Larry Rand

Diversity of the Vaginal Microbiome Correlates With Preterm Birth

Reproductive tract infection is a major initiator of preterm birth (PTB). The objective of this prospective cohort study of 88 participants was to determine whether PTB correlates with the vaginal microbiome during pregnancy. Total DNA was purified from posterior vaginal fornix swabs during gestation. The 16S ribosomal RNA gene was amplified using polymerase chain reaction primers, followed by chain-termination sequencing. Bacteria were identified by comparing contig consensus sequences with the Ribosomal Database Project. Dichotomous responses were summarized via proportions and continuous variables via means ± standard deviation. Mean Shannon Diversity index differed by Welch t test (P = .00016) between caucasians with PTB and term gestation. Species diversity was greatest among African Americans (P = .0045). Change in microbiome/Lactobacillus content and presence of putative novel/noxious bacteria did not correlate with PTB. We conclude that uncultured vaginal bacteria play an important role in PTB and race/ethnicity and sampling location are important determinants of the vaginal microbiome.

Prenatal steroids for microcystic congenital cystic adenomatoid malformations

OBJECTIVE The purpose of this study is to evaluate the effect of prenatal steroid treatment in fetuses with sonographically diagnosed congenital cystic adenomatoid malformations (CCAMs). METHODS This was an institutional review board-approved retrospective review of 372 patients referred to the University of California, San Francisco (UCSF), for fetal CCAM. Inclusion criteria were (1) a predominately microcystic CCAM lesion sonographically diagnosed at our institution, (2) maternal administration of a single course of prenatal corticosteroids (betamethasone), and (3) no fetal surgery. CCAM volume-to-head ratio (CVR), presence of hydrops, mediastinal shift, and diaphragm eversion were assessed before and after administration of betamethasone. The primary end points were survival to birth and neonatal discharge. RESULTS Sixteen patients with predominantly microcystic CCAMs were treated with prenatal steroids. Three were excluded because of lack of follow-up information. All remaining fetuses (13/13) survived to delivery and 11/13 (84.6%) survived to neonatal discharge. At the time of steroid administration, all patients had CVR greater than 1.6, and 9 (69.2%) also had nonimmune hydrops fetalis. After a course of steroids, CVR decreased in 8 (61.5%) of the 13 patients, and hydrops resolved in 7 (77.8%) of the 9 patients with hydrops. The 2 patients whose hydrops did not resolve with steroid treatment did not survive to discharge. CONCLUSION In high-risk fetal patients with predominantly microcystic CCAM lesions, betamethasone is an effective treatment. This series is a pilot study for a prospective randomized trial comparing treatment of CCAM with betamethasone to placebo.

Post-term induction of labor revisited.

Post-term pregnancy (longer than 42 weeks or 294 days) occurs in approximately 10% of all singleton gestations. The adverse outcomes of post-term pregnancy include a substantial increase in perinatal mortality and morbidity. ACOG currently recommends induction of labor for low-risk pregnancy during the 43rd week of gestation. However, that recommendation dates from 1989. Recent reports mandate reconsideration of the management of post-term pregnancy, including reinterpretation of the statistical risk of stillbirth in post-term pregnancies using ongoing (undelivered) rather than delivered pregnancies as the denominator, which shows a far higher risk to post-term fetuses than believed. Recent data also suggest that the risk of cesarean delivery after induction of labor at term is lower than reported, possibly because of improvements in methods for cervical ripening. Those findings provide rationale for earlier labor induction in low-risk pregnancies.

Prenatal surgery for myelomeningocele and the need for cerebrospinal fluid shunt placement

