Morten Hedegaard - Academia.edu (original) (raw)

Papers by Morten Hedegaard

Research paper thumbnail of Maternal salivary cortisol levels during pregnancy are positively associated with overweight children

Psychoneuroendocrinology, 2015

Research paper thumbnail of Red blood cell antibodies in pregnancy and their clinical consequences: synergistic effects of multiple specificities

Transfusion, 2009

The objective was to determine clinical consequences of various specificities for the infant/fetu... more The objective was to determine clinical consequences of various specificities for the infant/fetus. The population was patients referred between 1998 and 2005 to the tertiary center because of detected red blood cell (RBC) alloimmunization. Altogether 455 infants were delivered by 390 alloimmunized women. This was a retrospective cohort study. Data were obtained from the blood bank register and the obstetric and neonatal database. As indicators of hemolytic activity of the antibodies, the frequency of the therapeutic interventions intrauterine transfusion, exchange transfusion, and simple transfusion was used. Anti-D was the most common antibody (46.6%), followed by anti-K (15.4%). A combination of antibodies was detected in 27%. All three types of therapeutic intervention were significantly more frequent in women with anti-D plus an additional antibody than in women with anti-D as the sole antibody. The anti-D titer closely paralleled the clinical importance of the antibody. One case of anti-s with a titer of 512 required all three types of transfusion. Anti-D was the single most frequent and harmful specificity closely followed by anti-K. Combinations of antibody specificities were more harmful than single specificities, and a potentially synergistic effect should be considered.

Research paper thumbnail of Massive fetomaternal hemorrhage: clearance of fetal red blood cells after intravenous anti-D prophylaxis monitored by flow cytometry

Transfusion, 2008

The clearance of D+ red blood cells (RBCs) from the circulation in D- individuals mediated by pas... more The clearance of D+ red blood cells (RBCs) from the circulation in D- individuals mediated by passively administered anti-D occurs by opsonization with the antibody and subsequent removal in the spleen. Few data exist on the kinetics of clearance of large volumes of D+ RBCs from the maternal circulation by anti-D in clinical cases of massive fetomaternal hemorrhage (FMH). A 33-year-old D- woman delivered a D+ female infant by emergency cesarean section for suspected fetal anemia. A massive FMH, initially estimated to be approximately 142 mL of RBCs, was found. In addition to the standard dose of intramuscular (IM) anti-D (300 microg) given immediately after delivery, 2700 microg of anti-D was administered intravenously (IV). The clearance of D+ fetal cells from the maternal circulation was monitored by flow cytometry in samples obtained on a daily basis using anti-D. The mother had no detectable anti-D 6 months after delivery. No clearance of fetal cells was apparent after the insufficient dose of IM anti-D. The IV administration of anti-D caused accelerated clearance of D+ fetal RBCs with a t1/2 of 24.5 hours. D+ reticulocytes comprised 4.2 percent of all D+ cells in the maternal circulation at delivery suggesting acute fetal blood loss. The approach used in this report allowed a detailed analysis of the kinetics related to the clearance of fetal D+ RBCs. Simultaneous measurements of fetal reticulocytes and fetal RBCs in maternal blood may establish the timing of an FMH.

Research paper thumbnail of Sports and leisure-time physical activity in pregnancy and birth weight: a population-based study

Scandinavian Journal of Medicine & Science in Sports, 2010

We examined the association between sports and other leisure-time physical activities during preg... more We examined the association between sports and other leisure-time physical activities during pregnancy and birth weight of babies born after 37 completed weeks of gestation. All Danish-speaking pregnant women attending routine antenatal care at the Department of Obstetrics, Aarhus University Hospital, Denmark, from August 1989 to September 1991 were invited to participate in the study. A total of 4458 healthy women who delivered after 37 completed gestational weeks participated in this study. The associations between sports (0, 1-2, 3+ h/week) or leisure-time physical activity (sedentary, light, and moderate to heavy) and birth weight were examined by linear and logistic regression and adjusted for potential confounding factors such as smoking, parity, schooling, pre-pregnancy body mass index and gestational age. The results showed that pregnant women who practiced sports or were moderate to heavy leisure-time physical active during the early second or the early third trimester gave birth to infants with a similar birth weight as inactive women. The proportion of newborns with a low (<2500 g) or a high birth weight (>/=4500 g) was also unchanged. In conclusion, in this large population-based study, we found no association between sports and leisure-time physical activity and low-birth weight, high-birth weight, or average-birth weight.

Research paper thumbnail of Phthalate monoesters in perfusate from a dual placenta perfusion system, the placenta tissue and umbilical cord blood

Reproductive Toxicology, 2007

Fetal exposure to phthalates may be associated with adverse reproductive effects, including crypt... more Fetal exposure to phthalates may be associated with adverse reproductive effects, including cryptorchidism and decreased semen quality. Information about human placental transfer is needed to qualify the hypotheses. A dual recirculating placenta perfusion system to monitor concentrations of eight phthalate monoesters in fetal and maternal perfusates was established. In addition to perfusate background measures of phthalate monoesters, the concentrations in umbilical cord plasma and placenta tissue were measured. Monomethyl phthalate (mMP), monoethyl phthalate (mEP), monobutyl phthalate (mBP), and mono (2-ethyl-hexyl) phthalate (mEHP) were detected in both maternal and fetal perfusate, demonstrating a release of compounds from tissue or blood to perfusates. The distribution of compounds between perfusate, umbilical cord plasma, and tissue was in accordance with the physical-chemical properties of the compounds. Results from the present study of compounds residing in the tissue are essential before studying human transplacental transfer, storage, and metabolism of selected phthalate monoesters.

