Expert review: preeclampsia Type I and Type II.

Pregnancy involves an interplay between maternal and fetal factors affecting changes to maternal anatomy and physiology to support the developing fetus and ensure the well-being of both the mother and offspring. A century of research has provided evidence of the imperative role of the placenta in the development of preeclampsia. Recently, a growing body of evidence has supported the adaptations of the maternal cardiovascular system during normal pregnancy and its maladaptation in preeclampsia. Debate surrounds the roles of the placenta vs the maternal cardiovascular system in the pathophysiology of preeclampsia. We proposed an integrated model of the maternal cardiac-placental-fetal array and the development of preeclampsia, which reconciles the disease phenotypes and their proposed origins, whether placenta-dominant or maternal cardiovascular system-dominant. These phenotypes are sufficiently diverse to define 2 distinct types: preeclampsia Type I and Type II. Type I preeclampsia may present earlier, characterized by placental dysfunction or malperfusion, shallow trophoblast invasion, inadequate spiral artery conversion, profound syncytiotrophoblast stress, elevated soluble fms-like tyrosine kinase-1 levels, reduced placental growth factor levels, high peripheral vascular resistance, and low cardiac output. Type I is more often accompanied by fetal growth restriction, and low placental growth factor levels have a measurable impact on maternal cardiac remodeling and function. Type II preeclampsia typically occurs in the later stages of pregnancy and entails an evolving maternal cardiovascular intolerance to the demands of pregnancy, with a moderately dysfunctional placenta and inadequate blood supply. The soluble fms-like tyrosine kinase-1-placental growth factor ratio may be normal or slightly disturbed, peripheral vascular resistance is low, and cardiac output is high, but these adaptations still fail to meet demand. Emergent placental dysfunction, coupled with an increasing inability to meet demand, more often appears with fetal macrosomia, multiple pregnancies, or prolonged pregnancy. Support for the notion of 2 types of preeclampsia observable on the molecular level is provided by single-cell transcriptomic survey of gene expression patterns across different cell classes. This revealed widespread dysregulation of gene expression across all cell types, and significant imbalance in fms-like tyrosine kinase-1 (FLT1) and placental growth factor, particularly marked in the syncytium of early preeclampsia cases. Classification of preeclampsia into Type I and Type II can inform future research to develop targeted screening, prevention, and treatment approaches.

Two distinct molecular faces of preeclampsia revealed by single-cell transcriptomics.

INTRODUCTION: Preeclampsia is a multisystemic, pregnancy-specific disorder united by new-onset hypertension but with considerable variation in clinical manifestation, onset, and severity. For symptoms to regress, delivery of the placenta is required. For symptoms to regress, delivery of the placenta is required, making the placenta central to preeclampsia pathophysiology. To dissect which placental functions were impacted in two forms of preeclampsia, we studied molecular changes across the cell types of the placenta. METHODS: We performed a transcriptomic survey of single-cells and single-nuclei on cases of early- and late-onset preeclampsia with gestation-matched controls. FINDINGS: Our data revealed massive dysregulation of gene expression in all cell classes that was almost exclusive to early preeclampsia. For example, an important known receptor/ligand imbalance hallmarking angiogenic disfunction, sFLT1/placental growth factor (PGF), was reflected in striking, cell-autonomous dysregulation of FLT1 and PGF transcription in the syncytium in early preeclampsia only. Stromal cells and vasculature echoed an inflamed, stressed, anti-angiogenic environment. Finally, the placental immune niche set the tone for inflammation in early but not late preeclampsia. Here, fetal-origin Hofbauer and maternal-origin TREM2 macrophages were revealed as surprising main actors, while local cells of the adaptive immune system were largely unaffected. Late preeclampsia showed minimal cellular impact on the placenta. CONCLUSIONS: Our survey provides systematic molecular evidence for two distinct diseases. We resolved systematic molecular dysregulation to individual cell types with strong implications for definition, early detection, diagnosis, and treatment. FUNDING: Funded by the Preeclampsia Foundation through the Peter Joseph Pappas Research Grant.

