-
Charlotte Kvist Ekelund,
Hans Jakob Andersen,
Jeanette Christensen,
Vibeke Ersbak,
Richard Farlie,
Carsten Henriques,
Anni Holmskov,
Lisa Neerup Jensen,
Finn Stener Jørgensen,
Anette Hessellund, [......],
Hedvig Poulsen,
Jan Ramb,
Lillian Skibsted,
Peter Skovbo,
Steffen Sommer,
Lene Sperling,
Karin Sundberg,
Susanne Vemmelund Juul,
Helle Zingenberg, Ann Tabor
[show abstract]
[hide abstract]
ABSTRACT: 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.
Ugeskrift for laeger 06/2010; 172(23):1759-61.
-
[show abstract]
[hide abstract]
ABSTRACT: Introduction: As a consequence of the introduction of effective screening methods, the number of invasive prenatal diagnostic procedures is steadily declining. The aim of this review is to summarize the risks related to these procedures. Material and Methods: Review of the literature. Results: Data from randomised controlled trials as well as from systematic reviews and a large national registry study are consistent with a procedure-related miscarriage rate of 0.5-1.0% for amniocentesis as well as for chorionic villus sampling (CVS). In single-center studies performance may be remarkably good due to very skilled operators, but these figures cannot be used for general counselling. Amniocentesis performed prior to 15 weeks had a significantly higher miscarriage rate than CVS and mid-trimester amniocentesis, and also increased the risk of talipes equinovarus. Amniocentesis should therefore not be performed before 15 + 0 weeks' gestation. CVS on the other hand should not be performed before 10 weeks' gestation due to a possible increase in risk of limb reduction defects. Discussion: Experienced operators have a higher success rate and a lower complication rate. The decreasing number of prenatal invasive procedures calls for quality assurance and monitoring of operators' performance.
Fetal Diagnosis and Therapy 01/2010; 27(1):1-7. · 1.05 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the association between cone depth of the loop electrosurgical excision procedure (LEEP) of the cervix and subsequent risk of spontaneous preterm delivery.
The study included all deliveries in Denmark over a 9-year period, 1997-2005, with information obtained from various public health registries. Of the 552,678 singleton deliveries included in the study, 19,049 were preterm and 8,180 were subsequent to LEEP. Of the 8,180 deliveries with prior LEEP, 273 were subsequent to two or more LEEPs. Of the deliveries subsequent to only one LEEP, we extracted information about cone depth on 3,605 deliveries, of which 223 were preterm (6.2%). Logistic regression analyses were used to evaluate association between cone characteristics and the subsequent risk of preterm delivery, with simultaneous adjustment for potential confounders.
Increasing cone depth was associated with a significant increase in the risk of preterm delivery, with an estimated 6% increase in risk per each additional millimeter of tissue excised (odds ratio 1.06, 95% confidence interval 1.03-1.09). Severity of the cone histology and time since LEEP were not associated with the risk of preterm delivery. Having had two or more LEEPs increased the risk almost fourfold for subsequent preterm delivery when compared with no LEEP before delivery, and almost doubled the risk when compared with one LEEP before delivery.
Increasing cone depth of LEEP is directly associated with an increasing risk of preterm delivery, even after adjustment for several confounding factors.
II.
Obstetrics and Gynecology 12/2009; 114(6):1232-8. · 4.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Prophylaxis with low-dose aspirin may reduce the risk of pre-eclampsia (PE) if introduced in first trimester. The performance of first trimester maternal serum screening for PE using free leptin index (fLI) and PAPP-A, where fLI = leptin/leptin soluble receptor was studied.
First trimester serum samples from 126 PE pregnancies and 289 control pregnancies were studied. fLI and PAPP-A were converted into gestational age and maternal weight independent log MoM values of PAPP-A and fLI. The screening performance of markers was studied by receiver-operator-characteristics curves. The performance of population screening was estimated by Monte Carlo simulation.
fLI was significantly (p < 0.001) elevated [mean log MoM 0.2165 (SD: 0.2604)] compared to controls [mean log MoM -0.0368 (SD: 0.3132)] and PAPP-A was significantly (p < 0.001) reduced [mean log MoM -0.0133 (SD: 0.2661)] compared to controls [mean log MoM 0.0474 (SD: 0.2521)] in PE pregnancies. There was no correlation between fLI and PAPP-A in control or PE pregnancies. Combined fLI and PAPP-A screening for PE had estimated population detection rates of 22% and 35% for false positives rates of 6% and 12%, respectively.
Combining PAPP-A and fLI improves screening performance for PE compared to single marker screening.
