The efficiency of cabergoline vs pyridoxine for lactation inhibition-a randomized controlled trial.

BACKGROUND: Some mothers may seek lactation inhibition on personal, social, or medical grounds. The common drug used for lactation inhibition is cabergoline. Several adverse effects and contraindications are known for this drug. Its use is contraindicated for patients with hypertensive disorders and fibrotic, cardiac, or hepatic diseases. In addition, pyridoxine (vitamin B6) has been used for this indication, with no significant adverse effect, following studies that demonstrated its efficacy. OBJECTIVE: This study aimed to compare the efficiency of cabergoline vs pyridoxine for lactation inhibition. STUDY DESIGN: A randomized controlled trial was conducted. Postpartum patients who requested lactation inhibition were randomly allocated to receive either cabergoline (1 mg once on postpartum day 1 or divided to 0.25 mg twice a day for 2 days thereafter, according to the departmental protocol, which is in line with the manufacturer recommendations) or pyridoxine (200 mg 3 times a day for 7 days). The patients enrolled were free of diseases in which contraindications to cabergoline are present. All patients completed a questionnaire for assessing breast engorgement, breast pain, and milk leakage on a scale of 0 (no symptom) to 5 (severe symptom) on days 0, 2, 7, and 14. The primary outcome was lactation inhibition success, defined as a score of 0 for both engorgement and pain on day 7. The secondary outcomes included the assessment of milk leakage, adverse effects, fever, mastitis, and treatment discontinuation or alteration. RESULTS: Of note, 45 and 43 patients received cabergoline or pyridoxine, respectively, and were included in the analysis following the intention-to-treat principle. Cabergoline was superior to pyridoxine in inhibiting lactation at day 7 (78% vs 35%, respectively; P<.0001). Mild symptoms, defined as a score of 0 to 2 for breast engorgement and pain, at day 7 were 40 (89%) in the cabergoline group and 29 (67%) in the pyridoxine group (P=.01). The incidence of milk leakage was lower in the cabergoline group after 7 and 14 days than in the pyridoxine group (9% vs 42% [P=.0003] and 11% vs 31% [P=.02], respectively). Cabergoline had more adverse effects than pyridoxine (31% vs 9%, respectively; P=.01), but all adverse effects were mild. The rates of mastitis and fever that were related to engorgement were similar in the cabergoline and pyridoxine groups (4 [9%] vs 2 [5%], respectively; P=.67). Furthermore, 9 patients (21%) in the pyridoxine group switched to or added cabergoline because of treatment failure. Accordingly, on day 7, the pyridoxine success rate was reduced from 35% (15 women) to 28% (12 women) and from 67% (29 women) to 53% (23 women) for a score of 0 and 0 to 2 for both engorgement and pain, respectively. CONCLUSION: Cabergoline was superior to pyridoxine in inhibiting lactation. Cabergoline had more adverse effects, but no major adverse effect was documented in either treatment group. As pyridoxine inhibited lactation successfully in previous studies and in 67% of patients in this study, its use should be considered in women with contraindications for cabergoline.

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 .

Addition of oral iron bisglycinate to intravenous iron sucrose for the treatment of postpartum anemia-randomized controlled trial.

BACKGROUND: Studies that have compared the effectiveness of oral with intravenous iron supplements to treat postpartum anemia have shown mixed results. The superiority of one mode of treatment vs the other has yet to be demonstrated. Therefore, despite guidelines and standards of care, treatment approaches vary across practices. A single 500 mg dose of iron sucrose, which is higher than what is usually administered, has not been evaluated to treat postpartum moderate to severe anemia. OBJECTIVE: This study aimed to compare the efficacy of intravenous iron sucrose alone with intravenous iron sucrose in combination with oral iron bisglycinate supplementation in treating moderate to severe postpartum anemia. STUDY DESIGN: A randomized controlled trial was conducted between February 2015 and June 2020. Women with postpartum hemoglobin level of ≤9.5 g/dL were treated with 500 mg intravenous iron sucrose after an anemia workup, which ruled out other causes for anemia. In addition to receiving intravenous iron, women were randomly allocated to receive either 60 mg of oral iron bisglycinate for 45 days or no further iron supplementation. The primary outcome was hemoglobin level at 6 weeks after delivery. Secondary outcomes were iron storage parameters and quality of life. RESULTS: Of 158 patients who participated, 63 women receiving intravenous and oral iron, and 44 women receiving intravenous iron-only, completed the study and were included in the analysis. Baseline and obstetrical characteristics were similar between the study cohorts. Although statistically significant, postpartum hemoglobin levels were only 0.4 g/dL higher in the intravenous and oral iron than intravenous iron-only cohort (12.4 g/dL vs 12.0 g/dL, respectively; P=.03), with a respective increase from baseline of 4.2 g/dL vs 3.7 g/dL (P=.03). There was no difference in the rate of women with hemoglobin level of <12.0 or 11.0 g/dL. Iron storage and health quality were not different between the cohorts. Oral iron treatment was associated with 29% rate of adverse effects. Compliance and satisfaction from treatment protocol were high in both cohorts. CONCLUSION: Intravenous 500 mg iron sucrose treatment alone is sufficient to treat postpartum anemia without the necessity of adding oral iron treatment.

