A longitudinal study on the effect of obesity upon circulating renin-angiotensin system in normal pregnancy.

BACKGROUND AND AIMS: Obesity is the most common health issue in women of reproductive age, which profoundly affects maternal-fetal health. Despite progress in understanding key inflammatory and metabolic changes, the pathogenesis of the cardiovascular phenotype of obese pregnant women remains to be fully understood. This study aimed at: (i) evaluating the changes of the renin-angiotensin system (RAS) throughout pregnancy in obese vs normal weight (control) women, and (ii) evaluating the presence of any associations between maternal hemodynamic status and RAS changes. METHODS AND RESULTS: Thirty-eight normal weight and nineteen obese pregnant women were included. Clinical assessment, blood samples and maternal hemodynamic evaluation were performed at 12, 20, 30, and 36 weeks, while ultrasound assessment was scheduled at 20, 30, and 36 weeks of gestation. Measurements of sFlt-1, PlGF, Angiotensinogen, Renin, AngII, Ang1-7, ACE and ACE2 were performed by ELISA. Our data show that normotensive obese women had lower placental blood supply, as assessed by UV-Q and UV-Q/EFW, as compared to controls, and significantly higher levels of AngII and AngII/Ang1-7 ratio, which were inversely related to placental blood supply. CONCLUSIONS: Our study shows for the first time that normotensive obese women exhibited a significant progressive increase of AngII and AngII/Ang1-7 throughout pregnancy, which were inversely related to placental blood supply as assessed by UV-Q and UV-Q/EFW. Our data shed light on the early changes in pregnant obese women and suggest that RAS dysregulation is a prerequisite rather than a consequence of hypertensive disorders of pregnancy and other maternal neonatal complications.

Maternal Hemodynamics from Preconception to Delivery: Research and Potential Diagnostic and Therapeutic Implications: Position Statement by Italian Association of Pre-Eclampsia and Italian Society of Perinatal Medicine.

OBJECTIVE: The Italian Association of Preeclampsia (AIPE) and the Italian Society of Perinatal Medicine (SIMP) developed clinical questions on maternal hemodynamics state of the art. STUDY DESIGN: AIPE and SIMP experts were divided in small groups and were invited to propose an overview of the existing literature on specific topics related to the clinical questions proposed, developing, wherever possible, clinical and/or research recommendations based on available evidence, expert opinion, and clinical importance. Draft recommendations with a clinical rationale were submitted to 8th AIPE and SIMP Consensus Expert Panel for consideration and approval, with at least 75% agreement required for individual recommendations to be included in the final version. RESULTS: More and more evidence in literature underlines the relationship between maternal and fetal hemodynamics, as well as the relationship between maternal cardiovascular profile and fetal-maternal adverse outcomes such as fetal growth restriction and hypertensive disorders of pregnancy. Experts agreed on proposing a classification of pregnancy hypertension, complications, and cardiovascular states based on three different hemodynamic profiles depending on total peripheral vascular resistance values: hypodynamic (>1,300 dynes·s·cm-5), normo-dynamic, and hyperdynamic (<800 dynes·s·cm-5) circulation. This differentiation implies different therapeutical strategies, based drugs' characteristics, and maternal cardiovascular profile. Finally, the cardiovascular characteristics of the women may be useful for a rational approach to an appropriate follow-up, due to the increased cardiovascular risk later in life. CONCLUSION: Although the evidence might not be conclusive, given the lack of large randomized trials, maternal hemodynamics might have great importance in helping clinicians in understanding the pathophysiology and chose a rational treatment of patients with or at risk for pregnancy complications. KEY POINTS: · Altered maternal hemodynamics is associated to fetal growth restriction.. · Altered maternal hemodynamics is associated to complicated hypertensive disorders of pregnancy.. · Maternal hemodynamics might help choosing a rational treatment during hypertensive disorders..

Reduced fetal growth velocity and weight loss are associated with adverse perinatal outcome in fetuses at risk of growth restriction.

