Small For Gestational Age Cases Research Articles

Maternal vascular indices at 36 weeks' gestation in pregnancy with small or growth-restricted fetus.

To compare maternal vascular indices and hemodynamic parameters at 35-37 weeks' gestation in pregnancies complicated by delivery of a small-for-gestational-age (SGA) or growth-restricted (FGR) neonate. This was a prospective observational study of women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The visit included recording of maternal demographic characteristics, medical history, vascular indices and hemodynamic parameters, which were obtained using a non-invasive operator-independent device and included pulse-wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressure, total peripheral resistance and heart rate. Women with hypertensive disorders of pregnancy were excluded. SGA was diagnosed if birth weight was < 10th percentile. FGR was diagnosed if, in addition to birth weight < 10th percentile, at the 35-37-week scan, uterine artery or umbilical artery pulsatility index (PI) was > 95th percentile or fetal middle cerebral artery PI was < 5th percentile. Among the 6413 women included in the study, there were 605 (9.4%) cases of SGA, 133 (2.1%) cases of FGR and 5675 (88.5%) cases that were unaffected by SGA or FGR. Women with SGA or FGR, compared to unaffected pregnancies, had increased peripheral vascular resistance and reduced cardiac output. Central systolic and diastolic blood pressure were increased in the FGR group compared with the unaffected group. Aortic stiffness, as assessed by pulse-wave velocity, and augmentation index did not differ between affected and unaffected pregnancies. In the FGR group, compared with the SGA group, central systolic and diastolic blood pressure were higher, whereas heart rate was lower. SGA and FGR pregnancies exhibit deranged maternal hemodynamic responses compared with unaffected pregnancies. Pregnancies with FGR have higher central blood pressure compared to those with SGA, but it remains unclear whether these differences are driven by the size of the fetus or pathological fetal growth. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Risque d'acidose en cas de déclenchement pour PAG avant 37 SA

ObjectiveIf a small for gestational age (SGA) foetus needs to be delivered because of severity (<3rd centile) attempting induction of labor theoretically increases the risk of caesarean section and neonatal acidosis, but these risks are poorly understood. This article aims to assess the risk of caesarean section and neonatal acidosis in attempted vaginal birth of a moderately preterm foetus in the setting of severe SGA. MethodA single-centre hospital-based observational study conducted over a period of 17 consecutive years in mothers with a single foetus in cephalic presentation with severe SGA (<3rd centile) needing foetal extraction. Neonatal acidosis was considered moderate if pH<7.10 and severe if pH<7.0. The degree of severity of SGA was estimated according to the birth weight ratio. ResultsFour hundred and thirty-four foetuses with severe SGA were included during the period, 140 of whom were born after induction (32.3%). In this group, 66.4% of women achieved a vaginal birth (66.4%; 95% CI [58.0-74.2]) and the risk of moderate or severe acidosis was doubled compared with the group of foetuses who had undergone a planned caesarean section (7.9% vs. 3.1%, OR=2.7 [1.1-6.7]). Neither gestational age nor the degree of growth restriction was significantly related to the risk of caesarean section or to the risk of moderate or severe neonatal acidosis. ConclusionIn cases of severe SGA before 37weeks' gestation, induction of labour allows vaginal delivery in two-thirds of cases. It is accompanied by a doubling of the risk of moderate or severe neonatal acidosis.

Factors influencing the occurrence of small for gestational age at different degrees

