Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID-19) Vaccination.

OBJECTIVE: To evaluate the association between antenatal messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination and risk of adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of individuals with singleton pregnancies with live deliveries between June 1, 2021, and January 31, 2022, with data available from eight integrated health care systems in the Vaccine Safety Datalink. Vaccine exposure was defined as receipt of one or two mRNA COVID-19 vaccine doses (primary series) during pregnancy. Outcomes were preterm birth (PTB) before 37 weeks of gestation, small-for-gestational age (SGA) neonates, gestational diabetes mellitus (GDM), gestational hypertension, and preeclampsia-eclampsia-HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Outcomes in individuals vaccinated were compared with those in propensity-matched individuals with unexposed pregnancies. Adjusted hazard ratios (aHRs) and 95% CIs were estimated for PTB and SGA using a time-dependent covariate Cox model, and adjusted relative risks (aRRs) were estimated for GDM, gestational hypertension, and preeclampsia-eclampsia-HELLP syndrome using Poisson regression with robust variance. RESULTS: Among 55,591 individuals eligible for inclusion, 23,517 (42.3%) received one or two mRNA COVID-19 vaccine doses during pregnancy. Receipt of mRNA COVID-19 vaccination varied by maternal age, race, Hispanic ethnicity, and history of COVID-19. Compared with no vaccination, mRNA COVID-19 vaccination was associated with a decreased risk of PTB (rate: 6.4 [vaccinated] vs 7.7 [unvaccinated] per 100, aHR 0.89; 95% CI, 0.83-0.94). Messenger RNA COVID-19 vaccination was not associated with SGA (8.3 vs 7.4 per 100; aHR 1.06, 95% CI, 0.99-1.13), GDM (11.9 vs 10.6 per 100; aRR 1.00, 95% CI, 0.90-1.10), gestational hypertension (10.8 vs 9.9 per 100; aRR 1.08, 95% CI, 0.96-1.22), or preeclampsia-eclampsia-HELLP syndrome (8.9 vs 8.4 per 100; aRR 1.10, 95% CI, 0.97-1.24). CONCLUSION: Receipt of an mRNA COVID-19 vaccine during pregnancy was not associated with an increased risk of adverse pregnancy outcomes; this information will be helpful for patients and clinicians when considering COVID-19 vaccination in pregnancy.

Placental Histopathological Lesions and Adverse Neonatal Outcomes in Patients with Inflammatory Bowel Diseases- A retrospective Cohort Study.

Inflammatory bowel diseases (IBD) are significantly associated with adverse pregnancy and neonatal outcomes, though the pathomechanism is yet unknown. To investigate the relationship between IBD and adverse pregnancy outcomes by comparing neonatal outcomes and placental histopathology in two matched groups of patients with and without IBD. In this retrospective study, data of all patients who gave birth between 2008-2021 and were diagnosed with IBD were reviewed and compared to a control group matching two control cases for every IBD case. Neonatal outcomes and placental pathology were compared between the groups. Compared to the control group (n=76), the placentas of patients with IBD (n=36) were characterized by significantly lower placental weight (p < 0.001), and higher rates of maternal vascular malperfusion lesions (MVM, p < 0.001) and maternal and fetal inflammatory response lesions (p < 0.001). Neonates of patients with IBD were more frequently small for gestational age (SGA) (p=0.01), with increased rates of need for phototherapy (p = 0.03), respiratory morbidity and NICU admission (p < 0.001 for both outcomes). Multivariate logistic regression analyses adjusting for possible confounders (including maternal age, gestational age, chronic hypertension, smoking, and thrombophilia) confirmed the independent association between IBD and composite MVM lesions (aOR 4.31, p < 0.001), maternal inflammatory responses (aOR 40.22, p < 0.001) and SGA infants (aOR 4.31, p = 0.013). IBD is associated with increased rates of placental histopathological lesions and adverse pregnancy outcomes, including SGA infants. These novel findings imply the role of placental malperfusion and inflammatory processes in pregnancy complications of IBD patients, which should be followed accordingly. Approval of local ethics committee # WOMC-0219-20.