Craniorachipagus symmetric conjoined twinning: Identification of a fourth case and delineation of the phenotype.

BACKGROUND: Symmetric craniorachipagus is an exceedingly rare type of bi-umbilical conjoined twinning, known from only three scantily described cases. CASE: We identified a fourth, previously described case that was misdiagnosed as janiceps and as pygopagus. It concerned dorsally conjoined twins that were part of a triplet pregnancy, spontaneously born at 22 weeks of gestation. Radiography confirmed union at the occipital craniums and the thoracolumbar vertebral columns. Both twins had their own separate umbilical cords. To delineate the phenotype of craniorachipagus and to differentiate it from rachipagus without cranial involvement, we compared the present case with the previous three reported cases and with the historical literature concerning comparable conditions. Furthermore, we discuss why exceedingly rare conditions such as these are presently underreported in the literature. CONCLUSION: Symmetric craniorachipagus is a type of bi-umbilical conjoined twinning, to date represented by four confirmed cases that share a similar phenotype. This includes dorsal conjunction at the sides of the occipital craniums and the vertebral columns, in the absence of any visceral connections. Details on its etiopathogenesis and apparent lethality await additional case investigations. No unequivocally confirmed cases of symmetric rachipagus without cranial involvement have been reported and its existence in humans has yet to be proven.

Intrapartum Atosiban Treatment During Tachysystole and Non-reassuring Fetal Monitoring: A Retrospective Cohort Study.

BACKGROUND: Uterine tachysystole during labor can lead to a decrease in fetal oxygen saturation and intracerebral oxygen saturation. Acute tocolysis using atosiban can inhibit uterine smooth muscle activity, potentially improving fetal status and facilitating vaginal delivery or allowing time to prepare for operative delivery. OBJECTIVES: To compare maternal and neonatal outcomes in cesarean and vaginal deliveries following atosiban administration during fetal prolonged deceleration and tachysystole at gestational age 37 0/7 to 43 0/7 weeks. METHODS: We conducted a single-center, descriptive retrospective cohort study at a large tertiary referral center. RESULTS: Of the 275 patients treated with atosiban, 186 (68%) delivered vaginally (either spontaneous delivery or instrumental delivery) and 89 (32%) underwent a cesarean delivery. In a univariate analysis, cesarean delivery was associated with higher body mass index (27.9 ± 4.3 vs. 30.2 ± 4.8, P = 0.003). Second stage atosiban administration was associated with vaginal delivery (89.3% vs. 10.7%, P = 0.01). Cesarean delivery was associated with lower Apgar at 1 and 5 minutes and a higher rate of neonatal intensive care unit admissions. The incidence of PPH among women treated with atosiban in our study (2.3-4.3%) was higher than the incidence reported in the literature (1-3%). CONCLUSIONS: Atosiban may be an effective acute intervention for non-reassuring fetal heart rate during tachysystole, increasing the rate of vaginal delivery and potentially reducing the need for cesarean delivery. However, the potential risk of postpartum hemorrhage should be taken into consideration.

Mothers' Knowledge of Infants' Fever Management: A National Prospective Study.

OBJECTIVES: The aim of this study was to describe mothers' knowledge of infant fever management after birth and six months later and its association with sociodemographic characteristics, perceived support, sources of consultation and health education; and to assess determinants of change in mother's knowledge from birth to six months. METHODS: Mothers (n = 2804) answered a self-reporting questionnaire after giving birth in maternity wards in six hospitals in Israel; six months later follow- up interviews were conducted by telephone. RESULTS: The mothers' knowledge level of infant fever management was low after birth (mean = 50.5, range 0-100, SD = 16.1), and rose to a moderate level six months later (mean = 65.2, SD = 15.0). Mothers having their first born, with lower household income or education were less knowledgeable about infant fever management after birth. However, these mothers showed the largest improvement after six months. Mothers' perceived support or sources of consultation and health education (partner, family, friends, nurses, and physicians) were not associated with their knowledge at either time. Moreover, mothers stated self-learning from internet and other media as often as receiving health education by health professionals. CONCLUSIONS FOR PRACTICE: Public health policy for health professionals in hospitals and community clinics is essential to promote clinical interventions promoting mothers' knowledge of infant fever management. Efforts should focus at first time mothers, those with non-academic education, and those with a moderate or low household income. Public health policy enhancing communication with mothers regarding fever management in hospitals and community health settings, as well as accessible means of self-learning is warranted.

