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Purpose:  The human aorta stores strain energy in the distended wall during systole through the extracellular matrix of the tunica media that could be influenced by blood pressure, flow, or increased peripheral resistance. In intrauterine growth restriction (IUGR) fetuses, the increased aorta intima media thickness (aIMT) could reflect a different extracellular matrix composition and, therefore, functionality. The aim of this study was to analyze the resistance to flow in the fetal descending aorta and its relation to aIMT and systolic and diastolic fetal abdominal aorta diameters in IUGR fetuses and controls., Materials and Methods: This is a prospective case control study of single pregnancies collected at a tertiary center for feto-maternal medicine in Northeast Italy. An IUGR group as cases and a group of fetuses appropriate for gestational age (AGA) as controls were included., Results:  We found a greater PI of the fetal abdominal aorta in the IUGR group (1.82) than in the AGA group (1.21) (p < 0.05). The change between the systolic and diastolic fetal abdominal aorta diameters was significantly greater in IUGR fetuses (0.10 mm (IQR 0.07 - 0.28)) than in the AGA group (0.04 mm (0.03 - 0.05)) (p < 0.05). In the IUGR group aIMT was significantly correlated with peak systolic velocity (PSV) and systolic-diastolic aorta diameter change, while these two correlations were not found in the control group., Conclusion:  The change between the systolic and diastolic fetal abdominal aorta diameters in IUGR cases during the early third trimester of pregnancy was significantly increased and aIMT in the IUGR group was significantly correlated to systolic-diastolic diameter change and PSV, probably reflecting aortic wall adaptation to blood flow changes in IUGR fetuses., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Recent studies reveal that offspring of pregnancies complicated by hypertensive disorders may have an increased cardiovascular risk. Genetic and nongenetic factors seem to play an important role in premature arterial disease. Endothelium may be significant for long-term remodeling of the arterial wall. The aim of the study was to assess fetal endothelial and renal function in late-onset gestational hypertension., Materials and Methods: This was a case-controlled study. Singleton pregnancies affected by late-onset gestational hypertension (after 34 weeks' gestation) and controls were included. Ultrasound examinations (fetal biometry, fetal Doppler, fetal aorta intima media thickness (aIMT), fetal kidney volumes, maternal Doppler, presence of uterine arteries protodiastolic notching from anomaly scan) and clinical data were collected. A sample of amniotic fluid was taken at delivery., Results: Fifty patients with late-onset hypertension and 50 controls were included. At growth scan (weeks 29-32) we found in the study group significantly higher fetal aIMT, umbilical artery pulsatility index (PI), fetal aorta PI, and mean uterine arteries PI with persistent bilateral notch. In the case group microalbuminuria levels were significantly higher than controls (1.32±0.11 vs. 1.10±0.13g/l, P < 0.0001), and there was a negative correlation between renal fetal volume at growth scan and amniotic microalbuminuria (r: -0.95, 95% C -0.97 to -0.90, P < 0.0001)., Conclusions: Gestational hypertension should be considered as one of the adverse early risk factors that might predispose to impaired fetal cardiovascular development during intrauterine life; therefore, this study provides further evidence to better understand the origins of cardiovascular diseases., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A number of metabolic abnormalities have been observed in pregnancies complicated by intrauterine growth restriction (IUGR). Metabolic fingerprinting and clinical metabolomics have recently been proposed as tools to investigate individual phenotypes beyond genomes and proteomes and to advance hypotheses on the genesis of diseases. Non-targeted metabolomic profiling was employed to study fetal and/or placental metabolism alterations in IUGR fetuses by liquid chromatography high-resolution mass spectrometry (LC-HRMS) analysis of cord blood collected soon after birth. Samples were collected from 22 IUGR and 21 appropriate for gestational age (AGA) fetuses. Birth weight differed significantly between IUGR and AGA fetuses (p < 0.001). Serum samples were immediately obtained and deproteinized by mixing with methanol at room temperature and centrifugation; supernatants were lyophilized and reconstituted in water for analysis. LC-HRMS analyses were performed on an Orbitrap mass spectrometer linked to a Surveyor Plus LC. Samples were injected into a 1.0 × 150-mm Luna C18 column. Spectra were collected in full-scan mode at a resolution of approximately 30,000. Data were acquired over the m/z range of 50-1,000, with measurements performed in duplicate. To observe metabolic variations between the two sets of samples, LC-HRMS data were analyzed by a principal component analysis model. Many features (e.g., ionic species with specific retention times) differed between the two classes of samples: among these, the essential amino acids phenylalanine, tryptophan, and methionine were identified by comparison with available databases. Logistic regression coupled to a receiver-operating characteristic curve identified a cut-off value for phenylalanine and tryptophan, which gave excellent discrimination between IUGR and AGA fetuses. Non-targeted LC-HRMS analysis of cord blood collected at birth allowed the identification of significant differences in relative abundances of essential amino acids between IUGR and AGA fetuses, emerging as a promising tool for studying metabolic alterations.

