Higher Risk Of Small For Gestational Age Research Articles

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.

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.

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.

Association between endometrial thickness and birthweight of singletons from vitrified-warmed cycles: a retrospective cohort study

Research questionWhat is the association between endometrial thickness (EMT) and the birthweight of singleton infants born from frozen-thawed embryo transfer cycles? DesignThis retrospective cohort study was conducted from January 2016 to December 2019. Participants were categorized into a natural cycle (NC, n = 8132) group and hormone replacement therapy (HRT, n = 4975) group. Only singleton deliveries were included. The primary outcomes were measures of birthweight and relevant indexes. Multivariable logistic regression and multivariable-adjusted linear regression models that incorporated restricted cubic splines were used. ResultsIn the HRT group, the risk of delivering a small for gestational age (SGA) infant was increased in women with an EMT <8.0 mm (adjusted odds ratio [aOR] 1.85, 95% confidence interval [CI] 1.17–2.91) compared with women with an EMT of 8.0 to <12.0 mm, and increased with an EMT ≥12.0 mm (aOR 1.85, 95% CI 1.03–3.33). An inverted U-shaped relationship was found between EMT and birthweight in women with HRT. No significant differences were shown in birthweight z-score, or being SGA or large for gestational age, in singletons among the three EMT groups in the natural cycles. ConclusionsA thinner endometrium seen in women undergoing HRT cycles was associated with a lower birthweight z-score, as well as a higher risk of SGA. However, no significant association was observed between EMT and birthweight z-score or SGA in the NC group. It is noteworthy that a thicker endometrium was not associated with a higher birthweight in frozen-thawed embryo transfer (FET) cycles. Women with a thin endometrium who achieve pregnancy require specialized attention, particularly if they are undergoing FET with HRT cycles.

Night work during pregnancy and small for gestational age: a Danish nationwide register-based cohort study

ObjectiveThe aim was to investigate the association between night work during pregnancy and risk of having a small for gestational age (SGA) child.MethodsThis cohort study had payroll data with detailed...

Adverse associations between maternal deoxynivalenol exposure and birth outcomes: a prospective cohort study in China

BackgroundDeoxynivalenol (DON), one of the most prevalent mycotoxins, has been found to cause fetal growth retardation in animals. However, limited evidence exists regarding its effects on pregnant women.MethodsMaternal urinary concentration of total DON (tDON) and free DON (fDON) in the second trimester was measured using liquid chromatography with tandem mass spectrometry. Provisional daily intake (PDI) of DON was calculated based on tDON concentration. Linear and logistic regression models were used to evaluate the association between DON exposure levels and birth weight, birth length, and the risk of small for gestational age (SGA).ResultsAmong 1538 subjects, the median concentrations of tDON and fDON were 12.1 ng/mL and 5.1 ng/mL, respectively. The PDI values revealed that the median DON intake was 0.7 µg/kg bw, and 35.9% of the total population exceeded the provisional maximum tolerable daily intake (PMTDI) of 1 µg/kg bw. Compared with the lowest tertile, birth weight decreased by 81.11 g (95% CI: -127.00, -35.23) for tDON (P-trend < 0.001) and 63.02 g (95% CI: -108.72, -17.32) for fDON (P-trend = 0.004) in the highest tertile. Each unit increase in Ln-tDON and Ln-fDON was also inversely associated with birth weight. Furthermore, compared to those who did not exceed PMTDI, pregnant women whose PDI exceeded PMTDI had lower birth weight (β = -79.79 g; 95% CI: -119.09, -40.49) and birth length (β = -0.21 cm; 95% CI: -0.34, -0.07), and a higher risk of SGA (OR = 1.48; 95% CI: 1.02, 2.15) in their offspring. Similar associations with birth weight, birth length, and SGA were found when comparing the highest tertile of PDI to the lowest tertile (all P-trend < 0.05).ConclusionsMaternal DON exposure is related to decreased birth weight. Our findings implicate that DON exposure during pregnancy may cause fetal growth faltering, and measures should be taken to reduce DON exposure in pregnant women.

Associations of Ambient Fine Particulate Matter and Its Chemical Constituents with Birth Weight for Gestational Age in China: A Nationwide Survey.

