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The Journal of Maternal-fetal &... Dec 2024It is currently unknown whether adjunctive azithromycin prophylaxis at the time of non-elective cesarean has differential effects on neonatal outcomes in the context of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
It is currently unknown whether adjunctive azithromycin prophylaxis at the time of non-elective cesarean has differential effects on neonatal outcomes in the context of prematurity. The objective of this study was to compare whether neonatal outcomes differ in term and preterm infants exposed to adjunctive azithromycin prophylaxis before non-elective cesarean delivery.
STUDY DESIGN
A planned secondary analysis of a multi-center randomized controlled trial that enrolled women with singleton pregnancies ≥24 weeks gestation undergoing non-elective cesarean delivery (during labor or ≥4 h after membrane rupture). Women received standard antibiotic prophylaxis and were randomized to either adjunctive azithromycin (500 mg) or placebo. The primary composite outcome was neonatal death, suspected or confirmed neonatal sepsis, and serious neonatal morbidities (NEC, PVL, IVH, BPD). Secondary outcomes included NICU admission, neonatal readmission, culture positive infections and prevalence of resistant organisms. Odds ratios (OR) for the effect of azithromycin versus placebo were compared between gestational age strata (preterm [less than 37 weeks] versus term [37 weeks or greater]). Tests of interaction examined homogeneity of treatment effect with gestational age.
RESULTS
The analysis includes 2,013 infants, 226 preterm (11.2%) and 1,787 term. Mean gestational ages were 34 and 39.5 weeks, respectively. Within term and preterm strata, maternal and delivery characteristics were similar between the azithromycin and placebo groups. There was no difference in the odds of composite neonatal outcome between those exposed to azithromycin versus placebo in preterm neonates (OR 0.82, 95% CI 0.48-1.41) and in term neonates (OR 1.06, 95% CI 0.77-1.46), with no difference between gestational age strata ( = 0.42). Analysis of secondary outcomes also revealed no differences in treatment effects within or between gestational age strata.
CONCLUSION
Exposure to adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery does not increase neonatal morbidity or mortality in term or preterm infants.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov, NCT01235546.
Topics: Humans; Azithromycin; Female; Antibiotic Prophylaxis; Infant, Newborn; Pregnancy; Cesarean Section; Anti-Bacterial Agents; Infant, Premature; Adult; Gestational Age; Term Birth; Infant, Newborn, Diseases
PubMed: 38873885
DOI: 10.1080/14767058.2024.2367082 -
Extracellular Vesicle Jun 2024Pregnant women and their fetuses are often excluded from clinical trials due to missing drug-related pre-clinical trial information at the human feto-maternal interface...
Pregnant women and their fetuses are often excluded from clinical trials due to missing drug-related pre-clinical trial information at the human feto-maternal interface (FMi). The two interfaces-placenta/decidua and fetal membranes/decidua are gatekeepers of drug transport; however, testing their functions is impractical during pregnancy. Limitations of current / models have hampered drug development and testing during pregnancy. Hence, major complications like preterm births and maternal and neonatal mortalities remain high. Advancements in organ-on-chip (OOC) platforms to test drug kinetics and efficacy and novel extracellular vesicle-based fetal drug delivery are expected to accelerate preclinical trials related to pregnancy complications. Here we report the development and testing of a humanized multi-organ fetal membrane/placenta (fetal)-decidua (maternal) interface OOC (FMi-PLA-OOC) that contains seven cell types interconnected through microchannels to maintain intercellular interactions as seen . Cytotoxicity, propagation, mechanism of action, and efficacy of engineered extracellular vesicles containing anti-inflammatory interleukin (IL)-10 (eIL-10) were evaluated to reduce FMi inflammation associated with preterm birth. A healthy and disease model (lipopolysaccharide-infectious inflammation) of the FMi-PLA-OOC was created and co-treated with eIL-10. eIL-10 propagated from the maternal to fetal side within 72-hours, localized in all cell types, showed no cytotoxicity, activated IL-10 signaling pathways, and reduced lipopolysaccharide-induced inflammation (minimized NF-kB activation and proinflammatory cytokine production). These data recapitulated eIL-10s' ability to reduce inflammation and delay infection-associated preterm birth in mouse models, suggesting FMi-PLA-OOC as an alternative approach to using animal models. Additionally, we report the utility of eIL-10 that can traverse through FMis to reduce inflammation-associated pregnancy complications.
PubMed: 38872854
DOI: 10.1016/j.vesic.2024.100035 -
PloS One 2024Human milk is optimal for infant nutrition. However, many mothers cease breastfeeding because of low milk supply (LMS). It is difficult to identify mothers at risk for...
