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Risks of Asphyxia-Related Neonatal Complications in Offspring of Mothers with Type 1 Or Type 2 Diabetes: the Impact of Maternal Overweight and Obesity

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Risks of Asphyxia-Related Neonatal Complications in Offspring of Mothers with Type 1 Or Type 2 Diabetes: the Impact of Maternal Overweight and Obesity Diabetologia DOI 10.1007/s00125-017-4279-2 ARTICLE Risks of asphyxia-related neonatal complications in offspring of mothers with type 1 or type 2 diabetes: the impact of maternal overweight and obesity Sven Cnattingius1 & Anna Lindam1 & Martina Persson1 Received: 25 November 2016 /Accepted: 20 March 2017 # The Author(s) 2017. This article is an open access publication Abstract diabetes. Maternal overweight/obesity is an important Aims/hypothesis We aimed to compare the risks of severe contributing factor. asphyxia-related neonatal complications in the offspring of mothers with type 1 or type 2 diabetes, and to assess the Keywords Apgar score . Asphyxia . Asphyxia-related impact of maternal overweight/obesity on these risks. neonatal morbidity . Body mass index (BMI) . Diabetes type Methods This was a population-based study of 1,343,751 1 . Diabetes type 2 . Obesity . Overweight live-born singleton infants in Sweden between 1997 and 2011, including 5941 and 711 infants of mothers with type 1 and type 2 diabetes, respectively. ORs with 95% CIs were Abbreviations calculated for low Apgar score (0–6) at 5 min after birth, HIE Hypoxic ischaemic encephalopathy hypoxic ischaemic encephalopathy and neonatal seizures. MBR Medical Birth Register Results The rates of a low Apgar score were 0.9%, 2.6% and 2.1% in the offspring of mothers without diabetes or with type 1 or type 2 diabetes, respectively. After controlling for Introduction maternal confounders (including BMI), the risk of a low Apgar score increased in the offspring of mothers with type In spite of advances in the management of pregnant women 1 diabetes (OR 2.67, 95% CI 2.23, 3.20) but not in the with type 1 or type 2 diabetes, the risks of neonatal morbidity offspring of mothers with type 2 diabetes (OR 1.25, 95% CI and mortality remain increased [1, 2]. Low Apgar scores are 0.66, 2.35). The ORs of hypoxic ischaemic encephalopathy or more frequent in the offspring of mothers with type 1 diabetes neonatal seizures were increased in the offspring of mothers [3] and are associated with markedly increased risks of with type 1 diabetes (OR 3.41, 95% CI 2.58, 4.49) and neonatal mortality and morbidity [4, 5]. It is, however, type 2 diabetes (OR 2.54, 95% CI 1.13, 5.69). Maternal unclear whether the risks of a low Apgar score or other overweight/obesity was a risk factor for asphyxia-related asphyxia-related neonatal complications are also increased in neonatal complications and low Apgar scores in the offspring the offspring of mothers with type 2 diabetes. of mothers with type 1 diabetes and mothers without diabetes. Maternal hyperglycaemia leads to fetal hyperglycaemia Conclusions/interpretation The risks of a low Apgar score and hyperinsulinaemia. Data from both experimental and and severe asphyxia-related neonatal complications are human studies support the hypothesis that fetal increased in the offspring of mothers with type 1 or type 2 hyperglycaemia increases the risk of fetal hypoxia [6, 7]. We have previously demonstrated that maternal obesity in early pregnancy increases the risks of low Apgar scores and * Martina Persson asphyxia-related neonatal complications in the infants of [email protected] mothers without diabetes [8]. The prevalence of severe obesity continues to increase in women of reproductive age 1 Clinical Epidemiology Unit (T2), Department of Medicine Solna, [9], as it does in women with type 1 or type 2 diabetes [10, 11]. Karolinska Institutet, SE-171 76 Stockholm, Sweden In the offspring of mothers with type 1 diabetes, maternal Diabetologia obesity increases the risks of major malformations and was based on measured weight and self-reported height at the macrosomia [12]. However, it is unclear whether maternal first antenatal visit, which usually took place in the first overweight and obesity also increase the risks of trimester [16]. Women were categorised as underweight asphyxia-related neonatal complications in the offspring of (BMI <18.5 kg/m2), normal weight (BMI 18.5 to mothers with type 1 diabetes. <25 kg/m2), overweight (BMI 25 to <30 kg/m2) or obese In this study, we investigated the offspring of mothers with (BMI ≥30 kg/m2) according to the WHO criteria [17]. type 1 or type 2 diabetes with respect to the risks of a low Apgar score (0–6) at 5 min and asphyxia-related neonatal Covariates The overall analyses included covariates of morbidity (neonatal seizures and hypoxic ischaemic maternal age, height, BMI, self-reported smoking status, level encephalopathy [HIE]). In addition, we investigated the of education, parity, mother’s country of birth and year