Research paper thumbnail of Stress and salivary cortisol during pregnancy

Psychoneuroendocrinology, 2005

The purpose of this study was to determine whether exposure to stressful life events was associat... more The purpose of this study was to determine whether exposure to stressful life events was associated with changes in levels of circulating cortisol during pregnancy in a population of 603 pregnant women. The participating pregnant women filled out a questionnaire and collected a morning and evening sample of saliva in early pregnancy (median 14th gestational week) and in late pregnancy (median and 30th gestational week). They were asked to report the number of life events experienced during first and second trimester, respectively, and were asked to rate the intensity of the experienced events. Complications related to the pregnancy such as vaginal bleeding and suspected growth retardation were registered and the women were asked about concerns about their pregnancy. The salivary samples were analyzed for cortisol and the levels were higher in late than in early pregnancy. In late pregnancy women exposed to more than one life event or were concerned about pregnancy complications during second trimester had a higher evening cortisol level, whereas morning values were unaffected. After adjustment for smoking women who experienced more than one very stressful life event had 27% higher evening cortisol concentrations (95% confidence intervals: 1-59%). Women with worries about pregnancy complications had 27% (95% confidence intervals: 2-57%) higher levels. In early pregnancy women reporting stressful life events did not have higher evening cortisol levels, but tended to have a blunted morning HPA response. In conclusion, we found differences in the associations between chronic stress in early and late pregnancy and cortisol levels indicating that the response to chronic stress is dependent on the stage of the pregnancy.

Research paper thumbnail of Reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD negative women

Prenatal Diagnosis, 2005

The objective of this study was to establish a reliable test for prenatal prediction of fetal RhD... more The objective of this study was to establish a reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD negative women. This test is needed for future prenatal Rh prophylaxis. A novel real-time PCR-based assay targeting RHD exon 7 combined with a published assay for RHD exon 10 were used to determine the fetal RHD status in DNA extracted from plasma, sampled from 56 pregnant RhD negative women in 15th-36th week of gestation. Thirty-eight samples were from ongoing pregnancies of Danish women and 21 samples from 18 pregnant women were stored anonymized samples from the International Blood Group Reference Laboratory, Bristol, United Kingdom. Prediction of fetal RhD type was compared with the serological result obtained after birth. The prediction of the fetal RhD type was in 100% concordance with the serological RhD type from the 16th week of gestation. One sample from the 15th week of gestation was inconclusive. The number of copies of fetal RHD DNA was found to increase with gestational age. Low levels of DNA were found to follow the Poisson distribution (p = 1.0000). Our set-up was very reliable for determination of fetal RhD genotype, and thus will be of value in prenatal Rh prophylaxis and in the management of immunized women.

Research paper thumbnail of Gestational Age and Birth Weight in Relation to School Performance of 10-Year-Old Children: A Follow-up Study of Children Born After 32 Completed Weeks

PEDIATRICS, 2006

Children born extremely premature (<28 weeks) or with a ve... more Children born extremely premature (<28 weeks) or with a very low birth weight (<1500 g) have a poorer school performance than children born at term with a normal birth weight. Much less is known about children of higher gestational ages and birth weights. We studied gestational age after 32 completed weeks and birth weight in relation to the child's school performance at the age of 10 years. We performed a follow-up study of 5319 children born between January 1990 and June 1992. We got the information on birth weight and gestational age from birth registration forms; when the children were between 9 and 11 years of age, we gathered information about their school performance (reading, spelling, and arithmetic) from questionnaires completed by the parents and the children's primary school teachers. The association between birth weight and reading, as well as spelling and arithmetic disabilities, showed a graded relationship, with children who weighed <2500 g having the highest risks. Even children who weighed between 3000 and 3499 g had an increased risk of all 3 learning disabilities compared with children who weighed between 3500 and 4000 g. This association persisted after adjustment for potential cofounders and when the analyses were restricted to children born at term (39-40 weeks of gestation), suggesting that the association could not be explained by a low gestational age. Compared with children born at term, reading and spelling difficulties were more often found among children born at gestational age 33 to 36 weeks and 37 to 38 weeks, whereas there was no relation between gestational age and arithmetic difficulties. Gestational age and birth weight were associated with school performance in the 10-year-old child and the association extended into the reference range of both birth weight and gestational age.

Research paper thumbnail of Histamine release from cord blood basophils is influenced by plasma IgE concentration, osmolarity, gestational age at birth and atopic disposition

Pediatric Allergy and Immunology, 1994

To characterize the normal values of histamine release from basophil leucocytes in cord blood aft... more To characterize the normal values of histamine release from basophil leucocytes in cord blood after stimulation with both IgE-mediating and non-IgE-mediating secretagogues, a population of 1,684 newborn infants was studied using a microfiber-based method for detecting histamine release. A wide variation in anti-IgE and Concanavalin A-induced histamine release in the population was found. An increase in osmolarity in the release media selectively enhanced the maximal IgE-mediated histamine release, in addition to an increase in sensitivity in the dose response for anti-IgE and Concanavalin A. Both anti-IgE and Concanavalin A mediated histamine release were found to be significantly associated with the concentration of IgE in cord blood. Furthermore, an increased sensitivity to the IgE-mediated response and a close correlation between anti-IgE and Concanavalin A histamine release were found in the group of newborns with high IgE levels. Gestational age at birth and histamine release after stimulation with both IgE-mediating, and non-IgE mediating secretagogues were found to be significantly related, thus suggesting a continuing maturation of the human basophil leucocytes in the last weeks of gestation. Parental atopic disposition also affected basophil releasability in cord blood.

