A germline chimeric KANK1-DMRT1 transcript derived from a complex structural variant is associated with a congenital heart defect segregating across five generations.

Structural variants (SVs) pose a challenge to detect and interpret, but their study provides novel biological insights and molecular diagnosis underlying rare diseases. The aim of this study was to resolve a 9p24 rearrangement segregating in a family through five generations with a congenital heart defect (congenital pulmonary and aortic valvular stenosis and pulmonary artery stenosis), by applying a combined genomic analysis. The analysis involved multiple techniques, including karyotype, chromosomal microarray analysis (CMA), FISH, genome sequencing (GS), RNA-seq, and optical genome mapping (OGM). A complex 9p24 SV was hinted at by CMA results, showing three interspersed duplicated segments. Combined GS and OGM analyses revealed that the 9p24 duplications constitute a complex SV, on which a set of breakpoints matches the boundaries of the CMA duplicated sequences. The proposed structure for this complex rearrangement implies three duplications associated with an inversion of ~ 2 Mb region on chromosome 9 and a SINE element insertion at the more distal breakpoint. Interestingly, this genomic structure of rearrangement forms a chimeric transcript of the KANK1/DMRT1 loci, which was confirmed by both RNA-seq and Sanger sequencing on blood samples from 9p24 rearrangement carriers. Altogether with breakpoint amplification and FISH analysis, this combined approach allowed a deep characterization of this complex rearrangement. Although the genotype-phenotype correlation remains elusive from the molecular mechanism point of view, this study identified a large genomic rearrangement at 9p24 segregating with a familial congenital heart defect, revealing a genetic biomarker that was successfully applied for embryo selection, changing the reproductive perspective of affected individuals.

Fetal ductus arteriosus constriction associated with citronella maternal use.

Constriction of the fetal ductus arteriosus is a condition that narrows the ductus arteriosus and can lead to death, so the importance of prior diagnosis. Citronella, due to its anti-inflammatory properties, should be avoided during pregnancy as it may cause constriction of the fetal duct.

Development of the Z-score for the measurement of myocardial thickness by two-dimensional echocardiography in normal fetuses.

BACKGROUND: In the current literature, there is a tendency to describe normal values of echocardiographic measurements by means of the Z-score. In fetal cardiology, these Z-score equations are still being established. Measurement of myocardial thickness is an important assessment, especially in fetuses of diabetic mothers, because of the risk of developing myocardial hypertrophy secondary to elevated maternal blood glucose levels. OBJECTIVE: To determine the percentiles and to develop the Z-score equations of right and left ventricular lateral walls and interventricular septum measurements using two-dimensional echocardiography in normal fetuses between 24 and 34 weeks of gestation. METHODS: This is a prospective cross-sectional study that was performed in single fetuses with normal heart from nondiabetic pregnant women. Measurements of the lateral walls of the right and left ventricles and the interventricular septum were made. RESULTS: Eight hundred and seventy three pregnant women were included. We determined the percentiles of the measurements for each gestational age. The Z-score equation was developed for each of the measurements: right ventricular lateral wall measurement [RVLW = x-(-1 + 0.109 * GA)/0.4], left ventricle lateral wall measurement [LVLW = x-(-1.366 + 0.12 * GA)/0.43], and interventricular septum, both at the four-chamber view [IVS4ch = (x-(-1.113 + 0.107 * GA)/0.4] and at the left ventricular outflow tract plane [IVSLVOT = (x-(-0.581 + 0.084 * GA)/0.35]. CONCLUSION: The present study allowed the demonstration of the percentiles and the Z-score equations for each of the measurements studied.

Pulmonary Vein Flow Impedance: An Early Predictor of Cardiac Dysfunction in Intrauterine Growth Restriction.

