Stillbirth risk by fetal size among 126.5 million births in 15 countries from 2000 to 2020: A fetuses-at-risk approach.

OBJECTIVE: To compare stillbirth rates and risks for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) pregnancies at 24-44 completed weeks of gestation using a birth-based and fetuses-at-risk approachs. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 high- and middle-income countries. POPULATION: Live births and stillbirths. METHODS: A total of 151 country-years of data, including 126 543 070 births across 15 countries from 2000 to 2020, were compiled. Births were categorised into SGA, AGA and LGA using INTERGROWTH-21st standards. Gestation-specific stillbirth rates, with total births as the denominator, and gestation-specific stillbirth risks, with fetuses still in utero as the denominator, were calculated from 24 to 44 weeks of gestation. MAIN OUTCOME MEASURES: Gestation-specific stillbirth rates and risks according to size at birth. RESULTS: The overall stillbirth rate was 4.22 per 1000 total births (95% CI 4.22-4.23) across all gestations. Applying the birth-based approach, the stillbirth rates were highest at 24 weeks of gestation, with 621.6 per 1000 total births (95% CI 620.9-622.2) for SGA pregnancies, 298.4 per 1000 total births (95% CI 298.1-298.7) for AGA pregnancies and 338.5 per 1000 total births (95% CI 337.9-339.0) for LGA pregnancies. Applying the fetuses-at-risk approach, the gestation-specific stillbirth risk was highest for SGA pregnancies (1.3-1.4 per 1000 fetuses at risk) prior to 29 weeks of gestation. The risk remained stable between 30 and 34 weeks of gestation, and then increased gradually from 35 weeks of gestation to the highest rate of 8.4 per 1000 fetuses at risk (95% CI 8.3-8.4) at ≥42 weeks of gestation. The stillbirth risk ratio (RR) was consistently high for SGA compared with AGA pregnancies, with the highest RR observed at ≥42 weeks of gestation (RR 9.2, 95% CI 15.2-13.2), and with the lowest RR observed at 24 weeks of gestation (RR 3.1, 95% CI 1.9-4.3). The stillbirth RR was also consistently high for SGA compared with AGA pregnancies across all countries, with national variability ranging from RR 0.70 (95% CI 0.43-0.97) in Mexico to RR 8.6 (95% CI 8.1-9.1) in Uruguay. No increased risk for LGA pregnancies was observed. CONCLUSIONS: Small for gestational age (SGA) was strongly associated with stillbirth risk in this study based on high-quality data from high- and middle-income countries. The highest RRs were seen in preterm gestations, with two-thirds of the stillbirths born as preterm births. To advance our understanding of stillbirth, further analyses should be conducted using high-quality data sets from low-income settings, particularly those with relatively high rates of SGA.

Neonatal mortality risk for vulnerable newborn types in 15 countries using 125.5 million nationwide birth outcome records, 2000-2020.

OBJECTIVE: To compare neonatal mortality associated with six novel vulnerable newborn types in 125.5 million live births across 15 countries, 2000-2020. DESIGN: Population-based, multi-country study. SETTING: National data systems in 15 middle- and high-income countries. METHODS: We used individual-level data sets identified for the Vulnerable Newborn Measurement Collaboration. We examined the contribution to neonatal mortality of six newborn types combining gestational age (preterm [PT] versus term [T]) and size-for-gestational age (small [SGA], <10th centile, appropriate [AGA], 10th-90th centile or large [LGA], >90th centile) according to INTERGROWTH-21st newborn standards. Newborn babies with PT or SGA were defined as small and T + LGA was considered as large. We calculated risk ratios (RRs) and population attributable risks (PAR%) for the six newborn types. MAIN OUTCOME MEASURES: Mortality of six newborn types. RESULTS: Of 125.5 million live births analysed, risk ratios were highest among PT + SGA (median 67.2, interquartile range [IQR] 45.6-73.9), PT + AGA (median 34.3, IQR 23.9-37.5) and PT + LGA (median 28.3, IQR 18.4-32.3). At the population level, PT + AGA was the greatest contributor to newborn mortality (median PAR% 53.7, IQR 44.5-54.9). Mortality risk was highest among newborns born before 28 weeks (median RR 279.5, IQR 234.2-388.5) compared with babies born between 37 and 42 completed weeks or with a birthweight less than 1000 g (median RR 282.8, IQR 194.7-342.8) compared with those between 2500 g and 4000 g as a reference group. CONCLUSION: Preterm newborn types were the most vulnerable, and associated with the highest mortality, particularly with co-existence of preterm and SGA. As PT + AGA is more prevalent, it is responsible for the greatest burden of neonatal deaths at population level.

