Risk Of Small For Gestational Age Research Articles

Perinatal Outcomes of Singleton, Twin and Triplet Gestations after Oocyte Donation: A Retrospective, Population-Based Cohort Analysis.

Although high live birth rates are associated with oocyte donation (OD), these pregnancies are associated with increased obstetric and perinatal risks. This study evaluated maternal and neonatal risks after OD compared to in vitro fertilization (IVF) with autologous oocytes, and to spontaneous pregnancies (SPs), among singletons, twins and triplets. A retrospective, large, population-based cohort study was conducted based on electronic data from Maccabi Healthcare Services. A total of 469,134 pregnancies were grouped according to the mode of conception. The main outcome measures were preterm birth (PTB), small for gestational age (SGA) and pregnancy-induced hypertension (PIH). The data were analyzed separately for singletons, twins and triplets. The mean maternal age was older in the OD group compared with the IVF and SP groups (singletons: 39.7 ± 4.1 vs. 34.5 ± 4.8 and 31.7 ± 5.3 years; twins: 39 ± 4.6 vs. 32.6 ± 4.4 and 31.2 ± 5.1 years; and triplets: 35.6 ± 2.5 vs. 32 ± 3.9 and 29.7 ± 5 years). The mean gestational age was younger among the OD group compared to the SP group (singletons: 37.5 ± 3 vs. 39 ± 2 p = 0.001, and twins: 35 ± 3 vs. 36 ± 2.5 p = 0.001). Higher rates of PTB < 37, PTB < 34 and PTB < 28 weeks were found among OD singletons. Multivariable logistic regressions for PTB < 37 weeks and SGA in singletons demonstrated that OD and IVF are significant risk factors (OR = 4.1, 95%CI = 3.3-5.2; OR = 4.3, 95%CI = 4.1-4.6; OR = 1.9, 95%CI = 1.3-2.6; OR = 2.2, 95%CI = 2-2.4, respectively). Significantly higher rates of PIH were demonstrated among the OD vs. IVF and SP groups in singleton (4.3% vs. 1.7% and 0.7%) and in twin pregnancies (7.5% vs. 4.3% and 3.4%). OD pregnancies are at increased risk for PTB, SGA and PIH.

The association between maternal fruit consumption before and during pregnancy and fetal growth: The Lanzhou birth cohort study

BackgroundThe association between maternal fruit consumption and fetal growth remains inconsistent. The current study aimed to determine whether maternal fruit consumption was associated with low birth weight (LBW) or small for gestational age (SGA) babies. MethodsA large birth cohort study was conducted in Lanzhou, China, from 2010 to 2012 and included 10,076 pregnant women at the 1st, 2nd, and 3rd trimester of pregnancy for analysis. Fruit consumption in the 1st, 2nd, and 3rd trimester of pregnancy was measured by a self-designed food frequency questionnaire (FFQ) and divided into three groups: 1) inadequate fruit consumption: <200 g/d for the1st, 2nd, and 3rd trimester; 2) adequate fruit consumption: 200–350 g/d for the 1st trimester or 200–400 g/d for the 2nd and 3rd trimester; 3) excessive fruit consumption: >350 g/d for the 1st trimester or > 400 g/d for the 2nd and 3rd trimester. A case-control study was used to analyze the association between fruit intake during pregnancy and low birth weight infants. ResultsCompared to adequate fruit consumption, excessive fruit consumption throughout each trimester of pregnancy was associated with a lower risk of LBW, with an odds ratio (OR) ranging from 0.70 to 0.79 (95 % confidence interval, CI: 0.57–0.98); while inadequate fruit consumption was associated with a higher risk of infant LBW, with an OR ranging from 1.26 to 1.36 (95%CI: 1.04–1.66). After stratifying by mother's pre-pregnancy body mass index (BMI), the results were similar among women with underweight BMI. No significance was found between fruit consumption and SGA in the general population. Still, stratified analyses showed that inadequate fruit consumption was associated with an increased risk of SGA in underweight mothers, with an OR ranging from 1.66 to 1.79 (95%CI: 1.13–2.64). ConclusionsFruit consumption during pregnancy reduces the risk of LBW in Chinese women, especially in women with low pre-pregnancy BMI.

Perinatal Outcomes Associated With Metformin Use During Pregnancy in Women With Pregestational Type 2 Diabetes Mellitus.

