Prenatal Risk Research Articles

Head growth in patients with myelomeningocele treated with prenatal and postnatal surgery.

The need for permanent CSF diversion is lower in patients who have undergone prenatal surgery for myelomeningocele (MMC) than in those who have undergone postnatal closure. Differences in brain development and head growth between treatment groups are not known, particularly for those who do not require surgical treatment for hydrocephalus. The objective of this study was to determine differences in head growth and to generate MMC-specific head circumference (HC) growth curves for patients who underwent either prenatal or postnatal surgery. The authors retrospectively identified patients from St. Louis Children's Hospital who were treated for MMC between 2016 and 2021. HC data were obtained from birth until the most recent follow-up or hydrocephalus treatment. Nonlinear least-squares regression analysis was performed to fit the data into four models: two-term power, Gompertz, West ontogenetic, and Weibull. Subsequently, the curves were assessed for their utility in predicting hydrocephalus treatment. Sixty-one patients (29 females [47.5%], 25 [41%] underwent prenatal surgery, mean gestational age at birth 36.6 weeks) were included in the study. The Weibull model best fit the HC data (prenatal adjusted R2 = 0.95, postnatal adjusted R2 = 0.95), while the Gompertz model had the worst fit (prenatal adjusted R2 = 0.56, postnatal adjusted R2 = 0.39) across both cohorts. Prenatal MMC repair patients had significantly larger HC measurements than their postnatal repair counterparts. The 50th percentile of the Weibull curve was determined as a useful threshold for hydrocephalus treatment: children with HC measurements that crossed and remained above this threshold were significantly more likely to have hydrocephalus treatment regardless of time of MMC repair (prenatal relative risk [RR] 10.0 [95% CI 1.424-70.220], sensitivity 85.7% [95% CI 0.499-0.984], and specificity 82.4% [95% CI 0.600-0.948]; postnatal RR 4.750 [95% CI 1.341-16.822], sensitivity 90.5% [95% CI 0.728-0.980], and specificity 75.0% [95% CI 0.471-0.924]). The HC growth curves of the MMC patients treated prenatally were significantly larger than the WHO HC curves (p < 0.001). The Weibull model was identified as the HC growth curve with the best fit for MMC patients and serves as a useful predictor of hydrocephalus treatment. For MMC patients with hydrocephalus, prenatal repair patients fit the model well but postnatal repair patients did not, potentially indicating different mechanisms of hydrocephalus development. Those treated prenatally had significantly larger HC measurements compared with both the general population and those treated postnatally. Further study is needed to understand the long-term cognitive outcomes and optimal management of clinically asymptomatic patients with large HC measurements who were treated prenatally for MMC.

عوامل الخطر قبل الولادة وأثناء الولادة و بعد الولادة المرتبطة باضطراب طيف التوحد في فلسطين: دراسة الحالات و الشواهد

