The effect of histological chorioamnionitis on the short-term outcome of preterm infants ≤32 weeks: a single-center study

Abstract

Background and objectives: Chorioamnionitis (CA) is an acute inflammation of the membranes and chorion of the placenta. The aim of this study was to determine the effect of histological CA on the short-term outcome of preterm infants.

Subjects and methods: The clinical characteristics and outcomes of the preterm infant including respiratory distress syndrome, duration of mechanical ventilation, patent ductus arteriosus (PDA) requiring medical treatment or ligation, necrotizing enterocolitis, bronchopulmonary dysplasia, death and intraventricular hemorrhage (IVH; grade III–IV) were analyzed.

Results: Two hundred and eighty-one infants born at ≤32 weeks gestational ages were included. Infants were divided into two groups: one with histological CA (n?=?145) and without histological CA (n?=?136). Mean gestational age was 28.8?±?2.6 weeks and 29.1?±?2.5 weeks, and mean birth weight was 1138?±?350?g and 1210?±?299?g, respectively. There were no differences in gestational age and birth weight among the groups. Compared with the group, histological CA was associated with early onset sepsis (p?=?0.007), PDA (p?=?0.003), IVH (p?=?0.03), and death (p?=?0.04).

Conclusion: Maternal histological CA is an important risk factor for preterm deliveries and associated with serious morbidities such as early onset sepsis, IVH, PDA and increased mortality.     

Method of delivery and intraventricular haemorrhage in extremely preterm infants

Objectives.?It has been reported that caesarean delivery (CD) protects against intraventricular haemorrhage (IVH) in the extremely preterm infant, but it is not known whether this effect involve the more severe grades of IVH. Thus, our aim was to confirm the correlation between the occurrence of IVH and the mode of delivery, and to evaluate this correlation for each grade of IVH.

Methods.?All infants with gestational age (GA)?≤?28 weeks admitted to the neonatal intensive care unit of a tertiary hospital were studied for each grade IVH and major complications rate.

Results.?We found that vaginally born infants had a higher rate of each grade of IVH, but the increase was statistically significant only for grade 3 IVH (18% vs. 2%, p?<?0.0001) and all grades IVH (45% vs. 20%, p?<?0.0001). Multivariate analysis demonstrated that CD (RR: 0.42, 95% CI 0.28–0.63), birth weight?≥?800?g (RR: 0.48, 95% CI 0.32–0.73), 27–28 weeks of GA (RR: 0.38, 95% CI 0.25–0.60) and antenatal steroids (0.66, 95% CI 0.22–0.46) decrease independently the risk of developing IVH.

Conclusions.?Our study demonstrates that CD decreases the risk of developing IVH in extremely preterm infants including the most severe grades of IVH.     

Cord blood erythropoietin and interleukin-6 for prediction of intraventricular hemorrhage in the preterm neonate

Objective.?To evaluate cord blood erythropoietin (EPO) and interleukin-6 (IL-6) levels to predict preterm infants at risk of developing intraventricular hemorrhage (IVH).

Methods.?Levels of umbilical cord EPO, acid–base status and IL-6 were analyzed in 116 consecutive, preterm newborns (GA at delivery: 29 [23–34 ] weeks) born to mothers who had a clinically indicated amniocentesis to rule out infection. Early-onset neonatal sepsis (EONS) was diagnosed using symptoms, hematological criteria and blood cultures.

Results.?IVH was diagnosed by cranial ultrasounds. The prevalence of IVH in our population was 25% (29/116). There was a direct relationship between cord blood EPO and cord blood IL-6 concentration (r?=?0.225, p?=?0.014), independent of GA at birth. Elevated cord blood EPO levels (r?=?0.182, p?=?0.016) and GA at birth (r?=??0.236, p?=?0.004) remained significant independent factors associated with the risk of IVH, when evaluated with stepwise logistic regression analyses. Cord blood IL-6, pH, and EONS were not associated with IVH. These relationships remained following correction for GA at birth (p?=?0.027).

