Early Postnatal Infection Research Articles

Early Postnatal Infection of Neonates Born to Mothers Infected by SARS-CoV-2 OmicronVariant.

To evaluate the rate of postnatal infection during the first month of life in neonates born to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive mothers during the predominant circulation of the omicron (B.1.1.529) variant. This prospective, 10-center study enrolled mothers infected by SARS-CoV-2 at delivery and their infants, if both were eligible for rooming-in, between December 2021 and March 2022. Neonates were screened for SARS-CoV-2 RNA at 1 day of life (DOL), 2 to 3 DOL, before discharge, and twice after hospital discharge. Mother-infant dyads were managed under a standardized protocol to minimize the risk of viral transmission. Sequencing data in the study area were obtained from the Italian Coronavirus Disease 2019 Genomic platform. Neonates were included in the final analysis if they were born when the omicron variant represented >90% of isolates. Eighty-two percent (302/366) of mothers had an asymptomatic SARS-CoV-2 infection. Among 368 neonates, 1 was considered infected in utero (0.3%), whereas the postnatal infection rate during virtually exclusive circulation of the omicron variant was 12.1%. Among neonates infected after birth, 48.6% became positive during the follow-up period. Most positive cases at follow-up were detected concurrently with the peak of coronavirus disease 2019 cases in Italy. Ninety-seven percent of the infected neonates were asymptomatic. The risk of early postnatal infection by the SARS-CoV-2 omicron variant is higher than that reported for previously circulating variants. However, protected rooming-in practice should still be encouraged given the paucity of symptoms in infected neonates.

Reduced structural connectivity in non-motor networks in children born preterm and the influence of early postnatal human cytomegalovirus infection.

Preterm birth is increasingly recognized to cause lifelong functional deficits, which often show no correlate in conventional MRI. In addition, early postnatal infection with human cytomegalovirus (hCMV) is being discussed as a possible cause for further impairments. In the present work, we used fixel-based analysis of diffusion-weighted MRI to assess long-term white matter alterations associated with preterm birth and/or early postnatal hCMV infection. 36 former preterms (PT, median age 14.8 years, median gestational age 28 weeks) and 18 healthy term-born controls (HC, median age 11.1 years) underwent high angular resolution DWI scans (1.5 T, b = 2 000 s/mm2, 60 directions) as well as clinical assessment. All subjects showed normal conventional MRI and normal motor function. Early postnatal hCMV infection status (CMV+ and CMV-) had been determined from repeated screening, ruling out congenital infections. Whole-brain analysis was performed, yielding fixel-wise metrics for fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). Group differences were identified in a whole-brain analysis, followed by an analysis of tract-averaged metrics within a priori selected tracts associated with cognitive function. Both analyses were repeated while differentiating for postnatal hCMV infection status. PT showed significant reductions of fixel metrics bilaterally in the cingulum, the genu corporis callosum and forceps minor, the capsula externa, and cerebellar and pontine structures. After including intracranial volume as a covariate, reductions remained significant in the cingulum. The tract-specific investigation revealed further reductions bilaterally in the superior longitudinal fasciculus and the uncinate fasciculus. When differentiating for hCMV infection status, no significant differences were found between CMV+ and CMV-. However, comparing CMV+ against HC, fixel metric reductions were of higher magnitude and of larger spatial extent than in CMV- against HC. Preterm birth can lead to long-lasting alterations of WM micro- and macrostructure, not visible on conventional MRI. Alterations are located predominantly in WM structures associated with cognitive function, likely underlying the cognitive deficits observed in our cohort. These observed structural alterations were more pronounced in preterms who suffered from early postnatal hCMV infection, in line with previous studies suggesting an additive effect.

