Prenatal detection of major congenital malformations in a cohort of 19 367 Danish fetuses with a complete follow-up six months after birth.

INTRODUCTION: To investigate the performance of the second-trimester ultrasound scan regarding ultrasound-detectable congenital malformations in a Danish region. The study sample was population-based, with 6 months of postnatal follow-up. Hospital records and autopsy reports were reviewed in each case to validate the prenatal ultrasound diagnosis. MATERIAL AND METHODS: This population-based cohort study included all fetuses (n = 19.367) alive at the second-trimester scan in four hospitals in a Danish region. The final diagnosis of the malformations was based on hospital records during the 6-month postnatal follow-up. In case of termination or stillbirth, the result from the autopsy report was used to validate the prenatal ultrasound diagnosis. RESULTS: The detection rate of congenital malformations in the prenatal screening program was 69%, where 18% was detected on the first-trimester scan and 51% on the second-trimester scan. Another 8% was detected in the third trimester. Specificity was 99.9%. The positive predictive value of the screening program was 94.5%, and the negative predictive value was 99.5%. The overall prevalence of malformations was 16.8 per 1000 fetuses, most frequently in the heart and the urinary tract. CONCLUSIONS: This study shows that the national screening program for congenital malformations can detect many severe malformations and is an effective screening test for malformations.

Parental information about the option to apply for pregnancy termination after the detection of a congenital abnormality and factors influencing parental decision-making: a cohort study.

BACKGROUND: The detection of an abnormality during prenatal screening implies that the parents are informed about possible treatment and management of the pregnancy, birth, and postnatal course. This information should enable the parents to make decisions regarding the pregnancy, especially in cases where termination of pregnancy may be an option. The objectives of this study were to investigate how often doctors informed parents about pregnancy termination when the fetus had an anomaly and which demographic factors were related to parental decision-making. METHODS: This was a retrospective cohort study with prospectively collected data of fetuses diagnosed with an abnormality during prenatal screening between 2014 and 2016 in Denmark. We categorized the abnormalities into five long-term prognosis groups and analyzed their association with the doctor provided information about termination. We tested the association between demographic variables and parental decisions using univariate and multivariate statistical analyses. RESULTS: Three hundred and twenty fetuses were diagnosed with an abnormality. In 67% of these cases, the parents were informed about termination. All parents whose fetus had a lethal prognosis were informed about termination. By comparison, the parents of 98% of fetuses with genetic disorders, 96% of fetuses with poor prognosis, 69% of fetuses with uncertain prognosis, and 12% of fetuses with good prognosis were informed about termination. Of these parents, 92% chose to terminate. A lethal long-term prognosis was the only factor related to parental decision to terminate a pregnancy. CONCLUSIONS: Doctors mainly informed parents about the option of pregnancy termination for conditions with a poor or lethal long-term prognosis or for genetic disorders. Only conditions with a lethal prognosis were significantly related to the parental decision to terminate the pregnancy.

Cerebral disorders in the first 7 years of life in children born post-term: a cohort study.

BACKGROUND: To estimate the association between post-term delivery and risk of physical disabilities, mental disabilities, and seizures during the first 7 years of life. METHODS: Data from 57,884 singleton infants born alive in week 39-45 by mothers included in the Danish National Birth Cohort (1997 to 2004) were analyzed, of these 51,268 were born at term (39-41 + 6) and 6616 post-term (42 + 0-44 + 6). Information on clinical endpoints was obtained from an interview at 18 months of gestational age, from a 7-year questionnaire, and from the Danish National Patient Register. Logistic regression and Cox regression were used to estimate odds ratios and hazard rate ratios for the outcome obtained from the interview/questionnaire data and from the register-based data, respectively. RESULTS: We found no statistically significant increased risk of physical disabilities, mental disabilities, and epilepsy among children born post-term, though for most outcomes studied a tendency towards more adverse outcomes was seen. When children born late term (week 41) were compared to children born in week 42 or later the same tendency was found. CONCLUSION: Post-term born children had a tendency to an excess risk of neurological disabilities as followed for up to 7 years of age.

Reasons for non-participation in malformation scans in Denmark: a cohort study.

