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1.  Diagnosis and Treatment of Fetal Arrhythmia 
American journal of perinatology  2014;31(7):617-628.
Detection and careful stratification of fetal heart rate (FHR) is extremely important in all pregnancies. The most lethal cardiac rhythm disturbances occur during apparently normal pregnancies where FHR and rhythmare regular and within normal or low-normal ranges. These hidden depolarization and repolarization abnormalities, associated with genetic ion channelopathies cannot be detected by echocardiography, and may be responsible for up to 10% of unexplained fetal demise, prompting a need for newer and better fetal diagnostic techniques. Other manifest fetal arrhythmias such as premature beats, tachycardia, and bradycardia are commonly recognized. Heart rhythm diagnosis in obstetrical practice is usually made by M-mode and pulsed Doppler fetal echocardiography, but not all fetal cardiac time intervals are captured by echocardiographic methods. This article reviews different types of fetal arrhythmias, their presentation and treatment strategies, and gives an overview of the present and future diagnostic techniques.
doi:10.1055/s-0034-1372430
PMCID: PMC4073210  PMID: 24858320
fetal arrhythmia; magnetocardiography; electrocardiography; tachycardia; bradycardia; stillbirth; long QT syndrome; fetal demise
2.  Postnatal Weight Gain in Preterm Infants with Severe Bronchopulmonary Dysplasia 
American journal of perinatology  2013;31(3):223-230.
Objectives
To characterize postnatal growth failure (PGF), defined as weight < 10th percentile for postmenstrual age (PMA) in preterm (≤27 weeks’ gestation) infants with severe bronchopulmonary dysplasia (sBPD) at specified time points during hospitalization, and to compare these in subgroups of infants who died/underwent tracheostomy and others.
Study Design
Retrospective review of data from the multicenter Children’s Hospital Neonatal Database (CHND).
Results
Our cohort (n = 375) had a mean ± standard deviation gestation of 25 ± 1.2 weeks and birth weight of 744 ± 196 g. At birth, 20% of infants were small for gestational age (SGA); age at referral to the CHND neonatal intensive care unit (NICU) was 46 ± 50 days. PGF rates at admission and at 36, 40, 44, and 48 weeks’ PMA were 33, 53, 67, 66, and 79% of infants, respectively. Tube feedings were administered to > 70% and parenteral nutrition to a third of infants between 36 and 44 weeks’ PMA. At discharge, 34% of infants required tube feedings and 50% had PGF. A significantly greater (38 versus 17%) proportion of infants who died/underwent tracheostomy (n = 69) were SGA, compared with those who did not (n = 306; p < 0.01).
Conclusions
Infants with sBPD commonly had progressive PGF during their NICU hospitalization. Fetal growth restriction may be a marker of adverse outcomes in this population.
doi:10.1055/s-0033-1345264
PMCID: PMC4451086  PMID: 23690052
nutrition; tracheostomy; growth; bronchopulmonary dysplasia
3.  Is Midtrimester Vitamin D Status Associated with Spontaneous Preterm Birth and Preeclampsia? 
American journal of perinatology  2013;31(6):541-546.
Objective
To evaluate whether midtrimester maternal vitamin D is associated with preeclampsia <37 weeks or spontaneous preterm birth (SPTB) <35 weeks.
Study Design
Nested case-control comprising 2 case-subsets: a) 100 women with preeclampsia <37 weeks and b) 100 women with SPB <35 weeks. Controls consisted of 200 women delivered between 39–40 weeks. Stored maternal serum obtained between 15–21 weeks was tested for total 25-hydroxy vitamin D levels (25-OH D) using liquid chromatography-tandem mass spectrometry. Mean 25-OH D levels and prevalence of vitamin D insufficiency (25-OH D < 30 ng/mL) and deficiency (25-OH D <15 ng/mL) were compared.
Results
89 preeclampsia, 90 spontaneous preterm birth cases, and 177 controls had valid measurements. Mean midtrimester vitamin D was not significantly different between women with preeclampsia (27.4 ng/mL±14.4) and controls (28.6±12.6) (p=0.46), or SPTB (28.8±13.2) and controls (p=0.92). After adjusting for potential cofounders, neither vitamin D insufficiency (aOR 1.1; 95% CI 0.6–2.0) nor deficiency (aOR 1.4; 95% CI 0.7–3.0) was significantly associated with preeclampsia. Likewise, SPTB was not significantly associated with either vitamin D insufficiency or deficiency (aOR 0.8; 95% CI 0.4–1.4, aOR 1.3; 95% CI0.6–3.0, respectively).
