Prevalence and duration of SARS-CoV-2 fecal shedding in breastfeeding dyads following maternal COVID-19 diagnosis.

Background: There is a paucity of data on the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in feces of lactating women with coronavirus disease 2019 (COVID-19) and their breastfed infants as well as associations between fecal shedding and symptomatology. Objective: We examined whether and to what extent SARS-CoV-2 is detectable in the feces of lactating women and their breastfed infants following maternal COVID-19 diagnosis. Methods: This was a longitudinal study carried out from April 2020 to December 2021 involving 57 breastfeeding maternal-infant dyads: 33 dyads were enrolled within 7 d of maternal COVID-19 diagnosis, and 24 healthy dyads served as controls. Maternal/infant fecal samples were collected by participants, and surveys were administered via telephone over an 8-wk period. Feces were analyzed for SARS-CoV-2 RNA. Results: Signs/symptoms related to ears, eyes, nose, and throat (EENT); general fatigue/malaise; and cardiopulmonary signs/symptoms were commonly reported among mothers with COVID-19. In infants of mothers with COVID-19, EENT, immunologic, and cardiopulmonary signs/symptoms were most common, but prevalence did not differ from that of infants of control mothers. SARS-CoV-2 RNA was detected in feces of 7 (25%) women with COVID-19 and 10 (30%) of their infants. Duration of fecal shedding ranged from 1-4 wk for both mothers and infants. SARS-CoV-2 RNA was sparsely detected in feces of healthy dyads, with only one mother's and two infants' fecal samples testing positive. There was no relationship between frequencies of maternal and infant SARS-CoV-2 fecal shedding (P=0.36), although presence of maternal or infant fever was related to increased likelihood (7-9 times greater, P≤0.04) of fecal shedding in infants of mothers with COVID-19.

Lifetime Duration of Breastfeeding and Cardiovascular Risk in Women With Type 2 Diabetes or a History of Gestational Diabetes: Findings From Two Large Prospective Cohorts.

OBJECTIVE: Breastfeeding duration is inversely associated with risks of cardiovascular disease (CVD) and type 2 diabetes in parous women. However, the association among women at high risk, including women with type 2 diabetes or gestational diabetes mellitus (GDM) is unclear. RESEARCH DESIGN AND METHODS: We included 15,146 parous women with type 2 diabetes from the Nurses' Health Study I and II (NHS, NHS II) and 4,537 women with a history of GDM from NHS II. Participants reported history of breastfeeding via follow-up questionnaires. Incident CVD by 2017 comprised stroke or coronary heart disease (CHD) (myocardial infarction, coronary revascularization). Adjusted hazard ratios (aHRs) and 95% CIs were estimated using Cox models. RESULTS: We documented 1,159 incident CVD cases among women with type 2 diabetes in both cohorts during 188,874 person-years of follow-up and 132 incident CVD cases among women with a GDM history during 100,218 person-years of follow-up. Longer lifetime duration of breastfeeding was significantly associated with lower CVD risk among women with type 2 diabetes, with pooled aHR of 0.68 (95% CI 0.54-0.85) for >18 months versus 0 months and 0.94 (0.91-0.98) per 6-month increment in breastfeeding. Similar associations were observed with CHD (pooled aHR 0.93 [0.88-0.97]) but not with stroke (0.96 [0.91-1.02]) per 6-month increment in breastfeeding. Among women with GDM history, >18 months versus 0 months of breastfeeding was associated with an aHR of 0.49 (0.28-0.86) for total CVD. CONCLUSIONS: Longer duration of breastfeeding was associated with lower risk of CVD in women with type 2 diabetes or GDM.

Passive antibody transfer from pregnant women to their fetus are maximized after SARS-CoV-2 vaccination irrespective of prior infection.

