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Aims: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy., Methods: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy., Results: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I 2 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I 2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I 2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW., Conclusions: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Dysregulation of the immune system has been associated with psychiatric disorders and pregnancy-related complications, such as perinatal depression. However, the immune characteristics specific to perinatal anxiety remain poorly understood. In this study, our goal was to examine specific immune characteristics related to prenatal anxiety within the context of a randomized controlled trial designed to alleviate anxiety symptoms-the Happy Mother - Healthy Baby (HMHB) study in Rawalpindi, Pakistan., Materials and Methods: Pregnant women (n = 117) were followed prospectively in the 1st, 2nd, and 3rd trimesters (T1, T2, T3) and at 6 weeks postpartum (PP6). Each visit included a blood draw and anxiety evaluation (as measured by the anxiety subscale of the Hospital Anxiety and Depression Scale - HADS -using a cutoff ≥ 8). We enrolled both healthy controls and participants with anxiety alone; those with concurrent depression were excluded., Results: K-means cluster analysis revealed three anxiety clusters: Non-Anxiety, High and Consistent Anxiety, and Decreasing Anxiety. Principal components analysis revealed two distinct clusters of cytokine and chemokine activity. Women within the High and Consistent Anxiety group had significantly elevated chemokine activity across pregnancy (in trimester 1 (β = 0.364, SE = 0.178, t = 2.040, p = 0.043), in trimester 2 (β = 0.332, SE = 0.164, t = 2.020, p = 0.045), and trimester 3 (β = 0.370, SE = 0.179, t = 2.070, p = 0.040) compared to Non-Anxiety group. Elevated chemokine activity was associated with low birthweight (LBW) and small for gestational age (SGA)., Conclusion: Our findings reveal a unique pattern of immune dysregulation in pregnant women with anxiety in a Pakistani population and offer preliminary evidence that immune dysregulation associated with antenatal anxiety may be associated with birth outcomes. The dysregulation in this population is distinct from that in our other studies, indicating that population-level factors other than anxiety may play a substantial role in the differences found. (Clinicaltrials.gov # NCT04566861)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Previous findings related to the association of adverse pregnancy outcomes with anorexia nervosa are mixed., Objective: This study aimed to investigate the association of adverse live-born pregnancy outcomes with anorexia nervosa using adjustment modeling accounting for confounding factors, and a mediation analysis addressing the contribution of underweight prepregnancy body mass index and gestational weight gain to those outcomes., Study Design: The sample included California live-born singletons with births between 2007 and 2021. The administrative data set contained birth certificates linked to hospital discharge records. Anorexia nervosa diagnosis during pregnancy was obtained from International Classification of Diseases codes on hospital discharge records. Adverse pregnancy outcomes examined included gestational diabetes, gestational hypertension, preeclampsia, anemia, antepartum hemorrhage, premature rupture of membranes, premature labor, cesarean delivery, oligohydramnios, placenta previa, chorioamnionitis, placental abruption, severe maternal morbidity, small for gestational age, large for gestational age, low birthweight, and preterm birth (by timing and indication). Risk of each adverse outcome was calculated using Poisson regression models. Unadjusted risk of each adverse outcome was calculated, and then the risks were adjusted for demographic factors. The final adjusted model included demographic factors, anxiety, depression, substance use, and smoking. A mediation analysis was performed to estimate the excess risk of adverse outcomes mediated by underweight prepregnancy body mass index and gestational weight gain below the American College of Obstetricians and Gynecologists recommendation., Results: The sample included 241 pregnant people with a diagnosis of anorexia nervosa and 6,418,236 pregnant people without an eating disorder diagnosis. An anorexia nervosa diagnosis during pregnancy was associated with many adverse pregnancy outcomes in unadjusted models (relative risks ranged from 1.65 [preeclampsia] to 3.56 [antepartum hemorrhage]) in comparison with people without an eating disorder diagnosis. In the final adjusted models, birthing people with an anorexia nervosa diagnosis were more likely to have anemia, preterm labor, oligohydramnios, severe maternal morbidity, a small for gestational age or low-birthweight infant, and preterm birth between 32 and 36 weeks with spontaneous preterm labor (adjusted relative risks ranged from 1.43 to 2.55). Underweight prepregnancy body mass index mediated 7.78% of the excess in preterm births and 18.00% of the excess in small for gestational age infants. Gestational weight gain below the recommendation mediated 38.89% of the excess in preterm births and 40.44% of the excess in low-birthweight infants., Conclusion: Anorexia nervosa diagnosis during pregnancy was associated with a number of clinically important adverse pregnancy outcomes in comparison with people without an eating disorder diagnosis. Adjusting for anxiety, depression, substance use, and smoking during pregnancy decreased this risk. A substantial percentage of the excess risk of adverse outcomes was mediated by an underweight prepregnancy body mass index, and an even larger proportion of excess risk was mediated by gestational weight gain below the recommendation. This information is important for clinicians to consider when caring for patients with anorexia nervosa. Considering and treating anorexia nervosa and comorbid conditions and counseling patients about mediating factors such as preconception weight and gestational weight gain may improve live-born pregnancy outcomes among people with anorexia nervosa., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: There are many studies regarding the increased relationship between pregnancy outcomes of singleton with endometriosis. However, there was limited evidence of twin pregnancies with endometriosis. This study aimed to compare the pregnancy outcomes and complications in twin pregnancies with or without endometriosis in a single institution., Materials and Methods: From January 2011 to July 2022, a retrospective analysis of twin pregnancies was conducted. The endometriosis group included patient with histological or visual confirmation before pregnancy or during cesarean section. Pregnancy outcomes and complications were compared between the two groups., Results: Out of 1714 patients examined, 127 (7.4%) were included in the endometriosis group. Maternal body mass index (BMI) was lower in the endometriosis group ( p <0.001). There were no significant differences in maternal age, mode of conception, chorionicity, and pregnancy outcomes, such as gestational age at delivery ( p =0.835) and the preterm birth rate ( p =0.579). The endometriosis group had a significantly higher rate of obstetrical complication: small for gestational age (SGA) <10% ( p =0.029). However, after adjustment for BMI, the endometriosis group showed no statistical significance in obstetrical complications, including SGA (adjusted odds ratio, 1.568; 95% confidence interval, 0.984-2.499; p =0.059)., Conclusion: Twin pregnancies with endometriosis were not related to adverse effects on pregnancy outcomes and obstetrical complications. To confirm these outcomes, further large prospective studies are required., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Background: Nausea and vomiting of pregnancy (NVP) occurs in approximately 70% of pregnant people, with varying severity and duration. Treatments include pharmacologic and herbal/natural medications. The associations between NVP and birth outcomes, including preterm birth, small for gestational age (SGA), and low birth weight are inconclusive., Objective: To determine whether NVP and reported medications are associated with adverse birth outcomes., Methods: We used data from the population-based, multisite National Birth Defects Prevention Study (1997-2011) to evaluate whether self-reported NVP according to timing, duration, and severity or its specific treatments were associated with preterm birth, SGA, and low birth weight among controls without birth defects. Odds ratios (aOR) and 95% confidence intervals (CI) were adjusted for sociodemographic, reproductive, and medical factors. For any NVP, duration, treatment use, and severity score analyses, the comparison group was participants with no reported NVP. For timing analyses, the comparison group was women with no reported NVP in the same trimester of pregnancy., Results: Among 6018 participants, 4339 (72.1%) reported any NVP. Among those with NVP, moderate or severe symptoms were more common than mild symptoms. Any versus no NVP was not associated with any of the outcomes of interest. NVP in months 4-6 (aOR 1.21, 95% CI: 1.00, 1.47) and 7-9 (aOR 1.57, 95% CI: 1.22, 2.01) of pregnancy were associated with an increase in the risk of preterm birth. NVP lasting one trimester in duration was associated with decrease in risk of SGA (aOR: 0.74, 95% CI: 0.58, 0.95), and NVP present in every trimester of pregnancy had a 50% increase in risk of preterm birth (aOR: 1.50, 95% CI: 1.11, 2.05). For NVP in months 7-9 and preterm birth, ORs were elevated for moderate (aOR: 1.82, 95% CI: 1.26, 2.63), and severe (aOR: 1.53, 95% CI: 1.06, 2.19) symptoms. NVP was not significantly associated with low birth weight. Our analyses of medications were limited by small numbers, but none suggested increased risk of adverse outcomes associated with use of the medication., Conclusion: Mild NVP and NVP limited to early pregnancy appear to have no effect or a small protective effect on birth outcomes. Long-lasting NVP, severe NVP, and NVP later in pregnancy may increase risk of preterm birth and SGA., (© 2024 Wiley Periodicals LLC.)

Previous systematic reviews have reported on the relationship between eating disorders (EDs) and birth outcomes, but there are no existing meta-analyses on this topic. This systematic review and meta-analysis examines the association between lifetime maternal EDs, including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) with low birth weight (LBW), preterm birth (PTB), small for gestational age (SGA), large for gestational age (LGA), and miscarriage. Four databases were systematically searched for quantitative literature on maternal EDs that preceded birth outcomes. Eighteen studies met the inclusion criteria and were included in the review. The meta-analyses included 6 studies on miscarriage, 11 on PTB, 4 on LBW, 9 on SGA, and 4 on LGA. The Mantel-Haenszel random effects model was used to test the associations between EDs and birth outcomes. The results showed significant positive associations between AN and LBW (OR 1.74, 95% confidence interval (CI) 1.49, 2.03), AN and SGA (OR 1.39, 95% CI 1.17, 1.65), BN and PTB (OR 1.19, 95% CI 1.04, 1.36), and BED and LGA (OR 1.43 95% CI 1.18, 1.72). EDs were not significantly correlated with miscarriage. These findings reveal the importance of screening for and treating EDs in pregnant women.

