RESUMEN
SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third-trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.
Asunto(s)
Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Inmunoglobulina G/inmunología , Intercambio Materno-Fetal/inmunología , Placenta/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , SARS-CoV-2/inmunología , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Tercer Trimestre del Embarazo/inmunología , Receptores de IgG/inmunología , Células THP-1RESUMEN
BACKGROUND: The SARS-CoV-2 virus activates maternal and placental immune responses. Such activation in the setting of other infections during pregnancy is known to impact fetal brain development. The effects of maternal immune activation on neurodevelopment are mediated at least in part by fetal brain microglia. However, microglia are inaccessible for direct analysis, and there are no validated non-invasive surrogate models to evaluate in utero microglial priming and function. We have previously demonstrated shared transcriptional programs between microglia and Hofbauer cells (HBCs, or fetal placental macrophages) in mouse models. METHODS AND RESULTS: We assessed the impact of maternal SARS-CoV-2 on HBCs isolated from 24 term placentas (N = 10 SARS-CoV-2 positive cases, 14 negative controls). Using single-cell RNA-sequencing, we demonstrated that HBC subpopulations exhibit distinct cellular programs, with specific subpopulations differentially impacted by SARS-CoV-2. Assessment of differentially expressed genes implied impaired phagocytosis, a key function of both HBCs and microglia, in some subclusters. Leveraging previously validated models of microglial synaptic pruning, we showed that HBCs isolated from placentas of SARS-CoV-2 positive pregnancies can be transdifferentiated into microglia-like cells (HBC-iMGs), with impaired synaptic pruning behavior compared to HBC models from negative controls. CONCLUSION: These findings suggest that HBCs isolated at birth can be used to create personalized cellular models of offspring microglial programming.
Asunto(s)
COVID-19 , Macrófagos , Microglía , Placenta , Complicaciones Infecciosas del Embarazo , SARS-CoV-2 , Femenino , Embarazo , Microglía/virología , Humanos , Placenta/virología , COVID-19/inmunología , Macrófagos/virología , Complicaciones Infecciosas del Embarazo/virología , Complicaciones Infecciosas del Embarazo/patología , SARS-CoV-2/patogenicidad , Feto , Adulto , Encéfalo/virología , Encéfalo/patología , Ratones , AnimalesRESUMEN
Widespread SARS-CoV-2 infection among pregnant individuals has led to a generation of fetuses exposed in utero, but the long-term impact of such exposure remains unknown. Although fetal infection is rare, children born to mothers with SARS-CoV-2 infection may be at increased risk for adverse neurodevelopmental and cardiometabolic outcomes. Fetal programming effects are likely to be mediated at least in part by maternal immune activation. In this review, we discuss recent evidence regarding the effects of prenatal SARS-CoV-2 infection on the maternal, placental, and fetal immune response, as well as the implications for the long-term health of offspring. Extrapolating from what is known about the impact of maternal immune activation in other contexts (e.g., obesity, HIV, influenza), we review the potential for neurodevelopmental and cardiometabolic morbidity in offspring. Based on available data suggesting potential increased neurodevelopmental risk, we highlight the importance of establishing large cohorts to monitor offspring born to SARS-CoV-2-positive mothers for neurodevelopmental and cardiometabolic sequelae.