This study examined the associations of fine particulate matter (PM2.5) and its chemical constituents with risks of small for gestational age (SGA) and large for gestational age (LGA). Based on the China Labor and Delivery Survey, we included 70,206 birth records from 24 provinces in China. Concentrations of PM2.5 mass and six main constituents were estimated using satellite-based models. Logistic regression analysis was used to examine the associations, adjusted for sociodemographic characteristics and time trends. We found that an interquartile range increase in PM2.5 exposure during pregnancy was associated with 16% (95% confidence interval [CI]: 3-30%) and 11% (95% CI: 1-22%) higher risk of SGA and LGA, respectively. Elevated risk of SGA was associated with exposure to black carbon [odds ratio (OR) = 1.15, 95% CI: 1.00-1.32], ammonium (OR = 1.12, 95% CI: 1.01-1.25), and sulfate (OR = 1.12, 95% CI: 1.04-1.21); while increased risk of LGA was associated with exposure to black carbon (OR = 1.13, 95% CI: 1.02-1.26), ammonium (OR = 1.13, 95% CI: 1.03-1.24), sulfate (OR = 1.08, 95% CI: 1.01-1.15), and nitrate (OR = 1.14, 95% CI: 1.03-1.27). Our findings provide evidence that PM2.5 exposure was associated with increased risks of SGA and LGA, and constituents related to emissions from anthropogenic sources may play important roles in these associations.

Association of Maternal Longitudinal Hemoglobin with Small for Gestational Age during Pregnancy: A Prospective Cohort Study.

Background: Few studies have investigated the association of maternal longitudinal hemoglobin (Hb) with small for gestational age during pregnancy. The current study examined the associations of maternal Hb concentrations and Hb changes throughout the middle and late stages of pregnancy with small for gestational age (SGA) in a large prospective cohort study. Methods: This was a prospective cohort study, which enrolled pregnant women at 8–16 weeks of gestation and followed up regularly. Maternal Hb concentrations were measured at the middle (14–27 weeks) and late (28–42 weeks) stages of pregnancy, and the Hb change from the middle to late stage of pregnancy was assessed. The Log-Poisson regression model was used to identify the association of maternal Hb with SGA, including the implications of Hb during specific pregnancy periods and Hb change across the middle to late stages of pregnancy. Of the total 3233 singleton live births, 208 (6.4%) were SGA. After adjusting for potential confounders, compared with Hb 110–119 g/L, Hb ≥ 130 g/L at late pregnancy was significantly associated with a higher risk of SGA (adjusted RR: 2.16; 95% CI: 1.49, 3.13). When Hb changes from the middle to late stages of pregnancy were classified by tertiles, the greatest change in the Hb group (<−6.0 g/L) was significantly associated with a lower risk of SGA (adjusted RR: 0.56; 95% CI: 0.37, 0.85) compared with the intermediate group (−6.0~1.9 g/L). In conclusion, for women at low risk of iron deficiency, both higher Hb concentrations in late pregnancy and less Hb reduction during pregnancy were associated with an increased risk of SGA.

Effects of household environmental exposure and ventilation in association with adverse birth outcomes: A prospective cohort study in rural China

Prenatal exposure to outdoor air pollution have been associated with birth outcomes. However, there is limited evidence on the adverse effects of household indoor air pollution worldwide, much less in rural areas of China. This study aimed to explore the associations of household environmental factors (primary cooking fuel, housing renovation, and home ventilation) with four adverse birth outcomes (preterm birth (PTB), small for gestational age (SGA), low birth weight (LBW), and term low birth weight (T-LBW)). We conducted a cohort study involving 10,324 pregnancies in women who delivered a live-born infant from 2015 to 2018 in Guangxi, China. Risk ratios and 95% confidence intervals (CI) were estimated with control for reproductive history, lifestyle, home environmental confounders, and other potential confounders. A total of 5.4% of the infants were PTB, 10.7% were SGA, 5.5% had LBW, and 3.0% had T-LBW. Household-use induction cookers as the primary cooking fuel during pregnancy was associated with SGA (RR = 1.31, 95% CI: 1.07–1.60), LBW (1.41, 1.09–1.82), and T-LBW(1.62, 1.16–2.26), as compared with household-use gas as the primary cooking fuel. Housing renovation within one year before pregnancy was associated with PTB (1.45, 1.06–1.98) and LBW (1.56, 1.17–2.09), while housing renovation during pregnancy was associated with a higher risk of SGA only in moderate home ventilation conditions (3.74, 1.69–8.28). Our findings suggested that household-use induction cookers as the primary cooking fuel increased the risks of SGA, LBW, and T-LBW. In addition, housing renovation within one year before pregnancy increased the risks of PTB and LBW. Proper home ventilation may reduce the effect on the association between housing renovation during pregnancy and SGA.

