Maternal Prepregnancy Diabetes Research Articles

Prenatal Diabetes and Obesity: Implications for Autism Spectrum Disorders in Offspring - A Comprehensive Review.

Fetal brain development is an important determinant of neuropsychological performance in children. Any alterations in the intrauterine environment at different stages of pregnancy, such as maternal metabolic disorders, can lead to the development of chronic conditions in the offspring. Therefore, maternal diabetes, especially gestational diabetes mellitus, is an important factor in the development of pathological changes, such as miscarriage, fetal macrosomia, or neurodevelopmental disorders. During pregnancy, the hyperglycemic intrauterine environment adversely affects fetal brain development. A growing body of scientific research indicates that prenatal environmental factors, by affecting fetal brain development, can contribute to the appearance of autism spectrum disorders. According to the latest estimates from the International Diabetes Federation (2021), approximately 21.1 million live births worldwide (16.7%) have been affected by some form of hyperglycemia during pregnancy. The condition is more prevalent in low- and middle-income countries, where access to obstetric care is limited. The following factors have been identified as potential risk factors for gestational diabetes: advanced maternal age, overweight and obesity, family history of diabetes, and any form of diabetes. The purpose of this review is to summarize recent studies evaluating the effect of prenatal and maternal risk factors such as maternal pre-pregnancy diabetes, gestational diabetes, and obesity on the risk of developing autism spectrum disorder in offspring.

In-utero and newborn factors and thyroid cancer incidence in adult women in the Sister Study cohort.

10560 Background: Thyroid cancer ranks as the fifth most common cancer in women globally, with 90% of cases classified as differentiated thyroid cancer (DTC). Currently, thyroid cancer etiology remains largely unknown, with childhood exposure to ionizing radiation and obesity among the few established modifiable risk factors. Considering that DTC is diagnosed at relatively younger ages compared to many other cancers, with higher incidence in females versus males, the current study aimed to investigate in-utero and newborn exposures in relation to adult female DTC incidence. Methods: From the Sister Study, a cohort of sisters of women with breast cancer living in the U.S. (including Puerto Rico), we included 47810 women who were cancer-free at baseline (2003–2009). At baseline, participants provided information on their birth and newborn characteristics, and characteristics of their parents before and during pregnancy. Using Cox proportional hazards regression models, we assessed the association between in-utero and newborn factors and self-reported DTC incidence during follow-up. The models were adjusted for attained age (timescale), race/ethnicity, BMI, smoking status, personal history of benign thyroid disease, educational level, household annual income, and Area Deprivation Index. Results: The median age at baseline of the study population was 55.4 (interquartile range [IQR]: 48.9-62.1). During follow-up (median: 13.1 years, IQR: 11.5-15), 233 women were diagnosed with DTC, with medical records available for 72% of cases. Factors associated with a higher incidence of DTC included gestational hypertension or hypertension-related disorders (15 exposed cases, HR= 1.87, 95%CI 1.10-3.16), and higher birth weight (for every additional kilogram HR=1.13, 95%CI 1.00-1.27). The HR for maternal pre-pregnancy or gestational diabetes was 2.33 (5 exposed cases, 95%CI 0.96-5.67). Conversely, being born at least two weeks before the due date was associated with a lower incidence (6 exposed cases, HR=0.35, 95%CI 0.15-0.79). These associations remained consistent when restricting to advanced-stage and large-sized DTCs. We observed no associations for participants’ birth order, time since last pregnancy of the participants' mother, multiple versus singleton birth, ever having been breastfed, parental smoking during pregnancy or age at delivery, maternal morning sickness, or paternal diabetes. Conclusions: In this study, maternal diabetes, maternal hypertension, and birth weight were associated with higher female DTC incidence while being born at least two weeks before the due date was associated with lower DTC incidence. These findings provide evidence that in-utero and newborn exposures may have a long-term influence on thyroid cancer development.

