Periconceptional maternal ultra-processed food (UPF) consumption impairs embryonic growth. Impacts of exposure to UPF on distinct components of fetal growth in late pregnancy are unknown. We investigated the influence of frequency of UPF consumption during pregnancy on fetal head circumference (HC), abdominal circumference (AC) and femur length (FL). This study included 417 live-born singleton pregnancies prospectively followed-up since the antenatal period in the MINA-Brazil Study, with an available ultrasound scan at >24 gestational weeks. Frequency of food groups consumption in the previous month was categorised as no/monthly, weekly or daily. Ultrasound scans were conducted at 27·8 (sd: 1·7) gestational weeks. HC, AC and FL z-scores were calculated for gestational age using the INTERGROWTH-21st Project standards. Simultaneous-quantile regression models were fitted at the 10th, 50th and 90th percentiles of the distribution of each ultrasound parameter according to UPF consumption, with adjustment for potential confounders. Participants were aged on average 24·7 (sd: 6·5) years, 44·8 % were primiparous, and 26·9 % and 24·9 %, respectively, had weekly and daily UPF consumption. Compared with no/monthly intake, daily UPF consumption impaired HC across its distribution, with significant effect sizes varying from –0·24 to –0·40 z-score. Weekly UPF consumption decreased HC at the 90th percentile by –0·39 z-score (95 % CI: –0·78, –0·01) and FL at the 50th percentile by –0·32 z-score (95 % CI: –0·60, –0·04). No association was noted with AC. Frequency of UPF consumption was negatively associated with skeletal components of fetal growth in late pregnancy. Infant body composition may benefit from healthy food practices since pregnancy.

Alcohol abuse among women is a public health importance that may impair prenatal and postnatal growth. Tella is among the most common homemade alcoholic beverages in rural Ethiopia, but little is known about the magnitude of tella intake during pregnancy and lactation or its effects on child growth. The present study investigated associations between maternal tella intake and the growth of their children. A cross-sectional mixed-methods study was conducted with mothers (n 228) and their 12–36-month-old children and with key informants (n 12). Tella intake during most recent pregnancy and lactation was estimated retrospectively by glasses per drinking event and frequency of events. Nearly 80 % of mothers had consumed some amount of tella during their most recent pregnancy and lactation. Furthermore, 72 % of children had tasted or drunk tella at some time during their life. Stunting was 42 % and was significantly associated with maternal tella consumption at least every other day during pregnancy (adjusted odds ratio (AOR) 4⋅97, 95 % confidence interval (CI) 2⋅20, 11⋅25), male sex (AOR 2⋅31, 95 % CI 1⋅27, 4⋅19), two or more under-5-year-old children in the household (AOR 3⋅52, 95 % CI 1⋅49, 8⋅33) and family size >5 (AOR 1⋅84, 95 % CI 1⋅01, 3⋅36). Underweight was 24⋅6 % and was associated with the child drinking tella with their mother (AOR 4⋅23, 95 % CI 1⋅99, 8⋅97), being male (AOR 3⋅73, 95 % CI 1⋅73, 7⋅94), having ≥3 diarrhoeal episodes in the last 3 months (AOR 11⋅83, 95 % CI 4⋅22, 33⋅14) and being in the older age group (AOR 2⋅98, 95 % CI 1⋅09, 8⋅13). The associations between tella intake and child growth suggest the need to mitigate the effects of tella on child anthropometry.

Animal and human data demonstrate independent relationships between fetal growth, hypothalamic-pituitary-adrenal axis function (HPA-A) and adult cardiometabolic outcomes. While the association between fetal growth and adult cardiometabolic outcomes is well-established, the role of the HPA-A in these relationships is unclear. This study aims to determine whether HPA-A function mediates or moderates this relationship. Approximately 2900 pregnant women were recruited between 1989-1991 in the Raine Study. Detailed anthropometric data was collected at birth (per cent optimal birthweight [POBW]). The Trier Social Stress Test was administered to the offspring (Generation 2; Gen2) at 18 years; HPA-A responses were determined (reactive responders [RR], anticipatory responders [AR] and non-responders [NR]). Cardiometabolic parameters (BMI, systolic BP [sBP] and LDL cholesterol) were measured at 20 years. Regression modelling demonstrated linear associations between POBW and BMI and sBP; quadratic associations were observed for LDL cholesterol. For every 10% increase in POBW, there was a 0.54 unit increase in BMI (standard error [SE] 0.15) and a 0.65 unit decrease in sBP (SE 0.34). The interaction between participant’s fetal growth and HPA-A phenotype was strongest for sBP in young adulthood. Interactions for BMI and LDL-C were non-significant. Decomposition of the total effect revealed no causal evidence of mediation or moderation.