Conclusion
Midtrimester maternal vitamin D was not significantly associated with preeclampsia <37 weeks or SPTB <35 weeks.
doi:10.1055/s-0033-1356483
PMCID: PMC4451220  PMID: 24022379
Adverse; 25-hydroxy vitamin D; Preeclampsia; Preterm birth
4.  Optimization of Vancomycin Dosing in Very Low-Birth-Weight Preterm Neonates 
Objective
To compare vancomycin serum trough concentrations and 24-hour area under the serum concentration-versus-time curve (AUC24) among very low-birth-weight (VLBW) premature infants before and after implementation of an institution-wide increase in neonatal vancomycin dosing.
Study Design
We performed a retrospective analysis of vancomycin concentrations among preterm VLBW neonates before (2007–2010) and after (2010–2013) implementation of a new vancomycin dosing protocol consisting of increased vancomycin daily dose and frequency of administration.
Results
Neonates weighing < 1,500 g and receiving the new vancomycin dosing regimen had lower rates of undetectable trough concentrations (24 vs. 50%, p = 0.04), higher median trough concentrations (10.8 vs. 5.9 µg/mL, p = 0.003), a higher proportion of goal trough concentrations of 10 to 20 µg/mL (35 vs. 4%, p = 0.005), and a significantly higher vancomycin AUC24 (438 vs. 320 mg·h/L, p = 0.004) compared with historical controls.
Conclusion
Increasing the vancomycin daily dose and dosing frequency led to an increase in vancomycin trough concentrations and AUC24, and a decrease in the proportion of undetectable (< 5.0 µg/mL) troughs, without an increase in toxicity among VLBW premature neonates.
doi:10.1055/s-0034-1376183
PMCID: PMC4418186  PMID: 24839147
vancomycin; neonates; preterm; VLBW; AUC24
5.  Maternal and Neonatal Nurse Perceived Value of Kangaroo Mother Care and Maternal Care Partnership in the Neonatal Intensive Care Unit 
American journal of perinatology  2013;30(10):875-880.
Background
Kangaroo Mother Care (KMC) enhances infant and maternal well-being and requires maternal-care partnerships (MCP) for implementation.
Objective
To examine maternal and neonatal nurse provider perspectives on the value of KMC and MCP.
Study Design
Prospective cohort design of neonatal nurses and mothers of preterm infants self-report anonymous questionnaire. Analyses of categorical independent variables and continuous variables were calculated.
Results
In all, 82.3% of nurses (42) and 100% (143) of mothers participated in the survey. compared with 18% of nurses, 63% of mothers believed “KMC should be provided daily” and 90% of mothers compared with 40% of nurses strongly believed “mothers should be partners in care.” In addition, 61% of nonwhite mothers identified that “KMC was not something they were told they could do for their infant” compared with 39% of white mothers. Nonwhite and foreign-born nurses were 2.8 and 3.1 times more likely to encourage MCP and KMC.
Conclusion
Mothers held strong positive perceptions of KMC and MCP value compared with nurses. Nonwhite mothers perceived they received less education and access to KMC. Barriers to KMC and MCP exist among nurses, though less in nonwhite, foreign-born, and/or nurses with their own children, identifying important provider educational opportunities to improve maternal KMC access in the NICU.
doi:10.1055/s-0033-1333675
PMCID: PMC4417481  PMID: 23359231
maternal; neonatal nurse; perceptions; kangaroo mother care
6.  Impact of Obesity on Maternal and Neonatal Outcomes in Insulin-Resistant Pregnancy 
American journal of perinatology  2013;31(5):383-388.
Objective
To determine the impact of obesity on pregnancies complicated by insulin resistance.
Study Design
Secondary analysis of prospective cohort of women with gestational diabetes (GDM) and type 2 diabetes (DM). Exclusion criteria were type 1 DM, multiple gestation, fetal anomalies, unknown prepregnancy body mass index (BMI). Primary maternal outcome was a composite of any: severe preeclampsia, eclampsia, 3rd-4th degree laceration, readmission, wound infection, or antepartum hospitalization. Primary neonatal outcome was a composite of any: hypoglycemia, preterm delivery, admission to level 3 nursery, oxygen requirement >6 hours after birth, shoulder dystocia, 5-minute Apgar≤3, cord pH<7.0, and cord base excess <-12 mmol/L. Obese women (BMI≥30.0 kg/m2) were compared to non-obese women (BMI < 30.0 kg/m2).
