Maternal obesity, interpregnancy weight changes and congenital heart defects in the offspring: a nationwide cohort study.

OBJECTIVE: To evaluate the association between maternal BMI and congenital heart defects (CHDs) in the offspring when including live births, stillbirths, aborted and terminated pregnancies and to investigate if maternal interpregnancy weight changes between the first and second pregnancy influences the risk of foetal CHDs. METHODS: A nationwide cohort study of all singleton pregnancies in Denmark from 2008 to 2018. Data were retrieved from the Danish Foetal Medicine Database, which included both pre- and postnatal diagnoses of CHDs. Children or foetuses with chromosomal aberrations were excluded. Odds ratios were calculated with logistic regression models for CHDs overall, severe CHDs and five of the most prevalent subtypes of CHDs. RESULTS: Of the 547 105 pregnancies included in the cohort, 5 442 had CHDs (1.0%). Risk of CHDs became gradually higher with higher maternal BMI; for BMI 25-29.9 kg/m2, adjusted odds ratio (aOR) 1.17 (95% CI 1.10-1.26), for BMI 30-34.9 kg/m2, aOR 1.21 (95% CI 1.09-1.33), for BMI 35-39.9 kg/m2, aOR 1.29 (95% CI 1.11-1.50) and for BMI ≥ 40 kg/m2, aOR 1.85 (95% CI 1.54-2.21). Data was adjusted for maternal age, smoking status and year of estimated due date. The same pattern was seen for the subgroup of severe CHDs. Among the atrioventricular septal defects (n = 231), an association with maternal BMI ≥ 30 kg/m2 was seen, OR 1.67 (95% CI 1.13-2.44). 109 654 women were identified with their first and second pregnancies in the cohort. Interpregnancy BMI change was associated with the risk of CHDs in the second pregnancy (BMI 2 to < 4 kg/m2: aOR 1.29, 95% CI 1.09-1.53; BMI ≥ 4 kg/m2: aOR 1.36, 95% CI 1.08-1.68). CONCLUSION: The risk of foetal CHDs became gradually higher with higher maternal BMI and interpregnancy weight increases above 2 BMI units were also associated with a higher risk of CHDs.

Clinical implementation of first trimester screening for congenital heart defects.

OBJECTIVE: To examine the feasibility and performance of implementing a standardized fetal cardiac scan at the time of a routine first-trimester ultrasound scan. METHOD: A retrospective, single-center study in an unselected population between March 2021 and July 2022. A standardized cardiac scan protocol consisting of a four-chamber and 3-vessel trachea view with color Doppler was implemented as part of the routine first-trimester scan. Sonographers were asked to categorize the fetal heart anatomy. Data were stratified into two groups based on the possibility of evaluating the fetal heart. The influence of maternal and fetal characteristics and the detection of major congenital heart disease were investigated. RESULTS: A total of 5083 fetuses were included. The fetal heart evaluation was completed in 84.9%. The proportion of successful scans increased throughout the study period from 76% in the first month to 92% in the last month. High maternal body mass index and early gestational age at scan significantly decreased the feasibility. The first-trimester detection of major congenital heart defects was 7/16, of which four cases were identified by the cardiac scan protocol with no false-positive cases. CONCLUSION: First-trimester evaluation of the fetal heart by a standardized scan protocol is feasible to implement in daily practice. It can contribute to the earlier detection of congenital heart defects at a very low false positive rate.

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.

Risks and pregnancy outcome after fetal reduction in dichorionic twin pregnancies: a Danish national retrospective cohort study.