Males and females have been proposed to have different prenatal growth strategies, whereby males invest more in fetal growth and less in placental development, leaving them more susceptible to early-life adversity. We tested predictions of this hypothesis using data from the National Collaborative Perinatal Project. Male newborns were heavier than females, but there was no difference in placental weight, adjusting for birthweight. Among infants born prior to 33 weeks, the difference in birthweight between males and females was greater among those who did not survive than among those who did, potentially reflecting a strategy whereby males maintained growth in the face of prenatal insults, while females adjusted growth. However, there was no significant difference in mortality between the sexes. Being born small-for-gestational age or very preterm (prior to 33 weeks) was associated with significantly reduced performance for most of the cognitive traits examined at 7 years, although maternal preeclampsia was associated with reduced performance in fewer traits. Generally, these effects of early-life adversity (poor fetal growth, prematurity, and preeclampsia) did not differ between the sexes. However, analyzing the sexes separately (rather than testing the interaction between sex and adversity) resulted in numerous spurious sex-specific effects, whereby the effect of early-life adversity appeared to be significant in one sex but not the other. Overall, we found little support for the hypothesis that males prioritize growth more than females, and that this makes them more susceptible to early-life adversity. Furthermore, our results show that analyzing the sexes separately, rather than testing the adversity by sex interaction, can be highly misleading.

Nutrition and maternal behavior are critical factors in fetal development. Maternal water intake is necessary to regulate metabolism and may influence fetal growth. This study aims to determine the effect of dehydration during pregnancy on birth weight and length. This cohort-prospective study took place in the area of Kebon Jeruk District Health Centre. A total of 38 subjects of pregnant women in their second trimester were examined. Subject characteristics were collected through direct measurements and interviews. Urine and blood samples were collected at the sixth trimester (32–34 and 35–37 weeks) to determine hydration status. Nutritional status was collected through food recall, while birth weight and length were obtained from the anthropometric measurements 30 min after birth. From a total of 38 subjects, 20 were dehydrated, and 18 were well hydrated. There was a significant relationship between hydration status and water intake, birth weight and length, head circumference, and chest circumference. After being corrected to the level of water intake, the difference in birth weight and length between the two groups were 500⋅6 g and 0⋅4 cm, and 0⋅8 cm and 1⋅4 cm for the head circumference and chest circumference (P < 0⋅05). It is recommended for mothers to monitor their weight and ensure fluid intake of 3⋅0 l per day. Further research requires more subjects to observe the effects of chronic maternal dehydration on pregnancy output and a cohort study that monitors infant development in the first six months of life.

Clinical trials show that protein supplement increases infant size in malnourished populations; however, epidemiological studies in high-income countries have reported mixed results. Although these findings suggest a non-linear relationship between maternal macronutrient intake and fetal growth, this relationship has not been closely examined. We assessed the association between maternal protein intake and fetal growth among 91 637 Japanese women with singletons in a nation-wide cohort study using validated FFQ. The respondents answered the FFQ twice, once during early pregnancy (FFQ1; 16·3 (sd 6·0) weeks), and second during mid-pregnancy (FFQ2, 28·1 (sd 4·1) weeks). Daily energy intake and percentage energy from protein, fats and carbohydrates were 7477 (sd 2577) kJ and 13·5 (sd 2·0), 29·5 (sd 6·5) and 55·3 (sd 7·8) %, respectively, for FFQ1, and 7184 (sd 2506) kJ and 13·6 (sd 2·1), 29·8 (sd 6·6) and 55·3 (sd 7·9) %, respectively, for FFQ2. The average birth weight was 3028 (sd 406) g, and 6350 infants (6·9 %) were small for gestational age (SGA). In both phases of the survey, birth weight was highest and the risk of SGA was lowest when the percentage energy from protein was 12 %, regardless of whether isoenergetic replacement was with fat or carbohydrates. Furthermore, when protein density in the maternal diet was held constant, birth weight was highest when 25 % of energy intake came from fat and 61 % came from carbohydrates during early pregnancy. We found maternal protein intake to have an inverse U-curve relationship with fetal growth. Our results strongly suggest that the effect of protein on birth weight is non-linear, and that a balanced diet fulfilling the minimum requirement for all macronutrients was ideal for avoiding fetal growth restriction.

