This study examines disparities in health and nutrition among native and Syrian refugee children in Turkey. To understand the need for targeted programs addressing child well-being among the refugee population, we analyze the Turkey Demographic and Health Survey (TDHS) – which provides representative data for a large refugee and native population. We find no evidence of a difference in infant or child mortality between refugee children born in Turkey and native children. However, refugee infants born in Turkey have lower birthweight and age-adjusted weight and height than native infants. When we account for a rich set of birth and socioeconomic characteristics that display substantial differences between natives and refugees, the gaps in birthweight and age-adjusted height persist, but the gap in age-adjusted weight disappears. Moreover, the remaining gaps in birthweight and anthropometric outcomes are limited to the lower end of the distribution. The observed gaps are even larger for refugee infants born before migrating to Turkey, suggesting that the remaining deficits reflect conditions in the source country before migration rather than deficits in access to health services within Turkey. Finally, comparing children by the country of their first trimester, we find evidence of the detrimental effects of stress exposure during pregnancy.

Birthweight has been associated with diabetes in a reverse J-shape (highest risk at low birthweight and moderately high risk at high birthweight) and inversely associated with hypertension in adulthood with inconsistent evidence for cardiovascular disease. There is a lack of population-based studies examining the incidence of cardiometabolic outcomes in young adults born with low and high birthweights. To evaluate the association between birthweight and diabetes, hypertension, and ischemic heart disease (IHD) in young adulthood, we conducted a retrospective cohort study of 874,904 singletons born in Ontario, Canada, from 1994 to 2002, identified from population-based health administrative data. Separate Cox regression models examined birthweight in association with diabetes, hypertension, and IHD adjusting for confounders. Among adults 18–26 years, the diabetes incidence rate was 18.15 per 100,000 person-years, hypertension was 15.80 per 100,000 person-years, and IHD was 1.85 per 100,000 person-years. Adjusted hazard ratios (AHR) for the hazard of diabetes with low (<2500g) and high (>4000g), compared with normal (2500–4000g) birthweight, were 1.46 (95% CI 1.28, 1.68) and 1.09 (0.99, 1.21), respectively. AHR for hypertension with low and high birthweight were 1.34 (1.15, 1.56) and 0.86 (0.77, 0.97), respectively. AHR for IHD with low and high birthweight were 1.28 (0.80, 2.05) and 0.97 (0.71, 1.33), respectively. Overall, birthweight was associated with diabetes in young adults in a reverse J-shape and inversely with hypertension. There was insufficient evidence of an association with IHD. Further evidence is needed to understand the causal mechanisms between birthweight and cardiometabolic diseases in young adults.

This study aimed to investigate how maternal birthweight is related to early pregnancy obesity, gestational diabetes mellitus (GDM), and offspring birthweight. Females born term and singleton in Sweden between 1973 and 1995 (N = 305,893) were studied at their first pregnancy. Information regarding their birthweight, early pregnancy body mass index, and pregnancy complications was retrieved from the Swedish Medical Birth Register, as were data on their mothers and offspring. High maternal birthweights (2–3 standard deviation scores (SDS) and >3 SDS) were associated with greater odds of early pregnancy obesity, odds ratio (OR) 1.52 (95% confidence interval (CI) 1.42–1.63) and OR 2.06 (CI 1.71–2.49), respectively. A low maternal birthweight (<2 SDS) was associated with greater odds of GDM (OR 2.49, CI 2.00–3.12). No association was found between high maternal birthweight and GDM. A maternal birthweight 2–3 SDS was associated with offspring birthweight 2–3 SDS (OR 3.83, CI 3.44–4.26), and >3 SDS (OR 3.55, CI 2.54–4.97). Corresponding ORs for a maternal birthweight >3 SDS were 5.38 (CI 4.12–7.01) and 6.98 (CI 3.57–13.65), respectively. In conclusion, a high maternal birthweight was positively associated with early pregnancy obesity and offspring macrosomia. A low, but not a high maternal birthweight, was associated with GDM.

