Evaluating the sensitivity to threat and affiliative reward (STAR) model in relation to the development of conduct problems and callous-unemotional traits across early adolescence.

BACKGROUND: The Sensitivity to Threat and Affiliative Reward (STAR) model proposes low threat sensitivity and low affiliation as risk factors for callous-unemotional (CU) traits. Preliminary evidence for the STAR model comes from work in early childhood. However, studies are needed that explore the STAR dimensions in late childhood and adolescence when severe conduct problems (CP) emerge. Moreover, it is unclear how variability across the full spectrum of threat sensitivity and affiliation gives rise to different forms of psychopathology beyond CU traits. METHODS: The current study addressed these gaps using parent- and child-reported data from three waves and a sub-study of the Adolescent Brain Cognitive Development Study® of 11,878 youth (48% female; ages 9-12). RESULTS: Consistent with the STAR model, low threat sensitivity and low affiliation were independently related to CU traits across informants and time. Moreover, there was significant interaction between the STAR dimensions, such that children with lower sensitivity to threat and lower affiliation had higher parent-reported CU traits. Unlike CU traits, children with higher threat sensitivity had higher parent-reported CP and anxiety. Finally, children with lower affiliation had higher parent-reported CP, anxiety, and depression. Results largely replicated across informants and time, and sensitivity analysis revealed similar findings in children with and without DSM-5 defined CP. CONCLUSIONS: Results support the STAR model hypotheses as they pertain to CU traits and delineate threat sensitivity and affiliation as independent transdiagnostic risk factors for different types of psychopathology. Future research is needed to develop fuller and more reliable and valid measures of affiliation and threat sensitivity across multiple assessment modalities.

Pregnancy outcomes in correlation with placental histopathology in pregnancies complicated by fetal growth restriction with vs. without reduced fetal movements.

PURPOSE: Fetal movements are crucial indicators of fetal well-being, with reduced fetal movements (RFM) suggesting potential fetal compromise. Fetal growth restriction (FGR), often linked to placental insufficiency, is a major cause of perinatal morbidity and mortality. This study aimed to investigate the neonatal, labor, and placental outcomes of FGR pregnancies with and without RFM at term. METHODS: In this retrospective study, data from all term, singleton deliveries with FGR and concomitant RFM were obtained and compared to an equal control group of FGR without RFM. Maternal characteristics, pregnancy and neonatal outcomes, and placental histology were compared. The primary outcome was a composite of adverse neonatal outcomes. A multivariable regression analysis was performed to identify independent associations with adverse neonatal outcomes. RESULTS: During the study period, 250 FGR neonates with concomitant RFM and an equal control group were identified. The groups did not differ in maternal demographics aside from significantly higher rates of maternal smoking in the RFM group (p < 0.001). Polyhydramnios and oligohydramnios (p = 0.032 and p = 0.007, respectively) and meconium-stained amniotic fluid (p < 0.001) were more prevalent in the FGR+RFM group. Additionally, the RFM group showed higher rates of adverse neonatal outcomes despite having larger neonates (p = 0.047 and p < 0.001, respectively). No significant differences were observed in placental findings. Logistic regression identified RFM as an independent predictor of adverse neonatal outcomes (aOR 2.45, 95% CI 1.27-4.73, p = 0.008). CONCLUSION: Reduced fetal movements are significant and independent predictors of worse neonatal outcomes in FGR pregnancies, suggesting an additional acute insult on top of underlying placental insufficiency.

Does the combination of four OGTT values enhance the prediction of adverse pregnancy outcomes? Insights from a retrospective cohort study.

