COVID-19 vaccination before or during pregnancy results in high, sustained maternal neutralizing activity to SARS-CoV-2 wild-type and Delta/Omicron variants of concern, particularly following a booster dose or infection.

OBJECTIVES: To investigate multi-dose and timings of COVID-19 vaccines in preventing antenatal infection. DESIGN: Prospective observational study investigating primary vaccinations, boosters, antenatal COVID-19 infections, neutralizing antibody (Nab) durability, and cross-reactivity to Delta and Omicron variants of concern (VOCs). RESULTS: Ninety-eight patients completed primary vaccination prepregnancy (29.6%) and antenatally (63.3%), 24.2% of whom had antenatal COVID-19, while 7.1% were unvaccinated (28.6% had antenatal COVID-19). None had severe COVID-19. Prepregnancy vaccination resulted in vaccination-to-infection delay of 23.3 weeks, which extended to 45.2 weeks with a booster, compared to 16.9 weeks following antenatal vaccination (P < 0.001). Infections occurred at 26.2 weeks gestation in women vaccinated prepregnancy compared to 36.2 weeks gestation in those vaccinated during pregnancy (P < 0.007). The risk of COVID-19 infection was higher without antenatal vaccination (hazard ratio [HR] 14.6, P = 0.05) and after prepregnancy vaccination without a booster (HR 10.4, P = 0.002). Antenatal vaccinations initially led to high Nab levels, with mild waning but subsequent rebound. Significant Nab enhancement occurred with a third-trimester booster. Maternal-neonatal Nab transfer was efficient (transfer ratio >1), and cross-reactivity to VOCs was observed. CONCLUSION: Completing vaccination during any trimester delays COVID-19 infection and maintains effective neutralizing activity throughout pregnancy, with robust cross-reactivity to VOCs and efficient maternal-neonatal transfer.

Embryo and fetal gene editing: Technical challenges and progress toward clinical applications.

Gene modification therapies (GMTs) are slowly but steadily making progress toward clinical application. As the majority of rare diseases have an identified genetic cause, and as rare diseases collectively affect 5% of the global population, it is increasingly important to devise gene correction strategies to address the root causes of the most devastating of these diseases and to provide access to these novel therapies to the most affected populations. The main barriers to providing greater access to GMTs continue to be the prohibitive cost of developing these novel drugs at clinically relevant doses, subtherapeutic effects, and toxicity related to the specific agents or high doses required. In vivo strategy and treating younger patients at an earlier course of their disease could lower these barriers. Although currently regarded as niche specialties, prenatal and preconception GMTs offer a robust solution to some of these barriers. Indeed, treating either the fetus or embryo benefits from economy of scale, targeting pre-pathological tissues in the fetus prior to full pathogenesis, or increasing the likelihood of complete tissue targeting by correcting pluripotent embryonic cells. Here, we review advances in embryo and fetal GMTs and discuss requirements for clinical application.

A scoping review of ChatGPT's role in healthcare education and research.

OBJECTIVES: To examine and consolidate literature regarding the advantages and disadvantages of utilizing ChatGPT in healthcare education and research. DESIGN/METHODS: We searched seven electronic databases (PubMed/Medline, CINAHL, Embase, PsycINFO, Scopus, ProQuest Dissertations and Theses Global, and Web of Science) from November 2022 until September 2023. This scoping review adhered to Arksey and O'Malley's framework and followed reporting guidelines outlined in the PRISMA-ScR checklist. For analysis, we employed Thomas and Harden's thematic synthesis framework. RESULTS: A total of 100 studies were included. An overarching theme, "Forging the Future: Bridging Theory and Integration of ChatGPT" emerged, accompanied by two main themes (1) Enhancing Healthcare Education, Research, and Writing with ChatGPT, (2) Controversies and Concerns about ChatGPT in Healthcare Education Research and Writing, and seven subthemes. CONCLUSIONS: Our review underscores the importance of acknowledging legitimate concerns related to the potential misuse of ChatGPT such as 'ChatGPT hallucinations', its limited understanding of specialized healthcare knowledge, its impact on teaching methods and assessments, confidentiality and security risks, and the controversial practice of crediting it as a co-author on scientific papers, among other considerations. Furthermore, our review also recognizes the urgency of establishing timely guidelines and regulations, along with the active engagement of relevant stakeholders, to ensure the responsible and safe implementation of ChatGPT's capabilities. We advocate for the use of cross-verification techniques to enhance the precision and reliability of generated content, the adaptation of higher education curricula to incorporate ChatGPT's potential, educators' need to familiarize themselves with the technology to improve their literacy and teaching approaches, and the development of innovative methods to detect ChatGPT usage. Furthermore, data protection measures should be prioritized when employing ChatGPT, and transparent reporting becomes crucial when integrating ChatGPT into academic writing.