To investigate the factors influencing the occurrence of small for gestational age (SGA) at different degrees and provide a basis for early identification of severe SGA cases. Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital. The neonates were divided into three groups: severe SGA group (birth weight below the 3rd percentile for gestational age and sex), mild SGA group (birth weight ≥3rd percentile and <10th percentile), and non-SGA group (birth weight ≥10th percentile). An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees. A total of 14 821 neonates were included, including 258 cases (1.74%) in the severe SGA group, 902 cases (6.09%) in the mild SGA group, and 13 661 cases (92.17%) in the non-SGA group. The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups (P<0.0125). The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group (P<0.0125). Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight (OR=1.838), maternal pre-pregnancy obesity (OR=3.024), in vitro fertilization-embryo transfer (OR=2.649), preeclampsia (OR=1.743), connective tissue disease during pregnancy (OR=1.795), nuchal cord (OR=1.213), oligohydramnios (OR=1.848), and intrauterine growth restriction (OR=27.691) were all associated with a higher risk of severe SGA (P<0.05). Maternal parity as a multipara (OR=0.457) was associated with a lower likelihood of severe SGA (P<0.05). Maternal pre-pregnancy underweight, maternal pre-pregnancy obesity, in vitro fertilization-embryo transfer, preeclampsia, connective tissue disease during pregnancy, oligohydramnios, nuchal cord, and intrauterine growth restriction are closely related to the occurrence of more severe SGA. Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.

Brain morphometric changes in children born as small for gestational age without catch up growth.

Most infants born as small for gestational age (SGA) demonstrate catch up growth by 2-4 years, but some fail to do so. This failure is associated with several health risks, including neuropsychological development issues. However, data on the morphological characteristics of the brains of infants born as SGA without achieving catch up growth are lacking. This study aims to determine the structural aspects of the brains of children born as SGA without catch up growth. We conducted voxel- and surface-based morphometric analyses of 1.5-T T1-weighted brain images scanned from eight infants born as SGA who could not achieve catch up growth by 3 years and sixteen individuals with idiopathic short stature (ISS) to exclude body size effects. Growth hormone (GH) secretion stimulation tests were used to rule out GH deficiency in all SGA and ISS cases. The magnetic resonance imaging data were assessed using Levene's test for equality of variances and a two-tailed unpaired t-test for equality of means. The Benjamini-Hochberg procedure was used to apply discovery rate correction for multiple comparisons. Morphometric analyses of both t-statical map and surface-based analyses using general linear multiple analysis determined decreased left insula thickness and volume in SGA without catch up growth compared with ISS. The brain scans of patients with SGA who lack catch up growth indicated distinct morphological disparities when compared to those with ISS. The discernible features of brain morphology observed in patients born as SGA without catch up growth may improve understanding of the association of SGA without catch up growth with both intellectual and psychological outcomes.

First trimester prediction models for small-for- gestational age and fetal growth restricted fetuses without the presence of preeclampsia

We established efficient first trimester prediction models for small-for-gestational age (SGA) and fetal growth restriction (FGR) without the presence of preeclampsia (PE) regardless of the gestational age of the onset of the disease [early FGR occurring before 32 gestational week or late FGR occurring after 32 gestational week]. The retrospective study was performed on singleton Caucasian pregnancies (n = 6440) during the period 11/2012–3/2020. Finally, 4469 out of 6440 pregnancies had complete medical records since they delivered in the Institute for the Care of Mother and Child, Prague, Czech Republic. The study included all cases diagnosed with SGA (n = 37) or FGR (n = 82) without PE, and 80 selected normal pregnancies. Four microRNAs (miR-1-3p, miR-20a-5p, miR-146a-5p, and miR-181a-5p) identified 75.68 % SGA cases at 10.0 % false positive rate (FPR). Eight microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-126-3p, miR-130b-3p, miR-146a-5p, miR-181a-5p, and miR-499a-5p) identified 83.80 % SGA cases at 10.0 % FPR. The prediction model for SGA based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by assisted reproductive technology (ART), first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm]. Then 81.08 % and 89.19 % pregnancies developing SGA were identified at 10.0 % FPR in case of utilization of 4 microRNA and 8 microRNA biomarkers. Simplified prediction model for SGA based on limited number of maternal clinical characteristics (maternal age and BMI, an infertility treatment by ART, and 4 microRNAs) does not improve the detection rate of SGA (70.27 % SGA cases at 10.0 % FPR) when compared with prediction model for SGA based just on the expression profile of 4 or 8 microRNAs biomarkers. Seven microRNAs only (miR-16-5p, miR-20a-5p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-342-3p, and miR-574-3p) identified 42.68 % FGR cases at 10.0 % FPR (AUC 0.725). However, the combination of 10 microRNAs only (miR-16-5p, miR-20a-5p, miR-100-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-342-3p, and miR-574-3p) reached a higher discrimination power (AUC 0.774). It identified 40.24 % FGR cases at 10.0 % FPR. The prediction model for any subtype of FGR based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by ART, the parity (nulliparity), the occurrence of SGA or FGR in previous gestation, and the occurrence of any autoimmune disorder, and the presence of chronic hypertension]. Then 64.63 % and 65.85 % pregnancies destinated to develop FGR were identified at 10.0 % FPR in case of utilization of 7 microRNA biomarkers or 10 microRNA biomarkers. When other clinical variables next to those ones mentioned above such as first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm, were added to the prediction model for FGR, the detection power was even increased to 74.39 % cases and 78.05 % cases at 10.0 % FPR.

