Multivitamin intake and the risk of congenital heart defects: A cohort study.

OBJECTIVE: Congenital heart disease (CHD) is the most common type of congenital birth defect, but little is known about possible modifiable behavioral risk factors. The study aimed to assess whether intake of periconceptional or postconceptional multivitamin was associated with a decreased risk of CHD in the offspring. STUDY DESIGN: The study population comprised 15,567 women from the Copenhagen Pregnancy Cohort with complete data on multivitamin intake before and during pregnancy, who gave birth to live-born singletons from October 2012 to October 2016. Main outcome measure was CHD defined according to the International Classification of Diseases (ICD), 10th revision. Cases of CHD were classified into five subgroups based on the clinical phenotype: 1) Conotruncal defects, 2) Left ventricular outflow tract obstruction, 3) Right ventricular outflow tract obstruction, 4) Septal defects, and 5) Other CHD. Multivariate logistic regression analyses were performed with adjustment for maternal age, chronic disease, assisted reproductive technology, smoking status, and alcohol consumption. RESULTS: Of the 15,567 included women, 31.9 % reported a daily multivitamin intake in the periconceptional period, 53.7 % in the postconceptional period, and 14.4 % women did not report a daily multivitamin intake. The prevalence of CHD in the population was 0.7 % (n = 112). Periconceptional and postconceptional multivitamin intake was not associated with risk of overall CHD in offspring: Adjusted OR was 0.64 (95 % CI 0.36-1.13) and 0.77 (95 % CI 0.47-1.30), respectively. CONCLUSION: The current large cohort study did not show a preventive effect of multivitamin intake in the periconceptional or postconceptional period on the risk of CHD in the offspring.

Mode of delivery and adverse short- and long-term outcomes in vertex-presenting very preterm born infants: a European population-based prospective cohort study.

OBJECTIVES: To compare mortality, morbidity and neurodevelopment by mode of delivery (MOD) for very preterm births with low prelabour risk of caesarean section (CS). METHODS: The study was a population-based prospective cohort study in 19 regions in 11 European countries. Multivariable mixed effects models and weighted propensity score models were used to estimate adjusted odds ratios (aOR) by observed MOD and the unit's policy regarding MOD. Population: Singleton vertex-presenting live births at 24 + 0 to 31 + 6 weeks of gestation without serious congenital anomalies, preeclampsia, HELLP or eclampsia, antenatal detection of growth restriction and prelabour CS for fetal or maternal indications. RESULTS: Main outcome measures: A composite of in-hospital mortality and intraventricular haemorrhage (grade III/IV) or periventricular leukomalacia. Secondary outcomes were components of the primary outcome, 5 min Apgar score <7 and moderate to severe neurodevelopmental impairment at two years of corrected age. The rate of CS was 29.6% but varied greatly between countries (8.0-52.6%). MOD was not associated with the primary outcome (aOR for CS 0.99; 95% confidence interval [CI] 0.65-1.50) when comparing units with a systematic policy of CS or no policy of MOD to units with a policy of vaginal delivery (aOR 0.88; 95% CI 0.59-1.32). No association was observed for two-year neurodevelopment impairment for CS (aOR 1.15; 95% CI 0.66-2.01) or unit policies (aOR 1.04; 95% CI 0.63-1.70). CONCLUSIONS: Among singleton vertex-presenting live births without medical complications requiring a CS at 24 + 0 to 31 + 6 weeks of gestation, CS was not associated with improved neonatal or long-term outcomes.

[Magnesium sulphate treatment decreases the risk of cerebral palsy after preterm birth].

Children born preterm have an increased risk of severe morbidity, e.g. cerebral palsy (CP), compared to children born at term. CP cannot be treated, which is why a prophylactic approach is essential, as argued in this review. Six randomised controlled trials (RCTs) have provided data on MgSO4 treatment as CP neuroprotection in preterm birth, including a new RCT from Denmark. Recently, an updated meta-analysis with trial sequential analysis detected a significant neuroprotective effect of MgSO4 treatment in preterm birth. There is now sufficient evidence, that MgSO4 treatment should be used as neuroprotection in preterm birth.

Multivitamin intake does not affect the risk of preterm and very preterm birth.

