Incidence Of Fetal Growth Restriction Research Articles

Impact of a Stage-Based Classification on the Incidence of Fetal Growth Restriction, Preterm Birth Rates, and Birthweight in a Rural Community of Central India

Introduction: The objective of this study was to determine the impact of the stage-based classification of fetal growth restriction (FGR) on the magnitude of FGR, preterm births (PTBs), and birthweight (BW) in a rural population of Madhya Pradesh in Central India. Methods: The program covered 168 public sector centers for pregnant women and infants that provided services to nearly 220,000 people. The third-trimester assessments included fetal biometry, growth and environment assessments, and Doppler assessments. Fetal growth was staged using the Barcelona protocol as stages 1–4 FGR, small for gestational age, and no FGR. The data from the last ultrasound assessment before childbirth were considered. Regular training programs covering preconception care, antenatal and postnatal care were organized in the local language for the public sector community health workers of the program district. Childbirth outcomes were collected from the obstetric service of the local public sector hospital. Results: The analysis included 1,229 pregnancies from 2019 to 2023. The overall magnitude of FGR using estimated fetal weight <10th centile was 19.61% and reduced to 13.34% with the stage-based classification. The magnitude of FGR using the stage-based classification reduced from 27.59% in 2019 to 8.95% in 2023. The PTB in the stage-based FGR subgroup declined from 35.0% in 2019 to 3.45% in 2023 and 96.55% of the stage 1 FGR babies in 2023 were delivered at term. The overall mean BW in the program area improved from 2,772.41 (357.11) g in 2019 to 2,819.68 (377.31) g in 2023. The perinatal mortality rate (8.95 per 1,000 pregnancies) in the program area for 2019–2023 was much lower than the 31.9 per 1,000 pregnancies reported for Madhya Pradesh. Conclusion: The change to a stage-based classification of FGR integrated with low-dose aspirin and fetal Doppler studies reduced the incidence of FGR and PTB and perinatal mortality and increased BW in this rural community.

Efficacy of Transcerebellar to Abdominal Circumference versus Head Circumference to Abdominal Circumference Ratio in Predicting Asymmetrical Intrauterine Growth Restriction

Background: Fetal growth restriction (FGR) is when a fetus is not able to achieve its genetic growth potential. The high incidence of FGR in the general obstetric population and its low recognition together lead to increased perinatal morbidity and mortality, and its early detection is useful in deciding the frequency of antenatal surveillance and optimizing the time of delivery to improve the neonatal outcome. The transverse cerebellar diameter/abdominal circumference (TCD/AC) ratio is a gestational age-independent parameter, which may be helpful in the early detection of FGR. Objectives: To compare the accuracy of transcerebellar to AC with head circumference (HC) to AC in predicting asymmetrical FGR after 20 weeks of gestation and to determine the significance of TCD and TCD/AC relationship in predicting fetal outcome as expressed by perinatal morbidity and mortality. Study Design: A prospective observational study. Materials and Methods: This prospective observational study was conducted in the Postgraduate Department of Obstetrics and Gynaecology. A total of 300 patients were taken and divided into two groups: Group A (patients of suspected FGR clinically) and Group B (healthy women with morphologically normal fetuses) in the age group of 18–35 years. Subjects with singleton, nonanomalous pregnancy, reliable dates, favorable lie to visualize posterior fossa, and gestation of 20 weeks or more, were taken from the said age group and followed for maternal and neonatal outcome. Results: The difference in TCD/AC ratio between patients with FGR (14.8 ± standard deviation [SD]) and without FGR (13.10 ± SD) is statistically significant with a P &lt; 0.0001 with good sensitivity (93%), specificity (94%), and diagnostic accuracy (93.66%) in predicting asymmetrical FGR when compared to HC/AC ratio with sensitivity 83%, specificity 93%, and diagnostic accuracy of 89.66%. Conclusion: The TCD/AC ratio is constant throughout pregnancy and is increased in FGR compared to normal pregnancy and can be used as a screening test to diagnose FGR.

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.

The impact of late pregnancy dating on the detection of fetal growth restriction at term.

