Transplacental Passage Research Articles

Gestational Pemphigoid-From Molecular Mechanisms to Clinical Outcomes: A Case Report and Review of Literature.

Gestational pemphigoid is a rare, autoimmune, subepidermal bullous disease with an incidence of 1 in 50,000 pregnancies, displaying itself through pruritic erythema and urticarial papules and plaques that evolve into tense bullae. Histopathological findings consist of subepidermal vesicles with perivascular eosinophils and lymphocytes, and direct immunofluorescence reveals C3 complement and, more rarely, IgG in a linear band along the basement membrane. The course is usually self-limiting within 6 months after delivery but, later, can be triggered by subsequent pregnancies, menstruation, or treatment with oral contraceptives. The newborn can be affected due to the transplacental passage of the maternal immunoglobulins, but, usually, less than 10% of newborns will develop lesions similar to pemphigoid gestationis. The diagnosis and management pose a difficult challenge and should be guided by the severity of the disease. We, therefore, provide a short literature review and discussion plus a case from our clinic, with a typical presentation but a delayed diagnosis and an undulating evolution, with severe manifestations and particularly difficult management due to unexpected complications.

Alloimmunization in Pregnancy: Implications for the Fetus and Neonate.

Blood group or red cell alloimmunization occurs when a pregnant patient has produced antibodies to a blood group antigen possessed by the fetus and not possessed by the pregnant patient. Maternal antibodies are usually produced as an immune response to fetal-maternal bleeding or blood product transfusion. Prevention remains the most important strategy to avoid the formation of maternal antibodies or alloimmunization. Maternal alloimmunization may result in transplacental passage of these antibodies into the fetal circulation and the potential for fetal or neonatal hemolysis and anemia. Red cell alloimmunization can result in significant perinatal morbidity and mortality. Management of alloimmunization in pregnant patients should be protocol-driven. Current strategies for assessment and therapies allow for more thorough and less invasive management with risks to mother and fetus.

Targeted lipid nanoparticles to prevent trans-placental passage in the ex vivo human placental cotyledon perfusion model.

Medication use during pregnancy poses risks to both the mother and the fetus. These risks include an elevated potential for fetotoxicity due to placental drug transport. Nanomedicines offer a promising solution by potentially preventing trans-placental passage. Targeted nanomedicines could enhance safety and efficacy in treating maternal or placental pathophysiology. Our study investigates placental transfer kinetics of targeted lipid nanoparticles (LNPs) in an ex vivo human placenta cotyledon perfusion model. We collected human placentas for dual-side ex vivo placental perfusions. Targeted LNPs with a fluorescence tag were introduced into the maternal circuit of each placenta. To establish if there was trans-placental passage of LNPs to the fetal circuit, we collected samples from maternal and fetal circuits throughout the six hours of the perfusion. We determined the fluorescence signal using a multi-mode microplate reader and Multiphoton microscopy to localize the LNPs in the placenta tissue. Data from perfused placenta tissue showed no significant transfer of the fluorescently labeled LNPs across the placental barrier to the fetal circuit. Localization of targeted LNPs in tissue samples is mainly observed in the maternal blood space of the placenta. Our results suggest that targeted LNPs present a promising strategic approach to prevent trans-placental passage to the fetus. Our future perspectives involve investigating the efficacy of targeted LNPs as well as loading targeted LNPs with nucleic acid-based therapeutics to investigate their therapeutic potential.

Neonatal Hyperthyroidism: Case Report and Literature Review

The onset of Graves' disease during pregnancy exposes the newborn to the risk of neonatal hyperthyroidism due to the transplacental passage of anti-thyroid-stimulating hormone (TSH) receptor antibodies. We report the case of a child whose mother was diagnosed with Graves' disease during pregnancy. Clinical hyperthyroidism appeared only a few days after birth and was confirmed by hormonal tests. Thanks to treatment with synthetic antithyroid drugs, the child's clinical and biological course was favorable. It is essential to systematically screen for neonatal hyperthyroidism in newborns of mothers with Graves' disease, as the absence of immediate clinical signs after birth does not rule out the diagnosis. The pediatrician must be aware of this thyroid condition even in the absence of an identified maternal history, in order to enable rapid therapeutic management.

