Platelet Counts during Pregnancy.

BACKGROUND: Platelet counts of less than 150,000 per cubic millimeter during uncomplicated pregnancies are described as gestational thrombocytopenia if no alternative cause is identified. Platelet counts may be even lower in women with pregnancy-related complications. However, the occurrence and severity of thrombocytopenia throughout pregnancy are not defined. METHODS: We evaluated platelet counts throughout pregnancy in women who delivered at Oklahoma University Medical Center between 2011 and 2014. These platelet counts were compared with those of nonpregnant women who were included in the National Health and Nutrition Examination Survey from 1999 through 2012. RESULTS: Among the 15,723 deliveries that occurred during the study period, 7351 women had sufficient data for our analyses. Of these women, 4568 had uncomplicated pregnancies, 2586 had pregnancy-related complications, and 197 had preexisting disorders associated with thrombocytopenia. Among the women who had uncomplicated pregnancies, the mean platelet count in the first trimester (mean gestation, 8.7 weeks) was 251,000 per cubic millimeter, which was lower than the mean platelet count in the 8885 nonpregnant women (273,000 per cubic millimeter) (P<0.001). At the time of delivery, 9.9% of the women with uncomplicated pregnancies had a platelet count below 150,000 per cubic millimeter. During the course of the uncomplicated pregnancies and deliveries, only 45 women (1.0%) had a platelet count below 100,000 per cubic millimeter. Among the 12 women with uncomplicated pregnancies who had a platelet count below 80,000 per cubic millimeter, only 5 (0.1%, among whom the range of platelet counts was 62,000 to 78,000 per cubic millimeter; median, 65,000) were identified by medical record review as having no alternative cause for the thrombocytopenia. Platelet counts of less than 150,000 per cubic millimeter at the time of delivery were more common among women who had pregnancy-related complications than among women who had uncomplicated pregnancies (11.9% vs. 9.9%, P=0.01). Throughout their pregnancies and deliveries, 59 women (2.3%) with pregnancy-related complications had a platelet count below 100,000 per cubic millimeter, and 31 (1.2%) had a platelet count below 80,000 per cubic millimeter. CONCLUSIONS: Mean platelet counts decreased during pregnancy in all the women, beginning in the first trimester. In women who have a platelet count of less than 100,000 per cubic millimeter, a cause other than pregnancy or its complications should be considered. (Funded by the National Heart, Lung, and Blood Institute.).

A randomized controlled trial of intramuscular versus vaginal progesterone for the prevention of recurrent preterm birth.

OBJECTIVE: To compare the efficacy of intramuscular hydroxyprogesterone caproate with that of vaginal progesterone for prevention of recurrent preterm birth. METHODS: A prospective randomized controlled trial was conducted at a US tertiary care center between June 1, 2007, and April 30, 2010. Women with singleton pregnancies (16-20 weeks) and a history of spontaneous preterm birth were randomly allocated using a computer-generated randomization sequence to receive either a weekly intramuscular injection of hydroxyprogesterone caproate (250 mg) or a daily vaginal progesterone suppository (100 mg). Participants, investigators, and assessors were not masked to group assignment. The primary outcome was birth before 37 weeks of pregnancy. Per-protocol analyses were performed: participants who completed follow-up were included. RESULTS: Analyses included 66 women given intramuscular progesterone and 79 given vaginal progesterone. Delivery before 37 weeks was recorded among 29 (43.9%) women in the intramuscular progesterone group and 30 (37.9%) in the vaginal progesterone group (P=0.50). CONCLUSION: Weekly intramuscular administration of hydroxyprogesterone caproate and daily vaginal administration of a progesterone suppository exhibited similar efficacy in reducing the rate of recurrent preterm birth. ClinicalTrials.gov: NCT00579553.

Fetal epicardial fat thickness in diabetic and non-diabetic pregnancies: A retrospective cross-sectional study.

