[Risk factors for cow's milk protein allergy in infants: a multicenter prospective nested case-control study]. / å©´å„¿ç‰›å¥¶è›‹ç™½è¿‡æ•çš„å±é™©å› ç´ ï¼šä¸€é¡¹å¤šä¸­å¿ƒå‰çž»æ€§å·¢å¼ç— ä¾‹å¯¹ç §ç ”ç©¶.

OBJECTIVES: To explore the risk factors associated with cow's milk protein allergy (CMPA) in infants. METHODS: This study was a multicenter prospective nested case-control study conducted in seven medical centers in Beijing, China. Infants aged 0-12 months were included, with 200 cases of CMPA infants and 799 control infants without CMPA. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for the occurrence of CMPA. RESULTS: Univariate logistic regression analysis showed that preterm birth, low birth weight, birth from the first pregnancy, firstborn, spring birth, summer birth, mixed/artificial feeding, and parental history of allergic diseases were associated with an increased risk of CMPA in infants (P<0.05). Multivariate logistic regression analysis revealed that firstborn (OR=1.89, 95%CI: 1.14-3.13), spring birth (OR=3.42, 95%CI: 1.70-6.58), summer birth (OR=2.29, 95%CI: 1.22-4.27), mixed/artificial feeding (OR=1.57, 95%CI: 1.10-2.26), parental history of allergies (OR=2.13, 95%CI: 1.51-3.02), and both parents having allergies (OR=3.15, 95%CI: 1.78-5.56) were risk factors for CMPA in infants (P<0.05). CONCLUSIONS: Firstborn, spring birth, summer birth, mixed/artificial feeding, and a family history of allergies are associated with an increased risk of CMPA in infants.

The use of late preterm antenatal corticosteroids in women with gestational diabetes : a puzzle worth solving.

BACKGROUND: To investigate the association between late preterm antenatal corticosteroid treatment and outcome in late preterm neonates born to mothers with gestational diabetes mellitus, METHODS: All patients with gestational diabetes mellitus who had a late preterm delivery at Etlik Lady Zübeyde Hospital between 2017 and 2021 were included. Women who met the inclusion criteria and were not given antenatal corticosteroid treatment during current pregnancy before 34 0/7 weeks of gestation were divided into two groups according to whether or not they received late preterm antenatal corticosteroid treatment. The two groups were compared in terms of adverse neonatal complications. The main outcomes were composite respiratory outcome and composite neonatal outcome. Logistic regression analysis was used to determine additional potential predictors of neonatal outcome. RESULTS: This retrospective cohort study included a total of 400 participants with gestational diabetes mellitus who had a late preterm delivery within the study period. Of these women, 196 (49%) received late preterm antenatal corticosteroid treatment. Main outcomes showed no difference. Decreasing gestational age at birth was identified as an independent risk factor predicting both composite respiratory outcome and composite neonatal outcome in multivariate logistic regression analysis. CONCLUSIONS: Antenatal corticosteroid treatment at or after 34 0/7 weeks of gestation in women with gestational diabetes mellitus who had a late preterm delivery was not associated with improvement in adverse neonatal outcomes. Decreasing gestational age at birth was the only independent risk factor predicting composite neonatal and composite respiratory outcomes.

Identifying pregnancy episodes and estimating the last menstrual period using an administrative database in Korea: an application to patients with systemic lupus erythematosus.

OBJECTIVES: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE). METHODS: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients. RESULTS: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy. CONCLUSIONS: This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.

RSV Prefusion F Protein-Based Maternal Vaccine - Preterm Birth and Other Outcomes.

