Growth Restriction Research Articles

Disrupted in Schizophrenia 1 (DISC1) is essential for neuronal development and has been implicated in various psychiatric disorders. Our transcriptomic and proteomic analyses identified Zika virus (ZIKV) infection enhanced DISC1 expression, however, its functional role in ZIKV infection and caused congenital Zika syndrome (CZS) and ZIKV-induced long-term neurodevelopmental defects remain unexplored. In this study, we demonstrate that DISC1 attenuates ZIKV infection in human placental and neuroglia cells, as well as in murine macrophages and primary cortical cells. DISC1 also decreases ZIKV dissemination from peripheral tissues to key organs of mice, including the uterus, testis, and brain, thereby reducing fetal abortion rates and intrauterine growth restriction. Notably, DISC1 is associated with brain damage and long-term ZIKV effects, including memory loss, reduced anxiety and depression, declines in sociability and social novelty. Mechanistically, DISC1 activates autophagy by enhancing AMPKα phosphorylation and reducing mTOR phosphorylation, protecting against ZIKV infection. Additionally, DISC1 interacts with LC3 to further activate autophagy, partially contributing to reduce ZIKV infection. In conclusion, DISC1 plays a critical factor in controlling ZIKV infection and mitigating CZS and ZIKV-induced neurocognitive decline.

Growth abnormalities in children with congenital diaphragmatic hernia (CDH) are a significant concern for long-term developmental outcomes. To explore growth in this population, the evolution of weight, height, body mass index (BMI), and head circumference as vital indicators of growth and developmental progress in CDH survivors were investigated. We analyzed 1247 CDH patients treated at our center from 2000 to 2022. Growth trends regarding weight, height, BMI, and head circumference of surviving patients without major comorbidities were compared with standard pediatric growth milestones for term and preterm children. Factors associated with growth disparities were assessed. A total of 835 CDH survivors without major comorbidities were identified who exhibited notably slower weight gain, which stabilized at a reduced level beyond the age of 2years. By 6years of age, height normalized in term-born children, while head circumference normalized at 1year of age. BMI remained low throughout childhood. Defect size and gestational age were important independent predictors of growth restriction, whereas ECMO therapy was not an independent risk factor for low weight or small stature. Preterm children tended to exhibit lower growth percentiles and delayed catch-up. Conclusion This study reveals that while initial growth is typically delayed in CDH survivors, a significant number achieve catch-up in childhood. The results lay the groundwork for personalized nutritional and therapeutic strategies to enhance growth outcomes in children with CDH. What is Known: • Children with congenital diaphragmatic hernia frequently experience early growth failure and undernutrition. • Existing studies include ≤ 200 patients and tend to provide only short-term follow-up data. What is New: • A cohort of 1247 CDH patients was treated at our center; in survivors without major comorbidities, growth was evaluated repeatedlyup to 14 years. • Height and head circumference normalize, whereas weight and BMI remain lower; large defect size and lower gestational age, but not ECMO, predict poor growth.

Fetal growth restriction (FGR) is associated with inhibition of placental mTOR signaling and amino acid transport. mTOR is a positive regulator of amino acid transport mediated by controlling the plasma membrane trafficking of SNAT2, a System A amino acid transporter isoform, and LAT1 an isoform involved in System L amino acid transport. Inhibition of mTOR complex 1 decreases SNAT2 and LAT1 plasma membrane trafficking by activating of Nedd4-2, an E3 ubiquitin ligase, and inhibition of mTOR Complex 2 decreases the protein expression of Cdc42 which limits transporter trafficking to the plasma membrane. We isolated human primary trophoblast (PHT) cells from FGR placentas and demonstrate that they maintain the in vivo FGR phenotype with increased expression of DEPTOR, an endogenous inhibitor of mTOR, reduced mTOR signaling, increased Nedd4-2 expression, lower expression of Cdc42, and decreased SNAT2 and LAT 1 protein expression in the plasma membrane, and decreased System A and L activity. We silenced DEPTOR in FGR PHT cells using siRNA and found normalized mTOR signaling, Nedd4-2 and Cdc42 protein expression, SNAT2 and LAT1 plasma membrane trafficking and System A and L amino acid transport activity. We also show that hypoxia induces DEPTOR upregulation in PHT cells. In the Healthy Start Study, a longitudinal pre-birth cohort, placental DEPTOR expression was correlated with lower birth weight percentile and with higher systolic and diastolic blood pressure in children at 4-6 years of age. Together, our studies provide mechanistic and translational insight into how placental DEPTOR may serve as potential mediator of fetal growth and long-term health risk. We identify a mechanistic link between increased trophoblast DEPTOR expression in FGR and decreased placental mTOR signaling and amino acid transport. Intervention strategies aimed at normalizing trophoblast mTOR signaling may be effective to improve trophoblast nutrient transport and fetal growth in FGR.