The inaccuracy of late pregnancy dating is often discussed, and the impact on diagnosis of fetal growth restriction is a concern. However, the magnitude and direction of this effect has not previously been demonstrated. In this study, we aimed to investigate the effect of late pregnancy dating by head circumference on the detection of late onset growth restriction, compared to first trimester crown-rump length dating. This was a cohort study of 14 013 pregnancies receiving obstetric care at a tertiary center over a three-year period. Universal scans were performed at 12 weeks, including crown-rump length; at 20 weeks including fetal biometry; and at 36 weeks, where biometry, umbilical artery doppler and cerebroplacental ratio were used to determine the incidence of fetal growth restriction according to the Delphi consensus. For the entire cohort, the gestational age was first calculated using T1 dating; and was then recalculated using head circumference at 20 weeks (T2 dating); and at 36 weeks (T3 dating). The incidence of fetal growth restriction following T2 and T3 dating was compared to T1 dating using four-by-four sensitivity tables. When the cohort was redated from T1 to T2, the median gestation at delivery changed from 40 + 0 to 40 + 2 weeks (p < 0.001). When the cohort was redated from T1 to T3, the median gestation at delivery changed from 40 + 0 to 40 + 3 weeks (p < 0.001). T2 dating resulted in fetal growth restriction sensitivity of 80.2% with positive predictive value of 78.8% compared to T1 dating. T3 dating resulted in sensitivity of 8.6% and positive predictive value of 27.7%, respectively. The sensitivity of abnormal CPR remained high despite T2 and T3 redating; 98.0% and 89.4%, respectively. Although dating at 11-14 weeks is recommended, late pregnancy dating is sometimes inevitable, and this can prolong the estimated due date by an average of two to three days. One in five pregnancies which would be classified as growth restricted if the pregnancy was dated in the first trimester, will be reclassified as nongrowth restricted following dating at 20 weeks, whereas nine out of 10 pregnancies will be reclassified as non-growth restricted with 36-week dating.

Impacts of β-thalassemia/hemoglobin E disease on pregnancy outcomes.

To compare obstetric outcomes between women with β-thalassemia/hemoglobin E (β-thal/HbE) disease and those of low-risk pregnancies, and also between the two subgroups, β-thal0/HbE and β-thal+/HbE disease. A retrospective cohort study was undertaken on pregnant women with β-thal/HbE disease and low-risk pregnancies, which were randomly selected with a case-to-control ratio of 1:10. Pregnancies with β-thal/HbE disease were identified in 0.19% of 59 152 pregnancies, including 104 women in the study group and 1040 women in the control group. The mean gestational age and mean birth weight were significantly lower in the study group. The prevalence of fetal growth restriction, preterm birth and low birth weight were significantly increased in the study group based on both univariate and multivariate analysis. The impacts were more striking in the β-thal0/HbE subgroup than in the β-thal+/HbE subgroup. The cesarean rate was significantly higher in the study group. No maternal death or serious complication was found in this cohort. Based on this cohort, the largest ever published, β-thal/HbE disease is significantly associated with increased incidence of fetal growth restriction, preterm birth and low birth weight. The impacts were more pronounced in the β-thal0/HbE subgroup. Pregnancy may be relatively safer for women with β-thal/HbE disease.

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.

Correlation analysis of maternal serum folate and 25(OH)D levels with the incidence of fetal growth restriction in patients with preeclampsia

Background The purpose of this study was to investigate the effect of folic acid (FA) and vitamin D supplementation on increasing maternal serum folate and 25-hydroxyvitamin D [25(OH)D] concentrations during pregnancy and further reveal its role in reducing the risk of fetal growth restriction (FGR) in patients with preeclampsia (PE). Methods A total of 300 preeclamptic patients (treatment group 204 and control group 96) who had undergone routine obstetric examinations were retrospectively analyzed in this study. Data that include maternal serum levels of folate and 25(OH)D detected during early, middle, and late gestational periods from the medical records were analyzed. Multifactorial logistic regression analysis was performed to investigate the correlation of serum folate and 25(OH)D concentrations with the incidence of FGR. Results Serum folate and 25(OH)D concentrations were similar between the treatment group and control group in the early gestation. During the middle and late gestation, the serum folate and 25(OH)D levels were both continuously increased in the treatment group, but persistently decreased in the control group, leading to significant differences between the two groups (p < .001). In addition, the incidence of FGR was significantly lower in the treatment group than in the control group (p < .001). Logistic regression analysis showed significant correlations of increased serum folate and 25(OH)D levels with lower risk of FGR. Conclusions FA and vitamin D supplementations facilitated to lower the risk of FGR in preeclamptic patients. These results would be the solid foundation for the further investigation of approaches to improve adverse outcomes of pregnancy, and have potential guiding implications for clinical practice.

