Small For Gestational Age Fetuses Research Articles

Effect of Maternal and Fetal Characteristics in Feto-Placental Doppler and Impact of Using Adjusted Standards in the Definition of Fetal Growth Restriction at Term

Introduction: This study aimed to determine the effect and clinical impact of physiological characteristics on the 95th/5th centile of the umbilical artery (UA) Doppler and the cerebroplacental ratio (CPR), at 36+ weeks. Methods: From the multicenter randomized trial “Ratio37,” we selected 4,505 low-risk pregnant women between June 2016 and January 2020. We registered physiological characteristics and the pulsatility indexes (PI) of the UA and middle cerebral artery (36–39 weeks). The 95th/5th centile of the UA PI and CPR was modeled by quantile regression. To evaluate the clinical impact of adjusting Doppler, we retrospectively applied gestational age (GA) and fully adjusted standards to 682 small for gestational age (SGA)-suspected fetuses (37 weeks) from a cohort of consecutive patients obtained between January 2010 and January 2020. Results: Several physiological characteristics significantly influenced the 95th/5th centile of the UA and CPR PI. The fully adjusted 95th centile of the UA was higher, and the 5th centile of the CPR was lower than GA-only-adjusted standards. Of the 682 SGA fetuses, 150 (22%) were classified as late fetal growth restricted only by GA and 112 (16.4%) when we adjusted Doppler. These 38 fetuses had similar perinatal outcome than the SGA group. Discussion: The 95th/5th centile of the UA and CPR PI is significantly influenced by physiological characteristics. Adjusting Doppler standards could differentiate better between FGR and SGA.

Intrapartum Fetal Electrocardiogram in Small- and Large-for-Gestational Age Fetuses.

This study aimed to evaluate whether intrapartum fetal electrocardiogram (ECG) tracings with ST-elevation or depression occur more frequently in each stage of labor in small-for-gestational age (SGA) or large-for-gestational age (LGA), as compared with appropriate-for-gestational age (AGA) fetuses. We conducted a secondary analysis of a large, multicenter trial in which laboring patients underwent fetal ECG waveform-analysis. We excluded participants with diabetes mellitus and major fetal anomalies. Birth weight was categorized as SGA (<10th percentile), LGA (>90th percentile), or AGA (10-90th percentile) by using a gender and race/ethnicity specific nomogram. In adjusted analyses, the frequency of ECG tracings with ST-depression or ST-elevation without depression was compared according to birthweight categories and labor stage. Our study included 4,971 laboring patients in the first stage and 4,074 in the second stage. During the first stage of labor, there were no differences in the frequency of ST-depression in SGA fetuses compared with AGA fetuses (6.7 vs. 5.5%; adjusted odds ratio [aOR]: 1.41, 95% confidence interval [CI]: 0.93-2.13), or in ST-elevation without depression (35.8 vs. 34.1%; aOR: 1.17, 95% CI: 0.94-1.46). During the second stage, there were no differences in the frequency of ST-depression in SGA fetuses compared with AGA fetuses (1.6 vs. 2.0%; aOR: 0.69, 95% CI: 0.27-1.73), or in ST-elevation without depression (16.2 vs. 18.1%; aOR: 0.90, 95% CI: 0.67-1.22). During the first stage of labor, there were no differences in the frequency of ST-depression in LGA fetuses compared with AGA fetuses (6.3 vs. 5.5%; aOR: 0.97, 95% CI: 0.60-1.57), or in ST-elevation without depression (33.1 vs. 34.1%; aOR: 0.80, 95% CI: 0.62-1.03); during the second stage of labor, the frequency of ST-depression in LGA compared with AGA fetuses (2.5 vs. 2.0%, aOR: 1.36, 95% CI: 0.61-3.03), and in ST-elevation without depression (15.5 vs. 18.1%; aOR: 0.83, 95% CI: 0.58-1.18) were similar as well. The frequency of intrapartum fetal ECG tracings with ST-events is similar among SGA, AGA, and LGA fetuses. · SGA and LGA neonates are at increased risk of cardiac dysfunction.. · Fetal ECG has been used to evaluate fetal response to hypoxia.. · Fetal ST-elevation and ST-depression occur during hypoxia.. · Frequency of intrapartum ST-events is similar among SGA, AGA and LGA fetuses..

