Journal of Neonatal-Perinatal Medicine

INTRODUCTION: Although antifibrinolytic agents are used to prevent and treat hemorrhage, there are concerns about a potential increased risk for peripartum venous thromboembolism. We sought to determine the impact of tranexamic acid and ɛ-aminocaproic acid on in vitro clotting properties in pregnancy.

METHODS: Blood samples were obtained from healthy pregnant, obese, and preeclamptic pregnant women (n = 10 in each group) prior to delivery as well as from healthy non-pregnant controls (n = 10). Maximum clot firmness (MCF) and clotting time (CT) were measured using rotation thromboelastometry in the presence of tranexamic acid (3, 30, or 300 μg/mL) or ɛ-aminocaproic acid (30, 300, or 3000 μg/mL). ANOVA and regression analyses were performed.

RESULTS: Mean whole blood MCF was significantly higher in healthy pregnant vs. non-pregnant women (66.5 vs. 57.5 mm, p < 0.001). Among healthy pregnant women, there was no significant difference between mean MCF (whole blood alone, and with increasing tranexamic acid doses = 66.5, 66.1, 66.4, 66.3 mm, respectively; p = 0.25) or mean CT (409, 412, 420, 424 sec; p = 0.30) after addition of tranexamic acid. Similar results were found using ɛ-aminocaproic acid. Preeclamptic women had a higher mean MCF after the addition of ɛ-aminocaproic acid and tranexamic acid (p = 0.05 and p = 0.04, respectively) compared to whole blood alone.

CONCLUSIONS: Pregnancy is a hypercoagulable state, as reflected by an increased MCF compared to non-pregnant women. Addition of antifibrinolytic therapy in vitro does not appear to increase MCF or CT for non-pregnant, pregnant, and obese women. Whether antifibrinolytics are safe in preeclampsia may require further study.

OBJECTIVE: To compare blood loss and the use for blood transfusion between elective (planned) and emergent cesarean hysterectomy performed for placenta accreta by a single, multidisciplinary team and to present the team’s pre-operative evaluation and the surgical technique.

STUDY DESIGN: Prospective cohort study at a single tertiary care center. Maternal and neonatal outcomes were compared between elective and emergent delivery of pregnancies complicated by placenta accreta. The primary outcomes were the need for blood transfusion and the number of units transfused.

RESULTS: A total of 28 cases of confirmed placenta accreta underwent peripartum hysterectomy, including 22 as elective and 6 as emergent. Eleven out of 22 (50%) subjects in the elective group received blood transfusion, while all subjects in the emergency group required transfusion (p = 0.03). More importantly, the number of units of packed red blood cells transfused was only 1.90 (±2.20) units in the elective cases compared to 7.83 (±4.90) units in cases performed emergently (p = 0.03).

CONCLUSION: Elective cesarean hysterectomy for this indication using a clearly outlined surgical approach is associated with significantly lower blood loss and hence less need for transfusion, compared to its emergent counterpart.

BACKGROUND: Although diabetic ketoacidosis (DKA) in pregnancy can result in significant adverse consequences for both mother and fetus, the response to treatment, time course of recovery, and perinatal outcomes have not been well studied in pregnancy.

OBJECTIVE: We examined the precipitating factors, laboratory abnormalities, treatment strategies, and clinical recovery in pregnancies complicated by DKA.

STUDY DESIGN: This is a retrospective cohort study of pregnancies complicated by DKA between October 1999 and June 2015. The diagnosis was verified by hyperglycemia; anion gap >12 mEq/L, pH <7.3, HCO3 <15 mEq/L; and the presence of ketones. Each episode of DKA was reviewed and subsequent perinatal outcomes analyzed.

RESULTS: During this period, we identified 33 women with 40 admissions (incidence: 0.2%). The majority of women had type 1 diabetes (67%), and almost all presented with nausea and vomiting (97%). Over half had poor compliance with prescribed insulin. The initial mean blood glucose was 380 mg/dL, within 6 hours, it was <200 mg/dL. By 12 hours, the acidosis had resolved in 90% of patients.