Adverse perinatal outcomes following the prenatal diagnosis of isolated single umbilical artery in singleton pregnancies: a systematic review and meta-analysis.

A systematic review and meta-analysis was conducted to quantitatively synthesize the current evidence on the association of prenatally diagnosed isolated single umbilical artery (iSUA) in singleton pregnancies with small for gestational age (SGA) neonates and other perinatal outcomes. A search of PubMed/Medline, Scopus and The Cochrane Library was conducted, from inception to February 2021, in order to identify studies comparing the risk of SGA and other perinatal adverse outcomes in prenatally diagnosed iSUA singleton pregnancies vs. those with a 3-vessel cord (3VC). The quality of eligible studies was assessed according to the improved Newcastle-Ottawa Scale (NOS). The heterogeneity of results across the studies was tested using the I2 test. Funnel plots and Egger's test were used to assess the possibility of publication bias. Prospero RN: CRD42020182586. The electronic search identified 7,605 studies, of which 11 were selected, including three retrospective cohort and eight retrospective case control studies, overall reporting on 1,533 iSUA cases. The risk of delivering SGA neonates was increased in cases with iSUA (OR: 2.90; 95% CI: 2.02-4.18; p<0.00001; I2=71%). Similarly, iSUA was associated with an increased risk of pregnancy-induced hypertension (PIH) (OR: 2.23; 95% CI: 1.41-3.54; p<0.000; I2=1%), intrauterine death (IUD) (OR: 2.62; 95% CI: 1.43-4.79; p=0.002; I2=0%), preterm birth (PTB) (OR: 2.48; 95% CI: 1.73-3.56; p<0.00001; I2=56%), cesarean section (CS) (OR: 1.64; 95% CI: 1.11-2.41; p=0.01; I2=78%) and admission to neonatal intensive care unit (NICU) (OR: 2.28; 95% CI: 1.52-3.44; p<0.000001; I2=73%). In prenatally diagnosed iSUA there is a higher risk of SGA, PIH, IUD, PTB, CS and NICU admission. These findings support the value of prenatal diagnosis of iSUA, which may subsequently intensify surveillance for the detection of specific pregnancy complications.

Association between endometrial thickness and birth weight in fresh IVF/ICSI embryo transfers: a retrospective cohort study of 9273 singleton births

Research questionWhat is the association between endometrial thickness (EMT) on HCG trigger day and outcomes related to birth weight in fresh IVF and intracytoplasmic sperm injection (ICSI) embryo transfer cycles? DesignA retrospective cohort study of 9273 singleton live births born to women undergoing fresh IVF/ICSI cycles in a single centre between January 2014 and December 2018. Multivariable logistic regression was used to investigate the associations between EMT, low birth weight (LBW) and small for gestational age (SGA). Multivariable-adjusted linear regression models incorporating restricted cubic splines were used to investigate the dose-response relationship between EMT, birth weight and birth weight z-score, respectively. An EMT of 8 mm was set as a reference value. ResultsCompared with women with an EMT of 8.0 to < 14.0 mm the risk of delivering a SGA infant was increased with EMT < 8.0 mm (adjusted odds ratio [aOR] 1.78, 95% confidence interval [CI] 1.09 to 2.90) and decreased with EMT ≥ 14.0 mm (aOR 0.57, 95% CI 0.35 to 0.93, respectively). Birth weights of infants born to women with an EMT of 8.0 mm compared with women with EMT of 5.0, 6.0, and 7.0 mm were lower by 120 g (95% CI –175 g to –66 g), 80 g (95% CI –116 g to –44 g), and 40 g (95% CI –58 g to –22 g) respectively; infant birth weight z-scores were also decreased by 0.19 (95% CI –0.27 to –0.10), 0.12 (95% CI –0.18 to –0.07) and 0.06 (95% CI –0.09 to –0.03), respectively. ConclusionsA thinner endometrium was associated with lower birth weight and birth weight z-score, and higher risk of SGA. Women with a thin endometrium warrant special attention during pregnancy.

