Changes in Visceral and Ectopic Adipose Tissue Stores Across Pregnancy and Their Relationship to Gestational Weight Gain.

BACKGROUND: Excessive gestational weight gain has been associated with increased total body fat (TBF), metabolic syndrome, and abdominal obesity. However, little is known about the relationship of gestational weight gain with changes in metabolically active visceral or ectopic (hepatic and skeletal muscle) lipid stores. OBJECTIVES: In a prospective study of 50 healthy, pregnant women, we assessed whether changes in weight were associated with changes in total, visceral, and ectopic lipid stores. METHODS: Participants (ages 19-39) were primarily White (84%). The mean preconception BMI was 25.8 kg/m2 (SD, 4.5 kg/m2; min-max, 17.1-35.9 kg/m2). Measurements were completed at visits 1 and 2 at means of 16 and 34 weeks gestation, respectively, and included TBF using BOD POD; abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) using MRI; and intrahepatic lipids (IHL), intramyocellular lipids (IMCL), and extramyocellular lipids (EMCL) using magnetic resonance spectroscopy. We used paired t-tests to examine changes in adipose tissue and Pearson's correlation to examine associations of adipose tissue changes and weight changes. We also examined whether changes in adipose tissue stores differed by preconception BMI (normal, overweight, and obese), using 1-way ANOVA. RESULTS: The TBF (mean change, +3.5 kg; 95% CI: 2.4-4.6 kg), SAT (mean change, +701 cm3; 95% CI: 421-981 cm3), VAT (mean change, +275 cm3; 95% CI: 170-379 cm3), and IHL (percentage water peak; median, +0.15; IQR = -0.01 to 0.32) values increased significantly; the IMCL and EMCL values did not change. Changes varied by BMI strata, with the least increase (or, for SAT, net loss) among women with obesity. Weight change was positively correlated with changes in TBF (r = 0.83; P < 0.001), SAT (r = 0.74; P < 0.001), and VAT (r = 0.63; P < 0.001) but not significantly correlated with changes in ectopic lipids (IHL, IMCL, and EMCL; -0.14 < r < 0.26). CONCLUSIONS: Preferential deposition of adipose tissue to the viscera in pregnancy, as seen in our sample, could serve an important metabolic function; however, excessive deposition in this region could negatively affect maternal health.

The importance of nutrition in pregnancy and lactation: lifelong consequences.

Most women in the United States do not meet the recommendations for healthful nutrition and weight before and during pregnancy. Women and providers often ask what a healthy diet for a pregnant woman should look like. The message should be "eat better, not more." This can be achieved by basing diet on a variety of nutrient-dense, whole foods, including fruits, vegetables, legumes, whole grains, healthy fats with omega-3 fatty acids that include nuts and seeds, and fish, in place of poorer quality highly processed foods. Such a diet embodies nutritional density and is less likely to be accompanied by excessive energy intake than the standard American diet consisting of increased intakes of processed foods, fatty red meat, and sweetened foods and beverages. Women who report "prudent" or "health-conscious" eating patterns before and/or during pregnancy may have fewer pregnancy complications and adverse child health outcomes. Comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) among women with inadequate nutrition has been associated with improved birth outcomes, including decreased rates of low birthweight. A diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats. User-friendly tools to facilitate a quick evaluation of dietary patterns with clear guidance on how to address dietary inadequacies and embedded support from trained healthcare providers are urgently needed. Recent evidence has shown that although excessive gestational weight gain predicts adverse perinatal outcomes among women with normal weight, the degree of prepregnancy obesity predicts adverse perinatal outcomes to a greater degree than gestational weight gain among women with obesity. Furthermore, low body mass index and insufficient gestational weight gain are associated with poor perinatal outcomes. Observational data have shown that first-trimester gain is the strongest predictor of adverse outcomes. Interventions beginning in early pregnancy or preconception are needed to prevent downstream complications for mothers and their children. For neonates, human milk provides personalized nutrition and is associated with short- and long-term health benefits for infants and mothers. Eating a healthy diet is a way for lactating mothers to support optimal health for themselves and their infants.