Asunto(s)
COVID-19 , Enfermedades Cardiovasculares , Complicaciones Infecciosas del Embarazo , Niño , Femenino , Humanos , Inmunidad , Transmisión Vertical de Enfermedad Infecciosa , Placenta , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , SARS-CoV-2RESUMEN
BACKGROUND: Although emerging data during the SARS-CoV-2 pandemic have demonstrated robust messenger RNA vaccine-induced immunogenicity across populations, including pregnant and lactating individuals, the rapid waning of vaccine-induced immunity and the emergence of variants of concern motivated the use of messenger RNA vaccine booster doses. Whether all populations, including pregnant and lactating individuals, will mount a comparable response to a booster dose is not known. OBJECTIVE: This study aimed to profile the humoral immune response to a COVID-19 messenger RNA booster dose in a cohort of pregnant, lactating, and nonpregnant age-matched women. STUDY DESIGN: This study characterized the antibody response against ancestral Spike and Omicron in a cohort of 31 pregnant, 12 lactating, and 20 nonpregnant age-matched controls who received a BNT162b2 or messenger RNA-1273 booster dose after primary COVID-19 vaccination. In addition, this study examined the vaccine-induced antibody profiles of 15 maternal-to-cord dyads at delivery. RESULTS: Receiving a booster dose during pregnancy resulted in increased immunoglobulin G1 levels against Omicron Spike (postprimary vaccination vs postbooster dose; P=.03). Pregnant and lactating individuals exhibited equivalent Spike-specific total immunoglobulin G1, immunoglobulin M, and immunoglobulin A levels and neutralizing titers against Omicron compared with nonpregnant women. Subtle differences in Fc receptor binding and antibody subclass profiles were observed in the immune response to a booster dose in pregnant vs nonpregnant individuals. The analysis of maternal and cord antibody profiles at delivery demonstrated equivalent total Spike-specific immunoglobulin G1 in maternal and cord blood, yet higher Spike-specific FcγR3a-binding antibodies in the cord relative to maternal blood (P=.002), consistent with the preferential transfer of highly functional immunoglobulin. Spike-specific immunoglobulin G1 levels in the cord were positively correlated with the time elapsed since receiving the booster dose (Spearman R, .574; P=.035). CONCLUSION: Study data suggested that receiving a booster dose during pregnancy induces a robust Spike-specific humoral immune response, including against Omicron. If boosting occurs in the third trimester of pregnancy, higher Spike-specific cord immunoglobulin G1 levels are achieved with greater time elapsed between receiving the booster and delivery. Receiving a booster dose has the potential to augment maternal and neonatal immunity.
Asunto(s)
Formación de Anticuerpos , COVID-19 , Recién Nacido , Embarazo , Femenino , Humanos , Vacuna BNT162 , Vacunas contra la COVID-19 , Lactancia , SARS-CoV-2 , Inmunoglobulina G , Anticuerpos AntiviralesAsunto(s)
Perfilación de la Expresión Génica , Transcriptoma , Femenino , Pruebas Hematológicas , Humanos , EmbarazoRESUMEN
There is limited information on the specific impact of maternal infection with the SARS-CoV-2 B.1.617.2 (delta) variant on pregnancy outcomes. We present 2 cases of intrauterine fetal demise and 1 case of severe fetal distress in the setting of maternal infection with delta-variant SARS-CoV-2. In all cases, fetal demise or distress occurred within 14 days of COVID-19 diagnosis. Evaluation revealed maternal viremia, high nasopharyngeal viral load, evidence of placental infection with delta-variant SARS-CoV-2, and hallmark features of SARS-CoV-2 placentitis. We suggest that delta-variant SARS-CoV-2 infection during pregnancy warrants vigilance for placental dysfunction and fetal compromise regardless of disease severity.
Asunto(s)
COVID-19/diagnóstico , Muerte Fetal , Sufrimiento Fetal , Placenta/virología , Complicaciones Infecciosas del Embarazo/virología , SARS-CoV-2 , Adulto , COVID-19/complicaciones , COVID-19/mortalidad , Prueba de COVID-19 , Corioamnionitis , Femenino , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Embarazo , Complicaciones Infecciosas del Embarazo/diagnósticoRESUMEN
Despite evidence to support the safety and efficacy of COVID-19 vaccination in pregnancy, and clear recommendations from professional organizations and the Centers for Disease Control and Prevention (CDC) for pregnant people to get vaccinated, COVID-19 vaccine hesitancy in pregnancy remains a significant public health problem. The emergence of the highly transmissible B.1.617.2 (Delta) variant among primarily unvaccinated people has exposed the cost of vaccine hesitancy. In this commentary, we explore factors contributing to COVID-19 vaccine hesitancy in pregnancy and potential solutions to overcome them. KEY POINTS: · Low COVID-19 vaccination coverage in pregnant people is a major public health problem in the United States.. · COVID-19 vaccine hesitancy in pregnancy is multifactorial.. · The "4 Cs" framework may be useful in countering COVID-19 vaccine hesitancy..
