Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood,adolescence, and young adulthood: A national population-based cohort study

BackgroundThe prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades. Exposure to adverse intrauterine environment in fetal life may contribute to the elevated risk of early-onset CVD. Many studies have shown that maternal hypertensive disorders of pregnancy (HDP) are associated with increased risks of congenital heart disease, high blood pressure, increased BMI, and systemic vascular dysfunction in offspring. However, empirical evidence on the association between prenatal exposure to maternal HDP and early-onset CVD in childhood and adolescence remains limited.Methods and findingsWe conducted a population-based cohort study using Danish national health registers, including 2,491,340 individuals born in Denmark from 1977 to 2018. Follow-up started at birth and ended at the first diagnosis of CVD, emigration, death, or 31 December 2018, whichever came first. Exposure of maternal HDP was categorized as preeclampsia or eclampsia (n = 68,387), gestational hypertension (n = 18,603), and pregestational hypertension (n = 15,062). Outcome was the diagnosis of early-onset CVD from birth to young adulthood (up to 40 years old). We performed Cox proportional hazards regression to evaluate the associations and whether the association differed by maternal history of CVD or diabetes before childbirth. We further assessed the association by timing of onset and severity of preeclampsia. The median follow-up time was 18.37 years, and 51.3% of the participants were males. A total of 4,532 offspring in the exposed group (2.47 per 1,000 person-years) and 94,457 in the unexposed group (2.03 per 1,000 person-years) were diagnosed with CVD. We found that exposure to maternal HDP was associated with an increased risk of early-onset CVD (hazard ratio [HR]: 1.23; 95% CI = 1.19 to 1.26; P < 0.001). The HRs for preeclampsia or eclampsia, gestational hypertension, and pregestational hypertension were 1.22 (95% CI, 1.18 to 1.26; P < 0.001), 1.25 (95% CI, 1.17 to 1.34; P < 0.001), and 1.28 (95% CI, 1.15 to 1.42; P < 0.001), respectively. We also observed increased risks for type-specific CVDs, in particular for hypertensive disease (HR, 2.11; 95% CI, 1.96 to 2.27; P < 0.001) and myocardial infarction (HR, 1.49; 95% CI, 1.12 to 1.98; P = 0.007). Strong associations were found among offspring of mothers with CVD history (HR, 1.67; 95% CI, 1.41 to 1.98; P < 0.001) or comorbid diabetes (HR, 1.56; 95% CI, 1.34 to 1.83; P < 0.001). When considering timing of onset and severity of preeclampsia on offspring CVD, the strongest association was observed for early-onset and severe preeclampsia (HR, 1.48, 95% CI, 1.30 to 1.67; P < 0.001). Study limitations include the lack of information on certain potential confounders (including smoking, physical activity, and alcohol consumption) and limited generalizability in other countries with varying disparities in healthcare.ConclusionsOffspring born to mothers with HDP, especially mothers with CVD or diabetes history, were at increased risks of overall and certain type-specific early-onset CVDs in their first decades of life. Further research is warranted to better understand the mechanisms underlying the relationship between maternal HDP and early-onset CVD in offspring.

Chen Huang and co-workers study associations between maternal hypertensive disorders and cardiovascular disease in offspring.     

Associations of demographic and perinatal factors with childhood neuroblastoma in Texas, 1995–2011

BackgroundNeuroblastoma, the most common extracranial solid tumor in children, contributes disproportionately to childhood cancer mortality and few risk factors have been identified. Our objective was to evaluate associations between parental and infant characteristics and neuroblastoma incidence.MethodsChildren born in Texas between January 1995 and December 2011 were eligible for the present study. Cases (N = 637) were diagnosed with neuroblastoma in Texas during the same period; controls (N = 6370) matched on year of birth were randomly selected from birth certificates that did not link to a record in the Texas Cancer Registry. We obtained data on birth and parental demographic/reproductive characteristics from birth certificates, and estimated odds ratios (OR) and 95% confidence intervals (CIs) for neuroblastoma using logistic regression.ResultsGestational age 34–36 weeks at birth was associated with neuroblastoma (OR 1.45, CI 1.09–1.90), whereas female sex was inversely associated (OR 0.68, CI 0.58–0.81). Relative to children of non-Hispanic White women, children of Hispanic (OR 0.53, CI 0.43–0.64) or non-Hispanic Black (OR 0.52, CI 0.38–0.71) women were at reduced odds of neuroblastoma. When maternal and paternal race/ethnicity were evaluated jointly, similar patterns were observed (two non-Hispanic Black parents: OR 0.55, 95%CI 0.36–0.79; two Hispanic parents: OR 0.53, 95%CI 0.41–0.67). Older maternal age was also positively associated with neuroblastoma (OR 1.41, CI 1.04–1.90 for 35–39 years; OR 1.62, CI 0.87–2.81 for ≥40 years, relative to 25–29 years).ConclusionsFindings provide further evidence of racial/ethnic disparities in neuroblastoma incidence, determinants of which are unknown. In contrast to most published studies, we observed an association between maternal age and neuroblastoma. Further studies with more robust control for confounding are warranted.     