Conclusions.?Our results suggest that elevation in cord blood EPO may predict newborns at risk for IVH, independent of fetal inflammatory status. Further studies are warranted to confirm this association.     

The use of 17-hydroxy progesterone in women with arrested preterm labor: a randomized clinical trial

Abstract

Background: The use of 17-alpha-hydroxyprogesterone caproate (17?P) has been shown to reduce preterm delivery in women who have had a prior preterm birth. The role of 17?P in women with arrested preterm labor is less certain.

Aims: To compare the preterm birth rate and neonatal outcome in women with arrested preterm labor randomized to receive 17?P or placebo.

Materials and methods: Women with arrested preterm labor were randomized to weekly injections of either 17?P (250?mg) or placebo. Maternal and neonatal outcome were evaluated.

Results: Forty-five singleton pregnancies were randomized after successful tocolysis; 22 received 17?P while 23 got placebo. Gestational age at delivery (p?=?0.067) and the interval from treatment to delivery (p?=?0.233) were not affected by 17?P. Significantly less women in the 17?P group delivered at <34 weeks (14 versus 21, p?=?0.035). There was also a significant reduction in the risk of neonatal sepsis (p?=?0.047) and gr III/IV intraventricular hemorrhage (IVH) (p?=?0.022) in the 17?P group.

Conclusion: In this study, 17?P did not delay the interval to delivery after successful preterm labor, but births <34 weeks as well as neonatal sepsis and IVH were reduced by 17?P treatment.     

Correlation between fetal heart rate reactivity and mortality and severe neurological morbidity in extremely low birth weight infants

Objective: To determine the correlation between specific fetal heart rate (FHR) abnormalities and the incidence of death, severe (grade 3–4) intraventricular hemorrhage (IVH) and periventricular echogenicity (PVE) in extremely low birth weight infants (ELBW) within the first 4 days after birth. Methods: The study included live-born ELBW infants ≤ 30 weeks’ gestation who were born in 2000–2007 at Kaplan Medical Center, Rehovot, Israel, and, who had FHR monitoring during the 24?h before delivery and cranial ultrasound during the first 4 days of life. FHR pattern was analyzed for the presence of baseline rate, reactivity, variability and decelerations. Results: 96 infants with mean birth weight 757?±?150?g and mean gestational age 25.8?±?1.5 weeks were included. By 4 days of life, 23/96 (24%) died, 17/96 (18%) developed severe IVH and 31/96 (32%) had PVE. Absence of reactivity was significantly associated with increase in both death (p?=?0.02, OR 3.45, 95% CI: 1.22–9.47 and severe IVH (p?=?0.029, OR 3.33, 95% CI: 1.25–10) but not with PVE. Other FHR parameters were not associated with adverse outcome. Conclusion: These results suggest that FHR reactivity may be of value in predicting short-term outcome in ELBW infants. This may be helpful in counseling parents with imminent extremely preterm birth.     

Total energy intake accounts for postnatal anthropometric growth in moderately/late preterm infants

Objective: Moderately preterm (MP) (32–33 weeks) and late preterm (LP) (34–36 weeks) infants have higher risks of mortality and growth and developmental problems. We, herein present a new concept of nutritional assessment, total energy intake (TEI), which is the sum total of kilocalories administered in all nutrient forms.

Methods: Fifty-two preterm infants were classified as MP (n?=?12), LP/appropriate for gestational age (LP/AGA) (n?=?33), or LP/small for gestational age (LP/SGA) (n?=?7). All groups received nutrient therapy by the same protocol. The sum of the daily energy intake at 14 and 28 days after birth was determined.

Results: TEI was 2822.1?±?162.1?kcal/kg/28 days in the MP group, 3187.2?±?265.0?kcal/kg/28 days in the LP/AGA group and 3424.6?±?210.4?kcal/kg/28 days in the LP/SGA group. In all groups, TEI for 28 days was significantly correlated with body weight gain (r?=?0.465, p?=?0.006). TEI for 14 days after birth was inversely correlated with the body weight loss rate after birth (r?=??0.491, p?=?0.0002).

