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Background: Nationwide evidence linking maternal ozone exposure with fetal growth restriction (FGR) was extensively scarce, especially in the Middle East with dry climate and distinct religious culture., Methods: We carried out a national retrospective birth cohort study using registry-based records from 749 hospitals across 31 provinces in Iran from 2013 to 2018. Monthly concentrations of maximum daily average 8-hour (MDA8) ozone at 0.125° × 0.125° resolution were extracted from well-validated spatiotemporal grid dataset. Linear and logistic regression models were employed to evaluate associations of maternal MDA8 ozone exposure with birthweight outcomes. Assuming causality, the comparative risk assessment framework was utilized to estimate the burden of low birthweight (LBW), small for gestational age (SGA), and birthweight loss per livebirth (BLL) attributable to ambient ozone pollution., Results: Of 4030383 livebirths included in the study, 264304 (6.6%) were LBW and 484405 (12.0%) were SGA. Each 10-ppb increase in MDA8 ozone exposure was associated with an odds ratio of 1.123 (95% confidence interval [CI]: 1.104 to 1.142) for LBW and 1.210 (95% CI: 1.197 to 1.223) for SGA, and a 30.5-g (95% CI: 29.0 to 32.0) reduction in birthweight. We observed approximately linear exposure-response relationships of maternal MDA8 ozone exposure with LBW (P nonlinear = 0.786), SGA (P nonlinear = 0.156), and birthweight reduction (P nonlinear = 0.104). Under the premise of causal association, we estimated 6.6% (95% CI: 5.7 to 7.5) of LBW, 10.1% (95% CI: 9.6 to 10.6) of SGA, and 18.8 g (95% CI: 17.9 to 19.7) of BLL could be attributable to maternal ozone exposure in Iran. Considerably greater risk and burden of ozone-related FGR were observed among younger, less-educated, and rural-dwelling mothers., Conclusions: Our study provided compelling evidence that maternal ozone exposure was associated with heightened FGR risk and burden, particularly among socioeconomically disadvantaged mothers. These findings underscored the urgent need for government to incorporate socioeconomic factors into future ozone-related health policies, not only to mitigate pollution, but also minimize inequality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The investigation of the fetal umbilical-portal venous system is based on the premise that congenital anomalies of this system may be related to adverse perinatal outcomes. Several small retrospective studies have reported an association between umbilical-portal-systemic venous shunts and intrauterine growth restriction. However, the prevalence of portosystemic shunts in the fetal growth restricted population is yet to be determined., Objective: The aims of this study were (1) to determine the prevalence of fetal umbilical-portal-systemic venous shunts in pregnancies complicated by intrauterine growth restriction and (2) to compare the perinatal and neonatal outcomes of pregnancies with intrauterine growth restriction with and without umbilical-portal-systemic venous shunts., Study Design: This was a prospective, cross-sectional study of pregnancies diagnosed with intrauterine growth restriction, as defined by the Society for Maternal-Fetal Medicine intrauterine growth restriction guidelines. All participants underwent a detailed anomaly scan, supplemented with a targeted scan of the fetal portal system. Venous shunts were diagnosed using color Doppler mode. The perinatal outcomes of pregnancies with intrauterine growth restriction with and without umbilical-portal-systemic venous shunts were compared., Results: A total of 150 cases with intrauterine growth restriction were recruited. The prevalence of umbilical-portal-systemic venous shunts in our cohort was 9.3% (n=14). When compared with the control group (intrauterine growth restriction without umbilical-portal-systemic venous shunts, n=136), the study group had a significantly lower mean gestational age at the time of intrauterine growth restriction diagnosis (29.7±5.6 vs 32.47±4.6 weeks of gestation; P=.036) and an earlier gestational age at delivery (33.50±6.0 vs 36.13±2.8; P=.005). The study group had a higher rate of fetal death (21.4% vs 0.7%; P<.001) and, accordingly, a lower rate of live births (71.4% vs 95.6%; P=.001). Additional associated fetal vascular anomalies were significantly more prevalent in the study group than in the control group (35.7% vs 4.4%; P≤.001). The rate of other associated anomalies was similar. The study group had a significantly lower rate of abnormal uterine artery Doppler indices (0% vs 40.4%; P=.011) and a higher rate of abnormal ductus venosus Doppler indices (64.3% vs 23%; P=.001). There were no cases of hypertensive disorders of pregnancy in the study group, whereas the control group had an incidence of 12.5% (P=.16). Other perinatal and neonatal outcomes were comparable., Conclusion: Umbilical-portal-systemic venous shunt is a relatively common finding among fetuses with growth restriction. When compared with pregnancies with intrauterine growth restriction with a normal portal system, these pregnancies complicated by intrauterine growth restriction and an umbilical-portal-systemic venous shunt are associated with a different Doppler flow pattern, an increased risk for fetal death, earlier presentation of intrauterine growth restriction, a lower gestational age at delivery, additional congenital vascular anomalies, and a lower rate of pregnancy-induced hypertensive disorders. Meticulous sonographic evaluation of the portal system should be considered in the prenatal workup of intrauterine growth restriction, as umbilical-portal-systemic venous shunts may affect perinatal outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The primary objective of this prospective cohort study was to assess the usefulness of a predefined multidisciplinary care pathway-based management on pregnancy outcome(s) in women with SLE who already had at least one adverse obstetric outcome(s)., Methods: Between March 2010 and March 2023, all consecutive, consenting women with SLE who already had at least one previous adverse obstetric outcome (preterm labour, pre-eclampsia, termination of pregnancy, miscarriage, intrauterine growth retardation (IUGR), preterm birth, low birth weight (LBW), intrauterine death (IUD) or stillbirth] were prospectively screened and counselled. The protocol comprised preconception and post-natal drug and disease status review, periodic ante-natal visits for the monitoring of pregnancy and drug and disease status review and post-natal drug and disease status review and contraception advice. Therapeutic changes were made as necessary at each visit., Results: A total of 213 women were screened and 197 women (age, 28 ± 6.34 years) were enrolled who had 226 pregnancies. Previous poor obstetric outcomes were miscarriage(s), 186; termination of pregnancy, 4; preterm labour, 51; IUGR, 36; IUD or stillbirth, 16; low birth weight (LBW), 44 and pre-eclampsia, 4. Seventy-seven (39%) women had secondary APS and 37 (19%) had a history of lupus nephritis. There were 194/226 (86%) live births [40 LBW (18%); caesarean section in 101 (45%)]. Thirty pregnancies culminated in miscarriages and 2 in IUDs (14%). Sixty-eight patients (30%) experienced lupus flare during pregnancy (36 mild, 20 moderate and 8 severe)., Conclusion: Our experience underscores the usefulness of a predefined multidisciplinary care pathway-based management for improving pregnancy outcomes in women with SLE who had previous adverse outcomes. Key Points • In women with SLE who had previous adverse obstetric outcome(s) a risk of poor outcome in subsequent pregnancy remains. • Good pregnancy outcomes in these women could be achieved by predefined  multidisciplinary care pathways focussed on addressing all relevant issues. • Improved access to rheumatology services and collaboration between rheumatologists and obstetricians is key to improving outcomes in SLE pregnancies., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Introduction: Objective: the aim of our study was to assess the effect of bariatric surgery on obstetric outcomes. Material and methods: a retrospective cohort study was conducted, including 54 pregnancies post-bariatric surgery and 219 pregnancies in non-operated obese women, from December 2018 to January 2023. Various maternal and obstetric characteristics were evaluated, ranging from baseline data to antepartum, intrapartum, postpartum, and neonatal outcomes. Results: bariatric surgery showed a significant 69 % reduction in the risk of gestational diabetes (GDM) (p = 0.045) and a 63.1 % reduction in cesarean sections (p = 0.014), but also a notable increase in the risk of miscarriage (3.5 times more, p = 0.046) and intrauterine growth restriction (35 times more, p = 0.009). Bariatric surgery was associated with a significant prolongation of postpartum hospital stay (7.5 times more, p = 0.001) and a decrease in the average weight of the newborn (213.71 g, p = 0.006). Conclusion: pregnancy after bariatric surgery presents benefits, such as a reduced risk of gestational diabetes (GDM) and cesarean section, but also presents challenges, such as an increased risk of miscarriage and intrauterine growth restriction (IUGR). These results highlight the importance of specialized obstetric care to optimize maternal-fetal outcomes in pregnant women with a history of bariatric surgery.

Importance: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, characterized by subfertility, increased risk of metabolic diseases, and pregnancy complications. Previous studies diverge regarding the association between maternal PCOS and newborn anthropometrics., Objective: To explore the association between maternal PCOS and newborn anthropometrics and the modifying effects of maternal body mass index, PCOS phenotype, and gestational diabetes., Design, Setting, and Participants: This cohort study followed up women from the first half of pregnancy to birth and combined data from 3 clinical trials of pregnant women with PCOS and a reference population consisting of participants in the Norwegian Mother, Father, and Child Cohort (MoBa) Study, with data from the Medical Birth Registry of Norway. The recruitment period for the clinical trials was between October 1, 2000, and August 31, 2017, and for MoBa, between July 1, 1999, and December 31, 2008. Participants included women with singleton pregnancies and live-born children. Data were analyzed from January 1 to June 15, 2023., Exposure: Maternal PCOS status., Main Outcomes and Measures: Newborn birth weight, birth length, and head circumference as continuous variables and z scores, and ponderal index (calculated as the birth weight in grams × 100 divided by the birth length in centimeters cubed), placenta weight, and ratio of birth weight to placenta weight (BWPW)., Results: The cohort included 390 pregnant women with PCOS (mean [SD] age, 29.6 [4.2] years) and 68 708 women in the reference group (mean [SD] age, 30.4 [4.5] years). Offspring in the PCOS group had lower birth weight, birth length, and head circumference than in the reference group offspring. The estimated mean differences in z scores were -0.26 (95% CI, -0.38 to -0.14) for birth weight, -0.19 (95% CI, -0.33 to -0.05) for birth length, and -0.13 (95% CI, -0.26 to -0.01) for head circumference. The PCOS group also had a lower ponderal index (-0.04 [95% CI, -0.07 to -0.004] g × 100/cm3) and placenta weight (-24 [95% CI, -43 to -5)] g), and higher BWPW ratio (0.4 [95% CI, 0.3 to 0.5]). The association between growth restriction and PCOS was more apparent when additionally adjusting for body mass index. Neither PCOS phenotype nor gestational diabetes diagnosis was associated with neonatal anthropometry in women with PCOS., Conclusions and Relevance: In this cohort of mother-infant pairs, maternal PCOS status was associated with lower birth weight, shorter birth length, and smaller head circumference in the offspring. This growth restriction was more pronounced when adjusting for BMI, providing insight into the association between PCOS and body mass index. The study contributed to the understanding of how PCOS affects the offspring.

