Birth Length Z-scores Research Articles

Improved estimates of foetal growth are associated with perinatal outcomes: A latent modelling approach in a population-based birth cohort.

We aimed to estimate latent foetal growth conditions and explore their determinants among maternal characteristics and ultrasound biometric parameters. We additionally investigated the influence of foetal growth conditions on perinatal variables. We used data from live-born singletons in the Maternal and Child Health and Nutrition in Acre, Brazil (MINA-Brazil Study) population-based birth cohort. Maternal and perinatal characteristics were assessed in medical records from the maternity hospital and interviews with participants from July 2015 to June 2016. A sub-sample went through ultrasound examinations during the antenatal period, with assessment of foetal head and abdominal circumferences, and femur length. We estimated latent foetal growth conditions with a structural equation modelling framework, informed by the child's birth weight z-scores (BWZ) and birth length z-scores (BLZ) according to gestational age. Odds ratios and 95% confidence intervals (CIs) for the occurrence of perinatal events were estimated according to linear predictions of the latent variable. We included 1253 participants. Latent foetal growth conditions explained 88.3% of BWZ and 53.7% of BLZ variation. Maternal elevated blood pressure, primiparity, smoking, malaria, and insufficient gestational weight gain negatively impacted foetal growth conditions. In the subsample (n = 499), ultrasound biometric parameters assessed at 28 weeks were positively associated with the latent variable, with the largest contribution from foetal abdominal circumference. Each standardised unit of predicted foetal growth conditions halved the chance for preterm birth (95% CI = 0.26, 0.74) and longer hospital stay (>3 days) (95% CI = 0.28, 0.88). Conversely, BWZ and BLZ were not independently associated with these perinatal variables in separate logistic regression models. Latent foetal growth conditions jointly encompassing weight gain and linear growth during gestation were negatively influenced by a scenario of dual burden of maternal morbidities, with perinatal implications.

Anthropometrics of neonates born to mothers with PCOS with metformin or placebo exposure in utero.

Fetal growth may be affected by both maternal polycystic ovary syndrome (PCOS) and metformin therapy. Here, we explore the effect of intrauterine metformin exposure on birth anthropometrics of infants born to women with PCOS. We also investigated whether the effect of metformin on birth anthropometrics is modified by maternal pre-pregnancy body mass index, PCOS hyperandrogenic phenotype, serum androgen levels, preconception use of metformin and offspring sex. Additionally, we assessed newborn anthropometrics in relation to a national reference population. Individual data from three randomized controlled triasl were pooled. The randomized controlled trials investigated the effects of metformin in pregnant women with PCOS. In all, 397 and 403 were randomized to the metformin and placebo groups, respectively. A Scandinavian growth reference was used to calculate sex and gestational age adjusted z-scores. Linear regression models were used to estimate the effect of metformin on offspring z-scores of head circumference, birth length, birthweight, placental weight, body mass index, ponderal index and birthweight:placental weight ratio. S-testosterone, s-androstenedione, and s-sex-hormone binding globulin from four timepoints in pregnancy were analyzed. Compared with the PCOS-placebo group, newborns in the PCOS-metformin group had larger head circumference (head circumference z-score: mean difference = 0.25, 95% CI = 0.11- 0.40). This effect of metformin on head circumference z-score was particularly observed among offspring of overweight/obese mothers and mothers with hyperandrogenic PCOS-phenotype. We observed no difference in other anthropometric measures between the metformin and placebo groups or any clear interaction between maternal androgen levels and metformin. Newborns in the PCOS-placebo group were shorter than in the reference population (birth length z-score: mean = -0.04, 95% CI = -0.05 to -0.03), but head circumference and birthweight were similar. Larger head circumference was observed at birth in metformin-exposed offspring of mothers with PCOS. PCOS-offspring were also shorter, with a similar birthweight to the reference population, indirectly indicating higher weight-to-height ratio at birth.

Associations of maternal plasma and umbilical cord plasma metabolomics profiles with birth anthropometric measures.

