Elevated Maternal Body Mass Index Research Articles

Impact of maternal body mass index on delivery complications and recurrent pregnancy loss (RPL)

Maternal Body Mass Index (BMI) is a crucial predictor of obstetric and delivery-related complications, significantly affecting maternal and neonatal outcomes. As global obesity rates continue to rise, the impact of elevated maternal BMI on pregnancy has garnered increasing attention. This comprehensive review examines the association between maternal BMI and various pregnancy complications, including gestational diabetes mellitus (GDM), hypertensive disorders, labor dystocia, cesarean section (C-section), postpartum hemorrhage (PPH), and adverse neonatal outcomes such as macrosomia. The aim of this review is to examine the impact of maternal Body Mass Index (BMI) on pregnancy and delivery outcomes, with a focus on identifying key complications associated with elevated maternal BMI and exploring the underlying mechanisms. As global obesity rates continue to rise, understanding the influence of maternal BMI on obstetric and neonatal outcomes is crucial for developing effective management strategies. This review synthesizes current research on the relationship between maternal BMI and complications such as gestational diabetes mellitus (GDM), hypertensive disorders, labor dystocia, cesarean section (C-section), postpartum hemorrhage (PPH), and adverse neonatal outcomes, including macrosomia. The review also delves into the physiological mechanisms, including insulin resistance, chronic inflammation, and altered uterine contractility, that contribute to these complications. Clinical implications are discussed, emphasizing the importance of preconception counselling, individualized weight management during pregnancy, and interdisciplinary care to optimize outcomes. The conclusion highlights Maternal BMI is a critical factor influencing pregnancy outcomes. Obesity increases the risk of delivery complications and RPL, while underweight status is associated with preterm birth, LBW, and RPL. Addressing maternal BMI through preconception care and continuous monitoring during pregnancy is essential for improving maternal and fetal health outcomes.

Cell free DNA screening for fetal aneuploidy in Ireland: An observational study of outcomes following insufficient fetal fraction

ObjectivesTo determine maternal factors associated with low fetal fraction (FF). To determine the proportion of women who receive a result from repeat non-invasive prenatal testing (NIPT) testing. To identify any significant associations between pregnancy interventions or outcomes and low FF. Study DesignRetrospective observational study of 4465 women undergoing antenatal screening by targeted cell free DNA (cfDNA) testing at an Irish tertiary maternity hospital between January 2017 and December 2022. Patients who failed to obtain a result after the first NIPT were analyzed in two cohorts; those who received a result on a repeat sample and those who failed to ever achieve a result despite a second, third or fourth cfDNA test. ResultsRisk of insufficient FF significantly increased with elevated maternal BMI (OR 1.07; 95% CI 1.01–1.13, p = 0.03) and in-vitro fertilization (IVF) (OR 3.4; 95% CI 1.19–9.4, p = 0.02). Women with no result were more likely to have diagnostic invasive testing (p < 0.01), but had no increased risk of aneuploidy. Repeated failed NIPT attempts due to low FF were significantly associated with the subsequent development of hypertensive diseases of pregnancy (p = 0.03). Greater than 70% of patients who were unsuccessful in a first or second attempt at NIPT due to low FF yielded a result following a second or third sample. ConclusionsHigh BMI and IVF conceptions are greater contributors to low FF than fetal aneuploidy. Repeating NIPT yields a result in greater than 70% of cases. What’s already known about this topic?Fetal fraction (FF) in prenatal cfDNA testing is influenced by maternal and pregnancy factors including body mass index (BMI) and IVF. Low FF has been associated with adverse pregnancy outcomes including fetal aneuploidy and hypertensive diseases of pregnancy. What does this study add?In a large Irish population, increasing maternal BMI and in-vitro fertilization are the most significant contributors to repeated test failures due to low FF.Greater than 70% of patients with test failure due to low FF will receive a result on 2nd and 3rd NIPT attempts.Patients with no result from NIPT were more likely to undergo diagnostic invasive testing but the risk of aneuploidy was not significantly increased.