Counseling and Behavioral Interventions for Healthy Weight and Weight Gain in Pregnancy: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Counseling and active behavioral interventions to limit excess gestational weight gain (GWG) during pregnancy may improve health outcomes for women and infants. The 2009 National Academy of Medicine (NAM; formerly the Institute of Medicine) recommendations for healthy GWG vary according to prepregnancy weight category. Objective: To review and synthesize the evidence on benefits and harms of behavioral interventions to promote healthy weight gain during pregnancy to inform the US Preventive Services Task Force recommendation. Data Sources: Ovid MEDLINE and the Cochrane Library to March 2020, with surveillance through February 2021. Study Selection: Randomized clinical trials and nonrandomized controlled intervention studies focused on diet, exercise, and/or behavioral counseling interventions on GWG. Data Extraction and Synthesis: Independent data abstraction and study quality rating with dual review. Main Outcomes and Measures: Gestational weight-related outcomes; maternal and infant morbidity and mortality; harms. Results: Sixty-eight studies (N = 25 789) were included. Sixty-seven studies evaluated interventions during pregnancy, and 1 evaluated an intervention prior to pregnancy. GWG interventions were associated with reductions in risk of gestational diabetes (43 trials, n = 19 752; relative risk [RR], 0.87 [95% CI, 0.79 to 0.95]; absolute risk difference [ARD], -1.6%) and emergency cesarean delivery (14 trials, n = 7520; RR, 0.85 [95% CI, 0.74 to 0.96]; ARD, -2.4%). There was no significant association between GWG interventions and risk of gestational hypertension, cesarean delivery, or preeclampsia. GWG interventions were associated with decreased risk of macrosomia (25 trials, n = 13 990; RR, 0.77 [95% CI, 0.65 to 0.92]; ARD, -1.9%) and large for gestational age (26 trials, n = 13 000; RR, 0.89 [95% CI, 0.80 to 0.99]; ARD, -1.3%) but were not associated with preterm birth. Intervention participants experienced reduced weight gain across all prepregnancy weight categories (55 trials, n = 20 090; pooled mean difference, -1.02 kg [95% CI, -1.30 to -0.75]) and demonstrated lower likelihood of GWG in excess of NAM recommendations (39 trials, n = 14 271; RR, 0.83 [95% CI, 0.77 to 0.89]; ARD, -7.6%). GWG interventions were associated with reduced postpartum weight retention at 12 months (10 trials, n = 3957; mean difference, -0.63 kg [95% CI, -1.44 to -0.01]). Data on harms were limited. Conclusions and Relevance: Counseling and active behavioral interventions to limit GWG were associated with decreased risk of gestational diabetes, emergency cesarean delivery, macrosomia, and large for gestational age. GWG interventions were also associated with modest reductions in mean GWG and decreased likelihood of exceeding NAM recommendations for GWG.

Maternal Pregravid Obesity Remodels the DNA Methylation Landscape of Cord Blood Monocytes Disrupting Their Inflammatory Program.

Prepregnancy maternal obesity is associated with adverse outcomes for the offspring, including increased incidence of neonatal bacterial sepsis and necrotizing enterocolitis. We recently reported that umbilical cord blood (UCB) monocytes from babies born to obese mothers generate a reduced IL-6/TNF-α response to TLR 1/2 and 4 ligands compared to those collected from lean mothers. These observations suggest altered development of the offspring's immune system, which in turn results in dysregulated function. We therefore investigated transcriptional and epigenetic differences within UCB monocytes stratified by prepregnancy maternal body mass index. We show that UCB monocytes from babies born to obese mothers generate a dampened response to LPS stimulation compared with those born to lean mothers, at the level of secreted immune mediators and transcription. Because gene expression profiles of resting UCB monocytes from both groups were comparable, we next investigated the role of epigenetic differences. Indeed, we detected stark differences in methylation levels within promoters and regulatory regions of genes involved in TLR signaling in resting UCB monocytes. Interestingly, the DNA methylation status of resting cells was highly predictive of transcriptional changes post-LPS stimulation, suggesting that cytosine methylation is one of the dominant mechanisms driving functional inadequacy in UCB monocytes obtained from babies born to obese mothers. These data highlight a potentially critical role of maternal pregravid obesity-associated epigenetic changes in influencing the function of an offspring's monocytes at birth. These findings further our understanding of mechanisms that explain the increased risk of infection in neonates born to mothers with high prepregnancy body mass index.