Background: Emerging evidence has demonstrated the benefits of greenness exposure on human health, while conflicts remain unsolved in issue of adverse birth outcomes., Methods: Utilizing data from project ELEFANT spanning the years 2011 to 2021, we assessed residential greenness using the NDVI from MODIS data and residential PM 2.5 exposure level from CHAP data. Our primary concerns were PTD, LBW, LGA, and SGA. Cox proportional hazard regression model was used to examine the association of residential greenness and air pollution exposure with risk of adverse birth outcomes. We performed mediation and modification effect analyses between greenness and air pollutant., Results: We identified 61,762 mother‑neonatal pairs in final analysis. For per 10 μg/m 3 increase in PM 2.5 concentration during entire pregnancy was associated with 19.8 % and 20.7 % increased risk of PTD and LGA. In contrast, we identified that an 0.1 unit increment in NDVI were associated with 24 %, 43 %, 26.5 %, and 39.5 % lower risk for PTD, LBW, LGA, and SGA, respectively. According to mediation analysis, NDVI mediated 7.70 % and 7.89 % of the associations between PM 2.5 and PTD and LGA. Residential greenness could reduce the risk of PTD among mothers under 35 years old, living in rural areas, primigravidae and primiparity.., Conclusions: In summary, our results highlighted the potential of residential greenness to mitigate the risk of adverse birth outcomes, while also pointing to the adverse impact of PM 2.5 on increased risk of multiple adverse birth outcomes (PTD and LGA). The significant mediation effect of NDVI emphasizes its potential as an important protective factor of PM 2.5 exposure. Additionally, the identification of susceptible subgroups can inform targeted interventions to reduce adverse birth outcomes related to air pollution and lack of green spaces. Further research and understanding of these associations can contribute to better public health strategies aimed at promoting healthier pregnancies and birth outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Adverse birth outcomes particularly preterm births and congenital anomalies, are the leading causes of infant mortality globally, and the burden is highest in developing countries. We set out to determine the frequency of adverse birth outcomes and the risk factors associated with such outcomes in a cohort of pregnant women in Kenya., Methods: From October 2017 to July 2019, pregnant women < 28 weeks gestation were enrolled and followed up until delivery in three hospitals in coastal Kenya. Newborns were examined at delivery. Among women with birth outcome data, we assessed the frequency of congenital anomalies defined as gastroschisis, umbilical hernia, limb abnormalities and Trisomy 21, and adverse birth outcomes, defined as either stillbirth, miscarriage, preterm birth, small for gestational age, or microcephaly. We used log-binomial regression to identify maternal characteristics associated with the presence of at least one adverse outcome., Results: Among the 2312 women enrolled, 1916 (82.9%) had birth outcome data. Overall, 402/1916 (20.9%; 95% confidence interval (CI): 19.1-22.8) pregnancies had adverse birth outcomes. Specifically, 66/1916 (3.4%; 95% CI: 2.7-4.4) were stillbirths, 34/1916 (1.8%; 95% CI: 1.2-2.4) were miscarriages and 23/1816 (1.2%; 95% CI: 0.8-1.9) had congenital anomalies. Among the participants with anthropometric measurements data, 142/1200 (11.8%; 95% CI: 10.1 - 13.8) were small for gestational age and among the participants with ultrasound records, 143/1711 (8.4%; 95% CI: 7.1-9.8) were preterm. Febrile illnesses in current pregnancy (adjusted risk ratio (aRR): 1.7; 95% CI: 1.1-2.8), a history of poor birth outcomes in prior pregnancy (aRR: 1.8; 95% CI: 1.3-2.4) and high blood pressure in pregnancy (aRR: 3.9, 95% CI: (1.7-9.2) were independently associated with adverse birth outcomes in a model that included age, education, human immunodeficiency virus status and high blood pressure at enrolment., Conclusion: We found similar rates of overall adverse birth outcomes, congenital anomalies, and small for gestational age but higher rates of stillbirths and lower rates of prematurity compared to the rates that have been reported in the sub-Saharan Africa region. However, the rates of adverse birth outcomes in this study were comparable to other studies conducted in Kenya. Febrile illnesses during the current pregnancy, previous history of poor birth outcomes and high blood pressure in pregnancy are predictive of an increased risk of adverse birth outcomes., (© 2024. The Author(s).)

Purpose: This cross-sectional study aimed to estimate the risks of adverse birth outcomes among pregnant smokers and the benefits of smoking cessation during pregnancy on birth outcomes across the United States., Methods: We performed an analysis of 203,437 pregnant women using data collected by the Pregnancy Risk Assessment Monitoring System (PRAMS) from 2012 to 2017. PRAMS uses questionnaires and birth certificates to collect information about the socio-demographic characteristics of pregnant women, smoking status before and during pregnancy, and birth outcomes. We assessed the relationship between self-reported smoking status during pregnancy and preterm birth, low birth weight, and small-for-gestational-age using multivariable logistic regression models., Results: In our study population, 80.43% of pregnant women never smoked, 10.55% of pregnant women quit smoking during pregnancy, and 9.02% continued smoking during pregnancy. Puerto Rico had the highest prevalence of non-smokers (94.12%), while West Virginia had the lowest prevalence of non-smokers (60.54%). Pregnant women who had a higher education level, were married, had less than 5 types of stress, and had government or private insurance before pregnancy had a higher prevalence of smokers who quit during pregnancy (quit smokers) than those that continued smoking (continuous smokers). Compared to non-smokers, continuous smokers had a significantly higher risk of low birth weight (AOR: 1.91, 95% CI 1.80, 2.03), preterm birth (AOR: 1.31, 95% CI 1.21, 1.41), and small-for-gestational-age (AOR: 2.22, 95% CI 2.07, 2.39). However, the relationships between quitting smoking and preterm birth and small-for-gestational-age were not significant., Conclusion: Our models suggest that smoking cessation during pregnancy can prevent adverse birth outcomes by significantly reducing the risk of preterm birth and small-for-gestational-age to almost comparable to not smoking., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Maternal infections during pregnancy have been linked to increased risk of adverse birth outcomes, including low birth weight (LBW), preterm birth (PTB), small for gestational age (SGA), and stillbirth (SB)., Objectives: The purpose of this article was to summarize evidence from published literature on the effect of key interventions targeting maternal infections on adverse birth outcomes., Methods: We searched MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and CINAHL Complete between March 2020 and May 2020 with an update to cover until August 2022. We included randomized controlled trials (RCTs) and reviews of RCTs of 15 antenatal interventions for pregnant women reporting LBW, PTB, SGA, or SB as outcomes., Results: Of the 15 reviewed interventions, the administration of 3 or more doses of intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine [IPTp-SP; RR: 0.80 (95% CI: 0.69, 0.94)] can reduce risk of LBW compared with 2 doses. The provision of insecticide-treated bed nets, periodontal treatment, and screening and treatment of asymptomatic bacteriuria may reduce risk of LBW. Maternal viral influenza vaccination, treatment of bacterial vaginosis, intermittent preventive treatment with dihydroartemisinin-piperaquine compared with IPTp-SP, and intermittent screening and treatment of malaria during pregnancy compared with IPTp were deemed unlikely to reduce the prevalence of adverse birth outcomes., Conclusions: At present, there is limited evidence from RCTs available for some potentially relevant interventions targeting maternal infections, which could be prioritized for future research., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: To identify first pregnancy risk factors for placental abruption in subsequent pregnancy., Methods: In a population-based nested case-control study, cases were defined as women with placental abruption in their second pregnancy, and controls as women without abruption. A total of 43 328 women were included in the study, 0.4% (n = 186) of second pregnancies had placental abruption. Multivariable logistic models were used to study the association between first pregnancy complications and placental abruption in subsequent pregnancy., Results: Having either small for gestational age, preterm delivery, pre-eclampsia or cesarean delivery during first pregnancy were independently associated with increased risk for placental abruption, and the risk was higher with any additional complication (age adjusted odds ratio [aOR] 2.00, 95% confidence interval [CI] 1.46-2.74; aOR 3.61, 95% CI 2.23-5.86; and aOR 3.86, 95% CI 1.56-9.56, for one, two, and three or more complications, respectively)., Conclusion: First pregnancy may serve as a window of opportunity to identify women at risk for future placental abruption., (© 2022 International Federation of Gynecology and Obstetrics.)

Background: Social deprivation is a major risk factor of adverse pregnancy outcomes. Yet, there is few studies evaluating interventions aiming at reducing the impact of social vulnerability on pregnancy outcomes., Objective: To compare pregnancy outcomes between patients that received personalized pregnancy follow-up (PPFU) to address social vulnerability versus standard care., Methods: Retrospective comparative cohort in a single institution between 2020 and 2021. A total of 3958 women with social vulnerability that delivered a singleton after 14 gestational weeks were included, within which 686 patients had a PPFU. Social vulnerability was defined by the presence of at least one of the following characteristics: social isolation, poor or insecure housing conditions, no work-related household income, and absence of standard health insurance (these four variables were combined as a social deprivation index (SDI)), recent immigration (< 12 month), interpersonal violence during pregnancy, being handicaped or minor, addiction during pregnancy. Maternal characteristics and pregnancy outcomes were compared between patients that received PPFU versus standard care. The associations between poor pregnancy outcomes (premature birth before 37 gestational weeks (GW), premature birth before 34 GW, small for gestational age (SGA) and PPFU were tested using multivariate logistic regression and propensity score matching., Results: After adjustment on SDI, maternal age, parity, body mass index, maternal origin and both high medical and obstetrical risk level before pregnancy, PPFU was an independent protective factor of premature birth before 37 gestational weeks (GW) (aOR = 0.63, 95%CI[0.46-0.86]). The result was similar for premature birth before 34 GW (aOR = 0.53, 95%CI [0.34-0.79]). There was no association between PPFU and SGA (aOR = 1.06, 95%CI [0.86 - 1.30]). Propensity score adjusted (PSa) OR for PPFU using the same variables unveiled similar results, PSaOR = 0.63, 95%CI[0.46-0.86] for premature birth before 37 GW, PSaOR = 0.52, 95%CI [0.34-0.78] for premature birth before 34 GW and PSaOR = 1.07, 95%CI [0.86 - 1.33] for SGA., Conclusions: This work suggests that PPFU improves pregnancy outcomes and emphasizes that the detection of social vulnerability during pregnancy is a major health issue., (© 2023. The Author(s).)