Investigating the Relationship Between Maternal Obesity and Disorders of Amniotic Fluid [ID: 1377151

INTRODUCTION: Prior studies show conflicting evidence as to whether obesity in the absence of other medical or pregnancy-related conditions contributes to amniotic fluid disorders. The purpose of this study is to determine the association between late-pregnancy obesity with oligohydramnios (amniotic fluid index [AFI]&lt;5 or maximum vertical pocket [MVP]&lt;2) and/or polyhydramnios (AFI&gt;24 or MVP&gt;8). METHODS: This is a retrospective cohort study of 966 women with singleton gestations who had one or more obstetrical ultrasounds at Mount Sinai South Nassau at 36 0/7 weeks of gestation or beyond between August 1, 2015, and May 1, 2020. Patients were included if they had valid pregnancy dating and a documented AFI and/or MVP. Patients were categorized based on body mass index (BMI) (eg, normal, overweight, class I obesity, class II obesity, or class III obesity). Chi-square analyses were performed to evaluate whether there was a relationship between BMI and AFI. A logistic regression analysis was then performed for any confounding variables. RESULTS: There was no significant association between oligohydramnios and increasing BMI, whether patients had overweight (P=.17), class I (P=.46), class II (P=.49), or class III obesity (P=.99). The same was true for polyhydramnios and increasing BMI, whether patients had overweight (P=.68), class I (P=.74), class II (P=.94), or class III obesity (P=.99). CONCLUSION: Elevated maternal BMI was not significantly associated with disorders of amniotic fluid, regardless of the severity of obesity.

Abstract P240: Higher Body Mass Index is Associated With Lower Placental Expression of EPYC: Results From a Genome-Wide Transcriptomic Study in the Gen3G Cohort

Background: Elevated maternal body mass index (BMI) in pregnancy is associated with adverse maternal and fetal outcomes. Identification of alterations in the placental transcriptome may elucidate molecular markers of the biological pathways underlying these associations. Methods: We investigated the association of first trimester maternal BMI with the placental transcriptome in Gen3G, a large population-based pregnancy cohort. We completed RNA sequencing of 449 placental samples and performed differential gene expression analysis of over 15,000 genes (Limma Voom). We used maternal BMI as a continuous variable, with estimates reported as change in normalized gene expression per 1-unit increase in BMI (kg/m2), as well as a categorical variable (participants with normal weight (N=270) vs. obesity (N=82)), with RNA expression estimates reported as log2 fold changes. We adjusted models for maternal age, fetal sex, gestational age and 6 surrogate variables inferred from the expression data to adjust for batch effects and other unmeasured sources of variability. We accounted for multiple testing using False Discovery Rate (FDR). Sensitivity analyses were performed by removing cases of gestational diabetes and hypertensive disorders in pregnancy. Results: At enrollment in early pregnancy, participants had a mean ± SD age of 28.2 ± 4.4 years and measured BMI of 25.4 ± 5.5 kg/m 2 ; 57% of participants were categorized in normal weight, 22% in overweight and 18% in obesity BMI categories. Maternal BMI was significantly associated with decreased expression of EPYC , a gene that regulates fibrillogenesis (slope= -0.14, FDR-adjusted P=1.68x10 -5 for continuous BMI; log2 fold change= -1.71, FDR-adjusted P=1.06x10 -2 for obesity vs. normal weight). Both sensitivity analyses with the removal of gestational diabetes and hypertensive disorders revealed similar associations for EPYC . Conclusions: We identified an association between elevated maternal BMI and downregulation of EPYC expression in the placenta. Additional studies are required to examine the role of placental EPYC expression in maternal and fetal health.

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.

Clinical presentation and maternal-fetal outcomes of Mirror Syndrome: A case series of 10 affected pregnancies.

