Risk factors for neonatal hypoxic ischemic encephalopathy and therapeutic hypothermia: a matched case-control study.

BACKGROUND: Peripartum asphyxia is one of the main causes of neonatal morbidity and mortality. In moderate and severe cases of asphyxia, a condition called hypoxic-ischemic encephalopathy (HIE) and associated permanent neurological morbidities may follow. Due to the multifactorial etiology of asphyxia, it may be difficult prevent, but in term neonates, therapeutic cooling can be used to prevent or reduce permanent brain damage. The aim of this study was to assess the significance of different antenatal and delivery related risk factors for moderate and severe HIE and the need for therapeutic hypothermia. METHODS: We conducted a retrospective matched case-control study in Helsinki University area hospitals during 2013-2017. Newborn singletons with moderate or severe HIE and the need for therapeutic hypothermia were included. They were identified from the hospital database using ICD-codes P91.00, P91.01 and P91.02. For every newborn with the need for therapeutic hypothermia the consecutive term singleton newborn matched by gender, fetal presentation, delivery hospital, and the mode of delivery was selected as a control. Odds ratios (OR) between obstetric and delivery risk factors and the development of HIE were calculated. RESULTS: Eighty-eight cases with matched controls met the inclusion criteria during the study period. Maternal and infant characteristics among cases and controls were similar, but smoking was more common among cases (aOR 1.46, CI 1.14-1.64, p = 0.003). The incidence of preeclampsia, diabetes and intrauterine growth restriction in groups was equal. Induction of labour (aOR 3.08, CI 1.18-8.05, p = 0.02) and obstetric emergencies (aOR 3.51, CI 1.28-9.60, p = 0.015) were more common in the case group. No difference was detected in the duration of the second stage of labour or the delivery analgesia. CONCLUSIONS: Smoking, induction of labour and any obstetric emergency, especially shoulder dystocia, increase the risk for HIE and need for therapeutic hypothermia. The decisions upon induction of labour need to be carefully weighed, since maternal smoking and obstetric emergencies can hardly be controlled by the clinician.

Perinatal outcome of dichorionic and monochorionic-diamniotic Finnish twins: a historical cohort study.

INTRODUCTION: Although the perinatal mortality of monochorionic twins has been reported to be higher, the role of chorionicity is debated and data from Finland are still lacking. To examine the effect of chorionicity on the main outcome measures, perinatal and neonatal mortality and neonatal morbidity of Finnish twins, a comprehensive population-based historical cohort study was performed at Helsinki University Hospitals. MATERIAL AND METHODS: All 1034 dichorionic and monochorionic-diamniotic twin pregnancies managed at Helsinki University Hospital area during 2006, 2010, 2014 and 2018 were collected from patient databases. Information on chorionicity was retrieved from ultrasound reports and all relevant clinical information from patient records. Differences in perinatal and neonatal mortality and neonatal morbidity were analyzed by performing group comparisons between the twins and chorionicity. The role of chorionicity was also assessed in logistic regression analyses. RESULTS: There were 1034 dichorionic-diamniotic (DCDA, n = 789, 76.3%, 95% confidence interval [CI] 73.6-78.9) and monochorionic-diamniotic (MCDA, n = 245, 23.7%, 95% CI 21.4-26.0) twin pregnancies during the studied years. Most (n = 580, 56.1%, 95% CI 52.8-59.2) twins were born at term, but 151 (61.6%, 95% CI 55.8-67.3) of MCDA twins were preterm and had lower birthweight and Apgar scores and higher risk of death of one twin. Perinatal and neonatal mortality did not differ between twins A and B, but the immediate outcome of twin B was worse, with lower arterial pH and Apgar scores and increased need of neonatal intensive care unit treatment. CONCLUSIONS: Chorionicity contributes to the perinatal and neonatal outcome in favor of dichorionic twins. This disadvantage of MCDA twinning is likely explained by earlier gestational age at birth and inequal placental sharing. Irrespective of chorionicity, twin B faces more complications.

Excellent perinatal outcome of monoamniotic twin pregnancy with timely diagnosis and optimal management - a retrospective cohort study.