The Association between Maternal Height, Body Mass Index, and Perinatal Outcomes.

OBJECTIVE: To test the hypothesis that maternal height is associated with adverse perinatal outcomes, controlling for and stratified by maternal body mass index (BMI). STUDY DESIGN: This was a retrospective cohort study of all births in California between 2007 and 2010 (n = 1,775,984). Maternal height was categorized into quintiles, with lowest quintile (≤20%) representing shorter stature and the uppermost quintile (≥80%) representing taller stature. Outcomes included gestational diabetes mellitus (GDM), preeclampsia, cesarean, preterm birth (PTB), macrosomia, and low birth weight (LBW). We calculated height/outcome associations among BMI categories, and BMI/outcome associations among height categories, using various multivariable logistic regression models. RESULTS: Taller women were less likely to have GDM, nulliparous cesarean, PTB, and LBW; these associations were similar across maternal BMI categories and persisted after multivariable adjustment. In contrast, when stratified by maternal height, the associations between maternal BMI and birth outcomes varied by specific outcomes, for example, the association between morbid obesity (compared with normal or overweight) and the risk of GDM was weaker among shorter women (adjusted odds ratio [aOR], 95% confidence interval [CI]: 3.48, 3.28-3.69) than taller women (aOR, 95% CI: 4.42, 4.19-4.66). CONCLUSION: Maternal height is strongly associated with altered perinatal risk even after accounting for variations in complications by BMI.

Impact of maternal obesity and breastfeeding intention on lactation intensity and duration.

Exclusive breastfeeding (EBF) has numerous maternal health benefits. However, EBF rates are lower in mothers with obesity. We sought to better understand whether maternal body composition measurements in early pregnancy are also predictive of lower rates of EBF. Healthy pregnant women with prepregnancy body mass index (BMI) of 17.5-51 kg/m2 underwent determination of percent body fat (% body fat) in early (12-16 weeks) and late (37 weeks) gestation. Intent and duration of EBF were determined by surveys completed at 6 weeks and 6 months postpartum (PP). Unadjusted and adjusted analyses were performed to compare EBF rates and weaning by maternal BMI and % body fat. Increasing BMI and % body fat in early pregnancy were significantly associated with lower rates of EBF among women intending EBF. Women with BMI ≥ 25 were less likely to be EBF at 6 weeks and 6 months PP compared with women of normal BMI (67 and 37% vs. 91 and 79%, P value 0.005 and 0.001, respectively). Among primiparous women intending EBF, 100% of women in the lowest two body fat quartiles in early pregnancy were EBF at 6 weeks PP compared with 66.7 and 63.6% of women in the higher quartiles (P = 0.03). Lactation cessation by 6 months PP was higher with increasing maternal BMI (P = 0.001). Maternal obesity in early gestation is associated with lower EBF rates among women intending EBF and earlier weaning. Excess adiposity in early pregnancy may impede EBF.

Maternal Body Mass Index and Regional Anaesthesia Use at Term: Prevalence and Complications.

BACKGROUND: There is an evidence gap regarding the use of regional anaesthesia (epidural, spinal, or combined epidural/spinal anaesthesia) and associated complications by maternal body mass index (BMI). We examine associations between regional anaesthesia, mode of delivery, and regional anaesthesia complications by pre-pregnancy BMI categories among term deliveries. METHODS: Retrospective cohort study of births in California, 2007-2010, utilizing linked birth certificate data and patient discharge data. Outcomes were mode of delivery (among laboured deliveries) and select regional anaesthesia complications. Multivariable Poisson regression was used to adjust for maternal characteristics. RESULTS: In women undergoing labour (i.e. laboured delivery), women with higher BMI categories were more likely to receive regional analgesia in a dose-response fashion (adjusted risk ratio [RR] 1.10, 95% confidence interval [CI] 1.10, 1.11 for primiparous women with category I obesity), and in those receiving regional anaesthesia, were less likely to deliver vaginally (e.g. RR 0.85, 95% CI 0.84, 0.85 for the same category of women). Regional anaesthesia complications displayed a complex relationship with maternal BMI, with women in intermediate obesity categories having decreased odds as compared to normal-weight women, and women in the highest BMI category having a twofold increased risk of complications (RR 2.34, 95% CI 1.37, 4.02 for primiparous women). CONCLUSION: Labouring women in higher BMI categories were more likely to receive regional anaesthesia and more likely to deliver via caesarean compared to normal weight women and women without regional anaesthesia. Rates of anaesthesia complications were highest among women in the highest BMI category.