The metabolomics profiles of maternal plasma during pregnancy and cord plasma at birth might influence fetal growth and birth anthropometry. The objective was to examine how maternal plasma and umbilical cord plasma metabolites are associated with newborn anthropometric measures, a known predictor of future health outcomes. Pregnant women between 24 and 28 weeks of gestation were recruited as part of a prospective cohort study. Blood samples from 413 women at enrollment and 787 infant cord blood samples were analyzed using the Biocrates AbsoluteIDQ® p180 kit. Multivariable linear regression models were used to examine associations of cord and maternal metabolites with infant anthropometry at birth. In cord blood samples from this rural cohort from New Hampshire of largely white residents, 13 metabolites showed negative associations, and 10 metabolites showed positive associations with birth weight Z-score. Acylcarnitine C5 showed negative association, and 4 lysophosphatidylcholines showed positive associations with birth length Z-score. Maternal blood metabolites did not significantly correlate with birth weight and length Z-scores. Consistent findings were observed for several acylcarnitines that play a role in utilization of energy sources, and a lysophosphatidylcholine that is part of oxidative stress and inflammatory response pathways in cord plasma samples. The metabolomics profiles of maternal plasma during pregnancy and cord plasma at birth may influence fetal growth and birth anthropometry. This study examines the independent effects of maternal gestational and infant cord blood metabolomes across different classes of metabolites on birth anthropometry. Acylcarnitine species were negatively associated and glycerophospholipids species were positively associated with weight and length Z-scores at birth in the cord plasma samples, but not in the maternal plasma samples. This study identifies lipid metabolites in infants that possibly may affect early growth.

Prenatal exposure to polybrominated diphenyl ethers and birth outcomes

BackgroundPolybrominated diphenyl ethers (PBDEs) were used as flame retardants and from their end-use products they can be released to accumulate within indoor environments. This may result in exposures to pregnant women with potential adverse effects on the developing fetus. While studies have shown associations between prenatal PBDE exposure and poor birth outcomes, research has mainly focused on birth weight and gestational age and may miss important indicators of newborn size. MethodsThe sample included a cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners (BDE-47, BDE-99, BDE-100, and BDE-153) were measured in cord serum at birth and dichotomized into low (<80th percentile) and high (>80th percentile) categories. Weight, length, head circumference, and gestational age were measured at birth and the ponderal index (birth weight/length x 100), size for gestational age, and population-based z-scores were calculated (n = 305). Separate regression analyses were conducted to estimate associations between PBDEs or PBDE sum (ng/g lipid) and birth outcomes. Quantile g-computation was performed to estimate the effect of total PBDE mixture. We also assessed effect modification by sex and ethnicity. ResultsAdjusting for relevant covariates, the high exposure category of BDE-153 was associated with lower birth weight z-score (−0.25, 95% CI: −0.5, 0.0) and longer gestation (0.43 weeks, 95% CI: 0.07, 0.79). The high exposure category of BDE-99 was associated with lower birth length z-score (−0.55, 95% CI: −0.98, −0.12). There was a negative association between the overall PBDE mixture and birth length z-score (−0.10, 95% CI: −0.21, 0.00) per 1 quintile increase in PBDEs. There was no effect modification by sex or ethnicity. ConclusionsThese results suggest that prenatal exposures to BDE-153, BDE-99, and total PBDE mixture are associated with birth outcomes in a cohort of Dominican and African American newborns.

Effects of a Liquefied Petroleum Gas Stove and Continuous Fuel Distribution Intervention on Anthropometric Outcomes at Birth

Background and Aims: Air pollution may contribute to childhood stunting and impaired cognitive development. Potential anthropometric markers of poor growth and cognition include head circumference and length at birth. The Household Air Pollution Intervention Network (HAPIN) trial in India, Guatemala, Peru, and Rwanda was a randomized controlled field trial among 3200 pregnant women that assessed the effect of liquefied petroleum gas (LPG) stove and continuous free fuel intervention compared to cooking with biomass on health outcomes. We conducted an intention-to-treat analysis of the LPG intervention delivered during pregnancy starting at 9-19 weeks of gestation on head circumference and length at birth among offspring. Methods: Length and head circumference were measured in centimeters within 24 hours of birth. Birth length and head circumference z-scores were calculated using INTERGROWTH-21st standards which accounts for gestational age at birth. Separate linear regression models (adjusted for 10 strata, representing settings in Guatemala (1 site), Rwanda (1 site), India (2 sites) and Peru (six sites)) were created for head circumference, head circumference z-score, birth length and birth length z-score. Results: A total of 3060 live births were included in the analysis. The intervention had small or no effect on birth length (β=0.14, 95% CI -0.01 to 0.29), birth length Z-scores (β=0.09, 95% CI 0.01 to 0.16), head circumference (β= -0.01, 95% CI -0.11 to 0.09) and head-circumference Z-scores (β= -0.01, 95% CI -0.08 to 0.07). More than 90% of the women had a full-term pregnancy (94.6% in control and 94.1% in intervention group), and the mean (SD) time with the intervention was 21.23 weeks (3.67 weeks). Conclusion: Our intervention strategy aimed at reducing household air pollution during pregnancy had small or no effects on length and head circumference at birth among offspring. Keywords: Household air pollution, liquefied petroleum gas, biomass fuel, head circumference, birth length, newborn

