Leena Rahkonen

Asphyxia, Neurologic Morbidity, and Perinatal Mortality in Early-Term and Postterm Birth.

BACKGROUND AND OBJECTIVES: Neonatal outcomes vary by gestational age. We evaluated the association of early-term, full-term, and postterm birth with asphyxia, neurologic morbidity, and perinatal mortality. METHODS: Our register-based study used retrospective data on 214 465 early-term (37+0–38+6 gestational weeks), 859 827 full-term (39+0–41+6), and 55 189 postterm (≥42+0) live-born singletons during 1989–2008 in Finland. Asphyxia parameters were umbilical cord pH and Apgar score at 1 and 5 minutes. Neurologic morbidity outcome measures were cerebral palsy (CP), epilepsy, intellectual disability, and sensorineural defects diagnosed by the age of 4 years. Newborns with major congenital anomalies were excluded from perinatal deaths. RESULTS: Multivariate analysis showed that, compared with full-term pregnancies, early-term birth increased the risk for low Apgar score (<4) at 1 and 5 minutes (odds ratio 1.03, 95% confidence interval 1.03–1.04 and 1.24, 1.04–1.49, respectively), CP (1.40, 1.27–1.55), epilepsy (1.14, 1.06–1.23), intellectual disability (1.39, 1.27–1.53), sensorineural defects (1.24, 1.17–1.31), and perinatal mortality (2.40, 2.14–2.69), but risk for low umbilical artery pH ≤7.10 was decreased (0.83, 0.79–0.87). Postterm birth increased the risk for low Apgar score (<4) at 1 minute (1.26, 1.26–1.26) and 5 minutes (1.80, 1.43–2.34), low umbilical artery pH ≤7.10 (1.26, 1.19–1.34), and intellectual disability (1.19, 1.00–1.43), whereas risks for CP (1.03, 0.84–1.26), epilepsy (1.00, 0.87–1.15), sensorineural defects (0.96, 0.86–1.07), and perinatal mortality (0.91, 0.69–1.22) were not increased. CONCLUSIONS: Early-term birth was associated with low Apgar score, increased neurologic morbidity, and perinatal mortality. Asphyxia and intellectual disability were more common among postterm births, but general neurologic morbidity and perinatal mortality were not increased.

Preliminary case control study to establish the correlation between novel peroxidation biomarkers in cord serum and the severity of hypoxic ischemic encephalopathy

BACKGROUND Hypoxic-ischemic encephalopathy (HIE) has deleterious neurological consequences. To identify patients at risk of neuronal damage deserving implementation of neuroprotective strategies clinicians have relied on prenatal sentinel events, postnatal clinical assessment (Apgar score), and blood gas analysis. This feasibility study aimed to assess if lipid peroxidation byproducts associated with neuronal damage correlated with cord blood metabolic acidemia in patients with HIE. POPULATION AND METHODS This is a case/control study in which cases were newborn infants with severe acidemia (pH<7.00; base excess ≥12mmol/L) while control babies exhibited normal gases (pH=7.20-7.40; base excess=-4 to +4mmol/L) in the first cord blood analysis performed immediately after birth. Concomitantly, lipid peroxidation byproducts were determined using ultra performance liquid chromatography coupled to mass spectrometry in the same cord blood sample. RESULTS A total of 19 controls and 20 cases were recruited. No differences in gestational characteristics were present. However, cases exhibited profound metabolic alterations as compared to controls (Cases vs. CONTROL pH=6.90±0.1 vs. 7.33±0.03; base excess=-15±3 vs. -1±2mmol/L), 85% were admitted to the NICU, and 50% developed symptoms of HIE. 8-iso-15(R)-PGF2α (P=0.01) and total isoprostanes (P=0.045) presented statistically significant differences between cases and control groups and correlated with level of HIE. CONCLUSIONS The 8-iso-15(R)-PGF2α and isoprostanes reflecting oxidative damage are significantly increased in severe postnatal acidemia. Follow up studies with adequate power are necessary to confirm if these biomarkers measured in cord blood serum could be predictive of neonatal encephalopathy.

Vaginally obtained amniotic fluid samples in the diagnosis of subclinical chorioamnionitis.

Preterm birth is often caused by infection or inflammation. High concentration of lactate dehydrogenase and low concentration of glucose in amniotic fluid obtained by amniocentesis are associated with subclinical chorioamnionitis. We evaluated amniotic fluid lactate dehydrogenase and glucose concentrations in relation to histologic chorioamnionitis in vaginally obtained samples.