Background: Pregnancy is associated with a higher risk of adverse symptoms and outcomes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for both mother and neonate. Antibodies can provide protection against SARS-CoV-2 infection and are induced in pregnant women after vaccination or infection. Passive transfer of these antibodies from mother to fetus in utero may provide protection to the neonate against infection. However, it is unclear whether the magnitude or quality and kinetics of maternally derived fetal antibodies differs in the context of maternal infection or vaccination. Objective: We aimed to determine whether antibodies transferred from maternal to fetus differed in quality or quantity between infection- or vaccination-induced humoral immune responses. Methods: We evaluated 93 paired maternal and neonatal umbilical cord blood plasma samples collected between October 2020 and February 2022 from a birth cohort of pregnant women from New Orleans, Louisiana, with histories of SARS-CoV-2 infection and/or vaccination. Plasma was profiled for the levels of spike-specific antibodies and induction of antiviral humoral immune functions, including neutralization and Fc-mediated innate immune effector functions. Responses were compared between 4 groups according to maternal infection and vaccination. Results: We found that SARS-CoV-2 vaccination or infection during pregnancy increased the levels of antiviral antibodies compared to naive subjects. Vaccinated mothers and cord samples had the highest anti-spike antibody levels and antiviral function independent of the time of vaccination during pregnancy. Conclusions: These results show that the most effective passive transfer of functional antibodies against SARS-CoV-2 in utero is achieved through vaccination, highlighting the importance of vaccination in pregnant women.

The association between preconception cannabis use and gestational diabetes mellitus: The Preconception Period Analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium.

BACKGROUND: The metabolic changes that ultimately lead to gestational diabetes mellitus (GDM) likely begin before pregnancy. Cannabis use might increase the risk of GDM by increasing appetite or promoting fat deposition and adipogenesis. OBJECTIVES: We aimed to assess the association between preconception cannabis use and GDM incidence. METHODS: We analysed individual-level data from eight prospective cohort studies. We identified the first, or index, pregnancy (lasting ≥20 weeks of gestation with GDM status) after cannabis use. In analyses of pooled individual-level data, we used logistic regression to estimate study-type-specific odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential confounders using random effect meta-analysis to combine study-type-specific ORs and 95% CIs. Stratified analyses assessed potential effect modification by preconception tobacco use and pre-pregnancy body mass index (BMI). RESULTS: Of 17,880 participants with an index pregnancy, 1198 (6.7%) were diagnosed with GDM. Before the index pregnancy, 12.5% of participants used cannabis in the past year. Overall, there was no association between preconception cannabis use in the past year and GDM (OR 0.97, 95% CI 0.79, 1.18). Among participants who never used tobacco, however, those who used cannabis more than weekly had a higher risk of developing GDM than those who did not use cannabis in the past year (OR 2.65, 95% CI 1.15, 6.09). This association was not present among former or current tobacco users. Results were similar across all preconception BMI groups. CONCLUSIONS: In this pooled analysis of preconception cohort studies, preconception cannabis use was associated with a higher risk of developing GDM among individuals who never used tobacco but not among individuals who formerly or currently used tobacco. Future studies with more detailed measurements are needed to investigate the influence of preconception cannabis use on pregnancy complications.

Prenatal Infection by Respiratory Viruses Is Associated With Immuno-Inflammatory Responses in the Fetus.