Chorioamnionitis: An Update on Diagnostic Evaluation.

Chorioamnionitis remains a major cause of preterm birth and maternal and neonatal morbidity. We reviewed the current evidence for the diagnostic tests of chorioamnionitis and how this relates to clinical practice today. A comprehensive literature search and review was conducted on chorioamnionitis and intra-uterine inflammation. Data from randomized control trials and systematic reviews were prioritized. This review highlights that sterile inflammation plays an important role in chorioamnionitis and that the current tests for chorioamnionitis including clinical criteria, maternal plasma and vaginal biomarkers lack diagnostic accuracy. Concerningly, these tests often rely on detecting an inflammatory response after damage has occurred to the fetus. Care should be taken when interpreting current investigations for the diagnosis of chorioamnionitis and how they guide obstetric/neonatal management. There is an urgent need for further validation of current diagnostic tests and the development of novel, accurate, minimally invasive tests that detect subclinical intra-uterine inflammation.

Maternal dendritic cells influence fetal allograft response following murine in-utero hematopoietic stem cell transplantation.

BACKGROUND: Intrauterine hematopoietic stem cell transplantation (IUT), potentially curative in congenital haematological disease, is often inhibited by deleterious immune responses to donor cells resulting in subtherapeutic donor cell chimerism (DCC). Microchimerism of maternal immune cells (MMc) trafficked into transplanted recipients across the placenta may directly influence donor-specific alloresponsiveness, limiting DCC. We hypothesized that dendritic cells (DC) among trafficked MMc influence the development of tolerogenic or immunogenic responses towards donor cells, and investigated if maternal DC-depletion reduced recipient alloresponsiveness and enhanced DCC. METHODS: Using transgenic CD11c.DTR (C57BL/6) female mice enabled transient maternal DC-depletion with a single dose of diphtheria toxin (DT). CD11c.DTR females and BALB/c males were cross-mated, producing hybrid pups. IUT was performed at E14 following maternal DT administration 24 h prior. Bone marrow-derived mononuclear cells were transplanted, obtained from semi-allogenic BALB/c (paternal-derived; pIUT), C57BL/6 (maternal-derived; mIUT), or fully allogenic (aIUT) C3H donor mice. Recipient F1 pups were analyzed for DCC, while maternal and IUT-recipient immune cell profile and reactivity were examined via mixed lymphocyte reactivity functional assays. T- and B-cell receptor repertoire diversity in maternal and recipient cells were examined following donor cell exposure. RESULTS: DCC was highest and MMc was lowest following pIUT. In contrast, aIUT recipients had the lowest DCC and the highest MMc. In groups that were not DC-depleted, maternal cells trafficked post-IUT displayed reduced TCR & BCR clonotype diversity, while clonotype diversity was restored when dams were DC-depleted. Additionally, recipients displayed increased expression of regulatory T-cells and immune-inhibitory proteins, with reduced proinflammatory cytokine and donor-specific antibody production. DC-depletion did not impact initial donor chimerism. Postnatal transplantation without immunosuppression of paternal donor cells did not increase DCC in pIUT recipients; however there were no donor-specific antibody production or immune cell changes. CONCLUSIONS: Though maternal DC depletion did not improve DCC, we show for the first time that MMc influences donor-specific alloresponsiveness, possibly by expanding alloreactive clonotypes, and depleting maternal DC promotes and maintains acquired tolerance to donor cells independent of DCC, presenting a novel approach to enhancing donor cell tolerance following IUT. This may have value when planning repeat HSC transplantations to treat haemoglobinopathies.

ChatGPT outscored human candidates in a virtual objective structured clinical examination in obstetrics and gynecology.

