Neonatal Genetic Variation in Steroid Metabolism and Key Respiratory Function Genes and Perinatal Outcomes in Single and Multiple Courses of Corticosteroids.

OBJECTIVE: The aim of the study is to evaluate the association of steroid metabolism and respiratory gene polymorphisms in neonates exposed to antenatal corticosteroids (ACS) with respiratory outcomes, small for gestational age (SGA), and response to repeat ACS. STUDY DESIGN: This candidate gene study is a secondary analysis of women enrolled in a randomized controlled trial of single versus weekly courses of ACS. Nineteen single nucleotide polymorphisms (SNPs) in 13 steroid metabolism and respiratory function genes were evaluated. DNA was extracted from placenta or fetal cord serum and analyzed with TaqMan genotyping. Each SNP was evaluated for association via logistic regression with respiratory distress syndrome (RDS), continuous positive airway pressure (CPAP)/ventilator use (CPV), and SGA. RESULTS: CRHBP, CRH, and CRHR1 minor alleles were associated with an increased risk of SGA. HSD11B1 and SCNN1B minor alleles were associated with an increased likelihood of RDS. Carriage of minor alleles in SerpinA6 was associated with an increased risk of CPV. CRH and CRHR1 minor alleles were associated with a decreased likelihood of CPV. CONCLUSION: Steroid metabolism and respiratory gene SNPs are associated with respiratory outcomes and SGA in patients exposed to ACS. Risks for respiratory outcomes are affected by minor allele carriage as well as by treatment with multiple ACS.

Perinatal outcome after fetoscopic release of amniotic bands: a single-center experience and review of the literature.

OBJECTIVES: To present two successful cases of fetoscopic release of amniotic bands with umbilical cord involvement and provide a review of the literature on fetal intervention for amniotic band syndrome (ABS). METHODS: Two cases of ABS were considered in conjunction with a review of the literature. A total of 14 fetuses with ABS underwent fetoscopic intervention between 1965 and 2012. Two of the authors independently completed literature searches in PubMed, Ovid and MEDLINE for articles related to ABS. RESULTS: Among 14 cases of ABS (12 published and our own two), 57% and 7% were complicated by preterm premature rupture of membranes and spontaneous preterm birth, respectively. Overall, fetoscopic intervention preserved limb function in 50% (7/14) of cases. Three cases involved intraoperative complications including intra-amniotic bleeding and uterine wall bleeding, and incomplete procedure due to ineffective equipment. CONCLUSION: Fetoscopic release of amniotic bands with minimally invasive surgery may allow preservation of life and/or limb function in cases of ABS. The acceptable functional outcome in 50% of cases is reassuring, although more experience and further studies are needed to determine the selection criteria that will justify the risk of this invasive in-utero therapy for ABS.

Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population?

OBJECTIVE: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. DESIGN: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. SETTING: A multicentre study in 16 academic medical centres in the USA. POPULATION: Low-risk nulliparous women. METHODS: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. MAIN OUTCOME MEASURES: Change in PlGF, sFlt-1 and sEng. RESULTS: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. CONCLUSION: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia.

Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women.

OBJECTIVE: To determine whether vitamin D status is associated with recurrent preterm birth, and any interactions between vitamin D levels and fish consumption. DESIGN: A nested case-control study, using data from a randomised trial of omega-3 fatty acid supplementation to prevent recurrent preterm birth. SETTING: Fourteen academic health centres in the USA. POPULATION: Women with prior spontaneous preterm birth. METHODS: In 131 cases (preterm delivery at <35 weeks of gestation) and 134 term controls, we measured serum 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography-tandem mass spectrometry (LC-MS) from samples collected at baseline (16-22 weeks of gestation). Logistic regression models controlled for study centre, maternal age, race/ethnicity, number of prior preterm deliveries, smoking status, body mass index, and treatment. MAIN OUTCOME MEASURES: Recurrent preterm birth at <37 and <32 weeks of gestation. RESULTS: The median mid-gestation serum 25(OH)D concentration was 67 nmol/l, and 27% had concentrations of <50 nmol/l. Serum 25(OH)D concentration was not significantly associated with preterm birth (OR 1.33; 95% CI 0.48-3.70 for lowest versus highest quartiles). Likewise, comparing women with 25(OH)D concentrations of 50 nmol/l, or higher, with those with <50 nmol/l generated an odds ratio of 0.80 (95% CI 0.38-1.69). Contrary to our expectation, a negative correlation was observed between fish consumption and serum 25(OH)D concentration (-0.18, P < 0.01). CONCLUSIONS: In a cohort of women with a prior preterm birth, vitamin D status at mid-pregnancy was not associated with recurrent preterm birth.