RATIONALE: Respiratory viral infections can be transmitted from pregnant women to their offspring, but frequency, mechanisms, and postnatal outcomes remain unclear. OBJECTIVES: This prospective cohort study compared frequencies of transplacental transmission of respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), analyzed the concentrations of inflammatory mediators in maternal and fetal blood, and assessed clinical consequences. METHODS: We recruited pregnant women who developed upper respiratory infections or tested positive for SARS-CoV-2. Maternal and cord blood samples were collected at delivery. Study questionnaires and electronic medical records were used to document demographic and medical information. RESULTS: From October 2020 to June 2022, droplet digital (dd)PCR was used to test blood mononuclear cells of 103 mother-baby dyads. Twice more newborns in our sample were vertically infected with RSV compared to SARS-CoV-2 (25.2% (26/103) versus 11.9% (12/101), p = 0.019). Multiplex ELISA measured significantly increased concentrations of several inflammatory cytokines and chemokines in maternal and cord blood from newborns with evidence of viral exposure in utero compared to the control dyads group. Prenatal infection was associated with significantly lower birth weight and postnatal weight growth. CONCLUSIONS: Data suggest a higher frequency of vertical transmission for RSV than SARS-CoV-2. Intrauterine exposure is associated with fetal inflammation driven by soluble inflammatory mediators with expression profiles dependent on the virus type and affecting the rate of viral transmission. Virus-induced inflammation may have pathological consequences already in the first days of life, as shown by its effects on birth weight and postnatal weight growth. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Diet Quality and Sleep Characteristics in Midlife: The Bogalusa Heart Study.

BACKGROUND: Sleep and diet contribute to cardiometabolic disease, but evidence is sparse for the association between these behaviors. This study analyzed the cross-sectional relationship between diet quality and multiple sleep outcomes in the Bogalusa Heart Study (BHS). METHODS: Diet and sleep characteristics, including insomnia and sleep apnea symptoms, were measured with validated questionnaires. Poisson regression using generalized estimating equations with a log link estimated prevalence rate ratios (PRR) of sleep outcomes by dietary pattern scores (quintile (Q) and per SD). Models were adjusted for body mass index (BMI), multi-level socioeconomic factors, physical activity, depressive symptoms, and other potential confounders. RESULTS: In 824 participants, higher diet quality, measured by the Alternate Healthy Eating Index-2010, was associated with lower sleep apnea risk score after adjustment (PRR [95% confidence interval (CI)] Q5 vs. Q1: 0.59 [0.44, 0.79], per SD increase: 0.88 [0.81, 0.95], p-trend < 0.0001). There were no statistically significant associations with the Healthy Eating Index 2015 or the Alternate Mediterranean dietary patterns, or for insomnia symptoms or a healthy sleep score. CONCLUSIONS: Higher diet quality, after adjustment for BMI, was associated with a lower sleep apnea risk score in a cohort with substantial minority representation from a semi-rural, lower-income community.

Large-Scale Data Harmonization Across Prospective Studies.

The Preconception Period Analysis of Risks and Exposures Influencing Health and Development (PrePARED) Consortium creates a novel resource for addressing preconception health by merging data from numerous cohort studies. In this paper, we describe our data harmonization methods and results. Individual-level data from 12 prospective studies were pooled. The crosswalk-cataloging-harmonization procedure was used. The index pregnancy was defined as the first postbaseline pregnancy lasting more than 20 weeks. We assessed heterogeneity across studies by comparing preconception characteristics in different types of studies. The pooled data set included 114,762 women, and 25,531 (22%) reported at least 1 pregnancy of more than 20 weeks' gestation during the study period. Babies from the index pregnancies were delivered between 1976 and 2021 (median, 2008), at a mean maternal age of 29.7 (standard deviation, 4.6) years. Before the index pregnancy, 60% of women were nulligravid, 58% had a college degree or more, and 37% were overweight or obese. Other harmonized variables included race/ethnicity, household income, substance use, chronic conditions, and perinatal outcomes. Participants from pregnancy-planning studies had more education and were healthier. The prevalence of preexisting medical conditions did not vary substantially based on whether studies relied on self-reported data. Use of harmonized data presents opportunities to study uncommon preconception risk factors and pregnancy-related events. This harmonization effort laid the groundwork for future analyses and additional data harmonization.

Age at menarche, type 2 diabetes and cardiovascular disease complications in US women aged under 65 years: NHANES 1999-2018.

