Association between prenatal phthalate exposure and ano-genital indices among offsprings in an Israeli cohort.

Background: In-utero phthalate exposure was shown to be associated with shortened anogenital distance (AGD) in male newborns, but findings among female are inconsistent. While phthalate exposure among pregnant women in Israel is widespread, no study has examined the association with offspring AGD. The objective of the current study was to investigate the association between maternal phthalates urinary concentration and offspring AGD at time of delivery among a birth cohort in Israel. Methods: We measured spot urinary concentration of monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexylphthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) among women presenting to the delivery room at Shamir Medical Center in Israel. Birthweight, length and AGD were measured in all newborns using a standardized protocol. Each AGD measurement was adjusted to weight (ano-genital index). Confounders included socio-demographic characteristics, comorbidities and obstetrical history. Univariate and multivariate analyses assessed the associations between phthalates, confounders and AGD. Results: Overall, 193 mother and infant were analyzed. All newborns were born at term and had normal Apgar scores. Mean maternal age was 32 ± 4.7 years old. Mean birth weight and pregnancy week were 3183 ± 498 g and 39 ± 1.3, respectively. Median (IQR) urinary phthalate concentration adjusted to creatinine (ug/g) were 3.96 (2.2-6.6), 1.22 (0.7-2), 10.84 (7-20.4), 6.36 (3.3-11.2) and 0.64 (0.4-1.1) for MBP, MBzP, MECPP, MEHHP and MEOHP, respectively. Univariate comparison showed a significant association between higher than median MBzP concentration, higher Ano-Fourchetal index (AFI: 4.4 vs. 4.1, p = 0.037) and Ano-clitoral index (ACI: 11.5 vs. 10.4, p = 0.032) in infants. Total urinary phthalates concentration ≥26.25 µg/g was significantly associated with smaller penile width index (3.5 vs. 3.7, p = 0.022), higher ACI (11.6 vs. 10.3, p = 0.013) and a trend towards significance for higher AFI (4.3 vs. 4.1, p = 0.055). Following multivariate linear regression only PWI remained significantly associated with total phthalate urinary concentration. Conclusions: Maternal urinary phthalates concentration at delivery were not associated with female AGD, but total urinary phthalate concentration were inversely associated with penile width.

Time of Birth and the Risk of Adverse Maternal and Neonatal Outcomes-A Retrospective Cohort Study.

Objectives: To determine whether in a labor floor housed continuously by senior physicians the risk of adverse maternal and neonatal outcome is affected by time of delivery. Methods: This retrospective cohort study, conducted at a tertiary medical center, assessed singleton term deliveries from 1 January 2011 to 30 January 2020. Participants were categorized based on delivery timing, correlating with nursing shifts, to evaluate perinatal outcomes. The primary endpoint included adverse maternal outcomes such as emergency Cesarean section, anal sphincter injuries, blood product transfusions, and postpartum surgeries (laparotomy/laparoscopy). Secondary outcomes focused on neonatal health indicators, including low Apgar scores, ICU admissions, respiratory issues, extended hospital stays, and neurological complications. Results: 87,863 deliveries were available for analysis with equal distribution during the day. The risk of adverse composite maternal outcome was highest during the evening (aOR 1.25, 95% CI 1.18-1.32) and lowest during the night (aOR 0.94, 95% CI 0.88-0.99) compared to daytime deliveries. This difference was primarily driven by the highest rate of emergency CD in the evening. Neonatal outcomes were comparable, except for length of stay > 5 days, which was more frequent among newborns delivered during the evening and night shifts compared to the morning shift (aOR 1.19, 95% CI 1.07-1.33 and aOR 1.17, 95% CI 1.05-1.31, respectively). Conclusions: In term pregnancies, the evening shift is associated with the highest risk of adverse maternal and neonatal outcomes despite physician seniority.

Outcomes in Maternal Graves' Disease: A Population-Based Mother-Infant Dyad Cohort Study.