The prevalence and perinatal repercussions of preeclampsia after the implementation of a prophylaxis protocol with aspirin.

To evaluate the prevalence and perinatal repercussions of preeclampsia (PE) after the implementation of a prophylaxis protocol with aspirin in singleton pregnancy at Maternity School of Federal University of Rio de Janeiro, Rio de Janeiro, Brazil (2015-2106). PE prevalence according to gestational age (GA) and the prevalence ratio (PR) between PE and prematurity, small for gestational age (SGA), and fetal death were calculated in patients assisted during 2015 and 2016. PE occurred in 373(10.75%) of 3468 investigated cases, where PE<37weeks was of 2.79% and PEgreater than37weeks was of 7.95%. A total of 413 (11.9%) prematurity cases, 320 SGA (9.22%), and 50 fetal deaths (1.44%) occurred. In the PE group, 97 premature newborns (PR 0.90) and 51 SGA (PR 1.16) were born, and two fetal deaths occurred (PR 7.46). Concerning PE<37weeks, 27 SGA cases (PR 1.42) and two fetal deaths (PR 2.62) were observed. Regarding PEgreater than37weeks, 24 SGA (PR 1.09) were born, and no fetal deaths were observed. Our findings were compared to previously published results. PE was significantly associated with SGA newborns, especially premature PE. Prescribing aspirin for PE prophylaxis based only on clinical risk factors in a real-life scenario does not appear to be effective but resulted in a PE screening and prophylaxis protocol review and update at ME/UFRJ.

Weight gain patterns among pregnancies with obesity and small- and large-for-gestational-age births.

This case-cohort study estimated associations between gestational weight gain (GWG) and small-for-gestational-age (SGA) and large-for-gestational-age (LGA) births stratified by obesity class (I: 30-34.9kg/m2 ; II: 35-39.9kg/m2 ; III: ≥40 kg/m2 ) (Magee-Womens Hospital, Pittsburgh, Pennsylvania, 1998-2011). First-trimester GWG was categorized as being below (<0.2kg), within (0.2-2.0kg), or above (>2.0kg) the Institute of Medicine recommendations. For second- and third-trimester GWG, four linear trajectorieswerederived: approximating maintenance (slope -0.05 ± 0.03 kg/wk), approximating the recommendations (0.27 ± 0.01 kg/wk; reference), higher than the recommendations (0.54 ± 0.01 kg/wk), and highest among those above the recommendations (0.91 ± 0.02 kg/wk). For classes I, II, and III, respectively, there were 1290, 1247, and 1198 pregnancies in the subcohort; 262, 171, and 123 SGA cases; and 353, 286, and 257 LGA cases. First-trimester GWG was not associated with SGA/LGA births. Second- and third-trimester weight maintenance was associated with potentially lower LGA risk (risk ratio [RR]: 0.80; 95% confidence interval [CI]: 0.55-1.1) but not higher SGA risk (RR: 0.98; 95% CI: 0.64-1.5) for class III. Inaddition,some sensitivity analyses supported no increased SGA risk with second- and third-trimester weight maintenance for classes I and II. Second- and third-trimester weight maintenance may be associated with more optimal birth weight for gestational age. However, how this could be achieved (e.g., through diet and exercise interventions) is unclear, given the observational design of our study.