Background: Diabetes and diabetes complications are on the rise in US adults aged <65 years, while onset of menarche at a younger age is also increasing. We examined the associations of age at menarche with type 2 diabetes among women aged <65 years and with cardiovascular disease (CVD) complications among women with diabetes. Methods: Using the nationally representative cross-sectional National Health and Nutrition Examination Survey 1999-2018, women aged 20-65 years free of cancer were included in the current analysis. Diabetes was defined as a self-reported diabetes diagnosis. CVD was defined as coronary heart disease or stroke. Age at menarche was self-reported age of first menstruation and categorised into ≤10, 11, 12, 13, 14 and ≥15 years. Results: Of 17 377 women included in the analysis, 1773 (10.2%) reported having type 2 diabetes. Earlier age at menarche was associated with type 2 diabetes compared with median age at menarche of 13 years, after adjustment for age, race/ethnicity, education, parity, menopause status and family history of diabetes, smoking status, physical activity, alcohol consumption and body mass index (p for trend=0.02). Among women with diabetes, earlier age at menarche was associated with stroke with similar adjustment (p for trend=0.03), but not with total CVD. Extremely early age at menarche (≤10 years) was significantly associated with stroke (adjusted OR 2.66 (95% CI 1.07 to 6.64)) among women aged <65 years with diabetes with similar adjustment. Conclusions: Earlier age at menarche was associated with type 2 diabetes among young and middle-aged women in the USA and with stroke complications among these women living with diabetes.

Habitual coffee consumption and subsequent risk of type 2 diabetes in individuals with a history of gestational diabetes - a prospective study.

BACKGROUND: Females with a history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes mellitus (T2D) later in life. OBJECTIVE: This study prospectively examined whether greater habitual coffee consumption was related to a lower risk of T2D among females with a history of GDM. METHODS: We followed 4522 participants with a history of GDM in the NHS II for incident T2D between 1991 and 2017. Demographic, lifestyle factors including diet, and disease outcomes were updated every 2-4 y. Participants reported consumption of caffeinated and decaffeinated coffee on validated FFQs. Fasting blood samples were collected in 2012-2014 from a subset of participants free of diabetes to measure glucose metabolism biomarkers (HbA1c, insulin, C-peptide; n = 518). We used multivariable Cox regression models to calculate adjusted HRs and 95% CIs for the risk of T2D. We estimated the least squares mean of glucose metabolic biomarkers according to coffee consumption. RESULTS: A total of 979 participants developed T2D. Caffeinated coffee consumption was inversely associated with the risk of T2D. Adjusted HR (95% CI) for ≤1 (nonzero), 2-3, and 4+ cups/d compared with 0 cup/d (reference) was 0.91 (0.78, 1.06), 0.83 (0.69, 1.01), and 0.46 (0.28, 0.76), respectively (P-trend = 0.004). Replacement of 1 serving/d of sugar-sweetened beverage and artificially sweetened beverage with 1 cup/d of caffeinated coffee was associated with a 17% (risk ratio [RR] = 0.83, 95% CI: 0.75, 0.93) and 9% (RR = 0.91, 95% CI: 0.84, 0.99) lower risk of T2D, respectively. Greater caffeinated coffee consumption was associated with lower fasting insulin and C-peptide concentrations (all P-trend <0.05). Decaffeinated coffee intake was not significantly related to T2D but was inversely associated with C-peptide concentrations (P-trend = 0.003). CONCLUSIONS: Among predominantly Caucasian females with a history of GDM, greater consumption of caffeinated coffee was associated with a lower risk of T2D and a more favorable metabolic profile.

SARS-CoV-2 specific antibody trajectories in mothers and infants over two months following maternal infection.