One elevated oral glucose tolerance test value in pregnancy increases the risk for future diabetes mellitus type 2.

PURPOSE: Women with only one elevated 100 g OGTT value are not considered as having gestational diabetes mellitus (GDM) and therefore there are no recommendations to address this population as a risk group for type 2 diabetes mellitus (T2DM). We aimed to elucidate whether one elevated OGTT value increases the risk for T2DM. METHODS: A retrospective population-based cohort study of women with a first diagnosis of GDM who delivered between 1991 and 2011 was conducted. Women were divided according to GDM diagnosis criteria into three groups: (1) at least two elevated values of Carpenter and Coustan criteria (C&C; N = 209), (2) At least two elevated values of the National Diabetes Data Group (NDDG) criteria (NDDG2; N = 290) and (3) only one elevated value of the NDDG criteria (NDDG1; N = 226). A fourth group comprising women without GDM was included (control; N = 352). The primary outcome was the development of T2DM. RESULTS: The mean follow-up was 12.4 ± 5.3 years and the mean age at follow-up was 43.0 ± 5.7 years. The rate of T2DM in the control, C&C, NDDG1 and NDDG2 groups were 5%, 18%, 19% and 31%, respectively. All GDM diagnoses were independent risk factors for T2DM in multivariable Cox regression when compared to controls, adjusted hazard ratio and 95% CI: C&C 7.8 [95% CI 3.7-16.4], NDDG1 5.5 [2.6-11.6], and NDDG2 10.5 [5.2-21.4]. Additional independent risk factors were parity, fasting and 1-h post-glucose load of the OGTT and insulin use. CONCLUSIONS: Women with one elevated OGTT value using the NDDG criteria are at increased risk for T2DM. Further studies are needed to decide whether those women should be considered a focus group for long-term surveillance and T2DM prevention interventions.

Good glycemic control of gestational diabetes mellitus is associated with the attenuation of future maternal cardiovascular risk: a retrospective cohort study.

BACKGROUND: To examine whether glycemic control of gestational diabetes mellitus (GDM) could modify the risk for future maternal metabolic and cardiovascular morbidities. METHODS: A retrospective cohort study of women with a first diagnosis of GDM who delivered between 1991 and 2011. Women were divided into groups of good and poor glycemic control, defined as a mean daily glucose of up to 95 mg/dL (N = 230) and more than 95 mg/dL (N = 216), respectively. In addition, a control group of women without GDM (N = 352) was also analyzed. The primary outcomes were the development of type 2 diabetes mellitus (T2DM), obesity, hypertension, or dyslipidemia. RESULTS: Mean follow-up time was 15.8 ± 5.1 years. Assessment was performed at a maternal age of 45 ± 7 years. The rates of the study outcomes in the control, GDM with good glycemic control and GDM with poor glycemic control were as follows: T2DM [19 (5.4%), 87 (38%), 127 (57%)]; hypertension [44 (13%), 42 (18%), 44 (20%)]; obesity [111 (32%), 112 (48%), 129 (58%)]; and dyslipidemia [49 (14%), 67 (29%), 106 (48%)]. Glycemic control was an independent risk factor for T2DM in multivariate Cox regression analysis (hazard ratio (HR) for poor glycemic control vs. controls 10.7 95% CI [6.0-19.0], good glycemic control vs. control HR 6.0 [3.3-10.8], and poor glycemic control vs. good glycemic control HR 1.8 [1.3-2.4]). Glycemic control was also an independent risk factor for dyslipidemia (poor glycemic control vs. controls HR 3.7 [2.3-5.8], good glycemic control vs. controls HR 2.0 [1.2-3.2], and poor glycemic control vs. good glycemic control HR 1.8 1.8 [1.3-2.6]). The fasting glucose level during oral glucose tolerance test (OGTT) was also an independent risk factor for these complications. The interaction term between glycemic control and the fasting value of the OGTT was not statistically significant, suggesting that the effect of glycemic control on the rate of future T2DM and dyslipidemia was not modified by the baseline severity of GDM. CONCLUSION: GDM and especially poor glycemic control are associated with T2DM and dyslipidemia. Strict glycemic control for reducing that risk should be evaluated in prospective trials.