Maternal urinary fluoride during pregnancy and birth weight and length: Results from ELEMENT cohort study

Epidemiological studies assessing prenatal fluoride exposure and anthropometry at birth are scarce, inconsistent and with methodological limitations. The aim of this study was to evaluate associations between maternal urinary fluoride (MUF) at each trimester of pregnancy and birth weight and length in 536 mother-child pairs in the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort study. MUF (mg/L) was measured using microdiffusion/fluoride-specific electrode from at least one trimester of pregnancy. Non-linear associations were assessed through segmented regression models (MUF and birth weight Z-score) and we used linear regression models for MUF and birth length Z-score. Models were adjusted for potential confounders including urinary creatinine concentrations as a covariate. Non-creatinine adjusted MUF levels at each trimester of pregnancy were 0.81, 0.86, and 0.82 mg/L, mean concentrations for first, second and third trimester, respectively. For birth weight, we identified a MUF breakpoint at 0.99, 0.68 and 0.58 mg/L, for first, second and third trimester of pregnancy, respectively. In the first trimester, an increase of 1 mg/L in MUF concentrations ≥0.99 mg/L was associated with an increase in weight Z-score at birth (β = 0.79; 95% CI: 0.10, 1.48; p = 0.02). Second trimester MUF (≥0.68 mg/L) was marginally associated with birth weight decrease (β = −0.25; 95% CI: −0.55, 0.04; p = 0.09) and third trimester MUF (≥0.58 mg/L) was significantly associated with birth weight decrease (β = −0.33; 95% CI: −0.63, −0.03; p = 0.03). We observed a linear and significant association between MUF and Z-score of length at birth only for the first trimester of pregnancy (β = 0.55; 95% CI: 0.07, 1.04; p < 0.02). Prenatal fluoride exposure was associated with birthweight z-score with different susceptibility windows. Our findings reinforce the hypothesis that maternal fluoride exposure may affect birth anthropometry.

Cord Blood Inflammation and Birth Size in the Bangladesh Projahnmo Pregnancy Cohort

ObjectivesTo examine the association between cord blood inflammation and infant birth size in a pregnancy cohort from rural Bangladesh MethodsIn Sylhet district, Bangladesh, we consecutively enrolled 297 pregnancies and collected prenatal data and umbilical cord dried blood spots at birth (December 2015- 6). Cord blood was analyzed for interleukin (IL)-1α, IL-1β, IL-6, IL-8, and C-reactive protein (CRP). Z score values for weight, length, and head circumference at birth were calculated using the Intergrowth-21 standard. The association between inflammation (>75% vs < = 75%) and birth size was assessed using logistic regression. For birth size outcomes, we assessed small for gestational age (SGA) (<3% and 10% birth weight for GA/sex using Intergrowth-21) as well as birth weight, length, and head circumference z-scores (lowest quartile Z-scores vs others). In model 1, we calculated direct crude associations between exposure (inflammation) and outcome (birth size), and in model 2, adjusted for factors which may be associated both exposure and - independently of exposure - outcome (socioeconomic status, maternal age, maternal nutritional status, infant gestational age and sex). ResultsStudy mothers were a mean (sd) age of 23.7 ± 4.7 years. 34.2% had a maternal upper arm circumference (MUAC) < 22 cm, and 19% exhibited stunting (height < 145 cm). Mean gestational age at birth was 38.9 ± 2.1; 11.5% infants were preterm, 27.3% low birthweight (<2500 g), and 41.3% SGA. Mean birth size z-scores were –1.0 ± 1.1 for weight, 0.1 ± 0.9 for length, and 0.2 ± 1.1 for head circumference. We found no significant associations between cord inflammation biomarkers and SGA status. In model 1, elevated IL-1α and IL-6 exhibited a negative trend with low birth length z scores in crude analysis (odds ratio (OR) = 1.9, 95% CI: 0.9, 3.9). In model 2, statistical trends were observed for IL-1α (OR = 2.2, 95% CI: 1.0, 5.1), IL-6 (OR = 2.1, 95% CI: 0.9, 4.7), and CRP (OR = 2.0, 95% CI: 0.9, 4.6). No associations were observed between cord blood inflammation and birth weight or head circumference z scores. ConclusionsAmong infants in rural Bangladesh, elevated cord blood inflammation was associated with trends of smaller birth length z-scores. Funding SourcesEunice Kennedy Shriver National Institute of Child Health and Development.