BACKGROUND: Natural language processing is a form of artificial intelligence that allows human users to interface with a machine without using complex codes. The ability of natural language processing systems, such as ChatGPT, to successfully engage with healthcare systems requiring fluid reasoning, specialist data interpretation, and empathetic communication in an unfamiliar and evolving environment is poorly studied. This study investigated whether the ChatGPT interface could engage with and complete a mock objective structured clinical examination simulating assessment for membership of the Royal College of Obstetricians and Gynaecologists. OBJECTIVE: This study aimed to determine whether ChatGPT, without additional training, would achieve a score at least equivalent to that achieved by human candidates who sat for virtual objective structured clinical examinations in Singapore. STUDY DESIGN: This study was conducted in 2 phases. In the first phase, a total of 7 structured discussion questions were selected from 2 historical cohorts (cohorts A and B) of objective structured clinical examination questions. ChatGPT was examined using these questions and responses recorded in a script. Of note, 2 human candidates (acting as anonymizers) were examined on the same questions using videoconferencing, and their responses were transcribed verbatim into written scripts. The 3 sets of response scripts were mixed, and each set was allocated to 1 of 3 human actors. In the second phase, actors were used to presenting these scripts to examiners in response to the same examination questions. These responses were blind scored by 14 qualified examiners. ChatGPT scores were unblinded and compared with historical human candidate performance scores. RESULTS: The average score given to ChatGPT by 14 examiners was 77.2%. The average historical human score (n=26 candidates) was 73.7 %. ChatGPT demonstrated sizable performance improvements over the average human candidate in several subject domains. The median time taken for ChatGPT to complete each station was 2.54 minutes, well before the 10 minutes allowed. CONCLUSION: ChatGPT generated factually accurate and contextually relevant structured discussion answers to complex and evolving clinical questions based on unfamiliar settings within a very short period. ChatGPT outperformed human candidates in several knowledge areas. Not all examiners were able to discern between human and ChatGPT responses. Our data highlight the emergent ability of natural language processing models to demonstrate fluid reasoning in unfamiliar environments and successfully compete with human candidates that have undergone extensive specialist training.

Gene modification therapies for hereditary diseases in the fetus.

Proof-of-principle disease models have demonstrated the feasibility of an intrauterine gene modification therapy (in utero gene therapy (IUGT)) approach to hereditary diseases as diverse as coagulation disorders, haemoglobinopathies, neurogenetic disorders, congenital metabolic, and pulmonary diseases. Gene addition, which requires the delivery of an integrating or episomal transgene to the target cell nucleus to be transcribed, and gene editing, where the mutation is corrected within the gene of origin, have both been used successfully to increase normal protein production in a bid to reverse or arrest pathology in utero. While most experimental models have employed lentiviral, adenoviral, and adeno-associated viral vectors engineered to efficiently enter target cells, newer models have also demonstrated the applicability of non-viral lipid nanoparticles. Amelioration of pathology is dependent primarily on achieving sustained therapeutic transgene expression, silencing of transgene expression, production of neutralising antibodies, the dilutional effect of the recipient's growth on the mass of transduced cells, and the degree of pre-existing cellular damage. Safety assessment of any IUGT strategy will require long-term postnatal surveillance of both the fetal recipient and the maternal bystander for cell and genome toxicity, oncogenic potential, immune-responsiveness, and germline mutation. In this review, we discuss advances in the field and the push toward clinical translation of IUGT.

The dependency of fetal left ventricular biomechanics function on myocardium helix angle configuration.

The helix angle configuration of the myocardium is understood to contribute to the heart function, as finite element (FE) modeling of postnatal hearts showed that altered configurations affected cardiac function and biomechanics. However, similar investigations have not been done on the fetal heart. To address this, we performed image-based FE simulations of fetal left ventricles (LV) over a range of helix angle configurations, assuming a linear variation of helix angles from epicardium to endocardium. Results showed that helix angles have substantial influence on peak myofiber stress, cardiac stroke work, myocardial deformational burden, and spatial variability of myocardial strain. A good match between LV myocardial strains from FE simulations to those measured from 4D fetal echo images could only be obtained if the transmural variation of helix angle was generally between 110 and 130°, suggesting that this was the physiological range. Experimentally discovered helix angle configurations from the literature were found to produce high peak myofiber stress, high cardiac stroke work, and a low myocardial deformational burden, but did not coincide with configurations that would optimize these characteristics. This may suggest that the fetal development of myocyte orientations depends concurrently on several factors rather than a single factor. We further found that the shape, rather than the size of the LV, determined the manner at which helix angles influenced these characteristics, as this influence changed significantly when the LV shape was varied, but not when a heart was scaled from fetal to adult size while retaining the same shape. This may suggest that biomechanical optimality would be affected during diseases that altered the geometric shape of the LV.

Monkeypox in pregnancy: virology, clinical presentation, and obstetric management.

