Maternal age and the risk of fetal aneuploidy: A nationwide cohort study of more than 500 000 singleton pregnancies in Denmark from 2008 to 2017.

INTRODUCTION: In this register-based study of pregnancies in Denmark, we assessed the associations between maternal age and the risk of fetal aneuploidies (trisomy 21, trisomy 18, trisomy 13, triploidy, monosomy X and other sex chromosome aberrations). Additionally, we aimed to disentangle the maternal age-related effect on fetal aneuploidies by cases with translocation trisomies and mosaicisms. MATERIAL AND METHODS: We followed a nationwide cohort of 542 375 singleton-pregnant women attending first trimester screening in Denmark between 2008 and 2017 until delivery, miscarriage or termination of pregnancy. We used six maternal age categories and retrieved information on genetically confirmed aneuploidies of the fetus and infant from the national cytogenetic register. RESULTS: We confirmed the known associations between advanced maternal age and higher risk of trisomy 21, 18, 13 and other sex chromosome aberrations, especially in women aged ≥35 years, whereas we found no age-related associations with triploidy or monosomy X. Cases with translocation trisomies and mosaicisms did not influence the overall reported association between maternal age and aneuploidies. CONCLUSION: This study provides insight into the accurate risk of fetal aneuploidies that pregnant women of advanced ages encounter.

Paracetamol use prior to and in early pregnancy: Prevalence and patterns among women with and without chronic medical diseases.

AIMS: Paracetamol is commonly consumed by pregnant women, even though recent data have questioned its safety. Having chronic medical diseases (CMDs) may influence the prevalence of use during pregnancy. We aimed to assess the prevalence and patterns of use 3 months prior to pregnancy and in the first trimester among women with and without CMDs and the potential influence of CMDs on frequent use in the first trimester. METHODS: We used patient-reported data from the Copenhagen Pregnancy Cohort from 1 October 2013 to 23 May 2019 with information on CMDs and paracetamol use. Prevalence and patterns of use were assessed descriptively and by multivariable logistic regression models. RESULTS: We included 24 019 pregnancies. Use of paracetamol prior to and in early pregnancy was significantly higher among women with CMDs compared to women without (40.7% vs. 35.8% and 9.1% vs. 5.1%, respectively). Women with CMDs were 2.7 times more likely to have a frequent intake compared to women without [aOR 2.69 (95% CI 2.05-3.32)]. Migraine, rheumatoid arthritis and mental disease were associated with a higher use of paracetamol [aOR 4.39 (3.20-6.02), aOR 4.32 (2.41-7.72) and aOR 2.74 (1.67-4.49), respectively]. CONCLUSIONS: Women with CMDs had a higher paracetamol use before and during pregnancy than women without CMDs. Women with migraine, rheumatoid arthritis and mental disease showed the highest risk of frequent use. This study highlights the importance of discussing pain relief in pregnancy and evaluating the influence of maternal CMDs when assessing adverse effects of paracetamol use during pregnancy.

Motivation towards first trimester screening for preeclampsia among pregnant women in Denmark: A cross-sectional questionnaire study.

INTRODUCTION: The aim of this cross-sectional questionnaire study was to investigate motivation to participate in a possible new screening for preeclampsia in the first trimester of pregnancy among Danish pregnant women through a questionnaire based on Theory of Planned Behavior developed for this specific purpose. The new screening combines maternal characteristics with mean arterial pressure, uterine artery pulsatility index and biochemical markers to predict the risk of preeclampsia, whereas the current Danish screening uses maternal characteristics alone. MATERIAL AND METHODS: Participation was offered to a proportion of women attending a first or a second trimester screening scan at two University Hospitals in Copenhagen. The questionnaire was set up in REDCap® and answers were entered directly into the database, which was accessed via a QR-code. RESULTS: We invited 772 pregnant women to participate in the questionnaire survey between November 2021 and April 2022 at Copenhagen University Hospital Rigshospitalet (study site one) (n = 238) and Copenhagen University Hospital Hvidovre (study site two) (n = 534). The response rate was 71.8% (171/238) at study site one and 33.9% (181/534) at study site two. A total of 352 women were included in the study (total participation rate 45.6%). Most women had a positive attitude towards preeclampsia screening in pregnancy, and 99.4% said they would participate in a risk assessment for preeclampsia if given the opportunity. A total of 97.4% answered "yes" to whether a first trimester preeclampsia screening should be offered to all pregnant women in Denmark. Positive motivation to participate in preeclampsia screening was correlated with having a network with a positive attitude towards preeclampsia screening. CONCLUSIONS: The results of this study indicate that Danish pregnant women have a positive attitude towards participation in a first trimester screening for preeclampsia. This observation might be useful in relation to possible future implementation in Denmark.

