RNA profiles reveal signatures of future health and disease in pregnancy.

Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden1. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method2. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.

National data on the early clinical use of non-invasive prenatal testing in public and private healthcare in Denmark 2013-2017.

INTRODUCTION: In Denmark, non-invasive prenatal testing (NIPT) has been used since 2013. We aimed to evaluate the early clinical use of NIPT in Danish public and private healthcare settings before NIPT became an integrated part of the national guidelines on prenatal screening and diagnosis in 2017. MATERIAL AND METHODS: NIPT data were collected between March 2013 and June 2017 from national public registries and private providers. Results from follow-up samples (chorionic villi, amniotic fluid, postnatal blood or fetal tissue) were included from The Danish Cytogenetics Central Registry and indications and outcome from The Danish Fetal Medicine Database. RESULTS: A total of 3936 NIPT results were included in the study from public hospitals (n = 3463, 88.0%) and private clinics (n = 473, 12.0%). The total number of prenatal tests was 19 713 during the study period: 20% were NIPT analyses (n = 3936) and 80% invasive procedures (n = 15 777). Twenty-five percent of NIPTs in the private clinics were performed before gestational week 11+0 , whereas NIPT in public settings was used only after combined first trimester screening (P < .001). Regardless of indication, the national public sensitivity was 96.9% (95% CI 82.0%-99.8%) for trisomy 21, 100% (95% CI 46.3%-100%) for trisomy 18, 100% (95% CI 5.5%-100%) for trisomy 13, and 87.0% (95% CI 74.5%-92.4%) for any fetal chromosomal aberration. Forty-seven true-positive NIPT results included cases of common aneuplodies (trisomy 21, n = 31; trisomy 18, n = 5; and trisomy 13, n = 1), sex chromosomal aberrations (n = 7) and atypical chromosomal aberrations (n = 3). One false-negative NIPT result occurred (trisomy 21). Of 47 cases, 21 (45%) cases with a true-positive NIPT result resulted in live births by choice; 11 of these children had Down and 4 had Edwards syndrome. CONCLUSIONS: The total number of NIPT analyses was low compared with the number of invasive procedures in the implementation period. In contrast to the generally high termination rate after a positive result following invasive testing in Denmark, a high proportion of true-positive NIPT results from the public setting resulted in live births. NIPT may be an important risk-free alternative to invasive testing for a minority of women in the public setting who wish to use prenatal genetic testing for information only and not for reproductive decision-making.

Plasma progesterone, estradiol, and unconjugated estriol concentrations in twin pregnancies: Relation with cervical length and preterm delivery.

INTRODUCTION: The aim of this study was to examine the association between plasma hormone concentrations, cervical length, and preterm delivery in twin pregnancies, including the effect of progesterone treatment. MATERIAL AND METHODS: This study included 191 women pregnant with twins from a randomized placebo-controlled trial. A baseline blood sample was collected at 18-24 weeks before treatment with vaginal progesterone (n = 95) or placebo pessaries (n = 96), and 167 (87.4%) women had a second sample collected after 4-8 weeks of treatment. At baseline, 155 (81.2%) women had their cervical length measured. Progesterone, estradiol, and unconjugated estriol concentration was measured, and the association between hormone concentrations, cervical length, and gestational age at delivery was examined. Hormone concentrations were compared in the placebo and progesterone group. Statistical analysis included Spearman's rho, Mann-Whitney U test, Cuzick's test for trends, and linear regression analyses. RESULTS: A short cervical length was associated with preterm delivery. Cervical length and hormone concentrations were not associated (Spearman's rho; progesterone -.05, estradiol .04, estriol .08). Decreasing gestational age at delivery was associated with higher progesterone and estradiol concentrations at baseline (P trend; progesterone 0.04, estradiol 0.02) but not in the second sample or in the weekly change between samples. Progesterone treatment did not increase the progesterone concentration. CONCLUSIONS: Plasma concentrations of progesterone, estradiol, and unconjugated estriol at 18-24 weeks are not associated with cervical length or preterm delivery in twin pregnancies. Vaginal progesterone treatment does not increase the circulating progesterone concentration in twin pregnancies. Cervical length, but not hormone concentration, is predictive of preterm delivery in twin gestations.

Short- and long-term perinatal outcome in twin pregnancies affected by weight discordance.