Background: Unfavorable lipid profile is associated with pregnancy disorders characterized by uteroplacental dysfunction, including hypertensive disorders of pregnancy, preterm birth and fetal growth restriction. None of current tools used to predict the risk of pregnancy complications include lipid levels., Objective(s): In this study, we examined the association of preconception lipid profile with pregnancy disorders characterized by uteroplacental dysfunction in a multi-ethnic population, aiming to improve the identification of women at high risk for uteroplacental dysfunction using current prediction models., Study Design: We conducted a linkage study combining lipid profile collected in the multi-ethnic HELIUS study (Amsterdam, 2011-2015), linked with national perinatal registry data on pregnancy complications after inclusion until 2019. We included 1177 women of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan origin. Associations were studied using Poisson regression. The discriminative ability was assessed for different pregnancy complications of significantly associated lipid parameters when added to commonly used prediction tools for preeclampsia., Results: Preconception triglyceride level was associated with prevalence of hypertensive disorders of pregnancy (e^triglyceride level (mmol/L) adjusted prevalence ratio 1.07, 95% CI 1.00 to 1.14). Age-adjusted prevalence of hypertensive disorders of pregnancy was also higher among women with high LDL-C level, high TC/HDL-C or ≥4 adverse lipid parameters, but most of these findings were not statistically significant when adjusted for demographic, lifestyle and medical characteristics. Addition of triglyceride level and other lipid parameters to the NICE guideline criteria and to the EXPECT prediction tool did not improve discriminative ability for hypertensive disorders of pregnancy, preterm birth or fetal growth restriction., Conclusion(s): Lipid profile did not aid in the identification of women at high risk for pregnancy disorders characterized by uteroplacental dysfunction. Further studies are needed to improve preconception prediction models for hypertensive disorders of pregnancy and other pregnancy disorders characterized by uteroplacental dysfunction using biomarkers or other easily available measurements., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: In recent years, there has been a change in the conceptualization of foetal growth restriction (FGR), which has gone from being defined solely based on weight criteria to being defined and staged based on Doppler criteria. The aim of our study was to evaluate neonatal risk in a cohort of neonates with moderate to severe early-onset FGR defined by Doppler criteria., Population and Methods: We conducted a multicentre prospective cohort study in a cohort of neonates with early-onset foetal growth restriction and abnormal Doppler findings and a control cohort without Doppler abnormalities matched for sex and gestational age., Results: A total of 105 patients (50 cases, 55 controls) were included. We found a higher frequency of respiratory morbidity in the FGR group, with an increased need of surfactant (30% vs. 27.3%; OR, 5.3 [95% CI, 1.1-26.7]), an increased need for supplemental oxygen (66% vs. 49.1%; OR, 5.6 [95% CI, 1.5-20.5]), and a decreased survival without bronchopulmonary dysplasia (70 vs. 87.3%; OR, 0.16 [95% CI, 0.03-0.99]). Patients with FGR required a longer length of stay and more days of parenteral nutrition and had a higher incidence of haematological abnormalities such as neutropenia and thrombopenia. The lactate level at birth was higher in the severe FGR subgroup (6.12 vs. 2.4 mg/dL; P = .02)., Conclusion: The diagnosis of early-onset moderate to severe FGR defined by Doppler criteria carries a greater risk of respiratory, nutritional and haematological morbidity, independently of weight and gestational age. These patients, therefore, should be considered at increased risk compared to constitutionally small for gestational age preterm infants or preterm infants without FGR., (Copyright © 2024 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: We conducted a systematic review and meta-analysis to examine the relationship between stillbirth and various perinatal outcomes in subsequent pregnancy., Data Sources: PubMed, the Cochrane Library, Embase, Web of Science, and CNKI databases were searched up to July 2023., Study Eligibility Criteria: Cohort studies that reported the association between stillbirth and perinatal outcomes in subsequent pregnancies were included., Methods: We conducted this systematic review and meta-analysis in accordance with the PRISMA guidelines. Statistical analysis was performed using R and Stata software. We used random-effects models to pool each outcome of interest. We performed a meta-regression analysis to explore the potential heterogeneity. The certainty (quality) of evidence assessment was performed using the GRADE approach., Results: Nineteen cohort studies were included, involving 4,855,153 participants. From these studies, we identified 28,322 individuals with previous stillbirths who met the eligibility criteria. After adjusting for confounders, evidence of low to moderate certainty indicated that compared with women with previous live births, women with previous stillbirths had higher risks of recurrent stillbirth (odds ratio, 2.68; 95% confidence interval, 2.01-3.56), preterm birth (odds ratio, 3.15; 95% confidence interval, 2.07-4.80), neonatal death (odds ratio, 4.24; 95% confidence interval, 2.65-6.79), small for gestational age/intrauterine growth restriction (odds ratio, 1.3; 95% confidence interval, 1.0-1.8), low birthweight (odds ratio, 3.32; 95% confidence interval, 1.46-7.52), placental abruption (odds ratio, 3.01; 95% confidence interval, 1.01-8.98), instrumental delivery (odds ratio, 2.29; 95% confidence interval, 1.68-3.11), labor induction (odds ratio, 4.09; 95% confidence interval, 1.88-8.88), cesarean delivery (odds ratio, 2.38; 95% confidence interval, 1.20-4.73), elective cesarean delivery (odds ratio, 2.42; 95% confidence interval, 1.82-3.23), and emergency cesarean delivery (odds ratio, 2.35; 95% confidence interval, 1.81-3.06) in subsequent pregnancies, but had a lower rate of spontaneous labor (odds ratio, 0.22; 95% confidence interval, 0.13-0.36). However, there was no association between previous stillbirth and preeclampsia (odds ratio, 1.72; 95% confidence interval, 0.63-4.70) in subsequent pregnancies., Conclusion: Our systematic review and meta-analysis provide a more comprehensive understanding of adverse pregnancy outcomes associated with previous stillbirth. These findings could be used to inform counseling for couples who are considering pregnancy after a previous stillbirth., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Necrotizing enterocolitis (NEC) primarily affects preterm, especially small for gestational age (SGA), infants. This study was designed to (1) describe frequency and timing of NEC in SGA versus non-SGA infants and (2) assess whether NEC is independently associated with the severity of intrauterine growth failure., Study Design: Retrospective cohort study of infants without severe congenital malformations born <33 weeks' gestational age (GA) carried out from 2009 to 2021. The frequency and time of NEC were compared between SGA and non-SGA infants. Multivariate logistic regression was used to assess whether NEC was independently associated with intrauterine growth restriction. Severe growth restriction was defined as birth weight Z -score <  -2., Results: Among 2,940 infants, the frequency of NEC was higher in SGA than in non-SGA infants (25/268 [9.3%] vs. 110/2,672 [4.1%], respectively, p  < 0.001). NEC developed 2 weeks later in SGA than non-SGA infants. In multivariate analysis, the adjusted odds of NEC increased with extreme prematurity (<28 weeks' GA) and with severe but not moderate growth restriction. The adjusted odds of NEC increased with urinary tract infection or sepsis within a week prior to NEC, were lower in infants fed their mother's own milk until discharge, and did not change over five epochs. NEC was independently associated with antenatal steroid (ANS) exposure in infants with birth weight (BW) Z -score < 0., Conclusion: NEC was more frequent in SGA than in non-SGA infants and developed 2 weeks later in SGA infants. NEC was independently associated with severe intrauterine growth failure and with ANS exposure in infants with BW Z -score < 0., Key Points: · We studied 2,940 infants <33 weeks' GA.. · We assessed NEC.. · NEC was more frequent in SGA infants.. · NEC occurred 2 weeks later in SGA infants.. · NEC was associated with severe growth restriction.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: There is growing evidence of bidirectional associations between rheumatoid arthritis and adverse pregnancy outcomes (APOs) in observational studies, but little is known about the causal direction of these associations. Therefore, we explored the potential causal relationships between rheumatoid arthritis and APOs using a bidirectional two-sample Mendelian randomization (MR) in European and Asian populations., Methods: We conducted a bidirectional two-sample Mendelian randomization analysis using available summary statistics from released genome-wide association studies. Summary statistics for instrument-outcome associations were retrieved from two separate databases for rheumatoid arthritis and adverse pregnancy outcomes, respectively. The inverse-variance weighted method was used as the primary MR analysis, and cML-MA-BIC was used as the supplementary analysis. MR-Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran Q statistic method were implemented as sensitivity analyses approach to ensure the robustness of the results., Results: Our study showed that a higher risk of rheumatoid arthritis in the European population was associated with gestational hypertension (OR: 1.04, 95%CI: 1.02-1.06), pre-eclampsia (OR: 1.06, 95%CI: 1.01-1.11), fetal growth restriction (OR: 1.08, 95%CI: 1.04-1.12), preterm delivery (OR:1.04, 95%CI: 1.01-1.07). Furthermore, we found no evidence that APOs had causal effects on rheumatoid arthritis in the reverse MR analysis. No association between rheumatoid arthritis and APOs was found in East Asian population. There was no heterogeneity or horizontal pleiotropy., Conclusions: This MR analysis provides the positive causal association from rheumatoid arthritis to gestational hypertension, pre-eclampsia, fetal growth restriction and preterm delivery genetically. It highlights the importance of more intensive prenatal care and early intervention among pregnant women with rheumatoid arthritis to prevent potential adverse obstetric outcomes., (© 2024. The Author(s).)

