The relationship between delivery and the PaO2 /FiO2 ratio in COVID-19: a cohort study.

OBJECTIVE: To study the effect of delivery on the pO2 /FiO2 ratio (P/F ratio) in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and to compare characteristics between delivered and undelivered pregnant patients with COVID-19. DESIGN: Retrospective cohort. SETTING: Four hospitals in Houston, Texas. POPULATION: Pregnant patients admitted to the hospital for COVID-19. METHODS: Among patients with ARDS who were delivered during their hospitalisation for COVID-19, linear mixed models were used to investigate time trends before and after delivery of the P/F ratio. Patient characteristics were compared between patients delivered during their hospitalisation for COVID-19 and those discharged undelivered. MAIN OUTCOME MEASURES: The P/F ratio, age, gestational age, length of stay and severity of illness, RESULTS: Between 4 May 2020 and 26 July 2020, a total of 61 pregnant patients were admitted for COVID-19. Baseline characteristics were similar between the study groups. Delivery occurred in 21 (34%) of patients during their hospitalisation for COVID-19. Delivered patients had more severe disease and were admitted at a later gestational age than patients not delivered. Ten of these 21 patients (48%) were delivered preterm; of these, six were delivered due to complications of COVID-19 and four were delivered for obstetric indications. In patients with ARDS who were delivered (n = 17), the P/F ratio had a negative slope that improved after delivery. CONCLUSIONS: COVID-19-related ARDS in pregnancy requires multidisciplinary care and individualised decision-making, but delivery slows the deterioration of the P/F ratio in these patients. TWEETABLE ABSTRACT: Delivery improves the P/F ratio in COVID-19-related ARDS, though individualised delivery management is needed.

PP179. The influence of prior abortion on rates of gestational hypertension/pre-eclampsia and spontaneous preterm delivery in nulliparous women.

INTRODUCTION: Gestational hypertension/preeclampsia (GH) is clearly a heterogeneous condition of which the pathogenesis could be different in women with various risk factors. Nulliparity is a known risk factor for GH, however a previous abortion (spontaneous or induced) may be associated with a lower risk of GH. OBJECTIVES: To examine the effect of abortion history on rates of GH and spontaneous preterm delivery (SPTD) and in nulliparous women. METHODS: Nulliparous women with an initial prenatal screening at <13 weeks' gestation and a current singleton gestation delivering between 6/2006 and 6/2011 that voluntarily enrolled for risk assessment-case management services were identified from a database of clinical information. Excluded were women reporting a history of both spontaneous (SAB) and induced (IAB) abortions, or with a priori diagnosis of diabetes. Rates of SPTD and GH were compared between women with SAB or IAB history (AB group) and a reference group of primigravid women using Pearson's chi-square, Student's t, Kruskal-Wallis H, and Mann-Whitney U statistics. RESULTS: Of the 75,487 women studied, 5.7% (n=4288) reported a history of IAB and 24.3% (n=18,328) reported a history of SAB. Overall, 301 women (0.4%) experienced a SAB at <20 weeks in the index pregnancy. Of those 75,186 with delivery ⩾20 weeks, the incidence of SPTD was 6.1% in controls vs. 6.0% in the IAB/SAB group (p=0.550). Rates of GH were 10.2% in controls vs. 8.0% (p<0.001) in the AB group despite the AB group having significantly (p<0.001) higher rates of women of African-American race (8.5% vs. 5.5%); age >34years (23.9% vs. 10.0%); and obesity (19.6% vs. 16.6%). For women with >2 AB's significant differences were observed in rates of SPTD vs. controls (8.2% vs. 6.0%, p<0.001), but rates of GH were similar (9.2% vs. 10.2%, p=0.188). (1)p<0.001 vs. 0 AB group. CONCLUSION: In nulliparous women, prior AB is associated with a reduction in risk for GH. Risk for SPTD increases only in those with >2 prior AB's.

Treatment of hypertensive complications in pregnancy.