Impact of an integrated health, nutrition, and early child stimulation and responsive care intervention package delivered to preterm or term small for gestational age babies during infancy on growth and neurodevelopment: study protocol of an individually randomized controlled trial in India (Small Babies Trial).

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating. METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata of 1300 preterm and 1300 term SGA infants each to receive the intervention package or routine care. Infants will be followed until 12 months of age. Outcome data will be collected by an independent outcome ascertainment team at infant ages 1, 3, 6, 9, and 12 months and at 2, 6, and 12 months after delivery for mothers. DISCUSSION: The findings of this study will indicate whether providing an intervention that addresses factors known to limit growth and neurodevelopment can offer substantial benefits to preterm or term SGA infants. The results from this study will increase our understanding of growth and development and guide the design of public health programs in low- and middle-income settings for vulnerable infants. TRIAL REGISTRATION: The trial has been registered prospectively in Clinical Trial Registry - India # CTRI/2021/11/037881, Registered on 08 November 2021.

Association between maternal blood or cord blood metal concentrations and catch-up growth in children born small for gestational age: an analysis by the Japan environment and children's study.

BACKGROUND: Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA. METHODS: Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children's Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women's cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders. RESULTS: We studied 4683 mother-child pairings from 103,060 pregnancies included in the Japan Environment and Children's Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children. CONCLUSION: Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children's growth.

Adherence to different forms of plant-based diets and pregnancy outcomes in the Danish National Birth Cohort: A prospective observational study.

INTRODUCTION: The number of people adhering to plant-based diets has been increasing dramatically in recent years, fueled by both environmental and animal welfare concerns. Beneficial or possible adverse consequences of such diets, particularly the most restrictive forms during pregnancy, have been minimally explored. The aim of this prospective observational study was to examine associations between different forms of plant-based diets during pregnancy with birth outcomes and pregnancy complications. MATERIAL AND METHODS: The Danish National Birth Cohort included 100 413 pregnancies to 91 381 women in 1996-2002. The population consisted of 66 738 pregnancies, about which sufficient dietary data were available and included in the study. Dietary and supplemental intake was assessed by Food Frequency Questionnaire in gestational week 25 and women were characterized as fish/poultry-vegetarians, lacto/ovo-vegetarians, vegans or omnivorous, based on their self-report in gestational week 30. Main outcome measures were pregnancy and birth complications, birthweight and small for gestational age. RESULTS: A total of 98.7% (n = 65 872) of participants were defined as omnivorous, whereas 1.0% (n = 666), 0.3% (n = 183) and 0.03% (n = 18) identified themselves as fish/poultry vegetarians, lacto/ovo-vegetarians or vegans, respectively. Protein intake was lower among lacto/ovo-vegetarians (13.3%) and vegans (10.4%) than among omnivorous participants (15.4%). Intake of micronutrients was also considerably lower among vegans, but when dietary supplements were taken into consideration, no major differences were observed. Compared with omnivorous mothers, vegans had a higher prevalence of preeclampsia and their offspring had on average -240 g (95% confidence interval -450 to -30) lower birthweight. CONCLUSIONS: The women reporting that they adhered to vegan diets during pregnancy had offspring with lower mean birthweight and higher risk of preeclampsia compared with omnivorous mothers. Low protein intake might be one plausible explanation for the observed association with birthweight.

Antenatal steroid as an independent risk factor for vitamin K2 deficiency in newborns: A Chinese single-center, retrospective study.