AIM: To explore the correlation between a singular value of additive OGTT scores and adverse maternal and neonatal outcomes. We postulated that a higher additive OGTT score would predict poorer maternal and neonatal outcomes. METHODS: In this retrospective cohort study, data were collected from all women with a documented complete OGTT result and subsequent diagnosis of GDM. The additive OGTT score was calculated by adding each individual hourly glucose measurement. Maternal demographics, pregnancy and labor characteristics, and neonatal outcomes were compared between the lower-sum and higher-sum OGTT groups. A multivariate regression analysis was performed to identify confounders associated with adverse outcomes. RESULTS: In this study, a total of 1497 patients were assessed. The group with higher-sum OGTT scores was characterized by increased rates of GDMA2 (p = 0.008), higher insulin doses (p = 0.009), and higher rates of composite maternal and neonatal adverse outcomes (p = 0.021 and p = 0.030, respectively) compared to the lower-sum OGTT group. CONCLUSION: The additive OGTT score may aid in predicting the need for insulin treatment, labor course, and neonatal outcomes in GDM patients.

Predictors of maternal and neonatal outcomes in labors complicated by shoulder dystocia: a comparative analysis.

INTRODUCTION: Studies investigating the risk factors associated with unfavorable maternal/neonatal outcomes in cases of shoulder dystocia are scarce. This study aims to uncover the predictive factors that give rise to unfavorable outcomes within the context of shoulder dystocia. MATERIALS AND METHODS: Medical records of pregnancies complicated by shoulder dystocia was obtained between 2008-2022 from a single tertiary center. This study involved the comparison of sociodemographic, sonographic, and delivery characteristics among pregnancies complicated by shoulder dystocia resulting in favorable vs. unfavorable maternal/neonatal outcomes. RESULTS: A total of 275 pregnancies were analyzed, with 111 (40.3%) classified as unfavorable outcomes and 164 (59.7%) as favorable outcomes. Employing a multivariable regression analysis, several independent associations were identified with unfavorable maternal/neonatal outcomes. Specifically, short maternal stature, pre-gestational diabetes, vacuum extraction, Wood's screw maneuver, and macrosomia merged as significant predictors of unfavorable maternal/neonatal outcomes. CONCLUSION: Short maternal stature, pre-gestational diabetes, vacuum extraction, Wood's screw maneuver, and macrosomia may all contribute to poor maternal/neonatal outcomes in shoulder dystocia cases. This knowledge allows clinicians to improve their decision-making, patient care, and counseling.

Pregnancy and placental outcomes according to maternal BMI in women with preeclampsia: a retrospective cohort study.

PURPOSE: Obesity and preeclampsia share similar patho-mechanisms and can both affect placental pathology. We aimed to investigate pregnancy outcomes in correlation with placental pathology among pregnancies complicated by preeclampsia in three different maternal body mass index (BMI, kg/m2) groups. METHODS: In this retrospective cohort study, medical and pathological records of patients with preeclampsia and a singleton pregnancy delivered between 2008 and 2021 at a single tertiary medical center were reviewed. Study population was divided into three BMI groups: BMI < 22.6 kg/m2 (low BMI group), 22.7 ≤ BMI ≤ 28.0 kg/m2 (middle-range BMI group), and BMI > 28.0 kg/m2 (high BMI group). Data regarding maternal characteristics, neonatal outcomes, and placental histopathological lesions were compared. RESULTS: The study groups included a total of 295 patients diagnosed with preeclampsia-98, 99, and 98 in the low, middle-range, and high BMI groups respectively. Neonatal birth weight was significantly decreased in the low maternal BMI group compared to both middle and high BMI groups (p = 0.04) with a similar trend seen in placental weight (p = 0.03). Villous changes related to maternal malperfusion were more prevalent in the low and high BMI groups compared to middle-range BMI group (p < 0.01) and composite maternal vascular malperfusion lesions were also more prevalent in the groups of BMI extremities compared to the middle-range BMI group (p < 0.01). CONCLUSION: Maternal BMI might influence neonatal outcomes and placental pathology in pregnancies complicated by preeclampsia. Both extremes of BMI were associated with higher rates of placental maternal vascular malperfusion. Balanced BMI in women at risk for preeclampsia may reduce the incidence of placental lesions.