Asunto(s)
COVID-19 , Complicaciones Infecciosas del Embarazo , COVID-19/prevención & control , Vacunas contra la COVID-19 , Femenino , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/prevención & control , SARS-CoV-2 , Estados Unidos , Vacunación , Vacilación a la VacunaciónRESUMEN
BACKGROUND: Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection. METHODS: Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA). RESULTS: Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2. CONCLUSIONS: Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection.
Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/diagnóstico , Sangre Fetal/inmunología , Placenta/metabolismo , SARS-CoV-2/inmunología , Serina Endopeptidasas/metabolismo , Factores Sexuales , Adulto , COVID-19/sangre , Femenino , Sangre Fetal/virología , Feto/virología , Expresión Génica , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/virologíaRESUMEN
BACKGROUND: Pregnant and lactating women were excluded from initial coronavirus disease 2019 vaccine trials; thus, data to guide vaccine decision making are lacking. OBJECTIVE: This study aimed to evaluate the immunogenicity and reactogenicity of coronavirus disease 2019 messenger RNA vaccination in pregnant and lactating women compared with: (1) nonpregnant controls and (2) natural coronavirus disease 2019 infection in pregnancy. STUDY DESIGN: A total of 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 nonpregnant women) were enrolled in a prospective cohort study at 2 academic medical centers. Titers of severe acute respiratory syndrome coronavirus 2 spike and receptor-binding domain immunoglobulin G, immunoglobulin A, and immunoglobulin M were quantified in participant sera (n=131) and breastmilk (n=31) at baseline, at the second vaccine dose, at 2 to 6 weeks after the second vaccine, and at delivery by Luminex. Umbilical cord sera (n=10) titers were assessed at delivery. Titers were compared with those of pregnant women 4 to 12 weeks from the natural infection (n=37) by enzyme-linked immunosorbent assay. A pseudovirus neutralization assay was used to quantify neutralizing antibody titers for the subset of women who delivered during the study period. Postvaccination symptoms were assessed via questionnaire. Kruskal-Wallis tests and a mixed-effects model, with correction for multiple comparisons, were used to assess differences among groups. RESULTS: Vaccine-induced antibody titers were equivalent in pregnant and lactating compared with nonpregnant women (pregnant, median, 5.59; interquartile range, 4.68-5.89; lactating, median, 5.74; interquartile range, 5.06-6.22; nonpregnant, median, 5.62; interquartile range, 4.77-5.98, P=.24). All titers were significantly higher than those induced by severe acute respiratory syndrome coronavirus 2 infection during pregnancy (P<.0001). Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. Neutralizing antibody titers were lower in umbilical cord than maternal sera, although this finding did not achieve statistical significance (maternal sera, median, 104.7; interquartile range, 61.2-188.2; cord sera, median, 52.3; interquartile range, 11.7-69.6; P=.05). The second vaccine dose (boost dose) increased severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G, but not immunoglobulin A, in maternal blood and breastmilk. No differences were noted in reactogenicity across the groups. CONCLUSION: Coronavirus disease 2019 messenger RNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in nonpregnant women. Vaccine-induced immune responses were statistically significantly greater than the response to natural infection. Immune transfer to neonates occurred via placenta and breastmilk.