The objective of this study was to determine the association between birthweight and risk of thyroid and autoimmune conditions in a large sample of postmenopausal women. Baseline data from the Women’s Health Initiative (n = 80,806) were used to examine the associations between birthweight category (<6 lbs., 6–7 lbs. 15 oz, 8–9 lbs. 15 oz, and ≥10 lbs.) and prevalent thyroid (underactive and overactive thyroid and goiter) and autoimmune (lupus, rheumatoid arthritis (RA), multiple sclerosis, ulcerative colitis/Crohn’s disease) conditions. Follow-up questionnaire data were used to examine the associations between birthweight and incident underactive and overactive thyroid, lupus, and RA. Logistic and Cox proportional hazards regression models were used to estimate crude and adjusted odds (OR) and hazards ratios (HR), respectively. Overall, women born weighing ≥10 lbs. had an increased risk for underactive thyroid [OR 1.14 (95% CI 1.02, 1.28)] and incident lupus [HR 1.51 (95% CI 1.12, 2.03)] and a decreased risk for overactive thyroid [OR 0.67 (95% CI 0.50, 0.92)] compared to women born weighing 6–7.99 lbs., after adjustment for adult BMI, demographic variables, and lifestyle factors. Further, women born weighing <6 lbs. were at increased risk for underactive thyroid [OR 1.13 (95% CI 1.04, 1.22)]. Birthweight was not associated with other thyroid or autoimmune disorders. High birthweight was associated with later-life thyroid and autoimmune conditions while low birthweight was associated with underactive thyroid. Preconception and prenatal interventions aimed at reducing the risk of both high and low birthweights may reduce the burden of later-life thyroid and autoimmune conditions.

Birthweight has been consistently related to risk of cardiometabolic disorders in later life. Twins are at higher risk of low birthweight than singletons, so understanding the links between birthweight and cardiometabolic health may be particularly important for twins. However, evidence for the association of birthweight with childhood markers of cardiometabolic health in twins is currently lacking. Previous studies have often failed to appropriately adjust for gestational age or fully implement twin regression models. Therefore, we aimed to evaluate the association of birthweight-for-gestational-age z-scores with childhood cardiometabolic health in twins, using within-between regression models. The Peri/Postnatal Epigenetic Twins Study is a Melbourne-based prospective cohort study of 250 twin pairs. Birthweight was recorded at delivery, and childhood anthropometric measures were taken at 18-month and 6-year follow-up visits. Associations of birthweight with markers of cardiometabolic health were assessed at the individual, between- and within-pair level using linear regression with generalised estimating equations. Birthweight-for-gestational-age z-scores were associated with height, weight and BMI at 18 months and 6 years, but not with blood pressure (twins-as-individual SBP: β = 0.15, 95% CI: −0.81, 1.11; twins-as-individual DBP: β = 0.22, 95% CI: −0.34, 0.77). We found little evidence to indicate that the within-between models improved on the twins-as-individuals models. Birthweight was associated with childhood anthropometric measures, but not blood pressure, after appropriately adjusting for gestational age. These associations were consistent across the within-between and twins-as-individuals models. After adjusting for gestational age, results from the twins-as-individuals models are consistent with singleton studies, so these results can be applied to the general population.

Frozen embryo transfer (FET) has been adopted by growing number of reproductive medicine centers due to the improved outcome compared with fresh embryo transfer. However, few studies have focused on the impact of embryo cryopreservation duration on pregnancy-related complications and neonatal birthweight. Thus, a retrospective cohort study including all FET cycles with livebirth deliveries in a university affiliated hospital from May 2010 to September 2017 was conducted. These deliveries were grouped by the cryopreservation duration of the transferred embryo (≤3 months, 4–6 months, 7–12 months, and >12 months). The associations between embryo cryopreservation duration and pregnancy-related complications were evaluated among the groups using multinomial logistic regression. Neonatal birthweight was compared according to the stratification of singletons and multiples using multinomial and multilevel logistic regression, respectively. Among all 12,158 FET cycles, a total of 3864 livebirth deliveries comprising 2995 singletons and 1739 multiples were included. Compared with those within 3 months, women undergoing FET after a cryopreservation time longer than 3 months did not show any increased risk of gestational diabetes mellitus, gestational hypertension, preeclampsia, meconium staining of the amniotic fluid, or preterm birth. Furthermore, the risk of lower birthweight, macrosomia, small-for-gestational-age, or large-for-gestational-age for either singletons or multiples was not affected by long-term cryopreservation. In summary, embryo cryopreservation duration does not have negative effects on pregnancy-related complications or birthweight after FET.