Background: Autism spectrum disorder (ASD) is a multifactorial neurodevelopment disorder. Several prenatal, perinatal, and postnatal factors are suggested as risk factors for ASD. This study aimed to correlate prenatal, perinatal, and postnatal factors in a limited number of cases in Palestine. Methods: A case-control study involved 120 children (60 typically diagnosed with ASD and 60 healthy matched with the ASD group). The parents of the children in both groups were asked to fill out the questionnaire. Results: The study showed a higher male-to-female ratio in the ASD group. A family history of ASD was reported in 38.3% of the ASD group and 11.7% in the healthy group. Three prenatal risk factors, including maternal passive smoking, preserving follow-up prenatal visits, and experiencing psychological stress by mothers, were significantly associated with ASD. Most of the postnatal factors were significantly associated with increased ASD risk. The studied perinatal factors were not significantly associated with ASD. The parental factors, such as paternal age greater than 30 years and lower levels of education, displayed significant risk factors associated with ASD. Conclusion: This study found significant associations between several prenatal, postnatal, and parental factors and ASD in a sample of Palestinian children. المقدمة: اضطراب طيف التوحد هو اضطراب نمائي عصبي متعدد العوامل. تم تحديد العديد من العوامل قبل الولادة و أثناء الولادة و بعد الولادة كعوامل قد تكون مرتبطة بالاصابة باضطراب طيف التوحد. هدفت هذه الدراسة لفحص ارتباط عدة عوامل قبل الولادة و أثناء الولادة و بعد الولادة في عدد محدود من حالات التوحد في فلسطين. المنهجية: تمت الدراسة من خلال جمع معلومات من عينة ضمت 120 طفل (60 تم تشخيصهم بطيف التوحد و 60 طفل سليم و متطابقين مع مجموعة التوحد). تمت الاجابة على الاستبيان من قبل أولياء الأمور في المجموعتين. النتائج: أظهرت الدراسة أن نسبة الذكور الى الاناث في مجموعة طيف التوحد كانت أعلى. تم تحديد نسبة وجود تاريخ عائلي في 38.3% من مجموعة طيف التوحد و 11.7% من مجموعة الاطفال السليمين. تم تحديد ثلاثة عوامل خطورة قبل الولادة مرتبطة بشكل وثيق مع اضطراب طيف التوحد و تشمل التدخين السلبي للأم، متابعة زيارات الرعاية قبل الولادة، و التعرص للاجهاد النفسي من قبل الأمهات. معظم عوامل الخطر بعد الولادة كانت مرتبطة بشكل وثيق بزيادة خطر الاصابة بطيف التوحد. عوامل الخطر أثناء الولادة التي تمت دراستها لم ترتبط بشكل وثيق باضطراب طيف التوحد. العوامل المتعلقة بالوالدين مثل عمر الأب أكثر من 30 عام و مستويات التعليم المتدنية أظهرت ارتباطا وثيقا بالإصابة بطيف التوحد. الاستنتاج: وجدت الدراسة ارتباطات وثيقة بين عدة عوامل قبل الولادة و أثناء الولادة و بعد الولادة مع طيف التوحد في عينة من الأطفال الفلسطينيين.

Epigenome-wide association study identifies neonatal DNA methylation associated with two-year attention problems in children born very preterm

Prior research has identified epigenetic predictors of attention problems in school-aged children but has not yet investigated these in young children, or children at elevated risk of attention problems due to preterm birth. The current study evaluated epigenome-wide associations between neonatal DNA methylation and attention problems at age 2 years in children born very preterm. Participants included 441 children from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a multi-site study of infants born < 30 weeks gestational age. DNA methylation was measured from buccal swabs collected at NICU discharge using the Illumina MethylationEPIC Bead Array. Attention problems were assessed at 2 years of adjusted age using the attention problems subscale of the Child Behavior Checklist (CBCL). After adjustment for multiple testing, DNA methylation at 33 CpG sites was associated with child attention problems. Differentially methylated CpG sites were located in genes previously linked to physical and mental health, including several genes associated with ADHD in prior epigenome-wide and genome-wide association studies. Several CpG sites were located in genes previously linked to exposure to prenatal risk factors in the NOVI sample. Neonatal epigenetics measured at NICU discharge could be useful in identifying preterm children at risk for long-term attention problems and related psychiatric disorders, who could benefit from early prevention and intervention efforts.

PM2.5 threshold exceedances during the prenatal period and risk of intellectual disability.

Research demonstrates that chronic exposure to fine particulates (PM2.5) increases risks of neurodevelopmental conditions, such as intellectual disability (ID). Few studies have examined neurodevelopmental health impacts of pollution spikes exceeding 24-h (24-h) PM2.5 guidelines, despite relevance to the regulatory landscape. The current potential for regulatory changes to 24-h PM2.5 standards in the United States makes research on exceedances relevant. To examine associations between 24-h PM2.5 exceedances and the risk of ID. We conducted a retrospective case-control study of a sample of children in Utah, USA. We used generalized estimating equations to predict odds of ID based on the number of 24-h PM2.5 exceedance days during the preconception period and three trimesters of pregnancy. Exceedance days are defined as per current World Health Organization (WHO) [≥15 μg/m3] and current US Environmental Protection Agency (EPA) [≥35 μg/m3] 24-h guidelines. PM2.5 exceedances are associated with ID risk during the preconception and first trimester periods and not the second and third trimesters. During the preconception period, each day exceeding 15 μg/m3 or 35 μg/m3 was associated with a 1.023 (CI: 1.011-1.040) or 1.042 (CI: 1.026-1.059, p < 0.001) increase in odds of ID, respectively. During the first trimester, each day exceeding 15 μg/m3 or 35 μg/m3 was associated with a 1.032 (CI: 1.017-1.047) or 1.059 (CI: 1.030-1.088) increase in odds of ID, respectively. Potential regulatory movement on the US 24-h PM2.5 standard makes research that explicitly studies exceedances highly relevant. Yet few studies examine health effects of exceeding 24-h guidelines for any air pollutants. This study fills important gaps in the literature by examining associations between odds of intellectual disability and the count of days exceeding current 24-h PM2.5 guidelines, as established by the World Health Organization and US Environmental Protection Agency, during the prenatal period. We find that exceedances of both sets of guidelines, during the preconception and first trimester periods, are associated with ID risk.