Lack of an association between first-trimester concentration of mid-regional pro-atrial natriuretic peptide and risk of early-onset preeclampsia <34 weeks' gestation.

AIM: We examined the heart failure biomarker mid-regional pro-atrial natriuretic peptide during the first trimester of pregnancy in relation to early-onset preeclampsia <34 weeks. MATERIALS AND METHODS: This case-control study included 34 women with singleton pregnancies with a preeclampsia diagnosis and delivery before 34 weeks of gestation who had attended the routine first-trimester ultrasound scan at 11-13+6 weeks of gestation between August 2010 and October 2015 at the Copenhagen University Hospital Rigshospitalet, Denmark, and 91 uncomplicated singleton pregnancies matched by time of the routine first-trimester blood sampling at 8-13+6 weeks. Descriptive statistical analyses were performed for maternal characteristics and obstetric and medical history for the case versus the control group. Concentrations of mid-regional pro-atrial natriuretic peptide, placental growth factor, soluble fms-like tyrosine kinase-1, and pregnancy-associated plasma protein A between early-onset preeclampsia cases and the control group were compared using Students t-test and the Mann-Whitney U test. Biochemical marker concentrations were converted into multiples of the expected median values after adjustment for gestational age. RESULTS: Mid-regional pro-atrial natriuretic peptide levels were not significantly different between early-onset preeclampsia cases and the control group in the first trimester of pregnancy. As expected, both placental growth factor and pregnancy-associated plasma protein A levels were significantly lower in early-onset preeclampsia, whereas soluble fms-like tyrosine kinase-1 levels were not statistically significantly different. CONCLUSION: The maternal first-trimester concentration of mid-regional pro-atrial natriuretic peptide, a peptide with multiple biological functions including a relation to cardiovascular disease, was not significantly different in women with early-onset preeclampsia.

Second-trimester cardiovascular biometry in growth-restricted fetuses; a multicenter cohort study.

BACKGROUND: Intrauterine growth restriction is associated with an increased risk of cardiovascular changes neonatally. However, the underlying pathways are poorly understood, and it is not clear whether the dysfunction is already present in the fetus. OBJECTIVE: This study aimed to investigate fetal cardiac dimensions assessed from images at the second trimester anatomy scan from fetuses classified postnatally as small for gestational age and intrauterine growth restricted and compare them with appropriate for gestational age fetuses. STUDY DESIGN: This was a substudy from The Copenhagen Baby Heart Study, a prospective, multicenter cohort study including fetuses from the second trimester of pregnancy in Copenhagen from April 2016 to October 2018. The mothers were recruited at the second trimester anatomy scan that included extended cardiovascular image documentation followed by consecutively measured heart biometry by 2 investigators blinded for the pregnancy outcome. The fetuses were classified postnatally as small for gestational age and intrauterine growth restricted according to the International Society of Ultrasound in Obstetrics and Gynecology 2020 guidelines using birthweight and with a retrospective assessment of Doppler flow. The mean differences in the cardiovascular biometry were adjusted for gestational age at the time of the second trimester scan and the abdominal circumference. The z-scores were calculated, and the comparisons were Bonferroni corrected (significance level of P<.005). Receiver operating characteristic curves were computed after performing backward regression on several maternal characteristics and biomarkers. RESULTS: We included 8278 fetuses, with 625 (7.6%) of them being small for gestational age and 289 (3.5%) being intrauterine growth restricted. Both small for gestational age and intrauterine growth restricted fetuses had smaller heart biometry, including the diameter at the location of the aortic valve (P<.005), the ascending aorta in the 3-vessel view (P<.005), and at the location of the pulmonary valve (P<.005). The intrauterine growth restricted group had significantly smaller hearts with respect to length and width (P<.005) and smaller right and left ventricles (P<.005). After adjusting for the abdominal circumference, the differences in the aortic valve and the pulmonary valve remained significant in the intrauterine growth restricted group. Achievement of an optimal receiver operating characteristic curve included the following parameters: head circumference, abdominal circumference, femur length, gestational age, pregnancy associated plasma protein-A multiples of median, nullipara, spontaneous conception, smoking, body mass index <18.5, heart width, and pulmonary valve with an area under the curve of 0.91 (0.88-0.93) for intrauterine growth restricted cases. CONCLUSION: Intrauterine growth restricted fetuses had smaller prenatal cardiovascular biometry, even when adjusting for abdominal circumference. Our findings support that growth restriction is already associated with altered cardiac growth at an early stage of pregnancy. The heart biometry alone did perform well as a screening test, but combined with other factors, it increased the sensitivity and specificity for intrauterine growth restriction.