BACKGROUND: Although fetal size is associated with adverse perinatal outcome, the relationship between fetal growth velocity and adverse perinatal outcome is unclear. OBJECTIVE: This study aimed to evaluate the relationship between fetal growth velocity and signs of cerebral blood flow redistribution, and their association with birthweight and adverse perinatal outcome. STUDY DESIGN: This study was a secondary analysis of the TRUFFLE-2 multicenter observational prospective feasibility study of fetuses at risk of fetal growth restriction between 32+0 and 36+6 weeks of gestation (n=856), evaluated by ultrasound biometry and umbilical and middle cerebral artery Doppler. Individual fetal growth velocity was calculated from the difference of birthweight and estimated fetal weight at 3, 2, and 1 week before delivery, and by linear regression of all available estimated fetal weight measurements. Fetal estimated weight and birthweight were expressed as absolute value and as multiple of the median for statistical calculation. The coefficients of the individual linear regression of estimated fetal weight measurements (growth velocity; g/wk) were plotted against the last umbilical-cerebral ratio with subclassification for perinatal outcome. The association of these measurements with adverse perinatal outcome was assessed. The adverse perinatal outcome was a composite of abnormal condition at birth or major neonatal morbidity. RESULTS: Adverse perinatal outcome was more frequent among fetuses whose antenatal growth was <100 g/wk, irrespective of signs of cerebral blood flow redistribution. Infants with birthweight <0.65 multiple of the median were enrolled earlier, had the lowest fetal growth velocity, higher umbilical-cerebral ratio, and were more likely to have adverse perinatal outcome. A decreasing fetal growth velocity was observed in 163 (19%) women in whom the estimated fetal weight multiple of the median regression coefficient was <-0.025, and who had higher umbilical-cerebral ratio values and more frequent adverse perinatal outcome; 67 (41%; 8% of total group) of these women had negative growth velocity. Estimated fetal weight and umbilical-cerebral ratio at admission and fetal growth velocity combined by logistic regression had a higher association with adverse perinatal outcome than any of those parameters separately (relative risk, 3.3; 95% confidence interval, 2.3-4.8). CONCLUSION: In fetuses at risk of late preterm fetal growth restriction, reduced growth velocity is associated with an increased risk of adverse perinatal outcome, irrespective of signs of cerebral blood flow redistribution. Some fetuses showed negative growth velocity, suggesting catabolic metabolism.

The clinical impact of the first-trimester nuchal translucency between the 95th-99th percentiles.

OBJECTIVES: To evaluate the clinical significance of nuchal translucency (NT) between the 95th-99th percentile in terms of typical and atypical chromosomal abnormalities (ACAs), associated fetal congenital defects and postnatal outcome. METHODS: A retrospective cohort study of fetuses with NT between the 95th-99th percentile. Data regarding the rate of associated fetal defects, genetic abnormalities and postnatal outcome were collected. RESULTS: A total of 306 cases of fetuses with an NT between the 95th-99th percentiles were included. The overall rate of genetic abnormalities was 12.1% (37/306). Chromosomal abnormalities were found in 10.1% (31/306) of cases and 2% were ACA (6/306). Within this group, two were pathogenic Copy Number Variants (CNVs) and four were single gene disorders. The overall rate of fetal congenital defects was 13.7% (42/306). All ACAs were found in fetuses with congenital defects. Postnatally, a new diagnosis of a single gene disorder was made in 0.85% of cases (2/236). CONCLUSIONS: The presence of an NT between the 95th-99th percentiles carries a 10-fold increased risk of fetal defects, representing an indication for referral for a detailed fetal anatomy evaluation. The risk of ACA is mainly related to the presence of fetal defects, irrespective of the combined test risk.

Obliterated cavum septi pellucidi: Clinical significance and role of fetal magnetic resonance.

INTRODUCTION: The objective of this study was to describe a cohort of fetuses with an ultrasound prenatal diagnosis of obliterated cavum septi pellucidi (oCSP) with the aim to explore the rate of associated malformations, the progression during pregnancy and the role of fetal magnetic resonance imaging (MRI). MATERIAL AND METHODS: This was a retrospective multicenter international study of fetuses diagnosed with oCSP in the second trimester with available fetal MRI and subsequent ultrasound and/or fetal MRI follow-up in the third trimester. Where available, postnatal data were collected to obtain information on neurodevelopment. RESULTS: We identified 45 fetuses with oCSP at 20.5 weeks (interquartile range 20.1-21.1). oCSP was apparently isolated at ultrasound in 89% (40/45) and fetal MRI found additional findings in 5% (2/40) of cases, including polymicrogyria and microencephaly. In the remaining 38 fetuses, fetal MRI found a variable amount of fluid in CSP in 74% (28/38) and no fluid in 26% (10/38). Ultrasound follow-up at or after 30 weeks confirmed the diagnosis of oCSP in 32% (12/38) while fluid was visible in 68% (26/38). At follow-up MRI, performed in eight pregnancies, there were periventricular cysts and delayed sulcation with persistent oCSP in one case. Among the remaining cases with normal follow-up ultrasound and fetal MRI findings, the postnatal outcome was normal in 89% of cases (33/37) and abnormal in 11% (4/37): two with isolated speech delay, and two with neurodevelopmental delay secondary to postnatal diagnosis of Noonan syndrome at 5 years in one case and microcephaly with delayed cortical maturation at 5 months in the other. CONCLUSIONS: Apparently isolated oCSP at mid-pregnancy is a transient finding with the visualization of the fluid later in pregnancy in up to 70% of cases. At referral, associated defects can be found in around 11% of cases at ultrasound and 8% at fetal MRI indicating the need for a detailed evaluation by expert physicians when oCSP is suspected.