Background: Systemic corticosteroids are often used to treat inflammatory bowel disease (IBD) flares during pregnancy as maintenance of disease remission is crucial to optimize pregnancy outcomes. However, there is little data regarding the effect of in utero exposure to corticosteroids on the risk of adverse birth outcomes and early-life infections in the offspring., Methods: We used the Danish national registries to establish a nationwide cohort of all singleton live births in women with IBD from 1995 to 2015. Outcomes in children exposed in utero to corticosteroids were compared to those who were not exposed. In logistic and Cox proportional hazard regression models, we adjusted the outcomes (major congenital malformation, preterm birth, small for gestational age, low 5-min Apgar score, and infections) for confounders such as body mass index, smoking, comorbidity, and additional medical IBD treatment., Results: After in utero exposure to corticosteroids at any time between 30 days prior to conception through the first trimester (n = 707), the adjusted hazard ratio of major congenital malformation was 1.28 (95% CI: 0.82-2.00) compared to children born to women with IBD, but not exposed to corticosteroids in utero (n = 9371). After in utero exposure to corticosteroids at any time during pregnancy (n = 1336), the adjusted odds ratios for preterm birth, small for gestational age, and low 5-min Apgar score were 2.45 (95% CI: 1.91-3.13), 1.21 (95% CI: 0.76-1.90), and 0.91 (95% CI: 0.33-2.52), respectively. Finally, the adjusted hazard ratio of overall infections in the first year of life was 1.14 (95% CI: 0.94-1.39)., Conclusions: This nationwide cohort study suggests that children of women with IBD exposed to corticosteroids in utero had an almost 2.5-fold increased risk of preterm birth. Use of corticosteroids is closely related to disease activity and we cannot adjust for the independent role of disease activity. It is however reassuring that the other examined birth and early-life outcomes were not statistically significantly increased., (© 2023. The Author(s).)

The importance of a fully functioning placenta for a good pregnancy outcome is unquestioned. Loss of function can lead to pregnancy complications and is often detected by a thorough placental pathologic examination. Placental pathology has advanced the science and practice of obstetrics and neonatal-perinatal medicine by classifying diseases according to underlying biology and specific patterns of injury. Many past obstacles have limited the incorporation of placental findings into both clinical studies and day-to-day practice. Limitations have included variability in the nomenclature used to describe placental lesions, a shortage of perinatal pathologists fully competent to analyze placental specimens, and a troubling lack of understanding of placental diagnoses by clinicians. However, the potential use of placental pathology for phenotypic classification, improved understanding of the biology of adverse pregnancy outcomes, the development of treatment and prevention, and patient counseling has never been greater. This review, written partly in response to a recent critique published in a major obstetrics-gynecology journal, reexamines the role of placental pathology by reviewing current concepts of biology; explaining the most recent terminology; emphasizing the usefulness of specific diagnoses for obstetrician-gynecologists, neonatologists, and patients; previewing upcoming changes in recommendations for placental submission; and suggesting future improvements. These improvements should include further consideration of overall healthcare costs, cost-effectiveness, the clinical value added of placental assessment, improvements in placental pathology education and practice, and leveraging of placental pathology to identify new biomarkers of disease and evaluate novel therapies tailored to specific clinicopathologic phenotypes of both women and infants., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Stillbirth, preterm birth, and small for gestational age (SGA) birth have an increased recurrence risk. The occurrence of one of these biologically related outcomes could also increase the risk for another one of these outcomes in a subsequent pregnancy., Objectives: We assessed cross-outcome risks for subsequent stillbirth, preterm birth, and SGA., Methods: We used live birth and fetal death records to identify singleton, sequential birth pairs in California (1997-2017). Stillbirth was defined as delivery at ≥20 weeks of gestation of a foetus that died in utero; preterm birth as live birth at 20-36 weeks; and small for gestational age as sex-specific birthweight <10th percentile for gestational age. Risk ratios (RR) were computed using modified Poisson regression and adjusted for potential confounders. Sensitivity analyses included analysing a cohort restricted to primiparous index births and using inverse-probability censoring weights., Results: Of 3,108,532 birth pairs, 16,668 (0.5%), 260,596 (8.4%) and 331,109 (10.7%) of index births were stillborn, preterm and SGA, respectively. Among individuals with an index stillbirth, the adjusted RRs were 1.90 (95% confidence interval [CI] 1.83, 1.98) for subsequent preterm and 1.35 (95% CI 1.28, 1.41) for subsequent SGA. Among those with index preterm birth, the adjusted RRs were 2.02 (95% CI 1.92, 2.13) for stillbirth and 1.42 (95% CI 1.41, 1.44) for SGA. Among those with index SGA, the adjusted RRs were 1.54 (95% CI 1.46, 1.63) for stillbirth and 1.45 (95% CI 1.44, 1.47) for preterm birth. Similar results were reported for sensitivity analyses., Conclusions: Individuals experiencing stillbirth, preterm birth, or SGA in one pregnancy had an increased risk of one of these biologically related outcomes in a subsequent pregnancy. These findings could encourage enhanced surveillance for individuals who experience stillbirth, preterm birth, or SGA and desire a subsequent pregnancy., (© 2022 John Wiley & Sons Ltd.)

Reducing protein intake in patients with chronic kidney disease (CKD) limits glomerular stress induced by hyperfiltration and can prevent the progression of kidney disease; data in pregnancy are limited. The aim of this study is to analyze the results obtained in CKD patients who followed a plant-based moderately protein-restricted diet during pregnancy in comparison with a propensity-score-matched cohort of CKD pregnancies on unrestricted diets. A total of 52 CKD pregnancies followed up with a protein-restricted plant-based diet (Torino, Italy) were matched with a propensity score based on kidney function and proteinuria with CKD pregnancies with unrestricted protein intake (Cagliari Italy). Outcomes included preterm (<37 weeks) and very preterm (<34 weeks) delivery and giving birth to a small-for-gestational-age baby. The median age in our cohort was 34 years, 63.46% of women were primiparous, and the median body mass index (BMI) was 23.15 kg/m 2 with 13.46% of obese subjects. No statistical differences were found between women on a plant-based diet and women who were not in terms of age, parity, BMI, obesity, CKD stage, timing of referral, or cause of CKD. No differences were found between the two groups regarding the week of delivery. However, the combined negative outcome (birth before 37 completed gestational weeks or birth-weight centile <10) occurred less frequently in women following the diet than in women in the control group (61.54% versus 80.77%; p = 0.03). The lower risk was confirmed in a multivariable analysis adjusted for renal function and proteinuria (OR: 0.260 [Q1:0.093-Q3:0.724]; p = 0.010), in which the increase in proteinuria from the first to the last check-up before delivery was lower in patients on plant-based diets (median from 0.80 to 1.87 g/24 h; p: ns) than in controls (0.63 to 2.39 g/24 h p <0.0001). Plant-based, moderately protein-restricted diets in pregnancy in patients with CKD are associated with a lower risk of preterm delivery and small-for-gestational-age babies; the effect may be mediated by better stabilization of proteinuria.

Background: The effect of COVID-19 in pregnancy on maternal outcomes and its association with preeclampsia and gestational diabetes mellitus have been reported; however, a detailed understanding of the effects of maternal positivity, delivery mode, and perinatal practices on fetal and neonatal outcomes is urgently needed., Objective: To evaluate the impact of COVID-19 on fetal and neonatal outcomes and the role of mode of delivery, breastfeeding, and early neonatal care practices on the risk of mother-to-child transmission., Study Design: In this cohort study that took place from March 2020 to March 2021, involving 43 institutions in 18 countries, 2 unmatched, consecutive, unexposed women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. COVID-19 in pregnancy was determined by laboratory confirmation and/or radiological pulmonary findings or ≥2 predefined COVID-19 symptoms. The outcome measures were indices of neonatal and perinatal morbidity and mortality, neonatal positivity and its correlation with mode of delivery, breastfeeding, and hospital neonatal care practices., Results: A total of 586 neonates born to women with COVID-19 diagnosis and 1535 neonates born to women without COVID-19 diagnosis were enrolled. Women with COVID-19 diagnosis had a higher rate of cesarean delivery (52.8% vs 38.5% for those without COVID-19 diagnosis, P<.01) and pregnancy-related complications, such as hypertensive disorders of pregnancy and fetal distress (all with P<.001), than women without COVID-19 diagnosis. Maternal diagnosis of COVID-19 carried an increased rate of preterm birth (P≤.001) and lower neonatal weight (P≤.001), length, and head circumference at birth. In mothers with COVID-19 diagnosis, the length of in utero exposure was significantly correlated to the risk of the neonate testing positive (odds ratio, 4.5; 95% confidence interval, 2.2-9.4 for length of in utero exposure >14 days). Among neonates born to mothers with COVID-19 diagnosis, birth via cesarean delivery was a risk factor for testing positive for COVID-19 (odds ratio, 2.4; 95% confidence interval, 1.2-4.7), even when severity of maternal conditions was considered and after multivariable logistic analysis. In the subgroup of neonates born to women with COVID-19 diagnosis, the outcomes worsened when the neonate also tested positive, with higher rates of neonatal intensive care unit admission, fever, gastrointestinal and respiratory symptoms, and death, even after adjusting for prematurity. Breastfeeding by mothers with COVID-19 diagnosis and hospital neonatal care practices, including immediate skin-to-skin contact and rooming-in, were not associated with an increased risk of newborn positivity., Conclusion: In this multinational cohort study, COVID-19 in pregnancy was associated with increased maternal and neonatal complications. Cesarean delivery was significantly associated with newborn COVID-19 diagnosis. Vaginal delivery should be considered the safest mode of delivery if obstetrical and health conditions allow it. Mother-to-child skin-to-skin contact, rooming-in, and direct breastfeeding were not risk factors for newborn COVID-19 diagnosis, thus well-established best practices can be continued among women with COVID-19 diagnosis., (Copyright © 2022. Published by Elsevier Inc.)