Associations of maternal and placental extracellular vesicle miRNA with preeclampsia.

Introduction: Gestational vascular complications (GVCs), including gestational hypertension and preeclampsia, are leading causes of maternal morbidity and mortality. Elevated levels of extracellular vesicles (EVs), in GVC have been linked to vascular injury. This study aims to characterize placental and circulating EV miRNA in GVCs, and explores the involvement of EV-miRNA in GVC, and whether they may be used to distinguish between placental and maternal pathologies. Methods: Blood samples were obtained from 15 non-pregnant (NP), 18 healthy-pregnant (HP), and 23 women with GVC during the third trimester. Placental sections were obtained after caesarian section. Platelet-poor-plasma (PPP) and EV pellets were characterized: EV size/concentration, protein content and miRNA expression were measured by nanoparticle tracking analysis, western blot, nano-string technology and RT-PCR. The effects of EVs on trophoblasts and EC miRNA expression were evaluated. Results: Higher EVs concentrations were observed in HP-PPP and GVC-PPP (p < 0.0001) compared to the NP-PPP. The concentration of large EVs (>100 nm) was higher in PPP and EV pellets of HP and GVC compared to the NP group. EV pellets of pregnant women demonstrated lower expression of exosomal markers CD63/CD81 compared to NP-EVs. GVC-EVs expressed more human placental lactogen (hPL) hormone than HP-EVs, reflecting their placental origin. Screening of miRNAs in EV pellets and in PPP identified certain miRNAs that were highly expressed only in EVs pellets of the HP (13%) and GVC groups (15%), but not in the NP group. Differences were detected in the expression of hsa-miR-16-5p, hsa-miR-210, and hsa-miR-29b-3p. The expression of hsa-miR-16-5p and hsa-miR-210 was low in EV pellets obtained from NP, higher in HP-EVs, and significantly lower in GVC-EVs. Except for hsa-miR-29b-3p, which was upregulated in GVC, no significant differences were found in the levels of other miRNAs in placental sections. Exposure to GVC-EVs resulted in higher expression of hsa-miR-29b-3p compared to cells exposed to HP-EVs in villous trophoblasts, but not in EC. Conclusion: Expression of hsa-miR-16-5p and hsa-miR-210 reflects maternal pathophysiological status, while hsa-miR-29b-3p reflects placental status. These findings suggest that EV-miRNA are involved in GVC, and that they may be used to distinguish between pathologies of placental and maternal origins in preeclampsia.

[PHYSICAL ACTIVITY DURING PREGNANCY AND AFTER BIRTH].

INTRODUCTION: Physical activity (PA) decreases morbidity, improves quality of life and elongates life span. PA during pregnancy is safe and decreases complications. Physical inactivity during pregnancy is an independent risk factor for maternal weight gain and complications. Pregnancy is a golden opportunity to promote a healthy lifestyle. OBJECTIVES: This article aims to review the latest recommendations regarding PA in pregnancy. In this article we focused on the following: The joint guidelines of the Society of Obstetricians and Gynaecologists of Canada's (SOGC) and the Canadian Society for Exercise Physiology (CSEP), the American College of Obstetricians and Gynecologists (ACOG) committee opinion, and the ACSM's (American College of Sports Medicine) Guidelines for Exercise Testing and Prescription, the 11th Edition published in 2019, 2020 and 2022 respectively. CONCLUSIONS: PA during pregnancy is safe and essential. Every pregnant woman without contraindications should perform 150 weekly minutes of aerobic exercise and resistance training. DISCUSSION: A weekly goal of 150 medium intensity aerobic exercise minutes spread over at least 3 separate days combined with resistance training is recommended for every pregnant woman, including women who were inactive prior to the pregnancy, those diagnosed with gestational diabetes and overweight or obese women. Pregnant women with absolute contraindication can continue to perform their daily activities but avoid more intense activities, those with relative contraindications should discuss the advantages and risks of PA with their attending physician. After birth, women can return to PA gradually depending on the mode of delivery and complications encountered.