INTRODUCTION: In intrauterine growth restriction (IUGR), increased uteroplacental vascular impedance contributes to preferential flow to left ventricle (LV), with consequent alteration of its compliance and increased left atrial (LA) pressure. Pulmonary vein pulsatility index (PVPI) reflects the increased impedance to LA filling and could be used as a cardiac monitoring parameter in IUGR. MATERIAL AND METHODS: A total of 27 IUGR fetuses (group 1), 28 fetuses with appropriate growth for gestational age from hypertensive mothers (group 2), and 28 controls (group 3) were studied. Pulsatility indices (PIs) of pulmonary veins and ductus venosus were calculated by Doppler echocardiography. Obstetric ultrasound was used to assess the PIs of uterine, umbilical, and middle cerebral arteries. Statistical analysis used analysis of variance, post-hoc Tukey, and Pearson's tests. RESULTS: Mean PVPI was higher in IUGR group (1.27 ± 0.39) when compared to groups 2 (1.02 ± 0.37; p = 0.01) and 3 (0.75 ± 0.12; p < 0.001). In group 2, moderate correlation between PVPI and ductus venosus pulsatility index (DVPI) was found but not between PVPI and cerebroplacental ratio (CPR). DISCUSSION: Higher PVPI in IUGR reflects decreased LV compliance and altered LA dynamics. As LV dysfunction precedes right ventricle, our results suggest that PVPI could be an early echocardiographic parameter of fetal diastolic function in IUGR.

Polyphenol-rich food general and on pregnancy effects: a review.

This review aimed to investigate possible protective or deleterious effects of polyphenol-rich foods (PRF) on chronic diseases, e.g. cardiovascular, and in pregnant women, along with their antioxidant and anti-inflammatory action. A great variety of foods and beverages, such as herbal teas, grape and orange derivatives, dark chocolate, and many others contain high concentrations of flavonoids and are freely consumed by the general population. In humans, PRF consumption reduces lipid peroxidation, and several studies have shown a positive correlation between an increased consumption of PRF and a decrease in the incidence of cardiovascular disease. On the other hand, current studies have suggested that maternal ingestion of PRF, especially during the third trimester of pregnancy, could be associated to fetal ductal constriction (DC). Fetuses exposed to this type of diet show higher ductal velocities and lower pulsatility indexes, as well as larger right ventricles than those exposed to minimal amounts of these substances. The underlying mechanism involved in these conditions has not been entirely elucidated, but it seems to be a result of the antioxidant and anti-inflammatory effects of polyphenols by some pathway. Furthermore, taking into account the deleterious effect in late-pregnancy against the numerous positive effects associated to polyphenols, this dual behavior deserves attention particularly to control the dietary ingestion of PRF during gestation. In this line, same PRF, natural constituents of human diet, may represent risk to fetal in late pregnancy compared to the use of nonsteroidal anti-inflammatory drugs.

Dynamics of pulmonary venous flow in fetuses with intrauterine growth restriction.

OBJECTIVE: To test the hypothesis that the pulmonary vein pulsatility index (PVPI) is higher in fetuses with growth restriction (IUGR) than in normal fetuses. METHODS: Twenty-two fetuses with IUGR and twenty-one (21) fetuses with appropriate growth for gestational age from healthy mothers were studied. PVPI was calculated by Doppler echocardiography [maximal velocity (systolic or diastolic peak) - pre-systolic peak / mean velocity]. Obstetric ultrasound was used to assess fetal biometry and Doppler to assess the uterine, umbilical and middle cerebral arteries PI. Statistical analysis used t test and Pearson's correlation. RESULTS: Mean gestational age was 31.5 +/- 2.1 weeks in the control group and 31.4 +/- 3.1 weeks in IUGR (P = 0.91). The PI of uterine and umbilical arteries were higher in IUGR than in controls (P < 0.001). Mean PVPI in IUGR fetuses was 1.31 +/- 0.41, and in controls it was 0.83 +/- 0.11 (P < 0.001). CONCLUSION: The pulsatility index of pulmonary venous flow in fetuses with growth restriction is higher than in normal fetuses, probably as a result of left atrial dynamics alteration secondary or not to fetal left ventricular diastolic dysfunction. © 2014 John Wiley & Sons, Ltd.

Development and validation of a food frequency questionnaire for consumption of polyphenol-rich foods in pregnant women.