Infants exposed to caregivers infected with SARS-CoV-2 may have heightened infection risks relative to older children due to their more intensive care and feeding needs. However, there has been limited research on COVID-19 outcomes in exposed infants beyond the neonatal period. Between June 2020 - March 2021, we conducted interviews and collected capillary dried blood spots from 46 SARS-CoV-2 infected mothers and their infants (aged 1-36 months) for up to two months following maternal infection onset (COVID+ group, 87% breastfeeding). Comparative data were also collected from 26 breastfeeding mothers with no known SARS-CoV-2 infection or exposures (breastfeeding control group), and 11 mothers who tested SARS-CoV-2 negative after experiencing symptoms or close contact exposure (COVID- group, 73% breastfeeding). Dried blood spots were assayed for anti-SARS-CoV-2 S-RBD IgG and IgA positivity and anti-SARS-CoV-2 S1 + S2 IgG concentrations. Within the COVID+ group, the mean probability of seropositivity among infant samples was lower than that of corresponding maternal samples (0.54 and 0.87, respectively, for IgG; 0.33 and 0.85, respectively, for IgA), with likelihood of infant infection positively associated with the number of maternal symptoms and other household infections reported. COVID+ mothers reported a lower incidence of COVID-19 symptoms among their infants as compared to themselves and other household adults, and infants had similar PCR positivity rates as other household children. No samples returned by COVID- mothers or their infants tested antibody positive. Among the breastfeeding control group, 44% of mothers but none of their infants tested antibody positive in at least one sample. Results support previous research demonstrating minimal risks to infants following maternal COVID-19 infection, including for breastfeeding infants.

Modifiable risk factors and long term risk of type 2 diabetes among individuals with a history of gestational diabetes mellitus: prospective cohort study.

OBJECTIVES: To evaluate the individual and combined associations of five modifiable risk factors with risk of type 2 diabetes among women with a history of gestational diabetes mellitus and examine whether these associations differ by obesity and genetic predisposition to type 2 diabetes. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study II, US. PARTICIPANTS: 4275 women with a history of gestational diabetes mellitus, with repeated measurements of weight and lifestyle factors and followed up between 1991 and 2009. MAIN OUTCOME MEASURE: Self-reported, clinically diagnosed type 2 diabetes. Five modifiable risk factors were assessed, including not being overweight or obese (body mass index <25.0), high quality diet (top two fifthsof the modified Alternate Healthy Eating Index), regular exercise (≥150 min/week of moderate intensity or ≥75 min/week of vigorous intensity), moderate alcohol consumption (5.0-14.9 g/day), and no current smoking. Genetic susceptibility for type 2 diabetes was characterised by a genetic risk score based on 59 single nucleotide polymorphisms associated with type 2 diabetes in a subset of participants (n=1372). RESULTS: Over a median 27.9 years of follow-up, 924 women developed type 2 diabetes. Compared with participants who did not have optimal levels of any of the risk factors for the development of type 2 diabetes, those who had optimal levels of all five factors had >90% lower risk of the disorder. Hazard ratios of type 2 diabetes for those with one, two, three, four, and five optimal levels of modifiable factors compared with none was 0.94 (95% confidence interval 0.59 to 1.49), 0.61 (0.38 to 0.96), 0.32 (0.20 to 0.51), 0.15 (0.09 to 0.26), and 0.08 (0.03 to 0.23), respectively (Ptrend<0.001). The inverse association of the number of optimal modifiable factors with risk of type 2 diabetes was seen even in participants who were overweight/obese or with higher genetic susceptibility (Ptrend<0.001). Among women with body mass index ≥25 (n=2227), the hazard ratio for achieving optimal levels of all the other four risk factors was 0.40 (95% confidence interval 0.18 to 0.91). Among women with higher genetic susceptibility, the hazard ratio of developing type 2 diabetes for having four optimal factors was 0.11 (0.04 to 0.29); in the group with optimal levels of all five factors, no type 2 diabetes events were observed. CONCLUSIONS: Among women with a history of gestational diabetes mellitus, each additional optimal modifiable factor was associated with an incrementally lower risk of type 2 diabetes. These associations were seen even among individuals who were overweight/obese or were at greater genetic susceptibility.