A discordant twin gestation, in which one fetus is significantly growth restricted, compared to the other normal twin, is a unique model that can be used to elucidate the mechanism(s) by which the intrauterine environment affects fetal growth. In many model systems, placental transcription factor genes regulate fetal growth. Transcription factors regulate growth through their activation or repression of downstream target genes that mediate important cell functions. The objective of this study was to determine the expression of the placental HLX homeobox gene transcription factor and its downstream target genes in dizygotic twins with growth discordance. In this cross-sectional study, HLX and its downstream target genes’ retinoblastoma 1 (RB1) and cyclin kinase D (CDKN1C) expression levels were determined in placentae obtained from dichorionic diamniotic twin pregnancies (n = 23) where one of the twins was growth restricted. Fetal growth restriction (FGR) was defined as small for gestational age with abnormal umbilical artery Doppler indices when compared with the normal control co-twin. Homeobox gene HLX expression was significantly decreased at both the mRNA and protein levels in FGR twin placentae compared with the normal control co-twin placentae (p < .05). Downstream target genes CDKN1C and RB1 were also significantly decreased and increased, respectively, at both the mRNA and protein levels in FGR twin placentae compared with normal control co-twin placentae (p < .05). Together, these observations suggest an important association between HLX transcription factor expression and abnormal human placental development in discordant twin pregnancies.

Maternal mental disorders during pregnancy are associated with a range of adverse health outcomes for offspring. This systematic review examines studies reporting on the relationship between maternal depression, anxiety or stress during pregnancy and fetal growth measured during pregnancy using ultrasound biometry. A systematic search of PsycINFO, Medline, Scopus, Web of Science and Embase was conducted and 1575 records were identified, with nine studies meeting inclusion criteria gathering data from over 7000 participants. All studies measured depression, six examined anxiety and depression, and five examined all three exposures. The majority measured symptoms rather than clinically diagnosable disorder. Studies consistently reported significant associations between maternal mental health, particularly anxiety symptoms, and reduced fetal head growth. Other fetal growth parameters showed inconsistent findings. A number of studies suggest that cortisol dysregulation associated with maternal mental health may play a role in fetal growth restriction. However, heterogeneity in the timing of growth measurement, assessment measures used for mental health and inconsistencies in adjustment for confounders, limits the synthesis and interpretation of findings. Future studies should consider differences in the timing, intensity and duration of mental health symptoms over pregnancy and should employ diagnostic assessment of mental disorders. Fetal growth should be repeatedly measured and further work is needed to establish the biological mechanisms involved.

Earlier research suggests that maternal pelvic size is associated with offspring’s stroke risk in later life. We followed 6362 men and women from Uppsala, Sweden, born between 1915 and 1929 from 1964 to 2008 to assess whether maternal pelvic size was associated with incidence of thrombotic stroke (TS), haemorrhagic stroke (HS) and other stroke (OS). Offspring whose mothers had a flat pelvis had lower birth weight and birth-weight-for-gestational-age compared with those who did not. Inverse linear associations of birth-weight-for-gestational-age were observed with TS and OS. Female offspring whose mothers had a flat pelvis had increased risk of TS, but flat pelvis was not associated with other types of stroke. A smaller difference between intercristal and interspinous diameters and a smaller external conjugate diameter were independently associated with HS, whereas no pelvic measurements were associated with OS. We conclude that a smaller pelvis in women may impact the health of their offspring in adulthood.