Background: Graves' disease has been associated with adverse pregnancy, labor and delivery, and neonatal outcomes. Thyroid function levels, assessed during newborn screening (NBS), can serve as indicators of the adaptation in the hypothalamic-pituitary-thyroid axis. We utilized data from the national thyroid NBS program to investigate the characteristics of the mother-infant dyad of term infants born to mothers with past or active Graves' disease. Methods: The dataset of the Israeli NBS for thyroid function was linked with the electronic records of a tertiary medical center to generate a unified database of mothers and their term infants born between 2011 and 2021. The MDClone big data platform extracted maternal, pregnancy, disease course, labor and delivery, and neonatal characteristics of the mother-infant dyads. Results: Out of 103,899 registered mother-infant dyads, 292 (0.3%) mothers had past or active Graves' disease. A forward multivariate linear regression demonstrated that Graves' disease did not significantly affect NBS total thyroxine (tT4) levels (p = 0.252). NBS tT4 levels in infants born to mothers with active Graves' disease were higher than those observed in the general Israeli population (p < 0.001). Mothers with Graves' disease more frequently used assisted reproductive technology (12.7% vs. 9.0%, respectively, p = 0.012; odds ratio [OR] = 1.46 [CI 1.03-2.07], p = 0.031), and had more gestational hypertension (3.9% vs. 1.1%, p < 0.001; OR = 3.53 [CI 1.92-6.47], p < 0.001), proteinuria (2.5% vs. 0.9%, p < 0.001; OR = 3.03 [CI 1.43-6.45], p = 0.004), cesarean sections (26.4% vs. 19.7%, p = 0.029; OR = 1.46 [CI 1.13-1.90], p = 0.004), prelabor rupture of membranes (15.4% vs. 4.1%, p < 0.001; OR = 4.3 [CI 3.13-5.91], p < 0.001), and placental abnormalities (5.1% vs. 2.0%, p < 0.001; OR = 2.64 [CI 1.57-4.44]; p < 0.001). Their infants had lower adjusted birthweight z-scores (-0.18 ± 0.94 vs. -0.03 ± 0.90, p = 0.007) and were more likely to be small for gestational age (12.0% vs. 8.1%, p = 0.005; OR = 1.54 [CI 1.08-2.19], p = 0.018). Conclusions: Neonatal thyroid function levels were affected by maternal Graves' disease only when the disease was active during gestation. Moreover, maternal Graves' disease was also associated with an increased risk of adverse outcomes for the mother-infant dyad.

Upper gastrointestinal series in healthy neonates with bilious vomiting-is it still obvious? A retrospective observational study.

AIM: Demand for upper gastrointestinal contrast series (UGI) to investigate bilious vomiting (BV) has increased in recent years, mostly due to greater awareness of the need to rule out malrotation and midgut volvulus (MGV). We aimed to examine predictive value of clinical parameters in the management of healthy neonates presenting with BV and re-assess the role of UGI in their management. METHODS: A retrospective cohort study including medical, imaging and surgical data of neonates who underwent UGI due to BV. RESULTS: A total of 157 term neonates, eight neonates (5.1%) had confirmed surgical diagnosis of malrotation, five of them had malrotation with MGV, including two neonates who underwent extensive intestinal resection due to necrosis. Neonates with a combination of abnormal plain radiograph and abdominal distention had 10 times higher odds of malrotation diagnosis, adjusting for age at first BV (p = 0.017). Neonates with a combination of abnormal plain radiograph, abdominal distention and abdominal tenderness had 25 times higher odds of MGV (p = 0.002). CONCLUSION: This study reaffirms the role of UGI as the current main diagnostic tool for malrotation and MGV. Physical examination and plain radiograph findings can help but cannot substitute UGI study.

Blood Glucose, Lactate and Platelet Count in Infants with Spontaneous Intestinal Perforation versus Necrotizing Enterocolitis-A Pilot Study.

