Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction.

PURPOSE: To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). MATERIALS AND METHODS: A prospective European multicenter observational study included women with a singleton pregnancy, 32+ 0-36+ 6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. RESULTS: 856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values. CONCLUSION: An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.

Fetal cerebral Doppler changes and outcome in late preterm fetal growth restriction: prospective cohort study.

OBJECTIVES: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. METHODS: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. RESULTS: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. CONCLUSION: In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Cost effectiveness of nifedipine compared with atosiban in the treatment of threatened preterm birth (APOSTEL III trial).

OBJECTIVE: To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. DESIGN: An economic analysis alongside a randomised clinical trial (the APOSTEL III study). SETTING: Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium. POPULATION: Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban. METHODS: We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses. MAIN OUTCOME MEASURES: Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes. RESULTS: Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: €34,897 versus €43,376, mean difference (MD) -€8479 [95% confidence interval (CI) -€14,327 to -€2016)]; multiple pregnancies: €90,248 versus €102,292, MD -€12,044 (95% CI -€21,607 to € -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group. CONCLUSION: Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation. TWEETABLE ABSTRACT: In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban.

Assessment of venous hemodynamics and volume homeostasis during pregnancy: recommendations of the International Working Group on Maternal Hemodynamics.

Venous hemodynamics and volume homeostasis are important aspects of cardiovascular physiology. However, today their relevance is still very much underappreciated. Their most important role is maintenance and control of venous return and, as such, cardiac output. A high-flow/low-resistance circulation, remaining constant under physiological circumstances, is mandatory for an uncomplicated course of pregnancy. In this article, characteristics of normal and abnormal venous and volume regulating functions are discussed with respect to normal and pathologic outcomes of pregnancy, and current (non-invasive) methods to assess these functions are summarized. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Maternal venous Doppler characteristics are abnormal in pre-eclampsia but not in gestational hypertension.

OBJECTIVE: To compare functional characteristics of maternal thoraco-abdominal arteries and veins in proteinuric and non-proteinuric hypertension in pregnancy. METHODS: This retrospective study included women with singleton pregnancies during the third trimester, which were either uncomplicated or complicated with different clinical types of hypertension: non-proteinuric gestational hypertension (GH), early-onset pre-eclampsia (PE) diagnosed < 34 weeks or late-onset PE diagnosed ≥ 34 weeks. Demographic maternal and neonatal data were recorded, together with maternal serum and urine analytes. All women underwent standardized automated blood-pressure measurement, together with non-invasive impedance cardiography (ICG), for measurement of cardiac output (CO), aortic flow velocity index (VI) and aortic flow acceleration index (ACI). A standardized combined Doppler-electrocardiography assessment of maternal venous hemodynamics was performed to measure renal interlobar vein impedance index (RIVI), hepatic vein impedance index (HVI) and venous pulse transit time (VPTT) in liver and kidneys. Finally, resistance index (RI), pulsatility index (PI) and arterial pulse transit time (APTT) were measured in the uterine arcuate arteries. Mann-Whitney U-tests and Fisher's exact tests were used for intergroup comparisons, and linear dependence between variables was assessed using Pearson's correlation coefficient (r). RESULTS: A total of 150 pregnancies were evaluated: 22 with uncomplicated pregnancy, 41 GH, 31 early PE and 56 late PE. Aortic VI and ACI were lower in GH, early PE and late PE than in uncomplicated pregnancy. Both early PE and late PE differed from GH by having shorter APTT in the uterine arcuate arteries and higher RIVI. Hemodynamic abnormalities were most pronounced in early PE, during which uterine arcuate artery RI was higher and VPTT in kidneys was shorter than in late PE. There was a significant correlation between degree of proteinuria and RIVI for the left (r = 0.381) and right (r = 0.347) kidney in late PE, but this was not true for early PE. CONCLUSIONS: There is a gradient of worsening arterial and venous hemodynamic abnormalities from GH to late PE and then to early PE. Venous hemodynamic abnormalities are present only in PE, with a linear correlation between proteinuria and RIVI in late PE. The role of the maternal venous compartment in the pathophysiology and etiology of PE-related symptoms may be much more important than considered at present.

