Risk of Neonatal Hypoglycemia in Infants of Mothers With Gestational Glucose Intolerance.

OBJECTIVE: To examine the relationship between gestational glucose intolerance (GGI) and neonatal hypoglycemia. RESEARCH DESIGN AND METHODS: This was a secondary analysis of 8,262 mother-infant dyads, with delivery at two hospitals between 2014 and 2023. We categorized maternal glycemic status as normal glucose tolerance (NGT), GGI, or gestational diabetes mellitus (GDM). We defined NGT according to a normal glucose load test result, GGI according to an abnormal glucose load test result with zero (GGI-0) or one (GGI-1) abnormal value on the 100-g oral glucose tolerance test, and GDM according to an abnormal glucose load test result with two or more abnormal values on the glucose tolerance test. Neonatal hypoglycemia was defined according to blood glucose <45 mg/dL or ICD-9 or ICD-10 diagnosis of neonatal hypoglycemia. We used logistic regression analysis to determine associations between maternal glucose tolerance category and neonatal hypoglycemia and conducted a sensitivity analysis using Δ-adjusted multiple imputation, assuming for unscreened infants a rate of neonatal hypoglycemia as high as 33%. RESULTS: Of infants, 12% had neonatal hypoglycemia. In adjusted models, infants born to mothers with GGI-0 had 1.28 (95% 1.12, 1.65), GGI-1 1.58 (95% CI 1.11, 2.25), and GDM 4.90 (95% CI 3.81, 6.29) times higher odds of neonatal hypoglycemia in comparison with infants born to mothers with NGT. Associations in sensitivity analyses were consistent with the primary analysis. CONCLUSIONS: GGI is associated with increased risk of neonatal hypoglycemia. Future research should include examination of these associations in a cohort with more complete neonatal blood glucose ascertainment and determination of the clinical significance of these findings on long-term child health.

Lactoferrin intake from maternal milk during the neonatal hospitalization and early brain development among preterm infants.

BACKGROUND: Lactoferrin is an immuno-modulatory nutrient in human milk that may be neuroprotective. METHODS: In 36 infants born <32 weeks' gestation, we sampled human milk at 14 and 28 days of chronologic age and measured lactoferrin by electrochemiluminescence multiplex immunoassay. Using 3T quantitative brain magnetic resonance imaging scans obtained at term equivalent, we estimated total and regional brain volumes. We compared outcomes between infants exposed to low (bottom tertile, range 0.06-0.13 mg/mL) vs. high (top tertile, range 0.22-0.35 mg/mL) lactoferrin using median regression in models adjusted for gestational age, birth weight z-score, sex, and postmenstrual age. RESULTS: Compared to infants exposed to low lactoferrin, infants exposed to high lactoferrin had 43.9 cc (95% CI: 7.6, 80.4) larger total brain volume, 48.3 cc (95% CI: 12.1, 84.6) larger cortical gray matter, and 3.8 cc (95% CI: 0.7, 7.0) larger deep gray matter volume at term equivalent age. Other regional brain volumes were not statistically different between groups. CONCLUSION: Higher lactoferrin exposure during the neonatal hospitalization was associated with larger total brain and gray matter volumes, suggesting that lactoferrin may have potential as a dietary supplement to enhance brain growth in the neonatal intensive care unit setting. IMPACT: This study suggests that lactoferrin, a whey protein found in human milk, may be beneficial for preterm infant brain development, and therefore has potential as a dietary supplement in the neonatal intensive care unit setting.

Mediators of the association between maternal body mass index and breastfeeding duration in 3 international cohorts.

BACKGROUND: Maternal obesity has been associated with shorter breastfeeding duration, but little is known about mediating factors explaining this association. It is important to assess these relationships across diverse populations because breastfeeding is culturally patterned. OBJECTIVES: We investigated the association of prepregnancy maternal body mass index (BMI) with breastfeeding outcomes and potential mediators of this relationship in 3 culturally diverse international cohorts. METHODS: We analyzed 5120 singleton pregnancies from mother-child cohorts in Spain (INfancia y Medio Ambiente), Greece (Rhea), and the United States (Project Viva). Outcome variables were duration of any and exclusive breastfeeding. A priori hypothesized mediators in the association of maternal prepregnancy BMI with breastfeeding were birthweight (BW), maternal prenatal C-reactive protein (CRP), cesarean delivery, maternal dietary inflammatory index (DII) during pregnancy, gestational age at delivery, and gestational diabetes mellitus (GDM). We estimated the association between BMI and breastfeeding duration using linear regression adjusting for confounders. Mediation analysis estimated direct and indirect effects of maternal overweight/obesity on breastfeeding for each mediator. RESULTS: Women with overweight and obesity had shorter duration of any and exclusive breastfeeding compared with normal-weight women (any: overweight ß = -0.79 mo, 95% CI: -1.17, -0.40; obese ß = -1.75 mo 95% CI: -2.25, -1.25; exclusive: overweight ß = -0.30 mo, 95% CI: -0.42, -0.16; obese ß = -0.73 mo, 95% CI: -0.90, -0.55). Significant mediators (% change in effect estimate) of this association were higher CRP (exclusive: 5.12%), cesarean delivery (any: 6.54%; exclusive: 7.69%), and higher DII (any: 6.48%; exclusive: 7.69%). GDM, gestational age, and BW did not mediate the association of maternal weight status with breastfeeding. CONCLUSIONS: Higher prepregnancy BMI is associated with shorter duration of any and exclusive breastfeeding. Maternal dietary inflammation, systemic inflammation, and mode of delivery may be key modifiable mediators of this association. Identification of mediators provides potential targets for interventions to improve breastfeeding outcomes.

