected by this trend in maternal obesity. This study assessed body composition in infants born at term to women with a BMI between 18.5 and 25. Infant % body fat, fat mass (FM), and fat free mass (FFM) were assessed at birth, 6 wk, 3 mo, and 4.5 mo of age by air displacement plethysmography, using the PEA POD body composition system. The effects of age, gender, GA, and feeding mode on these parameters were assessed. The % body fat doubled between birth and 6 wk of age and then increased at a slower rate. FFM was higher in male infants at all ages, whereas % body fat was higher in female infants at 4.5 mo. There was a trend to increased % fat and decreased FFM in breastfed (BF) infants. The study provides unique data regarding changes in infant body composition and growth in infants born to women in the healthy weight range.161 Prenatal Nicotine Exposure Increases the Risk of Neonatal Apnea -A National Birth-Cohort Study