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Pre-Antiretroviral Therapy Vertical HIV-1 Transmission Risk in Uganda Varies by Sex of Child and Maternal Viral Subtype.

We analyzed perinatal transmission in a pre-antiretroviral therapy Ugandan cohort by maternal human immunodeficiency virus type 1 subtype and infant sex in 131 mother-child pairs. Among all children, if the mother was infected with subtype A there was a nearly 3-fold increased risk of perinatal transmission compared with subtype D (risk ratio [RR], 2.96 [95% confidence interval (CI), 1.46-6.01]; P = .008). When stratifying infants by both sex and maternal subtype, significantly more female (56.3% [9 of 16]) than male (9.1% [1 of 11]) infants born to mothers with subtype A were infected (RR, 6.19 [95% CI, .91-42.12]; P = .02). In contrast, among infants born to mothers with subtype D, transmission rates were comparable across sex (RR, 1.59 [95% CI, .57-4.41]; P = .39).

Humans

Hepatitis B outbreak among chimpanzees at the London Zoo.

Persistent carriage of hepatitis B virus in extremely high titre was identified in 5 out of 9 chimpanzees kept at the London Zoo. Antibody to this virus was present in the other 4 chimpanzees. Serological survey of the other primates in the Regent's Park collection did not reveal the presence of the surface antigen in 2 gorillas, 11 orang-utans, and 2 gibbons, although surface antibody was present in the serum of 1 gorilla and 2 orang-utans. 3 of the carrier chimpanzees were born at the Zoo and were the offspring of either a carrier mother or a carrier father, and perinatal transmission may have occurred. A strict safety code of practice was introduced and hepatitis B immunoglobulin was given at intervals to designated staff members. Sero-conversion did not occur in any of the 38 staff members under surveillance for more than 2 years. Treatment of the carrier state in the chimpanzees was attempted with human leucocyte interferon, with and without ribavirin ('Virazole'), and with adenine arabinoside, but the effects were mostly temporary.

Animals

Maternal Tuberculosis and Infant Gut and Immune Development: Implications for Maternal-Child Health.

BACKGROUND: Maternal tuberculosis (TB) during pregnancy involves chronic infection, immune activation, and antimicrobial therapy, which may alter the maternal gut, vaginal, and breast milk microbiomes and influence neonatal immune development. METHODS: We conducted a narrative review of studies identified through PubMed and GoogleScholar addressing the maternal TB-microbiome-infant immunity axis. Where evidence from pregnant women with TB was limited, findings were extrapolated from non-pregnant TB populations, antibiotic exposure studies, and broader maternal-infant microbiome research. RESULTS: Maternal TB and its treatment may alter gut, vaginal, and breast milk microbiomes and the immune-metabolic composition of milk. These changes could influence perinatal microbial transmission, mucosal maturation, and infant immune responses, including vaccine responsiveness, BCG immunogenicity, and IGRA conversion. Treatment timing, antibiotic exposure, and maternal nutrition may modify these effects. CONCLUSION: Understanding the maternal TB-microbiome-immune axis may help optimize infant immune outcomes. Longitudinal mother-infant studies, multi-omic analyses, and mechanistic models are needed to clarify these interactions and evaluate microbiome informed strategies, including nutritional optimization, targeted probiotics/prebiotics, and antibiotic stewardship.

Infant gut colonization

Natural history of perinatal cytomegaloviral infection.

Epidemiological data presented here indicate that cytomegaloviral (CMV) infection is one of the most common perinatal infections found in human beings. Transmission to the offspring occurs in utero at birth and postnatally. Intrauterine infection results from primary or recurrent maternal involvement, the latter being more common in populations where infection is initially acquired during childhood or adolescence, such as in low socioeconomic settings. Congenital infection is usually subclinical with either type of maternal involvement but primary infection has a greater tendency to produce disease in the fetus. About 20% of the offspring infected in utero are damaged, infrequently with generalized disease, but more often with auditory involvement. The latter can develop in utero or postnatally and can be progressive. The major cause of recurrent maternal infection according to restriction enzyme analysis is reactivation of latent virus, which occurs in the face of substantial maternal humoral immunity, even with intrauterine transmission of virus. Reinfection by exogenous virus remains a lesser possibility for maternal recurrences. Even more commonly, CMV can be transmitted at birth from the infected maternal genital tract and postnatally through infected breast milk, especially in highly immune populations. With the possible exception of early pneumonia, these infections appear to be innocuous.

Adolescent

How do women with a history of childhood sexual abuse experience the preconception and perinatal period? A qualitative systematic review.

