Late-pregnancy dysglycemia in obese pregnancies after negative testing for gestational diabetes and risk of future childhood overweight: An interim analysis from a longitudinal mother-child cohort study.
Late-pregnancy dysglycemia in obese pregnancies after negative testing for gestational diabetes and risk of future childhood overweight: An interim analysis from a longitudinal mother-child cohort study.
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DOI：
10.1371/journal.pmed.1002681
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发表时间：
2018-10
期刊：
影响因子：
15.8
通讯作者：
Ensenauer R
中科院分区：
文献类型：
--
作者：
Gomes D;von Kries R;Delius M;Mansmann U;Nast M;Stubert M;Langhammer L;Haas NA;Netz H;Obermeier V;Kuhle S;Holdt LM;Teupser D;Hasbargen U;Roscher AA;Ensenauer R
母亲孕前肥胖是儿童超重的一个重要危险因素。然而，产前机制及其在易受影响的妊娠期对这种风险的影响尚不清楚。我们的目的是评估妊娠期糖尿病（GDM）阴性肥胖孕妇妊娠后期血糖异常对长期母婴结局的影响。前瞻性队列研究Programming of Enhanced obesity Risk in child - early Screening (PEACHES) （n = 1671）于2010年8月至2015年12月招募了肥胖和正常体重的母亲，收集了妊娠中期葡萄糖代谢的特异性数据，包括妊娠中期末的GDM状态和分娩时母亲的糖化血红蛋白（HbA1c≥5.7% [39 mmol/mol]）作为妊娠晚期血糖异常的标志物。我们评估了孩子4年的短期和长期结局，以及产后3.5年的母亲葡萄糖代谢。采用多变量线性回归和对数二项回归，以平均增量（Δ）或相对危险度（rr）表示，95%置信区间（ci）用于检查妊娠后期血糖异常与结局之间的关系。采用线性混合效应模型研究子代体重指数（BMI） z分数的纵向发展。使用中介分析估计妊娠晚期血糖异常对母亲孕前肥胖和后代BMI之间的关系的贡献。总共有898对母子被纳入这一计划外的中期分析。在GDM检测呈阴性的肥胖母亲中（n = 448），妊娠晚期血糖异常的母亲（n = 135, 30.1%）的总妊娠体重增加（GWG）、妊娠晚期体重增加（GWG）和后代出生体重大于胎龄的比例高于未检测的母亲。除了较高的出生体重（Δ 192 g, 95% CI 100-284）和脐带血c肽浓度（Δ 0.10 ng/ml, 95% CI 0.02-0.17）外，这些妇女的后代在幼儿期体重增加更大（Δ BMI z-score每年0.18,95% CI 0.06-0.30, n = 262）， 4岁时BMI z-score更高（Δ 0.58, 95% CI 0.18 - 0.99, n = 43），分娩时HbA1c值正常的肥胖、gdm阴性母亲的后代。gdm阴性母亲的妊娠后期血糖异常约占母亲肥胖与子女4岁时BMI相关的四分之一（n = 151）。相比之下，肥胖孕妇的儿童BMI z分数不受GDM诊断的影响（GDM阳性：0.58,95% CI 0.36-0.79，与GDM阴性：0.62,95% CI 0.44-0.79）。导致肥胖、gdm阴性母亲妊娠后期血糖异常的一种机制与妊娠晚期体重增加过多有关（RR 1.72, 95% CI 1.12-2.65）。此外，在产妇人群中，我们发现，如果肥胖，gdm阴性妇女分娩时HbA1c高于正常妇女，未来糖尿病前期或糖尿病的风险增加4倍（RR 4.01, 95% CI 1.97-8.17）（绝对风险：43.2%对10.5%）。由于主要使用的GDM测试程序在入组期间发生了变化，因此有可能出现误分类偏倚。需要进一步的研究来验证这些发现，并阐明可能影响未来母婴健康状况的妊娠晚期因素。这一中期分析的结果表明，由于诊断为GDM而接受治疗的肥胖母亲的后代在儿童期的BMI结果似乎比那些在妊娠后期未接受治疗并出现血糖异常的肥胖母亲的后代更好。妊娠后期血糖异常与不受控制的体重增加有关，可能导致儿童超重和母亲糖尿病的发展。我们的数据表明，肥胖孕妇的GDM检测阴性并不是一个“完全清楚的信号”，不应导致医生和肥胖妇女降低对糖尿病的关注和风险意识。需要有效的策略来维持妊娠晚期血糖和体重增加的控制，否则健康的肥胖孕妇。Regina Ensenauer和他的同事们研究了肥胖母亲围产期血糖异常与其孩子后来的身体质量指数之间的关系。孕前肥胖与妊娠并发症的风险增加以及对母亲和孩子不利的长期健康结果有关。尽管之前妊娠期糖尿病（GDM）检测呈阴性，但肥胖孕妇在妊娠后期仍可能出现糖代谢障碍。然而，到目前为止，关于妊娠期肥胖和GDM的指南只关注早期血糖筛查，而不是针对与妊娠最后三个月相关的因素。为了评估关于肥胖妊娠管理的建议是否需要优化，需要更多的证据来证明妊娠后期血糖异常对儿童和孕产妇长期预后的影响。我们对898名肥胖和正常体重的母亲及其后代进行了中期分析，这些母亲和她们的后代来自2010年至2015年在德国招募的孕妇的儿童早期筛查中增加肥胖风险（PEACHES）队列研究（总n = 1671）。妊娠后期血糖异常易使gdm阴性的肥胖母亲的后代在儿童早期体重增加，4岁时体重指数更高。由于诊断为GDM而接受治疗的肥胖母亲的孩子，其体重结果似乎比那些在GDM测试呈阴性后仍未接受治疗并出现妊娠后期血糖异常的肥胖母亲的孩子更好。妊娠后期血糖异常的肥胖、gdm阴性的妇女在分娩几年后患前驱糖尿病或糖尿病的风险比妊娠后期糖代谢正常的妇女高4倍。我们建议，妊娠中期末GDM检测阴性不应被理解为“一切正常”的信号，也不应导致照顾者的注意力减少和母亲的虚假安全感。对于“高风险”肥胖妇女来说，管理和维持妊娠晚期血糖和体重增加控制的指南是必要的。进一步的分析和研究应证实这些发现，并调查妊娠晚期因素对未来母婴健康的可能作用。