Investigate the effect of long-term COVID-19 on maternal and fetal complications. A retrospective cohort study was conducted. A total of 623 pregnant women who delivered in Kunming First People's Hospital from November 1, 2022 to July 31, 2023 were selected. By employing statistical methods, we compared the associations between maternal and fetal complications in pregnant women with acute COVID-19 during pregnancy, long-term COVID-19, and non-COVID-19 pregnant women. In the final 623 samples, there were 209 pregnant women with acute COVID-19, 72 pregnant women with long-term COVID-19, and 342 pregnant women without COVID-19. The epidemiological and clinical characteristics of all subjects were similar. Pregnant individuals who developed long-term COVID-19 during their pregnancy had an increased risk of experiencing gestational hypertension (OR 3.344, 95% CI 1.544-7.243), gestational diabetes mellitus (OR 2.301, 95% CI 1.290-4.102), and fetal intrauterine growth restriction (OR 2.817, 95% CI 1.385-5.952). Multivariate binary logistic regression analysis showed that this association remained consistent even after adjusting for confounders and performing subgroup analyses. Other maternal and fetal complications, such as premature rupture of membranes, preterm delivery, neonatal asphyxia, and transfer of neonates to NICU, did not exhibit statistically significant associations. After linear regression analysis, the platelet count (β: - 0.127, 95% CI - 0.001-0.000) of pregnant women with long-term COVID-19 was slightly lower than that of non-COVID-19 pregnant women, and the other coagulation parameters were not statistically significant. The incidence of gestational hypertension, gestational diabetes mellitus and fetal intrauterine growth restriction in pregnant women with long-term COVID-19 is significantly increased, but it does not further increase the coagulation status., (© 2024. The Author(s).)

It is unclear whether polycystic ovary syndrome (PCOS) is an independent risk factor for adverse birth outcomes in the offspring of affected women. Here, we investigate the association of PCOS with birth outcomes in the offspring of women with PCOS overall and by potential confounders. This systematic review and meta-analysis included 73 studies and 92,881 offspring of women with and without PCOS from inception until 13 th July 2022. We report that mothers with PCOS are younger and have higher body mass index (BMI) around conception and have greater gestational weight gain. The odds of preterm birth, fetal growth restriction and low birth weight are higher and mean birthweight is lower in PCOS of which a lower mean birthweight and a higher small for gestational age are probably independent of BMI. This work informed the recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome, emphasizing that PCOS status should be captured at pregnancy to identify risk and improve birth outcomes in the offspring., (© 2024. The Author(s).)

Background: To assess pregnancy outcomes in women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection., Methods: This was a retrospective cohort study that included pregnant women who contracted coronavirus disease 2019 (COVID-19) once or twice during pregnancy and who gave birth between 1 October 2022 and 15 August 2023 in Shanghai First Maternity and Infant Hospital (Shanghai, China). We collected their clinical data and compared the frequency of adverse pregnancy outcomes between the reinfection group and the primary infection group, such as preterm birth, fetal growth restriction (FGR), hypertensive disorders of pregnancy (HDP), common pregnancy-related conditions, birth weight, and neonatal unit admission., Results: We observed a 7.7% reinfection rate among the 1,405 women who contracted COVID-19 during pregnancy. There were no significant differences in the frequency of preterm birth, FGR, HDP, other common pregnancy-related conditions, birth weight, or rate of neonatal unit admission between the reinfection and single infection groups. All our participants were unvaccinated, and all had mild symptoms., Conclusion: Our study showed no significant association between SARS-CoV-2 reinfection and adverse pregnancy outcomes., (© 2024. The Author(s).)

Purpose: 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., Methods: 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)., Results: 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)]., Discussion: 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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: 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-thal 0 /HbE and β-thal + /HbE disease., Methods: 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., Results: 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-thal 0 /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., Conclusion: 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-thal 0 /HbE subgroup. Pregnancy may be relatively safer for women with β-thal/HbE disease., (© 2024 International Federation of Gynecology and Obstetrics.)

Purpose: High caffeine intake during pregnancy is associated with restricted fetal growth. We aimed to evaluate the association between maternal caffeine intake during early and late pregnancy and the risk of delivering a small for gestational age (SGA) baby., Methods: Kuopio Birth Cohort (KuBiCo) is a prospective cohort study including women whose pregnancies and deliveries were treated at the prenatal clinics in outpatient healthcare centers and in Kuopio University Hospital, Finland. Maternal diet and caffeine intake during the first (n = 2007) and third (n = 4362) trimester of pregnancy were assessed using a 160-item food frequency questionnaire (2013-2022). SGA was defined as birth weight corrected for gestational age below  - 2 standard deviations from the mean, according to the sex-specific Finnish fetal growth curves., Results: Altogether in 32 and 38% (1st and 3rd trimester) of all women and in 44 and 52% of coffee drinkers, caffeine intake exceeded the recommendation for caffeine intake ( ≤ 200 mg/day) during pregnancy. The women with moderate (51-200 mg/day) (aOR 1.87; 95% CI: 1.16-3.02) and high (> 200 mg/day) (aOR 1.51; 95% CI: 1.08-2.10) caffeine intake during the first trimester were in the highest risk of having an SGA newborn. Caffeine intake in the third trimester of pregnancy was not associated with SGA., Conclusions: Moderate and high caffeine intake during early pregnancy is associated with SGA. As the results suggest that even moderate caffeine intake during the first trimester may increase the risk of SGA, the intake within recommendation limits does not necessarily appear to be safe for pregnant women and their newborns., (© 2024. The Author(s).)

Importance: Preeclampsia has direct influences on a developing fetus and may impact postnatal health, and fetal growth restriction (FGR) is often seen co-occurring with preeclampsia. The development of children born very preterm after preeclampsia diagnosis with and without FGR is not well characterized., Objective: To examine the associations of preeclampsia and FGR with developmental and/or behavioral outcomes in a cohort of very preterm infants., Design, Setting, and Participants: In this cohort study, infants in the prospective Neonatal Neurobehavior and Outcomes in Very Preterm Infants study were enrolled between April 2014 and June 2016 from 9 US university-affiliated neonatal intensive care units (NICUs). Eligible infants were born before 30 weeks' gestation. Infants were excluded for any major congenital anomalies and for maternal age younger than 18 years or cognitive impairment impacting the ability to provide informed consent. Data analysis was performed from November 2023 to January 2024., Exposure: Maternal preeclampsia and FGR in very preterm infants., Main Outcomes and Measures: The Bayley-III cognition, motor, and language scores less than 85 (-1 SD) indicated developmental delay. Child Behavior Checklist/Preschool 1.5-5 T-scores greater than or equal to 64 for internalizing, externalizing, or total problems indicated clinical importance., Results: Of 704 infants enrolled, 529 (mean [SD] gestational age, 27.0 [1.9] weeks; 287 male [54.3%]) were studied at 24-month follow-up. A total of 94 infants' mothers had preeclampsia (23.2%), and 46 infants (8.7%) had FGR. In adjusted models, preeclampsia was not associated with Bayley-III (cognitive, B = 3.43 [95% CI, -0.19 to 6.66]; language, B = 3.92 [95% CI, 0.44 to 7.39]; motor, B = 1.86 [95% CI, -1.74 to 5.47]) or Child Behavior Checklist/Preschool 1.5-5 (internalizing, B = -0.08 [95% CI, -2.58 to 2.73]; externalizing, B = 0.69 [95% CI, -1.76 to 3.15]; total, B = 0.21 [95% CI, -2.48 to 2.91]) outcomes. FGR was associated with significantly lower Bayley-III scores (cognitive, B = -8.61 [95% CI, -13.33 to -3.89]; language, B = -8.29 [95% CI, -12.95 to -3.63]; motor, B = -7.60 [95% CI, -12.40 to -2.66]), regardless of preeclampsia status., Conclusions and Relevance: In this cohort study of preterm infants, preeclampsia was not associated with developmental and/or behavioral outcomes, but infants with FGR may be prone to developmental delays. These findings suggest future areas of research for understanding the roles of preeclampsia and FGR separately and together in early child development for preterm infants.

Background: The mitigation measures implemented to face the healthcare emergency brought by COVID 19 pandemic generated an increase in socioeconomic inequities in the most underprivileged population which is also the most threatened in their human rights. In Uruguay, this population is assisted in the public health care system. To analyze how these measures impacted on these mothers and their neonates we selected outcomes that most contributed to neonatal mortality., Objective: To analyze the incidence of Preterm Birth (PB), Intrauterine Growth Restriction (IUGR) and Low Birth Weight (LBW) in the public health care system in Uruguay, during the period of time in which the strictest measures were adopted to mitigate the COVID 19 pandemic in 2020 (para-pandemic period) compared to the same period in 2019 (pre-pandemic)., Methods: A retrospective, cross sectional, descriptive study was performed to compare PB, IUGR and LBW from 15 March to 30 September 2019 (before COVID 19 pandemic) to the same period of 2020 (when COVID 19 pandemic bloomed), in the public health care subsystem. The analysis was performed with data from the national perinatal database system (SIP)., Results: In 2020, a significative increase in PB, RR: 1.14 (CI 95%: 1.03-1.25), and in LBW, RR: 1.16 (CI 95% 1.02-1.33), was registered compared to 2019 (pre-pandemic period). IUGR also showed an increase, but without statistical significance (4.6% in 2019 vs 5.2% in 2020, RR 1.13 CI 95% 0.98-1.31). The compared groups showed no differences in the distribution of biological confounding variables that could explain the increase in incidence of the main outcomes., Conclusions: In the absence of other factors that could explain the results we consider that social crisis associated to the restrictive measures implemented in the country to dwindle the effect of the pandemic exacerbated the adverse conditions that affect the reproductive process for those underprivileged women assisted in the public sector, increasing PB and LBW. It is important to consider the future impact of these results on neonatal and infant mortality and to implement social measures to reduce the damage as soon as possible.

