Overweight or obesity in children born after assisted reproductive technologies in Denmark: A population-based cohort study.
Overweight or obesity in children born after assisted reproductive technologies in Denmark: A population-based cohort study.
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DOI：
10.1371/journal.pmed.1004324
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发表时间：
2023-12
期刊：
影响因子：
15.8
通讯作者：
中科院分区：
文献类型：
--
作者：
辅助生殖技术（ART）与儿童体重指数（BMI）之间的关系仍然存在争议。与父母不孕症相关的发病率和其他因素的混淆可能会导致对ART后出生的儿童与未治疗后出生的儿童进行比较的偏倚研究。我们调查了5至8岁儿童的不同生育治疗与BMI之间的关系，并根据父母不孕的原因进行调整和分层。这项丹麦队列研究包括2007年至2012年出生的327，301名儿童（51%为男性，随访时的中位年龄为7岁）。其中，13，675人在ART后出生，7，728人在促排卵后出生，有或没有宫内授精[OI/IUI]，305，898人在没有生育治疗后出生。使用国际肥胖工作组（IOTF）标准，我们定义了超重（BMI ≥ IOTF-25）和肥胖（BMI ≥ IOTF-30）。我们比较了ART与OI/IUI后出生的儿童;卵胞浆内单精子注射（ICSI）与常规体外受精（IVF）;冷冻解冻与新鲜胚胎移植，并估计了5至8岁超重或肥胖儿童的粗患病率和校正患病率比值比（POR）以及平均BMI z评分的差异。使用稳定的治疗权重逆概率进行调整，包括胎次、受孕年份、父母不孕原因、年龄、教育水平、合并症、母亲原籍国、BMI和吸烟作为协变量。ART后出生的儿童肥胖的粗患病率为1.9%，OI/IUI后出生的儿童为2.0%，未接受生育治疗的儿童为2.7%。校正后，ART和OI/IUI后出生的儿童超重（11%; POR 1.00，95%置信区间[CI] 0.91至1.11; p = 0.95）或肥胖（1.9%; POR 1.01，95% CI 0.79至1.29; p = 0.94）的患病率相同。ICSI与传统IVF的比较产生了相似的模式（对于超重，POR 0.95，95% CI 0.83至1.07; p = 0.39;对于肥胖，POR 1.16，95% CI 0.84至1.61; p = 0.36）。冷冻-解冻胚胎移植后肥胖的发生率（2.7%）高于新鲜胚胎移植（1.8%）（POR 1.54，95% CI 1.09 - 2.17; p = 0.01）。生育治疗和BMI之间的关联在不孕原因定义的亚组中仅略有不同。研究的局限性包括潜在的残留混杂因素，活产限制，以及缺乏有关IVF程序的详细技术信息。当比较ART与OI/IUI或ICSI与传统IVF时，我们发现5至8岁时BMI与年龄无关。然而，与新鲜胚胎移植相比，使用冷冻-解冻胚胎移植与肥胖风险增加1.5倍相关。尽管相对风险升高，但绝对风险差异很低。在一项基于人群的队列研究中，Kristina Laugesen及其同事调查了丹麦辅助生殖技术后出生的儿童的不同生育治疗与体重指数之间的关系。体外受精（IVF）后出生的孩子数量正在增加。关于这些儿童长期健康的信息有限，IVF与儿童体重指数（BMI）之间的关联仍然存在争议。各种程序，如受精和胚胎移植的类型，以及不孕症的根本原因可能会影响相关性。研究人员使用丹麦国家登记处进行了一项队列研究，研究5至8岁儿童的不同生育治疗与BMI之间的关系，同时考虑到不孕症的潜在原因。IVF后出生的孩子与促排卵后出生的孩子（有或没有宫腔内人工授精）和没有生育治疗后出生的孩子相比，BMI相似。与新鲜胚胎移植后出生的儿童相比，冷冻胚胎移植后出生的儿童具有更高的BMI和更高的肥胖患病率，与促排卵后出生的儿童相比（有或没有宫腔内人工授精），与没有生育治疗后出生的儿童相比。结果是一致的亚组定义的不孕症的根本原因。我们的研究为寻求帮助怀孕的夫妇提供了令人放心的结果。我们发现冻融胚胎移植的原因需要进一步调查。需要对与代谢健康相关的其他结果进行更长时间的随访和评估。研究的局限性包括潜在的残留混杂，仅包括活产，以及缺乏有关IVF程序的详细技术信息。
The association between assisted reproductive technologies (ARTs) and the body mass index (BMI) of children remains controversial. Confounding by morbidity and other factors associated with parental infertility may have biased studies comparing children born after ART with children born after no treatment. We investigated the associations between different fertility treatments and BMI in children at age 5 to 8 years, adjusting for and stratifying by causes of parental infertility. This Danish cohort study included 327,301 children born between 2007 and 2012 (51% males, median age at follow-up 7 years). Of these, 13,675 were born after ART, 7,728 were born after ovulation induction with or without intrauterine insemination [OI/IUI], and 305,898 were born after no fertility treatments. Using the International Obesity Task Force (IOTF) standards, we defined overweight (BMI ≥ IOTF-25) and obesity (BMI ≥ IOTF-30). We compared children born after ART versus OI/IUI; intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilization (IVF); and frozen-thawed versus fresh embryo transfer and estimated crude and adjusted prevalences of children with overweight or obesity at age 5 to 8 years, prevalence odds ratios (PORs), and differences in mean BMI z-scores. Adjustment was performed using stabilized inverse probability of treatment weights, including parity, year of conception, parental causes of infertility, age, educational level, comorbidities, maternal country of origin, BMI, and smoking as covariates. The crude prevalence of obesity was 1.9% in children born after ART, 2.0% in those born after OI/IUI, and 2.7% in those born after no fertility treatment. After adjustment, children born after ART and OI/IUI had the same prevalence of being overweight (11%; POR 1.00, 95% confidence interval [CI] 0.91 to 1.11; p = 0.95) or obese (1.9%; POR 1.01, 95% CI 0.79 to 1.29; p = 