OBJECTIVES: Monoamniotic twins represent a high-risk pregnancy requiring intense follow-up, elective birth and careful consideration of the mode and timing of delivery. We conducted this study to evaluate the perinatal and neonatal outcomes of monoamniotic twin pregnancies in the largest tertiary hospital in Finland. METHODS: This was a retrospective cohort study including all monoamniotic twin pregnancies during a 17-year period (2002-2018) managed in Helsinki University Hospital. Data on mothers and children were collected from patient files. Chorionicity and amnionicity were defined in first-trimester ultrasound screening. RESULTS: There were altogether 31 monoamniotic twin pregnancies during the study period, including four cases of conjoined twins which all underwent termination of pregnancy, and three miscarriages. In the remaining 24 pregnancies that continued past 24 weeks of gestation there was 97.9% survival (one intrauterine death). Three pregnancies were complicated with twin-to-twin transfusion syndrome. All children were delivered by cesarean section with a mean gestational age of 32 + 5 weeks (27 + 1-34 + 2 weeks). Respiratory distress syndrome (RDS) was observed in 57% (27/47) of neonates and grade I-II intraventricular haemorrhage (IVH) in 6.3% (3/47) of neonates. There were no neonatal deaths and no maternal complications. CONCLUSIONS: Monoamniotic twinning is a rare form of pregnancy and carries risks for perinatal and neonatal complications. With timely diagnosis, close monitoring in specialized feto-maternal unit and elective delivery at 32-34 weeks the outcome is usually excellent.

Vaginal streptococcus B colonization is not associated with increased infectious morbidity in labor induction.

INTRODUCTION: Labor induction rates are increasing and, in Finland today, one of three labors is induced. Group B streptococcus (GBS) is a bacterium found in 10%-30% of pregnant women and it can be transmitted to the neonate during vaginal delivery. Although GBS is rarely harmful in the general population, it is the leading cause of severe neonatal infections such as sepsis, pneumonia, and meningitis. In addition, GBS can cause maternal morbidity. Labor induction in GBS-positive women has not yet been investigated but concerns of infectious morbidity associated with balloon catheters have been raised. MATERIAL AND METHODS: A historical cohort study of 1959 women undergoing labor induction by balloon catheter in Helsinki University Hospital, Finland, between January 1, 2014 and December 31, 2017. Women with viable singleton term pregnancy in cephalic presentation, unfavorable cervix (Bishop score <6), and intact amniotic membranes were included. GBS was screened by rapid qualitative in vitro test (XPert® GBS) from vaginal and perineal culture upon admission for labor induction. All women testing positive received prophylactic antibiotics. RESULTS: Of the women, 469 (23.9%) were GBS-positive. The rate of maternal intrapartum infection was 7.4%, being lower in the GBS-positive group compared with the GBS-negative group (4.7% vs 8.3%; p = 0.01). The rate of maternal postpartum infection was 3.9%, and the rate of neonatal infection was 3.3%, both being similar between the groups. Also, no difference in the rates of other adverse neonatal outcomes was seen. No GBS sepses occurred in the study. In multivariable logistic regression, rupture of membranes to delivery interval ≥12 hours was associated with maternal intrapartum and postpartum infection, as well as neonatal infection. Other risk factors for maternal intrapartum infection were GBS-negativity, nulliparity, prolonged pregnancy (≥41 weeks), and Bishop score <3 at the start of induction. Cesarean section was associated with postpartum endometritis, while nulliparity, gestational diabetes, and maternal intrapartum infection were associated with neonatal infection. CONCLUSIONS: Regarding maternal and neonatal infectious morbidity, labor induction with balloon catheter appears safe in women colonized with GBS when prophylactic antibiotics are administered at the onset of labor or at membrane rupture.

Balloon catheter use for cervical ripening in women with term pre-labor rupture of membranes: A 5-year cohort study.