Genital Dysbiosis and Different Systemic Immune Responses Based on the Trimester of Pregnancy in SARS-CoV-2 Infection.

Respiratory infections are common in pregnancy with conflicting evidence supporting their association with neonatal congenital anomalies, especially during the first trimester. We profiled cytokine and chemokine systemic responses in 242 pregnant women and their newborns after SARS-CoV-2 infection, acquired in different trimesters. Also, we tested transplacental IgG passage and maternal vaginal-rectal microbiomes. IgG transplacental passage was evident, especially with infection acquired in the first trimester. G-CSF concentration-involved in immune cell recruitment-decreased in infected women compared to uninfected ones: a beneficial event for the reduction of inflammation but detrimental to ability to fight infections at birth. The later the infection was acquired, the higher the systemic concentration of IL-8, IP-10, and MCP-1, associated with COVID-19 disease severity. All infected women showed dysbiosis of vaginal and rectal microbiomes, compared to uninfected ones. Two newborns tested positive for SARS-CoV-2 within the first 48 h of life. Notably, their mothers had acute infection at delivery. Although respiratory infections in pregnancy are reported to affect babies' health, with SARS-CoV-2 acquired early during gestation this risk seems low because of the maternal immune response. The observed vaginal and rectal dysbiosis could be relevant for neonatal microbiome establishment, although in our series immediate neonatal outcomes were reassuring.

Prevalence of neonatal lupus in a small group of antibody-carrying mothers and frequency of complete atrioventricular block.

Neonatal lupus (NL) is extremely rare and is caused by the transplacental passage of maternal IgG autoantibodies against Ro, La, and/or RNP proteins into the fetal circulation, which can cause congenital complete atrioventricular block (CCAB), permanent skin lesions, and liver involvement. To know the prevalence of NL in patients with CCAB and the clinical course in long-term follow-up. From January 1992 to December 2017, patients with CCAB were included. The presence of anti-SSA/Ro and anti-SSB/La antinuclear antibodies in maternal serum confirmed NL. Eight patients were included with a follow-up of 10 ± 6 years; NL was concluded in 62.5%; two were male. One of them was diagnosed in utero, two at birth, and a pacemaker was implanted in them, one at 12 years of age and another at 15. The other two cases were diagnosed at 18 and 26 years of age, and permanent pacemakers were implanted 8 and 5 years later, respectively. In one case, a definitive pacemaker was not implanted in a newborn with only 1 year of follow-up. At delivery, 60% of the mothers were free of rheumatic disease, and altogether, they all had 19 children; none of them presented NL manifestations. CCAB is rare and frequently associated with a maternal autoimmune disease, practically all of them will require a definitive pacemaker at some point in their lives.

Forecasting Fetal Buprenorphine Exposure through Maternal-Fetal Physiologically Based Pharmacokinetic Modeling.

Buprenorphine readily crosses the placenta, and with greater prenatal exposure, neonatal opioid withdrawal syndrome (NOWS) likely grows more severe. Current dosing strategies can be further improved by tailoring doses to expected NOWS severity. To allow the conceptualization of fetal buprenorphine exposure, a maternal-fetal physiologically based pharmacokinetic (PBPK) model for sublingual buprenorphine was developed using Simcyp (v21.0). Buprenorphine transplacental passage was predicted from its physicochemical properties. The maternal-fetal PBPK model integrated reduced transmucosal absorption driven by lower salivary pH and induced metabolism observed during pregnancy. Maternal pharmacokinetics was adequately predicted in the second trimester, third trimester, and postpartum period, with the simulated area under the curve from 0 to 12 h, apparent clearance, and peak concentration falling within the 1.25-fold prediction error range. Following post hoc adjustment of the likely degree of individual maternal sublingual absorption, umbilical cord blood concentrations at delivery (n = 21) were adequately predicted, with a geometric mean ratio between predicted and observed fetal concentrations of 1.15 and with 95.2% falling within the 2-fold prediction error range. The maternal-fetal PBPK model developed in this study can be used to forecast fetal buprenorphine exposure and would be valuable to investigate its correlation to NOWS severity.