Associations between size at birth and size at 6 years among preterm infants: a retrospective cohort study.

Little is known about the relationship between fetal growth and size at school age in children born prematurely. We evaluated the relationships between gestational age and anthropometric z-scores at birth and size at 6 years of age in very-low-birthweight infants born at <30 weeks' gestation. We collected data from the medical records of 187 preterm children at birth and 6 years of age. We evaluated correlations between gestational age and z-scores for weight, body length, and head circumference at birth and z-scores for weight, height, and body mass index at 6 years of age. Simple regression analysis showed that, in boys and the overall group, gestational age and z-scores for weight, body length, and head circumference at birth had significant association with z-scores for weight, height, and body mass index at 6 years of age. No significant associations were found in girls, except for weight z-scores at 6 years with gestational age and head circumference z-scores at birth. Multiple regression analysis showed that gestational age and length z-score at birth were significantly and independently associated with weight and height z-score at 6 years. Gestational age was also significantly and independently associated with body mass index z-score at 6 years. Gestational age and fetal growth in length (assessed with the birth-length z-score) were associated with anthropometric z-scores at 6 years in very-low-birthweight children born at <30 weeks of gestation, especially in boys.

Effects of mid-pregnancy exposure to phthalate acid esters and polycyclic aromatic hydrocarbons on offspring size at birth

BACKGROUND AND AIM: Phthalate acid esters (PAEs) and polycyclic aromatic hydrocarbons (PAHs) are the environmental endocrine disruptors and threaten human health especially for pregnant women and fetuses. Evidence on how these contaminants affect fetal growth in newborns is lacking and inconsistent. We therefore conducted a prospective cohort study to assess the associations of prenatal PAEs and PAHs exposure with fetal growth. METHODS: This study included 835 mother-infant pairs from the Tongji Birth Cohort in Wuhan, China. We detected the concentrations of 9 PAEs metabolites and 10 PAHs metabolites in urine samples collected during mid-pregnancy (13~28 weeks’ gestation). The fetal biometric parameters for head circumference (HC), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW) were collected during pregnancy (weeks 28~37). We measured birth size. The associations of urinary metabolites with fetal growth parameters were estimated by using linear regression models. RESULTS:We observed each ln-unit increase in monoethyl phthalate (MEP) was associated with decrement in EFW (-128 g, 95% CI: -233, -23), birth weight (-44 g, 95% CI: -88, -1), birth weight z-scores (-0.10 SDs, 95% CI: -0.20, 0.00) among boys but not in girls. Elevated maternal 2-hydroxyfluorene concentrations were associated with the decline of birth length (-0.22 cm, 95% CI: -0.37, -0.07) and birth length z-scores (-0.12 SDs, 95% CI: -0.21, -0.04) in boys. However, we observed a positive association between 4-hydroxyphenanthrene and birth length z-scores in girls with a β = 0.11 SDs, (95% CI: 0.00, 0.21). Meanwhile, gestational levels of MEP, monoisobutyl phthalate, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 9-hydroxyphenanthrene, and 9- hydroxyfluorene were also positively associated with HC and AC in girls. CONCLUSIONS:This study suggested that the impact of mid-pregnancy PAEs and PAHs exposure on fetal and birth size maybe in a sex-specific manner and MEP was negatively associated with some fetal growth parameters among boys. More findings are required in future research. KEYWORDS: Phthalates, Multi-pollutant, Endocrine disrupting chemicals, Pregnancy outcomes

Isolated fetal neural tube defects associate with increased risk of placental pathology: Evidence from the Collaborative Perinatal Project

