Risk Of Fetal Growth Restriction Research Articles

The impact of prepregnancy body mass index on pregnancy and neonatal outcomes.

The obesity epidemic in the United States is continuing to worsen. Obesity is a known risk factor for pregnancy morbidity. However, many studies use the patient's body mass index (BMI) at the time of delivery, do not stratify by class of obesity, or utilize billing codes as the basis of their study, which are noted to be inaccurate. This study aims to investigate the prepregnancy BMI class specific risks for pregnancy and neonatal complications based on a prepregnancy BMI class. We conducted a retrospective cohort study of40,256 pregnant women with 55,202 singleton births between October 16, 2007 and December 3, 2023. We assessed the risk of pregnancy and neonatal morbidity based on the maternal prepregnancy BMI category. The primary outcome was composite maternal morbidity, including hypertensive disorders of pregnancy (i.e.,gestational hypertension [GHTN] and preeclampsia), and gestational diabetes mellitus (GDM), adjusted for pregestational diabetes mellitus and chronic hypertension (cHTN). Secondary maternal outcomes included preterm premature rupture of membranes (PPROM), preterm delivery (PTD<37 and <32weeks), induction of labor (IOL), cesarean delivery (CD), and postpartum hemorrhage (PPH). Neonatal outcomes included a composite adverse outcome (including stillbirth, intraventricular hemorrhage (IVH), hypoglycemia, respiratory distress syndrome [RDS], APGAR [Appearance, Pulse, Grimace, Activity, and Respiration] <7 at 5 min, and neonatal intensive care unit [NICU] admission), birthweight, fetal growth restriction (FGR), and macrosomia. Composite maternal morbidity (odds ratio [OR] 4.40,confidence interval [CI] 3.70-5.22 for class III obesity [BMI≥40.0 kg/m2] compared with normal BMI), hypertensive disorders of pregnancy (HDP), GDM, PTD, IOL, CD, PPH, neonatal composite morbidity, hypoglycemia, RDS, APGAR<7 at 5 min, NICU admission, and macrosomia showed a significant increasing test of trend among BMI classes. Increased BMI was protective for FGR. Our data provides BMI-class specific odds ratios (ORs) for adverse pregnancy outcomes. Increased BMI class significantly increases the risk of HDP, GDM, IOL, CD, composite adverse neonatal outcomes, and macrosomia, and decreases the risk of FGR. Attaining a healthier BMI category prior to conception may lower pregnancy morbidity.

Outcomes of dichorionic twin pregnancies with fused versus separate placentas.

In a certain proportion of dichorionic twin pregnancies, the two placentas are fused. The clinical significance of this finding remains unclear. Our objective was to compare outcomes of dichorionic twin pregnancies with fused versus separate placentas as determined on first-trimester ultrasound. Retrospective study of patients with dichorionic twins followed at a tertiary center between 2014 and 2022. The co-primary outcomes were fetal growth restriction and preeclampsia. Associations between fused placentas and the study outcomes were estimated using multivariable Poisson regression and were reported as adjusted relative risk (aRR) with a 95%-confidence interval (CI). Of the 328 eligible patients, 175 (53.4%) and 153 (46.6%) had fused and separate placentas, respectively. Compared with pregnancies with separate placentas, patients with fused placentas had a lower risk of preeclampsia [aRR 0.48 (95%-CI 0.24-0.97)] but a higher risk of fetal growth restriction [aRR 1.23 (95%-CI 1.02-1.48)] and admission to the neonatal intensive care unit [aRR 1.31 (95%-CI 1.01-1.71)]. In addition, pregnancies with fused placentas were more likely to have a total placental weight below the 10th percentile than those with separate placentas [aRR 1.93 (95%-CI 1.16-3.21)]. Dichorionic twin pregnancies with fused placentas have a lower risk of preeclampsia but are more likely to be complicated by fetal growth restriction, observations that may be attributed to the lower total placentas mass in pregnancies with fused compared with separate placentas. Fused placentas can be used as a potential biomarker for the prediction of pregnancy complications in dichorionic twin pregnancies.

Reduced T2*-weighted placental MRI predicts foetal growth restriction in women with chronic rheumatic disease-a Danish explorative study.