The incidence of spontaneous intestinal perforation (SIP) increases up to 10% with decreasing gestational age (GA). We aimed to explore early biomarkers for predicting SIP in preterm infants. In this case-control study, neonates born at ≤34 weeks GA diagnosed with SIP were compared with GA and/or birth-weight-matched neonates diagnosed with necrotizing enterocolitis (NEC). Laboratory markers assessed prior and adjacent to the day of SIP or NEC diagnosis were evaluated. The cohort included 16 SIP and 16 matched NEC infants. Hyperlactatemia was less frequent in SIP than in NEC infants (12% vs. 50%, p = 0.02). The platelets count was lower in SIP than in NEC infants (p < 0.001). Glucose levels strongly correlated with lactate levels (p = 0.01) only in the NEC group. The odds of being diagnosed with SIP decreased as lactate levels increased (OR = 0.607, 95% CI: 0.377-0.978, p = 0.04). Our results suggest that a combination of laboratory markers, namely glucose and lactate, could help differentiate SIP from NEC at early stages so that, in the presence of an elevated blood glucose, an increase in blood lactate was associated with a decrease in the odds of being diagnosed with SIP.

Neonatal outcomes in women with preterm premature rupture of membranes at periviable gestational age.

To examine the outcomes of preterm infants born to women with preterm premature rupture of membranes (PPROM) at periviable gestational age. This is an observational retrospective cohort study analyzing data collected on singleton deliveries complicated by prolonged premature rupture of membranes occurring between 17 and 33 weeks of gestation. Neonatal outcomes including birth weight, Apgar score, retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, hearing impairment and mortality were evaluated. Ninety-four preterm infants who were born after a prolonged premature rupture of membranes of at least 7 days were included in the study. Median gestational week at onset of membrane rupture was 27.1 ± 4.2 weeks (range 17-33) and median latency period in days was 16 ± 21.8 (range 7-105). The cohort was stratified by gestational week (GW) at onset of PPROM (group 1: 17-23, group 2: 24-27, and group 3: 28-33). We found that the survival rate to discharge within neonates born after prolonged rupture of membrane at gestational week less than 24 weeks is 79.2% and 88.9% in group 2. These neonates did not show an increased rate of major morbidities compared to neonates born following membrane rupture at gestational week 24 to 27. We described a high survival rate to discharge without major morbidities following prolonged preterm membrane rupture of at least 7 days of latency before viability.

Maternal Exposure to Polychlorinated Biphenyls and Asthma, Allergic Rhinitis and Atopic Dermatitis in the Offspring: The Environmental Health Fund Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are persistent organic pollutants banned for use worldwide. Due to their biodegradation resistance, they accumulate along the food chain and in the environment. Maternal exposure to PCBs may affect the fetus and the infant. PCBs are immunotoxic and may damage the developing immune system. PCBs are associated with elevated IgE antibodies in cord blood and are considered to be predictive of atopic reactions. Several studies on the association between prenatal exposure to PCBs and atopic reactions were previously published, albeit with conflicting results. Objectives: To examine the association between maternal PCBs levels and atopic reactions in their offspring. Methods: During the years 2013-2015, a prospective birth cohort was recruited at the delivery rooms of Shamir Medical Center (Assaf Harofeh) and "Dana Dwek" Children's Hospital. Four PCBs congeners were investigated: PCBs 118, 138, 153, and 180. In 2019, when children reached the age of 4-6 years, mothers were interviewed using the ISAAC questionnaire to assess symptoms of atopic reactions, including asthma, allergic rhinitis, and atopic dermatitis. Results: One hundred and fifty mother-child dyads were analyzed. No significant differences were found in the median serum PCBs concentrations of each studied congener or total PCBs for asthma, allergic rhinitis, atopic dermatitis diagnosis, or parent-reported symptoms. No association was found between exposure to total PCBs and the risk for asthma symptoms or diagnosis, adjusted to maternal age and family member with atopic condition: aOR = 0.94, 95%CI: (0.88; 0.99). No association was observed between each studied PCB congener and asthma symptoms or diagnosis. The same results were found also for other studied outcomes-allergic rhinitis and atopic dermatitis. Conclusion: Our study joins a series of previous studies that attempt to shed light on environmental exposures in utero as influencing factors for atopic conditions in children. Our results reflect the complexity of the pathophysiology of these phenomena. No relationship between maternal serum PCBs levels was demonstrated for asthma, allergic rhinitis, or atopic dermatitis. However, additional multi-participant studies, with longer, spanning into later pediatric age follow up are needed.