Maternal obesity alters immune cell frequencies and responses in umbilical cord blood samples.

BACKGROUND: Maternal obesity is one of the several key factors thought to modulate neonatal immune system development. Data from murine studies demonstrate worse outcomes in models of infection, autoimmunity, and allergic sensitization in offspring of obese dams. In humans, children born to obese mothers are at increased risk for asthma. These findings suggest a dysregulation of immune function in the children of obese mothers; however, the underlying mechanisms remain poorly understood. The aim of this study was to examine the relationship between maternal body weight and the human neonatal immune system. METHODS: Umbilical cord blood samples were collected from infants born to lean, overweight, and obese mothers. Frequency and function of major innate and adaptive immune cell populations were quantified using flow cytometry and multiplex analysis of circulating factors. RESULTS: Compared to babies born to lean mothers, babies of obese mothers had fewer eosinophils and CD4 T helper cells, reduced monocyte and dendritic cell responses to Toll-like receptor ligands, and increased plasma levels of IFN-α2 and IL-6 in cord blood. CONCLUSION: These results support the hypothesis that maternal obesity influences programming of the neonatal immune system, providing a potential link to increased incidence of chronic inflammatory diseases such as asthma and cardiovascular disease in the offspring.

The association of cord serum cytokines with neurodevelopmental outcomes.

OBJECTIVE: To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD). STUDY DESIGN: Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated preterm birth (PTB) for prevention of CP, with evaluation of surviving children at the age of 2. NDD was defined as a Bayley psychomotor developmental index (PDI) and/or mental developmental index (MDI) < 70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥ 85, were matched by race and gestational age. Cord serum was analyzed for interleukin-8 (IL-8) interleukin-1 beta (IL-1ß), and tumor necrosis factor-α (TNF-α) levels. Elevated cytokine levels were defined as ≥ 75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity, and sociodemographic differences. RESULTS: Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1ß were more common in cord blood serum from infants with subsequent low MDI as compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1ß, and TNF-α) were not elevated with CP or low PDI. CONCLUSION: Cord serum IL-8, IL-1ß, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.

The effect of maternal body mass index on perinatal outcomes in women with diabetes.

OBJECTIVE: To determine the effect of increasing maternal obesity, including superobesity (body mass index [BMI] ≥ 50 kg/m2), on perinatal outcomes in women with diabetes. STUDY DESIGN: Retrospective cohort study of birth records for all live-born nonanomalous singleton infants ≥ 37 weeks' gestation born to Missouri residents with diabetes from 2000 to 2006. Women with either pregestational or gestational diabetes were included. RESULTS: There were 14,595 births to women with diabetes meeting study criteria, including 7,082 women with a BMI > 30 kg/m2 (48.5%). Compared with normal-weight women with diabetes, increasing BMI category, especially superobesity, was associated with a significantly increased risk for preeclampsia (adjusted relative risk [aRR] 3.6, 95% confidence interval [CI] 2.5, 5.2) and macrosomia (aRR 3.0, 95% CI 1.8, 5.40). The majority of nulliparous obese women with diabetes delivered via cesarean including 50.5% of obese, 61.4% of morbidly obese, and 69.8% of superobese women. The incidence of primary elective cesarean among nulliparous women with diabetes increased significantly with increasing maternal BMI with over 33% of morbidly obese and 39% of superobese women with diabetes delivering electively by cesarean. CONCLUSION: Increasing maternal obesity in women with diabetes is significantly associated with higher risks of perinatal complications, especially cesarean delivery.