INTRODUCTION: The aim of this study was to assess the association between multivitamin intake during pregnancy and the risk of preterm birth and very preterm birth. METHODS: The study population comprised 15,629 women from the Copenhagen Pregnancy Cohort with data on pregnancy multivitamin intake during their first trimester who gave birth to singletons from October 2012 to October 2016. Data on pregnancy multivitamin intake were linked to the Medical Birth Registry to identify the birth outcome. The main outcome measures were preterm birth before 37 weeks of gestation and very preterm birth before 32 weeks of gestation. RESULTS: Among the included women, 85.6% had taken daily pregnancy multivitamins during their first trimester. We found no evidence that pregnancy multivitamin intake during the first trimester was associated with a decreased risk of preterm birth (adjusted odds ratio (OR) = 1.01; 95% confidence interval (CI): 0.77-1.33) or very preterm birth (adjusted OR = 1.06; 95% CI: 0.63-1.77). Stratification for BMI into lesser-than 25 kg/m2 and ≥ 25 kg/m2 did not alter these findings. CONCLUSIONS: Pregnancy multivitamin intake during the first trimester was not associated with a decreased risk of preterm birth or very preterm birth among women in a high-income population. FUNDING: none. TRIAL REGISTRATION: not relevant.

Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE Cohort.

Importance: Administration-to-birth intervals of antenatal corticosteroids (ANS) vary. The significance of this variation is unclear. Specifically, to our knowledge, the shortest effective administration-to-birth interval is unknown. Objective: To explore the associations between ANS administration-to-birth interval and survival and morbidity among very preterm infants. Design, Setting, and Participants: The Effective Perinatal Intensive Care in Europe (EPICE) study, a population-based prospective cohort study, gathered data from 19 regions in 11 European countries in 2011 and 2012 on 4594 singleton infants with gestational ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated courses of ANS. Data were analyzed November 2016. Exposure: Time from first injection of ANS to delivery in hours and days. Main Outcomes and Measures: Three outcomes were studied: in-hospital mortality; a composite of mortality or severe neonatal morbidity, defined as an intraventricular hemorrhage grade of 3 or greater, cystic periventricular leukomalacia, surgical necrotizing enterocolitis, or stage 3 or greater retinopathy of prematurity; and severe neonatal brain injury, defined as an intraventricular hemorrhage grade of 3 or greater or cystic periventricular leukomalacia. Results: Of the 4594 infants included in the cohort, 2496 infants (54.3%) were boys, and the mean (SD) gestational age was 28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g. Mortality for the 662 infants (14.4%) unexposed to ANS was 20.6% (136 of 661). Administration of ANS was associated with an immediate and rapid decline in mortality, reaching a plateau with more than 50% risk reduction after an administration-to-birth interval of 18 to 36 hours. A similar pattern for timing was seen for the composite mortality or morbidity outcome, whereas a significant risk reduction of severe neonatal brain injury was associated with longer administration-to-birth intervals (greater than 48 hours). For all outcomes, the risk reduction associated with ANS was transient, with increasing mortality and risk for severe neonatal brain injury associated with administration-to-birth intervals exceeding 1 week. Under the assumption of a causal relationship between timing of ANS and mortality, a simulation of ANS administered 3 hours before delivery to infants who did not receive ANS showed that their estimated decline in mortality would be 26%. Conclusions and Relevance: Antenatal corticosteroids may be effective even if given only hours before delivery. Therefore, the infants of pregnant women at risk of imminent preterm delivery may benefit from its use.

Persistence and reappearance of high-risk human papillomavirus after conization.

OBJECTIVE: Women with early cervical cancer or intraepithelial neoplasia grades 2 and 3 (CIN2+) are treated by conization; however, they still have a higher risk for subsequent CIN2+ than the general female population. Persistence of high-risk (HR) human papillomavirus (HPV) is a key factor in the development of CIN2+. We investigated persistence and reappearance of type-specific HR HPV infection after conization and evaluated possible co-factors. METHODS: During 2002-2006, cervical swabs from 604 women were collected before conization, at 4-6 months and at 8-12 months after conization. HPV was detected by HC2 and genotyped by LiPAv2. Information on co-factors was collected through a questionnaire. Associations were assessed by multivariate logistic regression analysis. RESULTS: HR HPV persistence rate was 9.5%. The α5/6 species were more likely to persist than α9 species (OR, 2.28; 95% CI, 1.11-4.70). For single infections, a doubling in viral load at enrolment increased the risk for persistence by 36% (95% CI, 1.13-1.63). In addition, margin status was associated with risk of persistence. Smoking, oral contraceptive use and severity of the cervical lesion did not significantly affect persistence. Among the HPV infections that had cleared, 2.2% reappeared. CONCLUSION: Our study indicates that viral load is important in predicting HPV persistence. The α5/6 species were most likely to persist. However, most of these HPV types have a lower carcinogenic potential than the α7/α9 species and may be by-standers. Further studies are needed to assess whether pre-conization viral load can also predict subsequent CIN2+.