Trophoblast stem cell-based organoid models of the human placental barrier

Human placental villi have essential roles in producing hormones, mediating nutrient and waste exchange, and protecting the fetus from exposure to xenobiotics. Human trophoblast organoids that recapitulate the structure of villi could provide an important in vitro tool to understand placental development and the transplacental passage of xenobiotics. However, such organoids do not currently exist. Here we describe the generation of trophoblast organoids using human trophoblast stem (TS) cells. Following treatment with three kinds of culture medium, TS cells form spherical organoids with a single outer layer of syncytiotrophoblast (ST) cells that display a barrier function. Furthermore, we develop a column-type ST barrier model based on the culture condition of the trophoblast organoids. The bottom membrane of the column is almost entirely covered with syndecan 1-positive ST cells. The barrier integrity and maturation levels of the model are confirmed by measuring transepithelial/transendothelial electrical resistance (TEER) and the amount of human chorionic gonadotropin. Further analysis reveals that the model can be used to derive the apparent permeability coefficients of model compounds. In addition to providing a suite of tools for the study of placental development, our trophoblast models allow the evaluation of compound transfer and toxicity, which will facilitate drug development.

Impact of Antenatal SARS-CoV-2 Exposure on SARS-CoV-2 Neutralization Potency.

A pregnancy booster dose significantly reduces the risk and severity of COVID-19, and it is widely recommended. A prospective cohort study was conducted to compare the transplacental passage of maternal antibodies from vaccination or infection during three trimesters against both the vaccine-targeted Wuhan strain and the Omicron strain of SARS-CoV-2. Maternal-infant dyads from vaccinated mothers were collected between 6 June 2022 and 20 September 2022. We analyzed 38 maternal-infant dyads from mothers who had been infected with COVID-19 and 37 from mothers without any previous infection. Pregnant women who received their last COVID-19 vaccine dose in the third trimester exhibited the highest anti-spike protein antibody levels and neutralizing potency against both the Wuhan strain and Omicron BA.2 variant in their maternal and cord plasma. Both second- and third-trimester vaccination could lead to a higher level of neutralization against the Wuhan and Omicron strains. COVID-19 infection had a negative effect on the transplacental transfer ratio of SARS-CoV-2 antibodies. A booster dose during the second or third trimester is encouraged for the maximum transplacental transfer of humoral protection against COVID-19 for infants.

The Effects of General Anesthetics on the Developing Brain of Fetus

The Effects of General Anesthetics on the Developing Brain of Fetus

Transplacental migration of maternal natural killer and T cells assessed by ex vivo human placenta perfusion