Breech presentation at term and associated obstetric risks factors-a nationwide population based cohort study

PurposeThe aim of this study was to estimate whether breech presentation at term was associated with known individual obstetric risk factors for adverse fetal outcome.MethodsThis was a retrospective, nationwide Finnish population-based cohort study. Obstetric risks in all breech and vertex singleton deliveries at term were compared between the years 2005 and 2014. A multivariable logistic regression model was used to determine significant risk factors.ResultsThe breech presentation rate at term for singleton pregnancies was 2.4%. The stillbirth rate in term breech presentation was significantly higher compared to cephalic presentation (0.2 vs 0.1%). The odds ratios (95% CIs) for fetal growth restriction, oligohydramnios, gestational diabetes, a history of cesarean section and congenital fetal abnormalities were 1.19 CI (1.07–1.32), 1.42 CI (1.27–1.57), 1.06 CI (1.00–1.13), 2.13 (1.98–2.29) and 2.01 CI (1.92–2.11).ConclusionsThe study showed that breech presentation at term on its own was significantly associated with antenatal stillbirth and a number of individual obstetric risk factors for adverse perinatal outcomes. The risk factors included oligohydramnios, fetal growth restriction, gestational diabetes, history of caesarean section and congenital anomalies.

Neurodevelopmental outcome at the age of 4 years according to the planned mode of delivery in term breech presentation: a nationwide, population-based record linkage study

Abstract Purpose: To evaluate whether a trial of planned vaginal breech labor affects neurologic development in children. Methods: This is a nationwide, Finnish, population-based record linkage study. An odds ratio with 95% confidence intervals was used to estimate the relative risk that a child delivered by planned vaginal breech labor would be diagnosed with adverse neurodevelopmental outcome (cerebral palsy, epilepsy, intellectual disability, sensor neural developmental outcome, hyperactivity, speech and language problems) at the age of 4 years. The reference group were children born by planned cesarean section. Results: During a study period of 7 years, 8374 infants were delivered in breech position. Among them, 3907 (46.7%) had an attempted labor and 4467 (53.3%) infants were delivered by planned cesarean section. There were no differences in the neurodevelopmental outcome. In the planned vaginal labor group, 133 (3.4%) children had an abnormal neurodevelopmental outcome at the age of 4 years compared to 142 (3.2%) in the planned cesarean section group. Conclusion: The absolute risk of abnormal neurological outcome in breech deliveries at term was low, regardless of planned mode of birth. Planned vaginal breech labor did not increase the risk for abnormal neurological outcome compared to planned cesarean section.

Comparison of Umbilical Serum Copeptin Relative to Erythropoietin and S100B as Asphyxia Biomarkers at Birth

Background: Birth asphyxia, estimated to account for a million neonatal deaths annually, can cause a wide variety of neurodevelopmental impairments. There is a need to develop new, swift methods to identify those neonates who would benefit from neuroprotective treatments such as hypothermia. Objectives: To examine the utility of cord serum copeptin, a stable byproduct of arginine vasopressin release, as a biomarker of birth asphyxia based on a comparison with 2 biomarkers of hypoxia and brain trauma: erythropoietin and S100B. Methods: The study population consisted of 140 singleton, term neonates: 113 controls and 27 with birth asphyxia (2/3 criteria met: umbilical artery pH <7.10, base excess ≤12 mmol/L, and 5-min Apgar score <7). All deliveries were planned vaginal, but 51 neonates were born by emergency cesarean section. Copeptin, S100B, and erythropoietin levels in umbilical artery samples were measured by immunoassays. Results: Copeptin correlated in the entire study population more strongly with umbilical artery base excess than S100B and erythropoietin, and only copeptin correlated with arterial pH. Furthermore, only copeptin levels were significantly higher in cases of birth asphyxia, and in vaginally born neonates they were found to increase as a function of labor duration. Copeptin was elevated in neonates born via vacuum extraction, whereas erythropoietin levels showed a slight increase after emergency cesarean section. Conclusions: In this study population, S100B and erythropoietin were not valid biomarkers of birth asphyxia. In contrast, our work suggests that copeptin has high potential to become a routinely used biomarker for acute birth asphyxia and neonatal distress.