Conclusion: TEI was well correlated with anthropometric changes after birth. TEI may be used to effectively assess preterm infants’ nutritional needs.     

Clamp late and maintain perfusion (CLAMP) policy: delayed cord clamping in preterm infants

Objective: Randomized controlled trials have demonstrated that delayed umbilical cord clamping (DCC) in preterm infants results in improved neonatal outcomes, including increased hematocrit, and decreased rates of intraventricular hemorrhage (IVH) and packed red blood cell transfusions. We hypothesized that implementation of a DCC policy in preterm infants would result in similarly improved outcomes, despite initial clinician resistance.

Study design: A DCC policy (30–60?s) for singleton infants <35 weeks gestation was implemented in September 2011. We conducted a pre-test/post-test analysis of neonatal outcomes among singletons delivered between 24 0/7 weeks and 34 6/7 weeks gestation from 2009 to 2013 (2 years pre-implementation and 2 years post-implementation). The primary outcomes were rates of policy compliance and four neonatal outcomes.

Results: Despite multiple routes of policy dissemination, DCC was attempted in only 49% of the deliveries. In spite of this, infants delivered post-policy implementation (n?=?196) had a significant decrease in IVH, significant increase in initial hematocrits, and improved temperatures compared with infants delivered pre-implementation (n?=?204).

Conclusion: After implementation of a DCC policy, preterm singleton infants had improved temperatures, increased hematocrits and a decreased prevalence of IVH without significant differences in adverse outcomes, suggesting that the benefits of DCC outweighed the risks.     

Neurodevelopmental outcomes of premature infants with severe intraventricular hemorrhage

Objective: Our objective was to determine the neurodevelopmental outcome at 18–24 months’ of corrected age (CA) in preterm infants with severe intraventricular hemorrhage (IVH).

Methods: This was a retrospective cohort study of all preterm infants who were <37 weeks’ gestation, had Grade 3–4 IVH, were admitted between January 2009 and December 2010 and discharged. The cohort was divided into three groups. Group 1 was defined as infants born with a birth weight (BW) less than 1000?g, group 2 was defined as infants born with a BW between 1000 and 1500?g and group 3 was defined as infants born with a BW between 1501 and 2500?g. Severe IVH was defined as the presence of grade 3–4 IVH on cranial ultrasound. Cranial ultrasound was performed in the first week of life and subsequently at weekly intervals by a radiologist. A comprehensive assessment including hearing, vision, neurological and developmental evaluation with Bayley Scales of Infant Development, Second edition was performed by the experienced researchers at 18–24 months’ CA. Neurodevelopmental impairment (NDI) was defined as at the presence of one or more of the following: cerebral palsy; Mental Developmental Index score lower than 70; Psychomotor Developmental Index score lower than 70; bilateral hearing impairment; or bilateral blindness.

Results: From January 2009 to December 2010, a total of 138 infants were diagnosed as severe IVH (grade 3–4). Of them, 74 (71.1%) infants (group 1?=?31, group 2?=?29 and group 3?=?14 infants) completed the follow-up visit and evaluated at 18–24 months’ CA. Median Apgar score (p?p?p?p?p?p?p?=?0.014, respectively). The duration of hospitalization and mortality rates consistent with the degree of prematurity were significantly higher in group 1 compared to groups 2 and 3 (p?=?0.03 and p?=?0.01). Among the long-term outcomes, the rates of CP and NDI did not differ between the groups (p?=?0.68 and p?=?0.068).

Conclusion: Our results demonstrated that long-term outcomes of preterm infants did not differ between the groups classified according to the BW at two years of age. This has leaded to the conclusion that severe IVH is alone represents a significant risk factor for poor neurodevelopmental outcome in this already high-risk population.     

Homocysteine levels and its association with intraventricular hemorrhage in preterm infants born to preeclamptic mothers

Abstract

Objective: To investigate the relation between serum homocysteine levels and intraventricular hemorrhage (IVH) in preterm infants born to preeclamptic mothers.

