Volume 42, Issue 6 - Selected papers from the Annual Conference of the New York Perinatal Society (pp. 673–724)

Objective: The placenta of mid-gestation mice is a known rich source of hematopoietic stem cells. We hypothesized that it is also a source of other multipotent stem cells. Methods: We isolated fetal cells from the murine placenta across the second half of gestation and characterized their expression of surface antigens known to be associated with mesenchymal stem cells (MSCs) on a subset of hematopoietic lineage-negative cells. Using real-time reverse-transcriptase quantitative polymerase chain reaction, we also evaluated the expression of intracellular transcription factors (TFs) known to be associated with renal development and/or multipotent stem cells. Results: Cell phenotypes with surface marker and TF expression consistent with multipotent stem cells of a mesenchymal lineage as well as renal cell progenitors were found in the placenta. The expression of MSC and renal progenitor surface markers varied throughout gestation, but was highest on E12–15 where such cells represented a small but significant percentage of the population. Of the studied TFs, 10 of 11 renal TFs were found at moderate to high levels, and all stem cell TFs were found. Conclusion: The mid-gestation murine placenta may serve as a source of multipotent stem cells and also contains cells which may be renal cell progenitors.

Background: Inhaled nitric oxide (iNO) is a well-established treatment for neonatal hypoxic respiratory failure (HRF). However, iNO therapy initiation criteria have not been standardized. This report describes a follow-up survey administered to neonatologists who had completed an Awareness, Trial, and Usage Survey. The objectives were to compare stated target oxygenation index (OI) versus actual OI at which iNO is initiated in respondents’ patients and identify factors associated with iNO initiation at other levels. Methods: Neonatologists provided iNO-treated HRF patient data. Target and actual OI at initiation were determined. Patient groups were stratified by actual OI deviation from target [<4; at (±3); above: 4–10, 11–20, >20; not measured]. Reasons for above-target OI were determined. Results: Of 83 invited neonatologists, 26 (31%) participated, providing data for 128 patients; 85/128 patients (66%) had OI measured at initiation with neonatologist-stated mean target OI 18.8±5.8. Actual mean OI was 26.2±10.3. iNO was initiated ≤ target in 30/85 patients (35%); most [55/85 (65%)] had iNO initiated when OI was above target. Patients aged ≤1 day and those receiving a fraction of inspired oxygen (FiO 2 ) of 1.0 for more than 1 h had highest OIs at initiation. Conclusions: Among surveyed neonatologists who treat infants with HRF with pulmonary hypertension (PH), there is a disparity between stated target versus actual OI for iNO initiation, particularly among infants <1 day old and those receiving FiO 2 of 1.0 for more than 1 h. In term/near-term neonates with HRF with PH, neonatologists should consider implementing treatment protocols to ensure iNO initiation at stated target OI levels.

Objective: Omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation during pregnancy remains controversial. We sought to examine the effects of ω-3 PUFA on inflammation and oxidative stress in vitro and in vivo using a model of preterm labor. Methods: In vivo. Female Swiss Webster mice were fed a normal diet or a 5% fish oil (FO) diet for 3 weeks then mated with normal-fed males. On gestational day 15, dams were injected with either saline (n=10 per group) or lipopolysaccharide (LPS, intrauterine) (n=10 per group). Maternal plasma, amniotic fluid, placentas, and uteri were collected 4 h later and assessed for cytokines; maternal plasma and amniotic fluids were analyzed for oxidative stress. In vitro . RAW264.7 mouse macrophage-like cells were treated with either: vehicle, H 2 O 2 , docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA) (0, 0.1–100 μM) and analyzed for oxidative stress. Results: In vivo . Administration of the 5% FO diet enhanced LPS-induced cytokines in the placenta (P<0.05–0.01) and increased tumor necrosis factor-α in the uterus (P<0.05) and amniotic fluid (P<0.01) when compared to LPS-treated normal-fed animals. Maternal plasma obtained from FO-fed dams showed higher LPS-induced oxidative stress than control-fed animals (P<0.035). However, no differences in oxidative stress were observed in the amniotic fluid. In vitro . Treatment of macrophage-like cells with ω-3 PUFA significantly and dose-dependently increased oxidative stress (P<0.001–0.0001). Conclusions: Supplementation with FO for prior to and during pregnancy significantly increased LPS-induced inflammation in the amniotic fluid, uterus, and placenta and significantly increased maternal systemic oxidative stress in vivo . Likewise, DHA and EPA induced oxidative stress in macrophage-like cells in vitro .