Treatment with sofosbuvir attenuates the adverse neurodevelopmental consequences of Zika virus infection in infant rhesus macaques

Zika virus (ZIKV) infection during infancy in a rhesus macaque (RM) model negatively impacts brain development resulting in long-term behavioral alterations. The current study investigated whether postexposure prophylaxis could alleviate these negative neurodevelopmental consequences. Three RM infants received a 14-day course of sofosbuvir (SOF; 15 mg/kg p.o.) treatment starting at 3 days post-infection with a Puerto Rican strain of ZIKV (PRVABC59) and were then monitored longitudinally for one year. In contrast to ZIKV-infected infant RMs who did not receive SOF, postexposure SOF treatment mitigated the neurodevelopmental, behavioral and cognitive changes seen after postnatal ZIKV infection even while not accelerating viral clearance from the blood. These data suggest that antiviral treatment may help ameliorate some, but not all, of the neurodevelopmental abnormalities associated with early postnatal ZIKV infection.

Maternal infection during pregnancy aggravates the behavioral response to an immune challenge during adolescence in female rats

Prenatal and early postnatal infection have been associated with changes in microglial activity and the development of psychiatric disorders. Here, we investigated the effect of prenatal immune activation and postnatal immune challenge, alone and combined, on behavior and microglial cell density in female Wistar rats. Pregnant rats were injected with poly I:C to induce a maternal immune activation (MIA). Their female offspring were subsequently exposed to a lipopolysaccharide (LPS) immune challenge during adolescence. Anhedonia, social behavior, anxiety, locomotion, and working memory were measured with the sucrose preference, social interaction, open field, elevated-plus maze, and Y-maze test, respectively. Microglia cell density was quantified by counting the number of Iba-1 positive cells in the brain cortex. Female MIA offspring were more susceptible to the LPS immune challenge during adolescence than control offspring as demonstrated by a more pronounced reduction in sucrose preference and body weight on the days following the LPS immune challenge. Furthermore, only the rats exposed to both MIA and LPS showed long-lasting changes in social behavior and locomotion. Conversely, the combination MIA and LPS prevented the anxiety induced by MIA alone during adulthood. MIA, LPS, or their combination did not change microglial cell density in the parietal and frontal cortex of adult rats. The results of our study suggest that the maternal immune activation during pregnancy aggravates the response to an immune challenge during adolescence in female rats.

MARKERS OF EARLY INFLAMMATION IN THE DIAGNOSIS OF NEONATAL SEPSIS

To date, neonatal sepsis remains one of the leading causes of death in newborns in the first month of life. The urgency of this problem is explained by the high level of mortality in prenatal and early postnatal infection. Diagnosis of the disease is complicated by the absence of specific symptoms and signs, which contributes to the deterioration of the condition of newborns with sepsis due to antibiotic therapy that has not been started in a timely manner. This article reviews the current literature on early markers of neonatal sepsis, which may be useful for healthcare practitioners.

Toxoplasma gondii seroprevalence in the endangered Australian sea lion (Neophoca cinerea)

Toxoplasma gondii is a ubiquitous parasite increasingly detected in marine mammals and suspected to contribute to limited recovery of endangered populations. This study reports on the exposure of the Australian sea lion (Neophoca cinerea) to this protozoon using archived adult and pup sera from three island colonies in South Australia. Modified agglutination testing (MAT) detected a seroprevalence of 30.4% (95% CI 13.2-52.9: n = 23) and high antibody titers (512 to > 2048 IU/ml) in adult females (median age 9.5 y, range 5.5-14.5 y) at Dangerous Reef, a felid-free island. Antibodies weren’t detected in any surveyed pup (97.5% CI 0.0-2.0%, n = 184) at two felid-free islands (Dangerous Reef: n = 21; Olive Island: n = 65), nor at Kangaroo Island (n = 98), which has a high-density feral cat population. Kangaroo Island pups of known age were 7-104 d old, while standard length and bodyweight comparison suggested younger and older pup cohorts at Dangerous Reef and Olive Island, respectively. This study provides the first quantification of disease risk in this endangered species from T. gondii exposure. The absence of detectable pup seroconversion supports the lack of detectable congenital transmission, maternal antibody persistence or early post-natal infection in the sampled cohort yet to commence foraging. An extended serosurvey of N. cinerea colonies is recommended to confirm the hypothesis of predominantly forage-associated exposure to T. gondii in this species. Findings have implications for parasitic disease risk in wildlife inhabiting Australia’s islands and for the feral cat control program on Kangaroo Island.

