Data were collected as part of a prospective cohort study on obese pregnant women [29]. Between November 2003 and December 2005, all obese pregnant women (n = 754), consecutively registered in early pregnancy in three antenatal clinics in Sweden, were approached to the study [29]. The inclusion criteria were early pregnancy BMI ≥ 30 and knowledge of the Swedish language. The exclusion criteria were pre-pregnant diagnosis of diabetes mellitus, thyroid dysfunction or psychiatric disease treated with neuroleptic drugs. A flow chart of the study is presented in Fig. 1. Out of the 615 women who were eligible and invited to participate, 368 women were included in the study and 348 completed the study. Additionally five women, who expected twins, were excluded, leaving 343 women with singleton pregnancies as the present study population.

The study-population was categorized in three obesity classes of early pregnancy BMI, based on the WHO definition; class I obesity = BMI 30–34.9, class II obesity = BMI 35–39.9 (morbid obesity) and class III obesity = BMI ≥ 40 (morbid obesity) [30]. BMI was defined as body weight in kilograms divided by height in meter squared (kg/m²). All women had their weight and height recorded in the gestation week eight to ten, which enabled calculation of BMI.

The study-population was also divided into three groups of GWG: < 5 kg, 5–9 kg and > 9 kg. In 2009 the IOM published guidelines advising optimal weight gain during pregnancy, based on pre-pregnancy BMI. According to these guidelines, the recommended GWG for obese women is 5–9 kg [28]. To calculate GWG we used maternal weight in delivery week minus early pregnancy weight. If maternal weight in delivery week was missing, the weight 1 or 2 weeks before delivery, was used. A total number of 304 women had information on GWG. Gestational age was calculated based on fetal biometry at the first trimester ultrasound. Data on maternal characteristics and pregnancy complications were retrieved from computerized patient records.

Maternal plasma leptin levels were measured in week 15 and 29 of gestation and 10 weeks postpartum. The women fasted prior to sampling of maternal blood. Maternal blood was collected in the morning in all patients.

For leptin analyses blood was collected in a test tube with a clot activator and gel for serum separation. One hour after sampling, the blood was centrifuged, aliquoted and serum was stored at −70° Celsius until analyses.

The maternal plasma leptin concentration was measured using a direct sandwich based ELISA (Millipore, Billerica, USA). Human leptin was captured by a polyclonal antibody on a 96-well microtiter plate and unbound material washed away. A secondary monoclonal biotinylated antibody was added to the captured human leptin complex followed by streptavidin-horseradish peroxidase. The enzyme activity was measured spectrophotometrically (Victor 3, PerkinElmer, Waltham, MA, USA) at 450 nm after a last step of acidification of the sample products. Increased absorbance was directly proportional to the amount of captured human leptin in unknown samples derived from a generated standard-curve. In a sample size of 25 μL, the limit of sensitivity of the assay was 0.2 ng +/− 2 SD. The within and between assay variation was 4.6 and 6.2 % respectively. The specificity of the assay was 100 % for human leptin. No cross-reactivity was found for human pro-insulin, insulin, insulin-growth factor I and II or Glucagon.

Differences in categorical demographic variables as well as obstetric outcomes, between maternal obesity class I-III, were analysed using Pearson’s Chi-square test and ANOVA was used for analysing differences in continuous variables and outcomes (maternal age, birth weight, GWG and gestational length in weeks.) Categorical variables and outcomes were expressed as numbers (percentage) and if continuous as mean (SD).

The mean value and confidence interval of plasma-leptin during and after pregnancy in women with obesity class I-III and in obese women in three different GWG groups were analysed with a two-way ANOVA model. (Bonferroni adjusted within each gestational week).

Interaction effect between Maternal BMI and GWG was tested with a two-way ANOVA model.

General linear models were used to test possible confounding in addition to the main effect model of BMI and gestational weight gain.

All analyses were performed using IBM SPSS version 23 (IBM Inc, Armonk, NY). A p-value <0.05 was considered statistically significant.

The Regional Ethical Review Board in Linköping, Sweden approved this study (No 03–231).

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