Daniela Caprara

Novel approaches to the diagnosis of fetal alcohol spectrum disorder.

The diagnosis of fetal alcohol spectrum disorder is a difficult task, especially in cases where clear, physical markers of in utero alcohol exposure are not apparent. Reviewed in the following paper are some older tools for screening alcohol use in pregnancy and present novel approaches to the diagnosis of FASD, including ethanol biomarker development to behavioural phenotyping. Improving current FASD diagnostic methodology through more novel approaches may provide the possibility of earlier and wider diagnosis, allowing intervention and treatment at stages where the advanced effects of alcohol can still be mitigated.

The Fetal Safety of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are known to cause fetal renal damage in pregnancy. Due to conflicting reports in the literature, their safety after first trimester exposure has been debated. Our aim was to determine whether the use of ACE inhibitors or ARBs in the first trimester of pregnancy is associated with an increased risk for major malformations or other adverse outcomes. All subjects were prospectively enrolled from among women contacting a teratogen information service. At initial contact, details of maternal medical history and exposures were collected and follow-up interviews were conducted to ascertain pregnancy outcomes. Two comparator groups, women with hypertension treated with other antihypertensives, and healthy controls were also recruited. Baseline maternal characteristics were not different among the three groups. There were no differences in rates of major malformations. Both the ACE-ARBs and disease-matched groups exhibited significantly lower birth weight and gestational ages than the healthy controls (P < 0.001 for both variables). There was a significantly higher rate of miscarriage noted in the ACE/ARB group (P < 0.001). These results suggest that ACE inhibitors/ARBs are not major human teratogens; however, they may be associated with an increased risk for miscarriage.

Baseline measures of fatty acid ethyl esters in hair of neonates born to abstaining or mild social drinking mothers.

Elevated levels of fatty acid ethyl esters have been documented in the meconium of neonates born to heavily drinking mothers. Recently, accumulation of FAEE has been documented in the hair of drinking adults. To be able to use this test in the diagnosis of Fetal Alcohol Spectrum Disorder, one needs to establish baseline FAEE levels in infants born to nonalcoholic women because ethanol occurs in the baby naturally even without drinking. Scalp hair of 56 infants born to nonalcoholic women attending a well-baby clinic was obtained. Levels of FAEE were measured by GC-MS. FAEE were detected in almost all hair samples. Offspring of women admitting to mild, infrequent drinking did not differ in FAEE hair levels from infants of total abstainers. Baseline levels of FAEE in neonatal hair of nonalcoholic mothers have been established. Mild infrequent maternal drinking does not elevate these baseline levels. This may help avoid false-positive determinations when assessing infants born to problem drinking mothers.

A Guinea pig model for the identification of in utero alcohol exposure using fatty acid ethyl esters in neonatal hair.

Measuring levels of fatty acid ethyl esters (FAEE) in hair has been a useful way to discriminate between adult heavy and nondrinkers. Extending the use of FAEE into neonatal hair to objectively identify children exposed to alcohol in utero may revolutionize current methods used to diagnose fetal alcohol spectrum disorder (FASD). Here we confirm for the first time that chronic exposure to alcohol during pregnancy in guinea pigs leads to increased levels of FAEE in both maternal and neonatal hair. The mean cumulative FAEE concentration in exposed maternal samples taken at GD57 was 0.431 ± 0.140 pmol/mg (mean ± SEM); levels observed in corresponding sucrose and water controls were 10-fold lower. Similarly, FAEE concentrations in exposed offspring samples taken at postnatal d 1 (mean cumulative FAEE = 0.491 ± 0.177 pmol/mg) were more than 15-fold higher than control counterparts. Sixty percent of all alcohol-exposed animal samples contained two or more quantifiable FAEE, whereas close to 90% of either water or sucrose control samples did not have more than one quantifiable level of a single FAEE. Results of this study suggest that FAEE in neonatal hair may be useful biomarkers in identifying in utero alcohol exposure and may facilitate the early diagnosis and treatment of FASD.

Demographic and Management Trends Among HIV-Positive Pregnant Women Over 10 Years at One Canadian Urban Hospital

OBJECTIVE There is limited information about changing trends in the management of HIV-positive pregnancies in Canada as Canadian and international guidelines are updated. We reviewed the experience over a 10-year period of one Canadian urban hospital with regard to trends in the demographics and management of HIV-positive pregnant women. METHODS We performed a retrospective chart review of all HIV-positive pregnant women delivering between March 2000 and March 2010. Demographic, pregnancy, and intrapartum data were collected and analyzed. RESULTS During the study period, there were 141 singleton pregnancies in HIV-positive women. The mean age of the cohort was 30.4 years. The number of women seen increased significantly over time (P < 0.001), with 63% of cases in care from 2007 to 2010. Most women were of African descent and had recently immigrated to Canada. There was a statistically significant trend towards increasing numbers of Afro-Caribbean women over the study period (P = 0.03). Only 4% reported illicit drug use in their current pregnancy. Although the majority of women had a known diagnosis of HIV before pregnancy, 30 (22.4%) had the diagnosis made on antepartum testing. Most women were compliant with their highly active antiretroviral therapy (94.3%) and had undetectable viral loads documented at the time of delivery (76.4%). A significant shift towards increased use of protease inhibitor antiretovirals in pregnancy was noted over time (P < 0.001). All neonates received zidovudine after delivery. There were no cases of vertical HIV transmission. CONCLUSION Our review documented increasing numbers of HIV-positive pregnant women over the past 10 years. The majority of these women were healthy with well-managed disease, and had favourable pregnancy outcomes. There were no infected children born during the study period.

Antiretroviral therapy during pregnancy and risk of preterm birth

BACKGROUND Antiretroviral therapy use in pregnancy, and specifically regimens containing protease inhibitors (PIs), has been associated with adverse infant outcomes including preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) infants. However, there are conflicting results in the literature with respect to the degree of risk. These results may be related to demographic factors and confounding of maternal HIV infection and degree of immune suppression. OBJECTIVE The primary objective of our study was to assess the risk of PTB in HIV-positive pregnant women on ART compared to HIV-negative pregnant women. Secondary objectives included: comparing the risks of LBW and SGA infants in HIV-positive women on ART to HIV-negative pregnant women; comparing the risks of PTB, LBW and SGA in HIV-positive women on PI-based regimens compared to HIV-negative women. METHODS A retrospective matched cohort study of 384 women was conducted between 2007 and 2012 comparing outcomes of HIV-positive women on ART to HIV-negative women. Univariate and multivariable logistic regression models were used, adjusting for potential confounding factors, to compare the two groups on adverse infant outcomes. RESULTS Unadjusted odds ratios revealed a >2-fold increase in rates: PTB OR 2.6 [95% CI 1.3-5.1]; LBW OR 2.9 [95% CI 1.4-6.3]; SGA OR 2.5 [95% CI 1.3-4.7]. Once odds ratios were adjusted to account for race (p<0.01), our results were no longer statistically significant as this study was underpowered to detect smaller differences: PTB aOR 1.4 [95% CI 0.5-3.6]; LBW OR 1.9 [95% CI 0.6-5.5]; SGA OR 1.8 [95% CI 0.8-4.6]. CONCLUSION Our preliminary results show an increase in PTB, LBW and SGA but due to lack of power, our adjusted results are not statistically significant. A larger prospective follow-up study is needed to further explore these findings in this population.