Exercise Capacity in Young Adults Born Small for Gestational Age

Being born small for gestational age (SGA), approximately 10% of all births, is associated with increased risk of cardiovascular mortality in adulthood, but mechanistic pathways are unclear. Cardiac remodeling and dysfunction occur in fetuses SGA and children born SGA, but it is uncertain whether and how these changes persist into adulthood. To evaluate baseline cardiac function and structure and exercise capacity in young adults born SGA. This cohort study conducted from January 2015 to January 2018 assessed a perinatal cohort born at a tertiary university hospital in Spain between 1975 and 1995. Participants included 158 randomly selected young adults aged 20 to 40 years born SGA (birth weight below the 10th centile) or with intrauterine growth within standard reference ranges (controls). Participants provided their medical history, filled out questionnaires regarding smoking and physical activity habits, and underwent incremental cardiopulmonary exercise stress testing, cardiac magnetic resonance imaging, and a physical examination, with blood pressure, glucose level, and lipid profile data collected. Being born SGA. Cardiac structure and function assessed by cardiac magnetic resonance imaging, including biventricular end-diastolic shape analysis. Exercise capacity assessed by incremental exercise stress testing. This cohort study included 81 adults born SGA (median age at study, 34.4 years [IQR, 30.8-36.7 years]; 43 women [53%]) and 77 control participants (median age at study, 33.7 years [interquartile range (IQR), 31.0-37.1 years]; 33 women [43%]). All participants were of White race/ethnicity and underwent imaging, whereas 127 participants (80% of the cohort; 66 control participants and 61 adults born SGA) completed the exercise test. Cardiac shape analysis showed minor changes at rest in right ventricular geometry (DeLong test z, 2.2098; P = .02) with preserved cardiac function in individuals born SGA. However, compared with controls, adults born SGA had lower exercise capacity, with decreased maximal workload (mean [SD], 180 [62] W vs 214 [60] W; P = .006) and oxygen consumption (median, 26.0 mL/min/kg [IQR, 21.5-33.5 mL/min/kg vs 29.5 mL/min/kg [IQR, 24.0-36.0 mL/min/kg]; P = .02). Exercise capacity was significantly correlated with left ventricular mass (ρ = 0.7934; P < .001). This cohort of young adults born SGA had markedly reduced exercise capacity. These results support further research to clarify the causes of impaired exercise capacity and the potential association with increased cardiovascular mortality among adults born SGA.

Ultrasound and Doppler findings in pregnant women withSARS-CoV-2 infection.

ABSTRACTObjectivesTo describe and compare ultrasound and Doppler findings in pregnant women who were positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with findings in those who were SARS‐CoV‐2‐negative, evaluated during the pandemic period.MethodsIn this retrospective case–control study, we analyzed data from 106 pregnant women who tested positive for SARS‐CoV‐2 at the time of, or within 1 week of, an ultrasound scan between 1 May and 31 August 2020. Scans were either performed for routine fetal evaluation or indicated due to a positive SARS‐CoV‐2 test. Forty‐nine women were symptomatic and 57 were asymptomatic. For comparison, we analyzed data from 103 pregnant women matched for maternal age, parity, body mass index and gestational age at the time of the ultrasound scan. These control women did not report symptoms of SARS‐CoV‐2 infection at the time of the ultrasound scan or at the time of admission for delivery and had a negative SARS‐CoV‐2 test at admission for delivery. Fetal biometry, fetal anatomy, amniotic fluid volume and Doppler parameters, including umbilical and fetal middle cerebral artery pulsatility indices, cerebroplacental ratio and biophysical profile (BPP), were evaluated as indicated. Biometric and Doppler values were converted to Z‐scores for comparison. Our primary outcome, an adverse prenatal composite outcome (APCO) included any one or more of: small‐for‐gestational‐age (SGA) fetus, oligohydramnios, abnormal BPP, abnormal Doppler velocimetry and fetal death. Comorbidities, delivery information and neonatal outcome were compared between the two groups.ResultsEighty‐seven (82.1%) women who were positive for SARS‐CoV‐2 had a body mass index > 25 kg/m2. SARS‐CoV‐2‐positive women had a higher prevalence of diabetes (26/106 (24.5%) vs 13/103 (12.6%); P = 0.03), but not of pre‐eclampsia (21/106 (19.8%) vs 11/103 (10.7%); P = 0.08), compared with controls. The prevalence of APCO was not significantly different between SARS‐CoV‐2‐positive women (19/106 (17.9%)) and controls (9/103 (8.7%)) (P = 0.06). There were no differences between SARS‐CoV‐2‐positive women and controls in the prevalence of SGA fetuses (12/106 (11.3%) vs 6/103 (5.8%); P = 0.17), fetuses with abnormal Doppler evaluation (8/106 (7.5%) vs 2/103 (1.9%); P = 0.08) and fetuses with abnormal BPP (4/106 (3.8%) vs 0/103 (0%); P = 0.14). There were two fetal deaths in women who were positive for SARS‐CoV‐2 and these women had a higher rate of preterm delivery ≤ 35 weeks of gestation (22/106 (20.8%) vs 9/103 (8.7%); odds ratio, 2.73 (95% CI, 1.19–6.3); P = 0.01) compared with controls.ConclusionsThere were no significant differences in abnormal fetal ultrasound and Doppler findings observed between pregnant women who were positive for SARS‐CoV‐2 and controls. However, preterm delivery ≤ 35 weeks was more frequent among SARS‐CoV‐2‐positive women. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Perinatal Outcome and its Prediction Using Longitudinal Feto-Maternal Doppler Follow-Up in Late Onset Small for GestationalAge Fetuses - A Prospective Cohort Study.

To describe the perinatal outcome of a prospective cohort of late-onset small-for-gestational-age (SGA) fetuses and to test adverse perinatal outcome (APO) prediction using Doppler measurements. Singleton pregnancies from 32 weeks with suspicion of SGA (followed-up each 2 weeks) and randomly selected healthy controls at a university hospital were included. The whole SGA group was divided into the FGR subgroup or SGA percentile 3-10 subgroup. The following Doppler measurements were evaluated prospectively: umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, cerebro-placental ratio (CPR), and mean uterine artery (mUtA) PI. APO was defined as arterial cord blood pH ≤ 7.15 and/or 5-minute Apgar ≤ 7 and/or emergency operative delivery and/or admission to the neonatal unit. Induction of labor was indicated according to a stage-based protocol. A total of 149 SGA and 143 control fetuses were included. The number of operative deliveries was similar between both groups (control: 29 %, SGA: 28 %), especially the cesarean delivery rate after the onset of labor (11 % vs. 10 %). Most SGA cases ended up in induction of labor (61 % vs. 31 %, p < 0.001). The areas under the curve (AUC) for APO prediction were similar using the last UA PI, MCA PI, CPR, and mUtA PI and barely reached 0.60. The AUC was best for the FGR subgroup, using the minimal CPR or maximum mUtA PI z-score of all longitudinal measurements (AUC = 0.63). SGA fetuses do not have a higher rate of operative delivery if managed according to a risk stratification protocol. Prediction of APO is best for SGA and FGR using the "worst" CPR or mUtA PI but it remains moderate.