Congenital hypothyroidism diagnosed by TSH assessment in bloodspot screening may be overlooked in preterm newborns due to immaturity of the hypothalamus-pituitary-thyroid axis in them. The purpose of the study was to determine the prevalence and causes of hypothyroxinemia in preterm newborns, determined by TSH and FT4 serum concentration measurement, performed on the 3-5 th day of life. We assessed TSH, FT4 and FT3 serum concentration on the 3-5 th day of life in preterm children born at our centre within three consecutive years. We assessed the incidence of hypothyroxinemia, and its cause: primary hypothyroidism, secondary hypothyroidism or low FT4 syndrome - with normal TSH concentration, its dependence - among others - on gestational age (GA), birth body weight (BBW) and being SGA. A total of 525 preterm children were examined. FT4 concentration was decreased in 14.9% of preterm newborns. The most frequent cause of hypothyroxinemia was low FT4 syndrome (79.5%). More than 92% cases of hypothyroxinemia occurred in children born before the 32 nd week and/or with BBW below 1500 g. Thus, every fourth child in these groups had a reduced FT4 concentration. Neonates with hypothyroxinemia were significantly lighter than those with normal FT4. In older and heavier neonates with hypothyroxinemia, serious congenital defects were observed. Neither IVH nor SGA nor twin pregnancies predispose children to hypothyroxinemia. Among newborns with untreated hypothyroxinemia in whom TSH and FT4 assessment was repeated within 2-5 weeks, a decreased FT4 concentration was confirmed in 56.1% of cases. As hypothyroxinemia affects 25% of newborns born before the 32 nd week of gestation and those in whom BBW is less than 1500g, it seems that in this group of children the newborn screening should be extended to measure serum TSH and FT4 concentration between the 3-5 th day of life. In older and heavier neonates, additional serum TSH and FT4 assessment should be limited to children with severe congenital abnormalities but not to all SGA or twins. Despite the fact that the most common form of preterm hypothyroxinemia is low FT4 syndrome, it should be emphasized that FT4 remains lowered on subsequent testing in more them 50% of cases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Stawerska, Nowak-Bednarek, Talar, Kolasa-Kicińska, Łupińska, Hilczer, Gulczyńska and Lewiński.)

Background: The severity of the COVID-19 pandemic is likely to exacerbate mental health problems during the prenatal period and increase the risk of adverse birth outcomes. This review assessed the published literature related to the impacts of prenatal mental health issues on birth outcomes during the COVID-19 pandemic., Methods: This scoping review was conducted using PROSPERO, Cochrane Library, OVID Medline, Ovid EMBASE, OVID PsycInfo, EBSCO CINAHL, and SCOPUS. The search was conducted using controlled vocabulary and keywords representing the concepts "COVID19", "mental health" and "birth outcomes". The main inclusion criteria were peer-reviewed published articles from late 2019 to the end of July 2021., Results and Discussion: After removing duplicates, 642 articles were identified, of which two full texts were included for analysis. Both articles highlighted that pregnant women have experienced increasing prenatal mental health issues during the COVID-19 pandemic and, further, increased the risk of developing adverse births. This scoping review highlighted that there is a lack of research on the impact of prenatal mental health issues on birth outcomes during the pandemic., Conclusion: Given the severity of the COVID-19 pandemic and the burdens of prenatal mental health issues and adverse birth outcomes, there is an urgent need to conduct further research.

Aim: We undertook this study to determine quantitative changes of the placenta, focusing on extravillous trophoblastic cells (EVTs) in pregnancies with intrauterine growth restriction (IUGR) and small for gestational age (SGA) compared to the control group., Methods: Placentas from pregnancies complicated with SGA-IUGR (n = 10) and control group (n = 10) were obtained after cesarean surgery and evaluated using stereological assays after routine tissue processing and Masson's trichrome staining. Mann-Whitney U-test was employed, and the level of statistical significance was set at p <0.05., Results: Our results showed that the volumetric parameters, including the total volume and volume density of chorionic villi, intervillous spaces, blood vessels in chorionic villi, and syncytiotrophoblast, decreased significantly in the SGA-IUGR group compared to control placentas (p <0.05). Also, total volume, number of EVTs, volume, the diameter of cytoplasm, and diameter of the nucleus in these cells were significantly lower in the SGA-IUGR group (p <0.05). In addition, the nucleus to cytoplasm ratio of EVTs was also higher in the SGA-IUGR group (p <0.05)., Conclusions: There are several significant histological and stereological differences in the placenta, particularly its EVTs from the SGA-IUGR group compared to the control group. It seems that histological changes in the placental tissues could be helpful for the retrospective explanations of pregnancy complications., (© 2022 Japan Society of Obstetrics and Gynecology.)

Introduction: Although non-Hispanic Black women have increased risks of adverse birth outcomes compared with non-Hispanic white women in the United States, there is a lack of research specifically focusing on non-Hispanic Black women. Thus, this study's purpose was to evaluate whether place of birth and type of attendant used during labor is associated with having a newborn born small for gestational age (SGA) among non-Hispanic Black Medicaid recipients., Methods: This study used 2017 Natality data from the National Vital Statistics System for non-Hispanic Black women who used Medicaid as a source of payment (N = 322,604). Type of attendant (ie, the medical professional who assisted during childbirth), place of birth (ie, setting where the woman gave birth), maternal factors, and SGA were obtained from birth certificates. We used multivariate logistic regression to investigate the association between place of birth, type of birth attendant, and newborns born SGA., Results: After adjustment, women who used a certified nurse-midwife or other midwife as an attendant during labor had statistically significant decreased odds of having a neonate born SGA compared with those who had a physician as an attendant (odds ratio [OR], 0.69; 95% CI, 0.66-0.71 and OR, 0.68; 95% CI, 0.55-0.85, respectively). Those who gave birth in a birthing center or had planned home births also had statistically significant decreased odds of having a neonate born SGA (OR, 0.52; 95% CI, 0.38-0.69 and OR, 0.37; 95% CI, 0.21-0.66, respectively). However, those who had an unplanned home birth had twice the odds of having a neonate born SGA compared with those who gave birth at a hospital or clinic (OR, 2.00; 95% CI, 1.50-2.64)., Discussion: Given the racial disparity in adverse birth outcomes for non-Hispanic Black women, the observed associations provide justification for future research to determine whether birthing location and birth attendant are related to SGA., (© 2022 by the American College of Nurse-Midwives.)

There is consistent evidence that many of the pregnancy complications that occur late in the second and third trimester can be predicted from an integrated 11-13 weeks visit, where a maternal and fetal assessment are comprehensively performed. The traditional aims of the 11-13 weeks visit have been: establishing fetal viability, chorionicity and dating of the pregnancy, and performing the combined screening test for common chromosomal abnormalities. Recent studies have shown that the first trimester provides important information that may help to predict pregnancy complications, such as preeclampsia and fetal growth restriction, stillbirth, preterm birth, gestational diabetes mellitus and placenta accreta spectrum disorder. The aim of this manuscript is to review the methods available to identify pregnancies at risk for adverse outcomes after screening at 11-13 weeks. Effective screening in the first trimester improves pregnancy outcomes by allowing specific interventions such as administering aspirin and directing patients to specialist clinics for regular monitoring.

Background Women with a history of obstetric complications are at increased risk of cardiovascular disease, but whether they should be specifically targeted for cardiovascular disease (CVD) risk screening is unknown. Methods and Results We used linked data from the Norwegian HUNT (Trøndelag Health) Study and the Medical Birth Registry of Norway to create a population-based, prospective cohort of parous women. Using an established CVD risk prediction model (A Norwegian risk model for cardiovascular disease), we predicted 10-year risk of CVD (nonfatal myocardial infarction, fatal coronary heart disease, and nonfatal or fatal stroke) based on established risk factors (age, systolic blood pressure, total and high-density lipoprotein cholesterol, smoking, antihypertensive use, and family history of myocardial infarction). Predicted 10-year CVD risk scores in women aged between 40 and 60 years were consistently higher in those with a history of obstetric complications. For example, when aged 40 years, women with a history of preeclampsia had a 0.06 percentage point higher mean risk score than women with all normotensive deliveries, and when aged 60 years this difference was 0.86. However, the differences in the proportion of women crossing established clinical thresholds for counseling and treatment in women with and without a complication were modest. Conclusions Findings do not support targeting parous women with a history of pregnancy complications for CVD screening. However, pregnancy complications identify women who would benefit from primordial and primary prevention efforts such as encouraging and supporting behavioral changes to reduce CVD risk in later life.

Objective: Inflammation as a risk factor for preterm birth is well-established. The primary objective of this analysis was to examine whether individual cytokines versus a composite indicator of mid-pregnancy inflammation are significantly associated with risk for adverse birth outcomes., Study Design: A multi-site prospective study was conducted in a socio-demographically diverse cohort of 610 pregnant participants. At a study visit between 12 and 20 6/7 weeks' gestation, low-grade inflammation was measured via log-transformed serum concentrations of the biomarkers IFN-γ, IL-10, IL-13, IL-6, IL-8, TNF-α, and CRP. Principal component analysis (PCA) was used to identify underlying dimensions of inflammatory activity from the seven biomarkers measured. Gestational age and birth weight at delivery were obtained from medical chart review. The associations between inflammatory profiles and birth outcomes were assessed via linear and logistic regression models. Results were compared with those from individual inflammatory biomarkers, and model fit was assessed using Akaike's Information Criterion (AIC)., Results: Principal component analysis analysis yielded a two-factor solution, with the first factor (IF1) composed of IL-8, IL-10, IL-13, IFN-ɣ, and TNF-α, and the second factor (IF2) containing IL-6 and CRP. When adjusted for race, education, BMI, smoking status, gestational age at time of blood draw, and study site, a one standard deviation (SD) increase in IF1 remained significantly associated with a decrease in standardized gestational age (β = -.13, 95% CI: -.21, -.05) and an increase in odds of preterm delivery (OR = 1.46, 95% CI: 1.13, 1.88) (Table 3). A one SD increase in IF2 was similarly associated with a decrease in standardized gestational age at delivery (β = -.13, 95% CI: -.23, -.04) and an increase in odds of preterm delivery (OR: 1.46, 95% CI: 1.04, 2.05). Neither IF1 nor IF2 was associated with measures of fetal growth. AIC identified that IL-6 was a slightly better fit for length of gestation compared to either composite measure, though all performed similarly., Conclusion: Independent of known sociodemographic risk factors, an elevated mid-pregnancy inflammatory profile was associated with a nearly 50% increase in odds of preterm delivery. The composite performed similarly to IL-6. These results suggest that maternal low-grade inflammation is a risk factor for preterm delivery, and that mid-pregnancy inflammatory biomarkers may be useful in predicting risk for preterm delivery., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Poor self-rated health (SRH) at time of childbirth has been associated with adverse birth outcomes. However, it is not known whether prepregnancy SRH contributes to these outcomes or whether SRH is a proxy for some other factors. Therefore, the purpose of this study was to explore the associations between poor SRH before pregnancy and adverse birth outcomes. In addition, maternal characteristics associated with SRH before pregnancy were explored., Methods: A population-based register study encompassing 261 731 deliveries in Sweden between January 2013 and July 2017 was conducted. The associations between poor SRH before pregnancy, rated at first antenatal visit, and the adverse birth outcomes of stillbirth, small for gestational age (SGA), and preterm birth were investigated with logistic regression analyses and presented as crude (OR) and adjusted odds ratios (aOR) with 95% confidence intervals (CI)., Results: Poor SRH before pregnancy was largely characterized by a history of psychiatric care and was associated with stillbirth (OR 1.37, 95% CI 1.04-1.79), SGA birth (OR 1.29, 95% CI 1.19-1.39), and preterm birth (OR 1.41, 95% CI 1.32-1.50). Adjusting for established risk factors for adverse birth outcomes, poor SRH remained associated with SGA birth (aOR 1.16, 95% CI 1.07-1.26) and preterm birth (aOR 1.25, 95% CI 1.17-1.33), but not with stillbirth (aOR 1.08, 95% CI 0.81-1.43)., Conclusions: SRH assessments could be used in early pregnancy to identify women in need of more extensive follow-up, as SRH appears to capture something beyond currently known risk factors for adverse birth outcomes., (© 2021 The Authors. Birth published by Wiley Periodicals LLC.)