Aims: To evaluate the effect of antenatal betamethasone and ritodrine in third trimester low risk singleton pregnancies by Doppler technology., Subjects and Methods: Eighty-four third trimester pregnant women who received a full course of betamethasone and delivering uneventfully were recruited. The Doppler examination included the assessment of the pulsatility index (PI) of the umbilical artery (UA PI) and the middle cerebral artery (MCA PI) prior to treatment (baseline), and 48, 72 and 96 h after the second dose of betamethasone., Results: No significant difference was found in UA PI and UA/MCA values following betamethasone therapy. In contrast, MCA PI decreased significantly 48 h from the last injection of betamethasone in the whole study group (P<0.001), and returned to basal values at 96 h. We also found that MCA PI was reduced significantly at 48 h in the subgroup under tocolysis (n=41) and in the subgroup not receiving tocolysis (n=43). We compared MCA PI values for both subgroups in the four timings, and found a non-significant difference comparing baseline and 96 h values. However, when comparing MCA PI values after 48 and 72 h, significantly lower differences in PI values in both subgroups were found., Conclusion: In low risk pregnancies, betamethasone therapy in the third trimester is related to a significant but transient reduction of MCA PI, which is more pronounced during tocolytic therapy. Although the physiological basis of this effect is currently unclear, it could be related to the local regulation of intracerebral blood flow.

Aim: To describe antenatal corticosteroids (ANCs) policies in European obstetric units and to determine factors that influence the use of multiple courses., Methods: 641 obstetricians from obstetric departments covering a geographical area in 14 European countries responded to a questionnaire on ANCs policies. Logistic regression was used to identify factors that were related to the use of multiple ANCs courses., Results: The survey response rate was 76% (inter-country range 33-94%): 11% (0-50%) of the respondents started ANCs from 23 to 24 wk gestation, 82% from 24 to 28 wk (50-100%) and 7% from 28 to 36 wk (0-32%). Eighty-five percent of the units (63-100%) used multiple ANCs courses. After adjustment for country, number of infants delivered at 24-32 wk annually in the unit, NICU and maternal hypertension, maternal hypertension tended to be an explicative factor (OR 1.97; 95% CI: 0.75-5.17)., Conclusions: The high proportion of departments that initiated ANCs between 24 and 28 wk of gestation is consistent with the high incidence of neonatal morbidity and mortality in that age range. Multiple courses are overwhelmingly prescribed in Europe, although their risk/benefit ratio compared with a single dose is not yet known. The likelihood of using repeated courses of ANCs may be related to the presence of maternal hypertension, and this highlights the importance of closely monitoring women at risk of premature delivery.

Objective: To verify the reliability of computerized cardiotocography (cCTG) in the prediction of the oxygen metabolism status of fetuses with growth restriction and Doppler velocimetry alterations., Methods: From 24 third-trimester cesarean section performed because of intrauterine growth restriction (IUGR) and Doppler velocimetry alterations, there were 11 cases of fetal heart rate alterations (Dawes-Redman criteria were not satisfied) and 13 cases of reactive cCTG. Fetal lung maturity was detected by amniocentesis and blood samples for umbilical blood gas analysis (UBGA) were collected before the first neonatal breath from the umbilical artery in a double-clamped segment of the cord., Results: Umbilical cord gas analysis showed arterial cord blood pH to be 7.20 or less in 11 newborns (45.8%), 7.10 or less in 6 (25%), and 7.00 or less in 3 (12.5%). Linear regression analysis showed short-term variation (STV) in the fetal heart rate to be significantly correlated with umbilical artery pH (r = 0.49; P = 0.01) and pCO2 (r = -0.50; P = 0.01). There were no significant correlations between cCTG and the other UBGA parameters considered. Receiver operator curves permitted to calculate the STV values at which pathological neonatal UBGA values can be expected (pH < 7.00 and pCO2 > 80 mmHg). A short-term variation less than 4.5 ms was found to predict acidemia with a sensitivity of 100% and a specificity of 70% (positive predictive value, 33%; negative predictive value, 100%), and hypercarbia with a sensitivity of 100% and a specificity of 77.8% (positive predictive value, 55.6%; negative predictive value, 100%)., Conclusion: In view of the results of this study, 4.5 ms for STV may be a threshold below which timing of delivery should be decided in cases of fetal growth restriction., (Copyright 2004 International Federation of Gynecology and Obstetrics)