Results
Of 356 subjects with DM, 233 (66%) were obese. Obese women were not at further increased risk of the composite maternal outcome (adjusted odds ratio (aOR) 0.68, 95% confidence interval (CI) 0.43–1.09), the composite neonatal outcome (aOR 0.76, 95% CI 0.48-1.21), or cesarean (58.8% vs 52.9%, p=0.28, aOR 1.47, 95% CI 0.91–2.39).
Conclusion
We did not find evidence that obesity worsened pregnancy outcomes in women with GDM and type 2 DM, suggesting that obese women may not require more stringent antepartum treatment strategies.
doi:10.1055/s-0033-1350057
PMCID: PMC4009984  PMID: 23877768
obesity; pregestational diabetes; gestational diabetes; type 2 diabetes
7.  Maternal Periodontal Disease is Associated with Oxidative Stress during Pregnancy 
American journal of perinatology  2010;28(3):247-252.
We sought to determine if maternal periodontal disease is associated with oxidative stress as measured by serum 8-isoprostane. A secondary analysis was conducted using prospective data from the Oral Conditions and Pregnancy Study. Healthy women enrolled at <26 weeks’ gestational age underwent oral examination and serum sampling. Maternal periodontal disease status was categorized as healthy, mild, or moderate to severe by clinical criteria. Maternal serum was analyzed for 8-isoprostane using ultrasensitive enzyme-linked immunosorbent assay. Elevated 8-isoprostane level was defined as ≥75th percentile. Maternal factors associated with elevated 8-isoprostane were determined using chi-square or t test. Multivariable logistic regression was used to assess association between elevated 8-isoprostane and maternal factors. Seven hundred ninety-one women had complete data. Median (interquartile) 8-isoprostane serum level was 1806 (16 to 81,870) pg/dL. Using bivariate analysis, maternal age, race, marital status, utilization of public assistance, and mild or moderate to severe periodontal disease were associated with elevated serum 8-isoprostane. Using logistic regression, moderate to severe periodontal disease (adjusted odds ratio 2.9, 95% confidence interval: 1.7 to 5.0) remained significantly associated with an elevated serum 8-isoprostane level. Maternal periodontal disease is associated with oxidative stress during pregnancy. Further study is needed to determine the role of maternal oxidative stress in periodontal disease-associated adverse pregnancy outcomes.
doi:10.1055/s-0030-1268706
PMCID: PMC4414032  PMID: 21082538
Periodontal disease; oxidative stress; pregnancy; 8-isoprostane; biomarker
8.  Factors That Influence Neonatal Nursing Perceptions of Family-Centered Care and Developmental Care Practices 
American journal of perinatology  2009;27(3):193-200.
The purpose of this study was to analyze the association of developmental care education and training and neonatal intensive care unit (NICU) developmental team structure in promoting neonatal nursing perception and beliefs of key characteristics of family-centered care (FCC), developmental care, and kangaroo mother care (KMC). A 24-item Likert scale survey of specific perceptions and beliefs of aspects of FCC, KMC, and developmental care characteristics was conducted with 59 neonatal nurses from three distinct level III NICUs in New York City where nurses had undergone recent reeducation and developmental team configuration. There was no difference in nursing beliefs of technical developmental care approaches to infant care at all three sites. Neonatal nurses who were supported by an on-site infant developmental specialist were more likely to have strong beliefs related to the affective areas of FCC and the technique of KMC. FCC and clinical care approaches that include a high level of parental participation such as KMC in the NICU are likely to be facilitated by a comprehensive approach of continuing training as well as a team structure that includes dedicated, specially trained infant developmental specialist personnel.
doi:10.1055/s-0029-1234039
PMCID: PMC4410360  PMID: 19653141
Developmental care; family-centered care; nurse; kangaroo mother care; neonatal intensive care unit; infant developmental specialist
9.  Maternal Obesity and Risk of Post-Cesarean Wound Complications 
American journal of perinatology  2013;31(4):299-304.
OBJECTIVE
To estimate the effect of increasing severity of obesity on post-cesarean wound complications and surgical characteristics.
STUDY DESIGN
We performed a retrospective cohort study of consecutive cesarean deliveries at a tertiary care facility from 2004-2008. Four comparison groups were defined by body mass index (BMI kg/cm2) <30 (n=728), 30-39.9 (n=1087), 40-49.9 (n=428), or ≥50 (n=201). The primary outcome was wound complication, defined as wound disruption or infection within 6 weeks post-operative. Surgical characteristics were compared between groups including: administration of pre-operative antibiotics, type of skin incision, estimated blood loss (EBL), operative time, and type of skin closure.