Context: It remains unclear if migrants have different odds for adverse outcomes associated with gestational diabetes mellitus (GDM)., Objective: We investigated if the associations between GDM and adverse pregnancy outcomes are modified by country of origin and examined the odds of these outcomes according to GDM status and country of origin., Methods: Data were extracted from a nationwide register-based study of singleton deliveries in Denmark, 2004-2015. We used logistic regression models and tested for interaction., Results: Among the 710 413 singleton deliveries, 2.6% had GDM and 14.4% were immigrants. Country of origin modified the association between GDM and pre-eclampsia, large for gestational age (LGA), and small for gestational age (SGA) but not between GDM and planned or emergency cesarean section and preterm delivery. GDM increased the risk of pre-eclampsia among women from Denmark (OR 1.28; 95% CI, 1.18-1.39), Lebanon (OR 3.34; 95% CI, 1.35-8.26), and Morocco (OR 2.28; 95% CI, 1.16-6.88). GDM was associated with increased odds of LGA among women from most countries, particularly women from Sri Lanka (OR 4.20; 95% CI, 2.67-6.61), and was associated with reduced odds of SGA in some countries. Compared with Danish-born women with GDM, the odds of LGA were significantly lower and the odds of SGA higher among women with GDM from India, Lebanon, Pakistan, Iraq, and Somalia., Conclusions: Our study documents that different immigrant groups have higher odds of different GDM-associated adverse pregnancy outcomes and also among countries of origin often grouped together. This highlights the importance of increased awareness to both immigrant background and GDM status in the clinical assessment., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: It is unclear whether the suggested link between COVID-19 during pregnancy and preeclampsia is an independent association or if these are caused by common risk factors., Objective: This study aimed to quantify any independent association between COVID-19 during pregnancy and preeclampsia and to determine the effect of these variables on maternal and neonatal morbidity and mortality., Study Design: This was a large, longitudinal, prospective, unmatched diagnosed and not-diagnosed observational study assessing the effect of COVID-19 during pregnancy on mothers and neonates. Two consecutive not-diagnosed women were concomitantly enrolled immediately after each diagnosed woman was identified, at any stage during pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed until hospital discharge using the standardized INTERGROWTH-21 st protocols and electronic data management system. A total of 43 institutions in 18 countries contributed to the study sample. The independent association between the 2 entities was quantified with the risk factors known to be associated with preeclampsia analyzed in each group. The outcomes were compared among women with COVID-19 alone, preeclampsia alone, both conditions, and those without either of the 2 conditions., Results: We enrolled 2184 pregnant women; of these, 725 (33.2%) were enrolled in the COVID-19 diagnosed and 1459 (66.8%) in the COVID-19 not-diagnosed groups. Of these women, 123 had preeclampsia of which 59 of 725 (8.1%) were in the COVID-19 diagnosed group and 64 of 1459 (4.4%) were in the not-diagnosed group (risk ratio, 1.86; 95% confidence interval, 1.32-2.61). After adjustment for sociodemographic factors and conditions associated with both COVID-19 and preeclampsia, the risk ratio for preeclampsia remained significant among all women (risk ratio, 1.77; 95% confidence interval, 1.25-2.52) and nulliparous women specifically (risk ratio, 1.89; 95% confidence interval, 1.17-3.05). There was a trend but no statistical significance among parous women (risk ratio, 1.64; 95% confidence interval, 0.99-2.73). The risk ratio for preterm birth for all women diagnosed with COVID-19 and preeclampsia was 4.05 (95% confidence interval, 2.99-5.49) and 6.26 (95% confidence interval, 4.35-9.00) for nulliparous women. Compared with women with neither condition diagnosed, the composite adverse perinatal outcome showed a stepwise increase in the risk ratio for COVID-19 without preeclampsia, preeclampsia without COVID-19, and COVID-19 with preeclampsia (risk ratio, 2.16; 95% confidence interval, 1.63-2.86; risk ratio, 2.53; 95% confidence interval, 1.44-4.45; and risk ratio, 2.84; 95% confidence interval, 1.67-4.82, respectively). Similar findings were found for the composite adverse maternal outcome with risk ratios of 1.76 (95% confidence interval, 1.32-2.35), 2.07 (95% confidence interval, 1.20-3.57), and 2.77 (95% confidence interval, 1.66-4.63). The association between COVID-19 and gestational hypertension and the direction of the effects on preterm birth and adverse perinatal and maternal outcomes, were similar to preeclampsia, but confined to nulliparous women with lower risk ratios., Conclusion: COVID-19 during pregnancy is strongly associated with preeclampsia, especially among nulliparous women. This association is independent of any risk factors and preexisting conditions. COVID-19 severity does not seem to be a factor in this association. Both conditions are associated independently of and in an additive fashion with preterm birth, severe perinatal morbidity and mortality, and adverse maternal outcomes. Women with preeclampsia should be considered a particularly vulnerable group with regard to the risks posed by COVID-19., (Copyright © 2021. Published by Elsevier Inc.)

Obstetrical complications, often referred to as the "great obstetrical syndromes," are among the most common global causes of mortality and morbidity in young women and their infants. However, treatments for these syndromes are underdeveloped compared with other fields of medicine and are urgently needed. This current paucity of treatments for obstetrical complications is a reflection of the challenges of drug development in pregnancy. The appetite of pharmaceutical companies to invest in research for obstetrical syndromes is generally reduced by concerns for maternal, fetal, and infant safety, poor definition, and high-risk regulatory paths toward product approval. Notably, drug candidates require large investments for development with an unguaranteed return on investment. Furthermore, the discovery of promising drug candidates is hampered by a poor understanding of the pathophysiology of obstetrical syndromes and their uniqueness to human pregnancies. This limits translational extrapolation and de-risking strategies in preclinical studies, as available for other medical areas, compounded with limited fetal safety monitoring to capture early prenatal adverse reactions. In addition, the ethical review committees are reluctant to approve the inclusion of pregnant women in trials, and in the absence of regulatory guidance in obstetrics, clinical development programs are subject to unpredictable regulatory paths. To develop effective and safe drugs for pregnancy complications, substantial commitment, and investment in research for innovative therapies are needed in parallel with the creation of an enabling ethical, legislative, and guidance framework. Solutions are proposed to enable stakeholders to work with a common set of expectations to facilitate progress in this medical discipline. Addressing this significant unmet need to advance maternal and possibly perinatal health requires the involvement of all stakeholders and specifically patients, couples, and clinicians facing pregnancy complications in the dearth of appropriate therapies. This paper focused on the key pharmaceutical research and development challenges to achieve effective and safe treatments for obstetrical syndromes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Being born small for gestational age is a strong predictor of the short- and long-term health of the neonate, child, and adult. Variation in the rates of small for gestational age have been identified across population groups in high income countries, including Australia. Understanding the factors contributing to this variation may assist clinicians to reduce the morbidity and mortality associated with being born small. Victoria, in addition to New South Wales, accounts for the largest proportion of net overseas migration and births in Australia. The aim of this research was to analyse how migration was associated with small for gestational age in Victoria., Methods: This was a cross sectional population health study of singleton births in Victoria from 2009 to 2018 (n = 708,475). The prevalence of being born small for gestational age (SGA; <10th centile) was determined for maternal region of origin groups. Multivariate logistic regression analysis was used to analyse the association between maternal region of origin and SGA., Results: Maternal region of origin was an independent risk factor for SGA in Victoria (p < .001), with a prevalence of SGA for migrant women of 11.3% (n = 27,815) and 7.3% for Australian born women (n = 33,749). Women from the Americas (aOR1.24, 95%CI:1.14 to 1.36), North Africa, North East Africa, and the Middle East (aOR1.57, 95%CI:1.52 to 1.63); Southern Central Asia (aOR2.58, 95%CI:2.50 to 2.66); South East Asia (aOR2.02, 95%CI: 1.95 to 2.01); and sub-Saharan Africa (aOR1.80, 95%CI:1.69 to 1.92) were more likely to birth an SGA child in comparison to women born in Australia., Conclusions: Victorian woman's region of origin was an independent risk factor for SGA. Variation in the rates of SGA between maternal regions of origin suggests additional factors such as a woman's pre-migration exposures, the context of the migration journey, settlement conditions and social environment post migration might impact the potential for SGA. These findings highlight the importance of intergenerational improvements to the wellbeing of migrant women and their children. Further research to identify modifiable elements that contribute to birthweight differences across population groups would help enable appropriate healthcare responses aimed at reducing the rate of being SGA.

Background: The prevalence of epilepsy in pregnant women is estimated at 0.3-1%. Anti-epileptic drug (AED) exposure in-utero has been associated with various adverse health outcomes in neonates, including adverse birth weight outcomes., Objective: This review aims to summarize the published evidence on the association between AED exposure in pregnancy and adverse birth weight outcomes METHODS: Studies assessing AED exposure in pregnancy and neonatal birth weight outcomes, including small for gestational age (SGA), low birth weight (LBW), birth weight (BW), length, head circumference, and cephalization index will be identified in MEDLINE®, EMBASE, Cochrane Library, Scopus, Cumulative Index of Nursing and Allied Health Literature (CINAHL), International Pharmaceutical Abstracts (IPA), and Global Health. Open grey, Theses Canada, and ProQuest Dissertations will be used to locate gray literature. Eligible study designs will include both intervention and non-interventional studies. We will not impose any time limit in the review. We will use the Newcastle-Ottawa Scale to assess the methodological quality of observational studies and quasi-experimental studies included in the review. The risk of bias of experimental studies will be appraised using the Cochrane risk-of-bias tool for randomized trials (RoB 2). A meta-analysis will be conducted using a random-effects model., Discussion: The results from this review could improve clinicians' prescribing decisions by highlighting the safest AEDs for women who are pregnant or planning to conceive based on the evidence currently available., Systematic Review Registration: PROSPERO CRD42020192713.