Objective: To evaluate cord blood concentrations of adrenocorticotropic hormone (ACTH) and cortisol in well term infants born with and without meconium-stained amniotic fluid (MSAF) and term infants born with MSAF who experienced respiratory distress (RD). Study design: This was a prospective observational study. Fifty-four term infants were enrolled in the study in three groups: group 1 consisted of 18 well infants who were born with clear amniotic fluid, group 2 had 18 well infants born with MSAF, and group 3 had 18 infants born with MSAF who experienced RD in the first 24 h of age. Cord blood ACTH and cortisol concentrations were measured in infants born in all three groups. Groups 2 and 3 had serum ACTH and cortisol levels re-measured at 22–26 h of age. Result: The mean ACTH and cortisol levels at birth in group 3 infants were 18.3 pg/mL and 12.6 mg/dL, respectively. These were significantly lower than those in group 2 infants. Conclusion: Term infants born with MSAF and who experienced respiratory distress had significantly lower levels of ACTH and cortisol at birth compared with well term infants born with MSAF or clear amniotic fluid. This study suggests that inadequate response of ACTH and cortisol hormones may play a role in the development of respiratory distress in term infants with MSAF.

Aims: It remains unclear if mode of delivery can have any impact on the neonatal brain. Our aim was to determine in term newborns any differences based on mode of delivery in either neuronal injury biomarkers, phosphorylated axonal neurofilament heavy chain (pNF-H) and ubiquitin C-terminal hydrolase (UCHL1), or brain oxygenation values, regional cerebral tissue oxygen saturation (CrSO2) and cerebral fractional tissue oxygen extraction (CFOE). Methods: An Institutional Review Board approved prospective observational pilot study of well newborns. Serum pNF-H and UCHL1 levels were measured on the day following delivery. CrSO2 values along with CFOE values were also measured using near-infrared spectroscopy (NIRS) and pulse oximetry. Results: There were 22 subjects, 15 born vaginally and seven born by cesarean section. No difference was found in mean pNF-H (107.9±54.3 pg/mL vs. 120.2±43.3 pg/mL, P=0.66) or mean UCHL1 (4.0±3.5 pg/mL vs. 3.0±2.2 pg/mL, P=0.68). No difference was found in mean CrSO2 (80.8±5.3% vs. 80.8±5.6%, P=0.99) or mean CFOE (0.17±0.06 vs. 0.15±0.08, P=0.51). Conclusions: We found no difference in neuronal injury markers between term neonates born vaginally compared to those born by cesarean section. From a neurologic standpoint, this supports current obstetric practice guidelines that emphasize vaginal birth as the preferred delivery method whenever possible.

Background: Influenza presents with increased morbidity and mortality in children ≤5 months of age. Vaccination of caregivers is indicated, but immunization rates are estimated at only 30%. The 2009 New York State Neonatal Influenza Protection Act (NIPA) mandated offering of influenza vaccine to caregivers during the post-partum hospitalization. The purpose of this study was to determine the impact of NIPA on infant influenza rates. Method: Data on laboratory-confirmed influenza cases between 2006 and 2012 were extracted from the New York State Electronic Clinical Laboratory Reporting System (ECLRS). Data on infant cases were categorized by age (0–5 months) and location [New York City (NYC), outside NYC] based on reporting laboratory site. The total number of influenza cases and the percentage of total cases in the infant age group were normalized to the number of reporting laboratory sites. The χ 2 -test was used to compare the proportions of cases pre- and post-implementation. Year-to-year trends were assessed by linear regression. All tests of significance were two-sided and evaluated at the P<0.05 level. Results: During the 6-year study period, 3154 cases of infant influenza were detected. In bivariate analysis, 1707 (54.1%) of cases occurred prior to NIPA implementation and 1447 (45.9%) of cases occurred after (P<0.001). Of the 1422 total infant cases detected in NYC, the percentages of influenza cases pre- and post-NIPA were 54.6% (777) and 45.4% (645), respectively (P<0.006). Outside NYC, the percentage of infant cases was reduced from 53.7% (930/1732) to 46.3% (802/1732, P<0.02). Prior to implementation, there was a year-to-year increase in the number of infant influenza cases statewide (P<0.04 for trend). The ratio of infant influenza cases normalized per ECLRS site in NYC increased each year after NIPA passage (P<0.01 for trend). The ratio of infant cases outside NYC decreased annually (P<0.05 for trend). No year-to-year trends were seen in the percentage of total influenza cases in the infant age group compared to total cases across all age groups either within or outside NYC. Conclusions: Comparison of three influenza seasons before and after NIPA suggests a total statewide reduction in infant influenza. However, the greatest driver of this reduction occurs from reduced disease in infants outside NYC. We speculate that, with increased crowding within NYC, parental immunization as encouraged by NIPA may not create cocoon immunity.

