Appropriate Growth For Gestational Age Research Articles

Early- and late-onset selective fetal growth restriction in monochorionic twin pregnancy with expectant management

ObjectiveThis study aimed to identify selective fetal growth restriction (sFGR) in monochorionic twin (MCT) pregnancy with expectant management. MethodsWe retrospectively analyzed cases of sFGR between January 2015 and December 2019 in Peking University Third Hospital. We included sFGR according to the International Society of Ultrasound in Obstetrics and Gynecology diagnostic criteria. We excluded those cases where a significant fetal structural abnormality, twin reversed arterial perfusion (TRAP), genetic syndrome or aneuploidy; cases terminated for maternal complications or for personal reasons; pregnancies that had a fetal intervention, such as fetoscopic laser photocoagulation (FLP) for vascular anastomoses, fetal reduction by radiofrequency ablation (RFA) and microwave ablation (MVA). We didn't excluded those cases that had amnioreduction therapy. According to the gestational age at onset (before 24 weeks or after), data were analyzed to identify the risk factors associated with fetal prognostic outcomes. Primary outcomes included survival of at least one twin and both twins. Secondary outcomes included gestational age of delivery, live birth weight, Apgar <7 in 5 min, admission to the neonatal unit and neonatal death. Kruskal-Wallis rank tests were used to compare non-normally distributed data, whereas categorical data were matched using Fisher's exact test or χ2 tests. ANOVA was used to compare normally distributed data, followed by a post-hoc Bonferroni analysis. Multivariate binary logistic regression was used to identify the factors connected with intrauterine death. ResultsThere were 119 pregnancies that qualified for investigation, 75 (63.0%) were categorized as early-onset sFGR and 44 (37.0%) as late-onset sFGR. The rate of survival of at least one twin (82.7% vs. 95.5%), survival of both twins (73.3% vs. 88.6%) were all reduced in the early-onset sFGR group, compared to the late-onset sFGR group. Babies born alive of fetal growth restriction (FGR) and appropriate growth for gestational age (AGA) fetuses showed similar results in the two groups regarding birth weight, 5-min Apgar score <7, neonatal death, and 28-day survival rate. A multivariable model was used to predict the intrauterine death of at least one twin. The odds ratio were significantly higher for superimposed twin-twin transfusion syndrome (TTTS) (OR 17.915, 95%CI 3.699∼86.756) and Types Ⅱ/Ⅲ sFGR (OR 4.619, 95%CI 1.074∼19.869). ConclusionsIn MCT pregnancies, early-onset sFGR had a poorer survival of at least one or both twins, but there was no statistical difference in the prognosis after live birth, neither for FGR babies nor those of AGA. Superimposed TTTS and Types Ⅱ/Ⅲ sFGR had a worse perinatal outcome. This information could be provided to the parents during prenatal counselling.

Foetal growth restriction has negative influence on narrative skills in 8-10-year-old children.

The risk for neurocognitive difficulties is increased in children born with foetal growth restriction (FGR), but no data exist yet on their narrative skills. The narrative skills of 8- to 10-year-old children born with FGR between 24 and 40weeks were compared with those of children born with appropriate growth for gestational age (AGA). A prospectively collected cohort of 36 children with FGR was recruited prenatally at a Finnish tertiary hospital from 1998-2001, and 31 children with AGA served as controls. Narrative skills were assessed using a standardised test, and correlations between narrative, communication, reading and spelling skills were studied. Children born with FGR produced significantly less information and shorter utterances in their narratives than the AGA group. Children born preterm with FGR performed significantly more poorly in their narratives than the preterm AGA group. Poor narrative skills correlated with poor communication, reading and spelling skills. Children born with FGR had poorer narrative skills compared with their AGA peers at the age of 8-10years, and narrative skills were linked to other language-based skills, which underlines the importance of early detection and preventive measures to optimise the educational outcome of children born with FGR.

Fetal growth restriction: From Polyvagal theory to developmental impairments?