Background: Stressful life events as important stressors have gradually been recognized as the potential etiology that may lead to adverse birth outcomes such as preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA). However, researches on this topic have shown relatively inconsistent results. This systematic review and meta-analysis was performed to synthesize available data on the association between prenatal stressful life events and increased risks of PTB, LBW, and SGA., Methods: Electronic databases were searched from their inception until September 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to assess the association between prenatal stressful life events and PTB, LBW, and SGA using random effects models. In addition, subgroup analyses, cumulative meta-analyses, sensitivity analyses, and publication bias diagnosis were conducted. STATA 14.0 was applied for statistical analyses., Results: Totally 31 cohort studies involving 5,665,998 pregnant women were included. Prenatal stressful life events were associated with a 20% higher risk of PTB (RR = 1.20, 95%CI = 1.10-1.32), a 23% increased risk for LBW (RR = 1.23, 95%CI = 1.10-1.39), and a 14% higher risk of SGA (RR = 1.14, 95%CI = 1.08-1.20). Sensitivity analysis indicated the results were stable., Conclusions: Findings indicated that pregnant women experiencing prenatal stressful life events were at increased risk of PTB, LBW, and SGA. This information provided additional supports that pregnant women experiencing prenatal stressful life events would benefit from receiving assessment and management in prenatal care services., (Copyright © 2021. Published by Elsevier B.V.)

Background: Previous studies have focused on pregnancy outcomes after frozen embryo transfer (FET) performed using different endometrial preparation protocols. Few studies have evaluated the effect of endometrial preparation on pregnancy-related complications. This study was designed to explore the association between different endometrial preparation protocols and adverse obstetric and perinatal complications after FET., Methods: We retrospectively included all FET cycles (n = 12,950) in our hospital between 2010 and 2017, and categorized them into three groups, natural cycles (NC), hormone replacement therapy (HRT) and ovarian stimulation (OS) protocols. Pregnancy-related complications and subsequent neonatal outcomes were compared among groups., Results: Among all 12,950 FET cycles, the live birth rate was slightly lower for HRT cycles than for NC (HRT vs. NC: 28.15% vs. 31.16%, p < 0.001). The pregnancy loss rate was significantly higher in OS or HRT cycles than in NC (HRT vs. NC: 17.14% vs. 10.89%, p < 0.001; OS vs. NC: 16.44% vs. 10.89%, p = 0.001). Among 3864 women with live birth, preparing the endometrium using OS or HRT protocols increased the risk of preeclampsia, and intrahepatic cholestasis of pregnancy (ICP) in both singleton and multiple deliveries. Additionally, OS and HRT protocols increased the risk of low birth weight (LBW) and small for gestational age (SGA) in both singletons and multiples after FET., Conclusion: Compared with HRT or OS protocols, preparing the endometrium with NC was associated with the decreased risk of pregnancy-related complications, as well as the decreased risk of LBW and SGA after FET.

Background: The association of antenatal depression with adverse pregnancy, birth, and postnatal outcomes has been an item of scientific interest over the last decades. However, the evidence that exists is controversial or limited. We previously found that one in five women in Kuwait experience antenatal depressive symptoms. Therefore, the aim of this study was to examine whether antenatal depressive symptoms are associated with preterm birth (PTB), small for gestational age (SGA), or large for gestational age (LGA) babies in this population., Methods: This was a secondary analysis based on data collected in the Transgenerational Assessment of Children's Environmental Risk (TRACER) Study that was conducted in Kuwait. Logistic regression analysis was used to examine whether antenatal depressive symptoms assessed using the Edinburgh Depression Scale (EDS) were associated with preterm birth, small for gestational age, and large for gestational age babies., Results: A total of 1694 women had complete information about the outcomes of interest. Women with depressive symptoms in pregnancy had increased, albeit non-significant, odds of having PTB (OR = 1.41; 95%CI: 0.81, 2.45), SGA babies (OR = 1.26; 0.80, 1.98), or LGA babies (OR = 1.27; 0.90, 1.79). Antenatal depressive symptoms had similar increased odds for the three outcomes even after adjusting for several covariates though none of these reached statistical significance., Conclusions: In the present study, the depressive symptoms in pregnancy did not predict adverse birth outcomes, such as PTB, SGA, and LGA, which adds to the currently non-conclusive literature. However, further research is needed to examine these associations, as the available evidence is quite limited.

The purpose of this study was to explore the impact of maternal thyroid hormone dysfunction in late pregnancy on birth outcomes in a Chinese population. We retrospectively examined hospitalisation records and laboratory data between April 2016 and March 2017 and obtained results from 11,564 consecutive pregnant women with singleton births in which serum thyroid hormone had been examined together with birth outcomes. We assessed the association between maternal thyroid level and dysfunction with adverse birth outcomes based on regression analysis. Hyperthyroidism was associated with an increased risk of preterm birth (PTB, adjusted OR: 2.41, 95% CI: 1.83-3.17) and hypothyroidism was associated with an increased risk of small for gestational age (SGA, adjusted OR: 1.56, 95% CI: 1.10-2.22), while hyperthyroxinaemia was associated with a decreased risk of large for gestational age (LGA, adjusted OR: 0.64, 95% CI: 0.45-0.90). In addition, compared to women with normal FT3 and TSH (≥the 5 th and ≤the 95 th percentiles), women with high free triiodothyronine (FT3 >the 95 th percentile) and low thyroid-stimulating hormone (TSH th percentile) had a 4.02- fold higher risk of PTB (95% CI: 2.05-7.88), and women with low FT3 and high TSH had a 4.22- fold greater risk of SGA (95% CI: 1.59-11.23). Our study supports associations between multiple types of maternal thyroid dysfunction in late pregnancy and adverse birth outcomes.

To investigate the potential associations between visit-to-visit blood pressure variability (VVV) and adverse birth outcomes in pregnancies, 48,209 pregnant women without proteinuria or chronic hypertension before 20 weeks of gestation who delivered live singletons between January 2014 and November 2019 in Taizhou or Taicang cities were recruited. VVV was estimated as the standard deviation and coefficient of variation of blood pressure [i.e., systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP)] measured from 20 weeks of gestation onwards. Pregnant women were classified into four groups according to the corresponding quartiles for each VVV index. It was found that VVV was significantly higher in women with small for gestational age (SGA) or low birth weight (LBW) infants than in their counterparts. Graded associations between VVV categories and poor birth outcomes were observed. In particular, when comparing the women with the highest to the lowest quartiles of standard deviation and coefficient variation of DBP, the odds ratios (95% confidence interval) for SGA was 1.15 (1.06-1.26) and 1.14 (1.05-1.25), respectively. Interestingly, the addition of DBP-VVV to established risk factors improved risk prediction of SGA; DBP-VVV demonstrated modestly superior predictive performance to VVV obtained from SBP or MAP. Similar results were found even among normotensive pregnancies. Our findings indicated that VVV during pregnancy, especially DBP-VVV, was independently associated with poor birth outcomes of pregnancies in East China. The inclusion of DBP-VVV with established risk factors may help in identifying pregnancies at high risk of SGA. Validations are needed.

Observational studies have suggested inconsistent results between maternal seafood consumption and the risk of adverse birth outcomes. We aimed to explore the possible dose-response relationship between seafood consumption during pregnancy and perinatal outcomes. A systematic search was performed with the use of PubMed, Web of Science, Embase and Cochrane Library from inception to October 27, 2019. Random-effects model was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Dose-response meta-analysis was carried out by using generalized least-squares regression and restricted cubic splines. Twenty-one studies with a total of 571641 participants were included in the analyses. A 45 g/day increment in seafood consumption was associated with a reduced risk of low birth weight (LBW) (OR: 0.65, 95% CI: 0.47 to 0.90) and small for gestational age (SGA) (OR: 0.84, 95% CI: 0.71 to 0.98). Additionally, there was a non-linear dose-response relationship between maternal seafood consumption and the risk of preterm birth (PTB), with no further benefit observed when intake above 45 g/day. The results for subtypes of seafood showed a modest J-shaped association between fatty fish and PTB, and the lowest risk was observed with the consumption of 30 g/day. In conclusion, higher total seafood consumption during pregnancy was associated with a lower risk of adverse birth outcomes, but the consumption of fatty fish should not exceed 30 grams per day. These findings could provide substantial evidence for dietary recommendations regarding seafood intake for pregnant women. This review was registered in PROSPERO (CRD42020152912).

Background: As cannabis consumption is increasing globally, including among pregnant women, there is a critical need to understand the effects of cannabis on fetal development and birth outcomes. We had two objectives: to determine 1) the factors associated with self-reported cannabis use in the pre/early-pregnancy period, and 2) whether cannabis use is associated with low birth weight, preterm birth, or small size for gestational age (GA) infants., Methods: Maternal questionnaire and birth outcome data was gathered from 2229 women and 1778 singleton infants in the Ontario Birth Study, a hospital-based prospective cohort study (2013-2019). Women self-reported cannabis use within 3 months of learning their pregnancy status. Multivariable linear and logistic regression was conducted to 1) identify factors associated with cannabis use, and 2) determine the associations between cannabis use with the selected birth outcomes., Results: Cannabis use increased in the cohort over time. Women who reported cannabis use (N = 216) were more likely to be younger and more likely to use alcohol, tobacco, and prescription pain medication, although most did not. These women had infants born at lower average birth weights and had 2.0 times the odds of being small for GA (95% confidence interval: 1.3, 3.3) after multivariable adjustment for socioeconomic factors and other substance use., Conclusion: Our results suggest that women who use cannabis around the time of conception have higher odds of having infants that are small for gestational age. Targeted clinical messaging may be most applicable to women actively trying to conceive.