Previous studies have shown that maternal consumption of polyphenol-rich foods after the third trimester of pregnancy may interfere with the anatomical and functional activity of the fetal heart as, to our knowledge, there are no validated instruments to quantify total polyphenols in pregnant women. The aim of this study was evaluate the reproducibility and validity of a food frequency questionnaire (FFQ), with 52 items, to assess the intake of polyphenol-rich foods in pregnant women in Brazil. This cross-sectional study included 120 pregnant women who participated in nutritional interviews in two moments. The intake of polyphenols estimated by the developed FFQ was compared with the average of two 24-h recalls (24HR), with the average intake measured by a 3-day food diary (D3days) and with the urinary excretion of total polyphenols. The triangular method was applied to calculate Pearson's correlation coefficients, intraclass correlation and Bland-Altman plots for the FFQ, using an independent biochemical marker, in addition to classification by quarters of consumption. The questionnaires were log transformed, adjusted for body mass index and gestational age. The adjustment for energy was applied only of 24HR and D3days. Analysis of the reproducibility between the FFQ showed a very high correlation (r = 0.72; P < 0.05). A low but significant association was observed between the FFQ and urinary excretion (0.23; P = 0.01). The association between the dietary survey methods was moderate to very high (r = 0.36 to r = 0.72; P < 0.001). In conclusion, this questionnaire showed reproducibility and validity for the quantification of consumption of total polyphenols in pregnant women.

Nitric oxide and reactive species are modulated in the polyphenol-induced ductus arteriosus constriction in pregnant sheep.

OBJECTIVE: Because we have previously demonstrated the relation between polyphenol-rich foods (PRF) consumption and ductus arteriosus constriction, in this work, pregnant sheep were submitted to oral PRF intake for 14 days to understand how this process occurs. Fetal Doppler echocardiography, oxidative and inflammatory biomarkers and total polyphenol excretion were evaluated. RESULTS: The high polyphenol intake induced ductus arteriosus constriction by 71.6% increase in systolic (P = 0.001) and 57.8% in diastolic velocities (P = 0.002), and 18.9% decrease in pulsatility index (P = 0.033), along with 1.7-fold increase in total polyphenol excretion, 2.3-fold decrease in inflammatory mediator nitric oxide and following redox status changes (mean ± standard deviation): higher protein carbonyls (1.09 ± 0.09 and 1.49 ± 0.31), catalase (0.69 ± 0.39 and 1.44 ± 0.33) and glutathione peroxidase (37.23 ± 11.19 and 62.96 ± 15.03) in addition to lower lipid damage (17.22 ± 2.05 and 12.53 ± 2.11) and nonprotein thiols (0.11 ± 0.04 and 0.04 ± 0.01) found before and after treatment, respectively. Ductal parameters correlated to NOx , catalase, glutathione peroxidase and protein carbonyl. CONCLUSION: Our results highlight the need to reduce maternal PRF intake in late pregnancy to prevent fetal duct constriction through NO-mediated vasoconstrictive action of polyphenols.

Prenatal diagnosis of critical congenital heart disease associated with lower postpartum depressive symptoms: a case-control study.

OBJECTIVE: When the expectant mother is faced with an unforeseen event during pregnancy, she may experience emotional fragility and depression. This study was carried out to test the association between the time of diagnosis of critical congenital heart disease (CCHD) and depressive symptoms in puerperal women. METHOD: A case-control study. All mothers answered a semi-structured questionnaire and the Edinburgh Postnatal Depression Scale (EPDS). Pearson's correlation and multiple linear regression analysis were used to determine factors associated with depression. RESULTS: 50 puerperal women, 23 cases and 27 controls. The proportion of puerperal depressive symptoms was 26.1 % among mothers of infants prenatally diagnosed with CCHD and 77.8 % among mothers of infants postnatally diagnosed (p = 0.001 [OR] 9.917; 95 % CI 2.703-36.379). Multiple linear regression analysis showed that the use of psychotropic drugs and time of diagnosis were significantly associated with puerperal depressive symptoms. CONCLUSION: Prenatal diagnosis of CCHD was associated with significantly lower levels of depressive symptoms.

Prenatal effects of maternal consumption of polyphenol-rich foods in late pregnancy upon fetal ductus arteriosus.