BackgroundThe Polyvagal theory argues that behavioral modulation is a fundamental neurodevelopmental process that depends on autonomic regulation. ObjectiveThe present study aimed to assess sleep architecture in newborns with fetal growth restriction (FGR) using polysomnography as an indicator of Polyvagal theory. MethodsWe studied polysomnography recordings from 68 preterm infants, 34 with FGR and 34 born with appropriate growth for gestational age (AGA), who were matched according to the corrected age for prematurity (CA). Total sleep time, arousals, the percentage of quiet sleep, active sleep, indeterminate sleep, and heart rate were compared between the groups. Linear multiple regression analyses were used to evaluate polysomnography data for the FGR and AGA groups. ResultsAverage heart rate was significantly lower in most FGR groups compared with AGA groups, and small to large effect sizes were observed in several sleep responses when comparing these groups. In the lineal regression model the CA explains significantly the differences in heart rate, controlled by FGR (p = .012). Additionally, there was evidence that sleeping states show similar trends, that is, increases in quiet and indeterminate sleep, as well as decreases in active sleep when CA was controlled by FGR. ConclusionFGR probably intensifies the unfavorable effect of preterm birth in the responses evaluated by polysomnography. It seems that FGR is associated with alteration in sleep regulation and with differences in heart rate modulation, which may serve as a strategy to preserve energy and such differences likely underlie neurodevelopmental impairments in affected newborns.

The impact of fetal umbilical artery Doppler pulsatility index on childhood respiratory function and atopy: a prospective case-control study

Objective: To determine if an elevated fetal umbilical artery Doppler pulsatility index is associated with abnormal respiratory function and atopy in children aged 12 years.Methods: This prospective case-control study compared children that had an elevated fetal umbilical artery Doppler pulsatility index (>90th centile) to those with a normal pulsatility index (<90th centile). All subjects were delivered at full-term and with appropriate growth for gestational age. Outcome measures included; (i) presence of asthma and/or atopy; (ii) spirometry measurements and (iii) serum C-reactive protein and leptin. Multiple regression was used to account for parental smoking, childhood age, gender and socioeconomic status.Results: 174 children with an average age of 12.1 (±0.6 SD), 48% of who were male were included in the analysis. Of the 174, 99 (57%) were in the normal umbilical artery Doppler pulsatility index group and 75 (43%) elevated umbilical artery Doppler pulsatility index groups. The overall proportion of subjects with asthma was 28% (48/174) and atopy 56% (98/174). No association was found between elevated fetal umbilical artery Doppler pulsatility index and asthma (p = .47) or atopy (p = .75) at age 12 years. Similarly there was no association between FEV1(%) (p = .96), forced vital capacity (FVC)(%) (p = .98), elevated serum C-reactive protein (p = .69) or leptin (p = .20) and an elevated fetal umbilical artery Doppler pulsatility index.Conclusions: An elevated umbilical artery Doppler at 28-weeks gestation in the absence of prematurity or fetal growth restriction is not associated with altered respiratory function or the presence of atopy in children aged 12 years. These findings support the theory that such disease has a multifactorial pathophysiology.

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.

Neural injury markers in intrauterine growth restriction and their relation to perinatal outcomes.

BACKGROUNDThe aims of this study were to (i) compare the concentrations of two neural injury markers, S100B protein and neuron-specific enolase (NSE), in intrauterine growth-restricted (IUGR) fetuses and in fetuses with appropriate growth-for-gestational-age (AGA), and (ii) investigate potential relationships between concentrations of these markers, Doppler abnormalities, and adverse perinatal or neonatal outcomes.METHODSThis was a case-controlled, cooperative, prospective study among Spanish Maternal and Child Health Network (Retic SAMID) hospitals. At inclusion, biometry for estimated fetal weight and feto-placental Doppler were measured. At the time of delivery, maternal venous blood and fetal umbilical arterial blood samples were collected. S100B and NSE concentrations were determined from these samples.RESULTSIn total, 254 pregnancies were included. Among these, 147 were classified as IUGR and 107 as AGA. There were no differences between the groups in S100B concentrations. However, levels of NSE in maternal and umbilical cord serum differed significantly between these groups (2.31 in AGA vs. 2.51 in IUGR in (P<0.05); and 2.89 in AGA vs. 3.25 in IUGR (P<0.05), respectively). No differences were observed in these neurological markers when stratified by perinatal or neonatal complications.CONCLUSIONAlthough some variations exist in these neurological markers, they did not correlate with perinatal or neonatal complications.