Developmental trajectories of empathic concern in infancy and their links to social competence in early childhood.

BACKGROUND: Empathic concern is an important component of children's social competence. Yet, little is known about the role of the development of concern for others during infancy as a predictor of social competence in early childhood. METHODS: Israeli infants (N = 165, 50% girls) were observed five times, from 3 to 36 months. Empathic concern was assessed at ages 3-18 months using observations, and four components of social competence were assessed at 36 months using observations and teacher reports. RESULTS: Four groups with distinct developmental trajectories of empathic concern from 3 to 18 months were identified: early-onset (starting high and increasing), low-empathy (starting low with minimal increase), rising (starting low and increasing considerably), and a very small group with a negative slope (decreasing). The first three trajectories differed on aspects of social competence at 36 months. Early-onset children continued to exhibit the highest empathic concern. Both the early-onset and rising groups had greater affective knowledge than the low-empathy group. Moreover, the rising group had better peer relations compared with low-empathy trajectory children. CONCLUSIONS: Children who exhibit high levels of empathy early in infancy are likely to show high social competence later on. However, even when initial empathy levels are low, subsequent growth in empathy from 3 to 18 months can occur, with positive consequences for children's social competence at 36 months. Only children with low initial empathic concern and minimal growth across infancy are at increased risk of having poorer socioemotional capabilities in early childhood.

Feasibility of Fetal Proximal Lateral Cerebral Ventricle Measurement.

OBJECTIVES: Measuring the posterior horn of the lateral ventricle in the fetus during ultrasound scans may be challenging. We aimed to examine this measurement feasibility, in relation to gestational age. METHODS: A cross-sectional study was conducted, including nonanomalous fetuses, in which both lateral ventricles measured less than 10 mm during anomaly scans. The measurements were performed according to the International Society of Ultrasound in Obstetrics and Gynecology guidelines. Success rate of measuring both ventricles was assessed at different gestational ages. Association between lateral ventricle width with contralateral ventricle width, gender, gestational age, and fetal head position were assessed. RESULTS: A total of 156 cases were recruited. The lateral ventricle distal to the probe was measured in all cases. In 10 cases proximal lateral ventricle could not be adequately measured (failed proximal ventricle measurement group). In 146 scans both ventricle measurements were available. All 10 cases of failed proximal ventricle measurement were in third trimester (30-38 weeks). Success rate of measurement of both ventricles was 100%, 96.2%, 71.4%, and 37.5% for gestational week 14-29, 30-32, 33-35, and 36-38, respectively (P <.001). Proximal lateral ventricle width was strongly associated with the distal ventricle width (B = 0.422, 95% confidence interval 0.29, 0.555, P <.001), but not with head position, fetal gender, or gestational age. CONCLUSIONS: Measurement of the proximal lateral ventricle is feasible in most cases, even during late third trimester scans. Efforts should be made to visualize both ventricles in every evaluation of the fetal brain.

Association of the Cerebro-Placental Ratio With Adverse Outcomes in Pregnancies Affected by Gestational Diabetes Mellitus.

OBJECTIVES: Cerebro-placental ratio (CPR) is a doppler tool contributes to clinical decision-making in pregnancies affected by small for gestational age weight (SGA). Pregnancies affected by gestational diabetes mellitus (GDM) tend to have higher newborn weight, but greater risk of adverse perinatal outcomes. We hypothesized that in GDM-complicated-pregnancies CPR will be associated with adverse perinatal outcomes even in the absence of SGA. METHODS: This prospective single-center cohort study included non-anomalous singleton pregnancies in women with GDM. Those with pre-pregnancy diabetes mellitus, hypertensive disorder or suspected SGA were excluded. Routine fetal sonographic assessment included CPR-defined as middle cerebral artery pulsatilty index/umbilical artery pulsatilty index. Masked CPR measurement closest to birth was used, classified as >10th (normal) or ≤10th centile (low). Primary outcome was a composite, consisting of stillbirth, Caesarean birth due to abnormal fetal heart rate pattern, 5-minute Apgar <7, cord arterial pH < 7.0, hypoxic ischemic encephalopathy, or NICU admission >24 hours. RESULTS: Of 281 participants, 24 (8.5%) had low CPR, at a mean gestational age of 36.3 weeks (IQR 34.0-37.4). Birthweight percentile was significantly lower among the low CPR group (35th [IQR 16-31] versus 60th [IQR 31-82]; P = .002). There was no statistically difference in the primary composite outcome between the groups (8.3% versus 7.0%, P = .68). Low CPR was significantly associated with a higher risk of neonatal hypoglycemia (adjusted odds ratio 3.2, 95% CI 1.2-8.3). CONCLUSION: In pregnancies affected by GDM, CPR ≤10th percentile was not associated with adverse perinatal outcome but was associated with neonatal hypoglycemia.