Prenatal exposure to heavy metal mixtures and anthropometric birth outcomes: a cross-sectional study.

BACKGROUND: Numerous studies have suggested significant associations between prenatal exposure to heavy metals and newborn anthropometric measures. However, little is known about the effect of various heavy metal mixtures at relatively low concentrations. Hence, this study aimed to investigate associations between prenatal exposures to a wide range of individual heavy metals and heavy metal mixtures with anthropometric measures of newborns. METHODS: We recruited 975 mother-term infant pairs from two major hospitals in Israel. Associations between eight heavy metals (arsenic, cadmium, chromium, mercury, nickel, lead, selenium, and thallium) detected in maternal urine samples on the day of delivery with weight, length, and head circumference at birth were estimated using linear and Bayesian kernel machine regression (BKMR) models. RESULTS: Most heavy metals examined in our study were observed in lower concentrations than in other studies, except for selenium. In the linear as well as the BKMR models, birth weight and length were negatively associated with levels of chromium. Birth weight was found to be negatively associated with thallium and positively associated with nickel. CONCLUSION: By using a large sample size and advanced statistical models, we could examine the association between prenatal exposure to metals in relatively low concentrations and anthropometric measures of newborns. Chromium was suggested to be the most influential metal in the mixture, and its associations with birth weight and length were found negative. Head circumference was neither associated with any of the metals, yet the levels of metals detected in our sample were relatively low. The suggested associations should be further investigated and could shed light on complex biochemical processes involved in intrauterine fetal development.

Development and validation of a computerized web-based quantitative food frequency questionnaire.

BACKGROUND & AIMS: Epidemiological research is progressing towards digital data collection. This study aimed to evaluate the validity and reproducibility of our new computerized, and easy-to-use Food Frequency Questionnaire (FFQ). METHODS: Participants' dietary intake was assessed using 24-h Dietary Recalls (DRs) and our FFQ, consisting of 133 food items and beverages. The software allows users to choose between three visualized portion sizes, categorizes the selections into food groups with three degrees of food processing levels, and produces a visualized output of the results. The reproducibility of the FFQ was evaluated based on two user submissions, and its validity was measured by comparing its calculated caloric intake and macro and micro-nutrient consumption to the equivalent mean values from three 24-h DRs. Thirty-nine women of fertility age [18-45] were recruited to the study, of whom twenty-six qualified for reproducibility testing and thirty-one qualified for validity testing. RESULTS: For most nutrient intakes, the FFQs yielded higher scores than the 24-h DRs, resulting in a less satisfactory agreement between them due to FFQs overestimation. The Intra Class Correlation (ICC) coefficient between the two FFQs ranged from moderate for calcium (0.55) to high for magnesium (0.83) (p < 0.05), indicating good reproducibility. Evaluation of food groups and processed food reproducibility scores yielded ICC coefficients ranging from moderate (0.53; super-processed foods) to high (0.83; non-processed foods) (p < 0.05). Spearman's correlation coefficient showed a moderate (sugar-sweetened beverages) to strong (non-processed foods) correlation (p < 0.05). CONCLUSIONS: The FFQ we developed and validated in this study showed moderate to high reproducibility and acceptable validity in a group of thirty-nine women of fertility age. Moreover, it is highly adjustable and easy to use, and its digital-based delivery enables large-scale, multilingual nutritional research.