RESUMEN
BACKGROUND: Collection of biospecimens is a critical first step to understanding the impact of COVID-19 on pregnant women and newborns - vulnerable populations that are challenging to enroll and at risk of exclusion from research. We describe the establishment of a COVID-19 perinatal biorepository, the unique challenges imposed by the COVID-19 pandemic, and strategies used to overcome them. METHODS: A transdisciplinary approach was developed to maximize the enrollment of pregnant women and their newborns into a COVID-19 prospective cohort and tissue biorepository, established on March 19, 2020 at Massachusetts General Hospital (MGH). The first SARS-CoV-2 positive pregnant woman was enrolled on April 2, and enrollment was expanded to SARS-CoV-2 negative controls on April 20. A unified enrollment strategy with a single consent process for pregnant women and newborns was implemented on May 4. SARS-CoV-2 status was determined by viral detection on RT-PCR of a nasopharyngeal swab. Wide-ranging and pregnancy-specific samples were collected from maternal participants during pregnancy and postpartum. Newborn samples were collected during the initial hospitalization. RESULTS: Between April 2 and June 9, 100 women and 78 newborns were enrolled in the MGH COVID-19 biorepository. The rate of dyad enrollment and number of samples collected per woman significantly increased after changes to enrollment strategy (from 5 to over 8 dyads/week, P < 0.0001, and from 7 to 9 samples, P < 0.01). The number of samples collected per woman was higher in SARS-CoV-2 negative than positive women (9 vs 7 samples, P = 0.0007). The highest sample yield was for placenta (96%), umbilical cord blood (93%), urine (99%), and maternal blood (91%). The lowest-yield sample types were maternal stool (30%) and breastmilk (22%). Of the 61 delivered women who also enrolled their newborns, fewer women agreed to neonatal blood compared to cord blood (39 vs 58, P < 0.0001). CONCLUSIONS: Establishing a COVID-19 perinatal biorepository required patient advocacy, transdisciplinary collaboration and creative solutions to unique challenges. This biorepository is unique in its comprehensive sample collection and the inclusion of a control population. It serves as an important resource for research into the impact of COVID-19 on pregnant women and newborns and provides lessons for future biorepository efforts.
Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/psicología , Participación del Paciente , Neumonía Viral/diagnóstico , Neumonía Viral/psicología , Complicaciones Infecciosas del Embarazo/diagnóstico , Manejo de Especímenes , Adulto , COVID-19 , Femenino , Humanos , Recién Nacido , Pandemias , Selección de Paciente , Atención Perinatal , Embarazo , Complicaciones Infecciosas del Embarazo/psicología , SARS-CoV-2RESUMEN
Both human epidemiologic and animal model studies demonstrate that prenatal and lactational exposure to maternal obesity and high-fat diet are associated with adverse neurodevelopmental outcomes in offspring. Neurodevelopmental outcomes described in offspring of obese women include cognitive impairment, autism spectrum disorder (ASD), attention deficit hyperactivity disorder, anxiety and depression, disordered eating, and propensity for reward-driven behavior, among others. This review synthesizes human and animal data linking maternal obesity and high-fat diet consumption to abnormal fetal brain development, and neurodevelopmental and psychiatric morbidity in offspring. It highlights key mechanisms by which maternal obesity and maternal diet impact fetal and offspring development, and sex differences in offspring programming. In addition, we review placental effects of maternal obesity, and the role the placenta might play as an indicator vs mediator of fetal programming.