Research paper thumbnail of Several genetic and environmental factors influence cord blood IgE concentration

Pediatric Allergy and Immunology, 1994

Cord blood samples were collected from a birth cohort of 2631 infants to elucidate the associatio... more Cord blood samples were collected from a birth cohort of 2631 infants to elucidate the association between genetic and environmental factors and fetal production of IgE. The cord blood IgE values were treated both as a continuous and as a dichotomous variable in the statistical analyses. Multivariate analysis was used to control for confounding factors. Infants with single and biparental atopic heritage had higher IgE concentrations in cord plasma than children of parents without atopy. Multiple logistic regression analysis revealed a significant association to maternal allergic eczema or perennial rhinitis. The cord blood IgE concentration varied with month of birth with peaks in late autumn. This seasonal variation was not related to parental atopic disease. Boys had significantly higher levels of IgE and more often elevated IgE values (> or = 0.5 kU/l) than girls. Alcohol and caffeine consumption by the mothers during pregnancy were both significantly associated with elevated IgE concentration. There was also a relation between mothers prepregnant weight and elevated CB-IgE levels. No significant association was observed between maternal smoking and cord plasma IgE levels. The fact that many factors presumably not related to child allergy seem to influence the regulation of fetal IgE production, could explain the questionable value of cord blood IgE in predicting allergy in childhood.

Research paper thumbnail of Time to pregnancy and preterm delivery

Obstetrics & Gynecology, 1997

To test whether subfertile women may be at higher risk of preterm delivery. We used data from two... more To test whether subfertile women may be at higher risk of preterm delivery. We used data from two population-based cohort studies on risk factors and pregnancy outcome for approximately 20,000 deliveries in three major Danish obstetric departments. The Aalborg-Odense study comprised all pregnant women attending routine antenatal care at two obstetric departments from 1984 to 1987. In all, 11,850 women (86%) filled in a questionnaire at about 36 weeks' gestation. The Aarhus study addressed women at the routine visit near 16 weeks' gestation from 1989 to 1991; a study questionnaire was returned by 6857 (80%). Both studies excluded women with chronic illnesses, multiple fetuses, and inability to speak Danish. Only women with planned pregnancies were included in the analysis. In all, 8855 and 3985 women from Aalborg-Odense and Aarhus, respectively, were eligible for the analyses. In both cohorts, women were categorized according to their waiting time to pregnancy (0-6 months, 7-12 months, and greater than 1 year) and according to examination or treatment for infertility (yes, no). Preterm delivery was defined as birth before 37 completed weeks. Compared with women who tried for 6 months or less before they conceived, women who tried for 7-12 months had 1.3 times (95% confidence interval [CI] 0.8, 2.1) the adjusted risk of preterm delivery in both cohorts, and women with a time to pregnancy of greater than 12 months had adjusted relative risks for preterm delivery of 1.6 (95% CI 1.1, 2.2) for Aalborg-Odense and 1.7 (95% CI 1.1, 2.6) for Aarhus. The results remained similar after excluding women with infertility treatment. Pregnant women with subfertility and clinically defined infertility are more prone to preterm delivery, even in the absence of infertility treatment.

Research paper thumbnail of Sports and Leisure Time Physical Activity During Pregnancy in Nulliparous Women

Maternal and Child Health Journal, 2011

Research paper thumbnail of Gestational age and birth weight in relation to n−3 fatty acids among inuit (Canada)

Research paper thumbnail of Transplacental Transfer of Monomethyl Phthalate and Mono(2-ethylhexyl) Phthalate in a Human Placenta Perfusion System

International Journal of Toxicology, 2007

The transplacental passage of monomethylphtalate (mMP) and mono (2-ethylhexyl) phthalate (mEHP) w... more The transplacental passage of monomethylphtalate (mMP) and mono (2-ethylhexyl) phthalate (mEHP) was studied using an ex vivo placental perfusion model with simultaneous perfusion of fetal and maternal circulation in a single cotyledon. Umbilical cord blood and placental tissue collected both before and after perfusion were also analyzed. Placentas were obtained immediately after elective cesarean section and dually perfused in a recirculation system. mMP or mEHP was added to maternal perfusion medium to obtain concentrations at 10 and 25 microg/L, respectively. The placental transfer was followed analyzing samples from fetal and maternal perfusion media by liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS). Four perfusions with mMP indicated a slow transplacental transfer, with a feto-maternal ratio (FM ratio) of 0.30 +/- 0.03 after 150 min of perfusion. Four perfusions with mEHP indicated a very slow or nonexisting placental transfer. mEHP was only detected in fetal perfusion media from two perfusions, giving rise to FM ratios of 0.088 and 0.20 after 150 min of perfusion. Detectable levels of mMP, mEHP, monoethylphthalate (mEP), and monobutylphthalate were found in tissue. Higher tissue levels of mMP after perfusions with mMP compared to perfusions with mEHP suggest an accumulation of mMP during perfusion. No tendency for accumulation of mEHP was observed during perfusions with mEHP compared to perfusions with mMP. Detectable levels of mEHP and mEP were found in umbilical cord plasma samples. mMP and possibly other short-chained phthalate monoesters in maternal blood can cross the placenta by slow transfer, whereas the results indicate no placental transfer of mEHP. Further studies are recommended.

Research paper thumbnail of Periconceptional smoking and the male to female ratio in the offspring--re-assessment of a recently proposed hypothesis

International Journal of Epidemiology, 2003

... Tokyo: Maternal and Child Health Division, Ministry of Health, Labour and Welfare, Japan. 200... more ... Tokyo: Maternal and Child Health Division, Ministry of Health, Labour and Welfare, Japan. 2002, pp. 54–56. ↵ Packer C, Collins DA, Eberly LE. Problems with primate sex ratios. Philos Trans R Soc Lond B Biol Sci 2000;355:1627–35. ...