Cancer in children born after frozen-thawed embryo transfer: A cohort study

BackgroundThe aim was to investigate whether children born after assisted reproduction technology (ART), particularly after frozen-thawed embryo transfer (FET), are at higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception.Methods and findingsWe performed a registry-based cohort study using data from the 4 Nordic countries: Denmark, Finland, Norway, and Sweden. The study included 7,944,248 children, out of whom 171,774 children were born after use of ART (2.2%) and 7,772,474 children were born after spontaneous conception, representing all children born between the years 1994 to 2014 in Denmark, 1990 to 2014 in Finland, 1984 to 2015 in Norway, and 1985 to 2015 in Sweden. Rates for any cancer and specific cancer groups in children born after each conception method were determined by cross-linking national ART registry data with national cancer and health data registries and population registries. We used Cox proportional hazards models to estimate the risk of any cancer, with age as the time scale.After a mean follow-up of 9.9 and 12.5 years, the incidence rate (IR) of cancer before age 18 years was 19.3/100,000 person-years for children born after ART (329 cases) and 16.7/100,000 person-years for children born after spontaneous conception (16,184 cases). Adjusted hazard ratio (aHR) was 1.08, 95% confidence interval (CI) 0.96 to 1.21, p = 0.18. Adjustment was performed for sex, plurality, year of birth, country of birth, maternal age at birth, and parity. Children born after FET had a higher risk of cancer (48 cases; IR 30.1/100,000 person-years) compared to both fresh embryo transfer (IR 18.8/100,000 person-years), aHR 1.59, 95% CI 1.15 to 2.20, p = 0.005, and spontaneous conception, aHR 1.65, 95% CI 1.24 to 2.19, p = 0.001. Adjustment either for macrosomia, birth weight, or major birth defects attenuated the association marginally. Higher risks of epithelial tumors and melanoma after any assisted reproductive method and of leukemia after FET were observed.The main limitation of this study is the small number of children with cancer in the FET group.ConclusionsChildren born after FET had a higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. The results should be interpreted cautiously based on the small number of children with cancer, but the findings raise concerns considering the increasing use of FET, in particular freeze-all strategies without clear medical indications.Trial registrationTrial registration number: ISRCTN 11780826.

Nona Sargisian and colleagues investigate the risk of childhood cancer in children born after Frozen-Thawed Embryo Transfer in Denmark, Finland, Norway, and Sweden.     

Type 2 diabetes,obesity, and breast cancer risk among Japanese women of the atomic bomb survivor cohort

BackgroundMuch less is known about diabetes than obesity as a predictor of breast cancer incidence and most previous studies have been conducted in white populations. Therefore, this project within the Radiation Effects Research Foundation’s cohort of Japanese atomic bomb survivors aimed to determine the independent contributions of obesity and diabetes to develop breast cancer.MethodsAfter excluding women with unknown A-bomb radiation dose, a radiation dose of ≥100 mGy, a pre-existing history of breast cancer, and missing body mass index (BMI), the analysis included 29,818 women. Breast cancer status and deaths until 2009 were identified from cancer registries and vital records. Cox regression with age as the time metric was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for BMI and diabetes status as time-varying exposures alone and in combination while adjusting for known confounders.ResultsDiabetes prevalence increased from 2.6% to 5.3% and 7.5% from the first to the second and third data collection. During 27.6 ± 12.2 years of follow-up, 703 women had developed breast cancer (mean age of 66.0 ± 12.9 years) and 31 (4.4%) had been diagnosed with diabetes. A diagnosis of diabetes was not significantly associated with breast cancer incidence without (HR 1.12, 95% CI 0.77–1.64) and with BMI (HR 1.01, 95% CI 0.69–1.49) as a covariate. The respective HRs for overweight and obesity were 1.61 (95% CI 1.34–1.93) and 2.04 (95% CI 1.40–2.97).ConclusionsAmong a long-time Japanese cohort, excess body weight but not a diabetes diagnosis was significantly associated with breast cancer risk.     