OBJECTIVES: To identified vitamin K2 deficiency rate and risk factors among newborns in China and assess the importance of high-risk maternal intakes of vitamin K2. METHODS: This retrospective study was performed at the Neonatology Department, the Affiliated Hospital of Guangdong Medical University, China. Routinely collected mother-neonate hospitalization data from July 2020 to January 2021 were analyzed. In total, data from 200 neonates who had completed vitamin K2 tests were utilized to assess the prevalence of vitamin K2 deficiency and identify the potential risk factors. According to the vitamin K2 level, the neonates were divided into 2 groups: cases (vitamin K2 deficiency) and controls (no vitamin K2 deficiency). The potential risk factors for vitamin K2 deficiency were evaluated by univariate and multivariate logistic regression. RESULTS: The vitamin K2 level in 24 of the 200 neonates was undetectable (<0.05 ng/mL). The prevalence of low serum vitamin K2 (<0.1 ng/ml) was 33%. Study subjects with antenatal corticosteroids use had an approximately 5-fold greater risk of developing vitamin K2 deficiency. In the univariate analyses, small-for-gestational-age (SGA), caesarean section, maternal gestational diabetes and premature rupture of the membranes were risk factors for vitamin K2 deficiency. In the multivariate logistic regression analysis, high antenatal corticosteroids use, cesarean section, and SGA were independently associated with vitamin K2 deficiency. CONCLUSION: The present study demonstrated that antenatal corticosteroids use is independently associated with vitamin K2 deficiency. This finding highlights the importance of routine vitamin K2 supplementation in late-stage pregnant women and neonates in China.

Exploring Factors Associated with Stunting in 6-Month-Old Children: A Population-Based Cohort Study in Sulawesi, Indonesia.

Stunting in children under the age of two is a significant global concern, particularly in low- and middle-income countries like Indonesia. Intervention efforts often come too late as many of the underlying causal factors have already occurred earlier. While antenatal multiple micronutrient supplements (MMS) have demonstrated positive effects on pregnancy outcomes, their impact on infant growth in the first six months remains inadequately explored in epidemiological studies. This study aims to identify factors associated with stunting at six months in infants whose mothers received MMS. A population-based cohort study was conducted in four subdistricts of Banggai, Indonesia. Pregnant women were recruited in their third trimester and followed up until their children were six months of age. Validated questionnaires were employed to gather data on social determinants of health and diet, and standardised methods were utilised for anthropometric measurements. Stunting was determined based on the WHO child growth standards. The analysis comprised data from 152 mother-child pairs. The prevalence of stunting during early infancy (first two months) was 18.4%, which decreased to 15.8% in later infancy (at six months). Factors such as small-for-gestational-age (AOR = 11.29; 2.73-46.66), preterm birth (AOR = 6.33; 1.25-31.97), short birth length (AOR = 4.31; 1.11-16.78), maternal mid-upper arm circumference (MUAC) below 23.5 cm, and female infants (AOR = 3.27; 95%CI: 1.04-10.27) were associated with stunting at six months. This study highlights that stunting in the first six months is present at birth, with small-for-gestational-age (SGA) as a strong predictor. In addition, there was a trend to improved growth (-0.30 [-0.79 to 0.18]) in infants born to mothers who received MMS supplementation pre-pregnancy rather than during pregnancy, although it was not statistically significant.

Correlation between crown-rump length in the first trimester of pregnancy and neonatal outcomes.

