Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.

Association between weight loss and health care resource utilization in adults living with obesity: Evidence from a UK primary care database.

AIMS: We investigated the impact of intentional weight loss on health care resource utilization (HCRU) and costs among people with obesity. MATERIALS AND METHODS: This retrospective, observational cohort study used data from the Clinical Practice Research Datalink (CPRD) GOLD database. Adults >18 years at index date [first recorded body mass index (BMI) of 30-50 kg/m2 between 2006 and 2015 with a further BMI record 4 years later] were assigned to an intentional weight loss cohort (-25% to -10% BMI change) or a stable weight cohort (-3% to +3%), based on their BMI change during a 4-year baseline period from index date. Evidence of intention to lose weight during the baseline period was required. Linked Hospital Episode Statistics datasets captured HCRU and costs over an 8-year follow-up period. Mixed effects models adjusted for demographics, total costs during baseline and baseline comorbidities were used. RESULTS: Baseline characteristics were similar between cohorts with weight loss (n = 8676) and stable weight (n = 44 519). Over follow-up, the weight loss cohort experienced a significantly lower mean annual increase in total costs [2.1% (95% confidence interval: 1.3-2.8)] than the stable weight cohort [4.3% (95% confidence interval: 4.0-4.6); p < .0001]. Weight loss was associated with a lower mean annual increase in multiple HCRU and cost components compared with maintaining a stable high weight. CONCLUSIONS: Our findings suggest that intentional weight loss of 10-25% is associated with lower HCRU and costs in the long term among individuals living with obesity, relative to stable weight.

Obesity, Cardiorenal Comorbidities, and Risk of Hospitalization in Patients With Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: To compare clinical features of patients with obesity-related heart failure (HF) with preserved ejection fraction (HFpEF) with those of patients with similar body mass index (BMI) but no HF and to examine the association between degree of obesity and risk for hospitalizations. METHODS: This was a retrospective analysis of 22,750 adults from a large US electronic health care data set (January 1, 2012, through July 31, 2019), including 4975 with HFpEF. Baseline characteristics were compared between patients with HFpEF and a control group matched on BMI, age, sex, and year of BMI record. Risk of first hospitalization was analyzed in the HFpEF sample with negative binomial and Cox proportional hazards models, adjusted for baseline comorbidities. RESULTS: Compared with controls without HF matched on BMI, age, sex, and year of BMI record, patients with HFpEF displayed worse kidney function, greater estimated plasma volume, and more cardiovascular comorbidities. Within the HFpEF cohort, patients with higher degree of obesity were younger and had fewer concomitant cardiovascular comorbidities than those with lower degree of obesity. The mean number of HF-related hospitalizations increased with higher degree of obesity (9.6 to 15.7/100 patient-years; P=.002), but higher degree of obesity was not associated with increased risk of non-HF-related hospitalizations. CONCLUSION: Among persons with obesity, increasing cardiorenal dysfunction and volume overload differentiate those with HFpEF. Among persons with established HFpEF, those with higher degree of obesity are younger and have fewer cardiovascular comorbidities but display a unique increased risk of HF-related hospitalizations, even as risk for other hospitalizations is not different.

Weight change and risk of obesity-related complications: A retrospective population-based cohort study of a UK primary care database.

AIMS: To examine associations between weight loss/gain and risk of developing 13 obesity-related complications (ORCs), stratified by baseline body mass index (BMI). MATERIALS AND METHODS: In this retrospective cohort study, we included adults with obesity (>30 kg/m2 ) from the UK Clinical Practice Research Datalink GOLD database with weight change (-50% to +50%) between Years 1 and 4 (N = 418 774 [median follow-up: 7 years]). Associations between weight change, baseline BMI and risk of developing ORCs during follow-up were assessed using Cox proportional hazard models. RESULTS: The impact of weight change on ORCs was generally dependent on baseline BMI. Four clear patterns were seen across the 13 outcomes. Pattern 1 showed greatest weight loss benefit for people with low baseline BMI (type 2 diabetes, sleep apnoea, hypertension and dyslipidaemia); Pattern 2 showed most weight loss benefit at lower baseline BMI but no significant weight loss effect at higher baseline BMI (asthma, hip/knee osteoarthritis and polycystic ovary syndrome); Pattern 3 showed benefit in most cardiovascular diseases with weight loss (chronic kidney disease, heart failure, atrial fibrillation and venous thromboembolism), but no additional benefit with >10% weight loss; Pattern 4 showed no clear relationship between weight change and unstable angina/myocardial infarction and depression. We found similar but opposite patterns for weight gain. CONCLUSIONS: Weight loss benefit is dependent on weight loss magnitude and initial BMI, and weight gain is associated with a similar risk increase. Four patterns of association were identified between degree of weight change, baseline BMI and 13 ORCs.

