A Ten-Year Review of Antenatal Complications and Pregnancy Outcomes Among HIV-Positive Pregnant Women.

OBJECTIVE: To review the incidence of antenatal complications among a cohort of HIV-positive pregnant women over a 10-year period. METHODS: A retrospective review was performed of all HIV-positive pregnant women receiving multidisciplinary prenatal care at an urban tertiary care centre from March 2000 to March 2010. Collected data included the presence of additional infectious or medical conditions, genetic screening information, and the presence or absence of antenatal complications. RESULTS: One hundred and forty-two singleton pregnancies during the study period were identified. Almost 95% of women were taking combination antiretroviral therapy during pregnancy, and greater than 90% had viral loads less than 1000 copies/ml at delivery. The presence of co-infections was low. Forty-one women (29%) had other medical comorbidities. Genetic screening occurred in 104 pregnancies (73%); 4% were abnormal screens. Rates of any hypertension, gestational diabetes, and fetal growth restriction were all low. Thirty-two percent of women were colonized with group B streptococcus. CONCLUSION: This study adds strength to the argument that good outcomes can be achieved for HIV-positive pregnant women with good access to both prenatal and HIV care, and appropriate management. Women with HIV should be optimally cared for in advance of and during pregnancy in order to maximize the likelihood of good pregnancy outcomes.

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.

Objectif : Nous ne disposons que de données limitées au sujet de l'évolution (au fur et à mesure que sont mises à jour les lignes directrices canadiennes et internationales) des tendances pour ce qui est de la prise en charge des grossesses séropositives pour le VIH au Canada. Nous avons analysé, sur une période de 10 ans, l'expérience d'un hôpital urbain canadien en ce qui concerne les tendances en matière de caractéristiques démographiques et de prise en charge des femmes enceintes séropositives pour le VIH. Méthodes : Nous avons mené une analyse rétrospective des dossiers de toutes les femmes enceintes séropositives pour le VIH ayant accouché dans cet hôpital entre mars 2000 et mars 2010. Les données liées aux caractéristiques démographiques, à la grossesse et à la période intrapartum ont été recueillies et analysées. Résultats : Au cours de la période d'étude, nous avons recensé 141 grossesses monofœtales chez des femmes séropositives pour le VIH. L'âge moyen au sein de cette cohorte était de 30,4 ans. Le nombre des femmes se présentant à cet hôpital a connu une hausse considérable avec le temps (P < 0,001), 63 % des cas étudiés ayant été pris en charge entre 2007 et 2010. La plupart des femmes étaient d'origine africaine et avaient récemment immigré au Canada. Nous avons constaté une tendance significative sur le plan statistique indiquant une hausse régulière du nombre de femmes d'origine afro-antillaise pendant la période d'étude (P = 0,03). Seulement 4 % des femmes ont signalé avoir consommé des drogues illicites pendant la grossesse alors en cours. Bien que la majorité des femmes aient présenté un diagnostic connu de VIH avant la grossesse, 30 d'entre elles (22,4 %) ont obtenu ce diagnostic à la suite d'un dépistage antepartum. La plupart des femmes faisaient preuve d'observance en ce qui concerne leur traitement antirétroviral hautement actif (94,3 %) et leurs charges virales étaient indétectables au moment de l'accouchement (76,4 %). Une tendance considérable indiquant un accroissement de l'utilisation d'inhibiteurs de protéase (antirétroviraux) pendant la grossesse a été constatée avec le temps (P < 0,001). Tous les nouveau-nés ont reçu de la zidovudine après l'accouchement. Aucun cas de transmission verticale du VIH n'a été constaté. Conclusion : Notre analyse a documenté une croissance du nombre de femmes enceintes séropositives pour le VIH au cours des 10 dernières années. La majorité de ces femmes étaient en santé et leur maladie était bien prise en charge; de plus, elles ont obtenu des issues de grossesse favorables. Aucun enfant infecté n'est né au cours de la période d'étude.

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.

Diagnosis of fetal alcohol spectrum disorder (FASD): fatty acid ethyl esters and neonatal hair analysis.

Measuring levels of fatty acid ethyl esters (FAEE) in hair has been recently shown to discriminate between adult heavy and non-drinkers. Here, we review the potential of neonatal FAEE measurement in detecting infants exposed to alcohol in utero by outlining current progress in the development of a neonatal hair test for the diagnosis of fetal alcohol spectrum disorder (FASD). Developing a reproducible, accurate and predictable hair test for FAEE measurements in neonatal hair may prove to be a powerful tool in the detection of in utero alcohol exposure which is needed for the diagnosis of FASD. Such a neonatal hair test can revolutionize current FASD diagnostic methodology by providing early diagnosis, allowing intervention and treatment at stages where the adverse effects of alcohol can still be mitigated.