Reduced Identification as a Mother Mediates the Effect of Prenatal Risk Factors on Mother and Infant Socio-Emotional Functioning

AbstractTo support good outcomes for mothers and babies, it is essential to understand the prenatal factors that place both at risk, such as birth trauma, the mother’s attachment history, and unplanned motherhood. However, for health professionals supporting mothers, interventions must target malleable intervening factors. One of these, we propose, is social identification as a mother. Among women who had become mothers in past 12 months (N = 317), we assessed prenatal risk factors, social identification as a mother, and three socio-emotional outcomes: mother’s depression, infant temperament, and mother-infant attachment. Consistent with hypotheses, all prenatal risk factors negatively predicted social identification as a mother, which was itself positively associated with socio-emotional functioning. Model fit was excellent. Reduced social identification as a mother may be a key mechanism through which prenatal risk factors produce poorer outcomes for mothers and babies. Interventions may be enhanced by supporting the development of strong and positive social identities.

Contributions of prenatal risk factors and neonatal epigenetics to cognitive outcome in children born very preterm.

Children born less than 30 weeks gestational age (GA) are at high risk for neurodevelopmental delay compared to term peers. Prenatal risk factors and neonatal epigenetics could help identify preterm children at highest risk for poor cognitive outcomes. We aimed to understand the associations among cumulative prenatal risk, neonatal DNA methylation, and child cognitive ability at age 3 years, including whether DNA methylation mediates the association between prenatal risk and cognitive ability. We studied 379 neonates (54% male) born less than 30 weeks GA who had DNA methylation measured at neonatal intensive care unit discharge along with 3-year follow-up data. Cumulative prenatal risk was calculated from 24 risk factors obtained from maternal report and medical record and epigenome-wide neonatal DNA methylation was assayed from buccal swabs. At 3-year follow-up, child cognitive ability was assessed using the Bayley Scales of Infant and Toddler Development (third edition). Cumulative prenatal risk and DNA methylation at two cytosine-phosphate-guanines (CpGs) were uniquely associated with child cognitive ability. Using high-dimensional mediation analysis, we also identified differential methylation of 309 CpGs that mediated the association between cumulative prenatal risk and child cognitive ability. Many of the associated CpGs were located in genes (TNS3, TRAPPC4, MAD1L1, APBB2, DIP2C, TRAPPC9, DRD2) that have previously been associated with prenatal exposures and/or neurodevelopmental phenotypes. Our findings suggest a role for both prenatal risk factors and DNA methylation in explaining outcomes for children born preterm and suggest we should further study DNA methylation as a potential mechanism underlying the association between prenatal risk and child neurodevelopment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Prenatal tobacco, tobacco-cannabis coexposure, and child emotion regulation: The role of child autonomic functioning and sensitive parenting.