RESULTS
Of the 2444 women with complete follow up data, 266 (10.9%) developed a wound complication. Compared to non-obese women (6.6%), increasing BMI was associated with an increased risk of wound complications: BMI 30.0-39.9, 9.2%, aOR 1.4 [95% CI 0.99-2.0]; BMI 40.0-49.9, 16.8%, aOR 2.6 [95% CI 1.7-3.8]; BMI ≥50, 22.9%, aOR 3.0 [95% CI 1.9-4.9]. Increasing BMI was also associated with increased rates of midline vertical incision, longer operative time, higher EBL, and lower rates of subcuticular skin closure.
CONCLUSION
A dose response relationship exists between increasing BMI and risk of postcesarean wound complications. Increasing obesity also significantly influences operative outcomes.
doi:10.1055/s-0033-1348402
PMCID: PMC3796045  PMID: 23765707
Obese; Cesarean; Wound; Surgical
10.  Adrenomedullin Signaling Pathway Polymorphisms and Adverse Pregnancy Outcomes 
American journal of perinatology  2013;31(4):327-334.
Objective
Reduced maternal plasma levels of the peptide vasodilator adrenomedullin have been associated with adverse pregnancy outcomes. We measured the extent to which genetic polymorphisms in the adrenomedullin signaling pathway are associated with birth weight, glycemic regulation, and preeclampsia risk.
Study Design
We genotyped 1353 women in the Pregnancy, Infection, and Nutrition Postpartum Study for 37 ancestry-informative markers and for single-nucleotide polymorphisms (SNPs) in adrenomedullin (ADM), complement factor H variant (CFH), and calcitonin receptor-like receptor (CALCRL). We used linear and logistic regression to model the association between genotype and birth weight, glucose loading test (GLT) results, preeclampsia, and gestational diabetes (GDM). All models were adjusted for pregravid BMI, maternal age, and probability of Yoruban ancestry. P values of <0.05 were considered statistically significant.
Results
Among Caucasian women, ADM rs57153895, a proxy for rs11042725, was associated with reduced birth weight z-score. Among African-American women, ADM rs57153895 was associated with increased birth weight z-score. Two CALCRL variants were associated with GDM risk. CFH rs1061170 was associated with higher GLT results and increased preeclampsia risk.
Conclusion
Consistent with studies of plasma adrenomedullin and adverse pregnancy outcomes, we found associations between variants in the adrenomedullin signaling pathway and birth weight, glycemic regulation, and preeclampsia.
doi:10.1055/s-0033-1349345
PMCID: PMC3982866  PMID: 23797962
adrenomedullin; genetics; gestational diabetes; preeclampsia; single nucleotide polymorphisms
11.  A Nested Case-Control Study of First-Trimester Maternal Vitamin D Status and Risk for Spontaneous Preterm Birth 
American journal of perinatology  2011;28(9):667-672.
We assessed if first-trimester vitamin D deficiency is more prevalent in women who experienced a spontaneous preterm birth compared with women who delivered at term. We conducted a nested case-control study of pregnant women who had previously given blood for first-trimester combined screening for trisomy 21 and subsequently delivered at a tertiary hospital between November 2004 and July 2009. From an overall cohort of 4225 women, 40 cases of spontaneous preterm birth (≥23 0/7 and ≤34 6/7 weeks) were matched by race/ethnicity with 120 women delivering at term (≥37 0/7 weeks) with uncomplicated pregnancies. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D]. The prevalence of first-trimester maternal vitamin D deficiency [25(OH)D <50 nmol/L] was comparable among women who subsequently delivered preterm compared with controls (7.5% versus 6.7%, p=0.90). The median 25(OH)D level for all subjects was 89 nmol/L (interquartile range, 73 to 106 nmol/L). Seventy-three percent (117/160) of the cohort had sufficient vitamin D levels [25(OH)D ≥75 nmol/L]. In a cohort of pregnant women with mostly sufficient levels of first-trimester serum 25(OH)D, vitamin D deficiency was not associated with spontaneous preterm birth.
doi:10.1055/s-0031-1276731
PMCID: PMC4372898  PMID: 21500145
Preterm birth; vitamin D; 25-hydroxyvitamin D
12.  The effect of magnesium sulfate administration for neuroprotection on latency in women with preterm premature rupture of membranes 
American journal of perinatology  2014;32(4):387-392.
Objective
To evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes between 24 and 31 6/7 weeks' gestation.