Prenatal Diagnosis 12/2009; 30(2):103-9. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the association between three cervical procedures (biopsy with no treatment, ablation, and loop electrosurgical excision procedure [LEEP]) and subsequent spontaneous preterm delivery in twin pregnancies using population-based data from various nationwide registries.
: The study population consisted of all twin deliveries in Denmark during a 9-year period, 1997-2005. Information on the deliveries, including cervical procedures, was obtained from various national registries. In all, 9,868 deliveries were eligible for analyses, of which 3,228 were delivered spontaneously preterm (32.7%). Preterm delivery was defined as gestational age between 21 weeks and 37 weeks. Logistic regression analyses were used to evaluate the association between cervical procedures and preterm delivery.
Twin pregnancies subsequent to LEEP had a significantly increased risk of overall subsequent spontaneous preterm delivery (43.4%) with an adjusted odds ratio of 1.58 (95% confidence interval 1.16-2.14) compared with pregnancies with no prior LEEP (32.5%). The association was consistent in various secondary analyses and especially strong for the very preterm and extremely preterm groups. We found no increase in risk of preterm delivery subsequent to biopsy without treatment or ablation.
Our study showed an overall significant increase in risk of preterm delivery in twin pregnancies subsequent to LEEP treatment, even after adjustment for several potential risk factors.
II.
Obstetrics and Gynecology 10/2009; 114(3):511-5. · 4.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to investigate the regulation of anti-Müllerian hormone (AMH) blood concentrations in mother and fetus during pregnancy. Serum concentrations of AMH, gonadotrophins, oestradiol and progesterone were measured in pregnant women in the first trimester and AMH concentrations in second-trimester fetuses, and these were compared in relation to the sex of the fetus. A total of 153 women undergoing elective termination of a first-trimester pregnancy and seven second-trimester pregnant women undergoing cordocentesis were included. Concentrations of AMH in the serum of first-trimester pregnant women were similar to non-pregnant women and were unrelated to the very high concentrations of human chorionic gonadotrophin and the undetectable concentrations of FSH and LH. Serum concentrations of oestradiol and progesterone were unrelated to the concentrations of AMH and the sex of the fetus. Serum concentrations of AMH of four, second trimester, male fetuses ranged from 64 to 92 ng/ml, whereas it was undetectable in female fetuses. It appears that AMH serum concentrations in first-trimester pregnant women seem to be independent of gonadotrophin concentrations and fetal sex. The concentration of AMH in the circulation of male fetuses is higher than previously reported and is a highly sensitive marker for fetal sex.
Reproductive biomedicine online 06/2009; 18(5):694-9. · 2.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Our aim was to assess the association between loop electrosurgical excision procedure (LEEP) and the subsequent risk for spontaneous preterm delivery, with the use of population-based data from various nationwide registries.
The study population consisted of all singleton deliveries in Denmark during a 9-year period, 1997-2005. Information on the deliveries that included different cervical procedures was obtained from various national registries. In all, 552,678 deliveries were eligible for analyses.
Of the deliveries in which the mother had no previous LEEP, 18,519 deliveries (3.5%) were preterm; when this data were applied to 530 preterm deliveries (6.9%) that were subsequent to LEEP, the yield was a significantly increased risk of preterm delivery, with an odds ratio of 2.07 (95% CI, 1.88-2.27; LEEP vs no LEEP).
Our study showed an overall 2-fold increase in the risk of spontaneous preterm delivery in singleton deliveries subsequent to LEEP treatment, even after adjustment for various potential risk factors.
American journal of obstetrics and gynecology 05/2009; 201(1):33.e1-6. · 3.28 Impact Factor
-
Prenatal Diagnosis 04/2009; 29(6):628-9. · 2.11 Impact Factor
-
Prenatal Diagnosis 04/2009; 29(5):525-7. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The Danish National Board of Health recommended in 2004 routine ultrasound scanning in week 12 with nuchal translucency measurement, combined with the double test to all pregnant women. Those who were found to have a risk of trisomy 21 higher than 1:300 were offered amniocentesis or chorionic villus sampling (CVS). The total number of pregnancies in Denmark with an invasive prenatal procedure decreased from 6,929 in 1996 to 3,103 in 2006, the percentage of CVS increased from 45 to 69%, and the percentage of women below 35 years among those undergoing invasive procedures increased from 38 to 52%. The mean gestational age at which the procedures were done increased--for CVS from week 11 to 13, and for amniocentesis from week 16 to 17. We thus achieved to more than double the offer of prenatal screening and at the same time reduce the number of invasive procedures by 55%.