Routine third-trimester ultrasound for the detection of small-for-gestational age in low-risk pregnancies (ROTTUS study): randomized controlled trial.

To compare the proportion of small-for-gestational-age (SGA) infants detected by routine third-trimester ultrasound vs those detected by selective ultrasound based on serial symphysis-fundus height (SFH) measurements (standard care) in low-risk pregnancy. This was an open-label randomized controlled trial conducted at a hospital in Kenya between May 2018 and February 2020. Low-risk pregnant women were randomly allocated (ratio of 1:1) to routine ultrasound for fetal growth assessment between 36 + 0 and 37 + 6 weeks' gestation (intervention group) or to standard care, which involved a selective growth scan on clinical suspicion of fetal growth abnormality based on serial SFH measurements (control group). During ultrasound examination, fetal growth was assessed by measurement of the abdominal circumference (AC), and AC < 10th centile was used to diagnose a SGA fetus. The main prespecified outcomes were the detection of neonatal SGA, defined as birth weight < 10th centile, and of severe neonatal SGA, defined as birth weight < 3rd centile. The predictive performance of routine third-trimester ultrasound and selective ultrasound based on serial SFH measurements was determined using receiver-operating-characteristics (ROC)-curve analysis. Of 566 women assessed for eligibility, 508 (89.8%) were randomized, of whom 253 were allocated to the intervention group and 255 to the control group. Thirty-six babies in the intervention group and 26 in the control group had a birth weight < 10th centile. The detection rate of SGA infants by routine third-trimester ultrasound vs that by standard care was 52.8% (19/36) vs 7.7% (2/26) (P < 0.001) and the specificity was 95.5% (191/200) and 97.9% (191/195), respectively (P = 0.08). The detection rate of severe SGA was 66.7% (12/18) by routine ultrasound vs 8.3% (1/12) by selective ultrasound based on SFH measurements (P < 0.001), with specificities of 91.7% (200/218) and 98.1% (205/209), respectively (P = 0.006). The area under the ROC curve of routine third-trimester ultrasound in prediction of SGA was significantly greater than that of selective ultrasound based on SFH measurements (0.92 (95% CI, 0.87-0.96) vs 0.68 (95% CI, 0.58-0.77); P < 0.001). In low-risk pregnancy, routine ultrasound performed between 36 + 0 and 37 + 6 weeks is superior to selective ultrasound based on serial SFH measurements for the detection of true SGA, with high specificity. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Third trimester ultrasound estimated fetal weight for increasing prenatal prediction of small-for-gestational age newborns in low-risk pregnant women

Aim The early detection of small-for-gestational age (SGA) fetuses and newborns is pivotal in the prevention of perinatal mortality. Objectives To compare the predictive capability of performing ultrasound-based estimated fetal weight (EFW) at 32 versus 36 weeks’ gestation on the detection rate of SGA fetuses and SGA newborns at delivery, and to find a better cutoff level to consider a fetus at risk of being born small. Material and methods Nine hundred fifteen low-risk pregnant women were assessed at both 32 and 36 weeks’ gestation. EFW centile was calculated in both occasions. The rate of SGA fetuses was compared. SGA fetuses were considered when both abdominal circumference (AC) and EFW were below the 10th centile from a total of 488 delivered at our Hospital. Paired comparisons between ultrasound at 32 and 36 weeks’ gestation were done to predict SGA at delivery. Percentages of SGA fetuses were compared by chi-squared test. ANOVA test was used for comparing centiles among groups. Receiver operating characteristic (ROC) curve was used to find the best cutoff ultrasound centile to predict SGA at delivery. Statistical significance was previously set at 95% level (p < .05). Results Ultrasound-based EFW at 32 weeks showed 23 cases of SGA (2.5%) while at 36 weeks this rate increased up to 4% (37/915) (p < .000001). When comparing both outcomes, 2.8% of those catalogued as adequate-for-gestational age (AGA) at 32 weeks were cases of SGA at 36 weeks. In addition, 47.8% of those diagnosed as SGA were not confirmed at 36 weeks. Only 12.3% of SGA neonates were identified at 32 weeks’ gestation ultrasound, while using the 36 weeks’ gestation approach this rate increased up to 30.9%. So, only a low proportion of SGA neonates were SGA fetuses at any of these two gestational ages. However, the area under the curve (AUC) at 36 weeks was as high as 0.86. Being a matter of cutoff rather than a matter of choosing the correct variable, ROC analysis showed that the best cutoff for prediction having the best sensitivity (0.80) with the best specificity (0.77) was 28th centile of EFW. This represents 24.9% of the studied women (228/915). Conclusions In general, ultrasound at 36 weeks has better performance detecting SGA fetuses than ultrasound at 32 weeks and we suggest to definitively change from 32 to 36 weeks in order to increase the detection rate of SGA fetuses. Moreover, in order to detect those fetuses who will grow below the lower level of the normal range in the last month of pregnancy, we suggest that those with EFW below the 28th centile at 36 weeks should be rescanned later in pregnancy to identify prenatally as many cases as we can of SGA newborns.

