Transplacental Transfer of SARS-CoV-2 Receptor-Binding Domain IgG Antibodies from Mothers to Neonates in a Cohort of Pakistani Unvaccinated Mothers.

The presence of COVID-19 antibodies in the maternal circulation is assumed to be protective for newborns against SARS-CoV-2 infection. We investigated whether maternal COVID-19 antibodies crossed the transplacental barrier and whether there was any difference in the hematological parameters of neonates born to mothers who recovered from COVID-19 during pregnancy. The cross-sectional study was conducted at the Saidu Group of Teaching Hospitals, located in Swat, Khyber Pakhtunkhwa. After obtaining written informed consent, 115 healthy, unvaccinated mother-neonate dyads were included. A clinical history of COVID-19-like illness, laboratory-confirmed diagnosis, and contact history were obtained. Serum samples from mothers and neonates were tested for SARS-CoV-2 anti-receptor-binding domain (anti-RBD) IgG antibodies. Hematological parameters were assessed with complete blood counts (CBC) and peripheral blood smear examinations. The study population consisted of 115 mothers, with a mean age of 29.44 ± 5.75 years, and most women (68/115 (59.1%)) were between 26 and 35 years of age. Of these mothers, 88/115 (76.5 percent) tested positive for SARS-CoV-2 anti-RBD IgG antibodies, as did 83/115 (72.2 percent) neonatal cord blood samples. The mean levels of SARS-CoV-2 IgG antibodies in maternal and neonatal blood were 19.86 ± 13.82 (IU/mL) and 16.16 ± 12.90 (IU/mL), respectively, indicating that maternal antibodies efficiently crossed the transplacental barrier with an antibody transfer ratio of 0.83. The study found no significant difference in complete blood count (CBC) parameters between seropositive and seronegative mothers, nor between neonates born to seropositive and seronegative mothers.

Transplacental Passage and Fetal Effects of Antineoplastic Treatment during Pregnancy.

The incidence of PAC is relatively infrequent among pregnant women. However, it has gradually increased in recent years, becoming a challenging area for clinicians that should take into account in the same way maternal benefits and fetal potential risks correlated to the antineoplastic treatment. None of the antineoplastic drugs is completely risk-free during the pregnancy, the timing of exposure and transplacental transfer properties influence the toxicity of the fetus. Despite the lack of guidelines about the management of PAC, several studies have described the use and the potential fetal and neonatal adverse events of antineoplastic drugs during pregnancy. We provide a review of the available literature about the transplacental passage and fetal effects of chemotherapy and targeted agents, to guide the clinicians in the most appropriate choices for the management of PAC.

Avaliação da transferência materno-infantil de anticorpos em pacientes com síndrome antifosfolípide / Evaluation of maternal-child antibody transfer of patients with antiphospholipid syndrome

Introdução: a síndrome antifosfolípide (SAF) é caracterizada por eventos trombóticos e perdas gestacionais de repetição sendo considerada a trombofilia adquirida mais comum. Objetivo: realizar uma revisão narrativa da passagem transplacentária de anticorpos em pacientes com SAF. Metodologia: revisão narrativa da literatura. Resultados: quando não está associada a alguma doença do tecido conectivo é dita primária e quando em associação com lúpus eritematosos sistêmico é dita secundária. A morbidade gestacional é frequente e torna-se de importância avaliar a passagem desses anticorpos transplacentariamente, desde que existem modelos animais da síndrome com transferência passiva desses anticorpos. A passagem transplacentária de anticorpos específicos já foi determinada em estudos, os quais demonstraram baixos níveis destes anticorpos no soro materno, porém uma eficiente passagem transplacentária para o neonato. Conclusão: existem poucos estudos sobre essa passagem materno-infantil em pacientes com SAF, que são aqui revisados.

Introduction: a antiphospholipid syndrome (APS) is characterized by thrombotic events and recurrent pregnancy losses and is considered the most common acquired thrombophilia. Objective: to carry out a narrative review of the transplacental passage and antibodies in patients with APS. Methodology: narrative literature review Results: when it is not associated with any connective tissue disease, it is said to be primary and when in association with systemic lupus erythematosus it is said to be secondary. Gestational morbidity is frequent and it is important to evaluate the passage of these antibodies transplacentally, since there are animal models of the syndrome with passive transfer of these antibodies. The transplacental passage of specific antibodies has already been determined in studies, which demonstrated low levels of these antibodies in the maternal serum, but an efficient transplacental passage for the newborn. Conclusion: there are few studies on this maternal-infant passage in patients with APS, which are reviewed here.