Type and timing of antiretroviral therapy during pregnancy: Impact on risk of preterm delivery and small-for-gestational age births in Canada, a retrospective cohort study.

To evaluate the impact of type and timing of antiretroviral therapy (ART) on the risk of preterm delivery (PTD) and small-for-gestational age (SGA) birth among pregnant women and people living with HIV in Canada. Data for this retrospective cohort study were analyzed from the Canadian Perinatal HIV Surveillance Program from 1990 to 2020. The association between ART and risk of PTD (<37 weeks) and SGA birth(<10th percentile)was explored using mixed effects logistic regression and time-dependent Cox proportional hazards models. Overall, there were 14.9% (654 of 4379) PTD and 18.5% (732 of 3947) SGA cases. A higher risk of PTD was observed with nonnucleoside reverse transcriptase inhibitor-(adjusted hazard ratio [aHR], 1.73; P=0.019) and boosted protease inhibitor-(aHR,186;P=0.007)based regimenscompared with integrase strand transfer inhibitor (INSTI)-based regimens. ART initiation prior to conception was associated with a lower risk of SGA birthcompared with ART initiation after conception at 1 to 14 weeks (adjusted odds ratio [aOR], 0.69; P=0.024) and > 14 weeks (aOR, 0.70; P=0.005). INSTI-based ART regimens were associated with lower risk of PTD compared with other regimens, and ART initiation before conception was associated with a lower risk of SGAbirth. These findings, with overall safety data, should be considered when providing pregnancy counseling to people living with HIV.

Air Pollution and Birth Outcomes: Health Impact and Economic Value Assessment in Spain.

Air pollution is considered an ongoing major public health and environmental issue around the globe, affecting the most vulnerable, such as pregnant women and fetuses. The aim of this study is to estimate the health impact and economic value on birth outcomes, such as low birthweight (LBW), preterm birth (PTB), small for gestational age (SGA), attributable to a reduction of PM10 levels in Spain. Reduction based on four scenarios was implemented: fulfillment of WHO guidelines and EU limits, and an attributable reduction of 15% and 50% in annual PM10 levels. Retrospective study on 288,229 live-born singleton children born between 2009-2010, using data from Spain Birth Registry Statistics database, as well as mean PM10 mass concentrations. Our finding showed that a decrease in annual exposure to PM10 appears to be associated with a decrease in the annual cases of LBW, SGA and PTB, as well as a reduction in hospital cost attributed to been born with LBW. Improving pregnancy outcomes by reducing the number of LBW up to 5% per year, will result in an estimate associated monetary saving of 50,000 to 7,000,000 euros annually. This study agrees with previous literature and highlights the need to implement, and ensure compliance with, stricter policies that regulate the maximum exposure to outdoor PM permitted in Spain, contributing to decreased environmental health risk, especially negative birth outcomes.

Performance of a risk factor-based approach in the detection of small for gestational age neonates: A cohort study.

Antenatal detection of fetal growth restriction allows the opportunity to increase surveillance and initiate intervention to prevent adverse outcomes. Detection of small for gestational age (SGA) fetuses with risk factor screening and selective ultrasonography is the standard of care in Australia, but evidence regarding performance is lacking. To evaluate the diagnostic performance of a risk factor-based screening approach in detection of SGA neonates. Retrospective cohort study conducted in a metropolitan maternity service, including all consecutive singleton deliveries over 20 weeks gestation from July 2016 to December 2017, and excluding terminations of pregnancy. An SGA neonate was defined by birthweight below the tenth percentile according to Australian reference ranges. Antenatally detected SGA cases were defined by estimated fetal weight or abdominal circumference below the tenth percentile for gestational age, or abnormal symphysio-fundal height. The diagnostic accuracy of the screening protocol was calculated using detection rates and false-positive rates. There were 13 384 singleton pregnancies included. There were 1330 infants (10.0%) who were SGA at birth. Antenatal detection rate of SGA neonates was 39.6% (95% confidence interval (CI) 37.0-42.3%), with a false-positive rate of 10.2% (95% CI 9.6-10.7%). There were 10 266 pregnancies (77.0%) which had at least one risk factor for an SGA infant. Of these, 6650 (64.8%) underwent at least one fetal growth ultrasound after 24 weeks gestation. Antenatal recognition of poor fetal growth is suboptimal using our current screening protocol. Three-quarters of pregnancies demonstrated risk factors for delivering an SGA infant, but growth ultrasonography may be underutilised.