INTRODUCTION: To investigate the safety of balloon catheter for cervical ripening in women with term pre-labor rupture of membranes (PROM) and to compare the incidence of maternal and neonatal infections in women with PROM and women with intact membranes undergoing cervical ripening with a balloon catheter. MATERIAL AND METHODS: This retrospective cohort study of 1923 women with term singleton pregnancy and an unfavorable cervix undergoing cervical ripening with a balloon catheter was conducted in Helsinki University Hospital between January 2014 and December 2018. For each case of PROM, two controls were assigned. The main outcome measures were the rates of maternal and neonatal infections. Statistical analyses were performed by SPSS. RESULTS: In all, 641 (33.3%) women following PROM and 1282 (66.6%) women with intact amniotic membranes underwent labor induction. The rates of intrapartum infection (3.7% vs 7.7%; P = .001) and neonatal infection (1.7% vs 3.8%; P = .01) were not increased in women induced by balloon catheter following PROM. Intrapartum infections were associated with nulliparity (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.6-6.5), history of previous cesarean section (OR 2.8, 95% CI 1.2-6.4), extended gestational age ≥41 weeks (OR 1.9, 95% CI 1.2-3.0) and an induction to delivery interval of 48 hours or more (OR 2.0, 95% CI 1.2-3.3). The risk of neonatal infection was associated with nulliparity (OR 3.3, 95% CI 1.4-8.0), gestational age ≥41 weeks (OR 1.9, 95% CI 1.09-3.36) and induction to delivery interval of 48 hours or more (OR 3.4, 95% CI 1.9-6.0). CONCLUSIONS: Use of balloon catheter in women with term PROM appears safe and was not associated with increased maternal or neonatal infectious morbidity.

Correction to: Perinatal outcomes in Finnish twins: a retrospective study.

An amendment to this paper has been published and can be accessed via the original article.

Correction to: Maternal complications in twin pregnancies in Finland during 1987-2014: a retrospective study.

An amendment to this paper has been published and can be accessed via the original article.

Maternal complications in twin pregnancies in Finland during 1987-2014: a retrospective study.

BACKGROUND: To investigate the trends and changes in the incidence and overall outcome of twin pregnancies in Finland, a retrospective study was conducted with emphasis on maternal complications, covering a 28-year study period. METHODS: All 23,498 twin pregnancies with 46,363 live born and 633 stillborn children in Finland during 1987-2014 were included in the study. Data were collected from the national Medical Birth Register and the Care Register on Hospital Care (Finnish Institute for Health and Welfare, Finland) regarding the parturients' characteristics and incidences of several pregnancy and childbirth complications. The incidences of twin pregnancies and maternal complications during pregnancy and childbirth are the main outcome measures of the study. The results are expressed in percentages, means, medians, ranges and standard deviations (SD), when appropriate. RESULTS: Twins comprised 1.4% of all births in Finland in 1987-2014. Parturients' mean age has remained stable, but the share of over 35 year-old parturients is increasing. The incidences of pre-eclampsia, intrahepatic cholestasis of pregnancy, gestational diabetes and postpartum haemorrhage have risen during the study period. Almost half (44.9%) of twins were born preterm, almost half via Caesarean section (47.1%), and 27.7% of twin labours were induced. CONCLUSIONS: Several pregnancy complications increased during the study period. Advanced maternal age among twin parturients has risen, enhancing the risks for developing complications in a pregnancy already of a high-risk category, and predisposing to preterm delivery. National and international guidelines are necessary to improve the overall outcome of twin pregnancies.

Perinatal outcomes in Finnish twins: a retrospective study.

BACKGROUND: To establish the changes in perinatal morbidity and mortality in twin pregnancies in Finland, a retrospective register research was conducted. Our extensive data from a 28-year study period provide important information on the outcome of twin pregnancies in Finland that has previously not been reported to this extent. METHODS: All 23,498 twin pregnancies with 46,996 children born in Finland during 1987-2014 were included in the study. Data were gathered from the Medical Birth Register and the Hospital Discharge Register (Finnish Institute for Health and Welfare, Finland) regarding perinatal mortality (PNM) and morbidity. For statistical analysis, binomial regression analysis and crosstabs were performed. The results are expressed in means, percentages and ranges with comparison to singletons when appropriate. Odds ratios from binomial regression analysis are reported. A p-value <0.05 was considered statistically significant. RESULTS: There were 46,363 liveborn and 633 stillborn twins in Finland during 1987-2014. Perinatal mortality decreased markedly, from 45.1 to 6.5 per 1000 for twin A and from 54.1 to 11.9 per 1000 for twin B during the study period. Yet, the PNM difference between twin A and B remained. Early neonatal mortality did not differ between twins, but has decreased in both. Asphyxia, respiratory distress syndrome, need for antibiotics and Neonatal Intensive Care Unit (NICU) stay were markedly more common in twin B. CONCLUSIONS: In Finland, PNM and early neonatal mortality in twins decreased significantly during 1987-2014 and are nowadays very low. However, twin B still faces more complications. The outline provided may be used to further improve the monitoring and thus perinatal outcome of twins, especially twin B.