Double-blind randomized trial of progesterone to prevent preterm birth in second-trimester bleeding.

INTRODUCTION: Second-trimester vaginal bleeding increases the risk of spontaneous preterm birth. We aimed to examine the efficacy of vaginal progesterone to reduce preterm birth rate in women with second-trimester vaginal bleeding. MATERIAL AND METHODS: Two-center, double-blind, placebo-controlled trial involving pregnant women with second-trimester vaginal bleeding. Women with documented uterine bleeding were randomly assigned in a 1:1 ratio to receive 200 mg of micronized vaginal progesterone or placebo once daily at 16-26 weeks until 36 weeks of gestation. Women who had prior preterm birth or short cervix diagnosed before recruitment were not eligible. The primary outcome was spontaneous delivery <37 weeks. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01269450. RESULTS: Between March 2011 and January 2017, 128 women gave consent and were randomized; 16 withdrew consent and 3 had a second-trimester termination of pregnancy. The final analysis included 109 women: 60 in the progesterone group and 49 in the placebo group. Demographic and obstetric characteristics did not differ between the groups. Primary outcome occurred in 19 (31.7%) and 12 (24.5%) in the progesterone and placebo groups, respectively (odds ratio [OR] 1.32; 95% confidence interval [CI] 0.55-3.16; P = 0.53). The proportion of births <34 weeks was similar between the groups (OR 1.19; 95% CI 0.47-3.02; P = 0.72), as were the survival curves from randomization to delivery (hazard ratio, 1.24; 95% CI, 0.60-2.56; P = 0.57). There were no significant differences in neonatal morbidities between the groups. The study was ended prematurely because of slow recruitment. CONCLUSIONS: Antepartum vaginal progesterone does not seem to reduce the incidence of preterm birth in women with second-trimester bleeding.

Labor induction versus expectant management at early term in pregnancies with second trimester elevated human chorionic gonadotropin or alpha fetoprotein.

AIM: Elevated human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) have been linked to placental dysfunction and associated morbidities. We aimed to compare the induction of labor with expectant management at term in those pregnancies for the prevention of neonatal and maternal morbidities. METHODS: Women with second trimester HCG ≥ 2 and/or AFP ≥ 2 multiples of the median, without additional maternal or fetal complications, from their 38th gestational week were offered the choice of labor induction or expectant management. The primary outcomes were maternal composite outcome (composed of cesarean deliveries, pre-eclampsia or placental abruption) and neonatal composite outcome (composed of antenatal or neonatal death, Apgar score at 5 min < 7, admission to the neonatal intensive care unit, need for phototherapy, respiratory abnormalities, birth trauma or neonatal infection). RESULTS: Of 305 women, 124 women chose to undergo labor induction, and 181 women chose expectant management. The composite maternal outcome in the expectant management group was twice the rate of the labor induction group, although it did not reach statistical significance (18 [10%] vs 6 [5%]; P = 0.1; relative risk [expectant/induced] 2.04; 95% confidence interval 0.8-5.0). Increased rate of phototherapy led to increased neonatal composite outcomes in the labor induction group compared with the expectant management group (34 [27%] vs 27 [15%], respectively = 0.007). CONCLUSION: In pregnancies with elevated AFP and/or HCG, early term labor induction initiated a trend towards improvement in maternal outcome but increased the rate of mild neonatal morbidity. The statistical insignificance of the large effect on the maternal outcome might reflect the lack of statistical power. Further research is needed to address this limitation.