BACKGROUND: To investigate the association of crown-rump length (CRL) during the first trimester of pregnancy with neonatal outcomes. METHODS: A total of 15,524 women with a reliable first day of the last menstrual period and a regular menstrual cycle (28 ± 4 days) were included from January 2015 to November 2016. CRL was measured by ultrasound from 7+0 to 13+6 weeks during pregnancy and transformed to a standard deviation score (SDS) adjusted for gestational age. Linear regression was used to explore risk factors for CRL. A generalised linear model was used to evaluate the association between CRL and neonatal outcomes. RESULTS: In the multivariate analysis, maternal age (0.25 mm, 95% CI = [0.22-0.28], P < 0.001; 0.04 SDS, 95% CI = [0.03-0.04], P < 0.001), multipara (0.30 mm, 95% CI = [0.08-0.52], P = 0.007; 0.04 SDS, 95% CI = [0.00-0.07], P = 0.031) and folic acid supplement use (0.78 mm, 95% CI = [0.49-1.08], P < 0.001; 0.05 SDS, 95% CI = [0.01-0.10], P < 0.019) were positively associated with CRL, while pre-pregnancy BMI (-0.17 mm, 95% CI = [-0.21 to -0.13], P < 0.001; -0.02 SDS, 95% CI = [-0.03 to -0.02], P < 0.001) was negatively related to CRL. For neonatal outcomes, CRL was negatively associated with small for gestational age (SGA) ([risk ratio] (RR) = 0.733, 95% [CI] = 0.673-0.8004, Padjusted < 0.001) and neonatal intensive care unit (NICU) admission ([RR] = 0.928, 95% [CI] = 0.883-0.976, Padjusted = 0.003), and preterm birth ([RR] = 1.082, 95% [CI] = 1.008-1.162, Padjusted = 0.029), but positively related to large for gestational age (LGA) ([RR] = 1.241, 95% [CI] = 1.184-1.301, Padjusted = 0.012). When stratified by pre-pregnancy BMI, the risk of SGA and LGA remained significant in all groups, while the increased risk of preterm birth was only observed in the lean group (BMI < 18.5 kg/m2) and decreased risk of NICU admission rate in the normal group (BMI 18.5-24 kg/m2). CONCLUSIONS: Maternal characteristics were independently associated with CRL in the first trimester, which was negatively related to foetal size, SGA, preterm birth, and admission rate to the NICU, but positively related to LGA.

The association of maternal vaginal bleeding and progesterone supplementation in early pregnancy with offspring outcomes: a prospective cohort study.

BACKGROUND: Progesterone is widely used to improve the adverse pregnancy outcomes related to vaginal bleeding during early pregnancy. However, the evidence of its effectiveness is equivocal. METHODS: Six thousand six hundred fifteen mother-infant pairs from Tongji Maternal and Child Health Cohort (TMCHC) were involved in the study. Information on vaginal bleeding, progesterone administration in early pregnancy were obtained at enrolment. Birth outcomes were obtained from the hospital notes. Body weight of the infants at 12 months of age was collected by telephone interview. Multivariable logistic regression was conducted to estimate the effect of vaginal bleeding and progesterone administration in early pregnancy on birth outcomes and weight status of infants at 12 months of age. RESULTS: 21.4% (1418/6615) participants experienced bleeding in early pregnancy, and 47.5% (674/1418) of them were treated with progesterone. There were no significant associations between progesterone supplementation in early pregnancy and offspring outcomes. Compared to women without bleeding or any therapy, women with bleeding and progesterone therapy experienced increased risk of preterm (OR 1.74, 95% CI 1.21-2.52), and delivering a small-for-gestational-age (SGA) (OR 1.46, 95% CI 1.07-1.98) or low birth weight (LBW) (OR 2.10, 95% CI 1.25-3.51) neonate, and offspring of them had an increased risk of weight for age z-score (WAZ) < -1 at 12 months of age (OR 1.79, 95%CI 1.01-3.19). CONCLUSIONS: Offspring of mothers with bleeding and progesterone therapy were more likely to be a premature, SGA or LBW neonate, and had lower weight at 12 months of age. Progesterone supplementation may have no beneficial effect on improving adverse offspring outcomes related to early vaginal bleeding. TRIAL REGISTRATION: TMCHC was registered at clinicaltrials.gov as NCT03099837 on 4 April 2017.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) I-Cognitive Function and Metabolic Risk.

Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, n = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; p = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, n = 438; aRR 0.94 [0.76, 1.17]; p = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, n = 1406; aRR 0.76 [0.60, 0.97]; p = 0.03), and improved motor scores overall (13 trials, n = 1406; adjusted mean difference 1.57 [0.14, 2.99]; p = 0.03) and in girls not boys (p = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth.

Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) -0.11[95% CI -0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.

Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth - Eight Integrated Health Care Organizations, United States, December 15, 2020-July 22, 2021.