OBJECTIVE: To evaluate fetal epicardial fat thickness (EFT) in diabetic and control pregnancies. METHODS: A retrospective cross-sectional study was performed in which fetal EFT was measured in the second trimester in 28 diabetics and 28 non-diabetic patients. Maternal BMI, estimated fetal weight, birth weight, fetal abdominal circumference, and subcutaneous fat thickness were also collected. Statistical analysis was carried out by means of chi-square, Wilcoxon rank-sum test, Student's T test, and linear regression as appropriate. RESULTS: EFT was significantly higher in diabetic (1.43 mm) vs. control fetuses (1.16 mm), P = 0.02. This relationship remained significant when controlling for covariates. CONCLUSIONS: EFT was higher in fetuses of diabetic mothers vs. fetuses from controls. If confirmed in prospective studies, this may represent a novel marker for altered fetal metabolism due to maternal diabetes.

Immediate compared with delayed cord clamping in the preterm neonate: a randomized controlled trial.

OBJECTIVE: The comparative risks and benefits of early compared with delayed cord clamping in the preterm neonate remain unclear. Our objective was to evaluate the short-term effects of delayed clamping of the umbilical cord in preterm neonates. METHODS: We conducted a randomized controlled trial comparing immediate with delayed cord clamping among preterm neonates born between 24 and 34 weeks of gestation. The primary study outcome was the need for blood transfusion. To detect a 33% reduction in this outcome (from 65 to 43.5%) with a two-tailed α of 0.5 and ß of 0.8 required 178 patients equally divided into two groups. RESULTS: A total of 200 women were randomized, 99 to the delayed and 101 to the immediate clamp group. The groups were similar with respect to baseline characteristics. The mean gestational age at delivery was 30.8±3.1 weeks in the delayed compared with 30.7±2.8 weeks in the immediate clamp group (P=.64). There was no statistically significant difference between groups with regard to the need for blood transfusion: 25 of 99 (25.3%) in the delayed cord clamp group received one or more blood transfusion compared with 24 of 101 (23.7%) in the immediate clamp group (P=.8). The rates of various neonatal outcomes including respiratory distress syndrome, periventricular leukomalacia, necrotizing enterocolitis, anemia of prematurity, and neonatal morality did not differ significantly between the groups. However, the mean initial hemoglobin (17.4±2.5 compared with 16.3±2.3 g/dL, P=.001) and hematocrit (51.3±7.3 compared with 47.4±7.3, P=.001) was significantly higher in the delayed group. In the delayed clamp group, 11.1% (11/99) of neonates had intraventricular hemorrhage compared with 19.8% (20/101) in the immediate clamp group (P=.09). CONCLUSION: Delayed cord clamping for 30 seconds did not decrease the need for blood transfusion among preterm neonates. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00579839.

Multiple myeloma presenting as hypercalcemic pancreatitis during pregnancy.

BACKGROUND: Multiple myeloma is typically a disease found in older women and is a rare diagnosis in pregnancy. CASE: A 22-year-old woman, gravida 1 para 0, at 32 3/7 weeks of gestation presented with nausea, vomiting, and rib and back pain. She was hypertensive, anemic, thrombocytopenic, and in acute renal insufficiency, with hypercalcemia and laboratory parameters indicative of pancreatitis. She was admitted to the obstetric intensive care unit with working diagnoses of preeclampsia, pancreatitis, nephrolithiasis, and renal insufficiency. She ultimately was delivered because of declining clinical status, and multiple myeloma eventually was diagnosed as the underlying cause of her myriad of problems. CONCLUSION: Multiple myeloma is unusual during pregnancy. However, in patients with significant and unexplained hypercalcemia, malignancy should remain high on the differential diagnosis.

Pregnancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura.