The association of hypertensive disorders of pregnancy with small for gestational age and intertwin birthweight discordance.

Available evidence shows conflicting results regarding the association between hypertensive disorders of pregnancy (HDPs)/preeclampsia (PE) and small for gestational age (SGA) and birthweight discordance (BWD). This retrospective study of 2131 twin pregnancies aimed to evaluate the association of HDPs/PE with the presence of SGA and BWD. The eligible pregnancies were categorized into four study groups: concordant pairs without SGA fetuses, discordant pairs without SGA fetuses, concordant pairs with SGA fetuses, and discordant pairs with SGA fetuses. We applied binary logistic regression models to compare the incidence of HDPs/PE and multinomial logit regression models to evaluate the severity of PE between the study groups. The models were adjusted for potential confounders. Increases in HDPs were observed in concordant (aOR, 2.33; 95% CI: 1.46–3.73) and discordant (aOR, 3.50; 95% CI: 2.26–5.43) pregnancies with SGA fetuses but not in discordant pregnancies without SGA fetuses (aOR, 1.42; 95% CI: 0.81–2.49); increases in PE were also found in concordant (aOR, 1.87; 95% CI: 1.08–3.23) and discordant (aOR, 3.75; 95% CI: 2.36–5.96) pregnancies with SGA fetuses but not in discordant pregnancies without SGA fetuses (aOR, 1.34; 95% CI: 0.71–2.52). Discordant pregnancies with SGA fetuses were associated with severe PE (aRRR, 3.48; 95% CI: 1.79–6.77), whereas concordant pregnancies with SGA fetuses were associated with only mild PE (aRRR, 2.54; 95% CI: 1.33–4.88). Our results suggest that SGA is associated with the development of HDP/PE, while discordant growth is associated with the severity of PE. These associations need to be further investigated using estimated fetal weight (EFW).

Maternal nutrient restriction alters thyroid hormone dynamics in placentae of sheep having small for gestational age fetuses

Thyroid hormones regulate a multitude of metabolic and cellular processes involved in placental and fetal growth, while maternal nutrient restriction (NR) has the potential to influence these processes. Those fetuses most impacted by NR, as categorized by weight, are termed small for gestational age (SGA), but the role of thyroid hormones in these pregnancies is not fully understood. Therefore, the aims of the present study were to determine effects of NR during pregnancy on maternal and fetal thyroid hormone concentrations, as well as temporal and cell-specific expression of mRNAs and proteins for placental thyroid hormone transporters, thyroid hormone receptors, and deiodinases in ewes having either SGA or normal weight fetuses. Ewes with singleton pregnancies were fed either a 100% NRC (n = 8) or 50% NRC (NR; n = 28) diet from Days 35 to 135 of pregnancy with a single placentome surgically collected on Day 70. Fetal weight at necropsy on Day 135 was used to designate the fetuses as NR NonSGA (n = 7; heaviest NR fetuses) or NR SGA (n = 7; lightest NR fetuses). Thyroid hormone levels were lower in NR SGA compared to NR NonSGA ewes, while all NR fetuses had lower concentrations of thyroxine at Day 135. Expression of mRNAs for thyroid hormone transporters SLC16A2, SLC16A10, SLCO1C1, and SLCO4A1 were altered by day, but not nutrient restriction. Expression of THRA mRNA and protein was dysregulated in NR SGA fetuses with protein localized to syncytial and stromal cells in placentomes in all groups. The ratio of deiodinases DIO2 and DIO3 was greater for NR SGA placentae at Day 70, while DIO3 protein was less abundant in placentae from NR SGA than 100% NRC ewes. These results identify mid-gestational modifications in thyroid hormone-associated proteins in placentomes of ewes having SGA fetuses, as well as a potential for placentomes from NonSGA pregnancies to adapt to, and overcome, nutritional restrictions during pregnancy.

Screening for Small for Gestational Age Fetus: Are we Succeeding? an Audit of Performance at a Regional Hospital

Background: Fetal growth restriction affects perinatal morbidity and mortality and in practice. symphysis fundal height measurement only identifies 17.3-24.8% of Small for Gestational Age (SGA) fetuses. Plotting on a growth chart and observation of trends has been reported to increase detection rate. Failure to diagnose such fetuses is a recurrent issue at the hospital. Aims: To determine rate of detection of SGA fetuses during the antenatal period and to determine effect of maternal factors on the detection rate. Materials and Methods: This was a retrospective chart review of all babies born at Ipswich General Hospital from 2016 to 2018 in singleton pregnancies with birthweight below the tenth percentile and born ≥28 weeks gestation confirmed by first trimester dating ultrasound. Results: Over 3 years, 760 singleton SGA infants were born. 86.4% had at least 3 antenatal visits after 20 weeks gestation. Although at some stage in pregnancy 52.5% had a symphysis fundal height (SFH) measurement ≥3cm less than gestational age, in only 273 (36%) this resulted in a request for an ultrasound scan to confirm SGA fetus. This happened 53.1% of women who had a scan. Statistical analysis showed the only factor to affect SFH measurement and ultrasound diagnosis of SGA was maternal BMI while maternal age, parity and smoking status had no significant effect. Conclusion: The rate of detection of SGA is low but may be improved with the introduction of a new program of education and plotting of SFH on charts to assess trend. Keywords: Small for gestational age; Symphysis-Fundal height; Antenatal care; Ultrasound