Placenta is highly susceptible to oxidative stress during pregnancy, which is a major cause of abnormal vascular development, fetal growth restriction and preterm birth. Methionine exhibits remarkable efficacy in promoting embryonic development and pregnancy outcomes, yet the role of methionine in placental antioxidant capacity and angiogenesis remains unclear. Pregnant rats and porcine iliac artery endothelial cells (PIECs) were used in our study. Pregnant rats were fed with methionine supplementation or methionine free diet. PIECs were treated with methionine, ROS inducer, VEGFR1 inhibitor, CTNNB1 knockdown or overexpressing. Our findings revealed that dietary methionine supplementation significantly increased the levels of glutathione, while reducing the levels of malondialdehyde in rat placentae. Moreover, experiments from PIECs treatment with ROS inducer, VEGFR1 inhibitor, knockdown or overexpressing of CTNNB1 revealed that methionine regulated angiogenesis in the placenta by modulating ROS levels and the CTNNB1 signaling pathway. Mechanistically, methionine enhanced the transsulfuration metabolism in placental vascular cells, leading to the production of the antioxidant glutathione and a reduction in ROS levels, followed by activating the WNT3A/CTNNB1 signaling pathway. CTNNB1 bind to PIGF, which promoted the phosphorylation of VEGFR1, thereby enhancing angiogenesis. This study elucidated that methionine promoted placental angiogenesis through the ROS-WNT3A/CTNNB1-PIGF-VEGFR1 axis, providing new therapeutic targets for pregnancy complications.

This study aims to evaluate the clinical utility of the Middle Cerebral Artery Diastolic Deceleration Area (MCA DDA) as a novel Doppler parameter for predicting hypoxia and adverse perinatal outcomes in pregnancies complicated by Fetal Growth Restriction (FGR). A prospective observational study was conducted at the Perinatology Clinic of Ankara Bilkent City Hospital between November 2023 and November 2024. A total of 102 singleton pregnancies were enrolled, including 51 FGR cases and 51 gestational age-matched controls. All participants underwent comprehensive ultrasonographic and Doppler assessments at 34 weeks of gestation. Doppler parameters, including Umbilical Artery Pulsatility Index (UA PI), Middle Cerebral Artery Pulsatility Index (MCA PI), Cerebroplacental Ratio (CPR), Cerebroplacental-Uterine Ratio (CPUR), and the novel MCA DDA, were recorded. Receiver Operating Characteristic (ROC) analysis was performed to evaluate the predictive performance of these parameters for composite adverse perinatal outcomes (CAPO), which included NICU admission, 5-min Apgar score < 7, umbilical artery pH < 7.20, and perinatal mortality. MCA DDA was significantly higher in the FGR group (9.26 ± 2.31) compared to controls (7.49 ± 2.98, p < 0.001). ROC analysis revealed that MCA DDA had an area under the curve (AUC) of 0.63 (95% CI: 0.52-0.75, p = 0.023) with an optimal cut-off value of 8.43 (sensitivity 63.6%, specificity 61.0%). In comparison, CPR demonstrated superior predictive performance with an AUC of 0.71 (95% CI: 0.59-0.82, p = 0.001), while CPUR showed an AUC of 0.66 (95% CI: 0.55-0.78, p = 0.006). The FGR group had significantly higher rates of CAPO (80%) and NICU admissions (42.2%) compared to the control group (p < 0.001). While MCA DDA is significantly elevated in FGR cases and provides valuable insights into cerebral diastolic blood flow, its predictive ability for adverse perinatal outcomes is moderate compared to traditional Doppler indices like CPR and CPUR. Integrating MCA DDA with established parameters may enhance fetal surveillance and improve perinatal outcome prediction in pregnancies complicated by FGR.