Study Design
This is a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Gravid women with a singleton pregnancy between 24 and 31 6/7 weeks' gestation with preterm premature rupture of membranes (pPROM) without evidence of labor were randomized to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour up to 12 hours, or placebo. Maternal outcomes for this analysis were delivery in less than 48 hours and in less than 7 days from randomization. Neonatal outcomes included a composite of respiratory distress, interventricular hemorrhage grades 3 or 4, periventricular leukomalacia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death.
Results
A total of 1259 women were included. The rate of delivery < 48 hours was not different in the magnesium sulfate and the placebo groups (22.2% and 20.7%, p=0.51). Delivery < 7 days was similar between groups (55.4% and 51.4%, p=0.16). Median latency was also similar between groups (median [interquartile range] 6.0 days [2.4–13.8] and 6.6 days [2.4–15.1], p =0.29). Composite neonatal outcomes did not differ between groups. Conclusion: Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with preterm premature rupture of membranes and without labor before 32 weeks does not impact latency.
doi:10.1055/s-0034-1387930
PMCID: PMC4369158  PMID: 25241107
latency; magnesium sulfate; neuroprotection; preterm premature rupture of membranes
13.  Central Auditory Processing Disorder Profile in Premature and Term Infants 
American journal of perinatology  2014;32(4):399-404.
Objective
The aim of this study is to compare central auditory processing disorder (CAPD) profile between children born prematurely and at term.
Methods
A retrospective study involving children 7 to 13 years of age who were referred for CAPD evaluation over the past 3 years. Parental reports and medical records were used to collect information. Children with a score ≥ two standard deviations below the mean for at least one ear on at least two different CAPD tests were considered to have CAPD.
Results
A total of 82 children were evaluated for CAPD of which 22 met exclusion criteria, resulting in 60 children with CAPD (15 premature and 45 term). Premature children had higher prevalence of cesarean section delivery and neonatal jaundice compared with term children. Premature children had a higher total number of failed CAPD tests compared with the term children. Among CAPD tests, there was an increased frequency of abnormal Phonemic Synthesis test (PST) and decreased frequency of abnormal Staggered Spondaic Word test (SSW) among premature children compared with term children.
Conclusion
Premature children differ in CAPD profile compared with term children. Findings suggest possible etiological differences for CAPD such as jaundice or differential susceptibility of premature children for altered PST and SSW performance when compared with the term children.
doi:10.1055/s-0034-1387928
PMCID: PMC4369183  PMID: 25261703
speech and language delay; central auditory nervous system; jaundice; attention deficit hyperactivity disorder
14.  UMBILICAL CORD SERUM INTERLEUKIN-6, C-REACTIVE PROTEIN, AND MYELOPEROXIDASE CONCENTRATIONS AT BIRTH AND ASSOCIATION WITH NEONATAL MORBIDITIES AND LONG TERM NEURODEVELOPMENTAL OUTCOMES 
American journal of perinatology  2013;31(8):717-726.
OBJECTIVE
To determine if umbilical cord serum concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and myeloperoxidase (MPO), in pregnancies at risk for preterm birth (PTB), are associated with neonatal morbidities and/or altered neurodevelopmental outcomes in the children.
STUDY DESIGN
Umbilical cord serum samples were collected at birth from 400 newborns delivered within a multicenter randomized controlled trial of repeated versus single course of antenatal corticosteroids (ACs), in women at increased risk for PTB. Newborns were followed through discharge and were evaluated between 36 and 42 months corrected age with neurological examination and Bayley Scales of Infant Development. Umbilical cord serum concentrations of IL-6, CRP, and MPO were determined using enzyme-linked immunoassays. Multivariate logistic regression analyses explored the relationship between umbilical cord serum IL-6, CRP and MPO levels, adverse newborn outcomes and PTB < 32 weeks of gestational age (GA).
RESULTS
Univariate analysis revealed that umbilical cord IL-6 above the 75th percentile was associated with increased respiratory distress syndrome (RDS) and chronic lung disease (CLD), but not with necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), or neonatal sepsis; however, this association was not significant after adjusting for gestational age at delivery and treatment group. No significant associations between CRP or MPO, and RDS, CLD, NEC, sepsis or IVH were evident. Regression analysis revealed that CRP above the 75th percentile was associated with a decreased risk of CLD (O.R. 0.10, 95% C.I. 0.02–0.41). No associations between umbilical cord IL-6, CRP or MPO, and MDI < 70 or PDI < 70 were evident. Umbilical cord serum IL-6, CRP, and MPO, above the 75th percentile, were associated with more frequent PTB < 32 weeks GA.