COVID-19 vaccines are recommended during pregnancy to prevent severe maternal morbidity and adverse birth outcomes; however, vaccination coverage among pregnant women has been low (1). Concerns among pregnant women regarding vaccine safety are a persistent barrier to vaccine acceptance during pregnancy. Previous studies of maternal COVID-19 vaccination and birth outcomes have been limited by small sample size (2) or lack of an unvaccinated comparison group (3). In this retrospective cohort study of live births from eight Vaccine Safety Datalink (VSD) health care organizations, risks for preterm birth (<37 weeks' gestation) and small-for-gestational-age (SGA) at birth (birthweight <10th percentile for gestational age) after COVID-19 vaccination (receipt of ≥1 COVID-19 vaccine doses) during pregnancy were evaluated. Risks for preterm and SGA at birth among vaccinated and unvaccinated pregnant women were compared, accounting for time-dependent vaccine exposures and propensity to be vaccinated. Single-gestation pregnancies with estimated start or last menstrual period during May 17-October 24, 2020, were eligible for inclusion. Among 46,079 pregnant women with live births and gestational age available, 10,064 (21.8%) received ≥1 COVID-19 vaccine doses during pregnancy and during December 15, 2020-July 22, 2021; nearly all (9,892; 98.3%) were vaccinated during the second or third trimester. COVID-19 vaccination during pregnancy was not associated with preterm birth (adjusted hazard ratio [aHR] = 0.91; 95% CI = 0.82-1.01). Among 40,627 live births with birthweight available, COVID-19 vaccination in pregnancy was not associated with SGA at birth (aHR = 0.95; 95% CI = 0.87-1.03). Results consistently showed no increased risk when stratified by mRNA COVID-19 vaccine dose, or by second or third trimester vaccination, compared with risk among unvaccinated pregnant women. Because of the small number of first-trimester exposures, aHRs for first-trimester vaccination could not be calculated. These data add to the evidence supporting the safety of COVID-19 vaccination during pregnancy. To reduce the risk for severe COVID-19-associated illness, CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant (including those who are lactating), who are trying to become pregnant now, or who might become pregnant in the future (4).

Postnatal Stature Does Not Largely Mediate the Relation between Adverse Birth Outcomes and Cognitive Development in Mid-Childhood and Early Adolescence in Rural Western China.

BACKGROUND: Preterm birth and fetal growth restriction are associated with linear growth faltering and suboptimal cognitive development in childhood. OBJECTIVES: We aimed to investigate whether and to what extent the associations between adverse birth outcomes and cognitive development in mid-childhood and early adolescence are mediated by postnatal stature. METHODS: We used data from a prospective birth cohort of children born to women who participated in a large cluster-randomized trial of antenatal micronutrient supplementation in rural western China. Children were followed up for anthropometric assessments at 6, 12, and 24 mo of age and in mid-childhood (7-9 y). Cognitive development was assessed in mid-childhood (n = 669) and early adolescence (n = 735; 10-12 y) using the Wechsler Intelligence Scale for Children-IV. We conducted a causal mediation analysis to evaluate the proportion of the association of low birth weight (LBW; <2500 g), small-for-gestational age (SGA; <10th percentile), and preterm birth (<37 weeks of gestation) with cognitive development in mid-childhood and early adolescence that was mediated by postnatal length/height-for-age and -sex z score (LAZ/HAZ) during the first 2 y of life and in mid-childhood. RESULTS: LBW and SGA, but not preterm birth, were associated with lower cognitive test scores in mid-childhood and early adolescence. The proportion of the total association of SGA with adolescent cognitive development that was mediated by LAZ/HAZ at 6, 12, and 24 mo of age and in mid-childhood was 25%, 32%, 32%, and 27%, respectively. The corresponding proportions for LBW were 25%, 32%, 16%, and 24%, respectively. CONCLUSIONS: The association of LBW and SGA with cognitive development in mid-childhood and adolescence is not largely mediated by postnatal stature during the first 2 y of life. Postnatal interventions that address the antecedent causes of poor child growth and development, rather than early childhood growth alone, are more likely to mitigate the risk of suboptimal development among SGA and LBW children. This trial was registered at www.isrctn.com as ISRCTN08850194.

