Associations between ambient air pollution and Hypertensive Disorders of Pregnancy.

BACKGROUND: Exposure to ambient air pollution is linked to adverse pregnancy outcomes. Previous reports examining the relationship between ambient air pollution and Hypertensive Disorders of Pregnancy have been inconsistent. OBJECTIVES: We evaluated the effects of ambient air pollution on the odds of Hypertensive Disorder of Pregnancy and whether these associations varied by body mass index (BMI). METHODS: We conducted a retrospective, case-control study among 298 predominantly Hispanic women (136 clinically confirmed cases) who attended the Los Angeles County+University of Southern California Women's and Children's Hospital during 1996-2008. Trimester-specific carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and particulate matter with aerodynamic diameter <10 µm and <2.5 µm (PM10, PM2.5) exposure were estimated based on 24-hour exposure level at residential address. Logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for two standard deviation increase in exposure levels. RESULTS: Exposures to CO and PM2.5 in the 1st trimester were significantly associated with Hypertensive Disorders of Pregnancy, and these associations were modified by BMI. In non-obese women (BMI <30), 1st trimester exposures to PM2.5 and CO were significantly associated with increased odds of Hypertensive Disorder of Pregnancy (ORs per 2-standard deviation increase in PM2.5 (7 µg/m(3)) and CO (1 ppm) exposures were 9.10 [95% CI: 3.33-24.6] and 4.96 [95% CI: 1.85-13.31], respectively). Additionally, there was a significantly positive association between exposure to O3 in the 2nd trimester and Hypertensive Disorder of Pregnancy (OR per 15 ppb=2.05; 95% CI: 1.22-3.46). CONCLUSION: Among non-obese women, 1st trimester exposure to PM2.5 and carbon monoxide are associated with increased odds of Hypertensive Disorder of Pregnancy.

Genetic admixture and risk of hypertensive disorders of pregnancy among Latinas in Los Angeles County.

BACKGROUND: Latinos are a heterogeneous population in terms of demographics, culture, and genetic admixture from three racial groups (white, African, and Native American). This study examines the role of genetic ancestry and environmental risk factors in the risk of hypertensive disorder of pregnancy among Latinas in Los Angeles County. METHODS: Gestational hypertension, preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome cases (n = 125), plus unaffected controls (n = 161), were recruited from Los Angeles County + University of Southern California Women's and Children's Hospital from 1999 through 2008. Diagnoses were confirmed with extensive chart review. Personal information, demographics, and biospecimens were collected from all participants. Ancestry informative markers were used to estimate genetic ancestry proportions. RESULTS: After adjusting for European ancestry and key risk factors, African ancestry was positively associated with hypertensive disorders of pregnancy risk for the highest vs. the lowest quartiles of African ancestry (odds ratio = 2.6 [95% confidence interval = 1.1-6.1]). This association was stronger among women born in Mexico with parents born in Mexico (4.3 [1.4-13]). The results from generalized additive models showed a positive association between joint European/African ancestry and hypertensive disorders of pregnancy risk and an inverse association between Native American ancestry and risk. These associations were stronger among women of Mexican origin. CONCLUSION: Our findings suggest that higher Native American ancestry among Latinas may protect against hypertensive disorders of pregnancy. Further studies are needed to determine whether this protective effect is driven by specific alleles present in this population or by other risk factors that correlate with Native American ancestry.

Risk factors, treatments, and outcomes associated with prolonged hyperemesis gravidarum.

