Kara B. Markham

Preterm birth rates in a prematurity prevention clinic after adoption of progestin prophylaxis.

OBJECTIVE: To evaluate whether progestin prophylaxis influenced the odds of recurrent spontaneous preterm birth among pregnant women with a previous preterm birth. METHODS: A retrospective cohort study was performed evaluating outcomes of pregnant women with one or more previous preterm births who received prenatal care in a single academic prematurity clinic. Care algorithms were determined and revised by a single supervising physician. Progestin prophylaxis was adopted in 2004 with accelerated access to the first clinic visit adopted in 2008. Rates of preterm birth before 37, 35, and 32 weeks of gestation were compared over time. RESULTS: One thousand sixty-six women with a history of one or more spontaneous preterm births received care in the prematurity clinic and were delivered between January 1, 1998, and June 30, 2012. The gestational age at initiation of prenatal care declined significantly after adoption of an accelerated appointment process (median of 19.1 weeks before 2003, 16.2 weeks from 2004 to 2007, and 15.2 weeks from 2008 to 2012, P<.01), and progestin use increased from 50.8% in 2004–2007 to 80.3% after 2008 (P<.01). After adjustment for race, smoking, cerclage, and number of prior preterm deliveries, we noted a statistically significant decreased odds of spontaneous preterm birth in years 2008–2012 compared with 1998–2007 before 37 (adjusted odds ratio [OR] 0.75, 95% confidence interval [CI] 0.58–0.97) and 35 (adjusted OR 0.70, 95% CI (.52–0.94) weeks of gestation. CONCLUSION: Adoption of prophylactic progestin treatment was associated with a decreased odds of recurrent preterm birth before 37 or 35 weeks of gestation after adoption of an aggressive program to facilitate early initiation of progestin treatment. LEVEL OF EVIDENCE: II

Placental dysferlin expression is reduced in severe preeclampsia.

Dysferlin (DYSF) and myoferlin (MYOF), members of the ferlin family of membrane proteins, are co-expressed in human placental syncytiotrophoblast (STB). Although the role of these ferlin proteins in the placenta has yet to be established, it has been suggested that DYSF and MYOF may contribute to the stability of the apical STB plasma membrane. The release of STB-derived cellular debris increases in the setting of preeclampsia (PE), suggesting relative destabilization of the hemochorial interface. To test whether PE was associated with alterations in placental expression of DYSF and/or MYOF, a cross-sectional study was performed using specimens of villous placenta collected form women with severe PE (n=10) and normotensive controls (n=10). DYSF and MYOF expression were examined using quantitative real-time RT-PCR, immunoblotting, and immunofluorescence labeling of tissue specimens. Placental DYSF expression was 57% lower at the mRNA level (p=0.03) and 38% lower at the protein level (p=0.026) in severe PE as compared to normotensive subjects. There were no differences in placental MYOF protein or mRNA expression between these groups. No appreciable changes in the distribution of DYSF or MYOF within placental villi was observed in PE relative to control specimens. We conclude that DYSF expression is reduced in severe PE relative to gestational age-matched controls. As DYSF has a role in membrane repair, these data suggest a role for DYSF in the stability of the apical STB plasma membrane and may account, at least in part, for the increased shedding of microparticles from this membrane in PE.

Prevention of Preterm Birth in Modern Obstetrics

Spontaneous preterm labor is a complex process characterized by the interplay of multiple different pathways. Prevention of preterm labor and delivery is also complicated. The most effective interventions for prevention of preterm birth (PTB) are progestin prophylaxis and lifestyle modifications, with cerclage placement also playing a role in selected populations. Interventions such as activity modification, home tocometry, and routine antibiotic use have fallen out of favor because of lack of effectiveness and possibility of harm. The solution to the problem of PTB remains elusive, and researchers and clinicians must collaborate to find a cure for preterm labor.