Objective: There is uncertainty around the safety of SSRIs for treating depression during pregnancy. Nevertheless, the use of SSRIs has been gradually increasing, especially during the COVID-19 pandemic period. We aimed to (1) characterize maternal depression rate and use of SSRIs in a recent 10-year period, (2) address confounding by indication, as well as socioeconomic and environmental factors, and (3) evaluate associations of the timing of SSRI exposure in pregnancy with risk for preterm birth (PTB), low birthweight (LBW), and small for gestational age (SGA) infants among women with depression before pregnancy., Methods: We conducted propensity score-adjusted regression to calculate odds ratios (ORs) of PTB, LBW, and SGA. We accounted for maternal/pregnancy characteristics, comorbidity, depression severity, time of delivery, social vulnerability, and rural residence., Results: There were 50.3% and 40.3% increases in the prevalence rate of prenatal depression and prenatal SSRI prescription rate during the pandemic. We identified women with depression ≤180 days before pregnancy ( n  = 8406). Women with no SSRI order during pregnancy ( n  = 3760) constituted the unexposed group. The late SSRI exposure group consisted of women with an SSRI order after the first trimester ( n  = 3759). The early-only SSRI exposure group consisted of women with SSRI orders only in the first trimester ( n  = 887). The late SSRI exposure group had an increased risk of PTB of OR = 1.5 ([1.2,1.8]) and LBW of OR = 1.5 ([1.2,2.0]), relative to the unexposed group. Associations between late SSRI exposure and risk of PTB/LBW were similar among a subsample of patients who delivered during the pandemic., Conclusions: These findings suggest an association between PTB/LBW and SSRI exposure is dependent on exposure timing during pregnancy. Small for gestational age is not associated with SSRI exposure.

The prevalence of fibroids during reproductive age is 20-25%. The presence of fibroids during pregnancy can impact perinatal outcomes., Objective: To determine whether fibroids affect perinatal outcomes and whether women who undergo fibroid surgery before pregnancy have better perinatal outcomes than those who have fibroids during pregnancy. The study also analyzes the optimal time interval between myomectomy and pregnancy and the characteristics of fibroids during pregnancy that affect perinatal outcomes. In both groups, fibroids' size, number, and location were analyzed to determine their influence on perinatal outcomes. The perinatal outcome is determined by gestational age, birth weight, Apgar score, intrauterine growth retardation, placental complications, and delivery method., Methods: A study was conducted on the perinatal outcomes of 338 women who had uterine fibroids during pregnancy and those who had undergone fibroid surgery before pregnancy. The medical records of women who gave birth at a tertiary university hospital were analyzed in this retrospective study., Results: Women with submucosal fibroids have a lower gestational age of delivery (P = 0.0371), and those who operated on a higher number of fibroids before pregnancy had newborns with lower birth weights (P < 0.0001). Submucosal fibroids during pregnancy increase the chances of cesarean delivery (P = 0.0354). 14% of newborns have an Apgar score of less than seven within the first minute of birth in fibroids larger than 7 cm (P < 0.0001)., Conclusion: There is a statistically significant difference in the perinatal outcome of newborns depending on the number, size and placement of uterine fibroids in both observed groups., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives : The aim of this study was to analyze the association between maternal risk factors, such as age, body mass index (BMI), and cigarette smoking, and perinatal outcomes. Materials and Methods : We conducted a retrospective analysis based on prospectively collected data at Hospital Universitario de Torrejón (Madrid, Spain) between September 2017 and December 2019. All pregnant women with singleton pregnancies and non-malformed live fetuses attending their routine ultrasound examination at 11+0 to 13+6 weeks' gestation were invited to participate. The association between preeclampsia, preterm birth, gestational diabetes mellitus (GDM), small-for-gestational-age (SGA) or fetal-growth-restricted (FGR) neonates, and type of delivery and maternal age, BMI, and cigarette smoking was studied. Logistic mixed models were used to analyze the data. Results : A total of 1921 patients were included in the analysis. Women who were ≥40 years old had a significantly higher risk of having GDM (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.08 to 2.36) and SGA neonates (OR 1.54, 95% CI 1.00 to 2.37). Women with a BMI < 18 had an increased rate of giving birth to SGA and FGR neonates (OR 3.28, 95% CI 1.51 to 7.05, and OR 3.73, 95% CI 1.54 to 8.37, respectively), whereas women with a BMI ≥ 35 had a higher risk of GDM (OR 3.10, 95% CI 1.95 to 4.89). Smoking increased the risk of having SGA and FGR neonates (OR 1.83, 95% CI 1.36 to 2.46, and OR 1.91, 95% CI 1.29 to 2.78). Conclusions : Advanced maternal age, low or high BMI, and smoking status are significant risk factors for pregnancy complications. Both clinicians and society should concentrate their efforts on addressing these factors to enhance reproductive health.

Background: COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia., Methods: Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed., Results: The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53-43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52-38.4]). Comorbidities were more frequent in the PE+ group (63.6% vs 31.5%, p  = 0.03), as well as prematurity (81.8% vs 41.6%, p  = 0.02), low birth weight (63.6% vs 24.7%, p  = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% vs 27.0%, p  = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34-4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant., Conclusions: Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia., Competing Interests: The authors declare there are no competing interests., (©2024 Sobieray et al.)

We aimed to measure the association between Trypanosoma cruzi infection in pregnancy and reduced fetal growth in the absence of T. cruzi congenital transmission. We conducted a cross-sectional study of secondary data of all singleton live births between 2011 and 2013 in five hospitals from Argentina, Honduras, and Mexico. We excluded newborns with T. cruzi infection. Noninfected pregnant people were those without any positive rapid tests. The main study outcomes were birth weight, head circumference, and length for gestational age and sex. Logistic regression models were adjusted for country, age, education level, and obstetric history. Of the 26,544 deliveries, 459 (1.7%) pregnant people were found by rapid tests to be positive for T. cruzi. Of these, 320 were positive by enzyme-linked immunosorbent assay and 231 had a positive polymerase chain reaction (PCR) test. Uninfected newborns from T. cruzi-infected pregnant people were more likely to have birth weights below the 5th and 10th percentiles and head circumferences below the 3rd and 10th percentiles. Among T. cruzi-infected pregnant people diagnosed by PCR, the odds ratios were 1.58 for birth weight below the 10th percentile (95% CI, 1.12-2.23) and 1.57 for birth weight below the 5th percentile (95% CI, 1.02-2.42). Higher T. cruzi parasitic loads in pregnancy had a stronger association with reduced fetal growth (both in birth weight and head circumference), with an odds ratio of 2.31 (95% CI, 1.36-3.91) for a birth weight below the 5th percentile. The association shows, irrespective of causality, that newborns of pregnancies with T. cruzi have an increased risk of reduced fetal growth. We recommend further studies to assess other potential confounders and the causality of these associations.

Objective: To determine if the presence of fetal growth restriction (FGR) is associated with an increased risk of genetic abnormalities in the setting of congenital heart disease (CHD)., Methods: This was a retrospective cohort study involving pregnancies that met the following criteria: (i) prenatal diagnosis of CHD, (ii) singleton live-birth, and (iii) genetic testing was performed either pre- or postnatally. Genetic results were reviewed by a clinical geneticist for updated variant classification. Fetal growth was stratified as appropriate for gestational age (AGA) or FGR., Results: Of the total of 445 fetuses that met the study criteria, 325 (73.0%) were AGA and 120 (27.0%) were FGR. Genetic abnormalities were detected in 131 (29.4%) pregnancies. There was a higher rate of genetic abnormalities (36.7% vs. 26.8%, p = 0.04), which was driven by aneuploidies (20.8% vs. 8.9%, p = 0.0006) in the FGR population. Early onset growth restriction was associated with a higher rate of genetic abnormalities (44.5% vs. 25.9%, p = 0.03). The rate of genetic abnormalities was significantly higher in the shunt category as compared to remainder of the cardiac anomalies (62.5% in shunt lesions vs. 24.7%, p < 0.00001). The rates of FGR (40.9% vs. 21.4%, p < 0.0001) and genetic abnormalities (52% vs. 20.4%, p < 0.0001) were significantly higher in the presence of extra-cardiac anomalies (ECA)., Conclusion: The presence of FGR in fetal CHD population was associated with underlying genetic abnormalities, specifically aneuploidies. Patients should be appropriately counseled regarding the higher likelihood of a genetic condition in the presence of FGR, early onset FGR, shunt lesions and ECA., (© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Introduction: Violence during pregnancy (VDP) is a prevalent global issue with dire consequences for the mother and the developing fetus. These consequences include prematurity, low birthweight, and intrauterine growth restriction (IUGR), but its pathways remain elusive. This study investigated the causal pathways between VDP and IUGR using mediation analysis. Methods: A prospective population-based birth cohort was followed from the beginning of the third gestational trimester to the second year of life. IUGR was defined by the Kramer index, and information on VDP was collected using the WHO-Violence Against Women (WHO VAW) questionnaire. Cases were considered positive only when no other life episodes were reported. Ten different mediators were analyzed as possible pathways based on previous research. Path analysis was conducted to evaluate these relationships. Results: The path analysis model included 755 dyads and presented an adequate fit. Violence during pregnancy showed a direct effect ( β = -0.195, p = 0.041) and a total effect ( β = -0.276, p = 0.003) on IUGR. Violence was associated with gestational depression or anxiety, tobacco and alcohol consumption, changes in blood pressure, and the need for emergency care, but these did not constitute mediators of its effect on IUGR. The sum of the indirect effects, however, showed a significant association with IUGR ( β = -0.081, p = 0.011). Conclusion: The acute experience of violence during pregnancy was associated with IUGR, primarily via a direct pathway. An indirect effect was also present but not mediated through the variables analyzed in this study. The robust strength of these associations underscores the negative health consequences of violence against women for the succeeding generation.