Fetal circulation has characteristic features, being morphologically and functionally different from extrauterine circulation. The ductus arteriosus plays a fundamental role in directing the blood flow to fetal inferior body parts. Basically, the ductus arteriosus directs 80-85% of the right ventricular output arising from the superior vena cava, coronary sinus, and a small part from the inferior vena cava to descending aorta. Its histological structure is made up predominantly by a thick muscular layer, differently from the aorta and the pulmonary artery, which increases with gestational age. The fibers have a circumferential orientation, especially at the external layers, facilitating and making effective ductal constriction. These factors may generate lumen alterations which may cause fetal and neonatal complications, such as heart failure, hydrops, neonatal pulmonary hypertension, and even death. Classically, maternal administration of indomethacin and/or other antiinflammatory drugs interfere in prostaglandins metabolism, causing ductal constriction. However, many cases of fetal ductal constriction, as well as of persistent neonatal pulmonary artery hypertension, remain without an established etiology, being referred as "idiopathic." In recent years, a growing body of evidence has shown that herbs, fruits, nuts, and a wide diversity of substances commonly used in daily diets have definitive effects upon the metabolic pathway of inflammation, with consequent inhibition of prostaglandins synthesis. This antiinflammatory action, especially of polyphenols, when ingested during the third trimester of pregnancy, may influence the dynamics of fetal ductus arteriosus flow. The goal of this review is to present these new observations and findings, which may influence dietary orientation during pregnancy.

A germline chimeric KANK1-DMRT1 transcript derived from a complex structural variant is associated with a congenital heart defect segregating across five generations.

Structural variants (SVs) pose a challenge to detect and interpret, but their study provides novel biological insights and molecular diagnosis underlying rare diseases. The aim of this study was to resolve a 9p24 rearrangement segregating in a family through five generations with a congenital heart defect (congenital pulmonary and aortic valvular stenosis, and pulmonary artery stenosis), by applying a combined genomic analysis. The analysis involved multiple techniques, including karyotype, chromosomal microarray analysis (CMA), FISH, whole-genome sequencing (WGS), RNA-seq and optical genome mapping (OGM). A complex 9p24 SV was hinted at by CMA results, showing three interspersed duplicated segments. Combined WGS and OGM analyses revealed that the 9p24 duplications constitute a complex SV, on which a set of breakpoints match the boundaries of the CMA duplicated sequences. The proposed structure for this complex rearrangement implies three duplications associated with an inversion of ~ 2Mb region on chromosome 9 with a SINE element insertion at the more distal breakpoint. Interestingly, this hypothesized genomic structure of rearrangement forms a chimeric transcript of the KANK1/DMRT1 loci, which was confirmed by RNA-seq on blood from 9p24 rearrangement carriers. Altogether with breakpoint amplification and FISH analysis, this combined approach allowed a deep characterization of this complex rearrangement. Although the genotype-phenotype correlation remains elusive from the molecular mechanism point of view, this study identified a large genomic rearrangement at 9p segregating with a familial congenital clinical trait, revealing a genetic biomarker that was successfully applied for embryo selection, changing the reproductive perspective of affected individuals.

Isolated atrioventricular block in the fetus: a retrospective, multinational, multicenter study of 175 patients.

BACKGROUND: Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome. METHODS AND RESULTS: We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000-2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1-21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age < 20 weeks, ventricular rate ≤ 50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥ 1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4 ± 2.9 versus 24.9 ± 4.9 weeks; P=0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age; 8 children developed cardiomyopathy. CONCLUSIONS: Risk factors associated with a poor outcome were gestation < 20 weeks, ventricular rate ≤ 50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen.

Fetal ductal constriction caused by maternal ingestion of green tea in late pregnancy: an experimental study.