Analysis of adverse neonatal outcomes in pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies

Objective: To investigate the relationship between positive anti-Ro/Sjögren syndrome antigen type A (SSA) antibody and anti-La/Sjögren syndrome antigen type B (SSB) antibody in pregnant women and neonatal adverse outcomes. Methods: This study was a retrospective study, and 145 deliveries of 136 anti-Ro/SSA and anti-La/SSB antibody positive pregnant women were selected who had prenatal examination and delivered in Peking University First Hospital from January 2017 to June 2022. According to whether adverse neonatal outcomes occurred, 145 deliveries were divided into adverse outcome group (26 cases) and no adverse outcome group (119 cases). According to the time when anti-Ro/SSA and anti-La/SSB antibodies were found positive, 145 deliveries were divided into the antibody positive during pregnancy group (69 cases) and the pre-pregnancy antibody positive group (76 cases). The pregnancy outcomes, treatment and maternal and infant antibody levels of pregnant women between the adverse outcome group and no adverse outcome group, between antibody positive during pregnancy group and the pre-pregnancy antibody positive group were compared. Results: (1) Most of the pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies were diagnosed as undifferentiated connective tissue disease, accounting for 40.4% (55/136), followed by Sjogren's syndrome (25.0%, 34/136), systemic lupus erythematosus (23.5%, 32/136), antiphospholipid antibody syndrome (6.6%, 9/136), idiopathic thrombocytopenic purpura (1.5%, 2/136), and 4 cases were not diagnosed. (2) The titers of anti-Ro/SSA and anti-La/SSB antibodies in the first trimester and the second trimester were compared, and there were no statistical significances (all P>0.05). (3) The proportion of high level anti-Ro/SSA antibody (>100 kU/L), positive level of anti-La/SSB antibody and positive rate of anti-La/SSB antibody in the adverse outcome group were higher than those in the no adverse outcome group, and the birth weight of newborns and live birth rate in the adverse outcome group were lower than that in the no adverse outcome group, all with statistical significances (all P<0.05). The anti-Ro/SSA antibody level, the proportion of drug treatment (hydroxychloroquine, glucocorticoid, gamma globulin), the incidence of fetal growth restriction (FGR), the rate of preterm birth, and the positive level of anti-Ro/SSA and anti-La/SSB antibodies in newborns were compared between the two groups, and there were no statistically significant differences (all P>0.05). (4) The anti-Ro/SSA antibody level of pregnant women in the pre-pregnancy antibody positive group, the proportion of hydroxychloroquine and glucocorticoid treatment, and the anti-Ro/SSA antibody positive rate of newborns were higher, while the incidence of FGR and gamma globulin treatment rate of newborns in the antibody positive during pregnancy group were higher, respectively, and the differences were statistically significant (all P<0.05). The levels of anti-La/SSB antibodies in pregnant women, anti-Ro/SSA and anti-La/SSB antibodies in newborns, the positive rate of anti-La/SSB antibodies in newborns and the incidence of adverse outcomes were compared between the antibody positive during pregnancy group and the pre-pregnancy antibody positive group, and there were no statistical significances (all P>0.05). Conclusions: High concentrations of anti-Ro/SSA antibodies and co-positive anti-La/SSB antibodies during pregnancy may increase the incidence of adverse neonatal outcomes. There is no significant difference in the incidence of adverse neonatal outcomes between antibody positive pregnant women and antibody positive pregnant women who were first found during pregnancy after comprehensive treatment in the rheumatology and immunology department.

Assessing the Impact of Uterine Artery Doppler and Low-Dose Aspirin on Fetomaternal Outcome: A Prospective Study in Low-Risk Pregnant Women in Western Part of India.

Introduction Fetal growth restriction (FGR) and pregnancy-induced hypertension (PIH) are significant and clinically relevant complications observed in many pregnancies. Early prediction of these complications may be possible through the assessment of the umbilical artery pulsatility index (UAPI). However, its utility in routine practice for otherwise normal pregnancy needs further exploration in India. Objectives This study aimed to evaluate the potential benefits of incorporating UAPI for the timely use of low-dose aspirin in preventing FGR and PIH in a tertiary care hospital in the western part of India. Methodology A prospective study was conducted involving 64 low-risk (i.e., not having any feature of high-risk pregnancy) pregnant women selected from routine antenatal care outpatient departments over a period of two years. All women underwent uterine artery Doppler examination during the 11-13+6 weeks of pregnancy and those who had high UAPI received low-dose (150 mg) aspirin till the 35th week. The incidence of FGR and PIH was analyzed and compared between high UAPI and normal UAPI pregnancy. Results A total of 64 pregnant women with a mean age of 27.11±4 years participated in the study. Among the women, eight (12.5%) were found to have high UAPI and were put on aspirin. Among those eight women, two developed PIH. In the normal UAPI group, nine (16.07%) developed PIH (p-value = 0.62). FGR was found in one case among the eight who received aspirin and in eight cases among the 56 who had normal UAPI (p-value > 0.99). Conclusion The study concluded that despite having normal UAPI, women categorized as low-risk may develop PIH and FGR. Hence, the routine use of UAPI should be investigated in further cohort studies using a large sample to draw a generalizable conclusion for the Indian population.