UNLABELLED: Pregnancy may precipitate acute episodes of thrombotic thrombocytopenic purpura (TTP), but pregnancy outcomes in women who have recovered from acquired TTP are not well documented. We analyzed pregnancy outcomes following recovery from TTP associated with acquired, severe ADAMTS13 deficiency (ADAMTS13 activity <10%) in women enrolled in the Oklahoma TTP-HUS Registry from 1995 to 2012. We also systematically searched for published reports on outcomes of pregnancies following recovery from TTP associated with acquired, severe ADAMTS13 deficiency. Ten women in the Oklahoma Registry had 16 subsequent pregnancies from 1999 to 2013. Two women had recurrent TTP, which occurred 9 and 29 days postpartum. Five of 16 pregnancies (31%, 95% confidence interval, 11%-59%) in 3 women were complicated by preeclampsia, a frequency greater than US population estimates (2.1%-3.2%). Thirteen (81%) pregnancies resulted in normal children. The literature search identified 382 articles. Only 6 articles reported pregnancies in women who had recovered from TTP associated with acquired, severe ADAMTS13 deficiency, describing 10 pregnancies in 8 women. TTP recurred in 6 pregnancies. CONCLUSIONS: With prospective complete follow-up, recurrent TTP complicating subsequent pregnancies in Oklahoma patients is uncommon, but the occurrence of preeclampsia may be increased. Most pregnancies following recovery from TTP in Oklahoma patients result in normal children.

Local anesthesia and pain perception during amniocentesis: a randomized double blind placebo-controlled trial.

OBJECTIVE: To determine the effect of local anesthesia on the maternal pain perception from amniocentesis. METHODS: We conducted a randomized double blind placebo controlled trial comparing use of local anesthesia (1% lidocaine) with placebo with regards to maternal perception of pain among women undergoing genetic amniocentesis. The primary outcome was the intensity of perceived maternal pain as measured by the Visual Analogue Scale (VAS) as well a 101 point Numerical Rating Scale. RESULTS: Seventy six women participated in the trial. 36 (47.4%) women were randomized to lidocaine, whereas 40 (52.6%) were randomized to placebo. There were no statistically significant differences between the groups in terms of baseline sociodemographic and clinical characteristics. However, pain perception as characterized by the median 9.5 (2.1-21.0) VSA scores was significantly lower among women in the lidocaine group compared with among women in the placebo group [18.4 (12.9-31.3), P = 0.005]. Similarly the mean VSA scores was significantly lower in the lidocaine group (P = 0.02). A trend toward lower scores was also observed when maternal pain perception was measured by the Numerical Rating Scale. CONCLUSION: Local anesthetic lidocaine significantly lowers maternal perceived pain during genetic amniocentesis.

Unsuccessful trial of labor in women with and without previous cesarean delivery.

OBJECTIVE: To compare maternal and neonatal outcomes after unsuccessful labor in women with and those without prior cesarean delivery. METHODS: This was a retrospective cohort study of all women in labor delivered by cesarean section (CS) from November 2004 through December 2006. The study population was dichotomized by previous CS and compared for various maternal and neonatal outcomes. Student t-test, χ² and Fisher exact tests were used for analysis. RESULTS: There was a significantly higher rate of symptomatic uterine rupture [3/100 (3%) vs. 0/449 (0%), p = 0.006], asymptomatic uterine scar dehiscence [6/100 (6%) vs. 0/449 (0%), p = 0.0001], and bladder injury [2/100 (2%) vs. 0/100 (0%), p = 0.001], among women with prior cesarean delivery compared to those without. The rate of respiratory distress syndrome [(6/100) (6%) vs. 10/449 (2.2%), p = 0.05] and meconium aspiration [4/100 (4%) vs. 2/449 (0.4%), p = 0.01] was also significantly higher among neonates of women with prior cesarean delivery. However, the rate of endomyometritis [3/100 (3%) vs. 50/449 (11.1%), p = 0.009] and febrile morbidity [17/100 (17%) vs. 144/449 (32.1%), p  = 0.003] was significantly lower among women with prior cesarean delivery compared to those without prior cesarean birth. CONCLUSIONS: Compared to laboring women without previous cesarean delivery, women with previous cesarean delivery have increased maternal and neonatal morbidity. Febrile morbidity was, however, lower among women with previous cesarean delivery. These differential findings should further inform our perinatal counseling of women contemplating trial of labor after a previous cesarean delivery.

A comparison of meningococcal carriage by pregnancy status.