Vulnerable newborn types: Analysis of population-based registries for 165 million births in 23 countries, 2000-2021.

OBJECTIVE: To examine the prevalence of novel newborn types among 165 million live births in 23 countries from 2000 to 2021. DESIGN: Population-based, multi-country analysis. SETTING: National data systems in 23 middle- and high-income countries. POPULATION: Liveborn infants. METHODS: Country teams with high-quality data were invited to be part of the Vulnerable Newborn Measurement Collaboration. We classified live births by six newborn types based on gestational age information (preterm <37 weeks versus term ≥37 weeks) and size for gestational age defined as small (SGA, <10th centile), appropriate (10th-90th centiles), or large (LGA, >90th centile) for gestational age, according to INTERGROWTH-21st standards. We considered small newborn types of any combination of preterm or SGA, and term + LGA was considered large. Time trends were analysed using 3-year moving averages for small and large types. MAIN OUTCOME MEASURES: Prevalence of six newborn types. RESULTS: We analysed 165 017 419 live births and the median prevalence of small types was 11.7% - highest in Malaysia (26%) and Qatar (15.7%). Overall, 18.1% of newborns were large (term + LGA) and was highest in Estonia 28.8% and Denmark 25.9%. Time trends of small and large infants were relatively stable in most countries. CONCLUSIONS: The distribution of newborn types varies across the 23 middle- and high-income countries. Small newborn types were highest in west Asian countries and large types were highest in Europe. To better understand the global patterns of these novel newborn types, more information is needed, especially from low- and middle-income countries.

Prevalence of autism spectrum disorder diagnosis by birth weight, gestational age, and size for gestational age: a systematic review, meta-analysis, and meta-regression.

We aimed to comprehensively pool the prevalence of autism spectrum disorder (ASD) diagnosis by birth weight, gestational age, and size for gestational age. PubMed, EMBASE, Web of Science, Ovid PsycINFO, and Cochrane Library were searched up to December 22, 2021. We pooled data using the random-effects model and quantified heterogeneity using the I2 statistic. Of 66 643 records initially identified, 75 studies were included in the meta-analysis. The pooled prevalence estimates of ASD diagnosis are as follows: very-low-birth weight, 3.1% (912 ASD/66,445 individuals); low-birth weight, 2.3% (5672 ASD/593,927 individuals); normal-birth weight, 0.5% (17,361 ASD/2,378,933 individuals); high-birth weight, 0.6% (4505 ASD/430,699 individuals); very preterm, 2.8% (2113 ASD/128,513 individuals); preterm, 2.1% (19 672 ASD/1 725 244 individuals); term, 0.6% (113,261 ASD/15,297,259 individuals); postterm, 0.6% (9419 ASD/1,138,215 individuals); small-for-gestational-age, 1.9% (6314 ASD/796,550 individuals); appropriate-for-gestational-age, 0.7% (21,026 ASD/5,936,704 individuals); and large-for-gestational-age, 0.6% (2607 ASD/635,666 individuals). Compared with the reference prevalence (those in normal-birth weight, term, and appropriate-for-gestational-age individuals), the prevalence estimates of ASD diagnosis in very-low-birth weight, low-birth weight, very preterm, preterm, and small-for-gestational-age individuals increased significantly, while those in high-birth weight, postterm, and large-for-gestational-age individuals did not change significantly. There were geographical differences in the prevalence estimates. This meta-analysis provided reliable estimates of the prevalence of ASD diagnosis by birth weight, gestational age, and size for gestational age, and suggested that low-birth weight (especially very-low-birth weight), preterm (especially very preterm), and small-for-gestational-age births, rather than high-birth weight, postterm, and large-for-gestational-age births, were associated with increased risk of ASD diagnosis. However, in view of marked between-study heterogeneity in most conditions, unknown effects of certain important confounders associated with ASD due to limited information in original articles, and included studies from a relatively small number of countries, the findings of this study should be interpreted with caution.