Cardiovascular disease,obesity, and type 2 diabetes in children born after assisted reproductive technology: A population-based cohort study

BackgroundSome earlier studies have found indications of significant changes in cardiometabolic risk factors in children born after assisted reproductive technology (ART). Most of these studies are based on small cohorts with high risk of selection bias. In this study, we compared the risk of cardiovascular disease, obesity, and type 2 diabetes between singleton children born after ART and singleton children born after spontaneous conception (SC).Methods and findingsThis was a large population-based cohort study of individuals born in Norway, Sweden, Finland, and Denmark between 1984 and 2015. Data were obtained from national ART and medical birth registers and cross-linked with data from national patient registers and other population-based registers in the respective countries. In total, 122,429 children born after ART and 7,574,685 children born after SC were included. Mean (SD) maternal age was 33.9 (4.3) years for ART and 29.7 (5.2) for SC, 67.7% versus 41.8% were primiparous, and 45.2% versus 32.1% had more than 12 years of education. Preterm birth (<37 weeks 0 days) occurred in 7.9% of children born after ART and 4.8% in children born after SC, and 5.7% versus 3.3% had a low birth weight (<2,500 g). Mean (SD) follow-up time was 8.6 (6.2) years for children born after ART and 14.0 (8.6) years for children born after SC. In total, 135 (0.11%), 645 (0.65%), and 18 (0.01%) children born after ART were diagnosed with cardiovascular disease (ischemic heart disease, cardiomyopathy, heart failure, or cerebrovascular disease), obesity or type 2 diabetes, respectively. The corresponding values were 10,702 (0.14%), 30,308 (0.74%), and 2,919 (0.04%) for children born after SC. In the unadjusted analysis, children born after ART had a significantly higher risk of any cardiovascular disease (hazard ratio [HR] 1.24; 95% CI 1.04–1.48; p = 0.02), obesity (HR 1.13; 95% CI 1.05–1.23; p = 0.002), and type 2 diabetes (HR 1.71; 95% CI 1.08–2.73; p = 0.02). After adjustment, there was no significant difference between children born after ART and children born after SC for any cardiovascular disease (adjusted HR [aHR]1.02; 95% CI 0.86–1.22; p = 0.80) or type 2 diabetes (aHR 1.31; 95% CI 0.82–2.09; p = 0.25). For any cardiovascular disease, the 95% CI was reasonably narrow, excluding effects of a substantial magnitude, while the 95% CI for type 2 diabetes was wide, not excluding clinically meaningful effects. For obesity, there was a small but significant increased risk among children born after ART (aHR 1.14; 95% CI 1.06–1.23; p = 0.001). Important limitations of the study were the relatively short follow-up time, the limited number of events for some outcomes, and that the outcome obesity is often not considered as a disease and therefore not caught by registers, likely leading to an underestimation of obesity in both children born after ART and children born after SC.ConclusionsIn this study, we observed no difference in the risk of cardiovascular disease or type 2 diabetes between children born after ART and children born after SC. For obesity, there was a small but significant increased risk for children born after ART.Trial registration numberISRCTN11780826.

Emma Norrman and co-workers study the health of children born with and without assisted reproductive technology.     

Assisted reproductive technology and the risk of pediatric cancer: A population based study and a systematic review and meta analysis

BackgroundThere is controversy whether exposure to assisted reproductive technology (ART) is associated with increased risk of pediatric cancer.We aimed at calculating the overall risk of pediatric cancers after ART in a large cohort of exposed women; and to conduct a systematic review and meta- analysis of cohort studies examining overall risk of pediatric cancers after ART.MethodsAll children born in Israel who were members of Maccabi Health Services (MHS) between 1999 and 2016 after ART, were linked to the Israeli Registry of Childhood Cancer (IGS) to identify those with cancer diagnosed before 16 years of age. In parallel we conducted a systematic review and meta-analysis of observational cohort studies with more than 5000 ART- exposed cases that measured pediatric cancer after ART.ResultsIn the cohort study, the risk ratio for pediatric cancer after ART in general was 0.95 (95% CI, 0.76–1.19). The RR was 1.09 (95% CI, 0.79–1.48) for IVF treatments. Meta- analysis of 13 cohort studies with a total of 750,138 women exposed to ART (with 1152 pediatric cancers) and 214,008,000 unexposed controls (with 30,458 pediatric cancers) did not reveal increased risk for pediatric cancers (RR 0.99; 95% CI, 0.85–1.15).ConclusionsBased on very large numbers, ART in general, and IVF in particular, are not associated with overall increased risk of pediatric cancer.     