Coagulation parameters in the newborn and infant - the Copenhagen Baby Heart and COMPARE studies.

OBJECTIVES: The coagulation system is not fully developed at birth and matures during the first months of infancy, complicating clinical decision making within hemostasis. This study evaluates coagulation parameters at birth and two months after birth, and tests whether cord blood can be used as a proxy for neonatal venous blood measurements. METHODS: The Copenhagen Baby Heart Study (CBHS) and the COMPARE study comprise 13,237 cord blood samples and 444 parallel neonatal venous blood samples, with a two month follow-up in 362 children. RESULTS: Because coagulation parameters differed according to gestational age (GA), all analyses were stratified by GA. For neonatal venous blood, reference intervals for activated partial thromboplastin time (APTT) and prothrombin time (PT) were 28-43 s and 33-61% for GA 37-39 and 24-38 s and 30-65% for GA 40-42. Reference intervals for international normalized ratio (INR) and thrombocyte count were 1.1-1.7 and 194-409 × 109/L for GA 37-39 and 1.2-1.8 and 188-433 × 109/L for GA 40-42. Correlation coefficients between umbilical cord and neonatal venous blood for APTT, PT, INR, and thrombocyte count were 0.68, 0.72, 0.69, and 0.77 respectively, and the distributions of the parameters did not differ between the two types of blood (all p-values>0.05). CONCLUSIONS: This study describes new GA dependent reference intervals for common coagulation parameters in newborns and suggests that cord blood may serve as a proxy for neonatal venous blood for these traits. Such data will likely improve clinical decision making within hemostasis among newborn and infant children.

Multivitamin use and risk of preeclampsia: A systematic review and meta-analysis.

INTRODUCTION: Preeclampsia is associated with adverse maternal and neonatal outcomes. It is unclear whether multivitamin use reduces the risk of preeclampsia. This systematic review and meta-analysis aimed to evaluate the association between multivitamin use and the risk of preeclampsia. MATERIAL AND METHODS: We searched PubMed, Embase and the Cochrane Library from database inception to July 2021. Randomized controlled trials (RCTs), case-control and cohort studies assessing the association between multivitamin use and risk of preeclampsia were eligible. Studies of treatment with a single micronutrient were excluded. Relative risks and 95% confidence intervals (95% CI) were calculated using random-effects models. RoB2, the Newcastle Ottawa Scale and GRADE were used to assess risk of bias and quality of evidence. The protocol was registered in PROSPERO (no. CRD42021214153). RESULTS: Six studies were included (33 356 women). Only two RCTs were found, both showing a significantly decreased risk of preeclampsia in multivitamin users. These studies were not compatible for meta-analysis due to clinical heterogeneity. A meta-analysis of observational studies using a random-effects model showed an unchanged risk of preeclampsia following multivitamin use (relative risk 0.85, 95% CI 0.69-1.03). The quality of evidence according to GRADE was very low. CONCLUSIONS: Very weak evidence suggests that multivitamin use might reduce the risk of preeclampsia; however, more research is needed. Large RCTs should be prioritized. The results of this review do not allow any final conclusions to be drawn regarding a preventive effect of multivitamin use in relation to preeclampsia.

Prenatally detected isolated ventricular septum defects and the association with chromosomal aberrations-A nationwide register-based study from Denmark.