OBJECTIVE: To identify factors associated with prolonged Hyperemesis Gravidarum (HG). STUDY DESIGN: About 395 women completed a survey regarding pre-existing conditions, treatments and outcomes. Responses were compared using two-sided t-tests or the F-test. RESULTS: Participants with prolonged HG are slightly younger and weigh more. Pre-existing factors associated with prolonged HG include allergies and a restrictive diet. Prolonged HG is associated with hematemesis, dizziness, fainting and antiemetic treatment. Following pregnancy, those with prolonged HG reported more posttraumatic stress, motion sickness, muscle weakness and infants with irritability, severe colic and growth restriction. CONCLUSION: Multiple pre-existing conditions and poor maternal and infant outcomes were associated with prolonged HG. The most significant condition prior to pregnancy was allergies suggesting a possible autoimmune component affecting duration of HG. In addition, the most significant lifestyle choice linked to prolonged HG was a restrictive diet. Future research is needed to determine whether a change in diet prior to pregnancy may lead to a shorter duration of HG and its associated outcomes.

Change in paternity and recurrence of hyperemesis gravidarum.

OBJECTIVE: To determine whether change in paternity changes recurrence risk of hyperemesis gravidarum (HG). STUDY DESIGN: Survey data on recurrence of HG was compared between cases who had a paternity change between pregnancies and cases who did not. RESULTS: The percentage of HG pregnancies in women with the same partner for all pregnancies was not significantly different from the percentage of HG pregnancies in women who changed partners for at least one pregnancy (78% vs 71%, p > 0.05). Participants who did and did not change partners between their first and second pregnancies, were asked to rate their first and second pregnancy in regards to symptoms of HG. Neither the ratings nor the change in rating between pregnancies was significantly different between the two groups. CONCLUSION: Women reported HG in over 70% of their pregnancies regardless of a paternity change. Paternal genes expressed through the fetus do not have a significant effect on incidence or recurrence of HG. This study supports a strong maternal genetic factor involved in HG. However, because the recurrence risk is not 100%, other factors play a role. Identification of the predisposing gene(s) and other factors will determine the cause of this poorly understood complication of pregnancy.

A fetal variant in the GCM1 gene is associated with pregnancy induced hypertension in a predominantly hispanic population.

The aim of the study was to determine whether polymorphism in the GCM1 gene is associated with pregnancy induced hypertension (PIH) in a case-control study of mother-baby dyads. Predominantly Hispanic women, ages 15-45, with (n=136) and without (n=169) PIH were recruited. We genotyped four polymorphisms in the GCM1 gene and examined the association with PIH using both logistic regression and likelihood expectation maximization (LEM) to adjust for intra-familial correlation between genotypes. Maternal genotype was not associated with PIH for any polymorphisms examined. Fetal genotype, however, was associated with maternal risk of PIH. Mothers carrying a fetus with ≥1 copy of the minor (C) allele for rs9349655 were less likely to develop PIH than women carrying a fetus with the GG genotype (parity-adjusted OR=0.44, 95% Cl: 0.21, 0.94). The trend of decreasing risk with increasing C alleles was also statistically significant (OR(trend)=0.41 95% Cl: 0.20, 0.85). The minor alleles for the other three SNPs also appear to be associated with protection. Multilocus analyses of fetal genotypes showed that the protective effect of carrying minor alleles at rs9349655 and rs13200319 (non-significant) remained unchanged when adjusting for genotypes at the other loci. However, the apparent (non-significant) effect of rs2816345 and rs2518573 disappeared when adjusting for rs9349655. In conclusion, we found that a fetal GCM1 polymorphism is significantly associated with PIH in a predominantly Hispanic population. These results suggest that GCM1 may represent a fetal-effect gene, where risk to the mother is conferred only through carriage by the fetus.

Recurrence risk of hyperemesis gravidarum.

INTRODUCTION: The purpose of this study is to describe the recurrence risk for hyperemesis gravidarum (HG). METHODS: Women who registered on a Web site sponsored by the Hyperemesis Education and Research Foundation as having had one HG-complicated pregnancy were contacted to follow-up on a subsequent pregnancy. Participants completed an online survey. RESULTS: One hundred women responded. Fifty-seven had become pregnant again, 2 were trying to conceive, 37 were not willing to get pregnant again because of HG, and 4 did not have a second pregnancy for other reasons. Among the 57 women who responded that they had become pregnant again, 81% reported having severe nausea and vomiting in their second pregnancy. Among the women reporting recurrent HG, 98% reported losing weight and taking prescribed medication for HG, 83% reported treatment with intravenous fluids, 20% reported treatment with total parenteral nutrition or nasogastric tube feeding, and 48% reported hospitalization for HG. DISCUSSION: This study demonstrates both a high recurrence rate of HG and a large percentage of women who change reproductive plans because of their experiences with HG.