Maternal nutritional status (MNS) is a strong predictor of growth and development in the first 1000 days of life and may influence susceptibility to non-communicable diseases in adulthood. However, the role of nutrition during this window of developmental plasticity in Africa is unclear. This paper reviews published data to address whether maternal nutrition during the first 1000 days is important for Africa, with a focus on MNS and its associations with fetal growth and birth, neonatal and infant outcomes. A systematic approach was used to search the following databases: Medline, EMBASE, Web of Science, Google Scholar, ScienceDirect, SciSearch and Cochrane Library. In all, 26 studies met the inclusion criteria for the specific objectives. MNS in Africa showed features typical of the epidemiological transition: higher prevalences of maternal overweight and obesity and lower underweight, poor diet quality 1 and high anaemia prevalence. Maternal body mass index and greater gestational weight gain (GWG) were positively associated with birth weight; however, maternal overweight and obesity were associated with increased risk of macrosomia and intrauterine growth restriction. Maternal anaemia was associated with lower birth weight. Macro- and micronutrient supplementation during pregnancy were associated with improvements in GWG, birth weight and mortality risk. Data suggest poor MNS in Africa and confirms the importance of the first 1000 days as a critical period for nutritional intervention to improve growth, birth outcomes and potential future health risk. However, there is a lack of data beyond birth and a need for longitudinal data through infancy to 2 years of age.

David Barker established growth as a seminal link between early development and later health attainment and disease risk. This was nothing less than a paradigm shift in health and medicine, turning the focus of disease causality away from contemporary environmental influences to earliest growth as a time when functional anatomy and physiology sets in place critical structures and function for a lifetime.

Barker’s prodigious work investigated time- and place-specific interactions between maternal condition and exogenous environmental influences, focusing on how growth unfolds across development to function as a mechanistic link to ensuing health. Subsequent applications do not always attend to the specificity and sensitivity issues included in his original work, and commonly overlook the long-standing methods and knowledge base of auxology. Methodological areas in need of refinement include enhanced precision in how growth is represented and assessed. For example, multiple variables have been used as a referent for ‘growth,’ which is problematic because different body dimensions grow by different biological clocks with unique functional physiologies. In addition, categorical clinical variables obscure the spectrum of variability in growth experienced at the individual level. Finally, size alone is a limited measure as it does not capture how individuals change across age, or actually grow.

The ground-breaking notion that prenatal influences are important for future health gave rise to robust interest in studying the fetus. Identifying the many pathways by which size is realized permits targeted interventions addressing meaningful mechanistic links between growth and disease risk to promote health across the lifespan.

Eukaryotic species commonly contain a diploid complement of chromosomes. The diploid state appears to be advantageous for mammals because it enables sexual reproduction and facilitates genetic recombination. Nonetheless, the effects of DNA ploidy on mammalian ontogeny have yet to be understood. The present study shows phenotypic features and expression patterns of imprinted genes in tripronucleate diandric and digynic triploid (DAT and DGT) mouse fetuses on embryonic day 10.5 (E10.5). Measurement of crown–rump length revealed that the length of DGT fetuses (1.87 ± 0.13 mm; mean ± standard error of the mean) was much smaller than that of diploid fetuses (4.81 ± 0.05 mm). However, no significant difference was observed in the crown–rump length between diploid and DAT fetuses (3.86 ± 0.43 mm). In DGT fetuses, the expression level of paternally expressed genes, Igf2, Dlk1, Ndn, and Peg3, remained significantly reduced and that of maternally expressed genes, Igf2r and Grb10, increased. Additionally, in DAT fetuses, the Igf2 mRNA expression level was approximately twice that in diploid fetuses, as expected. These results provide the first demonstration that imprinted genes in mouse triploid fetuses show distinctive expression patterns independent of the number of parental-origin haploid sets. These data suggest that both DNA ploidy and asymmetrical functions of parental genomes separately influence mammalian ontogeny.