Prepregnancy body mass index and adverse perinatal outcomes in the presence of other maternal risk factors

High prepregnancy body mass index is one of the most common risk factors for adverse perinatal events. This study aimed to assess whether the association between maternal body mass index and adverse perinatal outcome is modified by other concomitant maternal risk factors. This was a retrospective cohort study of all singleton live births and stillbirths in the United States from 2016 to 2017, using data from the National Center for Health Statistics. Logistic regression was used to estimate the adjusted odds ratios and 95% confidence intervals between prepregnancy body mass index and a composite outcome of stillbirth, neonatal death, and severe neonatal morbidity. Modification of this association by maternal age, nulliparity, chronic hypertension, and prepregnancy diabetes mellitus was assessed on both multiplicative and additive scales. The study population included 7,576,417 women with singleton pregnancy; 254,225 (3.5%) were underweight, 3,220,432 (43.9%) had normal body mass index, 1,918,480 (26.1%) were overweight, and 1,062,177 (14.4%), 516,693 (7.0%), and 365,357 (5.0%) had class I, II, and III obesity, respectively. Rates of the composite outcome increased with increasing body mass index above normal values, compared with women with normal body mass index. Nulliparity (289,776; 38.6%), chronic hypertension (135,328; 1.8%), and prepregnancy diabetes mellitus (67,744; 0.89%) modified the association between body mass index and the composite perinatal outcome on both the additive and multiplicative scales. Nulliparous (vs parous) women had a higher rate of increase in adverse outcomes with increasing body mass index. For example, in nulliparous women, class III obesity was associated with 1.8-fold higher odds compared with normal body mass index (adjusted odds ratio, 1.77; 95% confidence interval, 1.73-1.83), whereas in parous women, the adjusted odds ratio was 1.35 (95% confidence interval, 1.32-1.39). Women with chronic hypertension or prepregnancy diabetes mellitus had higher outcome rates overall; however, the dose-response relationship with increasing body mass index was absent. Although the composite outcome rates increased with maternal age, the risk curves were relatively similar across obesity classes in all maternal age groups. Overall, underweight women had 7% higher odds of the composite outcome, and this increased to 21% in parous women. Women with elevated prepregnancy body mass index are at increased risk of adverse perinatal outcomes, and the magnitude of these risks differs by concomitant risk factors, including prepregnancy diabetes mellitus, chronic hypertension, and nulliparity. In particular, in woman with chronic hypertension or prepregnancy diabetes mellitus, there is no impact of increasing body mass index on adverse perinatal outcomes. However, overall rates remain high, and prepregnancy prevention of hypertension and diabetes mellitus should be emphasized among all women irrespective of body mass index.

Abstract 12219: Social Vulnerability and Cardiometabolic Risk Factors in Pregnant Women in the United States

Background: In recent years, pregnancy-related mortality rates in the US have increased, with cardiovascular disease accounting for a third of all pregnancy-related mortality. The association between cardiometabolic (CM) health and social determinants of health have not been well understood. Objectives: We sought to investigate the relationship between social vulnerability and prevalence of CM risk factors in pregnant women in the US. Methods: In this cross-sectional analysis, we linked natality files including all pregnancies resulting in live births in the US (aggregated 2016-2020) with county-level social vulnerability index (SVI), a composite metric of social risk factors with four major domains: socioeconomic, household composition/disability, minority status/language, and housing type/transportation. We investigated the association between SVI and its subdomains with county-level prevalence of maternal pre-pregnancy diabetes, pre-pregnancy hypertension, tobacco use, and obesity. Results: A total of 18,953,511 pregnancies were analyzed across 577 counties. All CM risk factors were associated with SVI and/or its 4 subcomponents to varying degrees. Obesity was strongly associated with overall SVI (R=0.52, P<0.001) with an even stronger relationship with socioeconomic vulnerability (R=0.6, P<0.001) and household composition/disability (R=0.66, P<0.001). The rate of pre-pregnancy diabetes was associated with overall SVI (R=0.27, p<0.001), with similar association with socioeconomic vulnerability (R=0.26, P<0.001) and household composition/disability (R=0.28, P<0.001). Chronic hypertension was weakly associated with overall SVI (R=0.15, P<0.001) with similar association with socioeconomic vulnerability (R=0.19, P<0.001) and household composition/disability (R=0.22, P<0.001). Tobacco use was not associated with overall SVI (R=0.034, p=0.41), but was strongly associated with minority status/language (R=-0.71, P<0.001). Conclusion: Social vulnerability and its domains are associated with prevalence of CM risk factors in pregnant women in the US. Further studies are needed to investigate the impact of targeting social determinants of health to improve CM risk and mortality in pregnant women.

Association of prenatal modifiable risk factors with attention-deficit hyperactivity disorder outcomes at age 10 and 15 in an extremely low gestational age cohort.