Loss of cutaneous microbial diversity during first 3 weeks of life in very low birthweight infants.

Neonatal sepsis (NS) is a frequent problem in neonatal intensive care, especially in preterm and very low birthweight (VLBW) infants. The objective of the study was to characterize the cutaneous bacterial microbiome in VLBW infants treated in the neonatal intensive care unit (NICU). Non-invasive skin microbiome specimens were taken repeatedly from 12 VLBW infants during treatment in NICU starting on the first day of life. All infants received benzylpenicillin and netilmicin during the first 1-5 postnatal days. Samples were also collected from incubators. High cutaneous microbial diversity was present at birth in 11 of 12 of the infants, but the diversity decreased substantially after the first weeks of life in all infants regardless of their infection status. After the loss of diversity, one Staphylococcus operational taxonomic unit dominated the skin microbiome. Recovery of microbial diversity was seen in six of 12 neonates. The microbiome of incubators showed typical environmental bacterial genera. Maternal antibiotic treatment, the aetiology of the preterm birth or being born by C-section did not appear to affect the diversity of skin microbiota at birth, and no correlation was found between cutaneous microbiome and NS.

Fetal left ventricular noncompaction cardiomyopathy and fatal outcome due to complete deficiency of mitochondrial trifunctional protein.

We report a fetal case with fatal outcome having a novel mutation in the HADHB gene, coding the beta-subunit of the mitochondrial trifunctional protein. Parents had a previous pregnancy loss due to fetal heart failure and hydrops. The next pregnancy led to left ventricular noncompaction and increasing pleural effusions after 29 gestational weeks. The fetus was small for gestational age, and long bones were abnormally short. The baby was born severely asphyxiated at 32 gestational weeks by cesarean section. Intensive care was withdrawn due to failure to thrive and suspicion of a severe mitochondrial disorder. Postmortem brain MRI suggested microcephaly with a simplified gyral pattern. The lateral cerebral ventricles were normal. Chromosome analysis was normal (46, XX). Fibroblasts cultured from a skin biopsy of the baby revealed the large homozygous deletion c.1109+243_1438-703del in the HADHB gene, and heterozygous mutations were detected in both parents. The deletion has not been reported earlier. CONCLUSION: It is important to differentiate systemic metabolic diseases from disorders that affect only the cardiac muscle. Trifunctional protein deficiency is a relatively rare disorder of the fatty acid ß-oxidation cycle. The mutation in the HADHB gene causes a systemic disease with early-onset cardiomyopathy. Understanding the molecular genetic defect of the patient allows appropriate genetic counseling of the family. WHAT IS KNOWN: • Mitochondrial disorders as a group are an important etiology for fetal cardiomyopathies including human trifunctional protein (TFP) disorders and several other mitochondrial diseases. WHAT IS NEW: • We report a fetal case with fatal outcome having a novel mitochondrial trifunctional protein mutation (c.1109+243_1438-703del in the HADHB gene).

Management of Foley catheter induction among nulliparous women: a retrospective study.

BACKGROUND: Induction of labour is associated with increased risk for caesarean delivery among nulliparous women. The aims of this study were to evaluate the risk factors for caesarean delivery and to investigate the risk of maternal and neonatal infections in nulliparous women undergoing induction of labour by Foley catheter. METHODS: This clinical retrospective study of 432 nulliparous women with singleton pregnancy and intact amniotic membranes at or beyond 37 gestational weeks scheduled for induction of labour by Foley catheter was conducted over the course of one year, between January 2012 and January 2013, in Helsinki University Hospital. The main outcome measures were caesarean section rate and maternal and neonatal infections. Univariate and multivariate logistic regressions were used to estimate relative risks by odds ratios with 95% confidence intervals. RESULTS: The caesarean section rate was 39.1% (n = 169). In multivariate regression analysis, the factors associated with caesarean section were the need for oxytocin for labour induction [OR 2.9 (95% CI 1.8-4.5) p < 0.001] and early epidural analgesia [OR 9.9 (95% CI 2.1-47.5), p = 0.004]. The maternal intrapartum infection rate was 6.3%, and the clinical neonatal infection rate was 2.8%. In multivariate analysis, gestational diabetes was associated with maternal intrapartum infection [OR 4.3 (95% CI 1.7-11.0, p = 0.002] and early epidural analgesia with neonatal clinical sepsis [OR 10.5 (95% CI 1.4-76), p = 0.02]. CONCLUSIONS: Oxytocin induction and early epidural analgesia were associated with caesarean delivery. Gestational diabetes and early epidural analgesia were associated with infectious morbidity. Since the first caesarean delivery has a major impact on subsequent pregnancies, optimising labour induction among nulliparous women is important.

