Journal of Neonatal-Perinatal Medicine

Chronic hypothalamic-pituitary-adrenal (HPA) axis activity role in the pathogenesis of preterm birth (PTB) remains unclear due to inconsistent measures with limited ability to monitor long-term cortisol concentrations. We explored this relationship using the novel method of assessing cortisol in hair, which is a valid and reliable measure of chronic HPA axis activity.

137 participants (40 PTB cases and 97 controls from a birth cohort of pregnant women in Peru) were interviewed and invited to provide a 9-cm hair sample from the posterior vertex position of the scalp (mean = 13 weeks gestation). Hair cortisol concentration (HCC) was determined using luminescence immunoassay and values were natural-log transformed. PTB cases were defined as women who delivered before 37 gestational weeks. Case-control differences were assessed using multivariable linear and logistic regressions.

Overall, combined pre-conception and first-trimester HCC was 13% lower among cases as compared with controls (p-value = 0.01). Compared with controls, maternal HCC among PTB cases were 14% (p = 0.11), 10% (p = 0.22) and 14% (p = 0.08) lower for 3–6 months pre-conception, 0–3 months pre-conception, and first trimester, respectively. After adjusting for putative confounders, a 1-unit increase in HCC was associated with 55% reduced odds of PTB (aOR = 0.45; 95% CI: 0.17–1.17). For a 1-unit increase in HCC in the scalp-intermediate and scalp-distal segments (representing HCC concentrations in 0–3 months pre-conception and first trimester), the corresponding odds for PTB were 0.53 (95% CI: 0.19–1.48) and 0.39 (95% CI: 0.13–1.13), respectively.

Women who deliver preterm, as compared with those who deliver at term, have lower preconception and first trimester HCC. Our findings suggest that HPA axis activation, integral to the adaptive stress-response system, may be chronically dysregulated in women at increased risk of PTB.

The objective of this study is to evaluate the obstetric outcomes of pregnancies with congenital diaphragmatic hernia (CDH).

Fifty one pregnancies prenatally diagnosed with CDH at our institution between January 1, 2002 and August 31, 2018 were retrospectively evaluated. The pregnancies were divided into two groups according to neonatal survival. Demographic features, clinical characteristics and prognostic factors were compared between the neonatal survival (n = 16) and non-survival (n = 28) groups. Cut-off values of fetal lung area to head circumference ratio (LHR), observed/expected LHR (o/e LHR) and observed/expected total fetal lung volume (o/e TFLV) for neonatal survival were calculated.

Thirty six (70.6%) and fifteen (29.4%) fetuses had left and right sided CDH respectively. Seven patients chose termination of their pregnancies (13.7%). Statistically significant differences were found between survival and non-survival groups in terms of parity, median gestational week at diagnosis, polyhydroamniosis rate, CDH type, stomach position, liver position, median LHR, o/e LHR, o/e TFLV, median 5th minute Apgar score and neonatal operation rate values (p values were 0.03,<0.001, 0.02, 0.006,<0.001, 0.006,<0.001,<0.001,<0.001, 0.04 and <0.001 respectively). According to ROC curve analysis, 1.05 (82% sensitivity, 74% specificity) for LHR, 22.5 (78.6% sensitivity, 73.9% specifity) for o/e LHR and 23.5 (85.7% sensitivity,74.2% specificity) for o/e TFLV were determined to be cut-offs for neonatal survival, respectively, with highest sensitivity and specificity.

Earlier gestational week at diagnosis, right sided CDH, presence of liver herniation, supradiaphragmatic stomach position, lower LHR, o/e LHR and o/e TFLV were associated with decreased rates of neonatal survival.

Both preeclampsia and neuraxial anesthesia can alter placental perfusion, potentially affecting the neonatal status. The objective of our study is to quantify the association between type of neuraxial anesthetic and short-term neonatal morbidity among preeclamptic patients undergoing cesarean delivery.

We performed a secondary analysis of a prospective observational cohort study. Women with singleton gestations and a diagnosis of preeclampsia who underwent cesarean delivery with neuraxial anesthesia were included in the analysis. Short-term neonatal morbidities, defined as neonatal intensive care unit (NICU) admission, arterial cord gas pH ≤7.2 and 5-minute Apgar <7, were compared based on type of neuraxial anesthetic.

A total of 4100 patients were included in the analysis, 1696 (41.4%) received spinal anesthesia 1848 (45.1%) received epidural anesthesia and 556 (13.5%) received a combined spinal-epidural (CSE). Antepartum and intrapartum characteristics significantly differed between the groups (p≤0.02). After adjusted analysis, spinal anesthesia was associated with reduced odds of NICU admission, compared with epidural or CSE (OR; 95% CI: 0.79; 0.63–0.98, 0.71; 0.53–0.94, respectively). Spinal anesthesia was also associated with lower odds of a 5-minute Apgar <7 compared with epidural anesthesia (OR 0.59; 95% CI; 0.43–0.83). We found no association between type of anesthesia and arterial cord pH ≤7.2. In stratiifed analysis by gestational age, no association between the type of neuraxial anesthesia and neonatal outcomes was noted among term infants, but associations persisted in preterm infants.