Predictive Value of Second-Trimester Biomarkers and Maternal Features for Adverse Pregnancy Outcomes.

OBJECTIVE: To establish the predictive probability for placenta-associated morbidities using second-trimester α-fetoprotein (AFP), human chorionic gonadotropin (HCG), and maternal features. PATIENTS AND METHODS: A retrospective database of all singleton deliveries with available second-trimester HCG and AFP results from 2005 to 2012 was built and divided into 0, 1, or 2 elevated markers (defined as ≥2 multiples of the median [MoM]). For each group, we analyzed the risk for adverse obstetric outcome - comprising preeclampsia, placental abruption, and birth weight below the 10th percentile - and the time of delivery in those pregnancies. Additionally, prediction models for adverse obstetric outcome, using logistic regression incorporating AFP, HCG, and other maternal characteristics, were calculated. RESULTS: Among 22,124 women who delivered, 16,197 (73%) had AFP and HCG results. Compared with the group with normal markers, the adverse obstetric outcome rate was mildly increased with elevated HCG or AFP, but it was markedly increased when both markers were elevated (13 vs. 31%, OR 2.9, 95% CI 2.0-4.3). Delivery of newborns with adverse obstetric outcome was earlier with each additional elevated marker. The accuracy of predicting adverse obstetric outcome was improved by using prediction models for women with HCG or AFP ≥1.2 MoM that incorporated maternal age, BMI, parity, and chronic hypertension (C-statistic 61-75%). CONCLUSION: HCG and AFP combined with other maternal characteristics are useful tools for predicting the risk for adverse obstetric outcome.

Measurement of betamethasone concentration in maternal serum treated for fetal lung maturity; Is it feasible?

BACKGROUND: The association between maternal serum concentration of betamethasone given for fetal lung maturity and perinatal outcome has not been investigated. This may be due to an absence of a reliable method for measuring serum betamethasone concentrations. We aimed in the current study to assess the feasibility of a specific ELISA kit to measure the concentrations of betamethasone in maternal serum and to examine the trend of sequential measurements after a course of betamethasone for fetal lung maturity. METHODS: Pregnant women at risk for preterm birth who received betamethasone between 24 and 34 weeks of gestation were prospectively included. Serum concentrations were determined before administering betamethasone (baseline), and 36 hours, 48 hours, 72 hours, and 5 to 7 days after the 1(st) dose. Betamethasone concentration in samples was determined using Corticosteroid ELISA kit. The Friedman test was used to test whether there were significant differences between the measurements. RESULTS: Five singleton pregnancies were included. Using the ELISA kit, betamethasone concentration in maternal serum samples was obtained for all women. Among the five measurements performed, the concentration was highest at 36 hours after the 1(st) dose and close to baseline at the 5(th) measurement performed after 5 to 7 days (p < 0.05). Serum concentration varied at each time point between the five women but similar trend was observed. CONCLUSION: Betamethasone concentration is measurable in the serum of pregnant women with this ELISA kit.

Pregnancy outcomes in patients with Alport syndrome.

PURPOSE: To analyze the maternal and obstetric outcomes of patients with Alport syndrome. METHODS: We describe the pregnancy course of 8 pregnancies of three family members with the autosomal dominant (the rarest) form of Alport syndrome. We also analyzed 10 previously reported pregnancies with other Alport mutations in order to explore risk factors for unfavorable obstetric outcomes and maternal renal deterioration. RESULTS: In 13 pregnancies (72 %), renal function did not deteriorate permanently. All of these women had pre-pregnancy mild chronic kidney disease (CKD stage G1). In all of them, only a transient increase in proteinuria was recorded and in one case there was a transient decrease in the estimated glomerular filtration rate. In four other pregnancies (22 %), renal function deteriorated following pregnancy. All of them were complicated with pre-eclampsia. One woman had pre-pregnancy CKD-G2A3 and chronic hypertension. Two women had CKD-G1A3 of whom one had pre-pregnancy proteinuria near the nephrotic range. In the fourth case, renal function deterioration was reported without information on the exact pre-pregnancy renal function. In the last case, CKD-G2 was reported after pregnancy without information on CKD stage prior to pregnancy. Severe proteinuria did not imply a permanent renal function deterioration if it developed during pregnancy. Ten pregnancies ended with preterm birth (56 %). Two stillbirths were reported (11 %); however, only one was attributed to maternal health deterioration. CONCLUSION: Data regarding pregnancy outcomes in Alport syndrome is limited. The outcome seems favorable when pre-pregnancy kidney function is normal or near normal and when chronic hypertension/pre-eclampsia is absent.