Clinical and Preclinical Evidence for Adverse Neurodevelopment after Postnatal Zika Virus Infection.

Although the Zika virus (ZIKV) typically causes mild or no symptoms in adults, during the 2015−2016 outbreak, ZIKV infection in pregnancy resulted in a spectrum of diseases in infants, including birth defects and neurodevelopmental disorders identified in childhood. While intense clinical and basic science research has focused on the neurodevelopmental outcomes of prenatal ZIKV infection, less is known about the consequences of infection during early life. Considering the neurotropism of ZIKV and the rapidly-developing postnatal brain, it is important to understand how infection during infancy may disrupt neurodevelopment. This paper reviews the current knowledge regarding early postnatal ZIKV infection. Emerging clinical evidence supports the hypothesis that ZIKV infection during infancy can result in negative neurologic consequences. However, clinical data regarding postnatal ZIKV infection in children are limited; as such, animal models play an important role in understanding the potential complications of ZIKV infection related to the vulnerable developing brain. Preclinical data provide insight into the potential behavioral, cognitive, and motor domains that clinical studies should examine in pediatric populations exposed to ZIKV during infancy.

Early Ultrasound Signs of Splenomegaly in Neonates

The purpose of the study is to determine early non-invasive (ultrasound) diagnostic criteria of splenomegaly in neonates with a high risk of congenital or postnatal infection.Materials and methods. In the prospective study, 163 newborn infants of the first week of live were included. All neonates included in the study were classified as possessing a high risk of an intra-uterine infection (IUI). Depending on the birth weight, the infants were split into two groups: group «А» — 80 full-term newborns with normal birth weight, and group «В» — 83 full-term newborns with fetal growth restriction (FGR). A comprehensive examination of newborns including spleen ultrasound was carried out.Results. An increased spleen weight coefficient (Km) was found in newborns with high risk of infection development that included congenital oromaxillofacial and gastrointestinal defects, perinatal contacts with various microorganism. The increased spleen weight and Km reflected conditions of the immune system organ of the newborn in response to an adverse exposure including infection.Conclusion. Ultrasound examination of morphometrical characteristics of the spleen in newborns with various medical conditions represents a convenient and simple method of early diagnosis of splenomegaly. The most sensitive index is the spleen weight coefficient (Km), which reflects the immune system organ response to an adverse perinatal exposure including contact with an infectious agent. The mean spleen weight coefficient is within the range of 1.1 to 3.0. When the index exceeds 4, the risk of development of an infectious disease increases. This method can be used as a screening approach for newborns of different gestation age who have been included in the high-risk group based on a congenital or early postnatal infection.

Suppression of pulmonary group B streptococcal proliferation and translocation by surfactants in ventilated near-term newborn rabbits.

The pathogenesis of neonatal group B Streptococcus (GBS) lung infection may be associated with surfactant dysfunction or deficiency. This study aimed to investigate the efficacy of surfactants on early postnatal GBS infection in ventilated newborn rabbit lungs. A near-term newborn rabbit model was established by intratracheal GBS instillation immediately at birth, followed by mechanical ventilation. At postnatal 1 h, a porcine surfactant was given intratracheally at 100 or 200 mg/kg. After 6 h, animals were euthanized, and lung and blood samples were collected for bacterial counting. Lung histopathology and messenger RNA (mRNA) expression of inflammatory mediators, surfactant proteins, and growth factors in lung tissue were assessed. The surfactants significantly suppressed (by >50%) pulmonary bacterial proliferation and systemic translocation, alleviated lung inflammatory injury, and improved alveolar expansion by morphometry, in favor of high-dose surfactants. Though the survival rate and lung mechanics were not improved, the surfactants significantly suppressed mRNA expression of proinflammatory mediators, while that for surfactant proteins and growth factors was differentially expressed, compared to the control and GBS infection groups. Exogenous surfactants may provide a therapeutic alternative for neonatal lung infection by suppressing pulmonary GBS proliferation and translocation into systemic circulation, alleviating inflammatory injury and regulating growth factor expression.

Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs.

Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.

Postnatal Persistent Infection with Classical Swine Fever Virus and Its Immunological Implications

It is well established that trans-placental transmission of classical swine fever virus (CSFV) during mid-gestation can lead to persistently infected offspring. The aim of the present study was to evaluate the ability of CSFV to induce viral persistence upon early postnatal infection. Two litters of 10 piglets each were infected intranasally on the day of birth with low and moderate virulence CSFV isolates, respectively. During six weeks after postnatal infection, most of the piglets remained clinically healthy, despite persistent high virus titres in the serum. Importantly, these animals were unable to mount any detectable humoral and cellular immune response. At necropsy, the most prominent gross pathological lesion was a severe thymus atrophy. Four weeks after infection, PBMCs from the persistently infected seronegative piglets were unresponsive to both, specific CSFV and non-specific PHA stimulation in terms of IFN-γ-producing cells. These results suggested the development of a state of immunosuppression in these postnatally persistently infected pigs. However, IL-10 was undetectable in the sera of the persistently infected animals. Interestingly, CSFV-stimulated PBMCs from the persistently infected piglets produced IL-10. Nevertheless, despite the addition of the anti-IL-10 antibody in the PBMC culture from persistently infected piglets, the response of the IFN-γ producing cells was not restored. Therefore, other factors than IL-10 may be involved in the general suppression of the T-cell responses upon CSFV and mitogen activation. Interestingly, bone marrow immature granulocytes were increased and targeted by the virus in persistently infected piglets. Taken together, we provided the first data demonstrating the feasibility of CSFV in generating a postnatal persistent disease, which has not been shown for other members of the Pestivirus genus yet. Since serological methods are routinely used in CSFV surveillance, persistently infected pigs might go unnoticed. In addition to the epidemiological and economic significance of persistent CSFV infection, this model could be useful for understanding the mechanisms of viral persistence.

Beneficial effect of social advantage and detrimental effect of early postnatal CMV infection