Asunto(s)
Encéfalo/embriología , Desarrollo Fetal/fisiología , Obesidad Materna/complicaciones , Animales , Encéfalo/crecimiento & desarrollo , Modelos Animales de Enfermedad , Femenino , Historia del Siglo XXI , Humanos , Masculino , Trastornos del Neurodesarrollo/etiología , Trastornos del Neurodesarrollo/metabolismo , Trastornos del Neurodesarrollo/patología , Obesidad Materna/embriología , Obesidad Materna/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/patologíaRESUMEN
Evidence from epidemiological, clinical, and animal model studies clearly demonstrates that prenatal and lactational maternal obesity and high-fat diet consumption are associated with cardiometabolic morbidity in offspring. Fetal and offspring sex may be an important effect modifier. Adverse offspring cardiometabolic outcomes observed in the setting of maternal obesity include an increased risk for obesity, features of metabolic syndrome (hypertension, hyperglycemia and insulin resistance, hyperlipidemia, increased adiposity), and non-alcoholic fatty liver disease. This review article synthesizes human and animal data linking maternal obesity and high-fat diet consumption in pregnancy and lactation to adverse cardiometabolic outcomes in offspring. We review key mechanisms underlying skeletal muscle, adipose tissue, pancreatic, liver, and central brain reward programming in obesity-exposed offspring, and how such malprogramming contributes to offspring cardiometabolic morbidity.
Asunto(s)
Enfermedades Cardiovasculares/etiología , Enfermedades Metabólicas/etiología , Obesidad Materna/complicaciones , Efectos Tardíos de la Exposición Prenatal , Animales , Factores de Riesgo Cardiometabólico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/metabolismo , Femenino , Humanos , Recién Nacido , Masculino , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/metabolismo , Obesidad Materna/epidemiología , Obesidad Materna/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/metabolismoRESUMEN
The need for cardiac surgery during pregnancy is rare. Only 1% to 4% of pregnancies are complicated by maternal cardiac disease and most of these can be managed with medical therapy and lifestyle changes. On occasion, whether due to natural progression of the underlying cardiac disease or precipitated by the cardiovascular changes of pregnancy, cardiac surgical therapy must be considered. Cardiac surgery is inherently dangerous for both, the mother and fetus with mortality rates near 10% and 30%, respectively. For some conditions, percutaneous cardiac intervention offers effective therapy with far less risk to the mother and her fetus. For others, cardiac surgery, including procedures that mandate the use of cardiopulmonary bypass, must be entertained to save the life of the mother. Given the extreme risks to the fetus, if the patient is in the third trimester, strong consideration should be given to delivery before surgery involving cardiopulmonary bypass. At earlier gestational ages when this is not feasible, modifications to the perfusion protocol including higher flow rates, normothermic perfusion, pulsatile flow, and the use of intraoperative external fetal heart rate monitoring should be considered.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Cardiopatías , Complicaciones Posoperatorias , Complicaciones Cardiovasculares del Embarazo , Ajuste de Riesgo/métodos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/métodos , Femenino , Cardiopatías/diagnóstico , Cardiopatías/cirugía , Humanos , Cuidados para Prolongación de la Vida , Mortalidad , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/prevención & control , Embarazo , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Complicaciones Cardiovasculares del Embarazo/cirugía , Resultado del EmbarazoRESUMEN
OBJECTIVE: To test the hypothesis that high fetal fraction (FF) on first trimester cell-free deoxyribonucleic acid (cfDNA) aneuploidy screening is associated with adverse perinatal outcomes. STUDY DESIGN: This is a single-institution retrospective cohort study of women who underwent cfDNA screening at <14 weeks' gestation and delivered a singleton infant between July 2016 and June 2018. Women with abnormal results were excluded. Women with high FF (≥95th percentile) were compared with women with normal FF (5th-95th percentiles). Outcomes investigated were preterm birth, small for gestational age, and hypertensive disorders of pregnancy. RESULTS: A total of 2,033 women met inclusion criteria. The mean FF was 10.0%, and FF >16.5% was considered high (n = 102). Women with high FF had a greater chance of delivering a small for gestational age infant Asunto(s)