Carbohydrate content of human milk is affected by seasonal variations: a retrospective observational study.

OBJECTIVE: The influence of seasonal variation upon human milk macronutrient content has not been elucidated. This study aimed to compare the macronutrient content of HM produced by lactating mothers during the winter and the summer seasons. STUDY DESIGN: Macronutrient content of colostrum milk samples collected from lactating mothers of healthy term infants between March 2012 and February 2016 was measured by mid-infrared spectroscopy and compared. RESULT: The carbohydrate content of the colostrum was significantly higher in the summer season than in the winter season (6.2 ± 1.3 vs. 5.5 ± 1.4, p-value < 0.001). Protein, fat, and energy contents were similar in summer and winter in both groups (protein 2.7 ± 2.1 vs. 2.6 ± 2.2 g/100 ml, fat 2.6 ± 1.9 vs. 2.35 ± 1.9 g/100 ml, and energy 62 ± 19.1 vs. 60.5 ± 21 kcal/100 ml, respectively). CONCLUSION: The carbohydrate content in colostrum obtained from mothers of term infants was affected by seasonal variations.

Does the delivery mode affect post-birth neonatal serum C-reactive protein levels? A causal effect analysis.

AIM: To determine if the delivery mode has a causal effect on neonatal serum C-reactive protein (CRP) levels. If such a causal effect exists, we aim to quantify its magnitude. METHODS: We investigated the causal effect of the delivery mode on serum CRP levels 6-8 h after delivery, with appropriate statistical tools for retrospective studies, combining classical and machine-learning methods. The statistical inference is followed by sensitivity analysis to quantify the magnitude of unobserved bias required in order to alter the study's conclusion. RESULTS: This retrospective study reviewed laboratory records of neonates after birth who underwent blood tests due to suspected sepsis. A total of 440 newborns were included, 324 of which underwent a vaginal delivery, 59 an urgent caesarean delivery, and 57 an elective caesarean delivery. Our results revealed that serum CRP values following elective caesarean deliveries were 50% less than those following a vaginal delivery (P = 0.030; -0.907; 95% CI [-1.545, -0.268] in log-CRP units). No significant effect was found for urgent caesarean deliveries compared to vaginal deliveries (P = 0.887). Those results were strengthened by (1) a sensitivity magnitude of 1.6 to unobserved bias and (2) non-significant effects when analysis is repeated on blood collected 12-24 h after birth. CONCLUSION: CRP concentrations in neonatal blood during the first 6-8 h of life are higher following vaginal deliveries compared to elective caesarean deliveries. Further studies with the intent of improving EONS detection should include information on the delivery mode.

Comprehensive Morphological Assessment of Cord Blood: Normal Values and the Prevalence of Morphologically Aberrant Leukocytes.

INTRODUCTION: Cord blood (CB) is becoming a valuable source for stem cells utilized in a variety of cell therapy applications, as well as for newborn diagnostics. Some parameters of the CB cellular components can be provided by automated analyzers, while others, such as immature or aberrant cells, require blood film morphological assessment. The objectives of the study were to establish normal CB morphology and to determine the prevalence of morphologically aberrant leukocytes in CB. METHODS: We performed a comprehensive morphological analysis of 100 CB samples taken from healthy term and appropriate-for-gestational-age neonates born to healthy mothers, preterm neonates, neonates of diabetic mothers, and small-for-gestational-age neonates. Blood counts were assessed, and manual morphological analyses were performed by laboratory specialists. RESULTS: The manual differential count of normal CB samples established the following values: 47.8 ± 10.7% neutrophils, 31.2 ± 9.8% lymphocytes, 10.0 ± 4.0% monocytes, and 3.0 ± 2.5% eosinophils, with no significant sex-related differences. Blasts were observed in 44/100 samples with an average of 0.5 ± 0.7% per sample, and only a minor left shift was observed. There were significant populations of large granular lymphocytes (19.1 ± 10.6% of the total lymphocytes) and morphologically aberrant lymphocytes (12.4 ± 5.4% of the total lymphocytes) in the samples, irrespective of neonatal status. The differentials of preterm CB samples differ significantly from normal term CB samples, including the reverse of neutrophils/lymphocytes ratio, and the lack of basophils. CONCLUSIONS: Normal values and unique morphological features in the CB of neonates are described. The abundant morphologically aberrant lymphocytes in CB may represent an immature state of the immune system at birth.