BackgroundMirror Syndrome, also known as Ballantyne syndrome, is a rare condition with fewer than 120 cases described in the literature. A simultaneous edematous state of the mother, fetus and placenta is pathognomonic, with the maternal condition frequently presenting with signs and symptoms similar to that of preeclampsia.ObjectiveOur aim was to add to the international body of literature through identification of all cases of Mirror Syndrome at two Canadian tertiary obstetric centres and characterize the maternal presentation, laboratory findings, and perinatal outcomes.MethodologyWe performed a retrospective chart review of all cases of fetal hydrops from two tertiary centres in Winnipeg (Manitoba, Canada) between 2000 and 2019. There were 276 cases of fetal hydrops during this period, of which 10 cases satisfied the diagnostic criteria for Mirror Syndrome where maternal and perinatal outcomes were analysed.ResultsThe median gestational age at diagnosis with Mirror Syndrome was 23 weeks and 3 days of gestation and at birth was 25 weeks and 0 days of gestation. The majority of women were multiparous (80%) and had elevated maternal body mass index (median 33 kg/m2). The most common maternal clinical findings included weight gain (100%) and hypertension (90%). The most common laboratory findings included low hematocrit (100%), hypoalbuminemia (80%), anemia (70%) and hyperuricemia (70%). Structural anomalies were observed in 50% of cases, over half of the fetuses were stillborn (66.7%) and one quarter of pregnancies resulted in neonatal deaths (25%). The median time until maternal improvement of Mirror Syndrome was 2 days postpartum.ConclusionMirror Syndrome affected 3.6% of all cases of fetal hydrops in our cohort, and showed associations with multiparity, elevated BMI, hemodilution, hypoalbuminemia, anemia and hyperuricemia. Delivery is frequently required for fetal and/or maternal indications and symptoms usually improved rapidly after delivery.

Risk Factors Associated with Uterine Rupture and Dehiscence: A Cross-Sectional Canadian Study.

To compare maternal and perinatal risk factors associated with complete uterine rupture and uterine dehiscence. Cross-sectional study of patients with uterine rupture/dehiscence from January 1998 to December 2017 (30 years) admitted at the Labor and Delivery Unit of a tertiary teaching hospital in Canada. There were 174 (0.1%) cases of uterine disruption (29 ruptures and 145 cases of dehiscence) out of 169,356 deliveries. There were associations between dehiscence and multiparity (odds ratio [OR]: 3.2; p = 0.02), elevated maternal body mass index (BMI; OR: 3.4; p = 0.02), attempt of vaginal birth after a cesarian section (OR: 2.9; p = 0.05) and 5-minute low Apgar score (OR: 5.9; p < 0.001). Uterine rupture was associated with preterm deliveries (36.5 ± 4.9 versus 38.2 ± 2.9; p = 0.006), postpartum hemorrhage (OR: 13.9; p < 0.001), hysterectomy (OR: 23.0; p = 0.002), and stillbirth (OR: 8.2; p < 0.001). There were no associations between uterine rupture and maternal age, gestational age, onset of labor, spontaneous or artificial rupture of membranes, use of oxytocin, type of uterine incision, and birthweight. This large cohort demonstrated that there are different risk factors associated with either uterine rupture or dehiscence. Uterine rupture still represents a great threat to fetal-maternal health and, differently from the common belief, uterine dehiscence can also compromise perinatal outcomes.

