Supplementation with antioxidant micronutrients in pregnant women with obesity: a randomized controlled trial.

BACKGROUND/OBJECTIVE: Obesity increases maternal morbidity and adversely affects child health. Maternal inflammation may play a role in adverse outcomes. The objective of this study was to determine whether providing a higher dose of antioxidant micronutrients to pregnant women with obesity would raise concentrations of key antioxidant vitamins and impact inflammation and oxidative stress during pregnancy. SUBJECTS/METHODS: This was a double-blind, randomized controlled trial. We recruited pregnant women with a body mass index (BMI) ≥ 30 kg/m2 at their initial prenatal visit ( < 13 weeks gestation) and collected blood and urine samples at baseline, 24-28 weeks, and 32-36 weeks to measure micronutrient concentrations (vitamin C, E, B6 and folate), markers of inflammation (C-reactive protein, interleukin-6, 8, and 1ß) and oxidative stress (8-epi-PGF2α and malondialdehyde). We collected maternal and infant health data from enrollment to delivery as secondary outcomes. We enrolled 128 participants (64 in each arm), and 98 (49 in each arm) completed follow-up through delivery. INTERVENTION: Both groups received a standard prenatal vitamin containing the recommended daily allowance of micronutrients in pregnancy. In addition, the intervention group received a supplement with 90 mg vitamin C, 30 αTU vitamin E, 18 mg vitamin B6, and 800 µg folic acid, and the control group received a placebo. RESULTS: The intervention group had higher vit B6 (log transformed (ln), ß 24-28 weeks: 0.76 nmol/L (95% CI: 0.40, 1.12); ß 32-36 weeks: 0.52 nmol/L (95% CI: 0.17, 0.88)) than the control group. Vitamins C, E, erythrocyte RBC folate concentrations did not differ by randomization group. The intervention did not impact biomarkers of inflammation or oxidative stress. There were no differences in maternal or neonatal clinical outcomes by randomization group. CONCLUSIONS: Higher concentrations of antioxidant vitamins during pregnancy increased specific micronutrients and did not impact maternal inflammation and oxidative stress, which may be related to dosing or type of supplementation provided. CLINICAL TRIAL REGISTRATION: Clinical Trial Identification Number: NCT02802566; URL of the Registration Site: www. CLINICALTRIALS: gov .

The simultaneous occurrence of gestational diabetes and hypertensive disorders of pregnancy affects fetal growth and neonatal morbidity.

BACKGROUND: Gestational diabetes is associated with increased risk of hypertensive disorders of pregnancy, but there are limited data on fetal growth and neonatal outcomes when both conditions are present. OBJECTIVE: We evaluated the risk of abnormal fetal growth and neonatal morbidity in pregnancies with co-occurrence of gestational diabetes and hypertensive disorders of pregnancy. STUDY DESIGN: In a retrospective study of 47,093 singleton pregnancies, we compared the incidence of appropriate for gestational age birthweight in pregnancies affected by gestational diabetes alone, hypertensive disorders of pregnancy alone, or both gestational diabetes and hypertensive disorders of pregnancy with that in pregnancies affected by neither disorder using generalized estimating equations (covariates: maternal age, nulliparity, body mass index, insurance type, race, marital status, and prenatal care site). Secondary outcomes were large for gestational age birthweight, small for gestational age birthweight, and a neonatal morbidity composite outcome (stillbirth, hypoglycemia, hyperbilirubinemia, respiratory distress, encephalopathy, preterm delivery, neonatal death, and neonatal intensive care unit admission). RESULTS: The median (interquartile range) birthweight percentile in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (50 [24.0-78.0]; N=179) was similar to that of unaffected pregnancies (50 [27.0-73.0]; N=35,833). However, the absolute rate of appropriate for gestational age birthweight was lower for gestational diabetes/hypertensive disorders of pregnancy co-occurrence (78.2% vs 84.9% for unaffected pregnancies). Adjusted analyses showed decreased odds of appropriate for gestational age birthweight in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy compared with unaffected pregnancies (adjusted odds ratio, 0.72 [95% confidence interval, 0.52-1.00]; P=.049), and in pregnancies complicated by gestational diabetes alone (adjusted odds ratio, 0.78 [0.68-0.89]; P<.001) or hypertensive disorders of pregnancy alone (adjusted odds ratio, 0.73 [0.66-0.81]; P<.001). The absolute risk of large for gestational age birthweight was greater in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (14.5%) than in unaffected pregnancies (8.2%), without apparent difference in the risk of small for gestational age birthweight (7.3% vs 6.9%). However, in adjusted models comparing pregnancies with gestational diabetes/hypertensive disorders of pregnancy co-occurrence with unaffected pregnancies, neither an association with large for gestational age birthweight (adjusted odds ratio, 1.33 [0.88-2.00]; P=.171) nor small for gestational age birthweight (adjusted odds ratio, 1.32 [0.80-2.19]; P=.293) reached statistical significance. Gestational diabetes/hypertensive disorders of pregnancy co-occurrence carried an increased risk of neonatal morbidity that was greater than that observed with either condition alone (gestational diabetes/hypertensive disorders of pregnancy: adjusted odds ratio, 3.13 [2.35-4.17]; P<.001; gestational diabetes alone: adjusted odds ratio, 2.01 [1.78-2.27]; P<.001; hypertensive disorders of pregnancy alone: adjusted odds ratio, 1.38 [1.26-1.50]; P<.001). CONCLUSION: Although pregnancies with both gestational diabetes and hypertensive disorders of pregnancy have a similar median birthweight percentile to those affected by neither condition, pregnancies concurrently affected by both conditions have a higher risk of abnormal fetal growth and neonatal morbidity.

