Date Published: July 27, 2017
Publisher: Public Library of Science
Author(s): Delphine Mitanchez, Sophie Jacqueminet, Jacky Nizard, Marie-Laure Tanguy, Cécile Ciangura, Jean-Marc Lacorte, Céline De Carne, Laurence Foix L’Hélias, Pascale Chavatte-Palmer, Marie-Aline Charles, Marc Dommergues, Umberto Simeoni.
To discriminate the effect of maternal obesity and gestational diabetes on birth weight and adipose tissue of the newborn.
Normal BMI women (group N, n = 243; 18.5≤ BMI<25 kg/m2) and obese women (group Ob, n = 253; BMI≥30 kg/m2) were recruited in a prospective study between 15 and 18 weeks of gestation. All women were submitted to a 75g oral glucose tolerance test in the second and third trimester. First trimester fasting blood glucose was also obtained from Ob women. All women with one measurement above normal values were considered positive for gestational diabetes and first treated by dietary intervention. When dietary measures were not efficient, they were treated by insulin. Neonatal anthropometrics, sum of skinfolds and cord serum hormones were measured. 222 N and 226 Ob mothers and their newborns were included in the analysis. Diabetes was diagnosed in 20% and 45.2% of N and Ob women, respectively. Birth weight was not statistically different between groups (boys: 3456g±433 and 3392g±463; girls: 3316g±402 and 3391g±408 for N and Ob, respectively). Multivariate analysis demonstrated that skinfold thickness and serum leptin concentrations were significantly increased in girls born to women with obesity (18.0mm±0.6 versus 19.7mm±0.5, p = 0.004 and 11.3ng/mL±1.0 versus 15.3ng/mL±1.0, p = 0.02), but not in boys (18.4mm±0.6 versus 18.5mm±0.5, p = 0.9 and 9.3ng/mL±1.0 versus 9.0ng/mL±1.0, p = 0.9). Based on data from 136 N and 124 Ob women, maternal insulin resistance at 37 weeks was also positively related to skinfold in girls, only, with a 1-point increase in HOMA-IR corresponding to a 0.33mm±0.08 increase in skinfold (p<0.0001). Regardless of gestational diabetes, maternal obesity and insulin resistance were associated with increased adiposity in girls only. Persistence of this sexual dimorphism remains to be explored during infancy.
Many countries currently face an increasing prevalence of obesity and related medical complications. Maternal pre-pregnancy body mass index (BMI) ≥30 kg/m2 is associated with increased rates of many complications during pregnancy for the mother, the fetus and the neonate , including fetal malformations, perinatal mortality [2, 3] and fetal overgrowth with subsequent neonatal macrosomia . The relationship between maternal obesity and macrosomia is well documented, but the specific effect of obesity versus gestational diabetes remains unclear. Indeed, a recent meta-analysis concluded that maternal obesity is associated with excessive fetal growth , but there was substantial clinical heterogeneity between the studies included in this meta-analysis, notably concerning the method for recording maternal weight and the inclusion of diabetic mothers.
This prospective exposure-matched cohort study was registered as clinical trial registration number: NCT02681588, ClinicalTrials.gov. The trial began before the clinical trial registration was required for this type of observational study. At that time, in 2010, the sponsor did not do it systematically. When this became required, compliance was made for all trials and new trials were registered before recruiting the first participant. The authors confirm that all ongoing and related trials for this intervention are registered. The study received the approval of the Ile-de-France ethics committee on November 18, 2009 (CPP: Committee of Protection of the People—n°79–09). All participants gave written informed consent. Patients were recruited in two Parisian hospitals (centers 1 and 2) before 18 weeks of gestation between August 31, 2010 and March 19, 2013. The delivery of the last patient included in the study occurred on September 23, 2013 and the end of follow-up for the baby was on October 21, 2013. Inclusion criteria were pregestational BMI ≥ 30 kg/m2 (obese mothers) or 18.5 ≤ BMI < 25 kg/m2 (normal weight mothers), maternal age 18 years or greater and below 41 years, singleton pregnancy. Exclusion criteria were: initiation of antenatal care after 18 weeks, known type 1 or type 2 diabetes, obesity due to a genetic disorder or secondary to intracranial tumor or radiotherapy, bariatric surgery, chronic diseases other than obesity and non-fluency in French. Four hundred and ninety-six pregnant women were recruited, 353 in center one, 143 in center two. Two hundred and forty-three pregnant women had normal BMI (group N, 18.5≤ BMI<25 kg/m2) and 253 were obese (group Ob, BMI≥30 kg/m2). Twelve women in the N group and 11 in the Ob group were lost to follow-up, and there were 3 and 4 fetal losses in each group respectively. There were 228 live births in the N group and 238 in the Ob group. Preterm births (<37 weeks) were excluded from the analysis (respectively 6 in the N group and 12 in the Ob group), resulting in 222 N and 226 Ob mothers and their newborns in the final study group (Fig 1). This study shows that regardless of gestational diabetes, maternal obesity was not associated with increased birthweight but it was nevertheless associated with higher fat mass and leptin in girls, but not in boys. A strong association between maternal insulin resistance and fat mass in girls was also found. Regardless of gestational diabetes, maternal obesity is not associated with increased birth weight but is associated with increased neonatal adiposity in girls only. Source: http://doi.org/10.1371/journal.pone.0181307