Umbilical Venous Volume Flow in Late-Onset Fetal Growth Restriction.

OBJECTIVES: Umbilical vein flow (UVF) is reduced in fetal growth restriction (FGR). We compared absolute and size-adjusted UVF (estimated fetal weight [EFW] and abdominal circumference [AC]) and rates of abnormal UVF parameters (<10th percentile) among FGR fetuses meeting Delphi criteria (FGR-D) against small for gestational age (SGA) fetuses and appropriate for gestational age (AGA) controls. METHODS: Absolute UVF, UVF/EFW, and UVF/AC were compared between 73 FGR pregnancies (35 FGR-D, 38 SGA) and 108 AGA controls. Rates of abnormal UVF were compared to abnormal umbilical artery pulsatility index (UAPI). Independent samples t-tests, Mann-Whitney U, odds ratio (OR), chi-squared, and Fisher's exact tests were used as appropriate. RESULTS: Mean absolute UVF was significantly decreased in FGR-D compared to AGA (P = .0147), but not between SGA and AGA fetuses. The incidence of both abnormal absolute UVF and UVF/AC values (<10th centile) was higher among late-onset FGR fetuses versus AGA fetuses (UVF: OR 2.7, confidence interval [CI] 1.37-5.4; UVF/AC: OR 2.73, CI 1.37-5.4). UVF was more frequently abnormal than UAPI and in only two fetuses were both Doppler values abnormal. CONCLUSION: Absolute UVF is altered in late-onset FGR, and most pronounced among FGR-D. UVF may provide additional insight into fetal compromise in those affected by growth restriction.

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.

Umbilical vein blood flow: State-of-the-art.

Placental blood supply to the fetus can be measured by evaluating the umbilical vein blood flow. Despite its potential application in healthcare, the umbilical vein blood flow volume is still used only in research setting. One of the reasons is a concern regarding its reproducibility, partly due to technology issues. Nowadays, technology improvements make this evaluation accurate and reproducible. The aim of this review is to refresh basic elements of the physiology of umbilical vein blood flow and its analysis. Its evaluation in normal and abnormal fetal growth is also discussed.

The Bacterial DNA Profiling of Chorionic Villi and Amniotic Fluids Reveals Overlaps with Maternal Oral, Vaginal, and Gut Microbiomes.

The in utero microbiome hypothesis has been long debated. This hypothesis will change our comprehension of the pioneer human microbiome if proved correct. In 60 uncomplicated pregnancies, we profiled the microbiome of chorionic villi (CV) and amniotic fluids (AF) in relation to maternal saliva, rectum, and vagina and the soluble cytokines cascade in the vagina, CV and AF. In our series, 12/37 (32%) AF and 10/23 (44%) CV tested positive for bacterial DNA. CV and AF harbored bacterial DNA of Streptococcus and Lactobacillus, overlapping that of the matched oral and vaginal niches, which showed a dysbiotic microbiome. In these pregnant women, the immune profiling revealed an immune hyporesponsiveness in the vagina and a high intraamniotic concentration of inflammatory cytokines. To understand the eventual role of bacterial colonization of the CV and AF and the associated immune response in the pregnancy outcome, further appropriate studies are needed. In this context, further studies should highlight if the hematogenous route could justify the spread of bacterial DNA from the oral microbiome to the placenta and if vaginal dysbiosis could favor the likelihood of identifying CV and AF positive for bacterial DNA.