Among women with preeclampsia undergoing cesarean delivery, spinal anesthesia may be associated with reduced short-term neonatal morbidity in preterm infants, compared with epidural or CSE.

The aim of this study was to asses the correlation of middle cerebral artery pulsatility index (MCA-PI) and perinatal outcomes in prolonged pregnancies.

This was a prospective study of all consecutive pregnant women beyond 41 weeks’ gestation attending for obstetric surveillance during a two years period. We evaluated the predictive value of MCA-PI lower than the 5th percentile (<p5) and the occurrence of: cesarean delivery for fetal distress, 5-min Apgar score <7, arterial cord pH < 7.15, presence of thick meconium at delivery, need for admission to the neonatal intensive care and/or neonatal death.

Three hundred and one pregnancies met the inclusion criteria and were managed expectantly. Of them, 31 (10.3%) fetuses had an MCA-PI < p5, which showed a significant relationship with the presence of thick meconium at birth (p < 0.001), but was not related to any of the other perinatal outcomes.

In prolonged pregnancies, the finding of MCA-PI < p5 is related to meconium emission at the time of delivery, but is not associated with an increased risk of adverse perinatal outcome.

To evaluate the utility of echocardiogram (ECHO) in detection and treatment of patent ductus arteriosus (PDA) and hemodynamically significant PDA (hsPDA) in preterm neonates.

This was a retrospective case-control study of all preterm infants born or admitted to the level III Neonatal Intensive Care Unit in McMaster Children’s Hospital from January 2009 to January 2013. These cases were further classified into the following sub-groups: group A) hsPDA confirmed on ECHO; and the control, group B) PDA (but not hemodynamically significant) confirmed on ECHO. Patients without an ECHO were excluded from all analyses. The primary outcome was incidence of treatment for PDA.

PDA treatment was administered in 83.3% and 11.2% of patients in groups A and B respectively (P < 0.05). Among patients with a hsPDA within group A, 17% did not receive treatment, while 11% of patients with non-hemodynamically significant PDA received treatment for the PDA. Within the cohort of patients who received treatment for a hsPDA, gestational age below 35 weeks as well as murmurs heard on auscultation were both found to be predictors of treatment.

While the ECHO remains the gold standard for detecting pathological PDA, there is evidence that other traditional clinical measures continue to guide clinical practice and treatment decisions. Further research is required to gain an understanding of how clinical measures and ECHO may be used in conjunction to optimize resource utilization.

There are limited evidence-based published blood pressure ranges for premature neonates. The aim of the study was to determine blood pressure ranges in a large cohort of premature neonates based on gestational and post-menstrual age.

Retrospective observational study of premature neonates admitted to the neonatal intensive care unit at our institution between January 2009 and October 2015. We stratified data by gestational and post-menstrual age groups as well as by method of blood pressure measurement (non-invasive vs. invasive).

Over two billion blood pressure values in 1708 neonates were analyzed to generate heat maps and establish percentile-based reference ranges. The median gestational age of the cohort was 31 weeks (IQR 28–33 weeks). We found moderate correlation (r = 0.57) between simultaneously obtained non-invasive and invasive blood pressure measurements.

Our results can serve as a reference during the bedside assessment of the critically-ill neonate.

Respiratory support in the form of mechanical ventilation is a crucial intervention in premature neonates, with respiratory problems. However, prolonged mechanical ventilation and endotracheal intubation may be associated with major adverse effects. The ideal time for extubation is based on clinical and laboratory parameters assessed at the time of planned extubation. However, such parameters are not very objective, which makes extubation in NICUs a trial-and-error approach.

This work was done to assess the use of extubation bundle including modified spontaneous breathing trial (SBT) (10 minutes) to reduce the rate of reintubation, among preterm neonates≤30 weeks who were mechanically ventilated and extubated to non-invasive ventilation in the NICU, Women’s Wellness and Research Center (WWRC), Hamad Medical Corporation (HMC), Doha, Qatar.

A prospective study based on the collection of data regarding preterm neonates≤30 weeks gestation admitted to the NICU, Women’s Wellness and Research Center (WWRC), from January, 2015 to December, 2017, who were subjected to mechanical ventilation (MV) and extubation. When the clinical team decides a newborn is ready for extubation based on the extubation bundle, a modified SBT (10 min) is used.