BACKGROUND: Vaccination against respiratory syncytial virus (RSV) during pregnancy may protect infants from RSV disease. Efficacy and safety data on a candidate RSV prefusion F protein-based maternal vaccine (RSVPreF3-Mat) are needed. METHODS: We conducted a phase 3 trial involving pregnant women 18 to 49 years of age to assess the efficacy and safety of RSVPreF3-Mat. The women were randomly assigned in a 2:1 ratio to receive RSVPreF3-Mat or placebo between 24 weeks 0 days and 34 weeks 0 days of gestation. The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract disease in infants from birth to 6 months of age and safety in infants from birth to 12 months of age. After the observation of a higher risk of preterm birth in the vaccine group than in the placebo group, enrollment and vaccination were stopped early, and exploratory analyses of the safety signal of preterm birth were performed. RESULTS: The analyses included 5328 pregnant women and 5233 infants; the target enrollment of approximately 10,000 pregnant women and their infants was not reached because enrollment was stopped early. A total of 3426 infants in the vaccine group and 1711 infants in the placebo group were followed from birth to 6 months of age; 16 and 24 infants, respectively, had any medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 65.5%; 95% credible interval, 37.5 to 82.0), and 8 and 14, respectively, had severe medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 69.0%; 95% credible interval, 33.0 to 87.6). Preterm birth occurred in 6.8% of the infants (237 of 3494) in the vaccine group and in 4.9% of those (86 of 1739) in the placebo group (relative risk, 1.37; 95% confidence interval [CI], 1.08 to 1.74; P = 0.01); neonatal death occurred in 0.4% (13 of 3494) and 0.2% (3 of 1739), respectively (relative risk, 2.16; 95% CI, 0.62 to 7.56; P = 0.23), an imbalance probably attributable to the greater percentage of preterm births in the vaccine group. No other safety signal was observed. CONCLUSIONS: The results of this trial, in which enrollment was stopped early because of safety concerns, suggest that the risks of any and severe medically assessed RSV-associated lower respiratory tract disease among infants were lower with the candidate maternal RSV vaccine than with placebo but that the risk of preterm birth was higher with the candidate vaccine. (Funded by GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT04605159.).

Prenatal phthalate exposure and adverse birth outcomes in the USA: a prospective analysis of births and estimates of attributable burden and costs.

BACKGROUND: Phthalates are synthetic chemicals widely used in consumer products and have been identified to contribute to preterm birth. Existing studies have methodological limitations and potential effects of di-2-ethylhexyl phthalate (DEHP) replacements are poorly characterised. Attributable fractions and costs have not been quantified, limiting the ability to weigh trade-offs involved in ongoing use. We aimed to leverage a large, diverse US cohort to study associations of phthalate metabolites with birthweight and gestational age, and estimate attributable adverse birth outcomes and associated costs. METHODS: In this prospective analysis we used extant data in the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program from 1998 to 2022 to study associations of 20 phthalate metabolites with gestational age at birth, birthweight, birth length, and birthweight for gestational age z-scores. We also estimated attributable adverse birth outcomes and associated costs. Mother-child dyads were included in the study if there were one or more urinary phthalate measurements during the index pregnancy; data on child's gestational age and birthweight; and singleton delivery. FINDINGS: We identified 5006 mother-child dyads from 13 cohorts in the ECHO Program. Phthalic acid, diisodecyl phthalate (DiDP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP) were most strongly associated with gestational age, birth length, and birthweight, especially compared with DEHP or other metabolite groupings. Although DEHP was associated with preterm birth (odds ratio 1·45 [95% CI 1·05-2·01]), the risks per log10 increase were higher for phthalic acid (2·71 [1·91-3·83]), DiNP (2·25 [1·67-3·00]), DiDP (1·69 [1·25-2·28]), and DnOP (2·90 [1·96-4·23]). We estimated 56 595 (sensitivity analyses 24 003-120 116) phthalate-attributable preterm birth cases in 2018 with associated costs of US$3·84 billion (sensitivity analysis 1·63- 8·14 billion). INTERPRETATION: In a large, diverse sample of US births, exposure to DEHP, DiDP, DiNP, and DnOP were associated with decreased gestational age and increased risk of preterm birth, suggesting substantial opportunities for prevention. This finding suggests the adverse consequences of substitution of DEHP with chemically similar phthalates and need to regulate chemicals with similar properties as a class. FUNDING: National Institutes of Health.

The changes in adrenal developmental programming and homeostasis in offspring induced by glucocorticoids exposure during pregnancy.