Effects of Mediterranean Diet or Mindfulness-Based Stress Reduction on Prevention of Small-for-Gestational Age Birth Weights in Newborns Born to At-Risk Pregnant Individuals: The IMPACT BCN Randomized Clinical Trial.

Importance: Being born small for gestational age (SGA) is a leading cause of perinatal morbidity and mortality with no effective prevention or therapy. Maternal suboptimal nutrition and high stress levels have been associated with poor fetal growth and adverse pregnancy outcomes. Objective: To investigate whether structured interventions based on a Mediterranean diet or mindfulness-based stress reduction (stress reduction) in high-risk pregnancies can reduce the percentage of newborns who were born SGA and other adverse pregnancy outcomes. Design, Setting, and Participants: Parallel-group randomized clinical trial conducted at a university hospital in Barcelona, Spain, including 1221 individuals with singleton pregnancies (19-23 weeks' gestation) at high risk for SGA. Enrollment took place from February 1, 2017, to October 10, 2019, with follow-up until delivery (final follow-up on March 1, 2020). Interventions: Participants in the Mediterranean diet group (n = 407) received 2 hours monthly of individual and group educational sessions and free provision of extra-virgin olive oil and walnuts. Individuals in the stress reduction group (n = 407) underwent an 8-week stress reduction program adapted for pregnancy, consisting of weekly 2.5-hour sessions and 1 full-day session. Individuals in the usual care group (n = 407) received pregnancy care per institutional protocols. Main Outcomes and Measures: The primary end point was the percentage of newborns who were SGA at delivery, defined as birth weight below the 10th percentile. The secondary end point was a composite adverse perinatal outcome (at least 1 of the following: preterm birth, preeclampsia, perinatal mortality, severe SGA, neonatal acidosis, low Apgar score, or presence of any major neonatal morbidity). Results: Among the 1221 randomized individuals (median [IQR] age, 37 [34-40] years), 1184 (97%) completed the trial (392 individuals assigned to the Mediterranean diet group, 391 to the stress reduction group, and 401 to the usual care group). SGA occurred in 88 newborns (21.9%) in the control group, 55 (14.0%) in the Mediterranean diet group (odds ratio [OR], 0.58 [95% CI, 0.40-0.84]; risk difference [RD], -7.9 [95% CI, -13.6 to -2.6]; P = .004), and 61 (15.6%) in the stress reduction group (OR, 0.66 [95% CI, 0.46-0.94]; RD, -6.3 [95% CI, -11.8 to -0.9]; P = .02). The composite adverse perinatal outcome occurred in 105 newborns (26.2%) in the control group, 73 (18.6%) in the Mediterranean diet group (OR, 0.64 [95% CI, 0.46-0.90]; RD, -7.6 [95% CI, -13.4 to -1.8]; P = .01), and 76 (19.5%) in the stress reduction group (OR, 0.68 [95% CI, 0.49-0.95]; RD, -6.8 [95% CI, -12.6 to -0.3]; P = .02). Conclusions and Relevance: In this randomized trial conducted at a single institution in Spain, treating pregnant individuals at high risk for SGA with a structured Mediterranean diet or with mindfulness-based stress reduction, compared with usual care, significantly reduced the percentage of newborns with birth weight below the 10th percentile. Due to important study limitations, these findings should be considered preliminary and require replication, as well as assessment in additional patient populations, before concluding that these treatments should be recommended to patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03166332.

[The association between calcium supplementation in antenatal childbearing aged women and risk of small for gestational age among neonatal singleton in Shaanxi province].