To compare obstetric and perinatal outcomes between assisted reproductive technologies (ART)-conceived and spontaneously conceived twin pregnancies using a nationwide Korean cohort. This retrospective cohort study used Korean National Health Insurance Service data from October 2017 to December 2021. Twin pregnancies were identified via International Statistical Classification of Diseases and Related Health Problems, 10th revision codes and classified by conception type based on embryo transfer procedure codes. Outcomes included miscarriage, preeclampsia, placenta previa, gestational diabetes mellitus (GDM), emergency cesarean section (CS), intrauterine growth restriction (IUGR), and macrosomia. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR), controlling for maternal age and comorbidities. Subgroup analyses stratified by maternal age were also performed. Among 36,013 twin pregnancies, those conceived via ART exhibited significantly higher risks of obstetric complications, including placenta previa (aOR, 1.81; 95% confidence interval [CI], 1.57-2.08), preeclampsia (aOR, 1.31; 95% CI, 1.17-1.47), GDM (aOR, 1.32; 95% CI, 1.22-1.43), emergency CS (aOR, 1.21; 95% CI, 1.08-1.34), and IUGR (aOR, 1.18; 95% CI, 1.07-1.31). In age-stratified analyses, the risks were more pronounced in women aged ≥35 years (preeclampsia: aOR, 1.38; 95% CI, 1.19-1.61; emergency CS: aOR, 1.22; 95% CI, 1.06-1.42) compared with those aged <35 years (preeclampsia: aOR, 1.26; 95% CI, 1.05-1.50; emergency CS: aOR, 1.17; 95% CI, 1.00-1.37). Twin pregnancies conceived via ART are associated with significantly increased risks of obstetric and perinatal complications compared with spontaneous conceptions. Given the growing utilization of ART, these findings underscore the importance of individualized prenatal care and vigilant perinatal monitoring in ART-conceived twin pregnancies, particularly among women of advanced maternal age.

In this introduction, we summarize the research papers, review articles, opinion pieces and important aspects of the facilitated discussion from the meeting 'The indirect effects of cytomegalovirus infection: mechanisms and consequences' held at the Royal Society, London, on 14-15 October 2024. The term 'indirect effects' describes a statistical excess of pathologies seen in people with human cytomegalovirus (CMV) in the absence of histopathological hallmarks of direct CMV tissue damage. This meeting brought together laboratory scientists, paediatric and adult clinical academics, epidemiologists, and trialists, to discuss the latest research on indirect effects, from biological mechanisms to potential clinical consequences. Important questions regarding the impact of CMV remain unanswered in areas important to human health, such as preterm birth and fetal growth restriction, asymptomatic congenital infection, susceptibility to non-CMV infections, cardiovascular and respiratory disease, transplant, cancer and mental health. Further research is needed to better describe the biology and, critically, to robustly quantify its clinical impact and develop interventions to mitigate any harms.This article is part of the discussion meeting issue 'The indirect effects of cytomegalovirus infection: mechanisms and consequences'.

Very low birth weight (VLBW) infants experience inadequate postnatal growth, which may be associated with poor neurodevelopmental outcomes. This statewide quality improvement collaborative aimed to improve VLBW infant growth. The collaborative was conducted from October 2018 to March 2020. The aim was to reduce the primary outcome measure of proportion of weight <10th percentile at discharge among VLBW infants by 20% in 1year. The secondary outcome measure was a z-score deficit ≥0.8 from birth. Process measures were early fortification, nutrition rounds, and feeding guideline compliance. Balancing measures were necrotizing enterocolitis and human milk feeding at discharge. Measures were analyzed with statistical process control charts. Outcome measures were compared among participant and nonparticipant neonatal intensive care units (NICUs) for a total of 6years including 2years after the collaborative. 22 NICUs participated in the collaborative. The 78-month analysis included 7856 VLBW infants. The participant group reduced growth restriction at discharge (45% to 37.6%) and z-score deficit ≥0.8 (44.4% to 33.3%). Postcollaborative improvement was sustained for 24months. The 114 nonparticipant NICUs did not reduce rates of growth outcome measures. Several process measures showed sustained improvement. Balancing measures were unchanged during the collaborative period. However, post hoc analysis showed a higher necrotizing enterocolitis rate when 2years after the collaborative were included. Quality improvement collaborative NICUs improved nutrition processes and VLBW growth. Improvement was sustained for 24months after the collaborative. Nonparticipant NICUs did not show similar improvement. Implementing NICU nutrition processes may lead to sustained improvements in VLBW infant growth.