Research Question: What is the association between congenital adrenal hyperplasia (CAH) and pregnancy, delivery and neonatal outcomes, using a population database cohort., Design: Retrospective study using the Health Care Cost and Utilization Project-Nationwide Inpatient Sample database from 2004-2014. ICD-9 code 255.2 was used to extract the cases of CAH. Pregnancies complicated with CAH were compared with the other pregnancies. All confounding variables were adjusted using multivariate logistic regression, based on any significant differences between the two groups., Results: A total of 9,096,788 deliveries occurred during the study period. Two hundred and ninety-nine pregnant women had CAH. Chorioamnionitis was higher in CAH compared with controls after controlling for risk factors (adjusted OR 2.67, 95% CI 1.17 to 6.06). The rates of caesarean section and maternal infection were also higher in CAH than controls (adjusted OR 2.10, 95% CI 1.44 to 3.07 and adjusted OR 2.63, 95% CI 1.22 to 5.63, respectively). Risk of gestational diabetes and pregnancy-induced hypertension rates were not significantly different in CAH (adjusted OR 1.53, 95% CI 0.91 to 2.58 and adjusted OR 0.87, 95% CI 0.49 to 1.56, respectively). At birth, 8% and 2.2% of the neonates were found to be small for gestational age in the CAH and the control groups, respectively (adjusted OR 3.37, 95% CI 1.86 to 6.11). Congenital anomalies were encountered in 2.7% and 0.4% in the CAH and control groups, respectively (adjusted OR 5.24, 95% CI 2.31 to 11.90)., Conclusions: Women with CAH were at risk of complications and fetal anomalies. Expected increases in rates of hypertension and gestational diabetes were not encountered. These patients will benefit from surveillance to decrease morbidity., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Irisin is an important crosstalk myokine between adipose and muscle tissue. Disorders in irisin secretion can lead to fetal growth abnormalities and even lead to metabolic syndromes in adult life. This study aimed to evaluate the association between irisin level in umbilical cord blood and maternal serum with neonatal birthweight. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline were followed. A comprehensive search of eight databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, CBM, CNKI, WANFANG and VIP) was performed from inception to November 2019. Studies with original date reporting irisin levels in newborns of small for gestational age (SGA) and newborns of large for gestational age (LGA) were included. Additionally, studies reporting correlation coefficients of irisin with birthweight were analyzed. Newcastle-Ottawa score system and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach were applied. Seventeen studies with 1866 participants were included. Pooled analysis indicated decreased cord irisin levels in SGA newborns (MD -10.57, 95 % CI -13.41 to -7.73) and increased irisin levels in LGA newborns (MD 3.80, 95 % CI 1.91-5.70). Umbilical cord irisin level was positively correlated with neonatal birthweight (r = 0.41 95 %CI 0.04 to 0.68). The pooled correlation coefficient of maternal serum irisin with birthweight has no statistical significance. This meta-analysis suggested that the umbilical cord irisin levels were impaired in fetal growth abnormalities. Umbilical cord blood irisin level was positively correlated with birthweight., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to determine whether first trimester trisomy screening (FTS) parameters are affected by alcohol and drug use., Methods: A routine combined FTS including measurements of maternal serum levels of free β-human chorionic gonadotropin subunit (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) were measured at 9-11 weeks of gestation, and fetal nuchal translucency thickness (NTT) at 11-13 weeks of gestation. In total 544 women with singleton pregnancies [71 alcohol and drug abusers, 88 smokers, 168 non-smokers delivering a small for gestational age (SGA) child, and 217 unexposed control women] were assessed., Results: Free β-hCG levels were higher in alcohol and drug abusing than in unexposed pregnant women [mean 1.5 vs. 1.2 multiples of medians (MoM); P = 0.013]. However, stepwise multiple linear regression analyses suggested that smoking could explain increased free β-hCG. Additionally, we observed lower PAPP-A levels in the smoking mothers (0.9 vs. 1.2 MoM; P = 0.045) and in those giving birth to an SGA child compared to the controls (1.1 vs.. 1.2 MoM; P < 0.001). Fetal NTT did not differ significantly between any of the groups., Conclusions: The present study shows increased free β-hCG levels in alcohol and drug abusers, but maternal smoking may explain the result. Maternal serum PAPP-A levels were lower in smoking than non-smoking mothers, and in mothers delivering an SGA child. However, FTS parameters (PAPP-A, free β-hCG and NTT) seem not to be applicable for the use as alcohol biomarkers because of their clear overlap between alcohol abusers and healthy controls.

Background & Aims: An inadequate nutrients intake during pregnancy has been related to an increase of having a small for gestational age (SGA) newborn. A diversity dietary (DD) intake could decrease the risk of SGA delivery, providing the adequate nutrient requirements during pregnancy. The aim of this study was to assess the effect of DD on adequate nutrient intake in a sample of Spanish pregnant women, further to investigate their association on SGA delivery., Methods: A matched case-control study of 518 cases and controls of pregnant women was performed in five hospitals in Eastern Andalusia (Spain). Cases were women with a newborn with SGA. Data about demographic characteristics and diet were collected by trained midwives. DD score (DDS) adjusted by total energy intake was gathered through a validated food frequency questionnaire (FFQ). Nutrient inadequacy was defined as an intake below 2/3 of the recommended dietary intake according to dietary recommendations intake (DRI) for pregnant women. The association between DDS and SGA was assessed by logistic regression models with adjustment for confounding factors., Results: The prevalence of nutrient inadequate intake decreased across total DDS quintiles (p < 0.05). Women in higher strata of total DDS presented less SGA risk (aOR = 0.50, C.I. 95%: 0.31, 0.80). According to each DDS component, the consumption of high diversity of dairy products showed a significative protection against the risk of having a SGA newborn (aOR = 0.48, C.I. 95%: 0.32, 0.71)., Conclusions: SGA mothers had higher prevalence of nutritional inadequacies and lower DDS compared to their counterparts. Poor total DDS and less variety of dairy products were associated with higher risk of SGA newborn. Efforts to promote DD during pregnancy need to be strengthened to reduce the prevalence of SGA in Spain., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: To assess the relationship between history of surgery for endometriosis and adverse obstetrical outcomes., Design: Retrospective study using prospectively recorded data., Setting: Referral center., Patient(s): Total of 569 women with history of surgery for endometriosis, postoperative conception, and pregnancy evolution over 22 weeks of gestation., Interventions(s): Surgery for endometriosis., Main Outcome Measure(s): Small for gestational age (SGA) status of the newborn, spontaneous preterm birth (PT, before 37 weeks' gestation), and placenta previa., Results: Among 733 pregnancies included in the study, 566 deliveries were recorded (77.2%), of which 535 were singleton (72.9% of pregnancies) and 31 twins (4.2%). SGA was observed in 81 of 535 (15.1%) singleton pregnancies and in 9 of 31 (29%) twin pregnancies. PT occurred in 53 of 535 (9.9%) singleton pregnancies and in 19 of 31 (61.2%) twin pregnancies. The number of singleton and multiple pregnancies complicated by placenta previa were, respectively, 9 of 535 (1.7%) and 0 of 31. The independent factor found to relate to SGA was the absence of endometriomas; conception with the use of assisted reproductive technologies (ART) only tended toward statistical significance. Independent factors found to increase risk of PT were conception with the use of ART, body mass index >30 kg/m 2 , and surgery of deep endometriosis infiltrating the rectum and the bladder. Independent factors associated with placenta previa were conception with the use of ART and history of stage III or IV endometriosis., Conclusion(s): The risk of SGA and PT is increased in women with a history of surgery for endometriosis, and a high rate of conception with the use of ART may jeopardize outcomes., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Maternal schizophrenia is associated with adverse birth outcomes, but the reasons for this remain unclear. In a population-based cohort of infants born to women with schizophrenia, we determined the occurrence of key perinatal outcomes and explored whether factors identifiable in our datasets explained any elevated risk., Methods: Using population-level health administrative data linked to clinical birth-registry data in Ontario, Canada (2006-2011), we examined the relative risk (RR) of preterm birth (< 37 weeks), small for gestational age (SGA), and Apgar scores < 8 in infants of women with schizophrenia (n = 4279) versus infants of unaffected women (n = 286,147). Generalized estimating equations determined whether reproductive history, maternal health conditions, pregnancy exposures, and complications explained elevated RRs., Results: Among infants of women with schizophrenia, risk was higher for prematurity (11.4% vs. 6.9%, aRR 1.64, 95% CI 1.51-1.79), SGA (3.5% vs. 2.5%, aRR 1.40, 95% CI 1.20-1.64), and Apgar score < 8 at 1 (19.0% vs. 12.8%, aRR 1.49, 95% CI 1.40-1.59) and 5 min (5.6% vs. 3.0%, aRR 1.90, 95% CI 1.68-2.16). Smoking, fourfold more common among women with schizophrenia, was the variable that explained the greatest proportion of the elevated aRR for prematurity (9.9%), SGA (28.7%), and Apgar < 8 at 1 and 5 min (9.8%, 5.6%). Illicit substance use, certain reproductive history variables, and pregnancy complications also contributed to the elevated aRR for preterm birth., Conclusions: Elevated risks of preterm birth, SGA, and low Apgar scores in infants of women with schizophrenia are partly explained by potentially modifiable factors such as smoking and illicit drug use, suggesting opportunities for targeted intervention.

