Dual BRCA1 and BRCA2 pathogenic variants in an adolescent with syndromic intellectual disability.

Pathogenic variants in the BRCA1 and BRCA2 genes are associated with increased risk for breast and ovarian cancers. Concurrent mutations in both genes in the same individual are rare but pose specific challenges when identified, usually through multigene panel testing or infrequently from a genome-wide analysis, such as whole-exome sequencing (WES). We present a 15-year-old female patient with syndromic intellectual disability whose exome reanalysis identified secondary findings of pathogenic BRCA1 and BRCA2 variants, both inherited paternally. We discuss the significant challenges posed by this finding in genetic counseling and cancer risk management of an adolescent with nonverbal intellectual disability, as well as the impact on their family. This rare case highlights the potential increased diagnostic yield of whole exome sequencing reanalysis and the consequences of secondary medically actionable results in a pediatric patient.

Water-fat magnetic resonance imaging of adipose tissue compartments in the normal third trimester fetus.

BACKGROUND: Assessment of fetal adipose tissue gives information about the future metabolic health of an individual, with evidence that the development of this tissue has regional heterogeneity. OBJECTIVE: To assess differences in the proton density fat fraction (PDFF) between fetal adipose tissue compartments in the third trimester using water-fat magnetic resonance imaging (MRI). MATERIALS AND METHODS: Water-fat MRI was performed in a 1.5-T scanner. Fetal adipose tissue was segmented into cheeks, thorax, abdomen, upper arms, forearms, thighs and lower legs. PDFF and R2* values were measured in each compartment. RESULTS: Twenty-eight women with singleton pregnancies were imaged between 28 and 38 weeks of gestation. At 30 weeks' gestation (n=22), the PDFF was statistically different between the compartments (P<0.0001), with the highest PDFF in cheeks, followed by upper arms, thorax, thighs, forearms, lower legs and abdomen. There were no statistical differences in the rate of PDFF change with gestational age between the white adipose tissue compartments (P=0.97). Perirenal brown adipose tissue had a different PDFF and R2* compared to white adipose tissue, while the rate of R2* change did not significantly change with gestational age between white adipose tissue compartments (P=0.96). CONCLUSION: Fetal adipose tissue accumulates lipids at a similar rate in all white adipose tissue compartments. PDFF variances between the compartments suggest that accumulation begins at different gestational ages, starting with cheeks, followed by extremities, trunk and abdomen. Additionally, MRI was able to detect differences in the PDFF between fetal brown adipose tissue and white adipose tissue.

Labour Progression in Obese Women: Are Women With Increased Body Mass Index Having Unnecessary Cesarean Sections?

OBJECTIVE: This study sought to determine whether obese pregnant women undergo cesarean sections without an adequate trial of labour. This may affect future birth and pregnancy outcomes. METHODS: A retrospective analysis was done on 526 parturients at Victoria Hospital in London, Ontario. Women were categorized according to parity and pre-pregnancy body mass index (BMI; normal weight, BMI 18.5-24.9 kg/m2; obese class II, BMI 35.0-39.9 kg/m2; obese class III, BMI ≥40 kg/m2). Patient charts and partograms were reviewed for labour progression (time at cervical dilation), demographics, and infant outcomes (Canadian Task Force Classification II-2). RESULTS: Obese class II and III primiparous women required an additional 1.62 and 2.67 hours (P = 0.012), respectively, to reach a dilation of 10 cm compared with their normal weight counterparts; obese class II and III multiparous women required an additional 1.25 and 2.05 hours (P = 0.003), respectively. A higher BMI was associated with increased oxytocin use and infant birth weight in primiparous women. Obese women had less gestational weight gain and required more cervical examinations. Cesarean section rates were low for obese parturients (primiparous, 19%; multiparous, 0.8%) and not significantly different among BMI categories. CONCLUSION: This study confirmed published results that labour progresses more slowly as maternal BMI increases. The study was performed in a centre with a specialized BMI pregnancy clinic; thus weight gain adherence, awareness of labour differences, and patient counselling may have contributed to low cesarean section rates. Obstetric care providers should consider differences in maternal BMI in labour progression before undertaking a potentially premature cesarean birth, especially in primiparous women.

Preeclampsia biomarkers: An assessment of maternal cardiometabolic health.

Preeclampsia is a serious pregnancy condition defined as new-onset hypertension and proteinuria, commonly characterized as either early, 'placental', or late onset, 'maternal', using a cut-off of 34 weeks gestation. However, it may be more useful to differentiate between the vascular remodelling and placental invasion vs. inflammation and metabolic pathophysiology that underlie these forms of preeclampsia. Due to rising rates of obesity, the late-onset, maternal form is increasingly occurring earlier in pregnancy. Predictive tests for preeclampsia typically include biophysical markers such as maternal body mass index and mean arterial pressure, indicating the importance of cardiovascular and metabolic health in its pathophysiology. In contrast, the placental, inflammatory, endothelial and/or metabolic biomarkers used in these tests are generally thought to indicate an abnormal response to placentation and predict the disease. However, many of these non-placental biomarkers are known to predict impaired metabolic health in non-pregnant subjects with obesity (metabolically unhealthy obesity) and coronary artery disease or stroke in people at risk for cardiovascular events. Similarities between the performance of these markers in the prediction of cardiovascular and metabolic health outside of pregnancy suggests that they may be more indicative of maternal health than predictive for preeclampsia. This paper reviews the biophysical and biochemical markers in preeclampsia prediction and compares their performance to tests assessing metabolic health and risk of cardiovascular disease, particularly in the obese population.