Distinct promoter methylation and isoform-specific expression of RASFF1A in placental biopsies from complicated pregnancies

IntroductionEpigenetic changes in the placenta have been postulated to act as mediators between environmental influences and poor fetal growth. We assessed if genes with a plausible influence on growth could be aberrantly methylated in placental samples from pregnancies complicated by intrauterine growth restriction (IUGR). MethodsA candidate gene approach was undertaken using a custom Illumina Goldengate® array on a collection of placental samples from growth restricted pregnancies and normally grown controls with confirmation using bisulphite pyrosequencing. ResultsThe custom array analysis revealed that the promoter of RASSF1A was the only region with significant methylation differences between IUGR placentas and those from pregnancies with appropriate growth for gestational age (AGA). The RASSF1A promoter had increased levels of DNA methylation in IUGR samples compared to controls. Interestingly, the methylation difference was also observed in preeclamptic samples. Higher methylation was associated with a concomitant decrease in expression of the RASSF1 transcript A, but not other isoforms that originate from an alternative, nearby promoter interval. DiscussionOur results do not support the hypothesis that altered DNA-methylation in the placenta is a mechanism generally involved in fetal growth restriction. A specific region corresponding to the promoter of RASSF1A does display methylation changes in placenta that could be used to identify at-risk pregnancies.

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

To test the hypothesis that the pulmonary vein pulsatility index (PVPI) is higher in fetuses with growth restriction (IUGR) than in normal fetuses. 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. 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). 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.

Cardiac dysfunction is associated with altered sarcomere ultrastructure in intrauterine growth restriction

The purpose of this study was to assess whether abnormal cardiac function in human fetuses with intrauterine growth restriction (IUGR) is associated with ultrastructural differences in the cardiomyocyte sarcomere. Nine severe early-onset IUGR fetuses and 9 normally grown fetuses (appropriate growth for gestational age) who died in the perinatal period were included prospectively. Cardiac function was assessed by echocardiography and levels of B-type natriuretic peptide and troponin-I. Heart sections were imaged by second harmonic generation microscopy, which allowed unstained visualization of cardiomyocyte's sarcomere length. Echocardiographic and biochemical markers showed signs of severe cardiac dysfunction in IUGR fetuses. Second harmonic generation microscopy demonstrated a significantly shorter sarcomere length in IUGR as compared with appropriate growth for gestational age fetuses. IUGR is associated with changes in the cardiomyocyte contractile machinery in the form of shorter sarcomere length, which could help to explain the cardiac dysfunction previously documented inIUGR.

Index of Suspicion in the Nursery

Twins are born at 37-5/7 weeks gestation to a 41-year-old G4P2 woman who had unremarkable serology results. The delivery is via cesarean section because of a nonreassuring fetal heart rate. Twin B appears to be acrocyanotic and initially requires positive-pressure ventilation for 30 seconds before being able to maintain her oxygen saturation on her own. Apgar scores are 7 and 8 at 1 and 5 minutes, respectively. She also appears to be “jittery,” and her screening glucose concentration is 24 mg/dL (1.3 mmol/L). She consumes 20 mL of infant formula and a 10% dextrose (D10) infusion is begun at a rate of 60 mL/kg per day. Three hours after birth, a follow-up glucose evaluation measures 30 mg/dL (1.7 mmol/L), prompting administration of a 4-mL/kg bolus of D10 over 20 minutes and increase of the maintenance infusion rate to 100 mL/kg per day. Six hours after birth, glucose measures 80 mg/dL (4.4 mmol/L), and the infusion rate is decreased to 60 mL/kg per day. She is transferred to a hospital that has a neonatal intensive care unit (NICU) for close monitoring. On transfer, the oxygen saturation dips into the upper 80s/lower 90s, and nasal cannula administration of oxygen is initiated. Furthermore, during transfer (8 to 9 hours after birth), the blood glucose value is 44 mg/dL (2.4 mmol/l), so the D10 infusion rate is increased back to 100 mL/kg per day. On arrival at the second hospital, her oxygen saturation is about 85% and glucose is 50 mg/dL (2.8 mmol/L). In the NICU, she receives noninvasive respiratory support as well as 15% dextrose (D15) at a rate of 70 mL/kg per day. Twin A remains stable and continues to receive routine newborn care in the newborn nursery of the first hospital. Two days after birth, twin B continues to have glucose …

Dynamics of the septum primum in fetuses with intrauterine growth restriction

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). 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. 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. 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.