Women with chronic rheumatic disease (CRD) are at greater risk of foetal growth restriction than their healthy peers. T2*-weighted magnetic resonance imaging of placenta (T2*P-MRI) is superior to conventional ultrasonography in predicting birth weight and works as a proxy metabolic mirror of the placental function. We aimed to compare T2*P-MRI in pregnant women with CRD and healthy controls. In addition, we aimed to investigate the correlation between T2*P-MRI and birth weight. Using a General Electric (GE) 1.5 Tesla, we consecutively performed T2*-weighted placental MRI in 10 women with CRD and 18 healthy controls at gestational week (GW)24 and GW32. We prospectively collected clinical parameters during pregnancy including birth outcome and placental weight. Women with CRD had significantly lower T2*P-MRI values at GW24 than healthy controls (median T2*(IQR) 92.1ms (81.6; 122.4) versus 118.6ms (105.1; 129.1), p = 0.03). T2*P-MRI values at GW24 showed a significant correlation with birth weight, as the T2*P-MRI value was reduced in all four pregnancies complicated by SGA at birth. Three out of four pregnancies complicated by SGA at birth remained undetected by routine antenatal ultrasound. This study demonstrates reduced T2*P-MRI values and a high proportion of SGA at birth in CRD pregnancies compared to controls, suggesting an increased risk of placental dysfunction in CRD pregnancies. T2*P-MRI may have the potential to focus clinical vigilance by identifying pregnancies at risk of SGA as early as GW24. Key Points • Placenta-related causes of foetal growth restriction in women with rheumatic disease remain to be investigated. • T2*P-MRI values at gestational week 24 predicted foetuses small for gestational age at birth. • T2*P-MRI may indicate pregnant women with chronic rheumatic disease (CRD) in need of treatment optimization.

Exploring Prenatal Exposure to Halogenated Compounds and Its Relationship with Birth Outcomes Using Nontarget Analysis.

Halogenated organic compounds (HOCs) are a class of contaminants showing high toxicity, low biodegradability, and high bioaccumulation potential, especially chlorinated and brominated HOCs (Cl/Br-HOCs). Knowledge gaps exist on whether novel Cl/Br-HOCs could penetrate the placental barrier and cause adverse birth outcomes. Herein, 326 cord blood samples were collected in a hospital in Jinan, Shandong Province from February 2017 to January 2022, and 44 Cl/Br-HOCs were identified with communicating confidence level above 4 based on a nontarget approach, covering veterinary drugs, pesticides, and their transformation products, pharmaceutical and personal care products, disinfection byproducts, and so on. To our knowledge, the presence of closantel, bromoxynil, 4-hydroxy-2,5,6-trichloroisophthalonitrile, 2,6-dibromo-4-nitrophenol, and related components in cord blood samples was reported for the first time. Both multiple linear regression (MLR) and Bayesian kernel machine regression (BKMR) models were applied to evaluate the relationships of newborn birth outcomes (birth weight, length, and ponderal index) with individual Cl/Br-HOC and Cl/Br-HOCs mixture exposure, respectively. A significantly negative association was observed between pentachlorophenol exposure and newborn birth length, but the significance vanished after the false discovery rate correction. The BKMR analysis showed that Cl/Br-HOCs mixture exposure was significantly associated with reduced newborn birth length, indicating higher risks of fetal growth restriction. Our findings offer an overview of Cl/Br-HOCs exposome during the early life stage and enhance the understanding of its exposure risks.

Evaluation of systemic immune-inflammation index for predicting late-onset fetal growth restriction.

To determine a cut-off value for systemic immune-inflammation index (SII) (neutrophil × platelet/lymphocyte) in the prediction of fetal growth restriction (FGR). This case-control study was conducted retrospectively at the Obstetrics-Gynecology and Perinatology Clinics of Etlik Zubeyde Hanim Women's Health Education and Training Hospital. Singleton pregnant women with late-onset FGR who were followed up in outpatient clinics or hospitalized and whose pregnancy resulted at our hospital were included in the study group (group I). Healthy early and full-term singleton pregnant women with spontaneous labor who were followed up in the same hospital and whose pregnancy resulted at the same hospital were included in the control group (group II). Receiver-operating characteristic curves were used to assess the performance of SII value in predicting FGR. We recruited 79 cases (pregnant with late-onset fetal growth restriction) and 79 controls (healthy pregnant), matched for age, body mass index, and parity. ΔSII was statistically significantly higher in the pregnant with late-onset FGR compared with healthy pregnant (123 vs -65; p = 0.039). The values in ROC curves with the best balance of sensitivity/specificity were > 152 109/L (49% sensitivity, 70% specificity) and > 586 109/L (27% sensitivity, 90% specificity) for late-onset FGR. Higher ΔSII levels in maternal blood indicate an inflammatory process causing FGR. The cut-off value for ΔSII (> 586 109/L) at 90% specificity can be used as a screening test. In the presence of ΔSII levels > 586 109/L (27% sensitivity and 90% specificity), the physicians should be more cautious about risk for FGR. Therefore, pregnant women at risk for FGR should be checked more frequently and monitored closely. However, further studies are needed to confirm our findings.

Isolated fetal umbilical vein varix and the association with intrauterine fetal death and fetal growth restriction: A systematic review, meta-analysis, and nested retrospective cohort study.