Potential biochemical events associated with initiation of labor.

Much of our understanding and knowledge of human parturition has been blurred by conjecture and extrapolation. The limited available data on human parturition reflect the inability to directly experiment with pregnant human subjects. In spite of this obvious impediment and the scarcity of longitudinal data on fundamental physiological changes in human pregnancy, recent reports have generated a better understanding of the synchronous activities leading to labor. The purpose of this review was to organize, in an evidence-based format, the current understanding of maternal physiologic phenomena leading from uterine quiescence to uterine labor activity. Recent discoveries have prompted a revision of pre-existing classical theories on the initiation of parturition, such as the progesterone block theory or the prostaglandins stimulation of the uterotonic action of oxytocin. The presence in the circulation of extrahypothalamic corticotrophin-releasing hormone (CRH) produced by the placenta and myometrium is an inciting unique feature of primate pregnancy and a promising field for research. The concept of anatomical regionalization in labor promotion, including the cervical physiological inflammatory reaction, is also discussed in the review, especially in support of the strong link between inflammatory activation and onset of preterm labor. Understanding the intimate chain of events leading to parturition is critical, and elucidating the interplay of signals and processes that initiate normal labor may help us to understand the abnormal variant, spontaneous preterm labor, and devise efficacious interventions against it.

In vitro quantification of dexamethasone-induced surfactant protein B expression in human lung cells.

OBJECTIVE: To determine whether the effect of a single 48-h exposure to dexamethasone in human lung cells is limited to 7-8 days. STUDY DESIGN: We used the NCI-H441 cell line, in which stability can be maintained beyond 7 days. The outcome was the stimulatory effect of dexamethasone on surfactant protein B (SP-B) gene transcription as expressed by SP-B mRNA accumulation. The experiment was conducted five times, in parallel with control. SP-B mRNA was determined at baseline, 48 h after dexamethasone exposure, and at 48-h intervals thereafter, up to 14 days, by quantitative reverse transcription polymerase chain reaction. Comparisons were made by the Mann-Whitney test. RESULTS: In conditions of our experiment, the inductive profile of SP-B mRNA after exposure to dexamethasone demonstrated maximal stimulation at 48 h (13-fold over control). Subsequently, there was a decline in mRNA, with return to near control levels by day 8, suggesting reversibility of dexamethasone action. CONCLUSION: Our data support the view that the surfactant-inducing properties of corticosteroids are limited to 7-8 days.

Onset and persistence of postpartum depression in an inner-city maternal health clinic system.

