Reduced gyrification in fetal growth restriction with prenatal magnetic resonance images.

Placental-related fetal growth restriction, resulting from placental dysfunction, impacts 3-5% of pregnancies and is linked to elevated risk of adverse neurodevelopmental outcomes. In response, the fetus employs a mechanism known as brain-sparing, redirecting blood flow to the cerebral circuit, for adequate supply to the brain. In this study we aimed to quantitatively evaluate disparities in gyrification and brain volumes among fetal growth restriction, small for gestational age and appropriate-for gestational-age fetuses. Additionally, we compared fetal growth restriction fetuses with and without brain-sparing. The study encompassed 106 fetuses: 35 fetal growth restriction (14 with and 21 without brain-sparing), 8 small for gestational age, and 63 appropriate for gestational age. Gyrification, supratentorial, and infratentorial brain volumes were automatically computed from T2-weighted magnetic resonance images, following semi-automatic brain segmentation. Fetal growth restriction fetuses exhibited significantly reduced gyrification and brain volumes compared to appropriate for gestational age (P < 0.001). Small for gestational age fetuses displayed significantly reduced gyrification (P = 0.038) and smaller supratentorial volume (P < 0.001) compared to appropriate for gestational age. Moreover, fetal growth restriction fetuses with BS demonstrated reduced gyrification compared to those without BS (P = 0.04), with no significant differences observed in brain volumes. These findings demonstrate that brain development is affected in fetuses with fetal growth restriction, more severely than in small for gestational age, and support the concept that vasodilatation of the fetal middle cerebral artery reflects more severe hypoxemia, affecting brain development.

Risk factors for relaparotomy after a cesarean delivery: a case-control study.

BACKGROUND: Relaparotomy following a cesarean delivery (CD) is an infrequent complication, with inconsistency regarding risk factors and indications for its occurrence. We therefore aimed to determine risk factors and indications for a relaparotomy following a CD at a single large tertiary center. METHODS: A retrospective case-control single-center study (2013-2023). We identified all women who had a relaparotomy up to six weeks following a CD (study group). Maternal characteristics, obstetrical and surgical data were compared to a control group in a 1:2 ratio. Controls were women with a CD before and immediately after each case in the study group, who did not undergo a relaparotomy. Included were CDs occurring after 24 gestational weeks. CD performed at different centers and indications for repeat surgery unrelated to the primary surgery (e.g., appendicitis) were excluded. Logistic regression was used to adjust for potential confounders. RESULTS: During the study period, 131,268 women delivered at our institution. Of them, 28,280 (21.5%) had a CD, and 130 patients (0.46%) underwent a relaparotomy. Relaparotomies following a CD occurred during the first 24 h, the first week, and beyond the first week, in 59.2%, 33.1%, and 7.7% of cases, respectively. In the multivariable logistic regression analysis, relaparotomy was significantly associated with Mullerian anomalies (aOR 3.33, 95%CI 1.08-10.24, p = 0.036); uterine fibroids (aOR 3.17, 95%CI 1.11-9.05,p = 0.031); multiple pregnancy (aOR 4.1, 95%CI 1.43-11.79,p = 0.009); hypertensive disorders of pregnancy (aOR 3.46, 95%CI 1.29-9.3,p = 0.014); CD during the second stage of labor (aOR 2.54, 95%CI 1.15-5.88, p = 0.029); complications during CD (aOR 1.62, 95%CI 1.09-3.21,p = 0.045); and excessive bleeding during CD or implementation of bleeding control measures (use of tranexamic acid, a hemostatic agent, or a surgical drain) (aOR 2.23, 95%CI 1.29-4.12,p = 0.012). Indications for relaparotomy differed depending on the time elapsed from the CD, with suspected intra-abdominal bleeding (36.1%) emerging as the primary indication within the initial 24 h. CONCLUSION: We detected several pregnancy, intrapartum, and intra-operative risk factors for the need for relaparotomy following a CD. Practitioners may utilize these findings to proactively identify women at risk, thereby potentially reducing their associated morbidity.

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

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

Risk factors for maternal complications following uterine rupture: a 12-year single-center experience.