To assess the risk of intrauterine fetal death (IUFD) and fetal growth restriction (FGR) in fetuses with an isolated fetal intra-abdominal umbilical vein varix (i-FIUVV). A retrospective cohort study combined with a systematic review and meta-analysis of the literature was performed. In the retrospective cohort study, all singleton fetuses with an i-FIUVV in the fetal medicine units of the Amsterdam UMC (between 2007 and 2023) were analyzed. The primary outcome measures were IUFD and FGR. The sample proportions of IUFD and FGR were depicted as risk percentages. The IUFD proportion was compared to the regional reference population and the FGR proportion was compared to the reported proportions in Europe. The secondary outcome measures were gestational age at diagnosis, initial and maximal FIUVV diameter, fetal monitoring in pregnancy, turbulent flow in the varix, thrombus formation in the varix, induction of labor, gestational age at birth, and birthweight centile. The proportion of fetuses with a birthweight below the 10th centile was compared with that of the regional reference population. The systematic review included all cases from eligible literature published between 2007 and 2023 supplemented by the data of our retrospective cohort study. In the systematic review and meta-analysis, the pooled proportions of IUFD and FGR were assessed in fetuses with i-FIUVV. The retrospective cohort included 43 singletons with an i-FIUVV. The IUFD risk was 0% [Confidence Interval, CI: 0%-8.2%], which did not differ significantly from 0.3% in the reference population, p=1.0. The risk of FGR was 16.3% [CI: 6.8%-30.7%] in the studied population, which is higher than the reported incidence of FGR in Europe ranging from 5%-10%. The proportion of fetuses with birthweights below the 10th centile was higher in our cohort compared with the reference population (23.3 vs. 9.9%, p<0.01). The systematic review included 12 articles, three abstracts, and our current cohort. In total, 513 cases with an i-FIUVV were included. The pooled risk was 0.4% [CI: 0.1%-1.7%] for IUFD and 5.2% [CI: 1.1%-21.3%] for FGR. The mean gestational age at birth did not exceed 39weeks in neither the cohort (38.7weeks) nor the pooled literature (37.6weeks). An i-FIUVV in singletons is not associated with an increased IUFD risk up to 39weeks of gestation but is possibly associated with FGR. The incidence of FGR in our cohort was higher than in the pooled literature (16.3% vs. 5%) but FGR definitions in the included studies varied. The proportion of birthweights below the 10th percentile in our cohort was significantly higher than in the reference group. Thus, based on these findings, we suggest conducting sonographic growth assessments while simultaneously assessing the i-FIUVV. No further monitoring and follow-up are indicated up to 39weeks of gestation. After 39weeks of gestation, data on fetuses with i-FIUVV and their outcomes are lacking.

Pregnancy After Bariatric Surgery—Experience from a Tertiary Center

IntroductionIt is estimated that most people undergoing bariatric surgery are women of reproductive age; nonetheless, its effects on pregnancy outcomes are not yet fully understood.MethodsRetrospective observational study, conducted in a tertiary center in Portugal, included participants in two groups: (1) pregnant women with a history of bariatric surgery (n = 89) and (2) pregnant women with a BMI ≥ 35 kg/m2, without previous bariatric surgery (n = 176). Data was collected from the medical files. Multivariate analysis was conducted to adjust for confounders.ResultsPregnancy after bariatric surgery was associated with lower risk of gestational diabetes (15.7% vs. 30.1%, p = 0.002) and cesarean delivery (20.7% vs. 33.5%, p = 0.007), and a higher gestational weight gain (10.58 ± 9.95 vs. 7.33 ± 6.00 kg, p < 0.001). Participants in the bariatric surgery who experienced a gestational weight gain ≤ 10.0 kg had a higher risk of preterm delivery (16.7% vs. 2.5%, p = 0.031). No significant differences were found regarding hypertensive diseases of pregnancy between groups (4.5% vs 11.4%, p = 0.147).Pregnancy after bariatric surgery was associated with lower neonate weight percentile (34.24 ± 21.09 vs. 48.77 ± 27.94, p < 0.001), higher risk of fetal growth restriction (5.6% vs. 0.6%, p = 0.018), and lower risk of fetal macrosomia (0.0% vs. 7.5%, p = 0.005). There were no significant differences in the risk of SGA (12.5% vs. 7.0%, p = 0.127) or LGA neonates (2.3% vs. 6.4%, p = 0.069).ConclusionPregnancy after bariatric surgery is associated with both risks and benefits, which should be considered by healthcare providers. Pregnancy after bariatric surgery requires individualized care, to ensure adequate gestational weight and avoid micronutrient deficiencies.Graphical

Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk.