Fetal Umbilical Vein Flow in the Classification of Fetuses with Growth Restriction

Objectives: To assess umbilical vein (UV) blood flow in fetal growth restriction (FGR) and in pregnancy with small for gestational age (SGA) fetus. To evaluate the predictive capacity of UV blood flow (QUV) in the discrimination of SGA fetuses from FGR before and after 32 weeks of pregnancy. Methods: Sixty-five women with a recent diagnosis of FGR or SGA fetuses were enrolled and underwent a complete fetal Doppler examination comprehending QUV. We collected SGA (n = 34), early-FGR (n = 9), and late-FGR (n = 22) fetuses. Results: UV diameter was lower in early and late-FGR compared to SGA, while time-averaged maximum velocity (TAMXV) was lower only in early-FGR. UV blood flow (QUV) and QUV corrected for estimated fetal weight (cQUV) were significantly lower in early-FGR and late-FGR compared to SGA. The receiver operating characteristic (ROC) curves analysis of cQUV showed a significant predictive capacity for SGA diagnosis before and after 32 weeks. Conclusions: The evaluation of UV blood flow allows distinguishing SGA fetuses from FGR. The assessment of UV flow should be taken into consideration in future research of new parameters to differentiate SGA from FGR.

Impact du parcours de soins sur le taux d’interventions obstétricales dans la prise en charge des fœtus petit pour l’âge gestationnel (Étude IATROPAG)

BackgroundWhile previous studies have demonstrated an improvement in implementation of clinical practices and an improved neonatal prognosis when growth restricted fetuses were followed within a standardized healthcare pathway, the objective of this study was to assess the prevalence of obstetric interventions in small-for-gestational-age (SGA) fetuses followed within a standardized care pathway compared to a traditional care pathway. MethodsWe conducted a retrospective study between 2015 and 2017, in a type III maternity hospital in Lyon, in a population of SGA fetuses, considered as such in case of antenatal diagnosis of fetal weight<10th percentile but>3rd centile without umbilical Doppler abnormality during antenatal surveillance and without ultrasound argument suggesting intrauterine growth retardation (IUGR). We collected the gestational age at diagnosis, obstetrical events and prevention of preterm delivery (antenatal corticosteroids), gestation age at birth, the method of delivery (spontaneous or induced), indication of induction, the method of birth (spontaneous, instrumental extraction or caesarean section), and the immediate neonatal outcome including cord pH, Apgar score at 5minutes, birth weight and fetal sex. After diagnosis, the choice of the pathway was left to the practitioner depending on their habit, their ability to manage the follow-up and their organizational constraints. ResultsOver the study period, and after exclusion of IUGR, 96 SGA were followed up in the traditional pathway and 106 SGA were followed up in the standardized pathway P=0.75. The traditional pathway showed in multivariate analysis a higher prevalence of antenatal corticosteroid therapy for SGA (16,6%) between 2015 and 2017 with OR 7.3 95% CI [1.41-38.43] when compared to the standardized pathway (3,7%). Similarly, the traditional pathway proposes a higher prevalence of induction of labor (54,1%) than the standardized pathway (33,9%) between 2015 and 2017 with OR 3.19 95% CI [1.70-7.80]. The “a posteriori” post-hoc power of the study is 82.9%. ConclusionThis study confirms the absence of excessive obstetrical intervention in the SGA population when followed in a standardized healthcare pathway. The latter would reduce unnecessary obstetrical interventions while respecting the intrinsic neonatal prognosis of small for gestational age fetuses.

FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction.

Fetal growth restriction (FGR) is defined as the failure of the fetus to meet its growth potential due to a pathological factor, most commonly placental dysfunction. Worldwide, FGR is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Ongoing advances in clinical care, especially in definitions, diagnosis, and management of FGR, require efforts to effectively translate these changes to the wide range of obstetric care providers. This article highlights agreements based on current research in the diagnosis and management of FGR, and the areas that need more research to provide further clarification of recommendations. The purpose of this article is to provide a comprehensive summary of available evidence along with practical recommendations concerning the care of pregnancies at risk of or complicated by FGR, with the overall goal to decrease the risk of stillbirth and neonatal mortality and morbidity associated with this condition. To achieve these goals, FIGO (the International Federation of Gynecology and Obstetrics) brought together international experts to review and summarize current knowledge of FGR. This summary is directed at multiple stakeholders, including healthcare providers, healthcare delivery organizations and providers, FIGO member societies, and professional organizations. Recognizing the variation in the resources and expertise available for the management of FGR in different countries or regions, this article attempts to take into consideration the unique aspects of antenatal care in low-resource settings (labelled “LRS” in the recommendations). This was achieved by collaboration with authors and FIGO member societies from low-resource settings such as India, Sub-Saharan Africa, the Middle East, and Latin America.

Aortic isthmus Doppler in normal and small-for-gestational-age fetuses and its association with prediction of adverse perinatal outcome.