CONCLUSION: Nausea and vomiting is a prominent presenting feature of DKA in pregnancy. With aggressive insulin and resuscitation, hyperglycemia and acidosis improve rapidly. With current treatment, good perinatal outcomes can be expected.

OBJECTIVE: Women with diabetes may need elective preterm delivery due to pregnancy or diabetes related complications. The aim of this study was to describe the neonatal outcomes arising from elective preterm delivery in diabetic women.

METHOD: Suitable patients were identified by the obstetric team at Hull Royal Infirmary Women and Children’s Hospital and data was extracted from their case notes. 45 diabetic women with planned preterm delivery were identified within a set time frame, resulting in 48 babies.

RESULTS: Of the 48 babies born, 47 survived. 36 out of 48 were delivered via caesarean section. Gestational ages ranged from 29+3 to 36+6 weeks, and 24 out of 48 (50%) had a birth weight greater than the 90th centile for gestational age.

34 out of the 48 babies experienced some form of neonatal complication and were admitted to the neonatal unit. The median duration of stay in the neonatal unit was 7 days. 14 of the surviving neonates suffered from respiratory distress, although only 4 required surfactant therapy to regain respiratory function. However, the incidence of serious neonatal complications in those born after 34 weeks was shown to be low.

CONCLUSIONS: Elective preterm delivery after 34 weeks had little effect on overall neonatal outcome. Therefore it could be proposed that elective preterm delivery after 34 weeks gestation may be an acceptable option in diabetic women if there are maternal or obstetric complications.

OBJECTIVE: The objective of this study was to determine if outcomes at our neonatal intensive care units (NICUs) since we began using calcium chloride (CaCl₂) as our preferred calcium additive in order to reduce aluminum (Al) exposure are within expected outcome ranges for NICUs in the U.S. where calcium gluconate in glass vials (CaGlu-Gl) has been the preferred additive.

STUDY DESIGN: A retrospective study of very low birth weight infants born between January 1, 2000 and December 31, 2014. Outcomes in two intensive care units (NICUs) using CaCl₂ were compared to all U.S. NICUs in the Vermont Oxford Network. Primary outcomes were chronic lung disease (CLD), percent requiring supplemental oxygen at 28 days, and mortality excluding early deaths (MEED). The incidence of IV infiltrates of all admissions to the study NICUs in 2013-2014 was compared to the literature.

RESULTS: The incidence of CLD and those requiring oxygen at 28 days were 24.0% vs 28.6% and 46.2% vs 51.8% for the study NICUs compared to all U.S. NICUs, respectively (both p < 0.0001). The MEED was 8.7% vs 10.3% (p < 0.002). All major morbidities were lower at the study NICUs. The incidence of infiltrates was lower than that in the literature.

CONCLUSION: The use of CaCl₂ was not associated with any detectable adverse effects. Calcium chloride appears to be a safe alternative to the use of CaGlu-Gl based upon studies of clinical outcomes.

OBJECTIVE: To determine the maximum dilution of human milk (HM) that yields reliable results for protein, fat and lactose when analyzed by mid-infrared spectroscopy.

STUDY DESIGN: De-identified samples of frozen HM were obtained. Milk was thawed and warmed (40°C) prior to analysis. Undiluted (native) HM was analyzed by mid-infrared spectroscopy for macronutrient composition: total protein (P), fat (F), carbohydrate (C); Energy (E) was calculated from the macronutrient results. Subsequent analyses were done with 1 : 2, 1 : 3, 1 : 5 and 1 : 10 dilutions of each sample with distilled water. Additional samples were sent to a certified lab for external validation.

RESULTS: Quantitatively, F and P showed statistically significant but clinically non-critical differences in 1 : 2 and 1 : 3 dilutions. Differences at higher dilutions were statistically significant and deviated from native values enough to render those dilutions unreliable. External validation studies also showed statistically significant but clinically unimportant differences at 1 : 2 and 1 : 3 dilutions.