Human milk is optimal for infant nutrition. However, many mothers cease breastfeeding because of low milk supply (LMS). It is difficult to identify mothers at risk for LMS because its biologic underpinnings are not fully understood. Previously, we demonstrated that milk micro-ribonucleic acids (miRNAs) may be related to LMS. Transforming growth factor beta (TGFβ) also plays an important role in mammary involution and may contribute to LMS. We performed a longitudinal cohort study of 139 breastfeeding mothers to test the hypothesis that milk levels of TGFβ would identify mothers with LMS. We explored whether TGFβ impacts the expression of LMS-related miRNAs in cultured human mammary epithelial cells (HMECs). LMS was defined by maternal report of inadequate milk production, and confirmed by age of formula introduction and infant weight trajectory. Levels of TGF-β1 and TGF-β2 were measured one month after delivery. There was a significant relationship between levels of TGF-β1 and LMS (X2 = 8.92, p = 0.003) on logistic regression analysis, while controlling for lactation stage (X2 = 1.28, p = 0.25), maternal pre-pregnancy body mass index (X2 = 0.038, p = 0.84), and previous breastfeeding experience (X2 = 7.43, p = 0.006). The model accounted for 16.8% of variance in the data (p = 0.005) and correctly predicted LMS for 84.6% of mothers (22/26; AUC = 0.72). Interactions between TGF-β1 and miR-22-3p displayed significant effect on LMS status (Z = 2.67, p = 0.008). Further, incubation of HMECs with TGF-β1 significantly reduced mammary cell number (t = -4.23, p = 0.003) and increased levels of miR-22-3p (t = 3.861, p = 0.008). Interactions between TGF-β1 and miR-22-3p may impact mammary function and milk levels of TGF-β1 could have clinical utility for identifying mothers with LMS. Such information could be used to provide early, targeted lactation support.
Topics: Humans; Female; Milk, Human; Transforming Growth Factor beta1; MicroRNAs; Adult; Breast Feeding; Lactation; Transforming Growth Factor beta2; Longitudinal Studies; Epithelial Cells; Infant; Mothers; Infant, Newborn; Mammary Glands, Human
PubMed: 38870243
DOI: 10.1371/journal.pone.0305421 -
JAMA Network Open Jun 2024Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders.
IMPORTANCE
Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders.
OBJECTIVE
To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management.
DESIGN, SETTING, AND PARTICIPANTS
This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022.
EXPOSURES
BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed.
MAIN OUTCOME AND MEASURES
Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables.
RESULTS
A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia.
CONCLUSIONS AND RELEVANCE
This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.
Topics: Humans; Female; Adult; Pregnancy; Pre-Eclampsia; Early Diagnosis; Quality Improvement; Patient Readmission; Postpartum Period; Hypertension; Infant, Newborn; Puerperal Disorders
PubMed: 38869897
DOI: 10.1001/jamanetworkopen.2024.16844 -
Croatian Medical Journal Jun 2024To determine the attitudes of pregnant couples toward carrier screening genomic tests.
AIM
To determine the attitudes of pregnant couples toward carrier screening genomic tests.
METHODS
A validated 22-item questionnaire was offered in person by medical staff to pregnant women ≥32 weeks' gestation and their partners attending prenatal classes from May to July 2014. The questionnaire inquired about demographic data, interest in various forms of genetic carrier screening tests, and genetic literacy.
RESULTS
Of 497 respondents, 69% expressed strong interest in carrier screening. The interested respondents exhibited substantial support for screening for common (82%) or all known genetic diseases (79%), as well as for treatable (79%) and untreatable diseases (85%). The majority of respondents believed that genetic test results could provide them with a sense of security but also provoke anxiety and fear. They were aware that these results could affect their perspective on life, work, and the atmosphere within their family, and acknowledged the potential effect on their relationship with their partner. However, none of these concerns diminished their desire to learn about their carrier status. Respondents with higher genetic literacy exhibited greater interest in screening tests (P=0.006). More non-religious respondents compared with practicing religious respondents (P=0.002), and more respondents with higher education compared with those with lower education, expressed interest in screening (P=0.003).
CONCLUSION
Most respondents expressed considerable interest in receiving information about their carrier status through genetic tests.
Topics: Humans; Female; Pregnancy; Adult; Surveys and Questionnaires; Genetic Testing; Male; Prenatal Diagnosis; Health Knowledge, Attitudes, Practice; Genetic Carrier Screening
PubMed: 38868965
DOI: 10.3325/cmj.2024.65.189 -
Croatian Medical Journal Jun 2024To develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing.
AIM
To develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing.
METHODS
We applied next generation sequencing (NGS) of maternal plasma to the non-invasive prenatal testing (NIPT) of autosomal recessive diseases, sickle cell disease and beta-thalassemia. Using the Illumina MiSeq, we sequenced plasma libraries obtained via a Twist Bioscience probe capture panel covering 4 Kb of chromosome 11, including the beta-globin (HBB) gene and >450 genomic single-nucleotide polymorphisms (SNPs) used to estimate the fetal fraction (FF). The FF is estimated by counting paternally transmitted allelic sequence reads present in the plasma but absent in the mother. We inferred fetal beta-globin genotypes by comparing the observed mutation (Mut) and reference (Ref) read ratios to those expected for the three possible fetal genotypes (Mut/Mut; Mut/Ref; Ref/Ref), based on the FF.