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.

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.

A Graded Approach to Intravenous Dextrose for Neonatal Hypoglycemia Decreases Blood Glucose Variability, Time in the Neonatal Intensive Care Unit, and Cost of Stay.

OBJECTIVE: To determine associations between a graded approach to intravenous (IV) dextrose treatment for neonatal hypoglycemia and changes in blood glucose (BG), length of stay (LOS), and cost of care. STUDY DESIGN: Retrospective cohort study of 277 infants born at ≥35 weeks of gestation in an urban academic delivery hospital, comparing the change in BG after IV dextrose initiation, neonatal intensive care unit (NICU) LOS, and cost of care in epochs before and after a hospital protocol change. During epoch 1, all infants who needed IV dextrose for hypoglycemia were given a bolus and started on IV dextrose at 60 mL/kg/day. During epoch 2, infants received IV dextrose at 30 or 60 mL/kg/day based on the degree of hypoglycemia. Differences in BG outcomes, LOS, and cost of hospital care between epochs were compared using adjusted median regression. RESULTS: In epoch 2, the median (IQR) rise in BG after initiating IV dextrose (19 [10, 31] mg/dL) was significantly lower than in epoch 1 (24 [14,37] mg/dL; adjusted ß = -6.0 mg/dL, 95% CI -11.2, -0.8). Time to normoglycemia did not differ significantly between epochs. NICU days decreased from a median (IQR) of 4.5 (2.1, 11.0) to 3.0 (1.5, 6.5) (adjusted ß = -1.9, 95% CI -3.0, -0.7). Costs associated with NICU hospitalization decreased from a median (IQR) $14 030 ($5847, $30 753) to $8470 ($5650, $19 019) (adjusted ß = -$4417, 95% CI -$571, -$8263) after guideline implementation. CONCLUSIONS: A graded approach to IV dextrose was associated with decreased BG lability and length and cost of NICU stay for infants with neonatal hypoglycemia.

Improving the uptake of Kangaroo Mother Care in neonatal units: A narrative review and conceptual framework.

Kangaroo Mother Care is a beneficial intervention for high-risk infants; however, global uptake is lacking. Recent systematic reviews have collated the numerous studies that identify diverse barriers and enablers to the use of Kangaroo Mother Care. In this narrative review, we combine the findings of these systematic reviews with more recent studies to propose a conceptual framework, encompassing factors that may affect the initiation and maintenance of Kangaroo Mother Care in neonatal units. CONCLUSION: This conceptual framework includes parental, healthcare professional, and healthcare system factors, and highlights the potential interplay between them. In line with this, we suggest strategies to improve the uptake of Kangaroo Mother Care in neonatal units.