Research paper thumbnail of The Relation between Psychosocial Job Strain, and Preterm Delivery and Low Birthweight for Gestational Age

International Journal of Epidemiology, 1994

The aim of this cohort study was to evaluate the relationship between psychosocial job demands an... more The aim of this cohort study was to evaluate the relationship between psychosocial job demands and job control during pregnancy and risk of small-for-gestational age (SGA) and preterm delivery. We studied 8711 Danish women with singleton pregnancies between 1989 and 1991. Information about medical and obstetric history, general psychosocial and lifestyle factors and occupational exposures were collected at 16 weeks gestation. The analyses were restricted to 3503 respondents who worked at least 30 hours per week during the first trimester. The women's scores on both the job demand and job control questionnaire were initially dichotomized at the median score, and combined into four exposure categories: relaxed jobs (low demands and high control), active jobs (high demands and high control), passive jobs (low demands and low control), and high-strain jobs (high demands and low control). After adjustment for confounders, women with relaxed jobs had the lowest risk of SGA and preterm delivery. Compared to this group the odds ratio (OR) for SGA delivery among women with passive jobs was 1.3 (95% confidence interval [CI]: 0.9-1.9), with high-strain jobs 1.1 (95% CI: 0.7-1.6), and with active jobs 1.1 (95% CI: 0.8-1.7). Compared to women with relaxed jobs, the OR for preterm delivery among women with passive jobs was 1.4 (95% CI: 0.8-2.3), high-strain jobs 1.3 (95% CI: 0.7-2.2) and active jobs 1.2 (95% CI: 0.7-2.2). All risks were consistently increased in women with low job control. The risks were higher for preterm than for SGA deliveries. However, none of the findings were statistically significant. The influence of work-related psychosocial strain on the risk of SGA and preterm delivery seems to be small in countries with highly developed social support systems and few other work-related hazards.

Research paper thumbnail of Characteristics of antenatal care attenders in a rural population in Tamil Nadu, South India: a community-based cross-sectional study

Health & Social Care in the Community, 2001

The objectives of the study were to identify factors associated with utilisation of antenatal car... more The objectives of the study were to identify factors associated with utilisation of antenatal care facilities in a rural population in South India. A community-based, cross-sectional questionnaire study of 30 randomly selected areas was used. A total of 1254 women (95%) had at least one antenatal care visit. The median number of visits was four. High utilisation of antenatal care facilities was associated with low parity and adverse obstetrical history, short distance to healthcare facilities and literacy. It was concluded that antenatal care coverage was high. Information about the above few aspects can be used to target women who are at risk of getting inadequate antenatal care.

Research paper thumbnail of Prediction of light-for-gestational age at delivery in twin pregnancies: an evaluation of fetal weight deviation and growth discordance measured by ultrasound

European Journal of Obstetrics & Gynecology and Reproductive Biology, 1992

The purpose of this retrospective study was to evaluate and discuss different ultrasound methods ... more The purpose of this retrospective study was to evaluate and discuss different ultrasound methods widely used, among other things, as predictors for light-for-gestational age (LGA) in twin pregnancies. The methods evaluated and compared as predictors for LGA at birth were: (1) Difference between twins in biparietal diameter; (2) difference in abdominal diameter; (3) the percentage difference in estimated fetal weight between twins; and (4) estimation of the weight deviation from the expected weight during pregnancy. The study comprised 66 twin pregnancies, examined by ultrasound scanning less than 15 days before delivery. Using Relative Operating Characteristic curves (ROC curves) estimated fetal weight deviation was the most sensitive and specific of the methods. It is stressed that fetal discordance is not the appropriate predictor of LGA at birth in twin pregnancies.

Research paper thumbnail of Duration of pregnancy in relation to seafood intake during early and mid pregnancy: prospective cohort

European Journal of Epidemiology, 2006

We examined the association between exposure to seafood intake during two periods of pregnancy on... more We examined the association between exposure to seafood intake during two periods of pregnancy on the one hand and risks of preterm delivery and postterm delivery on the other. In a prospective cohort of 8729 pregnant Danish women, we assessed frequency of fish meals during the first and second trimester of pregnancy by questionnaires completed around gestation weeks 16 and 30, respectively. When fish intake was based solely on intake reported for the early period of pregnancy, mean gestation length was shorter by 3.91 (95% CI: 2.24-5.58) days and odds of preterm delivery were increased 2.38 (1.23-4.61) times in those who never consumed fish (n = 308) vs. those who consumed both fish as main meal and fish in sandwiches at least once per week (n = 785). These measures were similar when fish intake was based solely on intake reported for mid-pregnancy. In the subgroup of women reporting same intake in the two trimesters, those who never consumed fish (n = 165) had 8.57 (5.46-11.7) days shorter mean gestation and 19.6 (2.32-165) times increased odds of preterm delivery, compared to high fish consumers (n = 127); odds of elective and postterm delivery were reduced by a factor 0.33 (0.11-1.02) and 0.34 (0.12-0.95), respectively, in zero fish consumers. All analyses were adjusted for potential confounding by factors such as maternal smoking, height, and prepregnant weight. We conclude that never consuming fish in the first two trimesters of pregnancy was an extremely strong risk factor for preterm delivery but was also associated with reduced risks of elective delivery and postterm delivery.

Research paper thumbnail of Do Stressful Life Events Affect Duration of Gestation and Risk of Preterm Delivery?

Epidemiology, 1996

The present study was designed to test the relation between stressful life events experienced dur... more The present study was designed to test the relation between stressful life events experienced during pregnancy and the risk of preterm delivery and shortened duration of pregnancy. We collected data prospectively in a general population sample, including repeated questionnaire measures of exposure to stressful life events during pregnancy. Between August 1989 and September 1991, 8,719 Danish-speaking women with singleton pregnancies attended antenatal care. Of these women, 5,873 (67%) completed all questionnaires. When indicating an event, the woman was asked to rate the amount of stress induced by this event. Measurement of gestational duration was primarily based on early ultrasound scan. When we evaluated life events independently of the individual's appraisal, we found no association with duration of gestation or risk of preterm delivery. In contrast, life events assessed by the subject as highly stressful were associated with shorter mean duration of gestation and increased risk of preterm delivery. This association was observed primarily with events experienced between the 16th and 30th week of gestation. Women who had one or more highly stressful life events had a risk of preterm delivery 1.76 times greater than those without stressful events (95% confidence interval = 1.15-2.71). We found no evidence for a buffering effect of social support.