To establish reference ranges for aortic isthmus Doppler indices in appropriate-for-gestational-age (AGA) fetusesand to evaluate its association with perinatal outcome in small-for-gestational-age (SGA) fetuses. Prospective cohort observational study in which 30 pregnant women with SGA fetuses and 60 women with AGA fetuses were recruited from the prenatal clinic of the hospital. The AGA group was eventually followed from 24weeks by 4-weekly Doppler assessment, and the SGA group was examined as per institutional protocol. We analyzed the data using STATA version 14.0 statistical software. Continuous variables were examined for normality assumption using the Kolmogorov-Smirnov test. To develop a nomogram for appropriate gestational age, we adopted a mixed linear model analysis. For each of the variables Ao pulsatility index (PI), Ao peak systolic velocity (PSV), Ao systolic nadir (Ns), and Ao isthmic systolic index (ISI) mean predicted values, 3rd centile and 97th centile were calculated based on the parameter estimation of mixed model. Observed data for each of the variables in the SGA group were plotted in the nomogram developed for the AGA group to show the trend of SGA data in comparison to AGA data. The total number of observations made on 60 AGA and 30 SGA fetuses were 240 and 67, respectively. Nomograms for the 3rd and 97th centiles were derived for Ao PI, Ao PSV, Ao Ns, and Ao ISI. Mean Ao PI values were significantly higher in SGA group (2.37 vs 2.22; P<.05); mean Ao PSV was significantly lower in the SGA group (67.1 vs 76.3; P<.05), but mean Ao Ns and mean Ao ISI values were significantly higher in the SGA group (-5.24 vs 2.0 and -0.04 vs -0.01; P<.05). Aortic Doppler assessment seems to provide beneficial information for monitoring small fetuses. Ao PI and Ao ISI, which were raised in fetuses with SGA, can be used in prognosis.

Ten-year experience of protocol-based management of small-for-gestational-age fetuses: perinatal outcome in late-pregnancy cases diagnosed after 32 weeks.

To report our 10-year experience of protocol-based management of small-for-gestational-age (SGA) fetuses, based on standardized clinical and Doppler criteria, in late-pregnancy cases. A retrospective cohort was constructed of consecutive singleton pregnancies referred for late-onset (> 32 weeks) SGA (defined as estimated fetal weight (EFW) < 10th centile) that were classified as fetal growth restriction (FGR) or low-risk SGA, based on the severity of smallness (EFW < 3rd centile) and the presence of Doppler abnormalities (uterine artery pulsatility index (UtA-PI) ≥ 95th centile or cerebroplacental ratio (CPR) < 5th centile). Low-risk SGA pregnancies were followed at 2-week intervals and delivered electively at 40 weeks. FGR pregnancies were followed at 1-week intervals, or more frequently if there were signs of fetal deterioration, and were delivered electively after 37 + 0 weeks' gestation. The occurrence of stillbirth and composite adverse outcome (CAO; defined as neonatal death, metabolic acidosis, need for endotracheal intubation or need for admission to the neonatal intensive care unit) was analyzed in low-risk SGA and FGR pregnancies. A total of 1197 pregnancies with EFW < 10th centile were identified and classified at diagnosis as low-risk SGA (n = 619; 51.7%) or FGR (n = 578; 48.3%). Of these, 160 were delivered before 37 weeks' gestation; for obstetric reasons in 93 (58.1%) cases, severe pre-eclampsia in 33 (20.6%), FGR with severe hypoxia in 47 (29.4%) and stillbirth in four (2.5%) (indications are non-exclusive). During follow-up, 52/574 (9.1%) low-risk SGA pregnancies were reclassified as FGR, whereas 22/463 (4.8%) FGR pregnancies were reclassified as low-risk SGA. Overall, there were no stillbirths in the low-risk SGA group and four in the FGR group, all of which occurred before 37 weeks. There were no instances of neonatal death in pregnancies delivered ≥ 37 weeks. The risk of CAO was higher in those meeting antenatal criteria for FGR at 37 weeks than in those classified as low-risk SGA (32/493 (6.5%) vs 15/544 (2.8%); odds ratio, 2.5 (95%CI, 1.3-4.6)). In FGR pregnancies, the adjusted odds ratio (95% CI) for CAO was 6.3 (1.8-21.1) in those with EFW < 3rd centile, while it was 3.2 (1.5-6.8) and 4.2 (1.9-8.9) in those with UtA-PI ≥ 95th centile and CPR < 5th centile, respectively, as compared to FGR pregnancies without each of these criteria. Protocol-based risk stratification with different management and monitoring schemes for late pregnancy with a suspected SGA baby, based on clinical and Doppler criteria, enables identification and tailored assessment of high-risk FGR, while allowing expectant management with safe perinatal outcome for low-risk SGA fetuses. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Performance of a local reference curve for predicting small for gestational age fetuses in pregnant women with HIV/AIDS.