INTRODUCTION: The objective was to investigate the association between chorionicity-specific intertwin birthweight discordance and adverse outcomes including long-term follow up at 6, 18, and 48-60 months after term via Ages and Stages Questionnaire. MATERIAL AND METHODS: In this secondary analysis of a cohort study (Oldenburg et al., n = 1688) and a randomized controlled trial (PREDICT study, n = 1045) twin pairs were divided into three groups according to chorionicity-specific birthweight discordance: <75th percentile, 75th-90th percentile and >90th percentile. Information on infant mortality, admittance to neonatal intensive care units, and gestational age at delivery was available for all pairs. Detailed neonatal outcomes were available for 656 pairs from PREDICT, of which 567 pairs had at least one Ages and Stages Questionnair follow-up. Logistic regression models were used for dichotomous outcomes. Ages and Stages Questionnair scores were compared using the method of generalized estimating equation to account for the correlation within twins. RESULTS: The 75th and 90th percentiles for birthweight discordance were 14.8 and 21.4% for monochorionic and 16.0 and 23.8% for dichorionic twins. After adjustment for small for gestational age and gender, birthweight discordance >75th and >90th percentile was associated with induced delivery <34 weeks [odds ratio 1.71 (95% confidence interval 1.11-2.65) and odds ratio 2.83 (95% confidence interval 1.73-4.64), respectively]. Discordance >75th-percentile was associated with an increased risk of infant mortality after 28 days [odds ratio 4.69 (95% confidence interval 1.07-20.45)] but not with major neonatal complications or with low mean Ages and Stages Questionnair scores at 6, 18, and 48-60 months after term. CONCLUSION: Chorionicity-specific intertwin birthweight discordance is a risk factor for induced preterm delivery and infant mortality, but not for lower scores for neurophysiological development at 6, 18, and 48-60 months.

Prenatal detection of congenital heart disease in a low risk population undergoing first and second trimester screening.

OBJECTIVES: The prenatal detection rate of congenital heart disease (CHD) is low compared with other fetal malformations. Our aim was to evaluate the prenatal detection of CHD in Eastern Denmark. METHODS: Fetuses and infants diagnosed with CHD in the period 01.01.2008-31.12.2010 were assessed regarding prenatal detection rate and accuracy, as well as correlation with nuchal translucency (NT) thickness. RESULTS: Out of 86 121 infants, 831 were born with CHD (0.96%). The prenatal detection rate of 'all CHD' was 21.3%, of 'Major CHD' 47.4%. Full agreement between prenatal and postnatal/autopsy findings was found in 96% of prenatally detected diagnoses. An NT thickness >95(th) percentile was found in 15.0% fetuses with 'Major CHD'. Of 'Major CHDs' detected prenatally, 77% were picked up at the time of the malformation scan at weeks 18-21. CONCLUSIONS: Nearly half of 'Major CHDs' were detected prenatally. The prenatal cardiac diagnoses showed a high degree of accuracy. Increased NT thickness as a screening tool for CHD performed moderately but is an important high risk group for specialist examination. A minority of the prenatally detected CHDs was identified because of extra scans performed in high risk pregnancies. © 2014 John Wiley & Sons, Ltd.

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

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

Serum YKL-40 and uterine artery Doppler -- a prospective cohort study, with focus on preeclampsia and small-for-gestational-age.

OBJECTIVE: To test if serum YKL-40 is increased in women developing preeclampsia or small-for-gestational age fetuses. We also assessed the association between uterine artery pulsatility index, notching and serum YKL-40 levels. DESIGN: Prospective cohort study. SETTING: A primary referral unit for obstetric ultrasound. POPULATION: A total of 1214 unselected pregnant women enrolled at nuchal translucency examination between 11(+3) and 13(+6)  weeks of gestation. METHODS: All women had ultrasound and blood sample collection at the nuchal translucency scan, a 20-week malformation scan and 25-week and 32-week fetal growth examinations. Uterine artery Doppler was assessed and outcome was registered from medical records. MAIN OUTCOME MEASURES: Preeclampsia, hypertension, small-for-gestational age. RESULTS: Serum YKL-40 was associated with increasing maternal age (p < 0.0001), body mass index (p = 0.0002), primiparity (p = 0.0003), and hypertension (p = 0.015). Serum YKL-40 increased from 12 to 20 weeks and decreased from 20-25 and 25-32 weeks of gestation. No association was found between preeclampsia and serum YKL-40. Small-for-gestational-age at birth was significantly associated with a 5.4% increase in serum YKL-40 at 32 weeks of gestation (95% CI 1.5-9.3, p = 0.005). An association was found between uterine artery pulsatility index at 32 weeks and small-for-gestational age (p = 0.0015) but not between YKL-40 and uterine artery notching (p = 0.83). CONCLUSIONS: Serum YKL-40 was not associated with preeclampsia. Increasing serum YKL-40 was related to maternal age, body mass index and small-for-gestational age and may reflect an exaggerated inflammatory response.