CONCLUSION
Elevated umbilical cord serum concentration of CRP is associated with reduced risk for CLD even after adjusting for gestational age at delivery. Occurrence of levels > 75th percentile of IL-6, CRP, and MPO in umbilical cord serum were associated with PTB < 32 weeks GA. Elevated umbilical cord serum concentrations of IL-6, CRP, and MPO at birth were not associated with poor neurodevelopmental outcomes.
doi:10.1055/s-0033-1359723
PMCID: PMC4359689  PMID: 24338120
Umbilical cord serum; cytokines; preterm birth; neonatal morbidity; neurodevelopmental infant outcome
15.  Neonatal death in Low-Middle Income Countries: A Global Network Study 
American journal of perinatology  2012;29(8):649-656.
Objective
To determine population-based neonatal mortality rates in low and middle income countries and to examine gestational age, birth-weight and timing of death to assess the potentially preventable neonatal deaths.
Methods
A prospective observational study was conducted in communities in five low-income countries (Kenya, Zambia, Guatemala, India, and Pakistan) and one mid-income country (Argentina). Over a two-year period, all pregnant women in the study communities were enrolled by trained study staff and their infants followed to 28 days of age.
Results
Between October 2009 and March 2011, 153,728 babies were delivered and followed through day 28. Neonatal death rates ranged from 41 per 1000 births in Pakistan to 8 per 1000 in Argentina. 54% of the neonatal deaths were >37 weeks and 46% weighed 2500 grams or more. Half the deaths occurred within 24 hours of delivery.
Conclusions
In our population-based low and middle income country registries, the majority of neonatal deaths occurred in babies >37 weeks gestation and almost half weighed at least 2500 grams. Most deaths occurred shortly after birth. With access to better medical care and hospitalization, especially in the intrapartum and early neonatal period, many of these neonatal deaths might be prevented.
doi:10.1055/s-0032-1314885
PMCID: PMC4337792  PMID: 22644832
Neonatal mortality; low-income countries; preterm birth
16.  The Stillbirth Collaborative Research Network Neuropathologic Examination Protocol 
American journal of perinatology  2011;28(10):793-802.
We describe the neuropathologic procedure utilized in the Stillbirth Collaborative Research Network (SCRN), focusing on the examination of central nervous system (CNS) in stillbirth (SB). The SCRN was organized to perform a case-control study to determine the scope and causes of SB. Pathologists at all the participating centers agreed on and used the same standardized neuropathologic techniques. Standardized sections were taken and detailed data were collected. Fresh brain tissue was saved for investigative purposes. A total of 663 women with SB were enrolled into the case-control study: 620 delivered a single stillborn, 42 delivered twins, and 1 delivered triplets. Of the 560 (84.5%) who consented to postmortem examination, 465 (70.1%) also gave consent to the examination of the CNS. In the 440 stillborn infants in whom CNS examination was possible, 248 (56.4%) of the brains were intact, 72 were fragmented (16.4%), and 120 (27.3%) were liquefied. In summary, this is the largest prospective study dedicated to investigate the causes of SB and collect essential information and biological samples in the United States. A protocol for neuropathologic examination was instituted, and a brain tissue repository was created to provide samples and related data for future investigations.
doi:10.1055/s-0031-1284229
PMCID: PMC4320122  PMID: 21780010
SCRN; neuropathology; stillbirth; central nervous system
17.  The Stillbirth Collaborative Research Network Postmortem Examination Protocol 
American journal of perinatology  2011;29(3):187-202.
After reviewing the state of knowledge about the scope and causes of stillbirth (SB) in a special workshop sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the participants determined that there is little guidance regarding the best use of postmortem examination (PM) to address the pathogenesis of stillbirth. In this report, we describe the PM procedure designed and used in the NICHD-supported Stillbirth Cooperative Research Network (SCRN). Perinatal pathologists, clinicians, epidemiologists, and biostatisticians at four tertiary care centers, a data coordinating center, and NICHD developed a standardized approach to perinatal PM, which was applied to a population-based study of stillbirth as part of the SCRN. The SCRN PM protocol was successfully instituted and used at the four medical centers. A total of 663 women with stillbirth were included: 620 delivered a single stillborn infant, 42 delivered twins, and one delivered triplets for a total of 676 stillborn infants. Of these women, 560 (84.5%) consented to PM (572 stillborn infants) that was conducted according to the SCRN protocol. A standardized PM protocol was developed to evaluate stillbirth consistently across centers in the United States. Novel testing and approaches that increase the yield of the PM can be developed using this model.
doi:10.1055/s-0031-1284228
PMCID: PMC4320124  PMID: 21815127
SCRN; postmortem examination; stillbirth; perinatal pathology
18.  The Stillbirth Collaborative Research Network (SCRN) Placental and Umbilical Cord Examination Protocol 
American journal of perinatology  2011;28(10):781-792.