Objective: This study explored the association between antenatal calcium supplementation in the childbearing aged women and risk of small for gestational age infant (SGA) among singleton in Shaanxi province,China. Methods: Multi-stage random cluster sampling method was employed to collect information about pregnant women, who were pregnant and had definite outcomes, and their infants, from 30 districts (counties) in 2010 to 2013. Information was collected by face-to-face questionnaire survey. Generalized linear mixed models were employed after adjusting covariates. Dependent variable was whether single-birth neonate was SGA, and independent variable was calcium supplementation of childbearing aged women in different pregnant periods. Results: A total of 28 357 childbearing aged women was recruited in this study. The age of these women was (28.08±4.74) years old, of which, 79.28% were rural residents and 60.90% had calcium supplementation intake. There was a number of 12 810 female in singleton neonates. The neonatal birth weight and gestational age were (3.27±0.16) kg and (277.44±8.80) day, respectively. The prevalence of SGA was 11.35% in total, and 10.48% in mothers with maternal calcium supplementation and 12.70% in mothers without maternal calcium supplementation in whole antenatal period. There were statistically significant differences seen in antenatal calcium supplementation within the subgroups of maternal age (whether the mother was an advanced maternal woman), residential area, maternal occupation, maternal parity, maternal education level, and household incomes (P<0.05). After adjusting these covariates, the risk of SGA among childbearing aged women with antenatal calcium supplementation showed 16% decreased risk (OR=0.84, 95%CI: 0.77-0.92). Further analysis of the different antenatal periods showed that calcium supplementation during the second and third trimester had a statistically significant difference in reducing the risk of neonatal SGA (P<0.05). Besides, subgroup analysis showed that there was a statistically significant difference between the perinatal calcium supplementation and the single-born neonates with SGA Significance (P<0.05) in non-advanced women, those who had a low education level and moderate household economic status groups. Conclusion: The risk reduction of SGA among singleton neonates is related to calcium supplementation during antenatal period in Shaanxi province.

Associations between periconceptional lifestyle behaviours and adverse pregnancy outcomes.

BACKGROUND: While the potential adverse outcomes of prenatal exposure to unhealthy lifestyle are widely evidenced, little is known about these exposures in the periconception period. We investigated the associations between lifestyle behaviours and adverse pregnancy outcomes with a unique distinction between preconceptional- and prenatal lifestyle behaviours. METHODS: A secondary analysis took place within a prospective multicentre cohort study in the Netherlands, including 3,684 pregnant women. Baseline characteristics and preconceptional and first trimester lifestyle behaviours were assessed through a self-administered questionnaire in the first trimester. Adverse pregnancy outcomes (hypertensive disorders in pregnancy (HDP), small for gestational age (SGA), gestational diabetes (GDM) and spontaneous preterm birth (sPTB)) were reported by healthcare professionals. Data were collected between 2012 and 2014 and analysed using multivariate logistic regression. RESULTS: Women who are overweight, and especially obese, have the highest odds of developing any adverse pregnancy outcome (adjusted odds ratio (aOR) 1.61 (95 % Confidence Interval (CI) 1.31-1.99) and aOR 2.85 (95 %CI 2.20-3.68), respectively), particularly HDP and GDM. Women who prenatally continued smoking attained higher odds for SGA (aOR 1.91 (95 %CI 1.05-1.15)) compared to the reference group, but these odds decreased when women prenatally quit smoking (aOR 1.14 (95 %CI 0.59-2.21)). Women who did not use folic acid supplements tended to have a higher odds of developing adverse pregnancy outcomes (aOR 1.28 (95 %CI 0.97-1.69)), while women who prenatally started folic acid supplements did not (aOR 1.01 (95 %CI 0.82-1.25)). CONCLUSIONS: Our results indicate that smoking cessation, having a normal body mass index (BMI) and initiating folic acid supplements preconceptionally may decrease the risk of adverse pregnancy outcomes. Therefore, intervening as early as the preconception period could benefit the health of future generations.

Zinc supplementation for improving pregnancy and infant outcome.