CONTEXT: Child sexual abuse (CSA) is a public health issue that predominantly affects women and has both short- and long-term consequences. The perinatal period can represent a challenge, but also an opportunity to identify a history of CSA and to provide sensitive care that may help prevent the intergenerational transmission of trauma. AIM: To describe and understand the experiences and coping strategies of women who are survivors of child sexual abuse and are transitioning to motherhood. METHOD: We conducted a systematic review of qualitative studies according to a protocol registered in PROSPERO, following methodological standards and reporting the results according to the ENTREQ guideline. A search was conducted on five databases up to July 2025. Two authors independently selected the articles and assessed their methodological quality. Data were analysed using thematic synthesis and the confidence in the findings was evaluated according to GRADE-CERQual. RESULTS: We included 21 qualitative studies that resulted in six themes. The findings reveal how women who experienced child sexual abuse and are transitioning to motherhood may experience this stage with ambivalence-ranging from revictimisation to identity reconstruction-where perinatal care emerges as a potential healing vehicle throughout this process. CONCLUSIONS: The perinatal period becomes a window of opportunity to heal deep wounds, with perinatal care playing a key role. The findings support trauma-informed perinatal care, underpinned by reflective practice and a holistic approach. Further work is needed to improve the identification of child sexual abuse, enhance professional training and review current practices to ensure sensitive care.

Humans

Controlled human infection model of Neisseria lactamica in late pregnancy investigating mother-to-infant transmission in the UK: a single-arm pilot trial.

BACKGROUND: The infant respiratory microbiome is derived largely from the mother and is associated with downstream health and disease. Manipulating maternal respiratory flora peripartum to influence the infant microbiome has not previously been investigated. Neisseria lactamica is a harmless pharyngeal commensal that correlates inversely with Neisseria meningitidis carriage and disease. Intranasal N lactamica inoculation is a safe and well characterised controlled human infection model (CHIM) in non-pregnant healthy adults. We hypothesised that N lactamica inoculation in pregnancy induces mother-to-infant N lactamica transmission postnatally. METHODS: In this single-arm trial, 21 healthy pregnant female participants aged 18 years or older were inoculated at 36-38 weeks' gestation with 105 colony-forming units of N lactamica Y92-1009 at University Hospital Southampton Clinical Research Facility, Southampton, UK. N lactamica selective culture, genome sequencing, and serological testing were performed on maternal and infant oral, nasopharyngeal, breastmilk, and serum samples over 15 weeks postpartum. Seven female participants naturally colonised with N lactamica at baseline were followed up, but not inoculated. Oral samples were obtained from 12 cohabiting siblings younger than 5 years. The primary endpoint was infant N lactamica colonisation. This study was registered with ClinicalTrials.gov, NCT04784845, and is now complete. FINDINGS: Between Oct 25, 2021, and March 7, 2022, 31 adult female participants (median age 33·5 years [range 23·1-39·9]; 26 [84%] were White, British) were screened and enrolled, of whom seven were already colonised with N lactamica. After exclusion of three participants, 21 participants were inoculated, of whom 15 (71%) became N lactamica-colonised, and no sustained N lactamica Y92-1009 transmission to their infants was observed. Conversely, non-Y92-1009 N lactamica strain sharing was observed in four (57%) of seven uninoculated mother-sibling pairs, and Moraxella catarrhalis strain sharing in nine (38%) of 24 mother-infant pairs completing the study. Anti-N lactamica serum IgG titres increased in seven (88%) of eight N lactamica Y92-1009-colonised female participants, but none of their infants (where paired sera were available). There were no serious adverse reactions to the inoculum. INTERPRETATION: As the world's first perinatal CHIM, this trial demonstrates that this model in pregnancy is feasible, and that N lactamica Y92-1009 can safely and efficiently colonise pregnant individuals. Lack of sustained mother-to-infant N lactamica transmission, despite evidence supporting mother-to-infant M catarrhalis and sibling-to-mother N lactamica transmission, challenges conventional perceptions of infants as passive recipients of maternal microbes, suggesting that respiratory commensal transmission is selective and microbe-specific. FUNDING: Medical Research Council and National Institute for Health Research Southampton Biomedical Research Centre.

Adult

Synaptic transmission between rat superior cervical ganglion neurons in dissociated cell cultures.

The principal neurons of the rat superior cervical ganglion (SCGN) when established as dissociated cells in tissue culture form synapses among themselves. In the present study we have examined this synaptic interaction when these neurons are co-cultured with several other types of tissues. Dissociated SCGN were prepared from perinatal rats and studied, after 3-4 weeks maturation, with intracellular recording techniques. Synaptic interactions between sympathetic neurons were demonstrated when these cells were: (a) grown with explants from newborn rat thoracic spinal cord, (b) when the SCGN had survived for several weeks subsequent to removal of the spinal cord explants, and (c) when the SCGN were grown in the presence of an adrenergic target (interscapular brown fat cells). Unidirectional, reciprocal, recurrent and complex chemical synaptic networks, consisting of convergence and divergence, characterized connections between SCGN. All synaptic responses were cholinergic since they were reversibly blocked by hexamethonium or mecamylamine but were not sensitive to 10(-5) M phenoxybenzamine. Removal of the spinal cord explants did not significantly alter the proportion of chemical synaptic interactions between SCGN (more than 25%) from matched cultures. Anatomical observations established that in cultures with brown fat, innervating neurites appeared on the fat cells; these neurites frequently expanded to form varicosities that resembled the adrenergic terminals normally seen on brown fat in the animal. Synaptic profiles also occurred on the neurons in these cultures and some of these were shown to be cholinergic. The proportion of neuronal interactions in the combined SCGN + fat cultures was low, however, suggesting that co-culture with target tissue might influence the frequency of interconnections developed between SCGN in culture. Other factors, such as the presence of non-neuronal cells, degree of dissociation, cellular density, culture age and the survival of certain types of SCGN in culture are discussed as variables related to the formation of synapses between SCGN. Non-rectified electrical coupling between SCGN was also observed in 17 out of 679 pairs (2.5%) of neurons. Attenuation factor for electrically coupled action potentials ranged between 1 and 43.5.