Research paper thumbnail of Maternal salivary cortisol levels during pregnancy are positively associated with overweight children

Psychoneuroendocrinology, 2015

Research paper thumbnail of Red blood cell antibodies in pregnancy and their clinical consequences: synergistic effects of multiple specificities

Transfusion, 2009

The objective was to determine clinical consequences of various specificities for the infant/fetu... more The objective was to determine clinical consequences of various specificities for the infant/fetus. The population was patients referred between 1998 and 2005 to the tertiary center because of detected red blood cell (RBC) alloimmunization. Altogether 455 infants were delivered by 390 alloimmunized women. This was a retrospective cohort study. Data were obtained from the blood bank register and the obstetric and neonatal database. As indicators of hemolytic activity of the antibodies, the frequency of the therapeutic interventions intrauterine transfusion, exchange transfusion, and simple transfusion was used. Anti-D was the most common antibody (46.6%), followed by anti-K (15.4%). A combination of antibodies was detected in 27%. All three types of therapeutic intervention were significantly more frequent in women with anti-D plus an additional antibody than in women with anti-D as the sole antibody. The anti-D titer closely paralleled the clinical importance of the antibody. One case of anti-s with a titer of 512 required all three types of transfusion. Anti-D was the single most frequent and harmful specificity closely followed by anti-K. Combinations of antibody specificities were more harmful than single specificities, and a potentially synergistic effect should be considered.

Research paper thumbnail of Massive fetomaternal hemorrhage: clearance of fetal red blood cells after intravenous anti-D prophylaxis monitored by flow cytometry

Transfusion, 2008

The clearance of D+ red blood cells (RBCs) from the circulation in D- individuals mediated by pas... more The clearance of D+ red blood cells (RBCs) from the circulation in D- individuals mediated by passively administered anti-D occurs by opsonization with the antibody and subsequent removal in the spleen. Few data exist on the kinetics of clearance of large volumes of D+ RBCs from the maternal circulation by anti-D in clinical cases of massive fetomaternal hemorrhage (FMH). A 33-year-old D- woman delivered a D+ female infant by emergency cesarean section for suspected fetal anemia. A massive FMH, initially estimated to be approximately 142 mL of RBCs, was found. In addition to the standard dose of intramuscular (IM) anti-D (300 microg) given immediately after delivery, 2700 microg of anti-D was administered intravenously (IV). The clearance of D+ fetal cells from the maternal circulation was monitored by flow cytometry in samples obtained on a daily basis using anti-D. The mother had no detectable anti-D 6 months after delivery. No clearance of fetal cells was apparent after the insufficient dose of IM anti-D. The IV administration of anti-D caused accelerated clearance of D+ fetal RBCs with a t1/2 of 24.5 hours. D+ reticulocytes comprised 4.2 percent of all D+ cells in the maternal circulation at delivery suggesting acute fetal blood loss. The approach used in this report allowed a detailed analysis of the kinetics related to the clearance of fetal D+ RBCs. Simultaneous measurements of fetal reticulocytes and fetal RBCs in maternal blood may establish the timing of an FMH.

Research paper thumbnail of Sports and leisure-time physical activity in pregnancy and birth weight: a population-based study

Scandinavian Journal of Medicine & Science in Sports, 2010

We examined the association between sports and other leisure-time physical activities during preg... more We examined the association between sports and other leisure-time physical activities during pregnancy and birth weight of babies born after 37 completed weeks of gestation. All Danish-speaking pregnant women attending routine antenatal care at the Department of Obstetrics, Aarhus University Hospital, Denmark, from August 1989 to September 1991 were invited to participate in the study. A total of 4458 healthy women who delivered after 37 completed gestational weeks participated in this study. The associations between sports (0, 1-2, 3+ h/week) or leisure-time physical activity (sedentary, light, and moderate to heavy) and birth weight were examined by linear and logistic regression and adjusted for potential confounding factors such as smoking, parity, schooling, pre-pregnancy body mass index and gestational age. The results showed that pregnant women who practiced sports or were moderate to heavy leisure-time physical active during the early second or the early third trimester gave birth to infants with a similar birth weight as inactive women. The proportion of newborns with a low (<2500 g) or a high birth weight (>/=4500 g) was also unchanged. In conclusion, in this large population-based study, we found no association between sports and leisure-time physical activity and low-birth weight, high-birth weight, or average-birth weight.

Research paper thumbnail of Phthalate monoesters in perfusate from a dual placenta perfusion system, the placenta tissue and umbilical cord blood

Reproductive Toxicology, 2007

Fetal exposure to phthalates may be associated with adverse reproductive effects, including crypt... more Fetal exposure to phthalates may be associated with adverse reproductive effects, including cryptorchidism and decreased semen quality. Information about human placental transfer is needed to qualify the hypotheses. A dual recirculating placenta perfusion system to monitor concentrations of eight phthalate monoesters in fetal and maternal perfusates was established. In addition to perfusate background measures of phthalate monoesters, the concentrations in umbilical cord plasma and placenta tissue were measured. Monomethyl phthalate (mMP), monoethyl phthalate (mEP), monobutyl phthalate (mBP), and mono (2-ethyl-hexyl) phthalate (mEHP) were detected in both maternal and fetal perfusate, demonstrating a release of compounds from tissue or blood to perfusates. The distribution of compounds between perfusate, umbilical cord plasma, and tissue was in accordance with the physical-chemical properties of the compounds. Results from the present study of compounds residing in the tissue are essential before studying human transplacental transfer, storage, and metabolism of selected phthalate monoesters.