Birth outcomes affecting infants of mothers with intellectual and developmental disabilities.

BACKGROUND: Women with intellectual and developmental disabilities (IDD) face increased risk of adverse maternal pregnancy outcomes, yet less is known about infant outcomes. OBJECTIVES: To examine birth outcomes of infants born to mothers with IDD and assess associations with demographics and IDD-type. METHODS: We used data from the Big Data for Little Kids project, which links Wisconsin birth records to Medicaid claims for live births covered by Medicaid from 2007 to 2016. We identified IDD using maternal prepregnancy Medicaid claims and ran Poisson regression (with a log link function) with robust variance clustered by mother to compare prevalence of outcomes between singleton births with and without mothers with IDD. We adjusted the associations for demographic factors and estimated prevalence ratios (PR) as the effect measure. We assessed outcomes by IDD-type (intellectual disability, genetic conditions, cerebral palsy, and autism spectrum disorder) to explore differences by categories of IDD. RESULTS: Of 267,395 infants, 1696 (0.6%) had mothers with IDD. A greater percentage of infants with mothers with IDD were born preterm (12.8% vs 7.8%; PR 1.64, 95% confidence interval [CI] 1.42, 1.89), small for gestational age (8.5% vs 5.4%; PR 1.42, 95% CI 1.25, 1.61), and died within 12 months of birth (3.2% vs 0.7%; PR 4.93, 95% CI 3.73, 6.43) compared to infants of mothers without IDD. Prevalence ratios were robust to adjustment for demographics factors. Estimates did not meaningfully differ when comparing different IDD-types. CONCLUSIONS: A greater porportion of infants born to mothers with IDD who were covered by Medicaid had poor outcomes compared to other infants. Prevalence of poor infant outcomes was greater for mothers with IDD even after accounting for demographic differences. It is imperative to understand why infants of mothers with IDD are at greater risk so interventions and management can be developed.

Second and third trimester fetal ultrasound population screening for risks of preterm birth and small-size and large-size for gestational age at birth: a population-based prospective cohort study

BACKGROUND: Preterm birth, small size for gestational age (SGA) and large size for gestational age (LGA) at birth are major risk factors for neonatal and long-term morbidity and mortality. It is unclear which periods of pregnancy are optimal for ultrasound screening to identify fetuses at risk of preterm birth, SGA or LGA at birth. We aimed to examine whether single or combined second and third trimester ultrasound in addition to maternal characteristics at the start of pregnancy are optimal to detect fetuses at risk for preterm birth, SGA and LGA. METHODS: In a prospective population-based cohort among 7677 pregnant women, we measured second and third trimester estimated fetal weight (EFW), and uterine artery pulsatility and umbilical artery resistance indices as placenta flow measures. Screen positive was considered as EFW or placenta flow measure < 10th or > 90th percentile. Information about maternal age, body mass index, ethnicity, parity, smoking, fetal sex and birth outcomes was available from questionnaires and medical records. Screening performance was assessed via receiver operating characteristic (ROC) curves and area under the curve (AUC) along with sensitivity at different false-positive rates. RESULTS: Maternal characteristics only and in combination with second trimester EFW had a moderate performance for screening for each adverse birth outcome. Screening performance improved by adding third trimester EFW to the maternal characteristics (AUCs for preterm birth 0.64 (95%CI 0.61 to 0.67); SGA 0.79 (95%CI 0.78 to 0.81); LGA 0.76 (95%CI 0.75; 0.78)). Adding third trimester placenta measures to this model improved only screening for risk of preterm birth (AUC 0.72 (95%CI 0.66 to 0.77) with sensitivity 37% at specificity 90%) and SGA (AUC 0.83 (95%CI 0.81 to 0.86) with sensitivity 55% at specificity 90%). Combining second and third trimester fetal and placental ultrasound did not lead to a better performance as compared to using only third trimester results. CONCLUSIONS: Combining single third trimester fetal and placental ultrasound results with maternal characteristics has the best screening performance for risks of preterm birth, SGA and LGA. As compared to second trimester screening, third trimester screening may double the detection of fetuses at risk of common adverse birth outcomes.