CONCLUSIONS: The Calais Human Milk Analyzer can be used with HM samples diluted 1 : 2 and 1 : 3 and return results within 5% of values from undiluted HM. At a 1 : 5 or 1 : 10 dilution, however, results vary as much as 10%, especially with P and F. At the 1 : 2 and 1 : 3 dilutions these differences appear to be insignificant in the context of nutritional management. However, the accuracy and reliability of the 1 : 5 and 1 : 10 dilutions are questionable.

OBJECTIVES: To determine differences in feeding tolerance amongst preterm small for gestational age (SGA) infants with normal versus abnormal umbilical artery Doppler flow defined as absent or reversed end diastolic flow (AREDF).

METHODS: This was a retrospective cohort study of infants <35 weeks gestational age (GA) and birth weight (BW) <10th percentile. Day of initiation of feeds, days to full feeds and CRIB II scores were the primary outcomes. Clinical characteristics were compared between the groups of SGA infants with normal and AREDF. Multivariable regression models were fit to the data to adjust for potential confounders of the association of AREDF and feeding intolerance.

RESULTS: 120 infants with normal and 64 infants with AREDF were included. The infants with AREDF were smaller (971 g vs. 1183 g, p = 0.0002), less mature (29.9 wks vs. 31.2 wks, p = 0.0009), had higher CRIB II score (7.2 vs. 5.2, p = 0.0033), started feeding later (4.1 days vs. 3.3 days, p = 0.020) and advanced slower to full feeds (17.7 days vs. 13.7 days, p = 0.0017). Necrotizing enterocolitis was similar between the groups (p = 0.18). After adjusting for confounders, Doppler flow was no longer a significant predictor of the initiation (p = 0.37) and advancement of feeds (p = 0.44).

CONCLUSIONS: Infants with AREDF are sicker at birth and have more feeding difficulties; after adjusting for BW and GA, Doppler flow was no longer a significant predictor of feeding intolerance.

BACKGROUND: Programmed changes in growth restricted fetuses can increase the risk of adulthood diseases due to elevated serum cholesterol and apolipoprotein-B (Apo-B) concentrations. Increasing evidence demonstrated the role of apoB/apoA-I ratio as a strong risk factor for cardiovascular diseases.

OBJECTIVE: To determine the concentration of cord blood lipoproteins and apolipoproteins as well as their correlation with birth weight.

METHODS: This cross-sectional study was conducted in a teaching institution in central India. Healthy full-term newborns, born out of normal vaginal deliveries, were recruited. Cases include term small for gestational age (SGA) babies while term appropriate for gestational age (AGA) babies were taken as controls. Their umbilical venous blood was collected and sent for biochemical analysis.

RESULTS: Out of 126 healthy newborns, 66 were cases and 60 were controls. Mean values of serum triglyceride (141.56±69.67 mg/dl vs. 113.67±33.38 mg/dl; p < 0.006; 95% CI = 8.31 to 47.46) and serum apo-B/apo-A-1 ratio (0.67±0.28 vs. 0.55±0.20; p < 0.007; 95% CI = 0.033 to 0.206) were significantly high and that of serum high density cholesterol (35.84±10.42 mg/dl vs. 40.73±11.70 mg/dl; p < 0.014; 95% CI = –8.79 to –0.98) and Apo-A1 [87.59±12.44 mg/dl vs. 101.87±35.07 mg/dl; p = 0.002; 95% CI = –23.39 to –5.16) were significantly low in SGA newborns. Serum cholesterol, very low-density cholesterol rlow-density cholesterol rand Apo-B did not show any significant difference. Among SGA newborns significant negative correlation was seen between birth weight and apo-B/apo-A1 and serum triglyceride, while birth weight and serum apo-A1 level showed significant positive correlation. There was no statistically significant correlation between birth weight and other parameters.

CONCLUSION: These findings further support the association of prenatal factors with lipid profile rand can serve as starting point for studying lipid transport system changes during early life in Indian population.