Variation of DNA methylation in candidate age-related targets on the mitochondrial-telomere axis in cord blood and placenta.

BACKGROUND: Epigenetics is tissue-specific and potentially even cell-specific, but little information is available from human reproductive studies about the concordance of DNA methylation patterns in cord blood and placenta, as well as within-placenta variations. We evaluated methylation levels at promoter regions of candidate genes in biological ageing pathways (SIRT1, TP53, PPARG, PPARGC1A, and TFAM), a subtelomeric region (D4Z4) and the mitochondrial genome (MT-RNR1, D-loop). METHODS: Ninety individuals were randomly chosen from the ENVIRONAGE birth cohort to evaluate methylation concordance between cord blood and placenta using highly quantitative bisulfite-PCR pyrosequencing. In a subset of nineteen individuals, a more extensive sampling scheme was performed to examine within-placenta variation. RESULTS: The DNA methylation levels of the subtelomeric region and mitochondrial genome showed concordance between cord blood and placenta with correlation coefficients ranging from r = 0.31 to 0.43, p ≤ 0.005, and also between the maternal and foetal sides of placental tissue (r = 0.53 to 0.72, p ≤ 0.05). For the majority of targets, an agreement in methylation levels between four foetal biopsies was found (with intra-class correlation coefficients ranging from 0.16 to 0.72), indicating small within-placenta variation. CONCLUSIONS: The methylation levels of the subtelomeric region (D4Z4) and mitochondrial genome (MT-RNR1, D-loop) showed concordance between cord blood and placenta, suggesting a common epigenetic signature of these targets between tissues. Concordance was lacking between the other genes that were studied. In placental tissue, methylation patterns of most targets on the mitochondrial-telomere axis were not strongly influenced by sample location.

Identification of peripartum near-miss for perinatal audit.

INTRODUCTION: Today, perinatal audit focuses basically on cases of perinatal mortality. In most centres in Western Europe, perinatal mortality is low. Identification of metabolic acidosis at birth may increase index cases eligible for evaluation of perinatal care, and this might improve quality of perinatal audit. The aim of this study is to assess the incidence of metabolic acidosis at birth in order to estimate its impact on perinatal audit. PATIENTS AND METHODS: Cord blood was analysed for every neonate born between January 1, 2010 and December 31, 2012 in Ziekenhuis Oost-Limburg, Genk. Acidosis was defined as an umbilical arterial pH ≤ 7.05 with or without a venous pH ≤ 7.17. Respiratory acidosis (RA) was defined as acidosis with normal base excess, and metabolic acidosis (MA) was defined as acidosis with an arterial or venous base excess ≤ -10 mmol/L. In case of failed cord blood sampling, 5 minute Apgar score ≤ 6 was considered as the clinical equivalent of MA. Retrospective chart review of obstetric and paediatric files was performed for all cases of MA, together with review of paediatric follow-up charts from at least 6 months after birth. Perinatal asphyxia was defined as biochemical evidence for MA at birth, associated with early onset neonatal encephalopathy and long-term symptoms of cerebral palsy. RESULTS: In a total of 6614 babies, perinatal death up to 7 days of life occurred in 40 babies (6.0‰). Acidosis was present in 183 neonates (2.8%), of which 130 (2.0%) had RA and 53 (0.8%) had MA. Of the 173 neonates with unknown pH values, 6 had Apgar scores ≤ 6. Of 59 babies born with MA or its clinical equivalent, 52 (88.1%) showed no neurologic symptoms at birth. Two (3.4%) died in the early neonatal period, one after abruptio placentae and one due to chorioamnionitis and severe prematurity. Five (8.5%) MA babies had symptoms of early onset neonatal encephalopathy, which recovered in three (5.1%), and persisted long-term in two others (3.4%). The two babies with cerebral palsy (prevalence 1/3300) were both born after instrumental vaginal delivery for foetal distress. CONCLUSION: In our study cohort, the incidence of perinatal mortality is 6‰. The incidence of metabolic acidosis is 9‰. Addition of cases of metabolic acidosis to those of mortality doubles index cases eligible for perinatal audit. The incidence of babies surviving with cerebral palsy after metabolic acidosis at birth is very low (0.3‰). Our results suggest that instrumental delivery for foetal distress might be a risk factor for metabolic acidosis with persisting neurologic dysfunction. Our study illustrates that identification of peripartum near-miss is useful for perinatal audit.