We aimed to explore the potential link of maternal age at menarche (mAAM) gene polymorphisms with risk of the fetal growth restriction (FGR). This case (FGR)-control (FGR free) study included 904 women (273 FGR and 631 control) in the third trimester of gestation examined/treated in the Departments of Obstetrics. For single nucleotide polymorphism (SNP) multiplex genotyping, 50 candidate loci of mAAM were chosen. The relationship of mAAM SNPs and FGR was appreciated by regression procedures (logistic/model-based multifactor dimensionality reduction [MB-MDR]) with subsequent in silico assessment of the assumed functionality pithy of FGR-related loci. Three mAAM-appertain loci were FGR-linked to genes such as KISS1 (rs7538038) (effect allele G-odds ratio (OR)allelic = 0.63/pperm = 0.0003; ORadditive = 0.61/pperm = 0.001; ORdominant = 0.56/pperm = 0.001), NKX2-1 (rs999460) (effect allele A-ORallelic = 1.37/pperm = 0.003; ORadditive = 1.45/pperm = 0.002; ORrecessive = 2.41/pperm = 0.0002), GPRC5B (rs12444979) (effect allele T-ORallelic = 1.67/pperm = 0.0003; ORdominant = 1.59/pperm = 0.011; ORadditive = 1.56/pperm = 0.009). The haplotype ACA FSHB gene (rs555621*rs11031010*rs1782507) was FRG-correlated (OR = 0.71/pperm = 0.05). Ten FGR-implicated interworking models were founded for 13 SNPs (pperm ≤ 0.001). The rs999460 NKX2-1 and rs12444979 GPRC5B interplays significantly influenced the FGR risk (these SNPs were present in 50% of models). FGR-related mAAM-appertain 15 polymorphic variants and 350 linked SNPs were functionally momentous in relation to 39 genes participating in the regulation of hormone levels, the ovulation cycle process, male gonad development and vitamin D metabolism. Thus, this study showed, for the first time, that the mAAM-appertain genes determine FGR risk.

The role of confined placental mosaicism in fetal growth restriction: A retrospective cohort study.

To evaluate which cytogenetic characteristics of confined placental mosaicism (CPM) detected in the first trimester chorionic villi and/or placentas in terms of chromosome aberration, cell lineage involved and trisomy origin will lead to fetal growth restriction and low birthweight. Cohort study using routinely collected perinatal data and cytogenetic data of non-invasive prenatal testing, the first trimester chorionic villi sampling and postnatal placentas. 215 CPM cases were found. Fetal growth restriction (FGR) and low birthweight below the 10th percentile (BW<p10) were seen in 34.0% and 23.1%, respectively. Excluding cases of trisomy 16, 29.1% showed FGR and 17.9% had a BW<p10. The highest rate of FGR and BW<p10 was found in CPM type 3, but differences with type 1 and 2 were not significant. FGR and BW<p10 were significantly more often observed in cases with meiotic trisomies. There is an association between CPM and FGR and BW<p10. This association is not restricted to trisomy 16, neither to CPM type 3, nor to CPM involving a meiotic trisomy. Pregnancies with all CPM types and origins should be considered to be at increased risk of FGR and low BW<p10. A close prenatal fetal monitoring is indicated in all cases of CPM.

Pregnancy course and outcomes in patients with non-insulin dependent gestational diabetes mellitus: An observational cohort study

Background. Gestational diabetes mellitus is the most frequent metabolic disorder during pregnancy. Its prevalence is steadily increasing worldwide. In the setting of hyperinsulinism, this pathology may cause various structural and functional changes in the placenta, as well as a reduction in oxygen supply to the fetus. This may result in fetal hypoxia and increased risk of fetal growth restriction. Therefore, research into the specific features of gestation course in patients with gestational diabetes mellitus in order to prevent its complications appears relevant. Objective. To study the specific features of gestation, delivery, and perinatal outcomes in patients with non-insulin dependent gestational diabetes mellitus. Methods. We conducted an observational cohort study of the case histories of 120 women with singleton pregnancies of the second and third trimesters with diagnosed non-insulin dependent gestational diabetes mellitus, their labor and delivery records, and the medical records of the newborns. All the patients were managed at the Ural Research Institute of Maternity and Child Care during 2021–2023. The main group comprised 70 patients whose pregnancy was complicated by sub- and decompensated forms of placental insufficiency. The comparison group comprised 50 pregnant women without pathologies of the fetoplacental complex. The obstetric history, gestation course of the present pregnancy and its outcomes, as well as the condition of the newborns, were analyzed. The obtained data were processed by the methods of variation statistics using Microsoft Excel spreadsheets (Microsoft, USA) and Statistica 13 (DellInc., USA) and MedCalc 15.8 (MedCalcSoftware, Belgium) applications. The null hypothesis was rejected at p &gt; 0.05. Results. Gestational diabetes mellitus in previous pregnancies was statistically significantly less frequent in the main group (2.9% (n = 2)) than in the comparison group (18.0% (n = 9)) ( p &gt; 0.05). Placental insufficiency in the main group was characterized by fetal growth restriction, which was associated with impaired uteroplacental blood flow in 58.6% (n = 41) of the cases. In the main group, the pregnancy ended in preterm delivery in 21.4% (n = 15) of the cases; in 78.6% (n = 55) of the cases, the delivery was at term. There were no preterm births in the comparison group, p &gt; 0.05. Cesarean section was performed in 62.9% (n = 44) of patients in the main group, compared to 20.0% (n = 10) in the comparison group ( p &gt; 0.05). Newborns of the main group required respiratory support more often (p &gt; 0.05). Conclusion. The mechanism of placental insufficiency in patients with non-insulin dependent gestational disorders of carbohydrate metabolism remains to be elucidated. Further research should investigate the predictors of fetoplacental complex pathologies in this group of patients in order to reduce the number of perinatal complications.