Aneuploidia
, Ácidos Nucleicos Libres de Células/sangre
, Feto
, Recién Nacido Pequeño para la Edad Gestacional
, Primer Trimestre del Embarazo
, Adulto
, Femenino
, Humanos
, Hipertensión Inducida en el Embarazo
, Recién Nacido
, Pruebas Prenatales no Invasivas
, Embarazo
, Resultado del Embarazo
, Nacimiento Prematuro
, Estudios Retrospectivos
, Riesgo
RESUMEN
OBJECTIVE: To determine the association between low fetal fraction and birth weight among women with a negative cell-free DNA (cfDNA) result for common aneuploidies in the first trimester. STUDY DESIGN: This is a retrospective cohort of women who delivered a singleton between July 2016 and June 2018 at a single institution and had normal cfDNA testing in the first trimester. The primary variable of interest was "low fetal fraction," which was defined as fetal fractions less than 5th percentile among all fetal fractions in the cohort (fetal fraction < 5.34%). The primary outcomes were birth weight ≤ 5th and ≤ 10th percentiles. Multivariable logistic regressions assessed for the association between low fetal fraction and birth weight. RESULTS: A total of 7,478 women delivered a singleton at ≥24 weeks' gestation, of which 2,387 (32%) underwent genetic screening through cfDNA; the majority were in the first trimester (n = 2,052 [86%]). 2,035 met the inclusion criteria. Birth weight ≤ 5th percentile was significantly higher in the low fetal fraction group (6.9 vs. 3.2%; p = 0.04). A low fetal fraction was associated with higher odds of an infant with a low birth weight: adjusted odds ratio (aOR) of 2.32 (95% CI 1.15-4.67) for birth weight ≤ 10th percentile (p = 0.02) and aOR of 3.73 (95% CI 1.40-9.03) for birth weight ≤ 5th percentile (p = 0.004). CONCLUSION: Low fetal fractions of ≤ 5th percentile were associated with an increased risk of birth weights ≤ 5th and ≤ 10th percentiles in women with negative cfDNA screening in the first trimester. Future work is needed to further investigate this relationship and to determine the potential clinical implications, such as third-trimester screening for growth restriction in women with low fetal fractions and negative cfDNA screening results.
Asunto(s)
Ácidos Nucleicos Libres de Células/sangre , Retardo del Crecimiento Fetal/diagnóstico , Recién Nacido de Bajo Peso , Recién Nacido Pequeño para la Edad Gestacional , Primer Trimestre del Embarazo , Adulto , Aneuploidia , Peso al Nacer , Femenino , Feto , Humanos , Hipertensión Inducida en el Embarazo , Recién Nacido , Modelos Logísticos , Pruebas Prenatales no Invasivas , Embarazo , Resultado del Embarazo , Estudios RetrospectivosRESUMEN
Objective: Postpartum depression (PPD) represents a major contributor to postpartum morbidity and mortality. Beyond efforts at routine screening, risk stratification models could enable more targeted interventions in settings with limited resources. Thus, we aimed to develop and estimate the performance of a generalizable risk stratification model for PPD in patients without a history of depression using information collected as part of routine clinical care. Methods: We performed a retrospective cohort study of all individuals who delivered between 2017 and 2022 in one of two large academic medical centers and six community hospitals. An elastic net model was constructed and externally validated to predict PPD using sociodemographic factors, medical history, and prenatal depression screening information, all of which was known before discharge from the delivery hospitalization. Results: The cohort included 29,168 individuals; 2,703 (9.3%) met at least one criterion for postpartum depression in the 6 months following delivery. In the external validation data, the model had good discrimination and remained well-calibrated: area under the receiver operating characteristic curve 0.721 (95% CI: 0.707-0.734), Brier calibration score 0.088 (95% CI: 0.084 - 0.092). At a specificity of 90%, the positive predictive value was 28.0% (95% CI: 26.0-30.1%), and the negative predictive value was 92.2% (95% CI: 91.8-92.7%). Conclusions: These findings demonstrate that a simple machine-learning model can be used to stratify the risk for PPD before delivery hospitalization discharge. This tool could help identify patients within a practice at the highest risk and facilitate individualized postpartum care planning regarding the prevention of, screening for, and management of PPD at the start of the postpartum period and potentially the onset of symptoms.