Predicting externalizing behavior in toddlerhood from early individual differences in empathy.

BACKGROUND: From middle childhood onward, there is often a negative link between empathy and externalizing behavior problems. Patterns at younger ages are still unclear, with mixed findings of no association, negative associations, and positive associations. This study examines links between empathy and externalizing problems, beginning in infancy. METHODS: A community sample of infants (N = 165) was assessed for empathy at 3, 6, 12, 18, and 36 months, using behavioral observations. Externalizing problems were reported at 18 months (by mothers) and 36 months (by mothers and daycare teachers). RESULTS: Boys showed more externalizing problems than girls. For boys, negative associations between empathy and externalizing appeared, particularly with teacher reports. For girls, there were positive associations between empathy and externalizing, which weakened with age. For both genders, empathy at ages 3, 6, and 18 months appeared to protect against increases in externalizing from 18 to 36 months. CONCLUSIONS: The role of empathy in the development of early externalizing depends on both gender and age; toddler boys' externalizing may more typically stem from low empathy, whereas girls' early externalizing appears to be underlain by heightened sensitivity and unregulated or assertive approach attempts.

Caring babies: Concern for others in distress during infancy.

Concern for distressed others is a highly valued human capacity, but little is known about its early ontogeny. Theoretical accounts of empathy development have emphasized stages, but this has been called into question. This study sheds new light on four key issues: onset, consistency, development, and predictive power of early manifestations of concern for others. Three-month-old Israei infants (N = 165) were followed longitudinally at ages 6, 12, and 18 months, and their observed responses to others' distress were assessed. Concern for distressed others was seen early in the first year of life, long before previous theories assumed. Empathic concern was moderately consistent across both situation and age, from as early as 3 months. Concern for others grew only modestly with age, plateauing during the second year, whereas prosocial behavior increased rapidly during the second year. Early individual differences in concern for others predicted later prosocial behavior on behalf of distressed others. Findings underscore the early roots of caring, and appear to refute assumptions of prior stage theories of empathy development, by showing that concern for others develops much earlier and more gradually than previously assumed.

Does parity affect pregnancy outcomes in the elderly gravida?

PURPOSE: To identify whether older primiparas have more complications than do women who continue to deliver children into their late reproductive age. Patients of at least 35 years of age at delivery were included. Within this cohort, data from primiparous and multiparous women were compared. METHODS: This retrospective study was based on electronic medical records from a single academic center, with more than 7000 deliveries annually. The impact of parity on maternal complications was assessed using a multivariate logistic regression model that adjusted for baseline maternal characteristics and medical history. RESULTS: During the study period, there were 54 283 deliveries in our medical center. A total of 13,982 (25.7%) patients were at least 35 years old at delivery. The rate of twin pregnancy was higher in the primiparous group (1.9%) as compared to the multiparous group (0.8%, 95% CI 0.30-0.64, P < 0.001), as was the incidence of delivery prior to 34 weeks (6.1% of the primiparas versus 2.9% of the multiparas, P < 0.001, OR 2.16, 95% CI 1.75-2.68); hypertensive disorders (3.9% versus 1.7%, P < 0.001, 95% CI 0.33-0.57); diabetes (4.6% versus 3.2%, P = 0.003, 95% CI 0.55-0.88); and IUGR (10.5% versus 4.7%, P < 0.001, 95% CI 0.35-049), respectively. The increased risk for pre-term delivery, hypertensive disorders, diabetes, and IUGR was maintained after logistic regression analysis. CONCLUSION: We found that pregnancy complications typical to older parous women are significantly more common among primiparas, indicating that not only older age, but also having a first child relatively late in the reproductive period contributes to adverse pregnancy outcomes.