Hemolytic disease of the fetus and newborn due to multiple maternal antibodies

OBJECTIVE The objective of the study was to determine whether women with combinations of red blood cell antibodies are more likely to develop significant hemolytic disease of the fetus and newborn than those with single antibodies. STUDY DESIGN A retrospective exposure cohort study was conducted of pregnant women with red blood cell antibodies. The development of significant hemolytic disease of the fetus and newborn was then compared between patients with single antibodies and those with multiple antibodies. Data analysis was limited to pregnancies delivering since the year 2000. RESULTS Thirteen percent of the patients referred to our program had multiple red blood cell antibodies. Odds of developing significant hemolytic disease of the fetus and newborn for patients with anti-Rh(D) combined with at least 1 additional red blood cell antibody were 3.65 times the odds for women with anti-Rh(D) antibodies in isolation (95% confidence interval, 1.84-7.33). In the setting of multiple antibodies including anti-Rh(D), Rh-positive fetuses/neonates have an increased odds of developing significant hemolytic disease even if the fetus is negative for the other corresponding red blood cell antigen. CONCLUSION Women with multiple red blood cell antibodies are more likely to develop significant hemolytic disease of the fetus and newborn than those with a single antibody especially in the presence of anti-(Rh)D. This pathophysiology may suggest a more aggressive immune response in women who develop more than 1 red blood cell antibody.

Bacteremia and intrauterine infection with Shigella sonnei in a pregnant woman with AIDS

Shigella species are virulent enteric bacteria that cause enterocolitis [1]. This organism is of particular importance in developing nations, where Shigella is responsible for approximately 165 million cases and 1 million deaths annually, but periodic outbreaks also occur in the US [2]. Transferred primarily via the fecal-oral route, Shigella enterocolitis is a very much preventable disease through basic hygiene, including frequent hand washing, disinfection of drinking water, and appropriate food preparation techniques [3]. It is thus an important public health concern, especially in poorer nations throughout the world. Four species of these aerobic, gram-negative rods exist (Shigella. bodyii, Shigella. dysenteriae, Shigella. flexnari, and Shigella. sonnei) [3]. A very small inoculum of only 10–200 organisms is sufficient to cause infection [3]. Symptoms of infection include watery, often bloody, diarrhea, abdominal pain/cramps, and fever [1, 3]. Enterocolitis occurs because the organisms invade colonic mucosa, causing extensive superficial destruction and triggering inflammation [3]. Infection usually does not result in longterm sequelae, but children and immunocompromised patients may experience significant morbidity and mortality [1]. Because of the self-limited nature of the infection in most healthy individuals, treatment centers around supportive care with fluid and electrolyte replacement [1]. Furthermore, some practitioners recommend treatment with antibiotics in all patients with positive stool cultures [4]. While such antimicrobial therapy has been shown to shorten the disease course by 2 days on an average, the use of antibiotics is recommended more in an effort to reduce community-wide dissemination of the organism than for individual concerns [4]. Treatment options include fluoroquinolones and ceftriaxone primarily, but other agents such as azithromycin and trimethoprim-sulfamethazole may be considered if susceptibility is proven [4]. In this publication, we will review the literature regarding infection with Shigella during pregnancy. We will also present the first reported case of Shigella bacteremia in this potentially high risk population, highlighting the potential for morbidity and mortality associated with chorioamnionitis and systemic infection.

Placental vasa previa

In April, 2010, a 25-year-old woman at 33 weeks’ gestation in her fi rst pregnancy presented to us for examination of a previously identifi ed velamentous umbilical cord insertion into the placenta. Ultrasonography showed a fundal placenta, and the cord insertion site was not visible inserting into the placental surface. Transvaginal ultrasonography was performed because of our patient’s reports of vaginal spotting. Doppler ultrasonography showed fetal blood vessels coursing over the internal cervical os, consistent with a diagnosis of vasa previa (fi gure A). Uterine tocometry demonstrated frequent contractions. After administration of betamethasone for enhancement of fetal lung maturity, a caesarean section was done because of the risk of impingement or laceration of the vulnerable cord vasculature. She delivered a vigorous male neonate weighing 2115 g. Examination of the placenta was consistent with our diagnosis of a velamentous cord insertion site, with fetal blood vessels present over the cervix indicating vasa previa (fi gure B). At last follow-up in June, 2010, our patient and her infant were doing well.