IntroductionNeural tube defects (NTDs) are amongst the most common congenital anomalies and are associated with significant postnatal morbidity, but also with a higher incidence of low birthweight and fetal growth restriction. Despite the placenta being a critical determinant of fetal growth, placental development has not been extensively studied in fetuses with NTDs. MethodsWe performed a matched case-cohort study using data from the Collaborative Perinatal Project to assess the risk of placental pathology in pregnancies with an isolated fetal NTD (cases; n = 74) compared to those without any congenital anomalies (controls; n = 148). We hypothesised that cases would be at an increased risk of placental pathology compared to controls. Data were analysed using adjusted generalized linear and nominal logistic regression models. Results are presented as adjusted β or adjusted odds ratio (aOR; 95% confidence interval). ResultsCases had lower placental weight (β = −22.2 g [-37.8 to −6.6]), surface area (β = −9.6 cm2 [-18.3 to −1.0]) and birth length z-scores (β = −0.4 [-0.7 to −0.001]) compared to controls. Cases were more likely to have a single umbilical artery (vs. two; 6 [8.1%] vs. 1 [0.7%]; aOR = 301 [52.6–1726]), placental hypermaturity (9 [12.2%] vs. 5 [3.4%]; aOR = 6.8 [3.1–14.7]), many (vs. few) Hofbauer cells (9 [12.2%] vs. 7 [4.7%]; aOR = 3.02 [1.2–7.3]), and stromal fibrosis (9 [12.2%] vs. 10 [6.8%]; aOR = 3.0 [1.4–6.3]) in placental terminal villi compared to controls. ConclusionsFetuses with isolated NTDs may be at increased risk of placental pathology, which could be contributing to poor fetal growth in these pregnancies and subsequent postnatal morbidities.

Modelling maternal and perinatal risk factors to predict poorly controlled childhood asthma.

Asthma is the most common non-communicable pulmonary condition, affecting prepubertal boys more often than girls. This study explored how maternal and perinatal risk factors are linked to poorly controlled childhood asthma in a sex dependent manner. This single centre study was performed at a metropolitan teaching hospital in Western Sydney, Australia, using electronical obstetric records from 2000 to 2017 and electronical pediatric records from 2007 to 2018. The data of 1694 children with complete entries were retrospectively analysed. Risk factors for multiple hospital admission for asthma were selected by backward-eliminated Poisson regression modelling. Selection stability of these parameters was independently confirmed using approximated exhaustive search. Sex-specific regression models indicated that most notably parity (RR[95%CI] for parity = 3; 1.85[1.22-2.81]), birth length z-score (1.45[1.23-1.70]) and birth weight z-score (0.77[0.65-0.90]) contributed to multiple asthma admissions in girls, while boys were affected most prominently by maternal BMI (e.g. BMI 35-39.9; 1.92[1.38-2.67]) and threatened preterm labor (1.68[1.10-2.58]). Allergic status was a risk factors for both boys and girls (1.47[1.18-1.83] and 1.46[1.13-1.89]). Applying ROC analysis, the predictive modelling of risk factors for hospital admissions showed an incremental increase with an AUC of 0.84 and 0.75 for girls and boys respectively for >3 hospital admissions. Multiple hospital admissions for asthma are associated with maternal and perinatal risk factors in a sex and birth order dependent manner. Hence, prospective risk stratification studies aiming to improve childhood asthma control are warranted to test the clinical utility of these parameters. Furthermore, the influence of the early in utero environment on male-female differences in other communicable and non-communicable respiratory conditions should be considered.

Umbilical Cord Blood Metal Mixtures and Birth Size in Bangladeshi Children.

Background:Studies have evaluated environmental exposure to toxic metals such as arsenic (As), cadmium (Cd), manganese (Mn), or lead (Pb) on birth size; however, information on potential effects of exposures to metal mixtures is limited.Objectives:We assessed the association between metal mixtures (As, Cd, Mn, Pb) in umbilical cord blood and neonate size in Bangladeshi children.Methods:In this birth cohort study, pregnant women who were of age with an ultrasound-confirmed singleton pregnancy of gestation were recruited from two Bangladesh clinics between 2008 and 2011. Neonate size metrics were measured at the time of delivery. Metals in cord blood were measured using inductively coupled plasma mass spectrometry. We employed multivariable linear regression and Bayesian kernel machine regression (BKMR) to estimate associations of individual metals and metal mixtures with birth size parameters.Results:Data from 1,088 participants was assessed. We found a significant negative association between metal mixture and birth length and head circumference when all metal concentrations were above the 60th and 55th percentiles, respectively, compared with the median. An interquartile range (IQR) increase in log Cd concentration {log[Cd (in micrograms per deciliter)] } was associated with a 0.13-standard deviation (SD) decrease in mean birth length (95% CI: , ) and a 0.17-SD decrease in mean head circumference (95% CI: , ), based on linear regression models adjusted for covariates and the other metals. An IQR increase in log Mn concentration {log[Mn (in micrograms per deciliter)] } was associated with a 0.07-SD decrease in mean birth weight (95% CI: , 0.002).Discussion:Metal mixtures in cord blood were associated with reduced birth size in Bangladeshi children. Results from linear regression models adjusted and the BKMR mixtures analyses suggest adverse effects of Cd and Mn, as individual metal exposures, on birth size outcomes. https://doi.org/10.1289/EHP7502