BACKGROUND: Twin pregnancies carry a higher risk of congenital and structural malformations, and pregnancy complications including miscarriage, stillbirth, and intrauterine fetal death, compared with singleton pregnancies. Carrying a fetus with severe malformations or abnormal karyotype places the remaining healthy fetus at an even higher risk of adverse outcome and pregnancy complications. Maternal medical conditions or complicated obstetrical history could, in combination with twin pregnancy, cause increased risks for both the woman and the fetuses. To our knowledge, no previous studies have evaluated and compared the outcomes of all dichorionic twin pregnancies and compared the results of reduced twins with those of nonreduced and primary singletons in a national cohort. These data are important for clinicians when counseling couples about fetal reduction and its implications. OBJECTIVE: This study aimed to describe and compare the risks of adverse pregnancy outcomes, including the risk of pregnancy loss, in a national cohort of all dichorionic twins-reduced, nonreduced, and primary singletons. In addition, we examined the implications of gestational age at fetal reduction on gestational age at delivery. STUDY DESIGN: This was a retrospective cohort study of all Danish dichorionic twin pregnancies, including pregnancies undergoing fetal reduction and a large proportion of randomly selected primary singleton pregnancies with due dates between January 2008 and December 2018. The primary outcome measures were adverse pregnancy outcomes (defined as miscarriage before 24 weeks, stillbirth from 24 weeks, or single intrauterine fetal death in nonreduced twin pregnancies), preterm delivery, and obstetrical pregnancy complications. Outcomes after fetal reduction were compared with those of nonreduced dichorionic twins and primary singletons. RESULTS: In total, 9735 dichorionic twin pregnancies were included, of which 172 (1.8%) were reduced. In addition, 16,465 primary singletons were included. Fetal reductions were performed between 11 and 23 weeks by transabdominal needle-guided injection of potassium chloride, and outcome data were complete for all cases. Adverse pregnancy outcome was observed in 4.1% (95% confidence interval, 1.7%-8.2%) of reduced twin pregnancies, and 2.4% (95% confidence interval, 0.7%-6.1%) were delivered before 28 weeks, and 4.2% (95% confidence interval, 1.7%-8.5%) before 32 weeks. However, when fetal reduction was performed before 14 weeks, adverse pregnancy outcomes occurred in only 1.4% (95% confidence interval, 0.0%-7.4%), and delivery before 28 and 32 weeks diminished to 0% (95% confidence interval, 0.0%-5.0%) and 2.8% (95% confidence interval, 0.3%-9.7%), respectively. In contrast, 3.0% (95% confidence interval, 2.7%-3.4%) of nonreduced dichorionic twins had an adverse pregnancy outcome, and 1.9% (95% confidence interval, 1.7%-2.1%) were delivered before 28 weeks, and 7.3% (95% confidence interval, 6.9%-7.7%) before 32 weeks. Adverse pregnancy outcomes occurred in 0.9% (95% confidence interval, 0.7%-1.0%) of primary singletons, and 0.2% (95% confidence interval, 0.1%-0.3%) were delivered before 28 weeks, and 0.7% (95% confidence interval, 0.6%-0.9%) before 32 weeks. For reduced twins, after taking account of maternal factors and medical history, it was demonstrated that the later the fetal reduction was performed, the earlier the delivery occurred (P<.01). The overall risk of pregnancy complications was significantly lower among reduced twin pregnancies than among nonreduced dichorionic twin pregnancies (P=.02). CONCLUSION: In a national 11-year cohort including all dichorionic twin pregnancies, transabdominal fetal reduction by needle guide for fetal or maternal indication was shown to be safe, with good outcomes for the remaining co-twin. Results were best when the procedure was performed before 14 weeks.

Triple trouble: uncovering the risks and benefits of early fetal reduction in trichorionic triplets in a large national Danish cohort study.