OBJECTIVE: To evaluate the association between prenatally detected isolated ventricular septum defects (VSDs) and chromosomal aberrations in a nationwide study in Denmark. METHOD: Nationwide, register-based study with prospectively collected data including all singleton pregnancies from 2014-2018. From the Danish Fetal Medicine Database, we retrieved data on maternal characteristics, first-trimester biomarkers, pre- and postnatal diagnoses, genetic test results, and pregnancy outcomes. VSDs were considered isolated in the absence of other malformations or soft markers, and with a low first-trimester risk assessment for trisomies 21, 18 and 13. All cases of an isolated VSD with a chromosomal anomaly were audited. The genetic tests included karyotyping and chromosomal microarray. RESULTS: We retrieved data on 292 108 singleton pregnancies; 323 registered with a prenatally detected VSD and 697 with a VSD detected postnatally (incidence of 0.35%). Only 1/153 (0.7%, 95% CI 0.02;3.6%) of the isolated prenatally detected VSDs had an abnormal genetic test result (del (8)(q23.1)). Moreover, they had a lower free ß-hCG MoM (0.9 MoM vs 0.99 MoM, P = 0.02), and were more likely born small for gestational age (SGA), defined as birthweight 2 or more SD below the mean, compared with the control population (5.2% vs 2.5%, P = 0.03). CONCLUSION: We found a prevalence of chromosomal aberrations of 0.7% in fetuses with a prenatally detected isolated VSD. Moreover, we found an association between isolated VSDs and a larger proportion being born SGA.

A prospective cohort study of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy evaluating SARS-CoV-2 antibodies in maternal and umbilical cord blood and SARS-CoV-2 in vaginal swabs.

INTRODUCTION: Evidence about the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy is rapidly increasing; however, data on antibody response and risk of transmission during pregnancy and delivery are still limited. The aim of this study was to evaluate if SARS-CoV-2 is detectable in vaginal swabs and whether antibodies against SARS-CoV-2 are present in maternal and umbilical cord blood of pregnant women with confirmed SARS-CoV-2. MATERIAL AND METHODS: A single-unit prospective cohort study in Denmark including pregnant women with SARS-CoV-2 infection confirmed by a pharyngeal swab between August 20, 2020, and March 1, 2021, who gave birth during the same period. All patients admitted to the maternity ward and antepartum clinic were screened for SARS-CoV-2 infection. A maternal blood sample and vaginal swabs were collected at inclusion. If included antepartum, these samples were repeated intrapartum when an umbilical cord blood sample was also collected. Swabs were analyzed for SARS-CoV-2 and blood samples were analyzed for SARS-CoV-2 total antibodies. Placental and neonatal swabs as well as placental histopathological examinations were performed on clinical indications. RESULTS: We included 28 women, of whom four had serious maternal or fetal outcomes including one case of neonatal death. Within the first 8 days after confirmed SARS-CoV-2 infection, SARS-CoV-2 was detectable in two vaginal swabs (2/28) and SARS-CoV-2 antibodies were detected in 1 of 13 women. From 16 days after confirmed infection, antibodies were observed in 19 of 21 of women. Antibodies in cord blood were not detected during the first 16 days after confirmed infection (n = 7). However, from 26 days, antibodies were present in 16 of 17 cord blood samples of seropositive mothers. Placental examination in two cases of severe fetal outcomes preceded by reduced fetal movements revealed SARS-CoV-2 in swabs and severe histopathological abnormalities. CONCLUSIONS: SARS-CoV-2 was detected in only 2 of 28 vaginal swabs within 8 days after confirmed infection in pregnant women. Our data suggest that maternal seroconversion occurs between days 8 and 16, whereas antibodies in cord blood of seropositive mothers were present in the majority from 26 days after confirmed infection. Additional data are needed regarding timing of seroconversion for the mother and appearance of antibodies in cord blood.

Placental Growth Factor and Adverse Obstetric Outcomes in a Mixed-Risk Cohort of Women Screened for Preeclampsia in the First Trimester of Pregnancy.

OBJECTIVE: The study aimed to investigate the association between placental growth factor (PlGF) and adverse obstetric outcomes in a mixed-risk cohort of pregnant women screened for preeclampsia (PE) in the first trimester. METHODS: We included women with singleton pregnancies screened for PE between April 2014 and September 2016. Outcome data were retrieved from the New South Wales Perinatal Data Collection (NSW PDC) by linkage to the prenatal cohort. Adverse outcomes were defined as spontaneous preterm birth (sPTB) before 37-week gestation, birth weight (BW) below the 3rd centile, PE, gestational hypertension (GH), stillbirth, and neonatal death. RESULTS: The cohort consisted of 11,758 women. PlGF multiple of the median (MoM) was significantly associated with maternal sociodemographic characteristics (particularly smoking status and parity) and all biomarkers used in the PE first trimester screening model (notably pregnancy-associated plasma protein A MoM and uterine artery pulsatility index [PI] MoM). Low levels of PlGF (<0.3 MoM and <0.5 MoM) were independently associated with sPTB, low BW, PE, GH, and a composite adverse pregnancy outcome score, with odds ratios between 1.81 and 4.44 on multivariable logistic regression analyses. CONCLUSIONS: Low PlGF MoM levels are independently associated with PE and a range of other adverse pregnancy outcomes. Inclusion of PlGF should be considered in future models screening for adverse pregnancy outcomes in the first trimester.