Clinical Opinion: The diagnosis and management of suspected fetal growth restriction: an evidence-based approach.

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicated that in the context of early suspected fetal growth restriction, the combination of computerized cardiotocography and fetal ductus venosus Doppler improves outcomes, such that 95% of surviving infants have a normal neurodevelopmental outcome at 2 years of age. A low middle cerebral artery pulsatility index is associated with an adverse perinatal outcome in late fetal growth restriction; however, there is no evidence supporting its use to determine the time of delivery. Nonetheless, an abnormality in middle cerebral artery Doppler could be valuable to increase the surveillance of the fetus at risk. We propose that fetal size, growth rate, uteroplacental Doppler indices, cardiotocography, and maternal conditions (ie, hypertension) according to gestational age are important factors in optimizing the outcome of suspected fetal growth restriction.

Assessment of pregnancy dietary intake and association with maternal and neonatal outcomes.

BACKGROUND: Maternal dietary habits are contributors of maternal and fetal health; however, available data are heterogeneous and not conclusive. METHODS: Nutrient intake during pregnancy was assessed in 503 women with uncomplicated pregnancies, using the validated Food Frequency Questionnaire developed by the European Prospective Investigation into Cancer and Nutrition (EPIC-FFQ). RESULTS: In all, 68% of women had a normal body mass index at the beginning of pregnancy, and 83% of newborns had an appropriate weight for gestational age. Maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and placental weight were independently correlated with birth weight. GWG was not related to the pre-pregnancy BMI. EPIC-FFQ evaluation showed that 30% of women adhered to the European Food Safety Authority (EFSA) ranges for macronutrient intake. In most pregnant women (98.1%), consumption of water was below recommendations. Comparing women with intakes within EFSA ranges for macronutrients with those who did not, no differences were found in BMI, GWG, and neonatal or placental weight. Neither maternal nor neonatal parameters were associated with the maternal dietary profiles. CONCLUSIONS: In our population, maternal pre-pregnancy BMI, GWG, and placental weight are determinants of birth weight percentile, while no association was found with maternal nutrition. Future studies should explore associations through all infancy. IMPACT: Maternal anthropometrics and nutrition status may affect offspring birth weight. In 503 healthy women, maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and placental weight were independently correlated to neonatal birth weight. GWG was not related to the pre-pregnancy BMI. In all, 30% of women respected the EFSA ranges for macronutrients. Neither maternal nor neonatal parameters were associated with maternal dietary profiles considered in this study. Maternal pre-pregnancy BMI, GWG, and placental weight are determinants of neonatal birth weight percentile, while a connection with maternal nutrition profiles was not found.

Current practice in the diagnosis and management of fetal growth restriction: An international survey.

INTRODUCTION: The aim of this survey was to evaluate the current practice in respect of diagnosis and management of fetal growth restriction among obstetricians in different countries. MATERIAL AND METHODS: An e-questionnaire was sent via REDCap with "click thru" links in emails and newsletters to obstetric practitioners in different countries and settings with different levels of expertise. Clinical scenarios in early and late fetal growth restriction were given, followed by structured questions/response pairings. RESULTS: A total of 275 participants replied to the survey with 87% of responses complete. Participants were obstetrician/gynecologists (54%; 148/275) and fetal medicine specialists (43%; 117/275), and the majority practiced in a tertiary teaching hospital (56%; 153/275). Delphi consensus criteria for fetal growth restriction diagnosis were used by 81% of participants (223/275) and 82% (225/274) included a drop in fetal growth velocity in their diagnostic criteria for late fetal growth restriction. For early fetal growth restriction, TRUFFLE criteria were used for fetal monitoring and delivery timing by 81% (223/275). For late fetal growth restriction, indices of cerebral blood flow redistribution were used by 99% (250/252), most commonly cerebroplacental ratio (54%, 134/250). Delivery timing was informed by cerebral blood flow redistribution in 72% (176/244), used from ≥32 weeks of gestation. Maternal biomarkers and hemodynamics, as additional tools in the context of early-onset fetal growth restriction (≤32 weeks of gestation), were used by 22% (51/232) and 46% (106/230), respectively. CONCLUSIONS: The diagnosis and management of fetal growth restriction are fairly homogeneous among different countries and levels of practice, particularly for early fetal growth restriction. Indices of cerebral flow distribution are widely used in the diagnosis and management of late fetal growth restriction, whereas maternal biomarkers and hemodynamics are less frequently assessed but more so in early rather than late fetal growth restriction. Further standardization is needed for the definition of cerebral blood flow redistribution.