Adipose Tissue, Brown

Synaptic transmission between rat spinal cord explants and dissociated superior cervical ganglion neurons in tissue culture.

Physiological properties of the synapses formed between explants of spinal cord and dissociated autonomic ganglion neurons in tissue culture were studied using intracellular and extracellular stimulation and recording techniques (as well as iontophoresis) with a culture perfusion system allowing continuous microscopic observation during repeated changes of the bathing medium. The principal neurons of the superior cervical ganglion (SCGN) were dissociated from perinatal rats and the spinal cord explants were obtained from 15-day rat fetuses; these were allowed to mature for 3-10 weeks in co-culture. Recordings from over 1000 SCGN established that: (a) spontaneous small depolarizations and action potentials occurred in 20% of the SCGN studied, (b) the EPSPs observed in SCGN after spinal cord stimulation were sensitive to decreased Ca2+ and increased Mg2+, as well as to D-tubocurare, hexamethonium and mecamylamine, but not to atropine (at 10(-6) M concentration) or to the alpha-adrenergic blocking agents phentolamine or phenoxybenzamine; no potentiation of the EPSPs was seen with neostigmate or eserine, (c) acetylcholine directly applied to the SCGN was seen to mimic the responses seen after spinal cord stimulation; tetrodotoxin blocked both direct and iontophoretically fired action potentials, with only a suprathreshold acetylcholine potential remaining. These synapses were not sensitive to alpha-bungarotoxin. It is concluded that the synapses formed by spinal cord neurites on principal SCGN in tissue culture are nicotinic cholinergic, and that the evoked EPSPs recorded in this study are thus similar to the orthodromic fast EPSPs observed in vivo. No slow synaptic responses were observed and no demonstrable effects were noted that could be attributed to adrenergic transmission.

Acetylcholine

Sequential analysis of hepatic carcinogenesis: the comparative architecture of preneoplastic, malignant, prenatal, postnatal and regenerating liver.

The organizational pattern of hepatocytes in hyperplastic nodules, probable precursors of hepatocellular carcinoma, was examined sequentially at different stages in the carcinogenic process, and compared with the patterns in hepatocellular carcinomas, in developing liver and in regnerating liver. Scanning as well as transmission electron microscopy, and histochemistry with light microscopy were used. The hepatocytes in the hyperplastic lesions were arranged in plates 2 or more cells thick and glands, in contrast to the one-cell-thick plates of hepatocytes in normal mature liver, and showed unusualy separation from eachother, with irregularly dilated bile canaliculi. The organizational pattern found in the hyperplastic lesions shared properties with developing liver in the perinatal period, regenerating liver following the peak of cell division, and some hepatocellular carcinomas. Unlike the normal, in which there is a highly predictable time scale for change, an apparent delay or interruption of maturation may be of importance in lesions that persist and ultimately evolve into hepatocullular carcinoma.

Animals

Gangliosides and thermal adaptation in vertebrates.

Gangliosides, which are highly enriched in synaptic membranes, show great differences in concentration and pattern constellation as well during early ontogenetical development as on interspecies level in vertebrates. As, up to now, there is no reasonable explanation for these findings, and as it is assumed the synapse to be the primary site of thermal adaptation, the attempt was made to investigate whether there are any correlations between brain gangliosides and the thermal adaptation phenomenon. 1. While in the brains of adult homeothermic vertebrates (with thermo-regulation: mammals, birds) the di-sialoganglioside GD1a predominates, in the brain of poikilotherms (without thermo-regulation: e.g. amphibia, teleost fishes) more polar polysialogangliosides are present. 2. In homeotherms during their early perinatal phase (heterothermic phase: thermor-regulation being not yet developed) a temporary poly-sialisation of brain-gangliosides occurs. 3. In poikilotherms, during the process of thermal adaptation to lowered environmental temperatures, a poly-sialisation of brain gangliosides can be observed, as well during the phase of acclimatization (adaptation to seasonal changes in temperature) as also to acclimation (experimentally induced changes in the environmental temperature). 4. The phenomenon of poly-sialisation of brain gangliosides during adaptation to lowered environmental temperatures can be correlated with changes in some behavioral (e.g. motorical activity) and electrophysiological parameters. 5. On the background of a general hypothesis on the involvement of gangliosides in the process of transmission [23, 24], a functional model on the participation of gangliosides in the process of thermal adaptation is discussed with special regard to the formation of Ca++-ganglioside-complexes, which are highly sensitive to temperature changes.

Acclimatization