Pregnancy after bariatric surgery: Effects of personalized nutrition counseling on pregnancy outcomes.

BACKGROUND & AIMS: Nutritional challenges following bariatric surgery can be intensified during pregnancy and may have crucial effects on the fetus, including lower birth weight. To the best of our knowledge, the effect of nutritional counseling during post-bariatric pregnancy to improve maternal diet quality and eating habits on neonatal outcome has not been evaluated. The aim of this research was to examine the effects of personal nutritional counseling during post-bariatric pregnancy on nutritional intake and neonatal outcomes. METHODS: We performed a non-randomized, intervention-control clinical trial. Women (n = 61) were divided into three groups; two prospective, and one retrospective: 1. An Intervention Bariatric Prospective group 2. A Control Prospective group without surgery, and 3. A Control Bariatric Retrospective group. Patient enrollment was performed from April 2016 to March 2018. The intervention program included biweekly visits with a pregnancy nutrition certified bariatric dietitian. Data collection was performed four times during pregnancy, and included demographic and eating habits questionnaires, 24 h dietary recall, and information about delivery outcomes. In the retrospective group delivery outcomes and Food Frequency Questionnaire was collected once, after delivery. RESULTS: There were no differences between groups at baseline except for a higher pre-pregnancy BMI in the post-bariatric groups. In the prospective groups, dietary protein, energy, and iron were found to be consumed in higher amounts in the Control-Prospective group than in the Intervention Bariatric-Prospective group (p < 0.05), without the addition of supplements. On the other hand, iron and calcium calculated from diet with supplements, were found to be significantly higher in the Intervention Bariatric Prospective group than in the Control Prospective group. In addition, consumption of saturated fats, oil, and salty snacks was lower in both prospective groups compared to the retrospective group (p < 0.05), suggesting better food quality habits for the bariatric group with nutritional counseling. Mean birth weight was significantly lower in the Control Bariatric Retrospective group than in the Control-Prospective group (3074 ± 368 g vs. 3396 ± 502 g, respectively. p = 0.023). In the Intervention Bariatric Prospective group, mean birth weight was 3168 ± 412 g, and no significant difference was observed from the Control Prospective group. Birth percentiles were also significantly lower in the Control Bariatric Retrospective group compared to the Control Prospective group (27th vs. 42nd, respectively. p < 0.05). In the Intervention Bariatric Prospective group, mean birth percentile was 35th, and no significant difference was observed from the Control Prospective group. As for the weight change of the woman during pregnancy, the highest variability was noted among the Control Bariatric Retrospective group with cases of weight loss up to 37 kg, due to conception close to the bariatric operation. Nevertheless, this variable was controlled, and showed no significant impact on birth weight results. CONCLUSIONS: Our results suggest that personalized nutritional counseling care during post bariatric pregnancy improved nutrient intake of mothers and may contribute to higher birth weight of offspring. Further research is needed to examine the effects of prenatal nutrition care intervention, in addition to repeating this trial with a larger sample size, to allow for clearer findings. CLINICAL TRIAL REGISTRATION: IRB number: 0310-15-RMB. IDENTIFICATION NIH NUMBER: NCT02697981 URL: https://www.nih.gov.

Optimizing cervical ripening in women presenting with decreased fetal movements.