Method: This study included 84 preterm infants (42 born to preeclamptic mothers and 42 born to normotensive healthy mothers) who were admitted to Izmir Tepecik Training and Research Hospital Neonatology Clinic on the postnatal first day. The measurement of homocysteine levels in all samples were performed with an Immulite 2000 analyzer, using the chemiluminescence method. Cranial ultrasounds were performed on the fourth day and in the 1 month of age.

Results: The mean plasma levels of homocysteine in infants born to preeclamptic mothers and in the control group were 8.2?±?5.9?μmol/L and 5.3?±?2.7?μmol/L, respectively. The plasma levels of homocysteine were significantly higher in the study group (p?=?0.006). There was no association between the plasma homocysteine levels and IVH or other neonatal complications including necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia and mortality.

Conclusion: Our data suggest that plasma levels of homocysteine are higher among infants born to preeclamptic mothers, but these high levels are not associated with IVH and other neonatal complications in preterm infants.     

Effects of lutein supplementation on biological antioxidant status in preterm infants: a randomized clinical trial

Abstract

Objective: To test the hypothesis that lutein, compared to the placebo, would enhance the total antioxidant status (TAS) in the preterm infants.

Methods: Infants with gestational age (GA) ≤34 weeks were randomly assigned to receive a daily dose of lutein and zeaxanthin (0.5?mg?+?0.02?mg/kg/d) or placebo from the 7th day of life until 40th week of postmenstrual age or until discharge.

Results: Seventy-seven preterm infants were randomized (38 in the Lutein group and 39 in the Placebo group) with mean GA of 30.4 (±2.3) weeks and the mean birth weight of 1415 (±457) grams. The TAS did not result statistically different between the two groups during all the study period, but a significant linear correlation was evidenced between plasma lutein concentration and TAS (r?=?0.14, p?=?0.012) and between plasma zeaxanthin concentration and TAS (r?=?0.13, p?=?0.02).

Conclusions: Supplementation of preterm infants with orally lutein was ineffective in enhancing biological antioxidant capacity. Further studies need to better understand the bioavailability of lutein in the neonatal period in order to identify any best form of supplementation.

Trial registration number: UMIN000007041.     

Second stage of labor and intraventricular hemorrhage in early preterm infants in the vertex presentation

Abstract

Objective: To investigate the association between exposure to second stage of labor and duration of second stage, and risk of intraventricular hemorrhage (IVH) among infants delivered <30 weeks of gestation.

Methods: We conducted a retrospective cohort study among 158 singleton vertex deliveries (97 vaginal and 61 cesarean). Multivariable logistic regression was used to evaluate the risk of IVH related to second stage.

Results: Infants exposed to second stage as compared to those not exposed to second stage irrespective of their mode of delivery had increased risk of mild IVH (odds ratio [OR] 2.69; 95% confidence interval [CI] 1.15, 6.29) but not of severe IVH (OR 1.14; 95% CI 0.33, 3.84). No relation with risk of mild (OR 0.98; 95% CI 0.95, 1.01) and severe (OR 1.00; 95% CI 0.95, 1.05) IVH was observed for each 1?min increase in duration of second stage. We also observed no significant association between quartiles of duration of second stage and risk of mild (p?=?0.20) and severe (p?=?0.29) IVH. We did not observe any significant interaction by gestational age, chorioamnionitis, birth weight or presenting complaint on admission.

Conclusion: The risk of mild IVH was increased in those exposed to a second stage of labor. However, no clear association was observed between duration of second stage and mild or severe IVH.     

The influence of birth weight amongst 33–35 weeks gestational age (wGA) infants on the risk of respiratory syncytial virus (RSV) hospitalisation: a pooled analysis

Objective: To investigate the association between birth weight and respiratory syncytial virus (RSV) hospitalisation during the first year of life in 33°–35⁶ weeks’ gestational age (wGA) infants.

Study design: Pooled analysis of data (n?=?1218) from Spain, Germany, France and Italy.