We emulated a modified randomized trial (Metformin in Women With Type 2 Diabetes in Pregnancy [MiTy]) to compare the perinatal outcomes in women continuing versus discontinuing metformin during pregnancy among those with type 2 diabetes treated with metformin plus insulin before pregnancy. This study used two health care claims databases (U.S., 2000-2020). Pregnant women age 18-45 years with type 2 diabetes who were treated with metformin plus insulin at conception were eligible. The primary outcome was a composite of preterm birth, birth injury, neonatal respiratory distress, neonatal hypoglycemia, and neonatal intensive care unit admission. Secondary outcomes included the components of the primary composite outcome, gestational hypertension, preeclampsia, maternal hypoglycemia, cesarean delivery, infants large for gestational age, infants small for gestational age (SGA), sepsis, and hyperbilirubinemia. We adjusted for potential baseline confounders, including demographic characteristics, comorbidities, and proxies for diabetes progression. Of 2,983 eligible patients, 72% discontinued use of metformin during pregnancy. The average age at conception was 32 years, and the prevalence of several comorbidities was higher among continuers. The risk of the composite outcome was 46% for continuers and 48% for discontinuers. The adjusted risk ratio was 0.92 (95% CI 0.81, 1.03). Risks were similar between treatments and consistent between databases for most secondary outcomes, except for SGA, which was elevated in continuers only in the commercially insured population. Our findings were consistent with those reported in the MiTy randomized trial. Continuing metformin during pregnancy was not associated with increased risk of a neonatal composite adverse outcome. However, a possible metformin-associated risk of SGA warrants further consideration.

Effect of Mediterranean diet or mindfulness-based stress reduction during pregnancy on placental volume and perfusion: A subanalysis of the IMPACT BCN randomized clinical trial.

The IMPACT BCN trial-a parallel-group randomized clinical trial where 1221 pregnant women at high risk for small-for-gestational age (SGA) newborns were randomly allocated at 19- to 23-week gestation into three groups: Mediterranean diet, Mindfulness-based Stress reduction or non-intervention-has demonstrated a positive effect of Mediterranean diet and Stress reduction in the prevention of SGA. However, the mechanism of action of these interventions remains still unclear. The aim of this study is to investigate the effect of Mediterranean diet and Stress reduction on placental volume and perfusion. Participants in the Mediterranean diet group received monthly individual and group educational sessions, and free provision of extra-virgin olive oil and walnuts. Women in the Stress reduction group underwent an 8-week Stress reduction program adapted for pregnancy, consisting of weekly 2.5-h and one full-day sessions. Non-intervention group was based on usual care. Placental volume and perfusion were assessed in a subgroup of randomly selected women (n = 165) using magnetic resonance (MR) at 36-week gestation. Small placental volume was defined as MR estimated volume <10th centile. Perfusion was assessed by intravoxel incoherent motion. While mean MR placental volume was similar among the study groups, both interventions were associated with a lower prevalence of small placental volume (3.9% Mediterranean diet and 5% stress reduction vs. 17% non-intervention; p = 0.03 and p = 0.04, respectively). Logistic regression showed that small placental volume was significantly associated with higher risk of SGA in both study groups (OR 7.48 [1.99-28.09] in Mediterranean diet and 20.44 [5.13-81.4] in Stress reduction). Mediation analysis showed that the effect of Mediterranean diet on SGA can be decomposed by a direct effect and an indirect effect (56.6%) mediated by a small placental volume. Similarly, the effect of Stress reduction on SGA is partially mediated (45.3%) by a small placental volume. Results on placental intravoxel incoherent motion perfusion fraction and diffusion coefficient were similar among the study groups. Structured interventions during pregnancy based on Mediterranean diet or Stress reduction are associated with a lower proportion of small placentas, which is consistent with the previously observed beneficial effects of these interventions on fetal growth.

Trimester-specific association between fetal growth and physical activity in pregnant women: total physical activity vs moderate-to-vigorous exercise.

To investigate the trimester-specific associations between maternal total physical activity level vs moderate-to-vigorous exercise and fetal growth disorders. We analyzed 2062 mother-neonate pairs participating in the longitudinal China Medical University Birth Cohort Study. The Pregnancy Physical Activity Questionnaire was used to assess the physical activity level of women during the three trimesters. A higher level of total physical activity was defined as meeting or exceeding the cohort-specific 75th percentile, and a higher level of exercise was defined according to the Physical Activity Guidelines for Americans. Fetal growth disorder was defined as small-for-gestational age (SGA) or large-for-gestational age (LGA) at birth. Of the neonates included in this study, 7.1% were SGA and 15.5% were LGA. A higher level of total physical activity during the first trimester (adjusted relative risk (aRR), 0.62 (95% CI, 0.42-0.91)) and second trimester (aRR, 0.62 (95% CI, 0.41-0.95)) was associated with a lower risk of SGA, and a higher level of total physical activity during the third trimester was associated with a lower risk of LGA (aRR, 0.73 (95% CI, 0.54-0.97)). When analyzing physical activity by subtype, a higher level of occupational physical activity during the first and second trimesters was associated negatively with SGA risk, and higher levels of occupational and low-intensity physical activity during the first trimester were associated negatively with LGA risk. No significant association was found between maternal adherence to the Physical Activity Guidelines for Americans and risk of fetal growth disorders. A higher total physical activity level during the first and second trimesters was associated with a decreased risk of SGA, whereas a higher total physical activity level in the third trimester was associated with a decreased risk of LGA. Pregnant women should be advised to increase their total physical activity levels instead of focusing on engaging in only moderate-to-vigorous exercise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes: the Rotterdam Periconception Cohort.

Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population? Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (<p3), compared to women using only FA. Periconceptional maternal FA intake in the general population is associated with increased embryonic and fetal growth, and reduced risks of neural tube defects, other congenital malformations, low birth weight, and neonates born SGA. A prospective tertiary hospital-based cohort study (the Rotterdam Periconceptional Cohort) was conducted from January 2010 to December 2020. We included 1076 women from the Rotterdam Periconceptional Cohort, before 10 weeks of pregnancy with follow-up until delivery. Embryonic growth was assessed by measurement of crown-rump length (CRL) and embryonic volume (EV), and embryonic morphology was described by Carnegie stages using longitudinal three-dimensional ultrasound scans and virtual reality techniques. Birth outcomes were extracted from medical records. General characteristics and supplement use were extracted from research questionnaires. This study showed increased embryonic growth trajectories (adjusted models, CRL: β = 0.052, 95% CI 0.012-0.090, EV: β = 0.022, 95% CI 0.002-0.042) in women using MMS compared to those using only FA. Moreover, a 45% reduced risk of a neonate-born SGA (<p3) was shown in women using MMS compared to FA users (adjusted OR = 0.546, 95% CI 0.308, 0.969). Embryonic morphological development (Carnegie stages) and the occurrence of miscarriages did not differ between women using MMS or solely FA. Following the heterogeneity of the composition and dose of MMS preparations, it is unclear which specific micronutrient, combination, or dose explains the increased embryonic growth trajectory and reduction in risk for SGA. This also hampers the possibility of differentiating between the effects of FA alone or as a component of MMS. Our findings emphasize the importance of periconceptional maternal MMS use as a potential preventative intervention against reduced embryonic growth and neonates born SGA. Therefore, we recommend the periconceptional use of MMS in women at risk of inadequate micronutrient intake. However, awareness of potentially harmful side effects of high doses and combinations of micronutrients is essential, therefore the optimal composition and dose need to be investigated, and careful surveillance is recommended. This research was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and the ZonMw grant Open Competition 2018 (09120011910046). The authors declare that they have no conflict of interest. NTR4356.

Preterm birth among women with HIV: impact of preconception cART initiation.

To examine the risk of preterm birth (PTB) and small for gestational age (SGA) among women with HIV compared to women without HIV. Secondary objectives were to explore the role of maternal immune activation (IA) and effect of cART timing on these outcomes. Prospective observational cohort. Urban government-run clinic at Chawama Hospital in Lusaka, Zambia. A total of 1481 women with and without HIV with singleton pregnancies enrolled before 26 weeks' gestation by ultrasound dating. From August 2019 to November 2022, pregnant women were enrolled in a 1 : 1 ratio of HIV infection. Maternal baseline clinical factors were collected, as well as CD4 + , viral load and CD8 + T-cell IA in women with HIV. Birth outcomes were also collected. The association of HIV-exposure and cART timing on outcomes was assessed by multivariable logistic regression. The independent role of IA was determined by mediation analysis. PTB (<37 weeks) and SGA. There were 38 fetal deaths and 1230 singleton live births. Maternal HIV infection was associated with PTB [adjusted odds ratio (AOR) 1.60, 95% confidence interval (CI) 1.11-2.32] and to a lesser extent SGA (AOR 1.29, 95% CI 0.98-1.70). Maternal cART timing impacted these associations, with highest risk in women who started cART after conception (PTB AOR 1.77, 95% CI 1.09-2.87, SGA AOR 1.52, 95% CI 1.04-2.22). Maternal IA was not associated with PTB independent of HIV infection. HIV is associated with PTB. Risk of PTB and SGA was highest in women with HIV who started cART in pregnancy, a modifiable risk factor.

O-092 Prevalence of multiple gestation births and perinatal outcomes in pregnancies secondary to clomiphene citrate treatment: a nationwide cohort study