PURPOSE: To determine maternal outcomes and risk factors for composite maternal morbidity following uterine rupture during pregnancy. METHODS: A retrospective cohort study including all women diagnosed with uterine rupture during pregnancy, between 2011 and 2023, at a single-center. Patients with partial uterine rupture or dehiscence were excluded. We compared women who had composite maternal morbidity following uterine rupture to those without. Composite maternal morbidity was defined as any of the following: maternal death; hysterectomy; severe postpartum hemorrhage; disseminated intravascular coagulation; injury to adjacent organs; admission to the intensive care unit; or the need for relaparotomy. The primary outcome was risk factors associated with composite maternal morbidity following uterine rupture. The secondary outcome was the incidence of maternal and neonatal complications following uterine rupture. RESULTS: During the study period, 147,037 women delivered. Of them, 120 were diagnosed with uterine rupture. Among these, 44 (36.7%) had composite maternal morbidity. There were no cases of maternal death and two cases of neonatal death (1.7%); packed cell transfusion was the major contributor to maternal morbidity [occurring in 36 patients (30%)]. Patients with composite maternal morbidity, compared to those without, were characterized by: increased maternal age (34.7 vs. 32.8 years, p = 0.03); lower gestational age at delivery (35 + 5 vs. 38 + 1 weeks, p = 0.01); a higher rate of unscarred uteri (22.7% vs. 2.6%, p < 0.01); and rupture occurring outside the lower uterine segment (52.3% vs. 10.5%, p < 0.01). CONCLUSION: Uterine rupture entails increased risk for several adverse maternal outcomes, though possibly more favorable than previously described. Numerous risk factors for composite maternal morbidity following rupture exist and should be carefully assessed in these patients.

Perinatal outcomes following uterine rupture during a trial of labor after cesarean: A 12-year single-center experience.

OBJECTIVE: To determine perinatal outcomes following uterine rupture during a trial of labor after one previous cesarean delivery (CD) at term. METHODS: A retrospective single-center study examining perinatal outcomes in women with term singleton pregnancies with one prior CD, who underwent a trial of labor after cesarean (TOLAC) and were diagnosed with uterine rupture, between 2011 and 2022. The primary outcome was a composite maternal outcome, and the secondary outcome was a composite neonatal outcome. Additionally, we compared perinatal outcomes between patients receiving oxytocin during labor with those who did not. RESULTS: Overall, 6873 women attempted a TOLAC, and 116 were diagnosed with uterine rupture. Among them, 63 (54.3%) met the inclusion criteria, and 18 (28%) had the maternal composite outcome, with no cases of maternal death. Sixteen cases (25.4%) had the composite neonatal outcome, with one case (1.6%) of perinatal death. No differences were noted between women receiving oxytocin and those not receiving oxytocin in the rates of maternal composite (35.7% vs 26.5%, P = 0.502, respectively) or neonatal composite outcomes (21.4% vs 26.5%, P = 0.699). CONCLUSION: Uterine rupture during a TOLAC entails increased risk for myriad adverse outcomes for the mother and neonate, though possibly more favorable than previously described. Oxytocin use does not affect these risks.

Outcomes in Maternal Graves' Disease: A Population-Based Mother-Infant Dyad Cohort Study.