This study included 465 premature babies from 24-≤30 weeks recruited in the NICU, Women’s Wellness and Research Center (WWRC). Extubation bundle with modified SBT was able to predict success of extubation with 95% sensitivity and 90.4% Positive Predictive Value (PPV) in the gestational age (GA) group 24 -≤27 weeks (245) and 95.3% sensitivity and 90% PPV in the GA group > 27 -≤30 weeks (220). As expected, successfully extubated babies had a higher GA and weighed more at extubation, compared to babies who required re-intubation.

We recommend the extubation bundle with modified SBT prior to elective extubation to be used in predicting successful extubation in premature babies. Guidelines for extubation among premature babies are needed in order to reduce unnecessary exposure to adverse effects of mechanical ventilation.

Preterm infants are fed by orogastric / nasogastric tube until they reach maturation and coordination of sucking, swallowing and respiration at approximately 32–34 weeks of corrected age. While being on non-invasive ventilation (NIV), they frequently present abdominal distension. Currently at our institution two techniques are used for the management of abdominal distension in preterm infants fed by bolus via orogastric tube: cenit and 2 x 1.The aim of this study was to compare the proportion of preterm infants presenting NIV-associated abdominal distension with each of these techniques.

We conducted a randomized clinical trial including infants of <  36.6 weeks of gestation and <  1500 g of birth weight who were admitted to our NICU during the period of April 1, 2016 to April 1, 2018 and received NIV. The presence of abdominal distension >  2 cm was the primary outcome. Secondary outcomes were presence of reflux, regurgitation, oxygen saturation during feeding and days to reach full feedings. Feeding tube drainage, stool characteristics and the use of prokinetics were confounding variables.

A total of 97 patients were included. Forty-six in the cenit group and 51 in the 2 x 1 group. There was no difference in the proportion of infants with abdominal distension >  2 cm between groups. Oxygen saturation during feeding at volume of 150 ml/kg/day was higher in the cenit group with statistical significance.

The use of cenit or 2 x 1 technique in preterm infants with NIV did not improve abdominal distension or other indicators of feeding tolerance.

Differences in the susceptibility of preterm infants to develop necrotizing enterocolitis (NEC) implicate potential genetic differences in response to the inflammatory stimuli leading to NEC. Dual specificity phosphatases (DUSPs) are a key suppressor pathway of the mitogen-activated protein kinase (MAPK) pro-inflammatory signaling pathway. We hypothesized that inherited single nucleotide polymorphisms (SNPs) in DUSP genes contribute to NEC susceptibility in premature infants.

Patients admitted between 2010 and 2015 born at <  32 weeks GA and≤1,500 g BW with stage II+NEC (cases; n = 50) and age, weight-matched controls (n = 38) were included. Blood samples were collected for DNA isolation. Agena Mass Array assay was used to examine 31 SNPs in 9 different DUSP genes. Calculated minor allele frequencies (MAF) for cases and controls were compared using χ² and logistic regression.

The presence of the rs704074 SNP was associated with a 48% decreased risk of developing NEC (OR 0.52; 95% CI 0.27– 1.01, p = 0.04). The odds of surgical NEC decreased by 78% (OR 0.22; 95% CI 0.06– 0.84, p = 0.027) for each copy of rs704074/G allele in patients with NEC.

In this small single-center pilot study, DUSP-6 SNP (rs704074) was associated with a lower risk of developing NEC and surgical NEC, the most severe form of NEC, in preterm infants.

Neonatal infections are a leading cause of morbi-mortality despite advances in antimicrobials and neonatal care. Preterm infants have greater susceptibility to sepsis due to an immature immune system and lower immunoglobulin levels. Intravenous immunoglobulins (IVIG) have been used in several studies as an adjuvant treatment to improve this physiological immune deficiency, with different outcomes.

Very low birth weight (VLBW) infants who developed sepsis in the neonatal ICU were studied. They were randomly divided in 2 groups: one group was treated with antibiotics (Group I), and the other received antibiotics plus a 500 mg/kg/day of IVIG during 7 days (Group II). Serum IgG concentration was determined at initiation, during and after treatment Group I, and daily during the 7 days of therapy in Group II.

The baseline IgG concentration in group II was 486 g/dL, and increased to 852 mg/dL after the first dose of IVIG (p < 0.01). After the seventh day of infusion a mean IgG level of 1898 mg/dL was achieved. A direct correlation (r = 0.94) between IgG concentration and days of treatment was observed. Blood cultures were positive in 70% of the infants in group I and 75.5% in group II. Staphylococcus epidermidis was the most frequent isolated bacteria in blood cultures. The lethality rate was 25.0% in group I and 5.0% in Group II (p < 0.03). We did not observe collateral effects with the administration of IVIG.

Prolonged therapy with IVIG seems to be safe and effective as an adjuvant treatment in VLBW infants with sepsis.