BACKGROUND: It has been suggested that low serum zinc levels may be associated with suboptimal outcomes of pregnancy, such as prolonged labour, atonic postpartum haemorrhage, pregnancy-induced hypertension, preterm labour and post-term pregnancies, although these associations have not yet been established. This is an update of a review first published in 1997 and subsequently updated in 2007, 2012 and 2015. OBJECTIVES: 1. To compare the effects on maternal, fetal, neonatal and infant outcomes in healthy pregnant women receiving zinc supplementation versus no zinc supplementation, or placebo. 2. To assess the above outcomes in a subgroup analysis reviewing studies performed in women who are, or are likely to be, zinc-deficient. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (3 July 2020), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials of zinc supplementation versus no zinc supplementation or placebo administration during pregnancy, earlier than 27 weeks' gestation. We excluded quasi-randomised controlled trials. We intended to include studies presented only as abstracts, if they provided enough information or, if necessary, by contacting authors to analyse them against our criteria; we did not find any such studies. DATA COLLECTION AND ANALYSIS: Three review authors applied the study selection criteria, assessed trial quality and extracted data. When necessary, we contacted study authors for additional information. We assessed the certainty of the evidence using GRADE. MAIN RESULTS: For this update, we included 25 randomised controlled trials (RCTs) involving over 18,000 women and their babies. The overall risk of bias was low in half of the studies. The evidence suggests that zinc supplementation may result in little or no difference in reducing preterm births (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.74 to 1.03; 21 studies, 9851 participants; low-certainty evidence). Further, zinc supplementation may make little or no difference in reducing the risk of stillbirth (RR 1.22, 95% CI 0.80 to 1.88; 7 studies, 3295 participants; low-certainty evidence), or perinatal deaths (RR 1.10, 95% CI 0.81 to 1.51; 2 studies, 2489 participants; low-certainty evidence). It is unclear whether zinc supplementation reduces neonatal death, because the certainty of the evidence is very low. Finally, for other birth outcomes, zinc supplementation may make little or no difference to mean birthweight (MD 13.83, 95% CI -15.81 to 43.46; 22 studies, 7977 participants; low-certainty evidence), and probably makes little or no difference in reducing the risk of low birthweight (RR 0.94, 95% CI 0.79 to 1.13; 17 studies, 7399 participants; moderate-certainty evidence) and small-for-gestational age babies when compared to placebo or no zinc supplementation (RR 1.02, 95% CI 0.92 to 1.12; 9 studies, 5330 participants; moderate-certainty evidence). We did not conduct subgroup analyses, as very few studies used normal zinc populations. AUTHORS' CONCLUSIONS: There is not enough evidence that zinc supplementation during pregnancy results in improvements in maternal or neonatal outcomes. Future research to address ways of improving the overall nutritional status of pregnant women, particularly in low-income regions, and not looking at zinc in isolation, should be an urgent priority.

Maternal selenium deficiency during gestation is positively associated with the risks for LBW and SGA newborns in a Chinese population.

BACKGROUND: Maternal selenium (Se) deficiency is associated with some adverse pregnant outcomes. However, it remains controversial whether maternal Se deficiency during gestation enhances the risks for low-birth-weight (LBW) and small-for-gestational-age (SGA) newborns. METHODS: For our cohort study, total 3133 mother-and-infant pairs were selected. Maternal serum Se concentration was detected by graphite furnace atomic absorption spectrometry. According to international references for maternal serum Se concentration, subjects were divided into Se deficiency (<45.0 µg/L), Se insufficiency (45.0-94.9 µg/L) and Se sufficiency (≥95.0 µg/L). RESULTS: There was a positive relation of maternal serum Se concentration in gestation and neonatal birth weight. Further analysis showed that the risks for LBW and SGA in SD group were significantly higher than that in SI and SS group, the adjusted ORs for LBW and SGA newborns were 1.87 (95%CI: 1.02, 3.45; P = 0.04) and 1.47 (95%CI: 1.07, 2.02; P = 0.02) in SI group, and 3.92 (95%CI: 2.03, 7.57; P < 0.001) and 2.77 (95%CI: 1.92, 4.02; P < 0.001) in SD group compared to SS group. In different gender subgroup, positive relations were observed between maternal Se deficiency and the risk for LBW girls, as well as the risks for both SGA girls and boys. CONCLUSION: Maternal Se deficiency in gestation was positively associated with the risk for LBW girls, as well as the risks for both SGA girls and boys.