Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Neurogenetics Unit, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
JAMA Pediatr. 2019 Apr 1;173(4):371-378. doi: 10.1001/jamapediatrics.2018.5541.
Maternal obesity, pregestational type 1 diabetes, and gestational diabetes have been reported to increase the risks for large birth weight and preterm birth in offspring. However, the associations for insulin-treated diabetes and non-insulin-treated type 2 diabetes, as well as the associations for joint diabetes disorders and maternal body mass index, with these outcomes are less well documented.
To examine associations of maternal diabetes disorders, separately and together with maternal underweight or obesity, with the offspring being large for gestational age and/or preterm at birth.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used nationwide registries to examine all live births (n = 649 043) between January 1, 2004, and December 31, 2014, in Finland. The study and data analysis were conducted from April 1, 2018, to October 10, 2018.
Maternal prepregnancy body mass index, pregestational diabetes with insulin treatment, pregestational type 2 diabetes without insulin treatment, and gestational diabetes.
Offspring large for gestational age (LGA) at birth and preterm delivery. Logistic regression models were adjusted for offspring birth year; parity; and maternal age, country of birth, and smoking status.
Of the 649 043 births, 4000 (0.62%) were delivered by mothers who had insulin-treated diabetes, 3740 (0.57%) by mothers who had type 2 diabetes, and 98 568 (15.2%) by mothers who had gestational diabetes. The mean (SD) age of mothers was 30.15 (5.37) years, and 588 100 mothers (90.6%) were born in Finland. Statistically significant interactions existed between maternal body mass index and diabetes on offspring LGA and prematurity (insulin-treated diabetes: LGA F = 3489.0 and prematurity F = 1316.4 [P < .001]; type 2 diabetes: LGA F = 147.3 and prematurity F = 21.9 [P < .001]; gestational diabetes: LGA F = 1374.6 and prematurity F = 434.3 [P < .001]). Maternal moderate obesity, compared with normal-weight mothers with no diabetes, was associated with a mildly increased risk of having an offspring LGA (1069 [3.5%] vs 5151 [1.5%]; adjusted odds ratio [aOR], 2.45; 95% CI, 2.29-2.62), and mothers with insulin-treated diabetes had markedly elevated risks of having an offspring LGA (1585 [39.6%] vs 5151 [1.5%]; aOR, 43.80; 95% CI, 40.88-46.93) and a preterm birth (1483 [37.1%] vs 17 481 [5.0%]; aOR, 11.17; 95% CI, 10.46-11.93). Mothers who were moderately obese with type 2 diabetes were at increased risks of LGA (132 [16.4%] vs 5151 [1.5%]; aOR, 12.44; 95% CI, 10.29-15.03) and prematurity (83 [10.3%] vs 17 481 [5.0%]; aOR, 2.14; 95% CI, 1.70-2.69). Mothers who were moderately obese with gestational diabetes had a milder risk of LGA (1195 [6.7%] vs 5151 [1.5%]; aOR, 4.72; 95% CI, 4.42-5.04). Among spontaneous deliveries, the risks were strongest for moderately preterm births, but insulin-treated diabetes was associated with an increased risk also for very and extremely preterm births.
Maternal insulin-treated diabetes appeared to be associated with markedly increased risks for LGA and preterm births, whereas obesity in mothers with type 2 diabetes had mild to moderately increased risks; these findings may have implications for counseling and managing pregnancies.
已经有研究报道，母体肥胖、孕前 1 型糖尿病和妊娠期糖尿病会增加后代巨大儿和早产的风险。然而，胰岛素治疗的糖尿病和非胰岛素治疗的 2 型糖尿病，以及联合糖尿病疾病和母亲体重指数与这些结果的关联，其相关研究则较少。
本研究旨在分别评估母亲糖尿病疾病，以及与母亲体重不足或肥胖联合，与后代巨大儿和/或早产之间的关联。
设计、地点和参与者：这项基于人群的队列研究使用全国性登记处，调查了 2004 年 1 月 1 日至 2014 年 12 月 31 日期间芬兰所有活产儿（n=649043）。研究和数据分析于 2018 年 4 月 1 日至 2018 年 10 月 10 日进行。
母亲孕前体重指数、胰岛素治疗的孕前糖尿病、无胰岛素治疗的孕前 2 型糖尿病和妊娠期糖尿病。
后代巨大儿（LGA）和早产。使用逻辑回归模型调整了后代出生年份、产次、母亲年龄、出生国和吸烟状况。
在 649043 例分娩中，有 4000 例（0.62%）是由接受胰岛素治疗的糖尿病母亲分娩的，3740 例（0.57%）是由患有 2 型糖尿病的母亲分娩的，98568 例（15.2%）是由患有妊娠期糖尿病的母亲分娩的。母亲的平均（SD）年龄为 30.15（5.37）岁，588100 名母亲（90.6%）出生在芬兰。母体体重指数和糖尿病对后代 LGA 和早产的影响存在显著的交互作用（胰岛素治疗的糖尿病：LGA F=3489.0，早产 F=1316.4[P<0.001]；2 型糖尿病：LGA F=147.3，早产 F=21.9[P<0.001]；妊娠期糖尿病：LGA F=1374.6，早产 F=434.3[P<0.001]）。与无糖尿病的正常体重母亲相比，母亲中度肥胖与后代 LGA 风险轻度增加相关（1069[3.5%]比 5151[1.5%]；调整后的优势比[aOR]，2.45；95%CI，2.29-2.62），而患有胰岛素治疗的糖尿病的母亲其后代 LGA 风险显著增加（1585[39.6%]比 5151[1.5%]；aOR，43.80；95%CI，40.88-46.93）和早产（1483[37.1%]比 17481[5.0%]；aOR，11.17；95%CI，10.46-11.93）的风险增加。患有 2 型糖尿病且中度肥胖的母亲发生 LGA（132[16.4%]比 5151[1.5%]；aOR，12.44；95%CI，10.29-15.03）和早产（83[10.3%]比 17481[5.0%]；aOR，2.14；95%CI，1.70-2.69）的风险也有所增加。患有妊娠期糖尿病且中度肥胖的母亲，其 LGA 风险略有增加（1195[6.7%]比 5151[1.5%]；aOR，4.72；95%CI，4.42-5.04）。在自发性分娩中，中度早产的风险最强，但胰岛素治疗的糖尿病也与极早产和超早产的风险增加相关。
胰岛素治疗的糖尿病母亲似乎与 LGA 和早产的风险显著增加有关，而患有 2 型糖尿病的肥胖母亲的风险则为轻度至中度增加；这些发现可能对妊娠的咨询和管理有意义。
