Antenatal corticosteroids and newborn respiratory outcomes in twins: A regression discontinuity study.

OBJECTIVE: To estimate the effect of antenatal corticosteroids on newborn respiratory morbidity in twins. DESIGN: Regression discontinuity applied to population-based birth registry data. SETTING: British Columbia, Canada, 2008-2018. POPULATION: Twin pregnancies admitted for birth between 31+0 and 36+6 weeks of gestation. METHODS: During our study period, Canadian clinical practice guidelines recommended antenatal corticosteroid administration for imminent preterm birth up to 33+6 weeks. We used a logistic model to compare the predicted risks of our outcomes among pregnancies admitted for birth immediately before this clinical cut-point (higher probability of exposure to antenatal corticosteroids) versus immediately after it (lower probability). MAIN OUTCOME MEASURES: Our primary outcome was a composite of newborn respiratory distress or in-hospital death. Our secondary outcome was a composite of newborn respiratory intervention or in-hospital death. RESULTS: Among 2524 pregnancies (5035 liveborn twins), 47% of admissions before 34+0 weeks of gestation were exposed to antenatal corticosteroids but only 4.2% of admissions after this cut-point were exposed. The risk of newborn respiratory distress or in-hospital mortality increased abruptly at 34+0 weeks, corresponding to a protective effect of treatment (risk ratio [RR] 0.69, 95% CI 0.53-0.90; risk difference [RD] -12 cases per 100 births, 95% CI -20 to -4.1). There was no clear evidence for or against an effect on newborn respiratory intervention or in-hospital death (RR 0.89, 95% CI 0.70-1.13; RD -4.2 per 100, 95% CI -13 to +4.2). CONCLUSIONS: Our findings provide evidence for the effectiveness of antenatal corticosteroids in preventing adverse newborn respiratory outcomes in twins.

Evaluation of Real and Perceived Risk to Health Care Workers Caring for Patients With the Omicron Variant of the SARS-CoV-2 Virus in Surgery and Obstetrics.

OBJECTIVES: The Omicron variant of the SARS-CoV-2 virus is described as more contagious than previous variants. We sought to assess risk to health care workers (HCWs) caring for patients with COVID-19 in surgical/obstetrical settings, and the perception of risk among this group. METHODS: From January to April 2022, reverse transcription polymerase chain reaction was used to detect the presence of SARS-CoV-2 viral ribonucleic acid in patient, environmental (floor, equipment, passive air) samples, and HCWs' masks (inside surface) during urgent surgery or obstetrical delivery for patients with SARS-CoV-2 infection. The primary outcome was the proportion of HCWs' masks testing positive. Results were compared with our previous cross-sectional study involving obstetrical/surgical patients with earlier variants (2020-2021). HCWs completed a risk perception electronic questionnaire. RESULTS: Eleven patients were included: 3 vaginal births and 8 surgeries. In total, 5/108 samples (5%) tested positive (SARS-CoV-2 Omicron) viral ribonucleic acid: 2/5 endotracheal tubes, 1/22 floor samples, 1/4 patient masks, and 1 nasal probe. No samples from the HCWs' masks (0/35), surgical equipment (0/10), and air (0/11) tested positive. No significant differences were found between the Omicron and 2020/21 patient groups' positivity rates (Mann-Whitney U test, P = 0.838) or the level of viral load from the nasopharyngeal swabs (P = 0.405). Nurses had a higher risk perception than physicians (P = 0.038). CONCLUSION: No significant difference in contamination rates was found between SARS-CoV-2 Omicron BA.1 and previous variants in surgical/obstetrical settings. This is reassuring as no HCW mask was positive and no HCW tested positive for COVID-19 post-exposure.

Long-Term Outcomes of Multiple versus a Single Course of Antenatal Steroids: A Systematic Review.