Abstract Study question Is the incidence of multiple gestation births higher in pregnancies obtained after clomiphene citrate (CC) treatment compared to spontaneous pregnancies? Summary answer The rate of multiple gestation births in pregnancies obtained after CC treatment is significantly increased compared to spontaneous pregnancies. What is known already CC is a selective estrogen modulator frequently used to induce ovulation in infertile women. Data regarding the prevalence of multiple gestation births and adverse perinatal outcomes after CC are contradicting and based on meta-analysis of small sample size studies. Multiple gestations are frequently associated with complications such as preeclampsia, premature labor, and growth restriction, which contribute to higher mortality and morbidity rates. Study design, size, duration Using the French National Health Data System (SNDS) spanning 2013 to 2019, we conducted a nationwide cohort study including all pregnancies lasting more than 22 weeks of gestation, in women aged between 18-43 years. Participants/materials, setting, methods For each women, the first pregnancy during study was included. Women with the dispensing of IVF/ICSI treatment and/or gonadotrophins were excluded. Pregnancies exposed to CC (during the period [-60days,-11days] before the beginning of the pregnancy) were 1:10 matched to unexposed pregnancies. Pregnancies exposed to CC between 12 to 2months or less than 11 days before the beginning of the pregnancy were excluded to mitigate misclassification bias. The primary outcome was the multiple gestation birth rate. Main results and the role of chance Of 3,173,013 pregnancies, 32,010 (10 ‰) occurred in women exposed to clomiphene. The multiple pregnancy rate was significantly higher in pregnant women exposed with CC compared to matched controls (odd ratio 4.1, 95% CI [3.9-4.3]) such as twin pregnancies (OR 4.1, 95% CI [3.9-4.3]) and triple or more pregnancies (OR 5.1, 95% CI [3.8-7.2]). Women exposed to CC presented significantly more adverse obstetrical and perinatal outcomes, including stillbirths, premature delivery threats, premature rupture of membranes, gestational diabetes, placenta previa, gravid hypertension, pre-eclampsia, preterm birth, small for gestational age (SGA), C-section rate, and major birth defect rate. After stratification on multiple pregnancy and adjustment on confounders (history of psychiatric disease, diabetes, arterial hypertension, obesity and embryo reduction during pregnancy), women exposed to CC had a significantly higher risk of stillbirth, gestational diabetes, placenta previa, pre-eclampsia, preterm delivery and SGA in case of singleton pregnancies. Additionally, in the case of multiple pregnancies, they had a higher risk of placenta previa, preterm delivery, and SGA compared to non-exposed women. Limitations, reasons for caution The use of filled prescriptions as a measure of drug exposure could be subject to bias such as misclassification bias, although we attempt to mitigate it. Wider implications of the findings Clomiphene use is strongly associated with multiple gestation births and with adverse obstetrical and perinatal outcomes even in singleton pregnancies. These findings should provide awareness of practitioners and patients about its use. It underscore the importance of attentively monitoring follicular growth during the treatment process to avoid multiple pregnancies. Trial registration number NA

Association between maternal lipid profiles and vitamin D status in second trimester and risk of LGA or SGA: a retrospective study.

Accumulating evidence has linked dyslipidemia during pregnancy to the risk of delivering infants born either large for gestational age (LGA) or small for gestational age (SGA). However, the effects of the vitamin D status on these relationships require further investigation. This study investigated whether the relationship between lipid profiles and the risk of LGA or SGA was influenced by vitamin D levels during the second trimester. Maternal lipid profile levels, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and vitamin D levels, were measured in a cohort of 6,499 pregnant women during the second trimester. Multivariate regression models and subgroup analyses were employed to evaluate the potential associations between maternal lipid profiles, vitamin D levels, and the risk of LGA or SGA. The prevalence of SGA infants was 9.8% (n=635), whereas that of LGA infants was 6.9% (n=447). Maternal TG levels were found to be positively associated with the risk of LGA (odds ratio [OR] = 1.41, 95% confidence interval [CI]:1.17-1.70), whereas a negative association was observed between maternal TG, TC, LDL-C levels, and risk of SGA. Additionally, mothers with higher HDL-C levels were less likely to give birth to an LGA infant (OR=0.58, 95% CI:0.39-0.85). Importantly, associations between TG, TC, LDL-c, and SGA as well as between TG and LGA were primarily observed among pregnant women with insufficient vitamin D levels. As for HDL-C, the risk of LGA was lower in mothers with sufficient vitamin D (OR = 0.42, 95% CI:0.18-0.98) compared to those with insufficient vitamin D (OR = 0.65, 95% CI:0.42-0.99). Vitamin D status during the second trimester exerts a modifying effect on the association between lipid profiles and the risk of LGA and SGA infants.

Associations of air pollution exposures in preconception and pregnancy with birth outcomes and infant neurocognitive development: analysis of the Complex Lipids in Mothers and Babies (CLIMB) prospective cohort in Chongqing, China

ObjectivesTo investigate the associations of traffic-related air pollution exposures in early pregnancy with birth outcomes and infant neurocognitive development.DesignCohort study.SettingEligible women attended six visits in the maternity clinics of two...