Clinically, synthetic glucocorticoids are often used to treat maternal and fetal related diseases, such as preterm birth and autoimmune diseases. Although its clinical efficacy is positive, it will expose the fetus to exogenous glucocorticoids. Adverse environments during pregnancy (e.g., exogenous glucocorticoids exposure, malnutrition, infection, hypoxia, and stress) can lead to fetal overexposure to endogenous maternal glucocorticoids. Basal glucocorticoids levels in utero are crucial in determining fetal tissue maturation and its postnatal fate. As the synthesis and secretion organ of glucocorticoids, the adrenal development is crucial for the growth and development of the body. Studies have found that glucocorticoids exposure during pregnancy could cause abnormal fetal adrenal development, which could last after birth or even adulthood. As the key organ of fetal-originated adult disease, the adrenal developmental programming has a profound impact on the health of offspring, which can lead to many chronic diseases in adulthood. However, the aberrant adrenal development in offspring caused by glucocorticoids exposure during pregnancy and its intrauterine programming mechanism have not been systematically clarified. Therefore, this review summarizes recent research progress on the short and long-term hazards of aberrant adrenal development induced by glucocorticoids exposure during pregnancy, which is of great significance for the analysis of aberrant adrenal development and clarify the intrauterine origin mechanism of fetal-originated adult disease.

Prenatal tobacco smoke exposure and risk for cognitive delays in infants born very premature.

Prenatal tobacco smoke exposure (TSE) and prematurity are independent risk factors for abnormal neurodevelopment. The objectives were to compare differences in Bayley-III cognitive, language, and motor scores at 2 years corrected age (CA) in 395 infants born very preterm (≤ 32 weeks gestation) with and without prenatal TSE. We performed multivariable linear regression analyses to examine associations between prenatal TSE and neurodevelopmental outcomes and a mediation analysis to estimate direct effects of prenatal TSE on outcomes and indirect effects through preterm birth. In total, 50 (12.6%) infants had prenatal TSE. Infants with prenatal TSE had lower mean [95% CI] Cognitive score (82.8 [78.6, 87.1]) vs. nonexposed infants (91.7 [90.1, 93.4]). In children with and without prenatal TSE, there were significant differences in mean [95% CI] Language scores (81.7 [76.0, 87.4] vs. 92.4 [90.2, 94.6], respectively) and mean [95% CI] Motor scores (86.5 [82.2, 90.7] vs. 93.4 [91.8, 95.0], respectively); scores remained significant after controlling for confounders. Preterm birth indirectly mediated 9.0% of the total effect of prenatal TSE on Cognitive score (P = NS). However, 91% of the remaining total effect was significant and attributable to TSE's direct harmful effects on cognitive development (ß = - 5.17 [95% CI - 9.97, - 0.38]). The significant association is largely due to TSE's direct effect on cognitive development and not primarily due to TSE's indirect effect on preterm birth.

Final analysis of 379 pregnancy outcomes after exposure to dimethyl fumarate in a prospective international registry.

BACKGROUND: Dimethyl fumarate (DMF) has a favorable benefit-risk profile treating people with multiple sclerosis and should be used in pregnant women only if the potential benefits outweigh potential risks to the fetus. OBJECTIVE: Assess pregnancy outcomes in a completed international registry (TecGistry) of women with MS exposed to DMF. METHODS: TecGistry included pregnant women with MS exposed to DMF, with data collected at enrollment, 6-7 months gestation, 4 weeks after estimated due date, and at postpartum weeks 4, 12, and 52. Outcomes included live births, gestational size, pregnancy loss, ectopic/molar pregnancies, birth defects, and infant/maternal death. RESULTS: Of 397 enrolled, median (range) age was 32 years (19-43). Median (range) gestational week at enrollment was 10 (0-39) and at first DMF exposure was 1 (0-13). Median (range) duration of gestational DMF exposure was 5 weeks (0-40). Fifteen (3.8%) spontaneous abortions occurred. Of 360 (89.1%) live births, 323 were full term and 37 were premature. One neonatal death and no maternal deaths occurred. Adjudicator-confirmed EUROCAT birth defects were found in 2.2%. CONCLUSION: DMF exposure during pregnancy did not adversely affect pregnancy outcomes; birth defects, preterm birth, and spontaneous abortion were in line with rates from the general population.