Objective: An ultrasound-based diagnosis implies that some fetuses suspected to be growth-restricted (FGR) are discovered at birth to be appropriately grown (appropriate for gestational age [AGA] birth weight, between the 10th and 90th percentile). These fetuses may thus be exposed to unnecessary medical interventions, including early labor induction. In this study, we have evaluated the long-term respiratory health of offspring misclassified as FGR., Study Design: A population-based cohort analysis was conducted, including deliveries of AGA singletons between 1991 and 2021 at a tertiary referral hospital. Incidence of morbidity due to various respiratory conditions was compared between AGA offspring with prenatal diagnosis of FGR, and those without a false diagnosis of FGR. The Kaplan-Meier approach was used to estimate cumulative morbidity incidence. The stratified Cox proportional-hazards model was used to control for confounders., Results: A total of 324,620 deliveries of AGA newborns were included in the analyses; 3249 of them (1.0%) were misclassified prenatally as FGR. The FGR subgroup delivered at an earlier gestational age (36.7 vs. 39.1 weeks, p < .001) and had more than 25% higher incidence of respiratory-related morbidity during childhood (33.2% vs. 26.5%), specifically related to asthma and obstructive sleep apnea (p < .001 for all). A higher cumulative morbidity rate due to respiratory conditions was observed in the Kaplan-Meier survival curve (log-rank p value < .001). This association between FGR and respiratory morbidity was independent of preterm delivery, maternal age, cesarean delivery, and child's birth year (adjusted hazard ratio = 1.14, 95% confidence interval: 1.07-1.21, p < .001), using a Cox proportional hazards model., Conclusion: AGA newborns misclassified as FGR, are at an increased risk for long-term respiratory morbidity during childhood and adolescence., (© 2024 Wiley Periodicals LLC.)

Objectives: This systematic review explores cardiac adaptation in monochorionic (MC) twins with twin-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) and assesses the risk of congenital heart defects (CHDs)., Methods: Adhering to PRISMA guidelines, 63 studies were reviewed (49 on cardiac adaptation, 13 on CHD, one on both). A narrative synthesis of cardiac adaptation patterns was performed. Additionally, a meta-analysis compared the livebirth prevalence of CHD in TTTS and sFGR against uncomplicated MC twins., Results: In TTTS recipients, cardiac function may be impaired for diastolic, systolic, as well as global functions, while in donors, cardiac function is generally preserved. In sFGR, large twins may show hypertrophic cardiomyopathy, and small twins may show impaired systolic function. Co-occurrence of TTTS and sFGR magnifies cardiac impact but is often underreported. Meta-analysis for CHD prevalence revealed a relative risk ratio of 3.5 (95% CI: 2.5-4.9) for TTTS and 2.2 (95%CI: 1.3-3.5) for sFGR compared with uncomplicated MC twins., Conclusions: This study highlights the well-documented cardiac adaptation in TTTS, contrasting with limited understanding in sFGR. Elevated CHD risks were observed in both conditions. Enhanced cardiovascular surveillance is warranted in complicated MC twin pregnancies. Future research should explore cardiac adaptation in sFGR and its long-term consequences., (© 2024 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Objective: This study aimed to compare adverse maternal outcomes between pregnancies complicated by fetal growth restriction (FGR) and those without FGR., Study Design: This was a secondary analysis of the data from the Consortium on Safe Labor, which was conducted from 2002 to 2008 in 12 clinical centers with 19 hospitals across 9 American College of Obstetricians and Gynecologists districts. We included singleton pregnancies without any maternal comorbidities or placenta abnormalities. We compared the outcomes of individuals with FGR with individuals without FGR. Our primary outcome was severe maternal morbidity. Our secondary outcome included various adverse maternal and neonatal outcomes. Multivariable logistic regression was performed to obtain adjusted odds ratios (aOR) and 95% confidence intervals (95% CI), adjusting for confounders. Missing values for maternal age and body mass index were imputed., Results: Of 199,611 individuals, 4,554 (2.3%) had FGR and 195,057 (97.7%) did not have FGR. Compared with the individuals without FGR, individuals with FGR had increased odds of severe maternal morbidity (0.6 vs. 1.3%; aOR: 1.97 [95% CI: 1.51-2.57]), cesarean delivery (27.7 vs. 41.2%; aOR: 2.31 [95% CI: 2.16-2.48]), pregnancy-associated hypertension (8.3 vs. 19.2%; aOR: 2.76 [95% CI: 2.55-2.99]), preeclampsia without severe features (3.2 vs. 4.7%; aOR: 1.45 [95% CI: 1.26-1.68]), preeclampsia with severe features (1.4 vs. 8.6%; aOR: 6.04 [95% CI: 5.39-6.76]), superimposed preeclampsia (18.3 vs. 30.2%; aOR: 1.99 [95% CI: 1.53-2.59]), neonatal intensive care unit admission (9.7 vs. 28.4%; aOR: 3.53 [95% CI: 3.28-3.8]), respiratory distress syndrome (2.2 vs. 7.7%; aOR: 3.57 [95% CI: 3.15-4.04]), transient tachypnea of the newborn (3.3 vs. 5.4%; aOR: 1.62 [95% CI: 1.40-1.87]), and neonatal sepsis (2.1 vs. 5.5%; aOR: 2.43 [95% CI: 2.10-2.80])., Conclusion: FGR was associated with increased odds of severe maternal outcomes in addition to adverse neonatal outcomes., Key Points: · FGR is associated with cesarean section.. · FGR is not associated with severe maternal morbidity.. · FGR is related to pregnancy-associated hypertension.. · FGR is associated with neonatal morbidity.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study aimed to compare obstetrical outcomes between women diagnosed with gestational diabetes mellitus (GDM) in the third trimester after testing negative for GDM in two-step screening in the second trimester and women diagnosed in the second trimester., Study Design: This retrospective study compared obstetrical outcomes between 375 women diagnosed with GDM in the second trimester and 125 diagnosed in the third trimester., Results: Among women diagnosed with GDM in the third versus second trimester, the incidences were higher of morbid obesity (body mass index ≥35 kg/m 2 ), macrosomia, and cesarean section (CS) due to suspected macrosomia: 23.2 versus 9.8%, p  < 0.001; 44.0 versus 10.1%, p  < 0.001; and 24.8 versus 6.3%, p  < 0.001, respectively. For those diagnosed in the third versus second trimester, the incidences were lower of hypertensive disorders of pregnancy and intrauterine growth restriction, and a lower proportion of women needed pharmacological therapy for glucose control: 2.4 versus 9.0%, p  = 0.016; 0.8 versus 8.2%, p  < 0.001; and 12.0 versus 29.7%, p  < 0.001, respectively. Multivariate analysis supported a correlation between third-trimester-diagnosed GDM and macrosomia, and between second-trimester-diagnosed GDM and hypertensive disorders of pregnancy., Conclusion: Among women diagnosed with GDM in the third compared with the second trimester, the incidence of morbid obesity was higher; accordingly, the risks were higher for large for gestational age infants and delivery by CS, and lower for hypertensive disorders. Guidelines regarding repeat oral glucose tolerance testing in the third trimester should be considered following prospective studies., Key Points: · Third-trimester GDM was 29.9% among women with normal second-trimester screening.. · Morbid obesity and macrosomia were more frequent in third- versus second-trimester GDM.. · Incidence of preeclampsia was lower in third- versus second-trimester-diagnosed GDM.., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: Placenta-mediated pregnancy complications, like growth restriction and hypertensive disorders, are leading causes of maternal, fetal and neonatal morbidity and mortality in high-income countries. The purpose was to investigate if there is a seasonal variation in placenta-mediated pregnancy complications (small for gestational age, intrauterine growth restriction, preeclampsia, preterm birth and intrauterine fetal death)., Methods: This is a Danish cohort study including all singleton deliveries at gestational week 22 up to and including week 41 conceived from December 2006 to November 2016 (N = 555,459). We used statistical process control charts to visualize data and to test for patterns of non-random variation in data over time for pregnancies with risk factors (BMI, diabetes, in vitro fertilization, maternal age > 40 years, primipara, previous caesarean and smoking) and each of the following outcome: fetal growth restriction, hypertensive disorders, preterm birth and intrauterine fetal death. The study was approved by the Danish Data Protection agency; REG-039-2019., Results: We found a seasonal pattern in hypertensive disorders during pregnancy with dips in pregnancies conceived in the fall season and highest risk by conception in the spring and summer season. We found no apparent seasonality in cases of preterm delivery, small for gestational age and intrauterine mortality. Individual risk factors (e.g. smoking and obesity) for placenta-mediated complicated over time were in consistency with the general trends., Conclusions: We found a significant seasonal variation in the risk of hypertensive disorders of pregnancy with highest risk by conception in the spring and summer season. This study found no seasonal variation in other placenta-mediated complications., (© 2023. The Author(s).)