Observational and genetic studies of short telomeres and Alzheimer's disease in 67,000 and 152,000 individuals: a Mendelian randomization study.

Short telomeres might lead to increased risk of Alzheimer's disease, but observational analyses have been inconclusive and potentially confounded by the strong association of both telomere length and risk of Alzheimer's disease with age and adverse lifestyle. To circumvent this, analyses including single nucleotide polymorphisms associated with telomere length used in an instrumental variable analysis produces risk estimates likely free of distortions from reverse causation and of most confounding. We tested the hypothesis that short telomeres are associated with increased risk of Alzheimer's disease, observationally and causal, genetically. Telomere length was measured in 66,567 individuals, and genotyped for rs2487999 in OBFC1, rs7726159 in TERT, and rs1317082 in TERC causing lifelong telomere shortening in 98,146 individuals from two Copenhagen studies. Genetic data on 54,162 individuals from the International Genomics of Alzheimer's Project were also included. Observationally, multifactorially adjusted hazard ratio for Alzheimer's disease was 1.02 (95% CI 1.00-1.03) per 200 base pair shorter telomeres. Telomere length was 335 base pairs shorter in individuals with 6 versus 0-1 alleles (p = 5 × 10-105). Genetically, odds ratio for Alzheimer's disease was 1.08 (1.01-1.16) per 200 base pairs shorter telomeres. Similar results were found in strata of age and comorbidities. In comparative analyses, genetically predicted shorter telomeres were associated with increased risk of myocardial infarction, and with decreased risks of lung cancer and melanoma as previously reported. Short telomeres were associated observationally and causal, genetically with increased risk of Alzheimer's disease. Telomere biology is therefore a potential pathway involved in the development of Alzheimer's disease.

Cell-Free Fetal DNA in the Early and Late First Trimester.

OBJECTIVE: The aim of this work was to investigate the association between maternal and fetal characteristics and the fetal fraction at 8-14 weeks' gestation, with emphasis on the change in the fetal fraction upon repeat sampling. METHOD: One sample for cell-free DNA (cfDNA) testing was collected at the same time as the biochemical markers for combined first trimester screening (visit 1) and another at the nuchal translucency scan (visit 2). Chromosome-selective cfDNA analysis was performed on frozen plasma. RESULTS: Overall, 321 women were included at visit 1, and 307 had a repeat blood sampling. A fetal fraction was obtained in 532 samples (238 samples with repeat fetal fraction). The fetal fraction decreased with maternal BMI (p < 0.001), was lower in Asian women (p = 0.03), and increased with ß-hCG levels (p < 0.001) and gestational age (p = 0.04). Before 10 weeks' gestation, the fetal fraction was lower (p = 0.02), as was the probability of a sufficient fetal fraction (p = 0.03) after adjustment for maternal BMI. Asian women had a higher increase in fetal fraction upon repeat sampling (p < 0.001). CONCLUSION: Before 10 weeks' gestation, the fetal fraction is significantly lower but seems to increase more rapidly compared to later gestations. Presently, combined first trimester screening with cfDNA testing should not include samples before 10 weeks' gestation.

Short-Term Flow Changes in Monochorionic Survivor Twins after Ultrasound-Guided Umbilical Cord Occlusion.