Abstract P169: Association Between Years Of Residency In The Usa Of Hispanic Immigrant Women And Small For Gestational Age

Maternal and fetal factors have been associated with small for gestational age (SGA) and cardiometabolic disease in adulthood. Acculturation in US Latino population has been correlated with negative effects on health, including during perinatal period. We hypothesized that acculturated Hispanic pregnant women have higher risk of SGA. Methods: Retrospective study from PeriBank participants born in Latin America. Length of stay (LOS) as proxy for acculturation. SGA defined as birth weight for gestational age &lt;10 th . Results: We included 13,613 women with 15,376 deliveries. Women with LOS &gt;6y showed higher gestational diabetes rates. (Table1) After adjustment, risk of SGA was lower for LOS 4-6y vs. 0-3y; risk was also lower for LOS &gt;6y vs. 0-3y. (Table2) Women with LOS 4-6y had a 1.12kg/m 2 [95% CI 0.84 - 1.39; p-value &lt;0.001] and &gt;6y 3.06kg/m 2 [95% CI 2.78 - 3.32; p&lt;0.001] higher BMI compared to LOS of 0-3 after adjustment. Conclusions: Highly acculturated Hispanic women born outside the US, do not have higher risk for having SGA offspring. Likely masked by higher pre-pregnancy BMI and gestational diabetes, alternative pathways for adverse perinatal outcomes.

Impact of Chronic Hypertension and Antihypertensive Treatment on Adverse Perinatal Outcomes: Systematic Review and Meta-Analysis.

BackgroundMaternal chronic hypertension is associated with adverse pregnancy outcomes. Previous studies examined the association between either chronic hypertension or antihypertensive treatment and adverse pregnancy outcomes. We aimed to synthesize the evidence on the effect of chronic hypertension/antihypertensive treatment on adverse pregnancy outcomes.Methods and ResultsMedline/PubMed, EMBASE, and Web of Science were searched; we included observational studies and assessed the effect of race/ethnicity, where possible, following a registered protocol (CRD42019120088). Random‐effects meta‐analyses were used. A total of 81 studies were identified on chronic hypertension, and a total of 16 studies were identified on antihypertensive treatment. Chronic hypertension was associated with higher odds of preeclampsia (adjusted odd ratio [aOR], 5.43; 95% CI, 3.85–7.65); cesarean section (aOR, 1.87; 95% CI, 1.6–2.16); maternal mortality (aOR, 4.80; 95% CI, 3.04–7.58); preterm birth (aOR, 2.23; 95% CI, 1.96–2.53); stillbirth (aOR, 2.32; 95% CI, 2.22–2.42); and small for gestational age (SGA) (aOR, 1.96; 95% CI, 1.6–2.40). Subgroup analyses indicated that maternal race/ethnicity does not influence the observed associations. Women with chronic hypertension on antihypertensive treatment (versus untreated) had higher odds of SGA (aOR, 1.86; 95% CI, 1.38–2.50).ConclusionsChronic hypertension is associated with adverse pregnancy outcomes, and these associations appear to be independent of maternal race/ethnicity. In women with chronic hypertension, those on treatment had a higher risk of SGA, although the number of studies was limited. This could result from a direct effect of the treatment or because severe hypertension during pregnancy is a risk factor for SGA and women with severe hypertension are more likely to be treated. The effect of antihypertensive treatment on SGA needs to be further tested with large randomized controlled trials.

Association between pre-pregnancy BMI and neonatal weight outcomes in twin pregnancies resulting from assisted reproductive technology: a 10-year cohort study.