SOCIOECONOMIC STATUS AND ADVERSE BIRTH OUTCOMES: A POPULATION-BASED CANADIAN SAMPLE.

This study assessed the strength of the association between socioeconomic status (SES) and low birth weight (LBW) and preterm birth (PTB) in Southwestern Ontario. Utilizing perinatal and neonatal databases at the London Health Science Centre, maternal postal codes were entered into a Geographic Information System to determine home neighbourhoods. Neighbourhoods were defined by dissemination areas (DAs). Median household income for each DA was extracted from the latest Canadian Census and linked to each mother. All singleton infants born between February 2009 and February 2014 were included. Of 26,654 live singleton births, 6.4% were LBW and 9.7% were PTB. Top risk factors for LBW were: maternal amphetamine use, chronic hypertension and maternal marijuana use (OR respectively: 17.51, 3.18, 2.72); previously diagnosed diabetes, maternal narcotic use and insulin-controlled gestational diabetes predicted PTB (OR respectively: 17.95, 2.69, 2.42). Overall, SES had little impact on adverse birth outcomes, although low maternal education increased the likelihood of a LBW neonate (OR: 1.01).

Factors that influence excessive gestational weight gain: moving beyond assessment and counselling.

One in four Canadian adults is obese, and more women are entering pregnancy with a higher body mass index (BMI) than in the past. Pregnant women who are overweight or obese have a higher risk of pregnancy-related complications than women of normal weight. Gestational weight gain (GWG) is also associated with childhood obesity. Although the factors influencing weight gain during pregnancy are multifaceted, little is known about the social inequality of GWG. This review will address some of the socioeconomic factors and maternal characteristics influencing weight gain and the impact that excessive GWG has on health outcomes such as post-partum weight retention. The effects of an overweight or obese pre-pregnancy BMI on GWG and neonatal outcomes will also be addressed. The timing of weight gain is also important, as recommendations now include trimester-specific guidelines. While not conclusive, preliminary evidence suggests that excessive weight gain during the first trimester is most detrimental.

A prospective study of diagnostic conversion of major depressive disorder to bipolar disorder in pregnancy and postpartum.

OBJECTIVES: The aim of the present study was to determine the rate of, and risk factors for, a change in diagnosis from major depressive disorder to bipolar disorder, and from bipolar II disorder to bipolar I disorder in pregnancy and postpartum. METHODS: Patients with a prior history of major depressive disorder or bipolar II disorder were recruited between 24 and 28 weeks' gestation and followed through to one year postpartum. Diagnostic interviews were conducted using the Structured Clinical Interview for DSM-IV at study intake and repeated using the Mini-International Psychiatric Interview at one, three, six, and 12 months after childbirth. Fisher's exact test was used to assess the association between various risk factors and diagnostic switch. RESULTS: A total of 146 participants completed the intake interview and at least one follow-up interview postpartum. Of these, 92 were diagnosed with major depressive disorder and 54 with bipolar II disorder at intake. Six women (6.52%) experienced a diagnostic change from major depressive disorder to bipolar II disorder during the first six months after childbirth. There were no cases of switching to bipolar I disorder, but in one participant the diagnosis changed from bipolar II disorder to bipolar I disorder during the three months after childbirth. Bipolar switch was associated with a family history of bipolar disorder. CONCLUSIONS: The postpartum period appears to be a time of high risk for a new onset of hypomania in women with major depressive disorder. Our rate of diagnostic switching to bipolar II disorder (6.52%) is at least 11- to 18-fold higher than the rates of switching in similar studies conducted in both men and women.

Influence of health information levels on postpartum depression.

While extensive research has been conducted on postpartum depression (PPD), the majority has been focused on psychological risk factors and treatments. There is limited research on the explicit relationship between the degree to which individuals are informed about relevant prenatal and postnatal health topics and whether this level of knowledge influences psychological outcome. This study assesses health information levels of new mothers and their influence on PPD as measured by Edinburgh Postnatal Depression Scale (EPDS) scores. Data from the 2006 Maternity Experiences Survey developed by the Canadian Perinatal Surveillance System (N = 6,421) were used. The study population included mothers ≥15 years of age at the time of the birth, who had a singleton live birth in Canada during a 3-month period preceding the 2006 Census and who lived with their infants at the time of the survey. Pre- and postnatal health information components were measured using latent variables constructed by structural equation modeling. EPDS score was added to the model, adjusting for known covariates to assess the effects of information levels on EPDS score. Pre- and postnatal health information levels are associated with decreased EPDS scores. More specifically, information on topics such as postnatal concerns and negative feelings was associated with the largest decrease in score for primiparous and multiparous women, respectively (p < 0.0001 for both). The pre-established predictors of PPD were confirmed for both samples, with life stress associated with the largest change in EPDS score for both samples (p < 0.0001 for both). This study demonstrates a distinct role for pre- and postnatal health information in influencing EPDS scores, supplementing previous literature. Primiparous and multiparous women benefited from different information content, with information on postnatal concerns had the largest effect on the primiparous group while information on negative feelings had the largest effect on the multiparous group. Therefore, information provision should be tailored to these two groups.

Screening for bipolar disorder during pregnancy and the postpartum period.

The postpartum period is a time of increased risk of illness onset and exacerbation of mood episodes in women with bipolar disorder. Because the onset of mood and psychotic episodes occurs so soon after birth and as this high-risk period is brief, antenatal screening is vital for identification of women who are at risk for mood instability. Screening facilitates prompt recognition and treatment of emerging psychopathology and thus addresses some of the key safety issues that affect women, their babies, and their families.