From negative reactivity to empathic responding: Infants high in negative reactivity express more empathy later in development, with the help of regulation.

Empathy has great effect on human well-being, promoting healthy relationships and social competence. Although it is increasingly acknowledged that infants show empathy toward others, individual differences in infants' empathy from the first year of life have rarely been investigated longitudinally. Here we examined how negative reactivity and regulation, two temperament traits that predict empathic responses in older children and adults, relate to infants' empathy. Infants were studied at the ages of nine (N = 275) and 18 (N = 301) months (194 infants were studied at both ages). Empathic responses were assessed by infants' observed reactions to an experimenter's simulated distress. Negative reactivity (fear, sadness, and distress to limitations) and regulation (soothability and effortful control) were assessed by parental reports. Negative reactivity was also examined by infants' observed reactions to an adult stranger (fear) and during interaction with their mothers (displays of sadness/distress). When examined cross-sectionally, infants' fear and distress to limitations associated with self-distress in response to others' distress. In contrast, when examined longitudinally, early sadness and distress to limitations, but not fear, associated with later empathic concern and inquisitiveness. Moreover, this longitudinal relation was moderated by infants' soothability and was evident only for children that had high soothability by the later time-point. Our findings suggest that infants who at an earlier age show negative reactivity, react later in development with more empathy if they achieve sufficient regulation abilities. By that, the findings stress the developmental nature of temperament-empathy relations during infancy.

Vaginal examination vs. cervical length - which is superior in predicting preterm birth?

OBJECTIVE: To compare the predictive value of preterm birth (PTB) by transvaginal sonographic cervical length (CL) measurement to digital examination of the cervix (Bishop score - BS), in patients with premature contractions (PC) and intact membranes. DESIGN: A retrospective case-control study. SETTING: Meir Medical Center, Kfar Saba, Israel. POPULATION: Women at 24-34 weeks of gestation who were hospitalized with PC and intact membranes. METHODS: All patients underwent CL and BS measurements upon admission. Power analysis revealed that 375 patients were needed to show a significant difference between the two methods for predicting PTB. Each one served as her own control. MAIN OUTCOME MEASURES: PTB<37 and<34 weeks. RESULTS: Receiver-operator characteristic curve (ROC) and logistic regression analyses indicated a correlation between both shortened CL and increased BS to PTB (P<0.001). Neither test offered an advantage in predicting PTB. Areas under the curve for BS and CL ROC were similar for PTB before 37 weeks gestation (0.611 vs. 0.640, P=0.28). For nulliparous women, CL predicted PTB better that BS (0.642 vs. 0.724, P=0.03). For singleton and multiple pregnancy pregnancies, BS and CL did not differ significantly in predicting PTB (P=0.9, P=0.2, respectively). For nulliparous with multiple pregnancy, the BS and CL ROC curves differ nearly significantly (0.554 vs. 0.709, P=0.07), with better predictive ability for CL. CONCLUSIONS: CL and BS have similar value in predicting PTB in patients with PC. For nulliparous women, CL is superior over the BS.

Telomere homeostasis in trophoblasts and in cord blood cells from pregnancies complicated with preeclampsia.

