Hypothermic treatment for neonatal asphyxia in low-resource settings using phase-changing material-An easy to use and low-cost method.

AIM: To evaluate whether phase-changing material can be used for therapeutic hypothermia of asphyxiated newborns in low-resource settings. METHODS: Prospective interventional study of asphyxiated term infants fulfilling criteria for hypothermia treatment at Vietnam National Children's Hospital from September 2014 to September 2016. Hypothermia was induced within 6 hours after birth and maintained for 72 hours by a phase-changing material mattress with melting point of 32°C. Rectal temperature was continuously measured, and deviations from target temperature range 33.5-34.5°C were recorded. RESULTS: In total 52 infants (mean gestational age 39.3 ± 1.1 weeks) included and cooled, the median temperature at initiation of cooling was 35.3 (IQR 34.5-35.9)°C. The median time to reach target temperature was 2.5 (IQR 2-3) hours. The mean temperature during the cooling phase was 33.95 ± 0.2°C. Throughout the cooling phase, the target temperature range (33.5-34.5°C) was maintained more than 80% of the time. Rate of rewarming was 0.5 ± 0.14°C/hour. CONCLUSION: Phase-changing material can be used as an effective cooling method. Though not a servo-controlled system, it is easy to induce hypothermia, maintain target temperature and rewarm infants in a slow and controlled manner without need for frequent changes and minimum risk of skin injury.

Midwives' Perception of Using a Knowledge Base on Fetal Impact of Drugs.

A non-commercial knowledge base providing assessments of fetal risks of medicinal drugs is a useful tool in the everyday work of midwives. The information is freely available on the internet, and according to a questionnaire study, nearly 95% of the midwives are familiar with the database, 30% use the information weekly, and 80% express that it affects their medical decisions. A vast majority of the midwives also state that it is time-saving.

A rapid smartphone-based lactate dehydrogenase test for neonatal diagnostics at the point of care.

There is a growing recognition of the importance of point-of-care tests (POCTs) for detecting critical neonatal illnesses to reduce the mortality rate in newborns, especially in low-income countries, which account for 98 percent of reported neonatal deaths. Lactate dehydrogenase (LDH) is a marker of cellular damage as a result of hypoxia-ischemia in affected organs. Here, we describe and test a POC LDH test direct from whole blood to provide early indication of serious illness in the neonate. The sample-in-result-out POC platform is specifically designed to meet the needs at resource-limited settings. Plasma is separated from whole blood on filter paper with dried-down reagents for colorimetric reaction, combined with software for analysis using a smartphone. The method was clinically tested in newborns in two different settings. In a clinical cohort of newborns of Stockholm (n = 62) and Hanoi (n = 26), the value of R using Pearson's correlation test was 0.91 (p < 0.01) and the R2 = 0.83 between the two methods. The mean LDH (±SD) for the reference method vs. the POC-LDH was 551 (±280) U/L and 552 (±249) U/L respectively, indicating the clinical value of LDH values measured in minutes with the POC was comparable with standardized laboratory analyses.

Relationship between various maternal conditions and lactic acid dehydrogenase activity in umbilical cord blood at birth.

BACKGROUND: Lactic acid dehydrogenase (LDH) is a valuable marker for some of the most important diseases in newborns and the plasma LDH activity in newborns correlates well with conditions such as asphyxia. If LDH should be considered as a useful tool also in obstetric care, key factors associated with maternal health before and during pregnancy which could affect umbilical cord LDH activity need to be known. The aims of this study were to explore relationships between selected maternal conditions and arterial lactic acid dehydrogenase activity (aLDH) in umbilical cord blood at delivery. METHODS: A prospective observational study was conducted at Sodersjukhuset, Stockholm, Sweden. Included in the study were 1247 deliveries, and cord blood samples from each were analyzed for aLDH. Background, delivery and neonatal data were collected from the medical records. RESULTS: Higher median values of aLDH were found (P=0.001) among women with chronic disorders not related to pregnancy but there was no increased frequency of high aLDH levels (>612 µ/L, P=0.30). No difference in aLDH was identified between infants born to women with pregnancy-related disorders compared with healthy women, neither in median values, nor in high values (>612 µ/L, P=0.95). CONCLUSION: Newborn infants born to women with non-pregnancy-related chronic disorders had a somewhat higher median value of aLDH in cord blood at delivery. The influence of common maternal conditions and diseases on umbilical cord arterial LDH levels is small compared to the increase reported in fetal distress and several other critical conditions in the newborn.