IntroductionThe transplacental passage of cells between a mother and her fetus, known as microchimerism, is a less studied process during pregnancy. The frequency of maternal microchimeric cells in fetal tissues in physiological pregnancies and mechanisms responsible for transplacental cell trafficking are poorly understood. This study aimed to evaluate the placental trafficking of maternal peripheral blood mononuclear cells (PBMC) using human ex vivo placenta perfusion. MethodsTen placentas and maternal PBMC were obtained after healthy pregnancies. Flow cytometry was used to characterize PBMC subtypes. They showed a higher percentage of CD3+ T cells compared to CD56+ NK cells. The isolated PBMC were stained with a fluorescent dye and perfused through the maternal circuit of the placenta in an ex vivo perfusion system. Subsequent immunofluorescence staining for CD3+ T cells and CD56+ NK cells was performed on placental tissue sections, and the number of detectable PBMC in different tissue areas was counted using fluorescence microscopy. ResultsThe applied method allowed discrimination of perfused autologous maternal cells from cells resident in the placenta before perfusion. Further, it allows additional immunohistochemical labelling and distinction of immune cell subsets. Perfused PBMC were detected in all analyzed placentas, mostly in contact to the syncytiotrophoblast. CD3+ T cells were identified more frequently than CD56+ NK cells and some CD3+ T cells were found inside fetoplacental tissues and vasculature. The results indicate that also other PBMCs than T or NK cells adhere to or enter villous tissue, but they have not been specified in this analysis. DiscussionPrevious studies have detected maternal cells in the fetal circulation which we could mimick in our ex vivo placenta perfusion experiments with fluorescence labelled autologous maternal PBMC. The applied experimental settings did not allow comparison of transmigration abilities of PBMC subsets, but slight modifications of the model will permit further studies of cell transfer processes and microchimerism in pregnancy.

1618. Assessing and Improving Accurate Diagnosis and Reporting of Congenital Syphilis in a Tertiary Care Children's Hospital

Abstract Background Congenital syphilis (CS) occurs due to transplacental passage of active infection to the fetus during pregnancy. Clinical presentation ranges from asymptomatic to severe permanent disability. Nationally, the incidence and prevalence of syphilis among cisgender females ages 15-44 have increased, with proportional increases in rates of CS. In 2020, 19 cases of CS were reported to the Chicago Department of Public Health (CDPH), a 138% increase from 2019 (8 cases). There are circumstances where infants with a non-reactive rapid plasma reagin (RPR-) may potentially contract syphilis in the context of inadequate maternal treatment per national guidelines. (Figure 1) Currently, only infants with RPR reactivity (RPR+) are reported to CDPH, potentially underestimating the true incidence. Our project sought to identify RPR- infants who received treatment to improve reporting to CDPH, more accurately reflect the prevalence of CS in Chicago, and ultimately guide interventions to reduce and eliminate CS.Figure 1:2021 Center for Disease Control (CDC) Possible Congenital Syphilis Definition Methods Data was collected via electronic medical record (EMR) review for infants born at Comer Children’s Hospital in Chicago, IL between 2012 and 2022, filtered using ICD-9 code (090) and ICD-10 code (A50.9) for CS. Infants were excluded if diagnosis code was used in error, there was no RPR result, or diagnosis occurred at an outside institution. (Figure 2) Infants were stratified as having CS with RPR+ or RPR-. Retrospectively, each infant was also classified with a diagnosis of less likely CS, possible CS, and proven CS per national guidelines.Figure 2:Patient Stratification by ICD-9 and ICD-10 Code for Congenital Syphilis and RPR Reactivity. RPR = Rapid Plasma Reagin Results 68 infants with CS were identified. 57 infants received IV PCN with diagnoses of proven or possible CS (84%). 51 (75%) patients were RPR+ and 17 (25%) were RPR-. (Figure 3) Of the 17 RPR-, 11 had a diagnosis of possible CS (65%) and received IV PCN while 6 (35%) had less likely CS and received one dose of intramuscular (IM) PCN (Table 1). None of the RPR- infants were reported to CDPH.Figure 3:Total Number of Congenital Syphilis Cases Based on CDC Definition. CS = Congenital Syphilis, CDC = Center for Disease ControlTable 1:Total Number of Days of Intravenous or Intramuscular Penicillin Administration per RPR reactivity.. Aq PCN = Aqueous Penicillin G, Ben PCN = Benzathine Penicillin G, IM = Intramuscular, IV = Intravenous Conclusion In this retrospective analysis, reporting CS based solely on a reactive infant RPR leads to underreporting. As we confront the rising incidence of CS, (Figure 4) it is critical that we have a complete understanding of the epidemiology which may lead to increased support for public health initiatives focused on decreasing and eliminating CS.Figure 4:Timeline of Total CS and RPR- CS Cases at Hospital per Year. CS = Congenital Syphilis Disclosures Allison H. Bartlett, MD, MS, CVS/Caremark: Honoraria Jessica Ridgway, MD, Gilead Sciences: Expert Testimony

Neonatal Abstinence Syndrome: An Insight Over Impact of Maternal Substance Use.