810 Essential factors and racial/ethnic disparities impacting the odds of vaginal birth after cesarean

We set out to evaluate the impact of several pregnancy characteristics on the odds of a vaginal birth after cesarean (VBAC). Retrospective analysis of the Centers for Disease Control & Prevention’s Natality Live Birth database (2016-2018). All term singleton births that underwent a trial of labor after cesarean (TOLAC) delivery were included and divided into two groups – failed TOLAC and VBAC. Maternal characteristics and neonatal weights were compared between the two groups using Pearson’s chi-square test with Bonferroni adjustment. Multivariate logistic regression was used to adjust outcomes for potential confounders. Results were presented as adjusted odds ratios (aOR) with 95% confidence intervals, and statistical significance was set as P value < 0.05. The study cohort included 246,594 births after TOLAC, with 178,396 (72.3%) achieving VBAC. All examined characteristics varied significantly between the two groups. Elevated maternal body mass index (BMI), and the extremes of neonatal birthweight were associated with the lowest odds of VBAC [aOR 0.46 (0.44-0.48) and 0.53 (0.49-0.57), for BMI >40 and birth weight >4500 grams, respectively] (table 1). All racial/ethnic groups evaluated were associated with lower odds of VBAC when compared to Non-Hispanic White race. Self-pay insurance status was associated with the highest odds of VBAC [aOR 1.72 (1.64-1.81) for self-pay]. Based on this large US population cohort, we found several factors which influence the likelihood of VBAC. Specifically, non-Hispanic Black and Asian race, Hispanic ethnicity, elevated maternal BMI, increasing birth weight (>3500 grams) and low birth weight (<2500 grams) were are all associated with a significantly lower odds of VBAC. Surprisingly, self-pay insurance status was associated with increased odds of VBAC. Our findings demonstrate healthcare disparities warranting further attention.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Management of prepregnancy, pregnancy, and postpartum obesity from the FIGO Pregnancy and Non‐Communicable Diseases Committee: A FIGO (International Federation of Gynecology and Obstetrics) guideline

Management of prepregnancy, pregnancy, and postpartum obesity from the FIGO Pregnancy and Non‐Communicable Diseases Committee: A FIGO (International Federation of Gynecology and Obstetrics) guideline

Maternal obesity adversely affects early breastfeeding in a multicultural, multi-socioeconomic Melbourne community.

Maternal breastfeeding support and maternal obesity are concerns effectively addressed at the community level. International, national and regional surveys have established that elevated maternal body mass index (BMI) is a risk factor for early cessation of breastfeeding. However, the extent of these concerns in the local community is often an unknown and related to variables such as socioeconomic status, education, culture and ethnicity. We believed that a survey of post-natal breastfeeding and BMI status would provide a valuable insight into developing targeted local health initiatives. In 2014, we teamed up with the Whittlesea Maternal and Child Health Service to complete a questionnaire of mothers and babies attending the eight-week infant review. Data included: infant and maternal weight, medical conditions, breastfeeding experience and satisfaction, prime language, education level, support. Maternal obesity at eightweeks postpartum was high at 28.9%, with 63.6% of mothers being overweight or obese. Obesity was associated with a lack of higher education (P<0.05) and with English as the prime language (P<0.05). Breastfeeding initiation was high across all BMI categories at 98.3%. By eight weeks, 32.2% of mothers had ceased breastfeeding. Breastfeeding continuation at eight weeks was negatively correlated with elevated BMI (P<0.01). Breastfeeding cessation in mothers with elevated BMI correlated with psycho-social concerns (P<0.05) and lack of previous breastfeeding experience (P<0.01). Elevated maternal BMI is prevalent in our community and significantly impacts the success of breastfeeding in the early post-natal period. The survey data have allowed targeted health responses to be developed.

Genetic testing on products of conception and its relationship with body mass index.