Result: RSV hospitalised infants overall had a significantly higher birth weight than non-hospitalised infants (2.24 versus 2.14?kg; p?p?=?0.049) and females (2.22 versus 2.11?kg, p?=?0.007). The effect was significant only in 34 wGA infants (33 wGA: hospitalised 1.95?kg versus non-hospitalised 1.95?kg, p?=?0.976; 34 wGA: 2.26 versus 2.14?kg, p?=?0.007; 35 wGA: 2.37 versus 2.29?kg, p?=?0.070), particularly female 34 wGA infants (female: 2.24 versus 2.08?kg, p?=?0.019; male: 2.27 versus 2.20, p?=?0.191). Birth weight was shown to be an independent risk factor for RSV hospitalisation.

Conclusions: In 33–35 wGA infants, a higher birth weight appeared independently associated with an increased risk of RSV hospitalisation.     

Late pregnancy associated plasma protein A levels decrease in preterm labor

Objective.?The purpose of the present study is to evaluate late, ‘at admission’, Pregnancy-associated plasma protein-A (PAPP-A) levels as a predictor of preterm birth in women with complaints of preterm labor or preterm painful contractions.

Methods.?Prospective cohort study of singleton gestations, 23–37 weeks, and symptoms of preterm labor. Primary end point was delivery?<?37 weeks. Predictive PAPP-A values were calculated both for preterm delivery and threatened preterm delivery on receiver operator curve.

Results.?In all, 41 women (38.3%) delivered before 37 weeks (Group 1); 32 women (30.7%) had symptoms of preterm labor but did not deliver preterm (Group 2); 31 women (29.7%) delivered term (Group 3, control). Mean PAPP-A levels in preterm-labor and its matched control were 33.4?±?19.9 and 52.5?±?25.4?mIU/ml, respectively, and difference was statistically significant (p?=?0.003). Mean PAPP-A level in threatened preterm labor group was 47.6?±?25.3?mIU/ml and difference was significant compared to preterm-labor, but not significant compared to control group (p?=?0.028 and p?=?0.74, respectively).

Conclusion.?Late PAPP-A levels decreased in preterm labor, levels?<?29.8?mIU/ml was associated with increased risk for preterm birth, supporting active management whereas cutoff value of 33.6?mIU/ml is useful for discrimination of preterm birth from threatened preterm birth reaching to term.     

Effect of maternal and neonatal interleukin-6 − 174 G/C polymorphism on preterm birth and neonatal morbidity

Objective: The aim of this study was to analyze maternal and neonatal interleukin 6 (IL-6) (?174?G/C) polymorphism and to determine effect on preterm birth and neonatal morbidity.

Study Design: One hundred and sixty-four mothers (100 term births, 64 preterm births) and 183 newborn infants who were 100 healthy term and 83 preterm babies followed in newborn intensive care units were evaluated. PCR-RFLP was performed for IL-6 (?174?G/C) genotyping.

Results: The rate of GG genotype in mothers of term and preterm infants were 54% (n?=?54/100), 75% (n?=?48/64), respectively (p?>?.05) and the rate of GC?+?CC genotype was 46% (n?=?46/100) and 25% (n?=?16/64) in mothers giving term and preterm birth (PTB), respectively (p?n?=?65/100) and 81.9% (n?=?68/83) in term infants and preterm infants, respectively. GC?+?CC genotype was 35% (n?=?35/100) in term infants and 18.1% (n?=?15/83) in preterm infants (p?Conclusion: The IL-6 174?G/C gene polymorphism was significantly different between mothers who were giving to term and preterm birth. The presence of polymorphism is protective against preterm birth and was not associated with neonatal outcome.     

Optimising enteral nutrition in growth restricted extremely preterm neonates – a difficult proposition

Background: Optimising enteral nutrition of extremely preterm neonates (EP: Gestation <28 weeks) with intrauterine growth restriction (IUGR) has always been difficult considering their higher risk of necrotising enterocolitis (NEC), and frequency of feed intolerance.