BACKGROUND: Telomeres are nucleoprotein structures, essential for chromosome stability and cell survival. Telomeres are progressively shortened with each cell division and by environmental factors. Telomere loss has been linked to age and stress-induced premature senescence. Dysfunctional telomeres tend to form aggregates, which consist of the end-to-end fusion of telomeres. Telomere elongation is carried out by telomerase, which is a specific reverse transcriptase capable of adding telomeric repeats to chromosome termini. The TERC gene encodes the RNA template of the telomerase. Another compensatory mechanism that is enhanced in response to telomere shortening and senescence is the telomere capture (TC). Telomere shortening and elevated aggregate formation have been observed in trophoblasts from pregnancies complicated with preeclampsia (PE). OBJECTIVE: We opted to study mechanisms of telomere shortening in trophoblasts from pregnancies complicated with PE and to assess telomere length and homeostasis in fetal cord blood cells from PE pregnancies. STUDY DESIGN: Placental specimens and cord blood samples from uncomplicated pregnancies and from pregnancies complicated with PE were collected. Staining with 4',6-diamidino-2-phenylindole was used to assess nuclear fragmentation: senescence-associated heterochromatin foci (SAHF). Fluorescence in situ hybridization was used to evaluate TERC gene copy number and TC. Telomere length and aggregate formation were assessed in cord blood using quantitative fluorescence in situ hybridization. Nonparametric Kruskal-Wallis and Mann-Whitney U tests were applied to test the differences between the study groups. RESULTS: Nine samples from pregnant patients with PE without intrauterine growth restriction and 14 samples from uncomplicated pregnancies that served as controls were collected. In cord blood cells, no differences were observed in telomere length, aggregate formation, TERC copy number, TC, or SAHF between PE and controls. In PE trophoblasts the percentage of cells with SAHF was higher in PE trophoblasts compared to controls (56.8 SD = 10.5% vs 35.2 SD = 10.7%, P = .028). The percentage of cells with abnormal TERC copy number was increased in PE trophoblasts compared to controls (31 ± 3.6% vs 12.97 SD = 5%, P = .004) as well as the percentage of cells with TC (27.4 SD = 9.4% vs 16 SD = 4.67%, P = .028). CONCLUSION: We suggest that telomere shortening in PE trophoblasts is linked to cellular increased senescence. Alterations in telomere homeostasis mechanisms are present in such cases. These findings support the role of telomeres in the pathogenesis of trophoblastic dysfunction in PE. The lack of telomere shortening, modified telomere homeostasis mechanisms, and increased senescence in cord blood from pregnancies complicated with PE suggests that these processes are probably restricted primarily to the placenta.

Adhesions at repeat cesarean delivery: is there a personal impact?

PURPOSE: The rise in the rate of cesarean deliveries highlights complications related to adhesion formation. This study evaluated whether the incidence and severity of adhesions secondary to repeat cesarean deliveries are a consequence of repeated surgeries or due to an individual's propensity to develop adhesions. METHODS: A retrospective chart review was conducted for 160 patients who had more than two repeat cesarean deliveries in a single teaching hospital. Data regarding intra-abdominal adhesions were collected. The severity, location, density and amount of adhesions were evaluated based on standard operative reports. Adhesion progression in subsequent cesarean deliveries was evaluated for each individual patient. RESULTS: 69/160 (43 %) patients developed significant adhesions following the primary cesarean delivery. Of these, 46 (67 %) had significant adhesions at the second surgery. Of the 91 (57 %) patients, who did not develop significant adhesions after the primary cesarean delivery, 34 (37 %) had significant adhesions at the third surgery. A patient presenting with significant adhesions at her second cesarean had a 1.88-fold risk for significant adhesions at her third cesarean (95 % CI 1.3-2.7). CONCLUSIONS: Our results suggest that adhesion development might be influenced by individual factors more than by the number of cesarean deliveries.

L-arginine improves endothelial function, independently of arginine uptake, in aortas from chronic renal failure female rats.

Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure (CRF). Defective nitric oxide (NO) generation due to decreased endothelial nitric oxide synthase (eNOS) activity is a crucial parameter characterizing ECD. Decreased activity of cationic amino acid transporter-1 (CAT-1), the selective arginine transporter of eNOS, has been shown to inhibit eNOS in uremia. Recently, we failed to demonstrate a decrease in glomerular arginine transport in uremic female rats (Schwartz IF, Grupper A, Soetendorp H, Hillel O, Laron I, Chernichovski T, Ingbir M, Shtabski A, Weinstein T, Chernin G, Shashar M, Hershkoviz R, Schwartz D. Am J Physiol Renal Physiol 303: F396-F404, 2012). The current experiments were designed to determine whether sexual dimorphism which characterizes glomerular arginine transport system in uremia involves the systemic vasculature as well and to assess the effect of L-arginine in such conditions. Contractile and vasodilatory responses, ultrastructural changes, and measures of the L-arginine-NO system were performed in thoracic aortas of female rats subjected to 5/6 nephrectomy. The contractile response to KCl was significantly reduced, and acetylcholine-induced vasodilation was significantly impaired in aortas from CRF dames compared with healthy rats. Both of these findings were prevented by the administration of arginine in the drinking water. The decrease in both cGMP generation, a measure of eNOS activity, and aortic eNOS and phosphorylated eNOS abundance observed in CRF rats was completely abolished by l-arginine, while arginine transport and CAT-1 protein were unchanged in all experimental groups. Arginine decreased both serum levels of advanced glycation end products and the asymmetrical dimethylarginine/arginine ratio and restored the endothelial ultrastructure in CRF rats. In conclusion. arginine administration has a profound beneficial effect on ECD, independently of cellular arginine uptake, in CRF female rats.

Vaginal Progesterone for Pregnancy Prolongation After Arrested Preterm Labor: A Randomized Clinical Trial.

Importance: Women with arrested preterm labor (APTL) are at very high risk for spontaneous preterm delivery (SPTD), the leading cause of neonatal mortality and morbidity. To date, no maintenance therapy has been found to be effective for pregnancy prolongation. A few clinical trials with considerable methodological limitations have demonstrated some efficacy for 400 mg vaginal micronized progesterone (VMP) in women with APTL. Objective: To investigate the effectiveness of daily 400 mg VMP for the prolongation of pregnancy after APTL. Design, Setting, and Participants: This randomized clinical trial was conducted between December 19, 2018, and February 27, 2023, in 3 university-affiliated medical centers in Israel. Participants included women with singleton and twin pregnancies after APTL following tocolysis at 24 weeks 0 days to 34 weeks 0 days' gestation. Women with a history of preterm delivery or asymptomatic cervical shortening in the current pregnancy were excluded. Interventions: Participants were randomly allocated to receive VMP 200 mg twice a day or no treatment until 36 weeks 6 days' gestation. Main Outcomes and Measures: The primary end points were mean number of days from study enrollment to delivery and the rate of SPTD prior to 37 weeks' gestation. Results: A total of 129 participants were enrolled (65 in the VMP group and 64 in the no-treatment group). Mean (SD) age was 27.6 (5.1) years. Between the VMP and no-treatment groups, there was no difference in pregnancy prolongation (mean [SD], 40.0 [17.8] vs 37.4 [20.3] days; P = .44) and the rate of SPTD (16 [25%] vs 19 [30%]; relative risk, 0.8; 95% CI, 0.5-1.5; P = .52). In twin pregnancies, including 12 and 15 pairs in the VMP and no-treatment groups, respectively, VMP prolonged pregnancy (mean [SD], 43.7 [18.1] vs 26.1 [15.2] days; P = .02), postponed the delivery week (36.5 [1.4] vs 34.7 [2.2] weeks; P = .01), shortened the length of stay in the neonatal intensive care unit (4.9 [10.6] vs 13.2 [18.5] days; P = .03) and overall hospital stay (8.3 [9.6] vs 15.1 [17.2] days; P = .03), and was associated with a higher birth weight (2444 [528] vs 2018 [430] g; P = .01). Conclusions and Relevance: These findings show that VMP given in a dosage of 200 mg twice a day following APTL is not an effective treatment to prolong pregnancy or prevent SPTD. However, VMP demonstrated beneficial effects in twin pregnancies, warranting further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02430233.