The study aimed to investigate the relationship between elevated maternal body mass index (BMI) and foetal chromosomal aberrations by performing single-nucleotide polymorphism (SNP) array-based genetic testing on products of conception (POC). We retrospectively reviewed the data for 1068 assisted reproductive technology (ART)-conceived POC originated from 1068 patients with early spontaneous miscarriage. First, all types of chromosomal abnormalities were defined. Then, the baseline characteristics, including maternal age, BMI, thyroid-stimulating hormone (TSH), gestational age, fertilization method, reasons for fertility treatment, embryo transfer (ET) cycle, stage of embryo development and the embryo morphology grade, were compared between chromosomally normal and abnormal POC groups. Finally, a multivariate logistic regression model was used to analyse various factors affecting the foetal chromosomal abnormality rate. The SNP array results showed that 45.3% (484/1068) of POC were chromosomally normal and that 54.7% (584/1068) of POC presented chromosomal abnormalities. Of these 584 chromosomally abnormal POC, 388 (66.4%) were trisomy, 42 (7.2%) had a monosomy, 68 (11.6%) were found with segmental aneuploidy, 46 (7.9%) were mosaic, 28 (4.8%) were identified as polyploidy and 12 (2.1%) were euploid samples with uniparental disomy (UPD). Multivariate logistic regression results showed that the risk of miscarrying chromosomally abnormal POC increased 1.424-fold in women with normal BMI compared to women with an elevated BMI (≥ 25kg/m2) (OR = 1.424, 95% CI = 1.074-1.888, p = 0.014). Women with an elevated BMI (≥ 25kg/m2) are more likely to miscarry chromosomally normal POC.

The association of euploid miscarriage with obesity

To calculate the rate of structural chromosome abnormalities in products of conception collected at the time of miscarriage and determine the association with maternal obesity. Retrospective cohort study in an academic medical center. All patients with spontaneous pregnancy loss less than 20 weeks gestation with available cytogenetic results from products of conception were included. Institutional Review Board approval was obtained. Obesity was defined as body mass index (BMI) ≥30kg/m2. Chi square and binary logistic regression was performed using SPSS. A total of 2,661 women with a mean age at time of loss of 34.8 years (+/- 4.95) and mean BMI of 25.3 kg/m2 (+/-5.57) were included in final analysis. Within the cohort, 63.8% of the losses were aneuploid, of which 40% were trisomies, 8% were monosomies, and 7% were polyploidies. Of the euploid losses, 18.1% were 46,XX and 18% were 46,XY, which suggests that the rate of maternal cell contamination was low. After adjusting for age and race, obese women were 59.2% more likely to have a euploid pregnancy loss compared to non-obese women (P<0.001, OR 1.59, 95%CI 1.32-1.92). Obesity is linked to a wide range of negative health outcomes including decreased fertility and pregnancy loss. Our data shows that elevated maternal BMI is associated with a higher rate of pregnancy loss before 20 weeks gestation that cannot be explained by structural chromosome abnormalities. Existing data in the recurrent early pregnancy loss population suggests a correlation between obesity and higher rates of euploid miscarriage. Our cohort included all patients who requested cytogenetic evaluation and is not limited to those with recurrent loss. Potential pathophysiologic effects of obesity on early pregnancy loss include hormonal dysregulation, changes to the endometrium, and influence on oocyte function and early embryo development. Continued research is needed to better understand the mechanisms for pregnancy loss in this population. Though miscarriage can be a difficult experience for patients, interventions aimed to encourage lifestyle modifications and weight loss in the obese population before subsequent conception could influence reproductive health outcomes including repeat miscarriage.

Body Mass Index and Adverse Neonatal Outcomes in Women Undergoing Elective Cesarean: A Nationwide Cohort Study [25O

INTRODUCTION: To examine the association between pre-pregnancy body mass index (BMI) and neonatal outcomes among women who underwent elective cesarean section (CS). METHODS: We conducted a retrospective cohort study using data from the Center for Disease Control and Prevention (CDC) for all reported births by elective CS in 2011-2013. Women's pre-pregnancy BMI was categorized as underweight (“less than”18.5), normal (18.5-24.5), overweight (25-29.9), obese (30-39.9) and morbidly obese (“equal or above”40). Odds ratio (OR) and 95% confidence intervals (CIs) adjusted for baseline characteristics were calculated to estimate the neonatal risks in relation to pre-pregnancy BMI, using normal BMI as our reference. RESULTS: Our cohort was composed of 737,548 women with available BMI data, of whom 2.8% were underweight, 38.8% had normal BMI, 26.3% were considered overweight, 25.0% obese, and 7.2% morbidly obese. Infant mortality rates were of 4.2/1000 births for normal weight women, and 5.5/1000 births among the morbidly obese group (OR 1.43; 95% CI 1.25-1.64). A dose-dependent relationship between maternal pre-pregnancy BMI and assisted ventilation was seen. Furthermore, infants born to morbidly obese women were at significantly increased risk for assisted ventilation over 6 hours (OR 1.24; 95% CI 1.15-1.35) and admission to intensive care units (OR 1.17; 95% CI 1.13-1.21). Risk for adverse outcomes is higher with elective CS at earlier gestational age, and this effect is intensified with abnormally elevated maternal BMI. CONCLUSION: Increasing maternal pre-pregnancy BMI in women undergoing elective CS was found to be associated with progressively higher risks of adverse neonatal outcomes and mortality.