Low gestational weight gain (GWG) is a known risk factor of low birthweight. Although studies have previously examined the associations between GWG and birthweight, the period-specific effects of low GWG in each trimester remain unclear. This study aimed to quantify the trimester-specific direct effects of low GWG in Japanese women on birthweight. Using perinatal data from a cohort study, we analyzed pregnant women delivered at an obstetrics/gynecology hospital between October 2006 and May 2010. We focused on women with a pre-pregnancy body mass index (BMI) below 25 kg/m2. The exposure was low GWG. The gestation period was subdivided into trimesters, and the direct effects of low trimester-specific GWG on birthweight were estimated using marginal structural models. These models were guided by a direct acyclic graph that incorporated potential confounders, including pre-pregnancy BMI, age, smoking during pregnancy, height, and parity. We analyzed 563 women and their families. The mean cumulative GWG by the end of the first, second, and third trimesters was 0.9, 6.2, and 10.7 kg, respectively. Approximately 14.0% of the women gained total weight below the range recommended by Japanese Ministry of Health, Labour and Welfare. The direct effects of low GWG on birthweight were 65.9 g (95% confidence interval: 11.4, 120.5), −195.4 g (−263.4, −127.4), and −188.8 g (−292.0, −85.5) for the first, second, and third trimesters, respectively. Insufficient weight gain in the second and third trimesters had a negative impact on birthweight after adjusting for pre-pregnancy BMI and other covariates.

Intergenerational links of chronic disease have been suggested, as birthweight (BW) is associated with cardiovascular disease (CVD) and type 2 diabetes (T2D) in both parents and grandparents. However, most studies investigating these relationships have used relatively homogenous, white, majority populations. This study aimed to investigate the association between BW and CVD and T2D in a multiethnic population, that is, where the parents and grandparents often developed in a different environment from that where the child was born. Participants were women from a population-based cohort study of pregnant women (STORK Groruddalen), attending Child Health Clinics for antenatal care in three administrative city districts in Oslo, Norway, 2008–2010. Information about socioeconomic and lifestyle factors were collected among mothers and fathers. Parents reported history of CVD or T2D among grandparents. In logistic regressions, higher BW z-scores were associated with lower odds of T2D among maternal (OR 0.71 (95% CI 0.53, 0.97) and paternal (0.68 (0.49, 0.94) grandmothers after adjustments for parental and grandmothers’ characteristics. BW was not associated with CVD, but the association in maternal grandfathers was borderline significant. Our results indicate intergenerational transmission of chronic diseases like T2D in a multiethnic population.

Epidemiological studies have demonstrated an increased risk of developing non-transmittable diseases in adults subjected to adverse early developmental conditions. Metabolic and cardiovascular diseases have been the focus of most studies. Nevertheless, data from animal models also suggest early programming of fertility. In humans, it is difficult to assess the impact of the in utero environment retrospectively. Birthweight is commonly used as an indirect indicator of intrauterine development. This research is part of the ALIFERT study. We investigated a potential link between ponderal index at birth and female fertility in adulthood. Data from 51 infertile and 74 fertile women were analysed. BW was on average higher in infertile women, whereas birth length did not differ between the two groups; thus, resulting in a significantly higher ponderal index at birth in infertile women. Ponderal index at birth has been identified as a risk factor for infertility. These results suggest the importance of the intra-uterine environment, not only for long-term metabolic health but also for fertility.