The Stillbirth Collaborative Research Network (SCRN) was organized to study the scope and causes of stillbirth (SB) in the United States. The objective of this report is to describe the approach used for the placental examination performed as part of the study. The SCRN consists of a multidisciplinary team of investigators from five clinical sites, the National Institute of Child Health and Human Development, and the Data Coordination and Analysis Center. The study is a population-based cohort and nested case-control study, with prospective enrollment of women with SB and live births (LB) at the time of delivery. Detailed and standardized postmortem examination was performed on SB and placental examination in both groups. A total of 663 women with SB and 1932 women with LB were enrolled into the case-control study. In the SB group, there were 707 fetuses. Of these cases, 654 (98.6%) had placental examination. Of these LB controls, 1804 (93.4%) had placental examination. This is the largest prospective study to include population-based SB and LB, using standardized postmortem and placental examination, medical record review, maternal interview, collection of samples, and a multidisciplinary team of investigators collaborating in the analyses. Thus it has the potential to provide high-level evidence regarding the contribution of placental abnormalities to stillbirth.
doi:10.1055/s-0031-1281509
PMCID: PMC4316371  PMID: 21717387
Stillbirth; placenta; umbilical cord; cause of death
19.  Does Maternal BMI Influence Treatment Effect in Women with Mild Gestational Diabetes? 
American journal of perinatology  2014;32(1):93-100.
Objective
To determine whether maternal body mass index (BMI) influences the beneficial effects of diabetes treatment in women with gestational diabetes (GDM).
Study Design
Secondary analysis of a multicenter randomized treatment trial of women with GDM. Outcomes of interest were elevated umbilical cord c-peptide levels (>90th percentile 1.77 ng/mL), LGA birth weight (>90th percentile), and neonatal fat mass (g). Women were grouped into five BMI categories adapted from the WHO International Classification of normal, overweight, and obese adults. Outcomes were analyzed according to treatment group assignment.
Results
A total of 958 women were enrolled (485 treated and 473 controls). Maternal BMI at enrollment was not related to umbilical cord c-peptide levels. However, treatment of women in the overweight, Class I, and Class II obese categories was associated with a reduction in both LGA birth weight and neonatal fat mass. Neither measure of excess fetal growth was reduced with treatment in normal weight (BMI <25) or Class III (BMI ≥ 40) obese women.
Conclusion
There was a beneficial effect of treatment on fetal growth in women with mild GDM who were overweight or Class I and II obese. These effects were not apparent for normal weight and very obese women.
doi:10.1055/s-0034-1374815
PMCID: PMC4314711  PMID: 24839145
Gestational diabetes; BMI; Treatment effect
20.  [No title available] 
PMCID: PMC3932308  PMID: 23546845
21.  [No title available] 
PMCID: PMC4013719  PMID: 23512321
22.  The Association of Cord Serum Cytokines with Neurodevelopmental Outcomes 
American journal of perinatology  2014;30(2):115-122.
OBJECTIVE
To test whether elevated umbilical cord serum inflammatory cytokine levels predicted subsequent cerebral palsy (CP) or neurodevelopmental delay (NDD).
STUDY DESIGN
Nested case-control analysis within a clinical trial of antenatal magnesium sulfate (MgSO4) before anticipated PTB for prevention of CP, with evaluation of surviving children at age 2. NDD was defined as a Bayley Psychomotor Developmental Index (PDI) and/or Mental Developmental Index (MDI) <70. Controls, defined as surviving children without CP and with Bayley PDI and MDI ≥85, were matched by race and gestational age. Cord serum was analyzed for IL-8, IL-1 β and TNF-α levels. Elevated cytokine levels were defined as ≥75th percentile in placebo-exposed controls. Analyses compared case/control cytokine levels, adjusting for MgSO4 exposure, gestational age, race/ethnicity and sociodemographic differences.
RESULTS
Logistic regression analysis with 339 cases and 276 controls showed that elevated IL-8 and IL-1β were more common in cord blood serum from infants with subsequent low MDI compared with controls. After adjusting for additional confounders, the significant differences were no longer evident. Cytokine levels (IL-8, IL-1β, and TNF-α) were not elevated with CP or low PDI.