Multiple courses versus a single course of antenatal corticosteroids (ACS) have been associated with mild respiratory benefits but also adverse outcomes like smaller head circumference and birth weight. Long-term effects warrant study. We systematically reviewed long-term outcomes (≥1 year) in both preterm and term birth after exposure to preterm multiple courses (including a rescue dose or course) versus a single course. We searched seven databases from January 2000 to October 2021. We included follow-up studies of randomized controlled trials (RCTs) and cohort studies with births occurring in/after the year 2000, given advances in perinatal care. Two reviewers assessed titles/abstracts, articles, quality, and outcomes including psychological disorders, neurodevelopment, and anthropometry. Six follow-up studies of three RCTs and two cohort studies (over 2,860 children total) met inclusion criteria. Among children born preterm, randomization to multiple courses versus a single course of ACS was not associated with adjusted beneficial or adverse neurodevelopmental/psychological or other outcomes, but data are scant after a rescue dose (120 and 139 children, respectively, low certainty) and nonexistent after a rescue course. For children born at term (i.e., 27% of the multiple courses of ACS 5-year follow-up study of 1,728 preterm/term born children), preterm randomization to multiple courses (at least one additional course) versus a single course was significantly associated with elevated odds of neurosensory impairment (adjusted odds ratio = 3.70, 95% confidence interval: 1.57-8.75; 212 and 247 children, respectively, moderate certainty). In this systematic review of long-term outcomes after multiple courses versus a single course of ACS, there were no significant benefits or risks regarding neurodevelopment in children born preterm but little data after one rescue dose and none after a rescue course. However, multiple courses (i.e., at least one additional course) should be considered cautiously: after term birth, there are no long-term benefits but neurosensory harms. KEY POINTS: · We systematically reviewed the long-term impact of multiple versus a single course of ACS.. · Long-term follow-up data were scant after a rescue dose and absent after one rescue course of ACS.. · In children born preterm, multiple courses of ACS were not associated with long-term benefits/harms.. · In children born at term, multiple courses of ACS were associated with neurosensory impairment.. · Preterm administration of multiple courses of ACS should be considered cautiously..

National and international guidelines on the management of twin pregnancies: a comparative review.

Twin gestations are associated with increased risk of pregnancy complications. However, high-quality evidence regarding the management of twin pregnancies is limited, often resulting in inconsistencies in the recommendations of various national and international professional societies. In addition, some recommendations related to the management of twin gestations are often missing from the clinical guidelines dedicated to twin pregnancies and are instead included in the practice guidelines on specific pregnancy complications (eg, preterm birth) of the same professional society. This can make it challenging for care providers to easily identify and compare recommendations for the management of twin pregnancies. This study aimed to identify, summarize, and compare the recommendations of selected professional societies from high-income countries on the management of twin pregnancies, highlighting areas of both consensus and controversy. We reviewed clinical practice guidelines of selected major professional societies that were either specific to twin pregnancies or were focused on pregnancy complications or aspects of antenatal care that may be relevant for twin pregnancies. We decided a priori to include clinical guidelines from 7 high-income countries (United States, Canada, United Kingdom, France, Germany, and Australia and New Zealand grouped together) and from 2 international societies (International Society of Ultrasound in Obstetrics and Gynecology and the International Federation of Gynecology and Obstetrics). We identified recommendations regarding the following care areas: first-trimester care, antenatal surveillance, preterm birth and other pregnancy complications (preeclampsia, fetal growth restriction, and gestational diabetes mellitus), and timing and mode of delivery. We identified 28 guidelines published by 11 professional societies from the 7 countries and 2 international societies. Thirteen of these guidelines focus on twin pregnancies, whereas the other 16 focus on specific pregnancy complications predominantly in singletons but also include some recommendations for twin pregnancies. Most of the guidelines are recent, with 15 of the 29 guidelines published over the past 3 years. We identified considerable disagreement among guidelines, primarily in 4 key areas: screening and prevention of preterm birth, using aspirin to prevent preeclampsia, defining fetal growth restriction, and the timing of delivery. In addition, there is limited guidance on several important areas, including the implications of the "vanishing twin" phenomenon, technical aspects and risks of invasive procedures, nutrition and weight gain, physical and sexual activity, the optimal growth chart to be used in twin pregnancies, the diagnosis and management of gestational diabetes mellitus, and intrapartum care.This consolidation of key recommendations across several clinical practice guidelines can assist healthcare providers in accessing and comparing recommendations on the management of twin pregnancies and identifies high-priority areas for future research based on either continued disagreement among societies or limited current evidence to guide care.

Maternal major depression during early pregnancy is associated with impaired child executive functioning at 4.5 years of age.

