Vertical transmission and humoral immune response following maternal infection with SARS-CoV-2: a prospective multicenter cohort study.

OBJECTIVE: To explore maternal humoral immune responses to SARS-CoV-2 infection and the rate of vertical transmission. METHODS: A prospective cohort study was conducted at two university-affiliated medical centers in Israel. Women positive for SARS-CoV-2 reverse-transcription-polymerase-chain-reaction (RT-PCR) test during pregnancy were enrolled just prior to delivery. Levels of anti-SARS-CoV-2 spike-IgM, spike IgG, and nucleocapsid IgG were tested in maternal and cord blood at delivery, and neonatal nasopharyngeal swabs were subjected to PCR testing. The primary endpoint was the rate of vertical transmission, defined as either positive neonatal IgM or positive neonatal PCR. RESULTS: Among 72 women, 36 (50%), 39 (54%) and 30 (42%) were positive for anti-spike-IgM, anti-spike-IgG, and anti-nucleocapsid-IgG, respectively. Among 36 neonates in which nasopharyngeal swabs were taken, one neonate (3%, 95% confidence interval 0.1-15%) had a positive PCR result. IgM was not detected in cord blood. Seven neonates had positive IgG antibodies while their mothers were seronegative for the same IgG. Anti-nucleocapsid-IgG and anti-spike-IgG were detected in 25/30 (83%) and in 33/39 (85%) of neonates of seropositive mothers, respectively. According to the serology test results during delivery with respect to the time of SARS-CoV-2 infection, the highest rate of positive maternal serology tests was 8 to 12 weeks post-infection (89% anti-spike IgG, 78% anti-spike IgM, and 67% anti-nucleocapsid IgG). Thereafter, the rate of positive serology tests declined gradually; at 20 weeks post-infection, only anti-spike IgG was detected in 33 to 50%. DISCUSSION: The rate of vertical transmission of SARS-CoV-2 was at least 3% (95% confidence interval 0.1-15%). Vaccination should be considered no later than 3 months post-infection in pregnant women due to a decline in antibody levels.

Oral analgesia in fixed-time interval administration versus spinal morphine for post-Cesarean pain: a randomised controlled trial.

PURPOSE: To compare the efficacy of fixed-time-interval oral analgesia and spinal-morphine for management of post-Cesarean pain. METHODS: In this open-label, parallel-group, randomized, controlled trial, 200 women due to undergo elective Caesarean section with spinal anaesthesia were enrolled between July 2015 and April 2016. Patients were randomly assigned to receive either spinal fentanyl followed by oral doses of tramadol, paracetamol, and diclofenac at predetermined regular intervals of 6 h for the first 48 h, and rescue treatment with percocet (oxycodone and paracetamol; oral analgesia group), or spinal morphine and rescue treatment with oral tramadol, paracetamol, and diclofenac (spinal-morphine group). The primary outcomes were pain intensity during the postoperative 48 h, measured on a 10-point numeric rating scale (NRS) and expressed as area under the curve (AUC), and the number of breakthrough events of moderate to severe pain (defined as NRS score ≥ 4). RESULTS: The oral analgesia group compared to the spinal-morphine group had similar mean pain intensity (AUC (120 ± 35 versus 121 ± 31, respectively; p = 0.8) but more events of moderate-to-severe breakthrough pain (4.8 ± 2 versus 3.8 ± 1.7, respectively; p = 0.0002). Higher rates and longer durations of pruritus, nausea, and vomiting were reported among patients receiving spinal morphine, as compared with oral analgesia. Satisfaction scores were high in both groups (8.2 ± 2.4 versus 8.7 ± 1.8 in the oral analgesia and spinal morphine, respectively; p = 0.23). CONCLUSIONS: Both oral analgesia at fixed time intervals and spinal morphine are satisfactory methods for treating post-Caesarean pain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02440399, date of registration: 07/05/ 2015. URL: https://clinicaltrials.gov/ct2/show/NCT02440399?term=enav+yefet&rank=7 .

