The additive effect of obesity in the incidence of neurocognitive disorders in offspring of women with gestational diabetes

Andreu Simó; Veronica Perea; Maite Valverde; Carmen Quirós; Aida Orois; Luis García-Pascual; MªJosé Barahona

doi:10.1530/endoabs.70.AEP377

Aim: Gestational diabetes (GDM) has been associated with an increased risk ofneurocognitive outcomes in offspring such as attention deficit/hyperactive disorders (ADHD) and autism spectrum disorders (ASD). However GDM-related comorbidities (obesity or excessive weight gain –EWG-) in this setting have been scarcely studied. So, the aim of our study was to estimate the risk of ADHD and ASD in this population.

Material and Methods: Cohort study. Singleton pregnancies complicated by GDM between 1991–2008 were selected. Maternal data was prospectively collected during pregnancy. ADHD and ASD diagnostic was obtained from medical records. Cox proportional hazards modeling adjusting for potential confounders were applied to estimate the effect of maternal obesity and EWG during pregnancy.

Results: A total of 1118 pregnancies were selected. The median follow-up was 17.5 years [14.5–21.4] with 12% (n = 142) and 0.01% (n = 14) of subjects diagnosed of ADHD and ASD, respectively. As table 1 shows, maternal obesity increased the risk of ADHD. EWG was only associated with increased risk of ADHD in the early-GDM subgroup. Neither maternal obesity nor EWG were associated with ASD. Insulin use during pregnancy did not modify the results.

**Table 1**
		Total cohort(n = 1118)	Early GDM (n = 202)	Late GDM (n = 916)
Maternal weight (kg/m²)
ADHD	18.5–24	Ref.	Ref.	Ref.
	<18.5	0.61^c (0.09–4.40) 0.63^a (0.09–4.53)	7.19^c (0.83–62.15) 11.80^a (1.26–110.0)	–
	25–29	1.26^c (0.85–1.86) 1.21^a (0.81–1.81)	2.82^c (0.94–8.42) 3.21^a (0.99–10.31)	1.08^c (0.70–1.67) 0.99^a (0.63–1.54)
	≥ 30	1.74^c (1.16–2.62) 1.68^a (1.11–2.55)	1.62^c (0.51–5.10) 1.83^a(0.55–6.10)	1.93^c (1.22–3.05) 1.84^a (1.16–2.94)
	EWG	1.52^c (1.02–2.58) 1.46^a(0.97–2.20)	2.73^c (1.13–6.59) 3.53^a (1.37–9.14)	1.23^c (0.76–1.97) 1.16^a (0.69–1.81)
Maternal weight (kg/m²)
ASD	18.5–24	Ref.	Ref.	Ref.
	<18.5	n/a	n/a	n/a
	25–29	1.90^c (0.55–6.59) 2.36^a (0.66–8.42)	n/a	1.61 (0.43–5.98) 2.42 (0.61–9.58)
	≥ 30	2.37^c (0.63–8.82) 2.76^a (0.72–10.6)	n/a	0.80 (0.09–6.91) 0.66 (0.074–6.11)
	EWG	0.44^c (0.57–3.42) 0.64^a (0.08–5.20)	2.09^c (0.18–23.08) 3.14^a (0.26–38.60)	n/a

Data was expressed as Hazard Ratio and 95% Confidential Interval. ^C: crude model. ^a: adjusted model including maternal age at pregnancy, weeks of gestation, C-section, Apgar <3 at min 1 or 5, small for gestational age (percentile <10) and current smoking during pregnancy.

ADHD: attention deficit/hyperactive disorder. ASD: autism spectrum disorder. EWG: excessive weight gain during pregnancy according to OMS criteria. Early/Late gestational diabetes mellitus (GDM): diagnosed </≥ 26 weeks of gestation, respectively.

Conclusions: Beyond deleterious effect of hyperglycaemia, maternal weight itself plays a role increasing the risk of ADHD in offspring. Regarding ASD, the low number of subjects did not allow reliable conclusions.

Endocrine Abstracts

AEP377