Disease Burden and Health Status among People with Severe Obesity Who Do Not Receive Bariatric Surgery: A Retrospective Study.

INTRODUCTION: The aim of the study was to compare eligible individuals who were or were not treated with bariatric surgery and describe disease burden, treatment, and healthcare costs over 3 years in individuals who were not. METHODS: Adults with obesity class II and comorbidities, or obesity class III, were identified in IQVIA Ambulatory EMR - US and PharMetrics® Plus administrative claims databases (January 1, 2007-December 31, 2017). Outcomes included demographics, BMI, comorbidities, and per patient per year (PPPY) healthcare costs. RESULTS: Of 127,536 eligible individuals, 3,962 (3.1%) underwent surgery. The surgery group was younger, a greater proportion were women, and mean BMI and rates of some comorbidities (obstructive sleep apnea, gastroesophageal reflux disease, and depression) were higher than in the nonsurgery group. Mean healthcare costs PPPY in the baseline year were USD 13,981 in the surgery group and USD 12,024 in the nonsurgery group. In the nonsurgery group, incident comorbidities increased during follow-up. Mean total costs increased by 20.5% from baseline to year 3, mostly driven by an increase in pharmacy costs; however, fewer than 2% of these individuals initiated antiobesity medications. CONCLUSIONS: Individuals who did not undergo bariatric surgery showed a progressive worsening of health and increasing healthcare costs, indicating a large unmet need for access to clinically indicated obesity treatment.

Smoking during pregnancy is associated with child overweight independent of maternal pre-pregnancy BMI and genetic predisposition to adiposity.

High maternal body mass index (BMI) and smoking during pregnancy are risk factors for child overweight. Maternal smoking tends to reduce her BMI and the association of smoking with child overweight may be confounded by or interacting with maternal genetic predisposition to adiposity. In the Danish National Birth Cohort, we investigated whether smoking during pregnancy is associated with child BMI/overweight independent of pre-pregnancy BMI and maternal genetic predisposition to adiposity estimated as total, transmitted and non-transmitted genetic risk scores (GRSs) based on 941 common genetic variants associated with BMI. Smoking during pregnancy was associated with higher child BMI and higher odds of child overweight in a dose-response relationship. The odds ratio (95% CI) for smoking 11 + cigarettes in third trimester versus no smoking was 2.42 (1.30; 4.50), irrespective of maternal BMI and maternal GRSs (total, transmitted or non-transmitted). There were no statistically significant interactions between maternal GRSs and smoking (all p-values for interactions > 0.05). In conclusion, in this study, smoking during pregnancy exhibits a dose-response association with increased child BMI/overweight, independent of maternal pre-pregnancy BMI, maternal transmitted, and non-transmitted genetic predisposition to adiposity. Avoidance of smoking during pregnancy may help prevent childhood obesity irrespective of the mother-child genetic predisposition.

Do genetic risk scores for childhood adiposity operate independent of BMI of their mothers?

OBJECTIVES: Genetic predisposition and maternal body mass index (BMI) are risk factors for childhood adiposity, defined by either BMI or overweight. We aimed to investigate whether childhood-specific genetic risk scores (GRSs) for adiposity-related traits are associated with childhood adiposity independent of maternal BMI, or whether the associations are modified by maternal BMI. METHODS: We constructed a weighted 26-SNP child BMI-GRS and a weighted 17-SNP child obesity-GRS in overall 1674 genotyped children within the Danish National Birth Cohort. We applied a case-cohort (N = 1261) and exposure-based cohort (N = 912) sampling design. Using logistic regression models we estimated associations of the GRSs and child overweight at age 7 years and examined if the GRSs influence child adiposity independent of maternal BMI (per standard deviation units). RESULTS: In the case-cohort design analysis, maternal BMI and the child GRSs were associated with increased odds for childhood overweight [OR for maternal BMI: 2.01 (95% CI: 1.86; 2.17), OR for child BMI-GRS: 1.56 (95% CI: 1.47; 1.66), and OR for child obesity-GRS 1.46 (95% CI: 1.37; 1.54)]. Adjustment for maternal BMI did not change the results, and there were no significant interactions between the GRSs and maternal BMI. However, in the exposure-based cohort design analysis, significant interactions between the child GRSs and maternal BMI on child overweight were observed, suggesting 0.85-0.87-fold attenuation on ORs of child overweight at higher values of maternal BMI and child GRS. CONCLUSION: GRSs for childhood adiposity are strongly associated with childhood adiposity even when adjusted for maternal BMI, suggesting that the child-specific GRSs and maternal BMI contribute to childhood overweight independent of each other. However, high maternal BMI may attenuate the effects of child GRSs in children.