The effect of possible mediators on the association between chewing khat during pregnancy and fetal growth and newborn size at birth in Eastern Ethiopia

IntroductionRestriction in the growth of the fetus is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Documented existing scientific evidence have shown the effects of maternal drugs use, alcohol drinking, tobacco smoking, cocaine use and heroin use on fetal growth restriction. However, data is lacking on the effects of khat chewing during pregnancy on fetal growth status and newborn size at birth. Therefore, the aim of the present study was to measure the effect of chewing khat during pregnancy on fetal growth and size at birth in eastern Ethiopia.MethodA cohort study was conducted in selected health institutions in eastern Ethiopia. All pregnant women fulfilled the eligibility criteria in the selected health institutions was the source population. The calculated sample size of exposed and unexposed groups included in the study, in total, was 344. Data collection was performed prospectively by interviewers administered questionnaires, and anthropometric, clinical and ultrasound measurements. Data was analyzed using SPSS version 27 and STATA version 16 software. The survival analysis (cox proportional hazards model) and generalized linear model (GLM) for the binomial family analysis were performed to estimate the crude and adjusted relative risk and attributable risk (AR) with corresponding 95% CI of chewing khat on fetal growth restriction. The mediation effect has been examined through Generalized Structural Equation Modeling (GSEM) analysis using the Stata ‘gsem’ command. Statistically significant association was declared at p-value less than 5%.ResultsIn the present study, the incidence of fetal growth restriction (FGR) among the study cohorts was 95 (29.7%); of this, 81 (85.3%) were among khat chewer cohorts. The relative risk of fetal growth restriction among khat chewer cohort mothers was significantly higher (aRR = 4.32; 95%CI 2.62–7.12). Moreover, the incidence of small for gestational age at birth among the present study cohorts was 100 (31.3%); 84 (84%) were from khat chewer cohorts’ deliveries. More importantly, in the present study, 98.95% of the ultrasound-identified fetuses with FGR were found to be SGA at birth. Hence, in the current study, FGR was highly associated with SGA at birth. In additional analysis, the regression coefficient of khat chewing during pregnancy on fetal growth restriction has been decreased in size from path o, β = 0.43, p < 0.001 to path o’, β = 0.32, p < 0.001, after adjusting for gestational hypertension and maternal anemia.ConclusionIn sum, the present study showed khat chewing during pregnancy is not simply affected the mothers, but it also affected the unborn fetuses. Therefore, the health workers as well as the local community and religious leaders should give high emphasis on provision of health education regarding the damage of chewing khat by pregnant mothers, with especial focus of the effects on their fetuses.

Gestational diabetes in twin pregnancies—a pathology requiring treatment or a benign physiological adaptation?

There is level-1 evidence that screening for and treating gestational diabetes in singleton pregnancies reduce maternal and neonatal morbidity. However, similar data for gestational diabetes in twin pregnancies are currently lacking. Consequently, the current approach for the diagnosis and management of gestational diabetes in twin pregnancies is based on the same diagnostic criteria and glycemic targets used in singleton pregnancies. However, twin pregnancies have unique physiological characteristics, and many of the typical gestational diabetes-related complications are less relevant for twin pregnancies. These differences raise the question of whether the greater increase in insulin resistance observed in twin pregnancies (which is often diagnosed as diet-treated gestational diabetes) should be considered physiological and potentially beneficial in which case alternative criteria should be used for the diagnosis of gestational diabetes in twin pregnancies. In this review, we summarize the most up-to-date evidence on the epidemiology, pathophysiology, and clinical consequences of gestational diabetes in twin pregnancies and review the available data on twin-specific screening and diagnostic criteria for gestational diabetes. Although twin pregnancies are associated with a higher incidence of diet-treated gestational diabetes, diet-treated gestational diabetes in twin pregnancies is less likely to be associated with adverse outcomes and accelerated fetal growth than in singleton pregnancies and may reduce the risk for intrauterine growth restriction. In addition, there is currently no evidence that treatment of diet-treated gestational diabetes in twin pregnancies improves outcomes, whereas preliminary data suggest that strict glycemic control in such cases might increase the risk for intrauterine growth restriction. Overall, these findings provide support to the hypothesis that the greater transient increase in insulin resistance observed in twin pregnancies is merely a physiological exaggeration of the normal increase in insulin resistance observed in singleton pregnancies (that is meant to support 2 fetuses) rather than a pathology that requires treatment. These data illustrate the need to develop twin-specific screening and diagnostic criteria for gestational diabetes to avoid overdiagnosis of gestational diabetes and to reduce the risks associated with overtreatment of diet-treated gestational diabetes in twin pregnancies. Although data on twin-specific screening and diagnostic criteria are presently scarce, preliminary data suggest that the optimal screening and diagnostic criteria in twin pregnancies are higher than those currently used in singleton pregnancies.