Case Report: Infantile Ischemic Stroke and Antiphospholipid Antibodies, Description of Four Cases.

Antiphospholipid syndrome (APS) is a rare condition in childhood, but even more in the neonatal age. Most neonatal cases are considered a passively acquired autoimmune disease, due to a transplacental passage of maternal antiphospholipid antibodies (aPL) from mothers with primary or secondary APS or, more often, from asymptomatic aPL carriers. Exceedingly unusual is the neonatal de novo production of aPL. We present four infants with presumed perinatal stroke in presence of increased and persistent aPL levels, even after 6 months of life, opening the window on a gray zone related to the origin of these antibodies (maternal or neonatal) and on their role in the pathogenesis of stroke.

Phospholipase A2 Receptor Antibody-Positive Pregnancy: A Case Report.

Renal course and clinical outcomes in pregnant women with primary membranous nephropathy are not completely understood. In addition, the use of autoantibodies to M-type phospholipase A2 receptor (PLA2R) as a serologic marker throughout pregnancy and postpartum in the mother and baby is not yet fully elucidated. We followed up a pregnant woman with primary membranous nephropathy during pregnancy and postpartum and describe the clinical course and outcomes of mother and baby and the course of PLA2R antibody titers. We show evidence of transplacental transfer of PLA2R antibody from mother to fetus. In addition, we observe the effect of breastfeeding in a PLA2R antibody-positive pregnancy and describe the transfer of this antibody into breast milk. Although pregnancy in women with underlying PLA2R antibody-positive membranous nephropathy is possible, there is an increase in risk to both mother and fetus, requiring a multidisciplinary team approach and careful monitoring of both neonate and mother during pregnancy and postpartum.

The transplacental passage of commonly used intrapartum antibiotics and its impact on the newborn management: A narrative review.

Neonates exposed to intra-amniotic infection are at increased risk of early-onset sepsis. Administration of antibiotics to the mother may offer some protection, however a comprehensive description of the determinants influencing their transplacental passage and delivery to the fetus has not been performed. While penicillin G, ampicillin, cefazolin and gentamicin reach therapeutic levels in the fetal serum rapidly following maternal administration, the transfer of second-line intrapartum antimicrobials, such as vancomycin and clindamycin, is slower and less predictable. Erythromycin, used in the context of preterm premature rupture of the membranes, has suboptimal influx into the fetal compartment. This evidence is predominantly drawn from term pregnancies and situations of low infectious risk; however, prematurity may negatively influence fetal exposure to intrapartum antibiotics. Optimal fetal antimicrobial concentrations to target are poorly defined and the extent to which our review findings apply to preterm early-onset neonatal sepsis prevention is unclear. Interpretation of blood cultures drawn in neonates with expected circulating levels of maternal antimicrobials above the minimal inhibitory concentration for Group B Streptococcus is challenging despite the use of contemporary optimized blood culture media.

Deficit of IgG2 in HIV-positive pregnant women is responsible of inadequate IgG2 levels in their HIV-uninfected children in Malawi.

BACKGROUND: Transplacental passage of IgGs is impaired in HIV + pregnant women, possibly determining an inadequate immunological protection in their children. We aimed to determine the impact of maternal immunological IgG profile and immunoactivation status on the efficiency of transplacental passage of IgG subclasses in HIV + mothers. METHODS: 16 mother/infants pairs were studied in Malawi. Mothers received antiretroviral therapy (ART) from the third trimester of pregnancy. Determinations of pre-ART levels of maternal sCD14, of IgG subclasses in mothers at delivery and in their 1-month-old infants, were performed using commercial ELISA kits. RESULTS: At delivery, after a median of 10 weeks of ART, 12/16 mothers were hypergammaglobulinemic, with IgG levels (20.5 mg/ml, 95% CI:18.8-26.8) directly correlated to the plasmatic levels of sCD14 (r = 0.640, p = 0.014). IgG1 levels (17.9 mg/ml) accounted for 82% of IgG, IgG3 and IgG4 levels were in the normal range. A profound deficit of IgG2 was observed both in mothers (0.60 mg/ml) and in infants (0.14 mg/ml). Placental transfer ratio (range 0.16-0.42) did not show a selective impairment between the different IgG subclasses. The transplacental passage of all IgG subclasses was decreased in the presence of maternal IgG over 16 mg/ml (significantly for IgG1, p = 0.031) and of high levels of sCD14 (p = 0.063). CONCLUSIONS: Transplacental passage was reduced for all IgG subclasses and inversely correlated to high levels of maternal IgGs and to the degree of immunoactivation. The profound depression of IgG2 in mothers suggests that IgG2 neonatal levels mostly reflect the maternal deficit rather than a selective impairment of IgG2 transfer.