BACKGROUND: Maternal depression is a serious condition that affects up to 1 in 7 pregnancies. Despite evidence linking maternal depression to pregnancy complications and adverse fetal outcomes, there remain large gaps in its identification and treatment. More work is needed to define the specific timing and severity of depression that most urgently requires intervention, where feasible, to protect maternal health and the developing fetus. OBJECTIVE: This study aimed to examine whether the timing and severity of maternal depression and/or anxiety during pregnancy affect child executive functioning at age 4.5 years. Executive functioning in the preschool years is a strong predictor of both school readiness and long-term quality of life. STUDY DESIGN: This longitudinal observational pregnancy cohort study included a sample of 323 mother-child dyads taking part in the Ontario Birth Study, an open pregnancy cohort in Toronto, Ontario, Canada. Maternal symptoms of depression and anxiety were assessed at 12 to 16 and 28 to 32 weeks of gestation and at the time of child testing at age 4.5 years using the 4-item Patient Health Questionnaire. Child executive functioning was measured during a home visit using standardized computerized administration of the Flanker test (a measure of attention) and the Dimensional Change Card Sort (a measure of cognitive flexibility). Stepwise linear regressions, controlling for possible confounding variables, were used to assess the predictive value of continuous measures of maternal depression and/or anxiety symptoms at each assessment time on the Flanker test and Dimensional Change Card Sort. Posthoc general linear models were used to assess whether maternal depression severity categories (no symptom, mild symptoms, or probable major depressive disorder) were helpful in identifying children at risk. RESULTS: Across all children, after controlling for potential confounds, greater maternal depressive symptoms at weeks 12 to 16 weeks of gestation predicted worse performance on both the Flanker test (ΔR2=0.058; P<.001) and the Dimensional Change Card Sort (ΔR2=0.017; P=.018). Posthoc general linear modeling further demonstrated that the children of mothers meeting the screening criteria for major depression in early pregnancy scored 11.3% lower on the Flanker test and 9.8% lower on the Dimensional Change Card Sort than the children of mothers without maternal depressive symptoms in early pregnancy. Mild depressive symptoms had no significant effect on executive function scores. There was no significant effect of anxiety symptoms or maternal antidepressant use in early pregnancy or pandemic conditions or maternal symptoms in later pregnancy or at the time of child testing on either the Flanker or Dimensional Change Card Sort results. CONCLUSION: This study demonstrated that fetal exposure to maternal major depression, but not milder forms of depression, at 12 to 16 weeks of gestation is associated with impaired executive functioning in the preschool years. Child executive functioning is crucial for school readiness and predicts long-term quality of life. This emphasizes an urgent need to improve the recognition and treatment of maternal major depression, particularly in early pregnancy, to limit its negative effects on the patient and on child cognitive development.

Outcomes and management of pregnancy and puerperal group A streptococcal infections: A systematic review.

INTRODUCTION: Group A streptococcus (Streptococcus pyogenes) is one of the most lethal bacterial pathogens of humans, with increased risk of progression to septic shock and multiorgan failure in the pregnant population. The objective of this study is to systematically review the outcomes and management strategies for pregnancy and puerperal group A streptococcus infections in an effort to provide further guidance for prevention and treatment of a rare but lethal infection worldwide. MATERIAL AND METHODS: A comprehensive search using puerperium and streptococcus pyogenes terms was completed across several registered databases. A total of 902 articles investigating pregnancy and puerperal group A streptococcus infection were identified, with 40 studies fulfilling inclusion criteria of original research articles in humans published from 1990 onwards reporting four or more unique cases of group A streptococcus in pregnancy or postpartum. This study was registered in PROSPERO: CRD42020198983. RESULTS: A total of 1160 patients with pregnancy and puerperal group A streptococcus infection were identified. Most infections occurred postpartum (91.9%), with 4.7% reported antepartum and 0.6% intrapartum. Bacteremia was present in 49.0% of patients and endometritis in 45.9%. Puerperal sepsis was described in 28.2% of cases and progressed to streptococcal toxic shock syndrome in one-third of such cases. Overall, the case fatality ratio was 2.0%, with one-third of the deaths from antenatal cases including 3/22 (13.6%) cases of septic abortion and 10/46 (21.7%) antenatal cases of group A streptococcus infection. CONCLUSIONS: Group A streptococcus infection remains an important contributor to pregnancy and puerperal morbidity and mortality. Early recognition, diagnosis and aggressive management are important for favorable outcomes given the serious risk of sepsis and streptococcal toxic shock syndrome.

Twin pregnancy and severe maternal mental illness: a Canadian population-based cohort study.