Cesarean section for the second twin: a population-based study of occurrence and outcome.

BACKGROUND: Although management of twin deliveries has been a topic of discussion for decades, a consensus on how to deliver twins is lacking. The objective of this study was to examine short-term neonatal outcome of the second twin delivered by cesarean section after vaginal delivery of the first-born twin (combined delivery) and to identify predictors of combined delivery. METHODS: This study was a 3-year, population-based, retrospective cohort investigation of 1,254 twin births in Denmark. The twin births were divided into three groups: vaginal deliveries, planned cesarean deliveries, and combined deliveries. Data were extracted from medical records, a fetal medicine software program (Astraia), and the National Birth Registry. Short-term poor neonatal outcome was measured as a 5-minute Apgar score ≤ 7, umbilical cord pH ≤ 7.10, and admission to neonatal intensive care unit for more than 3 days. RESULTS: Vertex-nonvertex fetal presentations were more prevalent in combined deliveries than vaginal deliveries (OR 4.4, 2.5-7.8). Nonvertex second twins born by combined delivery had a higher risk of Apgar score ≤ 7 and umbilical cord pH ≤ 7.10 compared with vaginal delivery, unadjusted OR 6.2 (2.1-18), and unadjusted OR 3.9 (1.6-9.5). Prenatal ultrasound scans were evaluated in combined deliveries, of which 48 percent were vertex-vertex at the last ultrasound scan in pregnancy (mean gestational age 34 + 0) and 37 percent were vertex-vertex at birth. CONCLUSIONS: Vertex-nonvertex presenting twins have an increased risk of combined delivery. Combined deliveries are associated with increased neonatal morbidity for the second twin.

Correlation between prenatal diagnosis by ultrasound and fetal autopsy findings in second-trimester abortions.

We evaluated the correlation between prenatal diagnosis by ultrasound and autopsy findings, based on 52 second-trimester pregnancies terminated due to fetal malformations or chromosome aberrations diagnosed at a gestational age of 12-25 weeks. In 24 pregnancies, there was full agreement between ultrasound and autopsy. In 23 fetuses, the main diagnosis was confirmed and additional or more specific findings were observed on autopsy. In five fetuses, there were considerable differences. Discrepancies between ultrasound and autopsy findings were mainly anomalies undetectable by ultrasound and thus expected; however, about one-third of the discrepancies were not expected, representing findings that were 'missed' at ultrasound. The main ultrasound diagnoses were confirmed in the majority of the pregnancies, but the additional information obtained at autopsy in more than half of the fetuses clearly shows the value and benefit of postmortem fetal examination following termination of a pregnancy.

Twin births: cesarean section or vaginal delivery?

OBJECTIVE: To assess morbidity and mortality in twin pregnancy deliveries, according to chorionicity and mode of delivery. DESIGN: Population-based retrospective cohort. SETTING: Fourteen obstetric departments in Denmark. POPULATION: One thousand one hundred and seventy-five twin pregnancies with two live fetuses at 36(+0) weeks of gestation. METHODS: Pregnancy outcomes assessed according to chorionicity and mode of delivery. MAIN OUTCOME MEASURES: Poor outcome defined as five min Apgar score ≤ 7, umbilical artery pH < 7.10, admission to neonatal unit for more than three days or death. RESULTS: Dichorionic (DC) twins, delivered after 36 gestational weeks, with intended vaginal delivery (n= 689) compared with DC twins with planned cesarean section (n= 371) had an increased risk of poor outcome [odds ratio (OR) 1.47, p= 0.037] after adjustment for body mass index, parity and weight discordance. There was no increased risk for poor outcome in monochorionic (MC) twins with intended vaginal delivery (n= 63) compared with planned cesarean section (n= 52; OR 0.87, 95% confidence interval 0.26-2.96). Nulliparity increased the risk of poor outcome in DC (OR 1.5, p= 0.03) and in MC twins (OR 4.01, p= 0.02), as well as birthweight discordance >300 g (DC, OR 1.50, p= 0.02; and MC, OR 6.02, p= 0.002). For DC twins, we found a significantly higher risk of poor outcome of the second-born twin compared with the first (OR 1.64, p= 0.001). CONCLUSIONS: Dichorionic twins born after 36 weeks of gestation had a higher risk of poor outcome by intended vaginal delivery than by planned cesarean section. For MC twins, statistical differences in outcome by mode of delivery could not be seen.