Background: Graves' disease has been associated with adverse pregnancy, labor and delivery, and neonatal outcomes. Thyroid function levels, assessed during newborn screening (NBS), can serve as indicators of the adaptation in the hypothalamic-pituitary-thyroid axis. We utilized data from the national thyroid NBS program to investigate the characteristics of the mother-infant dyad of term infants born to mothers with past or active Graves' disease. Methods: The dataset of the Israeli NBS for thyroid function was linked with the electronic records of a tertiary medical center to generate a unified database of mothers and their term infants born between 2011 and 2021. The MDClone big data platform extracted maternal, pregnancy, disease course, labor and delivery, and neonatal characteristics of the mother-infant dyads. Results: Out of 103,899 registered mother-infant dyads, 292 (0.3%) mothers had past or active Graves' disease. A forward multivariate linear regression demonstrated that Graves' disease did not significantly affect NBS total thyroxine (tT4) levels (p = 0.252). NBS tT4 levels in infants born to mothers with active Graves' disease were higher than those observed in the general Israeli population (p < 0.001). Mothers with Graves' disease more frequently used assisted reproductive technology (12.7% vs. 9.0%, respectively, p = 0.012; odds ratio [OR] = 1.46 [CI 1.03-2.07], p = 0.031), and had more gestational hypertension (3.9% vs. 1.1%, p < 0.001; OR = 3.53 [CI 1.92-6.47], p < 0.001), proteinuria (2.5% vs. 0.9%, p < 0.001; OR = 3.03 [CI 1.43-6.45], p = 0.004), cesarean sections (26.4% vs. 19.7%, p = 0.029; OR = 1.46 [CI 1.13-1.90], p = 0.004), prelabor rupture of membranes (15.4% vs. 4.1%, p < 0.001; OR = 4.3 [CI 3.13-5.91], p < 0.001), and placental abnormalities (5.1% vs. 2.0%, p < 0.001; OR = 2.64 [CI 1.57-4.44]; p < 0.001). Their infants had lower adjusted birthweight z-scores (-0.18 ± 0.94 vs. -0.03 ± 0.90, p = 0.007) and were more likely to be small for gestational age (12.0% vs. 8.1%, p = 0.005; OR = 1.54 [CI 1.08-2.19], p = 0.018). Conclusions: Neonatal thyroid function levels were affected by maternal Graves' disease only when the disease was active during gestation. Moreover, maternal Graves' disease was also associated with an increased risk of adverse outcomes for the mother-infant dyad.

Deep learning-based segmentation of whole-body fetal MRI and fetal weight estimation: assessing performance, repeatability, and reproducibility.

OBJECTIVES: To develop a deep-learning method for whole-body fetal segmentation based on MRI; to assess the method's repeatability, reproducibility, and accuracy; to create an MRI-based normal fetal weight growth chart; and to assess the sensitivity to detect fetuses with growth restriction (FGR). METHODS: Retrospective data of 348 fetuses with gestational age (GA) of 19-39 weeks were included: 249 normal appropriate for GA (AGA), 19 FGR, and 80 Other (having various imaging abnormalities). A fetal whole-body segmentation model with a quality estimation module was developed and evaluated in 169 cases. The method was evaluated for its repeatability (repeated scans within the same scanner, n = 22), reproducibility (different scanners, n = 6), and accuracy (compared with birth weight, n = 7). A normal MRI-based growth chart was derived. RESULTS: The method achieved a Dice = 0.973, absolute volume difference ratio (VDR) = 1.8% and VDR mean difference = 0.75% ([Formula: see text]: - 3.95%, 5.46), and high agreement with the gold standard. The method achieved a repeatability coefficient = 4.01%, ICC = 0.99, high reproducibility with a mean difference = 2.21% ([Formula: see text]: - 1.92%, 6.35%), and high accuracy with a mean difference between estimated fetal weight (EFW) and birth weight of - 0.39% ([Formula: see text]: - 8.23%, 7.45%). A normal growth chart (n = 246) was consistent with four ultrasound charts. EFW based on MRI correctly predicted birth-weight percentiles for all 18 fetuses ≤ 10thpercentile and for 14 out of 17 FGR fetuses below the 3rd percentile. Six fetuses referred to MRI as AGA were found to be < 3rd percentile. CONCLUSIONS: The proposed method for automatic MRI-based EFW demonstrated high performance and sensitivity to identify FGR fetuses. CLINICAL RELEVANCE STATEMENT: Results from this study support the use of the automatic fetal weight estimation method based on MRI for the assessment of fetal development and to detect fetuses at risk for growth restriction. KEY POINTS: • An AI-based segmentation method with a quality assessment module for fetal weight estimation based on MRI was developed, achieving high repeatability, reproducibility, and accuracy. • An MRI-based fetal weight growth chart constructed from a large cohort of normal and appropriate gestational-age fetuses is proposed. • The method showed a high sensitivity for the diagnosis of small fetuses suspected of growth restriction.