Two prospective studies published in this issue of The Journal deal with neurocognitive outcome of preterm infants. The study by Manley et al from Australia took advantage of their randomized 35-center trial of caffeine for apnea of prematurity in very low birth weight infants (500g to 1250g) from 1999 to 2004, with subsequent follow-up at 31 sites to corrected age of 5 years. They aimed to determine the extent of influence of social variables in children's cognitive development. Three social advantages (higher maternal education, higher paternal education, and caregiver employment) had strong, independent, additive effects on cognitive gain between 18 months and 5 years of age. In the second report, Brecht et al from Germany performed a longitudinal study to investigate long-term cognitive effects of early postnatally-acquired infection with cytomegalovirus (CMV) transmitted by human milk. They report the neuropsychological sequelae of a well characterized group of adolescents born very preterm (22 to 32 weeks' gestation) who had been studied prospectively to prove whether they did or did not acquire CMV through human milk in early postnatal life. They compared results of neurocognitive testing of these two groups when adolescents as well as a group of adolescents born at term (whose CMV status was not studied). Despite inevitable problems of attrition over the long study period, results in 19 adolescents with CMV compared with 23 adolescents without CMV born preterm and 24 adolescents born at term suggest adverse effect of early CMV infection on neurocognitive function. Their data also would suggest that CMV infection from breastfeeding in preterm infants could be responsible for a substantial proportion of the adverse outcomes associated with premature birth. Should hard-to-come-by findings of this small number of well characterized study subjects change practice? Should preventive measures against transmission of CMV by human milk in preterm infants be implemented? At what potential risk? The accompanying editorial by Wright and Permar is a must read in order to place the latter study in its proper context. Article page 834▶ Article page 870▶ Editorial page 795▶ Postnatal Human Cytomegalovirus Infection in Preterm Infants Has Long-Term Neuropsychological SequelaeThe Journal of PediatricsVol. 166Issue 4PreviewTo evaluate whether an early postnatal infection poses a long-term risk for neuropsychological impairment to neonates born very prematurely. Full-Text PDF Social Variables Predict Gains in Cognitive Scores across the Preschool Years in Children with Birth Weights 500 to 1250 GramsThe Journal of PediatricsVol. 166Issue 4PreviewTo determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. Full-Text PDF Preventing Postnatal Cytomegalovirus Infection in the Preterm Infant: Should It Be Done, Can It Be Done, and at What Cost?The Journal of PediatricsVol. 166Issue 4PreviewIn 2012, 56 252 very low birth weight (VLBW, <1500 g) infants were born in the US, accounting for 1.4% of all live births.1 These infants encounter numerous morbidities, and 25%-30% experience long-term neurodevelopmental impairment (NDI).2 Consequently, there has been an intense and elusive search for modifiable risk factors encountered in the neonatal intensive care unit (NICU) that impact long-term neurodevelopment. Whether preventing or minimizing exposure to these risk factors will prevent NDI, however, remains unclear. Full-Text PDF

Postnatal Human Cytomegalovirus Infection in Preterm Infants Has Long-Term Neuropsychological Sequelae

To evaluate whether an early postnatal infection poses a long-term risk for neuropsychological impairment to neonates born very prematurely. Adolescents born very preterm (n = 42, 11.6-16.2 years, mean = 13.9; 15 girls; 19 with and 23 without an early postnatal human cytomegalovirus [CMV] infection) and typically developing, term born controls (n = 24, 11.3-16.6 years, mean = 13.6; 12 girls) were neuropsychologically assessed with the German version of the Wechsler Intelligence Scale and the Developmental Test for Visual Perception. As expected, the full cohort of adolescents born preterm had significantly lower scores than term born controls on IQ (preterm: mean [SD] = 98.43 [14.83], control: 110.00 [8.10], P = .015) and on visuoperceptive abilities (95.64 [12.87] vs 106.24 [9.95], P = .016). Furthermore, adolescents born preterm with early postnatal CMV infection scored significantly lower than those without this infection regarding overall cognitive abilities (92.67 [14.71] vs 102.75 [13.67], P = .030), but not visuoperceptive abilities (91.22 [10.88] vs 98.96 [13.45], P > .05). In our small but well-characterized group, our results provide evidence for adverse effects of early postnatal CMV infection on overall cognitive functions in adolescents born preterm. If confirmed, these results support the implementation of preventive measures.

Long‐term neurobiological consequences of early postnatal hCMV‐infection in former preterms

Early postnatal infection with human cytomegalovirus (hCMV) may contribute to an adverse cognitive outcome in early preterm-born children (PT). We here set out to explore whether long-term neurobiological consequences of such an infection are detectable using fMRI in children and adolescents who were born very preterm and who either did (PThCMV+ ) or did not (PT(hCMV-)) suffer from an early postnatal hCMV-infection, when compared with typically developing healthy control (HC) subjects. Overall, data from 71 children and adolescents could be included, 34 PT (of which 15 were PT(hCMV+) and 19 were PT(hCMV-)) and 37 HC. Using a recently established "dual use" fMRI task, we investigated language and visuospatial functions. There were significant activation differences in the left hippocampus (PT > HC and PT(hCMV+) > HC), and in the right anterior cingulate cortex (PT(hCMV-) > PT(hCMV+)) when performing the language task. Surprisingly, only a small region in the occipital cortex showed a significant activation difference (HC > PT(HCMV-)) when performing the visuospatial task. Targeted analyses revealed differences in gray matter volume, but not density, in several brain regions. Our results suggest that long-term neurobiological consequences of an early postnatal hCMV infection are detectable even in older children and adolescents formerly born very preterm, compatible with a higher effort when performing a cognitive task. This suggests that measures to prevent such an infection are warranted. Furthermore, an interrelation of brain structure and function was detected that may constitute a severe confound when using fMRI to compare structurally differing groups.