Neonatal complications and neurophysiological development in twins - a long-term follow-up study.

OBJECTIVES: To investigate the association between neonatal complications and neurophysiological development in twins at 18 and 48-60 months of age. METHODS: This was a secondary analysis of 841 Danish mono- and dichorionic diamniotic twins from a randomized controlled trial (PREDICT study), which included an assessment of the twin's neurophysiological development using the Ages and Stages Questionnaire (ASQ) that had been filled out by the parents at 18 and 48 or 60 months. The correlation within twin pairs was accounted for by the method of generalized estimating equation. Models were adjusted for maternal educational score and gestational age at delivery. RESULTS: ASQ data were available for 823 children at 18 months and 425 children at 48 or 60 months. Low maternal educational score and preterm delivery <34 weeks were associated with a lower ASQ score at 48-60 months (-15.4 points (95%CI -26.4; -4.5) and -13.2 points (95%CI -23.8; -2.5), respectively). Neonatal sepsis and a compound of intraventricular hemorrhage, retinopathy of prematurity and necrotizing enterocolitis (IVH/ROP/NEC) were associated with lower ASQ score at 18 months (-15.3 points (95%CI -28.1; -2.5) and -30.8 points (95%CI -59.5; -2.1), respectively). Children with IVH/ROP/NEC had a lower ASQ score at 48-60 months (-34.2 points (95%CI -67.9; -0.6)). The associations were not specific to only one ASQ domain. CONCLUSION: Several neonatal complications are associated with poorer neurophysiological development in twins during childhood, even after adjustment for gestational age at delivery.

Diagnosis and prediction of parental origin of triploidies by fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A at 11-14 weeks of gestation.

The study objective was to determine the parental origin of triploidy in relation to findings from early risk assessment in a combined screening program between 2004 and the end of 2006. Triploidy was diagnosed in six chorion villus samples and two samples from missed abortions. After informed consent, quantitative fluorescence polymerase chain reaction analysis was performed on the five cases where we received blood from both parents and tissue from fetuses. In four cases the origin of the triploidy was paternal and in one maternal, in accordance with previous findings in type I and type II triploidies. Finding triploidy is possible by risk assessment (ultrasound and double test), and thereby women may have the opportunity for early termination of pregnancy.

Fetal goiter and bilateral ovarian cysts.

A unique case of fetal goiter accompanied by bilateral ovarian cysts in a mother treated with methimazole for Graves'disease is reported. The abnormal findings were detected by ultrasound at 31 weeks of gestation. Umbilical fetal blood sampling revealed elevated serum TSH, normal concentrations of free T 4 , normal FSH and LH and high concentrations of E 2 . A series of weekly amniocenteses and intra-amniotic injections of levothyroxine was initiated, along with a reduction of the mother's methimazole dosage. The level of TSH in amniotic fluid was initially high, but was considerably reduced by each injection and followed by a gradual reduction of fetal goiter as well as the left ovarian cyst. The right cyst ruptured spontaneously. At 36 weeks + 4 days, the patient underwent elective caesarean section and gave birth to a female, weighing 2,880 g with 1- and 5-min Apgar scores of 10. The thyroid gland appeared normal in size, and cord blood TSH and free T 4 were both within normal limits. At ultrasound control 6 days later, the right ovarian cyst was not visible, while the left cyst was still present. Thus, our report supports previous findings that fetal goiter can be treated successfully with intra-amniotic injection of levothyroxine.More importantly, it shows that fetal hypothyroidism with elevated levels of TSH can be accompanied by ovarian cysts,suggesting interference between thyreotropic and gonadotropic hormones.

Serum YKL-40 and gestational diabetes - an observational cohort study.