To examine the effect of pre-pregnancy maternal body mass index (BMI) on neonatal weight outcomes of twin infants who were conceived by assisted reproductive technology (ART). A 10-year (2006-2015) Chinese sample of 3431 mothers and their twin infants conceived by ART from a retrospective cohort were included. The effects of pre-pregnancy maternal BMI on gestational age and birth weight were assessed by generalized linear model and generalized estimating equation model. Compared with a normal weight group, pre-pregnancy maternal underweight was associated with lower birth weight and increased risk of small for gestational age (SGA) in twins conceived by ART (birth weight: difference -59.22 g, 95% CI -93.16 to -25.27 g; SGA: RR 1.25, 95% CI 1.09 to 1.43). Pre-pregnancy maternal obesity was associated with higher birth weight and increased risk of preterm birth (birth weight: difference 65.82 g, 95% CI 10.66 to 120.99 g; preterm birth: RR 1.19, 95% CI 1.03-1.37). A nonlinear relationship between pre-pregnancy maternal BMI and SGA was observed. The risk of SGA decreased with the pre-pregnancy maternal BMI up to the turning point (BMI = 21) (RR 0.90, 95% CI 0.86-0.95). Among mothers undergoing ART, pre-pregnancy maternal obesity is associated with higher birth weight and higher risk of preterm birth for twin pregnancy, and pre-pregnancy maternal underweight is associated with lower birth weight and higher risk of SGA. Women preparing for ART should maintain a normal BMI to lower the chances of adverse neonatal outcomes.

Associations of maternal dietary inflammatory potential and quality with offspring birth outcomes: An individual participant data pooled analysis of 7 European cohorts in the ALPHABET consortium.

BackgroundAdverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes.Methods and findingsWe harmonized and pooled individual participant data (IPD) from up to 24,861 mother–child pairs in 7 European mother–offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal height, parity, cigarettes smoking, and alcohol consumption), with subsequent random-effects meta-analyses.Overall, the study mothers had a mean ± SD age of 29.5 ± 4.9 y at delivery and a mean BMI of 23.3 ± 4.2 kg/m2. Higher pregnancy DASH score (higher dietary quality) was associated with higher birth weight [β(95% CI) = 18.5(5.7, 31.3) g per 1-SD higher DASH score; P value = 0.005] and head circumference [0.03(0.01, 0.06) cm; P value = 0.004], longer birth length [0.05(0.01, 0.10) cm; P value = 0.010], and lower risk of delivering LBW [odds ratio (OR) (95% CI) = 0.89(0.82, 0.95); P value = 0.001] and SGA [0.87(0.82, 0.94); P value < 0.001] infants. Higher maternal prepregnancy E-DII score (more pro-inflammatory diet) was associated with lower birth weight [β(95% CI) = −18.7(−34.8, −2.6) g per 1-SD higher E-DII score; P value = 0.023] and shorter birth length [−0.07(−0.14, −0.01) cm; P value = 0.031], whereas higher pregnancy E-DII score was associated with a shorter birth length [−0.06(−0.10, −0.01) cm; P value = 0.026] and higher risk of SGA [OR(95% CI) = 1.18(1.11, 1.26); P value < 0.001]. In male, but not female, infants higher maternal prepregnancy E-DII was associated with lower birth weight and head circumference, shorter birth length, and higher risk of SGA (P-for-sex-interaction = 0.029, 0.059, 0.104, and 0.075, respectively). No consistent associations were observed for maternal E-DII and DASH scores with gestational age, preterm and postterm birth, or macrosomia and LGA. Limitations of this study were that self-reported dietary data might have increased nondifferential measurement error and that causality cannot be claimed definitely with observational design.ConclusionsIn this cohort study, we observed that maternal diet that is of low quality and high inflammatory potential is associated with lower offspring birth size and higher risk of offspring being born SGA in this multicenter meta-analysis using harmonized IPD. Improving overall maternal dietary pattern based on predefined criteria may optimize fetal growth and avert substantial healthcare burden associated with adverse birth outcomes.

Further evidence that a supraphysiologic estradiol level during ovarian stimulation affects birthweight: findings of fresh and frozen embryo transfer with comparable estradiol levels on human chorionic gonadotropin trigger

Studies have reported a supraphysiologic estradiol (E2) level during ovarian stimulation may be related to low birthweight after fresh embryo transfer (ET), but whether a high E2 level in the stimulation cycle affects birthweight via frozen ET remained controversial. The study was to investigate whether a supraphysiologic E2 level in ovarian stimulation cycle affects birth weight in infants conceived via subsequent FET. In this retrospective cohort study, 2525 singletons conceived via FET and 2668 singletons conceived via fresh ET were analyzed. The birthweight and incidences of small for gestational age (SGA) in infants conceived via FET in groups with low and high levels of E2 did not differ significantly. Multivariate analyses showed that the peak E2 level was not predictive of SGA in infants conceived via FET. Singletons conceived via fresh ET had a higher risk of SGA than those conceived via FET even after comparable previous exposure to a high level of E2 > 3000 pg/mL. Our study results indicated that the increased risk of SGA was at least partly a result of the supraphysiologic E2 exposure to the intrauterine environment.