Prenatal tobacco exposure (PTE) and tobacco-cannabis coexposure (PTCE) co-occur with negative maternal emotional functioning (termed prenatal risks) and together increase risk for child regulatory problems at early school age (ESA). Little is known about developmental processes in early childhood that may mediate this association. We examined two hypothesized mediational processes linking prenatal risks to ESA emotion regulation (ER) and lability-negativity; parasympathetic functioning at toddler age and chronic risk reflected by continued postnatal maternal negative emotional functioning (i.e., depression, anger/hostility, and emotion dysregulation) and substance exposure. Congruent with differential susceptibility theory, we examined interactions between sensitive parenting and toddler parasympathetic functioning predicting ESA ER. Finally, we explored the role of child sex as a moderator. Mothers (N = 247; 53% male infants; 51% Black, 31% White, 19% Hispanic, and 8% other or mixed race) were recruited in the first trimester of pregnancy into one of three groups: PTE (n = 81), PTCE (n = 97), and no substance exposure (n = 69) matched on age and education. Substance exposure was assessed using multiple methods, maternal negative emotional functioning via self-reports, parenting with observations, and child ER using teacher, maternal, and lab assessor reports. Results supported a chronic risk pathway with less support for a parasympathetic pathway. Toddlers who demonstrated respiratory sinus arrhythmia withdrawal to frustration were susceptible to the positive context of sensitive parenting in predicting higher ER. Results emphasize the importance of chronicity of postnatal risks including substance exposure and evaluating the differential impact of positive environments for children with substance exposure. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for Contributions of Prenatal Risk Factors and Neonatal Epigenetics to Cognitive Outcome in Children Born Very Preterm

Supplemental Material for Contributions of Prenatal Risk Factors and Neonatal Epigenetics to Cognitive Outcome in Children Born Very Preterm

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms

Prenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined. To determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations. This was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023. Levels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy. Self-reported depressive symptoms at adolescent follow-up. A total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75). In this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

Prenatal identification of fetal growth restriction and risk of stillbirth

The aim of the work is to determine the frequency and impact of prenatal identification of fetal growth restriction (FGR) on obstetric and perinatal outcomes based on a retrospective analysis. Materials and methods. In total, 618 birth histories in singleton normal pregnancies complicated by FGR in the city of Zaporizhzhia were analyzed. Of these, in 546 cases of FGR, women gave birth to live infants (group I), and in 72 such cases, pregnancies ended up in a stillbirth (group II). The mean age of pregnant women in the studied groups was 28.7 ± 3.1 and 31.7 ± 3.1 years and it was significantly greater in group II (p &lt; 0.0001). In all the cases, the gestational age was ≥22 weeks, and the fetal weight was less than the 10th percentile for the relevant gestational age according to the current Order of the Ministry of Health of Ukraine No. 1718 dated 02.10.2023. Growth restriction in newborns was determined according to the criteria of the Consensus Definition (2018) including birth weight the &lt;3rd percentile, or a combination of three of the following criteria: birth weight the &lt;10th percentile; head circumference the &lt;10th percentile; prenatal diagnosis of FGR; prenatal risk factors associated with FGR. A stillbirth was defined as death of a fetus after 22 weeks of gestation without any signs of life. Exclusion criteria from the study were: multiple pregnancy, the presence of a chromosomal abnormality in a fetus, an undetermined gestational age in the 1st trimester. Results. A significant proportion of fetuses with FGR signs has been revealed in group II, which was 17 times more than that in group I. The study data have demonstrated a rather low level of prenatal FGR identification in both groups (35.6 %), while in group II, the diagnosis of FGR was made before delivery only in every fifth case (p &lt; 0.05). Data analysis has shown a higher percentage of preterm births among pregnant women in group II (p &lt; 0.0001) with the maximum number of births in this group at 28- and 36-weeks’ gestation. The average weight percentile was significantly higher in group II, namely 4.12 compared to 3.77 (p &lt; 0.0001), however, the number of fetuses with a weight the &lt;1st percentile occurred significantly more often in group I (p &lt; 0.05). The frequency of fetal distress in group I was greater among fetuses with the birth weight 10th percentile than among those with fetal weight less than the 3rd percentile. Conclusions. The conducted study results have shown a large percentage of FGR fetuses in the structure of stillbirths with no downward trend. A low level of FGR prenatal identification has been found in both groups (35.6 %), while in the group of stillbirths, the indicator was significantly lower and amounted to 22.22 %. The presence of FGR has resulted in a significant increase in the relative risk of stillbirth – 28.4, 95 % CI [21.2; 38.3]. Besides, the additional risk was increased (11.0, 95 % CI [8.7; 13.8]) if FGR was not diagnosed during pregnancy. At the same time, the odds ratio was 32.1, 95 % CI [23.3; 44.1].