Validation of 3D power Doppler and VOCAL software in the sonographic assessment of hepatic venous flow.

UNLABELLED:  AIM: To evaluate the reproducibility of three-dimensional power Doppler ultrasonography (3D-PDU) and the repeatability of Virtual Organ Computer-aided AnaLysis (VOCAL) software in the assessment of hepatic venous flow in ten healthy non-pregnant individuals. METHODS: Visualization of hepatic veins was performed using both intra- and subhepatic approaches; These examinations were repeated twice. Vascular indices were obtained for each examination in a reference point using both small and large volume samples (3 times per type of volume sample). Intraclass Correlation Coefficients and Pearson's Product-Moment Correlation Coefficient were calculated to assess reproducibility and repeatability, respectively. RESULTS: Intraclass Correlation Coefficients were more than 0.60 in small volumes, but variable in large volumes for both approaches. However, re-identification of the reference point failed in 30% using the subhepatic approach. Repeatability was high for all VOCAL analyses (Pearson's Product-Moment Correlation Coefficient > 0.98). CONCLUSIONS: These results indicate reliable use of intrahepatic small volume samples in clinical application and invite to explore the role of this technology in the assessment of hepatic venous hemodynamics.

Effects of lifestyle intervention in obese pregnant women on gestational weight gain and mental health: a randomized controlled trial.

OBJECTIVE: Lifestyle intervention could help obese pregnant women to limit their weight gain during pregnancy and improve their psychological comfort, but has not yet been evaluated in randomized controlled trials. We evaluated whether a targeted antenatal lifestyle intervention programme for obese pregnant women influences gestational weight gain (GWG) and levels of anxiety or depressed mood. DESIGN AND SUBJECTS: This study used a longitudinal interventional design. Of the 235 eligible obese pregnant women, 205 (mean age (years): 29±4.5; body mass index (BMI, kg m(-)(2)): 34.7±4.6) were randomized to a control group, a brochure group receiving written information on healthy lifestyle and an experimental group receiving an additional four antenatal lifestyle intervention sessions by a midwife trained in motivational lifestyle intervention. Anxiety (State and Trait Anxiety Inventory) and feelings of depression (Edinburgh Depression Scale) were measured during the first, second and third trimesters of pregnancy. Socio-demographical, behavioural, psychological and medical variables were used for controlling and correcting outcome variables. RESULTS: We found a significant reduction of GWG in the brochure (9.5 kg) and lifestyle intervention (10.6 kg) group compared with normal care group (13.5 kg) (P=0.007). Furthermore, levels of anxiety significantly decreased in the lifestyle intervention group and increased in the normal care group during pregnancy (P=0.02); no differences were demonstrated in the brochure group. Pre-pregnancy BMI was positively related to levels of anxiety. Obese pregnant women who stopped smoking recently showed a significant higher GWG (ß=3.04; P=0.01); those with concurrent gestational diabetes mellitus (GDM) (ß=3.54; P=0.03) and those who consumed alcohol on a regular base (ß=3.69; P=0.04) showed significant higher levels of state anxiety. No differences in depressed mood or obstetrical/neonatal outcomes were observed between the three groups. CONCLUSIONS: A targeted lifestyle intervention programme based on the principles of motivational interviewing reduces GWG and levels of anxiety in obese pregnant women.