Maternal body mass index and spontaneous contractility of human myometrium in pregnancy.

There is controversy as to whether maternal body mass index (BMI) influences the contractility of human myometrium in pregnancy. The aim of this study was to examine spontaneous contractile activity of human pregnant myometrium in vitro, with respect to maternal BMI. Myometrial tissue specimens were obtained at cesarean delivery from 74 women with BMI values ranging from 19 to 50.1 kg m-2. By recording in vitro from eight strips per donor (590 strips in total), several parameters of spontaneous contractile activity were monitored. The relationship between BMI and contractility was evaluated using linear regression analysis. There was a significant correlation between maximum amplitude (P=0.007) and mean contractile force (P=0.001) with increasing BMI. However, the time to onset of contractions (P=0.009), and time taken to reach maximal amplitude (P=0.020) also increased with increasing BMI. No significant correlation was observed with BMI for other parameters studied. The mean maximum amplitude value for spontaneous contractions was 37±1 mN, the mean contractile force for spontaneous contractions was 4.1±0.1 mN, the average time to the first spontaneous contraction was 11.3±0.6 min and the average frequency of contractions was 6.5±0.2 per hour. These results suggest that the time to onset of contractions is increased with increasing maternal BMI, but that the force developed is greater. In all other respects, human uterine contractility is unaffected by increasing BMI. These findings underline the complexity of regulation of uterine contractility in labor with elevated maternal BMI.

Serum inhibin and leptin: Risk factors for pre-eclampsia?

BackgroundPre-eclampsia and eclampsia are parts of the broader spectrum of hypertensive disorders complicating pregnancy. This study aims to examine the association between serum inhibin and leptin levels and pre-eclampsia. MethodsThis study included 98 consecutive cases of pregnant women with pre-eclampsia, together with their 98 pregnant controls, matched for age, gestational week and time period of delivery. Maternal venous blood samples were obtained within 24h before delivery. In addition to serum inhibin and leptin, birth order, multiple pregnancy, maternal age, maternal overweight/obesity, maternal education, maternal smoking and family history of diabetes/hypertension, were examined as risk factors. Multivariate logistic regression analysis was performed. ResultsAt the univariate analysis, serum inhibin and leptin levels were significantly higher in cases vs. controls. Pre-eclampsia occurred more frequently in primiparous women, whereas overweight and obesity were also associated with pre-eclampsia. At the multivariate analysis, higher serum inhibin levels were associated with pre-eclampsia (multivariate OR=1.09, 95%CI: 1.03–1.17, p=0.004, increase per 0.1ng/mL). On the other hand, leptin was not independently associated with the occurrence of pre-eclampsia (multivariate OR=1.02, 95%CI: 0.95–1.09, p=0.631, increase per 10ng/mL). ConclusionsElevated serum inhibin levels seem to be associated with pre-eclampsia, reflecting placental dysfunction. Increased serum leptin levels may merely reflect an elevated maternal body mass index, which is a well-known risk factor for pre-eclampsia.

Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight

Importance Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain. Objective To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. Design, Setting, and Participants Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30 487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included. Exposures Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level. Main Outcome and Measure Offspring birth weight from 18 studies. Results Among the 30 487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele ( P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele ( P = 7 × 10 −14 ) and −4 g (95% CI, −6 to −2g) per SBP-raising allele ( P = 1×10 −5 ), respectively. A 1-SD ( ≈ 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD ( ≈ 7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD ( ≈ 10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, −394 to −21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions. Conclusions and Relevance In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.

Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight.

Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain. To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight. Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included. Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level. Offspring birth weight from 18 studies. Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P = .008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P = 7 × 10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P = 1×10(-5)), respectively. A 1-SD ( ≈ 4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD ( ≈ 7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD ( ≈ 10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions. In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.

Maternal body mass index during early pregnancy, gestational weight gain, and risk of autism spectrum disorders: Results from a Swedish total population and discordant sibling study.

Background: Prenatal environmental factors such as maternal adiposity may influence the risk of offspring autism spectrum disorders (ASD), though current evidence is inconsistent. The objective of this study was to assess the relationship of parental BMI and gestational weight gain (GWG) with risk of offspring ASD in a population-based cohort study using family-based study designs.Methods: The cohort was based in Stockholm County, Sweden, including 333 057 individuals born 1984–2007, of whom 6420 were diagnosed with an ASD. We evaluated maternal body mass index (BMI) at first antenatal visit, GWG and paternal BMI at the time of conscription into the Swedish military as exposures using general estimating equation (GEE) models with logit link.Results: At the population level, maternal overweight/obesity was associated with increased risk of offspring ASD [odds ratio (OR)25 ≤ BMI < 30 1.31, 95% confidence interval = 1.21–1.41; ORBMI ≥ 30 1.94, 1.72–2.17], as was paternal underweight (ORBMI < 18.5, 1.19, 1.06–1.33) and obesity (ORBMI ≥ 30 1.47, 1.12–1.92) in mutually adjusted models. However, in matched sibling analyses, the relationship between elevated maternal BMI and ASD risk was not apparent. GWG had a U-shaped association with offspring ASD at the population level (ORinsufficient 1.22, 1.07–1.40; ORexcessive 1.23, 1.08–1.40). Matched sibling analyses were suggestive of elevated risk with excessive GWG (ORinsufficient 1.12, 0.68–1.84; ORexcessive 1.48, 0.93–2.38).Conclusions: Whereas population-level results suggested that maternal BMI was associated with ASD, sibling analyses and paternal BMI analyses indicate that maternal BMI may also be a proxy marker for other familial risk factors. Evidence is stronger for a direct link between GWG and ASD risk.

Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways.

Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated maternal cytokines and activation of placental p38-MAPK and STAT3 inflammatory pathways, without changes in fetal systemic inflammatory profile. Activation of p38-MAPK by MCP-1 and TNFalpha, and STAT3 by TNFalpha, suggests a link between elevated proinflammatory cytokines in maternal plasma and activation of placental inflammatory pathways. We suggest that inflammatory processes associated with elevated maternal BMI may influence fetal growth by altering placental function.

Factors associated with weight loss dieting among adolescents: the 11-year follow-up of the 1993 Pelotas (Brazil) birth cohort study

Evidence has shown the negative effects of unsupervised diets and those with excessive calorie restriction. The aim of this study was to determine the proportion of adolescents engaging in weight loss dieting and associated factors. This was a cross-sectional study of 4,452 adolescents born in Pelotas, Rio Grande do Sul State, Brazil, in 1993. The outcome was defined as adolescents that reported having practiced some type of weight loss dieting in the previous 12 months. Prevalence of such dieting was 8.6% (95%CI: 7.7;9.4), and was higher in girls. Elevated maternal body mass index (BMI) was associated with dieting among girls. The adolescent's and parents' view of the adolescent's weight, excess weight, and consumption of diet or light soft drinks were associated with adolescent dieting. There was a positive association between dieting and socioeconomic status. The findings provide important backing for policies aimed at improving adolescents' diet, since they express a major concern over weight and thus a significant percentage of individuals with erroneous and unhealthy behaviors.