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.

Correction: Maternal obesity and offspring cognition: the role of inflammation.

Following publication of this article, the authors noted that the name of the last author was incorrectly displayed as 'Sen Sarbattama'. This authors name has now been corrected to 'Sarbattama Sen'. This has been corrected in both the PDF and HTML versions of the article.

Maternal obesity and offspring cognition: the role of inflammation.

BACKGROUND: High pre-pregnancy body mass index (ppBMI) has been linked to neurodevelopmental impairments in childhood. However, very few studies have investigated mechanisms in human cohorts. METHODS: Among 1361 mother-child pairs in Project Viva, we examined associations of ppBMI categories with the Peabody Picture Vocabulary Test III [PPVT] and Wide Range Assessment of Visual Motor Abilities [WRAVMA] in early childhood (median 3.2y); and with the Kaufman Brief Intelligence test (KBIT) and WRAVMA in mid-childhood (7.7y). We further examined the role of maternal inflammation in these associations using the following measures from the 2nd trimester of pregnancy: plasma C-reactive protein (CRP), dietary inflammatory index (DII), and plasma omega-6 (n-6): n-3 fatty acid ratio. RESULTS: Children of mothers with prenatal obesity (ppBMI ≥30 kg/m2) had WRAVMA scores that were 2.1 points lower (95% CI: -3.9, -0.2) in early childhood than children of normal weight mothers (ppBMI 18.5-<25 kg/m2), in a covariate adjusted model. This association was attenuated when we additionally adjusted for maternal CRP (ß -1.8 points; 95% CI: -3.8, 0.2) but not for other inflammatory markers. PpBMI was not associated with other cognitive outcomes. CONCLUSION: Maternal inflammation may modestly mediate the association between maternal obesity and offspring visual motor abilities.

Maternal Obesity, 25-Hydroxy Vitamin D Concentration, and Bone Density in Breastfeeding Dyads.

OBJECTIVE: To examine the association between maternal body mass index (BMI) and serum 25-hydroxy vitamin D [25(OH)D] concentration and bone density in mother-infant pairs. STUDY DESIGN: The study was a secondary analysis of 234 exclusively breastfeeding dyads who were recruited in the first postpartum month for a randomized controlled trial of maternal vs infant vitamin D supplementation. Mean 25(OH)D concentrations and bone mineral density (BMD) were compared by BMI group. The adjusted association between maternal BMI and 25(OH)D and bone density was examined at 1, 4, and 7 months postpartum. RESULTS: Obese breastfeeding women had lower 25(OH)D concentrations and higher BMD than lean women at all 3 time points (P < .01). Higher maternal BMI was associated with lower maternal serum levels of 25(OH)D at 1, 4, and 7 months postpartum (adjusted ß = -0.45 ng/ml per kg/m2, 95% CI -.076, -0.14, at 1 month) and higher BMD at the same time points (ß = 0.006 BMD z score; 95% CI 0.003, 0.01 at 1 month). Seventy-six percent of infants were vitamin D deficient at 1 month of age. Infants born to overweight and obese mothers had lower 25(OH)D concentrations than infants of lean mothers (P < .01). For infants in the maternal supplementation group, higher maternal BMI was associated with lower 25(OH)D concentrations at 4 months (ß = -0.68; 95% CI -1.17, -0.20) and lower bone density at 7 months (ß = -0.001; 95% CI -0.002, -0.0001). CONCLUSIONS: In exclusively breastfeeding dyads, maternal obesity is associated with lower maternal and infant serum 25(OH)D concentrations, which may impact infant bone density. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00412074.

Dietary Inflammatory Potential during Pregnancy Is Associated with Lower Fetal Growth and Breastfeeding Failure: Results from Project Viva.