U-shaped relationship between ozone exposure and preterm birth risk associated with preconception telomere length.

There are conflicting findings regarding the association of ozone (O3) exposure with preterm birth (PTB) occurrence. In the present study, two cohorts were combined to explore the relationship between maternal O3 exposure during pregnancy and PTB risk, and analyze the underlying mechanisms of this relationship in terms of alterations in the preconception telomere length. Cohort 1 included mothers who participated in the National Free Preconception Health Examination Project in Henan Province from 2014 to 2018 along with their newborns (n = 1,066,696). Cohort 2 comprised mothers who conceived between 2016 and 2018 and their newborns (n = 1871) from six areas in Henan Province. The telomere length was assessed in the peripheral blood of mothers at the preconception stage. Data on air pollutant concentrations were collected from environmental monitoring stations and individual exposures were assessed using an inverse distance-weighted model. O3 concentrations (100.60 ± 14.13 µg/m3) were lower in Cohort 1 than in Cohort 2 (114.09 ± 15.17 µg/m3). Linear analyses showed that PTB risk decreased with increasing O3 exposure concentrations in Cohort 1 but increased with increasing O3 exposure concentrations in Cohort 2. Nonlinear analyses revealed that PTB risk tended to decrease and then increase with increasing O3 exposure concentrations in both cohorts. Besides, PTB risk was reduced by 88% for each-unit increase in telomere length in those exposed to moderate O3 concentrations (92.4-123.7 µg/m3, P < 0.05). While no significant association was observed between telomere length and PTB at extreme O3 concentration exposure during entire pregnancy (<92.4 or >123.7 µg/m3, P > 0.05) in Cohort 2. These findings reveal a nonlinear (U-shaped) relationship between O3 exposure and PTB risk. Furthermore, telomere with elevated length was associated with decreased risk of PTB only when exposed to moderate concentrations of O3, but not when exposed to extreme concentrations of O3 during pregnancy.

Weekly Paclitaxel for Pregnancy Associated Breast Cancer.

BACKGROUND: Pregnancy associated breast cancer is the most common cancer diagnosed during pregnancy. When chemotherapy is indicated, although it is more common to use anthracycline-based chemotherapy as a first treatment, we suggest weekly paclitaxel as a valid alternative both in the adjuvant and neoadjuvant setting, as this allows for weekly assessment of maternal-fetal well-being and a quicker maternal and fetal bone marrow recovery in cases of unexpected preterm delivery. PATIENTS AND METHODS: We present a case series of pregnant breast cancer patients treated with weekly paclitaxel between 2016 and 2022. Patient demographics and tumor characteristics, data on management, delivery, and maternal-neonatal outcomes were extrapolated from institutional electronic databases. RESULTS: Eighteen patients underwent weekly paclitaxel for breast cancer during pregnancy (PrBC); 17 were primary diagnoses and 1 was a recurrence. None of the patients had severe adverse reactions to CT. Two cases of preterm prelabour rupture of membranes were reported while in 1 case treatment was stopped due to threatened preterm birth. Two babies were born large for gestational age, 2 were small for gestational age and 2 babies were growth restricted at birth. At a mean follow up of 42.9 months, 1 patient died, 1 patient was diagnosed with disease recurrence and another patient was diagnosed with disease progression. CONCLUSION: Weekly paclitaxel can be safely administered during pregnancy and should be included in the current therapeutic options for PrBC.

Exposure to atrazine by drinking water and the increased risk of neonatal complications in consequence: a meta-analysis.