The prevalence of gestational diabetes mellitus recurrence--effect of ethnicity and parity: a metaanalysis.

Reports on the gestational diabetes mellitus (GDM) recurrence rate have been highly variable. Our objectives were to examine the possible causes of GDM recurrence rate variability and to obtain pooled estimates in subgroups. We have carried out a systematic review and metaanalysis based on the Metaanalysis Of Observational Studies in Epidemiology statement. We identified papers published from 1973 to September 2014. We identified papers using Medline (PubMed and Ovid), ClinicalTrials.gov and Google Scholar databases, and published references. We included only English-language, population-based studies that reported specified GDM criteria and GDM recurrence rate. A total of 18 eligible studies with 19,053 participants were identified. We used the Cochrane's Q test of heterogeneity to choose the model for estimating the pooled GDM recurrence rate. Metaregression was also used to explore the possible causes of variability between studies. The pooled GDM recurrence rate was 48% (95% confidence interval, 41-54%). A significant association between ethnicity and GDM recurrence rate was found (P = .02). Non-Hispanic whites had lower recurrence rate compared with other ethnicities (39% and 56%, respectively). Primiparous women had a lower recurrence rate compared with multiparous women (40% and 73%, respectively; P < .0001) No evidence for association between family history of diabetes and GDM recurrence was found. The overall GDM recurrence rate is high. Non-Hispanic whites and primiparous women have substantially lower GDM recurrence rates, which contributes to the variability between studies. Because no association between family history of diabetes and GDM recurrence was found, the large differences between ethnic groups may have also resulted from nongenetic factors. Thus, intervention programs could reduce the GDM recurrence rates.

Vaginal Progesterone for Pregnancy Prolongation After Arrested Preterm Labor: A Randomized Clinical Trial.

Importance: Women with arrested preterm labor (APTL) are at very high risk for spontaneous preterm delivery (SPTD), the leading cause of neonatal mortality and morbidity. To date, no maintenance therapy has been found to be effective for pregnancy prolongation. A few clinical trials with considerable methodological limitations have demonstrated some efficacy for 400 mg vaginal micronized progesterone (VMP) in women with APTL. Objective: To investigate the effectiveness of daily 400 mg VMP for the prolongation of pregnancy after APTL. Design, Setting, and Participants: This randomized clinical trial was conducted between December 19, 2018, and February 27, 2023, in 3 university-affiliated medical centers in Israel. Participants included women with singleton and twin pregnancies after APTL following tocolysis at 24 weeks 0 days to 34 weeks 0 days' gestation. Women with a history of preterm delivery or asymptomatic cervical shortening in the current pregnancy were excluded. Interventions: Participants were randomly allocated to receive VMP 200 mg twice a day or no treatment until 36 weeks 6 days' gestation. Main Outcomes and Measures: The primary end points were mean number of days from study enrollment to delivery and the rate of SPTD prior to 37 weeks' gestation. Results: A total of 129 participants were enrolled (65 in the VMP group and 64 in the no-treatment group). Mean (SD) age was 27.6 (5.1) years. Between the VMP and no-treatment groups, there was no difference in pregnancy prolongation (mean [SD], 40.0 [17.8] vs 37.4 [20.3] days; P = .44) and the rate of SPTD (16 [25%] vs 19 [30%]; relative risk, 0.8; 95% CI, 0.5-1.5; P = .52). In twin pregnancies, including 12 and 15 pairs in the VMP and no-treatment groups, respectively, VMP prolonged pregnancy (mean [SD], 43.7 [18.1] vs 26.1 [15.2] days; P = .02), postponed the delivery week (36.5 [1.4] vs 34.7 [2.2] weeks; P = .01), shortened the length of stay in the neonatal intensive care unit (4.9 [10.6] vs 13.2 [18.5] days; P = .03) and overall hospital stay (8.3 [9.6] vs 15.1 [17.2] days; P = .03), and was associated with a higher birth weight (2444 [528] vs 2018 [430] g; P = .01). Conclusions and Relevance: These findings show that VMP given in a dosage of 200 mg twice a day following APTL is not an effective treatment to prolong pregnancy or prevent SPTD. However, VMP demonstrated beneficial effects in twin pregnancies, warranting further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02430233.