Gaps and Future Challenges of Italian Apps for Pregnancy and Postnatal Care: Systematic Search on App Stores.

BACKGROUND: Despite the availability of thousands of health apps worldwide, when considering those addressing children's first 1000 days of life, most apps fail to consider the continuity between the prenatal and postnatal stages, and their joint impact on maternal and child health. The reliability, quality, and effectiveness of these apps are largely unknown, and the provided content seems questionable in terms of completeness, updating, and trustworthiness. OBJECTIVE: This study evaluates available Italian pregnancy and postnatal care apps to highlight the main gaps to be overcome and the resulting future challenges to be met in this mobile health-related field. METHODS: A systematic search was conducted on the Apple App Store and Google Play Store, and basic information was collected for all identified apps. After deduplication and further selection based on the exclusion criteria, an in-depth analysis of each app was performed by two researchers independently. A 71-item six-domain questionnaire about the desirable features of apps was used to assess information, functionalities, and technical features, while the Mobile Application Rating Scale (MARS) was employed for app quality evaluation. RESULTS: From an initial sample of 684 apps, 22 were deeply analyzed. Most apps did not fulfill the expectations, as just one achieved 50% of all desirable aspects. Postnatal care and counselling for both the mother and child was the least accomplished domain. Moreover, the quality of app information was generally rated more negatively than the quality of their functionality and esthetic features. The lacking aspects were information about methods for postpartum family planning and birth spacing (1/22, 5%) and immunization (2/22, 9%). CONCLUSIONS: The identified gaps could serve as a basis for designing and implementing increasingly high-quality, targeted, and effective apps for pregnancy and postnatal health care, which provide comprehensive, reliable, and evidence-based information, as well as appropriate esthetic and functional characteristics, with relevant implications in terms of maternal and newborn health prevention and promotion.

First-trimester absent nasal bone: is it a predictive factor for pathogenic CNVs in the low-risk population?

OBJECTIVE: To evaluate the association of first-trimester absent nasal bone (NB) and genetic abnormalities at G-banding karyotype and chromosomal microarray analysis (CMA) according to the nuchal translucency (NT) thickness. METHODS: This is a retrospective cohort study of fetuses that underwent the first-trimester scan for the combined test at 11+0 to 13+6 weeks' gestation. Invasive test with G-banding karyotype and/or CMA was performed based on the result of the combined test or if fetal defects were detected or for patient's choice, after genetic counseling. All cases with absent NB in the first and second trimester underwent a detailed anomaly scan with echocardiography in the second trimester, had a longitudinal ultrasound, and postnatal follow-up up to at least 1 year. RESULTS: Between 2013 and 2018, 7228 women underwent the first-trimester scan at 11+0 to 13+6 weeks. Overall prevalence of absent NB was 1.3% (96/7228). Of those, in 86 pregnancies (1.2%), the absence of NB was confirmed also in the second trimester: 0.58% (40/6909) in the group with NT <95th centile; 6%(14/233) in the group with NT between 95 and 99th centile; and 37.2% (32/86) in the group with NT >99th centile, respectively. CMA pathogenic variants were found only in the group with NT >99th centile with a diagnostic yield of 9.4%. Fetuses with absent NB and NT between 95 and 99th centile had in 57% (8/14) a major chromosomal anomaly, while in the NT <95 centile group, there were 5% (2/40) of chromosomal abnormalities (one inherited from the father). CONCLUSION: In the first trimester, the risk for genetic syndromes detectable by CMA is related mainly to the NT thickness rather than to the absence of NB per se. In fetuses with absent NB and NT >99th centile, CMA should be performed after karyotype analysis, while for NT between 95 and 99th centile, a karyotype should be proposed as first-line procedure. Data provided by our study may be helpful in counseling women/couples when an absent NB is identified in the first trimester.

Retrospective study 2005-2015 of all cases of fetal death occurred at ≥23 gestational weeks, in Friuli Venezia Giulia, Italy.