The increased risk of developing attention-deficit hyperactivity disorder (ADHD) in extremely preterm infants is well-documented. Better understanding of perinatal risk factors, particularly those that are modifiable, can inform prevention efforts. We examined data from the Extremely Low Gestational Age Newborns (ELGAN) Study. Participants were screened for ADHD at age 10 with the Child Symptom Inventory-4 (N = 734) and assessed at age 15 with a structured diagnostic interview (MINI-KID) to evaluate for the diagnosis of ADHD (N = 575). We studied associations of pre-pregnancy maternal body mass index (BMI), pregestational and/or gestational diabetes, maternal smoking during pregnancy (MSDP), and hypertensive disorders of pregnancy (HDP) with 10-year and 15-year ADHD outcomes. Relative risks were calculated using Poisson regression models with robust error variance, adjusted for maternal age, maternal educational status, use of food stamps, public insurance status, marital status at birth, and family history of ADHD. We defined ADHD as a positive screen on the CSI-4 at age 10 and/or meeting DSM-5 criteria at age 15 on the MINI-KID. We evaluated the robustness of the associations to broadening or restricting the definition of ADHD. We limited the analysis to individuals with IQ ≥ 70 to decrease confounding by cognitive functioning. We evaluated interactions between maternal BMI and diabetes status. We assessed for mediation of risk increase by alterations in inflammatory or neurotrophic protein levels in the first week of life. Elevated maternal BMI and maternal diabetes were each associated with a 55-65% increase in risk of ADHD, with evidence of both additive and multiplicative interactions between the two exposures. MSDP and HDP were not associated with the risk of ADHD outcomes. There was some evidence for association of ADHD outcomes with high levels of inflammatory proteins or moderate levels of neurotrophic proteins, but there was no evidence that these mediated the risk associated with maternal BMI or diabetes. Contrary to previous population-based studies, MSDP and HDP did not predict ADHD outcomes in this extremely preterm cohort, but elevated maternal pre-pregnancy BMI, maternal diabetes, and perinatal inflammatory markers were associated with increased risk of ADHD at age 10 and/or 15, with positive interaction between pre-pregnancy BMI and maternal diabetes.

Association between maternal prepregnancy diabetes mellitus and preconception folic acid supplement use by Hispanic ethnicity: Findings from Georgia, New York City, and Puerto Rico PRAMS 2016–2018

AbstractBackgroundMaternal ethnicity, prepregnancy diabetes, and preconception folic acid intake, are all associated with increased risk of neural tube defects in the United States. We assessed the association between prepregnancy diabetes and preconception folic acid use by Hispanic ethnicity.MethodsWe used population‐based, cross‐sectional survey data from New York City, Georgia and Puerto Rico's 2016–2018 Pregnancy Risk Assessment Monitoring System (PRAMS). Prepregnancy Type 1 or Type 2 diabetes was self‐reported. Adequate preconception folic acid intake was defined as intake of a multivitamin, a prenatal vitamin, or a folic acid vitamin 4–7 times/week during the month before pregnancy. Multivariable logistic regression was used to calculate adjusted prevalence odds ratio (aPORs) and 95% confidence intervals (CI), stratified by Hispanic ethnicity.ResultsPrepregnancy diabetes was reported by 2.9% of Hispanic and 3.6% of non‐Hispanic participants. Adequate preconception folic acid use was reported by 25.9% and 39.9% of Hispanics and non‐Hispanics, respectively. There was an inverse association between prepregnancy diabetes and preconception folic acid use among Hispanics (aPOR = 0.75; 95% CI = 0.31, 1.81), while the association was positive among non‐Hispanics (aPOR = 1.26; 95% CI = 0.70, 2.26); however, the 95% confidence intervals for both groups contained the null value.ConclusionsThe association between prepregnancy diabetes and folic acid intake varied by Hispanic ethnicity. Our hypothesis that reproductive‐aged women with prepregnancy diabetes may receive timely diabetic care, including health counseling to take preconception folic acid, was not supported by our study data. Future studies should examine the association in additional PRAMS sites. Preconception health screening, and folic acid intake among Hispanics, should be strengthened.