Intergenerational Impact of Maternal Early Life Stress on Infant Development: Risk and Protective Factors From the BABIP Birth Cohort

BackgroundMaternal early life stress may exert an intergenerational impact, leading to adverse infant outcomes. Recent studies suggest moderation of this impact by characteristics of the perinatal environment and physiology. In the Bogazici Mother Baby Relationship Project (BABIP) birth cohort from Istanbul, Turkey, we investigated the role of pregnancy-related worries, fetal bonding and cortisol awakening response as potential risk and protective factors on infant development. MethodsParticipants were pregnant women (N = 187) and their babies from BABIP birth cohort. Maternal early life stress, pregnancy-related worries and fetal bonding was measured by Childhood Trauma Questionnaire, Cambridge Worry Scale, and Fetal Attachment Scale, respectively. Cortisol awakening response was measured from saliva samples collected during pregnancy as the difference between awakening and peak cortisol after awakening. Infant development was measured at 4 months after birth using the Ages & Stages Questionnaire. ResultsMaternal early life stress was associated with worse infant development at 4 months. This effect was exacerbated in mothers with high pregnancy-related worries (p <.05) and low fetal bonding (p <.01) during pregnancy. There was a trend for more pronounced effects for both factors in women with higher cortisol awakening response. There were no differences by infant sex. ConclusionThe results suggest that the intergenerational impact of maternal early life stress on infant development may be moderated by prenatal risk and resilience factors, suggesting that infant development is influenced by interactions between maternal early and prenatal environment and physiology. FundingBogazici University BAP #11662&18983&19357, TUBITAK #221K039 (EAD).

In Utero Origins of Acute Leukemia in Children.

Acute leukemias, mainly consisting of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), comprise a major diagnostic group among hematologic cancers. Due to the early age at onset of ALL, particularly, it has long been suspected that acute leukemias of childhood may have an in utero origin. This supposition has motivated many investigations seeking direct proof of prenatal leukemogenesis, in particular, twin and "backtracking studies". The suspected in utero origin has also focused on gestation as a critical window of risk, resulting in a rich literature on prenatal risk factors for pediatric acute leukemias. In this narrative review, we recount the circumstantial and direct evidence for an in utero origin of childhood acute leukemias.

Prenatal tobacco smoke exposure and risk for cognitive delays in infants born very premature

Prenatal tobacco smoke exposure (TSE) and prematurity are independent risk factors for abnormal neurodevelopment. The objectives were to compare differences in Bayley-III cognitive, language, and motor scores at 2 years corrected age (CA) in 395 infants born very preterm (≤ 32 weeks gestation) with and without prenatal TSE. We performed multivariable linear regression analyses to examine associations between prenatal TSE and neurodevelopmental outcomes and a mediation analysis to estimate direct effects of prenatal TSE on outcomes and indirect effects through preterm birth. In total, 50 (12.6%) infants had prenatal TSE. Infants with prenatal TSE had lower mean [95% CI] Cognitive score (82.8 [78.6, 87.1]) vs. nonexposed infants (91.7 [90.1, 93.4]). In children with and without prenatal TSE, there were significant differences in mean [95% CI] Language scores (81.7 [76.0, 87.4] vs. 92.4 [90.2, 94.6], respectively) and mean [95% CI] Motor scores (86.5 [82.2, 90.7] vs. 93.4 [91.8, 95.0], respectively); scores remained significant after controlling for confounders. Preterm birth indirectly mediated 9.0% of the total effect of prenatal TSE on Cognitive score (P = NS). However, 91% of the remaining total effect was significant and attributable to TSE’s direct harmful effects on cognitive development (β = − 5.17 [95% CI − 9.97, − 0.38]). The significant association is largely due to TSE’s direct effect on cognitive development and not primarily due to TSE’s indirect effect on preterm birth.