The effect of oral probiotics on glycemic control of women with gestational diabetes mellitus-a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Gestational diabetes mellitus should be treated adequately to avoid maternal hyperglycemia-related complications. Previously, probiotic supplements were suggested to improve fasting blood glucose in women with gestational diabetes mellitus. However, a major limitation of previous studies was that preprandial and especially postprandial glucose values, which are important predictors of pregnancy outcomes, were not studied. OBJECTIVE: This study aimed to examine the effect of a mixture of probiotic strains on maternal glycemic parameters, particularly preprandial and postprandial glucose values and pregnancy outcomes among women with gestational diabetes mellitus. STUDY DESIGN: A multicenter prospective randomized, double-blind, placebo-controlled trial was conducted. Women newly diagnosed with gestational diabetes mellitus were randomly allocated into a research group, receiving 2 capsules of oral probiotic formula containing Bifidobacterium bifidum, B lactis, Lactobacillus acidophilus, L paracasei, L rhamnosus, and Streptococcus thermophilus (>6 × 109/capsule), and a control group, receiving a placebo (2 capsules/day) until delivery. Glycemic control was evaluated by daily glucose charts. After 2 weeks, pharmacotherapy was started in case of poor glycemic control. The primary outcomes were the rate of women requiring medications for glycemic control and mean daily glucose charts after 2 weeks of treatment with the study products. RESULTS: Forty-one and 44 women were analyzed in the treatment and placebo cohorts, respectively. Mean daily glucose during the first 2 weeks in the probiotics and placebo groups was 99.7±7.9 and 98.0±9.3 mg/dL, respectively (P=.35). The rate of women needing pharmacotherapy because of poor glycemic control after 2 weeks of treatment in the probiotics and placebo groups was 24 (59%) and 18 (41%), respectively (P=.10). Mean preprandial and postprandial glucose levels throughout the study period were similar between the groups (P>.05). There were no differences in maternal and neonatal outcomes, including birthweight and adverse effect profile between the groups. CONCLUSION: The oral probiotic product tested in this study did not affect glycemic control of women with gestational diabetes mellitus.

Comparison of postpartum anti-Xa levels following enoxaparin administration to prevent venous thromboembolism using 2 weight-based protocols: a randomized controlled trial.

BACKGROUND: During the postpartum period, enoxaparin is given to high-risk women to prevent venous thromboembolism, a leading cause of maternal mortality. Enoxaparin activity is measured by peak plasma anti-Xa levels. The prophylactic range of anti-Xa is 0.2 to 0.6 IU/mL. Values above and below this range represent subprophylactic and supraprophylactic levels, respectively. Weight-based enoxaparin administration was superior to fixed-dose enoxaparin administration in achieving an anti-Xa prophylactic range. However, it is unknown which weight-based enoxaparin administration is superior (once daily weight categories vs 1 mg/kg body weight). OBJECTIVE: This study aimed to compare the efficacy in reaching prophylactic anti-Xa levels and adverse effects profile of the 2 weight-based enoxaparin dosing protocols. STUDY DESIGN: A randomized open-label controlled trial was conducted. Women after delivery, who were intended to receive enoxaparin, were randomized to receive either enoxaparin treatment according to 1 mg/kg (up to 100 mg) or weight categories (≤90 kg, 40 mg; 91-130 kg, 60 mg; 131-170 kg, 80 mg; >170 kg, 100 mg). Plasma anti-Xa levels were obtained 4 hours after the second enoxaparin administration (day 2 of enoxaparin treatment). If the woman was still hospitalized, anti-Xa levels were also obtained on day 4. The primary endpoint was the proportion of women with anti-Xa levels within the prophylactic range at day 2. In addition, data regarding anti-Xa levels in different weight groups and rates of venous thromboembolism and adverse effects were evaluated. RESULTS: Of note, 60 and 64 women received enoxaparin according to 1 mg/kg and weight categories, respectively; moreover, 55 (92%) and 27 (42%) women reached the prophylactic range of anti-Xa at day 2, respectively (P<.0001). The mean anti-Xa levels on day 2 were 0.34±0.09 and 0.19±0.06 IU/mL, respectively (P<.0001). The anti-Xa levels were higher in the 1 mg/kg group than in the weight categories group in the subanalysis of different weight categories (51-70, 71-90, and 91-130 kg). There was no difference in anti-Xa levels on day 4 compared with day 2 in both cohorts (n=25). There was no case of supraprophylactic anti-Xa levels, venous thromboembolism events, or serious hemorrhage. CONCLUSION: Postpartum enoxaparin administration at 1 mg/kg was superior to weight categories in reaching anti-Xa prophylactic levels without leading to serious adverse effects. Given the high efficacy and safety profile, enoxaparin at 1 mg/kg once daily should be considered the preferred protocol for postpartum venous thromboembolism prophylaxis.

