Mills J L, Knopp R H, Simpson J L, Jovanovic-Peterson L, Metzger B E, Holmes L B, Aarons J H, Brown Z, Reed G F, Bieber F R
Epidemiology Branch, National Institute of Child Health and Human Development, Bethesda, Md 20892.
N Engl J Med. 1988 Mar 17;318(11):671-6. doi: 10.1056/NEJM198803173181104.
To determine how much insulin-dependent diabetes increases a woman's risk of giving birth to a malformed infant and how that risk is influenced by metabolic control, we followed 347 diabetic and 389 control women who enrolled in the study within 21 days of conception (the early-entry group) and 279 diabetic women who entered later (the late-entry group). We detected major malformations in the infants of 4.9 percent of the early-entry diabetic women, 2.1 percent of the controls, and 9.0 percent of the late-entry diabetic women. Malformation rates were significantly higher among offspring of early-entry diabetic women than among those of controls (odds ratio, 2.45; lower one-sided 95 percent confidence limit, 1.12; P = 0.027), and higher among late-entry than among early-entry diabetic women (odds ratio, 1.91; lower one-sided 95 percent confidence limit, 1.07; P = 0.032). Mean blood glucose and glycosylated hemoglobin levels during organogenesis were not significantly higher in women whose infants were malformed. Hypoglycemia (glucose, less than or equal to 50 mg per deciliter [2.8 mmol per liter]) was not significantly more common in the same group. Hyperglycemia and glycosylated hemoglobin were not correlated with malformation. The data suggest that more sensitive measures are needed to identify the teratogenic mechanisms, or that not all malformation can be prevented by good glycemic control. Despite the increased malformation rate among infants of the early-entry diabetic women, as compared with the controls, the more favorable outcome seen in the former group as compared with the late-entry group justifies the attempt to achieve good metabolic control around the time of conception.
为了确定胰岛素依赖型糖尿病会在多大程度上增加女性生出畸形婴儿的风险，以及这种风险如何受到代谢控制的影响，我们对347名糖尿病女性和389名对照女性进行了随访，这些女性在受孕后21天内纳入研究（早期入组组），还有279名糖尿病女性较晚纳入（晚期入组组）。我们在早期入组的糖尿病女性所生婴儿中检测到4.9%有严重畸形，对照组为2.1%，晚期入组的糖尿病女性为9.0%。早期入组的糖尿病女性后代的畸形率显著高于对照组（优势比为2.45；单侧95%置信下限为1.12；P = 0.027），晚期入组的糖尿病女性后代的畸形率高于早期入组的糖尿病女性（优势比为1.91；单侧95%置信下限为1.07；P = 0.032）。器官形成期的平均血糖和糖化血红蛋白水平在婴儿有畸形的女性中并无显著升高。低血糖（血糖≤50毫克/分升[2.8毫摩尔/升]）在同一组中也没有显著更常见。高血糖和糖化血红蛋白与畸形并无关联。数据表明，需要更敏感的指标来识别致畸机制，或者并非所有畸形都能通过良好的血糖控制来预防。尽管早期入组的糖尿病女性所生婴儿的畸形率高于对照组，但与晚期入组组相比，前一组有更有利的结局，这证明在受孕前后努力实现良好的代谢控制是合理的。