To compare the performance of a local estimated fetal weight curve with curves established for other populations to predict small for gestational age (SGA) fetuses. A retrospective and cross-sectional study involving 231 fetuses in which the performance of a local curve (proposed model) was compared with the Hadlock and Intergrowth-21st curves in the prediction of SGA fetuses, by applying them to a population of high-risk pregnant woman with HIV/AIDS. For each model, a receiver operating characteristic curve was adjusted, considering the SGA classification by the neonatal Intergrowth method as the gold standard, and the area under the curve (AUC) was calculated. The models presented linear correlations with each other. The agreement of the proposed model with Hadlock was very good (kappa = 0.83), whereas the proposed model and Intergrowth-21st had moderate agreement (kappa = 0.44). The SGA fetus detection sensitivities of the proposed model and Hadlock were 61.9% and 57.1%, with specificity of 84.1% and 86.2% and accuracy of 80.1% and 81%, respectively, without statistical difference. The sensitivity of the Intergrowth-21st model was 33.3%, while the accuracy was 85.7% and the specificity was 97.4%. The AUC estimated values for the Hadlock, proposed, and Intergrowth-21st models were 0.834, 0.832, and 0.835, respectively. The proposed model and Hadlock were interchangeable in the prediction of SGA fetuses and superior to the Intergrowth-21st model.

Hemodynamic findings in normotensive women with small-for-gestational-age and growth-restricted fetuses.

Fetal growth restriction (FGR) in most instances is a consequence of primary placental dysfunction due to inadequate trophoblastic invasion. Maternal cardiac maladaptation to pregnancy has been proposed as a possible determinant of placental insufficiency and impaired fetal growth. This study aimed to compare the maternal hemodynamic parameters between normotensive women with small-for-gestational-age (SGA) and FGR fetuses and to evaluate their correlation with neonatal outcome. An observational cohort study including singleton pregnancies referred to our tertiary care center due to fetal smallness. At the time of diagnosis, fetuses were classified as SGA or FGR according to the Delphi consensus criteria, and pregnant women underwent hemodynamic assessment using a cardiac output monitor. A group of women with singleton uncomplicated pregnancies ar ≥35weeks of gestation were recruited as controls. Cardiac output, systemic vascular resistance, stroke volume, and heart rate were measured and compared among the three groups (controls vs FGR vs SGA). The correlation between antenatal findings and neonatal outcome was also evaluated by multivariate logistic regression analysis. A total of 51 women with fetal smallness were assessed at 34.8±2.6weeks. SGA and FGR were diagnosed in 22 and 29 cases, respectively. The control group included 61 women assessed at 36.5±0.8weeks of gestation. Women with FGR had a lower cardiac output Z-score (respectively, -1.3±1.2 vs -0.4±0.8 vs -0.2±1.0; P<.001) and a higher systemic vascular resistance Z-score (respectively, 1.2±1.2 vs 0.2±1.1 vs -0.02±1.2; P<.001) compared with both SGA and controls, whereas no difference in the hemodynamic parameters was found between women with SGA and controls. The incidence of neonatal intensive care unit admission did not differ between SGA and FGR fetuses (18.2% vs 41.4%; P=.13), but FGR fetuses had a longer hospitalization compared with SGA fetuses (14.2±17.7 vs 4.5±1.6days; P=.02). Multivariate analysis showed that the cardiac output Z-score at diagnosis (P=.012) and the birthweight Z-score (P=.007) were independent predictors of the length of neonatal hospitalization. Different maternal hemodynamic profiles characterize women with SGA or FGR fetuses. Furthermore, a negative correlation was found between the maternal cardiac output and the length of neonatal hospitalization.

The PLANES study: a protocol for a randomised controlled feasibility study of the placental growth factor (PlGF) blood test-informed care versus standard care alone for women with a small for gestational age fetus at or after 32 + 0\u2009weeks\u2019 gestation

BackgroundStillbirth remains a major concern across the globe and in some high-resource countries, such as the UK; efforts to reduce the rate have achieved only modest reductions. One third of stillborn babies are small for gestational age (SGA), and these pregnancies are also at risk of neonatal adverse outcomes and lifelong health problems, especially when delivered preterm. Current UK clinical guidance advocates regular monitoring and early term delivery of the SGA fetus; however, the most appropriate regimen for surveillance of these babies remains unclear and often leads to increased intervention for a large number of these women. This pilot trial will determine the feasibility of a large-scale trial refining the risk of adverse pregnancy outcome in SGA pregnancies using biomarkers of placental function sFlt-1/PlGF, identifying and intervening in only those deemed at highest risk of stillbirth.MethodsPLANES is a randomised controlled feasibility study of women with an SGA fetus that will be conducted at two tertiary care hospitals in the UK. Once identified on ultrasound, women will be randomised into two groups in a 3:1 ratio in favour of sFlt-1/PlGF ratio led management vs standard care. Women with an SGA fetus and a normal sFlt-1/PlGF ratio will have a repeat ultrasound and sFlt-1/PlGF ratio every 2 weeks with planned birth delayed until 40 weeks. In those women with an SGA fetus and an abnormal sFlt-1/PlGF ratio, we will offer birth from 37 weeks or sooner if there are other concerning features on ultrasound. Women assigned to standard care will have an sFlt-1/PlGF ratio taken, but the results will be concealed from the clinical team, and the woman’s pregnancy will be managed as per the local NHS hospital policy. This integrated mixed method study will also involve a health economic analysis and a perspective work package exploring trial feasibility through interviews and questionnaires with participants, their partners, and clinicians.DiscussionOur aim is to determine feasibility through the assessment of our ability to recruit and retain participants to the study. Results from this pilot study will inform the design of a future large randomised controlled trial that will be adequately powered for adverse pregnancy outcome. Such a study would provide the evidence needed to guide future management of the SGA fetus.Trial registrationISRCTN58254381. Registered on 4 July 2019