Timing of Fetal Growth Restriction Development in Patients With Preeclampsia [ID: 1363469

INTRODUCTION: Preeclampsia (PEC) and fetal growth restriction (FGR) share common pathophysiology of placental insufficiency. In pregnancies complicated by PEC, the incidence of FGR increases significantly. We sought to examine the timing of FGR development in patients with PEC. METHODS: This was a retrospective cohort study of patients with PEC and singleton pregnancy who delivered at 23 weeks or greater. Patients who had been diagnosed with FGR prior to PEC diagnosis, those who were diagnosed with FGR at the same time as PEC, and those who delivered immediately after PEC diagnosis were excluded. Demographics were compared between patients with FGR and those without FGR. We plotted Kaplan-Meier curves for the interval from the diagnosis of PEC to the development of FGR. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (HRs) for FGR. Our IRB approved this analysis. RESULTS: Of 392 patients with PEC, 31 (7.9%) developed FGR. Compared to patients who did not develop FGR, patients who developed FGR were more likely to have early-onset PEC and lower maternal weight and were less likely to have gestational diabetes (P&lt;.05). The incidence rate of FGR increased by 11.6% each week from the PEC diagnosis. Compared to patients with late-onset PEC, those with early-onset PEC had a significantly higher cumulative incidence of FGR (P&lt;.01). The Cox proportional hazards model showed that early-onset PEC was associated with FGR (adjusted HR 4.12, 95% CI 1.19–14.33) compared to late-onset PEC. CONCLUSION: Patients with early-onset PEC had a significantly higher incidence of FGR compared to those with late-onset PEC. There was a high cumulative incidence rate of FGR in patients with early-onset PEC. Patients with PEC should be followed by serial fetal growth ultrasound.

Effect of the New Diagnostic Criteria of Fetal Growth Restriction on Obstetric and Neonatal Outcomes [ID: 1376466

INTRODUCTION: The diagnostic criteria of fetal growth restriction (FGR) was modified by the Society of Maternal-Fetal Medicine in 2020 to include both an abdominal circumference (AC) and estimated fetal weight (EFW) less than the 10th percentile as opposed to previous definition using only the EFW. We sought to evaluate the outcomes of this criteria modification. METHODS: This retrospective study compared the incidence, obstetrical and neonatal outcomes before (group 1, 2020) and after (group 2, 2021) the implementation of the modified diagnostic criteria at a single institution. This is an IRB-approved study. RESULTS: Of the 459 pregnancies with FGR included in this study, 100 were diagnosed in 2020 (group 1) and 359, in 2021 (group 2). An increase in the incidence of FGR was noted after the modification, 1.5% versus 5.3% (P&lt;.05). Median gestational age (weeks) at delivery decreased from 38.1 (Q1, 37.1; Q3, 39.1) in 2020 to 37.4 (Q1, 36.1; Q3, 38.3) in 2021 (P&lt;.05). There were no statistically significant differences in obstetrical outcomes. An increase in the frequency of respiratory distress syndrome was observed, 6 (6%) versus 51 (14.2%), P&lt;.05, and median length of neonatal stay 2.0 (Q1, 1.0; Q3, 3.0) and 2.0 (Q1, 2.0; Q3, 12.0) in group 1 compared to group 2 (P&lt;.05). CONCLUSION: The new diagnostic criteria for FGR is associated with increased incidence of diagnosis, neonatal respiratory distress, longer neonatal hospital admissions, and lower gestational age of delivery with no difference in obstetrical outcomes. It remains uncertain whether this modification will translate to improved outcomes, and larger multicenter prospective studies are needed.