Acta Obstetricia Et Gynecologica Scandinavica 02/2009; 88(3):362-5. · 1.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A Cochrane review in 2006 concluded that further knowledge is required before recommendation can be made with regard to progesterone in the prevention of preterm birth.
To provide an update on the preventive effect of progesterone on preterm birth in singleton pregnancies.
A search in the PubMed, Embase, and Cochrane database was performed using the keywords: pregnancy, progesterone, preterm birth/preterm delivery, preterm labor, controlled trial, and randomized controlled trial.
Studies on singleton pregnancies.
A meta-analysis was performed on randomized trials including singleton pregnancies with previous preterm birth.
Two new randomized controlled trials of women with previous preterm birth were added to the four analyzed in the Cochrane review, and the meta-analysis of all six studies now showed that progesterone supplementation was associated with a significant reduction of delivery before 32 weeks and of perinatal mortality. Furthermore, a third trial showed a positive effect on women with a short cervix at 23 weeks, and a fourth study showed that progesterone reduces the risk of preterm delivery in women with preterm labor.
In women with a singleton pregnancy and previous preterm delivery, progesterone reduces the rates of preterm delivery before 32 weeks, perinatal death, as well as respiratory distress syndrome and necrotizing enterocolitis in the newborn. Women with a short cervix or preterm labor may also benefit from progesterone, but further evidence is needed to support such a recommendation. Follow-up studies should focus on possible metabolic complications in the mother or the offspring.
Acta Obstetricia Et Gynecologica Scandinavica 01/2009; 88(11):1180-9. · 1.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the association between fetal size and growth between the first and second trimesters and subsequent adverse pregnancy outcome.
A cohort was created of 7,642 singleton pregnancies cared for in three obstetric units associated with Copenhagen University. Data were obtained from ultrasound measurements at 11-14 weeks (crown-rump length, biparietal diameter) and 17-21 weeks (biparietal diameter). Fetal size was assessed by gestation-specific z scores, and fetal growth between the first and second trimester was calculated individually using conditional centiles. The main outcome measures were preterm delivery, smallness for gestational age, and perinatal death.
Slow growth of the biparietal diameter less than the 10th and less than the 2.5th conditional centiles between first and second trimesters occurred in 10.4% and 3.6% of the population, respectively. Biparietal diameter growth less than the 10th centile was associated with perinatal death before 34 weeks (risk 0.5% compared with 0.04%, odds ratio [OR] 16.0, confidence interval [CI] 2.9-88.7). Biparietal diameter growth less than the 2.5th centile was the best predictor of perinatal death at any gestation, with a positive likelihood ratio of 4.7 and an OR of 7.3 (CI 2.4-22.2). In contrast, the biparietal diameter, dated by crown-rump length, did not have an increased risk of perinatal death; however, there was a mildly increased risk of small for gestational age birth weight (less than the 10th customized centile) if the biparietal diameter was below the 10th centile in the first trimester (risk 17% compared with 12%, OR 1.5, CI 1.2-1.8) or in the second trimester (risk 15.8% compared with 12.4%, OR 1.3, CI 1.1-1.5).
Slow growth of the fetal biparietal diameter between the first and second trimesters of pregnancy is a strong predictor of perinatal death before 34 weeks.
Obstetrics and Gynecology 11/2008; 112(4):765-71. · 4.73 Impact Factor
-
Mads Vilhelm Hollegaard,
Jakob Grove,
Poul Thorsen,
Xiaobin Wang,
Susanne Mandrup,
Michael Christiansen,
Bent Norgaard-Pedersen,
Karen R Wojdemann, Ann Tabor,
Jorn Attermann,
David Michael Hougaard
[show abstract]
[hide abstract]
ABSTRACT: To investigate the relation between 19 selected single nucleotide polymorphisms in three cytokine genes, tumor necrosis factor alpha (TNFA), interleukin 1-beta (IL1B) and interleukin 6 (IL6) and preterm birth (<37 weeks' gestation).
Case-control association study.
A total of 117 singleton pregnant Danish Caucasian women, including 62 preterm birth cases and 55 controls (birth>or=37 weeks).
Genotyping was performed using TaqMan probes and traditional sequencing. Descriptive statistics were carried out with Fisher's exact test and Wilcoxon rank-sum test. All genetic data were tested for Hardy-Weinberg equilibrium and analyzed using logistic regression, 2x2 proportions or chi(2). Haplotypes were estimated for each gene and permutation used for association testing.