To examine serum YKL-40 in women developing gestational diabetes mellitus (GDM). In the present large observational cohort study of 1179 pregnant women, we determined serum YKL-40 four times during pregnancy (at gestational age 12, 20, 25, and 32 weeks). Pregnancy outcome was obtained from medical records. Sixty-eight women (5.8%) developed GDM. Serum YKL-40 increased from gestational age (GA) 12 weeks and the following weeks in the women who developed GDM and was independent of BMI, parity, and maternal age (OR = 2.69, 95% CI: 1.45-5.00, p = 0.002). No association was found between serum YKL-40 and the oral glucose tolerance test results. In conclusion, YKL-40 significantly increased in pregnant women with GDM compared with women without GDM, probably reflecting the low-grade inflammation of GDM. However, we did not find an association between serum concentrations of YKL-40 in early pregnancy and the development of GDM and thus we conclude that YKL-40 alone is not usable as a biomarker for early prediction of GDM.

A Phenotypic Analysis of Regulatory T Cells and Uterine NK Cells from First Trimester Pregnancies and Associations with HLA-G.

PROBLEM: The prevalence of regulatory T cells and NK cells expressing activation and HLA-G receptors, and the influence of in vivo sHLA-G and mHLAG on HLA-G receptors expressed by NK cells in the uterine compartment is unclear. METHOD OF STUDY: KIR2DL4 and/or ILT2 expression on regulatory T cells and NK cells from the placental bed and peripheral blood in first trimester was assessed using flow cytometry. Expression of mHLA-G on trophoblast cells and sHLA-G in 'uterine' and peripheral blood was determined with ELISA and flow cytometry, and specific associations with expression levels of cognate receptors or activation markers on immune cells were determined. RESULTS: In the placental bed, CD45RA surface expression on Tregs was similar to peripheral Tregs in pregnant women, but T cells with lower CD4 and CD8 expression were accumulated. HLA-G receptor expression was increased on NK cells from 'uterine blood'. Soluble HLA-G was significantly increased in 'uterine blood' compared with peripheral blood, but no correlation was found between sHLA-G and mHLA-G in the uterine compartment. A correlation was found between sHLA-G and the fraction of KIR2DL4-positive NK cells in the uterine compartment, and a tendency was observed between mHLA-G and the fraction of ILT2-positive NK cells in the uterine compartment. CONCLUSION: The NK subset in the placental bed displays a unique phenotype that may be influenced by mHLA-G on trophoblast cells and locally accumulated sHLA-G in the uterus.

Longitudinal study of serum placental GH in 455 normal pregnancies: correlation to gestational age, fetal gender, and weight.

Placental GH is thought to be responsible for the rise in maternal IGF-I during pregnancy and is considered to be important for fetal growth. In this prospective longitudinal study of healthy pregnant women, we investigated determinants of placental GH in maternal serum. Serum was obtained from 455 women with normal singleton pregnancies at approximately 19 and 28 wk gestation. Serum placental GH concentrations were measured by a highly specific immunoradiometric assay, and fetal size was measured by ultrasound. Data on birth weight, gender, prepregnancy body mass index (BMI), parity, and smoking habits were obtained from medical records. Serum placental GH concentrations were detectable in serum from all women as early as 14 wk gestation and increased during pregnancy in all individuals (P < 0.001). Placental GH levels at second examination were found to be higher in women carrying female fetuses [median, 9.0 ng/ml; 95% confidence interval (CI), 4.7-23.0] compared with women carrying male fetuses (median, 8.2 ng/ml; 95% CI, 3.96-19.4; P = 0.004). Similarly, the increase in placental GH between 19 and 28 wk gestation was significantly larger in female fetus bearers than in male fetus bearers (P = 0.002). Placental GH at second examination was positively correlated with gestational age (P = 0.002) and negatively correlated with prepregnancy BMI (P = 0.039). Placental GH correlated with fetal weight at approximately 28 wk gestation (P = 0.002) but did not predict birth weight at term. Our study supports the role of maternal placental GH in the regulation of fetal growth. In conclusion, we found that 1) placental GH levels correlated significantly with fetal size at 28 wk gestation; 2) GH levels were measurable in serum from all women as early as 14 wk gestation; 3) maternal prepregnancy BMI and smoking were determinants of placental GH levels, although their specific effects on the serum maternal levels of placental GH remain to be seen; and 4) women carrying female fetuses have significantly higher placental GH levels compared with women carrying male fetuses at 28 wk gestation.

The need for pain relief in uncomplicated deliveries in an alternative birth center compared to an obstetric delivery ward.