BACKGROUND: Triplet pregnancies are high risk for both the mother and the infants. The risks for infants include premature birth, low birthweight, and neonatal complications. Therefore, the management of triplet pregnancies involves close monitoring and may include interventions, such as fetal reduction, to prolong the pregnancy and improve outcomes. However, the evidence of benefits and risks associated with fetal reduction is inconsistent. OBJECTIVE: This study aimed to compare the outcomes of trichorionic triplet pregnancies with and without fetal reduction and with nonreduced dichorionic twin pregnancies and primary singleton pregnancies. STUDY DESIGN: All trichorionic triplet pregnancies in Denmark, including those with fetal reduction, were identified between 2008 and 2018. In Denmark, all couples expecting triplets are informed about and offered fetal reduction. Pregnancies with viable fetuses at the first-trimester ultrasound scan and pregnancies not terminated were included. Adverse pregnancy outcome was defined as a composite of miscarriage before 24 weeks of gestation, stillbirth at 24 weeks of gestation, or intrauterine fetal death of 1 or 2 fetuses. RESULTS: The study cohort was composed of 317 trichorionic triplet pregnancies, of which 70.0% of pregnancies underwent fetal reduction to a twin pregnancy, 2.2% of pregnancies were reduced to singleton pregnancies, and 27.8% of pregnancies were not reduced. Nonreduced triplet pregnancies had high risks of adverse pregnancy outcomes (28.4%), which was significantly lower in triplets reduced to twins (9.0%; difference, 19.4%, 95% confidence interval, 8.5%-30.3%). Severe preterm deliveries were significantly higher in nonreduced triplet pregnancies (27.9%) than triplet pregnancies reduced to twin pregnancies (13.1%; difference, 14.9%, 95% confidence interval, 7.9%-21.9%). However, triplet pregnancies reduced to twin pregnancies had an insignificantly higher risk of miscarriage (6.8%) than nonreduced twin pregnancies (1.1%; difference, 5.6%; 95% confidence interval, 0.9%-10.4%). CONCLUSION: Triplet pregnancies reduced to twin pregnancies had significantly lower risks of adverse pregnancy outcomes, severe preterm deliveries, and low birthweight than nonreduced triplet pregnancies. However, triplet pregnancies reduced to twin pregnancies were potentially associated with a 5.6% increased risk of miscarriage.

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.

The impact of anti-hypertensive treatment on foetal growth and haemodynamics in pregnant women with pre-existing diabetes - An explorative study.

OBJECTIVES: To explore the impact of anti-hypertensive treatment of pregnancy-induced hypertension on foetal growth and hemodynamics in women with pre-existing diabetes. METHODS: A prospective cohort study of 247 consecutive pregnant women with pre-existing diabetes (152 type 1 diabetes; 95 type 2 diabetes), where tight anti-hypertensive treatment was initiated and intensified (mainly with methyldopa) when office blood pressure (BP) ≥135/85 mmHg and home BP ≥130/80 mmHg. Foetal growth was assessed by ultrasound at 27, 33 and 36 weeks and foetal hemodynamics were assessed by ultrasound Doppler before and 1-2 weeks after initiation of anti-hypertensive treatment. RESULTS: In 215 initially normotensive women, anti-hypertensive treatment for pregnancy-induced hypertensive disorders was initiated in 42 (20%), whilst 173 were left untreated. Chronic hypertension was present in 32 (13%). Anti-hypertensive treatment for pregnancy-induced hypertensive disorders was not associated with foetal growth deviation (linear mixed model, p = 0.681). At 27 weeks, mainly before initiation of anti-hypertensive treatment, the prevalence of small foetuses with an estimated foetal weight <10th percentile was 12% in women initiating anti-hypertensive treatment compared with 4% in untreated women (p = 0.054). These numbers were close to the prevalence of birth weight ≤10th percentile (small for gestational age (SGA)) (17% vs. 4%, p = 0.003). Pulsatility index in the umbilical and middle cerebral artery remained stable after the onset of anti-hypertensive treatment in a representative subgroup (n = 12, p = 0.941 and p = 0.799, respectively). CONCLUSION: There is no clear indication that antihypertensive treatment causes harm in this particular at-high-risk group of pregnant women with diabetes, such that a larger well-designed study to determine the value of tight antihypertensive control would be worthwhile.

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.

A Rare Dichorionic Triamniotic Triplet Pregnancy with Spontaneous Twin Anemia-Polycythemia Sequence between Two Dichorionic Fetuses.

