Longitudinal Measures of Leptin in Pregnant Women Who Developed Preeclampsia
Condition: High-Risk Pregnancy
MeSH terms: Pre-Eclampsia
Study type: Observational

Summary: 
      Background: Obesity in pregnancy is increasing and is a risk factor for metabolic pathology
      such as preeclampsia. Leptin is an adipokine which has a direct relationship to obesity.

      Aim: to measure leptin in lean, obese and diabetic pregnant women at three months intervals
      throughout their pregnancies.

      Methods: Pregnant women were recruited in the 1st trimester of pregnancy, and three groups
      were formed: a) with pregestational Body Mass Index (BMI) less than 25 kg/m2, b) BMI higher
      than 25 kg/m2 and c) with Gestational Diabetes Mellitus (GDM). Serum levels of leptin were
      measured with radioimmunoassay (RIA) technique.
    

Detailed description: 
      1. Introduction Obesity and type 2 diabetes (2DM) are worldwide health issues, and the
      incidences of both diseases are increasing rapidly. Recent research has shown that maternal
      nutrition during pregnancy may have long-term metabolic consequences in offspring. Many
      pregnant women are obese (body mass index (BMI) > 30 kg/m2). The prevalence of maternal
      obesity is rising, up to 20% in some antenatal clinics, which is in line with the prevalence
      of obesity in the general population. Obesity in pregnancy has been linked to several adverse
      pregnancy outcomes, including spontaneous abortion, preeclampsia, gestational diabetes (GDM),
      fetal macrosomia, cesarean delivery, and wound complications post-cesarean section. Both
      intrapartum and postpartum management of obese gravidas require multidisciplinary
      consultations between obstetricians, anesthesiologists, nurses, and pediatricians in order to
      improve the pregnancy outcomes of the mother and neonate. The American College of
      Obstetricians and Gynecologists (ACOG) and several authors currently support risk-reducing
      strategies for obese pregnant patients including limiting weight gain.

      Preeclampsia is a multisystem disorder characterized by pregnancy-induced or gestational
      hypertension and new-onset proteinuria during the second half of pregnancy.

      The aim of this study was to measure leptin in lean, obese and diabetic pregnant women at
      three-month intervals throughout their pregnancies to determine if this hormone could serve
      as a prognostic marker for preeclampsia risk.

      Recruitment Women were recruited at their first visit at 10-15 weeks gestation. They were
      asked to attend after an overnight fast and were tested between 0700 and 0900 h. Three groups
      of pregnant women were formed: a) normal weight (pregestational (PG) BMI < 25 kg/m2), b)
      overweight-obese (PGBMI ≥ 25 kg/m2) and c) hyperglycemic in the first trimester of pregnancy
      confirmed as GDM in women previously known to be normoglycemic. Positive cases for
      preeclampsia were then subdivided.

      Clinical follow-up Three examinations were performed in the 1st, 2nd, and 3rd trimesters. In
      each visit, the women were weighed. Blood pressure (BP) was recorded at each visit using a
      standard sphygmomanometer and appropriately sized cuff. If diagnosed with pregnancy-induced
      hypertension, the women were hospitalized and clinically supervised with an electronic
      monitor (Mercury, Mennem Medical) until the diagnosis of preeclampsia was confirmed or
      excluded.

      Laboratory During each consult, blood samples were collected in Vacutainer tubes after a
      fasting period of 8 hours and centrifuged to separate the plasma from serum. The
      investigators measured albumin (mg/dl), cholesterol (mg/dl), creatinine (mg/dl), glucose
      (mg/dl), triglycerides (mg/dl), uric acid (mg/dl), liver enzymes (Dimension Rx L Max, Dade
      Behring), and hemoglobin (g/dl) (Advia 120, Bayer Health) and performed a general urine test
      (URiSCAN Pro). These tests were measured in the HMPMP according to standardized procedures
      recommended by the International Federation of Clinical Chemistry and Laboratory Medicine
      (IFCC).

      Diagnosis of GDM At the time of recruitment, women with hyperglycemia who fulfilled the
      criteria and were recently diagnosed with diabetes were included in the same group as those
      women who were submitted to an OGT after 24 weeks' gestation and confirmed to have GDM
      because they had normal values of glucose prior to their pregnancies.

      During pregnancy follow-up, gynecologists at the obstetric outpatient clinic used the
      following risk factors to screen women for GDM: a first-degree relative with diabetes, a
      history of GDM or macrosomia, a suspicion of macrosomia in the current pregnancy, persistent
      glucosuria, a rapid or excessive weight gain during early pregnancy, obesity or a random
      plasma glucose ≥ 7.0 mmol/l. Women with one or more of these factors underwent the standard
      100 g 3-h OGTT after an overnight fast (solution provided by Laboratorio Silanes).

      The diagnosis of GDM was made according to the National Diabetes Data Group (NDDG) criteria
      (≥ 2 abnormal values; glucose concentrations of ≥ 5.8 mmol/l for fasting, ≥ 10.6 mmol/l at 1
      h, ≥ 9.2 mmol/l at 2 h, and ≥ 8.1 mmol/l at 3 h) [16].

      In women with GDM, the therapeutic aims were blood glucose levels before meals < 5.0 mmol/l
      and 2 h postprandial < 6.5 mmol/l. If two blood glucose levels in one to two weeks were above
      these aims despite adequate dietary measures, then insulin of the rapid type was started or
      doses were increased. If these measures were insufficient to reach the therapeutic aims, then
      basal insulin was added.

      Preeclampsia was diagnosed and classified according to the criteria specified by the
      technical bulletin of the ACOG and the National High Blood Pressure Education Program
      (NHBPEP) Working Group Report on High Blood Pressure in Pregnancy. Hypertension was described
      as an increase of 30 mm Hg systolic or 15 mm Hg diastolic BP as compared to the values before
      20 weeks of pregnancy, or an absolute BP > 140/90 mm Hg after 20 weeks gestation if the
      earlier values were unknown.

      Leptin Serum levels of leptin (Millipore/Linco., USA, Cat. HL-8IHK) and adiponectin
      (Millipore/Linco., USA, Cat. No. HADP-61HK) were determined by means of a double antibody
      radioimmunoassay (RIA) using materials and protocols supplied by the provider
      (Millipore/Linco., USA, Cat. HL-8IHK). All samples of each trimester were assayed
      simultaneously. The assays were run according to the manufacturer's recommendations.

      Statistical analysis It was used the SPSS version 16. Continuous variables were expressed in
      means ± standard deviation (SD). Kruskal Wallis and Mann-Whitney U tests were considered
      statistically significant with a P value ≤ 0.05. Receiver Operating Characteristic (ROC)
      curves were used with each variable and in the cases of preeclampsia.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Women who had received medical attention during pregnancy at the HMPMP in Toluca, Mexico.
      
Biospecimen description: 
      Serum
    
Keywords: body mass index; gestational diabetes; leptin; obesity; pregnancy.