Riitta Ojala

Short versus prolonged indomethacin therapy for patent ductus arteriosus in preterm infants

OBJECTIVE To evaluate whether a prolonged low-dose course of indomethacin would produce an improved closure rate and have fewer side effects compared with a short standard dosage schedule in the management of patent ductus arteriosus (PDA) in preterm infants. STUDY DESIGN Sixty-one infants of gestational ages 24 to 32 weeks with a PDA confirmed with echocardiography were randomized to receive 0.2 to 0.1 to 0.1 mg/kg indomethacin in 24 hours (short course, n = 31) or 0.1 mg/kg every 24 hours 7 times (long course, n = 30). Echocardiography was done 3, 9, and 14 days after the treatment was started, and side effects were monitored. RESULTS Primary PDA closure occurred more often in the short course group (94% vs 67%, P =.011), but the sustained closure rates were not different (74% vs 60%). Surgical PDA ligations were less frequent in the short course group than in the long course group. The short course group had a shorter duration of oxygen supplementation, less frequent symptoms of necrotizing enterocolitis, and a lower rate of urea retention. Mortality and other neonatal morbidity rates were similar. CONCLUSION A prolonged low-dosage indomethacin regimen offers no advantage compared with a standard-dosage short course in the management of a hemodynamically significant PDA in preterm infants.

Cerebral Palsy Among Children Born Moderately and Late Preterm

OBJECTIVE: To compare the incidence of and risk factors for cerebral palsy (CP) in moderately preterm (MP) (32+0–33+6 weeks) and late preterm (LP) (34+0–36+6 weeks) infants with those in very preterm (VP) (<32+0 weeks) and term infants (≥37 weeks). METHODS: The national register study included all live-born infants in Finland from 1991 to 2008. Infants who died before the age of 1 year, had any major congenital anomaly, or had missing data were excluded. A total of 1 018 302 infants were included in the analysis and they were analyzed in 4 subgroups (VP, MP, LP, and term) and 3 time periods (1991–1995, 1996–2001, and 2002–2008). RESULTS: By the age of 7 years, 2242 children with CP were diagnosed (0.2%). CP incidence was 8.7% in the VP, 2.4% in the MP, 0.6% in the LP, and 0.1% in the term group. The risk of CP was highest in the study period 1991–1995 in all groups. Factors predictive of an increased CP risk in the MP and LP groups included resuscitation at birth (odds ratio 1.60; 95% CI 1.01–2.53 and 1.78; 1.09–2.90), antibiotic treatment during the first hospitalization (1.63; 1.08–2.45 and 1.67; 1.13–2.44), 1-minute Apgar score <7 (1.70; 1.15–2.52 and 1.80; 1.21–2.67) and intracranial hemorrhage (7.18; 3.60–14.3 and 12.8; 5.58–29.2). CONCLUSIONS: The incidence of CP is higher in LP and MP infants compared with term infants. There is a nonlinear decrease in incidence over time and with increasing gestational age.

Perinatal indomethacin treatment and neonatal complications in preterm infants.

Abstract To evaluate the incidence of neonatal complications among infants exposed to indomethacin antenatally, postnatally or both ante-and postnatally (combined), the records of 240 infants of gestational ages between 23 to 32 weeks were analysed retrospectively. Antenatal indomethacin treatment for longer than 2 days with a daily or cumulative dosage ≥150 mg correlated with a significantly higher incidence of grade I-II intraventricular haemorrhage. Combined exposure, cumulative antenatal exposure ≥150 mg and duration of antenatal exposure of more than 2 days was associated with necrotising enterocolitis and a cumulative exposure with sepsis. There was no independent association between indomethacin exposure and pneumothorax, bronchopulmonary dysplasia or respiratory distress syndrome. Conclusion Preterm infants with exposure to antenatal indomethacin might be at increased risk of grade I and II intraventricular haemorrhage and those with both ante- and postnatal exposure at an increased risk of necrotising enterocolitis and sepsis.

Tubular proteinuria in pre-term and full-term infants

Predictors of tubular proteinuria (alpha 1-M/ crea ratio >10 mg/mmol) were sought in 100 infants of 24–32 weeks’ (group 1) and 69 of 34–42 weeks’ gestation (group 2). Random spot urine samples were obtained in the former group at the ages of 0–3 days, at 1–2 weeks and thereafter at 2-week intervals until the disappearance of tubular proteinuria, and in the latter one sample at a mean (SD) of 3.0 days’ (1.3) age. In group 1, gestational age correlated negatively with the first urinary alpha 1-M/ crea ratio. The highest urinary alpha 1-M/crea ratios [median (range) 39.1 mg/mmol (9.5–268.9)] occurred at a median (range) of 5 days’ (1–42) age. Low gestational age and the need for inotropes predicted tubular proteinuria early after birth, whereas low gestation and long duration of ventilator treatment predicted the highest alpha 1-M/crea ratios. Prolonged vancomycin treatment and low gestational age were associated with delayed normalization of tubular proteinuria. In group 2 no significant risk factors for tubular proteinuria were found. The urinary alpha 1-M/crea ratio seems to be a sensitive indicator of renal tubular function in neonates, with low gestational age, the need for inotropes and prolonged assisted ventilation being predictors of increased tubular proteinuria. Long vancomycin courses should be avoided in pre-term infants in view of the prolonged adverse renal effects.