While national guidelines are available for the evaluation and management of term infants at risk for herpes simplex virus (HSV) infection, such guidelines are lacking for preterm infants. We sought to determine the risk factors and clinical characteristics of preterm vs. term infants who were evaluated and treated empirically for HSV infection in the neonatal intensive care unit (NICU).

In a retrospective cohort study, medical records of all infants who were admitted to our NICU (2009-2016) and who were evaluated and empirically treated for HSV were reviewed for mothers’ and infants’ demographics, clinical characteristics, and laboratory findings.

During the study period 4.2% (103/2,471) of all preterm infants, and 6.0% (112/1,865) of all term infants were evaluated and treated empirically for neonatal HSV. Among all infants who were evaluated and treated for HSV, 5.5% (12/215) had neonatal HSV disease, of whom 83.3% (10/12) were preterm infants. In comparison to term, preterm infants were more likely to be evaluated and treated, if they had a maternal history of HSV [OR 2.51 (95% CI: 1.41–4.48)], prolonged rupture of membranes [2.64 (1.221–5.73)], leukopenia [3.65 (1.94–6.87)] and thrombocytopenia [2.25 (0.85–5.89)]. HSV disease was associated with a higher mortality compared to those without disease [25% (3/12) vs. 4.4% (9/203) respectively; p = <0.05].

Preterm infants evaluated and empirically treated for HSV have a higher burden of HSV infection than term infants. HSV should be considered in the management of preterm infant with a maternal history of HSV, prolonged rupture of membranes, and thrombocytopenia.

The aim of this study is (1) to observe the effect of the background music (BGM) in the incubator on heart rate variability (HRV) during the first few weeks of life in preterm infants in the neonatal intensive (NICU) and growing care units (GCU) and (2) to investigate the effect of environmental music on autonomic function in the infants.

Thirty infants, including premature (26 3/7 – 38 4/7 weeks) and low-birth weight (LBW) (946–2,440 g) infants, admitted to the NICU or GCU were involved. The heart rate, low- (LF, 0.05–0.15 Hz) and high- (HF, 0.15–0.4 Hz) frequency HRV components, and LF/HF ratio were measured. The BGM, lullabies for a baby, was delivered through a speaker in the incubator, and the HRV components were compared among before, during, and after intervention with BGM.

The mean HR did not change among the experimental conditions. The LF and HF values decreased during the BGM condition, but not LF/HF, compared with the condition before BGM.

The present results showed that an auditory environment affected the autonomic function of infants with a range of BGM in the NICU/GCU. The present study also suggested that BGM, a non-invasive and non-pharmacological intervention, could be an evaluation tool for autonomic function in infants in NICU/GCU.

The objective was to assess stress in fathers of preterm infants and use of “Kangaroo Father Care (KFC)” to mitigate it.

Stress levels of 30 fathers of preterm infants admitted in the NICU were assessed using the parental stressor scale: neonatal intensive care unit (PSS: NICU) before and after three sessions of KFC. The data was analysed using Wilcoxon signed rank sum test.

There was a statistically significant reduction in stress levels after KFC (p = 0.006). Amongst all the four subscales, stress levels were found to be reduced in ‘staff behaviour and communication’ (p = 0.001) domain and ‘baby looks and behaves’ domain (p = 0.05).

Fathers of preterm infants admitted in the NICU experience a lot of stress, which can adversely affect their mental health. Kangaroo care is very effective in reducing this paternal stress levels.

Premature infants often require long-term indwelling intravascular catheters. Occasionally, catheters fracture and migrate into cardiovascular structures, risking perforation, infection, thrombosis, and interference with cardiac and valve function. This case series describes our experience with percutaneous retrieval of broken intravascular catheters.

A gooseneck micro-snare was used to retrieve fractured catheters in four premature infants, weighing between 840 and 1930 grams.

All procedures were successful without complications.

Gooseneck-snare retrieval of broken indwelling intravascular catheters can be performed safely and successfully in premature infants even those that weigh less than 1000 grams.

Fetal pleural effusions are a rare fetal anomaly that may result from congenital chylothorax. Severe cases lead to chest compression with resulting pulmonary hypoplasia and possible neonatal demise. Fetal thoracoamiontic shunt (TAS) placement may decrease the amount of pleural effusion and improve lung expansion.

A 30-year-old primigravida at 29 2/7 weeks’ gestation presented with fetal bilateral pleural effusions with no identifiable genetic or structural abnormalities. TAS placement accomplished decompression of the left fetal chest. The neonate was delivered at 33 3/7 weeks and required minimal respiratory support with no apparent long term complications at discharge.

This case demonstrated that fetal intervention with TAS placement can improve neonatal outcomes. Referral to an MFM specialist capable of TAS should be considered for isolated fetal bilateral pleural effusion.