Iron deficiency is a global problem in women of child-bearing age and is associated with adverse maternal and newborn outcomes. Repeated blood donations deplete iron stores and decrease hemoglobin levels. However, the clinical impact of iatrogenic iron deficiency on mothers and neonates due to blood donation is uncertain. The objective of this study was to assess the association between repeated blood donations in female donors of child-bearing age and the associated risk of adverse maternal and neonatal outcomes. We undertook an observational cohort study of all women who delivered a live or stillborn infant in Ontario, Canada, between 1 January 2010 and 31 March 2012 using birth record data from the Better Outcomes Registry & Network, Canadian Blood Services, and the Institute of Clinical Evaluative Sciences. Only a woman's first pregnancy within the study time frame was included for analysis. We excluded women <18 years or >50 years of age at the time of delivery and multiple birth pregnancies. Data on all female donors who made whole blood donations between 1 January 2007 and 31 March 2012 were obtained from Canadian Blood Services. The primary newborn outcome was diagnosis of a small-for-gestational-age neonate (less than 10th centile). Secondary outcomes were preterm birth, stillbirth, APGAR <4 at 5 minutes, cord pH <7, neonatal death, maternal transfusion, infection, preeclampsia, gestational hypertension, gestational diabetes, placental abruption, and maternal death. Regression models evaluated the effect of repeated donation and the time interval between donations and conception on neonatal and maternal outcomes while adjusting for important clinical and demographic risk factors. A total of 260 037 women delivered live or stillborn singleton infants between 1 January 2010 and 31 March 2012. A total of 7919 (3.0%) women were blood donors, with a mean of 2.43 ± 2.10 lifetime donations. Mean maternal age at the time of delivery for nondonors and donors was 30.30 ± 5.38 and 29.74 ± 4.94 years, respectively. Small for gestational age occurred in 23 706 (9.4%) of neonates born to nondonors and 526 (6.6%) of neonates born to donors. There was a reduction in the risk of small for gestational age with increasing number of lifetime donations (adjusted odds ratio 0.89 [0.86-0.92] per additional donation). For the prespecified secondary outcomes, we observed a reduction in the risk of low birth weight (adjusted odds ratio 0.95 [0.91-0.98] per additional donation). There was no association with other secondary neonatal or maternal outcomes except for maternal hypertension. Proximity of donation to conception had no effect on risk of a small-for-gestational age neonate. Our data suggest that there is no increased risk of deleterious neonatal and maternal outcomes associated with repeated blood donations prior to pregnancy. Although possibly a result of a healthy donor effect, our findings are reassuring to female donors and their children as well as to clinicians and blood system stakeholders seeking to inform policy decisions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to assess whether diet variables can neutralize the risk produced by three well-known risk factors for being small for gestational age: smoking, body mass index (BMI) ˂20 kg/m 2 , and having a previous preterm/low birth weight (LBW) newborn., Methods: A matched case control study was conducted (518 cases and 518 controls of pregnant women) in Spain. We collected data on demographic characteristics, socioeconomic status, toxic habits, and diet. Dietary intake during pregnancy was assessed using a validated food frequency questionnaire, categorized into quintiles. Adjusted odds ratios (aORs) and their 95% confidence intervals (CI) were estimated by conditional regression logistic models., Results: Women who smoked during pregnancy had a 78% increased risk for having an SGA newborn (aOR, 1.78; 95% CI, 1.28-2.74). Lean women (BMI ˂ 20 kg/m 2 before pregnancy) augmented the risk 139% (aOR, 2.39; 95% CI, 1.68-3.40), and those with a previous SGA-LBW an increase of 160% (aOR, 2.60; 95% CI, 1.53-4.37). Smoking in women with a fruit intake of ≥421 g/d was not associated with a higher risk for SGA versus non-smoking women with the same fruit intake (aOR, 0.98; 95% CI, 0.41-2.33). A BMI <20 kg/m 2 with an intake of ≥33 g/d of legumes did not increase the risk for SGA versus women with a BMI ≥20 kg/m 2 with the same legume intake (aOR, 1.35; 95% CI, 0.54-3.37). Diet did not modify the risk by having a previous SGA-LBW newborn., Conclusions: Smoking and leanness increased the SGA risk; nevertheless foods such as fruit, fish, and legumes, as well as intake of vitamins D and B 3 and ω-3 marine fatty acids, may "at" least partially counteract this increase., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Most studies have showed that maternal depression is associated with pregnancy complications. However, there were limited evidences in Chinese population. We examined the associations of antenatal depression symptoms with pregnancy outcomes, especially for low birth weight., Methods: A total of 1377 singleton pregnant women were recruited from Nanshan Maternity & Child Healthcare Hospital of Shenzhen in this prospective cohort study. Depression symptoms were assessed by the Edinburgh postnatal depression scale (EPDS) questionnaire in the second trimester of gestation; cut-points for the indication of antenatal depression were ≧12 scores in this study. Socio-demographic data, life-style and pregnancy outcomes were collected through Shenzhen Maternity & Child Healthcare database. The risks of adverse outcomes in pregnant women with antenatal depression were determined by multivariate logistic regression and represented as odds ratio(OR) and 95% confidence interval (CI)., Results: Of the 1377 subjects, the prevalence of antenatal depression was 19.1%. The EPDS scores were 13.8 ± 2.0 and 6.5 ± 2.9 (P < 0.001) in subjects with and without antenatal depression, respectively. After adjustment for maternal age, education, parity, pre-pregnancy body mass index (BMI), residential area, fetal gender, an EPDS score ≥ 12 (versus. < 12) was associated with an increased risk for low birth weight (odds ratio: 2.05, 95% CI: 1.12-4.64), but not for preterm birth, large for gestational age, small for gestational age or macrosomia., Conclusion: Pregnant women presenting antenatal depressive symptoms are at elevated risk of low birth weight. Mental health problems of pregnancy should be addressed for the prevention of low birth weight.

Aims: To evaluate if neonatal complications or death were poorer for neonates born small for gestational age (SGA) than for those born with adequate weight or large for gestation age (LGA) to women with gestational diabetes mellitus (GDM)., Methods: Retrospective analysis of the clinical outcomes of neonates born to 3413 women with GDM. The prevalence of neonatal hypoglycaemia, hypocalcaemia, hyperbilirubinemia, polycythaemia, and death was compared among three birthweight groups: SGA, adequate, and LGA. A two-sided chi-squared or Fisher's exact test was used for between-group comparisons. A forward multiple logistic regression was performed to determine the odds ratio (OR) associated with SGA., Results: Neonatal complications were more frequent in the SGA group (20.1%) than in the adequate (9.9%) or LGA (15.2%) groups. There were four deaths (1.6%) in the SGA group compared to one in the LGA (0.4%) and six in the adequate (0.2%) groups (P = 0.002). SGA was a risk factor for neonatal complications or death (OR. 2.122; 95% confidence interval, 1.552-2.899), independent of maternal age, weight gain, fasting glucose, glycaemic control, gestational hypertension, pre-eclampsia, smoking, or neonatal prematurity., Conclusion: SGA birthweight is an important risk factor for neonatal complications or death among neonates born to mothers with GDM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We examined the associations of plasma vitamin D concentration and adverse pregnancy outcomes among HIV-negative women in Dar-es-Salaam, Tanzania. We used an unmatched case-control study design, with 25-hydroxyvitamin D [25(OH)D] concentration assessed in the first trimester. Cases were individuals with adverse pregnancy outcomes, including stillbirth, premature birth, or small for gestational age births (SGA). Unconditional logistic regression and weighted logistic regression models were used to describe the associations of 25(OH)D concentration with the composite of adverse pregnancy outcome and individual adverse pregnancy outcomes, respectively. We included 310 cases and 321 controls. In controls, 5(2%) were vitamin D deficient (25(OH)D < 20 ng/mL), and 17(5%) had insufficient 25(OH)D concentration (20.0-29.9 ng/mL). Women with 25(OH)D < 20 ng/mL had 1.82 times the odds of occurrence of the composite adverse pregnancy outcome (OR = 1.82, 95% CI: 0.56-5.93; p = 0.32), however we noted a non-linear association between 25(OH)D concentration and adverse pregnancy outcome ( p = 0.02). We found a 3-fold increased odds of stillbirth in women with low 25(OH)D concentration (OR = 3.11, 95% CI: 1.18-8.23, p = 0.02). Vitamin D concentration in early pregnancy may be an important factor in determining the course of pregnancy. Further research is needed to investigate whether the association of maternal 25(OH)D concentration in early pregnancy and stillbirth is causal.

Objective: To evaluate the association between marijuana use and a composite adverse pregnancy outcome using biological sampling., Design: Retrospective cohort study., Setting: Single tertiary center., Population: Young women (13-22 years old) with singleton, non-anomalous pregnancies delivered from September 2011 to May 2017., Methods: Exposure was defined as marijuana detected on universal urine toxicology testing or by self-report. Multivariable logistic regression modelling was used to estimate the effect of any marijuana use on the primary composite outcome. The effect of marijuana exposure was also estimated for self-reported use, toxicology-detected use, and multiple use detected by toxicology., Main Outcome Measure: The primary composite outcome included spontaneous preterm birth, hypertensive disorders of pregnancy, stillbirth, or small for gestational age., Results: Of 1206 pregnant young women, 17.5% (n = 211) used marijuana. Among the women who used marijuana, 8.5% (n = 18) were identified by self-report alone, 63% (n = 133) by urine toxicology alone, and 28.4% (n = 60) by both. Urine toxicology testing results were available for 1092 (90.5%) births. The composite outcome occurred more frequently in pregnancies exposed to marijuana (46 versus 34%, P < 0.001). This remained significant after adjusting for race/ethnicity and tobacco in the multivariable model (adjusted OR 1.50, 95% CI 1.09-2.05). When marijuana exposure was defined by self-report only, the association with adverse pregnancy outcome became non-significant (adjusted OR 1.01, 95% CI 0.62-1.64)., Conclusion: In a population of young women with nearly universal biological sampling, marijuana exposure was associated with adverse pregnancy outcomes. The heterogeneity of findings in existing studies evaluating the impact of marijuana on mothers and neonates may result from the incomplete ascertainment of exposure., Tweetable Abstract: Marijuana use, as detected by universal urine testing, was associated with a composite adverse pregnancy outcome among young mothers., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Normal maternal thyroid function during pregnancy is essential for fetal development and depends upon an adequate supply of iodine. Little is known about how iodine status is associated with preterm birth and small for gestational age (SGA) in mildly iodine insufficient populations. Our objective was to evaluate associations of early pregnancy serum iodine, thyroglobulin (Tg), and thyroid-stimulating hormone (TSH) with odds of preterm birth and SGA in a prospective, population-based, nested case-control study from all births in Finland (2012-2013). Cases of preterm birth ( n = 208) and SGA ( n = 209) were randomly chosen from among all singleton births. Controls were randomly chosen from among singleton births that were not preterm ( n = 242) or SGA ( n = 241) infants during the same time period. Women provided blood samples at 10-14 weeks' gestation for serum iodide, Tg and TSH measurement. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for preterm birth and SGA. Each log-unit increase in serum iodide was associated with higher odds of preterm birth (adjusted OR = 1.19, 95% CI = 1.02-1.40), but was not associated with SGA (adjusted OR = 1.01, 95% CI = 0.86-1.18). Tg was not associated with preterm birth (OR per 1 log-unit increase = 0.87, 95% CI = 0.73-1.05), but was inversely associated with SGA (OR per log-unit increase = 0.78, 95% CI = 0.65-0.94). Neither high nor low TSH (versus normal) were associated with either outcome. These findings suggest that among Finnish women, iodine status is not related to SGA, but higher serum iodide may be positively associated with preterm birth.