1371-P: Effect of Omega-3 Supplementation in Pregnant Women with Obesity on Offspring Growth and Body Composition

Background: Maternal obesity is a growing health burden associated with adverse cardiometabolic health outcomes in the offspring. Higher omega-3 polyunsaturated fatty acids (n3 PUFA) status in pregnancy is associated with higher birthweight. However, the effect of n3 supplementation, specifically in pregnant women with overweight and obesity, on fetal growth and adiposity has not been explored. Objective: To examine the effect of n-3 supplementation in overweight and obese pregnancy on offspring anthropometry and body composition. Methods: A secondary analysis of a double-blind randomized controlled trial of pregnant women with pre-pregnancy BMI≥ 25 randomized to daily DHA plus EPA (2 g/d) or placebo (wheat germ oil) from 10-16 weeks gestation to delivery. We compared the following newborn outcomes i) birthweight z-score derived from anthropometrics, ii) % adiposity, fat-mass and fat-free mass using PeaPodTM and skin fold thickness measurement, by randomization group using Student T-test and Wilcoxon rank-sum for bivariate analyses, and linear regression adjusting for gestational age (GA) and sex. Results: For the 46 mother-child dyads with complete exposure and outcome data, median (IQR) maternal BMI was 30.2 (27.9, 35.5) kg/m2. Gestation was longer in the treatment vs. placebo group (40 (38.6,40.1) vs. 38.9 (38.0,39.4) weeks, p=0.009). Sex- and GA- specific birthweight z-score (-0.2 ± 0.7 vs. -0.6 ± 0.6-unit, p =0.035), but not birth length z-score (-0.3 ± 0.7 vs. -0.6 ± 0.6-unit, p =0.21), was higher in the treatment vs. placebo group. N-3 treatment was associated with higher fat-free mass (β 131.4g higher for treatment vs. control, 95% CI 3.1, 259.7) by skinfolds but not %bodyfat or fat mass at birth. Conclusion: n-3 supplementation early in pregnancy in women with obesity increased birthweight, but this results from increased fetal lean mass accrual. Future investigations should explore the long-term impact of this intervention on offspring cardiometabolic health. Disclosure C. Monthe-Dreze: None. S. Enstad: None. S. Sen: None. S. Hauguel de Mouzon: None. P. Catalano: None. Funding National Institutes of Health (RHD057236); Case Western Reserve University/Cleveland Clinic Clinical and Translational Science Award (UL1RR024989)

Preliminary Comparison of Lactobacillus reuteri and Bifidobacterium longum Subspecies Infantis Probiotics Impact on Preterm Infant Gut Microbiome and Length Growth

Abstract Objectives The gut microbiome is associated with term infant growth. Here, we examine if use of a L. reuteri or a B. infantis probiotic in preterm infants is associated with changes in the gut microbiome and growth. Methods In this observational study, 26 preterm infants received L. reuteri and 13 infants received B. infantis. Infant length delta z-score was calculated by subtracting the birth length z-score (Fenton Growth Chart) from the discharge z-score value. Association between length delta z-score and probiotic was tested with a t-test. Gut microbiome was assessed by V4 sequencing using the first fecal sample collected in week 2 or 3 of life from each infant. Data analysis was done in QIIME2 and R. Alpha diversity (Shannon index) was compared by probiotic and length delta z-score using regression. Beta diversity (Bray-Curtis distance) was compared between probiotics and above/below median length delta z-score by PERMANOVA. Songbird was used for differential abundance testing. Results There was no association between length and the probiotic infants received, P = 0.34. There was no association between alpha diversity and probiotic, P = 0.58, or length, P = 0.43. There was an association between beta diversity and probiotic (P = 0.001), but not between beta diversity and length, P = 0.43. Songbird top and bottom ranked amplicon sequence variants (ASVs) are those most likely to be differentially abundant. For probiotic, top ranked ASVs (associated with L. reuteri) were Lactobacillus and L. reuteri. Bottom ranked ASVs (B. infantis) were Bifidobacterium and an Escherichia-Shigella. For length, top ranked ASVs (higher delta z-score) were Staphylococcus and probiotic associated Lactobacillus and L. reuteri. Bottom ranked ASVs (lower delta z-score) were Enterococcus, probiotic associated Escherchia-Shigella, Enterobacteriaceae, and Clostridium perfinigens. Conclusions Type of probiotic given was not associated with infant length growth, however, songbird identified ASVs that are likely to be differentially abundant by both probiotic and length. Additional work is needed to confirm the songbird results, and investigation into differences in probiotic administration methods and timing are on-going. Funding Sources F32HD093185 (DHT) and Peter J. Shields Endowed Chair in Dairy Food Science (DAM).