Exploring the Driving Factors that Influence the Design, Function, and Use of Urban Wetlands in the United Kingdom.

This paper aimed to investigate the driving factors for the creation of urban wetlands and their functions and uses. A mixed methods approach was used, comprising an online survey for the general public and structured interviews with four urban wetland 'experts'. Quantitative data was obtained from the survey, and cross tabulation was used to analyse relationships between variables. Thematic analysis was used for the qualitative data from the interviews. It was found that one of the urban wetlands was created for flood control and to create an amenity space, whilst the driving factors for the other three urban wetlands were associated with biodiversity and habitat creation, which was also perceived as the most important function of an urban wetland from the survey participants. Three themes emerged from the thematic analysis: 'wildlife conservation interest'; 'landscape character development'; and 'urban wetland as an amenity space'. The survey found that participants perceived climate resiliency as an important function of wetlands, despite this not being a driving factor for the four wetlands in the interviews. Survey participants would be willing to invest time in visiting a non-local wetland landscape to encounter nature and contribute to their quality of life and wellbeing. The results of this research may be useful to inform the planning, design and management of urban wetlands as they evolve towards being a multi-use spaces. More education and awareness are needed about the benefits of these landscapes to wildlife, the environment and local communities. Supplementary Information: The online version contains supplementary material available at 10.1007/s13157-022-01610-1.

Maternal Predictors of Breast Milk Plasmalogens and Associations with Infant Body Composition and Neurodevelopment.

PURPOSE: Ethanolamine-containing plasmalogens (pPEs) are a unique class of breastmilk (BM) glycerophospholipids containing a vinyl-ether at the sn-1 and a polyunsaturated fatty acid (PUFA) at the sn-2 position of the glycerol moiety. pPEs are present in the milk fat globule membrane, accumulate in the infant brain, and have been implicated in infant development. The study objectives were to: (1) describe the composition of BM pPEs and the variation in monomers at both the sn-1 and sn-2 positions; and (2) quantify the associations between BM pPEs and maternal predictors (body mass index, race, dietary fatty acid intake, gestational age at birth, and days' postpartum). Secondary objectives were to explore the relationship between BM pPEs and infant anthropometrics and neurodevelopment. METHODS: This was a secondary analysis of 39 mother-infant dyads in the control group of a randomized controlled trial of vitamin D supplementation during lactation. BM samples and data regarding maternal diet, infant anthropometrics (weight, fat mass index, and fat-free mass index by dual-energy X-ray absorptiometry), and infant development were collected at 1 month (visit 1 [V1], n = 37) and 4 months' (visit 4 [V4], n = 39) postpartum. BM pPEs were extracted and quantified by using ultra-HPLC/high-resolution MS/MS at V1 and V4 and expressed as percent mass of total phospholipids. Associations of pPEs with infant development and anthropometrics were modeled using linear regression. FINDINGS: C(18:0) vinyl ethers and C(18:2) polyunsaturated fatty acid-enriched pPEs predominate in BM. Specific pPEs, as a proportion of total phospholipids, decreased between V1 and V4. Higher maternal body mass index was associated with lower BM pPEs in unadjusted models, but this association was attenuated after adjustment for race, diet, and days' postpartum. Maternal fatty acid intake, gestational age, and days' postpartum were not associated with BM pPEs. Total pPEs at V1 were negatively associated with infant fat mass index and positively associated with fat-free mass index at V1 and V4. BM pPE concentrations were not correlated with neurodevelopmental outcomes. IMPLICATIONS: BM pPEs decrease over lactation and are associated with lower infant adiposity and higher lean mass. CLINICALTRIALS: gov identifier: NCT00412074.

Plasma-glycated CD59 as an early biomarker for gestational diabetes mellitus: prospective cohort study protocol.