Fetal macronutrient requirements for oxidative metabolism and growth are met by placental transport of glucose, amino acids, and, to a lesser extent that varies with species, fatty acids. It is becoming possible to relate the maternal–fetal transport kinetics of these molecules in vivo to the expression and distribution of specific transporters among placental cell types and subcellular membrane fractions. This is most true for glucose transport, although apparent inconsistencies among data on the roles and relative importance of the predominant placenta glucose transporters, GLUT-1 and GLUT-3, remain to be resolved. The quantity of macronutrients transferred to the fetus from the maternal bloodstream is greatly influenced by placental metabolism, which results in net consumption of large amounts of glucose and, to a lesser extent, amino acids. The pattern of fetal nutrient supply is also altered considerably by placental conversion of glucose to lactate and, in some species, fructose, and extensive transamination of amino acids. Placental capacity for transport of glucose and amino acids increases with fetal demand as gestation advances through expansion of the exchange surface area and increased expression of specific transport molecules. In late pregnancy, transport capacity is closely related to placental size and can be modified by maternal nutrition. Preliminary evidence suggests that placental expression and function of specific transport proteins are influenced by extracellular concentrations of nutrients and endocrine factors, but, in general, the humoral regulation of placental capacity for nutrient transport is poorly understood. Consequences of normal and abnormal development of placental transport functions for fetal growth, especially during late gestation, and, possibly, for fetal programming of postnatal disorders, are discussed.

Genetic variants in the FTO (fat mass- and obesity-associated) gene have the highest association of all obesity-associated genes. Its placental expression was shown to relate to birth weight, suggesting that it may participate in the control of fetal weight gain. To gain more insight into the implication of FTO in fetal growth, we measured its placental expression in samples including extremes of abnormal fetal growth, such as after intrauterine growth restriction (IUGR) or macrosomia in both rats and humans. In rats, fetal growth was modulated by maternal nutritional modifications. In humans, placental villi were collected from pathological pregnancies (i.e. with IUGR or fetal macrosomia). Placental FTO mRNA expression was reduced by IUGR but was not significantly affected by macrosomia in either rats or humans. Our data suggest that placental FTO may participate in interactions between the in utero environment and the control of fetal growth under IUGR conditions by modulating epigenetic processes.

This study aims to determine whether fetal growth is related to insulin-like growth factor-1 in dichorionic and monochorionic twins and also aims to investigate the correlation of insulin-like growth factor-1 to birthweight discordance in twins. We studied 100 women with twin pregnancies. The correlation tests of 36 discordant twins (15 monochorionic, 21 dichorionic) showed correlation between insulin-like growth factor-1 difference and birthweight discordance (insulin-like growth factor-1 vs. birthweight of first twin, r = +0.915, at 0.01 level, IGF-1 vs birthweight of second twin r = +0.790, at 0.01 level). In 49 monochorionic twins, independent of discordance, there was a correlation between birthweight discordance and insulin-like growth factor-1 difference (r = .538, at the 0.01 level). This correlation was not significant in dichorionic twins, r = .144, p = .01. These data suggest that growth discordances of twins exposed to the same maternal environment may be due to variations in IGF-1, depending upon the genetic similarity.

Both reductions in birth weight and preeclampsia (PE) have been associated with decrements in scores on tests of intelligence in children and adolescents. We examined whether these decrements persist into middle adulthood and expand into other domains of cognitive functioning. Using data from the Early Determinants of Adult Health project and from the ancillary project, Fetal Antecedents of Major Depression and Cardiovascular Disease, we selected term same-sex sibling sets or singletons from these sets, from the New England Family Study (NEFS) and the Child Health and Development Studies (CHDS), discordant on either fetal growth or PE, to test the hypotheses that prenatal exposure to inflammation was associated with decrements in attention, learning and executive function 40 years later. Exposure was defined as a continuous measure of percentile birth weight for gestational age, reduced fetal growth (<20th percentile of birth weight for gestational age) or maternal PE. Given that the sample was comprised, in part, of sibling sets, the analyses were performed using mixed models to account for the inter-sibling correlations. Analyses were performed separately by study site (i.e. NEFS and CHDS). We found few statistically significant associations (suggesting a possible type II error) consistent with previous literature, suggesting that the associations with low birth weight do not persist into midlife. We discuss the possible reasons for the lack of associations, which include the possible mediating effects of the postnatal environment.