INTRODUCTION: This report presents a rare case of spontaneous twin anemia-polycythemia sequence (TAPS) between two dichorionic fetuses in a spontaneous, homozygotic, dichorionic, triamniotic, triplet pregnancy treated with multiple intrauterine blood transfusions (IUTs) and partial exchange transfusions (PETs). CASE PRESENTATION: The pregnancy was diagnosed with stage IV TAPS at gestational week 25+1. The patient was treated with laser surgery combined with multiple IUTs and PETs. The triplets were delivered at a planned caesarean section at gestational week 28+1 with postnatal hemoglobin values of 18.21, 26.43, and 11.92 g/dL in triplet 1, 2, and 3, respectively. At 4 years of age, triplet 1 is considered healthy, triplet 2 is diagnosed with mild mental retardation, and triplet 3 with profound mental retardation and dystonic cerebral palsy. DISCUSSION: This is an extremely rare case of TAPS between dichorionic fetuses in a triplet pregnancy, and routine surveillance with measurement of middle cerebral artery peak systolic velocity in dichorionic pregnancies may contribute to the detection of similar cases in the future. Furthermore, this case contributes with rare long-term follow-up data of children treated for high-stage TAPS with multiple IUTs and PETs.

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.

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.

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.

Refractory Fetal Supraventricular Tachycardia with Hydrops Successfully Converted by Intraperitoneal Flecainide in the Fetus: A Case Report.

INTRODUCTION: Supraventricular tachycardia is the most common fetal tachyarrhythmia and if persistent often associated with fetal hydrops which can cause intrauterine and neonatal death. CASE PRESENTATION: We present a case of early second trimester supraventricular tachycardia in a hydropic fetus, initially refractory to transplacental treatment. CONCLUSION: The supraventricular tachycardia was successfully treated when supplemented with intraperitoneal flecainide in the fetus.

Risk of miscarriage in women conceiving after medically assisted reproduction with an ultrasound-verified viable pregnancy at 6-8 weeks' gestation.

RESEARCH QUESTION: What is the risk of miscarriage after a viable fetus verified on ultrasound at 6-8 weeks' gestation among women who conceive with medically assisted reproduction (MAR), stratified by type of fertility treatment? DESIGN: A nationwide register-based cohort study of women identified in the Danish ART-Registry with a viable singleton pregnancy at 6-8 weeks' gestation between 2007 and 2010 (n = 10,011). Women were identified from The Danish Fetal Medicine Database (DFMD), which holds information on early (between 6-8 and 11-14 weeks) and late (between 11-14 and 22 weeks) miscarriages. The late miscarriage rate was compared with a control group of naturally conceived pregnancies with a viable fetus at 11-14 weeks' gestation from 2008 to 2010, identified in the DFMD (n = 146,932). RESULTS: In the MAR1 cohort, the overall miscarriage rate was 11.8% (1091/9261) after an ultrasound verified viable pregnancy at 6-8 weeks' gestation. Most miscarriages occurred before the 11-14-week scan (1035/1091 [94.9%]). The early miscarriage rate was slightly higher in women who conceived with frozen embryo transfer compared with intrauterine insemination (IUI), corresponding to an adjusted OR of 1.31 (1.02 to 1.68). We found no significant risk associated with IVF and intracytoplasmic sperm injection compared with IUI pregnancies. The late miscarriage rate was 0.8% in women conceiving with MAR and 0.6% among controls (P = 0.013). CONCLUSIONS: After adjustment for maternal characteristics, none of the fertility treatment types were associated with an increased risk of miscarriage compared with naturally conceiving women.

Population-Based Screening for Trisomies and Atypical Chromosomal Abnormalities: Improving Efficacy using the Combined First Trimester Screening Algorithm as well as Individual Risk Parameters.