Association between preconception dietary fiber intake and hypertensive disorders of pregnancy: The Japan Environment and Children’s Study

ObjectivesHypertensive disorders of pregnancy (HDP) are a significant cause of morbidity and mortality. This study aimed to investigate whether preconception dietary fiber intake is associated with new-onset HDP. Study designWe identified 84,873 (primipara, 33,712; multipara, 51,161) normotensive participants from the Japan Environmental Children’s Study database who delivered between 2011 and 2014. The participants were subsequently categorized into five groups based on their preconception dietary fiber intake quintiles (Q1–Q5). Main outcome measuresThe main obstetric outcome was HDP, and the secondary obstetric outcomes included early-onset (Eo, <34 weeks)-HDP, late-onset (Lo, ≥34 weeks)-HDP, small for gestational age (SGA) births, and HDP with/without SGA. ResultsMultiple logistic regression analysis showed that in primiparas, the risks of HDP, Lo-HDP, and HDP without SGA were lower in the Q5 group compared with the Q3 group (HDP: adjusted odds ratio [aOR] = 0.73, 95 % confidence intervals [95 % CI] = 0.58–0.93; Lo-HDP: aOR = 0.72, 95 % CI = 0.55–0.94; and HDP without SGA: aOR = 0.68, 95 % CI = 0.53–0.88). However, the risks of Eo-HDP and HDP with SGA were higher in the Q1 group compared with the Q3 group (Eo-HDP: aOR = 1.66, 95 % CI = 1.02–2.70; and HDP with SGA: aOR = 1.81, 95 % CI = 1.04–3.17). In multiparas, the risks of Lo-HDP and SGA were higher in the Q1 group compared with the Q3 group (Lo-HDP: aOR = 1.47, 95 % CI = 1.10–1.97; SGA: aOR = 1.17, 95 % CI = 1.02–1.35). ConclusionsPreconception dietary fiber intake is beneficial in preventing HDP onset. Therefore, new recommendations should be considered to encourage higher dietary fiber intake as part of preconception care.

BMI modifies the effect of pregnancy complications on risk of small- or large-for-gestational-age newborns.

Maternal physical condition (reflected by maternal body mass index (BMI) at delivery) and pregnancy complications influence neonatal health outcomes. High BMI during pregnancy increases various health problems' risks, but studies about the synthesized effect of these factors on fetal growth, are scarce. The retrospective cohort study was conducted in Zhejiang Province, China from 1 January 2019 to 31 December 2021. The associations between complications and small-for-gestational-age (SGA) and large-for-gestational-age (LGA) were measured by the Fine-Gray model and subgroup analysis. Effect modification and interaction analyses were conducted to explore BMI's modification effect and complications' interaction. Several complications increased the risk for SGA and LGA, some significance varied in different subgroups. There was a positive effect modification of gestational diabetes mellitus (GDM) across BMI strata on LGA (relative excess risk due to interaction (RERI) [95% CI] = 0.57 [0.09,1.04]). Several pairwise complications' interactions were synergistic (e.g., pregestational diabetes and intraamniotic infection for SGA (ratio of ORs [95% CI] = 8.50 [1.74,41.37]), pregestational diabetes and assisted reproductive technology (ART) for LGA (ratio of ORs [95% CI] = 2.71 [1.11,6.62])), one was antagonistic (placental problems and ART for LGA (ratio of ORs [95% CI] = 0.58 [0.35,0.96])). High-BMI positively modified the risk of GDM on LGA. Many interactions existed when two specific pregnancy complications occurred simultaneously. This is the largest retrospective study covering more than 10 pregnancy complications to date in this aspect. High-BMI (BMI > 28 kg/m2) positively modifies the risk of GDM on LGA. Many pregnancy complications influence the risk of SGA and LGA, with several interactions that may create a "syndrome" effect. Pregnant women with different BMIs should consider the additional risks caused by pregnancy complications for their heterogeneous effects on abnormal fetal growth. Measures should be taken to prevent the occurrence of other exposure factors in the "syndrome". This study may aid in developing a new strategy for improving neonatal outcomes.

A prospective study on maternal periodontal diseases and neonatal adverse outcomes.

It is evident that periodontitis is linked to various adverse pregnancy outcomes. This prospective study explored the potential link of maternal periodontal diseases to neonatal adverse outcomes. A total of 193 generally healthy females in their third trimester (34-36 weeks) of pregnancy were enrolled. All subjects received full-mouth periodontal assessment, and the periodontal inflamed surface area (PISA) was calculated. Demographic data, lifestyles and anthropometric measurements of the neonates (e.g., body length and head circumference) were recorded. Herein, small-for-gestational age (SGA) referred to gender- and age-adjusted birth weight below the 10th percentile in line with the standard reference. Multivariable logistic regression analysis and restricted cubic spline were performed for examining the association of periodontal parameters with SGA. Results: There were 8.3% (16/193) of neonates with SGA. Significantly positive correlation existed between the percentage of tooth sites with increased probing depth and an elevated risk of SGA (OR: 1.052; P < 0.05). Yet, the PISA was positively associated with the risk of SGA (OR: 1.002; P < 0.05) as well. No significant link occurred between maternal periodontal status and other neonatal outcome measures. Within the limitations of this study, the findings suggest that there could be a link between maternal periodontal diseases and neonatal adverse outcomes like SGA. Further investigation is required to clarify the current findings and potential implications for promoting maternal oral/periodontal health and newborn health.