Влияние непрерывного профилактического приема ацетилсалициловой кислоты на гистологическую картину плаценты у беременных группы высокого риска развития задержки роста плода

Background: fetal growth restriction (FGR) is the main cause of perinatal mortality. We have relatively effective methods of predicting and preventing this condition, however, it has not yet been possible to achieve a significant reduction of the FGR incidence. Acetylsalicylic acid (ASA) is the only effective pharmacological method for the prevention of FGR, but the mechanism of its action is still in doubt. Aim: to study the placental morphology in pregnant women at high risk of FGR according to the first trimester screening (FTS), depending on whether female patients took ASA for the FGR prevention or not. Patients and Methods: the study was conducted in 2019–2021. By that time, the clinical recommendations concerning «Insufficient fetal growth requiring the provision of medical care to the mother (fetal growth restriction)», developed by the Ministry of Health of the Russian Federation, had not yet come into effect. In a prospective analysis, the placental morphology of 125 pregnant women at high risk of FGR and 554 placentas of pregnant women at low risk was studied according to the FTS results. Pregnant women at high risk of FGR were divided into 2 groups: 51 female patients received ASA from 14 to 36 weeks pregnant, 74 did not receive ASA; the control group consisted of 554 pregnant women at low risk of FGR according to the FTS. The placenta was examined in 3 stages according to the conventional management scheme, including macroscopic analysis, material incisure and histology. Results: placental pathological changes (dystrophic changes, syncytial knots formation, fibrinoid deposition, disorders of placental villous maturation) in patients who did not receive ASA were significantly more common than in the control group and in the subgroup receiving ASA. Conclusion: FGR incidence decrease in patients receiving ASA was due to an improvement in the histological structure of the placenta. KEYWORDS: fetal growth restriction, small for gestational age, placenta, acetylsalicylic acid. FOR CITATION: Shamugiya V.V., Kuznetsov P.A., Dobrokhotova Yu.E. Effect of the continuous prophylaxis with acetylsalicylic acid on the placental histological image in pregnant women at high risk of fetal growth restriction. Russian Journal of Woman and Child Health. 2024;7(1):12–17 (in Russ.). DOI: 10.32364/2618-8430-2024-7-1-2.

Supplementation with fortified balanced energy–protein during pregnancy and lactation and its effects on birth outcomes and infant growth in southern Nepal: protocol of a 2×2 factorial randomised trial

IntroductionMany women in low and middle-income countries enter pregnancy with low nutritional reserves with increased risk of fetal growth restriction and poor birth outcomes, including small-for-gestational-age (SGA) and preterm birth....

Biomarkers for Diagnosing and Treating Fetal Growth Restriction.

Fetal growth restriction (FGR), a common obstetric complication, significantly increases the risks of fetal intrauterine death and neonatal death, and fetuses with growth restriction are prone to cognitive retardation and various diseases in adulthood. The early determination of FGR risk is contentious in clinical research, and few indicators are available for the early prediction and diagnosis of FGR. This review focuses on the prediction and diagnosis of FGR, as well as the significance of biomarkers for FGR, such as those related to gene regulation, apoptosis, mitochondrial function, and inflammation. Although many of these biomarkers are still in the early stages of research, they are good predictors of the threats to fetal health and safety, and they provide new insights for the treatment of FGR.

Objective measures of smoking and caffeine intake and the risk of adverse pregnancy outcomes.

In pregnancy, women are encouraged to cease smoking and limit caffeine intake. We employed objective definitions of smoking and caffeine exposure to assess their association with adverse outcomes. We conducted a case cohort study within the Pregnancy Outcome Prediction study to analyse maternal serum metabolomics in samples from 12, 20, 28 and 36 weeks of gestational age. Objective smoking status was defined based on detectable cotinine levels at each time point and objective caffeine exposure was based on tertiles of paraxanthine levels at each time point. We used logistic and linear regression to examine the association between cotinine, paraxanthine and the risk of pre-eclampsia, spontaneous pre-term birth (sPTB), fetal growth restriction (FGR), gestational diabetes mellitus and birthweight. There were 914 and 915 women in the smoking and caffeine analyses, respectively. Compared with no exposure to smoking, consistent exposure to smoking was associated with an increased risk of sPTB [adjusted odds ratio (aOR) = 2.58, 95% CI: 1.14 to 5.85)] and FGR (aOR = 4.07, 95% CI: 2.14 to 7.74) and lower birthweight (β = -387 g, 95% CI: -622 g to -153 g). On univariate analysis, consistently high levels of paraxanthine were associated with an increased risk of FGR but that association attenuated when adjusting for maternal characteristics and objective-but not self-reported-smoking status. Based on objective data, consistent exposure to smoking throughout pregnancy was strongly associated with sPTB and FGR. High levels of paraxanthine were not independently associated with any of the studied outcomes and were confounded by smoking.