OBJECT The Management of Myelomeningocele Study (MOMS) was a multicenter randomized trial comparing the safety and efficacy of prenatal and postnatal closure of myelomeningocele. The trial was stopped early because of the demonstrated efficacy of prenatal surgery, and outcomes on 158 of 183 pregnancies were reported. Here, the authors update the 1-year outcomes for the complete trial, analyze the primary and related outcomes, and evaluate whether specific prerandomization risk factors are associated with prenatal surgery benefit. METHODS The primary outcome was a composite of fetal loss or any of the following: infant death, CSF shunt placement, or meeting the prespecified criteria for shunt placement. Primary outcome, actual shunt placement, and shunt revision rates for prenatal versus postnatal repair were compared. The shunt criteria were reassessed to determine which were most concordant with practice, and a new composite outcome was created from the primary outcome by replacing the original criteria for CSF shunt placement with the revised criteria. The authors used logistic regression to estimate whether there were interactions between the type of surgery and known prenatal risk factors (lesion level, gestational age, degree of hindbrain herniation, and ventricle size) for shunt placement, and to determine which factors were associated with shunting among those infants who underwent prenatal surgery. RESULTS Ninety-one women were randomized to prenatal surgery and 92 to postnatal repair. The primary outcome occurred in 73% of infants in the prenatal surgery group and in 98% in the postnatal group (p < 0.0001). Actual rates of shunt placement were only 44% and 84% in the 2 groups, respectively (p < 0.0001). The authors revised the most commonly met criterion to require overt clinical signs of increased intracranial pressure, defined as split sutures, bulging fontanelle, or sunsetting eyes, in addition to increasing head circumference or hydrocephalus. Using these modified criteria, only 3 patients in each group met criteria but did not receive a shunt. For the revised composite outcome, there was a difference between the prenatal and postnatal surgery groups: 49.5% versus 87.0% (p < 0.0001). There was also a significant reduction in the number of children who had a shunt placed and then required a revision by 1 year of age in the prenatal group (15.4% vs 40.2%, relative risk 0.38 [95% CI 0.22-0.66]). In the prenatal surgery group, 20% of those with ventricle size < 10 mm at initial screening, 45.2% with ventricle size of 10 up to 15 mm, and 79.0% with ventricle size ≥ 15 mm received a shunt, whereas in the postnatal group, 79.4%, 86.0%, and 87.5%, respectively, received a shunt (p = 0.02). Lesion level and degree of hindbrain herniation appeared to have no effect on the eventual need for shunting (p = 0.19 and p = 0.13, respectively). Similar results were obtained for the revised outcome. CONCLUSIONS Larger ventricles at initial screening are associated with an increased need for shunting among those undergoing fetal surgery for myelomeningocele. During prenatal counseling, care should be exercised in recommending prenatal surgery when the ventricles are 15 mm or larger because prenatal surgery does not appear to improve outcome in this group. The revised criteria may be useful as guidelines for treating hydrocephalus in this group.

Perinatal Outcome of Conservative Management versus Fetal Intervention for Twin Reversed Arterial Perfusion Sequence with a Small Acardiac Twin

Objective: To examine the outcomes of patients with twin reversed arterial perfusion (TRAP) sequence in which the acardiac twin was ≤50% the weight of the pump twin. Methods: This was a retrospective study conducted with institutional review board approval. The records of all patients referred to UCSF for suspected diagnosis of TRAP between 1994 and 2009 were reviewed (n = 76). Patients with pregnancies complicated by TRAP with an acardiac twin ≤50% the weight of the pump twin were included (21 patients). Exclusion criteria were loss to follow-up (1 patient) and syndromic abnormalities in the pump twin (2 patients). Results: Of the 18 patients with viable pregnancies that met the criteria for analysis, 7 (39%) underwent radiofrequency ablation (RFA) of the acardiac twin and 11 (61%) underwent conservative management. None of the pump twins in either group had hydrops fetalis. Three of the 11 acardiac twins in the conservative management group did not undergo RFA because they did not have blood flow at presentation to UCSF. Survival to delivery was 100% (7/7) in the RFA group and 91% (10/11) in the conservative management group. When we eliminated from our analysis the 3 pregnancies in the conservative management group without blood flow to the acardiac twin, survival to delivery was 88% (7/8). The single death occurred in 1 of the 3 monochorionic-monoamniotic pregnancies in the conservative management group, all of whom had blood flow to the acardiac twin. There were no statistically significant differences in gestational age at delivery, birth weight or survival between the RFA and conservative management groups, even after stratification by blood flow. Conclusions: Conservative management with close monitoring appears to be a safe option for TRAP pregnancies in which the acardiac twin is ≤50% the weight of the pump twin.

Postpartum follow-up for women with gestational diabetes mellitus.

We sought to determine the frequency of postpartum follow-up for women diagnosed with gestational diabetes mellitus. A retrospective cohort study of women with gestational diabetes mellitus from 2002 to 2008 ( N = 745) at an academic center was conducted. The primary outcome was either fasting blood glucose or 2-hour oral glucose tolerance, both measured at ≤6 months postpartum. Chi-square test and multivariable logistic regression analysis were used for statistical comparisons, and statistical significance was indicated by P < 0.05 and 95% confidence intervals. The frequency of follow-up for the study cohort was 33.7%. Of these women, 28.3% had values consistent with impaired glucose tolerance and 2.0% were diagnosed with type 2 diabetes mellitus. Asian women were the most likely to follow up (43%), and Latinas had the lowest follow-up frequency (18%; P < 0.001). Compared with their counterparts, women ≥35 years old, nulliparas, and women with GDM subtype A2 were more likely to return for postpartum glucose testing (odds ratio [OR] = 1.7, 95% confidence interval [CI] 1.2 to 2.5; OR = 1.9, 95% CI 1.3 to 2.7; OR = 2.28, 95% CI 1.4 to 3.6, respectively). The frequency of postpartum follow-up for women diagnosed with gestational diabetes mellitus is exceedingly low. More effective strategies are needed to increase the postpartum and longitudinal follow-up for all women with gestational diabetes mellitus.