Association of cord plasma metabolites with birth weight: results from metabolomic and lipidomic studies of discovery and validation cohorts.

Birth weight is a good predictor of fetal intrauterine growth and long-term health. Although several studies have evaluated the relationship between metabolites and birth weight, no prior study has comprehensively investigated the metabolomic and lipidomic and further validated and quantified meaningful metabolites. Firstly, a pseudotargeted metabolomics approach was applied to detect 2418 metabolites in 504 cord blood samples in the discovery set enrolled from the Wuhan Healthy Baby Cohort (HBC), China. Metabolome-wide association scan (MWAS) analysis and pathway enrichment were applied to discover metabolites and metabolic pathways that were significantly associated with birth weight for gestational age (BWGA) z-score. Logistic regression models were used to analyze the association of metabolites in the most significantly associated pathways with small for gestational age (SGA) and low birth weight (LBW). Subsequently, 350 cord blood samples in a validation cohort were subjected to targeted analysis to validate the metabolites screened from the discovery cohort. In the discovery set, 513 metabolites were significantly associated with BWGA z-score (PFDR <0.05), of which 298 KEGG-annotated metabolites were included in the pathway analysis. The primary bile acid biosynthesis pathway was the most relevant metabolic pathway associated with BWGA z-score in our study. Elevated cord plasma primary bile acids were associated with lower BWGA z-score and higher odds of SGA or LBW in the discovery and validation cohorts. In the validation set, a 2-fold increase in taurochenodeoxycholic acid (TCDCA) and taurocholic acid (TCA) was associated with 0.10 (95% CI: 0.00, 0.20) and 0.18 (95 %CI: 0.04, 0.31) decrease in BWGA z-score, respectively, after adjusting for covariates. In addition, a 2-fold increase in cord plasma TCDCA and TCA was associated with an adjusted odds ratio of 1.52 (1.00, 2.30) and 1.77 (1.05, 2.98) for SGA, respectively. The adjusted ORs for a 2-fold increase in TCDCA and TCA concentrations were 2.39 (95% CI 1.00, 5.71) and 3.21 (0.96, 10.74) for LBW, respectively. The results indicate a significant association between primary bile acids and lower BWGA z-score, as well as higher risk of SGA and LBW. Abnormalities of primary bile acid metabolism may play an important role in restricted fetal development. This article is protected by copyright. All rights reserved.

Maternal caffeine intake during pregnancy and the risk of delivering a small for gestational age baby: Kuopio Birth Cohort

PurposeHigh caffeine intake during pregnancy is associated with restricted fetal growth. We aimed to evaluate the association between maternal caffeine intake during early and late pregnancy and the risk of delivering a small for gestational age (SGA) baby.MethodsKuopio Birth Cohort (KuBiCo) is a prospective cohort study including women whose pregnancies and deliveries were treated at the prenatal clinics in outpatient healthcare centers and in Kuopio University Hospital, Finland. Maternal diet and caffeine intake during the first (n = 2007) and third (n = 4362) trimester of pregnancy were assessed using a 160-item food frequency questionnaire (2013–2022). SGA was defined as birth weight corrected for gestational age below − 2 standard deviations from the mean, according to the sex-specific Finnish fetal growth curves.ResultsAltogether in 32 and 38% (1st and 3rd trimester) of all women and in 44 and 52% of coffee drinkers, caffeine intake exceeded the recommendation for caffeine intake (≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le $$\\end{document}200 mg/day) during pregnancy. The women with moderate (51–200 mg/day) (aOR 1.87; 95% CI: 1.16–3.02) and high (> 200 mg/day) (aOR 1.51; 95% CI: 1.08–2.10) caffeine intake during the first trimester were in the highest risk of having an SGA newborn. Caffeine intake in the third trimester of pregnancy was not associated with SGA.ConclusionsModerate and high caffeine intake during early pregnancy is associated with SGA. As the results suggest that even moderate caffeine intake during the first trimester may increase the risk of SGA, the intake within recommendation limits does not necessarily appear to be safe for pregnant women and their newborns.

Association of common maternal infections with birth outcomes: a multinational cohort study.

It is unclear whether common maternal infections during pregnancy are risk factors for adverse birth outcomes. We assessed the association between self-reported infections during pregnancy with preterm birth and small-for-gestational-age (SGA) in an international cohort consortium. Data on 120,507 pregnant women were obtained from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA. Self-reported common infections during pregnancy included influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections, cystitis, urinary tract infection, and the symptoms fever and diarrhoea. Birth outcomes included preterm birth, low birth weight and SGA. Associations between maternal infections and birth outcomes were first assessed using Poisson regression in each cohort and then pooled using random-effect meta-analysis. Risk ratios (RR) and 95% confidence intervals (CI) were calculated, adjusted for potential confounders. Vaginal infections (pooled RR, 1.10; 95% CI, 1.02-1.20) and urinary tract infections (pooled RR, 1.17; 95% CI, 1.09-1.26) during pregnancy were associated with higher risk of preterm birth. Similar associations with low birth weight were also observed for these two infections. Fever during pregnancy was associated with higher risk of SGA (pooled RR, 1.07; 95% CI, 1.02-1.12). No other significant associations were observed between maternal infections/symptoms and birth outcomes. Vaginal infections and urinary infections during pregnancy were associated with a small increased risk of preterm birth and low birth weight, whereas fever was associated with SGA. These findings require confirmation in future studies with laboratory-confirmed infection diagnosis.