Perinatal Outcomes After Treatment With ADHD Medication During Pregnancy.

OBJECTIVES: To analyze perinatal outcomes after maternal use of attention-deficit/hyperactivity disorder (ADHD) medication during pregnancy. METHODS: The study included singletons born between 2006 and 2014 in Sweden. Data on prescription drug use, pregnancies, deliveries, and the newborn infants' health were obtained from the Swedish Medical Birth Register, the Prescribed Drug Register, and the Swedish Neonatal Quality Register. We compared infants exposed to ADHD medication during pregnancy with infants whose mothers never used these drugs and infants whose mothers used ADHD medication before or after pregnancy. Analyses were performed with logistic regression. RESULTS: Among 964 734 infants, 1591 (0.2%) were exposed to ADHD medication during pregnancy and 9475 (1.0%) had mothers treated before or after pregnancy. Exposure during pregnancy increased the risk for admission to a NICU compared with both no use and use before or after pregnancy (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.3-1.7; and aOR, 1.2; 95% CI, 1.1-1.4, respectively). Infants exposed during pregnancy had more often central nervous system-related disorders (aOR, 1.9; 95% CI, 1.1-3.1) and were more often moderately preterm (aOR, 1.3; 95% CI, 1.1-1.6) than nonexposed infants. There was no increased risk for congenital malformations or perinatal death. CONCLUSIONS: Treatment with ADHD medication during pregnancy was associated with a higher risk for neonatal morbidity, especially central nervous system-related disorders such as seizures. Because of large differences in background characteristics between treated women and controls, it is uncertain to what extent this can be explained by the ADHD medication per se.

Neonatal Morbidity After Maternal Use of Antidepressant Drugs During Pregnancy.

OBJECTIVES: To estimate the rate of admissions to NICUs, as well as infants' morbidity and neonatal interventions, after exposure to antidepressant drugs in utero. METHODS: Data on pregnancies, deliveries, prescription drug use, and health status of the newborn infants were obtained from the Swedish Medical Birth Register, the Prescribed Drug Register, and the Swedish Neonatal Quality Register. We included 741 040 singletons, born between July 1, 2006, and December 31, 2012. Of the infants, 17 736 (2.4%) had mothers who used selective serotonin reuptake inhibitors (SSRIs) during pregnancy. Infants exposed to an SSRI were compared with nonexposed infants, and infants exposed during late pregnancy were compared with those exposed during early pregnancy only. The results were analyzed with logistic regression analysis. RESULTS: After maternal use of an SSRI, 13.7% of the infants were admitted to the NICU compared with 8.2% in the population (adjusted odds ratio: 1.5 [95% confidence interval: 1.4-1.5]). The admission rate to the NICU after treatment during late pregnancy was 16.5% compared with 10.8% after treatment during early pregnancy only (adjusted odds ratio: 1.6 [95% confidence interval: 1.5-1.8]). Respiratory and central nervous system disorders and hypoglycemia were more common after maternal use of an SSRI. Infants exposed to SSRIs in late pregnancy compared with early pregnancy had a higher risk of persistent pulmonary hypertension (number needed to harm: 285). CONCLUSIONS: Maternal use of antidepressants during pregnancy was associated with increased neonatal morbidity and a higher rate of admissions to the NICU. The absolute risk for severe disease was low, however.