RESUMEN
OBJECTIVE: The objective of this study is to determine whether in utero exposure to SARS-CoV-2 is associated with increased risk for a cardiometabolic diagnosis by 18 months of age. METHODS: This retrospective electronic health record (EHR)-based cohort study included the live-born offspring of all individuals who delivered during the COVID-19 pandemic (April 1, 2020-December 31, 2021) at eight hospitals in Massachusetts. Offspring exposure was defined as a positive maternal SARS-CoV-2 polymerase chain reaction test during pregnancy. The primary outcome was presence of an ICD-10 code for a cardiometabolic disorder in offspring EHR by 18 months. Weight-, length-, and BMI-for-age z scores were calculated and compared at 6-month intervals from birth to 18 months. RESULTS: A total of 29,510 offspring (1599 exposed and 27,911 unexposed) were included. By 18 months, 6.7% of exposed and 4.4% of unexposed offspring had received a cardiometabolic diagnosis (crude odds ratio [OR] 1.47 [95% CI: 1.10 to 1.94], p = 0.007; adjusted OR 1.38 [1.06 to 1.77], p = 0.01). Exposed offspring had a significantly greater mean BMI-for-age z score versus unexposed offspring at 6 months (z score difference 0.19 [95% CI: 0.10 to 0.29], p < 0.001; adjusted difference 0.04 [-0.06 to 0.13], p = 0.4). CONCLUSIONS: Exposure to maternal SARS-CoV-2 infection was associated with an increased risk of receiving a cardiometabolic diagnosis by 18 months preceded by greater BMI-for-age at 6 months.
Asunto(s)
COVID-19 , Complicaciones Infecciosas del Embarazo , Efectos Tardíos de la Exposición Prenatal , SARS-CoV-2 , Humanos , Femenino , COVID-19/epidemiología , Embarazo , Estudios Retrospectivos , Lactante , Adulto , Masculino , Complicaciones Infecciosas del Embarazo/virología , Complicaciones Infecciosas del Embarazo/epidemiología , Massachusetts/epidemiología , Recién Nacido , Índice de Masa Corporal , Factores de Riesgo Cardiometabólico , Desarrollo Infantil , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/etiologíaRESUMEN
Maternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many mediated by in utero microglial programming. As microglia remain inaccessible throughout development, identification of noninvasive biomarkers reflecting fetal brain microglial programming could permit screening and intervention. We used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells) in a mouse model of maternal diet-induced obesity, and single-cell RNA-seq to demonstrate shared transcriptional programs. Comparison with human datasets demonstrated conservation of placental resident macrophage signatures between mice and humans. Single-cell RNA-seq identified common alterations in fetal microglial and Hofbauer cell gene expression induced by maternal obesity, as well as sex differences in these alterations. We propose that Hofbauer cells, which are easily accessible at birth, provide insights into fetal brain microglial programs and may facilitate the early identification of offspring vulnerable to neurodevelopmental disorders.
Asunto(s)
Encéfalo , Feto , Microglía , Microglía/metabolismo , Microglía/patología , Animales , Femenino , Embarazo , Encéfalo/metabolismo , Encéfalo/patología , Ratones , Humanos , Macrófagos/metabolismo , Obesidad Materna/metabolismo , Transcriptoma/genética , Masculino , Placenta/metabolismo , Ratones Endogámicos C57BL , Dieta Alta en Grasa/efectos adversos , Obesidad/patología , Obesidad/metabolismoRESUMEN
The intrauterine environment plays a critical role in shaping chronic disease risk over the life course. We prospectively evaluated cardiometabolic outcomes in toddlers born to mothers with versus without prenatal severe acute respiratory syndrome coronavirus 2 infection. Children with in utero severe acute respiratory syndrome coronavirus 2 exposure had higher left ventricular mass in association with altered maternal immunologic indices.