Management of prolonged pregnancy by induction with a Foley catheter.

OBJECTIVES: To describe labor outcomes in women with prolonged pregnancy and induction of labor with a Foley catheter, as compared with women with spontaneous onset of labor. DESIGN: Retrospective study. SETTING: Helsinki University Hospital. SAMPLE: 553 women with uncomplicated prolonged pregnancies between January 2011 and January 2012, divided into 303 women (54.8%) with Foley catheter induction and 250 (45.2%) with spontaneous labor. METHODS: Maternal and neonatal characteristics of women with uncomplicated singleton pregnancy of ≥41(+5) weeks of gestation were analyzed. MAIN OUTCOME MEASURES: Cesarean delivery rates, maternal and neonatal morbidity. RESULTS: The cesarean delivery rate was 30.7% (n = 93/303) in women with labor induction and 4.8% (12/250) in women with spontaneous onset of labor (p < 0.001). The cesarean delivery rate was 37.3% (91/244) among nulliparous women with labor induction and 8.7% (11/126) among women with spontaneous labor, a sixfold increased risk (odds ratio 6.2). Among parous women, cesarean section rates were low and not significantly different (3.4% vs. 0.8%, p = 0.2). There were no differences in maternal intrapartum or postpartum infection rates or adverse neonatal outcomes between the groups. CONCLUSIONS: Foley catheter induction of labor in prolonged pregnancy did not increase maternal or perinatal morbidity compared with spontaneous onset of labor but was associated with a considerably increased cesarean section rate, particularly among nulliparous women.

Diagnosis and treatment of severe hemolytic disease of the fetus and newborn: a 10-year nationwide retrospective study.

OBJECTIVE: Outcome after intrauterine transfusions due to severe hemolytic disease of the fetus and newborn. DESIGN: Nationwide population-based retrospective cohort study. SETTING: All women treated with intrauterine transfusions for hemolytic disease of the fetus and newborn in Finland in 2003-2012. POPULATION: 339 intrauterine transfusions, performed in 104 pregnancies of 84 women. METHODS: Information on antenatal screening of red cell antibodies and red cell units issued for intrauterine transfusion was obtained from the Finnish Red Cross Blood Service database, and obstetric and neonatal data from hospital records. MAIN OUTCOME MEASURES: Procedure-related complications, perinatal mortality, neonatal morbidity. RESULTS: Overall survival was 94.2% (95% confidence interval 89.7-98.7). There were four fetal and two neonatal deaths. Procedure-related fetal loss rate was 1.2% (95% confidence interval 0.04-2.4) per procedure and 3.8% (95% confidence interval 0.1-7.5) per pregnancy. Of the four procedure-related losses, three were due to technically difficult intrauterine transfusions causing infection and preterm birth. Of the live born infants, 19% (95% confidence interval 11.3-26.7) were born before 32 weeks' gestation. The incidence of severe neonatal morbidity (respiratory distress syndrome, severe cerebral injury, sepsis) was 22.2% (95% confidence interval 13.4-30.2). Poor outcome (death, severe neonatal morbidity) was negatively associated with gestational age at first transfusion (p = 0.001) and at birth (p = 0.00006). Follow-up of the infants was too incomplete to assess the neurodevelopmental outcome. CONCLUSIONS: Although overall survival is comparable with previous studies, our concern is procedure-related infections and preterm births. Close collaboration between the university hospitals is needed to ensure timely treatment, operator skills and systematic follow-up of the children.

Mode of delivery of Finnish dichorionic and monochorionic-diamniotic twins: A retrospective observational study including a risk score for intrapartum cesarean birth.