The need for pain relief during uncomplicated labour and delivery was studied in 125 women attending an Alternative Birth Center (ABC) and 170 women attending an obstetrical ward. The ABC was staffed only with midwives and assistant nurses who took care of all deliveries. In case of complications the doctor on duty at the obstetrical ward could come in a few minutes and the patient was transferred to the obstetrical ward. At the ABC the delivery room was next to the sleeping rooms and the living room and the woman in labour could have a chat with the women, who had given birth. At the obstetrical ward this was not possible. The delivery rooms were on one floor, and after giving birth the woman was moved to another floor. Women at the ABC were older and had a higher social status than women at the obstetrical ward. Twenty four of the 170 women had initially planned to give birth at the ABC but gave birth at the obstetrical ward due to accommodation restrictions at the ABC. Women refused by the ABC resembled women giving birth at the ABC but their need for pain relief was identical with the other women giving birth at the obstetrical ward. Pain relief with pethidine was 4 times more frequent among women giving birth at the obstetrical ward (18%) than at the ABC (4.8%). Pethidine was predominantly administered to young women and primiparas at the obstetrical ward and to women with prolonged labour at both birthplaces.

[Webbing of the neck and nasal bone--prenatal screening for Down syndrome]. / Nakkefold og naeseben--praenatal screening for Downs syndrom.

The risk of giving birth to a child with Down syndrome increases with maternal age. If in Denmark the mother is older than 35-years she belongs to a high-risk group and will be offered amniocentesis or chorionic villus sampling. We describe different scenarios of risk calculation for Down syndrome based on combinations of nuchal translucency, nasal bone, and/or integrated hormone test. The combination of nuchal translucency and visualisation of the nasal bone between gestational age 11 weeks and 13 + 6 has turned out to be as good a predictive marker as nuchal translucency and integrated hormone test.

[Array-comparative genomic hybridization is a new and promising method for prenatal chromosomal diagnosis]. / Array-komparativ genomisk hybridisering er en ny og lovende metode til prænatal kromosomundersøgelse .

Array-comparative genomic hybridization (array-CGH) is a very sensitive method for identifying chromosomal imbalances and is now used on a clinical basis for prenatal diagnosis. This article reviews the advantages and disadvantages of the method, the ethical considerations and the current recommendations for prenatal use in Denmark according to a new national guideline from The Danish Society of Foetal Medicine and the Danish Society of Medical Genetics.

Cytokines and the risk of preterm delivery in twin pregnancies.

OBJECTIVE: To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment. METHODS: This secondary analysis of a randomized placebo-controlled trial investigating the effect of progesterone treatment on preterm delivery in twin pregnancies included 523 women with available dried blood spot samples collected before treatment with progesterone (n=258) or placebo (n=265) and after 4-8 weeks of treatment. Samples were analyzed for cytokines using a sandwich immunoassay. Cytokine levels in spontaneous preterm delivery at 34-37 weeks of gestation and spontaneous preterm delivery before 34 weeks of gestation were compared with delivery at 37 weeks of gestation or more for placebo-treated women. The association between interleukin (IL)-8 and risk of spontaneous preterm delivery before 34 weeks of gestation was estimated further, including comparison according to treatment. Statistical analyses included Kruskal-Wallis test, Mann-Whitney U test, linear regression, and Cox regression analysis. RESULTS: We found a statistically significant association between IL-8 and spontaneous preterm delivery. At 23-33 weeks of gestation, the median IL-8 level was 52 pg/mL (interquartile range 39-71, range 19-1,061) for term deliveries compared with 65 pg/mL (interquartile range 43-88, range 14-584) for spontaneous preterm delivery at 34-37 weeks of gestation and 75 pg/mL (interquartile range 57-102, range 22-1,715) for spontaneous preterm delivery before 34 weeks of gestation (P<.001). Risk of spontaneous preterm delivery was associated with a large weekly increase in IL-8 (hazard ratio 2.0, 95% confidence interval [CI] 1.2-3.3). There was no effect of progesterone treatment on IL-8 levels. Levels of IL-8 at 18-24 weeks of gestation were associated with a cervix less than 30 mm (odds ratio 1.8, 95% CI 1.2-2.7). CONCLUSION: Risk of spontaneous preterm delivery before 34 weeks of gestation is increased in women with high IL-8 levels. Progesterone treatment does not affect IL-8 levels.