[Careful medical history taking is worthwhile in child sleep disorders]. / Noggrann anamnes lönar sig vid sömnstörningar hos barn - Läkemedel avråds som förstahandsbehandling.

Sleeping disturbances are common in children and adolescents and in rare cases signal underlying disease. Complete history and diagnosis are mandatory for treatment. The basis for pharmacologic treatment is unsatisfactory but phenotiazides and benzodiazepines should not be used because of lack of documented effects and potentially serious side effects. Melatonin may be used in selected cases.

Pregnant women's view on the Swedish internet resource Drugs and Birth Defects intended for health care professionals.

INTRODUCTION: Pregnant women often have questions concerning fetal effects of drugs but there is limited reliable information specifically intended for them. This study investigated how pregnant women perceive and value the scientific resource Drugs and Birth Defects (www.janusinfo.se/fosterpaverkan) and compared their opinions with those of health care professionals. MATERIAL AND METHODS: Electronic questionnaire study. Pregnant women were recruited at their regular visits, and health care professionals via e-mail, at 10 antenatal clinics. Altogether, 275 pregnant women, 38 midwives and 30 physicians participated. RESULTS: Among the pregnant women, 81% found the information valuable, 70% that it was easy to understand, and 92% that it strengthened information from the staff. Concerning anxiety for negative fetal effects, 68% of the women answered that the anxiety decreased or was not influenced by the texts and 22% that it increased. Among physicians and midwives, 44% saw risks associated with pregnant women reading the texts and 24% answered that they would fully recommend them to use the database. The corresponding figures among pregnant women were 17 and 65%, respectively (P < 0.001). The professionals preferred, to a greater extent than pregnant women did, lay people to use a special edition. CONCLUSIONS: The majority of pregnant women seem to benefit from using a scientific resource on fetal impact of drugs intended for health care professionals. Some women are more worried after having read the information, but most of them still find it valuable. It is important that pregnant women who use the database can reach a medical professional to discuss the contents.

Drugs and Birth Defects: a knowledge database providing risk assessments based on national health registers.

PURPOSE: To present concept, methods and use of a knowledge database providing assessments of potential fetal risks for all drugs on the Swedish market. METHODS: Assessments of fetal risks are made primarily by analyzing prospective epidemiological data from the Swedish Medical Birth Register on drug intake in relation to birth outcome. This is complemented by evaluation of the scientific literature. Following standardized working procedures, a statement is compiled for each substance, which is also classified into one of three categories depending on the estimated risk level. The final documents include drug product names on the market, via linkage to a medicinal products register. The information is free and published on the website www.janusinfo.se . It can also be used as an integrated part of electronic health records. RESULTS: The database covers assessments of fetal risks for close to 1,250 medicinal drug substances on the Swedish market. Each year, 96,000 searches are made, which might be compared to the around 100,000 children born in Sweden yearly. Apart from the Swedish Physicians' Desk Reference (Fass), the database is the most commonly used resource among specialists within gynaecology and perinatal medicine for information on drugs during pregnancy. CONCLUSIONS: A non-commercial knowledge base with assessments of fetal risk of different drugs is valued by health care professionals and is used extensively in Sweden. Based on analyses of national health registers, the database provides unique information on teratogenic drug risks.

Lactate dehydrogenase as an indicator of severe illness in neonatal intensive care patients: a longitudinal cohort study.