Effects of Gestational Arsenic Exposures on Placental and Fetal Development in Mice: The Role of Cyr61 .

Several epidemiological investigations demonstrated that maternal arsenic (As) exposure elevated risk of fetal growth restriction (FGR), but the mechanism remains unclear. This study aimed to investigate the effects of gestational As exposure on placental and fetal development and its underlying mechanism. Dams were exposed to 0.15, 1.5, and throughout pregnancy via drinking water. Sizes of fetuses and placentas, placental histopathology, and glycogen content were measured. Placental RNA sequencing was conducted. Human trophoblasts were exposed to () to establish an in vitro model of As exposure. The mRNA stability and protein level of genes identified through RNA sequencing were measured. () modification was detected by methylated RNA immunoprecipitation-quantitative real-time polymerase chain reason (qPCR). The binding ability of insulin-like growth factor 2 binding protein 2 to the gene of interest was detected by RNA-binding protein immunoprecipitation-qPCR. Intracellular S-adenosylmethionine (SAM) and methyltransferase activity were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and colorimetry, respectively. In vitro methyltransferase (As3MT) knockdown or SAM supplementation and invivo folic acid (FA) supplementation were used to evaluate the protective effect. A case-control study verified the findings. Sizes of fetuses (exposed to 1.5 and ) and placentas (exposed to ) were lower in As-exposed mice. More trophoblasts accumulated and the expression of markers of interstitial invasion was lower in the mouse group in comparison with control. Placental RNA sequencing identified cysteine-rich angiogenic inducer 61 (Cyr61) as a candidate gene of interest. Mechanistically, mice and cells exposed to As had lower protein expression of CYR61, and this was attributed to a lower incidence of Cyr61 . Furthermore, cells exposed to As had lower methyltransferase activity, suggesting that this could be the mechanism by which Cyr61 was affected. Depletion of intracellular SAM, a cofactor for methyltransferase catalytic domain, partially contributed to As-induced methyltransferase activity reduction. Either As3MT knockdown or SAM supplementation attenuated As-induced Cyr61 down-regulation. In mice, FA supplementation rescued As-induced defective trophoblastic invasion and FGR. In humans, a negative correlation between maternal urinary As and plasma CYR61 was observed in infants who were small for gestational age. Using in vitro and invivo models, we found that intracellular SAM depletion-mediated Cyr61 down-regulation partially contributed to As-induced defective trophoblastic invasion and FGR. https://doi.org/10.1289/EHP12207.

The Impact of Prenatal Environmental Tobacco Smoking (ETS) and Exposure on Chinese Children: A Systematic Review.

Background: There is considerable evidence to support the association between exposure to environmental tobacco smoke (ETS) and children's burden of disease. However, the literature on the health outcomes of prenatal ETS exposure among Chinese children has not yet been comprehensively reviewed. Objective: This systematic review examines the currently available evidence and identifies gaps for further research on the health consequences of prenatal ETS exposure on Chinese children. Methods: Following the JBI systematic-scoping review methodological framework, we conducted a computer-aided search of three electronic databases-PubMed, EBSCOhost, and ProQuest to include studies from January 2011 to May 2023 that addressed the health outcomes of Chinese children whose mothers were exposed to ETS at any stage of pregnancy. Furthermore, a methodological quality assessment of the selected articles was conducted using JBI critical appraisal checklists. Results: A total of 30 articles were reviewed, including eleven high-quality studies and nineteen moderate-quality studies. Five main themes, including hypertension, fetal and children's development, behavioural disorders, respiratory outcomes, and "other health outcomes", were encompassed. The majority of the studies showed a positive link between prenatal ETS exposure and an increased risk of preterm birth, and moderate risk of fetal growth restriction. A few studies explored other potential adverse outcomes of ETS, including hypertension, respiratory morbidity, lung function, and asthma in children. Conclusions: The currently available evidence on prenatal ETS exposure in Chinese children has unveiled a wide range of health outcomes, including preterm birth, fetal development, behavioural disorders, and much more. However, Chinese studies in this area are still lacking and a gap still exists in relation to the strength of association between prenatal ETS exposure and some health risks. Efficient anti-smoking policies and smoking cessation programs should be developed to promote maternal and child health. Further research is also needed to provide better evidence in this field.