BACKGROUND: The aim of the study was to estimate the proportion of women giving birth in two hospitals in the Region of Southern Denmark who did not attend the malformation scan and to elucidate the reasons for not participating. METHODS: In this register-based descriptive study, we used patient administration systems to identify women who had given birth at two Danish hospitals between March 2013 and January 2015. We then linked this information with the hospital database for fetal medicine (Astraia) to identify women who did not attend the malformation scan at week 18-20. We reviewed the medical records of these women to validate the data and to identify the reason for non-participation. RESULTS: Of 7690 births, 153 (2%) women did not attend the malformation scan. The main reason for non-participation was a passive deselection (81%). Most of these women were not present in Denmark at the time of the malformation scan (61%) and few women declined (8%). CONCLUSIONS: Less than 2% of a birth cohort in two major hospitals in Denmark did not attend the free offer of a malformation scan. Most of these women (81%) did not actively decide against the malformation scan. Very few (0.2%) declined the malformation scan. Non-attendance is not always due to an active decision made by the pregnant woman.

Neonatal BCG vaccination has no effect on recurrent wheeze in the first year of life: A randomized clinical trial.

BACKGROUND: Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG are not fully understood, but a shift from a TH2 to a TH1 response has been suggested as a possible explanation. OBJECTIVE: We hypothesized that BCG at birth would reduce the cumulative incidence of RW during the first year of life. METHODS: The Danish Calmette Study is a multicenter randomized trial conducted from 2012-2015 at 3 Danish hospitals. The 4262 newborns of 4184 included mothers were randomized 1:1 to BCG (SSI strain 1331) or to a no-intervention control group within 7 days of birth; siblings were randomized together as one randomization unit. Exclusion criteria were gestational age of less than 32 weeks, birth weight of less than 1000 g, known immunodeficiency, or no Danish-speaking parent. Information was collected through telephone interviews and clinical examinations at 3 and 13 months of age; data collectors were blind to randomization group. RW was defined in several ways, with the main definition being physician-diagnosed and medically treated RW up to 13 months of age. RESULTS: By 13 months, 211 (10.0%) of 2100 children in the BCG group and 195 (9.4%) of 2071 children in the control group had received a diagnosis of RW from a medical doctor and received antiasthma treatment (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW. CONCLUSION: Neonatal BCG had no effect on the development of RW before 13 months of age.

Neonatal BCG has no effect on allergic sensitization and suspected food allergy until 13 months.

BACKGROUND: Vaccination with Bacillus Calmette-Guérin (BCG) is used in many countries as protection against tuberculosis. Studies have suggested that BCG may also have non-specific effects, reducing non-tuberculosis mortality, morbidity, and atopic manifestations. In this study, we evaluated the effect of neonatal BCG vaccination on allergic sensitization and suspected food allergy at 13 months of age. METHODS: The Danish Calmette Study was conducted from 2012 to 2015 at three Danish hospitals. Within 7 days of birth, the 4262 newborns of 4184 included mothers were randomized 1:1 to BCG or to a no-intervention control group. Exclusion criteria were gestational age <32 weeks, birth weight <1000 g, known immunodeficiency, or no Danish-speaking parent. Follow-up information was collected through telephone interviews at 3 and 13 months of age. Subgroups of participants were offered blood sampling at 13 months of age. RESULTS: By 13 months of age, the parents and/or general practitioners of 5.6% (117/2089) of the children in the BCG group and 6.1% (126/2061) of the control group suspected food allergy, resulting in a risk ratio comparing BCG-vaccinated children with control children of 0.91 (95% CI 0.71-1.16). Among 1370 blood samples, sensitization (Phadiatop Infant >0.35 kUA/L) was found in 55 of 743 (7.4%) children in the BCG group and 50 of 627 (8.0%) of the control group (risk ratio 0.94 [0.65-1.36]). CONCLUSION: In this randomized clinical trial, neonatal BCG had no significant effect on suspected food allergy or on sensitization at 13 months of age.

The Danish Fetal Medicine Database: establishment, organization and quality assessment of the first trimester screening program for trisomy 21 in Denmark 2008-2012.

