In 2017, 25.0% of Canada’s female population aged 18–34 years were considered overweight and 19.3% were considered to have obesity . Pregnant women with obesity are at greater risk for developing gestational diabetes mellitus (GDM) or gestational hypertension (with or without proteinuria) [2–4], putting the fetus at risk for premature birth, caesarian section delivery, macrosomia, birth defects, premature death, and stillbirth [3, 4]. A 2017 systematic review suggested that women with obesity are at increased risk for antenatal depression . There is a strong association with pre-pregnancy obesity and screening positive for postpartum depression [6, 7]; and it is estimated that 10–13% of women will develop a depressive episode postpartum . Peripartum depression, which refers to a major depressive episode occurring during pregnancy or within 4 weeks following delivery, is observed in 8–13% of mothers with negative effects on the mother during and after pregnancy and on the offspring . Despite the seriousness of the condition, it is difficult to diagnose and treat depression both during and shortly after birth [10, 11]. Treatment options include psychotherapy and selective serotonin reuptake inhibitor (SSRI) antidepressants, but their efficacy has been controversial and it dependent on severity and duration [12, 13]. Furthermore, treatment should be individualized and may require 6–8 weeks to see a response, which could also affect compliance [12–14]. The new drug brexanolone, while promising, is costly and requires intravenous administration for three days in hospital with continuous monitoring . Thus, it is necessary to identify markers and potential therapeutic targets for early diagnosis, treatment and prevention of postpartum depression.
Pregnancy is a dynamic condition involving systemic changes in the mother that are largely mediated by the placenta ― an organ that produces and secretes hormones to support pregnancy and fetal growth [16, 17]. Several hormones are involved in the physiological and neurological changes that occur in the mother in response to pregnancy, some of which are steroids (e.g., estrogens, progesterone), neuropeptides (e.g., oxytocin) and lactogenic hormones (e.g., prolactin (PRL), placental lactogen) . Placental lactogens (PLs; also known as chorionic somatomammotropin (CS) hormone, bind the PRL receptor with high affinity in order to mediate their effects in the body and brain [18, 19]. PL also binds the growth hormone receptor, although with much lower affinity . Metabolically, PLs support pregnancy by increasing insulin production through expansion of pancreatic β-cells. Together with human placental growth hormone, this helps offset the effects of insulin resistance that normally occurs in pregnancy , and facilitates maternal energy production by metabolizing fats instead of carbohydrates (i.e. glucose) which are alternatively being delivered to the growing fetus [19, 20]. In the case of obesity, there is a surplus of fats and glucose in the body which leads to increased insulin resistance. This in turn can result in fetal hyperglycemia in utero and macrosomia at birth . Equally so, certain neurological changes in the mother must also occur in order to facilitate appropriate and proper care for her newborn . In two recent studies, PL was linked to depression [22, 23]. In the first study , placenta samples from women with clinically diagnosed prenatal depression and as well as in those self-reporting significant symptoms of depression during pregnancy were found to have a significantly decreased level of PL ribonucleic acid (RNA) . In the second study , maternal serum PL taken just before birth was negatively associated with depression and anxiety scores assessed 10 weeks after birth. Interestingly, this observation was only seen among mothers who gave birth to girls. The authors also found a statistically significant relationship between PL serum levels and maternal body mass index (BMI) .
Previously, our research group conducted a study using placental samples taken at the time of birth from three groups of women: with obesity (BMI of 40.1 ± 1.6), with obesity and GDM treated with insulin (BMI of 38.7 ± 1.7), and without obesity (“lean”; BMI of 22.5 ± 0.5) [24, 25] in order to measure the effect of maternal obesity on PL levels in both tissue and in maternal serum. We reported a significant decrease in both PL RNA levels in placenta and serum PL levels in pregnant women with obesity at 28 weeks gestation . When including mothers with obesity who received insulin during pregnancy to treat GDM, insulin treatment increased placental PL RNA and protein levels, meeting and exceeding the levels detected in the otherwise healthy lean group of women . In another independent study, levels of PL were measured at birth in placentas from three groups of women: GDM controlled by diet, GDM controlled by glyburide or insulin, and BMI-matched controls . BMI values ranged from 26.3 to 32.7, classifying these women as overweight/class I obese. Among the GDM controlled by glyburide/insulin, there were significantly higher PL levels in comparison to GDM controlled by diet and BMI-matched controls . In a recent comprehensive review, decreased placental lactogen levels have been suggested to be a marker for maternal obesity, while increased levels is associated with maternal diabetes . In addition, several studies have also linked obesity in pregnancy and GDM to the development of peripartum depression, both antenatal and postpartum [28–31].
Taken together, we hypothesize that: 1) maternal obesity, estimated as women weighing ≥ 85 - <186 kg (with obesity group) versus those without (> 38 - <65.6 kg; lean group), is associated with an increased rate of postpartum psychological distress; and 2) insulin treatment given during the gestational period will result in a reduced rate of postpartum psychological distress (abbreviated here as PPD) in women with obesity. This will be effectuated utilizing population health data housed at the Manitoba Centre for Health Policy.