Prenatal exposure to benzotraizoles and benzothiazoles in relation to fetal and birth size: A longitudinal study

The presence of benzotriazoles and benzothiazoles (BTs) in maternal urine and amniotic fluid indicated the widespread fetal exposure to the contaminants. We investigated the associations of prenatal BTs exposure with fetal and birth size and explored the window of susceptibility. Participants consisted of 856 mother-infant pairs drawn from a prospective birth cohort between 2014 and 2015 in Wuhan, China. Prenatal BTs exposure were measured in multiple urine samples collected across three trimesters. We observed positive associations between prenatal exposure to specific BTs (e.g., 1-H-benzotriazole, 1-hydroxy-benzotriazole and 2-amino-benzothiazole) and femur length (FL) and birth length z-scores among girls. In boys, a 2-fold increase of averaged concentration of urinary benzothiazole (BTH) was associated with decrement in FL (β = -0.068, p < 0.001) and birth length (β = -0.055, p = 0.005) z-scores. Further analysis indicated that the negative associations between urinary concentrations of BTH and birth length z-score among boys were observed at exposure measurement in 25–35 gestational weeks. This study reported the associations between prenatal exposure to BTs and fetal and birth size, suggests the associations maybe in a sex-specific manner and the window of exposure may influence susceptibility. These findings require replication in future research.

Cohort profile: the Maternal and Child Health and Nutrition in Acre, Brazil, birth cohort study (MINA-Brazil)

PurposeMaternal and Child Health and Nutrition in Acre, Brazil (MINA-Brazil) is a longitudinal, prospective population-based birth cohort, set-up to understand the effects of early environmental exposures and maternal lifestyle choices...

Which modifiable prenatal factors mediate the relation between socio-economic position and a child's weight and length at birth?

Although several studies have shown a positive association between socio-economic position and size at birth, not enough is known about the modifiable factors that may be involved. We aimed to investigate whether maternal prepregnancy body mass index (BMI), smoking, diet, and depression during pregnancy mediate the positive association between maternal education and birth size. Weight and length z-scores specific for gestational age and sex were calculated for 1,500 children from the EDEN mother-child cohort. A mediation analysis of the associations between maternal education and birth size was conducted with a counterfactual method, adjusted for recruitment centre, parity, maternal height, and age. In the comparison of children of mothers with low versus intermediate education levels, maternal smoking during pregnancy explained 52% of the total effect of education on birth weight. Similar findings were observed with birth length z-score (37%). The comparison of children of mothers with high versus intermediate education levels yielded a non-significant total effect, which masked opposite mediating effects by maternal BMI and smoking during pregnancy on both birth weight and length. Prepregnancy BMI and maternal smoking during pregnancy mediate the positive association between maternal education and birth weight and length z-scores. These mediators, however, act in opposite directions, thereby masking the extent to which healthy prenatal growth is socially differentiated.

Placental proteases PAPP-A and PAPP-A2, the binding proteins they cleave (IGFBP-4 and -5), and IGF-I and IGF-II: Levels in umbilical cord blood and associations with birth weight and length

BackgroundA newborn's birth weight for gestational age provides important insights into his or her fetal growth and well-being. While the underlying mechanisms regulating fetal growth remain to be fully elucidated, the IGF axis plays an important role. Some components of this axis have been well-characterized in umbilical cord blood, but others have not yet been studied. We measured the proteases PAPP-A and PAPP-A2, the binding proteins they cleave (IGFBP-4 and -5), and the established molecules IGF-I and –II in umbilical cord blood to better characterize the IGF axis in relation to birth weight and length. MethodsWe performed a case-control study of 180 neonates born at a tertiary teaching hospital in Boston. To maximize power, infants were recruited in a 1:3:1 ratio with 37 SGA, 111 AGA, and 37 LGA infants matched by gestational age, sex, and delivery mode. IGF-I, IGF-II, IGFBP-4, IGFBP-5, PAPP-A, and PAPP-A2 were measured in umbilical cord blood by ELISA. Associations between birth weight and birth length Z-scores and the Z-scores of the above molecules were analyzed using linear regression models and analysis of covariance. ResultsBirth weight and length Z-scores were positively associated with Z-scores of IGF-I, IGF-II, total IGFBP-4, and IGFBP-5, with IGF-I having the strongest association. Birth weight and length Z-scores were negatively associated with Z-scores of intact IGFBP-4, PAPP-A, and PAPP-A2 levels. ConclusionsWe confirm previous findings of significant associations between the IGFs in cord blood and newborn size and for the first time show positive associations between cord blood total IGFBP-4 and -5 and birth weight and a negative association between intact IGFBP-4 and birth weight. We also show for the first time a reciprocal relationship between cord blood levels of PAPP-A and PAPP-A2 and newborn size. The implications of these findings need to be further examined in large longitudinal studies and likely have diagnostic and therapeutic potential.