The Yield of Targeted Examination for the Detection of Symptomatic Congenital Cytomegalovirus Infection.

BACKGROUND: The incidence of congenital cytomegalovirus (CMV) infection in Israel is 0.7%. Only 10-15% are symptomatic. Valganciclovir has been shown to improve hearing and neurodevelopmental outcomes in neonates with symptomatic congenital CMV infection. Targeted examination of infants who fail routine neonatal hearing screening or have clinical or laboratory findings suggestive of symptomatic congenital CMV infection may be a cost-effective approach. OBJECTIVES: To assess the possibility of targeted examination for the detection of newborns with symptomatic congenital CMV infection. METHODS: A prospective observational study was conducted in 2014-2015 at two medical centers in northern Israel. Included were all newborns who were tested in the first 3 days of life by polymerase chain reaction (PCR) for urine CMV DNA (n=692), either for failure the hearing screening (n=539, 78%), clinical or laboratory findings suggestive of symptomatic congenital CMV infection, or primary CMV infection during pregnancy (n=153, 22%). RESULTS: During the study period 15,433 newborns were born. The predicted rate of infection was 10-15% (symptomatic) of 0.7% of newborns, namely 0.07-0.105% or 10-15 infants. In fact, 15 infants (0.11%, 95% confidence interval 0.066-0.175) were diagnosed with symptomatic congenital CMV infection, 2/539 (0.37%) in the failed hearing group and 13/153 (8%) in the clinical/laboratory findings group. The incidence of symptomatic congenital CMV infection was within the predicted range. CONCLUSIONS: Targeted examination of only 4.5% (n=692) of newborns detected the predicted number of infants with symptomatic congenital CMV infection in whom valganciclovir therapy is recommended.

Reducing Neonatal Hypothermia in Premature Infants in an Israeli Neonatal Intensive Care Unit.

BACKGROUND: Neonatal hypothermia (< 36°C) has been associated with both neonatal morbidity and mortality. OBJECTIVES: To develop a multifactorial approach to reduce the incidence of neonatal hypothermia at admission to the neonatal intensive care unit. METHODS: The approach involved a detailed quality improvement (QI) plan, which included the use of occlusive wrapping and exothermic mattresses as well as higher delivery and operating room environmental temperatures. The improvement plan was implemented over a 10-month period. Retrospective comparison to the same 10-month period during the previous year assessed the effectiveness of the approach in reducing the incidence of admission hypothermia. RESULTS: The QI project included 189 patients. These patients were compared to 180 patients during the control period. The characteristics of the patient groups were similar and included preterm infants, who were subsequently analyzed as a subgroup. We found a significant reduction in the incidence of hypothermia, which was most profound for the subgroup of premature infants born at < 32 weeks gestation. Neonatal hyperthermia was identified as an unintended consequence of the project, and subsequently improved after initiating simple preventive measures. CONCLUSIONS: Occlusive wrapping, exothermic mattresses, and higher delivery and operating room environmental temperature may be successful in reducing admission neonatal hypothermia.

Inverse association between 1,5-anhydroglucitol and neonatal diabetic complications.

PURPOSE: A glycemic control marker to predict neonatal diabetic complications is unavailable. We aimed to examine if 1,5-anhydroglucitol (1,5-AG) can predict neonatal complications in women with diabetes in pregnancy. METHODS: Prospective observational study from December 2011 to August 2013. We recruited 105 women, 70 diabetic (gestational and pregestational) and 35 nondiabetic. 1,5-AG at birth was compared between the two groups. In the diabetic group 1,5-AG, HbA1c, and fructosamine were measured before glycemic control initiation (first visit), after 4-6 weeks (second visit), and at delivery. Women were divided to poor (1,5-AG values below median at birth) and good (1,5-AG values at median and above) glycemic control groups. Mean daily glucose charts were collected. The primary outcome was a composite of neonatal diabetic complications: respiratory distress, hypoglycemia, polycythemia, hyperbilirubinemia, and large for gestational age. RESULTS: Mean 1,5-AG in the nondiabetic group was similar to that of the diabetic group without the composite outcome and was significantly higher than in the diabetic group with the composite outcome. The rate of the composite outcome was higher in the poor glycemic control group compared with the good glycemic control group (adjusted odds ratio (OR) 3.8 95% CI [1.2-12.3]). Only 1,5-AG was inversely associated with the composite outcome at all time points; the second visit was the only independent risk factor in multivariable logistic regression (OR 0.7 95% CI 0.54-0.91). The rest of the glycemic markers were not associated with neonatal composite outcome. CONCLUSIONS: 1,5-AG is inversely associated with neonatal diabetic complications and is superior to other glycemic markers in predicting those complications.