The Association between Gestational Diabetes Mellitus and Infections in Pregnancy-Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis to evaluate the association between gestational diabetes mellitus and infections during pregnancy. We included cross-sectional, case-control, cohort studies and clinical trials, evaluating the frequency of infections in women with and without gestational diabetes mellitus. A search was conducted in Embase, PubMed, and Web of Science electronic databases and by manually searching references, until 23 March 2022, resulting in 16 studies being selected for review, with 111,649 women in the gestational diabetes mellitus group, and 1,429,659 in the controls. Cochrane's Q test of heterogeneity and I² were used to assess heterogeneity. Pooled odds ratio (OR) was calculated. Funnel plots and Egger test were used for assessment of publication bias. The results showed a significant association between gestational diabetes mellitus and infections (pooled-OR 1.3 95% CI [1.2-1.5]). Sub-analyses showed a significant association for urinary tract infections (pooled-OR of 1.2 95% CI [1.1-1.3]), bacterial infections (pooled-OR were 1.2 95% CI [1.1-1.4]), and SARS-CoV-2 (pooled-OR 1.5 95% CI [1.2-2.0]) but not to gingivitis or vaginal candidiasis. The results underscore the significance of acknowledging gestational diabetes mellitus as a risk factor for infections.

Effects of Probiotics on Glycemic Control and Metabolic Parameters in Gestational Diabetes Mellitus: Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the effects of probiotic supplements on glycemic control and metabolic parameters in women with gestational diabetes mellitus (GDM) by performing a systematic review and meta-analysis of randomized controlled trials. The primary outcome was glycemic control, i.e., serum glucose and insulin levels. Secondary outcomes were maternal weight gain, neonatal birth weight, and lipid parameters. Weighted mean difference (WMD) was used. Cochrane's Q test of heterogeneity and I2 were used to assess heterogeneity. RESULTS: Of the 843 papers retrieved, 14 (n = 854 women) met the inclusion criteria and were analyzed. When compared with placebo, women receiving probiotic supplements had significantly lower mean fasting serum glucose, fasting serum insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, total cholesterol, and VLDL levels. Decreased neonatal birth weight was witnessed in supplements containing Lactobacillus acidophilus. CONCLUSION: Probiotic supplements may improve glycemic control and lipid profile and reduce neonatal birth weight in women with GDM.

Intermittent vs continuous catheterization for postpartum urinary retention: A multicenter randomized controlled trial.