The Association Between Maternal and Umbilical Cord Selenium Status and Fetal and Infant Growth in a Birth Cohort in Dhaka, Bangladesh

Abstract Objectives To estimate the associations of maternal and fetal selenium status [whole blood selenium (WBSe), serum selenium (SerumSe) and selenoprotein P (SEPP1)] with infant growth at birth and 12 months. Methods This study included a sub-sample from the randomized, placebo-controlled, multi-arm Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh (n = 986). Selenium markers were measured in maternal and cord blood at delivery and scaled to one standard deviation for analyses. WBSe and SerumSe were analyzed by inductively coupled plasma dynamic reaction cell mass spectrometry. SEPP1 was analysed by enzyme-linked immunoassay. Growth outcomes of interest were weight-for-gestational age z score (WAZ), low birthweight (LBW, &amp;lt;1500 g) and small for gestational age (SGA) based on measurements within 48 hours of birth, and infant length-for-gestational-age (LAZ), weight-for-length (WFL) and head circumference-for-gestational age (HCAZ) z scores at birth and 12 months. Associations were estimated by multivariable linear and modified Poisson regression models, adjusting for vitamin D and other potential confounders. Results Maternal SerumSe and SEPP1 were not associated with any of the growth outcomes at birth or at 12 months. None of the markers were associated with growth outcomes at 12 months. In adjusted models, higher maternal WBSe (1 SD = 18.5 ug/L) was associated with lower WAZ (β = −0.09, 95% CI: −0.168, −0.007) and an increased risk of LBW (RR: 1.20, 95% CI: 1.03, 1.39). Higher cord WBSe (1 SD = 23.2 ug/L) was associated with lower LAZ at birth (β = −0.089, 95% CI: −0.176, −0.001), lower WAZ (β = −0.10, 95% CI: −0.176, −0.023) and a higher risk of SGA (RR: 1.18, 95% CI: 1.07, 1.31). Higher cord SEPP1 (1 SD = 533.6 ng/mL) was associated with higher LAZ at birth (β = 0.098, 95% CI: 0.018, 0.178), higher WAZ (β = 0.086, 95% CI: 0.019, 0.154) and a decreased risk of SGA (RR: 0.87, 95% CI: 0.79, 0.97). Conclusions Both maternal and cord WBSe were negatively associated with measures of fetal growth, yet cord SEPP1 had a positive association. There were no associations with infant size at 12 months. These results do not provide evidence of a beneficial effect of higher maternal or fetal selenium status on fetal or infant growth. Yet, observed discrepancies between cord WBSe and SEPP1 require further investigation. Funding Sources This study was funded by the Bill and Melinda Gates Foundation.

Association of maternal thyroid function with birthweight: a systematic review and individual-participant data meta-analysis