Mid-arm circumference and mid-arm/head circumference ratio in term newborns.

Mid-arm circumference of the newborn is strongly associated with birth weight and is a very good indicator of low and insufficient birth weight. However, there are few Brazilian studies on the relationship between mid-arm and head circumferences and, thus, this does not form part of the routine evaluation for newborns. To establish the mid-arm circumference and mid-arm/head circumference ratio in a population of term newborns. Cross-sectional study carried out between June 1997 and August 1999. Hospital Maternidade Leonor Mendes de Barros, São Paulo. Term newborns (66 males and 65 females) of appropriate growth for gestational age, whose mothers were healthy, were included in the study. Arm circumference, arm circumference/head circumference ratio, birth weight and gestational age were measured within 48 hours of birth. Data were considered significant when p < 0.01. The mean values for the mid-arm circumference were 10.76 cm (standard deviation, SD = 0.68) for females and 10.76 (SD = 0.81) for males. The mean value for the mid-arm/head circumference ratio was 0.31 (SD = 0.02) for both sexes. Mid-arm circumference values were significantly related to birth weight and gestational age, whereas mid-arm/head circumference ratio was related only to birth weight. Mid-arm circumference and mid-arm/head circumference ratio values were established for the studied population. It was possible to obtain curves for both mid-arm circumference and mid-arm/head circumference ratio in relation to birth weight. However, for mid-arm circumference, it was only possible to obtain curves in relation to gestational age. The use of the regression curves did not seem powerful enough to predict the mid-arm circumference and mid-arm/head circumference ratio in this population of term newborns. There were no gender differences for either of the measurements studied.

Determinants of bronchial responsiveness to methacholine at school age in twin pairs.

The methacholine inhalation challenge test (MIC) was used to evaluate bronchial responsiveness in 67 children who were the products of multiple pregnancies when they were 7-15 years old. At birth, 30 (45%) infants had intrauterine growth retardation (IUGR; birth weight <2 SD below normal birth weight, or birth weight difference >1.3 SD between twin-pairs), and 59 (88%) were born before 37 weeks of gestation. None of the children had doctor-diagnosed asthma. The provocative dose of methacholine causing a 20% fall in Wright's peak expiratory flow (WPEF) (PD20) was below 1,000 microg in 10 (15%) children, and they were classified as MIC responders. There were no differences in perinatal or neonatal factors between MIC responders and nonresponders; in particular, MIC responses did not differ between IUGR infants, and children with appropriate growth for gestational age (AGA) at birth. There were seven discordant pairs in which one child was a MIC responder and the other was not; 5 responders were IUGR, and 2 were AGA children (ns). Respiratory tract infections after the neonatal period were equally common in IUGR and AGA children. However, these infections were associated with later bronchial hyperresponsiveness. Doctor-diagnosed respiratory infections, numbers of antibiotic courses, episodes of otitis media, and the need for adenoidectomy, tonsillectomy, and tympanostomy were more common in MIC responders than in nonresponders. We conclude that IUGR was not associated with subsequent bronchial hyperresponsiveness in twin pairs assessed by the MIC test. A significant relationship was seen between bronchial hyperresponsiveness and infections after the neonatal period.

Correlation of Confined Placental Mosaicism with Fetal Intrauterine Growth Retardation

Objective: Our purpose was to determine if the frequency of confined placental mosaicism in newborns with unexplained intrauterine growth retardation (IUGR) was higher compared with infants with appropriate growth in utero and the outcome of these pregnancies. Study Design: A total of 20 cases with unexplained IUGR and 20 cases with appropriate growth for gestational age has been studied. Amnion, chorion and villi biopsy specimens were obtained from growth-retarded cases and controls at delivery. Cord blood specimens for 48-hour lymphocyte cultures were obtained from all infants with IUGR. Results: Karyotype analysis revealed confined placental mosaicism in two of 20 (10%) cases with IUGR. In one growth retarded case and one appropriate growth for gestational age case, mosaicism was also confirmed in the amnion. Cytogenetic analysis from peripheral blood of newborns showed normal karyotype in all cases. Three pregnancies in the group of fetuses with IUGR (15%) ended with fetal death compared with normal fetal surveillance of all cases from the control group. Conclusion: Confined placental mosaicism was detected two times more frequently from placentas of growth- retarded infants compared with those of newborns with appropriate growth. The fetal loss was significantly higher in the group of cases with IUGR compared with the control group.