Fetal MRI-Based Body and Adiposity Quantification for Small for Gestational Age Perinatal Risk Stratification.

BACKGROUND: Small for gestational age (SGA) fetuses are at risk for perinatal adverse outcomes. Fetal body composition reflects the fetal nutrition status and hold promise as potential prognostic indicator. MRI quantification of fetal anthropometrics may enhance SGA risk stratification. HYPOTHESIS: Smaller, leaner fetuses are malnourished and will experience unfavorable outcomes. STUDY TYPE: Prospective. POPULATION: 40 SGA fetuses, 26 (61.9%) females: 10/40 (25%) had obstetric interventions due to non-reassuring fetal status (NRFS), and 17/40 (42.5%) experienced adverse neonatal events (CANO). Participants underwent MRI between gestational ages 30 + 2 and 37 + 2. FIELD STRENGTH/SEQUENCE: 3-T, True Fast Imaging with Steady State Free Precession (TruFISP) and T1 -weighted two-point Dixon (T1 W Dixon) sequences. ASSESSMENT: Total body volume (TBV), fat signal fraction (FSF), and the fat-to-body volumes ratio (FBVR) were extracted from TruFISP and T1 W Dixon images, and computed from automatic fetal body and subcutaneous fat segmentations by deep learning. Subjects were followed until hospital discharge, and obstetric interventions and neonatal adverse events were recorded. STATISTICAL TESTS: Univariate and multivariate logistic regressions for the association between TBV, FBVR, and FSF and interventions for NRFS and CANO. Fisher's exact test was used to measure the association between sonographic FGR criteria and perinatal outcomes. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated. A P-value <0.05 was considered statistically significant. RESULTS: FBVR (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.2-0.76) and FSF (OR 0.95, CI 0.91-0.99) were linked with NRFS interventions. Furthermore, TBV (OR 0.69, CI 0.56-0.86) and FSF (OR 0.96, CI 0.93-0.99) were linked to CANO. The FBVR sensitivity/specificity for obstetric interventions was 85.7%/87.5%, and the TBV sensitivity/specificity for CANO was 82.35%/86.4%. The sonographic criteria sensitivity/specificity for obstetric interventions was 100%/33.3% and insignificant for CANO (P = 0.145). DATA CONCLUSION: Reduced TBV and FBVR may be associated with higher rates of obstetric interventions for NRFS and CANO. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 5.

The Association between Advanced Maternal Age and the Manifestations of Preeclampsia with Severe Features.

This retrospective cohort study aimed to explore the association between advanced maternal age and the clinical manifestations as well as laboratory parameters of preeclampsia with severe features. This study included 452 patients who were diagnosed with preeclampsia with severe features. The clinical and laboratorial characteristics of patients with preeclampsia with severe features aged ≥40 years old (study group) were compared to those of patients aged <40 years old (control group). Multivariant analysis was applied to assess the association between advanced maternal age and the manifestations of preeclampsia with severe features, adjusting for the variables that exhibited significant differences between the study and control groups. The multivariate analysis revealed that a maternal age of ≥40 years old was an independent risk factor for acute kidney injury (OR = 2.5, CI = 1.2-4.9, p = 0.011) and for new-onset postpartum preeclampsia (OR = 2.4, CI = 1.0-5.6, p = 0.046). Conversely, a maternal age ≥ 40 years old was associated with a reduced risk of HELLP syndrome (OR = 0.4, CI = 0.2-0.9, p = 0.018) and thrombocytopenia (OR = 0.5, CI = 0.3-0.9, p = 0.016) compared to that of the patients < 40 years of age. In conclusion, this study demonstrates that maternal age is significantly associated with the clinical manifestations and laboratory parameters of preeclampsia with severe features, highlighting the importance of age-specific management.

Anti-Phospholipid Antibodies in Women with Placenta-Mediated Complications Delivered at >34 Weeks of Gestation.

