Gray R H, Pardthaisong T
Department of Population Dynamics, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205.
Am J Epidemiol. 1991 Oct 15;134(8):804-11. doi: 10.1093/oxfordjournals.aje.a116153.
A cohort study was conducted in Chiang Mai, northern Thailand, in 1,431 children of women who had used the injectable contraceptive Depo-Provera (The Upjohn Company, Kalamazoo, Michigan), 565 children of women who had used oral contraceptives during pregnancy, and a group of 2,307 control infants with no hormonal contraceptive exposures. In follow-up interviews, information was obtained on stillbirths and deaths. Cause of death was ascertained by interview, death certificate, or medical record, and underlying causes of death were ascribed by a panel. The children exposed in utero to Depo-Provera had higher neonatal and infant mortality rates (44.3 and 62.9 per 1,000 live births, respectively) than did the controls (19.8 and 29.1 per 1,000 live births). Mortality in infants exposed in utero to oral contraceptives was intermediate between that in the other two groups. Adjustment by logistic regression showed no significantly increased risk of mortality among infants exposed to oral contraceptives, but the odds ratio for death was significantly increased with Depo-Provera exposures due to accidental pregnancy (odds ratio (OR) = 1.8 (95% confidence interval (Cl) 1.1-3.0) for neonatal deaths; OR = 2.0 (95% Cl 1.3-3.2) for infant deaths). Adjustment for low birth weight reduced the risks, suggesting that low birth weight may act as an intermediate determinant of Depo-Provera-associated mortality. Among the accidental pregnancies with Depo-Provera, there was a relation between shorter injection-to-conception intervals, when maternal blood levels of the drug are high, and an increased risk of mortality. The odds ratios for neonatal mortality were 2.5 (95% Cl 1.1-5.7), 2.1 (95% Cl 1.0-4.6), and 0.9 (95% Cl 0.4-2.4) for injection-to-conception intervals of less than or equal to 4, 5-8, and greater than 9 weeks, respectively. Adjustment for low birth weight reduced these risks. Chi-square tests for trend were highly significant. Similar associations were also observed between Depo-Provera accidental pregnancies and risks of low birth weight. Thus, infants from accidental pregnancies that occur 1-2 months after a 150-mg Depo-Provera injection may be at increased risk for low birth weight and death. However, the attributable risk is low, because such pregnancies are uncommon.
在泰国北部清迈进行了一项队列研究，研究对象包括1431名母亲曾使用注射用避孕药醋酸甲羟孕酮（美国密歇根州卡拉马祖的Upjohn公司生产）的儿童、565名母亲在孕期曾使用口服避孕药的儿童，以及2307名未接触过激素避孕药的对照婴儿。在随访访谈中，获取了死产和死亡的信息。通过访谈、死亡证明或病历确定死亡原因，并由一个专家小组确定潜在死因。子宫内接触醋酸甲羟孕酮的儿童的新生儿和婴儿死亡率（分别为每1000例活产44.3例和62.9例）高于对照组（每1000例活产19.8例和29.1例）。子宫内接触口服避孕药的婴儿的死亡率介于其他两组之间。逻辑回归调整显示，接触口服避孕药的婴儿死亡率没有显著增加，但因意外怀孕而接触醋酸甲羟孕酮的婴儿死亡的优势比显著增加（新生儿死亡的优势比（OR）=1.8（95%置信区间（Cl）1.1 - 3.0）；婴儿死亡的OR = 2.0（95% Cl 1.3 - 3.2））。对低出生体重进行调整后降低了风险，这表明低出生体重可能是醋酸甲羟孕酮相关死亡率的一个中间决定因素。在因醋酸甲羟孕酮导致的意外怀孕中，当母亲血液中药物水平较高时，注射到受孕间隔较短与死亡风险增加之间存在关联。注射到受孕间隔小于或等于4周、5 - 8周和大于9周的新生儿死亡优势比分别为2.5（95% Cl 1.1 - 5.7）、2.1（95% Cl 1.0 - 4.6）和0.9（95% Cl 0.4 - 2.4）。对低出生体重进行调整后降低了这些风险。趋势的卡方检验具有高度显著性。在醋酸甲羟孕酮意外怀孕与低出生体重风险之间也观察到了类似的关联。因此，在注射150毫克醋酸甲羟孕酮后1 - 2个月发生意外怀孕所生的婴儿，低出生体重和死亡风险可能会增加。然而，归因风险较低，因为这种怀孕并不常见。
