There is an established link between birth parameters and risk of adult-onset cancers. The Developmental Origins of Health and Disease concept provides potential underlying mechanisms for such associations, including intrauterine exposure to endogenous hormones (androgens and estrogens), insulin-like growth factors, etc. However, there is conflicting evidence on the association between birth parameters and the cancer mortality risk. Therefore, we aimed to review and analyse the available data on the association linking birth weight and birth length with cancer mortality. Eleven studies were identified, published until April 2019. A significant association between birth weight and the prognosis of cancer (overall) was found (relative risk, RR 1.06, 95% confidence interval, CI: 1.01, 1.11), with low heterogeneity (I2 = 27.7%). In addition, higher birth weight was associated with poorer prognosis of prostate cancer (RR 1.21, 95% CI: 1.02, 1.44). However, the association of birth weight with breast cancer mortality risk in women was not significant (RR 1.16, 95% CI: 0.93, 1.44), which might be due to high statistical heterogeneity (I2 = 67.9%). Birth length was not associated with cancer mortality risk (RR 1.0, 95% CI: 0.90–1.11). It might be inferred that birth parameters are not associated with cancer mortality as strongly as with the risk of developing cancer. Also, the association between birth parameters and cancer mortality risk is not uniform and varies according to its subtypes, and study characteristics/design. This highlights the need for further prospective studies.

Adverse birth outcomes and infant undernutrition remain the leading causes of morbidity and mortality in sub-Saharan Africa (SSA). Impaired infant growth and development, which often begins during foetal development, may persist during the first 2 years of life and has been associated with higher risks of cardiometabolic diseases. This systematic review assessed the associations between maternal demographic characteristics and household socio-economic status (SES), and preterm birth (PTB), small for gestational age, low birth weight (LBW), stunting, wasting and underweight in children under 2 years of age in SSA countries. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, we searched for publications in three electronic databases (PubMed, Scopus and ScienceDirect). Eleven studies on children under 2 years of age, in four SSA regions, published in English between 1990 and 2018, were included. All the studies were observational in design (cross-sectional or cohort studies). Maternal education was the most commonly explored exposure. Most studies (63.3%) focused on undernutrition during the first 2 years of life: LBW, PTB and stunting. Lower maternal education, maternal unemployment and lower household wealth index were the SES factors most commonly associated with adverse birth outcomes and infant undernutrition. Maternal marital status was not associated with any infant outcomes. The definitions of the SES varied, which may explain discrepancies between studies. Nutrition intervention programs in SSA need to promote education and poverty alleviation in women at reproductive age, starting from pre-pregnancy, to optimise infant growth and development and prevent the increase in the prevalence of cardiometabolic diseases.

This study aimed to assess the evidence regarding the relationship between early-life antibiotic exposure and childhood overweight/obesity by reviewing observational studies on prenatal antibiotic exposure and systematic reviews on infant antibiotic exposure. A search in Pubmed, Embase and Google Scholar covering the period 1st January till 1st December 2018 led to the identification of five studies on prenatal antibiotic exposure and four systematic reviews on infant antibiotic exposure. Positive trends between prenatal antibiotic exposure and overweight/obesity were reported in all studies; two studies reported a significant overall relationship and the other three reported significant relationships under certain conditions. Effect sizes ranged from odds ratio (OR): 1.04 (0.62–1.74) to relative risk (RR): 1.77 (1.25–2.51). Regarding infant antibiotics, one review concluded there was substantial evidence that infant antibiotic exposure increased the risk of childhood overweight/obesity [pooled effect sizes: RR: 1.21 (1.09–1.33) for overweight and RR: 1.18 (1.12–1.25) for obesity]. Two reviews concluded there was some evidence for a relationship [pooled effect sizes: OR: 1.05 (1.00–1.11) and OR: 1.11 (1.02–1.20)]. The fourth review concluded the studies were too heterogeneous for meta-analyses and the evidence regarding the relationship between infant antibiotic exposure and childhood overweight/obesity was inconclusive. More well-designed studies are needed that include data on intra-partum antibiotics and address important potential confounders (including maternal and childhood infections). This review points to some evidence of a relationship between early-life antibiotic exposure and childhood overweight/obesity; this is especially evident in certain children (i.e. exposed to multiple and broad-spectrum antibiotics, earlier postnatal exposure and male gender) and merits further research.