Indications and diagnosis-specific features of maternal and neonatal peripartum intensive care unit admissions: A retrospective study.

BACKGROUND: Although peripartum intensive care unit admission indications are well-reported, clinical and laboratory details rarely are. We described admission indications and categorised laboratory values and vital signs according to admission diagnosis. METHODS: Retrospective Institutional Review Board approved study. We identified intensive care unit admission diagnosis, laboratory values and vital signs from patient charts. Groups were compared according to admission diagnoses. Data were analysed using descriptive statistics. RESULTS: We included 91 general intensive care unit admissions among 56,865 deliveries (2011-2015) with complete data. The most common admission diagnosis was postpartum haemorrhage followed by hypertensive diseases of pregnancy and respiratory complications. Women with postpartum haemorrhage had lower mean (standard deviation) platelet counts (120.2 (45.8) vs. 181.2 (109.9), p = .003) and temperatures (35.7 (1.1) vs. 36.5 (1.2), p = .002). Women with hypertensive diseases of pregnancy had higher mean (standard deviation) blood pressures (systolic 150.4 (29.1) vs. 127.4 (21.0), p = .013, diastolic 100.3 (18.7) vs. 76.1 (16.1), p = .001), creatinine (1.1 (0.6) vs. 0.8 (0.3), p = .003), urea (14.6 (7.7) vs. 10.5 (4.7), p = .005) and liver enzymes, including aspartate transaminase (258.4 (297.0) vs. 41.4 (42.9), p = .000), alanine transaminase (184.4 (199.2) vs. 35.1 (75.9), p = .000), and alkaline phosphatase (166.6 (112.6) vs. 96.0 (60.0), p = .006). Women with respiratory complications had lower mean (standard deviation) oxygen saturations (93.7 (6.1) vs. 98.0 (2.6), p = .000), and higher mean (standard deviation) temperatures (37.1 (0.8) vs. 36.0 (1.2), p = .001). CONCLUSIONS: We report differences in laboratory values and vital signs, according to intensive care unit admission diagnosis. Recognising these differences might help individualise patient assessment and care.

C-reactive protein in early-onset neonatal sepsis - a cutoff point for CRP value as a predictor of early-onset neonatal sepsis in term and late preterm infants early after birth?

OBJECTIVE: To identify whether the first plasma C-reactive protein values taken 6-8 h postpartum are predictive of the clinical early-onset neonatal sepsis (cEONS). STUDY DESIGN: We retrospectively analyzed C-reactive protein (CRP) values of 400 neonates, including 28 with cEONS, who underwent plasma CRP measurements as part of sepsis work-up. To determine whether the first CRP measurement is predictive of cEONS, logistic regression was used with CRP as an independent variable and cEONS (yes/no) as a dependent variable. RESULT: A moderate predictive ability of the first CRP measurement (odds ratio 1.4, CI: [1.13, 1.76], p=.003) was revealed, at a 5.3 mg/L threshold. However, it resulted in poor sensitivity of 50%, and a false positive rate of 30%. Increasing the sensitivity to 75% or 90% lead to increased false-positive rates of 55% and 75%, respectively. CONCLUSIONS: Our findings suggest that the first CRP value taken in neonates is a weak predictor of cEONS.

Effects of maternal aspirin treatment on hemodynamically significant patent ductus arteriosus in preterm infants - pilot study.