Favorable outcome of pregnancy with an elective use of epoprostenol and sildenafil in women with severe pulmonary hypertension.

BACKGROUND: Pulmonary hypertension carries significant maternal and fetal risk during pregnancy and the postpartum period. As maternal mortality is high, specific targeted therapy for pulmonary hypertension may be required during pregnancy. CASES: We describe 2 pregnant patients who presented with severe secondary pulmonary arterial hypertension during their last trimester. They were electively treated in the late antepartum and early postpartum periods with sildenafil and intravenous epoprostenol and successfully delivered healthy infants via cesarean section without postpartum complications. CONCLUSION: Although pulmonary hypertension is associated with a risk of maternal mortality and most women are advised against pregnancy, new therapies may improve the outcome of pregnancy in patients with pulmonary hypertension.

Patients with a history of hyperemesis gravidarum have similar symptoms during egg stimulation and develop ovarian hyperstimulation syndrome: case series.

OBJECTIVE: To investigate the symptoms and outcomes of ovarian stimulation in patients with a history of hyperemesis gravidarum. DESIGN: Retrospective case series. SETTING: Research laboratory of a university hospital. PATIENT(S): Participants in an ongoing study on hyperemesis gravidarum that reported ovarian stimulation for gestational surrogacy. INTERVENTION(S): Review of medical records. MAIN OUTCOME MEASURE(S): Pregnancy history, symptoms, estradiol level and mature oocyte number in cases, and nausea and vomiting level reported in surrogate. RESULT(S): Three cases in their early thirties with a history of hyperemesis gravidarum presented with severe nausea and vomiting during ovarian stimulation and ovarian hyperstimulation syndrome. Gestational carriers reported normal nausea and vomiting of pregnancy. CONCLUSION(S): This series provides lessons for in vitro fertilization for cases with a history of hyperemesis gravidarum and their gestational carriers as well as insight into the cause of hyperemesis gravidarum and its potential role in fertility. A link between hyperemesis gravidarum and an evolutionary advantage of increased fertility suggests a novel theory to explain the selection for nausea and vomiting in pregnancy.

Maternal and fetal variants in the TGF-beta3 gene and risk of pregnancy-induced hypertension in a predominantly Latino population.

OBJECTIVE: We sought to determine whether polymorphisms in the transforming growth factor (TGF)-beta3 gene are associated with risk of pregnancy-induced hypertension (PIH) in case-control mother-baby dyads. STUDY DESIGN: Patients (n = 136) and control subjects (n = 169) were recruited from our hospital. We genotyped 4 TGF-beta3 polymorphisms and examined association with PIH using logistic regression, adjusting for parity, maternal age, gestational age at delivery, fetal (or maternal) genotypes for the polymorphism in question, and the 3 other polymorphisms within the TGF-beta3 gene. RESULTS: Only 1 of the TGF-beta3 polymorphisms (rs11466414) was associated with PIH. Mothers who carried a baby with a minor allele were at decreased risk (odds ratio(multi-locus adj), 0.32; 95% confidence interval, 0.14-0.77). Maternal TGF-beta3 variants had no effect on risk of PIH. CONCLUSION: A fetal TGF-beta3 polymorphism (rs11466414) is associated with PIH in a predominantly Hispanic population.

Quantitative detection of EP3-II, III and VI messenger RNA in gravid and non-gravid human myometrium using real-time RT-PCR.