Twin pregnancy is a risk factor for postpartum depression and anxiety. Whether this translates into a higher risk of severe maternal mental illness in the short-term or long-term is unknown. This study was a population-based retrospective cohort study, using linked health administrative databases for the entire province of Ontario, Canada. Included were primiparas aged 15-50 years with a twin vs. singleton hospital livebirth, between January 1, 2003, and March 31, 2019. Propensity-score inverse probability of treatment weights accounted for potential confounding. The primary outcome of severe mental illness comprised a composite of an emergency department visit or hospitalization for mental illness or self-injury, or death by suicide, assessed in the first year after birth, and in long-term follow-up, up to 17 years thereafter. Fifteen thousand twenty-four twin and 796,804 (15,022 weighted) singleton births were included, with a mean (IQR) duration of follow-up of 9 (5-13) years. After weighting, the mean (SD) maternal age was 31.3 (5.5) years. In the first 365 days postpartum, severe mental illness occurred at rates of 10.5 and 8.7 per 1000 person-years in twin and singleton mothers, respectively, corresponding to a hazard ratio (HR) of 1.21 (95% CI 1.07-1.47). From 366 days onward, the corresponding figures were 5.9 and 6.1 per 1000 person-years (HR 0.96, 95% CI 0.89-1.04). Individuals with a twin birth appear to experience an increased risk for severe mental illness in the first year postpartum, but not thereafter. This suggests a potential need for targeted counselling and mental health services for mothers within the first year after birth.

The Impact of Infant Sex on Multiple Courses versus a Single Course of Antenatal Corticosteroids: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: Animal literature has suggested that the impact of antenatal corticosteroids (ACS) may vary by infant sex. Our objective was to assess the impact of infant sex on the use of multiple courses versus a single course of ACS and perinatal outcomes. STUDY DESIGN: We conducted a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth trial, which randomly allocated pregnant people to multiple courses versus a single course of ACS. Our primary outcome was a composite of perinatal mortality or clinically significant neonatal morbidity (including neonatal death, stillbirth, severe respiratory distress syndrome, intraventricular hemorrhage [grade III or IV], cystic periventricular leukomalacia, and necrotizing enterocolitis [stage II or III]). Secondary outcomes included individual components of the primary outcome as well as anthropometric measures. Baseline characteristics were compared between participants who received multiple courses versus a single course of ACS. An interaction between exposure to ACS and infant sex was assessed for significance and multivariable regression analyses were conducted with adjustment for predefined covariates, when feasible. RESULTS: Data on 2,300 infants were analyzed. The interaction term between treatment status (multiple courses vs. a single course of ACS) and infant sex was not significant for the primary outcome (p = 0.86), nor for any of the secondary outcomes (p > 0.05). CONCLUSION: Infant sex did not modify the association between exposure to ACS and perinatal outcomes including perinatal mortality or neonatal morbidity or anthropometric outcomes. However, animal literature indicates that sex-specific differences after exposure to ACS may emerge over time and thus investigating long-term sex-specific outcomes warrants further attention. KEY POINTS: · We explored the impact of infant sex on perinatal outcomes after multiple versus a single course of ACS.. · Infant sex was not a significant effect modifier of ACS exposure and perinatal outcomes.. · Animal literature indicates that sex-specific differences after ACS exposure may emerge over time.. · Further investigation of long-term sex-specific outcomes is warranted..

Maternal prenatal psychological distress and vitamin intake with children's neurocognitive development.

BACKGROUND: Maternal prenatal psychological distress (PPD) is increasingly linked to sub-optimal child neurodevelopment. Daily intake of prenatal vitamin during pre-conception and early pregnancy may ameliorate the effects of PPD on cognition in the offspring. METHODS: PPD was assessed in early (12-16 weeks) and late (28-32 weeks) gestation in the Ontario Birth Study. Prenatal vitamin supplement intake information was collected in early gestation. Child cognition at 4 years was assessed using the NIH Toolbox. Poisson regression was used to investigate associations between PPD and/or prenatal vitamin intake and child cognition. RESULTS: Four hundred and eighteen mother-child dyads were assessed. Moderate-severe PPD experienced during early gestation was associated with reduced cognition (adjusted incidence rate ratio (IRRadj) = 3.71, 95% confidence interval (CI): 1.57-8.77, P = 0.003). Daily intake of prenatal vitamins was not associated with cognition (IRRadj = 1.34, 95% CI: 0.73-2.46, P = 0.34). Upon stratification, the experience of mild-severe PPD with daily intake of prenatal vitamins was associated with higher incident rates of suboptimal cognition compared to children of women with daily prenatal vitamin intake without any episode of PPD (IRRadj = 2.88, 95% CI: 1.1-7.4). CONCLUSIONS: Moderate-severe PPD in early pregnancy is associated with poor cognition in children and daily intake of prenatal vitamin did not ameliorate this association. IMPACT: Our findings expand on existing literature by highlighting that exposure to prenatal psychological distress (PPD), in moderate-to-severe form, in the early stages of pregnancy, can have detrimental effects on the offspring's cognitive development at 4 years. Overall, prenatal vitamin intake did not ameliorate the effects of PPD. Early screening and treatment of prenatal maternal mental illness is crucial.