Hypertension is the most common medical disorder during pregnancy. Approximately 70 percent of women diagnosed with hypertension during pregnancy will have gestational hypertension-preeclampsia. The term gestational hypertension-preeclampsia is used to describe a wide spectrum of patients who may have only mild elevation in blood pressure to those with severe hypertension with various organ dysfunctions (acute gestational hypertension, preeclampsia, eclampsia, and the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). The exact incidence of gestational hypertension-preeclampsia in the United States is unknown. Estimates range from 6% to 8% of all pregnancies. The treatment of hypertensive disorders in pregnancy requires careful assessment of the maternal and fetal conditions. Therapeutic decisions must take into account fetal age, maternal symptoms, tests of fetal well-being, as well as maternal status, in order to ensure the best overall outcome. Treatment of mild gestational hypertension with antihypertensive medications has not been shown to improve outcome, however, in cases of severe disease treatment has been shown to be beneficial. The purpose of this review is to discuss the different treatment modalities used in the hypertensive disorders of pregnancy. Management strategies will not be discussed.

Chronic hypertension in pregnancy.

Hypertension is the most common medical disorder during pregnancy. Chronic hypertension is a serious medical complication in pregnancy with increased maternal and perinatal morbidity and mortality. Those who develop uncontrolled severe hypertension, those with target organ damage, and those who are poorly compliant with prenatal visits are at high risk for poor perinatal outcome. Maternal complications include abruptio placenta, stroke, and superimposed pre-eclampsia. Fetal complications include prematurity, low birth weight, and perinatal death. Careful antepartum, intrapartum and postpartum management of women with high-risk chronic hypertension in pregnancies may reduce morbidity and mortality.

Is the use of insulin lispro safe in pregnancy?

OBJECTIVE: To provide a review of the use and safety of insulin lispro during pregnancy. METHODS: This is a review of the available literature on the use of insulin lispro in pregnancy. A MEDLINE search was performed which included published manuscripts and abstracts in the English language to June 2001. RESULTS: The extensive search revealed that data on insulin lispro use during pregnancy are limited. Most of the reports on the use of insulin lispro during pregnancy demonstrated improvement of glycemic control, an increase in patient satisfaction, decreased hypoglycemic episodes, improved maternal and neonatal outcomes, and no deterioration in retinal status. However, there were two reports where it was suggested that there was an association with the use of insulin lispro in pregnancy and increased risk for the development of congenital anomalies and/or development or progression of diabetic retinopathy. CONCLUSIONS: Preliminary data suggest that insulin lispro does not have adverse maternal or fetal effects during pregnancy in women with diabetes. The use of insulin lispro during pregnancy results in improved glycemic control, fewer hypoglycemic episodes, improved patient satisfaction, improved maternal and neonatal outcomes and no deterioration in retinal status. There is no evidence that the use of insulin lispro during pregnancy results in an increased rate of congenital malformations. A prospective randomized clinical trial is imperative for further evaluation of any possible association with the use of insulin lispro during pregnancy and an increased rate of congenital malformations or change in retinal status.

Use of angiotensin-converting enzyme inhibitors in patients with diabetic nephropathy.

Diabetic nephropathy is the most common cause of end-stage renal failure in the Western world. It accounts for 15-25% of all renal failure in patients requiring chronic dialysis. About 20% of patients with insulin-dependent diabetes and less than 15% of patients with non-insulin-dependent diabetes develop clinically significant nephropathy. The prevalence of diabetic nephropathy in pregnant patients with insulin-dependent diabetes is estimated to be 6%. Angiotensin converting enzyme (ACE) inhibitors are the drug of choice in treating women with diabetic nephropathy. In addition, many of these drugs may be started before conception. Unfortunately, these agents might be fetotoxic when taken during pregnancy. This article reviews the epidemiology and natural history of diabetic nephropathy, discusses the renoprotective effect of ACE inhibitors, reviews the effect of ACE inhibitors on fetomaternal outcome when used prior to and during pregnancy in women with diabetic nephropathy and discusses the new class of drugs, angiotensin II receptor antagonists, in the management of diabetics who have or are prone to developing diabetic nephropathy.

A comparison of various routes and dosages of misoprostol for cervical ripening and the induction of labor.