0.94). Comparison of ICSI with conventional IVF yielded similar pattern (POR 0.95, 95% CI 0.83 to 1.07; p = 0.39 for overweight and POR 1.16, 95% CI 0.84 to 1.61; p = 0.36 for obesity). Obesity was more prevalent after frozen-thawed (2.7%) than fresh embryo transfer (1.8%) (POR 1.54, 95% CI 1.09 to 2.17; p = 0.01). The associations between fertility treatments and BMI were only modestly different in subgroups defined by the cause of infertility. Study limitations include potential residual confounding, restriction to live births, and lack of detailed technical information about the IVF procedures. We found no association with BMI at age 5 to 8 years when comparing ART versus OI/IUI or when comparing ICSI versus conventional IVF. However, use of frozen-thawed embryo transfer was associated with a 1.5-fold increased risk of obesity compared to fresh embryo transfer. Despite an elevated relative risk, the absolute risk difference was low. In a population-based cohort study, Kristina Laugesen and colleagues investigate the associations between different fertility treatments and body mass index in children born after assisted reproductive technologies in Denmark. The number of children born after in vitro fertilization (IVF) is increasing. Information about long-term health of these children is limited, and the association between IVF and body mass index (BMI) of the children remains controversial. Various procedures, such as type of fertilization and embryo transfer, and underlying causes of infertility may influence associations. The researchers used Danish national registries to conduct a cohort study on the association between different fertility treatments and BMI in children at age 5 to 8 years, taking into account underlying causes of infertility. Children born after IVF had similar BMI compared with those born after ovulation induction (with or without intrauterine insemination) and compared with those born after no fertility treatment. Children born after frozen-thawed embryo transfer had higher BMI and higher prevalence of obesity compared with those born after fresh embryo transfer, compared with those born after ovulation induction (with or without intrauterine insemination), and compared with those born after no fertility treatment. Findings were consistent across subgroups defined by underlying cause of infertility. Our study provides reassuring results for couples who seek help to conceive. Reasons behind our findings for frozen-thawed embryo transfer need further investigation. Longer follow-up and assessment of other outcomes related to metabolic health is needed. Study limitations include potential residual confounding, inclusion of live births only, and lack of detailed technical information about the IVF procedures.
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影响因子：
13.8
作者：
Elhakeem, Ahmed;Taylor, Amy E.;Inskip, Hazel M.;Huang, Jonathan;Tafflet, Muriel;Vinther, Johan L.;Asta, Federica;Erkamp, Jan S.;Gagliardi, Luigi;Guerlich, Kathrin;Halliday, Jane;Harskamp-van Ginkel, Margreet W.;He, Jian-Rong;Jaddoe, Vincent W. V.;Lewis, Sharon;Maher, Gillian M.;Manios, Yannis;Mansell, Toby;McCarthy, Fergus P.;McDonald, Sheila W.;Medda, Emanuela;Nistico, Lorenza;de Moira, Angela Pinot;Popovic, Maja;Reiss, Irwin K. M.;Rodrigues, Carina;Salika, Theodosia;Smith, Ash;Stazi, Maria A.;Walker, Caroline;Wu, Muci;Asvold, Bjorn O.;Barros, Henrique;Brescianini, Sonia;Burgner, David;Chan, Jerry K. Y.;Charles, Marie-Aline;Eriksson, Johan G.;Gaillard, Romy;Grote, Veit;Haberg, Siri E.;Heude, Barbara;Koletzko, Berthold;Morton, Susan;Moschonis, George;Murray, Deirdre;O'Mahony, Desmond;Porta, Daniela;Qiu, Xiu;Richiardi, Lorenzo;Rusconi, Franca;Saffery, Richard;Tough, Suzanne C.;Vrijkotte, Tanja G. M.;Nelson, Scott M.;Andersen, Anne-Marie Nybo;Magnus, Maria C.;Lawlor, Deborah A.
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