OBJECTIVE: To determine the optimal method for cervical ripening in women presenting with decreased fetal movements at term. We hypothesized that women who undergo induction of labor for decreased fetal movements represent a higher risk group, and will benefit from mechanical intervention with cervical ripening balloon rather than with pharmacological prostaglandin E2 vaginal insert. STUDY DESIGN: Retrospective cohort study from January 2014 and January 2019. We recommended induction of labor to every woman ≥39 weeks' gestation with complaints of persistent decreased fetal movements. We excluded women with major fetal anomalies, Bishop score of ≥6 on admission, and cases with contraindications to prostaglandins. Women were allocated into one of two groups based on the cervical ripening agent used. In group 1 we introduced the prostaglandin E2 vaginal insert (10 mg dinoprostone in a timed-release formulation). In group 2 we placed the mechanical cervical ripening balloon. The primary outcome of the study, analyzed separately to nulliparous and multiparous women, was the rate of cesarean delivery in each of the groups. RESULTS: During the 5-years study, 294 women were included in the final analysis, of which 201 were in the prostaglandin E2 vaginal insert group and 93 were in the cervical ripening balloon group. The rate of cesarean delivery was comparable between the groups (nulliparous: 20.8%, 16/77 versus 21.3%, 10/47. multiparous: 16.9%, 21/124 versus 7%, 3/46, respectively). Other maternal and neonatal secondary outcomes, including the induction-to-delivery time (nulliparous: 32.5 ± 25.3 h versus 26.5 ± 12.2 h. multiparous: 24.6 ± 17.2 h versus 21.25 ± 12.3 h, respectively), were also not different between the two induction methods used. A longer induction-to-delivery time was observed in nulliparous women who had repeat prostaglandin E2 vaginal insert compared with the cervical ripening balloon group (74.6 ± 27.3 h versus 26.5 ± 12.2 h, p < .01). CONCLUSION: Both pharmacological and mechanical methods can safely and efficiently be used for cervical ripening in women presenting with decreased fetal movements at term. With repeat prostaglandin E2 use, nulliparous women may experience a prolong labor compared with the cervical ripening balloon group, but maternal or fetal safety are not compromised.

Silent voices that must be heard - women's perceptions of gynecologic examinations.

PURPOSE: To analyze the perception of gynecologic examination from the patients' point of view. MATERIALS AND METHODS: This anonymous electronic cross-sectional survey aimed to evaluate the subjective experiences of women during gynecologic examinations (levels of pain, embarrassment and trauma), the manner the examination was conducted, and women's suggestions for improving their experience. RESULTS: Overall, 6,508 women answered the survey. The examination was considered an embarrassing event by 47%, painful by 35% and traumatic by 19%. Importantly, only 43% of the respondents stated they would notify the gynecologist in case of physical discomfort or pain during the examination. The quality of physician-to-patient communication was rated as the most important aspect of gynecologic examination, and showed a significant association with the general quality of the experience (levels of pain, embarrassment, and trauma). Matters relating to women's privacy during gynecologic examination were also considered important. An option for a companion was rated as important by 64% of the respondents. Significant differences with large effect-sizes were found between the respondents' preferences and their reports of the observed situation. CONCLUSION: The findings highlight the need for establishing guidelines for gynecologic examinations, according to a patient-centered care approach. This study constitutes a first discourse on the subject of gynecologic examinations in Israel in order to provide an overview and initial insights, serving as a starting point for further specific and more in-depth research.

Foley catheter versus cervical double balloon for labor induction: a prospective randomized study.

OBJECTIVE: Cervical ripening by mechanical methods enhances labor induction success. We compared Cervical Ripening Double Balloon catheter (CRDB) to Foley catheter. STUDY DESIGN: This prospective blind study randomized 85 nulliparas and 95 multiparas to labor induction by either Foley catheter or CRDB. Primary outcomes were Bishop score increment, time from catheter withdrawal to delivery, and cesarean section rate. RESULTS: In multiparas, mean Bishop score increment between pre- and post-catheter was significantly higher in the CRDB catheter than in the Foley group (4.4 ± 1.9 and 3.4 ± 2.0, respectively, p = .02). Mean interval from catheter withdrawal to delivery was shorter in the CRDB catheter (14.6 ± 12.3 and 8.6 ± 5.4) than in the Foley catheter group (22.6 ± 27.2 and 13.9 ± 17.7), in both nulliparas and multiparas (p = .05 and p = .03, respectively). In nulliparas, no statistically significant differences were found in mean Bishop score increment between the two catheters, but cesarean section rate was higher in the Foley group than the CRDB group (46.5% and 20%, respectively, p = .02). CONCLUSION: Bishop score increment by CRDB catheter is more effective than induction by Foley catheter in multiparas. CRDB catheter is associated with decreased time to delivery in both nulliparas and multiparas and a lower cesarean section rate in nulliparas. ClinicalTrials.gov Identifier: NCT00501033.