Trends in incidence of borderline ovarian tumors in Denmark 1978-2006.

OBJECTIVE: To examine period-, age- and histology-specific trends in the incidence rate of borderline ovarian tumors in Denmark in 1978-2006. DESIGN: Register-based cohort study. SETTING: Denmark 1978-2006. POPULATION: 5079 women diagnosed with a borderline ovarian tumor in at least one of two nationwide registries (4312 epithelial tumors and 767 non-epithelial/unspecified tumors). METHODS: Estimation of overall incidence rates and period-, age- and histology-specific incidence rates. Age-adjustment was done using the World Standard POPULATION. To evaluate incidence trends over time, we estimated average annual percentage change and 95% confidence intervals (CI) using log-linear Poisson models. MAIN OUTCOME MEASURES: Age-standardized and age-specific incidence rates and average annual percentage change. RESULTS: The incidence of epithelial borderline ovarian tumors increased from 2.6 to 5.5 per 100,000 women-years between 1978 and 2006, with an average annual percentage change of 2.6% (95% CI: 2.2-3.0). The median age at diagnosis was 52 years. Women 40 years or older had a higher average annual percentage change than women younger than 40 years. Most tumors were mucinous (49.9%) and serous tumors (44.4%). Women with mucinous tumors were younger at diagnosis (50 years) compared with women with serous tumors (53 years). Women with serous tumors had a higher average annual percentage incidence change than women with mucinous tumors. CONCLUSIONS: The incidence rate of borderline ovarian tumors increased significantly in Denmark in 1978-2006. In line with results for ovarian cancer, Denmark had a higher incidence rate of borderline ovarian tumors compared with the other Nordic countries in 1978-2006.

[Primary ovarian cancer. A comparison of registrations in the Danish Cancer Registry and the Pathology Data Bank]. / Primaer ovariecancer. En sammenligning af registreringer i Cancerregisteret og Patologidatabanken.

INTRODUCTION: Ovarian cancer (OC) registrations in the Danish Cancer Registry (CR) and the Danish Pathology Data Bank (PDB) 1978-99 were compared in order to assess the possibility of identifying OC cases from another data source than the CR. MATERIAL AND METHODS: A total of 13,320 OC were identified in the CR/PDB and comparisons of the registrations were performed. RESULTS: The frequency of cases registered in both registries increased during 1978-99. Agreement in registration of histological subtypes in the two registries was found in 82% of the cases. Diagnosis among the rest was most often consistent; however, a more specific diagnosis was often found in one or the other registry. The frequency of women only registered with OC in the CR decreased from 81% to 35%, as the number of women with no diagnoses at all in the PDB declined from 1978 to 1997, whereafter it stabilised, primarily because all pathology departments now reported data to the PDB. In 1997-99, 29% of OC registered in the CR with a histologically verified OC diagnosis was still not registered with cancer in the ovaries in the PDB. Most of these, however, could be identified in the PDB with diagnoses consistent with metastases from OC. In total, 749 OC were not registered in the CR, though explanations for their missing registrations could be found in most cases. CONCLUSION: Data from the PDB may not be useful in complete identification of ovarian cancer cases for research purposes. However, it is a good supplement to data from the CR.

Association of reproductive factors, oral contraceptive use and selected lifestyle factors with the risk of ovarian borderline tumors: a Danish case-control study.