Cumulative Lactation and Clinical Metabolic Outcomes at Mid-Life among Women with a History of Gestational Diabetes.

Lactation is associated with a lower risk of subsequent cardiometabolic disease among parous women; however, the underlying mechanisms are unknown. Further, the potential protective effects of lactation on cardiometabolic risk markers at mid-life among high-risk women with past gestational diabetes (GDM) are not established. Using data from the Diabetes & Women's Health Study (2012−2014; n = 577), a longitudinal cohort of women with past GDM from the Danish National Birth Cohort (1996−2002), we assessed associations of cumulative lactation duration (none, <6 months, 6−12 months, ≥12−24 months, and ≥24 months) with clinical metabolic outcomes (including type 2 diabetes [T2D], prediabetes, and obesity) and cardiometabolic biomarkers (including biomarkers of glucose/insulin metabolism, fasting lipids, inflammation, and anthropometrics) 9−16 years after enrollment when women were at mid-life. At follow-up, women were 43.9 years old (SD 4.6) with a BMI of 28.7 kg/m2 (IQR 24.6, 33.0); 28.6% of participants had T2D, 39.7% had prediabetes, and 41.2% had obesity. Relative risks (95% CI) of T2D for 0−6, 6−12, 12−24, and ≥24 months of cumulative lactation duration compared to none were 0.94 (0.62,1.44), 0.88 (0.59,1.32), 0.73 (0.46,1.17), and 0.71 (0.40,1.27), respectively. Cumulative lactation duration was not significantly associated with any other clinical outcome or continuous biomarker. In this high-risk cohort of middle-aged women with past GDM, T2D, prediabetes, and obesity were common at follow-up, but not associated with history of cumulative lactation duration 9−16 years after the index pregnancy. Further studies in diverse populations among women at mid-age are needed to understand associations of breastfeeding with T2D.

Associations of Metabolic and Obstetric Risk Parameters with Timing of Lactogenesis II.

Lactogenesis II is the onset of copious milk production following parturition. Delayed onset of lactogenesis II (DLII) often contributes to poorer lactation performance, which may adversely affect maternal and child health. The present study aims to identify the metabolic and obstetric risk factors for DLII in a secondary analysis of a prospective cohort study following pregnant women through postpartum. We defined the onset of lactogenesis II as delayed if it occurred ≥72 h postpartum. Multiple logistic regression analyses were conducted to evaluate the associations of metabolic and obstetric variables with DLII. Median onset of lactogenesis II was 72.4 h (IQR 60.4-91.6) postpartum, and 55.4% (98 of 177) of women experienced DLII. Time to first breast contact ≥ 2 h postpartum compared to ≤1 h postpartum was associated with DLII (OR 2.71 95% CI 1.12-6.53) with adjustment for age, race, pregravid BMI, primiparity, and mode of delivery, while metabolic variables were not significantly associated with DLII. In this comprehensive examination of potential metabolic and obstetric parameters, earlier timing of putting the infant to the breast remained significantly associated with earlier onset of milk coming in after consideration of the other potential risk factors. Obstetrical practices, including putting the baby to the breast later, may have an important impact on the timing of lactation, and interventions are needed to address this concern.

Prepregnancy plant-based diets and the risk of gestational diabetes mellitus: a prospective cohort study of 14,926 women.