OBJECTIVE: To compare chest X-ray with echocardiogram (ECHO) in the localization of an umbilical venous catheter (UVC) tip in very low birth weight infants (VLBW). Secondary objectives determined the association between techniques for tip placement by the vertebral body level on X-ray, as well as the length of the thoracic inferior vena cava-right atrial (TIVC-RA) junction by ECHO.

STUDY DESIGN: Prospective, sequentially enrolled, masked, single regional perinatal center study. Shortly after birth, one or more anterior-posterior X-rays were ordered by the clinical team to verify that the UVC tip was fixed in the central right atrium (cRA) or at the TIVC-RA junction. An echocardiogram was performed as soon as possible after the last X-ray and UVC tip location was interpreted by a pediatric cardiologist. The pediatric radiologist and cardiologist were masked with regard to each other’s reading.

RESULTS: The newborns (n = 51) were 27 (±3) weeks by gestational age with birth weights of 1029 (±288) grams (mean±SD). The radiologist read 50 UVC tips (98%) in the cRA or TIVC-RA junction and 1 (2%) in the LA. The cardiologist read 22 (43%) in the cRA or TIVC-RA, 21 (41%) in the LA and 8 (16%) tips could not be located in the heart. When the UVC tip was interpreted by X-ray as located in the TIVC-RA junction 8/29 (28%) were in the LA by echocardiogram. There was no agreement between vertebral level and tip position in the TIVC-RA junction, RA or LA. The TIVC-RA junction measured 6±1 mm and correlated with birth weight r = 0.54 (p < 0.001).

CONCLUSION: In VLBW newborns, placement of the UVC tip into the cRA or TIVC-RA junction by X-ray does not avoid misplacement in the left atrium as demonstrated by echocardiography. For VLBW infants, it is suggested that echocardiography may be helpful in verifying that the original placement or migration of the UVC tip into the LA has not occurred.

OBJECTIVE: To evaluate the duration of catheter stay, incidence of non-elective removal and rates of complications associated with peripherally inserted central catheters (PICCs) in relation to different catheter positions in extremely preterm infants (EPT, <28 weeks of gestation).

METHODS: A retrospective analysis of Peripherally Inserted Central Catheters (PICCs) inserted in EPT infants over a 10-year period, from January 2004 through December 2013 (mean gestational age, 25.2 weeks; mean birth weight, 727 g).

RESULTS: Of the 379 PICCs analyzed, the majority of lines (68%) were placed in the central position, and 259 PICCs (56%) were removed electively after fulfilment of the treatment. Significantly more PICCs in the lower extremities compared to the upper extremities were in central positions (86% vs 61%, p < 0.001, respectively). Significantly more PICCs that were removed electively after fulfilment of the treatment were in a central position compared to a non-central position (p < 0.001). Of the 166 catheters that were removed because of complications, most (71%) of them had mechanical problems, and 13% had sepsis resulting in an incidence rate of 4.4/1000 catheter days.

CONCLUSION: PICCs inserted in the lower extremity were more likely to have a centrally placed tip position compared to PICC lines inserted in the upper extremities.

OBJECTIVE: To evaluate the incidence of otherwise undiagnosed congenital heart disease (CHD) in a population of children born in a hospital with routine pulse oximetry (RPO) screening compared to children born at home.

METHODS: We reviewed 15 years of births at 2 hospitals for incidence of undiagnosed CHD with RPO. The Health Department reviewed the same data for out of hospital births.

RESULTS: A total of 50,545 hospital births were screened and 1,274 children were born outside the hospital. There were 28 hospital-born babies diagnosed with cyanotic CHD prior to nursery discharge. Only one of these babies would not have been diagnosed without RPO. Three children were missed and there were 3 false positives. Sensitivity and positive predictive value of RPO was 25%, specificity and negative predictive value of RPO exceed 99%. The incidence of CHD requiring RPO diagnosis was roughly one birth per 50,000. Two children born at home with undiagnosed CHD were missed. One of these children presented with neonatal demise.