Secondhand smoke (SHS), found in about 57.6% of global public areas as a widespread environmental hazard, has been associated with negative effects during pregnancy, such as preeclampsia (PE) and intrauterine growth restriction (IUGR). Our research investigated the impact of SHS on placental issues in a C57BL/6 model that simulates PE and IUGR in mice. We administered SHS to pregnant mice through a nose-only delivery method, beginning either on embryonic day 12.5 (prior to spiral artery (SA) invasion; labeled SHS-6D) or day 14.5 (following SA invasion; labeled SHS-4D), continuing up to E18.5. Control animals received only ambient air. We employed bulk RNA sequencing to assess and describe changes in placental gene expression patterns. For the SHS-4D group, which mimicked IUGR, compared to untreated controls, results showed elevated levels of inflammation-related genes (IL11RA, CHI3L1) alongside likely interference in pathways for antibody-triggered complement activation, marked by reduced expression of C1QA, C1QB, and C1QC. Immune profiling also indicated decreased macrophage activity in the placentas of the SHS-4D group relative to those from normal pregnancies at term. In contrast, the SHS-6D versus control analysis revealed lowered expression of collagen-related genes (COL1A1, COL4A5, COL4A6, COL17A1). Additionally, SHS-6D exhibited higher levels of genes associated with cell-based lysis processes compared to SHS-4D. An evaluation of the existing literature revealed that nearly every differentially expressed gene (DEG) identified in our work has been reported in studies associated with SHS exposure. Yet, few of these DEGs are discussed alongside PE or IUGR in prior reports, highlighting gaps in knowledge about how SHS triggers these conditions. Overall, we determined that the timing of SHS exposure in pregnant mice results in unique patterns of gene regulation and involvement in biological pathways.

BackgroundHypertensive disorders of pregnancy (HDP) remain a major cause of maternal and perinatal morbidity and mortality globally. Quantifying the effects of HDP on complications during pregnancy is vital for enhancing risk prediction and improving pregnancy outcomes.MethodsThis study leveraged data from a cohort of 3652 women from a prior study investigating the prevalence of HDP at a tertiary maternity hospital in Kenya - between 1st January, 2018 and 31st December, 2019. Sociodemographic characteristics, pregnancy outcomes, and complications among women diagnosed with HDP compared with normotensive women were analysed. The maternal complications explored included acute renal injury, antepartum haemorrhage and postpartum haemorrhage. The perinatal complications included intrauterine foetal demise, intrauterine growth restriction, small-for-gestational-age neonates, preterm birth and low APGAR (7 or below). Log-binomial regression was used to estimate the risk ratios of maternal and perinatal complications between these groups. Both composite and individual complication analyses were done.ResultsThe rate of maternal complications within the study was 1.3% (46/3652), whereas perinatal complications occurred in 13.0% (474/3652). After adjusting for maternal age ≥ 35 years and caesarean delivery, women with HDP had 3.34 times the risk of maternal composite complications compared to normotensive women (adjusted risk ratio 3.34; 95% CI 1.81– 6.16). These complications included acute renal injury and postpartum haemorrhage. Furthermore, there was a significant association between HDP and composite perinatal complications (adjusted risk ratio 1.38; 95% CI 1.07– 1.77). Specifically, the risk of intrauterine foetal demise and intrauterine growth restriction was elevated among the HDP group compared to normotensive women.ConclusionHDP continues to pose a significant burden on pregnancy and childbirth in Kenya. A strong association between pregnancy complications and HDP has been demonstrated. Regionally adapted pregnancy surveillance and optimised management approaches for acute kidney injury, post partum haemorrhage and perinatal morbidity prevention are urgently needed.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12884-025-07941-1.