Neisseria meningitidis is the second leading cause of invasive meningitis. A prerequisite for infection is colonization of the nasopharynx, and asymptomatic carrier rates are widely reported in the range of 10-15%. Recent reports have indicated an increased likelihood that a pediatric admission for Neisseria meningitidis will have a mother who is pregnant in the home. We hypothesized that this association may relate to immunologic changes in pregnancy leading to higher carrier rates.We compared the carrier status by performing nasopharyngeal swabs for Neisseria meningitidis in 100 pregnant and 99 non-pregnant women.Average age of the participants was 28.9 +/- 6.7 years. The average gestational age at specimen collection was 27.5 +/- 9.4 weeks. Non pregnant women were significantly more likely to use tobacco (38% vs 24%, p < 0.0001). In the entire 199 patients, only one pregnant patient tested positive for Neisseria meningitidis (0.5%; 95% CI: 0.01%-2.8%).The meningococcal carrier rate in our population is well below what is widely reported in the literature. Assuming a 1% carrier rate in the pregnant group and a 0.5% carrier rate in the non pregnant group, 4,763 patients would be required to detect a difference of this magnitude, given 80% power and an alpha of 0.05.

Evaluation of outcomes after transabdominal cervicoisthmic cerclage.

PURPOSE: To evaluate maternal and neonatal outcomes after transabdominal cerclage. METHODS: Retrospective analysis of 15 patients receiving transabdominal cerclage. Using the patient's prior pregnancy as her own control, we assessed the effect of this procedure on gestational age and neonatal survival. RESULTS: All patients had experienced a prior pregnancy loss. Twelve out of the 15 patients (80%) had at least one prior failed vaginal cerclage. The median gestational age at surgery was 14 (range 12-16) weeks. There was one case of surgical site infection. After cerclage, the proportion of women delivered beyond 32 weeks was significantly higher [11/15 (73.3%) vs. 1/15 (6.7%), P=0.0016], as was neonatal survival [12/15 (80%) vs. 1/15 (6.7%), P=0.0009]. CONCLUSIONS: While transabdominal cerclage is a major surgical procedure, subsequent pregnancy outcomes were improved.

The effect of digital cervical examination on group B streptococcal culture.

OBJECTIVE: We sought to evaluate whether group B streptococcus (GBS) detection is altered by the digital cervical examination. STUDY DESIGN: A total of 302 women undergoing the clinical GBS culture had a digital cervical examination and a repeated GBS culture. Statistical comparison of pre-post culture results were performed with kappa and McNemar tests. RESULTS: The clinical prevalence of GBS was 19.5%. Discordant results were seen in 30/302 (9.9%) paired cultures (kappa = 0.68; 95% confidence interval, 0.568-0.783). An initially negative GBS culture result was positive on repeated testing in 13/243 (5.3%) pairs. Initially positive cultures were negative on repeated testing in 17/59 (28.8%) pairs. Patients with discordant results had similar characteristics as the remainder of the study group. Given the observed proportion of discordant results (9.9%), the study had 80% power to detect a 5% difference between discordant pairs. CONCLUSION: Paired GBS cultures showed a good level of agreement. The 28.8% rate of positive cultures becoming negative is clinically concerning and warrants further study.

Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length.

OBJECTIVE: The objective of the study was to assess cerclage to prevent recurrent preterm birth in women with short cervix. STUDY DESIGN: Women with prior spontaneous preterm birth less than 34 weeks were screened for short cervix and randomly assigned to cerclage if cervical length was less than 25 mm. RESULTS: Of 1014 women screened, 302 were randomized; 42% of women not assigned and 32% of those assigned to cerclage delivered less than 35 weeks (P = .09). In planned analyses, birth less than 24 weeks (P = .03) and perinatal mortality (P = .046) were less frequent in the cerclage group. There was a significant interaction between cervical length and cerclage. Birth less than 35 weeks (P = .006) was reduced in the less than 15 mm stratum with a null effect in the 15-24 mm stratum. CONCLUSION: In women with a prior spontaneous preterm birth less than 34 weeks and cervical length less than 25 mm, cerclage reduced previable birth and perinatal mortality but did not prevent birth less than 35 weeks, unless cervical length was less than 15 mm.