AIM: To examine the performance of the combined First Trimester Screening (cFTS) algorithm when outliers of 4 risk parameters (maternal age, nuchal translucency (NT) thickness, PAPP-A and ß-hCG) were included in the classification of "high-risk". METHODS: A retrospective analysis of singleton pregnancies undergoing cFTS between 2008 and 2011 in Denmark. Abnormal karyotypes were classified as trisomy 21 (T21), trisomy 13 (T13) and trisomy 18 (T18), sex chromosome aberrations and atypical abnormal karyotypes. RESULTS: cFTS was completed in 193,638 pregnancies. In 10,205 (5.3%) cases, cytogenetic or molecular analysis was performed pre- or postnatally. An abnormal karyotype was seen in 1,122 (11.0%). The algorithm identified 87% of T21, 80% of T13, 75% of T18, 79% of sex chromosome aberrations and 35% of atypical abnormal karyotypes. Additional classification of a single risk parameter outlier (low PAPP-A or free ß-hCG (< 0.2 MoMs), high ß-hCG (≥5.0 MoMs), maternal age ≥45 years or NT ≥3.5 mm) as being at high-risk would have improved detection rates to 88, 80, 81, 81 and 37% respectively. The screen positive rate increased from 4.4 to 4.8%. DISCUSSION: Addition of outliers of the 4 parameters used in cFTS algorithm will lead to a statistically significant increase in detection rates for chromosomal abnormality.

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.

Parental Decisions about Prenatal Screening and Diagnosis among Infants with Trisomy 21 in a National Cohort with High Uptake of Combined First-Trimester Screening.

INTRODUCTION: The aim was to investigate the parental decisions about prenatal screening and diagnosis among infants with trisomy 21 (T21) in a national cohort with high uptake of combined first-trimester screening (cFTS). MATERIAL AND METHODS: This was a nationwide population-based study including infants born in 2009-2012. Information from the cFTS, fetal karyotype results and pregnancy outcome was obtained from the Danish Fetal Medicine Database on all women with a cFTS risk assessment. Cut-off for referral for invasive testing was ≥1:300. Karyotype results from pregnancies with no cFTS were obtained from the Danish Cytogenetic Central Registry. RESULTS: The uptake rate of cFTS was 91.6%, and 82.8% (8,032/9,704) of the screen-positive women opted for invasive testing. Overall, 82.2% (454/552) chose to terminate an affected pregnancy. In the 4-year period, 102 of 232,962 singletons were born alive with T21. The cFTS risk was true-positive, false-negative or not obtained in 21.6, 48.0 and 30.4%, respectively, of these pregnancies. DISCUSSION: In this large national cohort, 4.4 per 10,000 live-born infants had T21. Of 102 infants with T21 from 2009 to 2012, 52.0% were born after the women had not opted for cFTS or were true-positive but declined invasive testing or termination, and 48.0% were born after a false-negative risk assessment.

Nuchal translucency distributions for different chromosomal anomalies in a large unselected population cohort.

OBJECTIVE: To describe the distribution of the fetal nuchal translucency thickness (NT) according to type of chromosomal aberration in a large unselected population. METHODS: Data on pregnancies with an NT measurement performed at gestational age 11 + 3 - 13 + 6 weeks from 2008 to 2011 were retrieved from the Danish National Fetal Medicine Database. Information on any genetic analysis for aneuploidy performed pre- or postnatally was also obtained. The abnormal results were grouped into 14 types of chromosomal anomalies. Distributions of NT measurements were summarized by aberration and compared with the normal/no karyotype group. RESULTS: A total of 215 223 singleton pregnancies were included in the cohort; 10548 had a normal karyotype and 1286 had an aberration. Plots of the NT measurements showed that like trisomy 21, 18 and 13 and monosomy X, the distribution for the unbalanced translocations was shifted towards larger NTs. The distributions for the balanced translocations, the uncommon trisomies and the triploidies more closely resembled that of the normal/no karyotype population. CONCLUSION: Fetuses with aneuploidies have NT distributions visually different from normal fetuses, with the exception of triploidies and uncommon autosomal trisomies. The distributions differ in shape according to type of chromosomal anomaly. © 2015 John Wiley & Sons, Ltd.