BACKGROUND: Emerging evidence suggests beneficial impacts of plant-based diets on glucose metabolism among generally healthy individuals. Whether adherence to these diets is related to risk of gestational diabetes mellitus (GDM) is unknown. OBJECTIVES: We aimed to examine associations between plant-based diets and GDM in a large prospective study. METHODS: We included 14,926 women from the Nurses' Health Study II (1991-2001), who reported ≥1 singleton pregnancy and without previous GDM before the index pregnancy. Prepregnancy adherence to plant-based diets was measured by an overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) as assessed by FFQs every 4 y. Incident first-time GDM was ascertained from a self-reported physician diagnosis, which was previously validated by review of medical records. We used log-binomial models with generalized estimating equations to calculate RRs and 95% CIs for associations of PDIs with GDM. RESULTS: We documented 846 incident GDM cases over the 10-y follow-up among 20,707 pregnancies. Greater adherence to the PDI and hPDI was associated with lower GDM risk. For the PDI, the multivariable-adjusted RR (95% CI) comparing the highest and lowest quintiles (Q5 compared with Q1) was 0.70 (0.56, 0.87) (Ptrend = 0.0004), and for each 10-point increment was 0.80 (0.71, 0.90). For the hPDI, the RR (95% CI) of Q5 compared with Q1 was 0.75 (0.59, 0.94) (Ptrend = 0.009) and for each 10-point increment was 0.86 (0.77, 0.95). After further adjustment for prepregnancy BMI, the associations were attenuated but remained significant: for the PDI, the RR (95% CI) for each 10-point increment was 0.89 (0.79, 1.00) and the corresponding RR (95% CI) was 0.89 (0.80, 0.99) for the hPDI. The uPDI was not associated with GDM. CONCLUSIONS: Our study suggests that greater prepregnancy adherence to a healthful plant-based diet was associated with lower risk of GDM, whereas an unhealthful plant-based diet was not related to GDM risk.

Oligosaccharides and Microbiota in Human Milk Are Interrelated at 3 Months Postpartum in a Cohort of Women with a High Prevalence of Gestational Impaired Glucose Tolerance.

BACKGROUND: Human milk is a rich source of human milk oligosaccharides (HMOs) and bacteria. It is unclear how these components interact within the breast microenvironment. OBJECTIVES: The objectives were first, to investigate the association between maternal characteristics and HMOs, and second, to assess the association between HMOs and microbial community composition and predicted function in milk from women with high rates of gestational glucose intolerance. METHODS: This was an exploratory analysis of a previously completed prospective cohort study (NCT01405547) where milk samples (n = 107) were collected at 3 mo postpartum. Milk microbiota composition was analyzed by V4-16S ribosomal RNA gene sequencing and HMOs by rapid high-throughput HPLC. Data were stratified and analyzed by maternal secretor status phenotype and associations between HMOs and microbiota were determined using linear regression models (ɑ-diversity), Adonis (B-diversity), Poisson regression models (differential abundance), and general linear models (predicted microbial function). RESULTS: Prepregnancy BMI, race, and frequency of direct breastfeeding, but not gestational glucose intolerance, were found to be significantly associated with a number of HMOs among secretors and non-secretors. Fucosyllacto-N-hexaose was negatively associated with microbial richness (Chao1) among secretors [B-estimate (SE): -9.3 × 102 (3.4 × 102); P = 0.0082] and difucosyllacto-N-hexaose was negatively associated with microbiota diversity (Shannon index) [-1.7 (0.78); P = 0.029] among secretors. Lacto-N-neotetraose (LNnT) was associated with both microbial B-diversity (weighted UniFrac R2 = 0.040, P = 0.036) and KEGG ortholog B-diversity (Bray-Curtis R2 = 0.039, P = 0.043) in secretors. Additionally, difucosyllactose in secretors and disialyllacto-N-hexaose and LNnT in non-secretors were associated with enrichment of predicted microbial genes encoding for metabolism- and infection-related pathways (P-false discovery rate < 0.1). CONCLUSIONS: HMOs are associated with the microbial composition and predicted microbial functions in human milk at 3 mo postpartum. Further research is needed to investigate the role these relations play in maternal and infant health.

Association of Habitual Alcohol Consumption With Long-term Risk of Type 2 Diabetes Among Women With a History of Gestational Diabetes.