Foley Catheter or Oral Misoprostol for Induction of Labor in Women with Term Premature Rupture of Membranes: A Randomized Multicenter Trial

Objectives To compare the Foley catheter and misoprostol for induction of labor in term women with premature rupture of membranes. Study Design A randomized controlled trial was performed in three university hospitals in Finland between March 2012 and September 2014. A total of 202 term women with ruptured membranes >18 hours, singleton pregnancies in cephalic presentation, unfavorable cervix, and no prior cesarean section were enrolled. Participants were randomly allocated to induction of labor by Foley catheter or oral misoprostol in a 1:1 ratio. All women received prophylactic antibiotics. The main outcomes were cesarean section and maternal and neonatal infections. Results Labor induction by Foley catheter or misoprostol showed no difference in cesarean delivery rates (23.6 vs. 18.2%; odds ratio [OR], 1.39; 95% confidence interval [CI], 0.69-2.82; p = 0.36), maternal intrapartum infections (2.2 vs. 2%; OR, 1.12; 95% CI, 0.15-8.9; p = 1.00), postpartum infections (1.1 vs. 2.0%; OR, 0.55; 95% CI, 0.05-6.18; p = 1.00), or neonatal infections (1.1 vs. 5.1%; OR, 0.21; 95% CI, 0.24-1.87; p = 0.22). The total time from induction to delivery was similar (1,311 vs. 1,435 minutes; p = 0.31) in the two groups. Conclusions Foley catheter or misoprostol can both be used for induction of labor in women with term premature rupture of membranes.

Amniotic fluid rapid biomarkers are associated with intra-amniotic infection in preterm pregnancies regardless of the membrane status

Objective:The objective of this study was to evaluate the association of amniotic fluid lactate dehydrogenase and glucose concentrations with microbial invasion of amniotic cavity and histologic chorioamnionitis before 37 pregnancy weeks in women with or without preterm premature rupture of membranes.Study Design:Amniocentesis was performed on 70 women with suspected intra-amniotic infection. Standard biochemical methods, molecular microbiology and culture techniques were used. Histopathological examination of the placenta was performed.Results:Thirty (48%) women had microbial invasion of the amniotic cavity (MIAC), 53 (76%) women had histological chorioamnionitis and 28 women had both. The cutoff values for MIAC and histological chorioamnionitis were 429 IU l−1 for lactate dehydrogenase and 0.7 mmol l−1 for glucose. Both end points occurred equally often regardless of the membrane status.Conclusion:Increased amniotic fluid lactate dehydrogenase and decreased glucose were associated with MIAC and histological chorioamnionitis. However, test performance was of limited value.

Amniotic Fluid Infection in Preterm Pregnancies with Intact Membranes

Introduction. Intra-amniotic infection (IAI) is a major cause of preterm labor and adverse neonatal outcome. We evaluated amniotic fluid (AF) proteolytic cascade forming biomarkers in relation to microbial invasion of the amniotic cavity (MIAC) and IAI in preterm pregnancies with intact membranes. Material and Methods. Amniocentesis was made to 73 women with singleton pregnancies; 27 with suspected IAI; and 46 controls. AF biomarkers were divided into three cascades: Cascade 1: matrix metalloproteinase-8 (MMP-8), MMP-9, myeloperoxidase (MPO), and interleukin-6; Cascade 2: neutrophil elastase (HNE), elafin, and MMP-9; Cascade 3: MMP-2, tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), MMP-8/TIMP-1 molar ratio, and C-reactive protein (CRP). MMP-8 was measured by an immunoenzymometric assay and the others were measured by ELISA. Standard biochemical methods, molecular microbiology, and culture techniques were used. Results. MMP-8, MMP-9, MPO, elafin, and TIMP-1 concentrations were higher in IAI suspected cases compared to controls and also in IAI suspected cases with MIAC compared to those without MIAC when adjusted by gestational age at amniocentesis. All biomarkers except elafin and MMP-2 had the sensitivity of 100% with thresholds based on ROC-curve. Odd ratios of biomarkers for MIAC were 1.2-38 and 95% confidential intervals 1.0-353.6. Conclusions. Neutrophil based AF biomarkers were associated with IAI and MIAC.

Foley catheter induction of labor as an outpatient procedure

Objective:The aim of our study was to introduce outpatient induction of labor by Foley catheter, and to compare outcomes and preferences between in-patients and outpatients.Study Design:This clinical cohort study was conducted in Helsinki University Hospital between January 2011 and January 2012. A total of 485 women scheduled for induction of labor by Foley catheter were included. The main outcome measures were cesarean delivery rate, and maternal and neonatal infectious morbidity. Maternal satisfaction of outpatients was measured after delivery.Results:Two hundred and four (42.1%) women were managed as outpatients and 281 (57.9%) women as in-patients. The rates of cesarean delivery, and maternal or neonatal infections did not differ between outpatients and in-patients. Of the outpatients, 85.3% were satisfied.Conclusion:Induction of labor by Foley catheter appears suitable for outpatients, and resulted in no differences in cesarean delivery or infection rates compared with in-patients. Most women were satisfied with the outpatient induction.