Pregnancy is a vulnerable period for poor sleep quality, and sleep disturbances might increase the risk of adverse pregnancy outcomes. Therefore, the present study aimed to identify the prevalence of poor sleep quality and examine the association of pregnancy-related anxiety, fear of childbirth, sociodemographic and obstetric factors with sleep quality among Iranian pregnant women. A multicenter cross-sectional study was conducted using multi-stage cluster sampling among 424 pregnant women attending health centers in Bandar Abbas, Iran, from 2023 to 2024. Data collection tools included a demographic and obstetric questionnaire, a checklist of pregnancy complications, the Pittsburgh Sleep Quality Index (PSQI), the Pregnancy-Related Anxiety Questionnaire (PRAQ), and the Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ). Data were analyzed using both univariate and multivariate linear regression in SPSS version 25 and quantile regression in R software version 4.3.0 with the quantreg package. The mean age and gestational age of the participants were 29.10 ± 6.81 years and 22.35 ± 9.28 weeks, respectively. Poor sleep quality was observed in 70.8% of the participants, with rates of 69.7%, 65.6%, and 79.1% in the first, second, and third trimesters, respectively. Pregnancy-related anxiety (B = 0.053, P < 0.001), fear of childbirth (B = 0.019, P = 0.006), occupation (B=-0.898, P = 0.026), unwanted pregnancy (B = 1.364, P < 0.001), hospitalization during pregnancy (B = 1.379, P < 0.001), and intrauterine growth restriction (IUGR) (B = 1.114, P = 0.033) were associated with sleep quality in pregnant women. The results of the quantile regression confirmed the significant association of these factors with the median PSQI score. Poor sleep quality was common among pregnant women in this study. Housewives and those reporting higher levels of pregnancy-related anxiety and fear of childbirth, unwanted pregnancies, hospitalization, and IUGR during pregnancy, were more likely to experience poorer sleep quality. Given the adverse effects of sleep disorders on maternal and fetal health, screening and managing sleep disturbances during pregnancy are essential.

Introduction: Preeclampsia is a multisystem progressive disease of pregnancy, characterized by a new onset of hypertension (≥ 140/90 mm Hg) with proteinuria after the 20th week of gestation. There is a conflict between United States guidelines that recommend Low-dose aspirin (LDA) and United Kingdom guidelines that recommend High-dose aspirin (HDA) for the prevention of preeclampsia in high-risk pregnant women. After the latest study that recommends HDA and the absence of pairwise meta-analyses comparing two doses, we aimed to conduct a comprehensive pairwise meta-analysis to assess whether HDA is better than LDA in the prevention of preeclampsia. Methods: We conducted a systematic search on PubMed, Scopus, Cochrane Central, and Web of Science (WOS) from inception until June 2025. All randomized controlled trials (RCTs) comparing LDA and HDA in high-risk pregnant women were included. Our primary outcome was the incidence of preeclampsia (PE), while secondary outcomes were Placental abruption, Pre-term delivery, and Intrauterine Growth Restriction (IUGR). Using random-effects models, we calculated risk ratios (RR) with 95% confidence intervals (CIs). Results: A total of 8 RCTs with 1,290 patients from the United States, Canada, England, and different Asian countries were included, among whom 642 (49.8%) patients were randomized to HDA. All studies compared HDA (≥ 150 mg) and LDA (75 mg to 81 mg). Patients with LDA had a higher risk of Preeclampsia (RR: 1.71, 95% CI: 1.19 to 2.44, p&lt;0.001) compared to HDA. There was no significant difference between the LDA and HDA regarding Placental abruption, Pre-term delivery, and IUGR. With a pooled RR with a 95% CI (1.8, [0.91 to 3.54], P = 0.09), (1.25, [0.79 to 1.97], P = 0.34), (1.5, [0.93 to 2.42], P = 0.1), respectively. Conclusion: Among high-risk pregnant women, LDA was associated with a 71% higher incidence of preeclampsia than HDA. These results support the use of HDA as a preventive medication for preeclampsia in high-risk pregnant women.