OBJECTIVE: The aim was to examine risk factors for ovarian borderline tumors overall, and according to histological subtype (serous vs. mucinous), in a large Danish population-based case-control study. METHODS: Ovarian borderline cases and controls were recruited from 1995 to 1999, and personal interviews were conducted. In all, 202 cases and 1,564 randomly selected controls were included. The analysis was performed using multiple logistic regression models. RESULTS: The risk of ovarian borderline disease decreased with increasing parity (OR=0.79 per birth, 95% CI: 0.63-0.98) and older age at first birth (OR=0.67 per 5 years, 95% CI: 0.53-0.84). Both a history of breastfeeding and use of oral contraceptives reduced the risk of borderline tumor, the effect being most pronounced for serous tumors. Increasing body mass index (BMI) was associated with elevated risk of serous borderline tumor (OR=1.05 per BMI unit; 95% CI: 1.00-1.10), whereas current smoking was a strong risk factor only for mucinous tumors (OR=2.10; 95% CI: 1.22-3.60). Finally, increasing consumption of milk (all types) was found to increase the risk of borderline disease (OR=1.04 per glass milk per week; 95% CI: 1.02-1.06), and increasing intake of total lactose also increased the risk significantly (OR=1.16 per 50 gram lactose per week; 95% CI: 1.06-1.26). CONCLUSION: The risk profile of ovarian borderline tumors is similar to that of ovarian carcinomas, and we observed significant etiological differences between serous and mucinous borderline tumors.

Trends in the incidence and mortality of ovarian cancer in Denmark 1978-2002. Comparison with other Nordic countries.

BACKGROUND: The Nordic countries are well-known high-incidence areas of ovarian cancer, but even within the Nordic countries, differences exist. METHODS: Focus in this descriptive epidemiological study is to assess developments in incidence and mortality of ovarian cancer in Denmark 1978-2002 and to make a comparison with the development in the other Nordic countries. The results are based on data from the nationwide Danish Cancer Registry as well as the other Nordic Cancer Registries. RESULTS: A total of 14,325 cases of ovarian cancer were registered from 1978 to 2002 in Denmark. In this period, the age-standardized incidence decreased slightly from 14.3 (1978-1982) to 13.3 per 100,000 woman-years (1998-2002). The histology-specific time trends showed a tendency towards more specified histological diagnoses. Iceland had the highest age-adjusted ovarian cancer incidence in the Nordic countries, whereas Denmark had the highest mortality rate. In the entire period, the Danish mortality rate declined from 10.8 (1978-1982) to 9.0 per 100,000 woman-years (1998-1999). Only 19% of ovarian cancers in Denmark from 1978 to 2002 were localized at the time of diagnosis, while 30% had distant metastases. Older women were more likely to have advanced disease at diagnosis. The Danish distribution of stage at diagnosis seems less favorable compared to results from other countries. CONCLUSIONS: The Danish incidence of ovarian cancer seemed to decrease slightly from 1978 to 2002. Even though the mortality rate of ovarian cancer also declined, Denmark had the highest mortality rate of ovarian cancer in the world. Part of it may be explained by a less-favorable distribution of stage at diagnosis.

Multiple birth and cerebral palsy in Europe: a multicenter study.

BACKGROUND: A European multicenter study (Surveillance of Cerebral Palsy in Europe, SCPE) was used to describe changes over time in multiple birth rates and cerebral palsy (CP) rates among multiple born infants, to compare CP rates and clinical types between multiples and singletons, and to analyse the influence of birth order in twins. METHODS: Data were collected from 12 European population-based CP registers on 6613 children born in 1975-90, as well as demographic data. RESULTS: The rate of multiple birth in the populations increased from 1.9% in 1980 to 2.4% in 1990, and the proportion of multiples among CP infants increased from 4.6% in 1976 to 10% in 1990. Multiples have a four times higher rate of CP than singletons [7.6 vs. 1.8 per 1000 live births, relative risk (RR) 4.36; 95% confidence interval (CI) 3.76-4.97] overall. The risk is marginally higher in multiples with birthweight > 2500 g (RR 1.60; 95% CI 0.95-2.28) and born at term (RR 1.65; 95% CI 0.91-2.40), and there is no difference in the risk for the low-birthweight and preterm groups. Correcting for differences in gestational age and birthweight, the clinical type of CP was the same in multiples and singletons. Twin CP infants are more often second than first born (56% vs. 44%, p < 0.05). CONCLUSIONS: Multiple born infants have a four times higher risk of developing cerebral palsy than singletons, mainly related to the higher risk of preterm birth in multiples. As the rate of multiples doubled through the 1980s, cerebral palsy cases in multiples increased in the same period.