Objective: The objective of this study was to compare the knowledge of mothers of newborns in a neonatal intensive care unit (NICU) and well-baby nursery (WBN) regarding their understanding of term gestation, delivery mode safety, and elective late preterm delivery. Methods: Mothers of newborns admitted to either an NICU (n=88) or a WBN (n=145) were surveyed (March 2008–September 2010). Results: Of all mothers, regardless of infant location, 7% were unable to define term gestation, 33% were unaware that scheduling delivery at 35–36 weeks is not advisable, and 30% lacked the knowledge that cesareans are not safer than vaginal deliveries. Multivariate regression models show that socioeconomic and demographic factors underlie many knowledge gaps, and surprisingly, models confirmed that the site (NICU versus WBN) of the infant was not a significant factor related to maternal knowledge. Conclusion: This study revealed gaps in mothers’ understanding of the medical implications of premature delivery even though most mothers knew the correct length of term gestation. Unexpectedly, NICU mothers who had a child with significant illness and who encountered multiple health care providers did not have improved understanding of perinatal risks. We conclude that all women need to be educated on the significance of the mode and the timing of delivery.

Mercury exposure in pregnancy has been associated with both pregnancy complications and developmental problems in infants. Apart from industrial accidents and contaminated food, mercury exposure is likely to arise from predatory fish consumption, environmental contamination and dental amalgam restorations placed before or during pregnancy. It would be prudent to recommend that pregnant women avoid these potential problems and minimize any risk. The available literature indicates a linear relationship with mercury levels and IQ deficit, and therefore a safe limit of mercury cannot be calculated.

Objective: We sought to determine whether cumulative evidence of perinatal inflammation was associated with increased risk in a “multi-hit” model of neonatal white matter injury (WMI). Methods: This retrospective cohort study included very preterm (gestational ages at delivery <32 weeks) live-born singleton neonates delivered at Hutzel Women’s Hospital, Detroit, MI, from 2006 to 2011. Four pathologists blinded to clinical diagnoses and outcomes performed histological examinations according to standardized protocols. Neurosonography was obtained per routine clinical care. The primary indicator of WMI was ventriculomegaly (VE). Neonatal inflammation-initiating illnesses included bacteremia, surgical necrotizing enterocolitis, other infections, and those requiring mechanical ventilation. Results: A total of 425 live-born singleton neonates delivered before the 32 nd week of gestation were included. Newborns delivered of pregnancies affected by chronic chorioamnionitis who had histologic evidence of an acute fetal inflammatory response were at increased risk of VE, unlike those without funisitis, relative to referent newborns without either condition, adjusting for gestational age [odds ratio (OR) 4.7; 95% confidence interval (CI) 1.4–15.8 vs. OR 1.3; 95% CI 0.7–2.6]. Similarly, newborns with funisitis who developed neonatal inflammation-initiating illness were at increased risk of VE, unlike those who did not develop such illness, compared to the referent group without either condition [OR 3.6 (95% CI 1.5–8.3) vs. OR 1.7 (95% CI 0.5–5.5)]. The greater the number of these three types of inflammation documented, the higher the risk of VE (P<0.0001). Conclusion: Chronic placental inflammation, acute fetal inflammation, and neonatal inflammation-initiating illness seem to interact in contributing risk information and/or directly damaging the developing brain of newborns delivered very preterm.

Objective: To evaluate the use of the Bakri balloon in postpartum hemorrhage (PPH) resistant to medical treatment. Methods: The Bakri balloon was applied to 45 women with PPH after failure of initial management. Bilateral internal iliac artery ligation (BIIAL) and hysterectomy were performed if necessary. Results: The Bakri balloon was applied in 45 women; an additional BIIAL was required in nine women. The mean inflation volume of the Bakri balloon was 571±264 mL (range: 240–1300 mL). Hemostasis was achieved in 34 (75.5%) women with the Bakri balloon alone, and in six women with an additional BIIAL. The Bakri balloon was effective with additional procedures overall in 40 of 45 (88.8%) women. In 34 women with uterine atony, the Bakri balloon was successful alone in 27 (79.4%) and with an additional BIIAL in 30 (88.2%) women. An inflation volume of >500 mL was necessary in 18 women with uterine atony. Conclusion: The Bakri balloon may be performed as a first line of treatment for PPH resistant to uterotonic agents, and can be used not only in tertiary centers but also in limited-resource centers. The inflation volume of the Bakri balloon should be adjusted according to the type of PPH; a volume exceeding 500 mL may be necessary in uterine atony.