Objective: Our purpose was to assess the feasibility of longitudinal assessment of the middle cerebral artery peak systolic velocity (MCA-PSV) to predict fetuses who will have severe anemia., Study Design: Doppler measurement of MCA-PSV was serially performed in 15 healthy fetuses (99 measurements; range: 4-9 per fetus), 8 fetuses who were mildly anemic (41 measurements; range: 3-10 per fetus), and 11 who were severely anemic (50 measurements; range: 2-7 per fetus) at their first cordocenteses. Linear models were fitted to the data from individual fetuses and the slopes were determined. The average rate of change (slope) of MCA-PSV as a function of gestational age in the 3 groups was calculated from these data. Estimated average slopes were computed using restricted maximum likelihood. F tests were used for hypothesis tests, with the degrees of freedom based on the Kenward and Roger approximation. The values of MCA-PSV and hemoglobin were expressed as multiples of the median (MoM). A P <.05 indicated statistical significance., Results: Gestational age at the time of the Doppler studies ranged from 15.1 to 41 weeks in the healthy fetuses. It was between 15 and 33.4 weeks in the fetuses who became anemic. The estimated average slopes increased with the degree of anemia (P =.03). The difference in mean slope between the severely anemic sample and the healthy sample was statistically significant (estimated difference = 2.2, SE =.65, P =.01). The difference in mean slope between the mildly anemic and healthy samples was not statistically significant (estimated difference = 1.1, SE =.06; P =.08)., Conclusions: We have demonstrated that the MCA-PSV slope is an excellent tool for identifying those fetuses who will become severely anemic and, therefore, need to be followed up more closely during the pregnancy. Our findings expand the clinical applications to which Doppler ultrasonography can be applied in monitoring pregnancies at risk for fetal anemia.

Nitric oxide (NO) and adrenomedullin (AM) are both involved in the regulation of fetoplacental circulation in human pregnancy. The aim of this study was to investigate the effect of maternal NO supplementation in pregnancies complicated by intrauterine growth retardation (IUGR) on maternal and fetal NO and AM concentrations and their correlation with uteroplacental and fetal blood flow. We studied 20 pregnant women with IUGR and impaired uteroplacental blood flow between 27 and 35 weeks of gestation randomly selected to receive either transdermal glyceryl trinitrate or placebo. Maternal NO metabolites (NOx) and AM concentrations did not change before and after NO treatment. AM levels were significantly higher in growth retarded fetuses whose mothers received NO donors (114.1 +/- 17.6 pg/ml) than in untreated fetuses (59.8 +/- 38.6 pg/ml), whereas NO treatment did not affect significantly fetal NOx levels. Fetal AM correlated with middle cerebral artery pulsatility index in untreated IUGR but not in NO treated pregnancies.

We report the case of a dipygus diagnosed by sonography in the second trimester that had 6 lower extremities, double external male genitalia, a megabladder, 3 dilated ureters, and a polycystic right and a pelvic left kidney. This complex malformation represents a rare type of caudal duplication.

With the recent introduction of Doppler technology, a non-invasive methodology which enables to evaluate qualitative changes in circulatory vessels, it is possible to investigate the possible effects of various drugs on several parameters of utero-placental-fetal circulation. In the present study we evaluate the flow velocity waveform (FVW) of umbilical artery (UA) during and after administration of aminophylline, atropine and ritodrine to healthy pregnant women. In our study we did not observe any significant short-term variation of PI after the administration of these drugs. Slight variations were detected, and they may be interpreted on the basis of the mode of action of these drugs. Doppler technology may be a useful tool for monitoring some effects on the fetus of the maternal administration of therapeutic agents.

The generation of spontaneous regular breathing by cutaneous stimulation and by direct electrical stimulation of the sciatic nerve was examined in six previously apneic mature fetal lambs in utero. The fetuses were stable throughout the course of the experiments: PaO2 less than or equal to 27 mm Hg, PaCO2 less than 44 mm Hg, pH 7.29-7.34, blood pressure and heart rate steady and normal. It is shown that electrical stimulation of the fetal skin (66 cps, 4.0 msec, 6 V, 0.77 ma) can be as effective as direct stimulation of the sciatic nerve (66 cps, 4.0 msec, 1.5 V, 0.08 ma) when the higher voltage and current are used. Mechanical cutaneous stimulation also produced spontaneous breathing which, however, was short lived compared with that produced by electrical stimuli. The results are consonant with our concept of activation and recruitment of quiescent respiratory center neurones by somatic sensory stimulation, and they give fundamental support to the clinical observation of others that cutaneous stimulation is effective for the treatment of apnea of prematurity. Speculation Somatic sensory stimuli from the skin may be important determinants of the onset of breathing in the fetus and newborn.