OBJECTIVE: Postpartum depressive disorders lead to maternal disability and disturbed mother-infant relationships, but information regarding the rates of major depressive disorder in minority women is noticeably lacking. The goal of this study was to determine whether the risk factors for and rate of postpartum major depressive disorder in a predominantly African American and Hispanic clinic population would be similar to those reported for Caucasian women. METHOD: Investigators systematically screened all women scheduled for their first postpartum visit on selected days at four publicly funded inner-city community maternal health clinics in Dallas County (N=802). A multistage screening process included the Edinburgh Postnatal Depression Scale, the Inventory of Depressive Symptomatology, and the Structured Clinical Interview for DSM-IV for a maximum of three assessments during the initial 3-5-week postpartum period. RESULTS: The estimated rate of major depressive disorder during the postpartum period among women in this setting was between 6.5% and 8.5%. Only 50% of the depressed women reported onset following birth. Bottle-feeding and not living with one's spouse or significant other were associated with depression at the first evaluation; persistent depressive symptoms were linked with the presence of other young children at home. Greater severity of depressive symptoms at first contact predicted major depressive disorder several weeks later. CONCLUSIONS: Rates of postpartum depression among Latina and African American postpartum women are similar to epidemiologic rates for Caucasian postpartum and nonpostpartum women. As previously shown for Caucasian women, major depressive disorder in many Latina and African American postpartum women begins before delivery, revealing the need to screen pregnant women for depression.

A randomized trial of labor analgesia in women with pregnancy-induced hypertension.

OBJECTIVE: The purpose of this study was to compare the peripartum and perinatal effects of epidural with intravenous labor analgesia in women with pregnancy-induced hypertension. STUDY DESIGN: Women with pregnancy-induced hypertension who had consented to participate were randomized to receive either epidural or intravenous analgesia for labor pain. Both methods were given according to standardized protocols. All women received magnesium sulfate seizure prophylaxis. Obstetric and neonatal outcomes were compared according to intent-to-treat allocation. RESULTS: Seven hundred thirty-eight women were randomized: 372 women were given epidural analgesia, and 366 women were given intravenous analgesia. Maternal characteristics were similar, including the severity of hypertension. Epidural analgesia was associated with a significantly prolonged second-stage labor, an increase in forceps deliveries, and an increase in chorioamnionitis. Cesarean delivery rates and neonatal outcomes were similar. Pain relief was superior with the epidural method. Hypotension required treatment in 11% of women in the epidural group. CONCLUSION: Epidural labor analgesia provides superior pain relief but no additional therapeutic benefit to women with pregnancy-induced hypertension.

Cardiac disease in pregnancy.

Cardiovascular adaptations of pregnancy are generally well tolerated in the healthy gravida; however, these changes can place undue stress on women with underlying cardiovascular disease and can result in increased risk for morbidity and mortality. In this article, we will review issues related to preconceptional counseling, cardiovascular adaptations of pregnancy, and the prognosis and management of the gravida with cardiac disease in pregnancy.

Urinary tract infections during pregnancy.

Urinary tract infections are relatively common in pregnancy and may result in significant morbidity for the pregnant woman and fetus. The authors recommend that all pregnant women be screened for the presence of bacteriuria at their first prenatal visit. Failure to treat bacteriuria during pregnancy may result in as many as 25% of women experiencing acute pyelonephritis. Women with acute pyelonephritis may sustain significant complications, such as preterm labor, transient renal failure, ARDS, sepsis and shock, and hematologic abnormalities. Pregnant women with urinary tract infections should be followed up closely after treatment because as many as one third will experience a recurrence.

Antenatal corticosteroids in women with preterm premature rupture of the membranes.

The authors believe that the literature provides sufficient evidence that antenatal corticosteroid administration is beneficial and safe even in conditions of ruptured membranes. The evidence by now is remarkably robust and one can be reasonably confident regarding the benefits of antenatal corticosteroids in the setting of ruptured membranes. As recently stated by a group of investigators from New Zealand, including Liggins, the originator of this historical medical intervention (antepartum corticosteroids), the safety and efficacy of corticosteroids in conditions of ruptured membranes is beyond any doubt. It is time to accept this reality and to move on to other unresolved issues, like the optimal dose and corticosteroid preparation, the optimal timing of treatment, or the optimal exposure interval.

Labor induction.

