Association between maternal mRNA covid-19 vaccination in early pregnancy and major congenital anomalies in offspring: population based cohort study with sibling matched analysis
Sarah C J JorgensenS.S.M. DroverDeshayne B. FellPeter C. AustinRohan D’SouzaAstrid GuttmannSarah A. BuchanSarah E WilsonSharifa NasreenKevin A. BrownKevin L. SchwartzMina TadrousKumanan WilsonJeffrey C. Kwong
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Objective To examine the association between maternal mRNA covid-19 vaccination during the first trimester of pregnancy and the prevalence of major congenital anomalies in offspring. Design Population based cohort study with sibling matched analysis. Setting Multiple health administrative databases, linked and analysed at ICES, an independent, non-profit research institute that collects and analyses healthcare and demographic data, Ontario, Canada, from 16 October 2021 to 1 May 2023. Population 174 296 singleton live births >20 weeks' gestation with an expected birth date between 16 October 2021 and 1 May 2023: 34 181 (20%) born to mothers who received one or two doses of an mRNA covid-19 vaccine in the first trimester and 34 951 (20%) born to mothers who did not receive a vaccine before or during pregnancy. The sibling matched analysis included 13 312 infants exposed to a covid-19 vaccine in the first trimester and 15 089 matched older siblings with the same mother, with an expected birth date after 16 October 2016 and no reported in utero exposure to a covid-19 vaccine. Main outcome measures Major congenital anomalies, overall and grouped by specific organ systems, diagnosed within 28 days of birth. Results Major congenital anomalies were present in 832 (24.3 per 1000 live births) infants exposed to an mRNA covid-19 vaccine in the first trimester compared with 927 (26.5 per 1000 live births) infants not exposed to a vaccine, resulting in an adjusted prevalence ratio of 0.89 (95% confidence interval (CI) 0.79 to 1.01). Major congenital anomalies were present in 283 (21.3 per 1000 live births) and 343 (22.7 per 1000 live births) infants exposed to an mRNA covid-19 vaccine in the first trimester and their older siblings not exposed to a vaccine, respectively (adjusted prevalence ratio 0.91, 95% CI 0.77 to 1.07). First trimester vaccination was not associated with an increase in major congenital anomalies grouped by specific organ system in the primary or sibling matched analyses. Results were similar across a range of subgroup and sensitivity analyses. Conclusions In this large population based cohort study and sibling matched analysis, mRNA covid-19 vaccination during the first trimester of pregnancy was not associated with an increase in major congenital anomalies in offspring, overall or grouped by organ system.Keywords:
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Abstract Parasites (or diseases) are major selective force for the evolution of life history traits and parasite-host evolution. Mothers can show a variety of responses to parasites during pregnancy with different consequences for them or their offspring. However, whether information in the maternal environment before pregnancy can cause a change in the phenotype of the offspring is unknown. To avoid the confounding effect of pathogens and to reduce the risk of direct effect of mother's immune activation, we injected female laboratory mice with lipopolysaccharides (LPS) before mating. In order to provide a constant information on the potential infectious risk of the environment, females were mated with males that were also exposed to LPS before mating. Offspring from immune-challenged parents were larger and grew at a faster rate than offspring from control parents (injected with PBS). Additionally, offspring from immune-challenged parents that suffered the most from inflammation grew at a faster rate than offspring from low suffering parents. Producing heavier offspring that will reach sexual maturity earlier is likely to have fitness benefit for parents and offspring through improved reproductive success.
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Abstract Food transfer is considered to provide infants with additional nutrients during weaning, and in fact, its frequency peaks around this time. However, the mechanisms underlying such food transfer remain unclear. In this study, we investigated whether adult common marmosets ( Callithrix jacchus ) change their tolerance to offspring begging for food depending on the offspring's age. We used four families consisting of breeding pairs, older offspring (29–49 weeks old), and younger offspring (7–15 weeks old). To directly compare the responses of a parent with its older and younger offspring, we placed one parent and one offspring in a testing space at one time. We presented foods where only the parent could reach them to ensure that the foods were transferred from the parent to offspring. Younger offspring showed more interest in food being held by the parents than older offspring. Parents refused older offspring more frequently than younger offspring and transferred food more often to younger offspring than to older offspring. There was no difference in all behavioral categories between fathers and mothers. These results suggest that both fathers and mothers are more tolerant to weanlings, but their tolerance decreases as offspring mature. Am. J. Primatol. 70:999–1002, 2008. © 2008 Wiley‐Liss, Inc.
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Summary Epidemiological studies have shown an association between low birthweight and adult disease development with transmission to subsequent generations. The aim of the present study was to examine the effect of intrauterine growth restriction in rats, induced by uteroplacental insufficiency, on cardiac structure, number, size, nuclearity, and adult blood pressure in first (F1) and second (F2) generation male offspring. Uteroplacental insufficiency or sham surgery was induced in F0 Wistar‐Kyoto pregnant rats in late gestation giving rise to F1 restricted and control offspring, respectively. F1 control and restricted females were mated with normal males, resulting in F2 control and restricted offspring, respectively. F1 restricted male offspring were significantly lighter at birth ( P < 0.05), but there were no differences in birthweight of F2 offspring. Left ventricular weights and volumes were significantly increased ( P < 0.05) in F1 and F2 restricted offspring at day 35. Left ventricular cardiomyocyte number was not different in F1 and F2 restricted offspring. At 6 months‐of‐age, F1 and F2 restricted offspring had elevated blood pressure (8–15 mmHg, P < 0.05). Our findings demonstrate the emergence of left ventricular hypertrophy and hypertension, with no change in cardiomyocyte number, in F1 restricted male offspring, and this was transmitted to the F2 offspring. The findings support transgenerational programming effects.