Elevated body mass index during pregnancy and gestational weight gain in HIV-infected and HIV-uninfected women in Cape Town, South Africa: association with adverse birth outcomes.

OBJECTIVES: To examine the association between maternal body mass index (BMI) and gestational weight gain (GWG) and adverse birth outcomes in HIV-infected and HIV-uninfected women. METHODS: In an urban South African community, 2921 consecutive HIV-infected and HIV-uninfected pregnant women attending primary healthcare services were assessed at their first antenatal visit. A subset of HIV-infected women enrolled in a longitudinal study was assessed three times during pregnancy. All women had birth outcome data from medical records and study questionnaires. In analyses, the associations between BMI, GWG, maternal factors and adverse birth outcomes were assessed with logistic regression models. RESULTS: The estimated pre-pregnancy BMI median was 29 kg/m2 (IQR, 24-34) overall, 29 kg/m2 (IQR, 24-34) for HIV-uninfected and 28 kg/m2 (IQR, 24-34) for HIV-infected women; HIV prevalence was 38%. In adjusted models, increased BMI in the overall cohort was positively associated with age, haemoglobin and parity at first antenatal visit. Maternal obesity was associated with increased likelihood of having high birthweight (aOR 2.54, 95% CI 1.39-4.66) and large size for gestational age (aOR 1.66, 95% CI 1.20-2.31) infants. In the subset cohort, GWG was associated with increased likelihood of spontaneous preterm delivery (aOR 4.35, 95% CI 1.55-12.21) and high birthweight (aOR 3.00, 95% CI 1.22-7.34) infants. CONCLUSION: Obesity during pregnancy is prevalent in this setting and appears associated with increased risk of adverse birth outcomes in both HIV-infected and HIV-uninfected women. Weight management interventions targeting women of child-bearing age are needed to promote healthy pregnancies and reduce adverse birth outcomes.

OBJECTIFS: Examiner l'association entre l'indice de masse corporelle maternelle (IMC) et le gain de poids gestationnel (GPG) et les résultats de naissance défavorables chez les femmes infectées et non infectées par le VIH. MÉTHODES: Dans une communauté urbaine sud-africaine, 2921 femmes enceintes consécutives infectées et non infectées par le VIH visitant les services de soins de santé primaires ont été évaluées lors de leur première visite prénatale. Un sous-ensemble de femmes infectées par le VIH inscrites à une étude longitudinale a été évalué trois fois pendant la grossesse. Toutes les femmes avaient des données sur les résultats à la naissance provenant des dossiers médicaux et des questionnaires d'étude. Dans les analyses, les associations entre l'IMC, le GPG, les facteurs maternels et les résultats de naissance défavorables ont été évalués en utilisant des modèles de régression logistique. RÉSULTATS: L'IMC médian estimé avant la grossesse était globalement de 29 kg/m2 (IQR, 24-34) pour les femmes non infectées par le VIH et 28 kg/m2 (IQR, 24 -34) pour celles infectées par le VIH; La prévalence du VIH était de 38%. Dans les modèles ajustés, l'augmentation de l'IMC dans la cohorte globale était positivement associée à l'âge, à l'hémoglobine et à la parité lors de la première visite prénatale. L'obésité maternelle a été associée à une augmentation de la probabilité d'avoir un nourrisson avec un poids élevé à la naissance (ORa 2,54, IC95%: 1,39-4,66) et une grande taille pour l'âge gestationnel (ORa 1,66, IC95%: 1,20-2,31). Dans la cohorte du sous-ensemble, le GPG était associé à une probabilité accrue d'accouchement prématuré spontané (aOR 4,35, IC95%: 1,55-12,21) et à des nourrissons avec un poids de naissance élevé (aOR 3,00, IC95%: 1,22-7,34). CONCLUSION: L'obésité pendant la grossesse est répandue dans ce contexte et semble associée à un risque accru d'accouchements défavorables chez les femmes infectées et non infectées par le VIH. Des interventions de prise en charge du poids ciblant les femmes en âge de procréer sont nécessaires pour promouvoir des grossesses saines et réduire les issues de naissance défavorables.