Perinatal outcomes in women living with HIV-1 and receiving antiretroviral therapy-a systematic review and meta-analysis.

INTRODUCTION: Antiretroviral therapy-naïve pregnant women living with HIV are at an increased risk for adverse pregnancy outcomes. It remains controversial whether this risk persists with antiretroviral therapy. We conducted a systematic review and meta-analysis to evaluate whether pregnant women living with HIV and receiving antiretroviral therapy antenatally, are at an increased risk of adverse outcomes compared with HIV-negative controls. MATERIAL AND METHODS: We searched MEDLINE, Embase, International Pharmaceutical Abstracts, EBM Reviews, PubMed (non-MEDLINE records), EBSCO CINAHL Complete, Clarivate Web of Science, African Index Medicus, LILACS and Google Scholar for all observational studies comparing pregnant women living with HIV on antiretroviral therapy with HIV-negative controls from 1 January 1994 to 10 August 2021 with no language or geographic restrictions. Perinatal outcomes included preterm birth (PTB), low birthweight, small-for-gestational age and preeclampsia. Using a random-effects model we pooled raw data to generate odds ratio (OR) with 95% confidence intervals (CI) for each outcome. Sub-analyses for high and low resource countries and time of antiretroviral therapy initiation were performed. This systematic review and meta-analysis is registered with PROSPERO, number CRD42020182722. RESULTS: Of the 7900 citations identified, 27 were eligible for analysis (12 636 pregnant women living with HIV on antiretroviral therapy and 7 812 115 HIV-negative controls). ORs (95% CI) of PTB (1.88 [1.63-2.17]), small-for-gestational age (1.60 [1.18-2.17]) and low birthweight (2.15 [1.58-2.92]) were significantly higher in pregnant women living with HIV than in HIV-negative women, while the risk of preeclampsia (0.86 [0.57-1.30]) was comparable. The risk of PTB and low birthweight was higher in both high resource and low resource countries, while the risk of small-for-gestational age was higher only in the former. Preconceptional antiretroviral therapy was associated with a higher risk of PTB compared with antenatal initiation. CONCLUSIONS: Pregnant women living with HIV on antiretroviral therapy have an increased risk of PTB, low birthweight and small-for-gestational age in high resource countries, as well as PTB and low birthweight in low income countries compared with HIV-negative controls.

Coronavirus disease 2019 pandemic and pregnancy and neonatal outcomes in general population: A living systematic review and meta-analysis (updated Aug 14, 2021).

INTRODUCTION: Conflicting reports of increases and decreases in rates of preterm birth (PTB) and stillbirth in the general population during the coronavirus disease 2019 (COVID-19) pandemic have surfaced. The objective of our study was to conduct a living systematic review and meta-analyses of studies reporting pregnancy and neonatal outcomes by comparing the pandemic and pre-pandemic periods. MATERIAL AND METHODS: We searched PubMed and Embase databases, reference lists of articles published up until August 14, 2021 and included English language studies that compared outcomes between the COVID-19 pandemic time period and the pre-pandemic time periods. Risk of bias was assessed using the Newcastle-Ottawa scale. We conducted random-effects meta-analysis using the inverse variance method. RESULTS: Forty-five studies with low-to-moderate risk of bias, reporting on 1 843 665 pregnancies during the pandemic period and 23 564 552 pregnancies during the pre-pandemic period, were included. There was significant reduction in unadjusted estimates of PTB (35 studies, unadjusted odds ratio [uaOR] 0.95, 95% CI 0.92-0.98), but not in adjusted estimates (six studies, adjusted OR [aOR] 0.95, 95% CI 0.80-1.13). This reduction was noted in studies from single centers/health areas (25 studies, uaOR 0.90, 95% CI 0.86-0.96) but not in regional/national studies (10 studies, uaOR 0.99, 95% CI 0.95-1.02). There was reduction in spontaneous PTB (six studies, uaOR 0.89, 95% CI 0.81-0.96) and induced PTB (five studies, uaOR 0.89, 95% CI 0.81-0.97). There was no difference in the odds of stillbirth between the pandemic and pre-pandemic time periods (24 studies, uaOR 1.11, 95% CI 0.97-1.26 and four studies, aOR 1.06, 95% CI 0.81-1.38). There was an increase in mean birthweight during the pandemic period compared with the pre-pandemic period (six studies, mean difference 17 g, 95% CI 7-28 g). The odds of maternal mortality were increased (four studies, uaOR 1.15, 95% CI 1.05-1.26); however, only unadjusted estimates were available and the result was mostly influenced by one study from Mexico. There was significant publication bias for the outcome of PTB. CONCLUSIONS: The COVID-19 pandemic may be associated with a reduction in PTB; however, referral bias cannot be excluded. There was no statistically significant difference in stillbirth between pandemic and pre-pandemic periods.