Impedance cardiography in uncomplicated pregnancy and pre-eclampsia: a reliability study.

It has been reported that cardiac contractility is altered in pre-eclampsia compared with normal pregnancy. Because of the non-invasive nature of impedance cardiography (ICG), this method is gaining popularity in the obstetric field. We assessed the reliability of ICG measurements in uncomplicated 3rd trimester pregnancies (UP) and pre-eclamptic pregnancies (PE). ICG measurements were recorded before and after three position changes, and this examination was done twice (session 1 and 2) per subject. For each of the 22 haemodynamic parameters, inter- and intrasession Pearson's correlation coefficients (PCC) were calculated for mean values of 30 measurements per position per subject. PCC was consistently ≥ 0.80 for contractility parameters 'acceleration-', 'velocity-' and 'heather-index' in both UP and PE. These data illustrate that correlation between repeated ICG measurements of cardiac contractility is high under standardised conditions, and that ICG may be useful to study changes of cardiac contractility in pregnancy.

Time interval between maternal electrocardiogram and venous Doppler waves in normal pregnancy and preeclampsia: a pilot study.

PURPOSE: To evaluate the time interval between maternal electrocardiogram (ECG) and venous Doppler waves at different stages of uncomplicated pregnancy (UP) and in preeclampsia (PE). MATERIALS AND METHODS: Cross-sectional pilot study in 40 uncomplicated singleton pregnancies, categorized in four groups of ten according to gestational age: 10 - 14 weeks (UP1), 18 - 23 weeks (UP2), 28 - 33 weeks (UP3) and ≥ 37 weeks (UP4) of gestation. A fifth group of ten women with PE was also included. A Doppler flow examination at the level of renal interlobar veins (RIV) and hepatic veins (HV) was performed according to a standard protocol, in association with a maternal ECG. The time interval between the ECG P-wave and the corresponding A-deflection of the venous Doppler waves was measured (PA), and expressed relative to the duration of the cardiac cycle (RR), and labeled PA/RR. RESULTS: In hepatic veins, the PA/RR is longer in UP 4 than in UP 1 (0.48 ± 0.15 versus 0.29 ± 0.09, p ≤ 0.001). When all UP groups were compared, the PA/RR increased gradually with gestational age. In PE, the HV PA/RR is shorter than in UP 3 (0.25 ± 0.09 versus 0.42 ± 0.14, p < 0.01) and this difference persisted under anti-hypertensive treatment (0.28 ± 0.06 versus 0.42 ± 0.14, p ≤ 0.01, n = 6). Similar results were found in both kidneys. In UP 1 but not in UP 3 or UP 4, the HV PA/RR is shorter in the liver than in the left and right kidney (0.29 ± 0.09 versus 0.38 ± 0.12, p < 0.01, and versus 0.36 ± 0.09, p ≤ 0.01). CONCLUSION: The PA/RR is organ-specific and gestation-dependent, and is considered to relate to venous vascular tone and/or intravascular filling. Increased values at advanced gestational stages are consistent with known features of maternal cardiovascular adaptation. Shorter values in preeclampsia are consistent with maternal cardiovascular maladaptation mechanisms. Our pilot study invites more research of the relevance of the time interval between maternal ECG and venous Doppler waves as a new parameter for studying the gestational cardiovascular (patho)physiology of the maternal venous compartment by duplex sonography.

OS095. Impedance cardiography: A straightforward and reliable tool to evaluate differences of cardiac reflex response between normal pregnancy and pre-eclampsia.