Effect of selective fetoscopic laser photocoagulation therapy for twin–twin transfusion syndrome on pulmonary valve pathology in recipient twins

To investigate the impact of selective fetoscopic laser photocoagulation (SFLP) on pre‐existing pulmonary valve pathology in the recipient twin in twin–twin transfusion syndrome (TTTS).

Antenatal antibiotic exposure in preterm infants with necrotizing enterocolitis

Objective:To determine whether an association exists between antenatal antibiotic exposure and incidence of necrotizing enterocolitis (NEC) in low birth weight infants.Study Design:A retrospective case-control study was performed on all infants with a diagnosis of NEC born at our institition between 1988 and 2006. Medical histories of all infants with a diagnosis of NEC ⩾Bells stage IIA and matched controls without NEC were reviewed. Maternal and neonatal characteristics were compared using the Mantel-Haenszel chi-square procedure, and logistic regression models were constructed to account for confounding.Result:Clinical data for 97 matched pairs were analyzed. The adjusted odds ratio (OR) for antenatal exposure to ampicillin was significantly greater for infants who developed NEC (OR 2.3, 95% confidence interval 1.1, 4.8, P=0.003) than for control infants.Conclusion:Infants who developed NEC were more likely to have a history of in utero exposure to ampicillin in the immediate antepartum period than infants who did not develop NEC.

Long-term outcomes after fetal therapy for congenital high airway obstructive syndrome

BACKGROUND/PURPOSE Congenital high airway obstructive syndrome (CHAOS) is a rare and devastating condition that is uniformly fatal without fetal intervention. We sought to describe fetal treatment and long-term outcomes of CHAOS at a single referral center. METHODS The medical records of patients with fetal CHAOS evaluated at our center between 1993 and 2011 were reviewed. Maternal history, radiographic findings, antenatal management, and postnatal outcomes were compared. RESULTS Twelve fetuses with CHAOS were identified. Eleven had concomitant hydrops at diagnosis. Six were electively terminated, and 2 had intra- or peripartum demise. Four patients underwent fetal intervention. Two underwent delivery via ex utero intrapartum treatment (EXIT) procedure with tracheostomy placement only, and 2 underwent fetal bronchoscopy with attempted wire tracheoplasty followed by EXIT with tracheostomy at delivery. All 4 patients who underwent EXIT were alive at last follow-up. One patient was ventilator and tracheostomy free and feeding by mouth. CONCLUSION Long-term and tracheostomy-free survival is possible with appropriate fetal intervention even in the presence of hydrops. Fetal intervention earlier in pregnancy may improve long-term outcomes, but patient selection for intervention remains challenging. Magnetic resonance imaging may help select those patients for whom fetal intervention before EXIT delivery may be beneficial.

Survival and Major Morbidity of Extremely Preterm Infants: A Population-Based Study.

OBJECTIVES: To assess the rates of mortality and major morbidity among extremely preterm infants born in California and to examine the rates of neonatal interventions and timing of death at each gestational age. METHODS: A retrospective cohort study of all California live births from 2007 through 2011 linked to vital statistics and hospital discharge records, whose best-estimated gestational age at birth was 22 through 28 weeks. Major morbidities were based on International Classification of Diseases, Ninth Revision, Clinical Modification codes. Survival beyond the first calendar day of life and procedure codes were used to assess attempted resuscitation after birth. RESULTS: A total of 6009 infants born at 22 through 28 weeks’ gestation were included. Survival to 1 year for all live births ranged from 6% at 22 weeks to 94% at 28 weeks. Seventy-three percent of deaths occurred within the first week of life. Major morbidity was present in 80% of all infants, and multiple major morbidities were present in 66% of 22- and 23-week infants. Rates of resuscitation at 22, 23, and 24 weeks were 21%, 64%, and 93%, respectively. Survival after resuscitation was 31%, 42%, and 64% among 22-, 23-, and 24-week infants, respectively. Improved survival was associated with increased birth weight, female sex, and cesarean delivery (P < .01) for resuscitated 22-, 23-, and 24-week infants. CONCLUSIONS: In a population-based study of extreme prematurity, infants ≤24 weeks’ gestation are at highest risk of death or major morbidity. These data can help inform recommendations and decision-making for extremely preterm births.