AIM: To assess the burden of hemodynamically significant patent ductus arteriosus (hs-PDA) in preterm infants exposed to aspirin in utero. METHODS: We retrospectively reviewed the medical records of 21 preterm infants <34 weeks whose mothers were treated with aspirin during gestation, and were screened for patent ductus arteriosus due to severe respiratory distress syndrome and the need for positive pressure ventilation. These infants were compared to 42 preterm infants born without exposure to aspirin in utero. RESULTS: We found significantly lower frequency of hs-PDA and higher rate of successful pharmacological PDA closure after single course of ibuprofen treatment along with significantly lower cumulative doses of ibuprofen in the study group. Furthermore, PDA closure was achieved significantly earlier in the study group (day 4 versus 11, p = .02). CONCLUSION: Aspirin treatment during pregnancy seemed to reduce the incidence of hs-PDA in preterm infant and to increase infant responsiveness to postnatal medical treatment of PDA.

Neonatal morbidity among African refugee women in Israel: a case-control study.

OBJECTIVES: Reports on neonatal morbidity (NM) among refugees in developed countries remain inconsistent. We aimed to compare NM among infants of African refugees in Israel to the native population based on a large population sample. DESIGN: A case-control study. SETTING: A tertiary hospital in Israel. PARTICIPANTS: Data on hospital-based live births of refugee women and their newborns who were born in 2014 and 2017 were retrieved from medical records. Perinatal and neonatal data were compared between the refugee group and the native residents matched for gestational age and year of birth as well as within the refugee group. PRIMARY OUTCOME: Prevalence of NM among African refugees in Israel. RESULTS: Newborns delivered by 357 refugee women (mean age 30.2 years) and 357 controls (mean age 32.2 years) were analysed. Both groups were similar for the newborns' weight and gestational age. There were no significant differences in NM between the groups. A within-refugee comparison conducted between 2014 and 2017 yielded significant differences in birth weight (3051.4 vs 3373.6 gr, p<0.001, 95% CI (198.3 to 446.2), d=0.56), the number of twin deliveries (10 vs 4, p=0.002, Φ=0.173), the number of neonates evaluated as small for gestational age (15 vs 10, p=0.003, Φ=0.167) and the use of human milk (71% vs 93%, p<0.001, Φ=-0.298). CONCLUSIONS: We conclude that NM among neonates born to refugee mothers was not higher than that of neonates born to native Israeli mothers. We suggest that successful implementation of health policies for refugees has improved their accessibility to mother-child health services.

Maternal and Newborn Thyroid Hormone, and the Association With Polychlorinated Biphenyls (PCBs) Burden: The EHF (Environmental Health Fund) Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants found in human tissues. PCBs can be transferred through the placenta and may disrupt the maternal thyroid homeostasis, and affect fetal thyroid hormone production. Several studies have shown that intrauterine exposure to PCBs might be associated with abnormal levels of thyroid hormones in mothers and their offspring. Objectives: To examine the associations between environmental exposure to PCBs and thyroid hormone levels in mothers and newborns. Methods: The EHF-Assaf-Harofeh-Ichilov cohort includes 263 mothers-newborns dyads. A total of 157 mother-newborn dyads had both PCBs and thyroid function measures. Regression models were used to estimate associations between maternal PCB exposure and maternal and newborn thyroid function, controlling for possible confounders. Results: Four PCBs congeners were analyzed: PCBs 118, 138, 153, and 180. ∑PCBs median (IQR) level was 14.65 (2.83-68.14) ng/g lipids. The median maternal thyroid-stimulating hormone (TSH) level was 2.66 (0.70-8.23) µIU/ml, the median maternal free thyroxine (FT4) level was 12.44 (11.27-13.53) µg/dL, the median maternal thyroid peroxidase antibodies (TPO Ab) level was 9.6 (7.36-12.51) IU/mL. Newborns' median total thyroxine (T4) level was 14.8 (7.6-24.9) µg/dL. No association was found between exposure to different congeners or to ∑PCBs and maternal TSH, FT4, thyroglobulin autoantibodies (Tg Ab), TPO Ab and newborn total T4 levels. In multivariable analysis a 1% change in ∑PCBs level was significantly associated with a 0.57% change in maternal TSH levels in women with body mass index (BMI) < 19. The same association was observed for each of the studied PCB congeners. Maternal TPO Ab levels statistically significantly increased by 0.53 and 0.46% for 1% increase in PCB 118 and 153 congeners, respectively. In women with BMI > 25, the association between the PCBs levels and maternal TSH levels was in the opposite direction. No association was found in women with normal BMI (19-24.9). Conclusions: Background exposure to environmentally relevant concentrations of some PCBs can alter thyroid hormone homeostasis in pregnant women and might be associated with abnormal TSH levels and TPO-Ab in women with low BMI. However, these findings require further investigation.