Maternal exposure to ambient air temperature during pregnancy and early childhood pneumonia

BackgroundPneumonia has been widely recognized as the leading cause of death in children worldwide, but its etiology still remains unclear.ObjectiveWe examined the association between maternal exposure to ambient air temperature during pregnancy and lifetime pneumonia in the offspring.MethodsWe conducted a cohort study of 2598 preschool children aged 3–6 years in Changsha, China. The lifetime prevalence of pneumonia was assessed using questionnaire. We backwards estimated each child's exposure to air temperature during prenatal and postnatal periods. Multiple regression model was used to examine the association between childhood pneumonia and exposure to air temperature in terms of odd ratios (OR) and 95% confidence interval (CI).ResultsPrevalence of childhood pneumonia in Changsha was high up to 38.6%. We found that childhood pneumonia was significantly associated with prenatal exposure to air temperature, with adjusted OR (95% CI) = 1.77 (1.23–2.54) for an interquartile range (IQR) increase in temperature, particularly during the second trimester with adjusted OR (95% CI) = 2.26 (1.32–3.89). Boys are more susceptible to the risk of pneumonia due to air temperature than girls. We further observed that maternal exposure to extreme heat days during pregnancy increased the risk of pneumonia in the offspring.ConclusionsMaternal exposure to air temperature during pregnancy, particularly the second trimester, was associated with pneumonia in the children, providing the evidence for fetal origins of pneumonia.     

High parental occupational social contact and risk of childhood hematopoietic,brain and bone cancers

BackgroundThe etiology of childhood cancer is largely unknown, though some research suggests an infectious origin of hematopoietic, central nervous system (CNS) and bone cancers.MethodsWe examined parental occupational social contact as a proxy for exposure to infectious agents and risk of childhood cancer. This population-based case-control study utilized a linkage of four Danish data-registries, and included 3581 cases (<17 years, diagnosed 1973–2012) and 358,100 age-matched controls. We examined the risks of leukemia, lymphoma, CNS and bone cancer related to high occupational social contact from (1) conception to birth and (2) birth to diagnosis.ResultsAcute lymphoblastic leukemia (ALL) and bone cancer were inversely associated with high maternal social contact from conception to birth (OR: 0.86, 95% CI: 0.67–1.10) and birth to diagnosis (OR: 0.54, 95% CI: 0.34–0.86). Children of fathers with high social contact from birth to diagnosis had an increased risk of bone cancers, particularly in rural areas (OR: 1.65, 95% CI: 1.03–2.63). Parental social contact was associated with increased risk of astrocytoma, with strongest associations found in first-born children (maternal: OR: 1.54, 95% CI: 1.02–2.32; paternal: OR: 1.82, 95% CI: 1.05–3.17).ConclusionOur results support the notion of a role of infections for some cancer types.     

Normal intellectual development in children born from women with hypothyroxinemia during their pregnancy

Proper maternal thyroid function is known to be essential for neural differentiation and migration in the fetus during the first half of pregnancy. The objectives of this study were to assess the relationship between thyroxin levels, in pregnant women with no thyroid disease and the intellectual development of their offspring in a non-iodine-deficient area, and to know specifically whether or not isolated hypothyroxinemia during pregnancy was associated with a lower intelligence in the offspring.Previously we had publicated values TSH, FT4, free T3 (FT3), anti-thyroid peroxidase antibodies (TPO Abs) and urinary iodine concentration (UIC) in 1322 pregnant women in our hospital area. Now we presented results of intelligence quotient in children born from these pregnancies. We assessed 455 children at one year of age using Brunet-Lezine scale. Of these, 289 children were evaluated again at 6–8 years of age using the WISC-IV. From the total group of children recruited, we established as control subgroup, children born of rigorously normal pregnancies (women with UIC > 150 μg/L, FT4 > 10th percentile and TPO-Ab negative in both trimesters). The remaining children were divided into two subgroups: those born to mothers with FT4 below the 10th percentile and the rest. No correlation was found between FT4 maternal levels, in either of trimesters studied, and the intellectual scores of offspring. No differences were found in intellectual scores comparing children born to mothers with hypothyroxinemia and those whose mothers were euthyroxinemic in both trimesters, or with the control subgroup.As conclusions we did not find any association between the levels of maternal FT4 during pregnancy and the subsequent intellectual development the offspring from these pregnancies. We attribute this result to the fact that all the pregnant women included had normal thyroid function.     

Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial

ObjectiveTo compare perinatal outcome and glycaemic control in two groups of pregnant diabetic patients receiving two insulin regimens.DesignRandomised controlled open label study.SettingUniversity affiliated hospital, Israel.Participants138 patients with gestational diabetes mellitus and 58 patients with pregestational diabetes mellitus received insulin four times daily, and 136 patients with gestational diabetes and 60 patients with pregestational diabetes received insulin twice daily.InterventionThree doses of regular insulin before meals and an intermediate insulin dose before bedtime (four times daily regimen), and a combination of regular and intermediate insulin in the morning and evening (twice daily regimen).ResultsMean daily insulin concentration before birth was higher in the women receiving insulin four times daily compared with twice daily: by 22 units (95% confidence interval 12 to 32) in patients with gestational diabetes and by 28 units (15 to 41) in patients with pregestational diabetes. Glycaemic control was better with the four times daily regimen than with the twice daily regimen: in patients with gestational diabetes mean blood glucose concentrations decreased by 0.19 mmol/l (0.13 to 0.25), HbA_1c by 0.3% (0.2% to 0.4%), and fructosamine by 41 μmol/l (37 to 45), and adequate glycaemic control (mean blood glucose concentration <5.8 mmol/l) was achieved in 17% (8% to 26%) more women; in patients with pregestational diabetes mean blood glucose concentration decreased by 0.44 mmol/l (0.28 to 0.60), HbA_1c by 0.5% (0.2% to 0.8%), and fructosamine by 51 μmol/l (45 to 57), and adequate glycaemic control was achieved in 31% (15% to 47%) more women. Maternal severe hypoglycaemic events, caesarean section, preterm birth, macrosomia, and low Apgar scores were similar in both dose groups. In women with gestational diabetes the four times daily regimen resulted in a lower rate of overall neonatal morbidity than the twice daily regimen (relative risk 0.59, 0.38 to 0.92), and the relative risk for hyperbilirubinaemia and hypoglycaemia was lower (0.51, 0.29 to 0.91 and 0.12, 0.02 to 0.97 respectively). The relative risk of hypoglycaemia in newborn infants to mothers with pregestational diabetes was 0.17 (0.04 to 0.74).ConclusionsGiving insulin four times rather than twice daily in pregnancy improved glycaemic control and perinatal outcome without further risking the mother.

Key messages

• Improving maternal glycaemic control during pregnancy is the key to better perinatal outcome
• In pregnant diabetic women insulin four times daily achieved better glycaemic control and lower rate of perinatal complications (hypoglycaemia, hyperbilirubinaemia) than insulin twice daily
• Better glycaemic control resulted from a larger total daily insulin dose
• The intensified regimen did not lead to higher rate of severe maternal hypoglycaemia

     

Measuring disparities in event-free survival among children with acute lymphoblastic leukemia in an academic institute in Oklahoma, 2005–2019

BackgroundAcute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. While there have been successes in the treatment of leukemia, less information is available on reasons for disparities in event-free survival (EFS) among underserved populations.MethodsWe partnered with a children’s hospital at an academic institution to abstract data from the institution’s cancer registry, the state cancer registry, and electronic medical records on cancer diagnosis, treatment, and outcomes for children with ALL (n = 275) diagnosed from 2005 to 2019 prior to age 20. We evaluated the relation between 1) race/ethnicity, 2) distance to the children’s hospital, and 3) area deprivation with EFS, defined as time from diagnosis to relapse, death, or the end of the study period. We evaluated differences in EFS using Kaplan-Meier analysis with the log-rank test. We used the Cox Proportional Hazards Model for multivariable survival analyses.ResultsMost children were diagnosed with ALL under five years of age (45%) and with Pre-B ALL (87%). Twelve percent of children experienced a relapse and 5% died during induction or remission. EFS at 5 years was 82%. Non-Hispanic (NH) Black children had worse, though imprecise, EFS compared to NH White children (Adjusted Hazard Ratio: 2.07, 95% CI: 0.80, 5.38). Children residing in areas with higher deprivation had a higher adjusted hazard of poor outcomes compared to the least deprived areas, though estimates were imprecise (2nd quartile HR: 1.51, 3rd quartile: 1.85, 4th quartile: 1.62). We observed no association between distance to the children’s hospital and EFS.ConclusionWe observed poorer EFS for NH Black children and children residing in areas with high deprivation, though the estimates were not statistically significant. Our next steps include further evaluating socioeconomic factors in both rural and urban children to identify disparities in outcomes for children with ALL and other childhood cancers.     