Women carrying the TNFA -857 C>T rare allele (T) and those homozygous for the IL1B -31 T>C and IL1B -511 C>T rare alleles (C and T) have an increased risk of preterm birth with OR 3.1 (95% CI: 1.0-10.3) and OR 6.4 (95% CI: 1.3-60.5), respectively. Two estimated TNFA haplotypes were associated with preterm birth with OR 3.1 (p=0.037) and OR 2.7 (p=0.045).
Polymorphisms in the cytokine genes TNFA and IL1B may increase the risk of preterm birth, possibly by a dysregulation of the immune system in pregnancy.
Acta Obstetricia Et Gynecologica Scandinavica 10/2008; 87(12):1285-90. · 1.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the impact of a screening strategy in the first trimester, introduced in Denmark during 2004-6, on the number of infants born with Down's syndrome and the number of chorionic villus samplings and amniocenteses, and to determine detection and false positive rates in the screened population in 2005 and 2006.
Population based cohort study.
19 Danish departments of gynaecology and obstetrics and a central cytogenetic registry 2000-7.
65 000 pregnancies per year.
The primary outcomes measured were number of fetuses and newborn infants with Down's syndrome diagnosed prenatally and postnatally and number of chorionic villus samplings and amniocenteses carried out. Secondary outcomes measured were number of women screened in 2005 and 2006, screen positive rate, and information on screening in 2005 and 2006 for infants with a postnatal diagnosis of Down's syndrome.
The number of infants born with Down's syndrome decreased from 55-65 per year during 2000-4 to 31 in 2005 and 32 in 2006. The total number of chorionic villus samplings and amniocenteses carried out decreased from 7524 in 2000 to 3510 in 2006. The detection rate in the screened population in 2005 was 86% (95% confidence interval 79% to 92%) and in 2006 was 93% (87% to 97%). The corresponding false positive rates were 3.9% (3.7% to 4.1%) and 3.3% (3.1% to 3.4%).
The introduction of a combined risk assessment during the first trimester at a national level in Denmark halved the number of infants born with Down's syndrome. The strategy also resulted in a sharp decline in the number of chorionic villus samplings and amniocenteses carried out, even before full implementation of the policy.
BMJ (Clinical research ed.). 02/2008; 337:a2547.
-
[show abstract]
[hide abstract]
ABSTRACT: In a population-based sample, the authors examined the validity of preeclampsia and related diagnoses recorded in a mandatory Danish national hospital discharge registry and in a standardized telephone interview of women who gave birth between 1998 and 2002. Using a "gold standard" for preeclampsia defined in accordance with the guidelines from the American College of Obstetricians and Gynecologists, the authors reviewed hospital charts of 3,039 women and found that 61 of 88 preeclampsia cases (69.3%) and 24 of 55 cases of serious subtypes of preeclampsia (43.6%) were recorded as such by the registry. A total of 21 of 2,951 women without preeclampsia (0.71%) had a preeclampsia diagnosis in the registry. All registrations of serious subtypes of preeclampsia reflected true cases. The positive predictive value of a preeclampsia diagnosis in the registry was 74.4%. Including interview data reduced the sample size to 2,307 women. In this sample, of 62 women with preeclampsia, 45 (72.6%) reported in the interview to have had preeclampsia. Of 2,245 women with no preeclampsia, 31 (1.4%) reported to have had preeclampsia. The positive predictive value of the women's own report on preeclampsia was 59.2%. The authors conclude, for the purpose of etiologic studies, that the registry had acceptable validity, whereas the usefulness of self-reported information may be limited.
American Journal of Epidemiology 08/2007; 166(2):117-24. · 5.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the association between maternal weight gain and birth weight less than 3,000 g and greater than or equal to 4,000 g in underweight (body mass index [BMI] less than 19.8 kg/m(2)), normal weight (BMI 19.8-26.0 kg/m(2)), overweight (BMI 26.1-29.0 kg/m(2)), and obese (BMI greater than 29.0 kg/m(2)) women, with emphasis on the use of the American Institute of Medicine (IOM) recommendations in Denmark.
We analyzed data from 2,248 women with singleton, term pregnancies. The relationship between weight gain and risk of birth weight less than 3,000 g and greater than or equal to 4,000 g was examined in the four BMI groups, and use of IOM recommendations was tested by logistic regression analyses.