Fetal Growth Restriction: Comparison of Biometric Parameters

The aim of this study was to identify growth-restricted fetuses using biometric parameters and to assess the validity and clinical value of individual ultrasound parameters and ratios, such as transcerebellar diameter/abdominal circumference (TCD/AC), head circumference/abdominal circumference (HC/AC), and femur length/abdominal circumference (FL/AC). In a retrospective single-center cross-sectional study, the biometric data of 9292 pregnancies between the 15th and 42nd weeks of gestation were acquired. Statistical analysis included descriptive data, quantile regression estimating the 10th and 90th percentiles, and multivariable analysis. We obtained clinically noticeable results in predicting small-for-gestational-age (SGA) and fetal growth restriction (FGR) fetuses at advanced weeks of gestation using the AC with a Youden index of 0.81 and 0.96, respectively. The other individual parameters and quotients were less suited to identifying cases of SGA and FGR. The multivariable analysis demonstrated the best results for identifying SGA and FGR fetuses with an area under the curve of 0.95 and 0.96, respectively. The individual ultrasound parameters were better suited to identifying SGA and FGR than the ratios. Amongst these, the AC was the most promising individual parameter, especially at advanced weeks of gestation. However, the highest accuracy was achieved with a multivariable model.

Delivery timing in dichorionic diamniotic twin pregnancies complicated by preeclampsia: a decision analysis

Objective To determine the optimal timing of delivery in Dichorionic-diamniotic (DCDA) pregnancies complicated by preeclampsia without severe features. Methods A decision-analytic model was created to compare outcomes of expectant management vs. delivery from 34 to 37w0d. Outcomes included quality-adjusted life years (QALYs), development of severe preeclampsia, maternal mortality, maternal stroke, small for gestational age (SGA) due to fetal growth restriction (FGR) detected antenatally, stillbirth, cerebral palsy (CP), and neonatal mortality. Probabilities, utilities, and life expectancies were derived from the literature. Univariate analysis was used to evaluate the impact of delivery at various gestational ages. Maternal and neonatal outcomes were calculated for a theoretical cohort of 10,000 DCDA pregnancies with preeclampsia. Results The optimal gestational age for delivery was 36w0d when the total QALYs (868,112) were highest. Delivery at 34w0d resulted in the fewest cases of severe preeclampsia, maternal mortality, and maternal stroke (0, 4, and 15 cases per 10,000, respectively). The incidence of each of these adverse outcomes increased with gestational age, with the greatest number of adverse outcomes at 37w0d (2452 cases of severe preeclampsia, eight maternal deaths, and 31 cases of maternal stroke per 10,000). Delivery at 34w0d resulted in the fewest cases of severe preeclampsia (0), maternal stroke (15), maternal mortality (4), stillbirth (0), and SGA (1183). However, this strategy was also associated with most cases of neonatal CP (91) and neonatal mortality (87). Conclusion DCDA twin pregnancies complicated by preeclampsia without severe features appear to have the best outcomes when delivered at 36w0d. Specifically, when compared to delivery at 37w0d, this strategy reduced maternal and neonatal morbidity and mortality.