BACKGROUND: Inflammation during pregnancy has been linked to adverse maternal and infant outcomes. There is limited information available on the contribution of maternal diet to systemic inflammation and pregnancy health. OBJECTIVE: The objective of this study was to examine associations of maternal prenatal dietary inflammatory index (DII), a composite measure of the inflammatory potential of diet, with markers of maternal systemic inflammation and pregnancy outcomes. METHODS: We studied 1808 mother-child pairs from Project Viva, a pre-birth cohort study in Massachusetts. We calculated the DII from first- and second-trimester food-frequency questionnaires by standardizing the dietary intakes of participants to global means, which were multiplied by the inflammatory effect score and summed. We examined associations of DII with maternal plasma C-reactive protein and white blood cell count in the second trimester and the following perinatal outcomes: gestational diabetes, preeclampsia, length of gestation, fetal growth, mode of delivery, and duration of breastfeeding. We used multivariable linear and logistic regression models to analyze the strength of these associations. RESULTS: Maternal age was (mean ± SD) 32.2 ± 5.0 y, prepregnancy body mass index (BMI; in kg/m(2)) was 24.9 ± 5.2, and DII was -2.56 ± 1.42 units with a range of -5.4 to 3.7. DII was positively correlated with prepregnancy BMI (Pearson'sr= 0.13,P< 0.0001). Higher DII scores, reflecting more proinflammatory dietary potential, were associated with higher second-trimester plasma CRP (ß: 0.08 mg/L per 1-unit increase in maternal DII; 95% CI: 0.02, 0.14) and lower birth weight for gestational agezscore in infants born to obese mothers (ß: -0.10zscore per 1-unit increase in maternal DII; 95% CI: -0.18, -0.02). Higher DII scores were associated with lower odds of breastfeeding for at least 1 mo (OR = 0.85; 95% CI: 0.74, 0.98). CONCLUSION: A proinflammatory diet during pregnancy is associated with maternal systemic inflammation and may be associated with impaired fetal growth and breastfeeding failure.

The role of systemic inflammation linking maternal BMI to neurodevelopment in children.

Children of obese mothers are at increased risk of developmental adversities. Maternal obesity is linked to an inflammatory in utero environment, which, in turn, is associated with neurodevelopmental impairments in the offspring. This is an integrated mechanism review of animal and human literature related to the hypothesis that maternal obesity causes maternal and fetal inflammation, and that this inflammation adversely affects the neurodevelopment of children. We propose integrative models in which several aspects of inflammation are considered along the causative pathway linking maternal obesity with neurodevelopmental limitations.

Maternal obesity and immune dysregulation in mother and infant: A review of the evidence.

Obesity is a worldwide public health epidemic. Increasing numbers of reproductive-age women enter pregnancy overweight or obese and there is now convincing data that this adverse in utero environment impacts both fetal and lifelong development. Epidemiologic evidence has shown a simultaneous increase in obesity and asthma rates in developed countries and maternal obesity is a risk factor for infant asthma and wheeze. Here we review the state of research linking maternal obesity and immunomodulation in both mother and infant, with specific attention to the relationship between maternal obesity and offspring asthma. We will also propose several different mechanisms by which maternal obesity may predispose offspring to this chronic condition and briefly summarize interventions that have been trialed to limit this association.

Lutein and preterm infants with decreased concentrations of brain carotenoids.

OBJECTIVES: Lutein and zeaxanthin are dietary carotenoids that may influence visual and cognitive development. The objective of this study was to provide the first data on distribution of carotenoids in the infant brain and compare concentrations in preterm and term infants. METHODS: Voluntarily donated brain tissues from 30 infants who died during the first 1.5 years of life were obtained from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Brain and Tissue Bank. Tissues (hippocampus and prefrontal, frontal, auditory, and occipital cortices) were extracted using standard lipid extraction procedures and analyzed using reverse-phase high-pressure liquid chromatography. RESULTS: Lutein, zeaxanthin, cryptoxanthin, and ß-carotene were the major carotenoids found in the infant brain tissues. Lutein was the predominant carotenoid accounting for 59% of total carotenoids. Preterm infants (n = 8) had significantly lower concentrations of lutein, zeaxanthin, and cryptoxanthin in their brain compared with term infants (n = 22) despite similarity in postmenstrual age. Among formula-fed infants, preterm infants (n = 3) had lower concentrations of lutein and zeaxanthin compared with term infants (n = 5). Brain lutein concentrations were not different between breast milk-fed (n = 3) and formula-fed (n = 5) term decedents. In contrast, term decedents with measurable brain cryptoxanthin, a carotenoid that is inherently low in formula, had higher brain lutein, suggesting that the type of feeding is an important determinant of brain lutein concentrations. CONCLUSIONS: These data reveal preferential accumulation and maintenance of lutein in the infant brain despite underrepresentation in the typical infant diet. Further investigation on the impact of lutein on neural development in preterm infants is warranted.

