The impact of obesity on pregnancy outcomes among women with psychiatric disorders: Results from a prospective pregnancy registry
Introduction
The rate of obesity in the United States has been increasing, and this is associated with higher rates of maternal morbidity and mortality associated with childbirth [1]. Maternal obesity is associated with obstetrical complications and adverse neonatal events [2,3], and pregnant women with psychiatric disorders may constitute an especially at-risk group. Data suggest that serious psychiatric disorders are associated with the development of obesity, and inversely, that obesity is associated with the subsequent onset of psychiatric disorders [4]. Individuals with psychiatric disorders suffer from greater medical comorbidity than the general population, and have a shorter life expectancy [5]. In addition to other variables that may underlie the association between obesity and psychiatric disorders, many psychiatric medications have weight gain and metabolic dysregulation as side effects [6]. Despite these serious clinical ramifications, obesity in pregnant women with comorbid psychiatric disorders has received little systematic study.
The Massachusetts General Hospital (MGH) National Pregnancy Registry for Atypical Antipsychotics (NPRAA) was established in 2008. The registry was developed per U.S. Food and Drug Administration (FDA) guidelines for pregnancy registries, and in line with those guidelines, internal groups with psychiatric disorders are included for comparison [7]. Therefore, from its inception, the MGH National Pregnancy Registry has included a prospectively ascertained cohort of women with psychiatric disorders, including those treated with atypical antipsychotics and those treated with other psychiatric medications. The original Registry has now been expanded to include other psychotropics, and is collectively referred to as the MGH National Pregnancy Registry for Psychiatric Medications (NPRPM) [8,9]. Study procedures are described in detail elsewhere, but in brief, women are followed prospectively during pregnancy and the postpartum period, and obstetrical and neonatal outcomes are verified with medical record review [10,11]. While the primary outcome of the Registry is the rate of birth defects, the study is also a rich source of prospectively gathered data for important secondary outcomes, including obstetrical adverse events and neonatal outcomes other than congenital anomalies.
We have previously reported that baseline pregnancy weights for women in the Registry taking atypical antipsychotic medications were higher than for the control group, comprised of women who also had psychiatric disorders but were not taking atypicals [12]. Both those exposed to atypicals and controls had similar gestational weight gain, with the majority of women gaining more weight during pregnancy than is recommended by established guidelines [13].
The objective of the current analyses was to ascertain the obstetrical and neonatal risks posed by obesity per se in a prospectively followed cohort of women with psychiatric disorders. Obesity was selected as the exposure variable given its public health significance, and its potential as a modifiable risk factor prior to and during pregnancy.
Section snippets
Methods
As described previously, the NPRAA was created in 2008 at MGH to delineate risk of major congenital anomalies in infants after first trimester exposure to atypical antipsychotic medications. The registry has been expanded to include other classes of psychotropic medications. A detailed description of Registry methodology and preliminary findings have been reported elsewhere [10,11]. All participants in the Registry provide verbal informed consent, and all study procedures were approved by the
Results
Demographic characteristics of the study sample are summarized in Table 1 for all three groups: normal weight, overweight, and obese categories of BMI; however, p-values reflect the comparison between women at a normal weight and women with obesity (in bold) unless otherwise stated. Women with normal weights were more likely to have a college education (83.3% vs. 60.5%), to be married (87.3% vs. 71.6%), and to have a planned pregnancy (84.8% vs. 64.8%). The normal weight group was also more
Discussion
Our aim in these analyses was to assess the risk for birth defects as well as obstetrical and neonatal risks associated with maternal obesity in a prospectively followed cohort of women with psychiatric disorders treated with a variety of psychiatric medications. While the primary outcome of the Registry is to assess risk of birth defects associated with exposure to psychotropic medications, this registry also allows us to examine the effect of other potentially detrimental exposures such as
Competing interests
Marlene Freeman, Lee Cohen, Adele Viguera received research support from Alkermes Biopharmaceuticals, Inc.; Forest/Actavis Pharmaceuticals; Otsuka Pharmaceuticals; Sunovion Pharmaceuticals, Inc.; Teva Pharmaceuticals for the submitted work.
Marlene Freeman has received research support from JayMac Pharmaceuticals, LLC; SAGE Therapeutics; National Institute of Mental Health; National Institute on Aging.
Medical Editing: GOED Omega-3 Newsletter.
Independent Data Monitoring Committee: Johnson &
References (32)
- et al.
Impact of maternal obesity on perinatal and childhood outcomes
Best Pract. Res. Clin. Obstet. Gynaecol.
(2015) - et al.
Obesity and psychiatric disorders: commonalities in dysregulated biological pathways and their implications for treatment
Prog. Neuro-Psychopharmacol. Biol. Psychiatry
(2013) - et al.
Metabolic side effects of antipsychotic drug treatment–pharmacological mechanisms
Pharmacol. Ther.
(2010) - et al.
A simulation study of the number of events per variable in logistic regression analysis
J. Clin. Epidemiol.
(1996) - et al.
Association between maternal obesity and autism Spectrum disorder in offspring: a meta-analysis
J. Autism Dev. Disord.
(2016) - et al.
A randomized clinical trial of exercise during pregnancy to prevent gestational diabetes mellitus and improve pregnancy outcome in overweight and obese pregnant women
Am. J. Obstet. Gynecol.
(2017) - et al.
Mighty mums - an antenatal health care intervention can reduce gestational weight gain in women with obesity
Midwifery.
(2015) - et al.
Pregnancy after bariatric surgery: the effect of time-to-conception on pregnancy outcomes. Surgery for obesity and related diseases
Off. J. Am. Soc. Bariatric Surg.
(2017) - et al.
Trends in obesity among adults in the United States, 2005 to 2014
JAMA.
(2016) - et al.
Risk of adverse pregnancy outcomes stratified for pre-pregnancy body mass index
J. Matern. Fetal Neonatal Med.
(2016)