Aim: To evaluate the nutritional outcomes in EP neonates with IUGR.

Methods: Data on demographic characteristics, feeding details (e.g. type of milk, postnatal age at start), and outcomes to discharge or death were collected from the medical notes for all EP neonates, who survived first 72?h of life, between January 2009 and December 2010. A standardised feeding protocol was followed during the study period.

Results: 38/220 (17.3%) EP neonates admitted during the study period had IUGR. The mean (IQR) age at start of minimal enteral nutrition [7 (5–10) versus 5 (4–8) days, p?=?0.005), and nutritional (1?ml/2hourly) feeds [12 (8–15) versus 9 (7–13) days, p?=?0.034] was significantly delayed in IUGR compared to non-IUGR neonates. IUGR neonates reached full enteral feeds (150?ml/kg/day) at a significantly late median (IQR) postnatal age [32 (21–40) versus 24 (17–31) days, p?=?0.009), taking longer time to achieve this milestone [20 (15–34) versus 16 (12–4) days, p?=?0.008). The incidence of postnatal growth restriction was significantly higher in IUGR versus non-IUGR (73% versus 45%, p?=?0.003) neonates. The incidence of?≥?Stage II NEC was low [18/220 (8.1%)] to make valid statistical comparisons.

Conclusion: Optimising enteral nutrition in growth restricted extremely preterm neonates is difficult using the current strategies for enteral nutrition.     

Echocardiography may cause significant pain response in preterm infants

Objective: The objective of this study is to evaluate if echocardiographic examination causes any pain response in term and preterm infants.

Methods: Term and preterm neonates who admitted to Neonatal Intensive Care Unit at Gazi University Hospital and Etlik Zubeyde Hanim Training and Research Hospital and were performed echocardiography for any reason were included into the study. Neonates were evaluated before, during and 10?minutes after the examination. Vital signs (heart rate, respiratory rate, blood pressure, transcutaneous oxygen saturation) were recorded. All subjects were also evaluated with Neonatal Infant Pain Scale during the examination.

Results: In this study, we evaluated 99 newborn infants. Five infants who received fentanyl treatment were excluded. The heart rate (p?=?0.000), respiratory rate (p?=?0.000), diastolic blood pressure (p?=?0.001) and oxygen saturation (p?=?0.000) during the examination were significantly different than the values before and 10?minutes after the examination. Infants whose gestational age ≤32 weeks (n:20) have significantly higher NIPS scores (mean?±?SEM?=?3.3?±?0.4) than the infants whose gestational age is greater than 32 weeks (n:71) (mean?±?SEM?=?2.4?±?0.2).

Conclusions: Echocardiographic examination which is known as noninvasive and painless causes significant pain in preterm infants.     

Measurement of interleukin-6 (IL-6) and erythropoietin (EPO) in umbilical cords of preterm infants with intraventricular hemorrhage in two hospitals in Tehran

Background: Intraventricular hemorrhage (IVH) is an important cause of death in premature infants. This study aimed to assess the association of the umbilical cord plasma levels of interleukin-6 (IL-6) and erythropoietin (EPO) with the occurrence and severity of IVH in premature infants.

Methods: Fifty premature newborns of mothers with chorioamnionitis risk factor were selected via nonprobability sampling. The concentration of the cord plasma’s IL-6 and erythropoietin were measured by enzyme-linked immunosorbent assay (ELISA) for 3 days. Finally, all samples underwent sonography for the diagnosis of IVH. Results analyzed statistically.

Results: Among the samples, 68.98% of them were diagnosed with IVH grade 1. The most severe IVH cases were detected on the second day. The mean and standard deviation of IL-6 level was 74.71?±?50.53 in the case group and 24.10?±?46.10 in the control group. There was a correlation between IL-6 levels and IVH (p?=?0.0005). The mean and standard deviation of EPO level was 18.38?±?15.23 in the IVH group and 6.45?±?13.48 in samples without IVH. A correlation was detected between EPO level and IVH (p?=?0.005).