Barriers to implementing good nutrition in pregnancy and early childhood: Creating equitable national solutions.

Exposure to deleterious stressors in early life, such as poor nutrition, underlies most adult-onset chronic diseases. As rates of chronic disease continue to climb in the United States, a focus on good nutrition before and during pregnancy, lactation, and early childhood provides a potential opportunity to reverse this trend. This report provides an overview of nutrition investigations in pregnancy and early childhood and addresses racial disparities and health outcomes, current national guidelines, and barriers to achieving adequate nutrition in pregnant individuals and children. Current national policies and community interventions to improve nutrition, as well as the current state of nutrition education among healthcare professionals and students, are discussed. Major gaps in knowledge and implementation of nutrition practices during pregnancy and early childhood were identified and action goals were constructed. The action goals are intended to guide the development and implementation of critical nutritional strategies that bridge these gaps. Such goals create a national blueprint for improving the health of mothers and children by promoting long-term developmental outcomes that improve the overall health of the US population.

Monoclonal Antibody Therapy of Breastfeeding Patient Infected with SARS-CoV-2: A Case Report.

Introduction: Although safety data demonstrated the efficacy and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination for all individuals over 6 months of age, including pregnant and breastfeeding individuals, optimal treatment courses for symptomatic pregnant and lactating individuals infected with SARS-CoV-2 remain to be defined. Case Description: A coronavirus disease 2019 (COVID-19)-vaccinated breastfeeding woman received anti-SARS-CoV-2 monoclonal antibody treatment casirivimab-imdevimab 5 days after diagnosis of a symptomatic breakthrough SARS-CoV-2 infection. Results and Conclusions: The patient did not present with obvious defects in innate or adaptive cellular subsets, but compared with controls had minimal maternal antibody response to recommended pregnancy vaccinations including SARS-CoV-2 and tetanus, diphtheria, pertussis (TDaP). The outcome of the monoclonal antibody infusion treatment was favorable as it transiently increased SARS-CoV-2 antibody titers in plasma and human milk compartments.

Mild/asymptomatic COVID-19 in unvaccinated pregnant mothers impairs neonatal immune responses.

Maternal SARS-CoV-2 infection triggers placental inflammation and alters cord blood immune cell composition. However, most studies focus on outcomes of severe maternal infection. Therefore, we analyzed cord blood and chorionic villi from newborns of unvaccinated mothers who experienced mild/asymptomatic SARS-CoV-2 infection during pregnancy. We investigated immune cell rewiring using flow cytometry, single-cell RNA sequencing, and functional readouts using ex vivo stimulation with TLR agonists and pathogens. Maternal infection was associated with increased frequency of memory T and B cells and nonclassical monocytes in cord blood. Ex vivo T and B cell responses to stimulation were attenuated, suggesting a tolerogenic state. Maladaptive responses were also observed in cord blood monocytes, where antiviral responses were dampened but responses to bacterial TLRs were increased. Maternal infection was also associated with expansion and activation of placental Hofbauer cells, secreting elevated levels of myeloid cell-recruiting chemokines. Moreover, we reported increased activation of maternally derived monocytes/macrophages in the fetal placenta that were transcriptionally primed for antiviral responses. Our data indicate that even in the absence of vertical transmission or symptoms in the neonate, mild/asymptomatic maternal COVID-19 altered the transcriptional and functional state in fetal immune cells in circulation and in the placenta.

Maternal obesity blunts antimicrobial responses in fetal monocytes.