Docosahexaenoic acid protects against lipopolysaccharide-induced fetal growth restriction via inducing the ubiquitination and degradation of NF-κB p65 in placental trophoblasts

Lipopolysaccharide (LPS) could induce adverse birth outcomes by evoking inflammation. We investigated the effect and mechanism of docosahexaenoic acid (DHA) on LPS-induced placental inflammation and fetal growth restriction (FGR). In vivo, pregnant CD-1 mice were divided into four groups: Ctrl, DHA, LPS and DHA+LPS group. We found that DHA pretreatment reduced the incidence of FGR induced by LPS and activated the expression of peroxisome proliferators-activated receptor gamma (PPARγ) in placental tissue. Moreover, the LPS-induced increase of mRNA levels of Tnf-α, Il-6, Il-1β, Mip-2 and Kc in placental tissue was significantly attenuated by DHA pretreatment. A similar effect of DHA was observed in serum of pregnant mice and amniotic fluid. In contrast, the levels of the IL-10 were significantly increased after DHA pretreatment. In vitro, we clarified that DHA antagonized the activation of the NF-κB signaling pathway induced by LPS, which was dependent on PPARγ. Subsequently, CHX (translation inhibitor) was used to indicated that PPARγ significantly increased the degradation rate of p65, an effect that was inhibited by MG132 (proteasome inhibitor) treatment. Finally, it was confirmed that the activation of PPARγ could significantly promote the ubiquitination and degradation of p65. Our results suggested that DHA alleviated LPS-induced inflammatory responses and FGR by activating PPARγ expression, leading to p65 ubiquitination and degradation.

Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species-mediated activation of placental GCN2/eIF2α pathway.

Epidemiological studies suggest that fetal growth restriction (FGR) caused by gestational cholestasis is associated with elevated serum cholic acid (CA). Here, we explore the mechanism by which CA induces FGR. Pregnant mice except controls were orally administered with CA daily from gestational day 13 (GD13) to GD17. Results found that CA exposure decreased fetal weight and crown-rump length, and increased the incidence of FGR in a dose-dependent manner. Furthermore, CA caused placental glucocorticoid (GC) barrier dysfunction via down-regulating the protein but not the mRNA level of placental 11β-Hydroxysteroid dehydrogenase-2 (11β-HSD2). Additionally, CA activated placental GCN2/eIF2α pathway. GCN2iB, an inhibitor of GCN2, significantly inhibited CA-induced down-regulation of 11β-HSD2 protein. We further found that CA caused excessive reactive oxygen species (ROS) production and oxidative stress in mouse placentas and human trophoblasts. NAC significantly rescued CA-induced placental barrier dysfunction by inhibiting activation of GCN2/eIF2α pathway and subsequent down-regulation of 11β-HSD2 protein in placental trophoblasts. Importantly, NAC rescued CA-induced FGR in mice. Overall, our results suggest that CA exposure during late pregnancy induces placental GC barrier dysfunction and subsequent FGR may be via ROS-mediated placental GCN2/eIF2α activation. This study provides valuable insight for understanding the mechanism of cholestasis-induced placental dysfunction and subsequent FGR.

Is bigger better? A comparison of growth restriction rates using the crown-rump length derived due date from the smaller versus larger twin

Although the smaller twin's crown-rump length is most accurate in establishing the estimated due date in dichorionic gestations, societal guidelines favor the use of the larger twin measurements based on concern for missing a diagnosis of fetal growth restriction. This study aimed to compare the accuracy of the diagnosis of early- and late-onset fetal growth restriction in dichorionic twin gestations conceived by assisted reproductive technology using the estimated due date as established by the crown-rump length of the smaller vs larger twin. This was a 10-year retrospective cohort study of nonanomalous, dichorionic gestations conceived with assisted reproductive technology at 2 institutions. The incidence of early-onset (<32 weeks of gestation) and late-onset (≥32 weeks of gestation) growth restriction derived from the Hadlock formula using the smaller and larger crown-rump length estimated due date was compared with the true estimated due date by assisted reproductive technology. Statistical significance was determined using the Fisher exact test. The incidence of missed fetal growth restriction cases, false-positive rate, and error were calculated along with the relative risk for a missed diagnosis using the smaller crown-rump length. A total of 176 subjects were screened: 81 had a fetal growth ultrasound at 24 to <32 weeks of gestation, and 58 had a fetal growth ultrasound at ≥32 weeks of gestation. There was a significant difference in the incidence of fetal growth restriction using the 3 dating strategies in both gestational age ranges (P<.001) with the smaller crown-rump length estimated due date more closely approximating the true rate. Before 32 weeks of gestation, the smaller crown-rump length estimated due date missed 2.5% of fetal growth restriction cases, whereas the larger crown-rump length estimated due date missed 0.6% of fetal growth restriction cases, with false-positive and error rates of 1.2% and 3.7% and 5.5% and 6.2%, respectively. After 32 weeks of gestation, the smaller crown-rump length estimated due date missed 1.8% of cases, whereas the larger crown-rump length estimated due date missed 0% of cases, with false-positive and error rates of 2.6% and 4.4% and 5.3% and 5.3%, respectively. The relative risk for a missed diagnosis of fetal growth restriction using the smaller crown-rump length estimated due date was 1.77 for early-onset growth restriction and 1.22 for late-onset growth restriction. Using the estimated due date derived from the smaller twin led to a more accurate detection of fetal growth restriction at a cost of a higher missed diagnosis rate.