Predictors of AVP and TSH Levels and the Timing of First Voiding in the Newborn

To evaluate obstetric predictors of umbilical cord plasma AVP levels, serum TSH levels and the timing of first voiding, 87 singleton term newborns were divided into three groups: group A, vaginal delivery (n = 30); group B, cesarean section (CS) during labor (n = 26); and group C, elective CS (n = 31). The AVP concentration was 120 (0.7–2170) ng/L in group A, 1.8 (0.01–183) ng/L in group B, and 0.8 (0.01–30) ng/L in group C (p < 0.001). In group A, the TSH concentration was 10.20 (3.5–30.80) mU/L; in group B, 5.40 (2.10–43.00) mU/L; and in group C, 5.30 (2.90–11.00) mU/L (p = 0.001). Duration of labor had a positive correlation with AVP (p < 0.001) and TSH (p = 0.001) concentrations. The timing of first voiding had a positive correlation with gestational age (p = 0.003), volume of additional feeding before first voiding (p < 0.001), and umbilical AVP concentration (p = 0.023). The AVP and TSH concentrations are associated with mode of delivery and duration of labor and AVP levels also with the timing of first voiding in the newborn.

Out-of-hospital deliveries have risen involving greater neonatal morbidity Risk factors in out-of-hospital deliveries in one University Hospital region in Finland

Most Finnish births take place in hospital, but out‐of‐hospital deliveries (OHDs) have increased. This study evaluated trends and reasons for OHDs in the Tampere University Hospital catchment area.

Out-of-hospital deliveries have risen involving greater neonatal morbidity: Risk factors in out-of-hospital deliveries in one University Hospital region in Finland.

Most Finnish births take place in hospital, but out‐of‐hospital deliveries (OHDs) have increased. This study evaluated trends and reasons for OHDs in the Tampere University Hospital catchment area.

Decreased Free Water Clearance Is Associated with Worse Respiratory Outcomes in Premature Infants

Objective The goal was to elucidate predictors of decreased free water clearance (DFWC) in very low birth weight (VLBW) infants. We hypothesized that DFWC and fluid retention are linked to the severity of pulmonary problems and prolonged respiratory support, especially to nCPAP treatment. Methods The investigation was carried out at Tampere University Hospital between 2001 and 2006. The study population comprised 74 VLBW infants born at 29.21 (24.57–34.14) weeks of gestation. Median birth weight was 1175 (575–1490) grams. We measured plasma and urine osmolality and 24-hour urine volume to calculate free water clearance (FWC) for each infant. If FWC was less than 30 ml/kg/day the infant was classified as having DFWC. Results There were 38 (51.4%) infants with DFWC in the study population. The median duration of the observed DFT period was 14 (4–44) days. The gestational age at birth was lower for DFWC infants compared to infants with normal FWC (NFWC), 28.29 (24.57–32.86) vs. 30.00 (25.57–34.14) weeks (p = 0.001). DFWC infants also needed longer ventilator treatment, 2 (0–23) vs. 0.50 (0–23) days (p = 0.046), nCPAP treatment 30 (0–100) vs. 3 (0–41) days (p<0.0001) and longer oxygen supplementation 47 (0–163) vs. 22 (0–74) days (p = 0.011) than NFWC infants. All values presented here are medians with ranges. Conclusions DFWC appears to be frequently connected with exacerbation and prolongation of pulmonary problems in VLBW infants. Cautious fluid administration seems to be indicated in VLBW infants with prolonged respiratory problems and DFWC.

Asthma and atopic dermatitis after early-, late-, and post-term birth

To assess the incidence and risk factors of asthma and atopic dermatitis by seven years of age after early‐term (ET) (37+0‐38+6 weeks), full‐term (FT) (39+0‐40+6 weeks), late‐term (LT) (41+0‐41+6 weeks), and especially post‐term (PT) (≥42 weeks) birth.

The incidence and risk factors of epilepsy in children born preterm: A nationwide register study

OBJECTIVES The aim was to compare the incidence of epilepsy between very preterm (VP) (<32+0 weeks), moderately preterm (MP) (32+0-33+6 weeks), late preterm (LP) (34+0-36+6 weeks) and term infants (≥37 weeks) and to establish and compare risk factors of epilepsy in these groups. METHODS The national register study included all live born infants in Finland in 1991-2008. Excluding infants with missing gestational age, a total of 1,033,349 infants were included in the analysis and they were analyzed in four subgroups (VP, MP, LP and term) and three time periods (1991-1995, 1996-2001 and 2002-2008). RESULTS 5611 (0.54%) children with epilepsy were diagnosed. The incidence of epilepsy was 2.53% in the VP, 1.08% in the MP, 0.75% in the LP and 0.51% in the term group. Intracranial hemorrhage (OR 3.48; 95% CI 2.47-4.89) and convulsions in the neonatal period (OR 13.4; 95% CI 10.2-17.6) were associated with an increased risk of epilepsy. Compared to the term group, preterm birth (VP OR 4.59; 95% CI 3.79-5.57, MP 1.97; 1.48-2.63, LP 1.44; 1.25-1.68) was associated with an increased risk of epilepsy after adjusting for maternal, pregnancy, delivery and sex variables. CONCLUSIONS The incidence of epilepsy decreased by advancing gestational age at birth and preterm birth predicted an increased risk of epilepsy in childhood. Intracranial hemorrhage and neonatal convulsions were strongly associated with an increased risk of epilepsy.