A Growing Dilemma: Antenatal Corticosteroids and Long-Term Consequences.

OBJECTIVE: A single course of synthetic antenatal corticosteroids is standard care for women considered to be at risk for preterm birth before 34 weeks of gestation. While the intended target is the fetal lung, the fetal brain contains remarkably high levels of glucocorticoid receptors in structures critical in the regulation of behavior and endocrine function. Negative programming signals may occur which can lead to permanent maladaptive changes and predispose the infant/child to an increased risk in physical, mental, and developmental disorders. METHODS: Framed around these areas of concerns for physical, mental, and developmental disorders, this narrative review drew on studies (animal and clinical), evaluating the long-term effects of antenatal corticosteroids to present the case that a more targeted approach to the use of antenatal corticosteroids for the betterment of the fetus urgently needed. RESULTS: Studies raised concerns about the potential negative long-term consequences, especially for the exposed fetus who was born beyond the period of the greatest benefit from antenatal corticosteroids. The long-term consequences are more subtle in nature and usually manifest later in life, often beyond the scope of most clinical trials. CONCLUSION: Continued research is needed to identify sufficient safety data, both short term and long term. Caution in the use of antenatal corticosteroids should be exercised while additional work is undertaken to optimize dosing strategies and better identify women at risk of preterm birth prior to administration of antenatal corticosteroids. KEY POINTS: · A single-course ACS is a remarkable therapy with substantial benefits.. · There is a potential of long-term neurodevelopmental consequences in the ACS-exposed fetus.. · There is a need to improve dosing strategies and identification of appropriate at risk women..

Timing of antenatal corticosteroids in relation to clinical indication.

PURPOSE: This study aimed at determining the proportion of women who receive antenatal corticosteroids (ACS) within the optimal time window before birth based on the indication for ACS, and to explore in more detail indications that are associated with suboptimal timing. METHODS: A retrospective cohort study of all women who received ACS in a single tertiary center between 2014 and 2017. The primary outcome was an ACS-to-birth interval ≤ 7 days. Secondary outcomes were ACS-to-birth interval of ≤ 14 days, and the proportion women who received ACS but ultimately gave birth at term (≥ 370/7 weeks). The study outcomes were stratified by the clinical indication for ACS. RESULTS: A total of 1261 women met the study criteria, of whom 401 (31.8%) and 569 (45.1%) received ACS within ≤ 7 days and ≤ 14 days before birth, respectively, and 203 (16.1%) ultimately gave birth at term. The proportion of women who received ACS within 7 days before birth was highest for women with preeclampsia (50.4%), and was lowest for women with an incidental finding of a short cervix (8.4%). In the subgroup of women with an incidental finding of a short cervix, the likelihood of optimal timing was not related to the magnitude of cervical shortening, history of preterm birth, multifetal gestation, presence of cervical funneling, or the presence of cervical cerclage. CONCLUSION: Over two-thirds of infants who are exposed to ACS do not get the maximal benefit from this intervention. The current study identified clinical indications for ACS that are associated with suboptimal timing of ACS where more research is needed to develop quantitative, indication-specific prediction models to guide the timing of ACS.

Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth.

BACKGROUND: It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group). RESULTS: Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, -0.93±1.05; prenatal 4200, -1.11±1.12; prenatal 16,800, -0.97±0.97; prenatal 28,000, -1.06±1.07; and prenatal and postpartum 28,000, -0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose. CONCLUSIONS: In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013 .).

Maternal weight gain and pregnancy outcomes in twin gestations.