Antibiotics during childhood and development of appendicitis-a nationwide cohort study.

BACKGROUND: Appendicitis is a common disease with a lifespan risk of approximately 8%. The full range of specific causes for the disease remains elusive, but an aberrant microbiota have been identified as a potential risk factor. AIM: To investigate if use of antibiotics in a paediatric population increases the risk of appendicitis in childhood and adolescence METHODS: We conducted a cohort study from 1 January 1995 to 31 December 2014. A total of 1 385 707 children (0-19 years of age) including 7 406 397 antibiotic prescriptions and 11 861 cases of appendicitis were included. Primary outcome was appendicitis requiring appendectomy according to previous use of antibiotics. Appendicitis and appendectomy were identified from nationwide hospital records, and exposure to antibiotics was identified from nationwide prescription register. Rate ratios (RRs) with 95% confidence intervals were estimated from Poisson and logistic regression models. RESULTS: Children who received at least one course of antibiotics were at increased risk of developing appendicitis compared to unexposed children (adjusted RR 1.72 [95% confidence interval 1.61-1.85]), mean age of developing appendicitis was 9.8 years (SD 4.1 years). The RR of appendicitis increased by 1.04 (1.04-1.04) per antibiotic course. A higher risk of appendicitis was observed in children exposed to antibiotics within the first 6 months of life (RR 1.46 [1.36-1.56]) and children exposed to broad-spectrum antibiotics (RR 1.33 [1.27-1.39]). After adjustment for number of antibiotic courses, the association between early age of antibiotic exposure and risk of appendicitis and the association between exposure to broad-spectrum antibiotics and the risk of appendicitis both disappeared. CONCLUSION: Children who receive antibiotics are at increased and dose-dependent risk of appendicitis. The underlying mechanisms merit further investigation.

Overweight in childhood of exclusively breastfed infants with a high weight at 5 months.

High infant weight increases the risk of childhood overweight, while breastfeeding may reduce the risk. However, some infants have a very high weight gain even though they are exclusively breastfed. We examined the risk of a high body mass index (BMI) and overweight in childhood for infants ≥2.5 SD above the median weight-for-age (WAZ) at age 5 months according to duration of exclusive breastfeeding (≤2, >2 to <4 or ≥4 months). The study is based on 13,401 7-year-old and 9,819 11-year-old children enrolled into the Danish National Birth Cohort (born 1997-2003). Linear and logistic regression analyses were used to examine the associations while adjusting for presumed confounders including birth weight. The results showed that infants ≥2.5 SD at 5 months, breastfed exclusively ≤2, >2 to <4 or ≥4 months had adjusted odds ratios (ORs) for overweight at age 7 at 3.67 (95% confidence interval [CI] [2.10, 6.43]), 3.42 (95% CI [2.32, 5.04]) and 3.19 (95% CI [1.90, 5.36]) respectively, when compared with infants <2.5 SD WAZ exclusively breastfed ≥4 months. The corresponding results for BMI z-scores were 0.82 (95% CI [0.60, 1.04]), 0.63 (95% CI [0.48, 0.78]) and 0.57 (95% CI [0.38, 0.77]). For the ≥2.5 SD infants, the differences in risk of overweight and BMI according to duration of exclusive breastfeeding were neither significantly different among the 7-year nor among the 11-year-old children. A high infant weight increases the odds of overweight and is associated with a higher BMI in childhood. Whereas the odds and BMI z-scores tended to be lower for those exclusively breastfed longer, the differences were not statistically significant.

Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America: An individual participant data meta-analysis of 229,000 singleton births.

BACKGROUND: Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. METHODS AND FINDINGS: We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. CONCLUSIONS: We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.

The influence of transmitted and non-transmitted parental BMI-associated alleles on the risk of overweight in childhood.