Increased Platelet-activating Factor–acetylhydrolase Activity in the Umbilical Venous Plasma of Growth-restricted Fetuses

In Brief Objective To determine whether platelet-activating factor–acetylhydrolase activity in fetal plasma obtained at birth from umbilical vessels is different from that in maternal plasma, and (2) to compare platelet-activating factor–acetylhydrolase activity in cord plasma from fetuses with fetal growth restriction (FGR) and those with appropriate growth for gestational age (AGA). Methods Platelet-activating factor–acetylhydrolase activity was measured in the plasma of 22 nonpregnant healthy women, 16 pregnant women at term during labor, 28 fetuses exhibiting AGA, and seven fetuses with FGR. Results Plasma platelet-activating factor–acetylhydrolase activity in normotensive pregnant women at 37–41 weeks' gestation was 28.1 ± 16.6 nmol/mL per minute, which was not statistically different from the activity in nonpregnant women (30.8 ± 11.1 nmol/mL per minute). Platelet-activating factor–acetylhydrolase activity in venous cord plasma from AGA fetuses was significantly (P < .01) lower than that in maternal plasma (6.3 ± 2.6 nmol/mL per minute), and there was no difference between the activities found in arterial and venous cord samples. In FGR fetuses, venous cord platelet-activating factor–acetylhydrolase activity was significantly (P < .01) higher (12.1 ± 1.4 nmol/mL per minute), than the activity seen in AGA fetuses, and when the data from AGA and FGR fetuses were considered together, there was a negative correlation between cord plasma platelet-activating factor–acetylhydrolase activity and neonatal body weight (r = .46, P = .006). Conclusion Platelet-activating factor hydrolysis is significantly lower in fetuses than adults. Further, the comparatively high platelet-activating factor–acetylhydrolase activity in FGR fetuses suggests the existence of a compensatory mechanism to maintain microcirculation within the placenta. Umbilical venous plasma from growth-restricted fetuses contained significantly more plasma platelet-activating factor–acetylhydrolase activity than plasma from fetuses of appropriate size.

Increased platelet-activating factor– acetylhydrolase activity in the umbilical venous plasma of growth-restricted fetuses

Objective: To determine whether platelet-activating factor–acetylhydrolase activity in fetal plasma obtained at birth from umbilical vessels is different from that in maternal plasma, and (2) to compare platelet-activating factor–acetylhydrolase activity in cord plasma from fetuses with fetal growth restriction (FGR) and those with appropriate growth for gestational age (AGA). Methods: Platelet-activating factor–acetylhydrolase activity was measured in the plasma of 22 nonpregnant healthy women, 16 pregnant women at term during labor, 28 fetuses exhibiting AGA, and seven fetuses with FGR. Results: Plasma platelet-activating factor–acetylhydrolase activity in normotensive pregnant women at 37–41 weeks’ gestation was 28.1 ± 16.6 nmol/mL per minute, which was not statistically different from the activity in nonpregnant women (30.8 ± 11.1 nmol/mL per minute). Platelet-activating factor–acetylhydrolase activity in venous cord plasma from AGA fetuses was significantly ( P < .01) lower than that in maternal plasma (6.3 ± 2.6 nmol/mL per minute), and there was no difference between the activities found in arterial and venous cord samples. In FGR fetuses, venous cord platelet-activating factor–acetylhydrolase activity was significantly ( P < .01) higher (12.1 ± 1.4 nmol/mL per minute), than the activity seen in AGA fetuses, and when the data from AGA and FGR fetuses were considered together, there was a negative correlation between cord plasma platelet-activating factor–acetylhydrolase activity and neonatal body weight ( r = .46, P = .006). Conclusion: Platelet-activating factor hydrolysis is significantly lower in fetuses than adults. Further, the comparatively high platelet-activating factor–acetylhydrolase activity in FGR fetuses suggests the existence of a compensatory mechanism to maintain microcirculation within the placenta.