Analysis of the Perinatal Care System in a Remote and Mountainous District of Nepal.

INTRODUCTION: Despite significant improvements in recent years, maternal and neonatal health outcomes remain poor in many regions of the world. One such area is in the remote mountainous regions of Nepal. The purpose of this study is to describe the current antenatal care practices and delivery support in a mountainous district of Nepal. METHODS: This study took place in Solukhumbu District between December 2015 and February 2018. A household survey was created using evidence-based maternal and neonatal care indicators. Women who had delivered within the previous two years were surveyed regarding antenatal and delivery care they received. A standardized health facility survey was used to evaluate the operational status of health facilities. The study was approved by the Nepal Ministry of Health and the University of Utah IRB. RESULTS: A total of 487 households and 19 facilities were surveyed. 35.7% (174/487) of deliveries occurred in a health facility (hospital, primary health care center or birthing center). 35.2% (171/486) of deliveries were attended by a skilled birth attendant. 52.8% (47/89) of women who did not deliver in a facility noted that transportation issues and not having sufficient time to travel during labor prevented them from delivering in a facility. No health posts had staff trained in obstetric and neonatal emergencies. DISCUSSION: The majority of women in Solukhumbu District do not receive high quality antenatal and delivery care. An intervention that would make antenatal care and delivery support more accessible could improve maternal and infant outcomes in this district and other similar regions.

Association of Intrapartum Drugs with Spontaneous Intestinal Perforation: A Single-Center Retrospective Review.

OBJECTIVE: Spontaneous intestinal perforation (SIP) occurs commonly in extremely low gestational age newborns (ELGANs; <30 weeks' GA). Early, concurrent neonatal use of indomethacin (Neo_IN) and hydrocortisone (Neo_HC) is a known risk for SIP. Mothers in premature labor often receive indomethacin (Mat_IN) for tocolysis and steroids (Mat_S) for fetal maturation. Coincidentally, ELGANs may receive Neo_IN or Neo_HC within the first week of life. There are limited data on the effect of combined exposures to maternal and neonatal medications. We hypothesized that proximity exposure to these medications may increase the risk of SIP. STUDY DESIGN: We reviewed the medical records of ELGANs from June 2014 to December 2019 at a single level III neonatal intensive care unit. We compared antenatal and postnatal indomethacin and steroid use between neonates with and without SIP. For analysis, chi-square, Student's t-test, Fisher's exact test, and Mann-Whitney U tests were used. RESULTS: Among 417 ELGANs, SIP was diagnosed in 23, predominantly in neonates < 26 weeks' GA (n = 21/126, 16.7%). Risk factors analysis focused on this GA cohort in which SIP was most prevalent. Mat_IN administration within 2 days of delivery increased SIP risk (odds ratio: 3; 95% confidence interval: 1.25-7.94; p = 0.036). Neo_HC was not independently associated with SIP (p = 0.38). A higher proportion of SIP group had close temporal exposure of Mat_IN and Neo_HC compared with the non-SIP group, though not statistically significant (14 vs. 7%, p = 0.24). CONCLUSION: Peripartum Mat_IN was associated with increased risk for SIP in this small study sample. Larger studies are needed to further delineate SIP risk from the interaction of peripartum maternal medication with early postnatal therapies and disease pathophysiology. KEY POINTS: · Perinatal indomethacin is associated with SIP in preterm infants born at less than 26 weeks.. · Temporal proximity of prenatal/postnatal medication exposure matters.. · Indomethacin and Hydrocortisone the risks, benefits, and timing related to SIP..

Vagus nerve stimulation in pregnant rats and effects on inflammatory markers in the brainstem of neonates.

BackgroundVagus nerve stimulation (VNS) is an Food and Drug Administration-approved method delivering electrical impulses for treatment of depression and epilepsy in adults. The vagus nerve innervates the majority of visceral organs and cervix, but potential impacts of VNS on the progress of pregnancy and the fetus are not well studied.MethodsWe tested the hypothesis that VNS in pregnant dams does not induce inflammatory changes in the cardio-respiratory control regions of the pups' brainstem, potentially impacting the morbidity and mortality of offspring. Pregnant dams were implanted with stimulators providing intermittent low or high frequency electrical stimulation of the sub-diaphragmatic esophageal segment of the vagus nerve for 6-7 days until delivery. After birth, we collected pup brainstems that included cardio-respiratory control regions and counted the cells labeled for pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6, tumor necrosis factor-α) and high mobility group box 1.ResultsNeither pup viability nor number of cells labeled for pro-inflammatory cytokines in nucleus tractus solitarii or hypoglossal motor nucleus was impaired by VNS. We provide evidence suggesting that chronic VNS of pregnant mothers does not impede the progress or outcome of pregnancy.ConclusionVNS does not cause preterm birth, affect well-being of progeny, or impact central inflammatory processes that are critical for normal cardiovascular and respiratory function in newborns.