Glycemic control and neonatal outcomes in twin pregnancies with gestational diabetes mellitus

Preliminary data suggest that strict glycemic control in twin pregnancies with gestational diabetes mellitus may not improve outcomes but might increase the risk of fetal growth restriction. This study aimed to investigate the association of maternal glycemic control with the risk of gestational diabetes mellitus-related complications and small for gestational age in twin pregnancies complicated by gestational diabetes mellitus. This was a retrospective cohort study of all patients with a twin pregnancy complicated by gestational diabetes mellitus in a single tertiary center between 2011 and 2020, and a matched control group of patients with a twin pregnancy without gestational diabetes mellitus in a 1:3 ratio. The exposure was the level of glycemic control, described as the proportion of fasting, postprandial, and overall glucose values within target. Good glycemic control was defined as a proportion of values within target above the 50th percentile. The first coprimary outcome was a composite variable of neonatal morbidity, defined as at least 1 of the following: birthweight >90th centile for gestational age, hypoglycemia requiring treatment, jaundice requiring phototherapy, birth trauma, or admission to the neonatal intensive care unit at term. A second coprimary outcome was small for gestational age, defined as birthweight <10th centile or <3rd centile for gestational age. Associations between the level of glycemic control and the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence interval. A total of 105 patients with gestational diabetes mellitus in a twin pregnancy met the study criteria. The overall rate of the primary outcome was 32.4% (34/105), and the overall proportion of pregnancies with a small for gestational age newborn at birth was 43.8% (46/105). Good glycemic control was not associated with a reduction in the risk of composite neonatal morbidity when compared with suboptimal glycemic control (32.1% vs 32.7%; adjusted odds ratio, 2.06 [95% confidence interval, 0.77-5.49]). However, good glycemic control was associated with higher odds of small for gestational age compared with nongestational diabetes mellitus pregnancies, especially in the subgroup of diet-treated gestational diabetes mellitus (65.5% vs 34.0%, respectively; adjusted odds ratio, 4.17 [95% confidence interval, 1.74-10.01] for small for gestational age <10th centile; and 24.1% vs 7.0%, respectively; adjusted odds ratio, 3.97 [95% confidence interval, 1.42-11.10] for small for gestational age <3rd centile). In contrast, the rate of small for gestational age in gestational diabetes mellitus pregnancies with suboptimal control was not considerably different when compared with non-gestational diabetes mellitus pregnancies. In addition, in cases of diet-treated gestational diabetes mellitus, good glycemic control was associated with a left-shift of the distribution of birthweight centiles, whereas the distribution of birthweight centiles among gestational diabetes mellitus pregnancies with suboptimal control was similar to that of nongestational diabetes mellitus pregnancies. In patients with gestational diabetes mellitus in a twin pregnancy, good glycemic control is not associated with a reduction in the risk of gestational diabetes mellitus-related complications but may increase the risk of a small for gestational age newborn in the subgroup of patients with mild (diet-treated) gestational diabetes mellitus. These findings further question whether the gestational diabetes mellitus glycemic targets used in singleton pregnancies also apply to twin pregnancies and support the concern that applying the same diagnostic criteria and glycemic targets in twin pregnancies may result in overdiagnosis and overtreatment of gestational diabetes mellitus and potential neonatal harm.

Silicone breast implants may contribute to early-onset fetal growth restriction.

There are many studies showing that silicone breast implants may affect lactation, but few analyzed whether these implants affect placentation. We observed that many mothers with growth-restricted pregnancies had inflammatory conditions, such as silicone breast implants or giardiasis. This single-center cohort study assessed the prevalence of inflammatory conditions in normotensive growth-restricted singleton pregnancies. Next, we stratified the patients according to the presence or absence of silicone breast implants, to determine whether these implants influence fetal growth restriction onset or severity. Twelve (32%) of the 38 participants underwent cosmetic breast augmentation 4-18years before pregnancy. Half of the patients with and 38% without silicone breast implants had giardiasis. Half of the mothers with and 35% without silicone breast implants had autoantibodies. Silicone breast implants were associated with a 70% increased risk of fetal growth restriction before 32weeks' gestation (95% confidence interval [CI], 1.2-2.5). Fetal growth restriction was diagnosed significantly earlier in mothers with than in those without silicone breast implants, respectively at 27 (95% CI, 25-30) and 30weeks' gestation (95% CI, 29-32). Silicone breast implants also tripled the risk of fetuses being below the third percentile, but the difference was not significant. Our results suggest that the association of inflammatory conditions, such as silicone breast implants, giardiasis, and autoantibodies may contribute to placental insufficiency. Silicone breast implants older than four years increased the risk of early-onset fetal growth restriction. Studies with large samples are needed to validate our findings and define whether silicone-related fetal growth restriction should be included in autoimmune/inflammatory syndrome induced by adjuvants (ASIA) criteria. Key Points • Fetal growth restriction (FGR), responsible for 30% of stillbirths, is the most common cause of prematurity and intrapartum asphyxia. • In this study, including 38 mothers with normotensive FGR, all participants had 2-4 inflammatory conditions, such as giardiasis, sinusitis, candidiasis, dysbiosis, extreme fear or autoantibodies. • Silicone breast implants were associated with a 70% increased risk of fetal growth restriction before 32 weeks' gestation. • FGR was diagnosed at 27 weeks' gestation (95% CI, 25-30) in mothers with and at 30 weeks' gestation (95% CI, 29-32) in mothers without silicone breast implants.