Neonatal SARS-CoV-2 Infections in Breastfeeding Mothers.

OBJECTIVES: To assess infection rates predischarge and postdischarge in breast milk-fed newborns with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive mothers who were separated postdelivery from their mothers and discharged from the hospital. Also, we aim to evaluate breastfeeding rates predischarge and postdischarge. METHODS: Nasopharyngeal swabs for SARS-CoV-2 were obtained from symptomatic and high-risk women in the delivery room. Mothers with positive SARS-CoV-2 test results were separated from the newborns. Newborns were screened within 48 hours of delivery, and anti-infectious guidelines were imparted to the mothers before discharge. Rescreening took place ≥14 days postdischarge. Data regarding SARS-CoV-2-positive household members and breastfeeding were obtained by follow-up phone calls. RESULTS: A total of 73 newborns of SARS-CoV-2-positive mothers were born in Israel during the ∼3-month period under study. Overall, 55 participated in this study. All neonates tested negative for the virus postdelivery. A total 74.5% of the neonates were fed unpasteurized expressed breast milk during the postpartum separation until discharge. Eighty-nine percent of the neonates were discharged from the hospital after their mothers were instructed in anti-infection measures. In 40% of the households, there were additional SARS-CoV-2-positive residents. A total of 85% of the newborns were breastfed postdischarge. Results for all 60% of the newborns retested for SARS-CoV-2 postdischarge were negative. CONCLUSIONS: No viral infection was identified in neonates born to and separated from their SARS-CoV-2-positive mothers at birth and subsequently fed unpasteurized breast milk. All infants breastfed at home remained SARS-CoV-2 negative. These findings may provide insights regarding the redundancy of postpartum mother-newborn separation in SARS-CoV-2-positive women and, assuming precautions are adhered to, support the safety of breast milk.

Tandem Breastfeeding and Human Milk Macronutrients: A Prospective Observational Study.

BACKGROUND: Tandem breastfeeding is defined as two or more offspring of different ages who are breastfed by their mother at the same time. Breastfeeding during pregnancy and tandem breastfeeding have not been widely investigated. RESEARCH AIM: To determine the influence of tandem breastfeeding on the macronutrient content of human milk. METHODS: This longitudinal study used a prospective and a retrospective group. Human milk samples from tandem-breastfeeding participants (n = 18) were compared to samples from non-tandem-breastfeeding participants (n = 31). Samples were collected during the last month of pregnancy (pregnancy milk), 72 hr after birth (colostrum) and 14-60 days post-delivery (mature milk). Macronutrients were measured by mid-infrared spectroscopy. RESULTS: Fat content in pregnancy milk was lower than in mature milk (p < .01). Protein content was higher in pregnancy milk than in colostrum and mature milk (p < .01 and p < .001, respectively). Inversely, carbohydrate content in pregnancy milk was lower than in colostrum and mature milk (p = .02 and p < .01, respectively). Fat and energy contents in pregnancy milk of tandem-breastfeeding participants were lower than in mature milk of non-tandem-breastfeeding participants (p < .001 and p < .01, respectively), and protein content was higher than in mature milk (p < .001). Carbohydrate content in colostrum and mature milk of tandem-breastfeeding participants was higher than that of non-tandem-breastfeeding participants (p < .001 for both). CONCLUSION: Human milk produced during pregnancy had different macronutrient content than human milk produced after delivery. Colostrum and mature milk of tandem-breastfeeding participants were similar to human milk produced by non-tandem-breastfeeding participants, with the exception of carbohydrate content.

C-reactive protein and the neonatal early-onset sepsis calculator for the diagnosis of neonatal sepsis.