Research paper thumbnail of Stress and salivary cortisol during pregnancy

Psychoneuroendocrinology, 2005

The purpose of this study was to determine whether exposure to stressful life events was associat... more The purpose of this study was to determine whether exposure to stressful life events was associated with changes in levels of circulating cortisol during pregnancy in a population of 603 pregnant women. The participating pregnant women filled out a questionnaire and collected a morning and evening sample of saliva in early pregnancy (median 14th gestational week) and in late pregnancy (median and 30th gestational week). They were asked to report the number of life events experienced during first and second trimester, respectively, and were asked to rate the intensity of the experienced events. Complications related to the pregnancy such as vaginal bleeding and suspected growth retardation were registered and the women were asked about concerns about their pregnancy. The salivary samples were analyzed for cortisol and the levels were higher in late than in early pregnancy. In late pregnancy women exposed to more than one life event or were concerned about pregnancy complications during second trimester had a higher evening cortisol level, whereas morning values were unaffected. After adjustment for smoking women who experienced more than one very stressful life event had 27% higher evening cortisol concentrations (95% confidence intervals: 1-59%). Women with worries about pregnancy complications had 27% (95% confidence intervals: 2-57%) higher levels. In early pregnancy women reporting stressful life events did not have higher evening cortisol levels, but tended to have a blunted morning HPA response. In conclusion, we found differences in the associations between chronic stress in early and late pregnancy and cortisol levels indicating that the response to chronic stress is dependent on the stage of the pregnancy.

Research paper thumbnail of Reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD negative women

Prenatal Diagnosis, 2005

The objective of this study was to establish a reliable test for prenatal prediction of fetal RhD... more The objective of this study was to establish a reliable test for prenatal prediction of fetal RhD type using maternal plasma from RhD negative women. This test is needed for future prenatal Rh prophylaxis. A novel real-time PCR-based assay targeting RHD exon 7 combined with a published assay for RHD exon 10 were used to determine the fetal RHD status in DNA extracted from plasma, sampled from 56 pregnant RhD negative women in 15th-36th week of gestation. Thirty-eight samples were from ongoing pregnancies of Danish women and 21 samples from 18 pregnant women were stored anonymized samples from the International Blood Group Reference Laboratory, Bristol, United Kingdom. Prediction of fetal RhD type was compared with the serological result obtained after birth. The prediction of the fetal RhD type was in 100% concordance with the serological RhD type from the 16th week of gestation. One sample from the 15th week of gestation was inconclusive. The number of copies of fetal RHD DNA was found to increase with gestational age. Low levels of DNA were found to follow the Poisson distribution (p = 1.0000). Our set-up was very reliable for determination of fetal RhD genotype, and thus will be of value in prenatal Rh prophylaxis and in the management of immunized women.

Research paper thumbnail of Gestational Age and Birth Weight in Relation to School Performance of 10-Year-Old Children: A Follow-up Study of Children Born After 32 Completed Weeks

PEDIATRICS, 2006

Children born extremely premature (<28 weeks) or with a ve... more Children born extremely premature (<28 weeks) or with a very low birth weight (<1500 g) have a poorer school performance than children born at term with a normal birth weight. Much less is known about children of higher gestational ages and birth weights. We studied gestational age after 32 completed weeks and birth weight in relation to the child's school performance at the age of 10 years. We performed a follow-up study of 5319 children born between January 1990 and June 1992. We got the information on birth weight and gestational age from birth registration forms; when the children were between 9 and 11 years of age, we gathered information about their school performance (reading, spelling, and arithmetic) from questionnaires completed by the parents and the children's primary school teachers. The association between birth weight and reading, as well as spelling and arithmetic disabilities, showed a graded relationship, with children who weighed <2500 g having the highest risks. Even children who weighed between 3000 and 3499 g had an increased risk of all 3 learning disabilities compared with children who weighed between 3500 and 4000 g. This association persisted after adjustment for potential cofounders and when the analyses were restricted to children born at term (39-40 weeks of gestation), suggesting that the association could not be explained by a low gestational age. Compared with children born at term, reading and spelling difficulties were more often found among children born at gestational age 33 to 36 weeks and 37 to 38 weeks, whereas there was no relation between gestational age and arithmetic difficulties. Gestational age and birth weight were associated with school performance in the 10-year-old child and the association extended into the reference range of both birth weight and gestational age.

Research paper thumbnail of Histamine release from cord blood basophils is influenced by plasma IgE concentration, osmolarity, gestational age at birth and atopic disposition

Pediatric Allergy and Immunology, 1994

To characterize the normal values of histamine release from basophil leucocytes in cord blood aft... more To characterize the normal values of histamine release from basophil leucocytes in cord blood after stimulation with both IgE-mediating and non-IgE-mediating secretagogues, a population of 1,684 newborn infants was studied using a microfiber-based method for detecting histamine release. A wide variation in anti-IgE and Concanavalin A-induced histamine release in the population was found. An increase in osmolarity in the release media selectively enhanced the maximal IgE-mediated histamine release, in addition to an increase in sensitivity in the dose response for anti-IgE and Concanavalin A. Both anti-IgE and Concanavalin A mediated histamine release were found to be significantly associated with the concentration of IgE in cord blood. Furthermore, an increased sensitivity to the IgE-mediated response and a close correlation between anti-IgE and Concanavalin A histamine release were found in the group of newborns with high IgE levels. Gestational age at birth and histamine release after stimulation with both IgE-mediating, and non-IgE mediating secretagogues were found to be significantly related, thus suggesting a continuing maturation of the human basophil leucocytes in the last weeks of gestation. Parental atopic disposition also affected basophil releasability in cord blood.