Prenatal Opioid Exposure and Risk for Adverse Brain and Motor Outcomes in Infants Born Premature

ObjectiveTo compare brain MRI biomarkers and neurodevelopmental test scores in infants born preterm with and without prenatal opioid exposure (POE). Study designWe examined 395 preterm infants (≤ 32 weeks gestational age[GA]) who had term-equivalent brain MRIs, composite scores from the Bayley Scales of Infant and Toddler Development-III(BSID-III) at 2 years corrected age, and POE data. MRI parameters included total/regional brain volumes and severe punctate white matter lesions (PWMLs). We conducted bivariable analysis and multivariable logistic regression analyses. ResultsThe mean(SD) gestational age was 29.3(2.5) weeks; 35(8.9%) had POE and 20(5.1%) had severe PWML. Compared with unexposed infants, those with POE exhibited higher rates of severe PWML (17.1% vs. 3.9%, respectively; p=0.002); findings remained significant with OR 4.16 (95% CI:1.26, 13.68) after adjusting for confounders. On mediation analysis, the significant relationship between POE and severe PWML was not indirectly mediated through preterm birth/GA (OR:0.93; 95% CI:0.78,1.10), thus suggesting the association was largely driven by a direct adverse effect of POE on white matter. In multivariable analyses, POE was associated with a significantly lower score by -6.2 (95%CI: -11.8,-0.6) points on BSID-III Motor subscale compared with unexposed infants. ConclusionsPOE was associated with severe PWML; this outcome may be a direct effect of POE rather than being mediated by premature birth. POE was also associated with worse motor development. Continued follow-up to understand the long-term effects of POE is warranted.

Soluble urokinase plasminogen activator receptor in vaginally collected amniotic fluid predicting fetal inflammatory response syndrome: a prospective cohort study

BackgroundImproving noninvasive antenatal diagnosis of fetal inflammatory response syndrome (FIRS) can assist in the evaluation of prenatal risk and reduce perinatal outcomes. This study aimed to determine whether soluble urokinase-type plasminogen activator receptor (suPAR) in vaginally collected amniotic fluid is significant in identifying FIRS after preterm premature rupture of membranes before 34 weeks of gestation.MethodsThis was a prospective cohort study of 114 pregnant women and their newborns after preterm premature rupture of membranes at 22–34+6 weeks of gestation. SuPAR was evaluated using an enzyme-linked immunosorbent assay in vaginally collected amniotic fluid. Patients were classified according to the presence or absence of FIRS. FIRS was defined by umbilical cord blood interleukin-6 level > 11 pg/mL or histological funisitis. The data were analyzed using the R package (R–4.0.5).ResultsSuPAR was detected in all amniotic fluid samples with a median of 26.23 ng/mL (interquartile range (IQR), 15.19–51.14). The median level of suPAR was higher in the FIRS group than in the non-FIRS group, 32.36 ng/mL (IQR, 17.27–84.16) vs. 20.46 ng/mL (IQR, 11.49–36.63) (P = 0.01), respectively. The presence of histological chorioamnionitis significantly increased the suPAR concentration in the FIRS group (P < 0.001). The areas under the curve for FIRS and FIRS with histological chorioamnionitis were 0.65 and 0.74, respectively, with an optimum cutoff value of 27.60 ng/mL. Controlling for gestational age, the cutoff of suPAR more than 27.60 ng/mL predicted threefold higher odds for FIRS and sixfold higher odds for FIRS with histologic chorioamnionitis.ConclusionSoluble urokinase-type plasminogen activator receptor in vaginally obtained amniotic fluid may assist in evaluating prenatal risk of FIRS in patients after preterm premature rupture of membranes before 34 weeks of gestation.