Prediction of gestational diabetes early in pregnancy: targeting the long-term complications.

Gestational diabetes (GD), defined as carbohydrate intolerance with onset or first recognition during pregnancy, has a prevalence of 7% and is a growing problem worldwide. Infants born to mothers with GD are more likely to be large for gestational age, incur traumatic birth injury, require a stay in the intensive care unit and develop postnatal metabolic disturbances. As the worldwide epidemic of obesity worsens, more women are entering pregnancy with metabolic alterations and preexisting insulin resistance, which is heightened by the hormonal milieu of pregnancy. The Hyperglycemia Adverse Pregnancy Outcome (HAPO) study has clearly shown that GD-related complications correlate with glycemic control. We will review the current understanding of the physiology of GD and the screening and treatment guidelines that are commonly utilized in clinical care. In addition, we will discuss the need for development of multiparametric models combining maternal clinical risk factors and biomarkers early in pregnancy to better stratify and predict risk of GD-related complications and offer targeted intervention.

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.

Obesity impairs cell-mediated immunity during the second trimester of pregnancy.

OBJECTIVE: Obese pregnancy is associated with significantly higher rates of infection, which can harm both mother and fetus. The objective of this study was to determine the impact of obesity on maternal blood immune function. STUDY DESIGN: This was a cross-sectional, case control study of 15 obese (Ob) and 15 lean (Lc) subjects. Immune cell subsets, intracellular and serum cytokine production, and lymphocyte proliferation were measured in maternal blood during the second trimester of pregnancy. RESULTS: Obese women had a significantly lower proportion of CD8+ and NKT cells and a higher proportion of B cells, impaired cytokine production when stimulated ex vivo, and impaired ability of lymphocytes to proliferate compared with their lean counterparts. CONCLUSION: Obese pregnancy is associated with impaired cell-mediated immunity. Because perinatal infections can have serious maternal and fetal consequences, it is imperative to better understand these mechanistic underpinnings to optimize prevention and devise targeted therapy.

The Role of Prenatal Psychosocial Stress in the Associations of a Proinflammatory Diet in Pregnancy With Child Adiposity and Growth Trajectories.

Importance: Prenatal psychosocial stress and nutrition may each program offspring adiposity, an important predictor of lifelong cardiometabolic health. Although increased stress and poor nutrition have been found to co-occur in pregnancy, little is known about their combined longitudinal associations in the offspring. Objective: To investigate whether the associations of the Dietary Inflammatory Index (DII) with offspring adiposity differ by prenatal stress levels and whether these associations change with age. Design, Setting, and Participants: Project Viva, a prospective prebirth cohort study of mother-child dyads in Massachusetts, included singleton children of mothers enrolled between April 1999 and July 2002, with follow-up visits at early childhood, midchildhood, and early adolescence. Data analysis was performed from October 31, 2020, to October 31, 2022. Exposures: Food frequency-derived DII score in pregnancy was the exposure. Effect modifiers included stress-related measures in pregnancy; depressive symptoms assessed using the Edinburgh Postnatal Depression Scale (EPDS), dichotomized at scores greater than or equal to 13 vs less than 13; and census tract-level social vulnerability (overall Social Vulnerability Index and its 4 main subindices), dichotomized at the 75th percentile. Main Outcomes and Measures: Overall adiposity, comprising sex- and age-standardized body mass index (BMI z), sum of subscapular and triceps skinfolds, fat mass index (FMI), and body fat percentage estimated using bioelectrical impedance analysis (BIA) and dual x-ray absorptiometry (DXA); and central adiposity, comprising waist circumference, ratio of subscapular to triceps skinfolds, and DXA-derived trunk FMI. Results: Among 1060 mother-child dyads, mean (SD) maternal age was 32.6 (4.6) years, and 811 (77%) mothers were non-Hispanic White. Mean (SD) DII score was -2.7 (1.3) units, Social Vulnerability Index level was 38th (27th) percentile, and 8% of mothers had depressive symptoms. Mean (SD) age of the children was 3.3 (0.3) years at the early childhood visit, 7.9 (0.8) years at the midchildhood visit, and 13.2 (0.9) years at the early adolescence visit. In adjusted analyses, children born to mothers in the highest (vs lowest) quartile of DII had slower decrease in BMI z scores (ß, 0.03 SD units/y; 95% CI, 0.01-0.05 SD units/y), and faster adiposity gain (eg, BIA total FMI ß, 0.11 kg/m2/y; 95% CI, 0.03-0.19 kg/m2/y) over time. Associations of prenatal DII quartiles with childhood adiposity were stronger (eg, BIA total FMI quartile 4 vs quartile 1 change in ß, 1.40 kg/m2; 95% CI, 0.21-2.59 kg/m2) among children of mothers with high vs low EPDS scores in pregnancy, although EPDS scores did not modify the change over time. Associations of prenatal DII with adiposity change over time, however, were greater among children whose mothers lived in neighborhoods with a high (BIA percentage body fat: ß, 0.55% per year; 95% CI, 0.04%-1.07% per year) vs low (ß, 0.13% per year; 95% CI, -0.20 to 0.46% per year), percentage of racial and ethnic minorities, and residents with limited English-language proficiency. Conclusions and Relevance: The findings of this cohort study suggest that it may be useful to simultaneously evaluate prenatal diet and psychosocial stress in women as targets for interventions intended to prevent excess childhood adiposity.