Background and Aims: Trial of labor is considered safe also among twins, yet nearly 50% are born via cesarean section in Finland. While planned cesarean births have declined among twins, intrapartum cesarean deliveries have risen, postulating evaluation of criteria for trial of labor. The objective of this study was to create an outline of the mode of delivery of dichorionic and monochorionic-diamniotic Finnish twins. By evaluating risk factors for intrapartum cesarean delivery (CD), we aimed at creating a risk score for intrapartum cesarean birth for twins. Methods: A retrospective observational study based on a cohort of dichorionic and monochorionic-diamniotic twin pregnancies considered as candidates for trial of labor in 2006, 2010, 2014, and 2018 (n = 720) was performed. Differences between parturients with vaginal delivery and intrapartum CD to identify potential risk factors for intrapartum CD were assessed. Logistic regression analysis (n = 707) was used to further define risk score points for recognized risk factors. Results: A total of 23.8% (171/720, 95% confidence interval [CI] = 20.7-26.9) of parturients experienced intrapartum CD. Induction of labor, primiparity, fear of childbirth, artificial reproductive technology, higher maternal age, and other than cephalic/cephalic presentation independently associated with intrapartum CD. The achieved total risk score ranged from 0 to 13 points with significantly higher points among the CD group (6.61 vs. 4.42, p < 0.001). Using ≥8 points as a cut-off, 51.4% (56/109) were delivered by intrapartum CD (sensitivity = 33.73%, specificity = 90.20%, positive predictive value = 51.38%, negative predictive value = 81.61%). The total risk score had a fair predictive capability for intrapartum CD (area under the curve = 0.729, 95% CI = 0.685-0.773). Conclusion: Fair-level risk stratification could be achieved with higher maternal age, primiparity, induction of labor, artificial reproductive technology, fear of childbirth, and other than cephalic/cephalic presentation increasing the risk. Parturients with low-risk score (0-7 points) appear to be the best candidates for trial of labor with acceptable CD rates in this group (18.4%).

Comparison of delivery outcomes in low-dose and high-dose oxytocin regimens for induction of labor following cervical ripening with a balloon catheter: A retrospective observational cohort study.

A variety of oxytocin regimens are used for labor induction and augmentation. Considering the increasing rates of labor induction, it is important to assess the most optimal oxytocin regimen without compromising maternal and fetal safety. The aim of this study was to compare delivery outcomes of low-dose and high-dose oxytocin induction protocols. This retrospective cohort study of 487 women comparing low-dose oxytocin protocol (n = 280) and high-dose oxytocin protocol (n = 207) in labor induction following cervical ripening by balloon catheter was performed in Helsinki University Hospital after implementation of a new oxytocin induction protocol. The study included two six-month cohorts from 2016 and 2019. Women with vital singleton pregnancies ≥37 gestational weeks, cephalic presentation, and intact amniotic membranes were included. The primary outcome was the rate of vaginal delivery. The secondary outcomes were the rates of maternal and neonatal infections, postpartum hemorrhage, umbilical artery blood pH-value, admission to neonatal intensive care, and induction-to-delivery interval. Statistical analyses were performed by using IBM SPSS Statistics for Windows (Armonk, NY, USA). The rate of vaginal delivery was higher [69.9% (n = 144) vs. 47.9% (n = 134); p<0.004] and the rates of maternal and neonatal infection were lower during the new high-dose oxytocin protocol [maternal infections 13.6% (n = 28) vs. 22.1% (n = 62); p = 0.02 and neonatal infection 2.9% (n = 6) vs. 14.6% (n = 41); p<0.001, respectively]. The rates of post-partum hemorrhage, umbilical artery blood pH-value <7.05 or neonatal intensive care admissions did not differ between the cohorts. The median induction-to-delivery interval was shorter in the new protocol [32.0 h (IQR 18.5-42.7) vs. 37.9 h (IQR 27.8-52.8); p<0.001]. In conclusion, implementation of the new continuous high-dose oxytocin protocol resulted in higher rate of vaginal delivery and lower rate of maternal and neonatal infections. Our experience supports the use of high-dose continuous oxytocin induction regimen with a practice of stopping oxytocin once active labor is achieved, and a 15-18-hour maximum duration for oxytocin induction in the latent phase of labor following cervical ripening with a balloon catheter.