Diagnostic and Prognostic Value of Deregulated Long Non-Coding RNA Plasmacytoma Variant Translocation 1 in Patients with Gestational Hypertension.

This study aimed to investigate the serum plasmacytoma variant translocation 1 (PVT1) level in pregnant women with gestational hypertension and pre-eclampsia and its diagnostic value for diseases and its influence on pregnancy outcome. Serum PVT1 levels in 72 pregnant women with gestational hypertension, 72 pregnant women with pre-eclampsia and 71 healthy pregnant women were evaluated by RT-qPCR, and the diagnostic significance of PVT1 for gestational hypertension was verified by receiver operator characteristic (ROC) curve. The correlation between PVT1 and clinical indicators were evaluated by Pearson correlation coefficient method. Logistic regression analysis evaluated the influencing factors in the development process of gestational hypertension to pre-eclampsia. The effect of PVT1 level on pregnancy outcome was evaluated by prognostic analysis. Results showed that PVT1 level was down-regulated in gestational hypertension group compared with healthy control group, whereas PVT1 level was down-regulated more significantly in pre-eclampsia group than in gestational hypertension group. ROC curve showed that PVT1 had high diagnostic accuracy for gestational hypertension. Pearson correlation coefficient and multiple linear regression analysis showed that PVT1 was correlated with systolic blood pressure, diastolic blood pressure, interleukin (IL)-6 and tumor necrosis factor-α. Logistic regression analysis revealed that IL-6 and PVT1 were the influencing factors of gestational hypertension to pre-eclampsia transition. Moreover, prognostic analysis manifested that the incidence of fetal growth restriction in low PVT1 expression group was significantly higher than that in high PVT1 expression group. The expression level of PVT1 has a high diagnostic accuracy for gestational hypertension, and the low PVT1 expression group is more prone to fetal growth restriction.

Https://thejmch.com/index.php?journal=thejmch&amp;page=issue&amp;op=view&amp;path%5B%5D=41

Background: Good antenatal care helps a woman face labour in good health and optimum conditions. The National Institute for Health and Care Excellence (NICE) and WHO guidelines suggest 15 visits in the whole pregnancy. Keeping in view the COVID-19 pandemic to reduce the exposure of pregnant ladies the number of antenatal visits was reduced to 7 milestone visits and outcome was noted. This study aimed to do a comparative study of feto-maternal outcome in antenatal cases at our centre using standard WHO protocol vs. revised antenatal protocol during COVID-19 pandemic. Subjects and Method: This was an observational study done at a tertiary care center of an Armed forces hospital with target population as pregnant ladies attending antenatal care Out patient department of the hospital during COVID19 pandemic Vs Antenatal cases in previous 1 year. A comparative analysis of pregnancy outcome, maternal variables during pregnancy and delivery along with neonatal variables was done. Results: There were lesser deliveries by 41.7% as compared to non-COVID times. There was an increase in the caesarean delivery rate and instrumental delivery rate during COVID times by 11% and 53% respectively. There was increase in Vaginal birth after caesarean (VBAC) by 26.6%. The incidence of fetal growth restriction, placental abruption, maternal anaemia and gestational diabetes mellitus, oligohydramnios and polyhydramnios was low. The incidence of spontaneous abortions was also low in our study. In contrast, the incidence of pre-term deliveries doubled from 7.4% to 13.4%. Neonatal morbidity and mortality indicators like Neonatal Intensive care unit (NICU) admissions showed a rising trend of 1.7% during the COVID (14.6% to 16.3%) with a minimal rise in early neonatal deaths by 0.2%. Conclusion: Our model doesn't show an increase in maternal, neonatal morbidity, and mortality. This model can be used as a standard of care for Antenatal patients during Pandemics. It reduces the risk exposure of the gravid mother without any significant increase in maternal and neonatal morbidity and mortality. Keywords: antenatal care, COVID-19 pandemic, revised antenatal schedule. Correspondence: Dr Vipin Kumar Prajapati, Graded Specialist Department of Obstetrics Gynecology, AFMC, Pune. E Mail: vipinafmc@gmail.com. Contact No: 8811015130. Journal of Maternal and Child Health (2023), 08(01): 125-133 https://doi.org/10.26911/thejmch.2023.08.01.12