Cord blood lipid correlation network profiles are associated with subsequent attention-deficit/hyperactivity disorder and autism spectrum disorder symptoms at 2 years: a prospective birth cohort study

BackgroundAttention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental conditions with early life origins. Alterations in blood lipids have been linked to ADHD and ASD; however, prospective early life data are limited. This study examined (i) associations between the cord blood lipidome and ADHD/ASD symptoms at 2 years of age, (ii) associations between prenatal and perinatal predictors of ADHD/ASD symptoms and cord blood lipidome, and (iii) mediation by the cord blood lipidome. MethodsFrom the Barwon Infant Study cohort (1074 mother-child pairs, 52.3% male children), child circulating lipid levels at birth were analysed using ultra-high-performance liquid chromatography-tandem mass spectrometry. These were clustered into lipid network modules via Weighted Gene Correlation Network Analysis. Associations between lipid modules and ADHD/ASD symptoms at 2 years, assessed with the Child Behavior Checklist, were explored via linear regression analyses. Mediation analysis identified indirect effects of prenatal and perinatal risk factors on ADHD/ASD symptoms through lipid modules. FindingsThe acylcarnitine lipid module is associated with both ADHD and ASD symptoms at 2 years of age. Risk factors of these outcomes such as low income, Apgar score, and maternal inflammation were partly mediated by higher birth acylcarnitine levels. Other cord blood lipid profiles were also associated with ADHD and ASD symptoms. InterpretationThis study highlights that elevated cord blood birth acylcarnitine levels, either directly or as a possible marker of disrupted cell energy metabolism, are on the causal pathway of prenatal and perinatal risk factors for ADHD and ASD symptoms in early life. FundingThe foundational work and infrastructure for the BIS was sponsored by the Murdoch Children's Research Institute, Deakin University, and Barwon Health. Subsequent funding was secured from the Minderoo Foundation, the European Union's Horizon 2020 research and innovation programme (ENDpoiNTs: No 825759), National Health and Medical Research Council of Australia (NHMRC) and Agency for Science, Technology and Research Singapore [APP1149047], The William and Vera Ellen Houston Memorial Trust Fund (via HOMER Hack), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane O'Brien Memorial Asthma Foundation, the Our Women Our Children's Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Ilhan Food Allergy Foundation, Geelong Medical and Hospital Benefits Association, Vanguard Investments Australia Ltd, the Percy Baxter Charitable Trust, and Perpetual Trustees.

Effects of permanent placental injury due to severe acute respiratory syndrome coronavirus 2 infection during pregnancy on the feto-placental circulation: a cross-sectional study.

The aim of this study was to evaluate the effects of permanent placental injury due to a severe acute respiratory syndrome coronavirus 2 infection during pregnancy on feto-placental circulation. In this cross-sectional study, 83 pregnant women with planned deliveries were divided into two groups according to their severe acute respiratory syndrome coronavirus 2 infection statuses during pregnancy. Their demographic parameters, obstetric histories, and prenatal risks were evaluated. A prenatal fetal Doppler ultrasound examination was performed for all participants, and umbilical artery and middle cerebral artery Doppler parameters were obtained. Postpartum placentas were examined for pathological findings under appropriate conditions. All placentas were evaluated according to the Amsterdam consensus criteria. Mann-Whitney U test, Student's t-test, and chi-square test were used for comparisons. Demographic parameters were statistically similar, except that they were borderline significant for gestational weeks at delivery (p=0.044). In the pathological examination of the placenta, regardless of the trimester of exposure to viral infection, perivillous fibrin deposition and villus dystrophic calcification were more common in group 2 (p=0.016 and p=0.048, respectively) than in group 1. In the prenatal Doppler examination between the groups, no statistically significant difference was found for all of the umbilical artery pulsatile index, middle cerebral artery pulsatile index, and cerebro-placental ratio values. Severe acute respiratory syndrome coronavirus 2 infection during pregnancy causes an increase in perivillous fibrin deposition and villus dystrophic calcification in the placenta. Placental injury caused by the severe acute respiratory syndrome coronavirus 2 virus does not affect fetal Doppler parameters.