Newborns of Preeclamptic Women Show Evidence of Sex-Specific Disparity in Fetal Growth

BackgroundEvidence suggests that in response to in utero insults, male versus female infants have greater disadvantages in pregnancy outcome. In addition, there is a growing body of evidence suggesting that there is a sex-specific fetal response to maternal disease during pregnancy. We considered that a sex-specific relationship may exist between preeclampsia and reduced fetal growth.ObjectiveWe investigated if the relationship between preeclampsia and fetal growth was modified by fetal sex.MethodsWe limited the study population to singleton pregnancies of black and white normotensive and preeeclamptic women enrolled in the Collaborative Perinatal Project (1959–1965). The patients were offspring of 516 preeclamptic and 8801 normotensive women. After adjustment for confounders, interaction terms between preeclamptic status and fetal sex were evaluated to determine if the influence of preeclampsia on fetal growth varied with fetal sex. Separate linear and logistic regression models were then fitted for males and females to report the estimate of the relationship between preeclampsia and fetal growth by fetal sex. The results were stratified by preterm status (<37 vs ≥37 completed weeks of gestation). The mean head and chest circumferences, birthweight, ponderal index, and frequency of small for gestational age were examined. A 2-sided P value of <0.05 was considered statistically significant.ResultsThe results were stratified by preterm status. Male preterm offspring of preeclamptic mothers had greater reductions in chest circumference, head circumference, and birthweight than preterm female offspring of preeclamptic women (P = 0.01, P = 0.02, and P = 0.05, respectively, for interaction). Female versus male preterm offspring exposed to preeclampsia were less susceptible to being small for gestational age (synergy index 0.38; 95% CI, 0.00–0.84). The influence of preeclampsia on the growth of term offspring was more modest, and the influence of sex was opposite that in preterm infants. Compared with term offspring of normotensive women, the reduction in mean ponderal index was greater for female versus term male offspring of preeclamptic women (P = 0.02, interaction).ConclusionFetal growth was more impaired among male versus female preterm infants born to preeclamptic women. Our study underlined the importance of incorporating sex differences in the study of biological mechanisms for immediate- and long-term consequences of suboptimal fetal growth.     

Surgically Induced Interpregnancy Weight Loss and Prevalence of Overweight and Obesity in Offspring

Introduction

According to the fetal overnutrition hypothesis, obesity in pregnancy predisposes the offspring to obesity. Previous studies have suggested that after biliopancreatic surgery for obesity, the offspring is less likely to be obese. This study aims to further compare the BMI development of children born before and after maternal surgical weight loss.

Method

Women with at least one child born before and one child born after bariatric surgery were identified by record-linkage. Information about maternal BMI was extracted from medical records, as was information about the children''s BMI from birth to 10 years of age. We retrieved BMI data at four years of age for 340 children, born to 223 women (164 children born before surgery (BS), 176 children born after surgery (AS)). We evaluated prevalence of overweight/obesity and mean BMI in children born BS and AS at the ages of four, six and ten using GEE regression models. For 71 families, where we had complete data on mother and both children, we used a fixed-effects regression model to explore the association between differences in maternal BMI in w10 of the pre- and post-operative pregnancies with siblings'' BMI differences at age four.

Results

In no age group did we see a significantly reduced prevalence of overweight/obesity AS. For 10-year-old girls, the AS group had significantly higher rates of obesity. There was no association between differences in maternal BMI in early pregnancy and differences in siblings'' BMI at four years of age (β = −0.01, CI 95% = −0.11; 0.09).

Conclusions

We have been unable to demonstrate any effect of bariatric surgery on weight development in offspring. It seems unlikely that restrictive bariatric surgery conveys a protective effect in offspring with regards to obesity.     

Maternal Gestational Diabetes Mellitus and Offspring Body Mass Index from 1 to 4 Years

ObjectiveUsing the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria to diagnose gestational diabetes mellitus (GDM), the association between GDM and offspring body mass index (BMI) gains in early childhood in China remains unclear. We aimed to assess the association between GDM diagnosed by the IADPSG criteria and BMI gain and the risk for overweight/obesity in offspring from 1 to 4 years.MethodsThis prospective cohort study was based on the healthcare records data from the Medical Birth Registry in Xiamen, China. We included 10,412 mother-child pairs tested for GDM using IADPSG criteria.ResultsA total of 1,786 (17.2%) offspring were exposed to GDM. The offspring exposed to GDM had higher mean BMI Z-score (difference, 0.07; 95% confidence interval [CI], 0.02 to 0.12) and risk for overweight/obesity (odds ratio [OR], 1.22; 95% CI, 1.06 to 1.40) compared to those unexposed to GDM from 1 to 4 years of age. However, after adjustment for maternal pre-pregnancy BMI (Model 2), these associations attenuated towards the null (difference in BMI Z-score, 0.02; 95% CI, -0.03 to 0.07; OR for overweight/obesity, 1.09; 95% CI, 0.95 to 1.25).ConclusionThe associations between GDM diagnosed using IADPSG criteria and BMI Z-score and the risk for overweight/obesity in offspring at the age of 1 to 4 years were largely explained by maternal pre-pregnancy BMI. Reducing the prevalence of childhood overweight and obesity in China should focus on maternal weight status before pregnancy, in addition to glycemia during pregnancy.     