OBJECTIVE: To determine the prevalence of positive antiphospholipid (aPL) antibodies among pregnant women with placenta-mediated complications delivered at >340/7 weeks of gestation. METHODS: This was a single-center retrospective observational study conducted between 2017 and 2022. Inclusion criteria included pregnant or post-partum women, >18 years, diagnosed with any of the following placenta-mediated complications and delivered at >340/7 weeks of gestation: small-for-gestational-age neonate (SGA ≤ 5th percentile according to local birthweight charts), preeclampsia with severe features, and placental abruption. The primary outcome was the prevalence of positive aPL antibodies: Lupus anticoagulant, Anticardiolipin, or Anti-ß2glycoprotein1. RESULTS: Overall, 431 women met the inclusion criteria. Of them, 378(87.7%) had an SGA neonate, 30 had preeclampsia with severe features (7%), 23 had placental abruption (5.3%), and 21 patients had multiple diagnoses(4.9%). The prevalence of aPL antibodies in the cohort was 4.9% and was comparable between the three subgroups (SGA-3.9%; PET with severe features-3.3%; and placental abruption-13% (p = 0.17)). CONCLUSION: aPL antibodies prevalence in women with placenta-mediated complications > 34 weeks of gestation was 4.9%, with comparable prevalence rates among the three subgroups. Future prospective studies are needed to delineate the need for treatment in those who tested positive for aPL antibodies and do not meet Anti-Phospholipid Antibody Syndrome clinical criteria.

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

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

Reduced adipose tissue in growth-restricted fetuses using quantitative analysis of magnetic resonance images.

OBJECTIVES: Fat-water MRI can be used to quantify tissues' lipid content. We aimed to quantify fetal third trimester normal whole-body subcutaneous lipid deposition and explore differences between appropriate for gestational age (AGA), fetal growth restriction (FGR), and small for gestational age fetuses (SGAs). METHODS: We prospectively recruited women with FGR and SGA-complicated pregnancies and retrospectively recruited the AGA cohort (sonographic estimated fetal weight [EFW] ≥ 10th centile). FGR was defined using the accepted Delphi criteria, and fetuses with an EFW < 10th centile that did not meet the Delphi criteria were defined as SGA. Fat-water and anatomical images were acquired in 3 T MRI scanners. The entire fetal subcutaneous fat was semi-automatically segmented. Three adiposity parameters were calculated: fat signal fraction (FSF) and two novel parameters, i.e., fat-to-body volume ratio (FBVR) and estimated total lipid content (ETLC = FSF*FBVR). Normal lipid deposition with gestation and differences between groups were assessed. RESULTS: Thirty-seven AGA, 18 FGR, and 9 SGA pregnancies were included. All three adiposity parameters increased between 30 and 39 weeks (p < 0.001). All three adiposity parameters were significantly lower in FGR compared with AGA (p ≤ 0.001). Only ETLC and FSF were significantly lower in SGA compared with AGA using regression analysis (p = 0.018-0.036, respectively). Compared with SGA, FGR had a significantly lower FBVR (p = 0.011) with no significant differences in FSF and ETLC (p ≥ 0.053). CONCLUSIONS: Whole-body subcutaneous lipid accretion increased throughout the third trimester. Reduced lipid deposition is predominant in FGR and may be used to differentiate FGR from SGA, assess FGR severity, and study other malnourishment pathologies. CLINICAL RELEVANCE STATEMENT: Fetuses with growth restriction have reduced lipid deposition than appropriately developing fetuses measured using MRI. Reduced fat accretion is linked with worse outcomes and may be used for growth restriction risk stratification. KEY POINTS: • Fat-water MRI can be used to assess the fetal nutritional status quantitatively. • Lipid deposition increased throughout the third trimester in AGA fetuses. • FGR and SGA have reduced lipid deposition compared with AGA fetuses, more predominant in FGR.

National and international guidelines on the management of twin pregnancies: a comparative review.