Antibiotics for pre-term pre-labour rupture of membranes: prevention of neonatal deaths due to complications of pre-term birth and infection

Background In high-income countries, it is standard practice to give antibiotics to women with pre-term, pre-labour rupture of membranes (pPROM) to delay birth and reduce the risk of infection. In low and middle-income settings, where some 2 million neonatal deaths occur annually due to complications of pre-term birth or infection, many women do not receive antibiotic therapy for pPROM.Objectives To review the evidence for and estimate the effect on neonatal mortality due to pre-term birth complications or infection, of administration of antibiotics to women with pPROM, in low and middle-income countries.Methods We performed a systematic review to update a Cochrane review. Standardized abstraction forms were used. The quality of the evidence provided by individual studies and overall was assessed using an adapted GRADE approach.Results Eighteen RCTs met our inclusion criteria. Most were from high-income countries and provide strong evidence that antibiotics for pPROM reduce the risk of respiratory distress syndrome [risk ratio (RR) = 0.88; confidence interval (CI) 0.80, 0.97], and early onset postnatal infection (RR = 0.61; CI 0.48, 0.77). The data are consistent with a reduction in neonatal mortality (RR = 0.90; CI 0.72, 1.12).Conclusion Antibiotics for pPROM reduce complications due to pre-term delivery and post-natal infection in high-income settings. There is moderate quality evidence that, in low-income settings, where access to other interventions (antenatal steroids, surfactant therapy, ventilation, antibiotic therapy) may be low, antibiotics for pPROM could prevent 4% of neonatal deaths due to complications of prematurity and 8% of those due to infection.

Early postnatal infection with neurotropic influenza A virus: effects on gene expression and behavior in mice

Introduction A number of genes have been associated to the development of schizophrenia, several of which are involved in central nervous system development. It has also been suggested that exposure to viral infections during early life increases the risk for later developing schizophrenia. In this study we investigate if an early postnatal infection by influenza A/WSN/33 virus in mice can cause changes in the expression of genes, including genes associated with schizophrenia, in the brain during development and if the early life infection affect the behavior in adult mice. In addition to wild type mice, an immunodeficient strain (Tap1-/-) was included in the study to model the potential influence of a genetic immune dysfunction.

Development of preterm children with early postnatally-acquired cytomegalovirus infection via breast milk

Background: Congenital infection with Human Cytomegalovirus (HCMV) frequently results in impairment of development and hearing function. In preterm infants there is a high risk for transmission of HCMV from seropositive mothers via brast milk. There is only limited information available on long term consequences of early postnatal HCMV infection via breast milk in preterm infants. In the context of a longitudinal prospective follow-up study in preterm children born at <32 weeks of gestation, results of first follow-up at age 2–4.5 years in 22 HVMC positive preterm children and 22 HCMV negative matched controls suggested no differences in neurological status or development between HCMV postive and HCMV negative children (1).