OBJECTIVE: To examine mRNA expression of prostaglandin E2 receptor isoforms EP3-II, III and VI in lower uterine segment myometrium in the non-pregnant and pregnant state using quantitative real-time RT-PCR. METHODS: Myometrial samples were obtained at the time of cesarean delivery or hysterectomy. Pregnant subjects were categorised based on the presence or absence of labour. Labour was defined as regular uterine contractions resulting in cervical change. Quantification for EP3 isoforms II, III and VI mRNA was performed using real-time RT-PCR. RESULTS: There were no differences between non-pregnant and non-labouring pregnant subjects in mRNA expression of EP3-II, III and VI. However, when compared to pregnant subjects not in labour, labouring subjects had a 3.8-fold reduction in EP3-II expression (p < 0.001) and 5.3-fold reduction in EP3-VI expression (p = 0.022). CONCLUSIONS: In human parturition, there is decreased mRNA expression of lower-uterine segment EP3 receptor isoforms II and VI during labour. This may reflect differential relaxation of the lower segment of the uterus allowing dilatation and descent of the fetus.

Sudden fetal death in intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with an increased risk of fetal death. The mechanism of death is unknown. CASES: The first case involved a young primipara with pruritus and a bile acid concentration of 79 mumol/dL. While undergoing fetal heart rate monitoring, the fetus had a prolonged deceleration resulting in intrauterine death. The second case involved a young multipara with cholestasis who received ursodeoxycholic acid. Her bile acid concentration improved to13 micromol/dL. At 34 weeks of gestation, she had uterine contractions with prolonged decelerations resulting in delivery of her fetus with Apgar scores of 0, 0, and 5 at 1, 5, and 10 minutes, respectively. CONCLUSION: Fetal death from intrahepatic cholestasis of pregnancy can be abrupt and not reliably predicted by the characteristics of the fetal heart rate tracing.

Symptoms and pregnancy outcomes associated with extreme weight loss among women with hyperemesis gravidarum.

OBJECTIVE: To report the weight loss and associated symptoms experienced by a large cohort of women with hyperemesis gravidarum (HG). METHODS: Data were obtained from an HG website registry, where women with HG were recruited on-line. Respondents were included if they experienced at least 1 live birth>27 weeks' gestation. Extreme weight loss was defined as a loss of >15% of prepregnancy weight. RESULTS: Of the 819 women surveyed, 214 (26.1%) met criteria for extreme weight loss. These women were twice as likely to be Hispanic or nonwhite. Extreme weight loss (p<0.001) was associated with indicators of the severity of HG, such as hospitalization and use of parenteral nutrition, and with multiple symptoms during pregnancy, such as gallbladder and liver dysfunction, renal failure, and retinal hemorrhage. Among all women surveyed, 22.0% reported that symptoms lasted throughout pregnancy; this finding was nearly twice as likely among women with extreme weight Loss: 63 of 214 (29.4%) vs. 117 of 605 (19.3%) (OR=1.73, 95% CI 1.2-2.5, p=0.003). For some women, symptoms continued postpartum and included food aversions, muscle pain, nausea, and posttraumatic stress. Approximately 16% of babies were born prematurely, and 8% reportedly weighed <2500 g. Among women with extreme weight loss, 9.3% reported having a child with a behavioral disorder. CONCLUSIONS: Extreme weight loss is common among women with HG, suggesting that HG is a form of prolonged starvation in pregnancy and that the long-term effects of this condition on women and their offspring warrant further investigation.

Free T4 immunoassays are flawed during pregnancy.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic accuracies of 2 free thyroxine immunoassays during pregnancy. STUDY DESIGN: Serum was collected from healthy, thyroid peroxidase antibody-negative women during each trimester and nonpregnant controls. Thyrotropin, total T4 (TT4), free T4 index (FT4I), and 2 different FT4 immunoassays were studied. RESULTS: As expected, TT4 was elevated in all 3 trimesters compared to controls (P < .001). FT4I was elevated in the 1st trimester as compared with controls (P < .05) and returned to the nonpregnant range in the 2nd and 3rd trimesters. In contrast, 1st trimester FT4 immunoassay values were either comparable or lower than controls and by the 2nd and 3rd trimesters had decreased to approximately 65% of controls. CONCLUSION: Neither FT4 immunoassay accurately reflects established free T4 changes during pregnancy. TT4 and the FT4I retained an appropriate inverse relationship with TSH throughout pregnancy and appear to provide a more reliable free T4 estimate.