An indicator-dilution method is described for measuring fetal pulmonary fluid, FPF, volume (Ve), and volume change with time (Vs) in the lamb fetus in utero. The indicator, albumin, which is the predominant protein of normal FPF, was administered directly to FPF in the form of radio-iodinated human serum albumin (RISA). We have shown that (1) RISA is distributed homogeneously throughout the FPF compartment, (2) it is not altered within FPF, (3) it does not alter the functional characteristics of FPF, and (4) it remains within the FPF compartment throughout the period of measurement. Ve varies directly with the weight of the fetus so that Ve per kilogram was 31.6-35.6 ml/kg in four of five fetuses. The Ve per kilogram was lower in one fetus at the start of the experiment but increased rapidly to 29.0 ml/kg within 45 min. Thus the relaxation volume of the fetus in utero is in the range of functional residual capacity (FRC) and thoracic gas volume of the air-breathing neonate, which indicates that the pulmonary transformation at birth is, in essence, an isovolumic change in state wherein the fetal liquid-lung becomes the neonatal air-lung. The rate at which FPF is formed (Vs) is about 1.5 ml/hr-kg; however, the rate may change in so far as both rapid increases and rapid decreases of FPF volume were observed. When breathing movements were induced in the fetus by stimulation of the sciatic nerve, FPF volume decreased rapidly (Vs equals -3.0 ml/hr-kg), which indicates that negative intrathoracic pressures promote its resorption. When FPF volume fell transiently or was low initially, there was subsequent rapid restoration of volume to the range of anticipated FRC.

Objective: To assess through pregnancy fetal breathing movements (FBMs) patterns detected by M-mode and Doppler velocimetry technology.Methods: In this cross-sectional study FBMs were investigated in 1882 uncomplicated pregnancies over a 4-year period. Abdominal and thoracic wall movements of fetuses between 14 and 40 weeks of gestation were studied by M-Mode scan, and color Doppler velocimetry with spectral imaging analysis was used to investigate the presence of FBMs associated with nasal fluid flow velocity waveforms (NFFVWs).Results: Abdominal movements were observed in 19% of cases when gestation was less than 20 weeks and in 61% of cases when it was between 21 and 25 weeks; chest movements were significant after 21 weeks; and NFFVWs were detected at 22 weeks and increased progressively to 93% of cases at term.Conclusions: Fetal breathing movements are a complex phenomenon with a composite, progressive pattern of development during gestation. [ABSTRACT FROM AUTHOR]

DV is usually used for timing the delivery in IUGR fetuses. Fetuses with abnormal DV had a significant increased risk of IUFD with a cumulative risk of 12% (CI.95 0-22%) during the first day versus 0% in normal DV (p<0.05). In normal DV fetuses the cumulative risk of IUFD at 10 days was 5% (CI.95 0-11%) and was lower respect to abnormal DV (p<0.05). [Extracted from the article]

OP19.06: Which Doppler parameter during the second trimester ultrasound should be assessed as predictor for late small-for-gestational-age fetus? To assess which Doppler parameter during the II trimester ultrasound scan might predict small for gestational age (SGA) fetuses at term of pregnancy. Umbilical and middle cerebral artery did not differ and thus excluded for the prediction of SGA fetuses at term. DV mean PI was 0.58 (±0.16) and was the best predictor for SGA fetuses at term. [Extracted from the article]

The aim of the study was to analyse right and left cardiac function in intrauterine growth restriction (IUGR), small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) fetuses. SGA fetuses were defined those with an estimated fetal weight (EFW) between the 3th and the10th percentile without fetal Doppler alterations; AGA fetuses as EFW between the 10 SP th sp and the 90 SP th sp percentile. Twenty SGA and 62 AGA fetuses were studied. [Extracted from the article]

An abstract of the research paper "Kidney volumes through pregnancy in adequate, small for gestational age, and intrauterine growth restricted fetuses," by S. Visentin and colleagues is presented.

An abstract of the research paper "Aortic wall thickness and amniotic fluid albuminuria in growth restricted twin fetuses," by S. Visentin and colleagues is presented.

An abstract of the article "Microscopic evaluation of aorta intima media thickness in IUGR stillborn fetuses," by S. Visentin, R. Salmaso, K. Ludwig, F. Gobbo, M. Bertin, and E. Cosmi is presented.

An abstract of the conference paper "Perinatal outcome does not differ in IUGR fetuses born from normotensive women versus IUGR from preeclamptic women: a multicenter study," by E. Cosmi, and colleagues is presented.

An abstract of the conference paper "Cardiovascular changes and neonatal outcome in IUGR fetuses born to normotensive and preeclamptic mothers," by E. Cosmi and colleagues is presented.