In Preterm Infants, Length Growth below Expected Growth during Hospital Stay Predicts Poor Neurodevelopment at 2 Years

Background: In preterm infants, neonatal weight growth is associated with neurodevelopmental outcome but is a poor indicator of growth quality. Objective: The aim of this work was to measure the relationship between neonatal length growth and the 2-year neurological outcome in preterm infants. Methods: A total of 2,403 infants enrolled in the LIFT cohort with gestational age less than 34 weeks were studied. Neonatal observed length growth (OLG) was calculated as the change in length Z-score between birth and discharge. Expected length growth (ELG) was estimated based on gestational age, birth weight Z-score, birth length Z-score, gender, and observed neonatal weight growth. The difference between OLG and ELG (∆_OLG-ELG) was calculated as OLG – ELG, and infants were ranked into 3 classes depending on their ∆_OLG-ELG (≤–0.5, –0.49 to 0.49, ≥0.50 Z-score). We explored the relationship between ∆_OLG-ELG and 2-year neurodevelopmental outcome (n = 2,036), and, in a subgroup (n = 85), between ∆_OLG-ELG and body composition at discharge. Results: ELG was strongly predicted from the above-mentioned parameters (R² = 0.73, p = 0.001). OLG correlated closely with gestational age (p = 0.001) but ∆_OLG-ELG did not (p = 1.0). OLG was not associated with a 2-year nonoptimal outcome after adjustment for gestational age, but ∆_OLG-ELG ≤–0.5 was; the crude and adjusted odds ratios were 1.63 and 1.56, respectively. ∆_OLG-ELG correlated negatively with fat mass (R² = 0.29, p = 0.006) before and after adjustment for gestational age. Conclusion: ∆_OLG-ELG is a marker of neonatal growth that does not depend on gestational age, and may reflect quality of growth. A ∆_OLG-ELG ≤–0.5 Z-score is associated with a higher risk for 2-year nonoptimal neurodevelopmental outcome.

The Hidden Burden of Plasmodium vivax Malaria in Pregnancy in the Amazon: An Observational Study in Northwestern Brazil.

We measured the prevalence of malaria in pregnancy and estimated its impact on birth weight and length and maternal hemoglobin in 1,180 women from Juruá Valley, the main malaria hotspot in Brazil. Antenatal malaria episodes, 74.6% of them due to Plasmodium vivax, were microscopically diagnosed in 8.0% of the women and were associated with an average reduction in birth weight z-scores of 0.35 (95% confidence interval [CI] = 0.14-0.57) and in birth length z-scores of 0.31 (95% CI = 0.08-0.54), compared with malaria-free pregnancies. Affected mothers had a mean decrease in hemoglobin concentration at delivery of 0.33 g/100 mL (95% CI = 0.05-0.62 g/100 mL); 51.6% were anemic. The timing and frequency of antenatal infections influenced pregnancy outcomes and first- or second-trimester infections were not associated with decreased birth weight and length and maternal hemoglobin at delivery. Although repeated antenatal vivax infections were associated with poorer birth outcomes, even a single vivax malaria episode was associated with a significant reduction in birth weight and length and maternal hemoglobin. Overall, 7.5% women had the parasite's DNA found in peripheral blood at delivery. Most (83.1%) of these 89 perinatal infections were due to P. vivax and only 7.9% of them progressed to symptomatic disease after delivery. Plasmodium vivax and Plasmodium falciparum DNA was found in 0.6% and 0.3% of 637 cord blood samples examined, respectively, but only one newborn developed clinical neonatal malaria. Our results further challenge the notion that vivax malaria is relatively benign during pregnancy and call for better strategies for its prevention.