This meta-analysis evaluates the association between atrazine (ATR) exposure and small for gestational age (SGA), preterm birth (PTB), and low birth weight (LBW). A comprehensive search was done on academic databases (e.g. PubMed, Scopus, Embase, and Google Scholar) to achieve all pertinent studies up to May 2023. A pooled odd ratio (OR) and corresponding 95% confidence interval (CI) were applied to evaluate this correlation. As a result, five eligible studies met the inclusion criteria and were included in our study, and the result of the present meta-analysis showed that ATR exposure increased the risk of SGA (OR = 1.11; 95% CI = 1.03-1.20 for highest versus lowest category of ATR), PTB (OR = 1.16; 95% CI = 1.03-1.30), and LBW (OR = 1.26; 95% CI = 1.10-1.44). This meta-analysis suggests that ATR in drinking water may be a risk factor for SGA, PTB, and LBW.

Early life corticosteroid overexposure: Epigenetic and fetal origins of adult diseases.

The relationship between events occurring during intrauterine development and later-life predisposition to long-term disease, has been described. The fetus responds to excess intrauterine exposure to high levels of corticosteroids, modifying their physiological development and stopping their growth. Fetal exposure to elevated levels of either endogenous (alterations in fetal hypothalamic-pituitary-adrenal axis) or synthetic corticosteroids, is one model of early-life adversity; to developing adult disease. At the molecular level, there are transcriptional changes in metabolic and growth pathways. Epigenetic mechanisms participate in transgenerational inheritance, not genomic. Exposures that change 11ß-hydroxysteroid dehydrogenase type 2 enzyme methylation status in the placenta can result in transcriptional repression of the gene, causing the fetus to be exposed to higher levels of cortisol. More precise diagnosis and management of antenatal corticosteroids for preterm birth, would potentially decrease the risk of long-term adverse outcomes. More studies are needed to understand the potential roles of factors to alter fetal corticosteroid exposure. Long-term infant follow-up is required to determine whether methylation changes in placenta may represent useful biomarkers of later disease risk. This review, summarize recent advances in the programming of fetal effects of corticosteroid exposure, the role of corticosteroids in epigenetic gene regulation of placental 11ß-hydroxysteroid dehydrogenase type 2 enzyme expression and transgenerational effects.

CD8+ T cells in fetal membranes display a unique phenotype, and their activation is involved in the pathophysiology of spontaneous preterm birth.

Preterm labor/birth is the leading cause of perinatal mortality and morbidity worldwide. Previous studies demonstrated that T cells were crucial for maintaining maternal-fetal immune tolerance during the first trimester of pregnancy; however, their phenotypes and functions in labor and delivery remain largely unknown. We recruited three cohorts of women at delivery for T-cell immunophenotyping in the placentas, fetal membranes, umbilical cord blood, and maternal peripheral blood. Our data showed a differential enrichment of T cells during the third trimester of human pregnancy, with CD4+ T cells being more observable within the umbilical cord blood, whereas CD8+ T cells became relatively more abundant in fetal membranes. CD4+ and CD8+ T cells derived from fetal membranes were dominated by effector memory T cells and exhibited extensive expression of activation markers but decreased expression of homing receptor. In comparison with term births, fetal membrane CD8+ T cells, especially the central memory subset, were significantly increased in frequency and showed more profound activation in spontaneous preterm birth patients. Finally, using an allogeneic mouse model, we found that T-cell-activation-induced preterm birth could be alleviated by the depletion of CD8+ T but not CD4+ T cells in vivo. Collectively, we showed that CD8+ T cells in fetal membranes displayed a unique phenotype, and their activation was involved in the pathophysiology of spontaneous preterm birth, which provides novel insights into the immune mechanisms of preterm birth and potential targets for the prevention of this syndrome. © 2023 The Pathological Society of Great Britain and Ireland.

Wildfire smoke exposure during pregnancy and perinatal, obstetric, and early childhood health outcomes: A systematic review and meta-analysis.