Research paper thumbnail of Several genetic and environmental factors influence cord blood IgE concentration

Pediatric Allergy and Immunology, 1994

Cord blood samples were collected from a birth cohort of 2631 infants to elucidate the associatio... more Cord blood samples were collected from a birth cohort of 2631 infants to elucidate the association between genetic and environmental factors and fetal production of IgE. The cord blood IgE values were treated both as a continuous and as a dichotomous variable in the statistical analyses. Multivariate analysis was used to control for confounding factors. Infants with single and biparental atopic heritage had higher IgE concentrations in cord plasma than children of parents without atopy. Multiple logistic regression analysis revealed a significant association to maternal allergic eczema or perennial rhinitis. The cord blood IgE concentration varied with month of birth with peaks in late autumn. This seasonal variation was not related to parental atopic disease. Boys had significantly higher levels of IgE and more often elevated IgE values (> or = 0.5 kU/l) than girls. Alcohol and caffeine consumption by the mothers during pregnancy were both significantly associated with elevated IgE concentration. There was also a relation between mothers prepregnant weight and elevated CB-IgE levels. No significant association was observed between maternal smoking and cord plasma IgE levels. The fact that many factors presumably not related to child allergy seem to influence the regulation of fetal IgE production, could explain the questionable value of cord blood IgE in predicting allergy in childhood.

Research paper thumbnail of Time to pregnancy and preterm delivery

Obstetrics & Gynecology, 1997

To test whether subfertile women may be at higher risk of preterm delivery. We used data from two... more To test whether subfertile women may be at higher risk of preterm delivery. We used data from two population-based cohort studies on risk factors and pregnancy outcome for approximately 20,000 deliveries in three major Danish obstetric departments. The Aalborg-Odense study comprised all pregnant women attending routine antenatal care at two obstetric departments from 1984 to 1987. In all, 11,850 women (86%) filled in a questionnaire at about 36 weeks' gestation. The Aarhus study addressed women at the routine visit near 16 weeks' gestation from 1989 to 1991; a study questionnaire was returned by 6857 (80%). Both studies excluded women with chronic illnesses, multiple fetuses, and inability to speak Danish. Only women with planned pregnancies were included in the analysis. In all, 8855 and 3985 women from Aalborg-Odense and Aarhus, respectively, were eligible for the analyses. In both cohorts, women were categorized according to their waiting time to pregnancy (0-6 months, 7-12 months, and greater than 1 year) and according to examination or treatment for infertility (yes, no). Preterm delivery was defined as birth before 37 completed weeks. Compared with women who tried for 6 months or less before they conceived, women who tried for 7-12 months had 1.3 times (95% confidence interval [CI] 0.8, 2.1) the adjusted risk of preterm delivery in both cohorts, and women with a time to pregnancy of greater than 12 months had adjusted relative risks for preterm delivery of 1.6 (95% CI 1.1, 2.2) for Aalborg-Odense and 1.7 (95% CI 1.1, 2.6) for Aarhus. The results remained similar after excluding women with infertility treatment. Pregnant women with subfertility and clinically defined infertility are more prone to preterm delivery, even in the absence of infertility treatment.

Research paper thumbnail of Sports and Leisure Time Physical Activity During Pregnancy in Nulliparous Women

Maternal and Child Health Journal, 2011

Research paper thumbnail of Gestational age and birth weight in relation to n−3 fatty acids among inuit (Canada)

Research paper thumbnail of Transplacental Transfer of Monomethyl Phthalate and Mono(2-ethylhexyl) Phthalate in a Human Placenta Perfusion System

International Journal of Toxicology, 2007

The transplacental passage of monomethylphtalate (mMP) and mono (2-ethylhexyl) phthalate (mEHP) w... more The transplacental passage of monomethylphtalate (mMP) and mono (2-ethylhexyl) phthalate (mEHP) was studied using an ex vivo placental perfusion model with simultaneous perfusion of fetal and maternal circulation in a single cotyledon. Umbilical cord blood and placental tissue collected both before and after perfusion were also analyzed. Placentas were obtained immediately after elective cesarean section and dually perfused in a recirculation system. mMP or mEHP was added to maternal perfusion medium to obtain concentrations at 10 and 25 microg/L, respectively. The placental transfer was followed analyzing samples from fetal and maternal perfusion media by liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS). Four perfusions with mMP indicated a slow transplacental transfer, with a feto-maternal ratio (FM ratio) of 0.30 +/- 0.03 after 150 min of perfusion. Four perfusions with mEHP indicated a very slow or nonexisting placental transfer. mEHP was only detected in fetal perfusion media from two perfusions, giving rise to FM ratios of 0.088 and 0.20 after 150 min of perfusion. Detectable levels of mMP, mEHP, monoethylphthalate (mEP), and monobutylphthalate were found in tissue. Higher tissue levels of mMP after perfusions with mMP compared to perfusions with mEHP suggest an accumulation of mMP during perfusion. No tendency for accumulation of mEHP was observed during perfusions with mEHP compared to perfusions with mMP. Detectable levels of mEHP and mEP were found in umbilical cord plasma samples. mMP and possibly other short-chained phthalate monoesters in maternal blood can cross the placenta by slow transfer, whereas the results indicate no placental transfer of mEHP. Further studies are recommended.

Research paper thumbnail of Periconceptional smoking and the male to female ratio in the offspring--re-assessment of a recently proposed hypothesis

International Journal of Epidemiology, 2003

... Tokyo: Maternal and Child Health Division, Ministry of Health, Labour and Welfare, Japan. 200... more ... Tokyo: Maternal and Child Health Division, Ministry of Health, Labour and Welfare, Japan. 2002, pp. 54–56. ↵ Packer C, Collins DA, Eberly LE. Problems with primate sex ratios. Philos Trans R Soc Lond B Biol Sci 2000;355:1627–35. ...