Neonatal abstinence syndrome (NAS) highlights the intricate interplay between maternal substance use during pregnancy and the challenges neonates face from the distressing global opioid crisis. This comprehensive review captures the multilayered landscape of NAS, encircling its underlying mechanisms, epidemiology, diagnostic intricacies, clinical manifestations, continuing developmental impacts, treatment paradigms, and the crucial role of multidisciplinary care. The core pathophysiology of NAS involves the transplacental passage of addictive substances, activating chemical dependence in the maturing fetus, which is characterized by neurotransmitter dysregulation, neuroadaptations, and receptor sensitization. A diverse clinical presentation ranges from central nervous system hyperactivity and autonomic dysregulation to gastrointestinal manifestations, necessitating homogenous assessment tools such as the Finnegan Neonatal Abstinence Scoring System. The demand for a multilayered approach is essential for comprehensive management, involving pharmacological interventions like morphine or methadone and non-pharmacological strategies such as swaddling. The complications of NAS are not only limited to but are also well beyond infancy, leading to behavioral, longstanding cognitive, and socioemotional consequences. Addressing these developmental arcs demands decisive longitudinal monitoring and early interventions. NAS management is fundamentally multidisciplinary, requiring the teamwork of nurses, social workers, psychologists, pediatricians, and neonatologists. Apart from the clinical realm, managing the psychosocial needs of families traversing NAS requires resources and empathy. A crucial comprehensive approach is essential to confront the challenges and limitations of NAS. From early identification and prevention to longstanding support through pharmacological, non-pharmacological, and psychological channels, it creates a holistic structure that emerges as the basis for understanding the complicated relationship between maternal substance use and its impact on neonates. An amalgamation of community engagement, society, policy initiatives, and medical expertise is essential to mitigate the repercussions of NAS and adopt healthier outcomes for affected infants.

FRI473 Central Hypothyroidism Following Neonatal Graves Presentation

Abstract Disclosure: E. Metzinger: None. K. Halpin: None. Background: Neonatal Graves’ disease is a rare disorder of neonatal autoimmune hyperthyroidism secondary to the transplacental passage of thyroid-stimulating hormone receptor antibodies. Although neonatal Graves’ disease is transient, it is associated with cardiac dysfunction, intrauterine growth restriction, prematurity, craniosynostosis, and developmental delay and can be life-threatening. Additionally, infants with neonatal Graves’ disease can rarely present with primary or central hypothyroidism later in infancy or childhood. This is suspected to be due to the disruption in the hypothalamic-pituitary-thyroid axis or development of the thyroid gland. Clinical Case: Here we describe a case of neonatal Graves’ disease that has been complicated by persistent central hypothyroidism requiring levothyroxine treatment. This was a preterm infant with tachycardia, biventricular heart failure, and hepatomegaly who was transferred to a higher level of care NICU for cardiac and respiratory failure. Pregnancy was complicated by history of maternal Graves’ disease status post radioiodine ablation. Maternal TRAB and thyroid levels were unavailable. Initial thyroid studies on DOL 1 were notable for suppressed TSH of <0.02mcIU/mL, elevated free T4 6.9ng/dL, and elevated total T4 >24.9mcg/dL. Total T3 was normal at 161ng/dL (50-452ng/dL) on DOL 2, and TSI was elevated at 4.8 (TSI Index, normal </= 1.3) on DOL 3. For neonatal thyrotoxicosis, the infant was treated with methimazole, potassium iodide (KI), propranolol, and hydrocortisone. Hydrocortisone was discontinued as the infant clinically improved, and KI was discontinued after 1 week. TFTs were closely followed during admission and methimazole dosing was adjusted as needed. He was discharged from the NICU on DOL 19 on methimazole and propranolol with close outpatient lab monitoring and follow-up. Propranolol was discontinued by 1.5 months of life, and methimazole was discontinued by 2 months of life as TFTs normalized. TSI was negative by four months of life. TSH remained low with decreasing free T4 levels. Ultimately, he was started on levothyroxine at 8.5mcg/kg/day at 2.5 months of age for central hypothyroidism. At that time, TSH was 0.06mcICU/mL and FT4 was 0.7ng/dL. TSH remained low through the first 14 months of treatment with normal free T4 levels on levothyroxine. He has been continued on levothyroxine (average 20mcg/day). Conclusion: This case highlights the severity of neonatal Graves’ disease and the possibility of the subsequent development and persistence of central hypothyroidism following neonatal Graves’ diagnosis despite the resolution of hyperthyroidism and normalization of TSI antibody. Due to the risk of the development of hypothyroidism, it may be worthwhile to continue to trend TSH and FT4 to ensure that the infant has not developed hypothyroidism. Presentation: Friday, June 16, 2023