Our aim was to evaluate the utility of the neonatal early-onset sepsis risk calculator (NEOSC) to the utility of C-reactive protein (CRP) for diagnosing neonatal EOS. This retrospective study reviewed the records of neonates who underwent sepsis workups due to equivocal symptoms and compared their CRP values to the calculator's recommendations and their cultures. A total of 382 newborns who underwent sepsis work-up due to equivocal symptoms were included in our study. The calculator's recommendations would have reduced the number of newborns who underwent sepsis workups by 82.5% and antibiotic treatment by 83.4% (n = 315). Considering that 373 of 382 (97.6%) ultimately had no sepsis, the calculator's specificity was higher than that of CRP (83.9% versus 76.1%). When comparing the maximal CRP value with the risk according to the neonatal sepsis calculator, a significant correlation was found between them (P < 0.01), but the relationship was not strong (Pearson's correlation = 0.27). We found a significant correlation between the risk of sepsis according to the NEOSC and the CRP values, although the correlation was not strong. The calculator's high specificity enables safe avoidance of multiple blood tests and antibiotic treatments for suspected neonates who are not infected. CRP tests can reduce the number of infected newborns the calculator may miss, at the cost of unnecessary blood tests and antibiotic therapy to many newborns.

Maternal presentation and neonatal outcome in peripartum enterovirus infection.

AIM: Enterovirus is a common pathogen. Although mostly asymptomatic, this infection has the potential to be life-threatening in neonates. This article aims to describe the early neonatal outcomes in peripartum infection. METHODS: We performed a retrospective cohort study in a tertiary hospital between 1/2014 and 5/2019. The enterovirus infection was established by real-time polymerase chain reaction analysis. RESULTS: Out of 161 neonates tested for the enterovirus infection 13 (8%) were positive. Maternal fever was the most common sign (n = 8, 66.7%). The mean gestational age at delivery was 36 + 5 (range 30 + 5 to 40 + 6 weeks). The mean time interval from birth to neonatal manifestations of infection was 5.2 (0-9) days. The most common presenting sign in the neonates was fever (n = 8, 61.5%). All neonates required the neonatal intensive care unit. The neonatal mortality rate was 3/13 (23%). CONCLUSION: The neonatal morbidity and mortality from the enterovirus infection may have been associated with the severity of maternal presentation at the time of admission. Enterovirus real-time polymerase chain reaction analysis should be considered as part of the maternal evaluation in cases of maternal fever of unknown origin. Deferral of the induction of delivery for term pregnancies with confirmed enterovirus infections should be considered.

The role of orotic acid measurement in routine newborn screening for urea cycle disorders.

Urea cycle disorders (UCDs), including OTC deficiency (OTCD), are life-threatening diseases with a broad clinical spectrum. Early diagnosis and initiation of treatment based on a newborn screening (NBS) test for OTCD with high specificity and sensitivity may contribute to reduction of the significant complications and high mortality. The efficacy of incorporating orotic acid determination into routine NBS was evaluated. Combined measurement of orotic acid and citrulline in archived dried blood spots from newborns with urea cycle disorders and normal controls was used to develop an algorithm for routine NBS for OTCD in Israel. Clinical information and genetic confirmation results were obtained from the follow-up care providers. About 1147986 newborns underwent routine NBS including orotic acid determination, 25 of whom were ultimately diagnosed with a UCD. Of 11 newborns with OTCD, orotate was elevated in seven but normal in two males with early-onset and two males with late-onset disease. Orotate was also elevated in archived dried blood spots of all seven retrospectively tested historical OTCD patients, only three of whom had originally been identified by NBS with low citrulline and elevated glutamine. Among the other UCDs emerge, three CPS1D cases and additional three retrospective CPS1D cases otherwise reported as a very rare condition. Combined levels of orotic acid and citrulline in routine NBS can enhance the detection of UCD, especially increasing the screening sensitivity for OTCD and differentiate it from CPS1D. Our data and the negligible extra cost for orotic acid determination might contribute to the discussion on screening for proximal UCDs in routine NBS.