First trimester supratentorial and infratentorial abnormalities in fetuses with open spina bifida.

OBJECTIVES: To examine whether supratentorial, infratentorial, and calvarial manifestations of open spina bifida (OSB) occur in the first-trimester. METHODS: Supratentorial (midbrain curvature, thalamic height), infratentorial (fourth ventricle diameter, brain-stem diameter [BSD], ratio of BSD to BSD-occipital bone diameter [BSOB]), and calvarial (frontomaxillary facial [FMF] angle) parameters were measured in stored midsagittal facial images at 110-136 weeks of 500 normal and 10 open spina-bifida fetuses by 3 blinded examiners. RESULTS: OSB fetuses displayed a larger midbrain curvature (93.26 ± 6.97 versus 97.79 ± 10.04, p < .05), decreased FMF angle (84.10 ± 5.44 versus 78.46 ± 5.82, p < .001), smaller fourth ventricle diameter (0.25 ± 0.04 mm versus 0.18 ± 0.05 mm, p < .001), smaller BSD (0.29 ± 0.04 mm versus 0.23 ± 0.04 mm; p < .001), and increased BSD to BSOB ratio (0.64 ± 0.71 versus 0.73 ± 0.93, p < .03) than normal controls, respectively. Thalamic height was not significantly altered. Detection rates of OSB were highest for fourth ventricle diameter and FMF angle (60% and 40%, respectively, at 95% specificity). BSD, BSD to BSOB ratio, midbrain curvature yielded sensitivities of 30% with 95% specificity. Two-dimensional discrimination for pairs of measures combining fourth ventricle diameter with FMF angle increased sensitivity to 90% with specificity of 90.7%. CONCLUSIONS: Our findings suggest that supratentorial, infratentorial, and calvarial changes consistent with the Chiari-II malformation are already established in first-trimester fetuses with OSB.

Antenatal betamethasone and the risk of neonatal hypoglycemia: it's all about timing.

INTRODUCTION: Our objective was to evaluate whether there is a relationship between the "time during the day" of maternal betamethasone administration between 24 and 34 weeks' gestation and the risk for neonatal hypoglycemia. MATERIAL AND METHODS: A retrospective study included cases between 2008 and 2018. Eligible cases were pregnant women with singleton pregnancies who received a single course of betamethasone between 24 and 34 weeks' gestation. Each woman was allocated into one of four pre-defined groups based on the time when intramuscular betamethasone was administered. Group 1 (23:00-04:59) represents the lowest daily natural corticosteroids' activity, group 2 (05:00-10:59) represents the peak daily natural corticosteroids' activity, whereas group 3 (11:00-16:59) and group 4 (17:00-22:59) present an intermediate natural state of steady corticosteroids' secretion and activity. The primary outcome of the study was the incidence of neonatal hypoglycemia (glucose level of less than 40 mg/dL). RESULTS: We have identified 868 women who received a single complete course of betamethasone, of which 353 women (40.7%) had a steroid treatment latency to delivery up to 14 days. The incidence of neonatal hypoglycemia was significantly higher in group 2 (39.5%, 30/76, p = 0.0063), compared to group 1, who had the lowest incidence of neonatal hypoglycemia (16.9%, 12/71), and to group 3 and group 4. CONCLUSIONS: The "time during the day" when betamethasone administered is important when considering the risk for neonatal hypoglycemia. The risk was significantly higher when betamethasone was administered during the peak time and significantly lower when administered at the nadir time of maternal endogenous corticosteroid activity.