Placental weight is a valuable indicator of its function, predicting both pregnancy outcome and lifelong health. Population-based centile charts of weight-for-gestational-age and parity are useful for identifying extremes of placental weight but fail to consider maternal size. To address this deficit, a multiple regression model was fitted to derive coefficients for predicting normal placental weight using records from healthy pregnancies of nulliparous/multiparous women of differing height and weight (n = 107,170 deliveries, 37–43 weeks gestation). The difference between actual and predicted placental weight generated a z-score/individual centile for the entire cohort including women with pregnancy complications (n = 121,591). The association between maternal BMI and placental weight extremes defined by the new customised versus population-based standard was investigated by logistic regression, as was the association between low placental weight and pregnancy complications. Underweight women had a greater risk of low placental weight [<10thcentile, OR 1.84 (95% CI 1.66, 2.05)] and obese women had a greater risk of high placental weight [>90th centile, OR 1.98 (95% CI 1.88, 2.10)] using a population standard. After customisation, the risk of high placental weight in obese/morbidly obese women was attenuated [OR 1.17 (95% CI 1.09, 1.25)]/no longer significant, while their risk of low placental weight was 59%–129% higher (P < 0.001). The customised placental weight standard was more closely associated with stillbirth, hypertensive disease, placental abruption and neonatal death than the population standard. Our customised placental weight standard reveals higher risk of relative placental growth restriction leading to lower than expected birthweights in obese women, and a stronger association between low placental weight and pregnancy complications generally. Further, it provides an alternative tool for defining placental weight extremes with implications for the placental programming of chronic disease.

Growth in early life is associated with various individual health outcomes in adulthood, but limited research has been done on associations with a more comprehensive measure of health. Combining information from multiple biological systems, allostatic load (AL) provides such a quantitative measure of overall physiological health. We used longitudinal data from the Birth to Twenty Plus cohort in South Africa to calculate an AL score at age 22 years and examined associations with birth weight and linear growth and weight gain from age 0 to 2 years and 2 to 5 years, as attenuated by trajectories of body mass index and pubertal development in later childhood and adolescence. Differences in total AL score between males and females were small, though levels of individual biological factors contributing to AL differed by sex. Increased weight gain from age 2 to 5 years among males was associated with an increased risk of high AL, but no other early-life measures were associated with AL. Increased adiposity through childhood and adolescence in females was associated with higher AL in early adulthood. These results illustrate that patterns of early-life growth are not consistently associated with higher AL. While more research is needed to link AL in young adulthood to later health outcomes, these results also suggest increased adiposity during childhood and adolescence represents a potential early sign of later physiological risk.

Placental lipids transfer is essential for optimal fetal development, and alterations of these mechanisms could lead to a higher risk of adverse birth outcomes. Low-density lipoprotein receptor (LDLR), LDL receptor-related protein 1 (LRP1), and scavenger receptor class B type 1 (SCARB1) genes are encoding lipoprotein receptors expressed in the placenta where they participate in cholesterol exchange from maternal to fetal circulation. The aim of this study was thus to investigate the association between maternal lipid changes occurring in pregnancy, placental DNA methylation (DNAm) variations at LDLR, LRP1, and SCARB1 gene loci, and newborn’s anthropometric profile at birth. Sixty-nine normoglycemic women were followed from the first trimester of pregnancy until delivery. Placental DNAm was quantified at 43 Cytosine-phosphate-Guanines (CpGs) at LDLR, LRP1, and SCARB1 gene loci using pyrosequencing: 4 CpGs were retained for further analysis. Maternal clinical data were collected at each trimester of pregnancy. Newborns’ data were collected from medical records. Statistical models included minimally newborn sex and gestational and maternal age. Maternal total cholesterol changes during pregnancy (ΔT3-T1) were correlated with DNAm variations at LDLR (r = −0.32, p = 0.01) and LRP1 (r = 0.34, p = 0.007). DNAm at these loci was also correlated with newborns’ cord blood triglyceride and leptin levels. Mediation analysis supports a causal relationship between maternal cholesterol changes, DNAm levels at LRP1 locus, and cord blood leptin concentration (pmediation = 0.02). These results suggest that LRP1 DNAm link maternal blood cholesterol changes in pregnancy and offspring adiposity at birth, which provide support for a better follow-up of blood lipids in pregnancy.

Lower birth weight is associated with a risk of type 2 diabetes in adulthood. However, it is not clear whether this association is modified by physical activity. This study aimed to examine the association between birth weight and glycemic status and whether this association is mediated by moderate- and vigorous-intensity activity (MVPA) in Japanese women. The participants were 103 nondiabetic women (47.4 ± 10.8 years), who underwent health checkups in which data of glycated hemoglobin (HbA1c) were collected. Abdominal circumference (AC) was measured at the umbilical region. Birth weight was obtained from the Maternal and Child Health Handbook records or reported based on the participant’s or his/her mother’s recall. Time (min/day) spent in MVPA (≥3.0 metabolic equivalents) was objectively measured using a triaxial accelerometer (Actimarker EW4800). Birth weight was inversely correlated with HbA1c (r = −0.32, P < 0.01). Multiple linear regression analyses revealed that lower birth weight was associated with increased HbA1c (β = −0.22, P < 0.05) even after adjusting for age, state of menstruation, AC, and family history of diabetes. This association was little changed when MVPA was introduced as an independent variable in the model (β = −0.23, P < 0.05). These results suggest that lower birth weight may be associated with higher HbA1c levels before the onset of type 2 diabetes, irrespective of adulthood physical activity. Early-life development should be taken into account when considering the risk of diabetes in Japanese women, even if they are physically active.