Imprinted genes uniquely drive and support fetoplacental growth by controlling the allocation of maternal resources to the fetus and affecting the newborn’s growth. We previously showed that alterations of the placental imprinted gene expression are associated with suboptimal perinatal growth and respond to environmental stimuli including socio-economic determinants. At the same time, maternal psychosocial stress during pregnancy (MPSP) has been shown to affect fetal growth. Here, we set out to test the hypothesis that placental imprinted gene expression mediates the effects of MPSP on fetal growth in a well-characterized birth cohort, the Stress in Pregnancy (SIP) Study. We observed that mothers experiencing high MPSP deliver infants with lower birthweight (P=0.047). Among the 109 imprinted genes tested, we detected panels of placental imprinted gene expression of 23 imprinted genes associated with MPSP and 26 with birthweight. Among these genes, five imprinted genes (CPXM2, glucosidase alpha acid (GAA), GPR1, SH3 and multiple ankyrin repeat domains 2 (SHANK2) and THSD7A) were common to the two panels. In multivariate analyses, controlling for maternal age and education and gestational age at birth and infant gender, two genes, GAA and SHANK2, each showed a 22% mediation of MPSP on fetal growth. These data provide new insights into the role that imprinted genes play in translating the maternal stress message into a fetoplacental growth pattern.

While birthweight of offspring is associated with pre-pregnancy body mass index (BMI) and later risk of obesity, its mediating effect between the association of maternal pre-pregnancy BMI and offspring’s childhood anthropometrics has rarely been investigated. This study aimed to examine whether offspring birthweight is a mediator in the association between pre-pregnancy BMI and offspring’s childhood anthropometrics. The study included 1,618 mother–child pairs from the Australian Longitudinal Study on Women’s Health and Mothers and their Children’s Health Study. Children’s anthropometrics [mean age 8.6 (s.d. =3.0) years] were calculated from the mothers’ self-reported child weight and height measures. G-computation was used to estimate the natural direct and indirect (via birthweight) effects of pre-pregnancy BMI. In the fully adjusted model for maternal sociodemographic and lifestyle factors, the natural direct effects of pre-pregnancy obesity on child BMI-for-age, height-for-age, weight-for-age and weight-for-height outcomes were, β (95% confidence interval, CI), 0.75 (0.55, 0.95), 0.13 (−0.07, 0.32), 0.62 (0.44, 0.80) and 0.57 (0.24, 0.90), respectively. The corresponding natural indirect effects were 0.04 (−0.04, 0.12), −0.01 (−0.09, 0.07), −0.01 (−0.08, 0.07) and 0.09 (−0.05, 0.23). Similar results were observed for pre-pregnancy overweight and pre-pregnancy BMI as a continuous scale. Most of the effect of pre-pregnancy obesity on childhood weight-related anthropometric outcomes appears to be via a direct effect, not mediated through offspring’s birthweight.

Despite many interventions aiming to reduce excessive gestational weight gain (GWG), it is currently unclear the impact on infant anthropometric outcomes. The aim of this review was to evaluate offspring anthropometric outcomes in studies designed to reduce GWG. A systematic search of seven international databases, one clinical trial registry and three Chinese databases was conducted without date limits. Studies were categorised by intervention type: diet, physical activity (PA), lifestyle (diet + PA), other, gestational diabetes mellitus (GDM) (diet, PA, lifestyle, metformin and other). Meta-analyses were reported as weighted mean difference (WMD) for birthweight and birth length, and risk ratio (RR) for small for gestational age (SGA), large for gestational age (LGA), macrosomia and low birth weight (LBW). Collectively, interventions reduced birthweight, risk of macrosomia and LGA by 71 g (WMD: −70.67, 95% CI −101.90 to −39.43, P<0.001), 16% (RR: 0.84, 95% CI 0.73–0.98, P=0.026) and 19% (RR: 0.81, 95% CI 0.69–0.96, P=0.015), respectively. Diet interventions decreased birthweight and LGA by 99 g (WMD −98.80, 95% CI −178.85 to −18.76, P=0.016) and 65% (RR: 0.35, 95% CI 0.17–0.72, P=0.004). PA interventions reduced the risk of macrosomia by 51% (RR: 0.49, 95% CI 0.26–0.92, P=0.036). In women with GDM, diet and lifestyle interventions reduced birthweight by 211 and 296 g, respectively (WMD: −210.93, 95% CI −374.77 to −46.71, P=0.012 and WMD:−295.93, 95% CI −501.76 to −90.10, P=0.005, respectively). Interventions designed to reduce excessive GWG lead to a small reduction in infant birthweight and risk of macrosomia and LGA, without influencing the risk of adverse outcomes including LBW and SGA.