Background: Cytomegalovirus (CMV) causes congenital infection with high mortality and morbidity rates in affected neonates. Objectives: To evaluate the maternal IgG avidity value for the prediction of congenital CMV infection. Study design: The serum IgG avidity in all mothers was measured, and the urine of their neonates was assessed for CMV DNA in a prospective cohort study. Results: Of 759 women with a positive test for CMV IgG, 14 had congenital CMV infection. CMV IgG avidity indices in the congenital infection group (median 35.1%) were significantly lower than those in the non-congenital infection group (70.4%). A cutoff value of <40% IgG avidity index with 96.1% specificity and 64.3% sensitivity for congenital infection was determined by receiver operating characteristic curve analyses. The highest sensitivity (88.9%), 96.2% specificity, 27.6% positive predictive value, 99.8% negative predictive value, and 96.1% accuracy were found when IgG avidity was measured in <28 weeks of gestation. Conclusion: The IgG avidity measurement with a cutoff value of <40% IgG avidity index might be helpful in predicting congenital CMV infection, especially in <28 weeks of gestation.

Objective: To identify the risks of sustaining obstetric anal sphincter injury (OASI) during childbirth. Methods: Data were analysed from 12,612 vaginal deliveries recorded at Northwick Park District General Hospital, London, from 1 January 2006 to 30 November 2009. Results: A total of 85.6% were spontaneous deliveries and 14.2% were instrument deliveries. The majority (64.5%) sustained some form of perineal damage, 3.7% being OASI. Logistic regression analyses revealed the risk factors for OASI to be Asian ethnicity [odds ratio (OR) 4.798, 95% confidence interval (CI) 2.998–7.679], a maternal age of >40 years (OR 2.722, 95% CI 1.315–5.636), higher foetal birth weight (>4500 g; OR 6.228, 95% CI 2.695–14.392), lower parity (para 0; OR 16.803, 95% CI 7.697–36.685), and instrumental delivery. Forceps delivery posed the greatest risk (OR 8.4, 95% CI 5.822–12.151). Not having an episiotomy increased the risk of OASI by five times compared with having one. Conclusions: Risk factors for OASI include maternal age >40 years, higher foetal birth weight, lower parity, instrumental delivery, and Asian ethnicity. Mediolateral episiotomy appears to reduce the risk of OASI. Specific variables have been identified for incorporation into a risk-reduction strategy that could be introduced antenatally to evaluate and assess OASI risk.

Aims: The association between the planned delivery mode and adverse perinatal outcomes of monochorionic diamniotic (MCDA) twin pregnancies at ≥36 weeks’ gestation was evaluated. Methods: This retrospective cohort study included uncomplicated MCDA twin pregnancies delivered after 36 weeks’ gestation during a 10-year period. Cases were classified into the trial of labor (TOL) or cesarean section (CS) group according to the planned delivery mode. The primary outcome was a composite of adverse outcomes for at least one twin, including intrauterine fetal death (IUFD) after 36 weeks, neonatal death, umbilical artery pH<7.1, 5-min Apgar scores<7, hypoxic ischemic encephalopathy (HIE), meconium aspiration syndrome (MAS), respiratory distress syndrome (RDS), or acute feto-fetal hemorrhage (AFFH). The relationship between outcomes and the planned delivery mode was evaluated using a multiple logistic regression analysis. Results: We included the 310 pregnancies delivered after 36 weeks’ gestation. After excluding 15 patients, the final analysis included 295 MCDA pregnancies: 63% had delivered through TOL and 37% through CS. The incidences of composite adverse outcomes in the TOL and CS groups were 4.3% and 1.9%, respectively. No IUFD, neonatal death, MAS, RDS, or AFFH was observed; two infants in each group developed HIE. Adverse outcomes were not significantly associated with any risk factor, including delivery through TOL. Conclusion: TOL may not influence the perinatal outcomes of MCDA twin pregnancies delivered at ≥36 weeks’ gestation.