Conclusion: The concentration of IL-6 and EPO levels of the cord plasma was higher in the premature newborns with IVH.     

Risk factors for periventricular echodensities and outcomes in preterm infants

Objectives: To determine the incidence, risk factors and outcomes associated with transient and/or persistent periventricular echodensities (PVED) among preterm infants.

Methods: Medical records of preterm infants born at?≤ 32 weeks gestational age (GA) with PVED and no other brain pathology were reviewed and compared to matched control infants in a case-controlled retrospective study. Neurodevelopmental outcomes at 8–24 months corrected age were documented.

Results: A 17.8% incidence of PVED was recorded, with the highest incidence of 30–40% recorded at 29–31 weeks GA. Study and control groups were similar for all maternal parameters and neonatal morbidities, except for a higher incidence of respiratory distress syndrome among the study group. PVED at one month of age was predicted by 5?min Apgar score?p?=?0.005)]. PVED was not associated with long-term neurodevelopmental disability.

Conclusions: No risk factors or specific associated morbidities were identified among preterm infants with transient PVED. PVED at one month of age was predicted by low 5?min Apgar scores, possibly suggesting different pathogenesis or timing between the groups. Long-term outcome studies are needed to determine PVED impact.     

Early paracetamol treatment associated with lowered risk of persistent ductus arteriosus in very preterm infants

Abstract

Objectives: Persistent ductus arteriosus (PDA) delays the recovery of very preterm infants (VLGA, gestation <32 weeks). Indomethacin/ibuprofen treatment and ligation of PDA have complications. As a prostaglandin synthase inhibitor paracetamol may also promote the closure of ductus arteriosus. We studied retrospectively whether early paracetamol therapy was associated with decreased incidence of PDA without adverse events.

Methods: On June 2009, we introduced intravenous paracetamol during early respiratory therapy. We included 105 VLGA infants who received paracetamol before the age of 72?h. The loading dose was 20?mg/kg followed by 7.5?mg/kg every 6 hours. The 96 VLGA infants admitted from January 2008 to May 2009 without lethal congenital disease were controls. Infants dying very early were excluded, leaving 102 paracetamol-exposed and 88 controls for analysis.

Results: After the introduction of paracetamol, the incidence of PDA decreased from 30.7% to 14.7% (p?=?0.008). Ibuprofen treatment was given to 15 paracetamol-treated and to 26 control infants (p?=?0.013). Three paracetamol-exposed and seven control infants required surgery. There was no detectable increase in adverse events.

Conclusions: Annual incidence of PDA decreased after introduction of paracetamol. Efficacy and safety in promoting the early closure of ductus arteriosus remains to be established.     

Feeding preterm neonates with patent ductus arteriosus (PDA): intestinal blood flow characteristics and clinical outcomes

Objective: To evaluate the effects of patent ductus arteriosus (PDA) on postprandial superior mesenteric artery blood flow velocities (SMA BFV)s and feeding tolerance in extremely low birth weight (ELBW) neonates.

Methods: Appropriate for gestational age, ELBW preterm neonates, tolerating bolus enteral feedings were eligible to participate in this prospective observational study. Pulsed Doppler was used to measure preprandial and postprandial (at 30 and 60?min) time-averaged mean velocity (TAMV), peak systolic velocity (PSV) and end diastolic velocity (EDV) once during the day of life 5–7; at the same time, PDA size was estimated using the PDA: left pulmonary artery (LPA) ratio.

Results: A total of 38 infants were studied, 16 in small, 13 in moderate and 9 in large PDA groups. The postprandial SMA BFVs were lower in the large PDA group, although not reaching statistical significance. Importantly, infants in the large PDA group reached full enteral intake later (p?=?0.02) and had higher incidence of death secondary of necrotizing enterocolitis (NEC; p?=?0.04).

Conclusions: ELBW preterm neonates with large PDA may have attenuated intestinal blood flow responses to feedings. There was also an association with higher rates of necrotizing enterocolitis and feeding intolerance in the large PDA group.