Maternal Height and Preterm Birth: A Study on 192,432 Swedish Women

BackgroundThere is increasing evidence that lower maternal stature is associated with shorter gestational length in the offspring. We examined the association between maternal height and the likelihood of delivering preterm babies in a large and homogeneous cohort of Swedish women.MethodsThis study covers antenatal data from the Swedish Medical Birth Register on 192,432 women (aged 26.0 years on average) born at term, from singleton pregnancies, and of Nordic ethnicity. Continuous associations between women''s heights and the likelihood of preterm birth in the offspring were evaluated. Stratified analyses were also carried out, separating women into different height categories.ResultsEvery cm decrease in maternal stature was associated with 0.2 days shortening of gestational age in the offspring (p<0.0001) and increasing odds of having a child born preterm (OR 1.03), very preterm (OR 1.03), or extremely preterm (OR 1.04). Besides, odds of all categories of preterm birth were highest among the shortest women but lowest among the tallest mothers. Specifically, women of short stature (≤155 cm or ≤-2.0 SDS below the population mean) had greater odds of having preterm (OR 1.65) or very preterm (OR 1.47) infants than women of average stature (-0.5 to 0.5 SDS). When compared to women of tall stature (≥179 cm), mothers of short stature had even greater odds of giving birth to preterm (OR 2.07) or very preterm (OR 2.16) infants.ConclusionsAmong Swedish women, decreasing height was associated with a progressive increase in the odds of having an infant born preterm. Maternal short stature is a likely contributing factor to idiopathic preterm births worldwide, possibly due to maternal anatomical constraints.     

Birth weight of offspring and insulin resistance in late adulthood: cross sectional survey

ObjectiveTo investigate the association between birth weight of offspring and mothers'' insulin resistance in late adulthood.DesignCross sectional survey.SettingGeneral practitioner''s surgeries in 23 towns in Great Britain.Participants4286 women aged 60-79 years.ResultsBirth weight of offspring was inversely related to maternal insulin resistance in late adulthood. For each 1 kg higher birth weight of offspring, women had a 15% reduction in the odds of being in the fourth with highest insulin resistance, compared to other fourths (odds ratio 0.85; 95% confidence interval 0.71 to 1.00). This increased to 27% (0.73; 0.60 to 0.90) after adjusting data for potential confounders. A U shaped relation between birth weight of offspring and diabetes in older age was found; women with the lightest and heaviest offspring had the highest prevalence of diabetes.ConclusionsBirth weight of offspring is inversely related to the mother''s insulin resistance in late adulthood, despite the association of glucose intolerance during pregnancy with heavier offspring at birth. Common genetic factors contribute to the relation between birth weight and risk of cardiovascular disease and diabetes in adults.

What is already known on this topic

Small birth weight is related to increased risk of cardiovascular disease and diabetes in adulthood; the underlying mechanisms are unclearSmall birth weight of offspring is related to parental cardiovascular disease, suggesting that common genetic factors affect birth weight and the risk of disease in adulthoodGenetic factors associated with the metabolism of insulin are plausible in linking birth weight and cardiovascular disease (the fetal insulin hypothesis)

What this study adds

Birth weight of offspring is inversely related to maternal insulin resistance in older ageGenetic factors related to both insulin resistance and birth weight explain at least part of the association between birth weight and risk of cardiovascular disease and diabetes in adulthood     

Survival disparities for childhood cancers exist when defined by race/ethnicity and sex