BACKGROUND: Intrauterine fetal death (IUFD) is a tragic event and, despite efforts to reduce rates, its incidence remains difficult to reduce. The objective of the present study was to examine the etiological factors that contribute to the main causes and conditions associated with IUFD, over an 11-year period in a region of North-East Italy (Friuli Venezia Giulia) for which reliable data in available. METHODS: Retrospective analysis of all 278 IUFD cases occurred between 2005 and 2015 in pregnancies with gestational age ≥ 23 weeks. RESULTS: The incidence of IUFD was 2.8‰ live births. Of these, 30% were small for gestational age (SGA), with immigrant women being significantly over-represented. The share of SGA reached 35% in cases in which a maternal of fetal pathological condition was present, and dropped to 28% in the absence of associated pathology. In 78 pregnancies (28%) no pathology was recorded that could justify IUFD. Of all IUFDs, 11% occurred during labor, and 72% occurred at a gestational age above 30 weeks. CONCLUSION: The percentage of IUFD cases for which no possible cause can be identified is quite high. Only the adoption of evidence-based diagnostic protocols, with integrated immunologic, genetic and pathologic examinations, can help reduce this diagnostic gap, contributing to the prevention of future IUFDs.

Is antiarrhythmic therapy safe in twin pregnancies?

AIM: The optimal treatment for foetal supraventricular tachycardia (SVT) in twin pregnancies is unclear because of the possible impact on the second twin. This review compared a foetus we treated with antiarrhythmic drugs with the previous case studies. METHODS: Our case was a dichorionic diamniotic twin pregnancy, where one twin developed foetal hydrops secondary to SVT at 22 weeks of gestation. We searched PubMed to look for previous cases of SVT in twin pregnancies. RESULTS: Treatment with transplacental antiarrhythmic therapy from 22 to 36 weeks of gestation successfully resolved the SVT in our affected twin without any impact on the healthy twin or mother. We only found seven similar cases of SVT in twin pregnancies from 1999 to 2017. Although there was no consensus on the treatment that should be provided, none of the studies reported side effects in the twins or the mothers. CONCLUSION: Despite a lack of data on SVT in twin pregnancies, our case, and the previous cases we identified, allowed us to conclude that transplacental antiarrhythmic treatment can successfully achieve cardioversion in the affected twin. It can do this without side effects for the healthy foetus or the mother, even if the treatment lasts for a long period of time.

Maternal hemodynamics: a method to classify hypertensive disorders of pregnancy.

BACKGROUND: The classification of hypertensive disorders of pregnancy is based on the time at the onset of hypertension, proteinuria, and other associated complications. Maternal hemodynamic interrogation in hypertensive disorders of pregnancy considers not only the peripheral blood pressure but also the entire cardiovascular system, and it might help to classify the different clinical phenotypes of this syndrome. OBJECTIVE: This study aimed to examine cardiovascular parameters in a cohort of patients affected by hypertensive disorders of pregnancy according to the clinical phenotypes that prioritize fetoplacental characteristics and not the time at onset of hypertensive disorders of pregnancy. STUDY DESIGN: At the fetal-maternal medicine unit of Ziekenhuis Oost-Limburg (Genk, Belgium), maternal cardiovascular parameters were obtained through impedance cardiography using a noninvasive continuous cardiac output monitor with the patients placed in a standing position. The patients were classified as pregnant women with hypertensive disorders of pregnancy who delivered appropriate- and small-for-gestational-age fetuses. Normotensive pregnant women with an appropriate-for-gestational-age fetus at delivery were enrolled as the control group. The possible impact of obesity (body mass index ≥30 kg/m2) on maternal hemodynamics was reassessed in the same groups. RESULTS: Maternal age, parity, body mass index, and blood pressure were not significantly different between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and hypertensive disorders of pregnancy/small-for-gestational-age groups. The mean uterine artery pulsatility index was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group. The cardiac output and cardiac index were significantly lower in the hypertensive disorders of pregnancy/small-for-gestational-age group (cardiac output 6.5 L/min, cardiac index 3.6) than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group (cardiac output 7.6 L/min, cardiac index 3.9) but not between the hypertensive disorders of pregnancy/appropriate-for-gestational-age and control groups (cardiac output 7.6 L/min, cardiac index 4.0). Total vascular resistance was significantly higher in the hypertensive disorders of pregnancy/small-for-gestational-age group than in the hypertensive disorders of pregnancy/appropriate-for-gestational-age group and the control group. All women with hypertensive disorders of pregnancy showed signs of central arterial dysfunction. The cardiovascular parameters were not influenced by gestational age at the onset of hypertensive disorders of pregnancy, and no difference was observed between the women with appropriate-for-gestational-age fetuses affected by preeclampsia or by gestational hypertension with appropriate-for-gestational-age fetuses. Women in the obese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and obese/hypertensive disorders of pregnancy/small-for-gestational-age groups showed a significant increase in cardiac output, as well as significant changes in other parameters, compared with the nonobese/hypertensive disorders of pregnancy/appropriate-for-gestational-age and nonobese/hypertensive disorders of pregnancy/small-for-gestational-age groups. CONCLUSION: Significantly low cardiac output and high total vascular resistance characterized the women with hypertensive disorders of pregnancy associated with small for gestational age due to placental insufficiency, independent of the gestational age at the onset of hypertension. The cardiovascular parameters were not significantly different in the women with appropriate-for-gestational-age or small-for-gestational-age fetuses affected by preeclampsia or gestational hypertension. These findings support the view that maternal hemodynamics may be a candidate diagnostic tool to identify hypertensive disorders in pregnancies associated with small-for-gestational-age fetuses. This additional tool matches other reported evidence provided by uterine Doppler velocimetry, low vascular growth factors in the first trimester, and placental pathology. Obesity is associated with a significantly higher cardiac output and outweighs other determinants of hemodynamics in pregnancy; therefore, in future studies on hypertensive disorders, obesity should be studied as an additional disease and not simply as a demographic characteristic.