The 2022 monkeypox outbreak, caused by the zoonotic monkeypox virus, has spread across 6 World Health Organization regions (the Americas, Africa, Europe, Eastern Mediterranean, Western Pacific, and South-East Asia) and was declared a public health emergency of international concern on July 23, 2022. The global situation is especially concerning given the atypically high rate of person-to-person transmission, which suggests viral evolution to an established human pathogen. Pregnant women are at heightened risk of vertical transmission of the monkeypox virus because of immune vulnerability and natural depletion of population immunity to smallpox among reproductive-age women, and because orthopoxviral cell entry mechanisms can overcome the typically viral-resistant syncytiotrophoblast barrier within the placenta. Data on pregnancy outcomes following monkeypox infection are scarce but include reports of miscarriage, intrauterine demise, preterm birth, and congenital infection. This article forecasts the issues that maternity units might face and proposes guidelines to protect the health of pregnant women and fetuses exposed to the monkeypox virus. We review the pathophysiology and clinical features of monkeypox infection and discuss the obstetrical implications of the unusually high prevalence of anogenital lesions. We describe the use of real-time polymerase chain reaction tests from mucocutaneous and oropharyngeal sites to confirm infection, and share an algorithm for the antenatal management of pregnant women with monkeypox virus exposure. On the basis of the best available knowledge from prenatal orthopoxvirus infections, we discuss the sonographic features of congenital monkeypox and the role of invasive testing in establishing fetal infection. We suggest a protocol for cesarean delivery to avoid the horizontal transmission of the monkeypox virus at birth and address the controversy of mother-infant separation in the postpartum period. Obstetrical concerns related to antiviral therapy with tecovirimat and vaccinia immune globulin are highlighted, including the risks of heart rate-corrected QT-interval prolongation, inaccuracies in blood glucose monitoring, and the predisposition to iatrogenic venous thromboembolism. The possibility of monkeypox vaccine hesitancy during pregnancy is discussed, and strategies are offered to mitigate these risks. Finally, we conclude with a research proposal to address knowledge gaps related to the impact of monkeypox infection on maternal, fetal, and neonatal health.

Mentoring a surgical team towards procedural competence in the early learning curve for selective fetoscopic laser photocoagulation.

INTRODUCTION: Selective fetoscopic laser photocoagulation (SFLP) for twin-to-twin transfusion syndrome (TTTS) is challenging for new surgeons at the start of their learning curve. We described an approach utilising telementoring and team-based training to facilitate rapid attainment of the skills required for safe and efficient practice with a limited caseload. METHODS: We conducted a prospective observational study of SFLP performed by the novice primary surgical team in three stages: under direct on-site supervision from an expert mentor (Group 1), with remote tele-guidance from that mentor (Group 2) and independently (Group 3), at an academic tertiary hospital in Singapore. The primary team undertook regular training on high-fidelity tissue models to accelerate skills acquisition and complement the surgical performance. RESULTS: 9 patients diagnosed with Stage 2 TTTS were assessed for procedural characteristics, surgical outcomes and perinatal survival following SFLP. There were no significant differences in operative duration, anastomoses ablated, gestational age or birth weight at delivery. The complications observed were: recurrent TTTS (22.2% of pregnancies), twin anaemia polycythaemia sequence (33.3%), preterm prelabour membrane rupture (22.2%) and delivery at < 32 weeks (44.4%). ≥ 1 twin was live-born in 88.9% of cases, while postnatal survival to six months of ≥ 1 twin occurred in 77.8% of cases. CONCLUSION: Systematic mentoring and specialised skills training are useful in aiding new surgeons to negotiate the steep learning curve and achieve good outcomes at the start of a new practice, particularly in the setting of low patient numbers. This is best paired with dedicated model training to achieve and maintain surgical dexterity for this complex procedure.

Interpreting the role of nuchal fold for fetal growth restriction prediction using machine learning.

The objective of the study is to investigate the effect of Nuchal Fold (NF) in predicting Fetal Growth Restriction (FGR) using machine learning (ML), to explain the model's results using model-agnostic interpretable techniques, and to compare the results with clinical guidelines. This study used second-trimester ultrasound biometry and Doppler velocimetry were used to construct six FGR (birthweight < 3rd centile) ML models. Interpretability analysis was conducted using Accumulated Local Effects (ALE) and Shapley Additive Explanations (SHAP). The results were compared with clinical guidelines based on the most optimal model. Support Vector Machine (SVM) exhibited the most consistent performance in FGR prediction. SHAP showed that the top contributors to identify FGR were Abdominal Circumference (AC), NF, Uterine RI (Ut RI), and Uterine PI (Ut PI). ALE showed that the cutoff values of Ut RI, Ut PI, and AC in differentiating FGR from normal were comparable with clinical guidelines (Errors between model and clinical; Ut RI: 15%, Ut PI: 8%, and AC: 11%). The cutoff value for NF to differentiate between healthy and FGR is 5.4 mm, where low NF may indicate FGR. The SVM model is the most stable in FGR prediction. ALE can be a potential tool to identify a cutoff value for novel parameters to differentiate between healthy and FGR.