AIM: Lactate dehydrogenase (LDH) increases in several critical conditions that cause cell damage and could potentially be used for early detection of serious illness in the newborn. Our aim was to investigate the relationship between the early clinical course of NICU infants and LDH in plasma at admission. METHODS: LDH was measured in a cohort of patients consecutively admitted to a major NICU in Hanoi. The infants were classified as 'obviously needing intensive care during the first week' (n = 83) or 'not receiving intensive care measures during the first week' (n = 260) by a senior neonatologist blinded to the LDH and lactate activity. RESULTS: LDH differed significantly between the groups in infants born after 32 gestational weeks. LDH differed with the vitality of the patient (F = 26.25, p < 0.0001) at admittance and correlated with lactate (R = 0.496, p < 0.0001). Also, the predictive value for obvious need of intensive care was higher for LDH than for lactate assessed by area under the curve calculated with ROC-curves [0.82 (0.77-0.88) vs. 0.67 (0.60-0.75)]. CONCLUSION: There is a strong relationship between bad clinical condition of infants during first week of life and elevated plasma LDH. The results suggest that LDH might be a valuable support in decision making in the neonatal period.

Association between adverse neonatal outcome and lactate concentration in amniotic fluid.

OBJECTIVE: To estimate whether a high lactate concentration in amniotic fluid, together with cardiotocography, can be used as an indicator for an increased risk of adverse neonatal outcome at delivery. METHOD: A prospective cohort study was performed at two tertiary center labor wards in Sweden. Healthy women with full-term, singleton pregnancies and cephalic presentation in spontaneous active labor were included in the study (N=825). Lactate concentration in samples of amniotic fluid collected in the course of vaginal examinations during labor were correlated with cardiotocography 30 minutes before delivery and a composite score for adverse neonatal outcome. RESULTS: High lactate concentration in amniotic fluid (greater than 10.1 mmol/L) was associated with an adverse neonatal outcome (odds ratio [OR] 4.4, 95% confidence interval [CI] 2.3-8.2). Fetal bradycardia within 30 minutes before delivery was also associated with an increased risk of adverse neonatal outcome (OR 7.4, 95% CI 3.04-18.11). If lactate in amniotic fluid was greater than 10.1 mmol/L and bradycardia was seen together, the risk of delivering a neonate with an adverse neonatal outcome was increased 11-fold (OR 10.7, 95% CI 3.7-31.7). CONCLUSION: High lactate concentration in amniotic fluid and fetal bradycardia during the last 30 minutes before delivery indicate an increased risk of adverse neonatal outcome at delivery.

Lactate concentration in amniotic fluid: a good predictor of labor outcome.

OBJECTIVE: Previous publications have suggested that high levels of lactate in amniotic fluid (AF) correlate with dysfunctional labor. The aim of this study was to investigate whether lactate concentration in AF together with the partogram is a better predictor of operative intervention in dysfunctional labor than the partogram alone. STUDY DESIGN: A prospective observational study was carried out of 825 laboring women. Samples of AF were collected and the lactate concentration was analyzed at the bedside during labor. The main outcome of the study was the method of delivery (operative/spontaneous vaginal) in relation to the concentration of lactate in AF. Logistic regression was used to estimate the association between lactate concentration in AF and labor outcome and to adjust for well-known risk factors for dysfunctional labor. RESULTS: 385/825 women had an arrested labor according to the partogram, and 193 of them were delivered operatively. High lactate in AF (>10.1 mmol/l) when labor arrested was associated with an increased risk of operative intervention due to dysfunctional labor (adjusted OR, 5.4, 95% CI, 3.2-9.1). Low levels of lactate in AF (<10.1 mmol/l) were associated with an increased probability of spontaneous vaginal delivery (adjusted OR, 2.7, 95% CI, 1.7-4.8). CONCLUSION: The partogram together with the concentration of lactate in AF is a better predictor of operative intervention in dysfunctional labor than the partogram alone.

Lactate dehydrogenase predicts hypoxic ischaemic encephalopathy in newborn infants: a preliminary study.