Viral shedding, and distribution of cytomegalovirus glycoprotein H (UL75), glycoprotein B (UL55), and glycoprotein N (UL73) genotypes in congenital cytomegalovirus infection.

BACKGROUND: Children with congenital CMV infection (cCMV) shed virus in urine and saliva for prolonged periods of time. Outcome of cCMV varies from asymptomatic infection with no sequelae in most cases, to severe longterm morbidity. The factors associated with asymptomatic cCMV are not well defined. We evaluated the viral shedding in a cohort of infants with cCMV identified on newborn screening. In addition, we describe the distribution of viral genotypes in our cohort of asymptomatic infants and previous cohorts of cCMV children in the literature. METHODS: Study population consisted of 40 children with cCMV identified in screening of 19,868 infants, a prevalence of 2/1000. The viral shedding was evaluated at 3 and 18 months of age by real-time CMV-PCR of saliva and plasma, and CMV culture of urine. CMV positive saliva samples were analyzed for genotypes for CMV envelope glycoproteins gB (UL55), and gH (UL75) by genotype specific real-time PCR, and gN (UL73) by cloning and sequencing RESULTS: At 3 months age 40/40 saliva and urine samples, and 19/40 plasma samples were positive for CMV. At 18 months age all urine samples tested (33/33), 9/37 of saliva samples, and 2/34 plasma samples were positive for CMV. The genotype distribution did not differ from the published data CONCLUSIONS: The urinary virus shedding is more persistent than salivary shedding in children with cCMV. The genotype distribution was similar to previous literature and does not explain the low disease burden of cCMV in our population.

The Burden of Congenital Cytomegalovirus Infection: A Prospective Cohort Study of 20 000 Infants in Finland.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most common congenital infection and causes significant morbidity. This study was undertaken to evaluate the benefits of screening newborns for cCMV and to understand the cCMV disease burden in Finland. METHODS: Infants born in Helsinki area hospitals were screened for CMV by testing their saliva with a real-time polymerase chain reaction assay. The CMV-positive infants and matched controls were monitored to determine their neurodevelopmental, audiological, and ophthalmological outcomes at 18 months of age. Griffiths Mental Development Scales, otoacoustic emission and sound field audiometry, and ophthalmologic examination were performed. RESULTS: Of the 19868 infants screened, 40 had confirmed cCMV infection (prevalence, 2 in 1000 [95% confidence interval, 1.4-2.6 in 1000]). Four (10%) infants had symptomatic cCMV. Griffiths general quotients did not differ significantly between the CMV-positive (mean, 101.0) and control (mean, 101.6) infants (P = .557), nor did quotients for any of the Griffiths subscales (locomotion, personal-social, hearing and language, eye and hand, performance) (P = .173-.721). Four of 54 CMV-positive ears and 6 of 80 CMV-negative ears failed otoacoustic emission testing (P = 1.000). The mean minimal response levels over the frequencies 500 Hz to 4 kHz in the sound field audiometry did not differ between CMV-positive (mean, 34.31-dB hearing level) and control (mean, 32.73-dB hearing level) infants (P = .338). No CMV-related ophthalmologic findings were observed. CONCLUSIONS: The prevalence of cCMV was low, and outcomes at 18 months of age did not differ between the infected infants and healthy control infants. With such a low burden in Finland, universal newborn screening for cCMV seems unwarranted.

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.

Meconium drug testing reveals maternal misuse of medicinal opioids among addicted mothers.

Meconium drug testing is a non-invasive method to detect prenatal drug exposure, which can cause severe problems for the infant, indicating the need for follow-up measures to ensure the welfare of the child. Meconium samples for drug testing were collected from 143 infants as part of routine clinical work among addicted mothers. The drug testing findings were combined with medical records including clinical background and follow-up data. The substances screened for included medicinal opioids, 6-monoacetylmorphine (a metabolite of heroin), amphetamines and tetrahydrocannabinolic acid. At least one of the 13 target drugs was detected in 57 (40%) meconium samples. In 21 cases, the findings were unexpected on the basis of clinical data or denied by the mother. Medicinal opioids, especially the opioid substitution treatment drugs buprenorphine and methadone, comprised the majority of the findings of both admitted and unexpected drug misuse. Meconium drug testing methods should target not just traditional illicit drugs but also prescription drugs with misuse potential.