OBJECTIVES: The aim of this study was to test the hypothesis that experimental maternal intake of green tea in late pregnancy causes fetal ductus arteriosus constriction, probably because of prostaglandin inhibition. METHODS AND RESULTS: Twelve fetal lambs (pregnancy > 120 days) were assessed before and after maternal administration of green tea (n = 8) or water (n = 4; controls) as the only source of liquid. After 1 week, echocardiography showed signs of constriction of the ductus arteriosus in all fetuses from mothers ingesting green tea, with increase in mean systolic velocity(from 0.70 ± 0.19 m/s to 0.92 ± 0.15 m/s, 31.4%, p = 0.001) and mean diastolic velocity (0.19 ± 0.05 m/s to 0.31 ± 0.01 m/s, 63.1%, p < 0.001), decrease of pulsatility index (2.2 ± 0.4 to 1.8 ± 0.3, 22.2%, p = 0.003) and increase of mean right ventricular/left ventricular diameter ratio (0.89 ± 0.14 to 1.43 ± 0.23, 60.6%, p < 0.001). In the four control fetuses, there were no significant changes. All lambs exposed to green tea also showed at autopsy dilated and hypertrophic right ventricles, which was not present in control fetuses. Histological analysis showed a significantly larger mean thickness of the medial avascular zone of the ductus arteriosus in fetuses exposed to green tea than in controls (747.6 ± 214.6 µm vs 255.3 ± 97.9 µm, p < 0.001). CONCLUSIONS: This study in fetal lambs shows a cause and effect relationship between experimental maternal exposure of green tea and fetal ductus arteriosus constriction in late pregnancy.

Aortic isthmus blood flow in fetuses of diabetic mothers.

OBJECTIVE: To test the hypothesis that the aortic isthmus flow index (IFI) is lower in fetuses of diabetic mothers than in fetuses of nondiabetic mothers. STUDY DESIGN: We performed a cross-sectional observational study to assess the IFI in fetuses, with (n = 13) and without (n = 37) myocardial hypertrophy, of mothers with diabetes mellitus and in fetuses of nondiabetic mothers (n = 23). Analysis of variance and Tukey test were used to assess differences among the groups. RESULTS: There were no differences in maternal or gestational age among the groups. In fetuses of diabetic mothers, the mean IFI in fetuses with myocardial hypertrophy was 1.19 ± 0.06, and in fetuses without it was 1.18 ± 0.09. The mean IFI in fetuses of nondiabetic mothers was 1.32 ± 0.07 (P < 0.001). CONCLUSIONS: The IFI in fetuses of diabetic mothers is lower than in fetuses of nondiabetic mothers, possibly as a result of a decreased left ventricular compliance.

Influence of fetal respiratory movements on left atrial functional status.

OBJECTIVE: Because fetal respiratory movements increase left ventricular compliance, we hypothesized that the left atrial shortening fraction increases during fetal respiratory motions. METHODS: A group of 26 normal fetuses with gestational ages between 28 and 38 weeks were assessed in a prospective cross-sectional study. Left atrial telesystolic and presystolic diameters were measured during apnea and after five consecutive respiratory movements. Left atrial shortening fraction was obtained by the ratio: [maximal left atrium diameter (telesystolic) - minimal left atrium diameter (presystolic)]/maximal left atrium diameter (telesystolic). The mean of three measurements were considered. Two-tailed Student's t-test was used. RESULTS: Mean gestational age was (mean ± SD) 30.7 ± 2.8 weeks. Mean left atrial telesystolic diameter in apnea was 10.6 ± 0.7 mm and during respiratory movements it was 10.5 ± 1.1 mm (p = 0.98). Presystolic left atrial diameter was 5.2 ± 0.1 mm in apnea and 4.4 ± 1.3 mm during respiratory movements (p < 0.001). Left atrial shortening fraction was 0.50 ± 0.05 in apnea and 0.58 ± 0.13 during respiratory movements (p < 0.001). CONCLUSION: Left atrial shortening fraction is higher during respiratory movements as a result of increased left ventricular compliance and consequent optimization of left atrial functional status.

Maternal ingestion of cocoa causes constriction of fetal ductus arteriosus in rats.