BackgroundThe predominant risk factors and outcomes of ROP in neonates with more than 34 weeks of gestation are not well described in low- and middle-income countries despite higher incidence of ROP in these neonates.ObjectivesTo determine the incidence and risk factors of ROP in neonates between 34 weeks and 38 weeks 6 days.Material and MethodsWe conducted a prospective observational study in a tertiary care paediatric hospital from January 2020 to June 2021. Neonates with gestational age between 34 and 38 weeks 6 days were included. Standardized screening protocols were adapted, with data on demographic characteristics, risk factors, ROP findings, and treatment collected systematically.ResultsAmong 267 neonates, 224 underwent ROP screening. Fifteen (6.7%) neonates had any ROP, with 6 (2.6%) having Type I ROP requiring treatment. Among the cohort, higher proportions of late preterm neonates had ROP 12 (8.5%) compared to early term neonates 3 (3.6%) and amongst the neonates who required treatment, 6 (2.6%) all were late preterm neonates. Significant risk factors for ROP development included being small for gestational age [12 (80%) versus 58 (28%), p < 0.01], postnatal weight gain [Mean Difference: 9.8 gm/kg/day; 95% CI, 6.7 - 13.0, p < 0.001] and associated comorbidities such as respiratory support [15 (100%) versus 128 (61%), p < 0.01], shock [13 (86.7%) versus 118 (56.5%), p < 0.01] and sepsis [3 (20% vs 22 (10%); p < 0.01].ConclusionsOur study supports extending ROP screening to neonates ≥34 weeks with growth restriction or comorbidities, particularly in low- and middle-income settings.

ABSTRACT Aim To determine the impact of a community‐oriented model integrating first‐trimester risk stratification, fetal Doppler and routine antenatal ultrasound on preeclampsia (PE) and perinatal mortality rates in a rural population of central India. Methods The program covered 168 public sector centres providing pregnancy care services to nearly 1500 pregnancies annually. First‐trimester assessments included measurement of mean arterial blood pressure, mean uterine artery pulsatility index, risk stratification for preterm PE, recommending low‐dose aspirin 150 mg for women at high risk for preterm PE, and health education for public sector community health workers, pregnant women and their families. Second and third trimester assessments included fetal biometry, growth, fetal Doppler studies of uterine, umbilical, middle cerebral arteries and estimation of the cerebroplacental ratio, staging and protocol‐based management of fetal growth restriction and individualised clinical management of PE. Results The analysis included 4808 pregnant women screened from September 2019 to May 2025. Childbirth outcomes were available for 4016 (83.5%) women. The first trimester screening protocol ( n = 2933) identified 4.2% ( n = 124) women only at high risk for preterm PE and 10.7% ( n = 313) women at high risk for both preterm PE and fetal growth restriction. PE was reported in 28 (0.7%) of the 4016 women with childbirth outcomes. The perinatal mortality rate was 16.4/1000 childbirths in 2025 compared to 37.0/1000 childbirths in 2016. Health education was provided to all screened pregnant women and healthcare staff of the healthcare centres. Conclusion The community‐oriented model reduced the magnitude of PE and perinatal mortality in this rural community.

Introduction: Substance use disorder (SUD) in pregnancy is associated with co-occurring psychological health conditions, and both are independently linked to an increased risk of adverse pregnancy outcomes (APOs). Previous studies have evaluated their effects on APOs in isolation, with limited research examining their combined effects. Research Question: What is the impact of SUD on APOs (hypertensive disorders of pregnancy, preterm delivery, fetal growth restriction, abruptio placentae, and gestational diabetes mellitus) among hospitalized pregnant women with psychological health conditions? Methods: Using ICD-10 codes for diagnoses and procedures, along with the National Inpatient Sample (NIS) data from 2016 to 2022, we identified the population hospitalized for pregnancy and delivery as well as those with a history of psychological disturbances (major depressive disorder, anxiety disorder, bipolar disorder, post-traumatic stress disorder, and adverse childhood experiences), and SUD (amphetamine/methamphetamine, cocaine, opioid, cannabis, or alcohol use disorder). Propensity scores for SUD were estimated using logistic regression based on sociodemographic and clinical variables. One-to-one greedy matching was used to create a balanced cohort. Logistic regression was then conducted on the matched sample to estimate odds ratios for APOs, comparing those with SUD to those without SUD. Results: There was a total of 1,154,465 weighted pregnancy and delivery-related hospitalizations with psychological concerns. After propensity score matching, 86,725 weighted pregnancy and delivery-related hospitalizations with SUD were matched with 89,460 hospitalizations without SUD. Compared to the group without SUD, the SUD group was associated with higher odds of all APOs OR: 1.21 (95% C.I.: 1.18 - 1.23), hypertensive disorders of pregnancy OR: 1.17 (95% C.I.: 1.14 - 1.20), preterm delivery OR: 1.57 (95% C.I.: 1.51 - 1.63), fetal growth restriction OR: 1.45 (95% C.I.: 1.40 - 1.51), and abruptio placenta OR: 1.79 (95% C.I.: 1.68 - 1.90) but not for gestational diabetes mellitus OR: 0.62 (95% C.I.: 0.59 - 0.64). Conclusions: SUD was associated with higher odds of all APOs except for gestational diabetes among pregnant patients with psychological health conditions. These patients may benefit from tailored interventions and support beyond routine screening. Further research is needed to evaluate the risk interactions between SUD and psychological conditions on APOs.