BACKGROUND: Data on the optimal gestational weight gain in twin pregnancies are limited. As a result, the Institute of Medicine currently provides only provisional recommendations on gestational weight gain in this population. OBJECTIVE: This study aimed to identify the optimal range of gestational weight gain in twin pregnancies and to estimate the association between inappropriate gestational weight gain and adverse pregnancy outcomes. STUDY DESIGN: This was a retrospective cohort study of all women with twin pregnancies that were followed up in a single, tertiary center between 2000 and 2014. We used 2 approaches to identify the optimal range of gestational weight gain: a statistical approach (the interquartile range of gestational weight gain in low-risk pregnancies with normal outcomes) and an outcome-based approach (by identifying thresholds of gestational weight gain below or above which the rate of adverse outcomes increases). The primary outcome was preterm birth. Associations of gestational weight gain below or above the normal range with the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence intervals. These associations were stratified by prepregnancy body mass index group. RESULTS: A total of 1274 women with twin pregnancies met the study criteria: 43 were classified as underweight, 777 were normal weight, 278 were overweight, and 176 were obese. Our estimates of the optimal gestational weight gain range were similar to those recommended by the Institute of Medicine except for the obese category, in which our optimal gestational weight gain range at 37 weeks (9.3-16.3 kg) was lower than in the provisional Institute of Medicine recommendations (11.3-19.1 kg). Nearly half of our cohort experienced inappropriate gestational weight gain: 30% (n=381) gained weight below and 17% (n=216) gained weight above current Institute of Medicine recommendations. In the normal weight group, gestational weight gain below recommendations was associated with an increased risk of preterm birth and birthweight at the <10th centile and with a reduction in the risk of hypertensive disorders, whereas gestational weight gain above recommendations was associated with an increased risk of hypertensive disorders and a reduction in the risk of birthweight at the <10th centile. Associations were less consistent in the overweight and obese groups. CONCLUSION: These findings identify gestational weight gain as a potentially modifiable risk factor for preterm birth and other pregnancy complications in twin gestations. Further prospective studies are needed to determine whether interventions aimed at optimizing gestational weight gain can improve the outcomes of these high-risk pregnancies.

COVID-19 pandemic and population-level pregnancy and neonatal outcomes: a living systematic review and meta-analysis.

INTRODUCTION: Conflicting reports of increases and decreases in rates of preterm birth (PTB) and stillbirth in the general population during the COVID-19 pandemic have surfaced. The objective of our study was to conduct a living systematic review and meta-analyses of studies reporting pregnancy and neonatal outcomes by comparing the pandemic and pre-pandemic periods. MATERIAL AND METHODS: We searched PubMed and Embase databases, reference lists of articles published up until 14 May 2021 and included English language studies that compared outcomes between the COVID-19 pandemic time period and pre-pandemic time periods. Risk of bias was assessed using the Newcastle-Ottawa scale. We conducted random-effects meta-analysis using the inverse variance method. RESULTS: Thirty-seven studies with low-to-moderate risk of bias, reporting on 1 677 858 pregnancies during the pandemic period and 21 028 650 pregnancies during the pre-pandemic period, were included. There was a significant reduction in unadjusted estimates of PTB (28 studies, unadjusted odds ratio [uaOR] 0.94, 95% confidence [CI] 0.91-0.98) but not in adjusted estimates (six studies, adjusted OR [aOR] 0.95, 95% CI 0.80-1.13). The reduction was noted in studies from single centers/health areas (uaOR 0.90, 95% CI 0.86-0.94) but not in regional/national studies (uaOR 0.99, 95% CI 0.95-1.03). There was reduction in spontaneous PTB (five studies, uaOR 0.89, 95% CI 0.82-0.98) and induced PTB (four studies, uaOR 0.90, 95% CI 0.81-1.00). There was no reduction in PTB when stratified by gestational age <34, <32 or <28 weeks. There was no difference in stillbirths between the pandemic and pre-pandemic time periods (21 studies, uaOR 1.08, 95% CI 0.94-1.23; four studies, aOR 1.06, 95% CI 0.81-1.38). There was an increase in birthweight (six studies, mean difference 17 g, 95% CI 7-28 g) during the pandemic period. There was an increase in maternal mortality (four studies, uaOR 1.15, 95% CI 1.05-1.26), which was mostly influenced by one study from Mexico. There was significant publication bias for the outcome of PTB. CONCLUSIONS: The COVID-19 pandemic time period may be associated with a reduction in PTB; however, referral bias cannot be excluded. There was no difference in stillbirth between the pandemic and pre-pandemic period.

Selecting contextually appropriate performance indicators in a circumpolar context: a modified Delphi approach.