Transplacental passage of nirmatrelvir in pregnant women with COVID-19.

SynopsisThe transplacental passage of nirmatrelvir in pregnant women with COVID‐19 is limited and reinforces the safety of using Paxlovid in pregnancy.

OP08_6. Novel therapeutic strategy in pregnancy: prevention of transplacental passage by lipid nanoparticles

OP08_6. Novel therapeutic strategy in pregnancy: prevention of transplacental passage by lipid nanoparticles

Maternal blood concentrations of toxic metal(loid)s and trace elements from preconception to pregnancy and transplacental passage to fetuses

Intrauterine exposure to heavy metals may adversely affect the developing fetus and health later in life, while certain trace elements may be protective. There is limited data on their dynamic fluctuation in circulating concentration of women from preconception to pregnancy and the degree of transplacental passage to fetus. Such information is critically needed for an optimal design of research studies and intervention strategies. In the present study, we profiled the longitudinal patterns and trajectories of metal(loid)s and trace elements from preconception to late pregnancy and in newborns. We measured whole blood metal(loid)s in women at preconception, 16, 24 and 32 weeks of gestation and in cord blood in 100 mother-newborn pairs. Our data showed that the mean concentrations of mercury (Hg), lead (Pb), rubidium (Rb), manganese (Mn), and iron (Fe) were lower during early-, mid-, and late-pregnancy than at preconception. Copper (Cu), and calcium (Ca) concentrations increased after pregnancy (Cu 798 versus 1353, 1488, and 1464 μg/L). Concentrations at preconception were correlated with those during pregnancy for all examined metal(loid)s. Maternal Hg, Pb, and Se concentrations at late-pregnancy were correlated with those in newborn cord blood in various degrees (correlation coefficients: Hg 0.66, Pb 0.29, Se 0.39). The estimated placental transfer ratio for toxic metal(loid)s ranging from 1.68 (Hg) to 0.18 (Cd). Two trajectory groups were identified for Hg, Pb, Cd, Se concentrations. Hg concentrations may be correlated with maternal education levels. The study is the first to present longitudinal circulating concentration trajectories of toxic metal(loid)s and trace elements from preconception to pregnancy stages. A high degree of transplacental passage was observed in toxic metals Pb and Hg which may pose hazards to the developing fetus.

Nanomedicines: An approach to treat placental insufficiency and the current challenges.