Evaluation of midtrimester ductus venosus diameter and peak systolic velocity to predict late onset small for gestational age fetuses

Objective The ductus venosus, a small blood vessel in the fetal venous system, has extraordinary physiologic significance because it connects the umbilical vein to the inferior vena cava in the fetus circulation system and transports highly oxygenated blood from the placenta to the fetus’ heart. Hence, assessment of ductus venosus flows is helpful in evaluating fetal hemodynamics. Considering the critical function of the ductus venosus, we hypothesized that the diameter of the midtrimester ductus venosus and its peak velocity index can be related to adequate fetal growth; therefore, the aim of this study was to evaluate the role of the midtrimester umbilical venous blood flow, ductus venosus diameter, and ductus venosus peak systolic velocity to help predict uncomplicated deliveries of late onset small for gestational age (SGA) fetuses. Methods In this prospective study we analyzed the pregnancies and deliveries of 398 pregnant women who met the inclusion criteria and divided them into three groups according to fetal birth weight as follows: birth weight <3 percentile SGA group (n = 16), birth weight 3–10 percentile SGA group (n = 42), and appropriate for the gestational age (AGA) group (n = 340). The midtrimester ductus venosus diameter and peak sistolic velocity, umbilical venous blood flow, and umbilical artery pulsatility index (PI) were recorded. In the absence of congenital anomalies, the diagnosis of fetal growth restriction (FGR) is made according to Delphi consensus criteria. In the absence of abnormal Doppler findings, late FGR was defined as occurring ≥32 weeks. Results Maternal age, nulliparity, mean gestational age at ultrasound evaluation, ethnicity, body mass index, and previous cesarean delivery rates were similar among the groups. In addition, mid-trimester fetal biometric measurements and amniotic fluid volume were similar among the groups. The gestational age at delivery, prematurity, fetal birth weight, vaginal delivery rates, and rate of admission to the neonatal intensive care unit were significantly different among the groups. The mean mid-trimester umbilical vein blood flow to abdominal circumference ratio (UVBF/AC) was similar among the groups (p=.740). In the <3 group, the mean peak systolic velocity of the ductus venosus was significantly lower and the mean diameter of the ductus venosus significantly higher than those in the 3–10 and AGA groups (both p<.001). Although the values are below the 95th percentile mid-trimester umbilical artery PI was significantly higher in the <3 percentile SGA group than in the 3–10 percentile SGA and AGA groups. Conclusion Our results suggest that the diameter and peak systolic velocity of the mid-trimester ductus venosus are useful noninvasive measurements that provide prediction of late onset SGA fetuses

Effect of maternal nutrient restriction on expression of glucose transporters (SLC2A4 and SLC2A1) and insulin signaling in skeletal muscle of SGA and Non-SGA sheep fetuses

Maternal nutrient restriction (NR) causes small for gestational age (SGA) offspring, which are at higher risk for accelerated postnatal growth and developing insulin resistance in adulthood. Skeletal muscle is essential for whole-body glucose metabolism, as 80% of insulin-mediated glucose uptake occurs in this tissue. Maternal NR can alter fetal skeletal muscle mass, expression of glucose transporters, insulin signaling, and myofiber type composition. It also leads to accumulation of intramuscular triglycerides (IMTG), which correlates to insulin resistance. Using a 50% NR treatment from gestational day (GD) 35 to GD 135 in sheep, we routinely observe a spectral phenotype of fetal weights within the NR group. Thus, we classified those fetuses into NR(Non-SGA; n = 11) and NR(SGA; n = 11). The control group (n = 12) received 100% of nutrient requirements throughout pregnancy. At GD 135, fetal plasma and gastrocnemius and soleus muscles were collected. In fetal plasma, total insulin was lower in NR(SGA) fetuses compared NR(Non-SGA) and control fetuses (P < 0.01), whereas total IGF-1 was lower in NR(SGA) fetuses compared with control fetuses (P < 0.05). Within gastrocnemius, protein expression of insulin receptor (INSRB; P < 0.05) and the glucose transporters, solute carrier family 2 member 1 and solute carrier family 2 member 4, was higher (P < 0.05) in NR(SGA) fetuses compared with NR(Non-SGA) fetuses; IGF-1 receptor protein was increased (P < 0.01) in NR(SGA) fetuses compared with control fetuses, and a lower (P < 0.01) proportion of type I myofibers (insulin sensitive and oxidative) was observed in SGA fetuses. For gastrocnemius muscle, the expression of lipoprotein lipase (LPL) messenger RNA (mRNA) was upregulated (P < 0.05) in both NR(SGA) and NR(Non-SGA) fetuses compared with control fetuses, whereas carnitine palmitoyltransferase 1B (CPT1B) mRNA was higher (P < 0.05) in NR(Non-SGA) fetuses compared with control fetuses, but there were no differences (P > 0.05) for protein levels of LPL or CPT1B. Within soleus, there were no differences (P > 0.05) for any characteristic except for the proportion of type I myofibers, which was lower (P < 0.05) in NR(SGA) fetuses compared with control fetuses. Accumulation of IMTG did not differ (P > 0.05) in gastrocnemius or soleus muscles. Collectively, the results indicate molecular differences between SGA and Non-SGA fetuses for most characteristics, suggesting that maternal NR induces a spectral phenotype for the metabolic programming of those fetuses.