Labor induction has become commonplace in modern obstetrics. The increasing rate of labor induction has probably played a role in the increased rate of cesarean delivery observed in the United States during the past few decades. Clearly, the favorability of the cervix has a substantial impact on the potential success of any labor induction. Induction in the setting of an unfavorable cervix can result in prolonged induction, prolonged hospitalization, failed induction, and an increased cesarean delivery rate. In this modern era of healthcare reform and cost containment, the identification of therapeutic strategies to enhance the success and cost-effectiveness of labor induction are of great interest. Ongoing research is needed to advance our knowledge of the mechanisms of parturition and cervical ripening in order to direct interventions for labor induction more effectively.

An appraisal of treatment guidelines for antepartum community-acquired pneumonia.

OBJECTIVE: The optimal strategy for the initial evaluation and management, including criteria for hospitalization, of pregnant women with pneumonia has not been defined. Our purpose was to evaluate a treatment protocol for antepartum pneumonia and to identify criteria for selection of women for potential outpatient treatment. STUDY DESIGN: A protocol based on British and American Thoracic Society guidelines was introduced and included prompt hospitalization and empiric initiation of erythromycin therapy. Maternal and neonatal outcomes were analyzed to assess the efficacy of the protocol. A second analysis involved the retrospective application of published guidelines to ascertain for which women outpatient management might have been appropriate. RESULTS: There were no maternal deaths among the 133 women studied, and in 14 (10%) women there was a misdiagnosis at admission. Erythromycin monotherapy was judged adequate in all but one of the 99 women so treated. Using a modified version of the American Thoracic Society guidelines, we project that only 25% of the women hospitalized with pneumonia could have been managed safely as outpatients. CONCLUSION: Most pregnant women with pneumonia respond well to monotherapy with erythromycin. Outpatient management may be a reasonable option for selected women.

Other factors/conditions associated with cerebral palsy.

The cause for most cases of cerebral palsy is unknown. There are however, risk factors that have been associated with this chronic neuromuscular disease. The objective of this article is to review the maternal and fetal conditions (other than asphyxia and infection) strongly associated with increased rate of cerebral palsy. What remains to be elucidated is whether or not these associations are causative.

Infection and cerebral palsy.

Recent data suggest a possible association of infection and cerebral palsy. The objective of this article is to examine the relationship between intrauterine infection, fetal infection, and long-term neurological dysfunction. In some children maternal infection is associated with brain white matter damage, periventricular leukomalacia, and cerebral palsy.

Fallopian tube prolapse after hysterectomy.

BACKGROUND: Fallopian tube prolapse is reported to most commonly occur after vaginal hysterectomy. Both diagnosis and management have varied, resulting in differing efficacies of treatment. METHODS: We reviewed the presentation, diagnosis, management, and outcomes of 18 cases of tubal prolapse in 17 women. RESULTS: Most cases (65%) occurred after abdominal hysterectomy. The post-hysterectomy course was complicated by cuff cellulitis in three women, an infected cuff hematoma in one, and post-extubation pulmonary edema in one; four were observed for elevated temperature only. At presentation, 44% complained of dyspareunia, 39% vaginal bleeding, 33% vaginal discharge, 28% abdominal pain, and 28% were asymptomatic. Seven women had vaginal excision (one requiring an additional abdominal procedure), three had laparotomy with salpingectomy, and seven (41%) had spontaneous disappearance of prolapsed fallopian tube without treatment. CONCLUSIONS: In our series, tubal prolapse most commonly occurred after abdominal hysterectomy. Moreover, women with tubal prolapse may be asymptomatic, and observation alone may lead to resolution.

Maternal cardiac troponin I levels during normal labor and delivery.

OBJECTIVE: Diagnosis of myocardial infarction in pregnant women on the basis of changes in biochemical markers is complicated by the release of some of these markers from noncardiac tissue sources. We compared troponin I levels with those of other markers in normal pregnant women. STUDY DESIGN: In 51 healthy women at term in labor, cardiac troponin I, myoglobin, creatine kinase, and creatine kinase MB levels were determined at admission, during the second stage of labor, and within 30 minutes, 12 hours, and 24 hours after delivery. RESULTS: Mean admission levels for all markers were below the upper limit of normal. Mean concentrations of myoglobin, creatine kinase, and creatine kinase MB mass were increased nearly twofold within 30 minutes after delivery. The highest level of troponin I (0.134 ng/mL) at all time points was below the cutoff value (0.15 ng/mL) for discriminating myocardial infarction. CONCLUSIONS: Because only troponin I levels remained undetectable during and after delivery, it is potentially the most useful biochemical marker for monitoring pregnant women for myocardial injury.