Despite the interest in the relationship of fetal exposures to adult cardiovascular disease, few studies have examined indicators of adult fatty liver disease as an outcome. Previous results are inconsistent, and indicate possible variation by sex. Adult liver enzymes [γ-glutamyl transferase (GGT), alanine transaminase (ALT) and aspartase transaminase (AST)] were measured in two cohort studies: the Bogalusa Heart Study (BHS; n=1803) and the Cardiovascular Risk in Young Finns (YF; n=3571) study, which also had ultrasound measures of liver fat (n=2546). Predictors of dichotomized (clinical cut-offs) and continuous (within the reference range) liver enzymes included low birthweight (<2500 g), macrosomia (>4000 g), small-for-gestational-age (birthweight <10th percentile for gestational age for population), large-for-gestational-age (>90th percentile), and preterm birth. Multiple logistic and linear regression were conducted, adjusted for medical, behavioral and socioeconomic indicators. Interactions with sex were also examined. In BHS, birth measures were not strongly associated with clinically high levels of liver enzymes, and within the reference range measures of reduced growth were associated with increased AST in women. In the YF study, at least one marker of reduced growth was associated with higher GGT, higher ALT and higher AST (in women). Probable fatty liver on ultrasound was associated with low birthweight (2.41, 1.42–4.09) and preterm birth (2.84, 1.70–4.76). These results suggest a link between birth parameters and adult fatty liver, but encourage consideration of population variation in these relationships.

The prevalence of placental malaria and its impact on maternal and newborn outcomes have been poorly documented in periurban settings of Burkina Faso. Peripheral and placental blood from 320 mothers, and cord blood from their newborns were collected through a cross-sectional study and used to prepare thick and thin blood films. Maternal haemoglobin concentration and birthweight were also measured. The overall malaria parasitaemia prevalence in peripheral, placental and cord blood was of 17·2, 9·1 and 0·9%, respectively. Plasmodium falciparum was the sole species found in all cases and the mean parasite density in placental blood was 4·5 ± 0·8 parasites µL−1. Primigravida (aOR: 3·5; 95% CI (1·1–11·2)) and women who did not use a bed net (aOR: 2·6; 95% CI (1·1–6·3)), were at higher odds of placental malaria infection. Women with placental parasitaemia were at increased odds of maternal anaemia (aOR: 3·1; 95% CI (1·3–7·4)). There was no odds difference for LBW between mothers with placental parasitaemia and those without. Placental malaria parasitaemia resulted in a significant mean birthweight reduction of 200 g. Placental malaria infection is higher in primigravida. Use of insecticide-treated bed nets should be therefore emphasized for primigravida during the first antenatal care visit.

We analyzed whether motor development in early life is different between singletons and triplets in Japan. The motor development was reported by mothers by postal questionnaire for 1,121 triplet children and in regular health check-ups for 13,906 singleton children. Children who were suspected of having neurological abnormality or disability were excluded from the analysis. The ages of milestone achievements were significantly higher in triplets for each outcome compared to singletons. Further, after adjustment for gestational age, birthweight, and birth length, the differences were significant for maintaining head, sitting alone and standing holding on. In children with birthweight of 2 kg or more, the ages of milestone achievements were significantly higher in triplets for each outcome compared to singletons, except walking holding on. Moreover, after adjustment for the confounding factors, the differences were significant for sitting alone and walking independently. On the contrary, singletons attained motor development facilitating crawling, walking holding on, and walking independently slower than triplets among those children with birthweight of 2 kg or less after adjustment for gestational age. In conclusion, triplets are overall at higher risk for the delay of gross motor milestones as compared to singletons independently of birth-related factors. In contrast, among children with a birthweight of less than 2 kg, singletons showed slower motor development than triplets after adjusting for gestational age. There is an obvious need to apply developmental standards that consider at least both multiple birth status (singleton, twin or triplet) and birthweight.