Is middle cerebral artery Doppler related to neonatal and 2-year infant outcome in early fetal growth restriction?

BACKGROUND: Reduced fetal middle cerebral artery Doppler impedance is associated with hypoxemia in fetal growth restriction. It remains unclear as to whether this finding could be useful in timing delivery, especially in the third trimester. In this regard there is a paucity of evidence from prospective studies. OBJECTIVES: The aim of this study was to determine whether there is an association between middle cerebral artery Doppler impedance and its ratio with the umbilical artery in relation to neonatal and 2 year infant outcome in early fetal growth restriction (26+0-31+6 weeks of gestation). Additionally we sought to explore which ratio is more informative for clinical use. STUDY DESIGN: This is a secondary analysis from the Trial of Randomized Umbilical and Fetal Flow in Europe, a prospective, multicenter, randomized management study on different antenatal monitoring strategies (ductus venosus Doppler changes and computerized cardiotocography short-term variation) in fetal growth restriction diagnosed between 26+0 and 31+6 weeks. We analyzed women with middle cerebral artery Doppler measurement at study entry and within 1 week before delivery and with complete postnatal follow-up (374 of 503). The primary outcome was survival without neurodevelopmental impairment at 2 years corrected for prematurity. Neonatal outcome was defined as survival until first discharge home without severe neonatal morbidity. Z-scores were calculated for middle cerebral artery pulsatility index and both umbilicocerebral and cerebroplacental ratios. Odds ratios of Doppler parameter Z-scores for neonatal and 2 year infant outcome were calculated by multivariable logistic regression analysis adjusted for gestational age and birthweight p50 ratio. RESULTS: Higher middle cerebral artery pulsatility index at inclusion but not within 1 week before delivery was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95% confidence interval, 1.02-1.52). Middle cerebral artery pulsatility index Z-score and umbilicocerebral ratio Z-score at inclusion were associated with 2 year survival with normal neurodevelopmental outcome (odds ratio, 1.33; 95% confidence interval, 1.03-1.72, and odds ratio, 0.88; 95% confidence interval, 0.78-0.99, respectively) as were gestation at delivery and birthweight p50 ratio (odds ratio, 1.41; 95% confidence interval, 1.20-1.66, and odds ratio, 1.86; 95% confidence interval, 1.33-2.60, respectively). When comparing cerebroplacental ratio against umbilicocerebral ratio, the incremental range of the cerebroplacental ratio tended toward zero, whereas the umbilicocerebral ratio tended toward infinity as the values became more abnormal. CONCLUSION: In a monitoring protocol based on ductus venosus and cardiotocography in early fetal growth restriction (26+0-31+6 weeks of gestation), the impact of middle cerebral artery Doppler and its ratios on outcome is modest and less marked than birthweight and delivery gestation. It is unlikely that middle cerebral artery Doppler and its ratios are informative in optimizing the timing of delivery in fetal growth restriction before 32 weeks of gestation. The umbilicocerebral ratio allows for a better differentiation in the abnormal range than the cerebroplacental ratio.