Glyburide Versus Metformin and Their Combination for the Treatment of Gestational Diabetes Mellitus: A Randomized Controlled Study.

OBJECTIVE: To compare the efficacy and safety of glyburide versus metformin and their combination for the treatment of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: In this prospective randomized controlled study, we randomly assigned patients with GDM at 13-33 weeks gestation and whose blood glucose was poorly controlled by diet to receive either glyburide or metformin. If optimal glycemic control was not achieved, the other drug was added. If adverse effects occurred, the drug was replaced. If both failed, insulin was given. The primary outcomes were the rate of treatment failure and glycemic control after the first-line medication according to mean daily glucose charts. RESULTS: Glyburide was started in 53 patients and metformin in 51. In the glyburide group, the drug failed in 18 (34%) patients due to adverse effects (hypoglycemia) in 6 (11%) and lack of glycemic control in 12 (23%). In the metformin group, the drug failed in 15 (29%) patients, due to adverse effects (gastrointestinal) in 1 (2%) and lack of glycemic control in 14 (28%). Treatment success after second-line therapy was higher in the metformin group than in the glyburide group (13 of 15 [87%] vs. 9 of 18 [50%], respectively; P = 0.03). In the glyburide group, nine (17%) patients were eventually treated with insulin compared with two (4%) in the metformin group (P = 0.03). The combination of the drugs reduced the need for insulin from 33 (32%) to 11 (11%) patients (P = 0.0002). Mean daily blood glucose and other obstetrical and neonatal outcomes were comparable between groups, including macrosomia, neonatal hypoglycemia, and electrolyte imbalance. CONCLUSIONS: Glyburide and metformin are comparable oral treatments for GDM regarding glucose control and adverse effects. Their combination demonstrates a high efficacy rate with a significantly reduced need for insulin, with a possible advantage for metformin over glyburide as first-line therapy.

Anthropometric parameters in infants of gestational diabetic women with strict glycemic control.

OBJECTIVE: Differences in weight and body composition have been reported between infants of nondiabetic and diabetic mothers. These differences may explain the propensity for shoulder dystocia in the diabetic population. We investigated whether differences in anthropometric measurements still exist between infants of nondiabetic and diabetic mothers following strict glycemic control. METHODS: This was a prospective cohort study. The study group included infants of well-controlled gestational diabetic mothers (mean capillary glucose less than 100 mg/dL). Controls were infants of nondiabetic mothers matched for gender, gestational age, ethnicity, and birth weight. Only singleton term pregnancies were included. Both groups were studied within 24 hours of delivery. The following measurements were obtained: birth weight, infant length, femur length, head, chest, abdomen and thigh circumferences, and biacromial distance. Student t tests were used to compare the measured parameters between groups. P < .05 was considered significant. A sample size of 63 subjects in each group was needed to demonstrate a difference of 0.5 cm (+/- 1.0 cm) of the biacromial distance between the 2 groups, which we considered clinically significant, with a probability of 95% and power of 80%. RESULTS: Sixty seven infants in each group were included in the study. Anthropometric measurements did not differ significantly between the groups. We did a secondary analysis on neonates who weighed 4,000 g or more at birth. Anthropometric measurements again did not differ significantly between the groups. CONCLUSION: Anthropometric measurements of infants of mothers with well-controlled gestational diabetes do not differ from infants of nondiabetic mothers. LEVEL OF EVIDENCE: II-2.