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Females vary in the size of offspring that they produce, often in a manner that depends on maternal age or stage. This is puzzling, given that offspring size is predicted to evolve to a single optimal value where the gain in fitness from being larger exactly offsets the fitness lost to the mother by producing fewer offspring. We used a stage-structured life-history model to determine the optimal offspring size for females in different stages. We found that optimal offspring size does not vary with maternal stage when offspring fitness depends only on its size and not on the stage of the mother. This negative result holds even with density dependence, when larger offspring compete better. However, a trade-off between offspring size and maternal survival affects the optimal offspring size. The future reproductive value of the female, coupled with the costs and benefits of offspring investment, drives the evolution of stage-dependent offspring size. If producing larger offspring is riskier for mothers, females produce smaller offspring when their reproductive value in the next time step is large relative to current reproductive prospects. These analyses provide a novel framework for understanding why offspring size varies in age- and stage-structured populations.
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Maternal effects are increasingly recognized as important drivers of population dynamics and determinants of evolutionary trajectories. Recently, there has been a proliferation of studies finding or citing a positive relationship between maternal size/age and offspring size or offspring quality. The relationship between maternal phenotype and offspring size is intriguing in that it is unclear why young mothers should produce offspring of inferior quality or fitness. Here we evaluate the underlying evolutionary pressures that may lead to a maternal size/age-offspring size correlation and consider the likelihood that such a correlation results in a positive relationship between the age or size of mothers and the fitness of their offspring. We find that, while there are a number of reasons why selection may favor the production of larger offspring by larger mothers, this change in size is more likely due to associated changes in the maternal phenotype that affect the offspring size-performance relationship. We did not find evidence that the offspring of older females should have intrinsically higher fitness. When we explored this issue theoretically, the only instance in which smaller mothers produce suboptimal offspring sizes is when a (largely unsupported) constraint on maximum offspring size is introduced into the model. It is clear that larger offspring fare better than smaller offspring when reared in the same environment, but this misses a critical point: different environments elicit selection for different optimal sizes of young. We suggest that caution should be exercised when interpreting the outcome of offspring-size experiments when offspring from different mothers are reared in a common environment, because this approach may remove the source of selection (e.g., reproducing in different context) that induced a shift in offspring size in the first place. It has been suggested that fish stocks should be managed to preserve these older age classes because larger mothers produce offspring with a greater chance of survival and subsequent recruitment. Overall, we suggest that, while there are clear and compelling reasons for preserving older females in exploited populations, there is little theoretical justification or evidence that older mothers produce offspring with higher per capita fitness than do younger mothers.
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Studies have investigated the associations between parental metabolic syndrome (MetS) and offspring MetS. This study aimed to uncover parental-offspring associations for MetS and its components according to offspring sex and age.A cross-sectional study in 1,403 fathers, 1,451 mothers, and 1,532 offspring (340 male and 404 female offspring aged 10-18 years; 283 male and 505 female offspring aged 19-25 years) using the Korea National Health and Nutrition Examination Survey data between 2010 and 2013.All categorized MetS components in fathers and mothers were significantly associated with the same components in male offspring, while high waist circumference, high triglycerides, and low high-density lipoprotein in fathers and mothers were associated with the same components in female offspring. The number of categorized MetS components which were significantly associated between parent-offspring pairs was greater in offspring aged 19-25 years than in those aged 10-18 years. All categorized MetS components were significantly associated between father-male offspring aged 19-25 years pairs, but not in other parent-offspring pairs. The MetS per se in fathers and mothers was significantly associated with that in male offspring aged 10-18 years.There were differential associations according to offspring sex and age group and parent's sex with respect to parental-offspring associations for MetS and its individual components. The associations for MetS and its components were stronger in young adult versus adolescent offspring, in male offspring versus female offspring.
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Maternal effects are increasingly recognized as important drivers of population dynamics and determinants of evolutionary trajectories. Recently, there has been a proliferation of studies finding or citing a positive relationship between maternal size/age and offspring size or offspring quality. The relationship between maternal phenotype and offspring size is intriguing in that it is unclear why young mothers should produce offspring of inferior quality or fitness. Here we evaluate the underlying evolutionary pressures that may lead to a maternal size/age–offspring size correlation and consider the likelihood that such a correlation results in a positive relationship between the age or size of mothers and the fitness of their offspring. We find that, while there are a number of reasons why selection may favor the production of larger offspring by larger mothers, this change in size is more likely due to associated changes in the maternal phenotype that affect the offspring size–performance relationship. We did not find evidence that the offspring of older females should have intrinsically higher fitness. When we explored this issue theoretically, the only instance in which smaller mothers produce suboptimal offspring sizes is when a (largely unsupported) constraint on maximum offspring size is introduced into the model. It is clear that larger offspring fare better than smaller offspring when reared in the same environment, but this misses a critical point: different environments elicit selection for different optimal sizes of young. We suggest that caution should be exercised when interpreting the outcome of offspring-size experiments when offspring from different mothers are reared in a common environment, because this approach may remove the source of selection (e.g., reproducing in different context) that induced a shift in offspring size in the first place. It has been suggested that fish stocks should be managed to preserve these older age classes because larger mothers produce offspring with a greater chance of survival and subsequent recruitment. Overall, we suggest that, while there are clear and compelling reasons for preserving older females in exploited populations, there is little theoretical justification or evidence that older mothers produce offspring with higher per capita fitness than do younger mothers.
Maternal effect
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Affect
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