BACKGROUND: Maternal exposure to air pollution during pregnancy is associated with adverse birth outcomes, although less is known for wildfire smoke. This systematic review evaluated the association between maternal exposure to wildfire smoke during pregnancy and the risk of perinatal, obstetric, and early childhood health outcomes. METHODS: We searched CINAHL Complete, Ovid/EMBASE, Ovid/MEDLINE, ProQuest, PubMed, Scopus, Web of Science, and Google Scholar to identify relevant epidemiological observational studies indexed through September 2023. The screening of titles, abstracts, and full-texts, data extraction, and risk of bias assessment was performed by pairs of independent reviewers. RESULTS: Our systematic search yielded 28,549 records. After duplicate removal, we screened 14,009 studies, identifying 31 for inclusion in the present review. Data extraction highlighted high methodological heterogeneity between studies, including a lack of geographic variation. Approximately 56.5% and 16% originated in the United States and Brazil, respectively, and fewer in other countries. Among the studies, wildfire smoke exposure during pregnancy was assessed using distance of residence from wildfire-affected areas (n = 15), measurement of air pollutant concentration during wildfires (n = 11), number of wildfire records (n = 3), aerosol index (n = 1), and geographic hot spots (n = 1). Pooled meta-analysis for birthweight and low birthweight were inconclusive, likely due to low number of methodologically homogenous studies. However, the reviewed studies provided suggestive evidence for an increased risk of birthweight reduction, low birthweight, preterm birth, and other adverse health outcomes. CONCLUSIONS: This review identified 31 studies evaluating the impacts of maternal wildfire smoke exposure on maternal, infant, and child health. Although we found suggestive evidence of harm from exposure to wildfire smoke during pregnancy, more methodologically homogenous studies are required to enable future meta-analysis with greater statistical power to more accurately evaluate the association between maternal wildfire smoke and adverse birth outcomes and other health outcomes.

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..

Influence of maternal endocrine disrupting chemicals exposure on adverse pregnancy outcomes: A systematic review and meta-analysis.

Maternal endocrine disrupting chemicals (EDCs) exposure, the common environmental pollutants, was capable of involving in adverse pregnancy outcomes. However, the evidence of their connection is not consistent. Our goal was to comprehensively explore the risk of EDCs related to adverse pregnancy outcomes. One hundred and one studies were included from two databases before 2023 to explore the association between EDCs and adverse pregnancy outcomes including miscarriage, small for gestational age (SGA), low birth weight (LBW) and preterm birth (PTB). We found that maternal PFASs exposure was positively correlated with PTB (OR:1.13, 95% CI:1.04-1.23), SGA (OR:1.10, 95% CI:1.04-1.16) and miscarriage (OR:1.09, 95% CI:1.00-1.19). The pooled estimates also showed maternal PAEs exposure was linked with PTB (OR:1.16, 95% CI:1.11-1.21), SGA (OR:1.20, 95% CI:1.07-1.35) and miscarriage (OR:1.55, 95% CI:1.33-1.81). In addition, maternal exposure to some specific class of EDCs including PFOS, MBP, MEHP, DEHP, and BPA was associated with PTB. Maternal exposure to PFOS, PFOA, PFHpA was associated with SGA. Maternal exposure to BPA was associated with LBW. Maternal exposure to MMP, MEHP, MEHHP, MEOHP, BPA was associated with miscarriage. Maternal PFASs, PAEs and BPA exposure may increase adverse pregnancy outcomes risk according to our study. However, the limited number of studies on dose-response hampered further explanation for causal association.

Individual ambient ozone exposure during pregnancy and adverse birth outcomes: Exploration of the potentially vulnerable windows.

BACKGROUND: Ambient ozone (O3) exposure during pregnancy might be associated with preterm birth (PTB) and low birth weight (LBW); however, existing evidence remains inconclusive. It is necessary to explore the relationships and potential susceptible periods further. METHODS: To explore the relationship between O3 exposure and adverse birth outcomes, a study using records of 34,122 singleton live births in Beijing between 2016 and 2019 was conducted. The O3 exposure in each gestational week of pregnant women was estimated, and Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Distributed lag nonlinear model (DLNM) incorporated in Cox proportional hazard models were used to explore potential critical windows. RESULTS: An increase of 10 µg/m3 in O3 exposure was associated with a 3.9% (95%CI: 0.6-7.3%) higher risk of PTB. Additionally, this increase in O3 exposure was positively linked to PTB during the 2nd - 7th, 22nd - 29th, and 37th gestational weeks, and LBW during the 2nd - 7th, 24th - 29th, and 37th gestational weeks. CONCLUSIONS: This study demonstrates a positive correlation between O3 exposure and PTB, and identified specific sensitive periods during pregnancy when the risk was higher.