Is Maternal Cardiovascular Performance Impaired in Altitude-Associated Fetal Growth Restriction?

Mundo, William, Lilian Toledo-Jaldin, Alexandrea Heath-Freudenthal, Jaime Huayacho, Litzi Lazo-Vega, Alison Larrea-Alvarado, Valquiria Miranda-Garrido, Rodrigo Mizutani, Lorna G. Moore, Any Moreno-Aramayo, Richard Gomez, Patricio Gutierrez, and Colleen G. Julian. Is maternal cardiovascular performance impaired in altitude-associated fetal growth restriction? High Alt Med Biol 00:000-000, 2022. Introduction: The incidence of fetal growth restriction (FGR) is elevated in high-altitude resident populations. This study aims to determine whether maternal central hemodynamics during the last trimester of pregnancy are altered in high-altitude FGR. Methods: In this cross-sectional study of maternal-infant pairs (FGR, n = 27; controls, n = 26) residing in La Paz, Bolivia, maternal heart rate, cardiac output (CO), stroke volume, and systemic vascular resistance (SVR) were assessed using continuous-wave Doppler ultrasound. Transabdominal Doppler ultrasound was used for uterine artery (UtA) resistance indices and fetal measures. Maternal venous soluble fms-like tyrosine kinase-1 (sFlt1) levels were measured. Results: FGR pregnancies had reduced CO, elevated SVR and UtA resistance, fetal brain sparing, and increased maternal sFlt1 versus controls. Maternal SVR was positively associated with UtA resistance and inversely associated with middle cerebral artery resistance and birth weight. Maternal sFlt1 was greater in FGR than controls and positively associated with UtA pulsatility index. Women with elevated sFlt1 levels also tended to have lower CO and higher SVR. Conclusion: Noninvasive assessment of maternal cardiovascular function may be an additional method for detecting high-risk pregnancies at high altitudes, thereby informing the need for increased surveillance and appropriate allocation of resources to minimize adverse outcomes.

High concentration of first-measured HCG after embryo transfer is associated with subsequent development of pre-eclampsia

Research questionAre outlier high values of first-measured human chorionic gonadotrophin (HCG) following embryo transfer related to pregnancy complications, specifically pre-eclampsia? DesignThis retrospective cohort study screened 3448 women aged 18–45 years who underwent IVF between 2014 and 2019 and evaluated 614 women who had an intrauterine pregnancy following single embryo transfer (SET), 423 of whom had a live birth. Pregnancy and birth outcome information was available for final analysis in 280 cases. The setting was a university-based IVF centre. HCG was measured at a standardized time after the embryo transfer and the values correlated with adverse pregnancy outcomes associated with poor placentation. ResultsWomen with first-measured HCG in the highest quintile had a higher incidence of pre-eclampsia than those with lower HCG concentrations (odds ratio [OR] 4.08, 95% confidence interval [CI] 1.41–11.82) even after controlling for age, body mass index, parity and type of embryo transfer. Additionally controlling for embryo stage at embryo transfer did not change the results (OR 3.97, 95% CI 1.37–11.46). No differences were found in the incidence of fetal growth restriction. ConclusionsThis is the first known report that links high first-measured HCG after SET to an adverse pregnancy outcome. If confirmed by future studies, initiation of preventive interventions at a very early stage of pregnancy merits further evaluation in this cohort of patients.

Fetal growth restriction, low birth weight, and preterm birth: Effects of active or passive smoking evaluated by maternal expired CO at delivery, impacts of cessation at different trimesters.