OBJECTIVE: To describe the establishment and organization of the Danish Fetal Medicine Database and to report national results of first-trimester combined screening for trisomy 21 in the 5-year period 2008-2012. DESIGN: National register study using prospectively collected first-trimester screening data from the Danish Fetal Medicine Database. POPULATION: Pregnant women in Denmark undergoing first-trimester screening for trisomy 21. METHODS: Data on maternal characteristics, biochemical and ultrasonic markers are continuously sent electronically from local fetal medicine databases (Astraia Gmbh software) to a central national database. Data are linked to outcome data from the National Birth Register, the National Patient Register and the National Cytogenetic Register via the mother's unique personal registration number. First-trimester screening data from 2008 to 2012 were retrieved. MAIN OUTCOME MEASURES: Screening performance was assessed for the years 2008-2012 by calculating detection rates and screen-positive rates. RESULTS: A total of 268 342 first-trimester risk assessments for trisomy 21 were performed in singleton pregnancies. Participation rate in first-trimester screening was >90%. The national screen-positive rate increased from 3.6% in 2008 to 4.7% in 2012. The national detection rate of trisomy 21 was reported to be between 82 and 90% in the 5-year period. CONCLUSION: A national fetal medicine database has been successfully established in Denmark. Results from the database have shown that at a national level first-trimester screening performance for trisomy 21 is high with a low screen-positive rate and a high detection rate.

Risk for developmental coordination disorder correlates with gestational age at birth.

BACKGROUND: Studies suggest that children born very preterm have a high risk of developmental coordination disorder (DCD). We examined the relation between the larger spectrum of gestational age at birth and the risk of DCD. METHODS: We used the 7-year follow-up data from 22898 singletons in the Danish National Birth Cohort. We calculated a total score from the Developmental Coordination Disorder Questionnaire (DCDQ), incorporated in the 7-year follow-up, and defined children with a score of 46 or below as having probable DCD. Information on gestational age was obtained from the Medical Birth Register. RESULTS: Gestational age at birth was inversely associated with the risk of DCD; a decline in gestational age by a week was associated with a 19% [95% confidence interval 14%, 25%] increased risk of DCD screening positive among children delivered before 40 weeks. No significant increased risk of DCD was seen for children born post-term. CONCLUSION: Our data indicate that short gestational age at birth in a range up to gestational week 37 is related to an increased risk of DCD.

A comparative study of the allergenic potency of wild-type and glyphosate-tolerant gene-modified soybean cultivars.

A large proportion of soybean cultivars grown in the USA are now genetically modified varieties and concern has been raised about the safety of these products for consumers. A study of the impact on allergenic potency in soybeans, comparable except for the newly introduced gene (CP4 EPSPS), was performed using soybean-sensitized patients. The allergenicity of 18 different (10 GM and 8 WT) soybean extracts was examined blindly by the following three methods: A) Sera from patients with specific IgE against soybean were used to determine concentrations inducing 50% RAST inhibition; B) Histamine release induced by the extracts was examined using blood from sensitized patients; C) SPT was performed on sensitized patients with all 18 extracts. All three methods showed variations in the allergenic potency between the individual extracts but allergenic potential was not affected by presence of the transgene. By using standard in vitro methods and SPT for determination of allergenicity we were not able to detect any significant difference in the allergenic potency between GM and WT soybeans.

[Pregnancy jeopardized by pseudoxanthoma elasticum].

Pseudoxanthoma elasticum (PXE) is a rare inherited systemic disorder characterized by progressive calcification in the elastic tissue. Information about pregnancy in women with PXE is sparse. We report of a 36-year-old Caucasian woman, diagnosed with PXE, with a dichorionic diamniotic twin pregnancy, whose antenatal ultrasound scans showed a hyperechogenic placenta due to calcification. The calcification was confirmed on post-partum placental histology. Both twins, delivered via caesarean section due to maternal bleeding at 27 weeks of gestation suffered from intraventricular haemorrhage.

[Down's syndrome risk assessment in Denmark--secondary publication]. / Risikovurdering for Downs syndrom i Danmark--sekundaerpublikation.