Fish Oil Supplementation in Pregnancy Increases Gestational Age, Size for Gestational Age, and Birth Weight in Infants: A Randomized Controlled Trial.

BACKGROUND: Randomized trials have reported that supplementation with n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in pregnancy can prolong pregnancy and thereby increase birth weight. OBJECTIVE: We aimed to examine the relations of n-3 LCPUFA supplementation in pregnancy with duration of pregnancy, birth weight, and size for gestational age (GA). METHODS: This was a double-blind randomized controlled trial conducted in 736 pregnant women and their offspring, from the Copenhagen Prospective Studies on Asthma in Childhood2010cohort. They were recruited between weeks 22 and 26 in pregnancy and randomly assigned to either of 2.4 g n-3 LCPUFA or control (olive oil) daily until 1 wk after birth. Exclusion criteria were endocrine, cardiovascular, or nephrologic disorders and vitamin D supplementation intake >600 IU/d. In this study we analyzed secondary outcomes, and further excluded twin pregnancies and extrauterine death. The primary outcome for the trial was persistent wheeze or asthma. RESULTS: The random assignment ran between 2008 and 2010. Six hundred and ninety-nine mother-infant pairs were included in the analysis. n-3 LCPUFA compared with control was associated with a 2-d prolongation of pregnancy [median (IQR): 282 (275-288) d compared with 280 (273-286) d, P = 0.02], a 97-g higher birth weight (mean ± SD: 3601 ± 534 g compared with 3504 ± 528 g, P = 0.02), and an increased size for GA according to the Norwegian population-based growth curves-Skjærven (mean ± SD: 49.9 ± 28.3 percentiles compared with 44.5 ± 27.6 percentiles, P = 0.01). CONCLUSION: Supplementing pregnant women with n-3 LCPUFAs during the third trimester is associated with prolonged gestation and increased size for GA, leading to a higher birth weight in this randomized controlled trial. This trial was registered at clinicaltrials.gov as NCT00798226.

Maternal diabetes mellitus and congenital anomalies of the kidney and urinary tract (CAKUT) in the child.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the primary cause of chronic kidney disease in children. The relevance of timing of diabetes mellitus (DM) exposure on risk of CAKUT in exposed children is unknown. STUDY DESIGN: Population-based nested case-control study. SETTING & PARTICIPANTS: Infants born between fiscal years 1996/1997 and 2009/2010 in Manitoba, Canada, identified using administrative data housed at the Manitoba Centre for Health Policy. PREDICTORS: Pregestational (including first 20 weeks' gestation) and gestational (>20 weeks) DM and relevant confounders (maternal age; renin-angiotensin-aldosterone system inhibitor use; low socioeconomic status; alcohol, illicit drug, and smoking use during pregnancy; region of residence; and size for gestational age [surrogate of glycemic control]). OUTCOME: CAKUT identified by International Classification of Diseases codes. RESULTS: 945 case patients with CAKUT and 4,725 controls (matched for gestational age, sex, and birth year) were identified. Maternal pregestational DM occurred in 39 (4.1%) of the CAKUT group and 111 (2.3%) controls (P = 0.002), whereas gestational DM occurred in 40 (4.2%) of the CAKUT group and 157 (3.3%) controls (P = 0.2). In the conditional multivariable logistic regression model, pregestational DM was associated with CAKUT (OR, 1.67; 95% CI, 1.14-2.46), whereas gestational DM was not (OR, 1.29; 95% CI, 0.90-1.85). Both large (LGA) and small for gestational age (SGA) also were associated significantly with CAKUT (LGA: OR, 1.34 [95% CI, 1.11-1.63]; SGA: OR, 1.59 [95% CI, 1.26-2.01]). LIMITATIONS: Lack of data for maternal glycemic control and body mass index. CONCLUSIONS: This study suggests that DM in the first 20 weeks of pregnancy is associated with CAKUT in exposed infants. The association between CAKUT and LGA suggests that poor glycemic control increases risk. Screening and intervention studies in women of childbearing age with DM are warranted to determine whether the risk of chronic kidney disease in children can be modified.

Determining optimal gestational weight gain in a multiethnic Asian population.