BACKGROUND: Meaningful performance measurement requires indicators to be scientifically robust and strategically focused. For many circumpolar states, indicators aligned with national strategies may ignore the priorities of northern, remote, or Indigenous populations. The aim of this project was to identify contextually appropriate performance indicators for maternity care in circumpolar regions. METHODS: Fourteen maternity care and health systems experts participated in a modified Delphi consensus process. The list of proposed indicators was derived from a previously published scoping review. Fourteen participants rated each proposed indicator according to importance, circumpolar relevance, validity, and reliability and suggested additional indicators for consideration. RESULTS: Consensus was achieved after two rounds, as measured by a Cronbach's alpha of 0.87. Eleven indicators, many of which represented physical health outcomes, were ranked highly on all four criteria. Twenty-nine additional indicators, largely focused on social determinants of health, health care responsiveness, and accessibility, were identified for further research. Travel for care, cultural safety and upstream structural determinants of health were identified as important themes. CONCLUSIONS: This study identified the important gaps between current performance measurement strategies and the context and values that permeate maternal-child health in circumpolar regions. The indicators identified in this study provide an important foundation for ongoing work. We recommend that future work encompass an appreciation for the intersectoral nature of social, structural, and colonial determinants of maternal-child health in circumpolar regions.

Neonatal and Maternal Outcomes of Lower Versus Standard Doses of Antenatal Corticosteroids for Women at Risk of Preterm Delivery: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: Our objective was to systematically review randomized and quasi-randomized trials on the neonatal and maternal effects of lower doses of antenatal corticosteroids (<24 mg of betamethasone or dexamethasone) compared with standard double doses of antenatal corticosteroids (24 mg of betamethasone or dexamethasone) administered to women at risk of preterm delivery. DATA SOURCES: Medline, Embase, CINAHL, Web of Science, Cochrane CENTRAL, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and the Australia New Zealand Clinical Trials Registry were searched from inception to December 8, 2019. STUDY SELECTION: A total of 2401 titles, abstracts, and protocols were independently screened by two reviewers, and subsequently 113 full-text articles were reviewed. DATA EXTRACTION: Our primary outcomes were perinatal death and severe respiratory distress syndrome. DATA SYNTHESIS: We identified one large in-progress trial comparing 11.4 mg versus 22.8 mg betamethasone and one published randomized controlled trial that compared a lower dose of dexamethasone (16 mg) to a standard dose of betamethasone (24 mg). The only relevant data from the published trial suggests minor changes in fetal heart rate variability between baseline and 24- to 48-hour follow-up between the two groups. Data for other outcomes had to be excluded due to the administration of weekly courses of antenatal corticosteroids. CONCLUSIONS: Randomized trial data comparing lower doses of antenatal corticosteroids to standard double doses are scarce. Given concerns regarding current antenatal corticosteroids dosing patterns, there is an urgent need for randomized controlled trials examining lower versus standard double doses of antenatal corticosteroids.

Do Maternal Pharmacogenetics Impact the Neonatal Abstinence Syndrome Following In Utero Exposure to Antidepressant Medications?

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the most commonly used medications for mood and anxiety disorders in women. Many women need to continue or initiate these medications during pregnancy, but there is concern about potential withdrawal effects in the newborn, referred to as neonatal abstinence syndrome (NAS). The reason why some infants remain asymptomatic while others are affected has not been elucidated. The objective of this study was to examine whether genetic differences in maternal drug metabolism influence the incidence of NAS. METHODS: Women who took Selective serotonin reuptake inhibitors s/SNRIs during pregnancy were recruited from obstetrical clinics. DNA was extracted from saliva samples for genetic analyses of cytochrome P450 (CYP) enzyme polymorphisms. Delivery and NAS data were collected from electronic medical records. RESULTS: Ninety-five women participated. The overall NAS rate was 16.2%. Mild NAS was seen in 13.8% of neonates and severe NAS, in 2%. One-quarter (25%) of the neonates with mild withdrawal symptoms were born to mothers with polymorphisms associated with slower metabolism of their particular antidepressant, but this association was not statistically significant. CONCLUSION: Importantly, the overall rate of NAS in our study was lower than previously reported. Maternal CYP polymorphisms did not affect the rate of NAS in neonates exposed to SSRIs/SNRIs in utero. This study lends added assurance to patients requiring SSRIs or SNRIs during pregnancy.

Two-Thirds of Preterm Parents Would Participate in a Randomized Controlled Trial Comparing Double Doses of Steroids to a Single Dose and Placebo.

Animal research strongly suggests that a single dose of antenatal corticosteroids (ACS) is as effective as a double dose to mature preterm lungs; however, a human randomized controlled trial (RCT) is urgently needed. From August to November 2020, we conducted an online survey of Canadian parents of preterm infants. Survey respondents watched a parent-to-parent video introducing an RCT to study whether the standard double dose of ACS is non-inferior to a single dose (and matching placebo). Approximately two-thirds of respondents reported they were either likely or very likely to participate in the RCT, indicating high parental interest in and support for such a trial.