OBJECTIVE: To determine hemodynamic changes by Doppler ultrasound of the living fetus during 24 h after umbilical cord occlusion (UCO) in monochorionic diamniotic (MCDA) twin pregnancies. METHOD: We conducted a prospective observational study on fetuses undergoing UCO from 2015 to 2017. Doppler parameters peak systolic velocity (PSV) and umbilical pulsatility index (PI) were obtained in the middle cerebral artery (MCA), umbilical artery (UA) and ductus venosus (DV) before and right after UCO, and at 1, 3, 6, 12, and 24 h after. We used multiple of the median (MoM) to adjust for gestational age. Spaghetti plots visualized flow changes over time. Mixed model adjusting for paired longitudinal data compared the values at different time points. RESULTS: A total of 16 women were included. MCA-PSV dropped within the first hour after surgery from 0.91 to 0.82 MoM (p = 0.08). MCA-PI and UA-PI increased in the first hour from 0.75 to 0.91 MoM (p = 0.02) and 0.94 to 0.98 MoM (p = 0.22), respectively. The DV-PIV increased to 1.14 MoM 3 h after surgery (p = 0.07). The spaghetti plots illustrated the small changes within the first hours and showed a stabilization of flow measurements near initial values 24 h after UCO. CONCLUSION: Within the first hours after UCO the circulation of the survivor twin undergoes small hemodynamic changes.

ß2-Adrenergic genotypes and risk of severe exacerbations in COPD: a prospective cohort study.

BACKGROUND: Individual susceptibility to exacerbations in chronic obstructive pulmonary disease (COPD) is likely influenced by genetic factors; however, most such variance is unexplained. We hypothesised that ß2-adrenergic receptor genotypes, Gly16Arg (rs1042713, c.46G>A) and Gln27Glu (rs1042714, c.79C>G) influence risk of severe exacerbations in COPD. METHODS: Among 96 762 individuals in the Copenhagen General Population Study, we identified 5262 with COPD (forced expiratory volume in one second divided by forced vital capacity, FEV1/FVC, below 0.7, FEV1 less than 80% of predicted value, age above 40 years and no asthma) who had genotyping performed. Severe exacerbations were defined as acute admissions due to COPD during 5 years of follow-up (mean 3.4 years). 923 individuals with COPD diagnosed similarly in the Copenhagen City Heart Study (CCHS) were used for replication analyses. RESULTS: We recorded 461 severe exacerbations in 5262 subjects. The HRs for severe exacerbations were 1.62 (95% CI 1.30 to 2.03, p=0.00002) for 16Gly/Arg heterozygotes and 1.41 (1.04 to 1.91, p=0.03) for 16Arg homozygotes, compared with 16Gly homozygotes. HRs were 1.35 (1.03 to 1.76, p=0.03) for 27Gln/Glu heterozygotes and 1.49 (1.12 to 1.98, p=0.006) for 27Gln homozygotes, compared with 27Glu homozygotes. Similar trends were observed in the CCHS. Among 27Gln homozygotes only, HRs were 5.20 (1.81 to 14.9, p=0.002) for 16Gly/Arg heterozygotes and 4.03 (1.40 to 11.6, p=0.01) for 16Arg homozygotes, compared with 16Gly homozygotes. CONCLUSION: Common ß2-adrenergic receptor genotypes influence risk of severe exacerbations in COPD, potentially mainly by genetic influence of the 16Arg allele in rs1042713.

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.

Physical activity during pregnancy and intelligence in sons; A cohort study.

The purpose was to examine the association between exercise during pregnancy and intelligence score in offspring. We analyzed data from 4008 women from the Aarhus Birth Cohort, Aarhus University Hospital, Denmark, recruited during pregnancy from July 1989 to November 1991 and their sons who were registered at conscription at 17-20 years of age. The women gave information by self-administered questionnaires during the first trimester including leisure-time physical activity and weekly hours of sport. This information was linked to the sons' measures of intelligence by Børge Priens test scores from the Danish Conscription Registry. Only sons were included since very few women register at conscription in Denmark. The main outcome measure was the Børge Priens test score as a continuous variable and with a low score defined as <10% of the population score. Analyses were adjusted for maternal body mass index, years in school, and smoking. Sons of women with light and moderate to heavy leisure-time physical activity had lower risk of having a low intelligence score compared with sons of women with sedentary activity: adjusted odds ratio (aOR) 0.66 (95% CI 0.49;0.88) and 0.46 (95% CI 0.23;0.93), respectively. Furthermore, sons of women engaged in sports had lower risk of a low intelligence score: aOR 0.50 (95% CI 0.30; 0.83) for 1-2 h/wk and 0.62 (95% CI 0.35; 1.10) for ≥3 h/wk compared with no weekly sports activity. In conclusion, a higher level of physical activity during pregnancy was associated with a lower risk of low intelligence score in early adulthood in sons.