AIM: To define the optimal gestational weight gain (GWG) for the multiethnic Singaporean population. METHODS: Data from 1529 live singleton deliveries was analyzed. A multinomial logistic regression analysis, with GWG as the predictor, was conducted to determine the lowest aggregated risk of a composite perinatal outcome, stratified by Asia-specific body mass index (BMI) categories. The composite perinatal outcome, based on a combination of delivery type (cesarean section [CS], vaginal delivery [VD]) and size for gestational age (small [SGA], appropriate [AGA], large [LGA]), had six categories: (i) VD with LGA; (ii) VD with SGA; (iii) CS with AGA; (iv) CS with SGA; (v) CS with LGA; (vi) and VD with AGA. The last was considered as the 'normal' reference category. In each BMI category, the GWG value corresponding to the lowest aggregated risk was defined as the optimal GWG, and the GWG values at which the aggregated risk did not exceed a 5% increase from the lowest aggregated risk were defined as the margins of the optimal GWG range. RESULTS: The optimal GWG by pre-pregnancy BMI category, was 19.5 kg (range, 12.9 to 23.9) for underweight, 13.7 kg (7.7 to 18.8) for normal weight, 7.9 kg (2.6 to 14.0) for overweight and 1.8 kg (-5.0 to 7.0) for obese. CONCLUSION: The results of this study, the first to determine optimal GWG in the multiethnic Singaporean population, concur with the Institute of Medicine (IOM) guidelines in that GWG among Asian women who are heavier prior to pregnancy, especially those who are obese, should be lower. However, the optimal GWG for underweight and obese women was outside the IOM recommended range.

Gestational weight gain and adverse birth outcomes in South African women with HIV on antiretroviral therapy and without HIV: a prospective cohort study.

INTRODUCTION: Outside of pregnancy, evidence shows that persons with HIV initiating or switching to dolutegravir (DTG)-based antiretroviral therapy (ART) experience greater weight gain compared to those on other ART classes. However, there are few data on the impact of DTG-based ART on gestational weight gain (GWG) in sub-Saharan Africa where HIV is most common. According to the National Academy of Medicine (NAM), GWG below and above NAM guidelines is associated with adverse birth outcomes. Therefore, the objective of this study was to describe GWG by HIV status and ART regimen, and examine the associations with adverse birth outcomes. METHODS: We enrolled pregnant women with HIV (WHIV) and without HIV (≥18 years) in a peri-urban primary healthcare facility in Cape Town, South Africa between 2019 and 2022. GWG was study-measured at 24-28 (baseline) and 33-38 weeks gestation and converted to GWG rate (kg/week) in accordance with NAM guidelines. GWG z-scores were generated using the INTEGROWTH-21 and US standards to account for differing lengths of gestation. Birth outcome data were obtained from medical records. Associations of GWG z-score with adverse birth outcomes were assessed using multivariable linear or log-binomial regression. RESULTS: Among 292 participants (48% WHIV), median age was 29 years (IQR, 25-33), median pre-pregnancy body mass index (BMI) was 31 kg/m2 (IQR, 26-36) and 20% were primiparous at baseline. The median weekly rate of GWG was 0.30 kg/week (IQR, 0.12-0.50), 35% had GWG below NAM standards (59% WHIV) and 48% had GWG above NAM standards (36% WHIV). WHIV gained weight more slowly (0.25 vs. 0.37 kg/week, p<0.01) than women without HIV. Weekly rate of GWG did not differ by ART regimen (DTG-based ART 0.25 vs. efavirenz-based ART 0.27 kg/week, p = 0.80). In multivariable analyses, GWG z-score was positively associated with continuous birth weight (mean difference = 68.53 95% CI 8.96, 128.10) and categorical high birth weight of >4000 g (RR = 2.18 95% CI 1.18, 4.01). CONCLUSIONS: Despite slower GWG among WHIV, nearly half of all women gained weight faster than recommended by the NAM. GWG was positively associated with infant birth weight. Interventions to support healthy GWG in sub-Saharan Africa are urgently needed.

Effect of vitamin A on the relationship between maternal thyroid hormones in early pregnancy and fetal growth: A prospective cohort study.