Effects of two commercial European modified-live vaccines against porcine reproductive and respiratory syndrome viruses in pregnant gilts

The purpose of this study was to assess the effects of two currently available commercial European-type modified-live virus (MLV) vaccines against porcine reproductive and respiratory syndrome in a reproductive pig model. Sixteen 90-day pregnant gilts were divided into four groups and allocated to one of the following intranasal treatments: group A gilts served as negative controls; group B gilts were exposed to a virulent European field strain; group C gilts were exposed to vaccine strain VP046 Bis and group D gilts to vaccine strain All-183. The results indicated that MLV strains can replicate in breeding animals and have the ability to cross the placenta. In particular, viraemia was detected in all gilts in group C and 2/4 gilts in group D, at least at one time point. In addition, transplacental infection was demonstrated in 3/4 gilts in group C and 2/4 gilts in group D. However, congenital and early postnatal infection did not have a marked detrimental effect on piglet performance when compared to negative controls, and no statistically significant differences were observed in most cases. Conversely, the reproductive performance of gilts in group B was significantly worse than that of the other groups. Specifically, the number of born-alive piglets, the survival rate of piglets during lactation and the mean weight of weaned pigs were significantly lower. It was concluded that the two commercial European-type MLV vaccines tested had no marked detrimental effects in pregnant gilts, although the MLV strains can cross the placenta leading to the birth of congenitally infected piglets.

Childhood socioeconomic circumstances and cause-specific mortality in adulthood: systematic review and interpretation.

There is convincing evidence that exposures acting across the life course influence adult health outcomes (1–3). Lifecourse epidemiology examines a range of potential processes through which exposures acting at different stages of life can, singly or in combination, influence disease risk (table 1) (4). In the critical period model, an exposure acting at a specific time has long-lasting effects on the structure or function of the body. The fetal origins hypothesis, in its original formulation, took this approach (5). Other examples of processes where outcomes appear to depend upon the time window during which an exposure acts are limb development (in relation to maternal thalidomide use); infection with hepatitis B and risk of adulthood liver cancer (with very early postnatal infection being most implicated); and environmental lead exposure, which results in serious neurodevelopmental deficits only if occurring in infancy and childhood (3). However, the influence of exposures acting during critical periods of susceptibility may be modified by later life exposures. This is the case for the associations of birth weight with coronary heart disease, high blood pressure, and insulin resistance, where associations are stronger (or only evident) among those who become obese during adolescence or adulthood (6–8).

Clinical effects of porcine reproductive and respiratory syndrome virus on pigs during the early postnatal interval

SUMMARY Objective To determine the effect of congenital and early postnatal infection of pigs with porcine reproductive and respiratory syndrome virus (PRRSV) on postnatal survival and growth. Animals 20 pregnant gilts and their pigs and fetuses. Procedure 16 pregnant gilts (principals) comprising 4 groups (4 gilts/group) were exposed oronasally to 4 strains of PRRSV (a vaccine strain, and 3 field strains) at or about day 90 of gestation. Four pregnant gilts (controls) were kept under similar conditions, except for exposure to PRRSV. Samples collected from pigs before ingestion of colostrum and samples and specimens collected from pigs at selected times thereafter were tested for PRRSV and homologous antibody. Pigs were observed for clinical signs and were weighed at birth and at weekly intervals until they were euthanatized and necropsied at about 3 weeks of age. Results At least some members of all litters of principal gilts were infected congenitally. Most noninfected, liveborn littermates became infected within the first week of life. Infection of pigs with field strains did, and infection of pigs with the vaccine strain did not, adversely affect postnatal survival and growth rate. All infected pigs had generalized lymph node enlargement. Conclusion Exposure of pregnant gilts to either attenuated (vaccine) or virulent (field) strains of PRRSV can result in congenital infection. Vaccine as well as field strains can be transmitted postnatally from infected to noninfected littermates. Pigs infected with field strains have a poorer rate of survival and growth than do noninfected pigs. Clinical Relevance Because attenuated (vaccine) PRRSV can cause congenital infection and be transmitted postnatally from congenitally infected to immune-naive pigs, the use of attenuated virus during gestation is, at best, questionable. (Am J Vet Res 1998;59:52–55)