We found an inverse relationship between maternal weight gain and the proportion of infants with a birth weight less than 3,000 g. Birth weight greater than or equal to 4,000 g increased with an increasing weight gain in underweight and normal-weight women, but the association was less apparent in overweight and obese women. Underweight women seemed to benefit from gaining more weight than recommended by the IOM, because the odds ratio (OR) of birth weight less than 3,000 g was 0.3 (95% confidence interval [CI] 0.1-0.9) and the OR was 1.7 for birthweight greater than or equal to 4,000 g (95% CI 0.8-3.6). The normal-weight women had an increased risk of birth weight less than 3,000 g (OR 2.4, 95% CI 1.5-3.7) if weight gain was below the recommended range, and the OR of birth weight greater than or equal to 4,000 g was 1.9 (95% CI 1.5-2.5) when the women gained more than recommended.
The IOM recommendations may provide a basis for Danish recommendations to pregnant women, although the upper recommended limit for underweight women may have to be increased.
Obstetrics and Gynecology 07/2007; 109(6):1309-15. · 4.73 Impact Factor
-
Obstetrics and Gynecology 06/2007; 109(5):1203-4; author reply 1204. · 4.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Women who get pregnant after infertility treatment differ from women with naturally conceived pregnancies concerning prenatal screening: on average they are older and therefore they have a greater risk of carrying a child with Down's syndrome, their children have an increased risk of congenital malformations, and they have a great wish to avoid invasive prenatal diagnostic tests. The conclusion of this review is that first trimester screening is an acceptable choice for these women, although larger studies are needed to clarify whether a correction factor is necessary for the biochemical markers.
Ugeskrift for laeger 02/2007; 169(5):414-9.
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to determine the incidence of polyhydramnios, the related maternal and perinatal morbidity, and to estimate the association between perinatal outcome and the degree of polyhydramnios in a Danish population.
The study population consisted of 168 women with singleton pregnancies and polyhydramnios diagnosed by ultrasound as a largest two-diameter pocket of > 50 cm2. Mild polyhydramnios defined as > 50 and < 100 cm2, and severe polyhydramnios defined as > or = 100 cm2. The background population consisted of 8,347 pregnant women from the same hospital. Outcome measures were compared using chi2 test or Fisher's exact test.
The incidence of polyhydramnios was 2%, with 66.7% of cases mild, and 33.3% were severe polyhydramnios. The study population had an increased risk of emergency (19 versus 10.5%, p<0.001) and elective (11.3 versus 5.0%, p<0.001) caesarean section, as well as perinatal death (1.2 versus 0.3%, p<0.05) compared to the background population. In cases of severe polyhydramnios, there was an increased risk of caesarean section (44.6 versus 23.1%, p<0.005), birth weight > 4,000 g (28.6 versus 14.3%, p<0.05), and need for neonatal care (8.9 versus 0.9%, p<0.01) compared to mild cases. Apgar score < 7, perinatal death and structural malformations only occurred in women with severe polyhydramnios.
It is reasonable to distinguish between mild and severe polyhydramnios regarding special attention and follow-up, as caesarean section and perinatal morbidity and mortality are related to the degree of polyhydramnios. A two-diameter pocket > or = 100 cm2 could be used to separate mild from severe cases.
Acta Obstetricia Et Gynecologica Scandinavica 01/2007; 86(12):1427-31. · 1.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the association between loop electrosurgical excision procedure (LEEP) and other potential risk factors, and subsequent preterm delivery (<37 weeks), using data from a large cohort study of Danish women.
The Danish prospective cohort study was initiated in 1991, with the original aim of investigating the role of human papillomavirus in the natural history of cervical neoplasia. The study included 11,088 women aged 20-29. The cohort was invited for 2 follow-up examinations in 1993-1995 and 1999-2000, respectively. At all 3 examinations, the women answered questions about a number of different lifestyle variables. We assessed the relationship between preterm delivery and potential risk factors, such as previous LEEP treatments, smoking during pregnancy, age, parity and previous preterm delivery. The cohort was followed until 2004, through linkages with the nationwide Pathology Data Bank and the Medical Birth Registry.
Of the 14,982 deliveries in the cohort during follow up, 542 were preterm (21-37 weeks). Among deliveries with no previous LEEP, 3.5% ended as a preterm delivery, whereas this applied to 6.6% among deliveries following a LEEP, yielding a significantly increased risk of preterm birth after LEEP (OR=1.8; 95% CI: 1.1-2.9). The strongest risk factor for preterm delivery was a previous preterm delivery (OR=2.3; 95% CI: 1.4-3.7). Other significant risk factors were smoking during pregnancy and low educational status.
Our study showed an almost 2-fold increase in the risk of preterm delivery after LEEP treatment. Thus, women in their reproductive age should be informed about the increased risk of preterm delivery, if treated with LEEP.
Acta Obstetricia Et Gynecologica Scandinavica 01/2007; 86(5):596-603. · 1.77 Impact Factor