Overweight in children is strongly associated with parental body mass index (BMI) and overweight. We assessed parental transmitted and non-transmitted genetic contributions to overweight in children from the Danish National Birth Cohort by constructing genetic risk scores (GRSs) from 941 common genetic variants associated with adult BMI and estimating associations of transmitted maternal/paternal and non-transmitted maternal GRS with child overweight. Maternal and paternal BMI (standard deviation (SD) units) had a strong association with childhood overweight [Odds ratio (OR): 2.01 (95% confidence interval (CI) 1.74; 2.34) and 1.64 (95% CI 1.43; 1.89)]. Maternal and paternal transmitted GRSs (SD-units) increased odds for child overweight equally [OR: 1.30 (95% CI 1.16; 1.46) and 1.30 (95% CI 1.16; 1.47)]. However, both the parental phenotypic and the GRS associations may depend on maternal BMI, being weaker among mothers with overweight. Maternal non-transmitted GRS was not associated with child overweight [OR 0.98 (95% CI 0.88; 1.10)] suggesting no specific influence of maternal adiposity as such. In conclusion, parental transmitted GRSs, based on adult BMI, contribute to child overweight, but in overweight mothers other genetic and environmental factors may play a greater role.

Attitudes to and experiences with body weight control and changes in body weight in relation to all-cause mortality in the general population.

BACKGROUND AND AIMS: Increased body mass index (BMI = weight/height2; kg/m2) and weight gain is associated with increased mortality, wherefore weight loss and avoided weight gain should be followed by lower mortality. This is achieved in clinical settings, but in the general population weight loss appears associated with increased mortality, possibly related to the struggles with body weight control (BWC). We investigated whether attitudes to and experiences with BWC in combination with recent changes in body weight influenced long-term mortality among normal weight and overweight individuals. POPULATION AND METHODS: The study population included 6,740 individuals attending the 3rd cycle in 1991-94 of the Copenhagen City Heart Study, providing information on BMI, educational level, health behaviours, well-being, weight half-a-year earlier, and answers to four BWC questions about caring for body weight, assumed benefit of weight loss, current and past slimming experiences. Participants reporting previous unintended weight loss (> 4 kg during one year) were excluded. Cox regression models estimated the associations of prior changes in BMI and responses to the BWC questions with approximately 22 years all-cause mortality with age as 'time scale'. Participants with normal weight (BMI < 25.0 kg/m2) and overweight (BMI ≥ 25.0 kg/m2) were analysed separately, and stratified by gender and educational level, health behaviours and well-being as co-variables. RESULTS: Compared with stable weight, weight loss was associated with significantly increased mortality in the normal weight group, but not in the overweight group, and weight gain was not significantly associated with mortality in either group. Participants with normal weight who claimed that it would be good for their health to lose weight or that they were currently trying to lose weight had significantly higher mortality than those denying it. There were no other significant associations with the responses to the BWC questions in either the normal weight or the overweight group. When combining the responses to the BWC questions with the weight changes, using the weight change as either a continuous or categorical variable, there were no significant interaction in their relation to mortality in either the normal weight or the overweight group. CONCLUSION: Attitudes to and experiences with BWC did not notably modify the association of changes in body weight with mortality in either people with normal weight or people with overweight.

Antibiotic use during pregnancy and childhood overweight: A population-based nationwide cohort study.

Studies in mice suggest that early life represents a critical time window, where antibiotics may exert profound and lasting effects on the gut microbiota and metabolism. We aimed to test the hypothesis that prenatal antibiotic exposure is associated with increased risk of childhood overweight in a population-based cohort study. We linked 43,365 mother-child dyads from a nationwide cohort of pregnant women and their offspring to the Danish National Prescription Registry. Linear and logistic regression models were used to examine associations between prenatal exposure to antibiotics and BMI z-score and overweight (including obesity) at age seven and 11 years. Prenatal antibiotic exposure and childhood overweight were both associated with high pre-pregnancy BMI, maternal diabetes, multi-parity, smoking, low socioeconomic status, high paternal BMI, and short duration of breastfeeding. After adjustment for confounders, no associations were observed between prenatal antibiotic exposure and odds of overweight at age seven and 11 years. Whereas no association was observed between broad-spectrum antibiotics and overweight at age 11 years, exposure to broad-spectrum antibiotics was associated with higher odds of overweight at age seven years with an odds ratio of 1.27 (95% CI, 1.05-1.53) for ampicillin and an odds ratio of 1.56 (95% CI, 1.23-1.97) for amoxicillin. As we did not account for underlying infections, the observed associations with early childhood overweight could be explained by confounding by indication. In conclusion, our population-based study suggests that prenatal exposure to narrow-spectrum antibiotics is not associated with overweight in offspring. Exposure to some broad-spectrum antibiotics may increase the odds of overweight in early childhood, but the association does not persist in later childhood.

Prenatal Exposure to Acetaminophen and Overweight in Childhood.