Resolution of hydrops secondary to cytomegalovirus after maternal and fetal treatment with human cytomegalovirus hyperimmune globulin.

BACKGROUND: Congenital cytomegalovirus (CMV) is a common infection with limited treatment options. Vertical transmission can lead to fetal death or long-term neurologic injury. We present a case wherein fetal hydrops resolved after maternal and fetal intravenous administration of CMV hyperimmune globulin. CASE: A 20-year-old gravida 3, para 0 was referred for Level II ultrasonography secondary to hydrops fetalis. Amniocentesis demonstrated in utero CMV infection. Resolution of hydrops occurred after the administration of CMV hyperimmune globulin to the patient and then to her fetus. CONCLUSION: Resolution of hydrops secondary to congenital CMV was temporally related to the administration of maternal and fetal hyperimmune globulin.

Abetalipoproteinemia complicating the puerperium.

BACKGROUND: Abetalipoproteinemia is a rare, autosomal recessive disease, in which the absence of beta-lipoprotein results in the malabsorption of fat-soluble vitamins. There are few reported complications from abetalipoproteinemia during pregnancy. We present a case of untreated abetalipoproteinemia complicating the puerperium. CASE: A 23-year-old, gravida 3, para 0020 woman presented to an outside facility in labor, and her delivery was complicated by postpartum hemorrhage and a large vulvar hematoma. She was coagulopathic and transferred for suspected disseminated intravascular coagulation. Her preexisting medical history was not appreciated by the transferring facility. CONCLUSION: Abetalipoproteinemia in pregnancy is rare. Untreated disease conveys multi-system organ dysfunction and has ramifications in labor and delivery. Clinicians must elicit a comprehensive medical history to properly manage complications in the puerperium.

The association of chronic endometritis with preterm birth.

OBJECTIVE: The purpose of this study was to determine whether chronic endometritis (CE) that is diagnosed by endometrial biopsy is associated with preterm birth at <37 weeks of gestation. STUDY DESIGN: Pathology reports for women aged 18-45 years who underwent clinically indicated endometrial biopsy between 1992 and 2002 were solicited from 3 participating clinical pathology laboratories. Reports were dichotomized into those with and those without CE by a standard definition. Results were linked to birth certificates at the Ohio Department of Health. Women who delivered singleton infants (1992-2002) within 3 years of biopsy were included. Biopsy specimens that were obtained from women with conditions that were associated with indicated preterm birth were excluded. Statistical analysis included logistic regression, Student's t-test, Fisher's exact test, and chi-square test, where appropriate. A probability value of <.05 was considered significant. RESULTS: The 1603 endometrial biopsy reports were identified and forwarded. The Ohio Department of Health linked birth certificate data to 193 reports, 157 of which met inclusion criteria and comprised the study group. Twenty-six of 157 women (16.6%) who were studied had CE. The odds of delivering at <37 weeks of gestation were not significantly higher for women with CE (odds ratio, 2.51; 95% CI, 0.86-7.29; P = .091). Infants who were born at <37 weeks of gestation were more likely to be black (P < .001); to have intrapartum fever, meconium, or fetal distress (P = .026) and to require assisted ventilation (P = .016). CONCLUSION: In our study group, women with CE were not more likely to deliver an infant at <37 weeks of gestation.

Serum homocysteine levels after preterm premature rupture of the membranes.