In 2004 The Danish National Board of Health introduced a new guideline regarding prenatal screening. All pregnant women are now offered a Down's syndrome risk assessment. The new guideline has had an impact on the number of invasive early prenatal procedures. The number of procedures fell by 50% from 2000 to 2006. 90% of the foetuses with Down's syndrome are detected prenatally. Denmark is one of the first countries in the world in which risk assessment for Down's syndrome has been successfully implemented at a national level.

Prenatal risk indicators of a prolonged pregnancy. The Danish Birth Cohort 1998-2001.

BACKGROUND: Few prenatal risk factors of prolonged pregnancy, a pregnancy of 42 weeks or more, are known. The objective was to examine whether sociodemographic, reproductive, toxicologic, or medical health conditions were associated with the risk of prolonged pregnancy. METHODS: Data from the Danish Birth Cohort in Denmark were used. Interview data from 53,392 participants with live-born singleton deliveries in the period 1998-2001 were available at the time of this study. The participants were interviewed by telephone at 12 and 30 weeks' gestation, and 6 and 18 months after delivery. Statistical analyses were done using logistic regression. RESULTS: Women with a pre-pregnancy body mass index of 25 kg/m2 or more had a high risk of prolonged pregnancy. If the pre-pregnancy body mass index was 35 kg/m2 or more the odds ratio was 1.52 (95% CI 1.28-1.82). Nulliparity also increased the risk of prolonged pregnancy (OR (95% CI) = 1.35 (1.27-1.44)). CONCLUSIONS: The risk of post-term delivery was high in women with a pre-pregnancy body mass index of 25 kg/m2 or more, and in nulliparous women.

Perinatal and maternal complications related to postterm delivery: a national register-based study, 1978-1993.

OBJECTIVE: This study was undertaken to estimate the risk of fetal and maternal complications associated with postterm delivery in Denmark. STUDY DESIGN: A cross-sectional study that used records from the Danish Medical Birth Registry from 1978 to 1993 was performed. All women with registered prolonged pregnancy (n = 78022) and a 5% random sample of all women who gave birth (n = 47021) were linked to the Danish National Discharge Register. We established a postterm group of 77956 singleton deliveries and a term group of 34140 singleton spontaneous deliveries. Logistic regression models were used to analyze data. RESULTS: The risk of perinatal and obstetric complications was high in postterm delivery compared with term delivery (adjusted odds ratios between 1.2 and 3.1). The risk of perinatal death was 1.33 (1.05-1.68). CONCLUSION: Postterm delivery was associated with significantly increased risks of perinatal and maternal complications in Denmark in the period from 1978 to 1993.

Correlation between self-reported gestational age and ultrasound measurements.

BACKGROUND: We studied the agreement between different measurements of gestational age, i.e. self-reported gestational age in the Danish National Birth Cohort Study, ultrasound-estimated gestational age from the medical records in one Danish county and gestational age from the Danish National Hospital Discharge Register. METHODS: The ultrasound-estimated gestational length was based on the size of the biparietal diameter. The ultrasound-estimated gestational length was related to corrected and uncorrected last menstrual period estimates in the Danish National Cohort Study, and to the gestational length recorded in the Danish National Discharge Register. Non-parametric statistics were used in the analysis. RESULTS: The gestational ages estimated by ultrasound were 2-3 days shorter than gestational ages estimated by the other methods. The gestational ages recorded by the Discharge Register and the gestational ages based on corrected last menstrual period did not differ significantly. CONCLUSION: The self-reported gestational age in The Danish National Birth Cohort is in good concordance both with data from the National Hospital Discharge Register and with ultrasound-estimated gestational age.

Genetic influence on prolonged gestation: a population-based Danish twin study.

OBJECTIVE: The purpose of this study was to test a possible genetic component to prolonged gestation. STUDY DESIGN: The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the Danish Medical Birth Register. A total of 2588 same-sex twin pairs of whom both cotwins became parents during 1978 to 1996 were identified. RESULTS: The concordance rate for female twin pairs for a gestation of > or =41 weeks and > or =42 weeks was higher for monozygotic twin pairs than for dizygotic twin pairs, which indicates genetic effects. Biometric modeling suggested that genetic factors account for 23% to 30% of the liability to prolonged gestation. The difference in concordance rate between monozygotic and dizygotic male twin pairs was small, and the best fitting model indicated no genetic factors. CONCLUSION: Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found.