Background: Fetal growth patterns are influenced by maternal thyroid function and vitamin A level during pregnancy. Vitamin A presents interactions with thyroid tissues and hormonal systems. We examined whether vitamin A status modified the associations of maternal thyroid hormones in early pregnancy and fetal growth outcomes among euthyroid pregnant women in a prospective cohort study (n = 637). Methods: We performed multiple linear regression and multinomial logistic regression analysis to investigate the effects of thyroid hormones in early pregnancy on fetal growth according to different levels of serum vitamin A based on median value. Results: A 1 pmol/L increase in maternal free triiodothyronine (FT3) levels was associated with an increased birth weight of 0.080 kg (p = 0.023) in women with lower maternal vitamin A levels in early pregnancy. Increased maternal free thyroxine (FT4) was associated with decreased odds for both small size for gestational age (SGA) [odds ratios (OR) = 0.66, 95% confidence interval (CI): 0.45-0.95] and large size for gestational age (LGA) (OR = 0.66, 95% CI: 0.45-0.98) in women with higher vitamin A level in early pregnancy after adjustment for maternal prepregnancy body mass index, gestational weight gain, maternal employed, parity, gestational week at sampling, and gestational diabetes mellitus. Conclusions: In Chinese pregnant women without overt thyroid dysfunction, maternal FT4 in early pregnancy was positively associated with optimal fetal growth among women with higher serum vitamin A concentrations.

Associations of maternal and infant metabolite profiles with foetal growth and the odds of adverse birth outcomes.

BACKGROUND: Adaptations in maternal and foetal metabolic pathways may predispose to altered foetal growth and adverse birth outcomes. OBJECTIVE: To assess the associations of maternal early-pregnancy metabolite profiles and infant metabolite profiles at birth with foetal growth from first trimester onwards and the odds of adverse birth outcomes. METHODS: In a prospective population-based cohort among 976 Dutch pregnant women and their children, serum concentrations of amino acids, non-esterified fatty acids (NEFA), phospholipids (PL) and carnitines in maternal early-pregnancy blood and in cord blood were obtained by liquid-chromatography tandem mass spectrometry. Information on foetal growth was available from first trimester onwards. RESULTS: After false discovery rate correction for multiple testing, higher infant total and individual NEFA concentrations were associated with a lower weight, length, and head circumference at birth. Higher infant total and individual acyl-lysophosphatidylcholine (lyso.PC.a) and alkyl-lysophosphatidylcholine concentrations were associated with higher weight and head circumference (lyso.PC.a only) at birth, higher odds of LGA and lower odds of SGA. Few individual maternal metabolites were associated with foetal growth measures in third trimester and at birth, but not with the odds of adverse birth outcomes. CONCLUSIONS: Our results suggest that infant metabolite profiles, particularly total and individual lyso.PC.a and NEFA concentrations, were strongly related to growth measures at birth and the odds of adverse birth outcomes. Few individual maternal early-pregnancy metabolites, but not total metabolite concentrations, are associated with foetal growth measures in third trimester and at birth.

Anthropometrics at birth and risk of a primary central nervous system tumour: A systematic review and meta-analysis.

BACKGROUND: The aetiology of primary central nervous system (CNS) tumours remains largely unknown, but their childhood peak points to perinatal parameters as tentative risk factors. In this meta-analysis, we opted to quantitatively synthesise published evidence on the association between birth anthropometrics and risk of primary CNS tumour. METHODS: Eligible studies were identified via systematic literature review; random-effects meta-analyses were conducted for the effect of birth weight and size-for-gestational-age on childhood and adult primary CNS tumours; subgroup, sensitivity, meta-regression and dose-response by birth weight category analyses were also performed. RESULTS: Forty-one articles, encompassing 53,167 CNS tumour cases, were eligible. Birth weight >4000 g was associated with increased risk of childhood CNS tumour (OR: 1.14, [1.08-1.20]; 22,330 cases). The risk was higher for astrocytoma (OR: 1.22, [1.13-1.31]; 7456 cases) and embryonal tumour (OR: 1.16, [1.04-1.29]; 3574 cases) and non-significant for ependymoma (OR: 1.12, [0.94-1.34]; 1374 cases). Increased odds for a CNS tumour were also noted among large-for-gestational-age children (OR: 1.12, [1.03-1.22]; 10,339 cases), whereas insufficient data for synthesis were identified for other birth anthropometrics. The findings remained robust across subgroup and sensitivity analyses controlling for several sources of bias, whereas no significant heterogeneity or publication bias were documented. The limited available evidence on adults (4 studies) did not reveal significant associations between increasing birth weight (500-g increment) and overall risk CNS tumour (OR: 0.99, [0.98-1.00]; 1091 cases) or glioma (OR: 1.03, [0.98-1.07]; 2052 cases). CONCLUSIONS: This meta-analysis confirms a sizeable association of high birth weight, with childhood CNS tumour risk, particularly astrocytoma and embryonal tumour, which seems to be independent of gestational age. Further research is needed to explore underlying mechanisms, especially modifiable determinants of infant macrosomia, such as gestational diabetes.