BACKGROUND: Enzyme leakage as a result of hypoxia-ischaemia induced cell damage in affected organs is seen together with hypoxic ischaemic encephalopathy (HIE) after perinatal asphyxia. AIM: To investigate whether plasma lactate dehydrogenase [LDH], alanine aminotransferase [ALT] and aspartate aminotransferase [AST] during the first 12 h after birth predict HIE and adverse neurodevelopment outcome in newborn term infants with intra-partum signs of foetal distress. METHODS: Enzymes were measured within 12 h post partum in newborn infants with differing degree of HIE (n = 41) and in infants with signs of foetal distress during birth (n = 205) without HIE (non-HIE group). All infants were randomized into two groups. One group (n = 123) was used for calculation of cut off limits for the enzymes studied and the other group (n = 123) was used for calculation of the predictive value of the enzymes for detection of HIE. RESULTS: Using ROC curves, a cut off level of 1049 U/L for [LDH] was the best predictor of HIE (sensitivity 100% and specificity 97%) but also for long term outcome after HIE. CONCLUSION: [LDH] is a good predictor of HIE during the first 12 h after birth. This result is of clinical interest offering a potential inexpensive and safe prognostic marker in newborn infants with perinatal asphyxia.

Preterm infants as young adults: a Swedish national cohort study.

OBJECTIVE: Increasing numbers of infants born preterm survive into adulthood. In this study, we analyzed the effect of having been born preterm on disability and vocational success in young adults. METHODS: A Swedish national cohort of 522,310 infants born in 1973-1979 were followed up for disabilities and income in national registers in 2002 at the age of 23 to 29. Hypotheses were tested in multivariate analysis with logistic regression models on the log scale for dichotomized outcomes and linear regression for continuous variables. RESULTS: There was a stepwise increase in disability in young adulthood with increasing degree of preterm birth. A total of 13.2% of children born at 24 to 28 weeks' gestation and 5.6% born at 29 to 32 weeks' gestation received economic assistance from society because of handicap or persistent illness, which is equivalent to nearly 4 [corrected] times the risk of those born at term after adjustment for socioeconomic and perinatal confounders. Moderate (33-36 weeks' gestation) and marginal (37-38 weeks' gestation) preterm birth also carried significantly increased risks for disability and were responsible for 74% of the total disability associated with preterm birth. Preterm birth was associated with a lower chance of completing a university education and a lower net salary in a stepwise manner. The total economic gain for Swedish society, in terms of taxes and decreased costs for benefits, if all long-term effects of preterm birth could have been prevented in the birth cohorts in this study, would have amounted to 65 million euros in 2002 alone. CONCLUSIONS: The majority of adults who were born very preterm lived an independent and self-supportive life. Moderately preterm birth carries a considerable risk for long-term impairment. There are strong economic incentives for secondary prevention of disability associated with preterm birth.

Dynamics of hepatic enzyme activity following birth asphyxia.

AIM: To investigate: 1) the occurrence of hypoxic hepatitis in full-term infants after birth asphyxia, 2) the temporal enzyme pattern in asphyxiated newborn infants, and 3) whether the degree of hypoxic hepatitis, as reflected by the rise in aminotransferase, correlates with the severity of the asphyxia and CNS symptomatology. METHODS: Serum aminotransferases, lactate dehydrogenase, gamma-glutamyl transferase, total and conjugated bilirubin, cholinesterase activity, albumin, international normalized ratio (INR), and nucleated red blood cell count were prospectively measured in full-term asphyxiated newborn infants (n=26). Samples were collected three times during the first 72 h and once between days 6 and 12 after birth. Samples from healthy newborns (n=56), collected 24-172 h after birth, served as controls. RESULTS: In 12 of the 26 asphyxiated infants, a serum alanine aminotransferase (S-ALAT) pattern compatible with hypoxic hepatitis was found. Five infants showed increased S-ALAT activity but with a different pattern. Similar patterns were seen in serum aspartate aminotransferase (S-ASAT). S-ALAT and -ASAT concentrations 0-72 h after birth correlated significantly with severity of hypoxic-ischaemic encephalopathy. CONCLUSION: Birth asphyxia can induce an enzyme pattern in serum compatible to hypoxic hepatitis. There seems to be a correlation between aminotransferases in serum and the extent of CNS injury.