Effect of thyroid peroxidase antibodies on thyroid-stimulating hormone reference limits in a primarily Latina population.

The aim of the paper is to determine the prevalence of thyroid peroxidase antibodies (TPOAb) and assess its effect on the thyroid-stimulating hormone (TSH) reference range during pregnancy in a primarily Latina population. Serum samples were collected from healthy pregnant women and non-pregnant controls. TSH reference ranges were calculated when TPOAb-positive patients were either included or excluded. A total of 134 pregnant women and 107 non-pregnant controls were recruited. Positive TPOAb titres were found in 23 (17.2%) of the 134 pregnant women, and in 14 (13.1%) of the 107 non-pregnant controls. When the TPOAb-positive women were included in the TSH analysis, the upper reference limit using two different methods was consistently higher: 0-2.2 fold in the non-pregnant women, 2.01-2.78 fold in the first trimester, 3.18-4.7 fold in the second and 1.05-1.42 fold in the third. The lower TSH reference limit was not affected by the inclusion of TPOAb-positive subjects. In conclusion, inclusion of TPOAb-positive patients results in higher upper reference limits during pregnancy.

Hyperemesis gravidarum.

Hyperemesis gravidarum occurs in 0.3% to 2% of pregnant women, although populations with significantly higher rates have been reported. In clinical practice, hyperemesis gravidarum is identified by otherwise unexplained intractable vomiting and dehydration. This article discusses the causes, presentation, diagnosis, and management of hyperemesis gravidarum.

AKR1C1 and SRD5A1 messenger RNA expression at term in the human myometrium and chorioamniotic membranes.

We sought to determine relative mRNA expression of AKR1C1 and SRD5A1, which respectively encode for the key progesterone metabolizing enzymes, 20alpha-hydroxysteroid dehydrogenase and 5alpha-reductase type 1, in the myometrium and chorioamniotic membranes during human spontaneous or induced labor and nonlabor. Quantitative real-time reverse-transcriptase polymerase chain reaction was used to compare relative mRNA expression of AKR1C1 and SRD5A1 in the myometrium and chorioamniotic membranes from 20 subjects during three different states of labor: not in labor ( N = 10), spontaneous labor ( N = 5), or induced labor ( N = 5). Labor was defined as regular uterine contractions that resulted in cervical dilation. Myometrial AKR1C1 mRNA expression was significantly greater in spontaneously laboring subjects compared with those not in labor (2.4-fold [1.97 to 2.98], P = 0.02). There was no difference in myometrial AKR1C1 mRNA expression between those with induced labor compared with those not in labor. Regardless of labor status, no differences were observed in the chorioamniotic membrane AKR1C1 mRNA expression between the groups. SRD5A1 mRNA expression was significantly lower in the membranes of both laboring groups when compared with those not in labor (spontaneous: 0.10-fold [0.06 to 0.18], P = 0.007; induced: 0.09-fold [0.03 to 0.25], P = 0.013). Regardless of labor status, there was no difference in SRD5A1 mRNA expression in the myometrium. Our study demonstrated tissue-specific changes in progesterone metabolizing enzyme mRNA expression in human intrauterine tissue at term associated with labor status. These observed changes in mRNA expression may have important implications for progesterone metabolism at those specific sites and thereby may differentially regulate the tissue-specific progesterone concentration and/or the level of specific progesterone metabolites.

Pregnancy outcomes during an era of aggressive management for intrahepatic cholestasis of pregnancy.