CONCLUSION: RPO screening is still valuable in diagnosing CHD only diagnosable with RPO. However, the incidence of CHD requiring RPO to diagnose is similar to other congenital diseases which are not mandated national screening tests. In our limited experience a patient is roughly 25 times more likely to have undiagnosed CHD if they are born outside of a hospital.

OBJECTIVE: We aimed to investigate if endothelin 1 concentration at day 3 postnatal age could be used as a predictive marker for development of bronchopulmonary dysplasia in preterm neonates with respiratory distress syndrome.

METHODS: This prospective observational study was done on 69 preterm neonates with gestational ages between 28 and 34 weeks and diagnosed as having respiratory distress syndrome. Serum concentrations of endothelin 1 was measured for all patients at day 3 of life and they were divided into BPD and No-BPD groups according to whether they developed bronchopulmonary dysplasia or not.

RESULTS: A total of 17 infants were in the BPD group and 52 infants were in the No-BPD group. Serum endothelin 1 was significantly higher in the BPD group (435.39±172.88) compared with the No-BPD group (302.65±49.32) (p < 0.001). Serum endothelin 1 correlated significantly with days spent on mechanical ventilation (r = 0.379, p = 0.022) and days spent on CPAP (r = 0.391, p = 0.001). A serum endothelin 1 cut off value of 302.7 ng/L could predict preterm that will develop bronchopulmonary dysplasia with a sensitivity of 88.24%, and specificity of 61.54%.

CONCLUSION: Serum endothelin 1 is significantly increased at day 3 of life in preterm neonates with respiratory distress syndrome who later develop bronchopulmonary dysplasia (BPD). It seems to be a promising predictive marker for BPD but further studies are needed to find the appropriate time for its measurement.

BACKGROUND: Retinopathy of prematurity (ROP) is a vaso-proliferative disease of the eye, which mainly affects preterm newborn infants with an incompletely vascularized retina. The incidence of ROP has increased in industrialized countries due to the increased survival of extremely low birth weight (ELBW) infants. ROP is also increasing in developing countries like Indonesia, where it is most likely due to the improved survival of ELBW infants.

OBJECTIVE: To ascertain the incidence of ROP and possible risk factors associated with the development of ROP in preterm infants in Indonesia.

METHODS: We reviewed the literature on the incidence and potential risk factors for the development of ROP in Indonesia, obtained data from three referral eye clinics and added data from our institution.

RESULTS: The reported incidence of all stages of ROP in infants with a gestational age of <32 weeks ranged from 18–30%. One study showed that ROP also occurred at older gestational ages. Blindness due to ROP was seen in infants up to 35 weeks and with a birth weight of 2000 g.

CONCLUSION: Retinopathy of prematurity is an important cause of ocular morbidity and blindness in Indonesia. The overall incidence of ROP in infants born below 32 weeks in Indonesia is higher than in developed countries, and it is seen in infants with older gestational ages. This might be due to a less strict monitoring during the use of oxygen in Indonesia compared to industrialized countries.

BACKGROUND: Group B streptococcus (GBS) is a leading cause of maternal and neonatal infectious morbidity. HIV is prevalent among pregnant women in Nigeria.

AIM: To determine the rates of anogenital GBS colonization in our institution and compare GBS colonization rates between HIV positive and negative pregnant women.

METHODS: A cross-sectional comparative study was conducted over 6 months. Patients were separated according to their HIV status: positive and negative. GBS colonization was assessed by vaginal and anal swabs collected at 35–37 weeks of gestation and cultured in Todd-Hewitt broth, followed by a confirmatory test. Socio-demographic characteristics and CD4 count were extracted from patient medical records. Secondary outcomes were identification of risk factors for GBS colonization, antibiotic sensitivity, and any association between CD4 count and GBS colonization. Appropriate statistical analysis was done.