Maternal consumption of polyphenol-rich foods has been associated with fetal ductus arteriosus constriction (DAC), but safety of chocolate exposure in fetal life has not been studied. This experimental study tested the hypothesis that maternal cocoa consumption in late pregnancy causes fetal DAC, with possible associated antioxidant effects. Pregnant Wistar rats, at the 21st gestational day, received by orogastric tube cocoa (720 mg/Kg) for 12 h, indomethacin (10 mg/Kg), for 8 h, or only water, before cesaren section. Immediately after withdrawal, every thorax was obtained and tissues were fixed and stained for histological analysis. The ratio of the narrowest part of the pulmonary artery to the fetal ductus inner diameter and increased ductal inner wall thickness characterized ductal constriction. Substances reactive to thiobarbituric acid were quantified. Statistical analysis used ANOVA and Tukey test. Cocoa (n = 33) and indomethacin (n = 7) reduced fetal internal ductus diameter when compared to control (water, n = 25) (p < 0.001) and cocoa alone increased ductus wall thickness (p < 0.001), but no change was noted in enzymes activity. This pharmacological study shows supporting evidences that there is a cause and effect relationship between maternal consumption of cocoa and fetal ductus arteriosus constriction. Habitual widespread use of chocolate during gestation could account for undetected ductus constriction and its potentially severe consequences, such as perinatal pulmonary hypertension, cardiac failure and even death. For this reason, dietary guidance in late pregnancy to avoid high chocolate intake, to prevent fetal ductal constriction, may represent the main translational aspect of this study.

Dynamics of the septum primum in fetuses with intrauterine growth restriction.

PURPOSE: To test the hypothesis that the linear displacement of the septum primum (SP) is lower in fetuses with intrauterine growth restriction (IUGR) than in fetuses with appropriate growth for gestational age (AGA). METHODS: In a cross-sectional study, the ratio between the SP displacement and left atrial diameter (excursion index [EI]) was compared in 27 fetuses with IUGR (group 1), 24 fetuses with AGA of hypertensive mothers (group 2), and 35 controls (group 3). Flow through the atrioventricular (AV) valves and the umbilical artery resistance index (RI) were also compared. RESULTS: Irrespective of gestational age, mean EI in group 1 (0.41 +/- 0.07) was significantly lower than in group 2 (0.48 +/- 0.07; p < 0.001) and than in group 3 (0.50 +/- 0.06; p < 0.001), with no significant differences between groups 2 and 3. In fetuses over 30 weeks of gestation of group 1, EI was lower (0.38 +/- 0.05) than in group 2 (0.49 +/- 0.07) and group 3 (0.51 +/- 0.06; p < 0.001). There was significant inverse correlation between EI and RI (r = 0.46; p < 0.01) and no correlation between EI and AV flow velocities. CONCLUSIONS: SP mobility is reduced in fetuses over 30 weeks with IUGR compared with AGA fetuses. These findings may depend on alterations of left ventricular diastolic function and are correlated to the degree of placental insufficiency.

Corrigendum to "Behaviour of the Foramen Ovale Flow in Fetuses with Intrauterine Growth Restriction".

[This corrects the article DOI: 10.1155/2018/1496903.].

Behaviour of the Foramen Ovale Flow in Fetuses with Intrauterine Growth Restriction.

Background: Foramen ovale (FO) flow may be altered in IUGR. This study was designed to test this hypothesis. Methods: Forty pregnant women (24-38 weeks) were divided into 3 groups: group I (IUGR), group II (adequate growth and maternal hypertension), and group III (normal controls). Impedance across the FO was assessed by the FO pulsatility index (FOPI): (systolic velocity - presystolic velocity)/mean velocity. Statistical analysis utilized ANOVA, Tukey test, and ROC curves. Results: Mean FOPI in IUGR fetuses (n = 15) was 3.70 ± 0.99 (3.15-4.26); in the group II (n = 12), it was 2.84 ± 0.69 (2.40-3.28), and in the group III (n = 13), it was 2.77 ± 0.44 (2.50-3.04) (p=0.004). FOPI and UtA RI were correlated (r = 0.375, p=0.017), as well as FOPI and UA RI (r = 0.356, p=0.024) and, inversely, FOPI and MCA RI (r = -0.359, p=0.023). Conclusions: The FO flow pulsatility index is increased in fetuses with IUGR, probably as a result of impaired left ventricular diastolic function.