Gestational Glucose Intolerance and Birth Weight-Related Complications.

OBJECTIVE: To evaluate the risks of large-for-gestational-age birth weight (LGA) and birth weight-related complications in pregnant individuals with gestational glucose intolerance, an abnormal screening glucose loading test result without meeting gestational diabetes mellitus (GDM) criteria. METHODS: In a retrospective cohort study of 46,989 individuals with singleton pregnancies who delivered after 28 weeks of gestation, those with glucose loading test results less than 140 mg/dL were classified as having normal glucose tolerance. Those with glucose loading test results of 140 mg/dL or higher and fewer than two abnormal values on a 3-hour 100-g oral glucose tolerance test (OGTT) were classified as having gestational glucose intolerance. Those with two or more abnormal OGTT values were classified as having GDM. We hypothesized that gestational glucose intolerance would be associated with higher odds of LGA (birth weight greater than the 90th percentile for gestational age and sex). We used generalized estimating equations to examine the odds of LGA in pregnant individuals with gestational glucose intolerance compared with those with normal glucose tolerance, after adjustment for age, body mass index, parity, health insurance, race and ethnicity, and marital status. In addition, we investigated differences in birth weight-related adverse pregnancy outcomes. RESULTS: Large for gestational age was present in 7.8% of 39,685 pregnant individuals with normal glucose tolerance, 9.5% of 4,155 pregnant individuals with gestational glucose intolerance and normal OGTT, 14.5% of 1,438 pregnant individuals with gestational glucose intolerance and one abnormal OGTT value, and 16.0% of 1,711 pregnant individuals with GDM. The adjusted odds of LGA were higher in pregnant individuals with gestational glucose intolerance than in those with normal glucose tolerance overall (adjusted odds ratio [aOR] 1.35, 95% CI 1.23-1.49, P <.001). When compared separately with pregnant individuals with normal glucose tolerance, those with either gestational glucose intolerance subtype had higher adjusted LGA odds (gestational glucose intolerance with normal OGTT aOR 1.21, 95% CI 1.08-1.35, P <.001; gestational glucose intolerance with one abnormal OGTT value aOR 1.77, 95% CI 1.52-2.08, P <.001). The odds of birth weight-related adverse outcomes (including cesarean delivery, severe perineal lacerations, and shoulder dystocia or clavicular fracture) were higher in pregnant individuals with gestational glucose intolerance with one abnormal OGTT value than in those with normal glucose tolerance. CONCLUSION: Gestational glucose intolerance in pregnancy is associated with birth weight-related adverse pregnancy outcomes. Glucose lowering should be investigated as a strategy for lowering the risk of these outcomes in this group.