Ethical considerations of preconception and prenatal gene modification in the embryo and fetus.

The National Academies of Sciences and Medicine 2020 consensus statement advocates the reinstatement of research in preconception heritable human genome editing (HHGE), despite the ethical concerns that have been voiced about interventions in the germline, and outlines criteria for its eventual clinical application to address monogenic disorders. However, the statement does not give adequate consideration to alternative technologies. Importantly, it omits comparison to fetal gene therapy (FGT), which involves gene modification applied prenatally to the developing fetus and which is better researched and less ethically contentious. While both technologies are applicable to the same monogenic diseases causing significant prenatal or early childhood morbidity, the benefits and risks of HHGE are distinct from FGT though there are important overlaps. FGT has the current advantage of a wealth of robust preclinical data, while HHGE is nascent technology and its feasibility for specific diseases still requires scientific proof. The ethical concerns surrounding each are unique and deserving of further discussion, as there are compelling arguments supporting research and eventual clinical translation of both technologies. In this Opinion, we consider HHGE and FGT through technical and ethical lenses, applying common ethical principles to provide a sense of their feasibility and acceptability. Currently, FGT is in a more advanced position for clinical translation and may be less ethically contentious than HHGE, so it deserves to be considered as an alternative therapy in further discussions on HHGE implementation.

The Influence of Web-Based Tools on Maternal and Neonatal Outcomes in Pregnant Adolescents or Adolescent Mothers: Mixed Methods Systematic Review.

BACKGROUND: Pregnant adolescent women increasingly seek support during pregnancy and the puerperium through digital platforms instead of the traditional support system of family, friends, and the community. However, it is uncertain whether digital, web-based tools are reliable and effective in providing information to the user on a variety of topics such as fetal development, pregnancy outcomes, delivery, and breastfeeding to improve maternal and infant outcomes. OBJECTIVE: We aimed to identify web-based tools designed to promote knowledge, attitudes, and skills of pregnant adolescents or adolescent mothers and determine the efficacy of such web-based tools compared with conventional resources in promoting good pregnancy and infant outcomes. METHODS: A systematic search was conducted using Medline, Scopus, CINAHL, and PsycINFO for articles published from January 2004 to November 2020 to identify randomized trials and observational studies that evaluated digital, web-based platforms to deliver resources to pregnant adolescents. All articles written in the author's languages were included. Two authors independently reviewed abstracts and full-text articles for inclusion and assessed study quality. Risk of bias in each study was assessed using appropriate tools recommended by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) and the Joanna Briggs Institute. We adopted a qualitative synthesis and presented the results in a narrative format due to the heterogenous nature of the studies. RESULTS: Seven articles met the inclusion criteria and were analyzed. The majority of the studies were graded to be of low to moderate risk for bias. The research methodologies represented were varied, ranging from randomized (n=1) and nonrandomized controlled trials (n=1) and prospective cohort studies (n=1) to mixed methods studies (n=1) and longitudinal surveys (n=3). Four studies included active web-based interventions, and 3 described exposure to web-based tools, including the use of social media and/or other internet content. Web-based tools positively influenced treatment-seeking intentions (intervention 17.1%, control 11.5%, P=.003) and actual treatment-seeking behavior for depression among postpartum adolescents (intervention 14.1%, control 6.5%, P<.001). In contrast, readily available information on the internet may leave adolescents with increased anxiety. The critical difference lies in information curated by health care professionals specifically to address targeted concerns versus self-acquired data sourced from various websites. CONCLUSIONS: Despite almost universal web use, few studies have used this platform for health promotion and disease prevention. Social media interventions or web-based tools have the potential to positively influence both maternal and infant outcomes in adolescent pregnancy, but there is a need for more well-conducted studies to demonstrate the effectiveness of these support programs. The vastness of the information available on the web limits the ability of health care professionals to monitor or control sources of information sought by patients. Thus, it is important to create professionally curated platforms to prevent or limit exposure to potentially misleading or harmful information on the internet while imparting useful knowledge to the user. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020195854; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=195854.