Twin gestations are associated with increased risk of pregnancy complications. However, high-quality evidence regarding the management of twin pregnancies is limited, often resulting in inconsistencies in the recommendations of various national and international professional societies. In addition, some recommendations related to the management of twin gestations are often missing from the clinical guidelines dedicated to twin pregnancies and are instead included in the practice guidelines on specific pregnancy complications (eg, preterm birth) of the same professional society. This can make it challenging for care providers to easily identify and compare recommendations for the management of twin pregnancies. This study aimed to identify, summarize, and compare the recommendations of selected professional societies from high-income countries on the management of twin pregnancies, highlighting areas of both consensus and controversy. We reviewed clinical practice guidelines of selected major professional societies that were either specific to twin pregnancies or were focused on pregnancy complications or aspects of antenatal care that may be relevant for twin pregnancies. We decided a priori to include clinical guidelines from 7 high-income countries (United States, Canada, United Kingdom, France, Germany, and Australia and New Zealand grouped together) and from 2 international societies (International Society of Ultrasound in Obstetrics and Gynecology and the International Federation of Gynecology and Obstetrics). We identified recommendations regarding the following care areas: first-trimester care, antenatal surveillance, preterm birth and other pregnancy complications (preeclampsia, fetal growth restriction, and gestational diabetes mellitus), and timing and mode of delivery. We identified 28 guidelines published by 11 professional societies from the 7 countries and 2 international societies. Thirteen of these guidelines focus on twin pregnancies, whereas the other 16 focus on specific pregnancy complications predominantly in singletons but also include some recommendations for twin pregnancies. Most of the guidelines are recent, with 15 of the 29 guidelines published over the past 3 years. We identified considerable disagreement among guidelines, primarily in 4 key areas: screening and prevention of preterm birth, using aspirin to prevent preeclampsia, defining fetal growth restriction, and the timing of delivery. In addition, there is limited guidance on several important areas, including the implications of the "vanishing twin" phenomenon, technical aspects and risks of invasive procedures, nutrition and weight gain, physical and sexual activity, the optimal growth chart to be used in twin pregnancies, the diagnosis and management of gestational diabetes mellitus, and intrapartum care.This consolidation of key recommendations across several clinical practice guidelines can assist healthcare providers in accessing and comparing recommendations on the management of twin pregnancies and identifies high-priority areas for future research based on either continued disagreement among societies or limited current evidence to guide care.

Pregnancy: The Impact of Maternal Nutrition on Intrauterine Fetal Growth.

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Maternal age and pregnancy outcomes in twin compared with singleton gestations.

OBJECTIVE: To estimate the association of advanced maternal age with pregnancy complications in twin pregnancies and compare it with that observed in singleton pregnancies. METHODS: A population-based retrospective cohort study of all patients with a singleton or twin hospital birth in Ontario, Canada, between 2012 and 2019. The primary outcome was preterm birth (PTB) less than 34 weeks. Pregnancy outcomes were stratified by maternal age groups in twin pregnancies and, separately, in singleton pregnancies. RESULTS: A total of 935 378 patients met the study criteria: 920503 (98.4%) had a singleton pregnancy and 14 875 (1.6%) had twins. In singletons, the rate of PTB less than 34 weeks increased progressively with increasing maternal age and was highest for patients aged 45 years or more (3.4%; adjusted risk ratio [aRR] 1.56, 95% confidence interval [CI] 1.05-2.33). By contrast, in twins, although the rate of PTB less than 34 was highest patients under 20 years of age (25.3%) and was lowest among patients aged 35-39 years (11.7%), the associations between maternal age group and the risk of PTB were not statistically significant in the adjusted analysis. CONCLUSION: Although the absolute rates of pregnancy complications are higher in twin pregnancies, there are considerable differences in the relationship between maternal age and the risk of certain complications between twin and singleton pregnancies.