Adequate transplacental passage of maternal thyroid hormone is important for normal fetal growth and development. Maternal overt hypothyroidism and hyperthyroidism are associated with low birthweight, but important knowledge gaps remain regarding the effect of subclinical thyroid function test abnormalities on birthweight-both in general and during the late second and third trimester of pregnancy. The aim of this study was to examine associations of maternal thyroid function with birthweight. In this systematic review and individual-participant data meta-analysis, we searched MEDLINE (Ovid), Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar from inception to Oct 15, 2019, for prospective cohort studies with data on maternal thyroid function during pregnancy and birthweight, and we issued open invitations to identify study authors to join the Consortium on Thyroid and Pregnancy. We excluded participants with multiple pregnancies, in-vitro fertilisation, pre-existing thyroid disease or thyroid medication usage, miscarriages, and stillbirths. The main outcomes assessed were small for gestational age (SGA) neonates, large for gestational age neonates, and newborn birthweight. We analysed individual-participant data using mixed-effects regression models adjusting for maternal age, BMI, ethnicity, smoking, parity, gestational age at blood sampling, fetal sex, and gestational age at birth. The study protocol was pre-registered at the International Prospective Register of Systematic Reviews, CRD42016043496. We identified 2526 published reports, from which 36 cohorts met the inclusion criteria. The study authors for 15 of these cohorts agreed to participate, and five more unpublished datasets were added, giving a study population of 48 145 mother-child pairs after exclusions, of whom 1275 (3·1%) had subclinical hypothyroidism (increased thyroid stimulating hormone [TSH] with normal free thyroxine [FT4]) and 929 (2·2%) had isolated hypothyroxinaemia (decreased FT4 with normal TSH). Maternal subclinical hypothyroidism was associated with a higher risk of SGA than was euthyroidism (11·8% vs 10·0%; adjusted risk difference 2·43%, 95% CI 0·43 to 4·81; odds ratio [OR] 1·24, 1·04 to 1·48; p=0·015) and lower mean birthweight (mean difference -38 g, -61 to -15; p=0·0015), with a higher effect estimate for measurement in the third trimester than in the first or second. Isolated hypothyroxinaemia was associated with a lower risk of SGA than was euthyroidism (7·3% vs 10·0%, adjusted risk difference -2·91, -4·49 to -0·88; OR 0·70, 0·55 to 0·91; p=0·0073) and higher mean birthweight (mean difference 45 g, 18 to 73; p=0·0012). Each 1 SD increase in maternal TSH concentration was associated with a 6 g lower birthweight (-10 to -2; p=0·0030), with higher effect estimates in women who were thyroid peroxidase antibody positive than for women who were negative (pinteraction=0·10). Each 1 SD increase in FT4 concentration was associated with a 21 g lower birthweight (-25 to -17; p<0·0001), with a higher effect estimate for measurement in the third trimester than the first or second. Maternal subclinical hypothyroidism in pregnancy is associated with a higher risk of SGA and lower birthweight, whereas isolated hypothyroxinaemia is associated with lower risk of SGA and higher birthweight. There was an inverse, dose-response association of maternal TSH and FT4 (even within the normal range) with birthweight. These results advance our understanding of the complex relationships between maternal thyroid function and fetal outcomes, and they should prompt careful consideration of potential risks and benefits of levothyroxine therapy during pregnancy. Netherlands Organization for Scientific Research (grant 401.16.020).

Hot Temperatures during Pregnancy: Evidence for an Impact on Fetal Growth.

Hot Temperatures during Pregnancy: Evidence for an Impact on Fetal Growth.

Socioeconomic characteristics of women with substance use disorder during pregnancy and neonatal outcomes in their newborns: A national registry study from the Czech Republic

BackgroundMaternal substance use can pose a risk to the fetal health. We studied the background characteristics of women with substance use disorders (SUDs) and selected neonatal outcomes in their children. Material and methodsA database-linkage study was performed. The sample consisted of pregnant women with a SUD during pregnancy (ICD-10 diagnosis F10-F19 except F17, n = 1710), women not diagnosed with a SUD (n = 1,511,310) in Czechia in 2000–2014, and their children. The monitored neonatal outcomes were gestational age, birth weight, preterm birth, and small-for-gestational age (SGA). Binary logistic regression adjusted for age, marital status, education, concurrent substance use, and prenatal care was performed. ResultsWomen with illicit SUDs were younger, more often unmarried, with a lower level of education, a higher abortion rate, a higher smoking rate, and lower compliance to prenatal care than women with a SUD related to alcohol, or sedatives and hypnotics (SH). Women with a SUD had worse socioeconomic situations, poorer pregnancy care, and worse neonatal outcomes than women without a SUD. After adjustment, we found no difference in SGA between the illicit SUD groups and the alcohol and the SH groups. The newborns from all SUD groups had a higher risk of SGA when compared to women without a SUD. However after adjustment, the difference remained significant just in the alcohol group (OR = 1.9, 95 % CI = 1.4–2.6). ConclusionMother’s SUD during pregnancy increased risk of fetal growth restriction as measured by SGA. The role of maternal socioeconomic and lifestyle factors for the risk of SGA was substantial.