Maternal pre-pregnancy (pregravid) obesity is associated with adverse outcomes for both mother and offspring. Amongst the complications for the offspring is increased susceptibility and severity of neonatal infections necessitating admission to the intensive care unit, notably bacterial sepsis and enterocolitis. Previous studies have reported aberrant responses to LPS and polyclonal stimulation by umbilical cord blood monocytes that were mediated by alterations in the epigenome. In this study, we show that pregravid obesity dysregulates umbilical cord blood monocyte responses to bacterial and viral pathogens. Specifically, interferon-stimulated gene expression and inflammatory responses to respiratory syncytial virus (RSV) and E. coli were significantly dampened, respectively . Although upstream signaling events were comparable, translocation of the key transcription factor NF-κB and chromatin accessibility at pro-inflammatory gene promoters following TLR stimulation was significantly attenuated. Using a rhesus macaque model of western style diet-induced obesity, we further demonstrate that this defect is detected in fetal peripheral monocytes and tissue-resident macrophages during gestation. Collectively, these data indicate that maternal obesity alters metabolic, signaling, and epigenetic profiles of fetal monocytes leading to a state of immune paralysis during late gestation and at birth.

Multimodal profiling of term human decidua demonstrates immune adaptations with pregravid obesity.

Leukocyte diversity of the first-trimester maternal-fetal interface has been extensively described; however, the immunological landscape of the term decidua remains poorly understood. We therefore profiled human leukocytes from term decidua collected via scheduled cesarean delivery. Relative to the first trimester, our analyses show a shift from NK cells and macrophages to T cells and enhanced immune activation. Although circulating and decidual T cells are phenotypically distinct, they demonstrate significant clonotype sharing. We also report significant diversity within decidual macrophages, the frequency of which positively correlates with pregravid maternal body mass index. Interestingly, the ability of decidual macrophages to respond to bacterial ligands is reduced with pregravid obesity, suggestive of skewing toward immunoregulation as a possible mechanism to safeguard the fetus against excessive maternal inflammation. These findings are a resource for future studies investigating pathological conditions that compromise fetal health and reproductive success.

Obesity trends and perinatal outcomes in black and white teenagers.

OBJECTIVE: Our objective was to explore the trends in prepregnancy body mass index (BMI) for black and white teenagers over time and the association between elevated BMI and outcomes based on race. STUDY DESIGN: This was a retrospective cohort study of singleton infants (n = 38,158) born to black (34%) and white (66%) teenagers (<18 years of age). We determined the prevalence of elevated prepregnancy BMI between 1993 and 2006 and the association between elevated prepregnancy BMI (primary exposure) and maternal and perinatal outcomes based on race (2000-2006). RESULTS: The percentage of white teenagers with elevated prepregnancy BMI increased significantly from 17-26%. White and black overweight and obese teenagers were more likely to have pregnancy-related hypertension than normal-weight teenagers; postpartum hemorrhage was increased only in obese black teenagers, and infant complications were increased only in overweight and obese white teenagers. CONCLUSION: Because the percentage of elevated prepregnancy BMI has increased in white teenagers, specific risks for poor maternal and perinatal outcomes in the overweight and obese teenagers varies by race.

Maternal superobesity and perinatal outcomes.

OBJECTIVE: The purpose of this study was to determine the effect of maternal superobesity (body mass index [BMI], ≥ 50 kg/m(2)) compared with morbid obesity (BMI, 40-49.9 kg/m(2)) or obesity (BMI, 30-39.9 kg/m(2)) on perinatal outcomes. STUDY DESIGN: We conducted a retrospective cohort study of birth records that were linked to hospital discharge data for all liveborn singleton term infants who were born to obese Missouri residents from 2000-2006. We excluded major congenital anomalies and women with diabetes mellitus or chronic hypertension. RESULTS: There were 64,272 births that met the study criteria, which included 1185 superobese mothers (1.8%). Superobese women were significantly more likely than obese women to have preeclampsia (adjusted relative risk [aRR], 1.7; 95% confidence interval [CI], 1.4-2.1), macrosomia (aRR, 1.8; 95% CI, 1.3-2.5), and cesarean delivery (aRR, 1.8; 95% CI, 1.5-2.1). Almost one-half of all superobese women (49.1%) delivered by cesarean section, and 33.8% of superobese nulliparous women underwent scheduled primary cesarean delivery. CONCLUSION: Women with a BMI of ≥ 50 kg/m(2) are at significantly increased risk for perinatal complications compared with obese women with a lower BMI.

Single-cell RNA sequencing reveals immunological rewiring at the maternal-fetal interface following asymptomatic/mild SARS-CoV-2 infection.