Integrated care of diabetes during pregnancy: a Qatari nationwide cohort

Diabetes in pregnancy (DIP) is associated with adverse fetal and maternal outcomes. DIP is classified as either pre-existing or new-onset diabetes mellitus (DM), which is classified into gestational DM (GDM) and newly detected type 2 (N-T2D). All pregnant women in Qatar who are not known to have pre-existing DM are offered screening for DIP during the first antenatal care visit and after 24 weeks gestation. The study aims to report the DIP screening rates, the prevalence of DIP, and the impact of the universal screening program on adverse pregnancy outcomes. This retrospective study included all women who gave birth in Hamad Medical Corporation (HMC) hospitals between 2019 and 2022. New-onset DIP was defined using the WHO-2013 criteria. The primary outcomes were the screening rates and the prevalence of DIP in Qatar. The secondary outcomes were the difference in preterm delivery, C-section, macrosomia, large for gestational age (LGA), small for gestational age (SGA), and intra-uterine fetal death (IUFD) between women with or without GDM. We included 94,422 women who gave birth to 96,017 neonates (85.7%) out of 112,080 neonates born nationwide. The number of women with pre-existing diabetes was 2496 women. Of 91,926 eligible women, 77,372 (84.2%) were screened for DIP. The prevalence of GDM is 31.6% (95% CI: 31.3-32.0%); N-T2D is 2.2% (95% CI: 2.1-2.3%), and pre-existing Type 2 DM and Type 1 DM was 2.6% (95% CI: 0.8-3.0%) and 0.2% (0.19-0.25), respectively. Compared to the non-GDM group, women with GDM were older (30.8±5.3 versus 29.7±5.2 years, p<0.001). After adjusting for age, women with GDM had lower risk of IUFD and SGA (0.63 [95% CI 0.50-0.80, p<0.001], 0.88 [95% CI 0.84-0.92, p<0.001] respectively) but higher risk of C-section and LFD (1.07 [95% CI 1.04-1.10, p<0.001], 1.09 [95% CI 1.01-1.15, p=0.01], respectively, compared to women with no-GDM. Of the women eligible for screening, 84.2% were screened by the DIP program in Qatar. The prevalence of DIP in Qatar is 36.9%. Integrated care is critical for the screening and management of diabetes during pregnancy. The authors did not receive any funding for this project.

Risk of Adverse Perinatal Outcomes Among African-born Black Women in California, 2011-2020.

African-born women have a lower risk of preterm birth and small for gestational age (SGA) birth compared with United States-born Black women, however variation by country of origin is overlooked. Additionally, the extent that nativity disparities in adverse perinatal outcomes to Black women are explained by individual-level factors remains unclear. We conducted a population-based study of nonanomalous singleton live births to United States- and African-born Black women in California from 2011 to 2020 (n = 194,320). We used age-adjusted Poisson regression models to estimate the risk of preterm birth and SGA and reported risk ratios (RR) and 95% confidence intervals (CI). Decomposition using Monte Carlo integration of the g-formula computed the percentage of disparities in adverse outcomes between United States- and African-born women explained by individual-level factors. Eritrean women (RR = 0.4; 95% CI = 0.3, 0.5) had the largest differences in risk of preterm birth and Cameroonian women (RR = 0.5; 95% CI = 0.3, 0.6) in SGA birth, compared with United States-born Black women. Ghanaian women had smaller differences in risk of preterm birth (RR = 0.8; 95% CI = 0.7, 1.0) and SGA (RR = 0.9; 95% CI = 0.8, 1.1) compared with United States-born women. Overall, we estimate that absolute differences in socio-demographic and clinical factors contributed to 32% of nativity-based disparities in the risk of preterm birth and 26% of disparities in SGA. We observed heterogeneity in risk of adverse perinatal outcomes for African- compared with United States-born Black women, suggesting that nativity disparities in adverse perinatal outcomes were not fully explained by differences in individual-level factors.

First trimester maternal tryptophan metabolism and embryonic and fetal growth: the Rotterdam Periconceptional Cohort (Predict Study).