RESULTS
We bioinformatically enriched the FF by excluding reads over a specified length via in-silico size selection (ISS), favoring the shorter fetal reads, which increased fetal genotype prediction accuracy. Finally, we determined the parental HBB haplotypes, which allowed us to use the read ratios observed at linked SNPs to help predict the fetal genotype at the mutation site(s). We determined HBB haplotypes via Oxford Nanopore MinION sequencing of a 2.2 kb amplicon and aligned these sequences using Soft Genetics' NextGENe LR software.
CONCLUSION
The combined use of ISS and HBB haplotypes enabled us to correctly predict fetal genotypes in cases where the prediction based on variant read ratios alone was incorrect.
Topics: Humans; Female; Pregnancy; High-Throughput Nucleotide Sequencing; Haplotypes; Polymorphism, Single Nucleotide; Prenatal Diagnosis; beta-Thalassemia; Noninvasive Prenatal Testing; beta-Globins; Genotype; Hemoglobinopathies; Anemia, Sickle Cell
PubMed: 38868964
DOI: 10.3325/cmj.2024.65.180 -
Frontiers in Endocrinology 2024Polycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Polycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within the normal range may influence fetal growth. Our aim was to investigate whether maternal thyroid function is associated with newborn anthropometrics in PCOS and explore the potential modifying effect of metformin.
METHODS
analyses of two RCTs in which pregnant women with PCOS were randomized to metformin or placebo, from first trimester to delivery. Maternal serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at gestational weeks (gw) 5-12, 19, 32 and 36 in 309 singleton pregnancies. The mean z-scores of birthweight, birth length, and head circumference were estimated in the offspring. Associations of maternal thyroid parameters with offspring anthropometrics and the outcomes large for gestational age (LGA) and small for gestational age (SGA) were studied using linear and logistic regression models, with adjustment for body mass index (BMI) when relevant.
RESULTS
Maternal fT4 at baseline was negatively associated with birth length (b= -0.09, p=0.048). Furthermore, ΔfT4 during pregnancy correlated positively to z-score of both birth weight and length (b=0.10, p=0.017 and b=0.10, p=0.047 respectively), independently of treatment group. TSH at baseline and gw19 was inversely associated with LGA (OR 0.47, p=0.012 and OR 0.58, p=0.042), while ΔTSH was positively associated with LGA (OR 1.99, p=0.023). There were inverse associations between TSH at baseline and SGA (OR 0.32, p=0.005) and between ΔfT4 and SGA (OR 0.59, p=0.005) in the metformin group only. There were no associations between maternal thyroid function and head circumference of the newborns.
CONCLUSION
In women with PCOS, a higher maternal fT4 in early pregnancy and a greater decrease in fT4 during pregnancy was associated with a lower offspring birthweight and shorter birth length. Higher TSH by mid-gestation and smaller increase in TSH during pregnancy was associated with less risk of LGA. Subclinical variations in maternal thyroid function might play a role for birth anthropometrics of PCOS offspring.
Topics: Humans; Female; Polycystic Ovary Syndrome; Pregnancy; Adult; Infant, Newborn; Birth Weight; Metformin; Thyrotropin; Thyroid Gland; Thyroid Function Tests; Pregnancy Complications; Thyroxine; Infant, Small for Gestational Age; Pregnancy Outcome; Anthropometry; Hypoglycemic Agents; Male
PubMed: 38868742
DOI: 10.3389/fendo.2024.1388473 -
Journal of the Turkish German... Jun 2024In this study, maternal and neonatal outcomes of pregnant women with positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) RNA tests were evaluated...
OBJECTIVE
In this study, maternal and neonatal outcomes of pregnant women with positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) RNA tests were evaluated according to their symptomatic status. The clinical progression of SARS-CoV-2-positive pregnant women and the effect of coronavirus disease-2019 (COVID-19) on newborns was investigated.
MATERIAL AND METHODS
This retrospective cohort study was conducted at a tertiary pandemic hospital specializing in caring for pregnant women infected with SARS-CoV-2. We included patients with a positive SARS-CoV-2 polymerase chain reaction test at delivery, subdividing them into symptomatic and asymptomatic groups.
RESULTS
Two hundred and forty-nine patients were included in the study. The mean age of the pregnant women in the symptomatic group was higher than those in the asymptomatic group (p=0.001). The iatrogenic preterm birth rates in the symptomatic and asymptomatic groups were 43.37% and 8.43%, respectively (p<0.001). Cesarean section rate was higher in symptomatic group (p=0.01). Maternal death was significantly higher in symptomatic pregnant women (p<0.001). The neonatal intensive care unit admission rate was higher in symptomatic pregnant women (p<0.001).
CONCLUSION
The maternal and fetal outcomes for mothers with symptomatic infections tend to be worse, highlighting the importance of careful management, good follow-up and the advisability of closer monitoring.
PubMed: 38867711
DOI: 10.4274/jtgga.galenos.2024.2023-6-4