Our objective was to examine whether delivery at 37 weeks of gestation alters adverse pregnancy outcomes in Latina patients with intrahepatic cholestasis of pregnancy (ICP). We conducted a retrospective chart review of Latina patients who delivered at our institution coded with ICP between 2000 and 2007. During this time period it was our practice to offer delivery to patients with ICP at 37 weeks of gestation. Subjects were classified into three groups according to total bile acid (TBA) concentration: < 20 micromol/L (mild ICP), > or = 20 micromol/L and < 40 micromol/L (moderate ICP), and > or = 40 micromol/L (severe ICP). Meconium passage was observed in no births in patients with mild IC, but was found in 18% of deliveries with moderate/severe ICP. The risk of meconium passage increased linearly, with a 19.7% increased risk for each 10 mumol/L increase in TBA concentration ( P = 0.001). There was no association with higher TBA concentration and other adverse outcomes. There was no difference in adverse outcomes between moderate and severe ICP. We concluded that in our Latina population with ICP, an association existed between meconium passage and moderate/severe ICP. Delivering at 37 weeks was associated with a low risk of adverse outcomes due to ICP among all patients, including those with higher TBA concentrations.

Secular trends in the treatment of hyperemesis gravidarum.

The purpose of this study was to describe the treatment of women with hyperemesis gravidarum (HG). Women with HG pregnancies of at least 27 weeks duration occurring between 1985 and 2004 described their treatment on an HG website from 2003 to 2005. The usage and effectiveness of > 20 treatment options were reported by 765 women for 1193 pregnancies. The women who used intravenous (IV) hydration, serotonin inhibitors, and parenteral nutrition (PN) reported the highest rates of effectiveness, with 84%, 83%, and 79% reporting that these respective treatments may have contributed to decreased nausea/vomiting. The use of conventional treatments increased from 20 to 30% to > 60% between 1985 and 1989 and 2000 and 2004; serotonin inhibitor use increased to 55% after its introduction in the 1990s. Over the past 20 years, multiple treatments have been used for women with HG, with a trend toward treatment with reportedly more effective modalities, such as IV hydration and serotonin inhibitors.

Elective pregnancy termination in a large cohort of women with hyperemesis gravidarum.

BACKGROUND: This study was conducted to describe characteristics of women who terminated their pregnancies secondary to hyperemesis gravidarum (HG). STUDY DESIGN: Data were obtained from a survey provided on an HG Web site from 2003 to 2005. RESULTS: Of 808 women who completed the survey, 123 (15.2%) had at least one termination due to HG, and 49 (6.1%) had multiple terminations. Prominent reasons given for the terminations were inability to care for the family and self (66.7%), fear that they or their baby could die (51.2%), or that the baby would be abnormal (22.0%). These same women were three times as likely to state that their health care providers were uncaring or did not understand how sick they were [64/123 (52.0%) vs. 168/685 (24.5%), odds ratio 3.34 (95% CI 2.21-5.05), p<.001]. CONCLUSION: These data suggest that the physical and psychological burden of HG has been underestimated, and that further education within the medical community may be warranted.

Massive subchorionic hematoma associated with enoxaparin.

BACKGROUND: The use of low-molecular-weight heparins is increasing for the prevention of thromboembolism in pregnancy. Subchorionic hematoma as a complication of anticoagulation therapy is rarely reported. CASE: A persistent, massive subchorionic hematoma was diagnosed in a pregnant patient with atrial fibrillation and mitral stenosis. Enoxaparin was administered to maintain her trough anti-Xa level 0.5 units/mL or higher. The patient's peak anti-Xa levels never exceeded 1.05 units/mL. The patient underwent cesarean delivery at 34 6/7 weeks of gestation for preterm premature rupture of membranes. CONCLUSION: Subchorionic hematoma is a potentially serious complication that can occur in pregnant patients receiving enoxaparin for the prevention of thromboembolism.