BackgroundThere are documented racial/ethnic and sex differences in pediatric cancer survival; however, it is unknown whether pediatric cancer survival disparities exist when race/ethnicity and sex are considered jointly.MethodsUsing SEER data (2000–2017), we estimated survival differences by race/ethnicity within sexes and by sex within race/ethnicity (White, Black, Hispanic, and Asian/Pacific Islander [API]) for 17 cancers in children aged (0–19 years). Kaplan-Meier curves (Log-Rank p-values) were assessed. Cox regression was used to estimate hazards ratios (HRs) and 95 % confidence intervals (95 % CIs) between race/ethnicity/sex and cancer.ResultsWe included 51,759 cases (53.6 % male, 51.9 % White). There were statistically significant differences in 18-year survival by race/ethnicity-sex for 12/17 cancers. Within sexes, minorities had an increased risk of death compared to Whites for various cancers including acute lymphoblastic leukemia (ALL) (females: HispanicHR: 1.78, 95 % CI: 1.52, 2.10; BlackHR: 1.70, 95 % CI: 1.29, 2.24; APIHR: 1.42, 95 % CI: 1.07–1.89; males ALL: HispanicHR: 1.58, 95 % CI: 1.39,1.79; BlackHR: 1.57, 95 % CI: 1.26,1,95; API-HR: 1.39, 95 % CI: 1.11, 1.75) and astrocytoma (females: HispanicHR: 1.49, 95 % CI: 1.19, 1.85; BlackHR: 1.67, 95 % CI: 1.29, 2.17; API-HR: 1.51, 95 % CI: 1.05, 2.15; males: HispanicHR:1.27, 95 % CI: 1.04, 1.56; BlackHR: 1.69, 95 % CI: 1.32, 2.17; API-HR: 1.92, 95 % CI: 1.43, 2.58). Sex differences in survival within racial/ethnic groups were observed for White (ALL, osteosarcoma), Hispanic (medulloblastoma), and API (Primitive Neuro-Ectodermal Tumor [PNET]) children.ConclusionsThere are disparities in survival by both race/ethnicity and sex highlighting the societal and biologic influences these features have on survival in children with cancer.     

The relationship between maternal and offspring birth weights after maternal prenatal famine exposure: the Dutch Famine Birth Cohort Study

We examined the impact of famine-induced changes in maternal birth weight (MBW) on the association between MBW and offspring birth weight (OBW). Women born before, during, and after the Dutch Famine of 1944-1945 were interviewed at ages 41 to 46 years. Women (n = 582) and their children (n = 1,111) were included in the analysis if both mother and child were singleton and the child was not delivered preterm. Mean birth weight (BW) of women with first-trimester exposure (n = 110) was 154 g higher (p = 0.008), and mean BW of women with third-trimester exposure (n = 138) was 251 g lower (p < 0.001) than mean BW of unexposed women (n = 302). First-born offspring of women with first-trimester exposure were 72 g heavier (95% confidence interval [CI], -57 to 201; p = 0.27), and offspring of women with third-trimester exposure were 43 g lighter (95% CI, -170 to 79; p = 0.47) than offspring of unexposed women. Among unexposed women, each 100 g increase in MBW was associated with 25 g (95% CI, 12 to 37) increase in OBW (adjusted for maternal age, smoking, weight, and height and offspring sex). This association was attenuated in famine-exposed women (first-trimester change in OBW = 20 g per 100 g MBW; 95% CI, -1 to 41; third-trimester change in OBW = 14 g per 100 g MBW; 95% CI, -9 to 37). When MBW and trimester of maternal famine exposure were considered in a joint model, there was no independent effect of trimester of maternal famine exposure on OBW. Associations were less consistent for later-born offspring. We conclude that maternal prenatal famine exposure does not affect the association between maternal and offspring BW. Trimester of exposure was not a determinant of OBW, other than through its effect on MBW. Nevertheless, acute famine may impact on second-generation BW distributions indirectly, through its effect on the distribution of MBW.     

Predictors of trisomy 21 in the offspring of older and younger women

BACKGROUND: Advanced maternal age is the only well‐established risk factor for trisomy 21, yet the majority of affected individuals are born to younger women. To identify factors associated with the risk of trisomy 21 in the offspring of younger and older women, we analyzed data for cases with trisomy 21 from the Texas Birth Defects Registry for 1999 to 2007. METHODS: Data were analyzed separately for younger (i.e., <35 years of age at delivery; n = 2306) and older (i.e., ≥35 years of age at delivery; n = 1811) women using Poisson regression. RESULTS: After adjustment for maternal age and several other covariates, the prevalence of trisomy 21 in the offspring of women in both maternal age groups was higher in male than in female infants and in offspring of women who were Hispanic (compared with non‐Hispanic white women) or who had at least one previous liveborn child compared to those with none. In the offspring of older women only, the prevalence of trisomy 21 was also significantly higher when the father was 20to 24 years old (compared with 25 to 29 years old; adjusted prevalence ratio [aPR], 2.27; 95% confidence interval [CI], 1.47–3.49) and Hispanic (compared with non‐Hispanic white; aPR, 1.34; 95% CI, 1.13–1.58) and among women with less than a high school education (compared with greater than high school). CONCLUSIONS: This study identified several factors, in addition to maternal age, that were associated with trisomy 21 risk. In general, these factors were similar for both maternal age groups, although paternal characteristics were significantly associated with risk of trisomy 21 only in offspring of older women. Birth Defects Research (Part A), 2012. © 2011 Wiley Periodicals, Inc.