Clinical phenotypes for risk stratification in small‐for‐gestational‐age fetuses

To evaluate whether clinical phenotypes of small-for-gestational-age (SGA) fetuses can be identified and used for adverse perinatal outcome risk stratification to facilitate clinical decision-making. This was a multicenter observational cohort study conducted in two tertiary care university hospitals. SGA fetuses were classified according to maternal, fetal and placental conditions using a two-step cluster algorithm, in which fetuses with more than one condition were assigned to the cluster associated with the highest mortality risk. Delivery and perinatal outcomes were compared using chi-square test among SGA clusters, and the associations between outcomes and each cluster were evaluated by calculating odds ratios (OR), adjusted for gestational age. The study included 17 631 consecutive singleton pregnancies, of which 1274 (7.2%) were defined as SGA at birth according to INTERGROWTH-21st standards. Nine SGA clinical phenotypes were identified using a predefined conceptual framework. All delivery and perinatal outcomes analyzed were significantly different among the nine phenotypes. The whole SGA cohort had a three-times higher risk of perinatal mortality compared with non-SGA fetuses (1.4% vs 0.4%; P < 0.001). SGA clinical phenotypes exhibited three patterns of perinatal mortality risk: the highest risk was associated with congenital anomaly (8.3%; OR, 17.17 (95% CI, 2.17-136.12)) and second- or third-trimester hemorrhage (8.3%; OR, 9.94 (95% CI, 1.23-80.02)) clusters; medium risk was associated with gestational diabetes (3.8%; OR, 9.59 (95% CI, 1.27-72.57)), preterm birth (3.2%; OR, 4.65 (95% CI, 0.62-35.01)) and intrauterine growth restriction (3.1%; OR, 5.93 (95% CI, 3.21-10.95)) clusters; and the lowest risk was associated with the remaining clusters. Perinatal mortality rate did not differ between SGA fetuses without other clinical conditions (54.1% of SGA fetuses) and appropriate-for-gestational-age fetuses (0.1% vs 0.4%; OR, 0.41 (95% CI, 0.06-2.94); P = 0.27). SGA combined with other obstetric pathologies increased significantly the risk of perinatal mortality, as demonstrated by the increased odds of perinatal death in SGA cases with gestational diabetes compared to non-SGA cases with the same condition (OR, 24.40 (95% CI, 1.31-453.91)). We identified nine SGA clinical phenotypes associated with different patterns of risk for adverse perinatal outcome. Our findings suggest that considering clinical characteristics in addition to ultrasound findings could improve risk stratification and decision-making for management of SGA fetuses. Future clinical trials investigating management of fetuses with SGA should take into account clinical information in addition to Doppler parameters and estimated fetal weight. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prospective evaluation of first-trimester screening strategy for preterm pre-eclampsia and its clinical applicability in China.

To evaluate, in a Chinese population, the performance of a screening strategy for preterm pre-eclampsia (PE) using The Fetal Medicine Foundation (FMF)'s competing-risks model and to explore its clinical applicability in mainland China. This was a prospective, multicenter, observational cohort study including 10 899 women with singleton pregnancy who sought prenatal care at one of 13 hospitals, located in seven cities in mainland China, between 1 December 2017 and 30 December 2019. Mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and maternal serum levels of placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation were measured and converted into multiples of the median using Chinese reference ranges. Individualized risk for preterm PE was calculated using the FMF algorithm. Prior risk was calculated based on maternal demographic characteristics and obstetric history. We evaluated the efficiency of the screening strategy using various combinations of biomarkers and analyzed its predictive performance for a composite of placenta-associated adverse pregnancy outcomes, including PE, placental abruption, small-for-gestational age (SGA) and preterm birth, at fixed false-positive rates for preterm PE. We identified 312 pregnancies that developed PE, of which 117 cases were diagnosed as preterm PE (< 37 weeks' gestation). There were 386 pregnancies complicated by severe composite placenta-associated adverse outcome, including preterm PE, 146 cases of severe SGA (birth weight < 3rd percentile) neonate, 61 cases with placental abruption and 109 cases of early preterm birth < 34 gestational weeks. The triple-marker model containing biomarkers MAP, UtA-PI and PAPP-A achieved, at fixed false-positive rates of 10%, 15% and 20%, detection rates for preterm PE of 65.0%, 72.7% and 76.1%, respectively, and detection rates for severe composite placenta-associated adverse outcome of 34.7%, 41.7% and 46.4%, respectively. Replacing PAPP-A with PlGF or adding PlGF to the model did not improve the performance. Of women screening positive for preterm PE at a fixed 5% false-positive rate, an estimated 30% developed at least one placenta-associated adverse pregnancy outcome, including PE, placental abruption, SGA (birth weight < 10th percentile) and preterm birth < 37 weeks. The FMF competing-risks model for preterm PE was found to be effective in screening a mainland Chinese population. Women who screened positive for preterm PE had increased risk for other placenta-associated pregnancy complications. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Association of mid-trimester maternal angiogenic biomarkers with small-for-gestational-age infants in an urban Zambian cohort: a nested case-control study.