of impact of overweight and obesity on these risks in the delivery. These variables were categorised as shown in offspring of mothers with type 1 diabetes and without Table 1. diabetes. Outcomes We estimated the risks of a low Apgar score (0–6) at 5 min, neonatal seizures (ICD-10 code P90) and HIE Methods (ICD-10 codes P 91.0, 91.3-P91.6, P918 and P919). Owing to limitations of statistical power, neonatal seizures and HIE Data sources This study was based on prospectively collected were analysed as one composite outcome. data from nationwide Swedish registries. The individual record linkage between registries was done by using the Statistical analysis The rates of all outcomes were calculated unique personal identification number assigned to all residents for the offspring of mothers with type 1 or type 2 diabetes and in Sweden [13]. The Medical Birth Register (MBR) contains for the infants of mothers without diabetes. ORs with 95% CIs data on more than 98% of all births in Sweden since 1973. The were calculated using logistic regression, with the offspring of MBR is continuously checked for quality by the National mothers without diabetes as the reference. The first adjusted Board of Health and Welfare, and the validity of most model included information on maternal age, height, smoking variables is considered to be high [14]. Using standardised status, level of education, parity, maternal country of birth and forms, physicians and midwives prospectively collect year of delivery. In a second model, we additionally adjusted information during pregnancy, delivery and the neonatal for maternal BMI. Height was included in the adjusted model period. Maternal and neonatal diagnoses are classified as it is independently associated with emergency Caesarean according to the ICD, and since 1997 the ICD-10 section [18], which may in turn reflect an increased risk of (www.who.int/classifications/icd/en/) has been used. Infants birth asphyxia-related complications. In stratified analyses, with diagnoses of neonatal seizures and/or HIE were the risks of a low Apgar score and asphyxia-related neonatal identified based on ICD-10 codes in the MBR and/or in the morbidity (neonatal seizures or HIE) were investigated in National Patient Register for inpatient care [15]. Information subgroups of infants born to normal-weight, overweight or on the mother’s country of birth and level of education was obese mothers. Owing to limitations of statistical power, retrieved from the Total Population Register and Education stratified analyses were confined to the offspring of Register, respectively. The study was approved by the mothers with type 1 diabetes and those without diabetes. Research and Ethics Committee at Karolinska Institutet Interactions between type 1 diabetes (yes/no) and maternal (No. 2012/1813-31/4). BMI (<25 vs ≥25 kg/m2) with risks of low Apgar score and asphyxia-related morbidity were tested for with likelihood Study population Between 1997 and 2011, the MBR tests. Interactions were judged significant at p < 0.05. included information on 1,441,623 live singleton births. We Sensitivity analyses, confined to term infants with a excluded infants with malformations (n = 84,711, ICD 10 birthweight for gestational age within the 10th–90th codes Q00-Q99), offspring of mothers with an unclear percentiles of mothers without hypertensive diseases diagnosis of diabetes (n = 64) and offspring of mothers with (chronic hypertension and pre-eclampsia), were also gestational diabetes (n = 13,097). Thus, the final study performed. A general estimation equation was applied to population included 1,343,751 live singleton births. account for repeated pregnancies. Exposures The main exposures were maternal pregestational diabetes and maternal BMI. Mothers with type 1 or type 2 Results diabetes were identified based on ICD-10 codes O240 and O241, respectively. The reference group included 1,337,099 From 1997 through 2011, there was a total of 5941 live offspring of mothers without diabetes. Maternal BMI (kg/m2) singleton births to mothers with type 1 diabetes, 711 to Diabetologia Table 1 Maternal and infant characteristics for pregnancies in mothers Table 1 (continued) with type 1 or type 2 diabetes and in women without diabetes Characteristic Diabetes No diabetes Characteristic Diabetes No diabetes Type 1 Type 2 n (%) Type 1 Type 2 n (%) n (%) n (%) n (%) n (%) Birthweight (g) Maternal age (years) <2500 291 (4.9) 39 (5.5) 37,568 (2.8) ≤ 24 767 (12.9) 35 (4.9) 203,418 (15.2) 2500–3999 3311 (55.7) 457 (64.3) 1,033,231 (77.3) – 25 29 1807 (30.4) 119 (16.7) 415,759 (31.1) 4000–4499 1457 (24.5) 141 (19.8) 209,887 (15.7) – 30 34 2062 (34.7) 221 (31.1) 459,539 (34.4) 4500–4999 581 (9.8) 53 (7.5) 44,719 (3.3) ≥ 35 1292 (21.7) 334 (47.0) 255,232 (19.1) >5000 105 (1.8) 12 (1.7) 6340 (0.5) Missing 13 (0.2) 2 (0.3) 3151 (0.2) Missing 196 (3.3) 9 (1.3) 5354 (0.4) Height (cm) Birthweight for gestational age (percentiles) ≤ 164
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