Maternal pre-conception obesity is a strong risk factor for childhood overweight. However, prenatal mechanisms and their effects in susceptible gestational periods that contribute to this risk are not well understood. We aimed to assess the impact of late-pregnancy dysglycemia in obese pregnancies with negative testing for gestational diabetes mellitus (GDM) on long-term mother–child outcomes. The prospective cohort study Programming of Enhanced Adiposity Risk in Childhood–Early Screening (PEACHES) (n = 1,671) enrolled obese and normal weight mothers from August 2010 to December 2015 with trimester-specific data on glucose metabolism including GDM status at the end of the second trimester and maternal glycated hemoglobin (HbA1c) at delivery as a marker for late-pregnancy dysglycemia (HbA1c ≥ 5.7% [39 mmol/mol]). We assessed offspring short- and long-term outcomes up to 4 years, and maternal glucose metabolism 3.5 years postpartum. Multivariable linear and log-binomial regression with effects presented as mean increments (Δ) or relative risks (RRs) with 95% confidence intervals (CIs) were used to examine the association between late-pregnancy dysglycemia and outcomes. Linear mixed-effects models were used to study the longitudinal development of offspring body mass index (BMI) z-scores. The contribution of late-pregnancy dysglycemia to the association between maternal pre-conception obesity and offspring BMI was estimated using mediation analysis. In all, 898 mother–child pairs were included in this unplanned interim analysis. Among obese mothers with negative testing for GDM (n = 448), those with late-pregnancy dysglycemia (n = 135, 30.1%) had higher proportions of excessive total gestational weight gain (GWG), excessive third-trimester GWG, and offspring with large-for-gestational-age birth weight than those without. Besides higher birth weight (Δ 192 g, 95% CI 100–284) and cord-blood C-peptide concentration (Δ 0.10 ng/ml, 95% CI 0.02–0.17), offspring of these women had greater weight gain during early childhood (Δ BMI z-score per year 0.18, 95% CI 0.06–0.30, n = 262) and higher BMI z-score at 4 years (Δ 0.58, 95% CI 0.18–0.99, n = 43) than offspring of the obese, GDM-negative mothers with normal HbA1c values at delivery. Late-pregnancy dysglycemia in GDM-negative mothers accounted for about one-quarter of the association of maternal obesity with offspring BMI at age 4 years (n = 151). In contrast, childhood BMI z-scores were not affected by a diagnosis of GDM in obese pregnancies (GDM-positive: 0.58, 95% CI 0.36–0.79, versus GDM-negative: 0.62, 95% CI 0.44–0.79). One mechanism triggering late-pregnancy dysglycemia in obese, GDM-negative mothers was related to excessive third-trimester weight gain (RR 1.72, 95% CI 1.12–2.65). Furthermore, in the maternal population, we found a 4-fold (RR 4.01, 95% CI 1.97–8.17) increased risk of future prediabetes or diabetes if obese, GDM-negative women had a high versus normal HbA1c at delivery (absolute risk: 43.2% versus 10.5%). There is a potential for misclassification bias as the predominantly used GDM test procedure changed over the enrollment period. Further studies are required to validate the findings and elucidate the possible third-trimester factors contributing to future mother–child health status. Findings from this interim analysis suggest that offspring of obese mothers treated because of a diagnosis of GDM appeared to have a better BMI outcome in childhood than those of obese mothers who—following negative GDM testing—remained untreated in the last trimester and developed dysglycemia. Late-pregnancy dysglycemia related to uncontrolled weight