Pregnancy, delivery, and neonatal complications after treatment with antiepileptic drugs.

AIM: To study the risk for complications during pregnancy, delivery, and neonatal period after the use of antiepileptic drugs (AEDs) during pregnancy. METHODS: Women treated with AEDs during pregnancy and with singleton deliveries were identified from the Swedish Medical Birth Registry during the period July 1 1995 to and including 2001 (n = 1350). Risk estimates were made using the Mantel-Haenszel procedure and comparisons with all singleton births in Sweden during this period (n = 559,491). Stratification was made for year of birth, maternal age, parity, and smoking habits. RESULTS: Most of the women (n = 1207, 89%) used AEDs in monotherapy. Carbamazepine was the most commonly used drug (n = 683), followed by valproic acid (n = 255). The rate of caesarean sections was significantly increased (OR = 1.64, 95% CI 1.43-1.89), but it was not possible to differentiate between elective and emergency sections. The risk for pre-eclampsia (OR = 1.66, 95% CI 1.32-2.08) and for hemorrhage after vaginal delivery was increased (OR = 1.29, 95% CI 1.02-1.63). The neonates showed an increased risk for respiratory distress (OR = 2.06, 95% CI 1.62-2.63). CONCLUSION: The study demonstrates a slightly increased risk only for preeclampsia, vaginal hemorrhage after delivery, and respiratory distress in the newborn after the use of AEDs during pregnancy.

Birth centre care over a 10-year period: infant morbidity during the first month after birth.

AIM: To study morbidity during the first month of life affecting infants of mothers booked for birth centre care during pregnancy. METHODS: 3238 live single-born infants whose mothers were admitted to an in-hospital birth centre, located at South Hospital in Stockholm, between 1989 and 2000 were compared with 179,502 infants whose mothers received standard maternity care in the Stockholm region during the same period, and who fulfilled the same medical inclusion criteria as those of the birth centre group. Information on other exposures and outcomes was collected from the Swedish Medical Birth and Hospital Discharge Registers. Logistic regression analyses were performed to calculate the odds ratio (OR), using 95% confidence intervals (95% CI). RESULTS: Compared with infants born in standard care, infants in the birth centre group had a higher risk of respiratory problems (OR 1.39; 95% CI 1.14-1.69), a difference correlated to less serious respiratory diagnoses. However, the difference was not statistically significant if the birth centre group was compared only with infants born in standard care at South Hospital (OR 1.18; 95% CI 0.94-1.47). Birth centre care was associated with a lower risk of fractures (OR 0.40; 95% CI 0.25-0.63). CONCLUSION: Birth centre care was not associated with severe infant morbidity and even appeared to reduce the risk of birth trauma, such as clavicle and other fractures.

Centres for Clinical Education (CCE): developing the health care education of tomorrow--a preliminary report.

A new interdisciplinary concept of medical and health care education has been introduced at Karolinska Institute in collaboration with the County Council in Stockholm under the motto Learning together to be able to work together. Centres of Clinical Education are built up in four major hospitals to promote meeting places during clinical education for students from different categories. During a three-year project more than 5000 students from four educational programmes have been involved--medicine, nursing, occupational therapy and physiotherapy. The project started in 1998 and will turn into regular activities in 2002. The Centres consist of three parts. First is the Clinical Training Ward, a ward without patients where manual skills as well as skills in communication are taught, practised and videotaped. Second is the Clinical Education Ward, a student-driven ward where students during two-week periods experience their own professional roles in day-to-day work and learn how to work together. Third is the Multidisciplinary Team, where teachers from the four programmes plan and provide opportunities for students to learn together. Opportunities to meet and learn together have promoted a wider understanding of each professional in health care teams among students and staff. The Centres of Clinical Education provide excellent opportunities to bridge professional borders and to coordinate undergraduate studies and clinical reality.