What is the association between first trimester maternal tryptophan (TRP) metabolites and embryonic and fetal growth? Higher 5-hydroxytryptophan (5-HTP) concentrations are associated with reduced embryonic growth and fetal growth and with an increased risk of small-for-gestational age (SGA), while higher kynurenine (KYN) concentrations are associated with a reduced risk of SGA. The maternal TRP metabolism is involved in many critical processes for embryonic and fetal growth, including immune modulation and regulation of vascular tone. Disturbances in TRP metabolism are associated with adverse maternal and fetal outcomes. This study was embedded within the Rotterdam Periconceptional Cohort (Predict Study), an ongoing prospective observational cohort conducted at a tertiary hospital from November 2010 onwards. A total of 1115 women were included before 11 weeks of gestation between November 2010 and December 2020. Maternal serum samples were collected between 7 and 11 weeks of gestation, and TRP metabolites (TRP, KYN, 5-HTP, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid) were determined using a validated liquid chromatography (tandem) mass spectrometry method. Serial 3D ultrasound scans were performed at 7, 9, and 11 weeks of gestation to accurately assess features of embryonic growth, including crown-rump length (CRL) and embryonic volume (EV) offline using virtual reality systems. Fetal growth parameters were retrieved from medical records and standardized according to Dutch reference curves. Mixed models were used to assess associations between maternal TRP metabolites and CRL and EV trajectories. Linear and logistic regression models were utilized to investigate associations with estimated fetal weight (EFW) and birthweight, and with SGA, respectively. All analyses were adjusted for potential confounders. Maternal 5-HTP concentrations and the maternal 5-HTP/TRP ratio were inversely associated with embryonic growth (5-HTP, √CRL: β = -0.015, 95% CI = -0.028 to -0.001; 5-HTP 3√EV: β = -0.009, 95% CI = -0.016 to -0.003). An increased maternal 5-HTP/TRP ratio was also associated with lower EFW and birthweight, and with an increased risk of SGA (odds ratio (OR) = 1.006, 95% CI = 1.00-1.013). In contrast, higher maternal KYN concentrations were associated with a reduced risk of SGA in the unadjusted models (OR = 0.548, 95% CI = 0.320-0.921). Residual confounding cannot be ruled out because of the observational design of this study. Moreover, this study was conducted in a single tertiary hospital, which assures high internal validity but may limit external validity. The novel finding that maternal 5-HTP concentrations are associated with a smaller embryo and fetus implies that disturbances of the maternal serotonin pathway in the first trimester of pregnancy are potentially involved in the pathophysiology of fetal growth restriction. The association between higher maternal KYN concentrations and a reduced risk of SGA substantiate the evidence that the KYN pathway has an important role in fetal growth. More research is needed to delve deeper into the potential role of the maternal TRP metabolism during the periconception period and pregnancy outcome for mother and offspring. This study was funded by the Department of Obstetrics and Gynecology and the Department of Clinical Chemistry of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands. The authors have no competing interests to disclose. N/A.

Factors influencing the occurrence of small for gestational age at different degrees

To investigate the factors influencing the occurrence of small for gestational age (SGA) at different degrees and provide a basis for early identification of severe SGA cases. Neonatal and maternal prenatal information were retrospectively collected from January 2018 to December 2022 at Peking University People's Hospital. The neonates were divided into three groups: severe SGA group (birth weight below the 3rd percentile for gestational age and sex), mild SGA group (birth weight ≥3rd percentile and <10th percentile), and non-SGA group (birth weight ≥10th percentile). An ordered multinomial logistic regression model was used to analyze the factors influencing the occurrence of SGA at different degrees. A total of 14 821 neonates were included, including 258 cases (1.74%) in the severe SGA group, 902 cases (6.09%) in the mild SGA group, and 13 661 cases (92.17%) in the non-SGA group. The proportions of preterm births and stillbirths were higher in the severe SGA group compared to the mild SGA and non-SGA groups (P<0.0125). The proportion of neonatal asphyxia was higher in both the severe SGA and mild SGA groups compared to the non-SGA group (P<0.0125). Ordered multinomial logistic regression analysis showed that maternal pre-pregnancy underweight (OR=1.838), maternal pre-pregnancy obesity (OR=3.024), in vitro fertilization-embryo transfer (OR=2.649), preeclampsia (OR=1.743), connective tissue disease during pregnancy (OR=1.795), nuchal cord (OR=1.213), oligohydramnios (OR=1.848), and intrauterine growth restriction (OR=27.691) were all associated with a higher risk of severe SGA (P<0.05). Maternal parity as a multipara (OR=0.457) was associated with a lower likelihood of severe SGA (P<0.05). Maternal pre-pregnancy underweight, maternal pre-pregnancy obesity, in vitro fertilization-embryo transfer, preeclampsia, connective tissue disease during pregnancy, oligohydramnios, nuchal cord, and intrauterine growth restriction are closely related to the occurrence of more severe SGA. Maternal parity as a multipara acts as a protective factor against the occurrence of severe SGA.