Impaired fecundity as a marker of health and survival: a Danish twin cohort study.
Impaired fecundity as a marker of health and survival: a Danish twin cohort study.
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DOI：
10.1093/humrep/deab077
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发表时间：
2021-07-19
期刊：
影响因子：
--
通讯作者：
Lindahl-Jacobsen R
中科院分区：
文献类型：
--
作者：
Ahrenfeldt LJ;Möller S;Wensink MJ;Eisenberg ML;Christensen K;Jensen TK;Lindahl-Jacobsen R
自我报告的首次怀孕时间（TTP）是生育力的一个标志，随后的健康和生存吗？TTP长是妇女死亡率增加和男女住院率较高的标志。精液质量差与多种疾病的死亡率和发病率增加有关。妇女的生育力、健康和生存之间的关系仍然不确定，关于生育力和健康结果的实际衡量标准的研究也很少。我们对7825名女性和6279名男性进行了一项前瞻性队列研究，年龄在18岁及以上，测量首次TTP，他们参加了1994年（1953-1976年出生的双胞胎）和1998年（1931-1952年出生的双胞胎）的丹麦全国性双胞胎调查。从采访到2018年，他们的死亡率和住院率都得到了随访。双胞胎是在丹麦双胞胎登记处确定的，并与丹麦登记处相关联。TTP仅限于第一次妊娠作为分类结局，截止点为2、10和18个月。我们使用考克斯比例风险模型（估计风险比（HR）和95%置信区间（CI））分析了TTP与生存之间的关联。使用Fine-Gray生存模型估计特定死亡原因的亚风险比，考虑竞争风险。使用负二项回归，我们估计了全因和特定原因住院的发病率比（IRR）及其95% CI。所有分析均按性别分层，并根据访谈时的年龄、出生队列、首次尝试怀孕时的年龄、吸烟、在校年限和BMI进行调整。在总研究人群中，49.9%的女性和52.7%的男性报告TTP小于2个月，30.8%的女性和29.6%的男性报告TTP为2-9个月，6.6%的女性和5.7%的男性报告TTP为10-17个月，13.3%的女性和12.0%的男性报告TTP为18个月或更长时间。在1305例死亡中，我们发现TTP ≥18个月的女性死亡率（HR = 1.46; 95% CI 1.15，1.87）高于TTP <2个月的女性，而TTP为10-17个月的男性死亡率最高（HR = 1.31; 95% CI 0.98，1.74）。在53799例住院治疗中，我们发现TTP ≥18个月的女性（HR = 1.21; 95% CI 1.0-1.41）和男性（HR = 1.16; 95% CI 1.00-1.35）以及TTP为2-9个月的男性（HR = 1.14; 95% CI 1.01-1.30）的住院率增加。在死亡率（P = 0.022）和住院率（P = 0.018）方面，发现女性存在剂量-反应关系。生育力受损与多种疾病和一些死亡原因有关，表明对生育力的因果影响是多因素的，特别是在妇女中。一个主要的局限性是，生殖力取决于双方的合作伙伴，这是没有考虑在这项研究中。此外，我们无法获得一些潜在混杂因素的信息。生育能力似乎与整体健康呈正相关，可能是未来健康和生存的普遍标志。这些结果为有限的发现增加了知识，这些发现表明女性生育能力降低和男性精液质量差可能反映了健康状况恶化和寿命缩短，特别是在女性中。本研究由NIH资助HD 096468（M.L.E.，和R. L. J.）。提交人声明，他们之间没有利益冲突。N/A.
Is fecundity, measured as self-reported time to first pregnancy (TTP), a marker for subsequent health and survival? Long TTP was a marker for increased mortality among women and higher hospitalization rates for both women and men. Poor semen quality has been linked to increased mortality and morbidity from a wide range of diseases. Associations among fecundity, health and survival among women are still uncertain and studies on actual measures of fecundity and health outcomes are rare. We performed a prospective cohort study of 7825 women and 6279 men, aged 18 and above with measures on first TTP, who participated in one of the Danish nation-wide twin surveys in 1994 (twins born 1953–1976) and 1998 (twins born 1931–1952). They were followed-up for mortality and hospital admissions from the interview until 2018. Twins were identified in the Danish Twin Registry and linked to Danish registers. TTP was restricted to the first pregnancy as a categorical outcome with cut-off points at 2, 10 and 18 months. We analysed the association between TTP and survival using a Cox proportional hazards model estimating hazards ratios (HRs) with 95% confidence intervals (CIs). Fine-Gray survival models were used to estimate sub-hazard ratios for specific causes of death allowing for competing risks. Using negative binomial regression, we estimated incidence rate ratios (IRRs) with 95% CIs for all-cause and cause-specific hospitalizations. All analyses were stratified by sex and adjusted for age at interview, birth cohorts, age at first attempt to become pregnant, smoking, years in school and BMI. In the total study population, 49.9% of women and 52.7% of men reported a TTP of less than 2 months, 30.8% of women and 29.6% of men reported a TTP of 2–9 months, 6.6% of women and 5.7% of men reported a TTP of 10–17 months, and 13.3% of women and 12.0% of men reported a TTP of 18 months or more. Among 1305 deaths, we found a higher mortality for women (HR = 1.46; 95% CI 1.15, 1.87) with a TTP of ≥18 months relative to those with a TTP of <2 months, while the highest mortality was indicated for men with a TTP of 10–17 months (HR = 1.31; 95% CI 0.98, 1.74). Among 53 799 hospitalizations, we found an increased hospitalization rate among women (HR = 1.21; 95% CI 1.0–1.41) and men (HR = 1.16; 95% CI 1.00–1.35) with a TTP of ≥18 months, and for men with a TTP of 2–9 months (HR = 1.14; 95% CI 1.01–1.30). A dose–response relationship was found for women regarding both mortality (P = 0.022) and hospitalizations (P = 0.018). Impaired fecundity was associated with a wide range of diseases and some causes of death, indicating a multi-factorial causal influence on fecundity, especially among women. A major limitation was that fecundity depends on both partners, which was not considered in this study. Moreover, we could not obtain information on a number of potential confounders. Fecundity seems positively correlated with overall health and may be a universal marker of future health and survival. These results add knowledge to the limited findings showing that reduced fecundity in women and poor semen quality in men may reflect worse health and a shorter life, particularly among women. This study was funded by NIH grant HD096468 (M.L.E., T.K.J. and R.L.J.). The authors declare that they have no competing interests. N/A.
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影响因子：
6.7
作者：
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通讯作者：
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DOI：
10.5653/cerm.2019.03419
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