ObjectiveTo investigate whether angiogenic biomarker concentrations differ between women who deliver small‐for‐gestational‐age (SGA) infants (<10th centile birth weight for gestational age) compared with controls, because identifying SGA risk early could improve outcomes.MethodsThis case‐control study compared serum concentrations of angiogenic biomarkers before 24 weeks of pregnancy from 62 women who delivered SGA infants (cases) and 62 control women from an urban Zambian cohort. Odds of delivering an SGA infant were calculated using conditional logistic regression.ResultsPlacental growth factor (PlGF), soluble fms‐like tyrosine kinase (sFLT‐1) and soluble endoglin (sEng) in controls were 37.74 pg/mL (interquartile range [IQR] 23.12–63.15), 2525.18 pg/mL (IQR 1502.21–4265.54) and 2408.18 pg/mL (IQR 1854.87–3017.94), respectively. SGA cases had higher PlGF (40.50 pg/mL, IQR 22.81–67.94) and sFLT‐1 (2613.06 pg/mL, IQR 1720.58–3722.50), and lower sEng (2038.06 pg/mL, IQR 1445.25–3372.26). Participants with sEng concentration below and concomitant sFLT‐1 concentration above their respective thresholds (n = 40) had five‐fold higher odds of SGA (adjusted odds ratio 4.77, 95% confidence interval 1.61–14.1; P = 0.005).ConclusionBiomarker concentrations were similar between cases and controls. Participants with concomitant low sEng and high sFLT‐1 had the highest odds of SGA, suggesting that a combination of biomarkers may better for predicting SGA than single biomarkers.

Anti-hypertensive use for non-severe gestational hypertension in Botswana: A case-control study.

The fetal risks and benefits of antihypertensives to treat gestational hypertension in pregnancy are understudied, particularly in low- and middle-income countries. We performed a nested case-control study within a retrospective cohort of obstetrical patients in Botswana from 2014 to 2019. We included women carrying singletons who developed new onset non-severe hypertension (140-159mmHg systolic or 90-109mmHg diastolic blood pressure) after 20weeks of pregnancy. Cases were defined as women with either small-for-gestational-age (SGA) infants or stillbirth, analyzed separately; controls were otherwise similar women without the adverse outcome in each analysis. We identified 1932 cases of SGA (7925 controls) and 316 cases of stillbirth (9619 controls). Cases with SGA were more likely to have used an anti-hypertensive than controls (33% vs 29%, adjusted odds ratio [aOR] 1.28, 95% confidence interval [CI] 1.15-1.43). Cases with stillbirth were more likely to have used an anti-hypertensive than controls (42% versus 29%, aOR 1.45, 95% CI 1.14-1.83). Anti-hypertensive use for new-onset gestational hypertension was associated with an increased risk of having an SGA infant or a stillbirth among women who never developed severe hypertension. These data support conduct of a randomized clinical trial to determine the appropriate use of anti-hypertensives in non-severe gestational hypertension.

Fetal neurosonography detects differences in cortical development and corpus callosum in late-onset small fetuses.