To identify preoperative risk factors associated with postlaser fetal death of the donor twin in a large cohort of pregnancies complicated by twin-twin transfusion syndrome (TTTS). This retrospective cohort study of prospectively collected data included monochorionic diamniotic pregnancies complicated by TTTS that underwent laser surgery between March 2006 and May 2024 at two specialized referral centers. Patients underwent a comprehensive ultrasound examination, including fetal Doppler evaluation, to assign a Quintero stage and to obtain the middle cerebral artery (MCA) peak systolic velocity (PSV) for each twin within 24 h before laser surgery. An isolated elevation of the donor MCA-PSV was defined as having an MCA-PSV > 1.5 multiples of the median (MoM) in the absence of twin anemia-polycythemia sequence (TAPS). TAPS was defined as donor MCA-PSV > 1.5 MoM and recipient MCA-PSV < 1.0 MoM or intertwin MCA-PSV difference of > 0.5 MoM. Patients underwent postoperative ultrasound the day after surgery to document cardiac activity in each twin. Univariate logistic and multivariable Poisson (Zou's method) regression models were used to estimate the odds ratio and adjusted relative risk (aRR) for donor twin demise, adjusted for TAPS, TTTS stage, selective fetal growth restriction (sFGR), donor MCA pulsatility index < 10th percentile, gestational age < 18 weeks at surgery and other risk factors. Fetal demise of the donor twin was noted in 14.3% (229/1602) of the study population. Preoperative isolated elevation of donor MCA-PSV conferred the highest aRR of any risk factor for postlaser donor fetal demise (aRR, 2.69 (95% CI, 1.91-3.81); P < 0.001) compared with Stage-III TTTS (aRR, 2.34 (95% CI, 1.36-4.02); P = 0.002), MCA pulsatility index < 10th percentile (aRR, 1.91 (95% CI, 1.48-2.46); P < 0.001), velamentous cord insertion in the donor twin (aRR, 1.86 (95% CI, 1.43-2.41); P < 0.001), TAPS (aRR, 1.63 (95% CI, 1.19-2.23); P = 0.001), gestational age < 18 weeks at laser surgery (aRR, 1.59 (95% CI, 1.21-2.08); P = 0.001) and sFGR (aRR, 1.58 (95% CI, 1.19-2.07); P = 0.001). The observed frequency of fetal demise of the donor twin increased with each additional concomitant risk factor included. Isolated elevation of donor MCA-PSV prior to laser surgery for TTTS conferred the highest aRR for donor fetal demise among risk factors including TAPS, TTTS staging, sFGR and other covariates. This risk increased progressively when more than one risk factor was present in pregnancies complicated by TTTS. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.

Investigation of pancreatic size and clinical effects in cases with late-onset fetal growth restriction