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.

Recent developments in meconium and hair testing methods for the confirmation of gestational exposures to alcohol and tobacco smoke.

The use of alcohol and tobacco is prevalent among pregnant women despite the well-known adverse effects of these substances imposed on the developing fetus and immense public health education efforts. Confirmation of gestational exposures to these compounds have relied mostly on maternal self-reporting, which is often underestimated because of guilt, embarrassment, and fear of punitive action. The presence of fatty acid ethyl esters in various biological matrices as a result of alcohol consumption initiated the development of neonatal screening tests for these emerging biological markers in meconium and hair. The levels of nicotine and cotinine in hair have long been used as objective indices for the quantification of exposure to active and passive smoking. Maternal segmental hair analysis in the study of pharmacokinetic changes in nicotine metabolism in the obstetric population is a novel application of this traditional analytical method. The latest developments and novel applications of meconium and hair testing for the confirmation of prenatal alcohol and tobacco exposure are discussed in this review.

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.

Fatty acid ethyl esters (FAEE); comparative accumulation in human and guinea pig hair as a biomarker for prenatal alcohol exposure.

AIMS: To compare the incorporation rate (ICR) of fatty acid ethyl esters (FAEE) in hair between guinea pigs and humans, and to assess the relationship between ethanol exposure and FAEE concentrations in hair. METHODS: Published data from pregnant guinea pigs, including maximum blood ethanol concentration (BEC), dosage regimen, and total hair FAEE concentration, were compared with published data from alcoholic patients, where dose of ethanol consumed and total hair FAEE concentration were reported. Mean values of ethanol Vmax for pregnant guinea pigs and humans were obtained from published data (26.2 and 24 mg/dl/h, respectively). RESULTS: Total and individual FAEE ICRs, defined as the ratio of hair FAEE to the area under the BEC-time curve (total systemic ethanol exposure), were found to be on average an order of magnitude lower in the guinea pig than in the human. The profiles of ester incorporation also differed slightly between species, with ethyl stearate being highly incorporated in guinea pig hair and less so in human hair. The results may reflect in the human greater FAEE production, greater FAEE deposition in hair, slower FAEE catabolism, differential sebum production and composition, or a combination thereof. Also, ethyl oleate was found to correlate with total systemic ethanol exposure for both guinea pigs and humans, correlation coefficients equalling 0.67 (P < 0.05) and 0.49 (P < 0.05), respectively. No other ethyl esters, nor total FAEE, were found to correlate with systemic ethanol exposure. CONCLUSION: When extrapolating FAEE concentrations in hair from guinea pigs to humans, an order of magnitude difference should be considered, with humans incorporating more FAEE per unit of ethanol exposure. Also, the results suggest caution should be taken when interpreting values of single esters because of their differential incorporation among species. Lastly, our findings suggest ethyl oleate may be of keen interest in FAEE hair analysis, particularly across species.

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.

Fetal safety of loratadine use in the first trimester of pregnancy: a multicenter study.

BACKGROUND: Women in their childbearing years often require drug therapy for allergic conditions. Loratadine, a newer nonsedating antihistamine, is often used because of its preferred side effect profile. To date no published data exist on the safety of loratadine use in pregnancy. OBJECTIVE: We sought to determine whether the use of loratadine in the first trimester of pregnancy was associated with an increased risk for major malformations. Secondary outcomes included rates of miscarriage, birth weights, and gestational age at delivery. METHODS: All women were prospectively enrolled from 4 participating centers. Detailed maternal medical history and drug exposures were collected at intake, whereas pregnancy complications and outcomes were collected at follow-up. A group of unexposed control subjects were recruited and followed up in a similar manner. RESULTS: This report includes follow-up on 161 loratadine exposed pregnancies and an equal number of unexposed control subjects. Maternal characteristics (age, pregnancy history, alcohol consumption, and smoking habits) were not different between the 2 groups. There were 5 malformations observed in the exposed group and 6 in the control group, which was not significantly different (P =.9) Similarly, the live birth rate, gestational age at delivery, and birth weights were not different between the 2 groups. CONCLUSION: These results suggest that loratadine use in pregnancy is not associated with a large risk for major malformations. Further studies are warranted to confirm these findings and to increase study power.