247-OR: Maternal Prepregnancy Obesity and Gestational Diabetes Are Associated with Epigenetic Gestational Aging in the Placenta

Pregnancy conditions like maternal pre-pregnancy obesity and gestational diabetes (GDM) have been linked with the development of placenta, a critical organ required for maternal-fetal interface during gestation, and can lead to adverse health outcomes in both mother and fetus. However, the molecular signatures associated with these conditions are not fully understood. Epigenetic clocks, which are based upon DNA methylation of age-related CpGs, are thought to better reflect biological age compared to chronological age and have been used in different tissues as potential biomarkers. In the present study, we hypothesized that altered placental epigenetic gestational aging is associated with pre-pregnancy obesity and GDM. We explored these relationships by leveraging data from three diverse cohorts in the Environmental influences on Child Health Outcomes (ECHO) program (overall N=830) . First, we investigated associations between maternal pre-pregnancy obesity and GDM and estimated placental epigenetic gestational age acceleration (eGAA) . Next, we examined associations between these two conditions and methylation of each CpG site within the robust placental clock (558 CpGs) . Significant associations were not observed between pre-pregnancy obesity and GDM and eGAA. Interestingly, pre-pregnancy obesity was associated with methylation levels at 28 placental clock CpGs (q<0.1) . These sites were annotated to 17 unique genes that enrich processes like circadian entrainment and cellular response to glucagon stimulus (GNAS, GNG2) . Additionally, GDM was associated with methylation levels at 22 CpGs that mapped to 14 genes related to apoptosis (TNFRSF10B, TRADD) and neurological development (CACNA1G, ATXN1) . Overall, findings suggest that maternal pre-pregnancy obesity and GDM are associated with CpG methylation of the placental epigenetic clock, revealing potential markers vital for healthy pregnancy and fetal development. Disclosure K.Huff: None. C.Marsit: None. S.Niemiec: None. H.Volk: None. T.M.O'shea: None. R.Fry: None. K.Roell: None. C.Bulka: None. K.E.Boyle: None. C.Breton: None. A.Burt: None. D.Dabelea: None. L.Kahn: None. M.R.Karagas: None. Funding National Institutes of Health (UH3OD023348)

Epidemiology of Nonsyndromic, Orofacial Clefts in Texas: Differences by Cleft Type and Presence of Additional Defects.

To describe the current epidemiology of nonsyndromic cleft palate alone (CP) and cleft lip with or without cleft palate (CL ± P) in Texas and examine differences in the characteristics of infants with CP and CL ± P based on the presence/absence of additional defects. We used data from the Texas Birth Defects Registry, a statewide active birth defect surveillance system, from 1815 cases with CP and 5066 with CL ± P, without a syndrome diagnosis (1999-2014 deliveries). All live births in Texas were used for comparison. Poisson regression was used to calculate crude and adjusted prevalence ratios (aPR) for each characteristic, separately for each cleft subphenotype. The prevalence of CL ± P and CP in our study was estimated as 8.3 and 3.0 per 10 000 live births, respectively. After adjusting for several characteristics, several factors were associated with CL ± P, CP, or both, including infant sex and maternal race/ethnicity, age, smoking, and diabetes. There were several differences between infants with isolated versus nonisolated clefts. For example, maternal prepregnancy diabetes was associated with an increased prevalence of CL ± P (aPR 7.91, 95% confidence interval [CI]: 5.53, 11.30) and CP (aPR 3.24, 95% CI: 1.43, 7.36), but only when additional defects were present. Findings from this study provide a contemporary description of the distribution of orofacial clefts in Texas accounting for differences between isolated and nonisolated clefts. They may contribute to increasing our understanding of the etiology of CP and CL ± P.

Early Nutrition among Infants Admitted to the NICU with Cleft Lip and Palate.

The objective of this study was to examine differences in human milk feeding outcomes among infants admitted to a neonatal intensive care unit (NICU) with and without cleft lip and palate (CLP). Data were used from a sample of infants admitted to the NICU with and without CLP from the 2018 National Vital Statistics System. For baseline comparisons, Chi-square tests of independence were used to compare categorical variables, and independent samples t tests were used for continuous variables. Logistic regression models were performed to determine the odds of human milk feeding at discharge in infants admitted to the NICU with CLP. The total sample included 345,429 infants admitted to the NICU, of which 660 had CLP. Significant differences were found among the following variables when baseline comparisons were made between infants admitted to the NICU with and without CLP: mother's race, mother's education, maternal smoking record, childbirth delivery method, presence of maternal pre-pregnancy diabetes, five-minute APGAR score, multiparity record (having more than one baby at birth), gestational age, and gestational weight. After controlling for baseline differences, results indicated reduced odds of human milk feeding at discharge in infants admitted to the NICU with CLP compared to those without CLP (OR = .543; 95% CI.455,.648). Results suggest reduced odds of human milk feeding at discharge among infants admitted to the NICU with CLP compared to those without CLP. These findings emphasize the necessity of awareness and facilitation of human milk feeding in this population.