INTRODUCTIONThe objectives of this study were to evaluate the effect of cessation of active smoking during the 1st, 2nd, and 3rd trimesters of pregnancy on the risk of reduced birth weight and prematurity using an exhaled carbon monoxide biomarker with a cut-off value ≥3 ppm as well as the effects of passive smoking.METHODSThis was a multicenter prospective cohort study involving pregnant smokers and non-smokers. Pregnant smokers were identified at the first prenatal visit before 15 weeks of amenorrhea by the number of cigarettes smoked per day and by the carbon monoxide breath test. Women were classified into 6 groups: non-smokers, passive smokers, first trimester cessation, second trimester cessation, third trimester cessation, and smoking throughout pregnancy. Smoking cessation was defined if the pregnant woman reported quitting smoking and if she achieved an exhaled CO level of <3 ppm. The association between smoking cessation and fetal growth restriction or prematurity was assessed by multivariate logistic regression. Passive smoking was defined for non-smoking women on declarative smoking status and exhaled CO ≥3 ppm. The association between passive smoking and fetal growth restriction or prematurity was assessed by multivariate logistic regression.RESULTSThe number of patients included was 5244. The incidence of fetal growth restriction below the 10th percentile was 10.6%, 12.1%, 8.5%, 9.1%, 21.1%, and 22.9%, respectively, for the non-smoking, passive smoking, first, second, third trimester cessation, and full-pregnancy smoking, groups. The risk of FGR compared to non-smokers was OR=2.3 (95% CI: 1.18–4.30, p=0.014) for patients who quit smoking in the third trimester, OR=2.5 (95% CI: 2.03–3.12, p<0.001) for women who smoked throughout pregnancy. After logistic regression, FGR (AOR=1.9; 95% CI: 0.96–3.82) for women who quit smoking in the 3rd trimester (AOR=1.8; 95% CI: 1.38–2.31, p<0.001). The risk of FGR <5th percentile was AOR=1.96 (95% CI: 1.36–2.48, p<0.001).CONCLUSIONSActive or passive smoking during pregnancy is associated with an increased risk of intrauterine growth restriction and low birth weight. Cessation in the 1st and 2nd trimester reduces the risk of intrauterine growth restriction or low birth weight. Passive smoking has a deleterious impact on fetal development, intermediate to that of active smoking.

Prenatal Prediction of Fetal Growth Restriction and Postnatal Outcomes by Ultrasound Assessment of Fetal Myocardial Performance Index and Blood Flow Spectrum.

Objective Fetal growth restriction (FGR) affects 5% to 10% of newborns and is a major determinant of perinatal morbidity and mortality. Myocardial performance index (MPI), also known as the Tei index, is a useful, noninvasive, and Doppler-derived myocardial performance tool for fetal cardiac function evaluation. The purpose of the study is to evaluate ultrasonic prediction on FGR and postnatal outcomes using MPI and blood flow spectrum. Methods This retrospective study included 240 pregnant women developing FGR and 240 healthy pregnant women. The blood flow spectrum of middle cerebral artery (MCA), umbilical artery (UA), and ductus venous including systolic to diastolic ratio (S/D), resistant index (RI), pulse index (PI), and peak ventricular systolic velocity/atrial contraction valley velocity (S/a) were examined using the GE Voluson E8 ultrasound system. Results The MPI, S/D, RI, PI of UA, and S/a were all higher but S/D, RI, and PI of MCA were lower in the FGR group than those in the control group (P < 0.001). The MPI, S/D, RI, PI of UA, S/D, RI, PI of MCA, and ductus venous S/a yielded AUC of 0.813, 0.835, 0.791, 0.804, 0.789, 0.796, 0.803, and 0.784 when they were used to predict the incidence of FGR. Of note, the pregnant women with poor pregnancy outcomes exhibited higher values of MPI, S/D, RI, PI of UA, and S/a with lower scores of 1 min Apgar concomitant with lower values regarding S/D, RI, and PI of MCA than those with favorable pregnancy outcomes (P < 0.001). The MPI (r = −0.623), S/D (r = −0.660), RI (r = −0.601), PI (r = −630) of UA, and S/a (r = −0.573) shared negative correlations with 1 min Apgar scores (P < 0.001). Of note, the S/D (r = 0.562), RI (r = 0.597), and PI (r = 0.619) of MCA were positively correlated with 1 min Apgar scores (P < 0.001). It was revealed that the MPI, S/D, RI, PI of UA, S/D, RI, PI of MCA, and ductus venous S/a yielded AUC of 0.806, 0.833, 0.774, 0.788, 0.807, 0.729, 0.748, and 0.770 when they were used to predict the incidence of poor pregnancy outcomes for pregnant women developing FGR. Conclusion Our study demonstrates good ultrasonic prediction on FGR and postnatal outcomes using MPI and blood flow spectrum.