OBJECTIVE: Preterm premature rupture of the membranes (PPROM) is believed to be caused, in part, by abnormalities of collagen and increased levels of oxidative stress. Elevated homocysteine levels have been shown to induce these same pathophysiologic changes. We tested the hypothesis that serum homocysteine levels would be higher in women with PPROM when compared with matched control women. STUDY DESIGN: A secondary analysis derived from 2 previously completed studies performed in the National Institutes of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. We identified 99 study cases with PPROM (24 to 32 weeks' gestation) and matched them with 99 asymptomatic control women from an observational study of preterm birth prediction. Cases and control women were matched for race, gestational age at sampling, and MFMU Network center. Serum homocysteine levels were determined by immunoassay in batch fashion by personnel masked to study arm and clinical outcomes. Serum homocysteine levels were compared between groups, as were the baseline characteristics of maternal age, cigarette smoking, nulliparity, infections during pregnancy, and body mass index (BMI) <19.8 kg/m 2. Serum homocysteine levels were dichotomized as >75th, 90th, and 95th %ile of control women, and the likelihood of elevated homocysteine levels was determined in women who smoked, had a BMI <19.8 kg/m 2, or who had PPROM. Statistical analyses included the Wilcoxon rank sum, chi-square, and Pearson correlation coefficient, where appropriate. Baseline characteristics were controlled with a logistic regression model. RESULTS: Serum homocysteine levels measured in patients with PPROM were not significantly different from matched control women: median and (25th to 75th %ile): 4.9 (3.5-6.2) vs 4.8 (3.9-6.2 micromol/L), P =.73. In our population, neither the number of cigarettes smoked ( r = -0.08, P =.57), nor BMI ( r = -0.08, P =.24) correlated with serum homocysteine levels. The strongest association was seen in women with PPROM having serum homocysteine levels >95th %ile of control women (odds ratio [OR] 2.7, P =.10). After adjusting for baseline characteristics, no correlation between serum homocysteine level and the presence of PPROM was seen, OR 1.0 (.9-1.1); P =.99. CONCLUSION: Women presenting with PPROM did not have significantly increased serum homocysteine levels when compared with control women.

Management of pregnancies complicated by anti-c isoimmunization.

OBJECTIVE: To review cases of anti-c isoimmunization and determine the most appropriate management strategies. METHODS: We performed a review of 102 pregnancies managed at The Ohio State University from 1967 to 2001 for anti-c isoimmunization. Of these, 55 had complete data and are included in this report. Information collected included serum titers, deltaOD450 values, Liley zones, fetal and neonatal hemoglobin levels and antigen typing, neonatal direct antiglobulin test, and neonatal outcomes. The appropriateness of traditional management was then evaluated. RESULTS: Of the 55 pregnancies, 46 had fetuses with positive direct antiglobulin test, and nine pregnancies had unaffected fetuses. Of the affected neonates, 12 (26%) had serious hemolytic disease of the newborn. Of these 12, 8 required fetal transfusion, and the remaining 4 newborns had hemoglobin levels of less than 10 g/dL at the time of delivery. A titer of 1:32 or greater or the presence of hydrops fetalis identified all such fetuses. There were 58 amniocenteses performed for deltaOD450 When plotted on modified Liley graphs, deltaOD450 values corresponded to disease severity. There were no perinatal deaths attributable to anti-c hemolytic disease of the newborn. CONCLUSION: Anti-c isoimmunization might cause significant fetal and newborn hemolytic disease. A titer of 1:32 or greater or evidence of hydrops fetalis identified all the serious hemolytic disease at our institution. The significance of antibody titers and deltaOD450 values was similar to Rh-D sensitized pregnancies, and management by the same modalities is appropriate.

Drug rash with eosinophilia and systemic symptoms syndrome and renal toxicity with a nevirapine-containing regimen in a pregnant patient with human immunodeficiency virus.

BACKGROUND: Antiretroviral therapy is associated with serious adverse events. We report the case of a pregnant human immunodeficiency virus type 1-infected woman who developed drug rash with eosinophilia and systemic symptoms syndrome and renal failure shortly after initiation of a nevirapine-containing antiretroviral regimen at 27 weeks' gestation. CASE: A 26-year-old primigravida presented with a fever of 40.2C, urticarial rash, and icteric sclera 6 weeks after starting a nevirapine-containing antiretroviral regimen. Eosinophils, serum creatinine, bilirubin, and liver enzymes were markedly elevated, and abnormal coagulation studies were noted on admission. Serology testing was negative for viral hepatitis and microbiologic cultures were negative for growth. Abnormal laboratory findings at discharge resolved within 4 months after discontinuation of antiretroviral agents and systemic corticosteroid therapy. CONCLUSION: Our case suggests the need for close monitoring of liver and renal function after initiation of nevirapine-containing antiretroviral regimens.