A reasoned approach towards administering COVID-19 vaccines to pregnant women.

There are over 50 SARS-CoV-2 candidate vaccines undergoing Phase II and III clinical trials. Several vaccines have been approved by regulatory authorities and rolled out for use in different countries. Due to concerns of potential teratogenicity or adverse effect on maternal physiology, pregnancy has been a specific exclusion criterion for most vaccine trials with only two trials not excluding pregnant women. Thus, other than limited animal studies, gradually emerging development and reproductive toxicity data, and observational data from vaccine registries, there is a paucity of reliable information to guide recommendations for the safe vaccination of pregnant women. Pregnancy is a risk factor for severe COVID-19, especially in women with comorbidities, resulting in increased rates of preterm birth and maternal morbidity. We discuss the major SARS-CoV-2 vaccines, their mechanisms of action, efficacy, safety profile and possible benefits to the maternal-fetal dyad to create a rational approach towards maternal vaccination while anticipating and mitigating vaccine-related complications. Pregnant women with high exposure risks or co-morbidities predisposing to severe COVID-19 infection should be prioritised for vaccination. Those with risk factors for adverse effects should be counselled accordingly. It is essential to support patient autonomy by shared decision-making involving a risk-benefit discussion with the pregnant woman.

Mending a broken heart: In vitro, in vivo and in silico models of congenital heart disease.

Birth defects contribute to ∼0.3% of global infant mortality in the first month of life, and congenital heart disease (CHD) is the most common birth defect among newborns worldwide. Despite the significant impact on human health, most treatments available for this heterogenous group of disorders are palliative at best. For this reason, the complex process of cardiogenesis, governed by multiple interlinked and dose-dependent pathways, is well investigated. Tissue, animal and, more recently, computerized models of the developing heart have facilitated important discoveries that are helping us to understand the genetic, epigenetic and mechanobiological contributors to CHD aetiology. In this Review, we discuss the strengths and limitations of different models of normal and abnormal cardiogenesis, ranging from single-cell systems and 3D cardiac organoids, to small and large animals and organ-level computational models. These investigative tools have revealed a diversity of pathogenic mechanisms that contribute to CHD, including genetic pathways, epigenetic regulators and shear wall stresses, paving the way for new strategies for screening and non-surgical treatment of CHD. As we discuss in this Review, one of the most-valuable advances in recent years has been the creation of highly personalized platforms with which to study individual diseases in clinically relevant settings.

Maternal microchimerism and cell-mediated immune-modulation enhance engraftment following semi-allogenic intrauterine transplantation.

Successful intrauterine hematopoietic cell transplantation (IUT) for congenital hemoglobinopathies is hampered by maternal alloresponsiveness. We investigate these interactions in semi-allogenic murine IUT. E14 fetuses (B6 females × BALB/c males) were each treated with 5E+6 maternal (B6) or paternal (BALB/c) bone marrow cells and serially monitored for chimerism (>1% engraftment), trafficked maternal immune cells, and immune responsiveness to donor cells. A total of 41.0% of maternal IUT recipients (mIUT) were chimeras (mean donor chimerism 3.0 ± 1.3%) versus 75.0% of paternal IUT recipients (pIUT, 3.6 ± 1.1%). Chimeras showed higher maternal microchimerism of CD4, CD8, and CD19 than non-chimeras. These maternal cells showed minimal responsiveness to B6 or BALB/c stimulation. To interrogate tolerance, mIUT were injected postnatally with 5E+6 B6 cells/pup; pIUT received BALB/c cells. IUT-treated pups showed no changes in trafficked maternal or fetal immune cell levels compared to controls. Donor-specific IgM and IgG were expressed by 1%-3% of recipients. mIUT splenocytes showed greater proliferation of regulatory T cells (Treg) upon BALB/c stimulation, while B6 stimulation upregulated the pro-inflammatory cytokines more than BALB/c. pIUT splenocytes produced identical Treg and cytokine responses to BALB/c and B6 cells, with higher Treg activity and lower pro-inflammatory cytokine expression upon exposure to BALB/c. In contrast, naïve fetal splenocytes demonstrated greater alloresponsiveness to BALB/c compared to B6 cells. Thus pIUT, associated with increased maternal cell trafficking, modulates fetal Treg, and cytokine responsiveness to donor cells more efficiently than mIUT, resulting in improved engraftment. Paternal donor cells may be considered alternatively to maternal donor cells for intrauterine and postnatal transplantation to induce tolerance and maintain engraftment.