INTRODUCTION: The significant maternal and neonatal outcomes of gestational diabetes mellitus (GDM) make it a major public health concern. Mothers with GDM are at greater risk of pregnancy complications and their offspring are at higher risk of diabetes and obesity. Currently, GDM is diagnosed with glucose load methods which are time-consuming and inconvenient to administer more than once during pregnancy; for this reason, there is a recognised need for a more accurate and simpler test for GDM. Previous studies indicate that plasma-glycated CD59 (pGCD59) is a novel biomarker for GDM. We present here the protocol of a prospective cohort study designed to (1) determine the accuracy of pGCD59 as an early, first trimester predictor of GDM and gestational impaired glucose tolerance and (2) assess the associations between pGCD59 levels and adverse maternal and neonatal outcomes. METHODS AND ANALYSIS: We will obtain discarded plasma samples from pregnant women at two time points: first prenatal visit (usually <14 weeks gestation) and gestational weeks 24-28. A study-specific medical record abstraction tool will be used to obtain relevant maternal and neonatal clinical data from the EPIC clinical database. The prevalence of GDM will be determined using standard of care glucose load test results. We will determine the sensitivity and specificity of pGCD59 to predict the diagnosis of GDM and gestational impaired glucose tolerance, as well as the associations between levels of pGCD59 and the prevalence of maternal and neonatal outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Mass General Brigham Institutional Review Board (protocol 2011P002254). The results of this study will be presented at international meetings and disseminated in peer-reviewed journals.

Consumption of animal source foods, especially fish, is associated with better nutritional status among women of reproductive age in rural Bangladesh.

In rural Bangladesh, intake of nutrient-rich foods, such as animal source foods (ASFs), is generally suboptimal. Diets low in nutrients and lacking in diversity put women of reproductive age (WRA) at risk of malnutrition as well as adverse birth outcomes. The objective of this study was to assess the relationship between maternal dietary diversity, consumption of specific food groups and markers of nutritional status, including underweight [body mass index (BMI) < 18.5 kg/m2 ], overweight (BMI ≥ 23 kg/m2 ) and anaemia (haemoglobin < 120 g/dl) among WRA in Bangladesh. This analysis used data from the third round of a longitudinal observational study, collected from February through May of 2017. Dietary data were collected with a questionnaire, and Women's Dietary Diversity Score (WDDS) was calculated. Associations between WDDS, food group consumption and markers of nutritional status were assessed with separate adjusted logistic regression models. Among WRA, the prevalence of underweight, overweight and anaemia was 13.38%, 40.94% and 39.99%, respectively. Women who consumed dark green leafy vegetables (DGLV) or eggs were less likely to be anaemic or underweight, respectively, and women who consumed ASFs, particularly fish, were less likely to be underweight compared with women who did not consume these foods. WDDS did not show any consistent relationship with WRA outcomes. Interventions that focus on promoting optimal nutritional status among WRA in Bangladesh should emphasise increasing consumption of specific nutrient-rich foods, including ASFs, DGLV and eggs, rather than solely focusing on improving diet diversity in general.

Maternal Diet, Infection, and Risk of Cord Blood Inflammation in the Bangladesh Projahnmo Pregnancy Cohort.

Inflammation may adversely affect early human brain development. We aimed to assess the role of maternal nutrition and infections on cord blood inflammation. In a pregnancy cohort in Sylhet, Bangladesh, we enrolled 251 consecutive pregnancies resulting in a term livebirth from July 2016-March 2017. Stillbirths, preterm births, and cases of neonatal encephalopathy were excluded. We prospectively collected data on maternal diet (food frequency questionnaire) and morbidity, and analyzed umbilical cord blood for interleukin (IL)-1α, IL-1ß, IL-6, IL-8 and C-reactive protein. We determined associations between nutrition and infection exposures and cord cytokine elevation (≥75% vs. <75%) using logistic regression, adjusting for confounders. One-third of mothers were underweight (BMI < 18.5 kg/m2) at enrollment. Antenatal and intrapartum infections were observed among 4.8% and 15.9% of the sample, respectively. Low pregnancy intakes of B vitamins (B1, B2, B3, B6, B9 (folate)), fat-soluble vitamins (D, E), iron, zinc, and linoleic acid (lowest vs. middle tertile) were associated with higher risk of inflammation, particularly IL-8. There was a non-significant trend of increased risk of IL-8 and IL-6 elevation with history of ante-and intrapartum infections, respectively. In Bangladesh, improving micronutrient intake and preventing pregnancy infections are targets to reduce fetal systemic inflammation and associated adverse neurodevelopmental outcomes.

Role of maternal glucose metabolism in the association between maternal BMI and neonatal size and adiposity.