RESULTS: A total of 200 patients attended the clinic; 67 HIV positive and 133 negative. Analyzed samples were 198; the overall prevalence of GBS was 18.2%. No significant difference in GBS colonization was noted between HIV positive (19.4% [13]) and negative patients (17.6% [23/131]). Most GBS isolates were susceptible to ampicillin (87%) and penicillin (81%). A high body mass index (BMI) was independently associated with GBS colonization (OR = 1.25, 95% CI: 1.04–1.51). No association was observed between CD4 counts and GBS colonization.

CONCLUSION: A high prevalence of GBS colonization was observed in our institution. Colonization rates were independent of the HIV status but associated with a high BMI in HIV positive women.

OBJECTIVE: Survival rates of premature infants are at a historical high and increasingly more pediatricians are caring for former premature infants. The goal of this study was to describe the perspectives and attitudes of pediatricians, as well as, the challenges of rendering post-neonatal intensive care unit (NICU) discharge care for premature infants.

METHODS: An anonymous 22-question web-based survey was emailed to pediatricians who are current members of the American Academy of Pediatrics (AAP) and practicing in Kings County, New York.

RESULTS: There were 148 completed surveys with 79% being general pediatricians. Of all respondents, 63% believed that premature infants should have a neonatal high risk follow-up visit within days after discharge and 64% were satisfied with the NICU discharge summary acquisition. While 74% of pediatricians felt comfortable following up with former extremely premature infants, 65% referred to specialists, most often to child development, neurology, and physical and/or occupational therapy. The majority (85%) were more likely to refer premature infants to early intervention. Participating pediatricians varied in their knowledge of immunization and breastfeeding guidelines. Finally, 88% of respondents acknowledged that caregivers of premature infants experience increased stress, with 53% stating that the stress should be addressed.

CONCLUSIONS: Understanding the perceptions and challenges of pediatricians who care for premature infants may help improve post NICU quality of care. Transition to the outpatient setting is a crucial step in the management of premature infants and a focus on improved hand-off procedures between hospital and physicians may prove beneficial. Also, pediatricians must stay abreast of current recommendations for breastfeeding and vaccinations. Furthermore, emphasis should be given to stress reduction and management for caregivers of former premature infants.

Twin infants born at 34 week gestation had frank blood in stools on day three of life on mixed feeds of formula and maternal breast milk. Sepsis work up was negative in these relatively well appearing infants with pneumatosis in the colon on abdominal x-ray. Blood in stools recurred on reintroduction of breast milk in Twin A. Both infants recovered from episodes of bloody stools on amino-acid based formula and were thriving at discharge. Early necrotizing enterocolitis in both twins is rare and has not been reported. Cow’s milk protein sensitivity, possibly from in-utero sensitization, could explain non-infectious colitis in these twins, precipitated by formula or breast milk after birth.

Congenital mesoblastic nephroma (CMN) is the most common renal tumor of infancy; however, it occurs infrequently with an incidence of 1 : 125,000. The cellular and classical variants are the most common subtypes of tumors, with a mixed variant occurring infrequently. We describe two cases of mixed variant CMN, which presented within days of each other differing in their clinical behavior. The first case followed a typical course, previously described in the literature, while the other deviated significantly. Traditionally, CMN presents as large abdominal mass in the neonatal period associated with a paraneoplastic syndrome, which can result in hypertension or hypercalcemia. Surgical resection is curative in most cases and long-term prognosis is excellent. Hypertension rarely persists after removal of the tumor, but remained in one of our two patients.

Infant delirium is an under-recognized clinical entity in neonatal intensive care, and earlier identification and treatment could minimize morbidities associated with this condition. We describe a case of a 6-month-old former 32 weeks gestation infant undergoing a prolonged mechanical ventilation course diagnosed with delirium related to the combination of his underlying illness and the use of multiple sedative and analgesic medications. Initiation of the atypical antipsychotic risperidone allowed for weaning from continuous infusions of benzodiazepines and opiods, and lower dosages of bolus-dosed sedation and analgesics. The patient experienced no adverse side effects from use of this neuroleptic.