OBJECTIVE: The purpose of this study was to compare the efficacy of different routes of misoprostol administration for cervical ripening and the induction of labor. STUDY DESIGN: Three hundred thirty women at > or = 32 weeks gestation with a Bishop score < or = 6 and an indication for induction were randomized to 1 of 3 double-blinded groups: (1) 25 microg orally administered misoprostol plus 25 microg vaginally administered misoprostol, (2) orally administered placebo plus 25 microg vaginally administered misoprostol, or (3) 25 microg orally administered misoprostol plus vaginally administered placebo. Doses were repeated every 4 hours until onset of labor or a maximum of 12 doses were given. The primary outcome of the trial was vaginal delivery within 24 hours of the initiation of induction. Secondary outcomes were the time from induction to delivery, need for oxytocin augmentation, mode of delivery, frequency of side effects, and neonatal and maternal outcome. Analysis of variance, chi-square test, and logistic regression were used for analysis. RESULTS: There were no significant differences in maternal characteristics or indications for induction. The percentage of women who achieved vaginal delivery within 24 hours was highest in the vaginally administered misoprostol group: 67% compared with 53% in the oral-plus-vaginal group (P < .05) and 36% in the oral group (P < .05). The median time to vaginal delivery was shorter in the vaginal and oral-plus-vaginal misoprostol groups, 13.5 hours and 14.3 hours, respectively, when compared with 23.9 hours in the oral group (P < .05). The rate of cesarean delivery was lowest in the vaginal misoprostol group (17% compared with 30% in the oral-plus-vaginal group and 32% in the oral group; P < .05). Uterine tachysystole occurred least frequently in the oral misoprostol group (10% compared with 32% in the vaginal group and 34% in the oral-plus-vaginal group; P < .05). Uterine hyperstimulation also occurred least frequently in the oral misopro-stol group (4% compared with 15% in the vaginal group and 22% in the oral-plus-vaginal group; P < .05). CONCLUSION: At the doses studied, induction of labor with vaginally administered misoprostol is more efficacious than either oral-plus-vaginal or oral-only route of administration.

No evidence for lipid peroxidation in severe preeclampsia.

OBJECTIVE: This study was undertaken to address the role of oxidative stress in preeclampsia. STUDY DESIGN: We measured urinary 8,12-iso-iPF(2alpha)-VI, a chemically stable, free-radical catalyzed product, in a case control study of severe preeclampsia nested within the trial of Calcium for Preeclampsia Prevention. Cases included 29 women who developed severe preeclampsia and from whom urine had been obtained 10 to 20 weeks before the diagnosis of preeclampsia, 3 to 9 weeks before, and 1 day before through delivery. Controls did not develop hypertension or proteinuria and were matched to cases by center, gestational age at each of 3 corresponding urine collections, and date of enrollment. RESULTS: Urinary 8,12-iso -iPF(2alpha)-VI did not differ significantly between cases and controls before or at diagnosis of preeclampsia, nor did it vary with gestational age. CONCLUSIONS: These results call into question the importance of oxidative stress in the disease and the biochemical rationale for clinical trials of antioxidants to prevent and treat preeclampsia.

Maternal and fetal inherited thrombophilias are not related to the development of severe preeclampsia.

OBJECTIVE: Thrombotic vascular disease may predispose patients to the development of preeclampsia. The purpose of this study was to determine whether maternal or fetal genotype frequencies of the inherited thrombophilic gene mutations (factor V Leiden, methylenetetrahydrofolate, and prothrombin) are altered in severe preeclampsia. STUDY DESIGN: We performed a prospective cross-sectional study to compare the maternal and fetal genotype frequencies of factor V Leiden, methylenetetrahydrofolate, and prothrombin. One hundred ten patients with severe preeclampsia were matched for gestational age to 97 normotensive pregnancies. Umbilical cord blood was obtained from 92 control patients and 75 patients with preeclampsia. Deoxyribonucleic acid was extracted from leukocytes and polymerase chain reaction was performed. Polymerase chain reaction products were digested with the appropriate restriction enzyme and fractionated by gel electrophoresis. Genotype frequencies were calculated. Statistical significance was determined by the chi(2) test. RESULTS: There were no significant differences between patients with severe preeclampsia and control patients regarding frequency of maternal factor V Leiden G/506/A mutation (4.4% vs 4.3%; P =.96), methylenetetrahydrofolate CC/667/TT mutation (9.6% vs 6.3%; P =.54), or prothrombin G/20210/A mutation (0% vs 1.1%; P =.92). In addition, no statistical difference could be found between fetal thrombophilias and the development of preeclampsia. Findings were similar in both white (n = 47) and African American (n = 63) preeclamptic subsets. Moreover, there was no association between any of the maternal or fetal genetic polymorphisms and the incidence of hemolysis, elevated liver enzymes, and low platelet count syndrome (n = 21); eclampsia (n = 12); or intrauterine growth restriction (n = 9). CONCLUSION: Inherited thrombophilias are not associated with severe preeclampsia.