Epidemiology of uterine rupture among pregnant women in China and development of a risk prediction model: analysis of data from a multicentre, cross-sectional study

ObjectivesTo describe the epidemiology of uterine rupture in China from 2015 to 2016 and to build a prediction model for uterine rupture in women with a scarred uterus.SettingA multicentre cross-sectional...

Socioeconomic impacts on the intergenerational associations of preterm birth

Background The impact of socioeconomic status on intergenerational associations of preterm birth (PTB) is poorly understood. Objective To estimate the socioeconomic status of intergenerational impact of PTB transmission. Study design This retrospective cohort study included all eligible singleton female infants born in Nebraska from 1995 to 2005 (n = 6631) and followed up from 2009 to 2019. Mothers' first singleton infants born 2009–2019 were linked to the mothers and included in the description and generalized estimating equations. Results Mothers born PTB were 37% more likely to have a PTB infant after controlling for maternal and grandmother's prenatal care adequacy, maternal residential poverty, pre-pregnancy diabetes, hypertension, C-section, and infants' gender. In poor neighborhoods, the adjusted preterm odds ratio of former born preterm mothers (compared with mother not born PTB) was 1.56 (95% confidence interval (CI): 1.02, 2.38). Moreover, moving from a poor neighborhood to a relatively well-off neighborhood was a protective factor for PTB with an adjusted odds ratio of 0.47 (95% CI: 0.23, 0.95). Conclusions Mothers born preterm were at increased risk of having PTB infants, especially in poor areas. Maternal upward social mobility was a protective factor for PTB recurrence.

Association of Maternal Prepregnancy Diabetes and Gestational Diabetes Mellitus With Congenital Anomalies of the Newborn.

To examine the association of maternal prepregnancy diabetes, gestational diabetes mellitus (GDM), and 12 subtypes of congenital anomalies of the newborn. We included 29,211,974 live births with maternal age ranging from 18 to 49 years old documented in the National Vital Statistics System in the U.S. from 2011 to 2018. Information on prepregnancy diabetes, GDM, and congenital anomalies was retrieved from birth certificates. Log-binomial regression was used to estimate risk ratios (RRs) and 95% CIs for congenital anomalies overall and by subtypes. Of the 29,211,974 live births, there were 90,061 infants who had congenital anomalies identified at birth. The adjusted RRs of congenital anomalies at birth were 2.44 (95% CI 2.33-2.55) for prepregnancy diabetes and 1.28 (95% CI 1.24-1.31) for GDM. The associations were generally consistent across subgroups by maternal age, race/ethnicity, prepregnancy obesity status, and infant sex. For specific subtypes of congenital anomalies, maternal prepregnancy diabetes or GDM was associated with an increased risk of most subtypes. For example, the adjusted RRs of cyanotic congenital heart disease were 4.61 (95% CI 4.28-4.96) for prepregnancy diabetes and 1.50 (95% CI 1.43-1.58) for GDM; the adjusted RRs of hypospadias were 1.88 (95% CI 1.67-2.12) for prepregnancy diabetes and 1.29 (95% CI 1.21-1.36) for GDM. Prepregnancy diabetes and, to a lesser extent, GDM were associated with several subtypes of congenital anomalies of the newborn. These findings suggest potential benefits of preconception counseling in women with preexisting diabetes or at risk for GDM for the prevention of congenital anomalies.

Maternal pre-pregnancy overweight and gestational diabetes and dietary intakes among young adult offspring

Background/ObjectivesMaternal pre-pregnancy overweight/obesity and gestational diabetes (GDM) are associated with increased fat deposition in adult offspring. The purpose of this study was to identify if maternal pre-pregnancy overweight (body mass index (BMI) ≥ 25 kg/m2) or GDM are associated with dietary quality or intake in adult offspring.Subjects/MethodsParticipants (n = 882) from two longitudinal cohort studies (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study) completed a validated food-frequency questionnaire at a mean age of 24.2 years (SD 1.3). Diet quality was evaluated by a Recommended Finnish Diet Index (RDI). The study sample included offspring of normoglycaemic mothers with pre-pregnancy overweight/obesity (ONO = 155), offspring of mothers with GDM regardless of BMI (OGDM = 190) and offspring of mothers with normal weight and no GDM (controls; n = 537).ResultsAmong men, daily energy and macronutrient intakes were similar in ONO and controls. However, after adjusting for current offspring characteristics, including BMI, daily carbohydrate intake relative to total energy intake was higher in ONO-men [2.2 percentages of total energy intake (95% confidence interval 0.4, 4.0)]. In ONO-women, macronutrient intakes relative to total energy intake were similar with controls, while total daily energy intake seemed lower [−587.2 kJ/day (−1192.0, 4.4)]. After adjusting for confounders, this difference was attenuated. Adherence to a healthy diet, as measured by RDI, was similar in ONO and controls [mean difference: men 0.40 (−0.38, 1.18); women 0.25 (−0.50, 1.00)]. In OGDM vs. controls, total energy and macronutrient intakes were similar for both men and women. Also adherence to a healthy diet was similar [RDI: men 0.09 (−0.62, 0.80); women −0.17 (−0.93, 0.59)].ConclusionsOur study suggested higher daily carbohydrate intake in male offspring exposed to maternal pre-pregnancy overweight/obesity, compared with controls. Prenatal exposure to GDM was not associated with adult offspring dietary intakes.