Objectives: 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)., Methods: 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 10 th 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., Results: 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 10 th 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 39 weeks in neither the cohort (38.7 weeks) nor the pooled literature (37.6 weeks)., Conclusion: An i-FIUVV in singletons is not associated with an increased IUFD risk up to 39 weeks 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 10 th 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 39 weeks of gestation. After 39 weeks of gestation, data on fetuses with i-FIUVV and their outcomes are lacking., (© 2024 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Objective: This study aimed to characterize the relationship between maternal obesity, fetal abdominal size, and neonatal morbidity in pregnancies complicated by fetal growth restriction (FGR)., Study Design: Pregnancies complicated by FGR, which resulted in delivery of a live, singleton, nonanomalous infant at a single center between 2002 and 2013 were identified in a large, National Institutes of Health-funded database of detailed pregnancy and delivery information extracted by trained research nurses. Pregnancies complicated by diabetes were excluded. Fetal biometry measurements from third trimester ultrasounds performed at the same institution were extracted from another institutional database. Pregnancies were divided into cohorts based on fetal abdominal circumference (AC) gestational age percentile (<10th centile, 10-29th centile, 30-49th centile, and ≥50th centile) at the ultrasound closes to the date of delivery. Obesity was defined by prepregnancy body mass index >30 kg/m 2 . The primary outcome was a composite of neonatal morbidity (CM) including 5-minute Apgar < 7, arterial cord pH <7.0, sepsis, respiratory support, chest compressions, phototherapy, exchange transfusion, hypoglycemia requiring treatment, or neonatal death. Outcomes were compared between women with versus without prepregnancy obesity overall and then stratified by AC cohort., Results: A total of 379 pregnancies met criteria; CM occurred in 136 (36%). Overall, there was no difference in CM between infants born to women with versus without obesity (risk ratio (RR): 1.11, 95% confidence interval: 0.79-1.56). When stratified according to AC at ultrasound closest to delivery, there was higher prevalence of CM occurring among women with prepregnancy obesity than those without prepregnancy obesity when the fetal AC was >50th or 30 to 49th centile However, these differences did not reach statistical significance., Conclusion: Our study identified no significant difference in risk of CM among growth-restricted infants of obese versus nonobese mothers, including among infants with very small AC. More research is needed to further examine the potential relationships postulated here., Key Points: · No significant differences in neonatal outcomes of FGR pregnancies in obese versus nonobese patients.. · No significant differences in AC percentile distribution in FGR pregnancies in obese versus nonobese.. · Pregnancies complicated by obesity had a higher need for cardiac support but not chest compressions.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Gestational weight gain (GWG) is an important indicator for monitoring maternal and fetal health., Objective: To evaluate the effect of GWG outside the recommendations of the Institute of Medicine (IOM) on fetal and neonatal outcomes., Study Design: A prospective cohort study with 1642 pregnant women selected from 2017 to 2023, with gestational age ≤ 18 weeks and followed until delivery in the city of Araraquara, Southeast Brazil. The relationship between IOM-recommended GWG and fetal outcomes (abdominal subcutaneous tissue thickness, arm and thigh subcutaneous tissue area and intrauterine growth restriction) and neonatal outcomes (percentage of fat mass, fat-free mass, birth weight and length, ponderal index, weight adequateness for gestational age by the Intergrowth curve, prematurity, and Apgar score) were investigated. Generalized Estimating Equations were used., Results: GWG below the IOM recommendations was associated with increased risks of intrauterine growth restriction (IUGR) (aOR 1.61; 95% CI: 1.14-2.27), low birth weight (aOR 2.44; 95% CI: 1.85-3.21), and prematurity (aOR 2.35; 95% CI: 1.81-3.05), and lower chance of being Large for Gestational Age (LGA) (aOR 0.38; 95% CI: 0.28-0.54), with smaller arm subcutaneous tissue area (AST) (-7.99 g; 95% CI: -8.97 to -7.02), birth length (-0.76 cm; 95% CI: -1.03 to -0.49), and neonatal fat mass percentage (-0.85%; 95% CI: -1.12 to -0.58). Conversely, exceeding GWG guidelines increased the likelihood of LGA (aOR 1.53; 95% CI: 1.20-1.96), with lower 5th-minute Apgar score (aOR 0.42; 95% CI: 0.20-0.87), and increased birth weight (90.14 g; 95% CI: 53.30 to 126.99)., Conclusion: Adherence to GWG recommendations is crucial, with deviations negatively impacting fetal health. Effective weight control strategies are imperative., (© 2024. The Author(s).)

Background:  Stillbirths are a global public health challenge, predominantly affecting low- and middle-income countries. The causes of most stillbirths are preventable., Objectives:  this study reviewed perinatal clinical audit data from Kgapane Hospital over a 4-year period with a special focus on the factors associated with stillbirths., Methods:  File audits were done for all stillbirths occurring at Kgapane Hospital and its catchment area from 2018 to 2021. The data from these audits were analysed to identify factors associated with stillbirths., Results:  A total of 392 stillbirths occurred during the study period at Kgapane Hospital and its surrounding clinics, resulting in a stillborn rate of 19.06/1000 births. Of the 392 stillbirths recorded, audits were conducted on 354 of the maternal case records. The five most common causes of stillbirths identified were: hypertensive disorders in pregnancy (HDP) (29.7%), intrauterine growth restriction without HDP (11.6%), birth asphyxia (7.1%), premature labour ( 1000 g) (6.5%) and maternal infections (5.9%) including HIV with unsuppressed VL, intrauterine infection, coronavirus disease (COVID) and syphilis. Modifiable factors that can form the basis of improvement strategies should include training, timeous referral, plus improved resources and staffing., Conclusion:  Understanding the causes of stillbirths can guide improvement strategies to reduce this heart-breaking complication of pregnancy.Contribution: Family physicians working in rural hospitals are also responsible for perinatal care. Understanding the factors associated with stillbirths will guide them to develop improvement strategies to reduce these preventable deaths.