CONCLUSION
Cord serum IL-8, IL-1β, and TNF-α levels in preterm infants are not associated with subsequent CP or NDD.
doi:10.1055/s-0034-1376185
PMCID: PMC4269581  PMID: 24936937
Cytokines; Cerebral Palsy; Neurodevelopmental Outcomes; Prematurity; Magnesium Sulfate
23.  Monitoring Apnea of Prematurity: Validity of Nursing Documentation and Bedside Cardiorespiratory Monitor 
American journal of perinatology  2012;30(8):643-648.
Objective
To compare apnea events recorded by bedside cardiorespiratory monitor and nursing documentation with those detected by visual inspection of continuous electronic cardiorespiratory waveform.
Methods
In a prospective observational study, 20 nonventilated infants of 28 to 33 weeks’ gestational age were monitored for apnea during the first 2 postnatal weeks. Apnea was defined as a respiratory pause > 20 seconds or > 15 seconds if associated with a heart rate < 80/min or oxygen saturation < 85%. True apnea was defined as one for which visual inspection of continuous electronic cardiorespiratory waveform on the central monitor verified apnea.
Results
The number of apnea episodes recorded by nursing documentation and bedside monitors were 207 and 418, respectively. Only 7.7% of apnea events recorded by nursing documentation were confirmed as true apnea compared with 50.4% of apnea recorded by bedside monitors and the difference was statistically significant. Of true apnea (n = 211) episodes recorded on central monitors, 99% were recorded by bedside monitors but only 7.6% of apnea occurrences were recorded by nursing personnel.
Conclusions
Nursing documentation does not provide accurate monitoring of apnea. Although bedside monitors have better sensitivity and specificity than nursing documentation, future research should be directed to improve the specificity of bedside monitoring.
doi:10.1055/s-0032-1329694
PMCID: PMC4285412  PMID: 23254381
neonatal intensive care unit; bradycardia; desaturation; premature infants
24.  Length of Latency with Preterm Premature Rupture of Membranes before 32 Weeks’ Gestation 
Objective
To describe latency for patients with preterm premature membrane rupture (PPROM) between 24 0/7 and 31 6/7 weeks’ gestation.
Study Design
Secondary analysis of data collected prospectively in a multicenter clinical trial of magnesium sulfate for cerebral palsy prevention. Women with PPROM and fewer than 6 contractions per hour at enrollment who were candidates for expectant management (n=1377) were included in this analysis. Length of latency was calculated in days by subtracting the time of delivery from the time of membrane rupture.
Results
At each week of gestation, median latency between 24-28 weeks was similar at approximately 9 days, but was significantly shorter with PPROM at 29, 30, and 31 weeks (p<0.001). In addition, the percentage of patients remaining undelivered at 7 days and 14 days was similar for PPROM between 24-28 weeks, but decreased significantly after that. For each gestational age, the proportion of patients remaining pregnant declined in a fashion similar to exponential pattern.
Conclusion
Median latency after PPROM is similar from 24-28 weeks’ gestation, but shortens with PPROM at and after 29 weeks.
doi:10.1055/s-0034-1373846
PMCID: PMC4250427  PMID: 24819145
latency; premature rupture of membranes; preterm birth
25.  Maternal Genotype and Gestational Diabetes 
American journal of perinatology  2013;31(1):10.1055/s-0033-1334451.
OBJECTIVE
To determine whether genetic variants associated with glucose homeostasis are associated with gestational diabetes (GDM).
STUDY DESIGN
We genotyped 899 self-identified Caucasian women and 386 self-identified African-American women in the Pregnancy, Infection and Nutrition (PIN) Studies cohorts for 36 single-nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) and/or glucose homeostasis in European populations.
RESULTS
GDM was diagnosed in 56 of 899 (6.2%) Caucasian and 24 of 386 (6.2%) African-American women. Among Caucasian women, GDM was associated with carriage of TCF7L2 rs7901695, MTNR1B rs10830963 and GCKR rs780094 alleles associated with T2DM and fasting glucose in non-pregnant populations. Among African-American participants, we found an increased risk among TSPAN8 rs7961581 C allele homozygotes and reduced risk among carriers of the JAZF1 rs864745 T allele.
CONCLUSION
We found several SNPs that are associated with GDM risk in the PIN cohorts. Maternal genotyping may identify women at risk for impaired gestational glucose tolerance.
doi:10.1055/s-0033-1334451
PMCID: PMC3884679  PMID: 23456907
diabetes; gestational diabetes; genetics; single nucleotide polymorphisms

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