Research paper thumbnail of The Relation between Psychosocial Job Strain, and Preterm Delivery and Low Birthweight for Gestational Age

International Journal of Epidemiology, 1994

The aim of this cohort study was to evaluate the relationship between psychosocial job demands an... more The aim of this cohort study was to evaluate the relationship between psychosocial job demands and job control during pregnancy and risk of small-for-gestational age (SGA) and preterm delivery. We studied 8711 Danish women with singleton pregnancies between 1989 and 1991. Information about medical and obstetric history, general psychosocial and lifestyle factors and occupational exposures were collected at 16 weeks gestation. The analyses were restricted to 3503 respondents who worked at least 30 hours per week during the first trimester. The women's scores on both the job demand and job control questionnaire were initially dichotomized at the median score, and combined into four exposure categories: relaxed jobs (low demands and high control), active jobs (high demands and high control), passive jobs (low demands and low control), and high-strain jobs (high demands and low control). After adjustment for confounders, women with relaxed jobs had the lowest risk of SGA and preterm delivery. Compared to this group the odds ratio (OR) for SGA delivery among women with passive jobs was 1.3 (95% confidence interval [CI]: 0.9-1.9), with high-strain jobs 1.1 (95% CI: 0.7-1.6), and with active jobs 1.1 (95% CI: 0.8-1.7). Compared to women with relaxed jobs, the OR for preterm delivery among women with passive jobs was 1.4 (95% CI: 0.8-2.3), high-strain jobs 1.3 (95% CI: 0.7-2.2) and active jobs 1.2 (95% CI: 0.7-2.2). All risks were consistently increased in women with low job control. The risks were higher for preterm than for SGA deliveries. However, none of the findings were statistically significant. The influence of work-related psychosocial strain on the risk of SGA and preterm delivery seems to be small in countries with highly developed social support systems and few other work-related hazards.

Research paper thumbnail of Characteristics of antenatal care attenders in a rural population in Tamil Nadu, South India: a community-based cross-sectional study

Health & Social Care in the Community, 2001

The objectives of the study were to identify factors associated with utilisation of antenatal car... more The objectives of the study were to identify factors associated with utilisation of antenatal care facilities in a rural population in South India. A community-based, cross-sectional questionnaire study of 30 randomly selected areas was used. A total of 1254 women (95%) had at least one antenatal care visit. The median number of visits was four. High utilisation of antenatal care facilities was associated with low parity and adverse obstetrical history, short distance to healthcare facilities and literacy. It was concluded that antenatal care coverage was high. Information about the above few aspects can be used to target women who are at risk of getting inadequate antenatal care.

Research paper thumbnail of Prediction of light-for-gestational age at delivery in twin pregnancies: an evaluation of fetal weight deviation and growth discordance measured by ultrasound

European Journal of Obstetrics & Gynecology and Reproductive Biology, 1992

The purpose of this retrospective study was to evaluate and discuss different ultrasound methods ... more The purpose of this retrospective study was to evaluate and discuss different ultrasound methods widely used, among other things, as predictors for light-for-gestational age (LGA) in twin pregnancies. The methods evaluated and compared as predictors for LGA at birth were: (1) Difference between twins in biparietal diameter; (2) difference in abdominal diameter; (3) the percentage difference in estimated fetal weight between twins; and (4) estimation of the weight deviation from the expected weight during pregnancy. The study comprised 66 twin pregnancies, examined by ultrasound scanning less than 15 days before delivery. Using Relative Operating Characteristic curves (ROC curves) estimated fetal weight deviation was the most sensitive and specific of the methods. It is stressed that fetal discordance is not the appropriate predictor of LGA at birth in twin pregnancies.

Research paper thumbnail of Duration of pregnancy in relation to seafood intake during early and mid pregnancy: prospective cohort

European Journal of Epidemiology, 2006

We examined the association between exposure to seafood intake during two periods of pregnancy on... more We examined the association between exposure to seafood intake during two periods of pregnancy on the one hand and risks of preterm delivery and postterm delivery on the other. In a prospective cohort of 8729 pregnant Danish women, we assessed frequency of fish meals during the first and second trimester of pregnancy by questionnaires completed around gestation weeks 16 and 30, respectively. When fish intake was based solely on intake reported for the early period of pregnancy, mean gestation length was shorter by 3.91 (95% CI: 2.24-5.58) days and odds of preterm delivery were increased 2.38 (1.23-4.61) times in those who never consumed fish (n = 308) vs. those who consumed both fish as main meal and fish in sandwiches at least once per week (n = 785). These measures were similar when fish intake was based solely on intake reported for mid-pregnancy. In the subgroup of women reporting same intake in the two trimesters, those who never consumed fish (n = 165) had 8.57 (5.46-11.7) days shorter mean gestation and 19.6 (2.32-165) times increased odds of preterm delivery, compared to high fish consumers (n = 127); odds of elective and postterm delivery were reduced by a factor 0.33 (0.11-1.02) and 0.34 (0.12-0.95), respectively, in zero fish consumers. All analyses were adjusted for potential confounding by factors such as maternal smoking, height, and prepregnant weight. We conclude that never consuming fish in the first two trimesters of pregnancy was an extremely strong risk factor for preterm delivery but was also associated with reduced risks of elective delivery and postterm delivery.

Research paper thumbnail of Do Stressful Life Events Affect Duration of Gestation and Risk of Preterm Delivery?

Epidemiology, 1996

The present study was designed to test the relation between stressful life events experienced dur... more The present study was designed to test the relation between stressful life events experienced during pregnancy and the risk of preterm delivery and shortened duration of pregnancy. We collected data prospectively in a general population sample, including repeated questionnaire measures of exposure to stressful life events during pregnancy. Between August 1989 and September 1991, 8,719 Danish-speaking women with singleton pregnancies attended antenatal care. Of these women, 5,873 (67%) completed all questionnaires. When indicating an event, the woman was asked to rate the amount of stress induced by this event. Measurement of gestational duration was primarily based on early ultrasound scan. When we evaluated life events independently of the individual's appraisal, we found no association with duration of gestation or risk of preterm delivery. In contrast, life events assessed by the subject as highly stressful were associated with shorter mean duration of gestation and increased risk of preterm delivery. This association was observed primarily with events experienced between the 16th and 30th week of gestation. Women who had one or more highly stressful life events had a risk of preterm delivery 1.76 times greater than those without stressful events (95% confidence interval = 1.15-2.71). We found no evidence for a buffering effect of social support.