Trichinella spiralis infection and transplacental passage in human pregnancy.

Infection by Trichinella spp. during pregnancy still arises many questions. Worldwide an important number of trichinellosis outbreaks have occurred over time where pregnant women were or might have been involved. Parasitological and immunoserological parameters, clinical background and transplacental passage of Trichinella spiralis of six pregnant women, from different outbreaks, were studied. Serum samples were collected from patients and their children: at pregnancy, at delivery, newborn and/or infant (≥1 year-old). Total immunoglobulins (Igs) and isotypes against excretion-secretion products from muscle larvae (ESP-ML) and newborn larvae (NBL) of T. spiralis were detected by immunoserological techniques. Sera helminthocytotoxic activity against NBL was evaluated by antibodies dependent cell cytotoxicity assay. Patients presented similar clinical symptoms. Mother's sera showed differences in the presence and titres of Igs, IgE, IgG1 and IgG4 against NBL surface. All of them showed helminthocytotoxic activity against NBL, four in progesterone dependent manner and the other two by antibodies. Igs anti ESP-ML were present in mother's sera, with differences in the isotypes detected. Anti-ESP-ML IgE, IgA and/or IgM in newborn sera were observed. Three out of four infants showed specific Igs; one even at 8 years-old. The distinct immune response between mothers at pregnancy evidenced by sera helminthocytotoxic activity and immunoserological parameters may be associated with a different parasite burden exposition. Specific Igs observed in newborns would be a suggestion of transplacental passage of this Igs and/or their production by the fetus. Specific Igs found in infants sera suggests that newborn larvae transplacental passage is possible.

Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women.

OBJECTIVES: To describe the pharmacokinetics of darunavir in pregnant HIV-infected women in the third trimester and post-partum. PATIENTS AND METHODS: This was a non-randomized, open-label, multicentre, Phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. HIV-infected pregnant women treated with darunavir (800/100 mg once daily or 600/100 mg twice daily) as part of their combination ART were included. Pharmacokinetic curves were recorded in the third trimester and post-partum. A cord blood sample and maternal sample were collected. The study is registered at ClinicalTrials.gov under number NCT00825929. RESULTS: Twenty-four women were included in the analysis [darunavir/ritonavir: 600/100 mg twice daily (n=6); 800/100 mg once daily (n=17); and 600/100 mg once daily (n=1)]. Geometric mean ratios of third trimester versus post-partum (90% CI) were 0.78 (0.60-1.00) for total darunavir AUC0-tau after 600/100 mg twice-daily dosing and 0.67 (0.56-0.82) for total darunavir AUC0-tau after 800/100 mg once-daily dosing. The unbound fraction of darunavir was not different during pregnancy (12%) compared with post-partum (10%). The median (range) ratio of darunavir cord blood/maternal blood was 0.13 (0.08-0.35). Viral load close to delivery was <300 copies/mL in all but two patients. All children were tested HIV-negative and no congenital abnormalities were reported. CONCLUSIONS: Darunavir AUC and Cmax were substantially decreased in pregnancy for both darunavir/ritonavir regimens. This decrease in exposure did not result in mother-to-child transmission. For antiretroviral-naive patients, who are adherent, take darunavir with food and are not using concomitant medication reducing darunavir concentrations, 800/100 mg of darunavir/ritonavir once daily is adequate in pregnancy. For all other patients 600/100 mg of darunavir/ritonavir twice daily is recommended during pregnancy.