Growth in the immediate postnatal period for extremely low birth weight (ELBW, birth weight < 1000 g) infants is an important topic in neonatal medicine. The goal is to ensure adequate postnatal growth and to minimize complications resulting from suboptimal growth. Past efforts have focused on postnatal nutrition as well as on minimizing comorbidities. It has not been systematically assessed whether antenatal factors play a role in postnatal growth. In this report, we conducted a retrospective study on 91 maternal–neonatal pairs. We prospectively collected maternal and neonatal demographic data, neonatal nutrition in the first 7 days of life and after enteral nutrition is fully established, comorbidity data, as well as weight data from birth to 50 weeks corrected gestational age. We developed a linear mixed-effects model to examine the role of placental insufficiency, as defined by fetal Doppler studies, in postnatal weight z-score trajectory over time in the ELBW population. We relied on Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) for model selection. Interestingly, the selected model included a quadratic term of time and a placental insufficiency-by-time interaction term. In a covariate analysis, AIC and BIC both favored a model that included calories intake in the first 7 days of life and the total duration of antibiotics as fixed-effects, but not their interaction terms with time. Overall, we demonstrated for the first time that placental insufficiency, an antenatal factor, is a major determinant of postnatal weight trajectory in the ELBW population. Prospective studies are warranted to confirm our findings.

Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.

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.

Extremely low birth weight (ELBW) survivors have higher rates of shyness, a risk factor for poorer outcomes across the life span. Due to advances in fetal and neonatal medicine, the first generation of ELBW survivors have survived to adulthood and become parents. However, no studies have investigated the transmission of their stress vulnerability to their offspring. We explored this phenomenon using a population-based cohort of ELBW survivors and normal birth weight (NBW) controls. Using data from three generations, we examined whether the shyness and parenting stress of ELBW and NBW participants (Generation 2) mediated the relation between the parenting style of their parents (Generation 1) and shyness in their offspring (Generation 3), and the extent to which exposure to perinatal adversity (Generation 2) moderated this mediating effect. We found that among ELBW survivors, parenting stress (in Generation 2) mediated the relation between overprotective parenting style in Generation 1 (grandparents) and child shyness in Generation 3. These findings suggest that perinatal adversity and stress may be transmitted to the next generation in humans, as reflected in their perceptions of their children as shy and socially anxious, a personality phenotype that may subsequently place their children at risk of later mental and physical health problems.

It is estimated that 80% of the world population trusts traditional medicine. A large number of Americans use infusions of Bocconia frutescens L. leaves to treat cough and gastrointestinal disorders. However, phytochemical studies reveal that this plant contains alkaloids and other potentially harmful substances. This study aimed to evaluate the teratogenic effects of B. frutescens L. in an experimental model. Pregnant Wistar rats were administered lyophilized B. frutescens L. extract at 300 mg/kg/day or vehicle by orogastric route during the organogenesis period (gestation days 7–13), and external and internal congenital malformations were analyzed on the progeny on gestational day 20. Bocconia frutescens L. produced a significant increase in the number of different malformations, relative to the control group. We conclude that the consumption of B. frutescens L. during pregnancy at a dose equivalent to that consumed by humans increases the risk of teratogenic effects.

Prenatal exposure to persistent organic pollutants (POPs) has been associated with the development of metabolic syndrome-related diseases in offspring. According to epidemiological studies, father’s transmission of environmental effects in addition to mother’s can influence offspring health. Moreover, maternal prenatal dietary folic acid (FA) may beneficially impact offspring health. The objective is to investigate whether prenatal FA supplementation can overcome the deleterious effects of prenatal exposure to POPs on lipid homeostasis and inflammation in three generations of male rat descendants through the paternal lineage. Female Sprague-Dawley rats (F0) were exposed to a POPs mixture (or corn oil) +/− FA supplementation for 9 weeks before and during gestation. F1 and F2 males were mated with untreated females. Plasma and hepatic lipids were measured in F1, F2, and F3 males after 12-h fast. Gene expression of inflammatory cytokines was determined by qPCR in epididymal adipose tissue. In F1 males, prenatal POPs exposure increased plasma lipids at 14 weeks old and hepatic lipids at 28 weeks old and prenatal FA supplementation decreased plasma total cholesterol at 14 weeks old. Prenatal POPs exposure decreased plasma triglycerides at 14 weeks old in F2 males. No change was observed in inflammatory markers. Our results show an impact of the paternal lineage on lipid homeostasis in rats up to the F2 male generation. FA supplementation of the F0 diet, regardless of POPs exposure, lowered plasma cholesterol in F1 males but failed to attenuate the deleterious effects of prenatal POPs exposure on plasma and hepatic lipids in F1 males.