Abstract MP64: Associations of Pre-pregnancy BMI and Maternal Glycemia in Pregnancy With Maternal and Child Microbiome Five Years After Birth: Results From the Genetics of Glucose Regulation in Gestation and Growth (Gen3G) Prospective Cohort

Introduction: Maternal pre-pregnancy obesity and gestational diabetes increase future risk of obesity in the mother and child. Obesity and diabetes have been associated with lower gut microbiome diversity. To our knowledge, no studies have examined if maternal pre-pregnancy body mass index (ppBMI) and maternal glycemia during pregnancy are prospectively associated with gut microbiome diversity in mothers and their children in mid-childhood. Hypothesis: We hypothesized that higher maternal ppBMI and maternal glycemia are associated with lower gut microbiome diversity in mothers and their children 5 years after birth. Methods: Gen3G is pre-birth cohort of mother-child dyads, >18 yrs who visited a pregnancy clinic in Sherbrooke, Canada. Oral glucose tolerance tests (OGTT) were administered in second trimester of pregnancy. A total of 178 mother-child pairs (not on antibiotics in the month prior to visit) provided stool, anthropometric measurements and lifestyle information 5 years after birth. Maternal overweight and obesity were defined as 25-30 kg/m 2 and >=30 kg/m 2 respectively. From the stool, we extracted microbial DNA and sequenced the V4 region of the 16S ribosomal subunit. We used linear regression to model the association of ppBMI and glucose values during OGTT with maternal and child gut microbiome Shannon diversity, adjusted for confounders ( see footnote of Figure ). Results: Maternal ppBMI showed U-shaped associations with gut microbiome diversity of both mothers and children 5 years after birth ( Figure, left panels ). Higher 1h-glucose post-OGTT was associated in a dose-response fashion with lower gut microbiome diversity in mothers (p for trend <0.001) and children (p for trend <0.001) 5 years after birth ( Figure, right panels ). Conclusion: Higher glycemia in pregnancy, and to a lesser extent ppBMI, was prospectively associated with lower gut microbiome diversity in mother-child pairs 5 years after birth, even after adjustment for confounders and mother and child BMI measured 5 years after birth.

In utero exposure to mercury and childhood overweight or obesity: counteracting effect of maternal folate status

BackgroundLow-dose mercury (Hg) exposure has been associated with cardiovascular diseases, diabetes, and obesity in adults, but it is unknown the metabolic consequence of in utero Hg exposure. This study aimed to investigate the association between in utero Hg exposure and child overweight or obesity (OWO) and to explore if adequate maternal folate can mitigate Hg toxicity.MethodsThis prospective study included 1442 mother-child pairs recruited at birth and followed up to age 15 years. Maternal Hg in red blood cells and plasma folate levels were measured in samples collected 1–3 days after delivery (a proxy for third trimester exposure). Adequate folate was defined as plasma folate ≥ 20.4 nmol/L. Childhood OWO was defined as body mass index ≥ 85% percentile for age and sex.ResultsThe median (interquartile range) of maternal Hg levels were 2.11 (1.04–3.70) μg/L. Geometric mean (95% CI) of maternal folate levels were 31.1 (30.1–32.1) nmol/L. Maternal Hg levels were positively associated with child OWO from age 2–15 years, independent of maternal pre-pregnancy OWO, diabetes, and other covariates. The relative risk (RR = 1.24, 95% CI 1.05–1.47) of child OWO associated with the highest quartile of Hg exposure was 24% higher than those with the lowest quartile. Maternal pre-pregnancy OWO and/or diabetes additively enhanced Hg toxicity. The highest risk of child OWO was found among children of OWO and diabetic mothers in the top Hg quartile (RR = 2.06; 95% CI 1.56–2.71) compared to their counterparts. Furthermore, adequate maternal folate status mitigated Hg toxicity. Given top quartile Hg exposure, adequate maternal folate was associated with a 34% reduction in child OWO risk (RR = 0.66, 95% CI 0.51–0.85) as compared with insufficient maternal folate. There was a suggestive interaction between maternal Hg and folate levels on child OWO risk (p for interaction = 0.086).ConclusionsIn this US urban, multi-ethnic population, elevated in utero Hg exposure was associated with a higher risk of OWO in childhood, and such risk was enhanced by maternal OWO and/or diabetes and reduced by adequate maternal folate. These findings underscore the need to screen for Hg and to optimize maternal folate status, especially among mothers with OWO and/or diabetes.