Objective: Conflicting evidence for the association between COVID-19 and adverse perinatal outcomes exists. This study examined the associations between maternal COVID-19 during pregnancy and adverse perinatal outcomes including preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA) and fetal death; as well as whether the associations differ by trimester of infection., Design and Setting: The study used a retrospective Mexican birth cohort from the Instituto Mexicano del Seguro Social (IMSS), Mexico, between January 2020 and November 2021., Participants: We used the social security administrative dataset from IMSS that had COVID-19 information and linked it with the IMSS routine hospitalisation dataset, to identify deliveries in the study period with a test for SARS-CoV-2 during pregnancy., Outcome Measures: PTB, LBW, SGA, LGA and fetal death. We used targeted maximum likelihood estimators, to quantify associations (risk ratio, RR) and CIs. We fit models for the overall COVID-19 sample, and separately for those with mild or severe disease, and by trimester of infection. Additionally, we investigated potential bias induced by missing non-tested pregnancies., Results: The overall sample comprised 17 340 singleton pregnancies, of which 30% tested positive. We found that those with mild COVID-19 had an RR of 0.89 (95% CI 0.80 to 0.99) for PTB and those with severe COVID-19 had an RR of 1.53 (95% CI 1.07 to 2.19) for LGA. COVID-19 in the first trimester was associated with fetal death, RR=2.36 (95% CI 1.04, 5.36). Results also demonstrate that missing non-tested pregnancies might induce bias in the associations., Conclusions: In the overall sample, there was no evidence of an association between COVID-19 and adverse perinatal outcomes. However, the findings suggest that severe COVID-19 may increase the risk of some perinatal outcomes, with the first trimester potentially being a high-risk period., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although aspirin therapy is being increasingly advocated with the intention of risk modification for a wide range of pregnancy complications, women with prepregnancy diabetes mellitus are commonly excluded from clinical trials., Objective: The primary aim of this study was to examine the effect of aspirin therapy on a composite measure of adverse perinatal outcome in pregnancies complicated by pregestational diabetes mellitus., Study Design: A double-blinded, placebo-controlled randomized trial was conducted at 6 university-affiliated perinatology centers. Women with type 1 diabetes mellitus or type 2 diabetes mellitus of at least 6 months' duration were randomly allocated to 150-mg daily aspirin or placebo from 11 to 14 weeks' gestation until 36 weeks. Established vascular complications of diabetes mellitus, including chronic hypertension or nephropathy, led to exclusion from the trial. The primary outcome was a composite measure of placental dysfunction (preeclampsia, fetal growth restriction, preterm birth <34 weeks' gestation, or perinatal mortality). The planned sample size was 566 participants to achieve a 35% reduction in the primary outcome, assuming 80% statistical power. Secondary end points included maternal and neonatal outcomes and determination of insulin requirements across gestation. Data were centrally managed using ClinInfo and analyzed using SAS 9.4. The 2 treatment groups were compared using t tests or chi-square tests, as required, and longitudinal data were compared using a repeated-measures analysis., Results: From February 2020 to September 2022, 191 patients were deemed eligible, 134 of whom were enrolled (67 randomized to aspirin and 67 to placebo) with a retrospective power of 64%. A total of 101 (80%) women had type 1 diabetes mellitus and 25 (20%) had type 2 diabetes mellitus. Reaching the target sample size was limited by the impact of the COVID-19 pandemic. Baseline characteristics were similar between the aspirin and placebo groups. Treatment compliance was very high and similar between groups (97% for aspirin, 94% for placebo). The risk of the composite measure of placental dysfunction did not differ between groups (25% aspirin vs 21% placebo; P=.796). Women in the aspirin group had significantly lower insulin requirements throughout pregnancy compared with the placebo group. Insulin requirements in the aspirin group increased on average from 0.7 units/kg at baseline to 1.1 units/kg by 36 weeks' gestation (an average 83% within-patient increase), and increased from 0.7 units/kg to 1.3 units/kg (a 181% within-patient increase) in the placebo group, over the same gestational period (P=.002). Serial hemoglobin A1c levels were lower in the aspirin group than in the placebo group, although this trend did not reach statistical significance., Conclusion: In this multicenter, double-blinded, placebo-controlled randomized trial, aspirin did not reduce the risk of adverse perinatal outcome in pregnancies complicated by prepregnancy diabetes mellitus. Compared with the placebo group, aspirin-treated patients required significantly less insulin throughout pregnancy, indicating a beneficial effect of aspirin on glycemic control. Aspirin may exert a plausible placenta-mediated effect on pregestational diabetes mellitus that is not limited to its antithrombotic properties., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This is a follow-up study to the pentaerythrityl tetranitrate randomized controlled multicenter trial that reports neonatal outcome data of newborns admitted to neonatal intensive care units and outcome data of the offspring at 12 months of age., Objective: We present data on adverse events reported during the study to document the safety of pentaerythrityl tetranitrate treatment during pregnancy. To further evaluate the effects of pentaerythrityl tetranitrate on neonatal and long-term outcomes, we present follow up data from of 240 children at 12 months of age, including information on height, weight, head circumference, developmental milestones, and the presence of chronic disease and of 144 newborns admitted to the neonatal intensive care unit during the trial., Study Design: The pentaerythrityl tetranitrate trial was a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of the nitric oxide-donor pentaerythrityl tetranitrate in the prevention of fetal growth restriction and perinatal death in pregnancies complicated by abnormal placental perfusion., Results: Results at 12 months demonstrated that significantly more children were age appropriately developed without impairments in the pentaerythrityl tetranitrate group (P=.018). In addition, the presence of chronic disease was lower in the pentaerythrityl tetranitrate group (P=.041). Outcome data of the 144 newborns admitted to the neonatal intensive care unit did not reveal differences between the treatment and placebo groups. There were no differences in the number or nature of reported adverse events between the study groups., Conclusion: The analysis shows that study children born in the pentaerythrityl tetranitrate cohort have a clear advantage compared with the placebo group at the age of 12 months, as evidenced by the increased incidence of normal development without the presence of chronic disease. Although safety has been proven, further follow-up studies are necessary to justify pentaerythrityl tetranitrate treatment during pregnancies complicated by impaired uterine perfusion., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Incorporation of umbilical artery Doppler in the surveillance of fetal growth restriction has been shown to reduce the risk of perinatal deaths. Systole/Diastole ratio, Pulsatility Index and Resistance Index are obtained upon Doppler interrogation of the umbilical artery however it is unknown which index predicts more advanced stages of placental deterioration., Objective: This study aimed to examine risk factors for the development of absent or reversed end-diastolic velocity and the time intervals of deterioration from normal umbilical artery end-diastolic velocity (indicated by systole/diastole ratio, pulsatility index, or resistance index) to decreased and absent or reversed end-diastolic velocity in fetuses with early-onset severe fetal growth restriction., Study Design: This was a retrospective cohort study performed from 2005 to 2020. All singleton pregnancies with severe (estimated fetal weight or abdominal circumference below the third percentile) and early-onset (diagnosed between 20 0/7 and 31 6/7 weeks of gestation) fetal growth restriction were included. Patients with fetal genetic or structural anomalies, suspected congenital infections, absent or reversed end-diastolic velocity at diagnosis, poor pregnancy dating, and absence of follow-up ultrasounds were excluded. Estimated fetal weight, abdominal circumference, and Doppler indices were reviewed longitudinally from diagnosis to delivery. To examine risk factors for absent or reversed end-diastolic velocity, we performed backward stepwise logistic regression and calculated odds ratios with 95% confidence intervals. Kaplan-Meier curves were compared using log-rank tests., Results: A total of 985 patients met the inclusion criteria, and 79 (8%) progressed to absent or reversed end-diastolic velocity. Factors associated with development of absent or reversed end-diastolic velocity included gestational age at diagnosis (adjusted odds ratio, 4.88 [95% confidence interval, 2.55-9.37] at 20 0/7 to 23 6/7 weeks; adjusted odds ratio, 1.56 [95% confidence interval, 0.86-2.82] at 24 0/7 to 27 6/7 weeks compared with 28 0/7 to 31 6/7 weeks) and presence of chronic hypertension (adjusted odds ratio, 2.37 [95% confidence interval, 1.33-4.23]). Rates of progression from diagnosis of fetal growth restriction with normal umbilical artery Doppler to absent or reversed end-diastolic velocity were significant after 4 weeks from diagnosis (5.84% [95% confidence interval, 4.50-7.57]). Regarding the Doppler indices, the progression from normal values to abnormal indices was similar at 1 and 2 weeks. However, the rate of progression from normal to abnormal systole/diastole ratio compared with the rates of progression from normal to abnormal pulsatility index or resistance index was higher at 4 and 6 weeks. Deterioration from abnormal indices to absent or reversed end-diastolic velocity was shorter with abnormal resistance index and pulsatility index when compared with the systole/diastole ratio at 2, 4, and 6 weeks after diagnosis and at 6 weeks, respectively., Conclusion: Earlier gestational age at diagnosis and chronic hypertension are considered as risk factors for Doppler deterioration and development of absent or reversed end-diastolic velocity in the umbilical artery. With normal Doppler indices, significant deterioration and progression to absent or reversed end-diastolic velocity is unlikely until 4 weeks after diagnosis. Abnormal systole/diastole ratio seems to appear first. However, abnormal pulsatility index or resistance index was associated with absent or reversed end-diastolic velocity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To compare morbidity, as measured by length of stay in the neonatal intensive care unit (NICU), in twin and singleton gestations classified as small-for-gestational age (SGA) according to estimated fetal weight < 10 th percentile on twin or singleton growth charts., Methods: NICU length of stay was compared in 1150 twins and 29 035 singletons that underwent ultrasound assessment between 35 + 0 and 36 + 6 weeks' gestation. Estimated fetal weight was obtained from measurements of head circumference, abdominal circumference and femur length using the Hadlock formula. Gestational age was derived from the first-trimester crown-rump length measurement, using the larger of the two twins. Singletons and twins were compared in terms of NICU admission rate and length of stay according to classification as SGA by the Fetal Medicine Foundation singleton and twin reference distributions., Results: The overall proportions of twins and singletons admitted to NICU were similar (7.3% vs 7.4%), but twins tended to have longer lengths of stay in NICU (≥ 7 days: 2.4% vs 0.8%; relative risk (RR), 3.0 (95% CI, 1.6-4.4)). Using the singleton chart, a higher proportion of twins were classified as SGA compared with singletons (37.6% vs 7.0%). However, the proportion of SGA neonates entering NICU was similar (10.2% for twins and 10.1% for singletons) and the proportion of SGA neonates spending ≥ 7 days in NICU was substantially higher for twins compared with singletons (3.7% vs 1.4%; RR, 2.6 (95% CI, 1.4-4.7))., Conclusions: When singleton charts are used to define SGA in twins and in singletons, there is a greater degree of growth-related neonatal morbidity amongst SGA twins compared with SGA singletons. Consequently, singleton charts do not inappropriately overdiagnose fetal growth restriction in twins and they should be used for monitoring fetal growth in both twins and singletons. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Fetal growth restriction (FGR) is one of the leading causes of perinatal morbidity and mortality. Many studies have reported an association between FGR and fetal Doppler indices focusing on umbilical artery (UA), middle cerebral artery (MCA), and ductus venosus (DV). The uteroplacental-fetal circulation which affects the fetal growth consists of not only UA, MCA, and DV, but also umbilical vein (UV), placenta and uterus itself. Nevertheless, there is a paucity of large-scale cohort studies that have assessed the association between UV, uterine wall, and placental thickness with perinatal outcomes in FGR, in conjunction with all components of the uteroplacental-fetal circulation. Therefore, this multicenter study will evaluate the association among UV absolute flow, placental thickness, and uterine wall thickness and adverse perinatal outcome in FGR fetuses. This multicenter retrospective cohort study will include singleton pregnant women who undergo at least one routine fetal ultrasound scan during routine antepartum care. Pregnant women with fetuses having structural or chromosomal abnormalities will be excluded. The U-AID indices (UtA, UA, MCA, and UV flow, placental and uterine wall thickness, and estimated fetal body weight) will be measured during each trimester of pregnancy. The study population will be divided into two groups: (1) FGR group (pregnant women with FGR fetuses) and (2) control group (those with normal growth fetus). We will assess the association between U-AID indices and adverse perinatal outcomes in the FGR group and the difference in U-AID indices between the two groups., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Choi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Most of the published literature on selective fetal growth restriction (sFGR) has focused on monochorionic twin pregnancies. The aim of this systematic review was to report on the outcome of dichorionic diamniotic (DCDA) twin pregnancies complicated by sFGR., Methods: MEDLINE, EMBASE and The Cochrane Library databases were searched. The inclusion criteria were DCDA twin pregnancies complicated by sFGR. The outcomes explored were intrauterine death (IUD), neonatal death and perinatal death (PND), survival of at least one and both twins, preterm birth (PTB) (either spontaneous or iatrogenic) prior to 37, 34, 32 and 28 weeks' gestation, pre-eclampsia (PE) or gestational hypertension, neurological, respiratory and infectious morbidity, Apgar score < 7 at 5 min, necrotizing enterocolitis, retinopathy of prematurity and admission to the neonatal intensive care unit (NICU). A composite outcome of neonatal morbidity, defined as the occurrence of respiratory, neurological or infectious morbidity, was also evaluated. Random-effects meta-analysis was used to analyze the data, and results are reported as pooled proportion or odds ratio (OR) with 95% CI., Results: Thirteen studies reporting on 1339 pregnancies with sFGR and 6316 pregnancies without sFGR were included. IUD occurred in 2.6% (95% CI, 1.1-4.7%) of fetuses from DCDA pregnancies with sFGR and 0.6% (95% CI, 0.3-9.7%) of those from DCDA pregnancies without sFGR, while the respective values for PND were 5.2% (95% CI, 3.5-7.3%) and 1.7% (95% CI, 0.1-5.7%). Spontaneous or iatrogenic PTB before 37 weeks complicated 84.1% (95% CI, 55.6-99.2%) of pregnancies with sFGR and 69.1% (95% CI, 45.4-88.4%) of those without sFGR. The respective values for PTB before 34, 32 and 28 weeks were 18.4% (95% CI, 4.4-38.9%), 13.0% (95% CI, 9.5-17.1%) and 1.5% (95% CI, 0.6-2.3%) in pregnancies with sFGR and 10.2% (95% CI, 3.1-20.7%), 7.8% (95% CI, 6.8-9.0%) and 1.8% (95% CI, 1.3-2.4%) in those without sFGR. PE or gestational hypertension complicated 19.9% (95% CI, 12.4-28.6%) of pregnancies with sFGR and 12.8% (95% CI, 10.4-15.4%) of those without sFGR. Composite morbidity occurred in 28.2% (95% CI, 7.8-55.1%) of fetuses from pregnancies with sFGR and 13.9% (95% CI, 6.5-23.5%) of those from pregnancies without sFGR. When stratified according to the sFGR status within a twin pair, composite morbidity occurred in 39.0% (95% CI, 11.1-71.5%) of growth-restricted fetuses and 29.9% (95% CI, 3.5-65.0%) of appropriately grown fetuses (OR, 1.9 (95% CI, 1.7-3.1)), while the respective values for PND were 3.0% (95% CI, 1.8-4.5%) and 1.6% (95% CI, 0.9-2.6%) (OR, 2.1 (95% CI, 1.0-4.1)). On risk analysis, DCDA pregnancies complicated by sFGR had a significantly higher risk of IUD (OR, 5.2 (95% CI, 3.2-8.6)) and composite morbidity or admission to the NICU (OR, 3.2 (95% CI, 1.9-5.6)) compared to those without sFGR, while there was no difference in the risk of PTB before 34 weeks (P = 0.220) or PE/gestational hypertension (P = 0.210)., Conclusions: DCDA twin pregnancies complicated by sFGR are at high risk of perinatal morbidity and mortality. The findings of this systematic review are relevant for counseling and management of complicated DCDA twin pregnancies, in which twin-specific, rather than singleton, outcome data should be used. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To derive reference distributions of estimated fetal weight (EFW) in twins relative to singletons., Methods: Gestational-age- and chorionicity-specific reference distributions for singleton percentiles and EFW were fitted to data on 4391 twin pregnancies with two liveborn fetuses from four European centers, including 3323 dichorionic (DC) and 1068 monochorionic diamniotic (MCDA) twin pregnancies. Gestational age was derived using the larger of the two crown-rump length measurements obtained during the first trimester of pregnancy. EFW was obtained from ultrasound measurements of head circumference, abdominal circumference and femur length using the Hadlock formula. Singleton percentiles were obtained using the Fetal Medicine Foundation population weight charts for singleton pregnancies. Hierarchical models were fitted to singleton Z-scores with autoregressive terms for serial correlations within the same fetus and between twins from the same pregnancy. Separate models were fitted for DC and MCDA twins., Results: Fetuses from twin pregnancies tended to be smaller than singletons at the earliest gestational ages (16 weeks for MCDA and 20 weeks for DC twins). This was followed by a period of catch-up growth until around 24 weeks. After that, both DC and MCDA twins showed reduced growth. In DC twins, the EFW corresponding to the 50 th percentile was at the 50 th percentile of singleton pregnancies at 23 weeks, the 43 rd percentile at 28 weeks, the 32 nd percentile at 32 weeks and the 22 nd percentile at 36 weeks. In MCDA twins, the EFW corresponding to the 50 th percentile was at the 36 th percentile of singleton pregnancies at 24 weeks, the 29 th percentile at 28 weeks, the 19 th percentile at 32 weeks and the 12 th percentile at 36 weeks., Conclusions: In DC and, to a greater extent, MCDA twin pregnancies, fetal growth is reduced compared with that observed in singleton pregnancies. Furthermore, after 24 weeks, the divergence in growth trajectories between twin and singleton pregnancies becomes more pronounced as gestational age increases. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: This retrospective study aimed to evaluate clinical outcomes of monochorionic diamniotic (MCDA) twins with selective intrauterine growth restriction (sIUGR)., Materials and Methods: MCDA twins, either sIUGR and non-sIUGR, underwent expectant management from 2016 to 2019 in our hospital were included. sIUGR fetuses were classified into three types according to umbilical artery Doppler assessment. Non-sIUGR were considered as the control group. Outcomes were pregnancy outcomes and maternal complications., Results: Forty-three sIUGR (type I: 23; type II: 14, and type III: 6) and 282 non-sIUGR fetuses were included. The sIUGR group had a significantly earlier birth, lower birth weight of the twins, larger inter-twin weight difference, lower Apgar score of the twins, and higher intrauterine fetal death (IUFD) than the non-sIUGR group (all p < 0.001). The same trend was found in the sIUGR type II group compared to type I and III groups. A significantly lower gestational diabetes rate (p = 0.01) and placenta weight (p < 0.001), and higher proportions of abnormal placental umbilical cord insertion (p < 0.001), and ultrasound Doppler monitoring indicators (p = 0.006) were found in the sIUGR group than the non-sIUGR group., Conclusions: The MCDA twins with sIUGR showed poorer outcomes than the non-sIUGR group. Doppler interrogation was a useful clinical marker for fetal outcome., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate whether different grades of subchorionic hematoma (SCH) are involved in the timing of birth and the development of adverse pregnancy outcomes in singleton pregnant women., Methods: A total of 171 women with singleton pregnancies, 72 of whom had SCH before 20 weeks and between 12 and 20 weeks of gestational age (GA), were included in this study conducted between January 2018 and December 2021. These patients were divided into three subgroups based on the size of the subchorionic hematoma on ultrasound imaging. Baseline demographic data, obstetric outcomes, and risk factors for subchorionic hematoma were compared for the two groups., Results: A higher number of pregnancies from the SCH group resulted in miscarriage (30.56% versus 2.02%, p < 0.0001), early preterm birth (8.33% versus 1.01%, p = 0.0035), premature rupture of membranes (15.28% versus 4.04%, p = 0.0103), fetal growth restriction (9.72% versus 0%, p = 0.0015), and delivery 13.18 days earlier (274.34 ± 11.25 versus 261.16 ± 29.80, p = 0.0013) than those from the control group. Compared with SCH detected before 12 weeks of GA, the rate of miscarriage increased, and the live birth rate decreased significantly in patients with SCH caught between 12 and 20 weeks of GA. With the increase in hematoma size, the likelihood of miscarriage increased significantly. Further analysis found that delivery occurred earlier in the medium/large SCH group (271.49 ± 23.61 versus 253.28 ± 40.68/261.77 ± 22.11, p = 0.0004/0.0073) but not in the small SCH group (274.34 ± 11.25 versus 267.85 ± 21.01, p = 0.2681) compared to the control group. Our results also showed that the anterior placenta (52.04% versus 33.33%, p = 0.0005, OR = 0.3137, 95% CI [0.1585, 0.601]) is a protective factor for subchorionic hematoma., Conclusion: Our study shows that women with SCH are at a higher risk of adverse pregnancy outcomes and are independently associated with miscarriage, early preterm birth, premature rupture of membranes, and fetal growth restriction. A subchorionic hematoma, especially detected between 12 and 20 weeks of GA, is very likely to cause miscarriage or preterm birth in women with a medium or large subchorionic hematoma., (© 2023. The Author(s).)