BACKGROUND: Postpartum urinary retention is a common complication in the immediate postpartum period. However, there is no consensus regarding optimal management. OBJECTIVE: This study aimed to compare 2 catheterization strategies for the treatment of postpartum urinary retention. STUDY DESIGN: A multicenter prospective randomized controlled trial was conducted at 4 university-affiliated medical centers between January 2020 and June 2022. Individuals with postpartum urinary retention (bladder volume of >150 mL) up to 6 hours after vaginal or cesarean delivery were randomly allocated to 1 of 2 protocols: intermittent catheterization every 6 hours, up to 4 times, or continuous catheterization with an indwelling urinary catheter for 24 hours. If postpartum urinary retention was not resolved after 24 hours, an indwelling catheter was inserted for an additional 24 hours in both groups. The primary endpoint was the mean time to postpartum urinary retention resolution. The secondary endpoints included postcatheter urinary tract infection rate and length of hospital stay. The satisfaction rate was estimated using the 30-Item Birth Satisfaction Scale questionnaire. RESULTS: After randomization, 73 individuals were allocated to the intermittent catheterization group, and 74 individuals were allocated to the continuous catheterization group. The mean time to postpartum urinary retention resolution was significantly shorter in the intermittent catheterization group than in the continuous catheterization group (10.2±11.8 vs 26.5±9.0 hours; P<.001), with 75% and 93% resolution rates after 1 and 2 catheterizations, respectively. The number of individuals who achieved resolution at 24 hours was 72 (99%) in the intermittent catheterization group and 67 (91%) in the continuous catheterization group (P=.043). The satisfaction rate was higher in all categories in the intermittent catheterization group than in the continuous catheterization group (P<.001). No intercohort difference was found in the urinary tract infection rates (P=.89) or hospital stay length (P=.58). CONCLUSION: Compared with indwelling catheterization, intermittent catheterization for urinary retention after delivery was associated with quicker postpartum urinary retention resolution and a higher satisfaction rate without increasing the complication rates.

Should pregnant women be screened for SARS-CoV-2 infection? A prospective multicenter cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranges from asymptomatic to severe infection. We aimed to compare the prevalence of COVID-19 in asymptomatic pregnant versus nonpregnant women in order to establish recommendations for a COVID-19 screening strategy. METHODS: A prospective multicenter cohort study was conducted. Asymptomatic pregnant or nonpregnant women after March 2020 (the time when COVID-19 was first detected in north Israel) were tested for SARS-CoV-2 using nasopharyngeal reverse transcription polymerase chain reaction test, anti-nucleocapsid IgG, and anti-spike IgG. Diagnosis was made if at least one test result was positive. Pregnant women were tested between 34 and 42 weeks, mostly at birth. RESULTS: Among the 297 participating women, 152 were pregnant and 145 were nonpregnant. The prevalence of asymptomatic COVID-19 was similar between the groups (4 [2.6%] and 8 [5.5%], respectively; P = 0.2). All women with COVID-19 delivered healthy appropriate-for-gestational-age babies without malformations, at term. CONCLUSIONS: The rate of asymptomatic COVID-19 in pregnant women is low and comparable to the rate among nonpregnant women. Pregnancy outcomes are favorable. Future screening programs should consider that one of 25 screened asymptomatic women will be positive.

Characteristics of pregnancy with gestational diabetes mellitus and the consecutive pregnancy as predictors for future diabetes mellitus type 2.

AIM: To explore possible obstetrical history-related, modifiable risk factors of future type 2 diabetes mellitus (T2DM), with focus on characteristics of the index gestational diabetes mellitus (GDM) pregnancy and the consecutive pregnancy. METHODS: This retrospective, population-based, cohort study included 788 women with GDM, who had consecutive deliveries at Emek Medical Center during 1991-2012. Women with pre-existing diabetes were excluded. Factors associated with T2DM development were examined using stepwise multiple Cox regression model. RESULTS: Overall 178 women developed T2DM (23%). Multivariable analysis demonstrated that the most significant independent risk factors for T2DM development were birth weight ≥ 4000 g (HRadj1.7 95% CI [1.001-2.8]), fasting oral glucose tolerance test value (OGTT, HRadj1.03 95% CI [1.01-1.04], 1-hour post-OGTT glucose value (HRadj1.01 95% CI [1.006-1.02]), earlier gestational week in which GDM was diagnosed (HRadj 0.96 95% CI [0.93-0.99]), higher parity (HRadj 1.15 95% CI [1.06-1.25] and GDM recurrence in the consecutive delivery (HRadj2.4 95% CI [1.6-3.7]). Kaplan Meier survival curve of the time from the consecutive pregnancy until T2DM development showed a statistically significant effect of GDM recurrence and the risk for T2DM. Body mass index (BMI) gain between pregnancies and inter-pregnancy interval were not independent risk factors for T2DM. CONCLUSIONS: Obstetric characteristics of women with GDM and particularly GDM recurrence are associated with increased risk for T2DM. Strategies to prevent those factors and especially GDM recurrence might reduce the risk of future T2DM.

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.