While severe coronavirus 2019 (COVID-19) is associated with immune activation at the maternal-fetal interface, responses to asymptomatic/mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain unknown. Here, we assess immunological adaptations in blood and term decidua in response to asymptomatic/mild disease in pregnant women. We report attenuated antigen presentation and type I interferon (IFN) signaling pathways, loss of tissue-resident decidual macrophages, and upregulated cytokine/chemokine signaling in monocyte-derived decidual macrophages. Furthermore, we describe increased frequencies of activated tissue-resident T cells and decreased abundance of regulatory T cells with infection while frequencies of cytotoxic CD4/CD8 T cells are increased in the blood. In contrast to decidual macrophages, type I IFN signaling is higher in decidual T cells. Finally, infection leads to a narrowing of T cell receptor diversity in both blood and decidua. Collectively, these observations indicate that asymptomatic/mild COVID-19 during pregnancy results in remodeling of the immunological landscape of the maternal-fetal interface, with a potential for long-term adverse outcomes for the offspring.

SARS-CoV-2 Vaccine Booster Elicits Robust Prolonged Maternal Antibody Responses and Passive Transfer Via The Placenta And Breastmilk.

Background: Infection during pregnancy can result in adverse outcomes for both pregnant persons and offspring. Maternal vaccination is an effective mechanism to protect both mother and neonate into post-partum. However, our understanding of passive transfer of antibodies elicited by maternal SARS-CoV-2 mRNA vaccination during pregnancy remains incomplete. Objective: We aimed to evaluate the antibody responses engendered by maternal SARS-CoV-2 vaccination following initial and booster doses in maternal circulation and breastmilk to better understand passive immunization of the newborn. Study Design: We collected longitudinal blood samples from 121 pregnant women who received SARS-CoV-2 mRNA vaccines spanning from early gestation to delivery followed by collection of blood samples and breastmilk between delivery and 12 months post-partum. During the study, 70% of the participants also received a booster post-partum. Paired maternal plasma, breastmilk, umbilical cord plasma, and newborn plasma samples were tested via enzyme-linked immunosorbent assays (ELISA) to evaluate SARS-CoV-2 specific IgG antibody levels. Results: Vaccine-elicited maternal antibodies were detected in both cord blood and newborn blood, albeit at lower levels than maternal circulation, demonstrating transplacental passive immunization. Booster vaccination significantly increased spike specific IgG antibody titers in maternal plasma and breastmilk. Finally, SARS-CoV-2 specific IgG antibodies in newborn blood correlated negatively with days post initial maternal vaccine dose. Conclusion: Vaccine-induced maternal SARS-CoV-2 antibodies were passively transferred to the offspring in utero via the placenta and after birth via breastfeeding. Maternal booster vaccination, regardless of gestational age at maternal vaccination, significantly increased antibody levels in breastmilk and maternal plasma, indicating the importance of this additional dose to maximize passive protection against SARS-CoV-2 infection for neonates and infants until vaccination eligibility.

Impact of multiple cesarean deliveries on maternal morbidity: a systematic review.

OBJECTIVE: The purpose of this study was to determine the impact of increasing numbers of cesarean deliveries on maternal morbidity. This study was performed for the 2010 National Institutes of Health Consensus Development Conference on Vaginal Birth After Cesarean: New Insights. STUDY DESIGN: We conducted a systematic review and metaanalysis of observational studies. RESULTS: Twenty-one studies (2,282,922 deliveries) were included. The rate of hysterectomy, blood transfusions, adhesions, and surgical injury all increased with increasing number of cesarean deliveries. The incidence of placenta previa increased from 10/1000 deliveries with 1 previous cesarean delivery to 28/1000 with ≥3 cesarean deliveries. Compared with women with previa and no previous cesarean delivery, women with previa and ≥3 cesarean deliveries had a statistically significant increased risk of accreta (3.3-4% vs 50-67%), hysterectomy (0.7-4% vs 50-67%), and composite maternal morbidity (15% vs 83%; odds ratio, 33.6; 95% confidence interval, 14.6-77.4). CONCLUSION: Serious maternal morbidity progressively increased as the number of previous cesarean deliveries increased.