Maternal vitamin D concentrations during pregnancy, fetal growth patterns, and risks of adverse birth outcomes.

BACKGROUND: Maternal vitamin D deficiency during pregnancy may affect fetal outcomes. OBJECTIVE: The objective of this study was to examine whether maternal 25-hydroxyvitamin D [25(OH)D] concentrations in pregnancy affect fetal growth patterns and birth outcomes. DESIGN: This was a population-based prospective cohort in Rotterdam, Netherlands in 7098 mothers and their offspring. We measured 25(OH)D concentrations at a median gestational age of 20.3 wk (range: 18.5-23.3 wk). Vitamin D concentrations were analyzed continuously and in quartiles. Fetal head circumference and body length and weight were estimated by repeated ultrasounds, and preterm birth (gestational age <37 wk) and small size for gestational age (less than the fifth percentile) were determined. RESULTS: Adjusted multivariate regression analyses showed that, compared with mothers with second-trimester 25(OH)D concentrations in the highest quartile, those with 25(OH)D concentrations in the lower quartiles had offspring with third-trimester fetal growth restriction, leading to a smaller head circumference, shorter body length, and lower body weight at birth (all P < 0.05). Mothers who had 25(OH)D concentrations in the lowest quartile had an increased risk of preterm delivery (OR: 1.72; 95% CI: 1.14, 2.60) and children who were small for gestational age (OR: 2.07; 95% CI: 1.33, 3.22). The estimated population attributable risk of 25(OH)D concentrations <50 nmol/L for preterm birth or small size for gestational age were 17.3% and 22.6%, respectively. The observed associations were not based on extreme 25(OH)D deficiency, but presented within the common ranges. CONCLUSIONS: Low maternal 25(OH)D concentrations are associated with proportional fetal growth restriction and with an increased risk of preterm birth and small size for gestational age at birth. Further studies are needed to investigate the causality of these associations and the potential for public health interventions.

Tracking of fetal growth characteristics during different trimesters and the risks of adverse birth outcomes.

BACKGROUND: Fetal growth characteristics are used to identify influences of several maternal characteristics and to identify individuals at increased risk of adverse outcomes. The extent to which fetal growth characteristics track in different trimesters is not known. METHODS: In a population-based prospective cohort study among 8636 pregnant women, we examined the extent to which fetal growth characteristics track, are influenced by maternal socio-demographic and lifestyle related determinants and are associated with birth outcomes. Fetal growth was assessed in each trimester and at birth. RESULTS: Correlation coefficient between first-trimester crown-rump length and birthweight was r = 0.12 (P-value < 0.05). Correlation coefficients for fetal-head circumference, (femur) length and (estimated) fetal weight ranged from r = 0.16 to r = 0.30 (all P-values < 0.05) between second trimester and birth and from r = 0.36 to r = 0.58 (all P-values < 0.05) between third trimester and birth, and were highest for (estimated) fetal weight. Correlation coefficients for (estimated) fetal weight tended to be lower among overweight mothers, as compared with normal weight mothers, but were not influenced by other maternal characteristics. First, second and third-trimester fetal growth characteristics were associated with risks of preterm birth and small size for gestational age at birth,with the strongest associations present in third trimester. CONCLUSION: Fetal growth characteristics track moderately throughout gestation, with stronger tracking coefficients present in later pregnancy. Tracking coefficients were not materially influenced by maternal socio-demographic and lifestyle characteristics. First, second and third trimester fetal growth characteristics were associated with the risk of adverse birth outcomes.