Severe Intrahepatic Cholestasis of Pregnancy-Potential Mechanism by Which Fetuses Are Protected from the Hazardous Effect of Bile Acids.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated total bile acids (TBA). Although elevated maternal TBA is a major risk factors for fetal morbidity and mortality, it is unclear why some fetuses are more prone to the hazardous effect of bile acids (BA) over the others. It is unclear whether fetuses are protected by placental BA uptake, or it is the fetal BA metabolism that reduces fetal BA as compared to maternal levels. Therefore, we aimed to compared TBA levels in the umbilical vein and artery to maternal TBA in women with ICP. The study included 18 women who had TBA > 40 µmol/L and their 23 fetuses. We found that the TBA level in umbilical vein was significantly lower compared to maternal TBA level. The TBA levels in umbilical vein and umbilical artery were similar. No fetus had a serious neonatal complication. Importantly, since TBA level remains low even though maternal TBA level is high the fetuses are protected from the hazardous effects of maternal BA. Our findings suggest that there is no effective metabolism of BA in the fetus and the main decrease in TBA in the fetus is related to placental BA uptake.

Twin Pregnancies-More to Be Done.

Over the past few decades, we have been experiencing an increase in the incidence of multiple gestations, mostly due to the widespread use of assisted reproduction technologies [...].

Screening Accuracy of the 50 g-Glucose Challenge Test in Twin Compared With Singleton Pregnancies.

CONTEXT: The optimal 50 g-glucose challenge test (GCT) cutoff for the diagnosis of gestational diabetes mellitus (GDM) in twin pregnancies is unknown. OBJECTIVE: This work aimed to explore the screening accuracy of the 50 g-GCT and its correlation with the risk of large for gestational age (LGA) newborn in twin compared to singleton pregnancies. A population-based retrospective cohort study (2007-2017) was conducted in Ontario, Canada. Participants included patients with a singleton (n = 546 892 [98.4%]) or twin (n = 8832 [1.6%]) birth who underwent screening for GDM using the 50 g-GCT. METHODS: We compared the screening accuracy, risk of GDM, and risk of LGA between twin and singleton pregnancies using various 50 g-GCT cutoffs. RESULTS: For any given 50 g-GCT result, the probability of GDM was higher (P = .0.007), whereas the probability of LGA was considerably lower in the twin compared with the singleton group, even when a twin-specific growth chart was used to diagnose LGA in the twin group (P < .001). The estimated false-positive rate (FPR) for GDM was higher in twin compared with singleton pregnancies irrespective of the 50 g-GCT cutoff used. The cutoff of 8.2 mmol/L (148 mg/dL) in twin pregnancies was associated with an estimated FPR (10.7%-11.1%) that was similar to the FPR associated with the cutoff of 7.8 mmol/L (140 mg/dL) in singleton pregnancies (10.8%). CONCLUSION: The screening performance of the 50 g-GCT for GDM and its correlation with LGA differ between twin and singleton pregnancies.

The prognostic value of the oral glucose tolerance test for future type-2 diabetes in nulliparous pregnant women testing negative for gestational diabetes.

AIM: To determine the prognostic value of the antepartum 75g-oral glucose tolerance test (OGTT) for future type 2 diabetes mellitus (T2DM) in nulliparous pregnant women who tested negative for GDM. METHODS: A population-based retrospective cohort study of nulliparous pregnant women who underwent testing for GDM using a 75g-OGTT in Ontario, Canada (2007-2017). The overwhelming majority of women in Ontario undergo screening using the preferred 2-step approach where the 75g-OGTT is performed following an abnormal non-fasting 1 h 50g-glucose challenge test. The relationship between the 75g-OGTT results in women who tested negative for GDM (defined as normal glucose at fasting, 1 and 2 h post 75g-glucose load) and future T2DM (as recorded in the Ontario Diabetes Database by the end date of follow up period) was explored. FINDINGS: Of the 162,622 women who underwent 75g-OGTT during the study period, there were 41,507 (75.0%) who met the study criteria. In women without GDM, the adjusted hazard ratios (aHR) for T2DM were-At fasting 2.82 (95%-CI 2.18-3.64), at 1 h 1.26 (1.15-1.37), at 2 h 1.14 (1.04-1.25) for a 1 mmol/L increase in glucose. A model that combined all 3 OGTT values and clinical characteristics could detect 43% (42.6%-43.4%) of those who developed T2DM at 5-years post the index pregnancy for a false-positive rate of 20%. INTERPRETATION: The results of the antepartum OGTT can be used to refine the future risk of T2DM even in nulliparous pregnant women who tested negative for GDM.