gain may contribute to the development of child overweight and maternal diabetes. Our data suggest that negative GDM testing in obese pregnancies is not an “all-clear signal” and should not lead to reduced attention and risk awareness of physicians and obese women. Effective strategies are needed to maintain third-trimester glycemic and weight gain control among otherwise healthy obese pregnant women. Regina Ensenauer and colleagues study the relationship between perinatal dysglycemia in obese mothers and later BMI in their children. Pre-conception obesity is associated with an increased risk of pregnancy complications and adverse long-term health outcomes for the mother and her child. Obese pregnant women can develop impairments in glucose metabolism in late pregnancy despite prior negative testing for gestational diabetes mellitus (GDM). Yet, to date, guidelines on obesity in pregnancy and GDM have focused only on early glucose screening rather than targeting factors relevant to the last trimester of pregnancy. To evaluate whether recommendations on management of obese pregnancies require optimization, additional evidence is needed on the consequences of late-pregnancy dysglycemia for long-term childhood and maternal outcomes. We performed an interim analysis of 898 obese and normal weight mothers and their offspring from the Programming of Enhanced Adiposity Risk in Childhood–Early Screening (PEACHES) cohort study (total n = 1,671) that recruited pregnant women in Germany from 2010 to 2015. Late-pregnancy dysglycemia predisposed the offspring of obese, GDM-negative mothers to higher weight gain in early childhood and a higher body mass index at age 4 years. Children of obese mothers treated because of a diagnosis of GDM appeared to have a better weight outcome than those of obese mothers who remained untreated following a negative GDM test and developed late-pregnancy dysglycemia. Obese, GDM-negative women with late-pregnancy dysglycemia also had a 4-fold higher risk of prediabetes or diabetes several years after delivery compared to those with normal glucometabolic status in late pregnancy. We suggest that a negative GDM test at the end of the second trimester should not be understood as an “all-clear signal” and should not result in reduced attention of caregivers and a false sense of security in the mothers. Guidelines to manage and maintain third-trimester glycemic and weight gain control are needed for “high risk” obese women. Further analyses and studies should validate the findings and investigate the possible role of third-trimester factors for future mother–child health.
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影响因子：
9.3
作者：
Ensenauer, Regina;Brandlhuber, Lena;von Kries, Ruediger
通讯作者：
von Kries, Ruediger
DOI：
10.1016/s2213-8587(16)30107-3
发表时间：
2017-01
期刊：
The lancet. Diabetes & endocrinology
影响因子：
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作者：
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通讯作者：
Broekman BF
影响因子：
8.2
作者：
Glinianaia, S. V.;Tennant, P. W. G.;Bell, R.
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影响因子：
16.2
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影响因子：
44.5
作者：
Hanson, Mark;Barker, Mary;Yang, Huixia
通讯作者：
Yang, Huixia