Breastfeeding duration in infancy and adult risks of type 2 diabetes in a high-income country.

Observed associations between breastfeeding and reduced risk of type 2 diabetes in adulthood may be confounded. We examined if the duration of breastfeeding in infancy was associated with the risk of type 2 diabetes in adulthood after adjustment for a range of prenatal and postnatal risk factors. We prospectively followed 6,044 individuals from the Copenhagen Perinatal Cohort born 1959-1961. Duration of any breastfeeding (≤0.5, >0.5-1, >1-2, >2-4, >4months) was assessed at the infant's 1-year health examination. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for type 2 diabetes (at age ≥30years, 237 persons) by breastfeeding duration without and with adjustment for parental social status and education, maternal pre-pregnancy body mass index (BMI), maternal diabetes and smoking during pregnancy, gestational weight gain, parity, preterm birth, birth weight, sex, and BMI at ages 7 and 41-43years. In the unadjusted analysis, compared with infants breastfed for ≤0.5month, those breastfed for >4months had a 51% reduced risk of type 2 diabetes (HR=0.49; 95% CI [0.32, 0.75]). After the stepwise adjustment for putative early life confounders, this was attenuated to a nonsignificant 31% reduced risk (HR=0.69; 95% CI [0.44, 1.07]). Adjustment for childhood and adulthood BMI minimally changed the results. We found that the inverse association between the duration of breastfeeding and risk of type 2 diabetes in adulthood is considerably weakened and no longer significant after adjustment for prenatal and postnatal factors in the infant and mother.

Organic food consumption during pregnancy and its association with health-related characteristics: the KOALA Birth Cohort Study.

To investigate the associations of organic food consumption with maternal pre-pregnancy BMI, hypertension and diabetes in pregnancy, and several blood biomarkers of pregnant women. Prospective cohort study. Pregnant women were recruited at midwives' practices and through channels related to consumption of food from organic origin. Pregnant women who filled in FFQ and donated a blood sample (n 1339). Participant groups were defined based on the share of consumed organic products; to discriminate between effects of food origin and food patterns, healthy diet indicators were considered in some statistical models. Consumption of organic food was associated with a more favourable pre-pregnancy BMI and lower prevalence of gestational diabetes. Compared with participants consuming no organic food (reference group), a marker of dairy products intake (pentadecanoic acid) and trans-fatty acids from natural origin (vaccenic and rumenic acids) were higher among participants consuming organic food (organic groups), whereas elaidic acid, a marker of the intake of trans-fatty acids found in industrially hydrogenated fats, was lower. Plasma levels of homocysteine and 25-hydroxyvitamin D were lower in the organic groups than in the reference group. Differences in pentadecanoic acid, vaccenic acid and vitamin D retained statistical significance when correcting for indicators of the healthy diet pattern associated with the consumption of organic food. Consumption of organic food during pregnancy is associated with several health-related characteristics and blood biomarkers. Part of the observed associations is explained by food patterns accompanying the consumption of organic food.