Factors related to Morbidity and Mortality in cases of Maternal death of the Mexican Social Security Institute of Sinaloa for the year 2021- 2022

Introduction: obstetric morbidity runs parallel to maternal mortality rates, so it is a way to evaluate the quality of care provided. Behind every maternal death lies a personal tragedy that can be resolved. The objective is to relate the factors of Maternal Morbidity and Mortality in cases of maternal death in the Mexican Social Security Institute, Sinaloa from 2021 to 2022.Method: study population integrated into a sample of 116 pregnant women from the IMSS Sinaloa, identified through the “PAMM” database and institutional records, associating sociodemographic variables, reproductive and prenatal risk factors, comorbidities in the pregnant stage and action protocols, achieving the creation of a logistic regression model. Non-probabilistic convenience sampling. Observational, analytical, retrospective and transversal research design.Results: the variables of pregestational care, BMI, transfer, place of occurrence, APP of DM2 and SAH, complications in previous pregnancies and immunization of COVID and influenza, explain maternal mortality by 55,2 % according to the Cox and Snell R2 coefficient.Conclusion: addressing the differences of the health institution by ethnicity, gender, social territory, life cycles will give the possibility of making visible the true scenarios behind a maternal death: Preconception risk factors and Specific Action Protocols

The predictive value of thromboelastography, routine blood indices, ultrasound parameters, and placental thickness in determining fetal outcome.

To evaluate the predictive value of thromboelastography, routine blood indices, ultrasound measurements, and placental thickness for fetal outcome. A retrospective analysis of 218 expectant mothers at our hospital from April 2020 to June 2022 was conducted. Mothers were classified into favorable (n=164) and adverse (n=54) fetal outcome groups. We compared thromboelastography, blood counts, and ultrasound parameters, including placental thickness, between the two groups. Predictive models using lasso regression were developed for individual assessment type and their combinations. Model efficacies were evaluated by ROC curves and Delong's test. Thromboelastography indicated significantly higher values of R (P=0.004), Angle (P<0.001), and MA (P=0.002) while notably lower K (P<0.001) in the adverse outcome group compared to the favorable outcome group. Peripheral blood analysis showed elevated levels of WBC (P<0.001), CRP (P=0.001), and PLR (P<0.001) in the adverse outcome group. Ultrasound assessments revealed significant increases in S/D (P<0.001), PI (P=0.016), RI (P<0.001), and placental thickness (P<0.001) in the adverse outcome group. The areas under the curve (AUCs) for the thromboelastography (4 features), peripheral blood indices (3 features), ultrasound parameters (4 features), and combined index model (11 features) were 0.774, 0.779, 0.961, and 0.978, respectively. Delong's test indicated that the combined model's AUC did not significantly differ from that of the ultrasound parameters (P>0.05) but was superior to the models based on thromboelastography, peripheral blood indices, and placental thickness alone (P<0.001). This study underscores the unparalleled predictive value of ultrasound metrics in identifying the risk of adverse pregnancy outcomes, highlighting their critical role in prenatal risk assessment and monitoring frameworks.

Regulatory T cell homing and activation is a signature of neonatal sepsis.

Regulatory T cells (Treg) play a prominent role in utero tolerating non-inherited maternal antigens and in regulating immune responses against pathogens at birth. This study investigates Treg immunity in newborns in West Africa, where sepsis remains a major public health problem. Treg phenotypes on neonates subgroups with early-onset sepsis (EOS), presumed sepsis, and healthy newborn with and without prenatal risk factors were evaluated. Treg phenotypes varied according to prenatal conditions, with increase in Treg frequency and Foxp3 expression in healthy newborns with prenatal risk factors compared to those with none risk. Compared to healthy newborns with prenatal risk factors, EOS neonates had a significantly reduced frequency of Treg and Foxp3 expression. In the Treg pool, higher frequency of activated Treg was observed in EOS neonates, suggesting an in-utero activation upstream of the sepsis onset. Their migration to the infection site may explain the reduced frequency of circulating Integrin α4β1+ Treg suggestive of homing to the endothelial tissue. EOS neonates show increases expression of CTLA-4, PD-1 and CD39 on Treg, which negatively regulate the activation of effector T cells (Teff) corroborating by the lower frequency of Teff in EOS neonates. The higher frequency of CD39+ Treg and the lower frequency of integrinα4β1+ Treg in EOS non-survivor suggests that Treg exhaustement and endothelial homing are associated with outcome severity. Neonates developing EOS are born with an altered Treg phenotypic profile. Treg expression of CTLA-4, PD-1, CD39, and integrinα4β1 cell markers can be considered as early warning or diagnostic markers of EOS.