Objective: To investigate adverse pregnancy outcomes in patients complicated with GDMA1 who delivered at term before or after 40 weeks of gestation., Study Design: A population-based cohort study including all women with GDMA1 during pregnancy was conducted. Deliveries occurred between 1988 and 2016 at a large university tertiary medical center., Results: During the study period, 11,765 women with GDMA1 met the inclusion criteria. Of these, 1303 (11 %) delivered after 40 weeks (post-date, study group), while 10,462 (89 %) delivered at term before 40 weeks of gestation (before date, control group). Those who delivered after 40 weeks of gestation (the study group) had a significantly lower percent of cesarean deliveries (CD), higher rates of spontaneous vaginal deliveries and induction of labor in comparison to those who delivered before 40 weeks of gestation (the control group). The control group had significantly higher rates of preeclampsia and intrauterine growth restriction than the study group. Using a multivariable logistic regression model, delivery after 40 weeks was noted as an independent protective factor for CD (adjusted OR = 0.78, 95 %CI 0.66-0.92, p value = 0.001). Delivery after 41 + 0 weeks had a significantly higher rate of CD and LGA., Conclusion: No significant increase in adverse pregnancy outcomes at term post-date pregnancies complicated with GDMA1 was demonstrated. Furthermore, there was no increase in the rate of CD with the increase in gestational age until 41 weeks of gestation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: SARS-CoV-2 is a viral disease with potentially devastating effects. Observational studies of pregnant women infected with SARS-CoV-2 report an increased risk for FGR. This study utilizes data from a prospective SARS-CoV-2 registry in pregnancy, investigating the progression of fetuses to fetal growth restriction (FGR) at birth following maternal SARS-CoV-2 and evaluating the hypothesis of whether the percentage of SGA at birth is increased after maternal SARS-CoV-2 taking into account the time interval between infection and birth., Materials & Methods: CRONOS is a prospective German registry enrolling pregnant women with confirmed SARS-CoV-2 infection during their pregnancy. SARS-CoV-2 symptoms, pregnancy- and delivery-specific information were recorded. The data evaluated in this study range from March 2020 until August 2021. Women with SARS-CoV-2 were divided into three groups according to the time of infection/symptoms to delivery: Group I<2 weeks, Group II 2-4 weeks, and Group III>4 weeks. FGR was defined as estimated and/or birth weight<10% ile, appropriate for gestational age (AGA) was within 10 and 90%ile, and large for gestational age (LGA) was defined as fetal or neonatal weight>90%ile., Results: Data for a total of 2,650 SARS-CoV-2-positive pregnant women were available. The analysis was restricted to symptomatic cases that delivered after 24+0 weeks of gestation. Excluding those cases with missing values for estimated fetal weight at time of infection and/or birth weight centile, 900 datasets remained for analyses. Group I consisted of 551 women, Group II of 112 women, and Group III of 237 women. The percentage of changes from AGA to FGR did not differ between groups. However, there was a significantly higher rate of large for gestational age (LGA) newborns at the time of birth compared to the time of SARS-CoV-2 infection in Group III (p=0.0024), respectively., Conclusion: FGR rates did not differ between symptomatic COVID infections occurring within 2 weeks and>4 weeks before birth. On the contrary, it presented a significant increase in LGA pregnancies in Group III. However, in this study population, an increase in the percentage of LGA may be attributed to pandemic measures and a reduction in daily activity., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: Poor intrauterine growth has negative impacts for child growth and development and disproportionately affects children living in low-resource settings. In the present study, we investigated relationships between placental pathologies and indicators of poor intrauterine growth., Methods: We enrolled a longitudinal cohort of 279 mother-infant pairs from Leyte, the Philippines. Placental measures included characteristics, pathological findings, and immunohistochemistry. At birth, intrauterine growth was assessed using anthropometric measures, weight-for-gestational age, and the clinical assessment of nutritional status score (CANSCORE) for determining fetal malnutrition. Multivariate linear regression and log-binomial regression models were applied, controlling for potential confounding factors., Results: Maternal vascular malperfusion (MVM) was related to reduced birthweight (P < 0.0001), birth length (P = 0.002), head circumference (P = 0.001), and weight-to-length ratio (P = 0.016). MVM increased the risk for preterm delivery (P = 0.0005) and small for gestational age (SGA) (P = 0.016). Acute chorioamnionitis (P = 0.013) and MVM (P = 0.021) both led to an increased risk for fetal malnutrition defined by CANSORE<25. Villous tissue activated caspase-3 was associated with lower birth length (P = 0.0006), higher weight-to-length ratio (P = 0.004), reduced risks for SGA (P = 0.011) and low weight-to-length ratio for gestational age (P = 0.004)., Conclusion: The present study applied comprehensive measures for intrauterine growth and demonstrates that low placental weight and placental pathology, chiefly MVM, contribute to poor intrauterine growth. A better understanding of the mechanistic role of specific placental pathologies on adverse newborn outcomes will provide opportunities for reducing incidence of poor intrauterine growth and associated long-term morbidities., (© 2023 International Federation of Gynecology and Obstetrics.)

Introduction: Restriction 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., Method: A 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%., Results: In 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., Conclusion: In 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., (© 2024. The Author(s).)