Automated Quantification of Fragmented Red Blood Cells: Neonatal Reference Intervals and Clinical Disorders of Neonatal Intensive Care Unit Patients with High Values.

BACKGROUND: Schistocytes are circulating erythrocyte fragments. They can be identified microscopically from a blood smear; but automated systems evaluate more cells and avoid inconsistencies in microscopy. Studies using adult subjects indicate that automated quantification of schistocytes can be clinically useful. However, reference intervals for automated schistocyte counts of neonates have not been published, and the relevance of a high automated schistocyte count from neonates has not been reported. OBJECTIVES: Using retrospective automated neonatal complete blood count (CBC) data, we created reference intervals for fragmented red cells (FRCs) and sought to discover the clinical conditions of neonates with high FRCs (above the upper reference interval). RESULTS: We created reference intervals based on 39,949 CBCs from 15,655 neonates 0-90 days old. The lower reference interval was 0 FRC/µL and the upper interval was 100,000/µL. The highest FRCs (96 CBCs from 44 neonates) were > 250,000/µL. These neonates clustered into the following groups: 37% had sepsis, 29% had disseminated intravascular coagulation (DIC), 17% had a genetic syndrome, 14% necrotizing enterocolitis (NEC), and 7% had iron deficiency (some had more than one diagnosis). Based on the reference intervals, we divided the 39,949 FRC values into 3 groups: (1) < 100,000/µL ("normal"), (2) 100,000-200,000/µL ("moderately elevated"), and (3) > 200,000/µL ("extremely elevated"). The odds that a microangiopathic condition (DIC, sepsis, NEC) or a microcytic disorder (iron deficiency) were present were significantly higher in the moderately elevated, and more so in the extremely elevated group. CONCLUSIONS: Our study suggests that a high FRC could prompt investigation into, or inform follow-up of, a neonatal microangiopathic or extremely microcytic disorder.

Neonates with suspected microangiopathic disorders: performance of standard manual schistocyte enumeration vs. the automated fragmented red cell count.

OBJECTIVES: To enhance the diagnosis of schistocyte-producing conditions, we compared routine manual schistocyte enumeration with automated fragmented red cell counts (FRCs). STUDY DESIGN: In neonates "suspected" of having sepsis, NEC, or DIC we compared manual schistocyte estimates vs. automated FRC counts. When the two disagreed, we used a "gold standard" from a  ≥ 1000 RBC differential. We also assessed the diagnostic accuracy of the FRC count in diagnosing sepsis, NEC, or DIC. RESULTS: We collected 270 CBCs from 90 neonates. The methods agreed in 63% (95% CI 55%-70%) of the CBCs. Among the 37% where they disagreed, the FRC count was more accurate in 100% (95% CI 88-100%). An elevated FRC count was specific for sepsis, and was sensitive and specific for necrotizing enterocolitis and DIC. CONCLUSIONS: Automated FRC counts have advantages over routine manual evaluation, larger sample size, lower expense, and superior accuracy in diagnosing schistocyte-producing conditions.

Non-Immune Hydrops, Hypotonia, Encephalopathy, and Liver Failure with Novel Compound Heterozygous AHCY Mutations.

A late-preterm infant with a prenatal diagnosis of non-immune hydrops was born with hypotonia, poor respiratory effort, chylothorax, encephalopathy, coagulopathy, progressive hepatic failure, and refractory pulmonary hypertension. Life support was withdrawn at 7 days of life due to multisystem organ failure. Rapid whole exome sequencing revealed novel compound heterozygous mutations in the gene encoding S-adenosylhomocysteine hydrolase (AHCY); each novel variant was carried by an asymptomatic parent. Reports of neonates with other AHCY mutations describe a pathology of varying severity. AHCY mutations should be considered when seeking an etiology for neonates with the combination of non-immune hydrops, hypotonia, encephalopathy, and liver failure.