A randomized study of combined spinal-epidural analgesia versus intravenous meperidine during labor: impact on cesarean delivery rate.

BACKGROUND: Combined spinal-epidural (CSE) analgesia produces rapid-onset pain relief and allows ambulation in early labor. Epidural local anesthetics may contribute to an increase in operative deliveries by decreasing perineal sensation and causing motor weakness. Operative delivery rates might be reduced with CSE, by avoiding or delaying administration of local anesthetics. This study compares the operative delivery rates associated with a CSE technique and those associated with intravenous meperidine for labor analgesia. METHODS: Healthy parturients at full term were assigned randomly to receive CSE or intravenous meperidine analgesia. The CSE group received 10 microg intrathecal sufentanil, followed by epidural bupivacaine and fentanyl at their next request for analgesia. Parturients receiving intravenous meperidine had 50 mg on demand (maximum, 200 mg in 4 h). Labor and delivery outcomes in both groups were recorded and compared. RESULTS: An intent-to-treat analysis of 1,223 women indicated that CSE does not increase the rate of cesarean delivery for dystocia in nulliparous and parous women (CSE, 3.5% vs. intravenous meperidine, 4; P=not significant) or in nulliparous women alone (CSE, 7% vs. intravenous meperidine, 8%; P=not significant). Profound fetal bradycardia that necessitated emergency cesarean delivery within 1 h of the time the mother received sufentanil occurred in 8 of 400 parturients (compared with 0 of 352 who received meperidine; P < 0.01). However, the method of fetal monitoring differed between the two groups. Despite this, neonatal outcomes were similar overall. CONCLUSIONS: Combined spinal-epidural analgesia during labor does not increase the cesarean delivery rate for dystocia in healthy parturient patients at full term, regardless of parity. However, an unexpected increase in the number of cesarean deliveries for profound fetal bradycardia after intrathecal sufentanil was observed. Further investigation is warranted.

The long-term consequences of thrombotic microangiopathy (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome) in pregnancy.

OBJECTIVE: To characterize perinatal outcomes and long-term maternal complications from thrombotic microangiopathy manifested during pregnancy, and to review the clinical course and long-term follow-up of pregnant women with this condition at our institution over the past 25 years. METHODS: We identified prospectively pregnant women who met clinical and laboratory criteria for thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. Their clinical and laboratory findings, response to treatment, perinatal outcomes, and long-term sequelae were then analyzed. RESULTS: Between 1972 and 1997, 11 women had 13 pregnancies complicated by thrombotic microangiopathy, representing an incidence of one per 25,000 births. In three pregnancies (23%), severe and refractory disease developed before midpregnancy. In ten other pregnancies, disease developed either peripartum (62%) or several weeks postpartum (15%). In only two pregnancies with peripartum or postpartum onset of disease was there a clinical picture of severe preeclampsia. In general, the response to treatment was prompt. One woman died of her initial disease in early pregnancy, and mean follow-up of nine survivors was 8.7 years. Disease recurred at least once in 50% of these, two during a subsequent pregnancy. There was at least one serious long-term sequela in all but two survivors; these included recurrence of thrombotic microangiopathy, renal failure, severe hypertension, chronic blood-borne infections, and death. CONCLUSION: Thrombotic microangiopathy complicating pregnancy is rare, and with careful evaluation, it should not be confused with atypical preeclampsia. With prompt and aggressive treatment including plasma exchange, the likelihood of immediate survival is high; however, long-term morbidity and mortality are common.