OBJECTIVE: Acetaminophen (paracetamol), a medication commonly used in pregnancy, has hormonal effects, as has been suggested in experimental studies. Developmental exposure to endocrine disruptors could predispose individuals to weight gain. This study evaluated the associations between prenatal acetaminophen exposure and overweight in childhood. METHODS: A total of 30,127 (age 7) and 24,934 (age 11) children in the Danish National Birth Cohort born during 1996 to 2002 were studied. Mothers reported acetaminophen use in telephone interviews conducted during pregnancy, and children's BMI and waist circumference were reported by parents at 7 and 11 years. Differences for BMI z score and waist circumference were estimated, as well as risk ratios for overweight in girls and boys adjusting for indications of use and other confounders. RESULTS: There were no consistent associations found for prenatal acetaminophen exposure and BMI z score or waist circumference in girls and boys at both ages. Prenatal acetaminophen exposure was associated with overweight in girls at age 11 (risk ratio 1.31, 95% CI: 1.10-1.56, if exposed in all three trimesters; P < 0.001 for cumulative weeks of exposure), but no association was found in boys. CONCLUSIONS: There was no strong association between prenatal acetaminophen exposure and childhood BMI, but the findings on frequent prenatal exposure to acetaminophen and overweight in girls warrant further investigation.

Association of Gestational Weight Gain With Adverse Maternal and Infant Outcomes.

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, Setting, and Participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures: Gestational weight gain. Main Outcomes and Measures: The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results: Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79). Conclusions and Relevance: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis.

BACKGROUND: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. METHODS AND FINDINGS: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. CONCLUSIONS: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.

Gestational weight gain charts for different body mass index groups for women in Europe, North America, and Oceania.

BACKGROUND: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies. METHODS: We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape. RESULTS: We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications. CONCLUSIONS: Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

Association between Maternal Fish Consumption and Gestational Weight Gain: Influence of Molecular Genetic Predisposition to Obesity.

BACKGROUND: Studies suggest that fish consumption can restrict weight gain. However, little is known about how fish consumption affects gestational weight gain (GWG), and whether this relationship depends on genetic makeup. OBJECTIVE: To examine the association between fish consumption and GWG, and whether this relationship is dependent on molecular genetic predisposition to obesity. DESIGN: A nested case-cohort study based on the Danish National Birth Cohort (DNBC) sampling the most obese women (n = 990) and a random sample of the remaining participants (n = 1,128). Replication of statistically significant findings was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 4,841). We included 32 body mass index (BMI) associated single nucleotide polymorphisms (SNPs) and 5 SNPs found associated with GWG. BMI associated SNPs were combined in a genetic risk score (GRS). Associations between consumption of fish, GRS or individual variants and GWG were analysed, and interactions between fish and the GRS or individual variants were examined. RESULTS: In the DNBC, each portion/week (150 g) of fatty fish was associated with a higher GWG of 0.58 kg (95% CI: 0.16, 0.99, P<0.01). For total fish and lean fish, similar patterns were observed, but these associations were not statistically significant. We found no association between GRS and GWG, and no interactions between GRS and dietary fish on GWG. However, we found an interaction between the PPARG Pro12Ala variant and dietary fish. Each additional Pro12Ala G-allele was associated with a GWG of -0.83 kg (95% CI: -1.29, -0.37, P<0.01) per portion/week of dietary fish, with the same pattern for both lean and fatty fish. In ALSPAC, we were unable to replicate these findings. CONCLUSION: We found no consistent evidence of association between fish consumption and GWG, and our results indicate that the association between dietary fish and GWG has little or no dependency on GRS or individual SNPs.

Socio-economic inequality in preterm birth: a comparative study of the Nordic countries from 1981 to 2000.

During the 1980s and 1990s, there were large social and structural changes within the Nordic countries. Here we examine time changes in risks of preterm birth by maternal educational attainment in Denmark, Finland, Norway and Sweden. Information on gestational age and maternal socio-economic position was obtained from the NorCHASE database, which includes comparable population-based register data of births from Denmark, Finland, Sweden and Norway from 1981 to 2000. The risks of very preterm birth (<32 gestational weeks) and moderately preterm birth (32-36 gestational weeks) were calculated by maternal educational attainment and analysed in 5-year intervals from 1981 to 2000. Compared with mothers with >12 years of education, mothers with <10 years of education had similarly increased risks of very, and to a lesser extent moderately, preterm birth in all four countries. The educational gradient increased slightly over time in very preterm births in Denmark, while there was a slight narrowing of the gap in Sweden. In moderately preterm births, the educational inequality gap was constant over the study period in Denmark, Norway and Sweden, but narrowed in Finland. The educational gradient in preterm birth remained broadly stable from 1981 to 2000 in all four countries. Consequently, the socio-economic inequalities in preterm birth were not strongly influenced by structural changes during the period.