INTRODUCTION: Reflex responses of cardiac cycle time intervals (CCTI) can be measured by echocardiography, and are reported to differ between uneventful pregnancy (UP) and pre-eclampsia (PE). It is unknown whether impedance cardiography (ICG) is a useful method to measure CCTI during pregnancy. OBJECTIVES: ICG measurements of CCTI before and after orthostatic challenge are evaluated in UP and in the clinical phase of PE. METHODS: Examinations were performed twice in 16 UP (30-36 weeks), and once in 30 early PE (EPE, <34 weeks) and in 32 late PE (LPE, ⩾34 weeks). A 3rd generation ICG device using a 4 electrode arrangement (NICCOMO, Medis, Germany) was used to measure CCTI in supine position and after moving to upright position. The pre-ejection period (PEP) is the time-interval between ventricular depolarisation and start of aortic flow. The left ventricular ejection time (LVET) is the time-interval between opening and closing of the aortic valve. Diastolic time (DT) is heart period duration - (PEP+LVET). Orthostatic-induced changes from supine to upright position (cardiac reflex response or CRR) were evaluated using One-sample Wilcoxon Signed Rank Tests. All CRRs in EPE and LPE were compared to UP using Mann-Whitney U tests. Data are represented as medians (interquartile ranges). RESULTS: Maternal age was comparable between all groups [29 (26-32) years; p⩾0.47]. Gestational age was comparable between both early [31 (28-32) vs 31 (27-33) weeks] and late [37 (36-39) vs 38 (36-39) weeks] third trimester UP and PE [p⩾0.38]. Pre-gestational BMI was higher in EPE compared to UP [26 (24-32) vs 23 (21-24); p<0.01]. This was not true for LPE [25 (23-28); p=0.06]. Birth weight percentiles were lower in both EPE and LPE compared to UP [UP: 44 (38-78), EPE: 18 (5-28), LPE: 31 (18-59); p<0.05], and also lower in EPE compared to LPE [p=0.03]. CRRs within each group are shown in Table 1. The CRRs of PEP were significantly different between UP and both EPE and LPE [p⩽0.01], due to orthostatic-induced increase in PE but not in UP . CONCLUSION: Our study confirms that orthostasis does not change PEP in UP but induces a significant increase of PEP in PE. The increased reflex-induced duration of isovolumetric contraction time can be explained by a decreased left ventricular performance in the clinical phase of PE as compared to UP. ICG turns out to be a straightforward and useful method to evaluate these hemodynamic features.

PP018 Cardiac reflex responses measured by impedance cardiography are different between low and high cardiac output pre-eclampsia.

INTRODUCTION: Pre-eclampsia (PE) has been categorised into subtypes depending on low or high cardiac output (CO) states. Are cardiac reflex responses (CRR) different between these two subtypes? OBJECTIVES: Impedance cardiography (ICG) measurements of cardiac cycle time intervals (CCTI) before and after orthostatic challenge are evaluated in the clinical phase of PE with low and high CO (LPE and HPE, respectively). METHODS: Examinations were performed in 25 LPE (CO⩽7l/min) and 16 HPE (CO⩾9l/min). A third generation ICG device using a four electrode arrangement (NICCOMO, Medis, Germany) was used to measure CCTI in supine position and after moving to upright position. The pre-ejection period (PEP) is the time-interval between ventricular depolarisation and start of aortic flow. The left ventricular ejection time (LVET) is the time-interval between opening and closing of the aortic valve. Systolic time ratio (STR) is PEP/LVET. Diastolic time (DT) is the heart period duration - (PEP+LVET). Time intervals were expressed as a percentage of the heart period duration, i.e. PEPi, LVETi and DTi. Orthostatic-induced changes from supine to upright position (cardiac reflex response or CRR) were evaluated using One-sample Wilcoxon Signed Rank Tests. All CRRs were compared between LPE and HPE using Mann-Whitney U tests. Data are presented as medians (interquartile ranges). RESULTS: Maternal age was comparable between LPE and HPE [29 (26-34) vs 28 (26-33) years; p=0.55]. This was also true for gestational age [34 (30-38) vs 36 (31-39) weeks; p=0.50], and pre-gestational BMI [24 (22-30) vs 25 (24-32); p=0.21]. Birth weight percentiles were lower in LPE compared to HPE [18 (5-31) vs 44 (18-83); p<0.01]. CRRs within each group are shown in Table 1. CRRs of PEP, PEPi and DT were different between LPE and HPE [p⩽0.04], whereas changes in LVET, LVETi, DTi and STR were not [p⩾0.09]. Reflex-induced changes of diastolic blood pressure and heart rate (HR) were not significantly different between LPE and HPE [p⩾0.41]. CONCLUSION: Orthostasis does not change PEP in HPE, but induces a significant increase of PEP in LPE. PEP is dependent on HR, preload, afterload and sympathetic activity. There is no difference in the reflex-induced response of HR, DBP (∼afterload), and STR (∼sympathetic activity) between the two groups. This suggests that the orthostatic-induced change in the isovolumetric contraction time in LPE is preload-induced. Our observations suggest that hemodynamic background mechanisms behind LPE and HPE are different, and support the view that these subtypes are two different clinical entities.