Measuring the Cervical Length.

An important step toward the goal of eradicating spontaneous preterm birth was achieved with the advent of cervical sonography, a tool that advanced our knowledge of the entity of preterm parturition, improved our ability to detect women at risk for early delivery, and allowed us to prevent some of these premature births. We will describe here the correct technique for obtaining such measurements and will review the literature regarding the use of this tool in specific pregnant populations.

Torsion of a Term Gravid Uterus: A Possible Cause of Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler Findings

Due to the increased uterine size and the presence of the rectosigmoid colon, dextro-rotation of the gravid uterus up to 45° is common. Uterine torsion, defined as rotation greater than 45°, is a rare occurrence, and, consequently, its potential implications and effects on pregnancy are underreported in the literature. The diagnosis is often made incidentally at the time of cesarean delivery, but complications such as abdominal pain, fetal malpresentation, and maternal death have previously been reported.1,2 The following represents the first reported case of concern for intrauterine growth restriction and newly diagnosed abnormal umbilical artery Doppler findings in the setting of uterine torsion. A 22-year-old woman, gravida 2, para 1, presented at a gestational age of 37 weeks 2 days for evaluation of fetal growth. The patient’s medical history included idiopathic thrombocytopenic purpura as well as new diagnoses of atrial tachycardia, a small perimembranous ventricular septal defect, and a slightly dilated aortic root and pulmonary artery. Previous sonography had revealed a velamentous cord insertion, for which serial growth assessment was recommended, with documentation of an appropriately grown fetus in the cephalic presentation at 35 weeks’ gestation. Follow-up growth sonography was then performed at 37 weeks 2 days due to concerns that her fundal height was measuring smaller than expected for gestational age. This sonogram revealed a singleton intrauterine fetus in the breech presentation with an estimated fetal weight of 2314 g (corresponding to <10th percentile) and a normal amniotic fluid index. Umbilical artery Doppler values were obtained because of these concerns about fetal weight, with an elevated systolic-to-diastolic ratio of 3.8 (corresponding to >97.5th percentile). Delivery was therefore recommended in light of the abnormal Doppler findings. On presentation to the labor suite, the patient’s platelet count was found to be 68,000/μL, and general anesthesia was therefore recommended for the planned cesarean delivery. In an effort to minimize fetal exposure to systemic anesthetic agents, delivery was conducted in an expeditious fashion. On entry into the abdominal cavity, one of the fallopian tubes and one of the ovaries were identified anterior to the uterus but not in such a position that the lower uterine segment was obstructed. A low transverse hysterotomy incision was made, and a 2500-g male neonate (consistent with 10th–25th percentile) was delivered in the breech presentation by standard breech maneuvers. Apgar scores were 1 and 9 at 1 and 5 minutes, respectfully. After delivery, the uterus was exteriorized for the repair, at which time it was found to be axially rotated by 180° to the right, such that the hysterotomy had been made on the posterior uterine wall (Figure 1A). The hysterotomy incision was repaired in a standard fashion using 1-0 Polypore sutures (Covidien, Mansfield, MA), resulting in excellent homeostasis. Examination of the uterus revealed no obvious anomalies or fibroids. The uterus was then rotated back to its normal anatomic position before returning the organ back into the abdomen without difficultly. The mother recovered uneventfully, and both the mother and neonate were discharged home on postoperative day 3. After delivery, the patient’s prior serial growth sonograms were reviewed in detail. Interestingly, an anterior placenta was identified at 17, 23, and 31 weeks’ gestation, with a posterior placenta visualized at 35 and 37 weeks (Figure 1, B and C). Fetal growth was likewise reviewed, with an estimated growth of 1856 g (56th percentile) at 31 weeks, 1993 g (17th percentile) at 35 weeks, and 2314 g (<10th percentile) at 37 weeks. Uterine torsion is defined as uterine rotation exceeding 45° along the long axis, with a maximum rotation of 720° reported in the literature.3 Since this finding is often inci-