BACKGROUND/OBJECTIVE: One potential mechanism by which maternal obesity impacts fetal growth is through hyperglycemia below the threshold for gestational diabetes. Data regarding which measures of maternal glucose metabolism mediate this association is sparse. The objectives of this study were to (i) quantify the associations of maternal pre-pregnancy body mass index (BMI) with neonatal size and adiposity and (ii) examine the role of markers of maternal glucose metabolism as mediators in these associations. SUBJECTS/METHODS: This is a secondary analysis of 6,379 mother-infant dyads from the Hyperglycemia and Adverse Pregnancy Outcome cohort. Markers of glucose metabolism, including plasma glucose and c-peptide values, Stumvoll first-phase estimate, modified Matsuda index, and oral disposition index were measured and calculated from an oral glucose tolerance test (OGTT) between 24- and 32-weeks' gestation. We calculated the direct effect of maternal BMI category, measured at the time of the OGTT and regressed to estimate pre-pregnancy BMI, on neonatal (1) birth weight (BW), (2) fat mass (FM), (3) % body fat (BF%), and (4) sum of skinfold thickness (sSFT). We then calculated the indirect effect of BMI category on these measures through markers of glucose metabolism. RESULTS: Maternal BMI category was positively associated with neonatal BW, FM, BF%, and sSFT. Additionally, mothers who were overweight or obese had higher odds of delivering an infant with BW, FM, BF%, or sSFT >90th percentile. Fasting glucose and c-peptide values were the strongest mediators in the linear associations between maternal BMI category and neonatal size and adiposity. CONCLUSIONS: Maternal overweight and obesity were associated with higher odds of neonatal BW and adiposity >90th percentile. Fasting measures of glucose metabolism were the strongest mediators of these associations, suggesting that future studies should investigate whether incorporation of these markers in pregnant women with obesity may improve prediction of neonatal size and adiposity.

Type of feeding provided with dextrose gel impacts hypoglycemia outcomes: comparing donor milk, formula, and breastfeeding.

OBJECTIVE: Examine neonatal hypoglycemia (NH) outcomes based on type of feeding provided with first dextrose gel. STUDY DESIGN: Retrospective matched cohort study of 99 infants ≥35 weeks gestational age who received dextrose gel in combination with breastfeeding, formula feeding, or donor milk feeding for NH. The exposure was feeding type. The outcomes were: (1) median change in blood glucose (Δ BG) concentration after first gel, (2) odds of second gel, and (3) odds of recurrent NH. RESULTS: Median Δ BG was greater in formula (17.0 mg/dL) and donor milk (19.0 mg/dL) fed vs. breastfed infants (7.0 mg/dL). Donor milk and formula feeding were both associated with lower odds of second gel and recurrent NH. Associations remained significant in late-preterm infants, but only formula feeding remained significant in full-term infants. CONCLUSIONS: Formula and donor milk feedings both raised blood sugar concentrations, but the impact differed by gestational age.

Care of Infants Born to Women with Diabetes.

PURPOSE OF REVIEW: Infants of women with diabetes are at risk for specific morbidities including congenital anomalies, abnormalities of fetal growth, neonatal hypoglycemia, electrolyte abnormalities, polycythemia, hyperbilirubinemia, and respiratory distress syndrome. Recent studies have shed light on long-term outcomes of these infants and presented advances in treatment. The purpose of this review is to outline the most common neonatal morbidities affecting infants of women with diabetes, the pathophysiology and prevalence of these conditions, and contemporary approaches to treatment. RECENT FINDINGS: Recent investigative findings have led to advances in treatment approaches for these infants, particularly regarding risks of neonatal hypoglycemia. Optimizing maternal glycemic control during pregnancy is imperative to improving infant outcomes. However, on a population level, maternal diabetes still poses significant risks to the infant. Timely and appropriate treatment of infants of women with diabetes is imperative to decrease short- and long-term morbidity.

Abnormal target detection and novelty processing neural response in posttraumatic stress disorder.

Attention impairments are common symptoms of posttraumatic stress disorder (PTSD); however, the nature of these impairments remains elusive. Attention impairment may arise as the result of either excessive response to task-irrelevant stimuli or reduced response to task-relevant information. To test the association between PTSD and response to task-relevant and task-irrelevant stimuli, we used a 3-tone novelty auditory oddball task (AOD). We hypothesized that participants with PTSD relative to trauma controls would have less response during novelty processing in the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex, as well as less response in the dlPFC and the orbitofrontal cortex during target detection. Thirty-one male veterans completed a 3-tone novelty AOD task during functional magnetic resonance imaging. Compared to trauma controls, the PTSD group had reduced response during novelty processing in ventromedial prefrontal cortex, superior/middle frontal gyrus (dlPFC), supplementary motor area/caudate, and in posterior regions including bilateral posterior cingulate cortex. The current results suggest PTSD is associated with a pattern of reduced response to novel stimuli. A disturbed orienting response in these brain regions could theoretically underlie PTSD attention-related symptoms.