Increasing prevalence of macrosomia in Flanders, Belgium: an indicator of population health and a burden for the future.

Macrosomia, defined as birth weight > 4 kg, increased in Flanders from 7.3% (4899/67143) in 1991 to 8.63% (6034/69924) in 2010 (p < 0.0001) in singleton pregnancies at term. There are at least 3 important factors contributing to this evolution. (1) Increase of maternal stature and length: during the last century, mean length of Belgian women increased with approximately 10cm to the current value of 1.66 m. (2) Increase of maternal age: the proportion of pregnant women aged 35 years or more increased significantly from 6.1% in 1991 to 14.3% in 2010. (3) Increase of maternal overweight or obesity: between 1994 and 2000, there was an increase of 4% for both overweight and obesity in women and today, 44% of Belgians are overweight (BMI > 25 kg/m²), and 12% are obese (BMI > 30 kg/m²). From these data, rate and increase of macrosomia can be -considered indirect indicators of general public health. Next to the risks for obstetrical complications, neonates > 4 kg are at risk for development of adult obesity and type 2 diabetes with related diseases, such as hypertension and metabolic syndrome. As adults, they also tend to deliver macrosomic baby's themselves. As such, macrosomia at birth is a burden for a community's future health status, health care and related costs. Prenatal health care workers should be aware of the relevance to prevent macrosomia in the first generation by -implementing guidelines on nutrition, physical activity and appropriate weight gain into routine preconceptional and prenatal care, screening for gestational diabetes with strict monitoring of blood sugar levels in affected -individuals, and promotion of breastfeeding.

Difficult prenatal diagnosis: fetal coarctation.

The prenatal diagnosis of fetal coarctation is still challenging. It is mainly suspected by ventricular disproportion (smaller left ventricle than right ventricle). The sensitivity of ventricular discrepancy is however moderate for the diagnosis of coarctation and there is a high false positive rate. Prenatal diagnosis of coarctation is important because the delivery can be arranged in a centre with a pediatric cardiac intensive careand this reduces postnatal complications and longterm morbidity. For many years the prenatal diagnosis of coarctation has been investigated to improve specificity and sensitivity by several of measurements. This article reviews all relevant articles from 2000 until 2011 searching pubmed and the reference list of interesting articles. An overview of specific measurements and techniques that can improve the diagnosis of coarctation has been made, such as the isthmus diameter, ductal diameter, isthmus/ductal ratio, z-scores derived from measurements of the distal aortic isthmus and arterial duct, the presence of a shelf andisthmal flow disturbance. Also 3-dimensional (3D) and 4-dimensional (4D) imaging with or without STIC has been -suggested to be used as newer techniques to improve diagnosis of coarctation in fetal life. Although more methods regarding prenatal diagnosis of coarctationare being investigated, the ultrasound specialist remains challenged to correctly diagnose this cardiac anomaly in prenatal life.