To explore whether neurosonography can detect differences in cortical development and corpus callosal length in late-onset small fetuses subclassified into small-for-gestational age (SGA) or growth restricted (FGR). This was a prospective cohort study in singleton pregnancies, including normally grown fetuses (birth weight between the 10th and 90th centiles) and late-onset small fetuses (estimated fetal weight < 10th centile, diagnosed after 32 weeks of gestation and confirmed by birth weight < 10th centile). Small fetuses were subclassified into SGA (birth weight between the 3rd and 9th centiles and normal fetoplacental Doppler) and FGR (birth weight < 3rd centile and/or abnormal cerebroplacental ratio and/or abnormal uterine artery Doppler). Neurosonography was performed at 33 ± 1 weeks of gestation to assess the depth of the insula, Sylvian fissure and parieto-occipital sulcus in the axial views and corpus callosal length in the midsagittal plane. Measurements were performed offline using Alma Workstation software and were adjusted by biparietal diameter or cephalic index. Linear regression analysis was used to assess the association between the neurosonographic variables and study group, adjusting for confounding factors such as gender, gestational age at neurosonography, nulliparity and pre-eclampsia. In total, 318 fetuses were included, of which 97 were normally grown and 221 were late-onset small fetuses that were further subdivided into late-onset SGA (n = 67) or late-onset FGR (n = 154). Compared to controls, both SGA and FGR cases showed significantly increased insular depth adjusted for biparietal diameter (median (interquartile range), controls 0.329 (0.312-0.342) vs SGA 0.339 (0.321-0.347) vs FGR 0.336 (0.325-0.349); P = 0.006). A linear tendency to reduced Sylvian fissure depth adjusted for biparietal diameter was also observed across the study groups (mean ± SD, controls 0.148 ± 0.021 vs SGA 0.142 ± 0.025 vs FGR 0.139 ± 0.022; P = 0.003). However, differences were significant only between the FGR and control groups. Corpus callosal length adjusted for cephalic index was significantly reduced in FGR cases compared with both controls and SGA cases, while there was no difference between SGA cases and controls (median (interquartile range), controls 0.500 (0.478-0.531) vs SGA 0.502 (0.487-0.526) vs FGR 0.475 (0.447-0.508); P = 0.005). No differences were found in parieto-occipital sulcus depth between the three study groups. Neurosonography seems to be a sensitive tool to detect subtle structural differences in brain development in late-onset small fetuses. © 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.

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.

Low Immune Activation in Early Pregnancy Is Associated With Preterm But Not Small-for-gestational-age Delivery in Women Infected With Human Immunodeficiency Virus Initiating Antiretroviral Therapy in Pregnancy: A Prematurity Immunology in HIV-infected Mothers and their Infants Study (PIMS) Case-control Study in Cape Town, South Africa.

BackgroundMechanisms underlying an association between human immunodeficiency virus (HIV) or antiretroviral therapy (ART) during pregnancy with risk of preterm delivery (PTD) and small-for-gestational-age (SGA) remain unclear. We explored the association between cellular immune activation and PTD or SGA in women with HIV initiating ART during or before pregnancy.MethodsWomen with HIV enrolled at median 15 weeks’ gestation, were analyzed for immune markers, and matched on ART initiation timing (15 women initiated pre- and 15 during pregnancy). There were 30 PTD (delivery <37 weeks), 30 SGA (weight for age ≤10th percentile) cases, and 30 controls (term, weight for gestational age >25th percentile) as outcomes. Lymphocytes, monocytes, and dendritic cell populations and their activation status or functionality were enumerated by flow cytometry.ResultsPTD cases initiating ART in pregnancy showed decreased CD8+ T cell, monocyte, and dendritic cell activation; increased classical (CD14+CD16–) and intermediate (CD14+CD16+) monocyte frequencies; and decreased inflammatory monocytes (CD14dimCD16+) compared with SGA cases and term controls (all P < .05). Allowing for baseline viral load, the immune markers remained significantly associated with PTD but only in women initiating ART in pregnancy. Lower monocyte activation was predictive of PTD. TLR ligand-induced interferon-α and macrophage inflammatory protein-1β levels in monocytes were significantly lower in PTD women initiating ART in pregnancy.ConclusionLow immune activation, skewing toward anti-inflammatory monocytes, and lower monocyte cytokine production in response to TLR ligand stimulation were associated with PTD but not SGA among women initiating ART in, but not before, pregnancy, suggesting immune anergy to microbial stimulation as a possible underlying mechanism for PTD in women initiating ART in pregnancy.