Chronic hypertension in pregnancy.

Pregnant women with chronic hypertension are at risk for maternal and perinatal morbidity. Careful assessment and management of these patients during pregnancy are the keys to reducing maternal and fetal complications. Antihypertensive treatment should be used in women with high-risk chronic hypertension, whereas drug therapy does not improve pregnancy outcome in women at low risk. Prophylactic low-dose aspirin started early in pregnancy in women with chronic hypertension is not effective in reducing the frequency of superimposed preeclampsia and should be avoided.

Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection.

BACKGROUND: Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery. It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery. METHODS: We screened pregnant women for trichomoniasis by culture of vaginal secretions. We randomly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation. The primary outcome was delivery before 37 weeks of gestation. RESULTS: Between randomization and follow-up, trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group (92.6 percent) and 92 of 260 women with follow-up cultures in the placebo group (35.4 percent). Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group. Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group (19.0 percent) and 31 women in the placebo group (10.7 percent) (relative risk, 1.8; 95 percent confidence interval, 1.2 to 2.7; P=0.004). The difference was attributable primarily to an increase in preterm delivery resulting from spontaneous preterm labor (10.2 percent vs. 3.5 percent; relative risk, 3.0; 95 percent confidence interval, 1.5 to 5.9). CONCLUSIONS: Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery. Routine screening and treatment of asymptomatic pregnant women for this condition cannot be recommended.

Antihypertensive drugs during pregnancy.

Hypertensive disorders are the most common medical disorders during pregnancy. Their presence is associated with increased adverse maternal and fetal outcomes both acute and long-term. Antihypertensive agents are widely used in the treatment of these pregnancies despite absent evidence of either benefits or harms from this therapy. Multiple agents are available and various guidelines recommend different agents and various doses and regimens in the absence of information about the pharmacokinetics, disposition, and pharmacodynamic effects of these drugs in pregnancy. Randomized trials comparing antihypertensive therapy to a placebo are lacking and the available data have not shown clinical benefits because of inadequate sample size to rule out even moderate to large effects on perinatal outcome. In addition, data on teratogenic effects, adverse fetal-neonatal effects, and long-term infant outcome are also scant. These problems resulted from lack of interest and support by the government and pharmaceutical companies to conduct research in pregnant women because of regulatory and medical-legal concerns. Consequently, there is an urgent need to conduct clinical research in this area.

Obstetric antecedents to apparent stillbirth (Apgar score zero at 1 minute only).

OBJECTIVE: To identify antecedent risk factors for the delivery of an infant with an Apgar score of 0 at 1 minute who is subsequently successfully resuscitated. METHODS: Infants born between January 1986 and February 1999 with 1-minute Apgar score of 0 followed by 5-minute Apgar score above 0 were studied. Each eligible infant was randomly matched with two control infants, born in the same year, with 1-minute Apgar score greater than 0. Hospital records of their mothers were reviewed. The variables were compared between the groups by univariate analysis. Those factors demonstrating significant differences were then analyzed by logistic regression. P <.05 was considered statistically significant. RESULTS: Seventy-four of 81,603 infants (0.9:1000 births) born with an Apgar score of 0 at 1 minute only were compared with 148 control babies. Univariate analysis revealed significant differences between study and control group regarding: gestational age, abruptio placentae, preterm premature rupture of membranes, chorioamnionitis, preeclampsia, small-for-gestational age, male gender, bradycardia, and abnormal fetal heart rate (FHR) other than bradycardia, respectively. Logistic regression of these factors found gestational age, bradycardia, and abnormal FHR to be independent risk factors for the delivery of an apparent stillborn infant. After exclusion of FHR criteria, logistic regression found gestational age (odds ratio [OR] 0.8 per week), male gender (OR 2.5), preeclampsia (OR 3.9), and abruptio placentae (OR 13.6) to be independent risk factors for the delivery of an apparent stillborn infant. CONCLUSION: Preterm birth, male gender, preeclampsia, and abruptio placentae are independently associated with an increased risk of apparent stillbirth.