Importance: Women with gestational diabetes are at high risk for type 2 diabetes. Identifying modifiable dietary and lifestyle factors, such as alcohol intake, that can be useful in delaying or preventing progression to overt type 2 diabetes is of particular interest. Objective: To evaluate the association between alcohol consumption and risk for type 2 diabetes among women with a history of gestational diabetes. Design, Setting, and Participants: This cohort study included women from the Nurses' Health Study II cohort who reported a history of gestational diabetes and were followed up from January 1, 1991, to December 31, 2017, as part of the Diabetes & Women's Health Study. Data analysis was performed from 2020 to 2021. Exposures: Dietary intakes, including alcohol, were assessed every 4 years using validated food-frequency questionnaires. Main Outcomes and Measures: Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for the association of alcohol intake with risk for incident type 2 diabetes after a pregnancy during which gestational diabetes was diagnosed. Results: A total of 4740 women were included in the study; the mean (SD) age at baseline was 38.2 (5.0) years, and the median follow-up time was 24 years (interquartile range, 18-28 years), resulting in 78 328 person-years of follow-up. During this period, 897 incident cases of type 2 diabetes were reported. After adjustment for major dietary and lifestyle factors, compared with women who did not consume any alcohol, only alcohol consumption of 5.0 to 14.9 g/d was associated with decreased risk for incident type 2 diabetes (HR, 0.45; 95% CI, 0.33-0.61); there was no association of alcohol consumption of 0.1 to 4.9 g/d or 15.0 g/d or more (maximum, 74.2 g/d) with risk of type 2 diabetes (0.1 to 4.9 g/d: HR, 0.87 [95% CI, 0.73-1.03]; ≥15.0 g/d: HR, 0.62 [95% CI, 0.37-1.04]). After additional adjustment for body mass index, women who reported alcohol consumption of 5.0 to 14.9 g/d had a 41% lower risk for developing incident type 2 diabetes (HR, 0.59; 95% CI, 0.42-0.81); consumption of 0.1 to 4.9 g/d and consumption of 15.0 g/d or more were still not associated with risk of type 2 diabetes, but the results were attenuated (0.1-4.9 g/d: HR, 1.02 [95% CI, 0.85-1.23]; ≥15.0 g/d: HR, 0.75 [95% CI, 0.42-1.33]). Conclusions and Relevance: In this cohort study, among women with a history of gestational diabetes, usual alcohol intake of 5.0 to 14.9 g/d (approximately 0.5-1 drinks per day) was associated with a lower risk for type 2 diabetes. These findings should be interpreted in the context of other known risks and benefits of alcohol consumption when considering clinical recommendations for individual women with a history of gestational diabetes.

COVID-19 in childhood: Transmission, clinical presentation, complications and risk factors.

Children less than 18 years of age account for an estimated 2%-5% of reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases globally. Lower prevalence of coronavirus disease 2019 (COVID-19) among children, in addition to higher numbers of mild and asymptomatic cases, continues to provide challenges in determining appropriate prevention and treatment courses. Here, we summarize the current evidence on the transmission, clinical presentation, complications and risk factors in regard to SARS-CoV-2 in children, and highlight crucial gaps in knowledge going forward. Based on current evidence, children are rarely the primary source of secondary transmission in the household or in child care and school settings and are more likely to contract the virus from an adult household member. Higher transmission rates are observed in older children (10-19 years old) compared with younger children ( <10 years old). While increasing incidence of COVID-19 in neonates raises the suspicion of vertical transmission, it is unlikely that breast milk is a vehicle for transmission from mother to infant. The vast majority of clinical cases of COVID-19 in children are mild, but there are rare cases that have developed complications such as multisystem inflammatory syndrome in children, which often presents with severe cardiac symptoms requiring intensive care. Childhood obesity is associated with a higher risk of infection and a more severe clinical presentation. Although immediate mortality rates among children are low, long-term respiratory, and developmental implications of the disease remain unknown in this young and vulnerable population.