Pregnancy outcomes following self-reported and objective-measured exposure to oral preexposure prophylaxis in South Africa.

OBJECTIVE: To compare pregnancy outcomes using self-reported and objective levels of intracellular tenofovir diphosphate (TFV-DP) in pregnant women using preexposure prophylaxis (PrEP). DESIGN: We enrolled pregnant women >15 years without HIV at first antenatal care visit in an observational cohort study to compare pregnancy outcomes by PrEP use. METHODS: Exposure defined as: any PrEP use [tenofovir disoproxil and emtricitabine (TDF/FTC]) prescription + reported taking PrEP], or objectively-measured TFV-DP in dried blood spots in PrEP-using pregnant women. The primary outcome was a composite of pregnancy loss, preterm birth (<37weeks), low birthweight (<2500 g), small for gestational age ([SGA] ≤ tenth percentile), or neonatal death. Multivariable logistic regression models evaluated individual and composite adverse outcomes by self-reported or objectively measured PrEP use adjusting for age, gestational age, gravidity and socio-economic status. RESULTS: Between August 19 and February 23, we followed 1195 pregnant women and ascertained 1145 pregnancy outcomes (96%); 72% ( n  = 826) reported taking PrEP while pregnant, 16% did not take PrEP ( n  = 178), 12% were unconfirmed ( n  = 141). Overall, 94.5% ( n  = 1082) had singleton live births with a median birthweight of 3.2 kg [interquartile range (IQR) = 2.9-3.5], with no difference in pregnancy loss between self-reported PrEP exposed vs. unexposed [4.0 vs. 5.6%; adjusted odds ratio (aOR) = 0.65, 95% confidence interval (CI) = 0.32-1.47]. Composite adverse outcomes did not differ by reported PrEP use (20% for both groups; aOR = 1.07, 95% CI = 0.71-1.63). Comparing objective PrEP use (any TFV-DP vs. no TFV-DP or not on PrEP), adverse outcomes did not differ (aOR = 0.64, 95% CI = 0.39-1.04), nor did other outcomes including preterm birth nor SGA. CONCLUSIONS: Pregnancy outcomes did not differ by PrEP exposure (self-reported or objective), suggesting real-world efficacy that TDF/FTC as PrEP is safe in pregnancy.

Effects of air pollution on adverse birth outcomes and pregnancy complications in the U.S. state of Kansas (2000-2015).

Neonatal mortality and morbidity are often caused by preterm birth and lower birth weight. Gestational diabetes mellitus (GDM) and gestational hypertension (GH) are the most prevalent maternal medical complications during pregnancy. However, evidence on effects of air pollution on adverse birth outcomes and pregnancy complications is mixed. Singleton live births conceived between January 1st, 2000, and December 31st, 2015, and reached at least 27 weeks of pregnancy in Kansas were included in the study. Trimester-specific and total pregnancy exposures to nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5), and ozone (O3) were estimated using spatiotemporal ensemble models and assigned to maternal residential census tracts. Logistic regression, discrete-time survival, and linear models were applied to assess the associations. After adjustment for demographics and socio-economic status (SES) factors, we found increases in the second and third trimesters and total pregnancy O3 exposures were significantly linked to preterm birth. Exposure to the second and third trimesters O3 was significantly associated with lower birth weight, and exposure to NO2 during the first trimester was linked to an increased risk of GDM. O3 exposures in the first trimester were connected to an elevated risk of GH. We didn't observe consistent associations between adverse pregnancy and birth outcomes with PM2.5 exposure. Our findings indicate there is a positive link between increased O3 exposure during pregnancy and a higher risk of preterm birth, GH, and decreased birth weight. Our work supports limiting population exposure to air pollution, which may lower the likelihood of adverse birth and pregnancy outcomes.

Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial.

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.