Effect of parental obesity and gestational diabetes on child neuropsychological and behavioral development at 4 years of age: the Rhea mother–child cohort, Crete, Greece

Studies have suggested an association between maternal obesity pre-pregnancy and gestational diabetes (GDM) with impaired offspring neurodevelopment, but it is not clear if these associations are explained by shared familiar characteristics. We aimed to assess the associations of maternal and paternal obesity, maternal glucose intolerance in early pregnancy and GDM, with offspring neurodevelopment at 4years of age. We included 772 mother-child pairs from the "Rhea" Mother-Child cohort in Crete, Greece. Data on maternal/paternal body mass index (BMI) and maternal fasting serum samples for glucose and insulin measurements were collected at 12weeks of gestation. GDM screening was performed at 24-28weeks. Neurodevelopment at 4years was assessed using the McCarthy Scales of Children's Abilities. Behavioral difficulties were assessed by Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Multivariate linear regression analyses showed that maternal obesity was associated with a significant score reduction in general cognitive ability (β-coeff -4.03, 95% CI: -7.08, -0.97), perceptual performance (β-coeff -4.60, 95% CI: -7.74, -1.47), quantitative ability (β-coeff -4.43, 95% CI: -7.68, -1.18), and executive functions (β-coeff -4.92, 95% CI: -8.06, -1.78) at 4years of age, after adjustment for several confounders and paternal BMI. Maternal obesity was also associated with increased behavioral difficulties (β-coeff 1.22, 95% CI: 0.09, 2.34) and ADHD symptoms (β-coeff 4.28, 95% CI: 1.20, 7.36) at preschool age. Paternal obesity maternal glucose intolerance in early pregnancy and GDM was not associated with child neurodevelopment. These findings suggest that maternal obesity may impair optimal child neurodevelopment at preschool age independently of family shared characteristics.

Towards national comprehensive gestational diabetes screening-consequences for neonatal outcome and care.

The change from risk-factor-based to nearly comprehensive screening of gestational diabetes (GDM) identifies more but milder cases of the disease. The main aim of this study was to evaluate the effect of this screening policy change on neonatal outcomes and care. A population-based register study in Finland. GDM cases during risk-factor-based (year 2006, n=5179) and comprehensive (2010, n=6679) screenings were identified through the Medical Birth Register. All singletons without maternal GDM or prepregnancy diabetes served as controls (n=51746 and n=52386, respectively). The main outcomes were macrosomia, neonatal hypoglycemia and the need for care in a neonatal ward. In the GDM group, the mean birthweight decreased between the study years from 3660g to 3595g and the prevalence of macrosomia from 5.6 to 4.1% even after adjustment for maternal age, parity and prepregnancy body mass index. The adjusted mean difference in birthweight between GDM and control newborns decreased from 70 to 22g between the study years. The prevalence of neonatal hypoglycemia increased from 18.0 to 22.1% in the GDM group. However, neonatal hypoglycemia was more often treated without care in a neonatal ward. The proportion of infants treated on a neonatal ward decreased in both the GDM and control groups between the study years. In newborns, comprehensive GDM screening led to decreased mean birthweight and macrosomia rates, but the prevalence of neonatal hypoglycemia increased. This places substantial demands for delivery hospitals and healthcare resources.

Maternal pre-pregnancy and gestational diabetes, obesity, gestational weight gain, and risk of cancer in young children: a population-based study in California.

We aimed to examine the influence of pre-pregnancy diabetes, pre-pregnancy body mass index (BMI), gestational diabetes, and gestational weight gain on childhood cancer risk in offspring. We identified cancer cases (n=11,149) younger than age 6years at diagnosis from the California Cancer Registry registered between 1988 and 2013. Controls (n=270,147) were randomly sampled from California birth records, and frequency matched by year of birth to all childhood cancers during the study period. Exposure and covariate information were extracted from birth records. Unconditional logistic regression models were generated to assess the importance of pre-pregnancy diabetes, pre-pregnancy BMI, gestational diabetes, and gestational weight gain on childhood cancer risk. We observed increased risks of acute lymphoblastic leukemia and Wilms' tumor in children of mothers with pre-pregnancy diabetes [odds ratio (OR) 95% confidence interval (CI) 1.37 (1.11, 1.69); OR (95% CI) 1.45 (0.97, 2.18), respectively]. When born to mothers who were overweight prior to pregnancy (BMI 25-<30), children were at increased risk of leukemia [OR (95% CI) 1.27 (1.01, 1.59)]. Insufficient gestational weight gain increased the risk of acute myeloid leukemia [OR (95% CI) 1.50 (0.92, 2.42)] while excessive gestational weight gain increased the risk of astrocytomas [OR (95% CI) 1.56 (0.97, 2.50)]. No associations were found between gestational diabetes and childhood cancer risk in offspring. We estimated elevated risks of several childhood cancers in the offspring of mothers who had diabetes and were overweight prior to pregnancy, as well as mothers who gained insufficient or excessive weight. Since few studies have focused on these factors in relation to childhood cancer, replication of our findings in future studies is warranted.