Improved neonatal outcomes in pregnancies with coexisting gestational diabetes and preeclampsia in normal birthweight neonates- insights from a retrospective cohort study.

INTRODUCTION: We aimed to assess neonatal and maternal outcomes in appropriate-for-gestational-weight (AGA) neonates of mothers with both gestational diabetes mellitus (GDM) and preeclampsia (PET). METHODS: Medical records of women diagnosed with GDM or PET were reviewed. Women with AGA neonates were divided into three groups- GDM, PET, and GDM + PET and maternal neonatal and placental outcomes were compared. The primary outcome was a composite of adverse neonatal outcomes, including intensive care unit admission (NICU), neurological morbidity, hypoglycemia, ventilation, respiratory distress syndrome (RDS), phototherapy, sepsis, blood transfusion, and neonatal death. Post-hoc analysis was performed to determine between-group significance. RESULTS: Composite adverse neonatal outcomes are significantly lower in women with multiple morbidities compared to women with confined PET (p = 0.015), and a similar trend is observed when comparing neonatal outcomes between women with GDM to those with GDM + PET, yet these results are underpowered (18.9 % vs. 12.8 % respectively, p = 0.243). Placentas of women with GDM + PET were larger, with a lower rate of placentas below the 10th percentile as compared to placentas of women with isolated PET (p < 0.001), but with similar rates of MVM lesions. DISCUSSION: While maternal and placental outcomes in patients of the GDM + PET group resemble the characteristics of the PET group, surprisingly, the neonatal outcomes in this group are significantly better compared to isolated morbidities. The paradoxical benefit attributed to the coexistence of GDM + PET may be explained by a balance of the opposing trends characterizing these morbidities-the reduced blood and nutrient supply characterizing PET vs. chronic overflow and abundance typical of GDM. CLINICAL TRIAL REGISTRATION: approval of local ethics committee WOMC-19-0152.

Placental Histopathological Lesions and Adverse Neonatal Outcomes in Patients with Inflammatory Bowel Diseases- A retrospective Cohort Study.

Inflammatory bowel diseases (IBD) are significantly associated with adverse pregnancy and neonatal outcomes, though the pathomechanism is yet unknown. To investigate the relationship between IBD and adverse pregnancy outcomes by comparing neonatal outcomes and placental histopathology in two matched groups of patients with and without IBD. In this retrospective study, data of all patients who gave birth between 2008-2021 and were diagnosed with IBD were reviewed and compared to a control group matching two control cases for every IBD case. Neonatal outcomes and placental pathology were compared between the groups. Compared to the control group (n=76), the placentas of patients with IBD (n=36) were characterized by significantly lower placental weight (p < 0.001), and higher rates of maternal vascular malperfusion lesions (MVM, p < 0.001) and maternal and fetal inflammatory response lesions (p < 0.001). Neonates of patients with IBD were more frequently small for gestational age (SGA) (p=0.01), with increased rates of need for phototherapy (p = 0.03), respiratory morbidity and NICU admission (p < 0.001 for both outcomes). Multivariate logistic regression analyses adjusting for possible confounders (including maternal age, gestational age, chronic hypertension, smoking, and thrombophilia) confirmed the independent association between IBD and composite MVM lesions (aOR 4.31, p < 0.001), maternal inflammatory responses (aOR 40.22, p < 0.001) and SGA infants (aOR 4.31, p = 0.013). IBD is associated with increased rates of placental histopathological lesions and adverse pregnancy outcomes, including SGA infants. These novel findings imply the role of placental malperfusion and inflammatory processes in pregnancy complications of IBD patients, which should be followed accordingly. Approval of local ethics committee # WOMC-0219-20.