Abstract Background Arterial stiffness independently predicts cardiovascular mortality and morbidity. It is shown to be increased in vascular mediated conditions, such as preeclampsia and foetal growth restriction. ARTSENS Plus device assesses arterial stiffness and is validated in older populations. The study aimed to validate its use for measuring arterial stiffness in pregnant women by comparing it with SphygmoCor XCEL as a reference standard. Methods This cross-sectional study was conducted in two centres in the south-eastern region of India, recruiting 147 pregnant women. Arterial stiffness was assessed by the carotid–femoral pulse wave velocity (cfPWV) using both devices and validated according to the ‘2024 recommendations for validation of non-invasive arterial pulse wave velocity measurement devices.’ Bland–Altman plot and coefficient of variation of the test–retest reproducibility were calculated. Results The mean age of the included women was 28 ± 4 years, and their mean gestational age was 24.6 ± 9.5 weeks. The mean difference in cfPWV values obtained from SphygmoCor XCEL and ARTSENS Plus was 0.16 ± 0.54 m/s ( p = 0.12) with a measurement error of 0.85 m/s, indicating good accuracy of the ARTSENS plus device in assessing arterial stiffness. Both devices demonstrated good intra-observer reproducibility, with coefficients of variation of 2.53% for ARTSENS Plus and 3.48% for SphygmoCor XCEL. Conclusions ARTSENS Plus assesses arterial stiffness with good accuracy and intra-observer reproducibility when validated amongst pregnant women.

Timing of birth is complex in early-onset fetal growth restriction (FGR) and the literature is limited regarding the exact sequence of changes in antenatal parameters. This study aimed to examine this sequence in a large early-onset FGR cohort. Multicenter, retrospective cohort study. Six tertiary care hospitals in the Netherlands. A post hoc analysis of the OPtimal TIming of antenatal COrticosteroids in early-onset fetal growth REstriction (OPTICORE) study was performed. Repeated measures of antenatal parameters were assessed routinely from diagnosis to birth. Mixed-effects models were used to determine the probability of abnormality (binary) and the trend (Z-score, continuous) over time for each parameter (< 32 and ≥ 32 weeks). The time sequence of changes in fetal and maternal health parameters from diagnosis to birth in early-onset FGR pregnancies. A total of 1453 patients were included, of whom 1025 patients gave birth < 32 weeks and 428 ≥ 32 weeks, with median gestational ages of 29 + 3 weeks (IQR 27 + 6, 30 + 5) and 34 + 4 weeks (IQR 33 + 0, 37 + 0), respectively. The most apparent changes in fetal parameters in the last days preceding birth comprised: absent/reversed end-diastolic velocity of the umbilical artery and cardiotocography abnormalities. Regarding maternal parameters, an increased probability of antihypertensive agent(s) use was seen shortly preceding birth < 32 weeks. This large cohort of early-onset FGR pregnancies provides a time sequence of fetal and maternal health parameters from diagnosis to birth, which could inform clinical management.

Background: Fetal Growth Restriction (FGR) secondary to placental insufficiency often leads to morbidity and mortality in the perinatal period. Fetal adaptations such as 'brain sparing' blood flow redistribution offer some protection but predicting whether a fetus in this state will survive is challenging. Objective(s): To identify vascular responses predictive of stillbirth or hypoxia based on serial Doppler ultrasound measurement in a mouse model of FGR. Methods: We performed serial Doppler ultrasound observations of fetal blood flow redistribution in a murine model of FGR where prolongation of pregnancy was induced pharmacologically with progesterone in CD-1 mice. Observations were made at E18.5 (physiologic term), E19.5 (term +1), and E20.5 (term +2). Flow velocity waveforms were obtained from the middle cerebral artery (MCA), ductus arteriosus (DA), main pulmonary artery (MPA), ductus venosus (DV), umbilical artery (UA), and umbilical vein (UV). Following sacrifice, pimonidazole immunohistochemistry quantified tissue hypoxia. Results: Among 56 pregnancies, the strongest predictor of stillbirth was low DA peak systolic velocity at E19.5 (<217 mm/s, p=0.021, R²=0.52). Among survivors, cerebral hypoxia was predicted by elevated MCA peak systolic (>26.6 mm/s, p=0.022, R²=0.59) and end-diastolic velocity (>10.1 mm/s, p=0.043, R²=0.53, while high MPA flow (>0.73 mL/min, p=0.029, R²=0.51) predicted hepatic hypoxia. Overall, fetuses with a weaker pulmonary blood flow redistribution response were found to have worse outcomes, despite cerebral vasodilation. Conclusion(s): This minimally invasive murine model offers valuable insights into this pathophysiology of FGR-related stillbirth and highlights the prognostic potential of assessing fetal brain flow and pulmonary perfusion in tandem during sonographic surveillance of high-risk pregnancies.