Long-Term Neurodevelopmental Outcome of Monochorionic Twins after Laser Therapy or Umbilical Cord Occlusion for Twin-Twin Transfusion Syndrome.

INTRODUCTION: We sought to assess the incidence of severe neurodevelopmental impairment (NDI) in monochorionic twins treated for twin-twin transfusion syndrome (TTTS) and compare it to the incidence in uncomplicated monochorionic twins. MATERIAL AND METHODS: We included TTTS pregnancies treated by fetoscopic selective laser coagulation (FSLC) or umbilical cord occlusion (UCO) in 2004-2015. Primary outcome was severe NDI defined as cerebral palsy, bilateral blindness or bilateral deafness (ICD-10 diagnoses), and severe cognitive and/or motor delay (assessed by the Ages and Stages Questionnaires [ASQ]). RESULTS: A total of 124 children after TTTS and 98 controls were followed up at 25 months of age (SD 11.4). Severe NDI was found in 8.9% of the TTTS children (10.5% [9/86] after FSLC; 5.3% [2/38] after UCO) compared to 3.1% in the control group (p = 0.10). The odds ratio for severe NDI was 1.8 in cases versus controls (p = 0.37). The total ASQ score was significantly lower in the TTTS group than in controls (p = 0.03) after FSLC (p = 0.03) and after UCO (p = 0.14). DISCUSSION: Children after TTTS appear to have a higher risk of severe NDI and score significantly lower on the ASQ compared to monochorionic twins from uncomplicated pregnancies.

Magnetic Resonance Imaging: A New Tool to Optimize the Prediction of Fetal Anemia?

INTRODUCTION: The false-positive rate in the prediction of fetal anemia is 10-15%. We investigated if a new, noninvasive MRI method used as a supplement to ultrasound could improve the prediction. METHODS: Fetuses suspected of anemia and controls were scanned in a 1.5-tesla MRI scanner 1-4 times during pregnancy. Cases were scanned before and after intrauterine blood transfusion with a T1-mapping MRI sequence in a cross-section of the umbilical vein. RESULTS: Inclusion of 8 cases and 11 controls resulted in 10 case scans (2 cases were included twice) and 33 control scans. In controls, the T1 relaxation time was 1,005-1,391 ms; in cases with severe anemia, 1,505-1,595 ms, moderate anemia 1,503-1,525 ms, and no/mild anemia 1,245-1,410 ms. After blood transfusions, values dropped to 1,123-1,288 ms. The mean value in moderate and severe anemic cases was 275 ms higher than in controls (95% CI 210-341 ms, p < 0.0001), and after blood transfusion it was comparable to controls (3 ms, 95% CI -62 to 68 ms, p = 0.934). A 1,450-ms cut-off would have identified all cases in need of blood transfusion with no false-positive cases. CONCLUSIONS: Our findings indicate a potential for this new MRI method to improve the prediction of fetal anemia as a supplement to ultrasound.

Positive view and increased likely uptake of follow-up testing with analysis of cell-free fetal DNA as alternative to invasive testing among Danish pregnant women.

INTRODUCTION: The aim of this study was to investigate the attitude (view, likely uptake and preferred strategy) towards cell-free fetal DNA (cfDNA) testing among pregnant women before a first-trimester risk assessment for trisomy 21 (unselected women) and after obtaining a high risk. MATERIAL AND METHODS: Unselected and high-risk women attending first-trimester screening (Rigshospitalet, Copenhagen University Hospital) were invited to fill out the questionnaire Antenatal testing for Down syndrome as an online survey. RESULTS: The survey included 203 unselected and 50 high-risk women (response rates of 74.8% and 84.7%, respectively). Nearly all considered cfDNA testing a positive development in antenatal care, and 97.2% would like it to be offered. Offering cfDNA testing as an alternative to invasive testing would increase the uptake of follow-up testing compared with invasive testing alone (98.8% vs. 90.7%, p < 0.001). Women who would only accept follow up by cfDNA testing were more likely to continue an affected pregnancy (30.0% vs. 3.6%, p < 0.001) or have doubts about termination (50.0% vs. 32.1%, p < 0.001). CONCLUSIONS: Offering cfDNA testing would likely increase the uptake of follow-up testing without a corresponding rise in the termination rate of affected fetuses as some women test for information only. However, both unselected and high-risk women had overwhelmingly positive views underlining attention to avoid routinization.