Preeclampsia and fetal growth restriction are common pregnancy complications that significantly impact perinatal health and offspring development later in life. The origin of these complex syndromes overlap in placental insufficiency. Progress in developing treatments for maternal, placental or fetal health is mainly limited by the risk of maternal and fetal toxicity. Nanomedicines are a promising approach to safely treat pregnancy complications since they can regulate drug interaction with the placenta to enhance efficacy of the treatment while minimizing exposure of the fetus. This narrative review discusses the current developments and challenges of nanomedicines during pregnancy with a focus on preclinical models of placenta insufficiency syndromes. Firstly, we outline the safety requirements and potential therapeutic maternal and placental targets. Secondly, we review the prenatal therapeutic effects of the nanomedicines that have been tested in experimental models of placental insufficiency syndromes. The majority of liposomes and polymeric drug delivery system show promising results regarding the prevention of trans-placental passage nanomedicines in uncomplicated and complicated pregnancies. The others two studied classes, quantum dots and silicon nanoparticles, have been investigated to a limited extent in placental insufficiency syndromes. Characteristics of the nanoparticles such as charge, size, and timing of administration have been shown to influence the trans-placental passage. The few available preclinical therapeutic studies on placental insufficiency syndromes predominantly show beneficial effects of nanomedicines on both maternal and fetal health, but demonstrate contradicting results on placental health. Interpretation of results in this field is complicated by the fact that results are influenced by the choice of animal species and model, gestational age, placental maturity and integrity, and nanoparticle administration route. Nanomedicines form a promising therapeutic approach during (complicated) pregnancies mainly by reducing fetal toxicity and regulating drug interaction with the placenta. Different nanomedicines have been proven to effectively prevent trans-placental passage of encapsulated agents. This can be expected to dramatically reduce risks for fetal adverse effects. Furthermore, a number of these nanomedicines positively impacted maternal and fetal health in animal models for placental insufficiency. Demonstrating that effective drug concentrations can be reached in the target tissue. While these first animal studies are encouraging, more research is needed to better understand the influence of the pathophysiology of this multi-factorial disease before implementation in clinical practice can be considered. Therefore, extensive evaluation of safety and efficacy of these targeted nanoparticles is needed within multiple animal, in vitro, and/or ex vivo models. This may be complemented by diagnostic tools to assess the disease status to identify the best time to initiate treatment. Together these investigations should contribute to building confidence in the safety of nanomedicines for treating mother and child, as safety has, understandably, the highest priority in this sensitive patient groups.

Management of foetal hyperthyroidism in a mother with autoimmune hypothyroidism: A case report

Foetal hyperthyroidism is mediated by transplacental passage of thyroid stimulating antibodies (TSAbs) and affects mothers with autoimmune (AI) thyroid disease. We report a case of a 33-year-old woman with a history of AI hypothyroidism and raised TSI after 2 stillbirths with suspect foetal hyperthyroidism. At 20.5 gestational weeks (GW) of her third pregnancy, foetal tachycardia and goitre were detected. TSI levels were 30.9mUI/mL. Methimazole (MMI) was started and adjusted based on ultrasound signs (foetal heart rate and thyroid gland vascularisation). The neonate was born at 35GW and cord blood revealed decreased TSH and normal free T4. MMI was started in the neonate at 2 days of life due to the appearance of asymptomatic hyperthyroidism. This case illustrates a rare recurrence of foetal hyperthyroidism in a mother with AI hypothyroidism. Pregestational thyroidectomy, TSAbs determination, early ultrasound diagnosis and foetal therapy helped us to improve obstetric outcomes.

Haemolytic Disease of the Newborn

Background: Immune-mediated haemolytic disease of the newborn refers to a specific category of haemolytic anaemia that results from transplacental passage of IgG antibodies from a pre-sensitized mother to her fetus in utero. This occurs due to blood group incompatibility between the mother and the fetus. The clinical presentation covers a wide spectrum spanning from still births and erythroblastosis fetalis as well as infants born with only mild haemolysis to those having severe anaemia snd severe indirect hyperbilirubinaemia followed by hydrops.Objective: We describe the journey of a Rh-D negative mother who endured through six pregnancies in order to have a healthy baby.Conclusion: To highlight the importance of blood grouping and Rh typing during the first antenatal visit and subsequent monitoring of antibody titers, especially in a mother who is Rh-D negative. KYAMC Journal Vol. 14, No. 01, April 2023: 54-56